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CD004846
|
[
"14745057",
"8826488"
] |
[
"Systemic lidocaine in pain due to peripheral nerve injury and predictors of response.",
"Lidocaine patch: double-blind controlled study of a new treatment method for post-herpetic neuralgia."
] |
[
"To investigate the effects of IV lidocaine on spontaneous and evoked pain (allodynia and hyperalgesia) due to peripheral nerve injury (postherpetic neuralgia or nerve trauma) using quantitative sensory testing.\n The authors randomized 22 patients to receive lidocaine 5 mg/kg IV during 30 minutes or placebo in a double-blind crossover design and 16 patients subsequently received mexiletine on an open basis titrated from 400 to 1,000 mg per day (mean 737 mg/day).\n Lidocaine induced a significant decrease in ongoing pain for up to 6 hours with a peak effect 60 to 120 minutes postinjection. The drug also decreased mechanical dynamic allodynia and static (punctate) mechanical allodynia/hyperalgesia, but not thermal allodynia and hyperalgesia. The effects of lidocaine and mexiletine on spontaneous pain intensity were significantly higher in patients with concomitant mechanical allodynia in comparison with those without allodynia.\n These data indicate modality-specific antihyperalgesic effects of IV lidocaine in patients with peripheral nerve injury. Patients with mechanical allodynia may be good candidates for treatment with local anesthetic-like drugs and possibly with other sodium-channel blockers.",
"Post-herpetic neuralgia (PHN) is a common and often intractable neuropathic pain syndrome predominantly affecting the elderly. Topical local anesthetics have shown promise in both uncontrolled and controlled studies. Thirty-five subjects with established PHN affecting the torso or extremities completed a four-session, random order, double-blind, vehicle-controlled study of the analgesic effects of topically applied 5% lidocaine in the form of a non-woven polyethylene adhesive patch. All subjects had allodynia on examination. Up to 3 patches, covering a maximum of 420 cm2, were applied to cover the area of greatest pain as fully as possible. Lidocaine containing patches were applied in two of the four 12-h-long sessions, in one session vehicle patches were applied, and one session was a no-treatment observation session. Lidocaine containing patches significantly reduced pain intensity at all time points 30 min to 12 h compared to no-treatment observation, and at all time points 4--12 h compared to vehicle patches. Lidocaine patches were superior to both no-treatment observation and vehicle patches in averaged category pain relief scores. The highest blood lidocaine level measured was 0.1 micrograms/ml, indicating minimal systemic absorption of lidocaine. Patch application was without systemic side effect and well tolerated when applied on allodynic skin for 12 h. This study demonstrates that topical 5% lidocaine in patch form is easy to use and relieves post-herpetic neuralgia."
] |
Since the last version of this review in Issue 2, 2007 no new studies have been found and the results therefore remain the same. There is still insufficient evidence to recommend topical lidocaine as a first-line agent in the treatment of postherpetic neuralgia with allodynia. Further research should be undertaken on the efficacy of topical lidocaine for other chronic neuropathic pain disorders, and also to compare different classes of drugs (e.g. topical anaesthetic applications versus anti-epileptic drugs).
|
CD004246
|
[
"15714420",
"12032877",
"15115831",
"18977721"
] |
[
"Development of HIV with drug resistance after CD4 cell count-guided structured treatment interruptions in patients treated with highly active antiretroviral therapy after dual-nucleoside analogue treatment.",
"SENC (Spanish efavirenz vs. nevirapine comparison) trial: a randomized, open-label study in HIV-infected naive individuals.",
"Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection.",
"Virologic, immunologic, clinical, safety, and resistance outcomes from a long-term comparison of efavirenz-based versus nevirapine-based antiretroviral regimens as initial therapy in HIV-1-infected persons."
] |
[
"For patients with human immunodeficiency virus (HIV) infection, structured treatment interruption (STI) is an attractive alternative strategy to continuous treatment, particularly in resource-restrained settings, because it reduces both side effects and costs. One major concern, however, is the development of resistance to antiretroviral drugs that can occur during multiple cycles of starting and stopping therapy.\n HIV genotypic drug resistance was investigated in 20 HIV-infected Thai patients treated with highly active antiretroviral therapy (HAART) and CD4 cell count-guided STI after dual nucleoside reverse-transcriptase inhibitor (NRTI) treatment. Resistance was tested at the time of the switch from dual-NRTI treatment to HAART and when HAART was stopped during the last interruption.\n After STI, one major drug-resistance mutation occurred (T215Y), and, in the 4 samples with preexisting major mutations (D67N [n=2], K70R [n=2], T215Y [n=2], and T215I [n=1]), the mutations disappeared. All mutations in the HIV protease gene were minor mutations already present, in most cases, before STI was started, and their frequency was not increased through STI, whereas the frequency of reverse-transcriptase gene mutations significantly decreased after the interruptions. After the 48-week study period, no patients had virological failure. Long-term follow-up (108 weeks) showed 1 case of virological failure in the STI arm and 1 in the continuous arm. No virological failure was seen in patients with major mutations.\n Major HIV drug-resistance mutations were not induced through CD4 cell count-guided treatment interruptions in HIV-infected patients successfully treated with HAART after dual-NRTI therapy.",
"A randomized, open-label, pilot study was undertaken to explore the antiviral activity and tolerability of two nonnucleoside reverse transcriptase inhibitors (NNRTIs), nevirapine (NVP) and efavirenz (EFV).\n HIV-infected antiretroviral-naive adults with CD4 counts >100 cells/mm(3) and detectable plasma HIV RNA below 100,000 copies/mL were randomized to receive didanosine (ddI) and stavudine (d4T) plus either NVP or EFV. Assessments were made every 12 weeks. Primary endpoints were the proportion of patients reaching plasma HIV RNA <50 copies/mL and/or developing NNRTI-related toxicities leading to drug discontinuation. Baseline characteristics were comparable for participants in the EFV (n = 31) and NVP arms (n = 36).\n At 48 weeks, 23/31 (74%) patients in the EFV group and 23/36 (64%) in the NVP group had <50 HIV RNA copies/mL (intention-to-treat analysis). Adverse events led to NNRTI discontinuation in 4 and 3 patients in the EFV and NVP arms, respectively. There were no statistically significant differences between groups regarding any primary endpoint. NVP and EFV along with two NRTIs may be equally well tolerated and effective at achieving <50 HIV RNA copies/mL in naive patients with CD4 counts >100 cells/mm(3) and HIV RNA <10(5) copies/mL.\n A much larger study is needed to demonstrate any significant differences between NVP and EFV, if they exist at all.",
"Regimens containing three nucleoside reverse-transcriptase inhibitors offer an alternative to regimens containing nonnucleoside reverse-transcriptase inhibitors or protease inhibitors for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection, but data from direct comparisons are limited.\n This randomized, double-blind study involved three antiretroviral regimens for the initial treatment of subjects infected with HIV-1: zidovudine-lamivudine-abacavir, zidovudine-lamivudine plus efavirenz, and zidovudine-lamivudine-abacavir plus efavirenz.\n We enrolled a total of 1147 subjects with a mean baseline HIV-1 RNA level of 4.85 log10 (71,434) copies per milliliter and a mean CD4 cell count of 238 per cubic millimeter were enrolled. A scheduled review by the data and safety monitoring board with the use of prespecified stopping boundaries led to a recommendation to stop the triple-nucleoside group and to present the results in the triple-nucleoside group in comparison with pooled data from the efavirenz groups. After a median follow-up of 32 weeks, 82 of 382 subjects in the triple-nucleoside group (21 percent) and 85 of 765 of those in the combined efavirenz groups (11 percent) had virologic failure; the time to virologic failure was significantly shorter in the triple-nucleoside group (P<0.001). This difference was observed regardless of the pretreatment HIV-1 RNA stratum (at least 100,000 copies per milliliter or below this level; P< or =0.001 for both comparisons). Changes in the CD4 cell count and the incidence of grade 3 or grade 4 adverse events did not differ significantly between the groups.\n In this trial of the initial treatment of HIV-1 infection, the triple-nucleoside combination of abacavir, zidovudine, and lamivudine was virologically inferior to a regimen containing efavirenz and two or three nucleosides.\n Copyright 2004 Massachusetts Medical Society",
"To compare long-term virologic, immunologic, and clinical outcomes in antiretroviral-naïve persons starting efavirenz (EFV)- versus nevirapine (NVP)-based regimens.\n The FIRST study randomized patients into three strategy arms: PI+NRTI, NNRTI+NRTI, and PI+NNRTI+NRTI. NNRTI was determined by optional randomization (NVP or EFV) or by choice. For this randomized substudy, the primary endpoint was HIV RNA >50 copies/mL after 8 months or death. Genotypic resistance testing was done at virologic failure (VF; HIV RNA >1,000 copies/mL at or after 4 months).\n 228 persons (111 randomized to EFV, 117 to NVP) were followed for median 5 years. Rates per 100 person years for the primary endpoint were 41.2 (EFV) and 42.8 (NVP; p = .59). The percent of persons with HIV RNA <50 copies/mL was similar throughout follow-up (p = .24), as were average increases in CD4+ cells (p = .30). 423 persons declining the substudy chose EFV; 264 chose NVP. There were 915 persons in the combined cohort (randomized and choice). In the combined cohort, the risk of VF and VF with any NNRTI or NRTI resistance or resistance of any class was significantly less for EFV compared to NVP.\n EFV-based regimens as initial therapy resulted in a lower risk of VF and VF with resistance than did NVP-based regimens, although immunologic and clinical outcomes were similar."
] |
Both drugs have equivalent efficacies in initial treatment of HIV infection when combined with two NRTIs, but different side effects.
|
CD004708
|
[
"7369850",
"17663615",
"15939927",
"11820343"
] |
[
"Psychosocial rehabilitation of gynecologic oncology patients.",
"Coping and communication-enhancing intervention versus supportive counseling for women diagnosed with gynecological cancers.",
"Effect of individual psychological intervention in Chinese women with gynecologic malignancy: a randomized controlled trial.",
"The effect of a clinical nurse specialist in gynaecological oncology on quality of life and sexuality."
] |
[
"This investigation studied the effectiveness of in-hospital, individual counseling on the psychosocial adjustment of patients with newly diagnosed gynecologic malignancies. Levels of psychologic distress, sexual functioning, and return to employment were assessed at 3, 6, and 12 months after counseling. The counseled patients were compared with a similar control group that was assessed but not counseled. In this study, levels of psychologic distress reported by cancer patients were similar to those reported in normal populations. However, at 3 months post-treatment, counseled cancer patients reported significantly less confusion and contradiction within areas of self-perception than did the noncounseled patients. Return to employment and sexual activities were both shown to be adversely affected by the diagnosis and treatment of genital cancer. Results suggested that counseling had a positive effect in enhancing return to normal vocational and sexual functions during the 1st year after treatment.",
"This study compared the efficacy of 2 psychological interventions, a coping and communication-enhancing intervention (CCI) and supportive counseling (SC), in reducing depressive symptoms and cancer-specific distress of women diagnosed with gynecological cancer. Demographic, medical, and psychological moderators of intervention effects were evaluated. Three hundred fifty-three women with gynecological cancer were randomly assigned to 7 sessions of CCI, 7 sessions of SC, or usual care. Intent-to-treat growth curve analyses indicated that participants assigned to CCI and SC reported lower depressive symptoms than participants assigned to usual care at the 6- and 9-month follow-ups. Women with greater than average increases in physician-rated physical symptoms and/or women who were more expressive of positive emotions benefited more from SC than women with lower than average increases in symptom scores and/or women who were less expressive of positive emotions. These findings suggest that both interventions may be effective in treating depressive symptoms among patients with gynecological cancer. Future research should evaluate whether bolstering both psychological interventions with additional intervention sessions and topics in the disease trajectory will result in persistent long-term effects.",
"To evaluate the effectiveness of psychological intervention in the care of cancer patients and to determine whether routine use of individual psychological therapies is indicated.\n Patients with newly diagnosed gynecologic malignancies from August 1999 to November 2000 were recruited and randomly assigned to either a control group receiving routine medical care or to an intervention group receiving individual psychotherapy. A set of fixed-choice, self-report questionnaires assessing the patients' psychological status, quality of life, and their perceptions related to the medical consultations was completed at recruitment and then every 3 months for 18 months. Data analysis was performed according to the intention-to-treat principle by fitting the data into a linear mixed-effects model. Multivariable analyses were performed to examine the effects of confounding factors.\n One hundred fifty-five patients participated in the trial. There were no statistically significant differences between the two groups at baseline. There was a trend toward better quality of life and functional status and also improvement of the symptoms over time for both groups. No differences were found between the groups in the scores measured by any of the instruments at baseline and at any time points after the cancer diagnosis. Psychological intervention had no significant effects on the psychosocial parameters.\n Routine use of psychological therapies as given in our format has no significant effect on the patients' quality of life and psychological status.",
"Gynaecological malignancy has an immense impact on the well-being of women. For many women, however, treatment such as surgery is curative and healthcare intervention focuses on the physiological status of the women. The psychological, social and sexual consequences of the malignancy and its treatment have received little attention in research or in practice. The present study used a mixed quantitative and qualitative design to analyse a specialist nurse intervention (including psychosexual intervention), and to explain the impact of the illness on women's lives. The qualitative arm of the study collected interview data from 20 women and six partners. The randomized controlled trial sample consisted of 36 women, with data collected using a quality of life measure (the EORTC QLQ-C30) and the Lasry Sexual Functioning scale. This paper focuses on the randomized controlled trial data, which identified that sexual functioning and quality of life were improved in the active group who received specialist psychosexual counselling. However, the validity of the sexual functioning scale is challenged by the qualitative results of the study, which emphasize the social meaning of sexuality."
] |
There is no convincing evidence to support the use of any interventions for psychosexual dysfunction in women treated for gynaecological cancer. There is a need for more studies of high methodological quality.
|
CD009672
|
[
"17085380",
"10989245",
"16822626",
"16143225",
"11770188",
"19731119",
"12034516",
"9932566",
"8861087",
"17217318",
"11109313",
"9800666",
"17995496",
"19034054",
"8861084",
"10515676",
"17893293",
"19297102",
"11304940",
"16183220",
"7616869"
] |
[
"Effect of different preparations of hormone therapy on sexual dysfunction in naturally postmenopausal women.",
"The comparison of effects of tibolone and conjugated estrogen-medroxyprogesterone acetate therapy on sexual performance in postmenopausal women.",
"The benefits of androgens combined with hormone replacement therapy regarding to patients with postmenopausal sexual symptoms.",
"Two hormone replacement therapy (HRT) regimens for middle-eastern postmenopausal women.",
"Quality of life and sexuality changes in postmenopausal women receiving tibolone therapy.",
"Comparative effects of conventional hormone replacement therapy and tibolone on climacteric symptoms and sexual dysfunction in postmenopausal women.",
"Prospective, randomised study with three HRT regimens in postmenopausal women with an intact uterus.",
"Continuous combined hormone replacement therapy compared with tibolone.",
"Tibolone versus conjugated estrogens and sequential progestogen in the treatment of climacteric complaints.",
"Monophasic estrogen-progestogen therapy and sexuality in postmenopausal women.",
"[Influence of hormone replacement therapy on the quality of life in postmenopausal women with hypertension].",
"Estrogen and estrogen-androgen replacement in postmenopausal women dissatisfied with estrogen-only therapy. Sexual behavior and neuroendocrine responses.",
"Tibolone and low-dose continuous combined hormone treatment: vaginal bleeding pattern, efficacy and tolerability.",
"A randomized study of low-dose conjugated estrogens on sexual function and quality of life in postmenopausal women.",
"17 beta-estradiol and norethisterone acetate in low doses as continuous combined hormone replacement therapy.",
"Comparison of transdermal estradiol and tibolone for the treatment of oophorectomized women with deep residual endometriosis.",
"Hormone therapy in menopausal women with cognitive complaints: a randomized, double-blind trial.",
"A randomized double-blind trial of the effects of hormone therapy on delayed verbal recall in older women.",
"Double-blind, placebo-controlled psychometric studies on the effects of a combined estrogen-progestin regimen versus estrogen alone on performance, mood and personality of menopausal syndrome patients.",
"Treatment with percutanous testosterone gel in postmenopausal women with decreased libido--effects on sexuality and psychological general well-being.",
"A comparative study of two hormone replacement therapy regimens on safety and efficacy variables."
] |
[
"To compare the effect of different formulations of continuous combined hormone therapy on sexual performance in naturally postmenopausal women.\n A total of 158 postmenopausal women were enrolled and prospectively randomized to the single-blind study. Fifty-four women received tibolone 2.5 mg, 53 received 2 mg estradiol and 2 mg dienogest (E2/dienogest), and 51 did not receive any menopausal therapy. The patients were monitored after 6 months. Attitudes of sexuality were evaluated by using the Rosen's female sexual function index.\n Compared with E2/dienogest and the control group, tibolone treatment was associated with more improvement of sexual performance, including sexual desire, sexual arousal and satisfaction. Both of the hormone therapies decreased frequencies of vaginal dryness and painful intercourse.\n Tibolone has more positive effects on the sexual dysfunction of postmenopausal women and may be an alternative to the E2/dienogest preparation in postmenopausal women with sexual dysfunction.",
"To compare the effects of two different postmenopausal regimens on sexual performance.\n A single blind prospective clinical study was planned on fifty natural postmenopausal women with no absolute contraindication for hormone replacement therapy (HRT). A total of 25 women were randomized for tibolone therapy (group T) and the rest 25 for continuous conjugated estrogen (CE) 0. 625 mg plus medroxyprogesterone acetate (MPA) 2.5 mg (group E) for a year. Two women in group T and four women in group E were excluded from the study as they didn't attend the control visit. At baseline and after a year, sexual performance parameters (sexual desire, coital frequency, orgasm frequency, vaginal dryness/dyspareunia) and after therapy subjective well-being, vasomotor symptoms, and side effects were assessed by score method designed by us.\n Treatment with either preparation significantly improved subjective well-being, vasomotor symptoms and vaginal dryness. The rates of overall side effects between two groups were not found statistically different (P=0.84). Tibolone therapy increased sexual desire and coital frequency (P=0.001, P=0.014).\n Both tibolone and continuous combined CE/MPA effectively improve the findings of hypoestrogenism and subjective well being. Moreover, tibolone effectively increases sexual performance. It is seen that tibolone with acceptable androgenic side effects can be an appropriate selection for HRT in postmenopausal women with decreased sexual desire.",
"To evaluate the benefits and risks of hormone replacement therapy (HRT) combined with methyltestosterone (MT) in postmenopausal women with sexual dysfunction.\n This study was a randomized, double-blind, placebo-controlled and crossover trial. Eighty-five women using HRT were divided into four treatment groups: GI-HRT plus placebo for 4 months; GII-HRT plus MT 2.5mg/day for 4 months; GIII-HRT plus placebo for 2 months and then replaced with HRT plus MT 2.5mg/day for 2 months; GIV-HRT plus MT 2.5mg/day and then replaced with HRT plus placebo for 2 months. Blood was collected at baseline, after 2 months (T1) and 4 months (T2) of treatment for hormone determinations of estradiol, FSH, total and free testosterone, GOT, GPT, glucose, total and fractions of cholesterol and triglycerides. All participants answered clinical questions and a validated questionnaire of modified McCoy's sex scale.\n The association of HRT with MT 2.5mg/day did not significantly change liver enzymes or increase cardiovascular risk factors. The patients of GII, GIIII and GIV when using MT presented amelioration of sex symptoms, mainly satisfaction and desire (p<0.01); however, GIII at T1 (1.3+/-0.3) presented similar problem score results as compared to GIII at T2 (1.5+/-0.6).\n All data suggest that combined HRT-androgen therapy may be beneficial for postmenopausal women receiving HRT who continue to complain of sexual difficulties or for postmenopausal women with sexual complaints who are not undergoing estrogen therapy.",
"Most previous studies designed to evaluate the efficacy of hormone replacement therapy (HRT) have been carried out in Europe, North America and Australia, involving Caucasian women for 6 months or less.\n To evaluate the 12-month effects of two different HRT regimens on postmenopausal symptoms of Middle-Eastern women.\n Hundred healthy Libyan women with postmenopausal symptoms, 12 months or more since their last menstrual period, were enrolled in a 12-month prospective study. Participants were randomly prescribed one of the two formulations, 50 in each group. These regimens were a continuous regimen of tibolone 2.5 mg oral tablets and a continuous regimen of 17beta-oestradiol sequentially combined with dydrogesterone (2/10 mg) oral tablets. The presence and severity of short- and intermediate-term symptoms were reported at 0, 3, 6 and 12 months of treatment. Observed symptoms were hot flushes, night sweating, palpitations, insomnia, depression, nervousness, loss of memory, vaginal dryness, loss of libido and joint pain.\n Forty-nine women (98%) in each group completed the 12-month study period. Participants, in the two groups, experienced a significant improvement within the first 3 months of treatment. The observed symptoms were completely relived by the sixth month without any significant difference between the two groups. Improvements were sustained over the 12-month period of the study. HRT users showed their acceptance to the two regimens.\n Tibolone and 17beta-oestradiol/dydrogesterone oral tablets were effective and safe to treat short- and intermediate-term symptoms in Middle-Eastern postmenopausal women, within 6 months, and with no significant differences between the groups. Thus, the use of HRT to relieve menopausal symptoms is highly recommended, at least in this region.",
"The goal of this study was to investigate the effects of hormone replacement therapy (HRT) and tibolone on the sexuality and quality of life of Taiwanese postmenopausal women.\n Forty-eight postmenopausal women were enrolled and prospectively randomized to receive either HRT or tibolone for 3 months. At the end of the 3-month period, quality of life measures were assessed using the Greene Climacteric Scale and attitudes of sexuality were evaluated using the McCoy Sex Scale.\n Based on subjective qualitative scores, tibolone treatment was at least as effective as continuous combined HRT in improving quality of life. It also effectively prevented withdrawal bleeding, which may occur during HRT use. Compared with continuous combined HRT, tibolone treatment was also associated with perceived improvement of sexual performance, including general sexual satisfaction, sexual interest, sexual fantasies, sexual arousal and orgasm, with decreased frequencies of vaginal dryness and painful intercourse.\n The findings of this study indicate that both tibolone and continuous combined HRT have positive effects on the quality of life of Taiwanese postmenopausal women. Sexuality is affected more by tibolone than by HRT.",
"To compare the effects of tibolone with those of conventional hormone replacement therapy on climacteric symptoms and sexual function in postmenopausal women.\n In a randomized, controlled trial, 140 postmenopausal women were allocated into three groups. Of the subjects included, 47 women received 2.5 mg tibolone + one Cal+D tablet (500 mg calcium and 200 IU vitamin D) daily; 46 women received 0.625 mg conjugated equine estrogen + 2.5 mg medroxyprogesterone (CEE/MPA) + one Cal+D tablet daily; and 47 women received only one Cal+D tablet as the control group. The Greene Climacteric Scale (GCS) questionnaire was used to detect the efficacy of treatment on climacteric symptoms. Rosen's Female Sexual Function Index (FSFI) was used for sexual function evaluation. Sex hormone binding globulin (SHBG), free estradiol index (FEI) and free testosterone index (FTI) were measured before and after treatment. The women were followed up for 6 months\n After treatment, all subscores in the GCS improved in the tibolone and CEE/MPA groups (p < 0.01), except the sexual subscore in the CEE/MPA group, compared with baseline. There were significant differences in the FSFI in the tibolone and CEE/MPA groups in comparison to the control group after treatment. Tibolone, in comparison to CEE/MPA, significantly lowered SHBG levels and increased the FTI and FEI and improved the desire, arousal and orgasm sexual domains of the FSFI (p < 0.001).\n Tibolone may be an alternative to conventional hormone replacement therapy in the treatment of climacteric symptoms and sexual dysfunction in postmenopausal women.",
"To compare compliance, symptom control, bleeding patterns, lipid and biochemical changes in postmenopausal women treated with three regimens of HRT.\n In a prospective, randomised, group comparative study, with 165 patients, the effects on the aforementioned parameters, as well as treatment compliance and side effects were studied with oral tibolone 2.5 mg per day, with cyclic combined regimen of transdermal oestrogen and progestogen (transdermal patch of 17beta-oestradiol 50 microg/day during 14 days and transdermal patch of 17beta-oestradiol 50 microg/day plus 0.25 mg/day NETA during the following 14 days), and with intermittent progesterone regimen (transdermal 17beta-oestradiol 50 microg/day and oral micronised natural progesterone 200 mg twice a week). Statistical analysis was carried out using the Fisher-test, analysis of the variance (ANOVA) and the Bouferoni test.\n Ten women dropped out of the tibolone group, 11 dropped out of the intermittent dosing group and 21 dropped out of the cyclid combined group. Irregular bleeding occurred at more rates in the cyclid combined group. Similar reductions in climacteric symptoms were found in the three groups. No differences were observed with respect to biochemical analysis.\n Efficacy and safety of the three treatment regimens being comparable, but the patients in our study preferred those that did not produce bleeding episodes.",
"To compare relief of vasomotor symptoms, changes in lipoproteins, and bleeding patterns in postmenopausal women receiving either continuous combined hormone replacement therapy (HRT) of estradiol valerate and norethisterone or tibolone 2.5 mg/day.\n In a multicenter, randomized, open-label study, 235 postmenopausal women received one of the above-mentioned treatments. Fasting lipoproteins were measured at baseline and at 3, 6, and 12 months. At each visit, participants completed Greene climacteric questionnaires and recorded any bleeding episodes. Data are presented as mean +/- standard deviation if normally distributed, median and interquartile range if non-normally distributed, or as frequency count. For menopausal symptoms and diary card data, the differences were tested by Wilcoxon rank-sum test.\n One hundred sixteen women received continuous combined HRT and 119 women received tibolone; 72 and 76 women, respectively, completed 12 months of therapy. Both treatments effectively relieved vasomotor symptoms and reduced serum total cholesterol. Continuous combined HRT, but not tibolone, significantly reduced low-density lipoprotein levels. Both treatments reduced high-density lipoprotein levels, but the effect was more profound with tibolone. The initial bleeding score was higher for women taking continuous combined HRT; however, by the end of the study, the percentages of amenorrheal women were comparable. Endometrial histology was similar for both treatments at the end of the study, although two cases of proliferative endometrium were found in the tibolone group.\n Estradiol valerate-norethisterone continuous combined HRT controls symptoms and is associated with a safe lipid profile.",
"Tibolone has been shown to alleviate climacteric symptoms. This study was designed to compare the effect of tibolone (Livial, 2.5 mg daily) on different climacteric complaints and its impact on the endometrium, determined by vaginal ultrasound, with that of conjugated estrogens (Premarin, 0.625 mg daily) continuously for 6 months in combination with the progestogen medrogestone (Colpron, 2 x 5 mg daily for 12 days each month).\n One hundred and twenty-nine postmenopausal women were recruited and the severity of climacteric symptoms as well as endometrial thickness were recorded at the pre-trial examination and after 1, 3, and 6 months.\n With the exception of vertigo, mood depression, mood disorder, loss of libido, and dryness of skin, where tibolone was found to be more effective than conjugated estrogens/medrogestone, climacteric symptoms improved significantly in both groups over the 6-month study period. Endometrial thickness did not increase significantly in the tibolone group, whereas in the conjugated estrogens/medrogestone group there was a highly significant increase after 1 month and still a trend towards significance after 6 months. Recurrence of vaginal bleeding occurred significantly less frequently in the tibolone group than in the comparison group.\n Tibolone seems to offer a complete treatment of the climacteric complaints whilst avoiding some of the problems associated with classical hormone replacement therapy.",
"This study aimed to evaluate the effects of monophasic estrogen-progestogen therapy on the sexuality and climacteric symptoms of postmenopausal women.\n A prospective, randomised, double-blind, crossover, placebo-controlled, single-centre study was carried out over a total of 12 consecutive months in 40 postmenopausal women with an intact uterus who had no contraindications to hormone therapy. Patients received 17beta-estradiol 2mg in combination with norethisterone acetate 1mg (Cliane) daily for 6 months or one placebo tablet daily for 6 months. The tablets were identical in appearance. After 6 months, the groups were crossed over and the patients were followed up for another 6 months. The groups were homogenous with respect to age, height, bodyweight, body mass index and race. For the statistical analysis, the group receiving hormone therapy was referred to as group A and the placebo group was designated group B, irrespective of the placebo/hormone therapy sequence.\n In group A there were fewer hot flashes (F=22.85, p<0.01) and an improvement in sexual interest (F=5.55, p<0.05). The sequence in which the medication was received resulted in a statistically significant difference with respect to dyspareunia (F=9.65, p<0.01) and satisfaction with the duration of penetration (F=6.58, p<0.05). In the intrapatient analysis of variation with respect to orgasmic capability and the presence of dialogue with partner regarding the couple's sexual life, whether the placebo was taken prior to or following hormone therapy was significant (F=17.12, p<0.001 and F=7.10, p<0.05, respectively).\n Monophasic estrogen-progestogen therapy has a beneficial effect on sexuality and on hot flashes in postmenopausal women.",
"The effect of hormone replacement therapy (HRT) on the quality of life in women with hypertension is still not clear. Thus, the aim of the study was to assess the effect of hormone replacement therapy on quality of life in postmenopausal women with essential hypertension by using a battery of standardized questionnaires.\n The study population consisted of 53 women (mean age 50.9 +/- 6.3 years) with mild and moderate essential hypertension (mean duration 6.4 +/- 6.4 years). The postmenopausal status was defined as the absence of menstrual blood loss during > 6 months and blood estradiol concentration < 50 pg/ml, accompanied by follicle-stimulating hormone (FSH) levels > 21 U/I. Twenty seven women were blindly randomised to transdermal hormone replacement therapy (HRT) and received 17-beta-estradiol and noretisterone acetate, TTS. Twenty six women were randomly selected as controls. The subjects were evaluated at baseline (after 2 weeks' wash-out from hypotensive drug period) and after three months of HRT using self-administered standardized quality of life questionnaires: the Psychological General Well-being Index (PGWB) and the Subjective Symptoms Assessment Profile (SSA-P).\n No differences were found in blood pressure values, heart rate, body mass index and distribution of body fat tissue between women receiving HRT and controls at baseline and after 3 months of follow-up. There were no significant differences in the baseline total PGWB score as well as in its subscale between two groups. Similarly, the frequency and intensity of subjective symptoms assessed by SSA-profile were the same in both groups at baseline. After 3 months, a significant improvement in PGWB total score was observed in women receiving HRT. This effect was due to improvement in anxiety, positive well-being and vitality. Moreover, emotional distress, symptoms of flushing, sweating and trembling hands also diminished and sexual capacity improved in women treated with HRT.\n A three-month hormone replacement therapy in hypertensive postmenopausal women slightly improves the general well-being, seems to decrease emotional tension, increase sexual capacity and markedly relieves some vasomotor symptoms.",
"To investigate the efficacy of esterified estrogens alone and combined with oral androgen on sexual function and menopausal symptoms in postmenopausal women.\n Twenty postmenopausal women dissatisfied with their estrogen or estrogen-progestin therapy volunteered to enter a double-blind, randomized trial in which they received either oral esterified estrogens or esterified estrogens + androgen for eight weeks after a single-blind, placebo, lead-in period. Sexual function was assessed with a questionnaire used in the Yale midlife survey, and plasma levels of estradiol, estrone, sex hormone binding globulin (SHBG) and beta-endorphin were measured at two- to four-week intervals.\n Estrogen-androgen therapy significantly improved sexual sensation and desire after four and eight weeks of double-blind treatment in comparison to previous estrogen therapy and postplacebo baseline assessments. Plasma levels of estradiol and estrone increased significantly in all patients as compared to the postplacebo baseline and decreased in comparison to circulating estrogen concentrations on previous therapy. Relative proportions of free and bound steroid hormone exhibited contrasting shifts during estrogen and estrogen-androgen therapy. SHBG increased in the estrogen group and decreased in the estrogen-androgen group, leading to lower amounts of free androgens during estrogen therapy and increased free androgen levels during estrogen-androgen therapy. Since proportions of free (bioavailable) ovarian steroids would correlate inversely with plasma protein binding capacity, the beneficial effects of oral estrogen-androgen therapy on sexual sensation and desire may be due either to the administered androgen or to the increased availability of endogenous and exogenous androgens, particularly in the central nervous system.\n Sexual desire, satisfaction and frequency in postmenopausal women taking hormonal therapy were improved significantly by combined estrogen-androgen therapy but not by estrogen or estrogen-progestin therapy. Sexual function improved with estrogen-androgen therapy even though circulating estrogen levels were lower than those measured during previous estrogen therapy. This leads to the conclusion that androgens play a pivotal role in sexual function but that estrogens are not a significant factor determining levels of sexual drive and enjoyment.",
"The primary objective was to compare the vaginal bleeding pattern during administration of tibolone and low-dose continuous combined estradiol plus norethisterone acetate (E2/NETA). The secondary objectives were efficacy on vasomotor symptoms and vaginal atrophy.\n A randomised, double-blind, double-dummy, group comparative intervention trial.\n Multicentre study executed in 32 centres in 7 European countries.\n Five hundred and seventy-two healthy symptomatic postmenopausal women, aged 45-65 years.\n Participants were randomised to receive 2.5 mg tibolone or 1 mg 17beta estradiol plus 0.5 mg norethisterone acetate (E2/NETA) daily for 48 weeks.\n Prevalence of vaginal bleeding, hot flushes and adverse events.\n The incidence of bleeding was significantly lower in the tibolone group during the first 3 months of treatment (18.3 versus 33.1%; P < 0.001) when compared with the E2/NETA group. This effect on the bleeding pattern was sustained throughout the study, although reaching statistical significance again only in 7-9 months of treatment (11 versus 19%; P < 0.05). In both treatment groups, vasomotor symptoms and vaginal atrophy were significantly reduced to a similar extent when compared with baseline. The prevalence of breast pain/tenderness was significantly lower with tibolone compared with E2/NETA (3.2 versus 9.8%; P < 0.001).\n Tibolone reduces menopausal symptoms to a similar extent as conventional low-dose continuous combined hormone therapy but causes significant less vaginal bleeding in the first 3 months of treatment. This constitutes an important argument for woman adherence to therapy.",
"To evaluate the effects of combined vaginal and oral low-dose estrogen plus progestogen therapy (EPT) on the frequency and severity of dyspareunia, sexual function, and quality of life in recently postmenopausal women.\n This outpatient, double-blind, randomized, placebo-controlled trial enrolled 285 healthy, sexually active postmenopausal women aged 45 to 65 years. Women received either one daily oral low-dose conjugated estrogens (0.45 mg)/medroxyprogesterone (1.5 mg) tablet for six 28-day cycles along with 1 g conjugated estrogens vaginal cream (0.625 mg), intravaginally for the first 6 weeks of the trial or a placebo cream and placebo tablet. Efficacy was evaluated using the McCoy Female Sexuality Questionnaire, self-reported daily diary cards, the Brief Index of Sexual Functioning-Women (BISF-W), and the Women's Health Questionnaire.\n The EPT group had a significant decrease in the frequency of dyspareunia compared with baseline and placebo in an analysis of responses to the McCoy Female Sexuality Questionnaire. Also, EPT was associated with a significant improvement in a woman's level of sexual interest, frequency of orgasm, and pleasure of orgasm. There was no effect of EPT use on coital frequency. The EPT group had significant improvement in receptivity/initiation and relationship satisfaction, although not in other BISF-W domains, versus placebo (BISF-W analysis) and significant improvement versus placebo on most Women's Health Questionnaire responses.\n EPT provided a statistically significant improvement compared with placebo in dyspareunia, sexual experience, and quality of life as measured in this study. In general, EPT also improved self-reported sexual perception and enjoyment significantly compared with placebo.",
"To evaluate low doses of 17 beta-estradiol (E2) and norethisterone acetate (NETA) as continuous combined hormone replacement therapy (HRT) in their effects on vasomotor symptoms, bleeding episodes, endometrial histology and mastalgia.\n Sixty postmenopausal women were randomly allocated to three treatment groups and were given 1 mg E2 and 0.25 mg NETA (A), 1 mg E2 and 0.5 mg NETA (B) and 2 mg E2 and 1.0 mg NETA (C) in daily doses. The treatment period was 1 year.\n A similar statistically significant reduction of climacteric symptoms (P < 0.05) was found in all groups. Bleedings, mainly as spottings, occurred most commonly during the first treatment months. Fewer bleeding episodes and a higher percentage of amenorrhea was noted in group B compared to the other groups but did not reach statistical significance. All endometrial biopsies showed atrophy. Women in group A and B had less severe mastalgia (P < 0.05) compared to group C, given higher doses of steroids.\n Postmenopausal women taking 1 mg of E2 plus 0.5 mg NETA as continuous combined HRT reported a marked reduction of climacteric complaints and good bleeding control. No endometrial proliferation was detected after 1 year of treatment. This type of therapy may be beneficial especially for elderly women, in whom bleeding may be annoying.",
"To compare the effect of HRT with transdermal estradiol and that of treatment with tibolone in post-menopausal women with residual endometriosis.\n 21 women with residual pelvic endometriosis after bilateral oophorectomy with or without hysterectomy were enrolled in the study and were randomized to HRT with transdermal estradiol 50 mg twice weekly (n = 10) associated with cyclic medroxyprogesterone acetate 10 mg daily in women who preserved uterus, and to treatment with tibolone 2.5 mg administered orally once a day (n = 11). The duration of both treatments was scheduled to last at least 12 months. Residual endometriosis was located in the bowel wall in four patients, in the rectovaginal septum in six and deeply in the retroperitoneal pelvic space in six. All women were symptomatic before oophorectomy.\n All the women were followed for 12 months. No patient suspended therapy because of side effects. Four patients of the estradiol group experienced moderate pelvic pain during treatment compared with only one patient in the tibolone group. One patient in the estradiol group reported severe dyspareunia.\n Although our series is very small, it seems that tibolone may be a safe hormonal treatment for post-menopausal women with residual endometriosis.",
"To evaluate the effects of hormone therapy (HT) on cognition and subjective quality of life (QoL) in recently postmenopausal women with cognitive complaints.\n Cognitive Complaints in Early Menopause Trial (COGENT) was a randomized, double-blind, placebo-controlled, multicenter, pilot study of 180 healthy postmenopausal women aged 45 to 55 years, randomly assigned to receive either placebo or conjugated equine estrogen 0.625 mg/medroxyprogesterone acetate 2.5 mg for 4 months. Outcome measures included memory, subjective cognition, QoL, sexuality, and sleep, which were assessed at baseline and month 4.\n The study was terminated before the expected final sample size of 275 due to a decrease in enrollment coinciding with the publication of findings from the Women's Health Initiative. There were no differences between groups on any cognitive or QoL measures, except for an increase in sexual interest and thoughts with HT. Modest negative effects on short- and long-term verbal memory approached significance (p < 0.10). Women with baseline vasomotor symptoms (VMS) showed a decrease in VMS and an improvement in general QoL, but no cognitive benefit vs placebo.\n With the power to detect an effect size of >or=0.45, this study suggests potential modest negative effects on verbal memory that are consistent with previous hormone therapy trials in older women.",
"We examined whether estradiol and norethindrone hormone therapy (HT) prevented decline in delayed verbal recall in older women with normal to mildly impaired memory functioning. This was a 2-year, randomized, double-blind, placebo-controlled trial of 142 women aged 61-87, randomly assigned to receive 1 mg 17-beta estradiol daily and 0.35 mg norethindrone 3 days/week or daily placebo for 2 years. The primary outcome was short-delay verbal recall of the California Verbal Learning Test (CVLT). To look for differences in response to HT by baseline short-delay recall, we examined the primary outcome in participants grouped according to whether their baseline scores were below average for the age group or greater than or equal to this score and according to whether they met criteria for Mild Cognitive Impairment (MCI) or not. 133 women completed 1 year of the trial and 128 completed 2 years. Prespecified covariates in all repeated measures analyses of covariance (RANCOVA) included age, education, APOE epsilon4, and prior HT use. RANCOVA showed no overall significant treatment effects at year 1 or year 2. After testing for an interaction, which was significant (p=0.02), we found that women in the HT group who scored at or above the average showed significantly less decline than the placebo group in short-delay verbal recall after 1 year, p=0.007 and 2 years, p=0.01. No treatment effects were found in women below the average in either year. When grouped according to whether the participant met criteria for MCI, the interaction between treatment group and MCI subgroup was not significant. These results suggest that benefits of estrogen exposure may be limited to those with average to above average scores on the delayed verbal recall. HT dose and formulation may have contributed to these beneficial outcomes. Replication is warranted before recommendations can be made in the clinical setting.",
"The influence of a combined estrogen-progestin regimen (Climodien) on noopsyche, thymopsyche, personality and psychophysiological measures of menopausal syndrome patients was investigated in a double-blind, placebo-controlled, comparative, randomized 3-arm trial phase (Climodien 2/3 = estradiol valerate (CAS 979-32-8) 2 mg + the progestin dienogest (CAS 65928-58-7) 3 mg = regimen A, estradiol valerate 2 mg = regimen EV, and placebo = regimen P) followed by an open-label phase in which all patients received Climodien 2/2 (estradiol valerate 2 mg + dienogest 2 mg) = regimen A*. 49 women (16, 17, 16 valid patients per arm) aged between 46 and 67 years (mean 58, 58, 56 years, respectively) with the diagnoses of insomnia (G 47.0) related to postmenopausal syndrome (N 95.1) were included in the analysis of the double-blind phase. Both the double-blind and the open-label phase lasted 2 months. Noopsychic investigations demonstrated an improvement in associative verbal memory after 2 months of regimen A, which was significant as compared with both baseline and placebo. Regarding visual memory, regimen A* induced an improvement, which was significantly different from the decline in correct reproductions in the Benton Test observed under estradiol. Errors in the Benton Test decreased significantly after regimen A* as compared with regimen EV. These findings suggest that hormone replacement therapy with estradiol, and even more in combination with dienogest, improves verbal and visual memory, which is in line with the improvement in information processing speed and capacity objectified by event-related potentials (ERP). Thymopsychic investigations demonstrated a significant improvement in somatic complaints and trait anxiety after both regimen A and regimen EV as compared with baseline. State anxiety decreased significantly under regimen A* as compared with EV. The Freiburger Personality Inventory showed an improvement in aggressivity after regimen A* as compared with the preceding placebo as well as an improvement in striving after dominancy after both regimen A and regimen EV as compared with pre-treatment, but also after regimen A* as compared with regimen EV. Extraversion increased after 2 months of regimen A as compared to regimen P. Psychophysiological findings including pupillary and skin conductance variables were not significant.",
"To elucidate if percutanous treatment with 10mg testosterone per day could enhance sexuality and psychological well-being in postmenopausal women presenting problems with low libido. Secondary to study the influence on blood lipids, hemoglobin and erythropoietin levels.\n Fifty-three postmenopausal women participated. As a complement to their already on-going HRT, 10mg of a testosterone gel (Testogel, Besins-Iscovesco) or placebo was administered. Treatment continued for three plus three months in a double blind, randomized, crossover design.\n The scores concerning \"frequency of sexual activity, orgasm and intercourse\", \"sexual arousal, fantasies and enjoyment\", \"satisfaction with orgasms\", and \"interest in sex\" were all significally improved for testosterone addition as compared to placebo both before and after crossover. Testosterone levels increased more than 10-fold during treatment while DHT-levels were more than doubled. Estrogen levels were not affected during the addition of testosterone. Liver enzymes, total cholesterol, triglycerides, HDL and LDL revealed no significant differences between any of the periods or groups. Endometrial thickness did not change significantly during treatment. Hemoglobin and erythropoietin remained unchanged. No significant differences in the number of experienced side effects were found.\n Testosterone gel of 10mg had positive effects on several aspects of sexual life such as frequency of sexual activity, orgasm, arousal, fantasies and sexual interest in postmenopausal women on HRT. Several psychological variables were positively influenced. The given dose resulted in too high serum levels. Even if no negative effects were observed, monitoring of serum levels and a decreased dose should be considered in future studies.",
"To assess the effect of tibolone on endometrial safety, plasma estradiol concentrations, lipid metabolism and climacteric symptoms in comparison to sequential conjugated equine estrogens and medroxyprogesterone acetate in postmenopausal women.\n In a randomised, open-label, 6-cycle, group-comparative study, the effects on the aforementioned parameters were studied with tibolone 2.5 mg/day (N = 13) continuously, and with conjugated equine estrogens 0.625 mg/day continuously, combined with medroxyprogesterone acetate 5 mg/day (N = 11) (CEE/MPA) sequentially, during 12 days of each 28-day cycle. Within-group statistical analysis was performed with Student's t-test for paired samples, whereas between-group statistics were performed using the Student's t-test for independent groups.\n Cytological evaluation revealed no endometrial stimulation in either group. In the tibolone group, there were no effects on estradiol levels, whereas in the CEE/MPA group, an increase in total and non-SHBG-bound estradiol plasma levels was reported. In the tibolone group, there were significant decreases in plasma total cholesterol, triglycerides, HDL-cholesterol and VLDL-cholesterol, whereas no significant changes in LDL-cholesterol and IDL-cholesterol were reported. In the CEE/MPA group there were significant decreases in plasma total cholesterol, HDL-cholesterol and LDL-cholesterol, whereas there were no significant changes in triglycerides, IDL-cholesterol and VLDL-cholesterol. Climacteric symptoms, particularly vasomotor episodes, decreased similarly in both groups.\n Both tibolone and CEE/MPA were safe with respect to effects on the endometrium and both treatments induced changes in the plasma profiles of certain lipid and lipoprotein parameters. However, the overall clinical implications of these changes are unknown. Finally, both regimens were equally effective in the treatment of climacteric symptoms."
] |
HT treatment with estrogens alone or in combination with progestogens was associated with a small to moderate improvement in sexual function, particularly in pain, when used in women with menopausal symptoms or in early postmenopause (within five years of amenorrhoea), but not in unselected postmenopausal women. Evidence regarding other HTs (synthetic steroids and SERMs) is of low quality and we are uncertain of their effect on sexual function. The current evidence does not suggest an important effect of tibolone or of SERMs alone or combined with estrogens on sexual function. More studies evaluating the effect of synthetic steroids, SERMS and the association of SERM + estrogens would improve the quality of the evidence for the effect of these treatments on sexual function in peri and postmenopausal women. Future studies should also evaluate the effect of HT solely among women with sexual complaints.
|
CD003844
|
[
"10793162",
"10470755",
"9847275",
"18270352",
"16557151",
"9449728"
] |
[
"Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network.",
"Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients.",
"Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS.",
"Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial.",
"A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial.",
"Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. Pressure- and Volume-Limited Ventilation Strategy Group."
] |
[
"Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients.\n Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter, randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less. The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28.\n The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0 percent vs. 39.8 percent, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean [+/-SD], 12+/-11 vs. 10+/-11; P=0.007). The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight (P<0.001), respectively, and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water (P<0.001), respectively.\n In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use.",
"To assess the safety and potential efficacy of a mechanical ventilation strategy designed to reduce stretch-induced lung injury in acute respiratory distress syndrome.\n Prospective, randomized, controlled clinical trial.\n Eight intensive care units in four teaching hospitals.\n Fifty-two patients with acute respiratory distress syndrome.\n Traditional tidal volume patients: tidal volume 10-12 mL/kg ideal body weight, reduced if inspiratory plateau pressure was > 55 cm H2O (7.3 kPa). Small tidal volume patients: tidal volume 5-8 mL/kg ideal body weight, to keep plateau pressure < 30 cm H2O (4.0 kPa).\n Mean tidal volumes during the first 5 days in traditional and small tidal volume patients were 10.2 and 7.3 mL/kg, respectively (p < .001), with mean plateau pressure = 30.6 and 24.9 cm H2O (3.3 kPa), respectively (p < .001). There were no significant differences in requirements for positive end-expiratory pressure or FIO2, fluid intakes/outputs, requirements for vasopressors, sedatives, or neuromuscular blocking agents, percentage of patients that achieved unassisted breathing, ventilator days, or mortality.\n The reduced tidal volume strategy used in this study was safe. Failure to observe beneficial effects of small tidal volume ventilation treatment in important clinical outcome variables may have occurred because a) the sample size was too small to discern small treatment effects; b) the differences in tidal volumes and plateau pressures were modest; or c) reduced tidal volume ventilation is not beneficial.",
"Because animal studies have demonstrated that mechanical ventilation at high volume and pressure can be deleterious to the lungs, limitation of airway pressure, allowing hypercapnia if necessary, is already used for ventilation of acute respiratory distress syndrome (ARDS). Whether a systematic and more drastic reduction is necessary is debatable. A multicenter randomized study was undertaken to compare a strategy aimed at limiting the end-inspiratory plateau pressure to 25 cm H2O, using tidal volume (VT) below 10 ml/kg of body weight, versus a more conventional ventilatory approach (with regard to current practice) using VT at 10 ml/kg or above and close to normal PaCO2. Both arms used a similar level of positive end-expiratory pressure. A total of 116 patients with ARDS and no organ failure other than the lung were enrolled over 32 mo in 25 centers. The two groups were similar at inclusion. Patients in the two arms were ventilated with different VT (7.1 +/- 1.3 versus 10.3 +/- 1.7 ml/kg at Day 1, p < 0.001) and plateau pressures (25.7 +/- 5. 0 versus 31.7 +/- 6.6 cm H2O at Day 1, p < 0.001), resulting in different PaCO2 (59.5 +/- 15.0 versus 41.3 +/- 7.6 mm Hg, p < 0.001) and pH (7.28 +/- 0.09 versus 7.4 +/- 0.09, p < 0.001), but a similar level of oxygenation. The new approach did not reduce mortality at Day 60 (46.6% versus 37.9% in control subjects, p = 0.38), the duration of mechanical ventilation (23.1 +/- 20.2 versus 21.4 +/- 16. 3 d, p = 0.85), the incidence of pneumothorax (14% versus 12%, p = 0. 78), or the secondary occurrence of multiple organ failure (41% versus 41%, p = 1). We conclude that no benefit could be observed with reduced VT titrated to reach plateau pressures around 25 cm H2O compared with a more conventional approach in which normocapnia was achieved with plateau pressures already below 35 cm H2O.",
"Low-tidal-volume ventilation reduces mortality in critically ill patients with acute lung injury and acute respiratory distress syndrome. Instituting additional strategies to open collapsed lung tissue may further reduce mortality.\n To compare an established low-tidal-volume ventilation strategy with an experimental strategy based on the original \"open-lung approach,\" combining low tidal volume, lung recruitment maneuvers, and high positive-end-expiratory pressure.\n Randomized controlled trial with concealed allocation and blinded data analysis conducted between August 2000 and March 2006 in 30 intensive care units in Canada, Australia, and Saudi Arabia.\n Nine hundred eighty-three consecutive patients with acute lung injury and a ratio of arterial oxygen tension to inspired oxygen fraction not exceeding 250.\n The control strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau airway pressures not exceeding 30 cm H2O, and conventional levels of positive end-expiratory pressure (n = 508). The experimental strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau pressures not exceeding 40 cm H2O, recruitment maneuvers, and higher positive end-expiratory pressures (n = 475).\n All-cause hospital mortality.\n Eighty-five percent of the 983 study patients met criteria for acute respiratory distress syndrome at enrollment. Tidal volumes remained similar in the 2 groups, and mean positive end-expiratory pressures were 14.6 (SD, 3.4) cm H2O in the experimental group vs 9.8 (SD, 2.7) cm H2O among controls during the first 72 hours (P < .001). All-cause hospital mortality rates were 36.4% and 40.4%, respectively (relative risk [RR], 0.90; 95% confidence interval [CI], 0.77-1.05; P = .19). Barotrauma rates were 11.2% and 9.1% (RR, 1.21; 95% CI, 0.83-1.75; P = .33). The experimental group had lower rates of refractory hypoxemia (4.6% vs 10.2%; RR, 0.54; 95% CI, 0.34-0.86; P = .01), death with refractory hypoxemia (4.2% vs 8.9%; RR, 0.56; 95% CI, 0.34-0.93; P = .03), and previously defined eligible use of rescue therapies (5.1% vs 9.3%; RR, 0.61; 95% CI, 0.38-0.99; P = .045).\n For patients with acute lung injury and acute respiratory distress syndrome, a multifaceted protocolized ventilation strategy designed to recruit and open the lung resulted in no significant difference in all-cause hospital mortality or barotrauma compared with an established low-tidal-volume protocolized ventilation strategy. This \"open-lung\" strategy did appear to improve secondary end points related to hypoxemia and use of rescue therapies.\n clinicaltrials.gov Identifier: NCT00182195.",
"It has been shown in a two-center study that high positive end-expiratory pressure (PEEP) and low tidal volume (LTV) improved outcome in ARDS. However, that study involved patients with underlying diseases unique to the study area, was conducted at only two centers, and enrolled a small number of patients. We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system (Pflex) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome (ARDS).\n Randomized, controlled clinical trial.\n Network of eight Spanish multidisciplinary intensive care units (ICUs) under the acronym of ARIES (Acute Respiratory Insufficiency: España Study).\n All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study. If 24 hrs after meeting ARDS criteria, the Pao2/Fio2 remained < or =200 mm Hg on standard ventilator settings, patients were randomized into two groups: control and Pflex/LTV.\n In the control group, tidal volume was 9-11 mL/kg of predicted body weight (PBW) and PEEP > or =5 cm H2O. In the Pflex/LTV group, tidal volume was 5-8 mL/kg PBW and PEEP was set on day 1 at Pflex + 2 cm H2O. In both groups, Fio2 was set to maintain arterial oxygen saturation >90% and Pao2 70-100 mm Hg, and respiratory rate was adjusted to maintain Paco2 between 35 and 50 mm Hg.\n The study was stopped early based on an efficacy stopping rule as described in the methods. Of 103 patients who were enrolled (50 control and 53 Pflex), eight patients (five in control, three in Pflex) were excluded from the final evaluation because the random group assignment was not performed in one center according to protocol. Main outcome measures were ICU and hospital mortality, ventilator-free days, and nonpulmonary organ dysfunction. ICU mortality (24 of 45 [53.3%] vs. 16 of 50 [32%], p = .040), hospital mortality (25 of 45 [55.5%] vs. 17 of 50 [34%], p = .041), and ventilator-free days at day 28 (6.02 +/- 7.95 in control and 10.90 +/- 9.45 in Pflex/LTV, p = .008) all favored Pflex/LTV. The mean difference in the number of additional organ failures postrandomization was higher in the control group (p < .001).\n A mechanical ventilation strategy with a PEEP level set on day 1 above Pflex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS.",
"A strategy of mechanical ventilation that limits airway pressure and tidal volume while permitting hypercapnia has been recommended for patients with the acute respiratory distress syndrome. The goal is to reduce lung injury due to overdistention. However, the efficacy of this approach has not been established.\n Within 24 hours of intubation, patients at high risk for the acute respiratory distress syndrome were randomly assigned to either pressure- and volume-limited ventilation (limited-ventilation group), with the peak inspiratory pressure maintained at 30 cm of water or less and the tidal volume at 8 ml per kilogram of body weight or less, or to conventional ventilation (control group), with the peak inspiratory pressure allowed to rise as high as 50 cm of water and the tidal volume at 10 to 15 ml per kilogram. All other ventilatory variables were similar in the two groups.\n A total of 120 patients with similar clinical features underwent randomization (60 in each group). The patients in the limited-ventilation and control groups were exposed to different mean (+/-SD) tidal volumes (7.2+/-0.8 vs. 10.8+/-1.0 ml per kilogram, respectively; P<0.001) and peak inspiratory pressures (23.6+/-5.8 vs. 34.0+/-11.0 cm of water, P<0.001). Mortality was 50 percent in the limited-ventilation group and 47 percent in the control group (relative risk, 1.07; 95 percent confidence interval, 0.72 to 1.57; P=0.72). In the limited-ventilation group, permissive hypercapnia (arterial carbon dioxide tension, >50 mm Hg) was more common (52 percent vs. 28 percent, P=0.009), more marked (54.4+/-18.8 vs. 45.7+/-9.8 mm Hg, P=0.002), and more prolonged (146+/-265 vs. 25+/-22 hours, P=0.017) than in the control group. The incidence of barotrauma, the highest multiple-organ-dysfunction score, and the number of episodes of organ failure were similar in the two groups; however, the numbers of patients who required paralytic agents (23 vs. 13, P=0.05) and dialysis for renal failure (13 vs. 5, P= 0.04) were greater in the limited-ventilation group than in the control group.\n In patients at high risk for the acute respiratory distress syndrome, a strategy of mechanical ventilation that limits peak inspiratory pressure and tidal volume does not appear to reduce mortality and may increase morbidity."
] |
Clinical heterogeneity, such as different lengths of follow up and higher plateau pressure in control arms in two trials, makes the interpretation of the combined results difficult. Mortality was significantly reduced at day 28 and at the end of the hospital stay. The effects on long-term mortality are unknown, although the possibility of a clinically relevant benefit cannot be excluded. Ventilation with lower tidal volumes is becoming a routine strategy of treatment of acute respiratory distress syndrome and acute lung injury, stopping investigators from carrying out additional trials.
|
CD007065
|
[
"8623811",
"8602320"
] |
[
"Efficacy of P6 acupressure in the treatment of nausea and vomiting during pregnancy.",
"A randomized controlled trial of smoking cessation intervention in pregnancy in an academic clinic."
] |
[
"Our purpose was to investigate the efficacy of P6 acupressure in reducing or relieving symptoms of nausea with or without vomiting and retching during pregnancy.\n Symptomatic pregnant volunteers (n=161) participated in a 7-day community-based clinical trial. All participants were assigned to one of three groups (i.e., P6 acupressure, placebo [acupressure bands inappropriately placed], or control) on the basis of a process of blocked randomization. Data were analyzed by error bar charts and analysis of variance of difference scores.\n Of 161 women, 149 (92.5%) completed the protocol. Irrespective of group assignment, participants reported significant decreases in nausea (p<0.0009) and vomiting or retching (p<0.0009). However, there was no differential treatment effect as a result of acupressure.\n There was no apparent medical benefit from the use of P6 acupressure. Our findings differ from other recently published studies that did not include a control group.",
"To evaluate the effectiveness of a physician-based intervention to promote smoking cessation during pregnancy, we conducted this randomized controlled trial in the resident-staffed prenatal clinics at the University of North Carolina Women's Hospital . Two hundred fifty prenatal patients who smoked were enrolled at their first visit and randomly assigned to the intervention or the usual-care group. Resident physicians provided self-help materials to intervention subjects and used a script to set goals with them at each prenatal visit. Subjects who set quit dates were contacted by volunteer cessation counselors. To verify smoking status, subjects provided a self-report and breath carbon monoxide (CO) sample at each visit. Controls were similarly assessed at enrollment and at three additional predetermined intervals. Twenty percent of intervention subjects and 10% of controls reported cessation, which was verified by CO level (P = .052). Fifty-one percent of subjects reduced their consumption by half or more, compared with 30% of controls (P = .002). The intervention is effective in promoting smoking cessation and reduction. In addition, this technique is inexpensive, readily accepted by staff, and efficient."
] |
There was little information to draw conclusions on the overall effectiveness of interventions to relieve heartburn in pregnancy.
[Note: the two citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]
|
CD003805
|
[
"15284112",
"16946304",
"15668467",
"18239086",
"15494430"
] |
[
"The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group.",
"Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG).",
"Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG).",
"Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage.",
"CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma."
] |
[
"In follicular lymphoma (FL) and mantle cell lymphoma (MCL) the monoclonal antibody rituximab may improve the prognosis when combined with chemotherapy. This was investigated in a prospective randomized study in patients with relapsed disease. A total of 147 patients were randomized to receive 4 courses of chemotherapy with 25 mg/m(2) fludarabine on days 1 to 3, 200 mg/m(2) cyclophosphamide on days 1 to 3, and 8 mg/m(2) mitoxantrone on day 1 (FCM), alone or combined with rituximab (375 mg/m(2); R-FCM). Of 128 evaluable patients, 62 were randomized for FCM and 66 for R-FCM. R-FCM revealed an overall response rate of 79% (33% complete remission [CR], 45% partial remission [PR]) as compared with 58% for FCM alone (13% CR, 45% PR; P = .01), with similar results in a subgroup analysis of FL (94% vs 70%) and MCL (58% vs 46%). In the total group, the R-FCM arm was significantly superior concerning progression-free survival (PFS; P = .0381) and overall survival (OS; P = .0030). In FL PFS was significantly longer in the R-FCM arm (P = .0139) whereas in MCL a significantly longer OS was observed (P = .0042). There were no differences in clinically relevant side effects in both study arms. Hence, the addition of rituximab to FCM chemotherapy significantly improves the outcome of relapsed or refractory FL and MCL.",
"In follicular lymphoma (FL) and mantle cell lymphoma (MCL) the monoclonal antibody rituximab (R) improves the prognosis when combined with chemotherapy. The present study investigated R-maintenance after R-chemotherapy. Patients with recurring or refractory FL and MCL were randomized to 4 courses of fludarabine, cyclophosphamide, and mitoxantrone (FCM) alone or combined with R (R-FCM). Responding patients underwent a second randomization for R-maintenance comprising 2 further courses of 4-times-weekly doses of R after 3 and 9 months. The first randomization was stopped after 147 patients, when R-FCM revealed a significantly better outcome. All subsequent patients received R-FCM. Of the 176 patients who are currently evaluable (as of October 2005), 138 received R-FCM for remission induction. Response duration was significantly prolonged by R-maintenance after R-FCM, with the median not being reached in this evaluation versus an estimated median of 16 months (P = .001). This beneficial effect was also observed when analyzing FL (P = .035) and MCL (P = .049) separately. Hence, R-maintenance is effective after salvage with R-chemotherapy and significantly prolongs response duration in patients with recurring or refractory FL or MCL.",
"Mantle cell lymphoma (MCL) is characterized by a poor prognosis with a low to moderate sensitivity to chemotherapy and a median survival of only 3 to 4 years. In an attempt to improve outcome, the German Low Grade Lymphoma Study Group (GLSG) initiated a randomized trial comparing the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and rituximab (R-CHOP) with CHOP alone as first-line therapy for advanced-stage MCL.\n One hundred twenty-two previously untreated patients with advanced-stage MCL were randomly assigned to six cycles of CHOP (n = 60) or R-CHOP (n = 62). Patients up to 65 years of age achieving a partial or complete remission underwent a second randomization to either myeloablative radiochemotherapy followed by autologous stem-cell transplantation or interferon alfa maintenance (IFNalpha). All patients older than 65 years received IFNalpha maintenance.\n R-CHOP was significantly superior to CHOP in terms of overall response rate (94% v 75%; P = .0054), complete remission rate (34% v 7%; P = .00024), and time to treatment failure (TTF; median, 21 v 14 months; P = .0131). No differences were observed for progression-free survival. Toxicity was acceptable, with no major differences between the two therapeutic groups.\n The combined immunochemotherapy with R-CHOP resulted in a significantly higher response rate and a prolongation of the TTF as compared with chemotherapy alone. Hence, R-CHOP may serve as a new baseline regimen for advanced stage MCL, but needs to be further improved by novel strategies in remission.",
"In this randomized multicenter study of 136 patients, 6 courses of CHOP (cyclo-phosphamide/doxorubicin/vincristine/prednisone) followed by rituximab (CHOP-R) were compared with rituximab-supplemented high-dose sequential chemotherapy with autografting (R-HDS) to assess the value of intensified chemo-therapy as a first-line treatment for high-risk follicular lymphoma (FL) after the introduction of monoclonal antibodies. The analysis was intention to treat with event-free survival (EFS) as the primary endpoint. Complete remission (CR) was 62% with CHOP-R and 85% with R-HDS (P < .001). At a median follow-up (MFU) of 51 months, the 4-year EFS was 28% and 61%, respectively (P < .001), with no difference in overall survival (OS). Molecular remission (MR) was achieved in 44% of CHOP-R and 80% of R-HDS patients (P < .001), and was the strongest independent outcome predictor. Patients relapsing after CHOP-R underwent salvage R-HDS in 71% of cases. Salvage R-HDS had an 85% CR rate and a 68% 3-year EFS (MFU, 30 months). We conclude that (1) achieving MR is critical for effective disease control, regardless of which treatment is used; (2) R-HDS ensures superior disease control and molecular outcome than CHOP-R, but no OS improvement; and (3) CHOP-R failures have a good outcome after salvage R-HDS, suggesting that relapsed/refractory FL could be the most appropriate setting for R-HDS-like treatments. This trial was registered at www.clinicaltrials.gov as no. NCT00435955.",
"The combination of cyclophosphamide, vincristine, and prednisone (CVP) is one of several standard treatment options for advanced follicular lymphoma. This, like similar chemotherapeutic regimens, induces response rates of 60% to 80%, with a median response duration of under 2 years. Rituximab, a chimeric monoclonal antibody against CD20, is active in follicular lymphoma, both as monotherapy and in combination with chemotherapy. Previously untreated patients with stages III to IV follicular lymphoma were randomly assigned to receive either 8 cycles of CVP plus rituximab (R-CVP; n = 162) or CVP (n = 159). Overall and complete response rates were 81% and 41% in the R-CVP arm versus 57% and 10% in the CVP arm, respectively (P < .0001). At a median follow-up of 30 months, patients treated with R-CVP had a very significantly prolonged time to progression (median 32 months versus 15 months for CVP; P < .0001). Median time to treatment failure was 27 months in patients receiving R-CVP and 7 months in the CVP arm (P < .0001). Rituximab did not add significantly to the toxicity of CVP. The addition of rituximab to the CVP regimen significantly improves the clinical outcome in patients with previously untreated advanced follicular lymphoma, without increased toxicity."
] |
The systematic review demonstrated improved OS for patients with indolent lymphoma, particularly in the subgroups of follicular and in mantle cell lymphoma when treated with R-chemo compared to chemotherapy alone.
|
CD004349
|
[
"19225038",
"8467308",
"12587810",
"12435255",
"490882",
"17161769"
] |
[
"Lowering blood pressure reduces renal events in type 2 diabetes.",
"Evaluation of a structured treatment and teaching programme on hypertension in general practice.",
"Physician-pharmacist comanagement of hypertension: a randomized, comparative trial.",
"Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial.",
"Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group.",
"Effect of intensive blood pressure control with valsartan on urinary albumin excretion in normotensive patients with type 2 diabetes."
] |
[
"BP is an important determinant of kidney disease among patients with diabetes. The recommended thresholds to initiate treatment to lower BP are 130/80 and 125/75 mmHg for people with diabetes and nephropathy, respectively. We sought to determine the effects of lowering BP below these currently recommended thresholds on renal outcomes among 11,140 patients who had type 2 diabetes and participated in the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study. Patients were randomly assigned to fixed combination perindopril-indapamide or placebo, regardless of their BP at entry. During a mean follow-up of 4.3 yr, active treatment reduced the risk for renal events by 21% (P < 0.0001), which was driven by reduced risks for developing microalbuminuria and macroalbuminuria (both P < 0.003). Effects of active treatment were consistent across subgroups defined by baseline systolic or diastolic BP. Lower systolic BP levels during follow-up, even to <110 mmHg, was associated with progressively lower rates of renal events. In conclusion, BP-lowering treatment with perindopril-indapamide administered routinely to individuals with type 2 diabetes provides important renoprotection, even among those with initial BP <120/70 mmHg. We could not identify a BP threshold below which renal benefit is lost.",
"Evaluation of a structured hypertension treatment and teaching programme in general practice.\n Prospective controlled trial; follow-up period 18 months.\n 10 primary health care practices. PRACTICES AND PATIENTS: From each practice 20 patients (30 to 60 years old, mean of the last two blood pressure measurements at or above 160 and/or 95 mmHg) were randomly selected; in 5 practices these patients were to participate in the treatment and teaching programme; in the remaining 5 practices hypertension care was continued without the availability of such a programme (controls).\n Structured treatment and teaching programme based upon four group sessions for patients mainly conducted by paramedical personnel.\n Blood pressure, body weight, prescription of antihypertensive drugs - as documented in the patient's records.\n Of the 100 control patients 26 and of the 100 intervention patients 14 were lost to observation; 46 patients had agreed to participate in the programme. The mean number of prescribed antihypertensive agents per patient decreased in the intervention group (1.8 +/- 1.3 at baseline, vs 1.2 +/- 1.2 at follow-up) compared to the control group (1.6 +/- 1.3 vs 1.8 +/- 1.6); difference 0.8 (95% CI 0.4 to 1.1), p < 0.0001. In the control group 9% and in the intervention group 33% of patients had documented reductions of body weight (p < 0.0001). Blood pressure decreased in the intervention group (162 +/- 14/100 +/- 7 mmHg at baseline, vs 154 +/- 16/95 +/- 9 mmHg at follow-up) compared to the control group (161 +/- 13/98 +/- 7 mmHg vs 158 +/- 18/96 +/- 11 mmHg); differences for systolic blood pressure 5 (95% CI 0 to 10) mmHg, p = 0.071; for diastolic blood pressure 4 (1 to 7) mmHg, p = 0.018.\n The introduction of a structured hypertension treatment and teaching programme in general practice may lead to significant improvements of hypertension care.",
"To compare the effectiveness of an evidence-based, systematic approach to hypertension care involving comanagement of patients by primary care physicians and clinical pharmacists versus usual care in reducing blood pressure in patients with uncontrolled hypertension.\n Patients in a staff model medical group with uncontrolled hypertension were randomized to either a usual care (UC) or a physician-pharmacist comanagement (PPCM) group. All physicians in the study received both group and individual education and participated in the development of an evidence-based hypertension treatment algorithm. Physicians were then given the names of their patients whose medical records documented elevated blood pressures (defined as systolic > or = 140 mm Hg and/or diastolic > or = 90 mm Hg for patients aged < 65 yrs, and systolic > or = 160 mm Hg and/or diastolic > or = 90 mm Hg for those aged > or = 65 yrs). Patients randomized to the UC group were managed by primary care physicians alone. Those randomized to the PPCM group were comanaged by their primary care physician and a clinical pharmacist, who provided patient education, made treatment recommendations, and provided follow-up. Blood pressure measurements, antihypertensive drugs, and visit costs/patient were obtained from medical records.\n One hundred ninety-seven patients with uncontrolled hypertension participated in the study. Both PPCM and UC groups experienced significant reductions in blood pressure (systolic -22 and -11 mm Hg, respectively, p < 0.01; diastolic -7 and -8 mm Hg, respectively, p < 0.01). The reduction in systolic blood pressure was greater in the PPCM group after adjusting for differences in baseline blood pressure between the groups (p < 0.01). More patients achieved blood pressure control in the PPCM than in the UC group (60% vs 43%, p = 0.02). Average provider visit costs/patient were higher in the UC than the PPCM group ($195 vs $160, p = 0.02).\n An evidence-based, systematic approach using physician-pharmacist comanagement for patients with uncontrolled hypertension resulted in improved blood pressure control and reduced average visit costs/patient.",
"Hypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD.\n To compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension.\n Randomized 3 x 2 factorial trial with enrollment from February 1995 to September 1998.\n A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years.\n Participants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual; n = 554) or 92 mm Hg or less (lower; n = 540), and to initial treatment with either a beta-blocker (metoprolol 50-200 mg/d; n = 441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d; n = 436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d; n = 217). Open-label agents were added to achieve the assigned BP goals.\n Rate of change in GFR (GFR slope); clinical composite outcome of reduction in GFR by 50% or more (or > or =25 mL/min per 1.73 m2) from baseline, ESRD, or death. Three primary treatment comparisons were specified: lower vs usual BP goal; ramipril vs metoprolol; and amlodipine vs metoprolol.\n Achieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (-2.21 [0.17] mL/min per 1.73 m2 per year) and the usual BP group (-1.95 [0.17] mL/min per 1.73 m2 per year; P =.24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group = 2%; 95% confidence interval [CI], -22% to 21%; P =.85). None of the drug group comparisons showed consistent significant differences in the GFR slope. However, compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22% (95% CI, 1%-38%; P =.04) and 38% (95% CI, 14%-56%; P =.004), respectively. There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups.\n No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal. Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline.",
"The Hypertension Detection and Follow-up Program (HDFP), in a community-based, randomized controlled trial involving 10,940 persons with high blood pressure (BP), compared the effects on five-year mortality of a systematic antihypertensive treatment program (Stepped Care [SC]) and referral to community medical therapy (Referred Care [RC]). Participants, recruited by population-based screening of 158,906 people aged 30 to 69 years in 14 communities througout the United States, were randomly assigned to SC or RC groups within each center and by entry diastolic blood pressure (DBP) (90 to 104, 105 to 114, and 115 + mm Hg). Over the five years of the study, more than two thirds of the SC participants continued to receive medication, and more than 50% achieved BP levels within the normotensive range, at or below the HDFP goal for DBP. Controls of BP was consistently better for the SC than for the RC group. Five-year mortality from all causes was 17% lower for the SC group compared to the RC group (6.4 vs 7.7 per 100, P less than .01) and 20% lower for the SC subgroup with entry DBP of 90 to 104 mm Hg compared to the corresponding RC subgroup (5.9 vs 7.4 per 100, P less than .01). These findings of the HDFP indicate that the systematic effective management of hypertension has a great potential for reducing mortality for the large numbers of people with high BP in the population, including those with \"mild\" hypertension.",
"Diabetes is the most common cause of renal failure in the United States, and data regarding the effects of aggressive blood pressure (BP) therapy in normotensive patients with type 2 diabetes are inadequate.\n A total of 129 type 2 diabetic patients with a BP of <140/80 to 90 mm Hg without overt albuminuria were randomized to either intensive BP control (diastolic BP goal 75 mm Hg) using an angiotensin II receptor blocker, valsartan, versus moderate BP control (diastolic BP 80 to 90 mm Hg with placebo initially) to evaluate the effect on the change in urinary albumin excretion (UAE) from baseline.\n The mean entrance BP was 126 +/- 8.8/84 +/- 2.4 mm Hg. The mean follow-up period was 1.9 +/- 1.0 years. During the follow-up period, the mean BP was 118 +/- 10.9/75 +/- 5.7 for the intensive v 124 10.9/80 6.5 mm Hg for the moderate BP groups (P < .001). No difference was observed in change in creatinine clearance or serum creatinine from baseline between the two groups. An analysis of covariance model for change in log (UAE + 1), adjusting for age, HBA(1c), duration of diabetes, baseline log (UAE + 1), sex, and ethnicity resulted in a significant treatment difference at 2 years (P = .007) with intensive BP control reducing log (UAE+1) compared with moderate BP control.\n Intensive BP control with valsartan to <120/80 mm Hg in normotensive patients with type 2 diabetes and normo- or microalbuminuria significantly decreased the progression of UAE and in some cases caused regression of UAE."
] |
Treating patients to lower than standard BP targets, ≤140-160/90-100 mmHg, does not reduce mortality or morbidity. Because guidelines are recommending even lower targets for diabetes mellitus and chronic renal disease, we are currently conducting systematic reviews in those groups of patients.
|
CD002245
|
[
"20613538",
"19050085",
"6190466",
"1718756",
"21178763"
] |
[
"A randomized controlled trial comparing an intraoperative goal-directed strategy with routine clinical practice in patients undergoing peripheral arterial surgery.",
"Fluid resuscitation in the management of early septic shock (FINESS): a randomized controlled feasibility trial.",
"Efficacy of hetastarch in the resuscitation of patients with multisystem trauma and shock.",
"Treatment of hemorrhagic shock with intraosseous or intravenous infusion of hypertonic saline dextran solution.",
"Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock: a randomized, placebo controlled trial."
] |
[
"We hypothesized that, in vascular surgery patients, the application of a goal-directed strategy based on a pulse contour-derived cardiac index would be associated with a better haemodynamic status than the application of routine perioperative care and that the amount of fluid and/or inotropes required in such a goal-directed therapy depended on the general anaesthetic technique used.\n Patients undergoing peripheral arterial bypass grafting were randomly assigned to three groups. In group 1, haemodynamic management was performed according to routine clinical practice. In the two other groups (groups 2 and 3) a goal-directed therapy was applied aiming to maintain the pulse contour-derived cardiac index above 2.5 l m min. Patients in groups 1 and 2 received sevoflurane-based anaesthesia and patients in group 3 propofol-based anaesthesia. Haemodynamic variables, amount of fluid and administration of inotropes were assessed at different time intervals.\n The amount of fluid administered was not significantly different between the groups. Two patients in group 1, 13 patients in group 2 and 12 patients in group 3 were treated with dobutamine (P < 0.001). None of the patients anaesthetized with sevoflurane (groups 1 and 2) experienced postoperative cardiovascular complications, whereas four patients in the total intravenous group (group 3) experienced major postoperative cardiovascular complications (P = 0.005).\n In the conditions of the present study, the application of a goal-directed therapy aiming to maintain the cardiac index above 2.5 l min m did not result in a higher tissue oxygen delivery than when applying the standard haemodynamic strategy nor did it depend on the anaesthetic technique used.",
"It is unknown whether fluid resuscitation with colloid or crystalloid in patients with severe sepsis or septic shock is associated with an improvement in clinical outcome. This randomized controlled trial determined the feasibility of conducting a large trial testing resuscitation with pentastarch vs normal saline in early septic shock, powered for a difference in mortality.\n At three Canadian and one New Zealand academic centre, 40 patients with early septic shock defined by at least two systemic inflammatory response syndrome criteria, infectious source, and persistent hypotension after >or= 1 L of crystalloid fluid were recruited. Feasibility measures were patient recruitment, blinding of the study fluids, and acceptability of the goal directed algorithms. Boluses of blinded normal saline or pentastarch (500 mL - maximum 3 L or 28 mL x kg(-1)) were administered within goal directed care for the first 12 hr.\n Of 161 patients screened, 121 were excluded and 40 patients were enrolled, for a recruitment rate of 0.75 patients/site/month. Only 57% of physicians and 54% of nurses correctly guessed the study fluid (P = 0.46 and P = 0.67, respectively). The goal directed algorithms were acceptable to 97% of physicians.\n The ability to recruit patients in this pilot randomized controlled trial was below expectations. Blinding of study fluids was adequate, and resuscitation algorithms were acceptable to most physicians. Methods to improve recruitment are required to enhance the feasibility of conducting a multicentre fluid resuscitation trial in early septic shock.",
"A prospective trial of 6% hetastarch (HES) v 5% plasma protein fraction (PPF) as the colloid component of intravenous (IV) fluid resuscitation was conducted in 32 patients with multisystem trauma and/or hemorrhagic shock. Patient age, mechanism and pattern of injury, and IV fluid requirements were similar in both groups. No intergroup differences were noted in indexes of hepatic, pulmonary, or renal function or in the incidence of infection. The frequency of other complications, including bleeding diatheses, and mortality were identical in the two groups. Although this investigation should be viewed as a pilot study, our results suggest that, compared with PPF, HES in large volumes is a safe, effective colloid solution in the resuscitation of patients with multisystem trauma and/or hemorrhagic shock. Further study of HES in a larger number of patients is warranted by these findings.",
"The efficacy of intravenous or intraosseous infusion of 250 ml of 7.5% NaCl and 6% dextran 60 (H/H) was compared with intravenous Ringer's lactate (RL) for the initial treatment of patients with hemorrhagic shock due to upper gastrointestinal bleeding. 49 patients were randomly assigned to receive either H/H (n = 26) or RL (n = 23). In the first 16 patients with H/H and in all RL patients, solutions were infused by the intravenous route, while the intraosseous route through sternal puncture was chosen for the last 10 H/H subjects. H/H patients were analyzed together since no differences were noticed between the routes of infusion. The H/H group also received 2.3 +/- 0.7 liters of intravenous crystalloid solutions in the first hour and 4.4 +/- 0.1 liters in the 24-hour period, while RL received 3.3 +/- 0.7 and 7.3 +/- 2.4 liters, respectively. Blood pressure (BP) increased during the first 15 min in the H/H group (from 61 +/- 17/30 +/- 12 to 85 +/- 30/48 +/- 14 mm Hg) and thereafter, while remaining unchanged in the RL group (from 75 +/- 18/40 +/- 12 to 75 +/- 17/40 +/- 14 mm Hg; p less than 0.05). The differences between groups were significant throughout 24 h. Urine output and improvement of the Glasgow Coma Score were also higher in H/H patients than in the control group (p less than 0.05). There were 5 deaths in RL group and 1 in the H/H group. Sternal of peripheral vein infusion of 250 ml of 7.5% NaCl/6% dextran 60 is an effective initial treatment of hemorrhagic shock.",
"To determine whether out-of-hospital administration of hypertonic fluids would improve survival after severe injury with hemorrhagic shock.\n Hypertonic fluids have potential benefit in the resuscitation of severely injured patients because of rapid restoration of tissue perfusion, with a smaller volume, and modulation of the inflammatory response, to reduce subsequent organ injury.\n Multicenter, randomized, blinded clinical trial, May 2006 to August 2008, 114 emergency medical services agencies in North America within the Resuscitation Outcomes Consortium. Inclusion criteria: injured patients, age ≥ 15 years with hypovolemic shock (systolic blood pressure ≤ 70 mm Hg or systolic blood pressure 71-90 mm Hg with heart rate ≥ 108 beats per minute). Initial resuscitation fluid, 250 mL of either 7.5% saline per 6% dextran 70 (hypertonic saline/dextran, HSD), 7.5% saline (hypertonic saline, HS), or 0.9% saline (normal saline, NS) administered by out-of-hospital providers. Primary outcome was 28-day survival. On the recommendation of the data and safety monitoring board, the study was stopped early (23% of proposed sample size) for futility and potential safety concern.\n : A total of 853 treated patients were enrolled, among whom 62% were with blunt trauma, 38% with penetrating. There was no difference in 28-day survival-HSD: 74.5% (0.1; 95% confidence interval [CI], -7.5 to 7.8); HS: 73.0% (-1.4; 95% CI, -8.7-6.0); and NS: 74.4%, P = 0.91. There was a higher mortality for the postrandomization subgroup of patients who did not receive blood transfusions in the first 24 hours, who received hypertonic fluids compared to NS [28-day mortality-HSD: 10% (5.2; 95% CI, 0.4-10.1); HS: 12.2% (7.4; 95% CI, 2.5-12.2); and NS: 4.8%, P < 0.01].\n Among injured patients with hypovolemic shock, initial resuscitation fluid treatment with either HS or HSD compared with NS, did not result in superior 28-day survival. However, interpretation of these findings is limited by the early stopping of the trial. Clinical Trial Registration: Clinical Trials.gov, NCT00316017."
] |
We found no evidence from randomised controlled trials for or against early or larger volume of intravenous fluid administration in uncontrolled haemorrhage. There is continuing uncertainty about the best fluid administration strategy in bleeding trauma patients. Further randomised controlled trials are needed to establish the most effective fluid resuscitation strategy.
|
CD007426
|
[
"20417038",
"19110245",
"15715034",
"16457423",
"16714913",
"10363537",
"18317710"
] |
[
"Effects of relaxation on psychobiological wellbeing during pregnancy: a randomized controlled trial.",
"Effect of integrated yoga on stress and heart rate variability in pregnant women.",
"Massage therapy effects on depressed pregnant women.",
"The effects of acute relaxation on indices of anxiety during pregnancy.",
"Does relaxation education in anxious primigravid Iranian women influence adverse pregnancy outcomes?: a randomized controlled trial.",
"The effect of relaxation therapy on preterm labor outcomes.",
"Effects of a mindfulness-based intervention during pregnancy on prenatal stress and mood: results of a pilot study."
] |
[
"Prenatal maternal stress is associated with adverse birth outcomes and may be reduced by relaxation exercises. The aim of the present study was to compare the immediate effects of two active and one passive 10-min relaxation technique on perceived and physiological indicators of relaxation. 39 healthy pregnant women recruited at the outpatient department of the University Women's Hospital Basel participated in a randomized controlled trial with an experimental repeated measure design. Participants were assigned to one of two active relaxation techniques, progressive muscle relaxation (PMR) or guided imagery (GI), or a passive relaxation control condition. Self-reported relaxation on a visual analogue scale (VAS) and state anxiety (STAI-S), endocrine parameters indicating hypothalamic-pituitary-adrenal (HPA) axis (cortisol and ACTH) and sympathetic-adrenal-medullary (SAM) system activity (norepinephrine and epinephrine), as well as cardiovascular responses (heart rate, systolic and diastolic blood pressure) were measured at four time points before and after the relaxation exercise. Between group differences showed, that compared to the PMR and control conditions, GI was significantly more effective in enhancing levels of relaxation and together with PMR, GI was associated with a significant decrease in heart rate. Within the groups, passive as well as active relaxation procedures were associated with a decline in endocrine measures except epinephrine. Taken together, these data indicate that different types of relaxation had differential effects on various psychological and biological stress systems. GI was especially effective in inducing self-reported relaxation in pregnant women while at the same time reducing cardiovascular activity.\n Copyright © 2010 Elsevier Ltd. All rights reserved.",
"To study the effect of integrated yoga practice and guided yogic relaxation on both perceived stress and measured autonomic response in healthy pregnant women.\n The 122 healthy women recruited between the 18th and 20th week of pregnancy at prenatal clinics in Bangalore, India, were randomized to practicing yoga and deep relaxation or standard prenatal exercises 1-hour daily. The results for the 45 participants per group who completed the study were evaluated by repeated measures analysis of variance.\n Perceived stress decreased by 31.57% in the yoga group and increased by 6.60% in the control group (P=0.001). During a guided relaxation period in the yoga group, compared with values obtained before a practice session, the high-frequency band of the heart rate variability spectrum (parasympathetic) increased by 64% in the 20th week and by 150% in the 36th week, and both the low-frequency band (sympathetic), and the low-frequency to high-frequency ratio were concomitantly reduced (P<0.001 between the 2 groups). Moreover, the low-frequency band remained decreased after deep relaxation in the 36th week in the yoga group.\n Yoga reduces perceived stress and improves adaptive autonomic response to stress in healthy pregnant women.",
"Eighty-four depressed pregnant women were recruited during the second trimester of pregnancy and randomly assigned to a massage therapy group, a progressive muscle relaxation group or a control group that received standard prenatal care alone. These groups were compared to each other and to a non-depressed group at the end of pregnancy. The massage therapy group participants received two 20 min therapy sessions by their significant others each week for 16 weeks of pregnancy, starting during the second trimester. The relaxation group provided themselves with progressive muscle relaxation sessions on the same time schedule. Immediately after the massage therapy sessions on the first and last days of the 16-week period the women reported lower levels of anxiety and depressed mood and less leg and back pain. By the end of the study the massage group had higher dopamine and serotonin levels and lower levels of cortisol and norepinephrine. These changes may have contributed to the reduced fetal activity and the better neonatal outcome for the massage group (i.e. lesser incidence of prematurity and low birthweight), as well as their better performance on the Brazelton Neonatal Behavior Assessment. The data suggest that depressed pregnant women and their offspring can benefit from massage therapy.",
"Antenatal maternal anxiety has adverse effects on the fetus and the child. In this study we determined whether a short period of directed or of passive relaxation reduced maternal self-rated anxiety, heart rate, plasma catecholamines, cortisol and uterine artery resistance index, in pregnant women.\n Fifty-eight women (28-32 wks gestation) were assigned randomly to a session of directed active or passive (sitting quietly) relaxation. Spielberger self-rating anxiety questionnaires were completed, and a venous blood sample taken, before and after a Doppler scan.\n Both active and passive relaxation significantly reduced State Anxiety and maternal heart rate, but the effect was significantly greater with the active relaxation. In contrast, the passive relaxation significantly reduced noradrenaline levels whereas active did not. Adrenaline levels were not changed significantly with either type of relaxation. Both methods significantly reduced cortisol, with a trend for the passive to have a greater effect. The active relaxation had no effect on uterine artery blood flow, whereas there was a statistically significant, but clinically negligible, increase in mean resistance index after passive relaxation.\n Both methods reduced maternal State Anxiety and heart rate, the active method more so. However there was a striking lack of correlation with the other biological indices studied. In order to reduce specific biological effects of anxiety during pregnancy, different methods may be needed from those which are most effective at reducing subjective anxiety.",
"Maternal anxiety and stress are found to be predictors of adverse pregnancy outcomes, including low birth weight and prematurity.\n The aim of the study was to determine whether relaxation education in anxious pregnant Iranian women in their first pregnancy affects selected pregnancy outcomes, including birth weight, preterm birth, and surgical delivery rate.\n A total of 110 obstetrically and medically low-risk primigravid women in Iran with a high anxiety level demonstrated by Spielberger's State-Trait Anxiety Inventory were randomly assigned into experimental and control groups.\n In this randomized controlled trial, the experimental group received routine prenatal care along with 7-week applied relaxation training sessions, while the control group received only routine prenatal care. Anxiety and perceived stress were measured by pre-educational and post-educational intervention. Data related to pregnancy outcomes include birth weight, gestational age at birth, and type of delivery.\n Significant reductions in low birth weight, cesarean section, and/or instrumental extraction were found in the experimental group compared with the control group. No significant differences were found in the rate of preterm birth.\n The findings suggest beneficial effects of nurse-led relaxation education sessions during the prenatal period. This intervention could serve as a resource for improving pregnancy outcomes in women with high anxiety.",
"To examine the effect of relaxation on preterm labor outcome.\n Quasi-experimental, with women who experienced preterm labor randomly assigned to a control or experimental group. The experimental group was to do a daily relaxation exercise. A third group was added to the study: women who were originally assigned to the relaxation group but were unable to adhere to the daily practice. Final data were analyzed for three groups: control (n = 40), experimental (n = 44), and nonadherent (n = 23) participants.\n Women were referred to the study from physician offices and a hospital-based obstetric triage clinic in the Northwest.\n Total sample was comprised of 107 women with singleton gestations, documented contractions with cervical change, and intact membranes.\n The experimental group was instructed in a progressive relaxation exercise. The participants were given tapes of the exercise and instructed to do it daily.\n Study outcomes included gestational age at birth, rate of pregnancy prolongation, and birth weight.\n The outcome variables were analyzed using analysis of covariance, with the preterm labor risk score entered as a covariate to compensate statistically for group differences. A positive response to the relaxation intervention was found: The experimental group had significantly longer gestations and larger newborns when compared to the control and nonadherent groups.\n Relaxation therapy made a difference in preterm labor outcome. Women who practiced relaxation had larger newborns, longer gestations, and higher rates of pregnancy prolongation. Given the low cost of the intervention, it should be offered to all women at risk for preterm labor.",
"Stress and negative mood during pregnancy increase risk for poor childbirth outcomes and postnatal mood problems and may interfere with mother-infant attachment and child development. However, relatively little research has focused on the efficacy of psychosocial interventions to reduce stress and negative mood during pregnancy. In this study, we developed and pilot tested an eight-week mindfulness-based intervention directed toward reducing stress and improving mood in pregnancy and early postpartum. We then conducted a small randomized trial (n=31) comparing women who received the intervention during the last half of their pregnancy to a wait-list control group. Measures of perceived stress, positive and negative affect, depressed and anxious mood, and affect regulation were collected prior to, immediately following, and three months after the intervention (postpartum). Mothers who received the intervention showed significantly reduced anxiety (effect size, 0.89; p<0.05) and negative affect (effect size, 0.83; p<0.05) during the third trimester in comparison to those who did not receive the intervention. The brief and nonpharmaceutical nature of this intervention makes it a promising candidate for use during pregnancy."
] |
According to the results of this review, there is some evidence that relaxation during pregnancy reduces stress and anxiety. However, there was no effect on PTL/PTB. These results should be interpreted with caution as they were drawn from included studies with limited quality.
|
CD004000
|
[
"2213395",
"7754764",
"1801560",
"15995024",
"10200128",
"2437278",
"7524263",
"21745374",
"9402378"
] |
[
"Treatment of Kawasaki syndrome: a comparison of two dosage regimens of intravenously administered immune globulin.",
"Optimal dosage and differences in therapeutic efficacy of IGIV in Kawasaki disease.",
"Intravenous gamma-globulin for Kawasaki disease.",
"Intravenously administered immunoglobulin in the treatment of childhood Guillain-Barré syndrome: a randomized trial.",
"Selective high dose gamma-globulin treatment in Kawasaki disease: assessment of clinical aspects and cost effectiveness.",
"High-dose gammaglobulin therapy for Kawasaki disease.",
"A multicenter, randomized, controlled trial of intravenous gamma globulin therapy in children with acute Kawasaki disease.",
"Comparison of intravenous immunoglobulin and plasma exchange in treatment of mechanically ventilated children with Guillain Barré syndrome: a randomized study.",
"Randomized comparison of ganciclovir plus intravenous immune globulin (IVIG) with IVIG alone for prevention of primary cytomegalovirus disease in children receiving liver transplants."
] |
[
"Because intravenously administered immune globulin (IVIG) is effective in reducing the incidence of coronary artery aneurysms in Kawasaki syndrome when given at a dose of 400 mg/kg daily for 4 days, we undertook a multicenter clinical trial comparing two dosage regimens of IVIG. Patients were randomly assigned to receive IVIG at either 400 mg/kg daily for 4 days (22 patients) or 1 gm/kg as a single dose (22 patients). All patients received aspirin therapy, and all were enrolled within 7 days of onset of fever. The presence of coronary artery aneurysms was evaluated by means of two-dimensional echocardiography before infusion; at days 4 to 6, 14 to 21, and 42 to 49 after infusion; and at 1 year. Coronary artery aneurysms were detected in 3 of the 44 patients, including one patient receiving 400 mg/kg and two patients receiving 1 gm/kg (p value not significant). No giant aneurysms were detected. No major side effects occurred with either dosage regimen. Patients receiving the 1 gm/kg dose had a faster resolution of fever and were discharged from the hospital approximately 1 day sooner than the 400 mg/kg group (p = 0.01). Although the relatively small sample size in this trial does not allow for a more definitive statement regarding the occurrence of coronary artery aneurysms, it appears that the 1 gm/kg dose is associated with a more rapid clinical improvement and a shorter hospital stay.",
"In an initial study, three groups of patients with Kawasaki disease received either aspirin alone or alkylated immunoglobulin G intravenous preparation (IGIV) 200 mg/kg daily x 3 days + aspirin, or 400 mg/kg alkylated IGIV daily x 3 days + aspirin. In a second study, three groups of patients were treated with either 100, 200 or 400 mg/kg of native IGIV in combination with aspirin daily for 5 days. While the regimen of 200 mg/kg native IGIV daily x 5 days was found to be effective, the incidence of coronary artery lesions (CAL) was even less on a regimen of 400 mg/kg daily x 5 days. It is therefore suggested that a better therapeutic effect can be achieved with a 400 mg/kg dose of native IGIV. Based on the results from these two studies, it is assumed that native IGIV is more effective in inhibiting CAL formation and persistence than the chemically modified preparation in which the biological activity of the Fc region in the immunoglobulin G molecule is altered.",
"We studied the effect of gamma-globulin (IVGG) and aspirin (ASA) on the development of the coronary artery lesions (CAL) of Kawasaki disease (KD) in three different protocols. Within 29 days of the onset of KD the echocardiographic evidence of CAL had developed in 39-42% of the patients in the ASA group, but only in 13.7-20.8% of the patients treated with IVGG (200 or 400 mg/kg X 5). In long-term follow-up observation of CAL of these patients the evidence of CAL in both the ASA and the IVGG group regressed gradually; however, the residual rate of CAL was significantly low in the IVGG group at all times up to 24 months after onset. These facts suggest that when using IVGG for KD, we should select a dose of intact gamma-globulin, 1,000 mg/kg or more in total, to prevent the occurrence of CAL. We have demonstrated not only a significant reduction in the occurrence of CAL in patients treated with IVGG but a reduction in the residual rate of CAL for two years as compared with those treated by ASA.",
"To determine the optimal treatment for childhood Guillain-Barré syndrome (GBS).\n We performed a randomized, multicenter study of GBS according to international diagnostic criteria. In study 1 (early treatment), children able to walk unaided for 5 meters were randomized for 1 g/kg intravenously administered immunoglobulin (IVIG) over 2 days or no treatment. The primary outcome measure was the degree of disability at nadir. In study 2 (treatment for severe GBS), children unable to walk 5 meters unaided were randomized for 1 g/kg IVIG over 2 days or 0.4 g/kg IVIG over 5 days. The primary outcome measure was the number of days needed to regain the ability to walk unaided. Children randomized for no treatment in study 1 could enter study 2 if loss of unaided walking occurred.\n Ninety-five children with GBS were registered in 40 months. Twenty-one children were randomized in study 1 and 51 in study 2 (5 after deterioration in study 1). Twenty-eight children were not randomized for various reasons. Eleven of 21 patients in study 1 lost the ability to walk unassisted and 6 were bedridden, with no statistically significant difference between the children initially randomized for treatment versus no treatment. Recovery occurred faster in the group randomized for early treatment. In study 2, recovery did not differ significantly between the children treated for 2 days versus 5 days (median time to unaided walking: 19 days vs 13 days). Secondary transient deterioration in the disability score occurred more frequently in the group with the 2-day regimen than in the group treated for 5 days (5 of 23 patients vs 0 of 23 patients). Multivariate analysis with Cox regression showed that disease severity at the nadir was the only prognostic factor for recovery.\n Treatment with IVIG before loss of unaided walking did not give rise to a less severe course, but recovery occurred somewhat faster. However, given the small number of patients, the power of this conclusion is low. For treatment after loss of unaided walking, there was no significant difference in the effectiveness of 2 g/kg IVIG administered over 2 days versus 5 days. Early \"relapses\" occurred more frequently after the shorter treatment regimen.",
"High-dose intravenous gamma-globulin (IVGG) plus aspirin (ASA) treatment is effective in preventing coronary artery complications in acute Kawasaki disease (KD). However, gamma-globulin is very expensive, especially in Japan. Furthermore the indication for IVGG treatment and the optimal dose of gamma-globulin remain controversial.\n To examine these two issues, we used Harada's scoring system to investigate whether a single 2 g/kg dose therapy has any advantage over the 5 day 400 mg/kg per day therapy.\n We studied 203 patients with KD who had no coronary artery complications on admission. Of these, 145 patients scored 4 or more on Harada score within the first 9 days of illness and were treated with IVGG treatment. Using a random number table, 72 patients were selected to receive a single 2 g/kg dose (2 g group), while the remaining 73 patients were treated with 400 mg/kg per day for 5 consecutive days (400 mg group). Those who had a Harada score of three or less received no IVGG (non-IVGG group) treatment (58 patients).\n The incidence rate of coronary artery complications in the 2 g group was significantly lower than in the 400 mg group. The duration of high fever, positive duration of C-reactive protein and the number of hospital days in the 2 g group were each significantly shorter than in the 400 mg group. The total medical expense in the 2 g group was significantly lower than in the 400 mg group. There were no coronary artery complications in the non-IVGG group.\n It was found to be clinically more effective and more cost effective to select a patient by Harada's scoring system and, where a score of four or more was obtained, to administer a single 2 g/kg intravenous dose of gamma-globulin for acute KD.",
"To evaluate the effectiveness of gammaglobulin in decreasing the incidence of coronary artery lesions in Kawasaki disease, a randomized controlled study in 136 patients was conducted using high doses of gammaglobulin 400 mg/kg/d for 3 days plus aspirin 30 mg/kg/d (gammaglobulin group) and aspirin alone at the same dosage (aspirin group). The total febrile period and the duration of fever after treatment were significantly shorter in the gammaglobulin group than in the aspirin group (P less than 0.001). The incidence of coronary artery lesions and of coronary artery aneurysms was significantly lower in the gammaglobulin group than in the aspirin group up to 30 days after the onset of Kawasaki disease (P less than 0.01 and P less than 0.05, respectively). In 16 of 69 patients given gammaglobulin, fever persisted for longer than 3 days, and there was a higher incidence of coronary artery lesions among them. The effectiveness of high doses of gammaglobulin in preventing coronary artery lesions has been demonstrated, but the indications and the optimal dose of gammaglobulin remain to be determined.",
"We studied the effect of intravenous, polyethyleneglycol-treated, human immunoglobulin, administered at 200 mg/kg per day (group A: n = 147; male 86, female 61; age < 1 year, 50) or 400 mg/kg per day (group B: n = 152; male 87, female 65; age < 1 year, 52) for five consecutive days and compared it with freeze-dried, sulfonated human immunoglobulin [group C: n = 152; male 87, female 65; age < 1 year, 51), administered at 200 mg/kg per day for five consecutive days, on the prevention of coronary artery abnormalities in Kawasaki disease. Echocardiograms were interpreted blindly and independently. Proportions of 87.1%, 95.4%, and 82.3% in groups A, B, and C, respectively, had no coronary artery abnormalities. The confidence limits of difference between the proportions of groups A and C, groups B and C, and groups B and A were -4.4% and 10.4%, 7.8% and 15.9%, and 4.0% and 10.8%, respectively. Duration of fever and serum immunoglobulin G (IgG) levels were correlated with the prevalence of coronary artery abnormalities. We concluded that intravenous, polyethyleneglycol-treated, human immunoglobulin and freeze-dried, sulfonated human immunoglobulin had clinically equivalent effects on coronary artery abnormalities, and that five daily doses of 400 mg/kg of intravenous, polyethyleneglycol-treated, human immunoglobulin is more effective than that of 200 mg/kg gamma globulin.",
"Respiratory failure is a life threatening complication of Guillain Barré syndrome (GBS). There is no consensus on the specific treatment for this subset of children with GBS.\n This was a prospective randomized study to compare the outcome of intravenous immunoglobulin (IVIG) and plasma exchange (PE) treatment in children with GBS requiring mechanical ventilation. Forty-one children with GBS requiring endotracheal mechanical ventilation (MV) within 14 days from disease onset were included. The ages of the children ranged from 49 to 143 months.Randomly, 20 children received a five-day course of IVIG (0.4 g/kg/day) and 21 children received a five-day course of one volume PE daily. Lumbar puncture (LP) was performed in 36 patients (18 in each group).\n Both groups had comparable age (p = 0.764), weight (p = 0.764), duration of illness prior to MV (p = 0.854), preceding diarrhea (p = 0.751), cranial nerve involvement (p = 0.756), muscle power using Medical Research Council (MRC) sum score (p = 0.266) and cerebrospinal fluid (CSF) protein (p = 0.606).Children in the PE group had a shorter period of MV (median 11 days, IQR 11.0 to 13.0) compared to IVIG group (median 13 days, IQR 11.3 to 14.5) with p = 0.037.Those in the PE group had a tendency for a shorter Pediatric Intensive Care Unit (PICU) stay (p = 0.094).A total of 20/21 (95.2%) and 18/20 (90%) children in the PE and IVIG groups respectively could walk unaided within four weeks after PICU discharge (p = 0.606).There was a negative correlation between CSF protein and duration of mechanical ventilation in the PE group (p = 0.037), but not in the IVIG group (p = 0.132).\n In children with GBS requiring MV, PE is superior to IVIG regarding the duration of MV but not PICU stay or the short term neurological outcome.The negative correlation between CSF protein values and duration of MV in PE group requires further evaluation of its clinical usefulness.\n Clinicaltrials.gov Identifier NCT01306578.",
"A randomized placebo-controlled trial was conducted to determine the benefit of ganciclovir (5 mg/[kg x d]) for 30 days in addition to intravenous immune globulin (IVIG) for 16 weeks for prevention of primary cytomegalovirus (CMV) disease in children receiving liver transplants. Patients were monitored for 6 months after transplantation. The two groups of patients (recipients of 29 ganciclovir plus IVIG and 27 recipients of IVIG alone) were similar in terms of age, sex, and underlying disease. The incidence of CMV disease among the ganciclovir plus IVIG recipients and the IVIG alone recipients was 17% and 26%, respectively, and the time to disease in these recipients was 46 days and 32 days, respectively. There was no difference between groups in terms of survival; episodes of rejection, bacteremia, or fungemia; use of immunosuppressive agents; and incidence of leukopenia or thrombocytopenia. These results suggest that a 4-week course of ganciclovir with IVIG is not more effective than IVIG alone for prevention of primary CMV disease. Since short-term prophylaxis with ganciclovir may delay the onset of CMV disease, further studies with a longer course of ganciclovir prophylaxis are warranted."
] |
Children fulfilling the diagnostic criteria for Kawasaki disease should be treated with IVIG (2 gm/kg single dose) within 10 days of onset of symptoms.
|
CD007126
|
[
"14693612",
"15976212",
"16085437",
"17022854",
"19105251",
"9540151",
"12631041",
"16480474",
"19487950",
"12351250",
"15791113",
"16238896",
"18580346",
"7541435",
"18419721",
"9161740",
"10027033",
"11464348",
"11307656",
"9542555",
"12905750",
"8948744",
"11375848",
"15790675",
"8738682",
"15352967",
"10957701",
"7917733",
"1489038",
"18581586",
"2257796"
] |
[
"Assessing analgesia in single and repeated administrations of propacetamol for postoperative pain: comparison with morphine after dental surgery.",
"Intravenous acetaminophen (paracetamol): comparable analgesic efficacy, but better local safety than its prodrug, propacetamol, for postoperative pain after third molar surgery.",
"Analgesic efficacy and safety of intravenous paracetamol (acetaminophen) administered as a 2 g starting dose following third molar surgery.",
"Clinical equivalence of IV paracetamol compared to IV dipyrone for postoperative analgesia after surgery for breast cancer.",
"[Analgesic and opioid-sparing effects of intravenous paracetamol in the early period after aortocoronary bypass surgery].",
"[Comparison of propacetamol and morphine in postoperative analgesia].",
"Analgesic effect of i.v. paracetamol: possible ceiling effect of paracetamol in postoperative pain.",
"Analgesic efficacy of parenteral paracetamol (propacetamol) and diclofenac in post-operative orthopaedic pain.",
"Paracetamol versus metamizol in the treatment of postoperative pain after breast surgery: a randomized, controlled trial.",
"Propacetamol as adjunctive treatment for postoperative pain after cardiac surgery.",
"Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery.",
"A comparison between IV paracetamol and IV metamizol for postoperative analgesia after retinal surgery.",
"Intravenous paracetamol improves the quality of postoperative analgesia but does not decrease narcotic requirements.",
"The morphine-sparing effect of propacetamol in orthopedic postoperative pain.",
"Effect of paracetamol and coxib with or without dexamethasone after laparoscopic cholecystectomy.",
"Postoperative analgesia with i.v. propacetamol and ketoprofen combination after disc surgery.",
"Lack of pre-emptive analgesic effect of (R)-ketamine in laparoscopic cholecystectomy.",
"Diclofenac and/or propacetamol for postoperative pain management after cesarean delivery in patients receiving patient controlled analgesia morphine.",
"Intravenous tramadol compared to propacetamol for postoperative analgesia following thyroidectomy.",
"Efficacy of propacetamol in the treatment of postoperative pain. Morphine-sparing effect in orthopedic surgery. Italian Collaborative Group on Propacetamol.",
"[A randomized, double blind, and controlled clinical trial of the non-addictive propacetamol in postoperative analgesia].",
"[Patient-controlled postoperative analgesia in orthopedic surgery: epidural PCA versus intravenous PCA].",
"Propacetamol versus ketorolac for treatment of acute postoperative pain after total hip or knee replacement.",
"Onset of acetaminophen analgesia: comparison of oral and intravenous routes after third molar surgery.",
"Additive analgesic effect of codeine and paracetamol can be detected in strong, but not moderate, pain after Caesarean section. Baseline pain-intensity is a determinant of assay-sensitivity in a postoperative analgesic trial.",
"Propacetamol and diclofenac alone and in combination for analgesia after elective tonsillectomy.",
"No effect of preoperative paracetamol and codeine suppositories for pain after termination of pregnancies in general anaesthesia.",
"Multimodal analgesia before thoracic surgery does not reduce postoperative pain.",
"The effect of paracetamol or diclofenac administered before operation on postoperative pain and behaviour after adenoidectomy in small children.",
"Comparison of parecoxib and proparacetamol in endoscopic nasal surgery patients.",
"[The efficacy of paracetamol (Tylenol) and acetyl salicylic acid (Aspirin) in treating postoperative pain]."
] |
[
"We conducted this double-blinded, randomized study to assess the analgesic effect of repeated administrations of paracetamol, administered as propacetamol, an injectable prodrug formulation of paracetamol, and to compare this with the analgesic effects of morphine. Patients experiencing moderate to severe pain after elective surgical removal of bone-impacted third-molar teeth under general anesthesia were randomly assigned to receive IV propacetamol 2 g (n = 31), IM morphine 10 mg (n = 30), or placebo (n = 34). Five hours later, the treatments were readministered at half of the previous dosages. Standard measures of analgesia were collected repeatedly for 10 h. Propacetamol and morphine were significantly more effective than placebo in all primary measures of analgesia over 5 h after the first administration and globally over 10 h (first and second administrations). After the first dose, 21 of the 34 patients in the placebo group required rescue medication, compared with 6 of the 31 in the propacetamol group (P < 0.0009) and 4 of the 30 in the morphine group (P < 0.0001). No statistically or clinically significant differences were found between propacetamol and morphine for any sum or peak measures of analgesia. No serious adverse events were reported; adverse events were significantly less frequent in the propacetamol group than in the morphine group (P < 0.027). Propacetamol administered IV in repeated doses (2 g followed by 1 g) has a significant analgesic effect that is indistinguishable from that of morphine administered IM (10 mg followed by 5 mg) after dental surgery, with better tolerability.\n After moderately painful surgical procedures, IV paracetamol, administered as propacetamol, may be an asset in the control of acute postoperative pain.",
"We compared an acetaminophen (paracetamol) 1 g (n = 51) formulation for infusion with propacetamol 2 g (n = 51) and placebo (n = 50) in a randomized, controlled, double-blind, parallel group trial in patients with moderate-to-severe pain after third molar surgery. Treatment efficacy was assessed in house for 6 h after starting the 15-min infusion. Significant effects versus placebo (P < 0.01) were obtained with both active treatments on pain relief, pain intensity difference on a 100-mm visual analog scale, and on a categorical scale (except for propacetamol at 6 h). No significant differences were noted between active groups except at 1 h. Six-hour weighted sums of primary assessments showed significantly better efficacy than placebo (P < 0.0001) and no difference between active treatments. Median stopwatch time to onset of pain relief for active treatment was 6-8 min after infusion start. Active treatments showed comparable efficacy with a significantly longer duration of analgesia and better patients' global evaluation compared with placebo. The incidence of patients reporting local pain at the infusion site was significantly less frequent after IV acetaminophen or placebo (0%) in comparison with propacetamol (49%). In conclusion, acetaminophen 1 g and propacetamol 2 g were superior to placebo regarding analgesic efficacy, with a more frequent incidence of local pain at the infusion site for propacetamol.",
"The recommended dose for intravenous (IV) paracetamol injection in adults is 1g, however pharmacokinetic and pharmacodynamic findings suggest that a better analgesia could be obtained with a 2 g starting dose.\n A single-centre, randomised, double-blind, placebo-controlled, 3-parallel group study was performed to demonstrate the analgesic efficacy and safety of IV paracetamol 2 g. Following third molar surgery, patients reporting moderate to severe pain received a single 15-min infusion of either IV paracetamol 2 g, IV paracetamol 1g or placebo. Efficacy and safety were evaluated over 8 h. Laboratory tests were performed before and 48 h after drug administration.\n Two hundred and ninety seven patients (132 = IV paracetamol 2g; 132 = IV paracetamol 1g; 33 = placebo) were randomised and completed the study. The summed pain relief over 6h (TOTPAR6) was significantly superior with IV paracetamol 2 g as compared to IV paracetamol 1g and placebo (p < 0.0001). Pain relief scores of IV paracetamol 2g were significantly superior to IV paracetamol 1g and to placebo from T30' to T8h (p < 0.0001). Median duration of analgesia was significantly longer following IV paracetamol 2 g compared to IV paracetamol 1g and placebo (p < 0.0001). Adverse events occurred with the same frequency in the 3 treatment groups. No clinically significant changes from baseline were observed for vital signs or laboratory tests.\n The analgesic efficacy of a 2 g starting dose of IV paracetamol was superior over the recommended dose of 1g in terms of magnitude and duration of analgesic effect for postoperative pain following third molar surgery, with no significant difference between groups regarding safety.",
"To assess clinical efficacy of IV paracetamol 1 g and IV dipyrone 1 g on a 24-h dosing schedule in this randomised, double-blinded study of 40 ASA I-III (American Society of Anesthesiologists classification of physical status) patients undergoing surgery for breast cancer.\n General anaesthesia using remifentanil and propofol was performed for surgery. The patients were randomly allocated to two groups, receiving infusions of paracetamol 1 g/100 mL (Para Group) or of dipyrone 1 g/100 mL (Dipy Group) 30 min before arrival in the recovery area and every 6 h up to 24 h postoperatively. All patients had unrestricted access to opioid rescue medication via an IV patient-controlled analgesia (PCA) device.\n The primary variables for clinical equivalence were the differences between the mean values for pain scores at rest and pain scores on coughing over 30 h postoperatively. The equivalence margin was determined as +/-10 mm on the visual analogue scale (VAS).\n Regarding pain scores at rest, the 90% CI of the mean differences between the treatment groups over 30 h postoperatively was found to be within the predefined equivalence margin [+7.5/-6.2], and the CI values for pain scores on coughing [+7.3/-9.0] were similar. The two groups did not differ in cumulative opioid rescue consumption (Dipy-Group 14.8 +/- 17.7 mg vs. Para Group 12.1 +/- 8.8 mg, p = 0.54) nor in piritramide loading dose (Dipy Group 0.95 +/- 2.8 mg vs. Para Group 1.3 +/- 2.8 mg, p = 0.545). Five patients in the Dipy Group experienced hypotension in contrast to none in the Para Group (p = 0.047). There were no significant between-treatment differences for other adverse events, patient satisfaction scores (p = 0.4) or quality of recovery scores (p = 0.3).\n IV paracetamol 1 g is clinically equivalent to IV dipyrone 1 g for postoperative analgesia after surgery for breast cancer.",
"The study was to evaluate the analgesic and opioid-sparing effect of intravenous paracetamol injections in cardiosurgical patients in the early postoperative period. Adequate analgesia within the first 12-18 hours of the early postoperative period is very important for a good prognosis of the further course of pain syndrome and for the reduction of a risk for its progression to its chronic form. In early studies, propacetamol lowered morphine use after orthopedic and gynecological operations. The efficacy of paracetamol used in cardiac surgery has been little studied and the results of the studies are conflicting. The randomized, blind, placebo-controlled study included patients after aortocoronary bypass surgery, of them 22 patients received paracetamol and 23 had placebo. The test drug (perfalgan 100 ml or placebo) was intravenously injected 30 min before extubation and then every 6 hours within succeeding 18 hours. The intensity of the pain syndrome was rated by a 5-score verbal scale every 2 hours. With pain score of 2 or more, promedol was intramuscularly administered in a dose of 10 mg. Inspiratory volume was recorded before extubation and the first administration of a drug just after extubation and then every 2 hours. The baseline indices did not differ in both groups. Throughout the observation, the inspiratory volume was lower in the paracetamol group than in the placebo group; however, there was a statistically significant difference (p = 0.012) in the reduction in the manifestations of the pain syndrome (by 81%) only just after tracheal extubation. During this period, inspiratory volume values were higher in the paracetamol group; however, a statistically significant (39%) difference between the groups in the mean values was obtained only during and 2 hours after extubation. In the perfalgan group, the mean total use of promedol was 36% less than in the placebo-group, which was statistically significant (p = 0.019). The early postoperative use of paracetamol after myocardial revascularization reduces the intake of opioids and diminishes the intensity of the pain syndrome within the first hours after extubation, which promotes a higher thoracic excursion, as confirmed by a statistically significant increase in the maximum inspiratory capacity.",
"To compare the analgesic efficacy and tolerance of propacetamol and morphine, 80 patients in good clinical condition were included in a prospective, parallel, randomized double blind trial after elective surgery expected to elicit light to moderate postoperative pain. At the end of general anesthesia, 40 patients received 30 mg/kg propacetamol and 40 0.2 mg/kg morphine, as a 15-min intravenous infusion. The groups were similar for age, weight and duration of anesthesia. Supplemental analgesia had to be given in 7 cases from the propacetamol group vs. 2 cases from the morphine group. The postoperative pain, evaluated 7 times during 4 h from the end of infusion with a visual analog scale, revealed a modest advantage for morphine at 0.5 and 4 h (p = 0.05). The respiratory rate was slightly lower after morphine (p = 0.02). No significant differences were observed in blood oxygen saturation, blood pressure, heart rate, body temperature and vigilance evaluated by the trailmaking test. Nausea was present in 4 cases under propacetamol and 3 under morphine, and pruritus in 2 and 7 cases, respectively. In conclusion, propacetamol may represent an alternative to morphine for pain prevention after mildly to moderately painful surgery in situations where the use of opioids is unsuitable.",
"Despite the widespread use of paracetamol for many years, the analgesic serum concentrations of paracetamol are unknown. Therefore the correlation between serum paracetamol concentrations and the analgesic effect was studied.\n Sixty-four women undergoing laparoscopic sterilization were included in a double-blind, placebo-controlled, randomized study. Patients were given i.v. propacetamol 40 mg kg(-1) (group H), 20 mg kg(-1) (group I), 10 mg kg(-1) (group L) or placebo after surgery. Alfentanil was available via patient-controlled analgesia (PCA) during the 4-h postoperative study period. The patients' self-reported pain was registered on the visual analog scale (VAS). A pharmacokinetic model was fitted to the paracetamol data.\n One to 3 h after injection of propacetamol the alfentanil consumption was significantly (P = 0.01-0.04) higher in the placebo group compared with groups H, I, and L receiving propacetamol. There were no significant differences between the amounts of alfentanil consumed in groups H, I, and L. Initial VAS-scores were moderate (5.4-6.2), and declined significantly (P < 0.0001) over time, with no difference between groups. Paracetamol followed an open two-compartment model with i.v. administration and first order elimination. The estimated concentrations immediately (t = 0) after injection were 56 mg l(-1) (H), 28 mg l(-1) (I) and 14 mg l(-1) (L).\n We showed a significant opioid-sparing effect of paracetamol in the immediate postoperative period. Pharmacokinetic data were in accordance with other studies. Our results suggest that a ceiling effect of paracetamol may be present at i.v. doses of 5 mg kg(-1), i.e. a serum concentration of 14 mg l(-1), which is a lower dose than previously suggested.\n Copyright Acta Anaesthesiologica Scandinavica 47 (2003)",
"Propacetamol is an injectable pro-drug of paracetamol (acetaminophen) with analgesic and antipyretic activities, especially used in the post-operative period. The aim of this study was to assess the analgesic efficacy and safety of intravenous paracetamol, administered as propacetamol, in comparison with placebo and intramuscular diclofenac in patients with post-operative pain.\n This was a randomized, double-blind, double-dummy study. One hundred and twenty patients with moderate to severe pain following total hip arthroplasty received either two administrations of propacetamol 2 g intravenously, 5 h apart (n = 40), one single administration of diclofenac 75 mg intramuscularly (n = 40) or placebo (n = 40). Efficacy measures were assessed before each drug administration, for the 5 h following each study treatment administration and for the total study duration of 10 h. Safety was assessed by reporting adverse events and changes in vital signs, electrocardiogram (ECG) and biochemical investigations before and 24 h after dosing.\n Both active treatments were effective and statistically superior to placebo over the whole study period, as indicated by the total pain relief score. No significant differences were found between propacetamol and diclofenac for any measures of analgesic activity. Only minor and common adverse events were reported, with no overall differences between the groups.\n Both active treatments were superior to placebo, and the overall efficacy of two intravenous infusions of propacetamol 2 g (equivalent to 1 g of paracetamol), 5 h apart, was not statistically different from that provided by a single intramuscular injection of diclofenac 75 mg over the first 5 h post-dose and over the total 10-h study period. The safety was good.",
"Intravenously administered paracetamol is an effective analgesic in postoperative pain management. However, there is a lack of data on the effect of intravenous (i.v.) paracetamol on pain following soft tissue surgery.\n Eighty-seven patients undergoing elective breast surgery with total i.v. anaesthesia (propofol/remifentanil) were randomized to three groups. Group para received 1 g i.v. paracetamol 20 min before and 4, 10 and 16 h after the end of the operation. Group meta and plac received 1 g i.v. metamizol or placebo, respectively, scheduled at the same time points. All patients had access to i.v. morphine on demand to achieve adequate pain relief.\n No significant difference in total morphine consumption between groups was detectable. The proportion of patients who did not receive any morphine in the postoperative period was significantly higher in group para (42%) than in group plac (4%). Ambulation was significantly (P < 0.05) earlier in group para (4.0 +/- 0.2 h) than in groups meta (4.6 +/- 0.2 h) and plac (5.5 +/- 1.0 h). No differences were observed between groups meta and plac. There were no differences between groups with regard to incidence of postoperative nausea and vomiting or changes in vigilance.\n Neither i.v. paracetamol nor i.v. metamizol provided a significant reduction in total postoperative morphine consumption compared with placebo in the management of postoperative pain after elective breast surgery. Administration of paracetamol resulted in a significant reduction in the number of patients needing opioid analgesics to achieve adequate postoperative pain relief.",
"Postoperative pain management after cardiac surgery has been mainly based on parenteral opioids. However, because opioids have numerous side effects, coadministration of non-opioid analgesics has been introduced as a method of reducing opioid dose. In this prospective, randomized, double-blinded study, we evaluated the efficacy of propacetamol, an IV administered prodrug of acetaminophen (paracetamol), as an adjunctive analgesic after cardiac surgery. Seventy-nine patients scheduled for elective coronary artery bypass grafting were randomized to receive either propacetamol 2 g (n = 40) or placebo (n = 39) IV in 6-h intervals for 72 h. From the time of extubation, patients had access to an opioid (oxycodone) via a patient-controlled analgesia device. Pain was evaluated on a visual analog scale four times daily, whereas respiratory function tests (forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow, and arterial blood gas measurements) were performed once a day. The prespecified primary efficacy variable (cumulative oxycodone consumption at the end of the 72-h postoperative period) was 123.5 mg (51.3 mg) (mean [SD]) in the propacetamol group and 141.8 mg (57.5 mg) in the placebo group (difference in mean, 18.3 mg = 13%; 95% confidence interval, 6.1-42.7 mg; P = 0.15). Pain scores did not differ between the groups at rest (P = 0.65) or during a deep breath (P = 0.72). The groups were also similar in terms of pulmonary function tests, postoperative bleeding, and hepatic function tests, and no significant differences were noted in the incidences of adverse effects. After completion of the study, apost hoc analysis was also performed analyzing the first 24 h as split into 6-h intervals. This analysis showed a significantly (P = 0.036) smaller consumption of oxycodone in the propacetamol group at 24 h (47.1 mg [20.7 mg] versus 57.9 mg [23.9 mg]; difference in mean, 10.8 mg; 95% confidence interval, 0.7-20.9 mg). In conclusion, propacetamol did not enhance opioid-based analgesia in coronary artery bypass grafting patients, nor did it decrease cumulative opioid consumption or reduce adverse effects within 3 days after surgery. However, post hoc analysis showed that oxycodone requirement was reduced within the first 24 h in the propacetamol group.\n This is the first placebo-controlled study to investigate the efficacy of propacetamol as a complementary analgesic to opioids after cardiac surgery. Propacetamol did not enhance analgesia, nor did it decrease cumulative opioid consumption or reduce adverse effects in a dose of 2 g given every sixth hour for 3 days after surgery.",
"Intravenous acetaminophen injection (paracetamol) is marketed in Europe for the management of acute pain. A repeated-dose, randomized, double-blind, placebo-controlled, three-parallel group study was performed to evaluate the analgesic efficacy and safety of intravenous acetaminophen as compared with its prodrug (propacetamol) and placebo. Propacetamol has been available in many European countries for more than 20 yr.\n After orthopedic surgery, patients reporting moderate to severe pain received either 1 g intravenous acetaminophen, 2 g propacetamol, or placebo at 6-h intervals over 24 h. Patients were allowed \"rescue\" intravenous patient-controlled analgesia morphine. Pain intensity, pain relief, and morphine use were measured at selected intervals. Safety was monitored through adverse event reporting, clinical examination, and laboratory testing.\n One hundred fifty-one patients (intravenous acetaminophen: 49; propacetamol: 50; placebo: 52) received at least one dose of study medication. The intravenous acetaminophen and propacetamol groups differed significantly from the placebo group regarding pain relief from 15 min to 6 h (P < 0.05) and median time to morphine rescue (intravenous acetaminophen: 3 h; propacetamol: 2.6 h; placebo: 0.8 h). Intravenous acetaminophen and propacetamol significantly reduced morphine consumption over the 24-h period: The total morphine doses received over 24 h were 38.3 +/- 35.1 mg for intravenous acetaminophen, 40.8 +/- 30.2 mg for propacetamol, and 57. 4 +/- 52.3 mg for placebo, corresponding to decreases of -33% (19 mg) and -29% (17 mg) for intravenous acetaminophen and propacetamol, respectively. Drug-related adverse events were reported in 8.2%, 50% (most of them local), and 17.3% of patients treated with intravenous acetaminophen, propacetamol, and placebo, respectively.\n Intravenous acetaminophen, 1 g, administered over a 24-h period in patients with moderate to severe pain after orthopedic surgery provided rapid and effective analgesia and was well tolerated.",
"To assess clinical efficacy of IV paracetamol 1 g and IV metamizol 1 IV metamizol 1 g on a 24-h dosing schedule in this randomized, double-blinded, placebo-controlled study of 38 ASA physical status I-III patients undergoing retinal surgery.\n General anaesthesia using remifentanil, propofol, and desflurane was performed for surgery. The patients were randomly allocated to three groups, receiving infusions of paracetamol 1 g/100 mL (Para Group), of metamizol 1 g/100 mL (Meta Group), or of 100 mL of saline solution as placebo control (Plac Group) 30 min before arrival in the recovery area and every 6 h up to 24 h postoperatively. All patients had unrestricted access to intravenous opioid rescue medication.\n The primary efficacy variables were pain scores at rest over 30 h postoperatively analysed by using repeated ANOVA measurement. Secondary efficacy variables were pain scores on coughing, also analysed by repeated ANOVA measurement.\n Five patients in the Plac Group and one patient in the Meta Group interrupted the study protocol. Regarding pain scores at rest, Mauchly-test of sphericity was significant (p = 0.03). For the p time effects a significant result was detected (p < 0.001). The main effect between the three treatment groups was significantly different (p = 0.01). The Bonferroni adjusted pair wise comparisons between p the Plac Group and the Para Group showed a significant difference in favour of IV paracetamol (p = 0.024; mean difference 14.8; p 95% CI 1.6-28.0), between the Plac Group and the Meta Group in favour of IV metamizol (p = 0.025; mean difference 14.4; 95% CI p 1.5-27.4), and no significant difference between the Para Group and the Meta Group (p = 1.0; mean difference 0.4; 95% CI-12.8 to 13.6). Pain scores on coughing showed a significant different main effect between the three treatment groups (p = 0.022). The Bonferroni adjusted pair wise comparisons between the Plac Group and the Para Group showed a significant difference in favour of IV paracetamol (p = 0.032; mean difference 17.9; 95% CI 1.3-34.6), a p difference, though not reaching statistical significance, in favour of IV metamizol between the Plac Group and the Meta Group (p = 0.081; p mean difference 15.0; 95% CI -1.4 to 31.4), and no significant difference between the Para Group and the Meta Group (p = 1.0; p mean difference 2.9; 95% CI -13.8 6 to 19.6). None of the patients experienced itching; one patient in the Meta Group developed a mild erythema. There was no statistical difference in the incidence of nausea (Plac vs. Para Group: p = 0.94, Plac vs. Meta Group: p = 0.98, Para vs Meta Group: p = 0.95) or vomiting (Plac vs. Para Group: p = 0.73, Plac vs. Meta Group: p = 0.85, Para vs Meta Group: p = 0.86) between the groups. Patients in the Plac Group experienced significantly more often sedation than patients in the Meta Group (p = 0.049). There was a trend of higher sedation in the Plac Group than in the Para Group, which did not reach statistical significance (p = 0.07). There was no difference in sedation between the Meta and the Para Groups (p = 0.84).\n IV paracetamol 1 g has a similar analgesic potency as IV metamizol 1 g for postoperative analgesia after retinal surgery.",
"Paracetamol, a centrally acting inhibitor of cyclooxygenase, has less gastrointestinal and platelet-inhibiting side effects and is clinically better tolerated than nonsteroidal anti-inflammatory drugs. Therefore, it will be ideally suited for postoperative pain relief. In this prospective, double-blind, randomized, placebo-controlled study, we evaluated the analgesic efficacy, opioid-sparing effect and effects on opioid-related adverse effects of intravenous (IV) paracetamol in combination with IV morphine after lumbar laminectomy and discectomy. Forty patients were divided into 2 groups (n=20 each) to receive either paracetamol 1 g (group 1) or 0.9% NaCl 100 ml (group 2) at the end of the operation and at 6-hour intervals over 24 hours. IV patient-controlled analgesia with morphine was used as a rescue analgesic in both groups. Pain was evaluated at rest and on movement at the 1st, 2nd, 4th, 6th, 12th, 18th, and 24th hours using a visual analog scale. Hemodynamic parameters, morphine usage, patient satisfaction, and probable side effects were also evaluated. Pain scores at rest and on movement at the 12th, 18th, and 24th hours were significantly lower in group 1 (P<0.001). Morphine consumption was not statistically significantly different between the groups (P>0.05). Vomiting in group 2 was significantly higher (P=0.027). Significantly more patients in the paracetamol group rated their pain management as excellent (45% vs. 5%). Although repeated IV paracetamol usage after lumbar laminectomy and discectomy did not demonstrate a significant opioid-sparing effect, it did decrease visual analog scale scores at certain evaluation times and incidence of vomiting and increase patient satisfaction.",
"The analgesic efficacy and safety of propacetamol (Pro-Dafalgan), an injectable prodrug of acetaminophen, in combination with morphine administered by patient-controlled analgesia (PCA) were studied in 60 patients (56 men, 4 women; age 18-40 years; mean age, 26 years) after knee ligamentoplasty. Using a double-blind, randomized, parallel-group design, the effects of four (every 6 hr) intravenous injections of 2 g propacetamol (= 1 g acetaminophen) were compared with four injections of placebo (PL) in the recovery room immediately after surgery. Efficacy was assessed over 24 hr by automatic recording on the PCA device of the cumulative dose of morphine and the number of boluses requested. It was also assessed on pain scores rated on a five-point verbal scale and a visual analogue scale before administration, at 1, 2, 3, and 4 hr, and then every 2 hr until the 24th hr after administration. A five-point global efficacy scale was also administered. Any side effects were recorded throughout the duration of the study, and the ability to tolerate the drug was assessed by recording arterial pressure, cardiac and respiratory frequency, and sedation at the same assessment times as the pain scores. The 24-hr morphine consumption was significantly decreased in the propacetamol group (number of 1 mg boluses: 14.7 +/- 11.3 versus 23.2 +/- 13.8, P = 0.01; PCA usage: 26.4 +/- 12.3 mg versus 34.6 +/- 15.4 mg, P = 0.03; PCA usage + titration: 34.5 +/- 12.7 mg versus 43.1 +/- 15.9 mg, P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)",
"Pain after laparoscopic cholecystectomy (LCC) is multifactorial. Effective post-operative pain control is necessary in LCC performed as day-case surgery. We studied the efficacy of paracetamol or valdecoxib with or without dexamethasone after LCC.\n One hundred sixty patients were randomized to four groups of 40 patients. Groups 1 and 3 received parecoxib 40 mg intravenously (IV) during surgery and valdecoxib 40 mg x 1 per os (PO) for 7 post-operative days. Groups 2 and 4 received paracetamol 1 g x 4 IV during surgery and 1 g x 4 PO for 7 days. In addition, Groups 3 and 4 were given dexamethasone 10 mg IV intra-operatively. Propofol and remifentanil were used during surgery. The patients were given oxycodone 0.05 mg/kg IV in phase 1 post-anaesthesia care unit (PACU 1) or 0.15 mg/kg PO in phase 2 post-anaesthesia care unit (PACU 2) as needed to keep visual analogue scale <3/10. The patients were supplied with the study drugs for 7 post-operative days.\n Pain intensity, nausea and the need of oxycodone in phase 1 PACU were similar in all groups. Dexamethasone reduced the need of oral oxycodone in phase 2 PACU (7.0 +/- 1.0 mg vs. 9.1 +/- 1.0 mg, P<0.05). Pain intensity was similar in all groups at home. More patients in the parecoxib/valdecoxib groups needed rescue medication on the 1st post-operative day (P<0.001) than paracetamol-treated patients.\n Paracetamol was as effective as parecoxib/valdecoxib for pain after LCC. Dexamethasone decreased the need of oxycodone in phase 2 PACU. The effect of dexamethasone was similar in paracetamol and parecoxib/valdecoxib patients.",
"The concept of balanced analgesia suggests that a combination of analgesic drugs may enhance analgesia and reduce side effects after surgery. This study evaluated the effect of the combination of propacetamol (Prodafalgan) and ketoprofen (Profenid) after surgery of a herniated disc of the lumbar spine.\n After randomization, 60 patients received: placebo (group 1); 2 g propacetamol (group 2); 50 mg ketoproten (group 3); or a combination of 2 g propacetamol and 50 mg ketoprofen (group 4). Drugs were administered every six hours for two days after surgery. The patients used morphine with patient controlled analgesia pumps (bolus 1 mg; lock out time 10 min) and were evaluated with a visual analogue scale (VAS) at rest and movement every six hours for two days. Side effects were noted.\n The patient characteristics and surgery were identical for each of the four groups. The VAS scores throughout the study were lower in group 4 than in groups 1, 2 and 3 both at rest (P < 0.05) and on movement (P < 0.01). The cumulative dose of morphine at 48 hr was lower in group 4 than in group 1 (23.4 +/- 5 mg vs. 58.9 +/- 9 mg; P < 0.01) or group 2 (23.4 +/- 5 mg vs 43.4 +/- 6.6 mg; P < 0.05) and similar to that in group 3 (34.2 +/- 4.5 mg). The incidence of side effects was similar in all groups.\n The combination of propacetamol and ketoprofen reduced pain scores both at rest and on movement. The drug combination did not reduce the morphine consumption and incidence of side effects.",
"This study evaluated the pre-emptive analgesic effect of intravenous (i.v.) (R)-ketamine in laparoscopic cholecystectomy. (R)-ketamine was used due to the lower incidence of side-effects.\n Sixty patients who underwent surgery under general anesthesia were randomly allocated to 3 groups and studied in a double-blind manner. Two i.v. injections were administered: one after induction of anesthesia, approximately 3 min before surgery, and one after surgery. The placebo group (PLA, n = 20) received saline in both injections. The preoperative group (PRE, n = 20) received (R)-ketamine 1 mg/kg and then saline. The postoperative group (POST, n = 20) received saline and then (R)-ketamine 1 mg/kg. Postoperatively, the patients used a patient-controlled analgesia (PCA) pump. Pain was evaluated with a visual analog scale (VAS) at 30 min and every hour for 4 h and with a verbal rating scale (VRS) at 24 h and after 7 days.\n There were no occurrence of side-effects from (R)-ketamine. VAS and VRS at 1, 2, 3, and 4 h postoperatively showed no statistical differences. In the POST group, extubation was delayed and pain score (VAS) at 30 min postoperatively was significantly lower (P < 0.05) than the two other groups. There were no statistical differences in meperidine consumption during the first 4 h postoperatively and no differences in consumption of analgesics at 24 h and 7 days.\n In this study a 1 mg/kg dose of (R)-ketamine given at the end of surgery exerted a short-lasting hypnotic and analgesic effect. The same dose given preoperatively did not show postoperative analgesic effect or pre-emptive effect.",
"A multimodal approach to postcesarean pain management may enhance analgesia and reduce side effects after surgery. This study evaluates the postoperative analgesic effects of propacetamol and/or diclofenac in parturients undergoing elective cesarean delivery under spinal anesthesia.\n After randomization, 80 healthy parturients received the following: placebo (group M), 100 mg diclofenac rectally every 8 hours (group MD), 2 g propacetamol intravenously every 6 hours (group MP), or a combination of 2 g propacetamol and 100 mg diclofenac (group MDP) as described above. Drugs were administered for 24 hours after surgery. Postoperative pain was controlled with a patient controlled analgesia pump, using morphine. The visual analog scale (VAS) at rest and on coughing, as well as the morphine consumption, were evaluated at 2, 6, and 24 hours postoperatively. Also, the side effects experienced after undergoing the different regimens were compared.\n The patients' characteristics did not differ significantly between the 4 groups. VAS score at 2 hours, both at rest and on coughing were lower in group MDP and MD compared with group M (P <.05). At 24 hours, there was still a tendency toward lower pain scores in the groups MDP and MD; however, this difference was only statistically significant at rest between the MDP group and the MP and M groups. Morphine consumption at 2, 6, and 24 hours was lower in the MDP and MD groups compared with the MP and M groups (P <.05). The morphine-sparing effect was higher in groups MDP and MD compared with group MP (57% and 46%, respectively, v 8.2%, P <.05). The incidence of side effects was similar in all groups. However, the power of the study was too low to permit an evaluation of potential side effects.\n Diclofenac after cesarean delivery improves analgesia and has a highly significant morphine-sparing effect. We were unable to demonstrate significant morphine-sparing effect of propacetamol or additive effect of propacetamol and diclofenac in this group of patients.",
"We compared the efficacy and side effects of propacetamol (P), an injectable prodrug of acetaminophen, 2 g and tramadol (T), a weak synthetic opioid, 1.5 mg.kg-1, given intravenously following thyroidectomy. 80 patients were randomly assigned to blindly receive one dose of P or T on request in the PACU. Residual pain was treated with i.v. PCA morphine. Pain and patient satisfaction were assessed with Visual Analog Scales. Demographic and peroperative data were comparable in both groups. Although the morphine consumption was comparable (p = 0.71), the decrease in VAS pain scores was significantly higher following tramadol (p = 0.03). More patients complained of nausea and vomiting (p = 0.01) during the first two hours following injection of tramadol, but there was no difference throughout the whole study. Oversedation was not observed in any group. We conclude that a single dose of tramadol provides a better quality of analgesia than propacetamol during the first six hours after thyroidectomy, but fails to ensure optimal analgesia, since VAS pain scores failed to fall below 3 despite the use of supplemental morphine.",
"Combined analgesic regimens have been suggested to improve the treatment of postoperative pain. The aim of our study was to evaluate the analgesic efficacy and tolerability of propacetamol, in combination with morphine.\n Four i.v. infusions of propacetamol 2 g or placebo were administered, in a double-blind fashion, after orthopedic surgery (n = 97). Morphine was administered by a patient-controlled analgesia (PCA) device. The total dose of morphine, pain intensity and global efficacy of treatment were evaluated. Tolerability was assessed by monitoring blood pressure, heart and respiratory rate, sedation scores, adverse events, and renal and hepatic parameters.\n The total dose of morphine was significantly decreased in the propacetamol group compared to placebo (9.4 +/- 8.5 mg vs 17.6 +/- 12 mg; P < 0.001), arriving at a sparing effect of 46%. The evolution of pain intensity showed a similar pattern in the two groups. Global efficacy of treatment was rated significantly better by patients receiving the combination propacetamol + PCA morphine (87% of \"good\"/\"excellent\" ratings vs 65%; P = 0.01). Tolerability was comparable in the two groups. Eight patients in the propacetamol and 4 patients in the placebo group reported adverse events, of mild/moderate intensity, most commonly nausea/vomiting. Renal and hepatic parameters were also seen to be comparable.\n These results confirm a significant morphine-sparing effect, significantly better scores in the final assessment by patients, and a good tolerability of propacetamol after orthopedic surgery. The drug may, therefore, represent a useful alternative to NSAIDs, as complementary drug to opioids, in the management of moderate/severe postoperative pain.",
"To compare the postoperative analgesic efficacy and safety of the non-addictive propacetamol hydrochloride (Pro-Bufferin) injection and dolantin in a prospective, randomized, double blind and controlled clinical trial.\n After the pain intensity was assessed when the patients were undergone thoracic and abdominal selective surgery became fully conscious, 40 consecutive patients with moderate to severe postoperative pain (equivalent to Pain Grade I and II of American Anesthesia Association classification) were randomized into the study against the control groups. The two groups were similar for age, sex, height/weight, disease categories, operation categories, anesthesia methods and duration, vital signs, hepatorenal function, and blood cell count (P = 0.06-0.93). In the study group, 2 g propacetamol in 100 ml normal saline (NS) intravenously with 1.0 ml NS intramuscularly as the placebo control to dolantin were administered. In the control group, 1.6 g mannitose in 100 ml NS intravenously as the placebo control to propacetamol with 50 mg dolantin (1.0 ml) intramuscularly as the positive control to propacetamol were administered. The intensity change of postoperative pain was then evaluated 10 times with visual analog scale and verbal describing scale during 6 h from the beginning of propacetamol infusion. Vital signs and adverse reactions were also documented. After all data were put into the computer, the blinding codes were decoded and the statistic analysis was then made.\n There was no significant difference (P = 0.93) about the area under the curve of \"Pain Relieve Score vs. Time\". The \"starting to effect\" time (15-30 min), analgesic duration (6 h) and the percentage of excellent or good analgesic effect (90%) in the two groups were the same. Adverse reactions didn't reached the statistic different level (P = 0.35).\n Propacetamol HCL injection 2 g intravenously could be an alternative to dolantin 50 mg intramuscularly for moderate to severe postoperative pain with its advantage of being non-addictive.",
"To evaluate both effectiveness and incidence of side effects of two techniques of postoperative pain treatment: intravenous and epidural PCA.\n Prospective analysis of data from two groups of randomized patients.\n Orthopedic and trauma center.\n Figty ASA class II-III patients undergoing total hip replacement under combined Spinal-Epidural Anesthesia.\n Patients were divided into 2 groups who received different postoperative pain treatment. One group (group PCA) received a patient-controlled intravenous analgesia with morphine 30 mg and ketorolac 90 mg in 100 ml of saline (back-ground infusion 2-4 ml, according to body weith, bolus 1 ml, lockout 5 min, 4 h dose limit 40 ml). PCEA group received a patient-controlled epidural analgesia with morphine 4 mg and bupivacaine 0.125% 100 ml, (background infusion 3-4 ml, according to patient' height, bolus 1 ml, lockout 10 min, 4 h dose limit 25 ml). Postoperative pain intensity was evaluated, through 24 postoperative hours, by a verbal analogue scale (VPS = 0 to 3) and a total pain score (TOTPAR) was calculated for each patient at 6 and 24 postoperative hours. Side effects were recorded and their incidence was obtained for each group. Statistical data analysis was performed by one-way ANOVA and non-parametric tests for ordinal data. Nominal data were analyzed by chi 2 test. p < 0.05 was considered significant.\n Patient receiving PCEA showed a significant (p < 0.005) decrease of incident pain, while VPS at rest was similar in the two groups. TOTPAR VPS was lower (p < 0.05) in PCEA group both at 6 and 24 postoperative hours. Somnolence was observed more often in PCA patients (8% vs 2%; p 0.05), while no significant differences were noted among other side effects incidence.\n Our data show a better control of postoperative pain arising from total hip replacement during PCEA when compared to PCA. It should be emphasized that incident pain is far more decreased by PCEA, so that this technique is particularly indicated when an early postoperative mobilization is required.",
"We assessed the analgesic efficacy of IV propacetamol and ketorolac in a double-blinded, placebo-controlled study involving patients undergoing total hip or knee replacement procedures. On the first morning after major joint replacement surgery, 164 patients experiencing moderate-to-severe pain were randomly assigned to receive an IV infusion of propacetamol (2 g), ketorolac (15 or 30 mg), or placebo (saline). Patient-controlled analgesia with morphine was made available as a \"rescue\" analgesic on patient's request during the 6-h postdosing evaluation period. The median time to onset of analgesia with propacetamol (8 [95% confidence interval 6,10] min) was shorter than ketorolac 15 mg (14 [7,16] min), and placebo (16 [8; not estimable] min) although the differences did not reach statistical significance. However, compared with ketorolac 30 mg, propacetamol had a shorter duration of analgesia (3.5 [2;5.4] vs 6 [3.3; not estimable] h). Analysis of pain intensity and pain relief scores demonstrated that propacetamol produced a significantly greater improvement in pain relief than saline from 45 min until 5 h after the injection. Propacetamol was not significantly different from ketorolac 15 mg and 30 mg with respect to the main analgesic efficacy variables during the 6-h assessment period. The most frequently reported adverse event with propacetamol was injection site pain (28% vs 19% for ketorolac 15 mg, 29% for ketorolac 30 mg, and 10% for placebo, respectively). In conclusion, propacetamol (2 g IV) possesses a similar analgesic efficacy to ketorolac (15 or 30 mg IV) after total hip or knee replacement surgery.",
"The purpose of this randomized double-blind study was to compare the efficacy and safety of propacetamol 2 g (an i.v. acetaminophen 1 g formulation) administered as a 2-min bolus injection (n=50) or a 15-min infusion (n=50) with oral acetaminophen 1 g (n=50) or placebo (n=25) for analgesia after third molar surgery in patients with moderate to severe pain after impacted third molar removal.\n All patients were evaluated for efficacy during the initial 6 h period after treatment administration (T(0)) and for safety during the entire week after T(0).\n The onset of analgesia after propacetamol was shorter (3 min for bolus administration, 5 min for 15-min infusion) than after oral acetaminophen (11 min). Active treatments were significantly better for all parameters (pain relief, pain intensity, patient's global evaluation, duration of analgesia) than placebo (P<0.05). Adverse events were more frequent after propacetamol, especially pain at the injection site. Propacetamol bolus resulted in a much higher incidence of local adverse events than the infusion (propacetamol bolus 90% vs propacetamol infusion 52%) with no clinically significant benefits in terms of analgesic efficacy.\n I.V. propacetamol, administered as a 15-min infusion, is a fast-acting analgesic agent. It is more effective in terms of onset of analgesia than a similar dose of oral acetaminophen.",
"A randomized, double-blind, placebo-controlled single oral dose study was done in order to examine whether codeine has an additive analgesic effect to that of paracetamol for moderate and strong postoperative pain after abdominal surgery. The maximum recommended single dose of paracetamol 1000 mg (Paracet) was compared with a combination of a submaximal dose of paracetamol 800 mg plus codeine 60 mg (Paralgin forte) and placebo for pain relief after Caesarean section in 125 patients.\n Visual analogue pain intensity score (VAS 0-100 mm) and categorical pain relief score were recorded for 6 hours after the study drug intake. The main efficacy variables analyzed were: pain intensity difference and summed pain intensity differences during the first 3 and 6 h after study drug intake, total pain relief during the first 3 and 6 h, global evaluation score at the end of the observation period, and time to rescue analgesic.\n Because of protocol violations, 17 patients were excluded from the analysis of effects. Among the 108 patients included in the analysis of analgesic effect, 49 patients had moderate baseline pain (VAS between 40 and 60 mm on a 100 mm scale), and 59 patients had strong baseline pain (VAS more than 60 mm). In patients with strong baseline pain, statistically highly significant differences were documented in efficacy variables between the active drugs and placebo and between the two active drugs. However, in patients with moderate baseline pain, no differences were found between the study drugs in any of the analgesic efficacy variables.\n This study thus confirms that codeine has additive analgesic effect to paracetamol in pain after surgery. Our results show the importance of initial pain intensity in postoperative assessment of analgesic drugs. Assay-sensitivity and test power are increased by selecting patients with sufficiently high initial pain intensity and by comparing groups of patients with identical surgery and similar demographic variables.",
"Diclofenac and paracetamol have different mechanisms and sites of action. Therefore, we tested if their combination is more effective for analgesia after tonsillectomy than either drug alone with respect to rescue analgesic consumption and visual analog scale values.\n The analgesic effects of intravenously administered propacetamol (injectable pro-drug of paracetamol) and diclofenac or a combination on postoperative pain were compared in 71 adult elective tonsillectomy patients in a randomized, double-blind study. After induction of anesthesia the patients received monotherapy with 2 g propacetamol (n = 25) or 75 mg diclofenac (n = 25), or a combined treatment with 2 g propacetamol and 75 mg diclofenac (n = 21) in physiologic saline as an infusion. Postoperatively the propacetamol dosage was repeated twice and diclofenac once on the ward. Oxycodone (0.03 mg kg(-1)) was used as a rescue analgesic by patient-controlled analgesia.\n On average the patients needed oxycodone 15.3, 13.2 and 10.6 times in the propacetamol, diclofenac and combination groups, respectively (NS). A verbal rating scale and a visual analog scale were employed for assessing post-tonsillectomy pain, nausea and patient satisfaction in all groups. No statistically significant differences were found between the groups. Twelve of the 25 (48%) patients having received propacetamol complained of pain at the cannulation site.\n Combined treatment with propacetamol and diclofenac with the dosages used provided clinically only a minor advantage over monotherapy with propacetamol or diclofenac with respect to postoperative analgesia or the incidence of side-effects in adult tonsillectomy patients.",
"Outpatient surgery demands rapid recovery and satisfied patients. The purpose of the study was to investigate whether rectal premedication with paracetamol and codeine would reduce the need of rescue analgesics, reduce the postoperative pain experience and result in faster eligibility for discharge. Ninety pregnant patients scheduled for day-case surgery with evacuation of the uterine cavity were randomly assigned into two groups. The paracetamol and codeine group was given a suppository with 60 mg of codeine and 800 mg of paracetamol together with standard premedication of intramuscular midazolam 0.08 mg/kg. The placebo group was given a placebo suppository and midazolam. All patients underwent the surgical procedure under general anaesthesia with alfentanil 15 microg/kg and propofol 1.5-2 mg/kg. There were no statistically significant differences between the groups in the postoperative pain experience as judged by Visual Analogue Scale (VAS-scale), verbal scale or the need for rescue analgesic medication with ketobemidone. Most of the patients experienced little postoperative pain with more than 70% scoring less than 20 mm on a VAS-scale from 0-100 mm at any time during the postoperative period. The paracetamol and codeine patients were significantly more sleepy at 30 min postoperatively. There were no differences between the groups in postoperative nausea or vomiting and no difference in discharge eligibility. The use of pre-operative suppository with paracetamol 800 mg and codeine 60 mg is unnecessary in this group of patients.\n Copyright 2000 European Federation of Chapters of the International Association for the Study of Pain.",
"Several reports have suggested that preoperative nociceptive block may reduce postoperative pain, analgesic requirements, or both, beyond the anticipated duration of action of the analgesic agents. We have investigated, in a double-blind, placebo-controlled study, pre-emptive analgesia and the respiratory effects of preoperative administration of a multimodal antinociceptive regimen. Thirty patients undergoing thoracotomy were allocated randomly to two groups. Before surgery, the treatment group (n = 15) received morphine 0.15 mg kg-1 i.m. with perphenazine 0.03 mg kg-1 i.m. and a rectal suppository of indomethacin 100 mg, while the placebo group (n = 15) received midazolam 0.05 mg kg-1 i.m. and a placebo rectal suppository. After induction of anaesthesia, the treatment group received intercostal nerve block with 0.5% bupivacaine and adrenaline 1:200,000 (3 ml) in the interspace of the incision and in the two spaces above and two spaces below. The placebo group received identical injections but with normal saline only. The treatment group consumed significantly less morphine by patient-controlled analgesia in the first 6 h after operation, but the total dose of morphine consumed on days 2 and 3 after surgery was significantly greater in the treatment group. There were no differences between the groups in postoperative VAS scores (at rest or after movement), PaCO2 values or postoperative spirometry. However, pain thresholds to pressure applied at the side of the chest contralateral to the site of incision decreased significantly from preoperative values on days 1 and 2 after surgery in both groups. The results of this study do not support the preoperative use of this combined regimen for post-thoracotomy pain.",
"We compared the effects of rectally administered diclofenac (12.5 mg) with paracetamol (125 mg) on pre- and postoperative behaviour and the need for supplementary analgesia in 44 children scheduled for adenoidectomy (with or without myringotomy). The study drugs were given in combination with diazepam (0.5 mg.kg-1) about 20 min before the children were taken to the operating theatre. On arrival there, the children who had received diclofenac were significantly quieter (< 0.05), easier to handle (p < 0.01) and cried less (p < 0.05) than those in the paracetamol group. During recovery, children in the diclofenac group needed fewer supplementary doses of intravenous pethidine than those receiving paracetamol (p < 0.001). There were no obvious differences between the groups in intra-operative bleeding (as estimated by the surgeon), or in measured blood loss. No postoperative complications became evident. The pre-operative rectal administration of diclofenac for pain relief after adenotomy is safe and effective.",
"The aim of the study was to compare the efficacy of parecoxib for postoperative analgesia after endoscopic turbinate and sinus surgery with the prodrug of acetaminophen, proparacetamol.\n Fifty American Society of Anesthesiology (ASA) physical status I-II patients, receiving functional endoscopic sinus surgery (FESS) and endoscopic turbinectomy, were investigated in a prospective, randomized, double-blind manner. After local infiltration with 1% mepivacaine, patients were randomly allocated to receive intravenous (i.v.) administration of either 40 mg of parecoxib (n=25) or 2 g of proparacetamol (n=25) 15 min before discontinuation of total i.v. anaesthesia with propofol and remifentanil. A blinded observer recorded the incidence and severity of pain at admission to the post anaesthesia care unit (PACU) at 10, 20, and 30 min after PACU admission, and every 1 h thereafter for the first 6 postoperative h.\n The area under the curve of VAS (AUC(VAS)) calculated during the study period was 669 (28-1901) cm x min in the proparacetamol group and 635 (26-1413) cm x min in the parecoxib group (p=0.34). Rescue morphine analgesia was required by 14 patients (56%) in the proparacetamol group and 12 patients (48%) in the parecoxib (p >or= 0.05), while mean morphine consumption was 5-3.5mg and 5-2.0 mg in the proparacetamol groups and parecoxib, respectively (p >or= 0.05). No differences in the incidence of side effects were recorded between the 2 groups. Patient satisfaction was similarly high in both groups, and all patients were uneventfully discharged 24 h after surgery.\n In patients undergoing endoscopic nasal surgery, prior infiltration with local anaesthetics, parecoxib administered before discontinuing general anaesthetic, is not superior to proparacetamol in treating early postoperative pain.",
"In a randomized, double-center, double-blind, parallel group study the analgesic effect of a single dose of paracetamol (1000 mg) and acetyl salicylic acid (1000 mg) was compared with placebo in patients with moderate to severe postoperative pain following the surgical removal of a wisdom tooth. The most important finding was the statistically significantly shorter period until the onset of the action of paracetamol as against acetyl salicylic acid."
] |
A single dose of both IV propacetamol and IV paracetamol provides around four hours of effective analgesia for about 37% of patients with acute postoperative pain. Both formulations are associated with few adverse events, although patients receiving IV propacetamol have a higher incidence of pain on infusion than both placebo and IV paracetamol.
|
CD000475
|
[
"1553169",
"7675371",
"11807358",
"8822429",
"7720911",
"8843257",
"14567807",
"8671270"
] |
[
"Use of Interceed(TC7) absorbable adhesion barrier to reduce postoperative adhesion reformation in infertility and endometriosis surgery. The Obstetrics and Gynecology Adhesion Prevention Committee.",
"Reduction of adhesion reformation after laparoscopic endometriosis surgery: a randomized trial with an oxidized regenerated cellulose absorbable barrier.",
"Fewer intraperitoneal adhesions with use of hyaluronic acid-carboxymethylcellulose membrane: a randomized clinical trial.",
"Prevention of de-novo adhesion formation after laparoscopic myomectomy: a randomized trial to evaluate the effectiveness of an oxidized regenerated cellulose absorbable barrier.",
"Expanded polytetrafluoroethylene (Gore-Tex Surgical Membrane) is superior to oxidized regenerated cellulose (Interceed TC7+) in preventing adhesions.",
"Prevention of postoperative abdominal adhesions by a sodium hyaluronate-based bioresorbable membrane: a prospective, randomized, double-blind multicenter study.",
"Initial feasibility study of a sprayable hydrogel adhesion barrier system in patients undergoing laparoscopic ovarian surgery.",
"Reduction of postoperative adhesion formation after laparoscopic ovarian cystectomy."
] |
[
"Interceed(TC7) is a fabric composed of oxidized, regenerated cellulose that was designed to reduce the formation of postsurgical adhesions. We evaluated Interceed(TC7) in a randomized, multicenter clinical study. Sixty-three infertility patients had bilateral pelvic sidewall adhesions removed at laparotomy. One pelvic sidewall was covered by Interceed(TC7) and the other was left uncovered. The deperitonealized areas (N = 205) of all sidewalls were divided into three groups: less than 100 mm2, N = 72; 100-1000 mm2, N = 95; and more than 1000 mm2, N = 38. The effectiveness of Interceed(TC7) was evaluated at laparoscopy 10-98 days after laparotomy. Significantly more adhesions were observed at laparoscopy on the control pelvic sidewalls (48 of 63, 76%) than on the treated sides (26 of 63, 41%) (P less than .0001). The Interceed(TC7)-treated sidewalls also had significantly less area involved with adhesions at laparoscopy (P less than .05, P less than .001, and P less than .001 in the three groups, respectively). Twenty-eight women with severe endometriosis also had significantly more adhesions on the control side (23 of 28, 82%) than on the treated side (14 of 28, 50%) (P less than .05). We conclude that Interceed(TC7) effectively reduced the incidence and extent of postoperative adhesions, even in patients with severe endometriosis.",
"To evaluate the effectiveness of an oxidized regenerated cellulose absorbable barrier (Interceed [TC7] Absorbable Adhesion Barrier) in the reduction of adhesion reformation after laparoscopic surgery for endometriosis.\n Thirty-two premenopausal nonpregnant women who had severe endometriosis and complete posterior cul-de-sac obliteration and were undergoing laparoscopic surgery were randomly assigned to either surgery alone or surgery and Interceed. None of the subjects received any other treatment for adhesion prevention. Second-look laparoscopy was performed 12-14 weeks after laparoscopic surgery by an investigator blinded to the treatment, and the incidence of adhesion-free subjects was assessed.\n Twelve of 16 (75%) women treated with the oxidized regenerated cellulose barrier were free of adhesions, compared with two of 16 (12.5%) controls, a statistically significant difference (P < .05).\n The oxidized regenerated cellulose absorbable barrier significantly reduces adhesion reformation after laparoscopic surgery for endometriosis.",
"To assess the effectiveness of bioresorbable Seprafilm membrane in preventing abdominal adhesions in a prospective clinical randomized multicenter trial.\n Adhesions occur frequently after abdominal operations and are a common cause of bowel obstruction, chronic abdominal pain, and infertility. To reduce the formation of adhesions, a mechanical barrier composed of hyaluronic acid and carboxymethylcellulose was developed, preventing adherence of tissues after abdominal surgery.\n Between April 1996 and September 1998, all patients requiring a Hartmann procedure for sigmoid diverticulitis or obstructed rectosigmoid were randomized to either intraperitoneal placement of the antiadhesions membrane under the midline during laparotomy and in the pelvis, or as a control. Direct visual evaluation of the incidence and severity of adhesions was performed laparoscopically at second-stage surgery for restoration of the continuity of the colon.\n A total of 71 patients were randomized; of these, 42 could be evaluated. The incidence of adhesions did not differ significantly between the two groups, but the severity of adhesions was significantly reduced in the Seprafilm group both for the midline incision and for the pelvic area. Complications occurred in similar numbers in both groups.\n Seprafilm antiadhesions membrane appears effective in reducing the severity of postoperative adhesions after major abdominal surgery, although the incidence of adhesions was not diminished. The authors recommend using Seprafilm when relaparotomy or second-look intervention is planned. Long-term studies are needed to assess the cost-effectiveness and value of Seprafilm in preventing bowel obstruction, chronic abdominal pain, and infertility.",
"To evaluate the effectiveness of the oxidized regenerated cellulose absorbable barrier (Interceed, TC7) in the prevention of de-novo adhesion formation after laparoscopic myomectomy, a prospective and randomized study was performed at the Department of Obstetrics and Gynaecology of the University of Cagliari, Cagliari, Italy. A total of 50 pre-menopausal non-pregnant women, aged 23-42 years, who submitted to laparoscopic myomectomy from January 1993 to June 1994, were randomized to surgery alone (control group, n = 25) or surgery and oxidized regenerated cellulose barrier (Interceed group, n = 25). Neither group received any other treatment for adhesion prevention. A second-look laparoscopy was performed 12-14 weeks after laparoscopic myomectomy. The incidence of adhesion-free patients was assessed at second-look laparoscopy by an investigator not informed of the treatment. The numbers of adhesion-free patients were three out of 25 (12%) in the control group and 15 out of 25 (60%) in the treatment group (P < 0.05). In conclusion, the oxidized regenerated cellulose absorbable barrier significantly reduced de-novo adhesion formation after laparoscopic myomectomy.",
"To compare the impact of expanded polytetrafluoroethylene (PTFE; Gore-Tex Surgical Membrane; W. L. Gore & Associates, Inc., Flagstaff, AZ) and oxidized regenerated cellulose (Interceed TC7, Johnson & Johnson Medical, Inc., Arlington, TX) on the development of postsurgical adhesions.\n A multicenter, nonblinded, randomized clinical trial.\n University medical centers.\n Each barrier was allocated randomly to the left or right sidewall of every patient.\n Thirty-two women with bilateral pelvic sidewall adhesions undergoing reconstructive surgery and second-look laparoscopy.\n Adhesion score (on a 0- to 11-point scale), the area of adhesion (cm2), and the likelihood of no adhesions.\n The use of both barriers was associated with a lower adhesion score and area of adhesion postoperatively. However, those sidewalls covered with PTFE had a significantly lower adhesion score (0.97 +/- 0.30 versus 4.76 +/- 0.61 points, mean +/- SEM) and area of adhesion (0.95 +/- 0.35 versus 3.25 +/- 0.62 cm2). Overall, more sidewalls covered with PTFE had no adhesions (21 versus 7) and, when adhesions were present on the contralateral sidewall, the number of sidewalls covered with PTFE without adhesions was greater than those covered with oxidized regenerated cellulose (16 versus 2).\n Expanded polytetrafluoroethylene was associated with fewer postsurgical adhesions to the pelvic sidewall than oxidized regenerated cellulose.",
"Postoperative abdominal adhesions are associated with numerous complications, including small bowel obstruction, difficult and dangerous reoperations, and infertility. A sodium hyaluronate and carboxymethylcellulose bioresorbable membrane (HA membrane) was developed to reduce formation of postoperative adhesions. The objectives of our prospective study were to assess the incidence of adhesions that recurred after a standardized major abdominal operation using direct laparoscopic peritoneal imaging and to determine the safety and effectiveness of HA membrane in preventing postoperative adhesions.\n Eleven centers enrolled 183 patients with ulcerative colitis or familial polyposis who were scheduled for colectomy and ileal pouch-anal anastomosis with diverting-loop ileostomy. Before abdominal closure, patients were randomly assigned to receive or not receive HA membrane placed under the midline incision. At ileostomy closure eight to 12 weeks later, laparoscopy was used to evaluate the incidence, extent, and severity of adhesion formation to the midline incision.\n Data were analyzed for 175 assessable patients. While only five (6 percent) of 90 control patients had no adhesions, 43 (51 percent) of 85 patients receiving HA membrane were free of adhesions (p < 0.00000000001). The mean percent of the incision length involved was 63 percent in the control group, significantly greater than the 23 percent observed in patients who received HA membrane (p < 0.001). Dense adhesions were observed in 52 (58 percent) of the 90 control patients, but in only 13 (15 percent) of the 85 receiving HA membrane (P < 0.0001). Comparison of the incidence of specific adverse events between the groups did not identify a difference (P > 0.05).\n This study represents the first controlled, prospective evaluation of postoperative abdominal adhesion formation and prevention after general abdominal surgery using standardized, direct peritoneal visualization. In this study, HA membrane was safe and significantly reduced the incidence, extent, and severity of postoperative abdominal adhesions.",
"To assess the safety and effectiveness of SprayGel as a barrier to reduce the frequency of adhesion formation and reformation after ovarian surgery, and to determine the feasibility of the study design for a larger, multicenter pivotal trial.\n Prospective, randomized, internally controlled trial (Canadian Task Force classification I).\n Two metropolitan, academic-affiliated, nonprofit hospitals.\n Fourteen women.\n Bilateral adnexal surgery.\n On completion of surgery, one adnexa was randomized to receive optimal surgical treatment plus application of the adhesion barrier, and the contralateral one to receive optimal surgical treatment alone. Patients returned in 3 to 16 weeks for second-look laparoscopy. All initial and second-look procedures were videotaped and reviewed by a blinded surgeon reviewer, and assessed for frequency, extent, and severity of adhesions. The frequency and extent of adhesion formation at second-look laparoscopy were statistically reduced on treatment sides compared with control sides (71% reduction in frequency, p = 0.0488; 69% reduction in extent, p = 0.0494). Adhesion severity score was reduced by 43% on the treatment side. SprayGel was associated with no adverse effects and was applied successfully in all patients.\n This material shows great promise in preventing postoperative adhesion formation in a population of patients greatly in need of such an adjunct. These findings warrant a larger, pivotal, multicenter study to evaluate SprayGel further.",
"The purpose of this randomized, open-label study was to assess the efficacy of the product Interceed absorbable adhesion barrier in the prevention of adhesion formation on the ovary after laparoscopic ovarian cystectomy. A total of 25 patients requiring laparoscopic bilateral ovarian cystectomy were enrolled into this study. After removal of ovarian cysts, peri-adnexal adhesions, and peritoneal irrigants, and the attainment of meticulous haemostasis, the random assignment of one ovary for wrapping with Interceed was revealed to the surgeon. The other ovary served as the untreated control. A follow-up laparoscopy was performed 8-30 weeks after the initial procedure in 17 patients. Significantly fewer adhesions formed at the Interceed treated ovaries compared with the control (untreated) ovaries (P < 0.05). In terms of adhesion-free outcome, 76% (13/17) of Interceed treated ovaries and 35% (6/17) of control ovaries were free of adhesions. A significant reduction was observed in the area of the sutured ovaries involved with adhesions when Interceed (6%) was used, compared with controls (20%). The reduction of adhesion formation was not related to the size of the cysts at the initial procedure. No adverse events were reported by any patient during the study. In conclusion, Interceed was found to be safe and effective in reducing the incidence of postoperative adhesion formation in patients undergoing laparoscopic ovarian cystectomy."
] |
The absorbable adhesion barrier Interceed reduces the incidence of adhesion formation following laparoscopy and laparotomy, but there are insufficient data to support its use to improve pregnancy rates. Gore-Tex may be superior to Interceed in preventing adhesion formation but its usefulness is limited by the need for suturing and later removal. There was no evidence of effectiveness of Seprafilm and Fibrin sheet in preventing adhesion formation.
|
CD004343
|
[
"7908570",
"2878174",
"10740301",
"6116952",
"10201714",
"3242186"
] |
[
"Ethamsylate in the prevention of periventricular-intraventricular hemorrhage in premature infants.",
"Multicentre trial of ethamsylate for prevention of periventricular haemorrhage in very low birthweight infants.",
"Role of ethamsylate in preventing periventricular-intraventricular hemorrhage in premature infants below 34 weeks of gestation.",
"Ethamsylate reduces the incidence of periventricular haemorrhage in very low birth-weight babies.",
"Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN trial. Neonatal Outcome and Prolonged Analgesia in Neonates.",
"The effect of ethamsylate on neonatal mortality in preterm infants."
] |
[
"A random and controlled trial was conducted to evaluate the efficacy and safety of ethamsylate in the prevention of periventricular-intraventricular hemorrhage (PIVH) in premature infants. Between January 1990 and July 1992, 171 premature infants with a birth weight of < 1,751 g who displayed no PIVH on initial cranial ultrasound scan, performed within an hour of delivery, were randomly divided into two groups. Group 1 consisted of 86 premature infants with a mean birth weight of 1.4 +/- 0.5 kg and a mean gestational age of 30.1 +/- 2.4 weeks. The first dose of ethamsylate 12.5 mg/kg (0.1 mL/kg from 250 mg/2mL ampoules) was given to group 1 intravenously within an hour of delivery and was followed by doses at six-hourly intervals for four days (total dose 200 mg/kg). Group 2 consisted of 85 premature infants with mean birth weight of 1.4 +/- 0.3 kg and mean gestational age of 30.4 +/- 2.2 weeks. Group 2 received 0.1 mL/kg normal saline intravenously in a similar fashion as the ethamsylate-treated group. Cranial ultrasound examinations were performed on postnatal days one, two, three, five, seven and 14. The incidence of PIVH in the ethamsylate-treated group was 24/86 (27.9%) and 39/85 (45.9%) in the control group (p < 0.02). In addition, the incidence of severe PIVH in the ethamsylate-treated group was 9/86 (10.5%) and 20/85 (23.5%) in the control group (p < 0.05). No adverse effects were attributed to ethamsylate therapy in this study.",
"The effectiveness of ethamsylate in the prevention of periventricular haemorrhage (PVH) in very low birthweight infants was evaluated by means of a multicentre, placebo-controlled, double-blind trial. In 330 infants without evidence of PVH on initial cranial ultrasound examination there was little difference between ethamsylate and placebo groups with respect to subependymal haemorrhage, but intraventricular and parenchymal haemorrhages developed in 30/162 infants (18.5%) in the treated group, compared with 50/168 (29.8%) in the control group (p less than 0.02). The incidence of intraventricular and parenchymal haemorrhage in survivors was 20/137 (14.6%) in the ethamsylate group and 37/146 (25.3%) in the controls (p less than 0.05). In 30 infants with evidence of PVH on the initial scan, ethamsylate treatment seemed to limit parenchymal extension. Analysis of the total cohort of 360 infants showed that the proportion of infants in whom an increase of two or more grades of severity of PVH was recorded during the trial was lower in the treated than in the placebo group (p less than 0.01). No adverse effects were attributed to ethamsylate therapy. The reported incidence of patent ductus arterious was lower in the treated than in the placebo group (p less than 0.02). Mortality was similar in the two groups.",
"To determine the role of ethamsylate in prevention of PVH-IVH in premature infants <34 weeks gestational age.\n Prospective, randomized, controlled study.\n Infants less than 34 weeks gestational age were included in the trial. Neonates with congenital malformations, family history of bleeding disorders and with Apgar scores <5 at 5 minutes were excluded. Subjects were randomized into two groups--Group A infants received intravenous ethamsylate (12.5 mg/kg) six hourly for four days and Group B infants served as a control group. Regular cranial ultrasounds to detect the presence of PVH-IVH were done between days 3-5, 10-14 and 28-30 of post natal age, and before hospital discharge in all infants and weekly in infants detected to have PVH-IVH on earlier scans. Various antenatal and postnatal factors known to affect the incidence of PVH-IVH were recorded.\n A total of 192 infants underwent the trial, 93 in Group A and 99 in Group B. Antenatal corticosteroids (1 or 2 doses) were administered to 32 ( 34.4%) and 36 (36.3%) women in Group A and Group B, respectively. None of the mothers received phenobarbitone, vitamin K or indomethacin antenatally and none of the infants received phenobarbitone, vitamin E or indomethacin postnatally during the study period. PVH-IVH was seen in 26 infants in Group A, of which Grade I IVH occurred in 9, Grade II in 14, Grade III in 2 and Grade IV in one infant. Twenty-nine infants had PVH-IVH in Group B of which 11 had Grade I, 15 Grade II and 3 Grade III. None of the differences were statistically significant.\n Postnatal administration of ethamsylate did not decrease the incidence of PVH-IVH in the study infants.",
"nan",
"Preterm neonates are exposed to multiple painful procedures after birth and exhibit acute physiological responses to pain. Occurrence of early intraventricular hemorrhage within 24 to 72 hours after birth suggests a role of pain and stress in the multifactorial causation of severe intraventricular hemorrhage and periventricular leukomalacia. We proposed that such neurologic outcomes in preterm neonates who require ventilatory support may be reduced by morphine analgesia or midazolam sedation compared with a placebo.\n To define the incidence of clinical outcomes in the target study population, to estimate the effect size and adverse effects associated with analgesia and sedation, and to calculate the sample size for a definitive test of this hypothesis.\n Sixty-seven preterm neonates were randomized in a pilot clinical trial from 9 centers. Neonates of 24 to 32 weeks gestation were eligible if they had been intubated and required ventilatory support for less than 8 hours and if they were enrolled within 72 hours after birth. Exclusion criteria included major congenital anomalies, severe intrapartum asphyxia, and participation in other research studies. Severity of illness was assessed by the Clinical Risk Index for Babies, and neonates were randomized to receive continuous infusions of morphine sulfate, midazolam hydrochloride, or 10% dextrose (placebo). Masked study medications were continued as long as clinically necessary, then weaned and stopped according to predefined criteria. Levels of sedation (COMFORT scores) and responses to pain (Premature Infant Pain Profile scores) were measured before, during, and 12 hours after discontinuation of drug infusion. Cranial ultrasound examinations were performed as part of routine practice, and poor neurologic outcomes were defined as neonatal death, severe intraventricular hemorrhage (grade III or IV), or periventricular leukomalacia.\n No significant differences occurred in the demographic, clinical, and socioeconomic variables related to mothers and neonates in the 3 groups or in the severity of illness at birth as measured by Clinical Risk Index for Babies scores. Two neonates in the placebo group and 1 neonate in the midazolam group died; no deaths occurred in the morphine group. Poor neurologic outcomes occurred in 24% of neonates in the placebo group, 32% in the midazolam group, and 4% in the morphine group (likelihood ratio chi2 = 7.04, P = .03). Secondary clinical outcomes and neurobehavioral outcomes at 36 weeks' postconceptional age were similar in the 3 groups. Responses elicited by endotracheal tube suction (Premature Infant Pain Profile scores) were significantly reduced during the morphine (P<.001) and midazolam (P = .002) infusions compared with the placebo group.\n This pilot trial suggests that preemptive analgesia given by continuous low-dose morphine infusion may reduce the incidence of poor neurologic outcomes in preterm neonates who require ventilatory support. Limitations in the sample size of this pilot study suggest that these results should be confirmed in a large multicenter randomized trial.",
"nan"
] |
Preterm infants treated with ethamsylate showed no reductions in mortality or neurodevelopmental impairment despite the reduction in any grade of intraventricular haemorrhage seen in infants < 35 weeks gestation.
|
CD001860
|
[
"16522834",
"9114186",
"16170117",
"8102427",
"16905024",
"19329003",
"8637698",
"21785663",
"17255240",
"17003397",
"17005549",
"9291741",
"18374301",
"9469269",
"18781287"
] |
[
"Effect of a single mass antibiotic distribution on the prevalence of infectious trachoma.",
"A comparison of oral azithromycin with topical oxytetracycline/polymyxin for the treatment of trachoma in children.",
"A randomised controlled trial of azithromycin following surgery for trachomatous trichiasis in the Gambia.",
"Randomised controlled trial of single-dose azithromycin in treatment of trachoma.",
"Intensive insecticide spraying for fly control after mass antibiotic treatment for trachoma in a hyperendemic setting: a randomised trial.",
"Assessment of herd protection against trachoma due to repeated mass antibiotic distributions: a cluster-randomised trial.",
"Single-dose azithromycin in the treatment of trachoma. A randomized, controlled study.",
"Efficacy of latrine promotion on emergence of infection with ocular Chlamydia trachomatis after mass antibiotic treatment: a cluster-randomized trial.",
"Chlamydia on children and flies after mass antibiotic treatment for trachoma.",
"Impact of annual targeted treatment on infectious trachoma and susceptibility to reinfection.",
"Efficacy and safety of short duration azithromycin eye drops versus azithromycin single oral dose for the treatment of trachoma in children: a randomised, controlled, double-masked clinical trial.",
"Health education and antibiotic therapy in trachoma control.",
"Clinical cure of bacterial conjunctivitis with azithromycin 1%: vehicle-controlled, double-masked clinical trial.",
"Chlamydia in pregnancy: a randomized trial of azithromycin and erythromycin.",
"Efficacy of topical azithromycin ophthalmic solution 1% in the treatment of posterior blepharitis."
] |
[
"The World Health Organization recommends mass antibiotic distributions in its strategy to eliminate blinding trachoma as a public health concern. Some hypothesize that a single distribution is sufficient to control the ocular strains of chlamydia that cause trachoma. Others believe infection will inevitably return and periodic treatments or other measures are essential.\n To determine whether ocular chlamydial infection returns to the community up to 24 months after a single mass antibiotic distribution in a hyperendemic region of Ethiopia.\n Longitudinal cohort study conducted March 2003 to March 2005 in the Gurage Zone of Ethiopia. Eight randomly selected villages were assessed for ocular chlamydial infection. Fifteen untreated villages were randomly chosen at 12 months to allow assessment of a secular trend.\n A single dose of oral azithromycin was offered to all residents of the 8 selected villages who were aged 1 year or older.\n Prevalence of ocular chlamydial infection in all children aged 1 to 5 years from each intervention village prior to treatment and 2, 6, 12, 18, and 24 months after mass antibiotic treatment, and also in untreated villages enrolled at 12 months.\n Five hundred fifteen children were examined for ocular chlamydial infection at baseline. For the follow-up examinations, the mean participation rate was 83%. The mean prevalence of infection in children aged 1 to 5 years decreased from 43.5% (95% confidence interval [CI], 35.0%-52.0%) to 5.1% (95% CI, 1.1%-9.2%) after treatment. On average, infection returned gradually over 24 months to 11.3% (95% CI, 4.5%-18.1%; P = .001). In 7 of 8 villages, infection was higher at 24 months than at 2 months. In the remaining village, no infection could be identified at any point after treatment. Villages enrolled at 12 months had significantly fewer infections than those enrolled 12 months earlier, suggesting a secular trend (P<.001).\n Ocular chlamydial infection was not eliminated in children aged 1 to 5 years after a single mass azithromycin distribution; it slowly returned over 24 months, although not to baseline levels. Repeated treatments or other effective measures will be necessary for elimination.",
"Trachoma, an infectious keratoconjunctivitis caused by Chlamydia trachomatis, is a leading cause of preventable blindness in developing countries. In this study we compared oral azithromycin with oxytetracycline/polymyxin eye ointment (once daily for 5 days every 4 weeks; total of six treatment cycles) for the treatment of active endemic trachoma in 168 rural Egyptian children. A suspension of azithromycin was administered to children as a dose of 20 mg/kg by one of three schedules: a single dose, one dose a week for 3 weeks, and one dose every 4 weeks for a total of six doses. The children's clinical status and chlamydial infection rates were evaluated for 1 year. The clinical cure rates were 35% 2 months after initial treatment, 16% at 8 months (during the annual autumn epidemic of purulent conjunctivitis), and 47% at 1 year. The pretreatment chlamydial infection rate of 33% (determined by direct immunofluorescence) decreased to 5% at 2 months and was 9% at 12 months. There were no significant clinical or laboratory differences among the four treatment groups. Thus, 1-6 doses of azithromycin were equivalent to 30 days of topical oxytetracycline/polymyxin ointment and may offer an effective alternative means of controlling endemic trachoma.",
"Trachomatous trichiasis frequently returns following surgery. Several factors may promote recurrence: preoperative disease severity, surgeon ability, surgical procedure, healing responses, and infection. This study investigates whether enhanced control of infection, both of Chlamydia trachomatis and other bacteria, with azithromycin can improve surgical outcome in a trachoma control programme.\n Individuals with trachomatous trichiasis were examined and operated. After surgery patients were randomised to the azithromycin or control group. The azithromycin group and children in their household were given a dose of azithromycin. Antibiotic treatment was repeated at 6 months. All patients were reassessed at 6 months and 12 months. Samples were collected for C trachomatis polymerase chain reaction and general microbiology at each examination.\n 451 patients were enrolled. 426 (94%) were reassessed at 1 year, of whom 176 (41.3%) had one or more lashes touching the eye and 84 (19.7%) had five or more lashes. There was no difference in trichiasis recurrence between the azithromycin and control group. Recurrent trichiasis was significantly associated with more severe preoperative trichiasis, bacterial infection, and severe conjunctival inflammation at 12 months. Significant variability in outcome was found between surgeons. Visual acuity and symptoms significantly improved following surgery.\n In this setting, with a low prevalence of active trachoma, azithromycin did not improve the outcome of trichiasis surgery conducted by a trachoma control programme. Audit of trichiasis surgery should be routine.",
"Blindness due to trachoma is a serious public health issue world wide. The currently recommended treatment of active trachoma with repeated doses of tetracycline eye ointment has many disadvantages. The new azalide antibiotic azithromycin is effective as a single oral dose in the chemotherapy of genital Chlamydia trachomatis infections, and we have assessed its efficacy for trachoma treatment. We carried out a randomised single-blind comparison of azithromycin (a single oral dose of 20 mg/kg) with conventional treatment (6 weeks of topical tetracycline plus erythromycin for severe cases) in two villages with endemic trachoma in The Gambia. The patients were followed up for 26 weeks from the start of treatment by an observer unaware of treatment allocation. By 6 months' follow-up, trachoma had resolved in 76 (78%) of 97 subjects who received azithromycin compared with 70 (72%) of 97 who were treated conventionally (95% CI for difference -6% to 18%). Compliance with both treatments was good, but that for conventional treatment could probably not be achieved outside the research setting. There were no significant differences in treatment effect, baseline characteristics, or re-emergent disease between the treatment groups. Azithromycin was well tolerated. As a systemic treatment effective in a single dose it has important potential for trachoma control.",
"There are no data on the cumulative effect of fly control and antibiotic distribution on trachoma in hyperendemic communities. We sought to determine whether insecticide spray intervention after mass antibiotic treatment could reduce trachoma and ocular infection with Chlamydia trachomatis in hyperendemic neighbourhoods in Tanzania.\n We did a single-blind, randomised clinical trial in 16 neighbourhoods (balozi) in Kongwa, Tanzania. All children aged 1-7 years were enrolled, with 119 children in the eight balozi of the intervention group and 183 in the eight control balozi. Children were examined at baseline, 6 months, and 1 year for clinical trachoma and ocular C trachomatis infection. One dose of azithromycin was offered to all residents of both intervention and control balozi after the baseline survey. Households (and surrounding areas) in the intervention group were then sprayed with insecticide throughout the ensuing year and monitored for reductions in fly counts. This study is registered at ClinicalTrials.gov, number NCT00347763.\n The intervention balozi had significantly lower fly counts than controls at all monitored weeks (p<0.05), apart from weeks 7-9. The trachoma rate did not differ significantly in the intervention and control balozi at 6 months post-treatment (20%vs 33%, p=0.07), nor did it at 1 year (43%vs 44%, p=0.90). Infection with C trachomatis did not differ between groups at 6 months post-treatment (9%vs 7%, p=0.45).\n Intensive insecticide spraying reduced flies in the environment, but our results suggest that fly reduction after mass antibiotic treatment has no added benefit on reduction of trachoma.",
"Trachoma-control programmes distribute oral azithromycin to treat the ocular strains of chlamydia that cause the disease and to control infection. Theoretically, elimination of infection is feasible if untreated individuals receive an indirect protective effect from living in repeatedly treated communities, which is similar to herd protection in vaccine programmes. We assessed indirect protection against trachoma with mass azithromycin distributions.\n In a cluster randomised trial, 24 subkebeles (government-defined units) in Amhara, Ethiopia, were randomised, with use of a simple random sample, to distribution four times per year of single-dose oral azithromycin to children aged 1-10 years (12 subkebeles, 4764 children), or to delayed treatment until after the study (control; 12 subkebeles, 6014 children). We compared the prevalence of ocular chlamydial infection in untreated individuals 11 years and older between baseline and 12 months in the treated subkebeles, and at 12 months between the treated and control subkebeles. Health-care and laboratory personnel were blinded to study group. Analysis was intention to treat. The study is registered with clinicaltrials.gov, number NCT00322972.\n At 12 months, 637 children aged 1-10 years and 561 adults and children aged 11 years and older were analysed in the children-treated group, and 618 and 550, respectively, in the control group. The mean prevalence of infection in children decreased from 48.4% (95% CI 42.9-53.9) to 3.6% (0.8-6.4) after four mass treatments. At 12 months, the mean prevalence of infection in the untreated age group (>/=11 years) was 47% (95% CI 33-57) less than baseline (p=0.002), and 35% (95% CI 1-57) less than that in untreated communities (p=0.04).\n Frequent treatment of children, who are a core group for transmission of trachoma, could eventually eliminate infection from the entire community. Herd protection is offered by repeated mass antibiotic treatments, providing a strategy for elimination of a bacterial disease when an effective vaccine is unavailable.\n National Institutes of Health.",
"To compare the safety and efficacy of single oral-dose azithromycin with a 7-week topical tetracycline ointment course in the treatment of active trachoma.\n A total of 64 patients with active trachoma were selected randomly to receive azithromycin (20 mg/kg) in a single dose or topical tetracycline eye ointment for 6 weeks. Clinical assessments were made before and at 4, 8, 12, and 24 weeks after treatment. Conjunctival scrapings were obtained before and after 24 weeks after treatment and fixed for Giemsa and direct immunofluorescence staining.\n Trachoma resolved in 17 (63.3%) patients who received azithromycin compared with 19 (65.4%) who were treated with tetracycline ointment. There were no significant differences in treatment effect or baseline characteristics between the treatment groups. Both treatments were well tolerated, and no adverse events were noted.\n Single-dose azithromycin is as effective as a 6-week course of topical tetracycline ointment in the treatment of active trachoma. The findings may help establish high compliance in treating trachoma and could contribute to the control of trachoma worldwide.",
"The World Health Organization (WHO) recommends environmental improvements such as latrine construction in the integrated trachoma control strategy, SAFE. We report a cluster-randomized trial assessing the effect of intensive latrine promotion on emergence of infection with ocular Chlamydia trachomatis after mass treatment with antibiotics.Twenty-four communities in Goncha Seso Enesie woreda, Amhara Regional State, Ethiopia, were enumerated, and a random selection of 60 children aged 0- 9 years in each was monitored for clinical signs of trachoma and ocular chlamydial infection at baseline, 12 and 24 months. All community members were offered treatment with a single dose of oral azithromycin or topical tetracycline. After treatment, 12 subkebeles were randomized to receive intensive latrine promotion. Mean cluster ocular infection in the latrine and the non-latrine arms were reduced from 45.5% (95% CI 34.1-56.8%) and 43.0% (95% CI 31.1-54.8%) respectively at baseline to 14.6% (95% CI 7.4-21.8%) and 14.8% (95% CI 8.9-20.8%) respectively at 24 months (P=0.93). Clinical signs fell from 72.0% (95% CI 58.2-85.5%) and 61.3% (95% CI 44.0-78.5%) at baseline to 45.8% (36.0-55.6%) and 48.5% (34.0-62.9%) respectively at 24 months (P=0.69). At 24 months, estimated household latrine coverage and use were 80.8% and 61.7% respectively where there had been intensive latrine promotion and 30.0% and 25.0% respectively in the single treatment only arm. We were unable to detect a difference in the prevalence of ocular chlamydial infection in children due to latrine construction.",
"There are various approaches to control trachoma. These include the elimination of the ocular strains of Chlamydia trachomatis that cause the disease and to decrease the spread of infection by other measures such as fly control. Here, we examined how these two are related (i.e., how treating children with antibiotics affects carriage of Chlamydia by flies). Flies were collected in villages that had received mass oral azithromycin distribution and were compared with flies in untreated villages. Polymerase chain reaction (PCR) was performed to detect chlamydial DNA on the flies. Conjunctival swabs were also taken to assay for chlamydial prevalence in the children. Chlamydia was found on 23% of the flies in the untreated villages but only 0.3% in treated villages. Prevalence of trachoma in children proved to be an excellent predictor of the prevalence on flies (correlation coefficient, 0.89). Thus, treating children with antibiotics may drastically reduce the role of flies as a vector.",
"The World Health Organization developed the SAFE strategy (Surgery for trichiasis; Antibiotics for Chlamydia trachomatis infection; Facial cleanliness; and Environmental improvement) to eliminate blinding trachoma globally by the year 2020. Despite a number of studies using various intervals of treatment for different prevalence rates, there has been a lack of sufficient follow-up beyond the final treatment point to determine rates of recurrence of disease and infection and the risk factors that may contribute to each.\n To evaluate the impact of 2 annual targeted azithromycin treatments on active trachoma and C trachomatis infection rates over 3 years in Vietnam.\n Three communes were randomly selected for a longitudinal study in Vietnam from November 2000 through November 2003. Individuals (n = 3186) were graded for trachoma followed by conjunctival sampling to detect chlamydiae by commercial polymerase chain reaction. Grading and chlamydial detection were repeated every 6 months for 3 years.\n Azithromycin was given to children aged 5 through 15 years with active trachoma and their household members in SAFE and SA communes at baseline and 12 months; these communes were compared with the S-only control commune that did not receive azithromycin targeted treatment.\n Prevalence and incidence of active trachoma and C trachomatis infection in all communes at baseline, 6, 12, 18, 24, and 36 months. Subgroup analysis evaluated new infection, continuing infection, and reinfection at 6, 12, 18, 24, and 36 months and risk factors for each.\n Reinfection rates increased significantly between 12 and 36 months for SAFE (from 1.6 to 29.3 per 1000; P<.001) and SA (5.1 to 25.3 per 1000; P = .002) communes but not for the S-only commune (13.4 to 6.7 per 1000; P = .55) after 24 months. Compared with the S-only commune, mixed-effects and generalized estimating equations (GEE) logistic models showed that reinfection risk was significantly higher for SAFE (odds ratio [OR], 4.1; 95% confidence interval [CI], 1.5-9.8; P = .005) and SA (OR, 4.2; 95% CI, 1.1-17.3; P = .04) communes at 36 months.\n Increasing reinfection rates suggest that treatment may interrupt the duration of infection required for developing immunity, increasing the number of individuals susceptible to reinfection and adversely affecting disease prevalence over time. Additional research is needed to determine optimal trachoma control strategies, including evaluation of the \"F\" and \"E\" components.\n www.actr.org.au Identifier: 12606000360516.",
"Efficacy and safety of a short-duration treatment of azithromycin 1.5% eye drops versus oral azithromycin to treat active trachoma.\n Randomised, controlled, double-masked, double-dummy, non-inferiority explanatory study including 670 children from Guinea Conakry and Pakistan if: 1-10 years old; active trachoma (TF+TI0 or TF+TI+ on simplified World Health Organisation (WHO) scale). Three groups received either: azithromycin 1.5% eye drops twice daily for 2 days, for 3 days or azithromycin single 20 mg/kg oral dose. Patients' contacts were treated whenever possible. Clinical evaluation was performed using a binocular loupe. Primary efficacy variable was the cure (no active trachoma (TF0)) at day 60. Non-inferiority margin for difference between cure rates was 10%.\n Cure rate in per protocol set was as follows: 93.0%, 96.3% and 96.6% in 2-day group 3-day group, and oral treatment group, respectively. Azithromycin 1.5% groups were non-inferior to oral azithromycin. The intend to treat (ITT) analysis supported the results. Clinical re-emergence rate was low: 4.2%. Ocular tolerance was similar for all groups. No treatment related adverse events were reported. Logistic regression analyses found prognostic factors such as: country (p<0.001) and trachoma severity (p = 0.003).\n In active trachoma, azithromycin eye drops twice daily for 2 or 3 days are as efficient as the WHO's reference treatment and represent an innovative alternative to oral azithromycin.",
"The objective of this study was to confirm whether the combination of a health education programme with a mass treatment campaign was able to improve the effectiveness of trachoma control. An open controlled clinical trial with a 2 x 2 factorial design was carried out. Four villages, matched for size and epidemiological, economic and social conditions, were included in the study. The first village received mass treatment with 1% oxytetracycline eye drops combined with a specific health education programme. The second village received only a health education programme. The third village received only mass treatment and the fourth village did not receive any intervention during the study (control village). 1810 subjects were enrolled of whom 76% were successfully followed for 6 months. The incidence of new cases ranged between 1.6% and 14.2%. In this study the combination of a health education programme with mass treatment failed to increase the cure rate. There was even a negative interaction (P = 0.03). The best results were obtained in the village where antibiotic treatment was used alone, both in terms of cure rate (82%) and reduction of C trachomatis transmission. These results suggest that the addition of a health education programme does not systematically improve the performances of a mass treatment campaign. The efficacy of this combination depends essentially on the capacity of the community to modify its hygiene behaviour.",
"To analyze the effect of azithromycin 1% ophthalmic solution in DuraSite (InSite Vision, Inc, Alameda, California, USA) on bacterial conjunctivitis.\n Prospective, randomized, vehicle-controlled, parallel-group, double-masked multicenter clinical study.\n Eligible male or female participants with a clinical diagnosis of acute bacterial conjunctivitis were randomized to either 1% azithromycin in DuraSite or vehicle for five days. Infected eyes were dosed twice daily on days 1 and 2 and once daily on days 3 through 5. Conjunctival cultures were obtained at baseline, visit 2 (day 3 or 4), and visit 3 (day 6 or 7). The primary end point was clinical resolution of signs and symptoms (rating of zero on ocular discharge, bulbar and palpebral injection) at visit 3. Efficacy measures were clinical resolution and bacterial eradication as evaluated in the per-protocol population. Safety was assessed by adverse events, slit-lamp findings, and ophthalmoscopy.\n Two hundred and seventy-nine participants (n = 130, 1% azithromycin in DuraSite; n = 149, vehicle), age one to 96 years, were evaluated for efficacy. Clinical resolution with azithromycin ophthalmic solution was statistically significant compared with that of vehicle (P = .030) at visit 3. Bacterial eradication rates with azithromycin ophthalmic solution reached 88.5% at visit 3 (P < .001) and included some pathogens resistant to azithromycin in vitro. Overall, adverse event rates were similar in both treatment groups.\n Azithromycin 1% ophthalmic solution in DuraSite showed statistically significant differences in clinical resolution and bacterial eradication rates when compared with vehicle. Because it was well tolerated in this population, it may be a viable treatment option for children and adults with bacterial conjunctivitis.",
"To determine side effect profiles and cure rates of azithromycin compared with erythromycin in the treatment of chlamydial cervicitis complicating pregnancy.\n Pregnant patients with positive DNA antigen assays for Chlamydia trachomatis were randomized to either azithromycin, 1 g oral slurry in a single dose, or erythromycin, 500 mg every 6 hours for 7 days. Repeat assays were planned for 3 weeks after therapy. Side effects, compliance, and treatment efficacy were assessed.\n One hundred six women were enrolled, and eighty-five women completed the protocol. Significantly fewer gastrointestinal side effects were noted in the azithromycin group than in the erythromycin group (11.9% versus 58.1%, P < or = .01). Enhanced compliance was noted with azithromycin, because it was given in a single observed dose. Similar treatment efficacy was noted between azithromycin and erythromycin (88.1% versus 93.0%, P > .05).\n Compared with erythromycin, azithromycin is associated with significantly fewer gastrointestinal side effects in pregnancy. This association, along with the ease of administration and similar efficacy, suggests that azithromycin should be considered for the initial treatment of chlamydial cervicitis in pregnancy.",
"Azithromycin, a broad-spectrum antibiotic with potent anti-inflammatory activities, has the potential to effectively treat blepharitis, an inflammatory disease of the eyelid with abnormal eyelid flora as an etiologic determinant. The present study compared the efficacy of topical azithromycin ophthalmic solution 1% (AzaSite; Inspire Pharmaceuticals, Inc, NC, USA) combined with warm compresses (azithromycin group) to warm compresses alone (compress group) in patients with posterior blepharitis.\n Twenty-one patients diagnosed with posterior blepharitis were randomized in an open-label study to receive either azithromycin plus warm compresses (10 patients), or compresses alone (11 patients). All patients were instructed to apply compresses to each eye for 5-10 minutes twice daily for 14 days. Each eye in the azithromycin group also received azithromycin solution (1 drop) twice daily for the first 2 days followed by once daily for the next 12 days. Patients were evaluated at study initiation (visit 1) and at end of treatment (visit 2) for the severity of five clinical signs: eyelid debris, eyelid redness, eyelid swelling, meibomian gland (MG) plugging, and the quality of MG secretion. At visit 2, patients also rated their degree of overall symptomatic relief.\n Twenty patients completed the study. At visit 2, patients in the azithromycin group demonstrated significant improvements in MG plugging, MG secretions, and eyelid redness as compared with the compress group. In the azithromycin group, MG plugging resolved completely in three patients and MG secretion returned to normal in two patients; no such results were seen in the compress group. Furthermore, a higher percentage of patients in the azithromycin group rated overall symptomatic relief as excellent or good. Visual acuity measurements and biomicroscopic evaluation revealed no ocular safety issues.\n Azithromycin ophthalmic solution in combination with warm compresses provided a significantly greater clinical benefit than warm compresses alone in treating the signs and symptoms of posterior blepharitis."
] |
Antibiotic treatment reduces the risk of active trachoma and ocular chlamydial infection in people infected with C. trachomatis, but we do not know for certain the size of the treatment effect in individuals. Mass antibiotic treatment with single-dose oral azithromycin reduces the prevalence of active trachoma and ocular infection in communities.
|
CD008602
|
[
"19398797",
"21357965",
"20419009",
"17323092",
"19350335",
"21542934",
"19940729",
"16495014",
"18441040",
"19827166",
"3896460"
] |
[
"Conservative management of idiopathic clubfoot: Kite versus Ponseti method.",
"An accelerated Ponseti versus the standard Ponseti method: a prospective randomised controlled trial.",
"Comparison of Ponseti and Kite's method of treatment for idiopathic clubfoot.",
"Ponseti's vs. Kite's method in the treatment of clubfoot--a prospective randomised study.",
"Comparison of Ponseti versus surgical treatment for idiopathic clubfoot: a short-term preliminary report.",
"Treatment success in pragmatic randomised controlled trials: a review of trials funded by the UK Health Technology Assessment programme.",
"Comparison of the effectiveness of three manual physical therapy techniques in a subgroup of patients with low back pain who satisfy a clinical prediction rule: a randomized clinical trial.",
"Short- and long-term efficacy of brief cognitive-behavioral therapy for patients with chronic temporomandibular disorder pain: a randomized, controlled trial.",
"Short- and long-term outcome of constraint-induced movement therapy after stroke: a randomized controlled feasibility trial.",
"Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis.",
"Participants in prospective, randomized clinical trials for resected non-small cell lung cancer have improved survival compared with nonparticipants in such trials."
] |
[
"To compare the long-term results of the Kite and Ponseti methods of manipulation and casting for clubfoot.\n 42 patients (with 64 idiopathic clubfeet) were equally randomised to Kite or Ponseti treatments in the early weeks of life. 14 males and 7 females (34 clubfeet) were treated by the Kite method, whereas 13 males and 8 females (30 clubfeet) were treated by the Ponseti method. All the clubfeet were manipulated, casted, and followed up (for a mean of 3 years) by one experienced orthopaedic surgeon. The final results were compared.\n The success rates for the Kite and Ponseti treatments were similar (79% vs 87%). With the Ponseti method, the number of casts was significantly fewer (7 vs 10); the duration of casting required to achieve full correction was significantly shorter (10 vs 13 weeks); the maximum ankle dorsiflexion achieved was significantly greater (12 vs 6 degrees); and the incidence of residual deformity and recurrence was slightly lower.\n The Ponseti method can achieve more rapid correction and ankle dorsiflexion with fewer casts, without weakening the Achilles tendon.",
"We conducted a prospective randomised controlled trial to compare the standard Ponseti plaster method with an accelerated method for the treatment of idiopathic congenital talipes equinovarus. The standard weekly plaster-change method was accelerated to three times per week. We hypothesised that both methods would be equally effective in achieving correction. A total of 40 consecutive patients (61 feet) were entered into the trial. The initial median Pirani score was 5.5 (95% confidence interval 4.5 to 6.0) in the accelerated group and 5.0 (95% confidence interval 4.0 to 5.0) in the standard control group. The scores decreased by an average 4.5 in the accelerated group and 4.0 in the control group. There was no significant difference in the final Pirani score between the two groups (chi-squared test, p = 0.308). The median number of treatment days in plaster was 16 in the accelerated group and 42 in the control group (p < 0.001). Of the 19 patients in the accelerated group, three required plaster treatment for more than 21 days and were then assigned to the standard control method. Of the 40 patients, 36 were followed for a minimum of six months. These results suggest that comparable outcomes can be achieved with an accelerated Ponseti method. The ability to complete all necessary manipulations within a three-week period facilitates treatment where patients have to travel long distances.",
"The manipulation and corrective cast application for club foot was known to be done by Kite's method. The Kite's method of manipulation (center of rotation of malaligned foot and fulcrum on cuboid) was modified by Ponseti (fulcrum on head of talus). Recently, Ponseti's method has gained popularity and vastly improved results are reported. We report randomized controlled trial where manipulation of club foot was done by Ponseti's and Kite's method and correction evaluated by Pirani score to compare the outcome of treatment.\n Sixty feet in 38 patients, 22 with bilateral and 16 with unilateral clubfeet in children less than two years of age and without any prior manipulation or surgical treatment were randomly allocated to the Ponseti (30 feet) and Kite (30 feet) methods of manipulation. This process resulted in the right and left feet of the same patient in 12 bilateral cases being compared with one another (Paired analysis). In the remaining 10 bilateral cases, four patients had both feet treated by Ponseti and six had both feet treated by Kite (unpaired analysis). Finally, in 16 unilateral cases, 10 feet were allocated to the Ponseti and six to Kite methods of manipulation (unpaired analysis). Feet were followed up weekly for 10 weeks for change of cast and recording of hindfoot, midfoot and total Pirani scores. Correction was measured as a difference between hindfoot, mid foot and total Pirani scores weekly from weeks 1 to 10 and corresponding baseline scores. Absolute correction and rate of correction in (i) bilateral clubfeet treated by Ponseti's method on one side and Kite's method on the other side in the same patient were compared using paired Student's t test and (ii) patients with unilateral clubfoot (where either of the methods was used) or those with bilateral clubfoot (where both feet treated by either of the two methods on both the sides) were compared using difference between means (mean correction by Ponseti minus mean correction by Kite) for magnitude of difference and unpaired Student's t test (if data was normally distributed) or Mann Whitney U statistics (otherwise) for significance of difference.\n In 12 bilateral clubfeet, where one foot received Kite's method and the other Ponseti's manipulation, feet treated by Ponseti's technique showed faster rates of decrease in Pirani score (improvement) as compared to feet treated by Kite's method with the mean of difference between baseline and follow up scores showing significantly greater (P<0.05) difference from zero from fourth week onwards to up to 10 weeks. In unpaired analysis, both for unilateral or bilateral clubfeet, regardless of side, mean Pirani scores in Ponseti feet improved much faster than Kite feet but the difference achieved statistical significance only at the 10(th) week from the start of treatment.\n Hind foot, midfoot and total Pirani scores reduce much faster with Ponseti than the Kite's method of manipulation of clubfoot. In paired analysis the difference becomes statistically significant at fourth week and in unpaired analysis at 10(th) week from the start of treatment.",
"Ponseti's and Kite's methods of conservative management in idiopathic congenital clubfoot were compared in a prospective randomised study consisting of 45 infants (67 feet) younger than 3 months, from March 2003 through February 2004. There were 36 and 31 feet that underwent treatment by Ponseti's and Kite's methods, respectively. After an average follow-up of 27.24 months in the Ponseti group, correction was achieved in 33 feet (91.7%), with only three patients requiring surgical management. There were seven relapses (21.1%), all of which were corrected conservatively. However, two of these required surgical intervention on showing a relapse again in the second year. In the Kite group, we achieved correction in 21 feet (67.7%) after an average follow-up of 24.8 months, with ten patients requiring surgical intervention. There were eight relapses of which only four could be corrected conservatively. We could also achieve correction in very severe feet (Dimeglio classification) in a significantly higher percentage using Ponseti's method, in significantly lesser time and with fewer casts. We are of the opinion that Ponseti's method is superior to Kite's method in achieving correction in idiopathic clubfeet in a relatively shorter period of time when used to treat young infants.",
"The Ponseti method of treatment for congenital clubfeet has gained widespread clinical acceptance. We have used manipulation, serial casting, and surgery to treat congenital clubfeet for almost 3 decades. Considering the Ponseti method of treatment to replace our traditional treatment method, we conducted a randomized, controlled trial evaluating the short-term outcome of the two treatment protocols. We evaluated foot function and applied a standardized measure of health status for children with orthopaedic problems. Nineteen patients (28 feet) were included in the trial. Nine infants (12 feet) were assigned to the Ponseti treatment group, and 10 (16 feet) were assigned to a group with initial casting and posteromedial release at the age of 6 to 8 months. The minimum followup was 3.3 years (mean, 3.5 years; range 3.3-3.8 years). Outcome measures included the Functional Rating System of Laaveg and Ponseti, the Pediatric Outcomes Data Collection Instrument (PODCI), and standardized radiographic measurements. At last followup the mean Functional Rating score was higher in the Ponseti group. Passive dorsiflexion and passive inversion-eversion were better in the Ponseti group. PODCI scales were comparable and radiographic outcome measures were similar in both groups. This trial has documented a favorable short-term outcome for the Ponseti method when compared with a traditional treatment protocol. Level of Evidence: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.",
"Previous research reviewed treatment success and whether the collective uncertainty principle is met in RCTs in the US National Cancer Institute portfolio. This paper classifies clinical trials funded by the UK HTA programme by results using the method applied to the US Cancer Institute trials, and compares the two portfolios.\n Data on all completed randomised controlled trials funded by the HTA programme 1993-2008 were extracted. Each trial's primary results was classified into six categories; 1) statistically significant in favour of the new treatment, 2) statistically significant in favour of the control treatment 3) true negative, 4) truly inconclusive, 5) inconclusive in favour of new treatment or 6) inconclusive in favour of control treatment. Trials were classified by comparing the 95% confidence interval for the difference in primary outcome to the difference specified in the sample size calculation. The results were compared with Djulbegovic's analysis of NCI trials.\n Data from 51 superiority trials were included, involving over 48,000 participants and a range of diseases and interventions. 85 primary comparisons were available because some trials had more than two randomised arms or had several primary outcomes. The new treatment had superior results (whether significant or not) in 61% of the comparisons (52/85 95% CI 49.9% to 71.6%). The results were conclusive in 46% of the comparisons (19% statistically significant in favour of the new treatment, 5% statistically significant in favour of the control and 22% true negative). The results were classified as truly inconclusive (i.e. failed to answer the question asked) for 24% of comparisons (20/85). HTA trials included fewer truly inconclusive and statistically significant results and more results rated as true negative than NCI trials.\n The pattern of results in HTA trials is similar to that of the National Cancer Institute portfolio. Differences that existed were plausible given the differences in the types of trials -HTA trials are more pragmatic. The results indicate HTA trials are compatible with equipoise. This classification usefully summarises the results from clinical trials and enables comparisons of different portfolios of trials.",
"Randomized clinical trial.\n The purpose of this randomized clinical trial was to examine the generalizability of 3 different manual therapy techniques in a patient population with low back pain that satisfy a clinical prediction rule (CPR).\n Recently a CPR that identifies patients with LBP who are likely to respond rapidly and dramatically to thrust manipulation has been developed and validated. The generalizability of the CPR requires further investigation.\n A total of 112 patients were enrolled in the trial and provided demographic information and completed a number of self-report questionnaires including the Oswestry Disability Questionnaire (ODQ) and the Numerical Pain Rating Scale (NPRS) at baseline, 1-week, 4-weeks, and 6-months. Patients were randomly assigned to receive 1 of the 3 manual therapy techniques for 2 consecutive treatment sessions followed by exercise regimen for an additional 3 sessions. We examined the primary aim using a linear mixed model for repeated measures, using the ODQ and NPRS as dependent variables. The hypothesis of interest was the group by time interaction, which was further explored with pair-wise comparisons of the estimated marginal means.\n There was a significant group x time interaction for the ODQ (P < 0.001) and NPRS scores (P = 0.001). Pair-wise comparisons revealed no differences between the supine thrust manipulation and side-lying thrust manipulation at any follow-up period. Significant differences in the ODQ and NPRS existed at each follow-up between the thrust manipulation and the nonthrust manipulation groups at 1-week and 4-weeks. There was also a significant difference in ODQ scores at 6-months in favor of the thrust groups.\n The results of the study support the generalizability of the CPR to another thrust manipulation technique, but not to the nonthrust manipulation technique that was used in this study. In general, our results also provided support that the CPR can be generalized to different settings from which it was derived and validated. However, additional research is needed to examine this issue.",
"We evaluated the short- and long-term efficacy of a brief cognitive-behavioral therapy (CBT) for chronic temporomandibular disorder (TMD) pain in a randomized controlled trial. TMD clinic patients were assigned randomly to four sessions of either CBT (n=79) or an education/attention control condition (n=79). Participants completed outcome (pain, activity interference, jaw function, and depression) and process (pain beliefs, catastrophizing, and coping) measures before randomization, and 3 (post-treatment), 6, and 12 months later. As compared with the control group, the CBT group showed significantly greater improvement across the follow-ups on each outcome, belief, and catastrophizing measure (intent-to-treat analyses). The CBT group also showed a greater increase in use of relaxation techniques to cope with pain, but not in use of other coping strategies assessed. On the primary outcome measure, activity interference, the proportion of patients who reported no interference at 12 months was nearly three times higher in the CBT group (35%) than in the control group (13%) (P=0.004). In addition, more CBT than control group patients had clinically meaningful improvement in pain intensity (50% versus 29% showed > or =50% decrease, P=0.01), masticatory jaw function (P<0.001), and depression (P=0.016) at 12 months (intent-to-treat analyses). The two groups improved equivalently on a measure of TMD knowledge. A brief CBT intervention improves one-year clinical outcomes of TMD clinic patients and these effects appear to result from specific ingredients of the CBT.",
"Constraint-induced movement therapy (CIMT) is a method to improve motor function in the upper extremity following stroke. The aim of this trial was to determine the effect and feasibility of CIMT compared with traditional rehabilitation in short and long term.\n A randomized controlled trial.\n An inpatient rehabilitation clinic.\n Thirty patients with unilateral hand impairment after stroke.\n Six hours arm therapy for 10 consecutive weekdays, while using a restraining mitten on the unaffected hand.\n The patients were assessed at baseline, post-treatment and at six-month follow-up using the Wolf Motor Function Test as primary outcome measure and the Motor Activity Log, Functional Independence Measure and Stroke Impact Scale as secondary measurements.\n The CIMT group (n=18) showed a statistically significant shorter performance time (4.76 seconds versus 7.61 seconds, P= 0.030) and greater functional ability (3.85 versus 3.47, P= 0.037) than the control group (n=12) on the Wolf Motor Function Test at post-treatment assessment. There was a non-significant trend toward greater amount of use (2.47 versus 1.97, P= 0.097) and better quality of movement (2.45 versus 2.12, P=0.105) in the CIMT group according to the Motor Activity Log. No such differences were seen on Functional Independence Measure at the same time. At six-month follow-up the CIMT group maintained their improvement, but as the control group improved even more, there were no significant differences between the groups on any measurements.\n CIMT seems to be an effective and feasible method to improve motor function in the short term, but no long-term effect was found.",
"Nonalcoholic steatohepatitis (NASH) is a chronic progressive liver disease that is strongly associated with obesity. Currently, there is no approved therapy for NASH. Weight reduction is typically recommended, but efficacy data are lacking. We performed a randomized controlled trial to examine the effects of lifestyle intervention using a combination of diet, exercise, and behavior modification, with a goal of 7% to 10% weight reduction, on clinical parameters of NASH. The primary outcome measure was the change in NASH histological activity score (NAS) after 48 weeks of intervention. Thirty-one overweight or obese individuals (body mass index [BMI], 25-40 kg/m(2)) with biopsy-proven NASH were randomized in a 2:1 ratio to receive intensive lifestyle intervention (LS) or structured education (control). After 48 weeks of intervention, participants assigned to LS lost an average of 9.3% of their weight versus 0.2% in the control group (P = 0.003). A higher proportion of participants in the LS group had a reduction of NAS of at least 3 points or had posttreatment NAS of 2 or less as compared with the control group (72% versus 30%, P = 0.03). NAS improved significantly in the LS group (from 4.4 to 2.0) in comparison with the control group (from 4.9 to 3.5) (P = 0.05). Percent weight reduction correlated significantly with improvement in NAS (r = 0.497, P = 0.007). Participants who achieved the study weight loss goal (>or=7%), compared with those who lost less than 7%, had significant improvements in steatosis (-1.36 versus -0.41, P < 0.001), lobular inflammation (-0.82 versus -0.24, P = 0.03), ballooning injury (-1.27 versus -0.53, P = 0.03) and NAS (-3.45 versus -1.18, P < 0.001).\n Weight reduction achieved through lifestyle intervention leads to improvements in liver histology in NASH.",
"The survival of 78 patients with resected non-small cell lung cancer entered in prospective, randomized investigational trials is compared to that of a population-based group of control patients not included in such trials. The survival of trial patients is significantly better than that of controls (P less than 0.001). This survival advantage for trial participants is most apparent among late Stage I patients, and is observed after matching for known prognostic factors (i.e., primary tumor size, nodal status, tumor histology) and after adjusting in the analysis for age, sex, and the administration of radiation therapy. Several explanations for the improved outcome for trial patients are explored, including differences in preoperative evaluation, staging, surgical technique, placebo effects, and patient motivation. These results suggest the possibility that inclusion in these controlled cancer trials may have had an inherent advantage for all participants."
] |
From the limited evidence available, the Ponseti technique may produce better short-term outcomes compared to the Kite technique. An accelerated Ponseti technique may be as effective as a standard technique. We could draw no conclusions from other included trials because of the limited use of validated outcome measures and lack of available raw data. Future randomised controlled trials should address these issues.
|
CD005521
|
[
"7966077",
"10890988",
"16682258"
] |
[
"Comparison of adrenocorticotropic hormone and triamcinolone acetonide in the treatment of acute gouty arthritis.",
"Ineffectiveness of cyclosporine as an adjuvant to corticosteroids in the treatment of pemphigus.",
"Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn's disease: a randomized controlled open-label trial."
] |
[
"To determine the best alternative therapy for acute gouty arthritis when nonsteroidal antiinflammatory drugs or colchicine are contraindicated.\n Thirty-one patients with crystal proven gout presenting with an acute attack of < 5 days' duration were treated prospectively with either a single intramuscular injection of adrenocorticotropic hormone (ACTH) 40 IU or triamcinolone acetonide 60 mg. The patients were followed for 30 days.\n Resolution of all symptoms occurred at an average of 8 days for both groups. No adverse reactions were noted in either group; however, there were 11 reinjections in the ACTH group and 5 reinjections in the triamcinolone acetonide group. Two patients from the ACTH arm were transferred to the triamcinolone acetonide arm because of rebound arthritis.\n Although recent studies of ACTH and triamcinolone acetonide have demonstrated efficacy and safety comparable to indomethacin, in a direct comparison of the 2 at the doses used, triamcinolone acetonide resulted in fewer rebound attacks and treatment failures than ACTH and required fewer reinjections.",
"To compare the effectiveness and the adverse effects of 2 different regimens for the treatment of pemphigus: corticosteroids alone compared with a combination of corticosteroids and cyclosporine.\n Concurrently randomized trial.\n Tertiary care medical center.\n We studied 33 sequential hospitalized patients with newly diagnosed pemphigus vulgaris (n=29) or pemphigus foliaceous (n=4) based on clinical, histological, and immunofluorescence criteria who had not previously been treated with systemic corticosteroids or immununosuppressive drugs. Patients were randomly assigned to treatment with methylprednisolone or prednisolone plus cyclosporine.\n Both groups were treated with similar initial doses of prednisolone (prednisone equivalent, 1 mg/kg), which were increased 50% every 5 to 10 days based on persistence of disease activity. One group was treated in addition with cyclosporine (5 mg/kg).\n Patients were followed up closely for clinical outcome based on time required to control active manifestations of the disease, induction of partial and complete remissions, total amount of corticosteroids administered, frequency of relapses, and development of complications.\n The 2 groups were similar in terms of demographics and baseline disease severity. There was no difference between groups in any of the variables used to measure response to treatment or total amount of corticosteroids administered. Complications were more common in patients who received combination therapy.\n Combination treatment with corticosteroids and cyclosporine, 5 mg/kg, offers no advantage over treatment with corticosteroids alone in patients with pemphigus.",
"Nutritional therapy has been reported to have an almost equivalent efficacy of corticosteroids in achieving clinical remission in active Crohn's disease (CD). However, the effects of both treatments on intestinal mucosal inflammation rarely are reported. In a randomized controlled trial in children with active CD we compared the efficacy of nutritional therapy alone or corticosteroids on clinical variables and intestinal mucosal healing.\n In a prospective, 10-week open-label trial, children with active, naive CD were randomized to orally polymeric formula alone or oral corticosteroids. The clinical activity index and nutritional and activity serum variables were evaluated at week 0 and then every 2 weeks; intestinal mucosal inflammation was assessed through endoscopy and histology at weeks 0 and 10. Primary efficacy outcomes were clinical remission and mucosal healing.\n Of the 37 children randomized, 19 received polymeric formula and 18 received corticosteroids. At week 10, on an intention-to-treat basis, the proportion of patients achieving clinical remission was comparable between the 2 groups (polymeric formula: 15/19 [79%; 95% confidence interval (CI), 56%-92%]; corticosteroid group: 12/18 [67%; 95% CI, 44%-84%]; P = .4; not significant). On the contrary, the proportion of children showing mucosa healing was significantly higher in the polymeric (14/19; 74%; 95% CI, 51%-89%) than the corticosteroid group (6/18 [33%; 95% CI, 16%-57%]; P < .05). At week 10 both endoscopic and histologic scores significantly decreased only in the polymeric group (P < .001).\n In children with active and recently diagnosed CD, a short course of polymeric diet is more effective than corticosteroids in inducing healing of gut inflammatory lesions."
] |
There is inconclusive evidence for the efficacy and effectiveness of systemic corticosteroids in the treatment of acute gout. Patients with gout did not report serious adverse effects from systemic corticosteroids, when used short term.
|
CD003270
|
[
"9864001"
] |
[
"An inhaled steroid improves markers of airway inflammation in patients with mild asthma."
] |
[
"Airway inflammation can be demonstrated in mildly asthmatic patients who are not treated with inhaled steroids. Current guidelines recommend that inhaled steroids should be introduced in mild asthmatics who use an inhaled beta2-agonist more than once daily. It was postulated that inhaled steroids can have anti-inflammatory effects in patients with even milder disease. The effect of 4 weeks of treatment with budesonide (800 microg twice daily by Turbohaler) was studied in 10 steroid-naive mildly asthmatic patients (forced expiratory volume in one second (FEV1) = 96+/-1.4% predicted) who required an inhaled beta2-agonist less than one puff daily, in a double-blind, placebo-controlled, crossover fashion. Spirometry, exhaled nitric oxide (NO), bronchial responsiveness (provocative concentration causing a 20% fall in FEV1 (PC20)), and sputum induction were performed before and after each treatment period. Following budesonide treatment, there were significant improvements in FEV1, and PC20, in association with a significant reduction in the percentage of eosinophils in induced sputum. Exhaled NO levels tended towards reduction, but the change was nonsignificant. There were also nonsignificant reductions in sputum eosinophil cationic protein and tumour necrosis factor-alpha levels. In conclusion inhaled budesonide can lead to improvements in noninvasive markers of airway inflammation, in association with a small improvement in lung function, even in mildly asthmatic patients who require an inhaled beta2-agonist less than once daily. This suggests a potential benefit of inhaled corticosteroids, even in relatively asymptomatic asthma."
] |
Currently there is a clear lack of evidence to support the use of azathioprine in the treatment of chronic asthma as a steroid sparing-agent. Large, long-term studies with pre-defined steroid reducing protocols are required before recommendations for clinical practice can be made.
|
CD001417
|
[
"8956919",
"8641230",
"12225311",
"10999555",
"10612342",
"10227615",
"8764816",
"8649569",
"16140593"
] |
[
"Double-blind, placebo-controlled study of topiramate in patients with refractory partial epilepsy.",
"Double-blind, placebo-controlled trial of topiramate as add-on therapy in patients with refractory partial seizures.",
"Low-dose topiramate in adults with treatment-resistant partial-onset seizures.",
"A double-blind, placebo-controlled study of topiramate in adult patients with refractory partial epilepsy.",
"Topiramate in medically intractable partial epilepsies: double-blind placebo-controlled randomized parallel group trial. Korean Topiramate Study Group.",
"A double-blind, randomized trial of topiramate as adjunctive therapy for partial-onset seizures in children. Topiramate YP Study Group.",
"Double-blind, placebo-controlled trial of topiramate (600 mg daily) for the treatment of refractory partial epilepsy.",
"Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 600-, 800-, and 1,000-mg daily dosages. Topiramate YE Study Group.",
"A randomized, double-blind, placebo-controlled trial of topiramate in adults with epilepsy and intellectual disability: impact on seizures, severity, and quality of life."
] |
[
"The efficacy and safety of topiramate 400 mg/day as adjunctive therapy to traditional antieleptic drugs for partial onset seizures with or without secondary generalization were assessed in a double-blind, parallel-group, placebo-controlled trial. Forty-seven patients with at least one seizure per week during an 8 week baseline were randomly assigned to topiramate (N = 23) or placebo (N = 24) double-blind treatment for a 3 week titration and an 8 week stabilization period. Median percent reduction from baseline in monthly seizure frequency during the double-blind phase was not significantly greater in the topiramate group than in the placebo group (41% vs. 1%; P = 0.065). Nevertheless, other efficacy variables evidenced statistically significant differences in favor of topiramate: a greater number of treatment responders (> or = 50% reduction in seizures; 35% vs. 8%; P = 0.033); better investigator (P = 0.002) and patient (P = 0.021) global assessments; and greater reductions in secondarily generalized seizures compared to placebo (P = 0.002). The most commonly reported topiramate treatment-emergent adverse events were somnolence, fatigue, abnormal vision, weight decrease, and anxiety. Most adverse events were mild or moderate in severity. Among 7 withdrawals due to limiting adverse events, 6 were CNS-related (in 5 topiramate-treated patients). Results of this trial strongly suggest that topiramate 400 mg/day is effective and well tolerated in the treatment of refractory partial epilepsy.",
"In a double-blind, randomized, parallel-group trial, we compared topiramate (TPM) with placebo as add-on therapy in patients with refractory partial epilepsy. TPM was titrated either to the target dosage of 800 mg/ day [400 mg twice daily (b.i.d)] or to the maximal tolerated dose if lower. Twenty-eight (28) patients were randomized to each treatment group. In the intent-to-treat analysis, the net median percent reduction relative to placebo in average monthly seizure rate was 54% for patients in the TPM group (p < 0.001). None of the placebo-treated patients and 43% of the patients treated with TPM experienced > or = 50% reduction in seizures (p = 0.001), and 36% of patients assigned to TPM had a 75-100% reduction in seizures (p < 0.01). Secondarily generalized seizures were also significantly reduced in the TPM group (p = 0.044). The most common adverse events (AE) reported in the TPM group were fatigue, impaired concentration, weight loss, dizziness, and paresthesias. AE occurring either during the rapid titration of TPM or at high dosages led 21% of TPM-treated patients to withdraw from the study. Half of these occurred during the titration study period. No serious AE or clinically important changes in clinical laboratory measures were observed. The present study further establishes the favorable profile and good benefit/risk ratio of TPM in resistant partial epilepsy.",
"Based on dose predictions from animal and human volunteer studies, most patients enrolled in initial randomized controlled trials of topiramate as adjunctive therapy in adults with partial-onset seizures were randomized to >or= 600 mg/day topiramate. Subsequent experience suggests that dosage needs were overestimated. This double-blind, placebo-controlled study evaluated 200 mg/day topiramate in adults with treatment-resistant partial-onset seizures receiving a concurrent enzyme-inducing antiepileptic agent (carbamazepine).\n After a 4-week baseline, 263 adults receiving carbamazepine who had at least three partial-onset seizures during the baseline period were randomized to placebo or one of two topiramate 200 mg/day treatment arms: topiramate escalated weekly 25 mg/day(8-week escalation) or 50 mg/day(4-week escalation). Therapy was then maintained for the remainder of the 12-week double-blind study.\n Median percent reduction in seizure frequency from baseline to study end was 44% with topiramate and 20% with placebo (P <or= 0.001). A significant therapeutic effect was present at 2 weeks with a dose of 100 mg/day. The most common adverse events (>or=10% incidence in topiramate-treated patients) were somnolence, fatigue, paresthesia, nervousness and anorexia; 8% of topiramate-treated patients and 2% of placebo-treated patients discontinued because of adverse events. As a result of the low incidence of adverse events, differences between titration rates in terms of tolerability were not detected.\n Topiramate 200 mg/day is an appropriate target dose as adjunctive therapy in adults with treatment-resistant partial-onset seizures, even when receiving an enzyme-inducing agent; 100 mg/day also appears to be effective. A significant therapeutic effect may be seen in the second week of treatment with a dose of 100 mg/day.",
"The efficacy and safety of topiramate (TPM) as adjunctive therapy in the treatment of adult Chinese patients with refractory partial epilepsy were investigated in a randomized, double-blind, placebo-controlled study.\n A total of 46 patients who had four or more complex partial seizures with or without secondary generalization within an 8-week baseline phase were enrolled. Patients were assigned randomly to receive TPM (n = 23) or placebo (n = 23). TPM or placebo was titrated to target doses of 300 mg/d for 6 weeks and maintained at stabilized levels for another 8 weeks. Concomitant antiepileptic drugs remained at constant previous levels during the trial.\n In all, 41 patients completed the trial (TPM group, n = 20; placebo group, n = 21). The proportion of patients with a > or =50% reduction from baseline in complex partial seizures was 11 of 23 (47.8%) in the TPM group and 3 of 23 (13.0%) in the placebo group (p = 0.01). In addition, patients treated with TPM had significantly better investigator (p = 0.014) and patient (p = 0.0005) global assessment scores than patients in the placebo group. Adverse events were mostly mild and transient, with no significant differences between treatment groups. Two patients with TPM therapy complained of weight loss. Routine blood cell counts and other laboratory results showed no significant changes from baseline in either treatment group.\n TPM 300 mg/d is effective and well tolerated as treatment for refractory partial epilepsy in adults.",
"To evaluate the efficacy and safety of topiramate (TPM) as add-on therapy in medically intractable partial epilepsies.\n We used a multicenter double-blind placebo-controlled randomized parallel-group trial consisting of 12 weeks of baseline phase, 10 weeks of titration phase, and 8 weeks of stabilization phase. The primary efficacy variable was the median seizure frequency reduction rate (MSFRR), and the other efficacy variables included responder rate, seizure-free rate, and global evaluations by the patient and the physician. The patient should have partial epilepsies refractory to the maximally tolerable doses of one to two antiepileptic drugs (AEDs) and should have two or more episodes of clinical seizures every 4 weeks during the baseline phase. The target dose of study drugs was 600 mg/day. The study drugs were started at the initial dose of 50 mg/day and gradually increased to the target dose over a 10-week period.\n A total of 177 patients was randomized into the TPM group (n = 91) and the placebo (PLC) group (n = 86). Baseline median seizure frequencies were 5.6 episodes/4 weeks in the TPM and the PLC groups. Among those who were randomized, 174 patients (TPM, 89 patients; PLC, 85 patients) were available for the efficacy measurement by intention-to-treat analysis. The MSFRR was 51.3% for TPM and 9.1% for PLC, which was highly in favor of TPM (p = 0.0001). The responder rate was 50.6% for TPM and 12.9% for PLC (p = 0.001). Seven (7.9%) of 89 patients taking TPM became seizure free compared with one (1.2%) of 85 patients taking PLC (p = 0.004). The global evaluation greatly favored TPM (p = 0.001). The incidence of adverse events (AEs) was higher in the TPM (81.3%) than in the PLC (48.9%) group, with central nervous system (CNS)-related AEs being the most frequent. Among individual AEs, anorexia (20.9%) and abdominal pain or discomfort (20.9%) were the most common AEs in the TPM group. AEs precipitated early drop-out in seven (7.6%) patients taking TPM and three (3.5%) patients taking PLC. No serious systemic AEs were observed.\n TPM was highly effective and safe as add-on therapy in medically intractable partial epilepsies. Slower titration of TPM might be responsible for the lesser drop-out rate than previous trials, but the incidence of AEs was still high. The AE profile of TPM in Koreans was different from that in whites.",
"To evaluate the efficacy and safety of topiramate 6 mg/kg/day in children (age 2 to 16 years) as adjunctive therapy for uncontrolled partial-onset seizures with or without secondarily generalized seizures in a multicenter, randomized, double-blind, placebo-controlled trial.\n Patients with at least six partial-onset seizures during the 8-week baseline phase were treated with either topiramate (n = 41) or placebo (n = 45) for 16 weeks.\n Topiramate-treated patients had a greater median percent reduction from baseline in average monthly partial-onset seizure rate than placebo-treated patients (33.1% versus 10.5%, p = 0.034), a greater proportion of treatment responders (i.e., patients with a > or = 50% seizure rate reduction; 16 of 41 [39%] versus 9 of 45 [20%], p = 0.080), and patients with a > or = 75% seizure rate reduction (7 of 41 [17%] versus 1 of 45 [2%], p = 0.019), and better parental global evaluations of improvement in seizure severity (p = 0.019). Emotional lability (12% versus 4%), fatigue (15% versus 7%), difficulty with concentration or attention (12% versus 2%), and forgetfulness/impaired memory (7% versus 0%) were more frequent among topiramate-treated than placebo-treated patients. Most treatment-emergent adverse events were mild or moderate in severity. No topiramate-treated patients discontinued the study due to adverse events.\n Topiramate was safe and effective in the treatment of partial-onset seizures in children.",
"We wished to evaluate adjunctive therapy for partial-onset seizures with topiramate (TPM) for efficacy and safety in a double-blind, placebo-controlled, randomized, parallel-group study.\n Sixty outpatients with epilepsy (47 men and 13 women, mean age 32.9 years) were studied. All had a documented history of partial-onset seizures with or without secondarily generalized seizures. After an 8-week baseline during which patients had at least one seizure per week, 30 patients each were randomized to TPM 300 mg twice daily (b.i.d.) or placebo for 12 weeks.\n TPM was significantly superior to placebo, as indicated by all efficacy assessments: greater median percent reduction from baseline in the average monthly seizure rate (46 vs. -12%, p = 0.004); greater number of treatment responders (patients with > or = 50% reduction in seizure rate) (47 vs. 10%, p = 0.001), and better investigator (p = 0.002) and patient (p = 0.010) global assessments of treatment. Among TPM-treated patients, the most commonly reported adverse events (AE) were headache, somnolence, fatigue, dizziness, and abnormal thinking. Most AE were mild or moderate in severity.\n The results of the present trial indicate that TPM 600 mg/day is effective in the treatment of refractory partial-onset seizures with or without secondarily generalized seizures.",
"We conducted a multicenter, double-blind, randomized, parallel, placebo-controlled trial in 190 patients to evaluate the safety and efficacy of three dosages of topiramate (600, 800, and 1,000 mg/day) as adjunctive therapy for patients with refractory partial epilepsy. During an 18-week double-blind treatment period, median percent reductions from baseline in average monthly seizure rates were 1% for placebo, 41% for topiramate 600 mg/day and topiramate 800 mg/day, and 38% for topiramate 1,000 mg/day. There was a 50% or greater reduction from baseline in seizure frequency in 9% of patients in the placebo group and in 44% for topiramate 600 mg/day, 40% for topiramate 800 mg/day, and 38% for topiramate 1,000 mg/day. No placebo patients were improved by 75 to 100% in seizure frequency, whereas 20% of the topiramate patients were improved to this degree. All intent-to-treat drug-placebo comparisons including seizure reduction, percent responders, and investigator and patient global evaluations significantly (p < or = 0.02) favored topiramate. Treatment-emergent adverse events consisted mainly of neurologic symptoms commonly observed during antiepileptic drug (AED) therapy. Sixteen percent of patients on topiramate discontinued therapy due to adverse events. Results of this study indicate that topiramate is a highly efficacious and generally well tolerated new AED. When large groups of patients are compared, incremental efficacy in the add-on setting is not observed at topiramate dosages above 600 mg/day; however, higher doses may prove beneficial to individual patients who tolerate them.",
"This randomized, double-blind, placebo-controlled UK trial evaluated the effect of topiramate as add-on therapy on seizure frequency, seizure severity, and quality of life in patients with epilepsy and intellectual disability. There were three phases: 4 weeks baseline, 18 weeks titration to 200-400 mg topiramate/day (adults) or 5-9 mg/kg/day (children), 12 weeks maintenance. Recruitment was low (88/120); analyses were underpowered. Seizure frequency varied enormously (median 17.7, maximum 1706.2). There was no significant difference in reduction in mean total seizure frequency or number of responders between the groups. Topiramate reduced seizure frequency by >30% from baseline (placebo 1%); post hoc analyses showed a trend toward significance (R ratio, P=0.052). There were no significant differences between the groups with respect to mean seizure severity or other outcome measures. Topiramate was generally well tolerated; body weight (P=0.015) and systolic blood pressure (P=0.043) were reduced. The study suggests that topiramate reduces seizure frequency in patients with epilepsy and intellectual disability without the added burden of behavior effects, and was potentially advantageous to physical well-being."
] |
Topiramate has efficacy as an add-on treatment for drug-resistant partial epilepsy. However, trials reviewed were of relatively short duration, and provide no evidence for the long-term efficacy of topiramate. Results cannot be extrapolated to monotherapy or treating other epilepsy types.
|
CD002126
|
[
"20159179",
"16487195",
"21092958",
"19897857",
"11476777",
"11214131",
"15790607",
"9241305",
"15039412",
"9647148"
] |
[
"A randomized prospective trial comparing the levonorgestrel-releasing intrauterine system with thermal balloon ablation for the treatment of heavy menstrual bleeding.",
"A randomised trial comparing the levonorgestrel intrauterine system and thermal balloon ablation for heavy menstrual bleeding.",
"A randomized clinical trial of a levonorgestrel-releasing intrauterine system and a low-dose combined oral contraceptive for fibroid-related menorrhagia.",
"Randomized placebo-controlled trial of CDB-2914 in new users of a levonorgestrel-releasing intrauterine system shows only short-lived amelioration of unscheduled bleeding.",
"Treatment of menorrhagia with the levonorgestrel intrauterine system versus endometrial resection.",
"Quality of life and cost-effectiveness of levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised trial.",
"Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis.",
"Levonorgestrel-releasing intrauterine device versus hysteroscopic endometrial resection in the treatment of dysfunctional uterine bleeding.",
"Clinical outcomes and costs with the levonorgestrel-releasing intrauterine system or hysterectomy for treatment of menorrhagia: randomized trial 5-year follow-up.",
"Randomised comparative trial of the levonorgestrel intrauterine system and norethisterone for treatment of idiopathic menorrhagia."
] |
[
"Use of the levonorgestrel-releasing intrauterine system (LNG-IUS) was compared with thermal balloon ablation (TBA) for the treatment of heavy menstrual bleeding (HMB).\n A prospective randomized trial comparing the LNG-IUS (n=30 women) and TBA (n=28 women).\n Hemoglobin levels increased (p<.001) and blood loss was reduced (p<.001) in both groups after 1 year of treatment. Menstrual bleeding was less in the LNG-IUS group compared to the TBA group at 6 and 12 months of treatment (p=.035 and p=.048, respectively). Intermenstrual bleeding was significantly less in the TBA group at 6 months compared to the LNG-IUS group (p=.044); however, there was no significant difference at 12 months (p=.129). No difference was found in psychological aspects between pre- and posttreatment variables in either of the groups (p=.537).\n Both the LNG-IUS and TBA appear to be effective in controlling HMB; however, posttreatment uterine bleeding patterns are different.\n Copyright (c) 2010 Elsevier Inc. All rights reserved.",
"To compare the levonorgestrel intrauterine system (LNG-IUS) (Mirena); Schering Co., Turku, Finland) and thermal balloon ablation (Thermachoice; Gynecare Inc., Menlo Park, CA, USA) for the treatment of heavy menstrual bleeding.\n An open, pragmatic, prospective randomised trial.\n A menstrual disorders clinic at National Women's Hospital, Auckland, New Zealand.\n Seventy-nine women with heavy menstrual bleeding randomised to the LNG-IUS (40 women) or the thermal balloon ablation (39 women).\n Women were randomised to treatment with the LNG-IUS or thermal balloon ablation and followed up by a postal and telephone questionnaire.\n Menstrual loss measured by a pictorial bleeding assessment chart (PBAC) at 3, 6, 12 and 24 months. Patient satisfaction, quality of life and menstrual symptoms were assessed by questionnaire administered at 3, 6, 12 and 24 months. Treatment side effects and treatment failures were also recorded.\n Both the treatments resulted in a significant reduction in PBAC scores. At 12 and 24 months, median PBAC scores were significantly lower in women treated with the LNG-IUS compared with women treated by thermal balloon ablation (11.5 versus 60.0 at 12 months [P= 0.002]; 12.0 versus 56.5 [P= 0.002] at 24 months). At 24 months, nine (35%) women still using the LNG-IUS had amenorrhoea compared with one (5%) woman successfully treated by thermal balloon ablation (P = 0.025). There were no significant differences in patient satisfaction between two treatments during follow up. Treatment failed in 11 (28%) women using the LNG-IUS and in 10 (26%) women treated with thermal balloon ablation. Overall, women in both groups showed an increased quality of life as a result of the treatment, with Short Form-36 scores increasing from 63.7 at randomisation to 76.1 at 24 months.\n At 12 and 24 months of follow up, women with heavy menstrual bleeding treated with the LNG-IUS have significantly lower PBAC scores than women treated with thermal balloon ablation. Both the treatments resulted in a significant increase in overall quality of life, but there were no significant differences between either treatment in quality of life, patient satisfaction or the number of women requesting an alternative treatment during 24 months of follow up.",
"To compare the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) with that of a low-dose combined oral contraceptive (COC) in reducing fibroid-related menorrhagia.\n In this single-center, open, randomized clinical trial, 58 women with menorrhagia who desired contraception were randomized to receive a LNG-IUS or COC. The outcomes included treatment failure, defined as the need for another treatment; menstrual blood loss (MBL) by the alkaline hematin method and a pictorial assessment chart (PBAC); hemoglobin levels; and \"lost days.\"\n Treatment failed in 6 women (23.1%) in the LNG-IUS group and 11 (37.9%) in the COC group, for a hazard ratio of 0.46 (95% CI, 0.17-1.17, P=0.101). Using the alkaline hematin test, the reduction of MBL was significantly greater in the LNG-IUS group (90.9% ± 12.8% vs 13.4% ± 11.1%; P<0.001). Using PBAC scores, the reduction was also significantly greater in the LNG-IUS group (88.0% ± 16.5% vs 53.5% ± 5 1.2%; P=0.02). Moreover, hemoglobin levels increased from 9.7 ± 1.9g/dL to 11.7 ± 1.2g/dL (P<0.001) and lost days decreased from 8.2 ± 3.3 days to 1.3 ± 1.5 days (P=0.003) in the LNG-IUS group.\n Although the rate of treatment failure was similar in both groups, the LNG-IUS was more effective in reducing MBL than the COC in women with fibroid-related menorrhagia.\n Copyright © 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.",
"The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly effective contraceptive. However, during early months of use unscheduled vaginal bleeding is common, sometimes leading to discontinuation. This study aimed to determine whether intermittent administration of progesterone receptor modulator CDB-2914 would suppress unscheduled bleeding during the first 4 months after insertion of the LNG-IUS.\n CDB-2914 150 mg, in divided doses, or placebo tablets, were administered over three consecutive days starting on Days 21, 49 and 77 after LNG-IUS insertion, in a double-blind randomized controlled trial of women aged 19-49 years, newly starting use of LNG-IUS. Daily bleeding diaries were completed for 6 months, and summarized across blocks as percentage days bleeding/spotting (BS%).\n Of 69 women randomized to receive CDB-2914, and 67 placebo, 61 and 55, respectively, completed the trial. BS% decreased with time in both arms, but showed a much steeper treatment-phase gradient in the placebo arm (P < 0.0001), so that a benefit of CDB-2914 in the 28 days after first treatment (-11% points, 95% CI -19 to -2), converted to a disadvantage by 64 days after the third treatment (+10% points, 95% CI 1-18).\n The effect of CDB-2914 on BS% was initially beneficial but then by third treatment was disadvantageous. Nevertheless, only 3% (4/136) of all women discontinued LNG-IUS. These findings give insight into possible mechanisms and suggest future research directions. ISRCTN Trial no. ISRCTN58283041; EudraCT no. 2006-006511-72.",
"Treatment of menorrhagia with levonorgestrel intrauterine system (LNG IUS) and transcervical resection.\n An open, therapeutic, randomized study.\n Central county hospital specializing in hysteroscopy.\n Two parallel groups of 30 subjects each.\n Thirty patients had a LNG IUS inserted within the first 7 days of menses; 29 patients underwent endometrial resection.\n A 12-month follow-up of menstrual blood loss and adverse events were evaluated.\n LNG IUS group: 13 patients reported one or more pelvic adverse events, bleeding disorders (n = 6), abdominal pain (n = 4), breast tenderness (n = 3), headache, acne (n = 2), and mood changes (n = 1). Six patients discontinued treatment because of irregular bleeding (n = 3), pain (n = 2), and acne (n = 1). In both groups, general feeling of genital health increased with Visual Analogue Scale score. Nine patients reported adverse events. This included pelvic pain indicating inflammation (n = 4), bleeding (n = 3), vaginitis (n = 1), and ulceration (n = 1). Treatment success at 12 months was achieved in 20 (67%) of the 30 patients in the LNG IUS group and in 26 (90%) of the 29 patients in the transcervical resection group. Adverse events were more often reported in the LNG IUS group.\n Both treatments effectively reduced the menstrual blood loss. Furthermore, the LNG IUS treatment is reversible and has no operative hazards.",
"Heavy menstrual blood loss is a common reason for women to seek medical care. The levonorgestrel-releasing intrauterine system (IUS) is an effective medical treatment for menorrhagia. We report a randomised comparison of this approach with hysterectomy in terms of the quality of life of women with menorrhagia and cost-effectiveness.\n Of 598 women referred with menorrhagia to five university hospitals in Finland, 236 were eligible and agreed to take part. They were randomly assigned treatment with the levonorgestrel-releasing IUS (n=119) or hysterectomy (n=117). The amount of menstrual blood loss was objectively measured. The primary outcome measure was health-related quality of life at 12-month follow-up. Analyses were by intention to treat.\n In the group assigned the levonorgestrel-releasing IUS, 24 (20%) women had had hysterectomy and 81 (68%) continued to use the system at 12 months. Of the women assigned to the hysterectomy group, 107 underwent the operation. Health-related quality of life improved significantly in both the IUS and hysterectomy groups (change 0.10 [95% CI 0.06-0.14] in both groups) as did other indices of psychological wellbeing. There were no significant differences between the treatment groups except that women with hysterectomy suffered less pain. Overall costs were about three times higher for the hysterectomy group than for the IUS group.\n The significant improvement in health-related quality of life highlights the importance of treating menorrhagia. During the first year the levonorgestrel-releasing IUS was a cost-effective alternative to hysterectomy in treatment of this disorder.",
"The objective of this multicentre randomized, controlled clinical trial was to compare the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) and a depot-GnRH-analogue in the control of endometriosis-related pain over a period of six months.\n Eighty-two women, 18 to 40 years of age (mean 30 years), with endometriosis, dysmenorrhoea and/or CPP, were randomized using a computer-generated system of sealed envelopes into either LNG-IUS (n = 39) or GnRH analogue (n = 43) treatment groups at three university centres. Daily scores of endometriosis-associated CPP were evaluated using the Visual Analogue Scale (VAS), daily bleeding score was calculated from bleeding calendars, and improvement in quality of life was evaluated using the Psychological General Well-Being Index Questionnaire (PGWBI). The pain score diary was based on the VAS in which women recorded the occurrence and intensity of pain on a daily basis. A monthly score was calculated from the result of the sum of the daily scores divided by the number of days in each observation period.\n CPP decreased significantly from the first month throughout the six months of therapy with both forms of treatment and there was no difference between the groups (P > 0.999). In both treatment groups, women with stage III and IV endometriosis showed a more rapid improvement in the VAS pain score than women with stage I and II of the disease (P < 0.002). LNG-IUS users had a higher bleeding score than GnRH-analogue users at all time points of observation with 34% and 71% of patients in the LNG-IUS and GnRH-analogue groups, respectively, reporting no bleeding during the first treatment month, and 70% and 98% reporting no bleeding during the sixth month. No difference was observed between groups with reference to improvement in quality of life.\n Both, the LNG-IUS and the GnRH-analogue were effective in the treatment of CPP-associated endometriosis, although no differences were observed between the two treatments. Among the additional advantages of the LNG-IUS is the fact that it does not provoke hypoestrogenism and that it requires only one medical intervention for its introduction every 5 years. This device could therefore become the treatment of choice for CPP-associated endometriosis in women who do not wish to conceive.",
"To compare the effect of a levonorgestrel-releasing intrauterine device with that of endometrial resection on menstrual bleeding, patient satisfaction, and quality of life in menorrhagic women during 12 months of follow-up.\n Seventy premenopausal women with dysfunctional uterine bleeding were enrolled in a prospective, open, parallel-group, controlled trial. They were randomized to either insertion of an intrauterine system releasing 20 micrograms/day of levonorgestrel (n = 35) or endometrial resection (n = 35). The women were evaluated at baseline, and thereafter, uterine bleeding was assessed monthly with a pictorial blood loss assessment chart. Clinical gynecologic examination was performed bimonthly, and the hematologic variables were measured at 6 and 12 months. On the latter occasion, the women were requested to rate the degree of satisfaction with the effect of their treatment and to complete the Short Form 36 General Health Survey questionnaire.\n Recurrent menorrhagia was observed at 12 months in four women in the intrauterine device group (including two with partial expulsion of the device) and in three women in the resection group. Compared with baseline values, at 1 year, the pictorial blood loss assessment chart score was reduced by 79% in the former group and by 89% in the latter. Amenorrhea or hypomenorrhea at 12 months was reported by 65% of the women with an intrauterine device compared with 71% who underwent endometrial resection. The degree of satisfaction with treatment was high in both groups, with 29 of 34 (85%) women being satisfied or very satisfied in the intrauterine device group versus 33 of 35 (94%) in the resection group. Health-related quality of life perception was not significantly different in the two treatment groups.\n Somewhat less satisfactory results were obtained with a levonorgestrel-releasing intrauterine system compared with endometrial resection for dysfunctional uterine bleeding at 1 year of follow-up.",
"Because menorrhagia is often a reason for seeking medical attention, it is important to consider outcomes and costs associated with alternative treatment modalities. Both the levonorgestrel-releasing intrauterine system (LNG-IUS) and hysterectomy have proven effective for treatment of menorrhagia but there are no long-term comparative studies measuring cost and quality of life.\n To compare outcomes, quality-of-life issues, and costs of the LNG-IUS vs hysterectomy in the treatment of menorrhagia.\n Randomized controlled trial conducted between October 1, 1994, and October 6, 2002, and enrolling 236 women (mean [SD] age, 43 [3.4] years) referred to 5 university hospitals in Finland for complaints of menorrhagia.\n Participants were randomly assigned to treatment with the LNG-IUS (n = 119) or hysterectomy (n = 117) and were monitored for 5 years.\n Health-related quality of life (HRQL) as measured by the 5-Dimensional EuroQol and the RAND 36-Item Short-Form Health Survey, other measures of psychosocial well-being (anxiety, depression, and sexual function), and costs.\n After 5 years of follow-up, 232 women (99%) were analyzed for the primary outcomes. The 2 groups did not differ substantially in terms of HRQL or psychosocial well-being. Although 50 (42%) of the women assigned to the LNG-IUS group eventually underwent hysterectomy, the discounted direct and indirect costs in the LNG-IUS group (2817 dollars [95% confidence interval, 2222 dollars-3530 dollars] per participant) remained substantially lower than in the hysterectomy group (4660 dollars [95% confidence interval, 4014 dollars-5180 dollars]). Satisfaction with treatment was similar in both groups.\n By providing improvement in HRQL at relatively low cost, the LNG-IUS may offer a wider availability of choices for the patient and may decrease costs due to interventions involving surgery.",
"To compare the efficacy and acceptability of the levonorgestrel intrauterine system and norethisterone for the treatment of idiopathic menorrhagia.\n A randomised comparative parallel group study.\n Gynaecology outpatient clinic in a teaching hospital.\n Forty-four women with heavy regular periods and a measured menstrual blood loss exceeding 80 ml.\n Twenty-two women had a levonorgestrel intrauterine system inserted within the first seven days of menses, and 22 women received norethisterone (5 mg three times daily) from day 5 to day 26 of the cycle for three cycles.\n The main outcome measure was the change in objectively assessed menstrual blood loss after three months of treatment.\n When menstrual blood loss at three months was expressed as a percentage of the control, the levonorgestrel intrauterine system reduced menstrual blood loss by 94% (median reduction 103 ml; range 70 to 733 ml), and oral norethisterone by 87% (median reduction 95 ml; range 56 to 212 ml). After three cycles of treatment 76% of the women in the levonorgestrel intrauterine system group wished to continue with the treatment, compared with only 22% of the norethisterone group.\n Both the levonorgestrel intrauterine system and oral norethisterone in this regimen provided an effective treatment for menorrhagia in terms of reducing menstrual blood loss to within normal limits. The levonorgestrel intrauterine system was associated with higher rates of satisfaction and continuation with treatment, and thus offers an effective alternative to currently available medical and surgical treatments for menorrhagia."
] |
The levonorgestrel-releasing intrauterine device (LNG IUS) is more effective than cyclical norethisterone (for 21 days) as a treatment for heavy menstrual bleeding. Women with an LNG IUS are more satisfied and willing to continue with treatment but experience more side effects, such as intermenstrual bleeding and breast tenderness.
The LNG IUS results in a smaller mean reduction in menstrual blood loss (as assessed by the PBAC chart) than endometrial ablation but there is no evidence of a difference in the rate of satisfaction with treatment. Women with an LNG IUS experience more progestogenic side effects compared to women having TCRE for treatment of their heavy menstrual bleeding but there is no evidence of a difference in their perceived quality of life.
The LNG IUS treatment costs less than hysterectomy but there is no evidence of a difference in quality of life measures between these groups.
There are no data available from randomised controlled trials comparing progesterone-releasing intrauterine systems to either placebo or other commonly used medical therapies for heavy menstrual bleeding.
|
CD005399
|
[
"9521264",
"19864187",
"8453943",
"15820346",
"2360466",
"14718691",
"8112232",
"17201719",
"10487186",
"16140593",
"2643513"
] |
[
"Randomized prospective study of early discontinuation of antiepileptic drugs in children with epilepsy.",
"Enhancing antiepileptic drug adherence: a randomized controlled trial.",
"Outcomes of add-on treatment with lamotrigine in partial epilepsy.",
"Efficacy and cognitive side effects of tiagabine and topiramate in patients with epilepsy.",
"Influence of surgery and antiepileptic drugs on seizures symptomatic of cerebral tumours.",
"Systematic screening allows reduction of adverse antiepileptic drug effects: a randomized trial.",
"Lamotrigine therapy for partial seizures: a multicenter, placebo-controlled, double-blind, cross-over trial.",
"Evaluation of acceptance and commitment therapy for drug refractory epilepsy: a randomized controlled trial in South Africa--a pilot study.",
"Long-term neuropsychological consequences of maternal epilepsy and anticonvulsant treatment during pregnancy for school-age children and adolescents.",
"A randomized, double-blind, placebo-controlled trial of topiramate in adults with epilepsy and intellectual disability: impact on seizures, severity, and quality of life.",
"A randomized, double-blind, placebo-controlled, clinical trial of D-alpha-tocopheryl acetate (vitamin E), as add-on therapy, for epilepsy in children."
] |
[
"We studied recurrence rate, risk factors for recurrence, and outcome after recurrence in children after early withdrawal of antiepileptic drugs (AEDs). One hundred sixty-one children with newly diagnosed epilepsy who had become seizure free within 2 months after starting treatment and remained so for 6 months were randomly assigned to immediate withdrawal of AEDs (n = 78) or continuation of treatment for another 6 months followed by withdrawal (n = 83). The probability of remaining seizure free at 24 months after randomization was 51% (95% CI, 40 to 62) in Group A and 52% (41 to 63) in Group B. Significant predictive factors for relapse were partial epilepsy, seizure onset at 12 years or older, defined etiology, and epileptiform EEG before randomization. At the end of follow-up (median, 41.9 months), 129 children (80.6%) had a terminal remission of at least 1 year, 88 without AEDs and 41 with AEDs. No significant difference in outcome was found between Groups A and B. In children with epilepsy and an early response to therapy, AED withdrawal after 6 or 12 months of treatment leads to seizure recurrence in approximately half of all patients regardless of the duration of therapy. More than 60% of those with one or more recurrences reach a terminal remission of at least 1 year after long-term follow-up with or without AEDs.",
"Suboptimal adherence to antiepileptic drug (AED) treatment is commonplace, and increases the risk of status epilepticus and sudden unexplained death in epilepsy. This randomized controlled trial was designed to demonstrate whether an implementation intention intervention involving the completion of a simple self-administered questionnaire linking the intention of taking medication with a particular time, place, and other activity can improve AED treatment schedule adherence. Of the 81 patients with epilepsy who were randomized, 69 completed a 1-month monitoring period with an objective measure of tablet taking (electronic registration of pill bottle openings, Medication Event Monitoring System [MEMS]). Intervention participants showed improved adherence relative to controls on all three outcomes: doses taken in total (93.4% vs. 79.1%), days on which correct dose was taken (88.7% vs. 65.3%), and doses taken on schedule (78.8% vs. 55.3%) (P<0.01). The implementation intention intervention may be an easy-to-administer and effective means of promoting AED adherence.",
"The need for new antiepileptic drugs (AEDs) and more sensitive methods of assessing their efficacy is well recognized. This study was designed to evaluate the efficacy and safety of lamotrigine (LTG), a potential new AED and to develop and test new outcome measures. A health-related quality of life (HRQL) model was developed which contains previously validated measures of anxiety, depression, happiness, overall mood, self-esteem, and mastery and a specifically designed seizure severity scale with patient- and caregiver-based components. This HRQL model was used in a randomized, placebo-controlled, double-blind, cross-over study of LTG in 81 patients with refractory partial seizures. Seizure frequency was the primary measure and seizure severity and the HRQL were secondary measures of efficacy. The reduction in seizure frequency with LTG, relative to placebo, was 29.7% [95% confidence interval (CI) 17.8%, 39.9%] for total seizure count, 33.4% (95% CI 14.8%, 47.9%) for complex partial seizures (CPS) and 20.3% (95% CI 0.3%, 36.2%) for secondarily generalized tonic-clonic seizures (GTCS). However, although 41 patients elected to continue with LTG, only 11 experienced at least 50% reduction in total seizures, indicating that other factors influenced their decision. The score with LTG, relative to placebo, was significantly lower for the ictal (p = 0.017) and caregivers (p = 0.035) subscales of the seizure severity scale and significantly higher for happiness (p = 0.003) and mastery (p = 0.003). Simple correlation and multiple-regression analyses indicate that the effects on seizure frequency, seizure severity, and psychological variables appear to be independent of each other. This study indicates that LTG is effective in reducing seizure frequency and has additional favorable effects on seizure severity, mood, and perceived internal control. Some of the scales used indicate the potential of secondary measures of efficacy to enhance the sensitivity of trials of new AEDs.",
"Whereas the efficacy of the newer antiepileptic drugs (AEDs) is well established, there remain questions regarding their cognitive side effects. Therefore, we performed a comparative open randomized trial with TPM and TGB as add-on therapy, with particular consideration of cognition, mood, and health-related quality of life (HRQOL).\n Forty-one patients with refractory epilepsy were randomly assigned to one of the two treatment groups (TPM vs TGB) and received neuropsychological testing at baseline (T1), after titration (3 months, T2), and during the maintenance phase (another 3 months, T3). Tests included measures of intelligence, attention, working memory, episodic memory, language, and self-report questionnaires regarding mood and HRQOL. Twenty patients (8 TPM, 12 TGB) discontinued the trial for different reasons (no group difference).\n Seizure outcome (intention-to-treat analysis) was comparably good in both groups (8.1% seizure free, 29.7% seizure reduction>50%). From baseline to after the titration paired sample t tests revealed significant deterioration in verbal fluency, language comprehension, working memory, and visual block tapping under TPM and a deterioration in verbal memory (delayed free recall) in the TGB group. These functions remained stable in the maintenance phase. Self-report measures initially indicated concerns about AED side effects in both groups and concerns about worse cognitive functioning and depression under TPM. In the maintenance phase the TGB group reported feeling a lack of energy, whereas patients on TPM demonstrated improvement on all QOLIE scales on a descriptive level.\n This study demonstrates the comparable efficacy of TPM and TGB. Consistent with previous reports, TPM but not TGB appears to be associated with persistent negative cognitive side effects on frontal lobe-associated functions, the degree of which may be estimated by the fact that this effect was observed with a very small sample size. In contrast, in patients taking TPM, initially negatively affected HRQOL returns to baseline in the long run on a descriptive level. The latter finding may be interpreted in accordance with the observation that objective performance and subjective self-report under TPM can be dissociated.",
"One hundred and twenty-eight adult patients presenting with and operated on for supratentorial neoplasms were studied. Sixty-five had preoperative seizures and were treated with antiepileptic drugs (AEDs). Among the 63 patients without preoperative epileptic fits, 41 were given AEDs (either phenobarbital or phenytoin) as prophylactic treatment and 22 were not treated. The preoperative epilepsy course was considered with respect to tumour site and histological type. Early and late postoperative seizure occurrence was considered in the different groups of patients. The results suggest the usefulness of a short term preventive treatment with AEDs after surgery in patients without preoperative seizures. In patients with preoperative epilepsy, AEDs should be continued after surgery. However long-term AEDs treatment should not be recommended in patients without preoperative epilepsy. In fact, no significant difference in late seizure occurrence was found between preventively treated and untreated patients.",
"To determine the effectiveness of systematic screening with a brief 19-item self-report instrument, the Adverse Events Profile (AEP), to reduce adverse effects of antiepileptic drugs (AEDs) and improve subjective health status.\n The authors performed a prospective randomized trial comparing the use of the AEP with usual care without the AEP. Sixty-two patients with an AEP score of >or=45 were enrolled from a consecutive group of 200 consenting adults with epilepsy.\n The mean percent improvement in AEP scores was greater in the patient group for which clinicians received the AEP compared with the usual care group (25% vs 5%; p < 0.01). Mean change in Quality of Life in Epilepsy Inventory (QOLIE)-89 total scores was not different between groups, but for the entire sample QOLIE-89 change was greater for patients having a 15-point improvement in AEP scores than for those with a 0- to 15-point improvement or a worsened score (24 vs 12 vs 3; analysis of variance, p < 0.008). More patients in the AEP group had a >15-point improvement in QOLIE-89 score (p < 0.03). Use of the AEP was associated with a 2.8-fold increase (95% CI, 1.7 to 4.8) in AED modifications. No difference in seizure rates was observed. Conclusions: Systematic screening for antiepileptic drug side effects may increase identification of toxicity and guide medication changes to reduce adverse effects and possibly improve subjective health status.",
"The efficacy and safety of lamotrigine (LTG), a new antiepileptic drug (AED), were evaluated in a multicenter, randomized, double-blind, placebo-controlled, cross-over study of 98 patients with refractory partial seizures. Each treatment period lasted 14 weeks. Most patients were titrated to a LTG maintenance dose of 400 mg/day. Seizure frequency with LTG decreased by > or = 50%, as compared with placebo, in one fifth of patients. Overall median seizure frequency decreased by 25% with LTG as compared with placebo (p < 0.001). With LTG, the number of seizure days decreased by 18% as compared with placebo (p < 0.01), and investigator global evaluation of overall patient clinical status favored LTG by 2:1 (p = 0.013). Plasma LTG concentrations appeared to be linearly related to dosage. LTG had no clinically important effects on the plasma concentrations of concomitant AEDs. Adverse experiences were generally minor and most frequently were CNS-related (e.g., ataxia, dizziness, diplopia, headache). Most were transient and resolved without discontinuing treatment. Five patients withdrew as a result of adverse experiences while receiving LTG, including 3 patients with rash. One placebo patient was also withdrawn because of rash. The addition of twice-daily LTG to an existing AED regimen was safe, effective, and well tolerated in these medically refractory partial seizure patients.",
"Psychological interventions in the treatment of epilepsy have been developed and evaluated for many years but the amount of research has hardly made an impact on how epilepsy is treated. The purpose of this study was to develop and evaluate a psychological treatment program consisting of acceptance and commitment therapy (ACT) together with some behavioral seizure control technology shown to be successful in earlier research.\n The method consisted of a randomized controlled trial group design with repeated measures (n=27). All participants had an EEG verified epilepsy diagnosis with drug refractory seizures. Participants were randomized into one of two conditions, ACT or supportive therapy (ST). Therapeutic effects were measured by examining changes in quality of life (SWLS and WHOQOL) and seizure index (frequency x duration). Both treatment conditions consisted of only nine hours of professional therapy distributed in two individual and two group sessions during a four-week period.\n The results showed significant effects over all of the dependent variables for the ACT group as compared to the ST group at six- and twelve-month follow-ups.\n The results from this study suggest that a short-term psychotherapy program combined with anticonvulsant drugs may help to prevent the long-term disability that occurs from drug refractory seizures.",
"Antiepileptic drugs (AEDs) are potential teratogenic agents. The purpose of this study was to examine the long-term effects of intrauterine AED exposure on neurologic and psychological functioning.\n Of a prospective study, \"Epilepsy, pregnancy, and child development,\" children could be retraced at school age and adolescence. Sixty-seven were born to mothers with epilepsy [no drugs during pregnancy (n = 13), monotherapy (n = 31), polytherapy (n = 23)]; 49 were nonafflicted control children. Assessments included an intelligence test (Wechsler), a neurologic examination (Touwen), and an EEG. Data analyses were performed, controlling for parental social status, type of maternal drug therapy and drug dosage, type of epilepsy, frequency of seizures during pregnancy, the original subgroups, and specific drug effects.\n Type of maternal epilepsy and type and kind of AED therapy, but not maternal seizures during pregnancy correlated with an increase in abnormal EEG patterns. Minor neurologic dysfunction was diagnosed, with increased frequency from the control to the risk/no drug or monotherapy to the polytherapy group. The compromised intelligence score of the polytherapy group was primarily due to those children who had been exposed to primidone (PRM). Level of IQ was negatively associated with PRM dosage.\n Maternal epilepsy and AED therapy during pregnancy appear to have long-term effects on the offspring well into adolescence, as evinced in EEG patterns, minor neurologic dysfunction, and intellectual performance. Severity of effects increased from control group to epilepsy/no-drug group to monotherapy group and was most marked in the polytherapy group. These group differences are assumed to reflect differential neural vulnerability to social and family factors.",
"This randomized, double-blind, placebo-controlled UK trial evaluated the effect of topiramate as add-on therapy on seizure frequency, seizure severity, and quality of life in patients with epilepsy and intellectual disability. There were three phases: 4 weeks baseline, 18 weeks titration to 200-400 mg topiramate/day (adults) or 5-9 mg/kg/day (children), 12 weeks maintenance. Recruitment was low (88/120); analyses were underpowered. Seizure frequency varied enormously (median 17.7, maximum 1706.2). There was no significant difference in reduction in mean total seizure frequency or number of responders between the groups. Topiramate reduced seizure frequency by >30% from baseline (placebo 1%); post hoc analyses showed a trend toward significance (R ratio, P=0.052). There were no significant differences between the groups with respect to mean seizure severity or other outcome measures. Topiramate was generally well tolerated; body weight (P=0.015) and systolic blood pressure (P=0.043) were reduced. The study suggests that topiramate reduces seizure frequency in patients with epilepsy and intellectual disability without the added burden of behavior effects, and was potentially advantageous to physical well-being.",
"In 24 epileptic children refractory to antiepileptic drugs (AEDs) with generalized tonic-clonic and other types of seizures, addition of D-alpha-tocopheryl acetate (Vitamin E 400 IU/day) to existing AEDs was accompanied by a significant reduction of seizures in 10 of 12 cases. This was significantly different from controls given placebo (0 of 12, p less than 0.05). This result did not appear to be due to the effects of changes in the plasma levels of the comedication. There were no adverse side effects. The Vitamin E levels steadily increased in the responders in the trial phase but this did not occur in two clinically noncompliant subjects or in 12 patients receiving placebo. No other clinically significant alterations in hematologic or biochemical test results were observed. No treatment-related changes in plasma concentration of concomitant AEDs were noted. These findings justify further clinical controlled trials of Vitamin E as adjunctive therapy for childhood epilepsy intractable to the usual antiepileptic therapy."
] |
This review broadly supports the use of AEDs to reduce seizure frequency in people with refractory epilepsy and intellectual disability. The evidence suggests that side effects are similar to those in the general population and that behavioural side effects leading to discontinuation are rare, but that other effects are under-researched.
|
CD008034
|
[
"14625698",
"17510766"
] |
[
"Lichtenstein vs anterior preperitoneal prosthetic mesh placement in open inguinal hernia repair: a prospective, randomized trial.",
"Pain after open preperitoneal repair versus Lichtenstein repair: a randomized trial."
] |
[
"Male veterans with unilateral primary inguinal hernia, classified intraoperatively as Gilbert Type III or IV, were randomized to subaponeurotic (Lichtenstein, n=126) or preperitoneal (Read-Rives, n=121) repair under general or spinal anesthesia. The two groups of patients were comparable in age, body weight index, comorbidities, and size and type of hernia. Of the 247 patients enrolled, 224 were followed for at least 2 years (median 82 months, range 24-110 months), 16 were lost to follow-up, and seven died from causes unrelated to the surgery. The average operative time of the Read-Rives repair was 9 min longer than that of the Lichtenstein repair. There were no wound infections, and the frequencies of other short- and long-term complications were low and similar in the two groups. Six patients developed hernia recurrence, five in the Lichtenstein group (4.3%), and one in the Read-Rives group (<1%), ( P=0.21). Both anterior repairs are associated with low postoperative morbidity and recurrence rates. The Lichtenstein repair is technically easier and less time consuming. There is no statistically significant difference in the recurrence rate between the two repairs.",
"The open preperitoneal approach in inguinal hernia repair might have the benefit of a mesh in the preferred space without the disadvantages of an endoscopic procedure.\n A total of 172 patients with primary inguinal hernia were randomized to undergo the open preperitoneal Kugel or the standard open anterior Lichtenstein procedure in a teaching hospital. The main outcome measures were operating variables, visual analog scale (VAS) pain scores, and consumed analgesics during the first 2 weeks postoperatively and at 3 months, neurological examination, and complications.\n In the Lichtenstein group the operation took longer (54 min versus 41 min; p < .001). There were no clinically important differences in VAS pain score or number of analgesics during the first 2 weeks postoperatively. In the Kugel group the mean VAS pain score at 3 months was less (0.3 versus 0.9; p = .002), as was the proportion of patients reporting pain (21 versus 40%; p = .007). Pain was merely described as neuropathic, especially in the Lichtenstein group. With the anterior repair significantly more nerves were encountered, numbness reported, and cutaneous sensory changes found with neurological examination (all p < .001).\n For those surgeons preferring an open approach, the Kugel procedure is a feasible alternative for the standard Lichtenstein procedure and is associated with less chronic pain at three months. Most likely the neuropathic pain and numbness with the Lichtenstein technique are results of more nerves at risk with the anterior approach."
] |
Both techniques are valid as they result in similar low recurrence rates. Evaluation of pain results in the individual trials shows some evidence that preperitoneal repair causes less or comparable acute and chronic pain compared to the Lichtenstein procedure. We emphasize the need for homogeneous high quality randomized trials comparing elective preperitoneal inguinal hernia techniques and Lichtenstein repair in terms of chronic pain.
|
CD009285
|
[
"11871363",
"17996436",
"20620037",
"20714373",
"17605774",
"21428765",
"16144890",
"11866001",
"16305289",
"16507855",
"12728159",
"10722768",
"17310045",
"17370096",
"18836213",
"16914336",
"18686739",
"15611808",
"18060091",
"14605043"
] |
[
"Improved health outcomes in patients with COPD during 1 yr's treatment with tiotropium.",
"A randomized study of tiotropium Respimat Soft Mist inhaler vs. ipratropium pMDI in COPD.",
"A one-year trial of tiotropium Respimat plus usual therapy in COPD patients.",
"Efficacy and safety of tiotropium Respimat SMI in COPD in two 1-year randomized studies.",
"Efficacy and safety of tiotropium in COPD patients in primary care--the SPiRiva Usual CarE (SPRUCE) study.",
"Tiotropium versus salmeterol for the prevention of exacerbations of COPD.",
"Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial.",
"A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease.",
"Absence of electrocardiographic findings and improved function with once-daily tiotropium in patients with chronic obstructive pulmonary disease.",
"The effect of tiotropium on exacerbations and airflow in patients with COPD.",
"Health outcomes following treatment for six months with once daily tiotropium compared with twice daily salmeterol in patients with COPD.",
"A randomised controlled comparison of tiotropium nd ipratropium in the treatment of chronic obstructive pulmonary disease. The Dutch Tiotropium Study Group.",
"Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial.",
"Modelling the 5-year cost effectiveness of tiotropium, salmeterol and ipratropium for the treatment of chronic obstructive pulmonary disease in Spain.",
"A 4-year trial of tiotropium in chronic obstructive pulmonary disease.",
"A pilot study to assess the effects of combining fluticasone propionate/salmeterol and tiotropium on the airflow obstruction of patients with severe-to-very severe COPD.",
"Effect of tiotropium on health-related quality of life as a primary efficacy endpoint in COPD.",
"The Canadian Optimal Therapy of COPD Trial: design, organization and patient recruitment.",
"A randomized controlled trial to assess the efficacy of tiotropium in Canadian patients with chronic obstructive pulmonary disease.",
"Improvement in resting inspiratory capacity and hyperinflation with tiotropium in COPD patients with increased static lung volumes."
] |
[
"Tiotropium, a novel once-daily inhaled anticholinergic, has been shown to improve lung function over a 24-h period. In order to extend these findings, health-outcomes were evaluated over 1 yr in chronic obstructive pulmonary disease (COPD) patients. Spirometric results, peak expiratory flow rate (PEFR), salbutamol use and effects on dyspnoea, health-related quality of life and COPD exacerbations were assessed in two identical 1-yr randomized double-blind double-dummy studies of tiotropium 18 microg once daily (n=356) compared with ipratropium 40 microg q.i.d. (n=179). Screening forced expiratory volume in one second (FEV1) were 1.25+/-0.43 L (41.9+/-12.7% of the predicted value) (tiotropium) and 1.18+/-0.37 L (39.4+/-10.7% pred) (ipratropium). Trough FEV1 at 1 yr improved by 0.12+/-0.01 L with tiotropium and declined by 0.03+/-0.02 L with ipratropium (p<0.001). Significant improvement in PEFR, salbutamol use, Transition Dyspnea Index focal score, and the St George's Respiratory Questionnaire total and impact scores were seen with tiotropium (p<0.01). Tiotropium reduced the number of exacerbations (by 24%, p<0.01), and increased time to first exacerbation (p<0.01) and time to first hospitalization for a COPD exacerbation (p<0.05) compared with ipratropium. Apart from an increased incidence of dry mouth in the tiotropium group, adverse events were similar between treatments. Tiotropium was effective in improving dyspnoea, exacerbations, health-related quality of life and lung function in patients with chronic obstructive pulmonary disease, and exceeds the benefits seen with ipratropium. The data support the use of tiotropium once-daily as first-line maintenance treatment in patients with chronic obstructive pulmonary disease.",
"The aim of these studies was to compare the efficacy and the safety of tiotropium, delivered via Respimat Soft Mist Inhaler (SMI), a novel multi-dose, propellant-free inhaler, with ipratropium pressurized metered-dose inhaler (pMDI) in chronic obstructive pulmonary disease (COPD) patients. Two identical, 12-week, multi-national, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled studies were performed. COPD patients were randomized to treatment with either inhaled tiotropium (5 or 10 microg) via Respimat SMI administered once daily, ipratropium (36 microg) pMDI QID or placebo. The primary endpoint was the mean trough forced expiratory volume in 1s (FEV(1)) response after 12 weeks of treatment. Secondary endpoints included other spirometry measures and rescue medication use. A total of 719 patients were randomized; the majority were male (69%) with a mean pre-bronchodilator FEV(1) (% predicted) of 40.7%. The mean treatment differences between tiotropium 5 and 10 microg and placebo for the primary endpoint (mean trough FEV(1) response at week 12) were 0.118 and 0.149L, respectively (both P<0.0001). Treatment differences between tiotropium 5 and 10 microg and ipratropium were 0.064L (P=0.006) and 0.095L (P<0.0001). The increases in peak FEV(1), FEV(1) AUC((0-6h)) and FVC for both tiotropium doses were statistically superior to placebo (P<0.01) and higher than ipratropium. All active treatments significantly reduced the rescue medication use compared with placebo, but only tiotropium 10 microg was statistically superior to ipratropium (P=0.04). The incidence of adverse events was comparable across groups. In conclusion, tiotropium 5 and 10 microg daily, delivered via Respimat SMI, significantly improved lung function compared with ipratropium pMDI and placebo.",
"In this randomised double-blind study, patients >or=40 years old with COPD, a smoking history of >or=10 pack-years, a pre-bronchodilator FEV(1) of <or=60% predicted and an FEV(1)/FVC of <or=70% received tiotropium 5 microg or placebo via Respimat inhaler once daily for 48 weeks. Other medications were permitted except inhaled anticholinergics. Co-primary endpoints were trough FEV(1) and the time to first exacerbation. Adverse events were followed and vital status regularly assessed. In all, 3991 patients (mean age, 65 years [SD, 9 years]) were evaluable. Mean baseline FEV(1) was 1.11 L (0.40 L) or 40% (12%) of predicted normal. Adjusted mean differences in trough FEV(1) and trough FVC at Week 48 (tiotropium minus placebo) were 102 and 168 ml respectively (p < 0.0001, both). Tiotropium delayed time to first exacerbation relative to placebo (hazard ratio [HR], 0.69 [95% CI, 0.63-0.77]) and time to first hospital-treated exacerbation (HR, 0.73 [0.59-0.90]). SGRQ score at Week 48 was 2.9 units lower with tiotropium (p < 0.0001). Adverse and serious adverse events were balanced across treatment groups and similar in profile to previous tiotropium trials. The rate ratio for a major adverse cardiovascular event during the treatment period + 30 days was 1.12 (0.67-1.86). By the end of planned treatment (Day 337) 52 patients on tiotropium (incidence rate per 100 years, 2.94) and 38 on placebo (2.13) had died (HR = 1.38 [0.91-2.10]; p = 0.13). Lung function, exacerbations and quality of life were improved by tiotropium 5 microg Respimat but a numerical imbalance was seen in all-cause mortality. The protocol is registered on the European Clinical Trials Database as trial number 2006-001009-27 and in the ClinicalTrials.gov database as NCT00387088.",
"Two 1-year studies evaluated the long-term efficacy and safety of tiotropium 5 or 10 microg versus placebo, inhaled via the Respimat Soft Mist Inhaler (SMI). The two studies were combined and had 4 co-primary endpoints (trough FEV(1) response, Mahler Transition Dyspnea Index [TDI] and St George's Respiratory Questionnaire scores all at week 48, and COPD exacerbations per patient-year). A total of 1990 patients with COPD participated (mean FEV(1): 1.09 L). The mean trough FEV(1) response of tiotropium 5 or 10 microg relative to placebo was 127 or 150 mL, respectively (both P < 0.0001). The COPD exacerbation rate was significantly lower with tiotropium 5 microg (RR = 0.78; P = 0.002) and tiotropium 10 microg (RR = 0.73; P = 0.0008); the health-related quality of life and Mahler TDI co-primary endpoints were significantly improved with both doses (both P < 0.0001). Adverse events were generally balanced except anticholinergic class effects, which were more frequent with active treatment. Fatal events occurred in 2.4% (5 microg), 2.7% (10 microg), and 1.6% (placebo) of patients; these differences were not significant. Tiotropium Respimat SMI 5 microg demonstrated sustained improvements in patients with COPD relative to placebo and similar to the 10 microg dose but with a lower frequency of anticholinergic adverse events.",
"Clinical trials of tiotropium have principally recruited patients from secondary care with more severe chronic obstructive pulmonary disease (COPD), and typically had included limitation of concomitant medication. In primary care, which is the most common setting for COPD management, many patients may have milder disease, and also may take a broad range of concomitant medication.\n This randomised, placebo-controlled, parallel-group, 12-week, 44-centre study investigated the efficacy (trough forced expiratory volume in 1 second [FEV1] response) and safety of additional treatment with once-daily tiotropium 18 mug via the HandiHaler in a primary care COPD population (tiotropium: N = 191, FEV1 = 1.25 L [47.91% predicted]; placebo: N = 183, FEV1 = 1.32 L [49.86% predicted]). Secondary endpoints included: trough forced vital capacity (FVC) response, weekly use of rescue short-acting beta-agonist, and exacerbation of COPD (complex of respiratory symptoms/events of >3 days in duration requiring a change in treatment). Treatment effects were determined using non-parametric analysis.\n At Week 12, median improvement in trough FEV1 response with tiotropium versus placebo was 0.06 L (p = 0.0102). The improvement was consistent across baseline treatment and COPD severity. Median improvement in FVC at 2, 6 and 12 weeks was 0.12 L (p < 0.001). The percentage of patients with > or =1 exacerbation was reduced (tiotropium 9.5%; placebo 17.9%; p = 0.0147), independent of disease severity. Rescue medication usage was significantly reduced in the tiotropium group compared with placebo. Adverse event profile was consistent with previous studies.\n Tiotropium provides additional benefits to usual primary care management in a representative COPD population.\n The identifier is: NCT00274079.",
"Treatment guidelines recommend the use of inhaled long-acting bronchodilators to alleviate symptoms and reduce the risk of exacerbations in patients with moderate-to-very-severe chronic obstructive pulmonary disease (COPD) but do not specify whether a long-acting anticholinergic drug or a β(2)-agonist is the preferred agent. We investigated whether the anticholinergic drug tiotropium is superior to the β(2)-agonist salmeterol in preventing exacerbations of COPD.\n In a 1-year, randomized, double-blind, double-dummy, parallel-group trial, we compared the effect of treatment with 18 μg of tiotropium once daily with that of 50 μg of salmeterol twice daily on the incidence of moderate or severe exacerbations in patients with moderate-to-very-severe COPD and a history of exacerbations in the preceding year.\n A total of 7376 patients were randomly assigned to and treated with tiotropium (3707 patients) or salmeterol (3669 patients). Tiotropium, as compared with salmeterol, increased the time to the first exacerbation (187 days vs. 145 days), with a 17% reduction in risk (hazard ratio, 0.83; 95% confidence interval [CI], 0.77 to 0.90; P<0.001). Tiotropium also increased the time to the first severe exacerbation (hazard ratio, 0.72; 95% CI, 0.61 to 0.85; P<0.001), reduced the annual number of moderate or severe exacerbations (0.64 vs. 0.72; rate ratio, 0.89; 95% CI, 0.83 to 0.96; P=0.002), and reduced the annual number of severe exacerbations (0.09 vs. 0.13; rate ratio, 0.73; 95% CI, 0.66 to 0.82; P<0.001). Overall, the incidence of serious adverse events and of adverse events leading to the discontinuation of treatment was similar in the two study groups. There were 64 deaths (1.7%) in the tiotropium group and 78 (2.1%) in the salmeterol group.\n These results show that, in patients with moderate-to-very-severe COPD, tiotropium is more effective than salmeterol in preventing exacerbations. (Funded by Boehringer Ingelheim and Pfizer; ClinicalTrials.gov number, NCT00563381.).",
"Patients with chronic obstructive pulmonary disease (COPD) frequently develop exacerbations, leading to major clinical and health resource use ramifications.\n To prospectively evaluate the effectiveness of a long-acting inhaled anticholinergic bronchodilator, tiotropium, in reducing COPD exacerbations and exacerbation-related health care utilization.\n Randomized, double-blind study.\n 26 Veterans Affairs medical centers.\n 1829 patients with moderate to severe COPD (mean baseline FEV(1), 36% predicted).\n Once-daily tiotropium (18 microg) or placebo for 6 months. Patients otherwise received usual care, except for other anticholinergic bronchodilators.\n The coprimary end points were the percentage of patients with a COPD exacerbation and the percentage of patients with a COPD-related hospitalization.\n Tiotropium significantly reduced the percentage of patients experiencing 1 or more exacerbations compared with placebo (27.9% vs. 32.3%, respectively; difference, -5.7 percentage points [95% CI, -10.4 to -1.0 percentage points]; P = 0.037). Fewer tiotropium patients were hospitalized because of COPD exacerbation (7.0% vs. 9.5%, respectively; difference, -3.0 percentage points [CI, -5.9 to -0.1 percentage points]; P = 0.056), although this difference was of borderline statistical significance. Analysis of secondary outcomes indicates that tiotropium may lengthen the time to first COPD exacerbation (P = 0.028) and reduce health care utilization for exacerbations, including the frequency of hospitalizations (P = 0.047), unscheduled clinic visits (P = 0.019), and days of antibiotic treatment (P = 0.015). Tiotropium did not statistically significantly reduce all-cause hospitalization rates.\n Trial participants were enrolled from 1 health care system, and 99% were men. The follow-up period extended for only 6 months.\n Tiotropium reduces COPD exacerbations and may reduce related health care utilization in patients with moderate to severe COPD.",
"Currently available inhaled bronchodilators used as therapy for chronic obstructive pulmonary disease (COPD) necessitate multiple daily dosing. The present study evaluates the long-term safety and efficacy of tiotropium, a new once-daily anticholinergic in COPD. Patients with stable COPD (age 65.2+/-8.7 yrs (mean+/-SD), n=921) were enrolled in two identical randomized double-blind placebo-controlled 1-yr studies. Patients inhaled tiotropium 18 microg or placebo (mean screening forced expiratory volume in one second (FEV1) 1.01 versus 0.99 L, 39.1 and 38.1% of the predicted value) once daily as a dry powder. The primary spirometric outcome was trough FEV1 (i.e. FEV1 prior to dosing). Changes in dyspnoea were measured using the Transition Dyspnea Index, and health status with the disease-specific St. George's Respiratory Questionnaire and the generic Short Form 36. Medication use and adverse events were recorded. Tiotropium provided significantly superior bronchodilation relative to placebo for trough FEV1 response (approximately 12% over baseline) (p<0.01) and mean response during the 3 h following dosing (approximately 22% over baseline) (p<0.001) over the 12-month period. Tiotropium recipients showed less dyspnoea (p<0.001), superior health status scores, and fewer COPD exacerbations and hospitalizations (p<0.05). Adverse events were comparable with placebo, except for dry mouth incidence (tiotropium 16.0% versus placebo 2.7%, p<0.05). Tiotropium is an effective, once-daily bronchodilator that reduces dyspnoea and chronic obstructive pulmonary disease exacerbation frequency and improves health status. This suggests that tiotropium will make an important contribution to chronic obstructive pulmonary disease therapy.",
"To examine electrocardiographic findings after short- and long-term tiotropium therapy in patients with chronic obstructive pulmonary disease (COPD), and to establish previously reported symptomatic efficacy.\n Randomized, double-blind, placebo-controlled, parallel-group study.\n Twelve outpatient investigational centers in the United States.\n One hundred ninety-six patients with COPD.\n Patients received either tiotropium 18 mug once/day or placebo, delivered by the HandiHaler device.\n Electrocardiography (predose and 5 min postdose) and 24-hour Holter monitoring were performed at baseline and after 8 and 12 weeks of treatment with tiotropium 18 microg once/day or placebo. Efficacy measures (spirometry, global COPD ratings, scores on the EuroQol Health Questionnaire [EQ-5D], albuterol inhaler as needed) were included to demonstrate that the study population exhibited the characteristic improvements observed in previous tiotropium studies. Mean baseline forced expiratory volume in 1 second (FEV1) was 1.03 L. Mean changes in heart rate from baseline were similar in both groups. No differences were noted in the percentage of patients developing rhythm or conduction abnormalities detected with electrocardiography or Holter monitoring. Frequency of premature beats and mean maximal changes in PR, QRS, QT, QTcB, and QTcF intervals were similar in both groups. No patients developed new-onset QT or QTc intervals greater than 500 msec, and no differences were noted in the percentage of patients developing new QT prolongation less than 30 msec, 30-60 msec, or greater than 60 msec. At 12 weeks, predose and postdose improvements in FEV1 were 184 and 265 ml, respectively, with tiotropium versus placebo (p<0.001). Physician and patient global COPD ratings and the EQ-5D visual analog scale scores were improved with tiotropium (p<0.05); as-needed albuterol was reduced by 25% relative to placebo (p<0.05).\n Tiotropium provided spirometric and symptomatic benefits in patients with COPD and was not associated with evidence of electrocardiographic changes in heart rate, rhythm, QT intervals, or conduction.",
"This randomised, double-blind, parallel-group, 1-yr study compared the effect of tiotropium 18 microg once daily (n=500) and placebo (n=510) on exacerbations, associated health resource use (HRU) and airflow limitation in chronic obstructive pulmonary disease (COPD) patients. The mean+/-sd number of exacerbations during the past year was 2.14+/-1.40, the mean weekly morning peak expiratory flow (PEF) was 259.6+/-96.1 L.min-1 and the mean forced expiratory volume in one second (FEV1) was 1.37+/-0.45 L. Tiotropium significantly delayed the time to first exacerbation by approximately 100 days, reduced the proportion of patients experiencing more than one exacerbation by 17%, and decreased the number of exacerbations by 35% and exacerbation days by 37% versus placebo. Tiotropium also decreased HRU versus placebo, as indicated by the significant reductions in the use of concomitant respiratory medications, antibiotics and oral steroids, and the number of unscheduled physician contacts. Mean weekly morning PEF improved significantly with tiotropium versus placebo from week 1 until the end of the study. At the end of the study, tiotropium significantly improved trough (pre-dose) FEV1, forced vital capacity, slow vital capacity and inspiratory capacity versus placebo. In conclusion, tiotropium reduced exacerbations and associated health resource use, and improved airflow over 1 yr in chronic obstructive pulmonary disease patients.",
"A study was undertaken to record exacerbations and health resource use in patients with COPD during 6 months of treatment with tiotropium, salmeterol, or matching placebos.\n Patients with COPD were enrolled in two 6-month randomised, placebo controlled, double blind, double dummy studies of tiotropium 18 micro g once daily via HandiHaler or salmeterol 50 micro g twice daily via a metered dose inhaler. The two trials were combined for analysis of heath outcomes consisting of exacerbations, health resource use, dyspnoea (assessed by the transitional dyspnoea index, TDI), health related quality of life (assessed by St George's Respiratory Questionnaire, SGRQ), and spirometry.\n 1207 patients participated in the study (tiotropium 402, salmeterol 405, placebo 400). Compared with placebo, tiotropium but not salmeterol was associated with a significant delay in the time to onset of the first exacerbation. Fewer COPD exacerbations/patient year occurred in the tiotropium group (1.07) than in the placebo group (1.49, p<0.05); the salmeterol group (1.23 events/year) did not differ from placebo. The tiotropium group had 0.10 hospital admissions per patient year for COPD exacerbations compared with 0.17 for salmeterol and 0.15 for placebo (not statistically different). For all causes (respiratory and non-respiratory) tiotropium, but not salmeterol, was associated with fewer hospital admissions while both groups had fewer days in hospital than the placebo group. The number of days during which patients were unable to perform their usual daily activities was lowest in the tiotropium group (tiotropium 8.3 (0.8), salmeterol 11.1 (0.8), placebo 10.9 (0.8), p<0.05). SGRQ total score improved by 4.2 (0.7), 2.8 (0.7) and 1.5 (0.7) units during the 6 month trial for the tiotropium, salmeterol and placebo groups, respectively (p<0.01 tiotropium v placebo). Compared with placebo, TDI focal score improved in both the tiotropium group (1.1 (0.3) units, p<0.001) and the salmeterol group (0.7 (0.3) units, p<0.05). Evaluation of morning pre-dose FEV(1), peak FEV(1) and mean FEV(1) (0-3 hours) showed that tiotropium was superior to salmeterol while both active drugs were more effective than placebo.\n Exacerbations of COPD and health resource usage were positively affected by daily treatment with tiotropium. With the exception of the number of hospital days associated with all causes, salmeterol twice daily resulted in no significant changes compared with placebo. Tiotropium also improved health related quality of life, dyspnoea, and lung function in patients with COPD.",
"A study was undertaken to evaluate and compare the efficacy and safety of tiotropium and ipratropium during long term treatment in patients with stable chronic obstructive pulmonary disease (COPD).\n 288 patients of mean (SD) age 65 (8) years and forced expiratory volume in one second (FEV(1)) 41 (12)% predicted participated in a 14 centre, double blind, double dummy, parallel group study and were randomised after a run in period of two weeks to receive either tiotropium 18 microg once daily from a dry powder inhaler (HandiHaler; two thirds of patients) or ipratropium 40 microg four times daily from a metered dose inhaler (one third of patients) for a period of 13 weeks. Outcome measures were lung function, daily records of peak expiratory flow (PEF), and the use of concomitant salbutamol. FEV(1) and forced vital capacity (FVC) were measured one hour before and immediately before inhalation (mean value of the two measurements on test day 1 was the baseline value while on all other test days it was known as the trough FEV(1) and FVC), and 0.5, 1, 2, 3, 4, 5, and 6 hours after inhalation of the study drug on days 1, 8, 50, and 92.\n During treatment tiotropium achieved a significantly greater improvement than ipratropium (p<0.05) in trough, average, and peak FEV(1) levels and in trough and average FVC levels. The trough FEV(1) response on days 8, 50, and 92 ranged between 0.15 l (95% CI 0.11 to 0.19) and 0.16 l (95% CI 0.12 to 0.20) for tiotropium and between 0.01 l (95% CI -0.03 to 0.05) and 0.03 l (95% CI 0.01 to 0. 07) for ipratropium. The trough FVC response on days 8, 50, and 92 ranged between 0.34 l (95% CI 0.28 to 0.40) and 0.39 l (95% CI 0.31 to 0.47) for tiotropium and between 0.08 l (95% CI 0.00 to 0.16) and 0.18 l (95% CI 0.08 to 0.28) for ipratropium. On all test days tiotropium produced a greater improvement in FEV(1) than ipratropium starting three hours after inhalation (p<0.05). During treatment weekly mean morning and evening peak expiratory flow (PEF) was consistently better in the tiotropium group than in the ipratropium group, the difference in morning PEF being significant up through week 10 and in evening PEF up through week 7 of treatment (p<0.05). The use of concomitant salbutamol was also lower in the tiotropium group (p<0.05). The only drug related adverse event was dry mouth (tiotropium 14.7%, ipratropium 10.3% of patients).\n Tiotropium in a dose of 18 microg inhaled once daily using the HandiHaler was significantly more effective than 40 microg ipratropium four times daily in improving trough, average, and peak lung function over the 13 week period. The safety profile of tiotropium was similar to ipratropium. These data support the use of tiotropium as first line treatment for the long term maintenance treatment of patients with airflow obstruction due to COPD.",
"Treatment of moderate or severe chronic obstructive pulmonary disease (COPD) with combinations of inhaled corticosteroids, long-acting beta-agonists, and long-acting anticholinergic bronchodilators is common but unstudied.\n To determine whether combining tiotropium with salmeterol or fluticasone-salmeterol improves clinical outcomes in adults with moderate to severe COPD compared with tiotropium alone.\n Randomized, double-blind, placebo-controlled trial conducted from October 2003 to January 2006.\n 27 academic and community medical centers in Canada.\n 449 patients with moderate or severe COPD.\n 1 year of treatment with tiotropium plus placebo, tiotropium plus salmeterol, or tiotropium plus fluticasone-salmeterol.\n The primary end point was the proportion of patients who experienced an exacerbation of COPD that required treatment with systemic steroids or antibiotics.\n The proportion of patients in the tiotropium plus placebo group who experienced an exacerbation (62.8%) did not differ from that in the tiotropium plus salmeterol group (64.8%; difference, -2.0 percentage points [95% CI, -12.8 to 8.8 percentage points]) or in the tiotropium plus fluticasone-salmeterol group (60.0%; difference, 2.8 percentage points [CI, -8.2 to 13.8 percentage points]). In sensitivity analyses, the point estimates and 95% confidence bounds shifted in the direction favoring tiotropium plus salmeterol and tiotropium plus fluticasone-salmeterol. Tiotropium plus fluticasone-salmeterol improved lung function (P = 0.049) and disease-specific quality of life (P = 0.01) and reduced the number of hospitalizations for COPD exacerbation (incidence rate ratio, 0.53 [CI, 0.33 to 0.86]) and all-cause hospitalizations (incidence rate ratio, 0.67 [CI, 0.45 to 0.99]) compared with tiotropium plus placebo. In contrast, tiotropium plus salmeterol did not statistically improve lung function or hospitalization rates compared with tiotropium plus placebo.\n More than 40% of patients who received tiotropium plus placebo and tiotropium plus salmeterol discontinued therapy prematurely, and many crossed over to treatment with open-label inhaled steroids or long-acting beta-agonists.\n Addition of fluticasone-salmeterol to tiotropium therapy did not statistically influence rates of COPD exacerbation but did improve lung function, quality of life, and hospitalization rates in patients with moderate to severe COPD. International Standard Randomised Controlled Trial registration number: ISRCTN29870041.",
"Our objective was to assess the 5-year cost effectiveness of bronchodilator therapy with tiotropium, salmeterol or ipratropium for chronic obstructive pulmonary disease (COPD) from the perspective of the Spanish National Health System (NHS). A probabilistic Markov model was designed wherein patients moved between moderate, severe or very severe COPD and had the risk of exacerbation and death. Probabilities were derived from clinical trials. Spanish healthcare utilisation, costs and utilities were estimated for each COPD and exacerbation state. Outcomes were exacerbations, exacerbation-free months, quality-adjusted life years (QALYs), and cost(-effectiveness). The mean (SE) 5-year number of exacerbations was 3.50 (0.14) for tiotropium, 4.16 (0.40) for salmeterol and 4.71 (0.54) for ipratropium. The mean (SE) number of QALYs was 3.15 (0.08), 3.02 (0.15) and 3.00 (0.20), respectively. Mean (SE) 5-year costs were 6,424 euro (305 euro) for tiotropium, 5,869 euro (505 euro) for salmeterol, and 5,181 euro (682 euro) for ipratropium (2005 values). Ipratropium and tiotropium formed the cost-effectiveness frontier, with tiotropium being preferred when willingness to pay (WTP) exceeded 639 euro per exacerbation-free month and 8,157 euro per QALY. In Spain, tiotropium demonstrated the highest expected net benefit for ratios of the willingness to pay per QALY, well within accepted limits.",
"Previous studies showing that tiotropium improves multiple end points in patients with chronic obstructive pulmonary disease (COPD) led us to examine the long-term effects of tiotropium therapy.\n In this randomized, double-blind trial, we compared 4 years of therapy with either tiotropium or placebo in patients with COPD who were permitted to use all respiratory medications except inhaled anticholinergic drugs. The patients were at least 40 years of age, with a forced expiratory volume in 1 second (FEV(1)) of 70% or less after bronchodilation and a ratio of FEV(1) to forced vital capacity (FVC) of 70% or less. Coprimary end points were the rate of decline in the mean FEV(1) before and after bronchodilation beginning on day 30. Secondary end points included measures of FVC, changes in response on St. George's Respiratory Questionnaire (SGRQ), exacerbations of COPD, and mortality.\n Of a total of 5993 patients (mean age, 65+/-8 years) with a mean FEV(1) of 1.32+/-0.44 liters after bronchodilation (48% of predicted value), we randomly assigned 2987 to the tiotropium group and 3006 to the placebo group. Mean absolute improvements in FEV(1) in the tiotropium group were maintained throughout the trial (ranging from 87 to 103 ml before bronchodilation and from 47 to 65 ml after bronchodilation), as compared with the placebo group (P<0.001). After day 30, the differences between the two groups in the rate of decline in the mean FEV(1) before and after bronchodilation were not significant. The mean absolute total score on the SGRQ was improved (lower) in the tiotropium group, as compared with the placebo group, at each time point throughout the 4-year period (ranging from 2.3 to 3.3 units, P<0.001). At 4 years and 30 days, tiotropium was associated with a reduction in the risks of exacerbations, related hospitalizations, and respiratory failure.\n In patients with COPD, therapy with tiotropium was associated with improvements in lung function, quality of life, and exacerbations during a 4-year period but did not significantly reduce the rate of decline in FEV(1). (ClinicalTrials.gov number, NCT00144339.)\n 2008 Massachusetts Medical Society",
"The aim of this pilot study was to explore the relative efficacy in terms of improvement in symptoms and lung function of combining fluticasone propionate/salmeterol combination (FSC) and tiotropium in patients with severe-to-very severe stable COPD. Ninety patients were randomized to receive 3 months of treatment in one of three treatment groups: (1) FSC 500/50 microg Diskus, 1 inhalation twice daily+placebo Handihaler 1 inhalation once-daily daily; (2) tiotropium 18 microg Handihaler, 1 inhalation once daily+placebo Diskus, 1 inhalation twice daily; (3) FSC 500/50 microg Diskus, 1 inhalation twice daily+tiotropium 18 microg Handihaler, 1 inhalation once-daily daily. Patients attended the clinic before and after 1 month, 2 months, and 3 months of treatment for evaluations of pulmonary function, and dyspnea, which was assessed using a visual analog scale (VAS). Also the supplemental salbutamol use was measured. Eighty-one patients completed the 3-month treatment period: 26 patients receiving FSC, 26 patients receiving tiotropium, and 29 patients receiving FSC+tiotropium. Patients were withdrawn for COPD exacerbation. Improvements in trough FEV(1) with all treatments medications were observed by the first month when trough FEV(1) had improved significantly above baseline by 74 mL (p<0.05) in the tiotropium group, by 117 mL (p<0.05) in the FSC group and by 115 mL (p<0.05) in FSC+tiotropium group. At the end of the study, trough FEV(1) had improved significantly above baseline by 141 mL (p<0.05) in the tiotropium group, by 140 mL (p<0.05) in the FSC group and by 186 mL (p<0.05) in FSC+tiotropium group. The difference between FSC and tiotropium appeared to decrease, that between FSC and FSC+tiotropium appeared to increase and that between tiotropium and FSC+tiotropium remained almost similar with study duration. Our results suggest that adding FSC and tiotropium may provide benefits in symptomatic patients with severe-to-very severe stable COPD.",
"Clinical manifestations of chronic obstructive pulmonary disease (COPD), including airflow limitation, dyspnea, and activity limitation, ultimately lead to impaired health-related quality of life (HRQoL). This 9-month, randomized, double-blind, multicenter study compared the effect of once-daily tiotropium 18 microg and placebo on HRQoL, spirometric parameters, and exacerbations in 554 patients with moderate-to-severe COPD. HRQoL was assessed using the St. George's Respiratory Questionnaire (SGRQ) and the new 8-item Visual Simplified Respiratory Questionnaire (VSRQ), which is currently being validated. The primary efficacy endpoint was the proportion of patients achieving a reduction of at least 4 units in the SGRQ total score at study end (Month 9). Mean +/- SD baseline SGRQ total score was 47.4 +/- 18.1. Significantly more tiotropium-treated patients achieved a reduction of at least 4 units in the SGRQ score vs placebo at study end (59.1% vs 48.2%, respectively; p = 0.029). Tiotropium significantly improved spirometric parameters (forced expiratory volume in 1 second [FEV1]: 0.11 +/- 0.02 L vs 0.01 +/- 0.02 L; between-group difference: 0.10 +/- 0.03 L, p = 0.0001) and reduced exacerbations vs placebo. Maintenance treatment with tiotropium provided significant and clinically relevant improvements in HRQoL, as measured by the SGRQ.",
"There are no published studies that have assessed whether adding long-acting beta 2-agonist bronchodilators and/or inhaled steroids to chronic therapy with tiotropium would provide additional clinical benefit to patients with moderate to severe chronic obstructive pulmonary disease (COPD).\n The Canadian Optimal Therapy of COPD Trial is a randomized, prospective, double-blind, placebo-controlled, multicentre trial funded by the Canadian Institutes of Health Research that has been designed to determine which combination of inhaled medications will most effectively prevent exacerbations and optimize disease-specific quality of life in patients with COPD. The trial is the first to evolve from the Canadian Thoracic Society Clinical Trials Group. The study will randomize 432 patients with moderate to severe COPD to one of three parallel treatment arms for 52 weeks: tiotropium and fluticasone/salmeterol; tiotropium and salmeterol; or tiotropium and placebo inhaler. The participants will be allowed to use salbutamol as required throughout the trial period.\n The primary outcome measure is the proportion of patients in the three treatment groups who experienced a respiratory exacerbation within 52 weeks of randomization. Other outcomes that will be assessed over the 52-week trial period will include: changes in disease-specific quality of life and changes in dyspnea, health care use and changes in lung function. A pharmacoeconomic analysis will also be performed to evaluate the cost of these therapies.\n The study commenced recruitment in October 2003. It is currently operating at 22 centres across Canada and has randomized 137 patients during the first four months of recruitment. Recruitment is scheduled to continue until April 2005 or until 432 patients have been randomized.\n The present randomized, placebo-controlled trial offers a unique opportunity to answer the question, what is the best combination of inhaled medications to use for COPD patients? It is hoped that optimal use of inhaled medications will improve patient health and quality of life, reduce patient respiratory exacerbations, and ultimately, reduce health care resource use.",
"Patients with chronic obstructive pulmonary disease (COPD) who smoke have a greater annual rate of decline in forced expiratory volume in 1 s (FEV(1)) than those patients who have stopped smoking.\n To assess the effect of tiotropium on pre-dose (trough) FEV(1) in patients with COPD followed in Canada.\n A total of 913 patients were randomly assigned to receive either tiotropium 18 mug once daily (n=608) or placebo (usual care minus inhaled anticholinergics) (n=305) for 48 weeks in the present randomized, double-blind, parallel-group study. The effect of tiotropium on measurements of lung function (FEV(1), FEV(6) and forced vital capacity), symptoms, health-related quality of life (St George's Respiratory Questionnaire) and exacerbations were examined.\n Tiotropium improved trough FEV(1) in both current and ex-smokers compared with placebo. Baseline FEV(1) in smokers and ex-smokers was 1.03 L and 0.93 L, respectively (P<0.001). At week 48, the mean difference between the tiotropium and placebo groups was 0.14+/-0.04 L (P<0.001) in the smoker group and 0.08+/-0.02 L (P<0.0001) in the ex-smoker group. Tiotropium also significantly improved trough forced vital capacity and FEV(6) compared with placebo throughout the treatment period (P<0.05, for all). Furthermore, tiotropium significantly improved the St George's Respiratory Questionnaire total score compared with placebo at week 48 (40.9 versus 43.7 units, P<0.005).\n Compared with the placebo group, tiotropium provides sustained improvements in lung function in patients with COPD, with improvements for smokers and ex-smokers.",
"In patients with COPD, changes in inspiratory capacity (IC) have shown a higher correlation to patient-focused outcomes, such as dyspnea with exercise, than other standard spirometric measurements. Changes in IC reflect changes in hyperinflation. Tiotropium is a once-daily inhaled anticholinergic that has its effect through prolonged M3 muscarinic receptor antagonism and has demonstrated sustained improvements in spirometric and health outcomes. We sought to evaluate changes in resting IC and lung volumes after long-term administration of tiotropium.\n To evaluate the effect of tiotropium, 18 micro g/d, on IC, a 4-week, randomized, double-blind, placebo-controlled study was conducted in 81 patients with stable COPD. At each of the visits (weeks 0, 2, and 4) FEV(1), FVC, IC, slow vital capacity (SVC), and thoracic gas volume (TGV) were measured prior to study drug (- 60 and - 15 min) and after study drug (30 min, 60 min, 120 min, and 180 min).\n Mean age was 64 years; 62% were men. Mean baseline FEV(1) was 1.12 L (43% predicted). The mean differences (tiotropium - placebo) in FEV(1) trough (morning before drug), peak, and area under the curve over 3 h values (adjusted for baseline and center differences) at week 4 were 0.16 L, 0.22 L, and 0.22 L, respectively (p < 0.01 for all); differences in IC for these variables were 0.22 L, 0.35 L, and 0.30 L (p < 0.01 for all). Differences in TGV were - 0.54 L, - 0.60 L, and - 0.70 L, respectively (p < 0.01 for all). The percentage improvement in area under the curve above baseline with tiotropium was similar among FEV(1) and lung volumes (FEV(1), 18%; FVC, 20%; SVC, 16%; IC, 16%; TGV, 14%).\n Observed improvements in IC and reductions in TGV with once-daily tiotropium reflect improvements in hyperinflation that are maintained over 24 h."
] |
This review shows that tiotropium treatment was associated with a significant improvement in patients' quality of life and it reduced the risk of exacerbations, with a number needed to treat to benefit (NNTB) of 16 to prevent one exacerbation. Tiotropium also reduced exacerbations leading to hospitalisation but no significant difference was found for hospitalisation of any cause or mortality. Thus, tiotropium appears to be a reasonable choice for the management of patients with stable COPD, as proposed in guidelines. The review however, shows that tiotropium delivered via the Respimat soft mist inhaler was associated with a significantly increased risk of mortality compared with placebo, which calls for caution with this device whilst awaiting the results of an ongoing head-to-head trial comparing tiotropium delivery devices and doses.
|
CD008552
|
[
"12781165",
"19765270",
"19141661",
"18486203",
"11323442"
] |
[
"Increasing children's acceptance of vegetables; a randomized trial of parent-led exposure.",
"Evaluation of a multiple ecological level child obesity prevention program: Switch what you Do, View, and Chew.",
"Effectiveness of a social support intervention on infant feeding practices: randomised controlled trial.",
"High 5 for Kids: the impact of a home visiting program on fruit and vegetable intake of parents and their preschool children.",
"Increasing fruit and vegetable intake and decreasing fat and sugar intake in families at risk for childhood obesity."
] |
[
"Despite considerable epidemiological evidence of the health benefits of a diet high in fruit and vegetables, consumption in pre-school children remains well below recommended levels. This study evaluated the effectiveness of an exposure-based intervention, carried out by parents in the home, in increasing children's liking for a previously disliked vegetable. 156 parents of 2-6 year old children were randomly assigned to Exposure, Information or Control groups after a pre-intervention taste test at which a 'target' vegetable was selected. Parents in the Exposure group gave their child a taste of this vegetable daily for 14 days, parents in the Information group were given nutritional advice and a leaflet, and parents in the Control group received no further intervention. All participants took part in a post-intervention taste test. Greater increases in liking, ranking and consumption of the 'target' vegetable from pre- to post-intervention occurred in the Exposure group than in either of the other two groups. Only the Exposure group showed significant increases across all three outcomes. It can be concluded that a parent-led, exposure-based intervention involving daily tasting of a vegetable holds promise for improving children's acceptance of vegetables. These findings suggest a parental advice strategy which could be disseminated directly to parents or by health professionals.",
"Schools are the most frequent target for intervention programs aimed at preventing child obesity; however, the overall effectiveness of these programs has been limited. It has therefore been recommended that interventions target multiple ecological levels (community, family, school and individual) to have greater success in changing risk behaviors for obesity. This study examined the immediate and short-term, sustained effects of the Switch program, which targeted three behaviors (decreasing children's screen time, increasing fruit and vegetable consumption, and increasing physical activity) at three ecological levels (the family, school, and community).\n Participants were 1,323 children and their parents from 10 schools in two states. Schools were matched and randomly assigned to treatment and control. Measures of the key behaviors and body mass index were collected at baseline, immediately post-intervention, and 6 months post-intervention.\n The effect sizes of the differences between treatment and control groups ranged between small (Cohen's d = 0.15 for body mass index at 6 months post-intervention) to large (1.38; parent report of screen time at 6 months post-intervention), controlling for baseline levels. There was a significant difference in parent-reported screen time at post-intervention in the experimental group, and this effect was maintained at 6 months post-intervention (a difference of about 2 hours/week). The experimental group also showed a significant increase in parent-reported fruit and vegetable consumption while child-reported fruit and vegetable consumption was marginally significant. At the 6-month follow-up, parent-reported screen time was significantly lower, and parent and child-reported fruit and vegetable consumption was significantly increased. There were no significant effects on pedometer measures of physical activity or body mass index in the experimental group. The intervention effects were moderated by child sex (for fruit and vegetable consumption, physical activity, and weight status), family involvement (for fruit and vegetable consumption), and child body mass index (for screen time). The perception of change among the experimental group was generally positive with 23% to 62% indicating positive changes in behaviors.\n The results indicate that the Switch program yielded small-to-modest treatment effects for promoting children's fruit and vegetable consumption and minimizing screen time. The Switch program offers promise for use in youth obesity prevention.",
"To assess whether monthly home visits from trained volunteers could improve infant feeding practices at age 12 months, a randomised controlled trial was carried out in two disadvantaged inner city London boroughs.\n Women attending baby clinics with their infants (312) were randomised to receive monthly home visits from trained volunteers over a 9-month period (intervention group) or standard professional care only (control group). The primary outcome was vitamin C intakes from fruit. Secondary outcomes included selected macro and micro-nutrients, infant feeding habits, supine length and weight. Data were collected at baseline when infants were aged approximately 10 weeks, and subsequently when the child was 12 and 18 months old.\n Two-hundred and twelve women (68%) completed the trial. At both follow-up points no significant differences were found between the groups for vitamin C intakes from fruit or other nutrients. At first follow-up, however, infants in the intervention group were significantly less likely to be given goats' or soya milks, and were more likely to have three solid meals per day. At the second follow-up, intervention group children were significantly less likely to be still using a bottle. At both follow-up points, intervention group children also consumed significantly more specific fruit and vegetables.\n Home visits from trained volunteers had no significant effect on nutrient intakes but did promote some other recommended infant feeding practices.\n Current Controlled Trials ISRCTN55500035.",
"The High 5 for Preschool Kids (H5-KIDS) program tested the effectiveness of a home based intervention to teach parents how to ensure a positive fruit-vegetable (FV) environment for their preschool child, and to examine whether changes in parent behavior were associated with improvements in child intake.\n A group randomized nested cohort design was conducted (2001 to 2006) in rural, southeast Missouri with 1306 parents and their children participating in Parents As Teachers, a national parent education program.\n When compared to control parents, H5-KIDS parents reported an increase in FV servings (MN=0.20, p=0.05), knowledge and availability of FV within the home (p=0.01), and decreased their use of noncoercive feeding practices (p=0.02). Among preschoolers, FV servings increased in normal weight (MN=0.35, p=0.02) but not overweight children (MN=-0.10, p=0.48), relative to controls. The parent's change in FV servings was a significant predictor of child's change in FV in the H5-KIDS group (p=0.001).\n H5-KIDS suggests the need for, and promise of, early home intervention for childhood obesity prevention. It demonstrates the importance of participatory approaches in developing externally valid interventions, with the potential for dissemination across national parent education programs as a means for improving the intake of parents and young children.",
"The goal of this study was to evaluate the effect of a parent-focused behavioral intervention on parent and child eating changes and on percentage of overweight changes in families that contain at least one obese parent and a non-obese child.\n Families with obese parents and non-obese children were randomized to groups in which parents were provided a comprehensive behavioral weight-control program and were encouraged to increase fruit and vegetable intake or decrease intake of high-fat/high-sugar foods. Child materials targeted the same dietary changes as their parents without caloric restriction.\n Changes over 1 year showed that treatment influenced targeted parent and child fruit and vegetable intake and high-fat/high-sugar intake, with the Increase Fruit and Vegetable group also decreasing their consumption of high-fat/high-sugar foods. Parents in the increased fruit and vegetable group showed significantly greater decreases in percentage of overweight than parents in the decreased high-fat/high-sugar group.\n These results suggest that focusing on increasing intake of healthy foods may be a useful approach for nutritional change in obese parents and their children."
] |
Despite the importance of encouraging fruit and vegetable consumption among children aged five years and under, this review identified few randomised controlled trials investigating interventions to achieve this.
|
CD008235
|
[
"18046028",
"7508826",
"14681639",
"9299856",
"17050891"
] |
[
"Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura.",
"Randomized trial of a GPIIb/IIIa platelet receptor blocker in refractory unstable angina. European Cooperative Study Group.",
"Randomized trial and local biological effect of autologous platelets used as adjuvant therapy for chronic venous leg ulcers.",
"Antiplatelet agents in thrombotic thrombocytopenic purpura (TTP). Results of a randomized multicenter trial by the Italian Cooperative Group for TTP.",
"AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP."
] |
[
"The pathogenesis of chronic idiopathic thrombocytopenic purpura (ITP) involves antibody-mediated platelet destruction and reduced platelet production. Stimulation of platelet production may be an effective treatment for this disorder.\n We conducted a trial in which 118 adults with chronic ITP and platelet counts of less than 30,000 per cubic millimeter who had had relapses or whose platelet count was refractory to at least one standard treatment for ITP were randomly assigned to receive the oral thrombopoietin-receptor agonist eltrombopag (30, 50, or 75 mg daily) or placebo. The primary end point was a platelet count of 50,000 or more per cubic millimeter on day 43.\n In the eltrombopag groups receiving 30, 50, and 75 mg per day, the primary end point was achieved in 28%, 70%, and 81% of patients, respectively. In the placebo group, the end point was achieved in 11% of patients. The median platelet counts on day 43 for the groups receiving 30, 50, and 75 mg of eltrombopag were 26,000, 128,000, and 183,000 per cubic millimeter, respectively; for the placebo group the count was 16,000 per cubic millimeter. By day 15, more than 80% of patients receiving 50 or 75 mg of eltrombopag daily had an increased platelet count. Bleeding also decreased during treatment in these two groups. The incidence and severity of adverse events were similar in the placebo and eltrombopag groups.\n Eltrombopag increased platelet counts in a dose-dependent manner in patients with relapsed or refractory ITP. (ClinicalTrials.gov number, NCT00102739.)\n 2007 Massachusetts Medical Society",
"Patients with unstable angina despite intensive medical therapy, ie, refractory angina, are at high risk for developing thrombotic complications: myocardial infarction or coronary occlusion during percutaneous transluminal coronary angioplasty (PTCA). Chimeric 7E3 (c7E3) Fab is an antibody fragment that blocks the platelet glycoprotein (GP) IIb/IIIa receptor and potently inhibits platelet aggregation.\n To evaluate whether potent platelet inhibition could reduce these complications, 60 patients with dynamic ST-T changes and recurrent pain despite intensive medical therapy were randomized to c7E3 Fab or placebo. After initial angiography had demonstrated a culprit lesion suitable for PTCA, placebo or c7E3 Fab was administered as 0.25 mg/kg bolus injection followed by 10 micrograms/min for 18 to 24 hours until 1 hour after completion of second angiography and PTCA. During study drug infusion, ischemia occurred in 9 c7E3 Fab and 16 placebo patients (P = .06). During hospital stay, 12 major events occurred in 7 placebo patients (23%), including 1 death, 4 infarcts, and 7 urgent interventions. In the c7E3 Fab group, only 1 event (an infarct) occurred (3%, P = .03). Angiography showed improved TIMI flow in 4 placebo and 6 c7E3 Fab patients and worsening of flow in 3 placebo patients but in none of the c7E3 Fab patients. Quantitative analysis showed significant improvement of the lesion in the patients treated with c7E3 Fab, which was not observed in the placebo group, although the difference between the two treatment groups was not significant. Measurement of platelet function and bleeding time demonstrated > 90% blockade of GPIIb/IIIa receptors, > 90% reduction of ex vivo platelet aggregation to ADP, and a significantly prolonged bleeding time during c7E3 Fab infusion, without excess bleeding.\n Combined therapy with c7E3 Fab, heparin, and aspirin appears safe. These pilot study results support the concept that effective blockade of the platelet GPIIb/IIIa receptors can reduce myocardial infarction and facilitate PTCA in patients with refractory unstable angina.",
"Platelet products have been proposed as adjuvant therapy for wound healing. We undertook this study to determine the healing effect of topically applied frozen autologous platelets (FAP) on chronic venous ulcers, compared with effect of placebo, and whether use of topical FAP modifies local expression of vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF), interleukin 8 (IL-8), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in wound fluid.\n This randomized, placebo-controlled, double-blind trial was carried out in institutional practice, with ambulatory patients with proved chronic venous leg ulcers. In all patients, whole venous blood was drawn for preparation of FAP. FAP or normal saline solution was applied three times per week for up to 12 weeks, together with hydrocolloids and standardized compression bandages. Leg ulcer surface was assessed with numerical pictures. IL-8, VEGF, KGF, and TIMP-1 levels were determined (enzyme-linked immunosorbent assay) in wound fluid after each 4 weeks of treatment.\n Fifteen patients were randomized into two groups with comparable leg ulcer characteristics. Mean percent reduction in ulcer area was 26.2% in the FAP group versus 15.2% in the placebo group (P =.94). One ulcer in each group was completely healed at study end. Levels of TIMP-1 increased significantly during FAP treatment. IL-8 concentration was significantly lower in wound fluid of healing ulcers than in the fluid of nonhealing ulcers, in both FAP and placebo groups. Growth factor levels were not modified with FAP treatment.\n Topical autologous platelets have no significant adjuvant effect on healing of chronic venous leg ulcers and increased wound fluid TIMP-1 concentration. Ulcer healing is associated with a decrease in wound fluid IL-8.",
"Antiplatelet agents are often included in plasma exchange-based regimens for thrombotic thrombocytopenic purpura (TTP) patients; however, the opportuneness of their use in TTP is still controversial. The italian Cooperative Group for TTP carried out a randomized trial to investigate their actual effectiveness, both in acute TTP and as maintenance treatment.\n Seventy-two TTP patients were randomized to receive plasma exchange and steroids with (group B) or without (group A) aspirin and dipyridamole. Treatment efficacy was evaluated after 15 days and salvage treatments were also considered for non-responders. Upon disease remission, the patients already treated with antiplatelet agents received ticlopidine for one year.\n Regarding the treatment of acute phase TTP, similar overall response rates were observed in the two groups (91.4% in group B vs. 75.6% in group A), but lower mortality rates were observed at 15 days in the patients treated with antiplatelet agents; as a matter of fact, 5 patients from arm A died in the first 15 days (13.5%) versus only one in arm B (2.8%). These figures, while not statistically significant, seem to suggest that antiplatelet agents might be useful in preventing deaths in acute TTP; moreover, bleeding did not worsen in antiplatelet agent-treated patients. As for the role of maintenance treatment, our results support the efficacy and safety of one-year ticlopidine therapy since the current relapse rate is significantly higher in non-treated patients; as a matter of fact, 6 patients (21.4%) in the non-ticlopidine group and only 2 (6.25%) in the ticlopidine group relapsed (P = .0182 in favor of maintenance treatment).\n Our results suggest the usefulness of antiplatelet agents in the treatment of acute phase TTP patients. Moreover, one-year ticlopidine maintenance therapy appears to be beneficial in preventing TTP relapses; however, only the completion of an adequate follow-up for all patients will definitively confirm this observation.",
"Most current treatments for chronic immune thrombocytopenic purpura (ITP) act by decreasing platelet destruction. In a phase 1-2 study, we administered a thrombopoiesis-stimulating protein, AMG 531, to patients with ITP.\n In phase 1, 24 patients who had received at least one treatment for ITP were assigned to escalating-dose cohorts of 4 patients each and given two identical doses of AMG 531 (0.2 to 10 microg per kilogram of body weight). In phase 2, 21 patients were randomly assigned to receive six weekly subcutaneous injections of AMG 531 (1, 3, or 6 microg per kilogram) or placebo. The primary objective was to assess the safety of AMG 531; the secondary objective was to evaluate platelet counts during and after treatment.\n No major adverse events that could be attributed directly to AMG 531 occurred during the treatment period; 4 of 41 patients had transient post-treatment worsening of thrombocytopenia. In phase 1, a platelet count that was within the targeted range (50,000 to 450,000 per cubic millimeter) and at least twice the baseline count was achieved in 4 of 12 patients given 3, 6, or 10 mug of AMG 531 per kilogram. Overall, a platelet count of at least 50,000 per cubic millimeter was achieved in 7 of 12 patients, including 3 with counts exceeding 450,000 per cubic millimeter. Increases in the platelet count were dose-dependent; mean peak counts were 163,000, 309,000, and 746,000 per cubic millimeter with 3, 6, and 10 microg of AMG 531 per kilogram [corrected], respectively. In phase 2, the targeted platelet range was achieved in 10 of 16 patients treated with 1 or 3 mug of AMG 531 per kilogram per week for 6 weeks. Mean peak counts were 135,000, 241,000, and 81,000 per cubic millimeter in the groups that received the 1-mug dose, the 3-mug dose, and placebo, respectively.\n AMG 531 caused no major adverse events and increased platelet counts in patients with ITP. (ClinicalTrials.gov number, NCT00111475 [ClinicalTrials.gov].).\n Copyright 2006 Massachusetts Medical Society."
] |
There was currently no evidence to support that TPO receptor agonists are effective in chronic ITP. Compared to placebo or SOC, despite significantly increased platelet response, there was no evidence to demonstrate that TPO receptor agonists did improve significant bleeding events in chronic ITP. The effect on overall survival awaits further analysis. Although long-term studies are lacking, current data demonstrated adverse effects of TPO receptor agonists were similar to that of placebo and SOC.
|
CD008300
|
[
"8426771",
"3673975",
"11796357",
"7826118",
"9295239"
] |
[
"Evaluation of oral erythromycin and local isoniazid instillation therapy in infants with Bacillus Calmette-Guérin lymphadenitis and abscesses.",
"Is medical therapy effective for regional lymphadenitis following BCG vaccination?",
"Randomized, double-blind, multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiases.",
"Needle aspiration for suppurative post-BCG adenitis.",
"A trial of three regimens to prevent tuberculosis in Ugandan adults infected with the human immunodeficiency virus. Uganda-Case Western Reserve University Research Collaboration."
] |
[
"A randomized placebo-controlled prospective trial was conducted to evaluate the efficacy of erythromycin therapy in 69 patients affected with Bacillus Calmette-Guérin lymphadenitis. When patients who developed subsequent regional abscesses were excluded, erythromycin caused significantly earlier resolution of lymphadenitis (5.1 months vs. 5.7 months for placebo; P < 0.01) compared with placebo. There was no significant difference in the proportion of patients who developed subsequent regional abscesses between the 2 groups (47% for erythromycin, 60% for placebo, P = 0.14). When the entire group of 69 patients was evaluated for \"duration to heal\" (regardless of subsequent abscess formation), erythromycin therapy (4.1 +/- 1.5 SD months) did not differ significantly from the placebo group (3.5 +/- 1.3 months, P = not significant). Patients who developed subsequent abscess (n = 36) along with those with B. Calmette-Guérin regional abscesses at presentation (n = 27) were further studied to compare oral erythromycin therapy with that of single dose 50-mg intranodal isoniazid instillation. Local isoniazid therapy caused significantly earlier resolution of the abscesses (3.9 months) compared with erythromycin therapy (5.2 months; P < 0.001).",
"We describe 120 patients with regional lymphadenitis following intradermal BCG vaccination. Seventy-eight of the patients were given medical therapy to prevent drainage and suppuration, and 42 patients were followed up without such treatment. The medical therapy group is divided into three subgroups: 36 were given erythromycin stearate, 21 isoniazid, and 21 isoniazid plus rifampin. No statistical difference in the incidence of spontaneous drainage and suppuration was found between the \"no therapy\" and the \"medical therapy\" groups. No significant superiority of any specific therapy was shown. If lymphadenitis develops rapidly (in two months), the incidence of spontaneous drainage and suppuration is significantly higher than in patients with slowly developing lesions. Total surgical excision is recommended to prevent spontaneous drainage and chronic suppuration in these rapidly evolving instances.",
"Caspofungin is an antifungal agent of the novel echinocandin class. We investigated its efficacy, safety, and tolerability as therapy for oropharyngeal and/or esophageal candidiasis in a phase II dose-ranging study. Patients were randomized in a double-blind manner to receive either caspofungin acetate (35, 50, or 70 mg) or amphotericin B (0.5 mg/kg of body weight) intravenously once daily for 7 to 14 days. A favorable response required both complete resolution of symptoms and quantifiable improvement of mucosal lesions 3 to 4 days after discontinuation of study drug. Efficacy was assessed using a modified intent-to-treat analysis. No hypothesis testing of efficacy was planned or performed. Of 140 enrolled patients, 63% had esophageal involvement and 98% were infected with the human immunodeficiency virus (HIV) (median CD4 count, 30/mm(3)). A modestly higher proportion of patients in each of the caspofungin groups (74 to 91%) achieved favorable responses compared to amphotericin B recipients (63%), but there was considerable overlap in the 95% confidence intervals surrounding these point estimates. Similar trends were found in the subgroups with esophageal involvement, a history of fluconazole failure, and CD4 counts of < or =50/mm(3). A smaller proportion of patients receiving any dose of caspofungin experienced drug-related adverse events compared to patients given standard doses of conventional amphotericin B (P < 0.01). Caspofungin provided a generally well-tolerated parenteral therapeutic option for HIV-infected patients with oropharyngeal and/or esophageal candidiasis in this study.",
"The effect of needle aspiration in suppurative post-BCG adenitis was studied. Nodes that had been aspirated (43 patients) regressed in 25 (58%) and 41 (95%) patients two and six months after aspiration. In the control group (34 patients) regression occurred in three (9%) and 22 (65%) patients. Spontaneous drainage with sinus tract formation was also significantly less in the aspirated group at six months (7% v 44%).",
"Infection with the human immunodeficiency virus (HIV) greatly increases the risk of reactivation tuberculosis. We evaluated the safety and efficacy of three preventive-therapy regimens in a setting where exposure to tuberculosis is common.\n We performed a randomized, placebo-controlled trial in 2736 HIV-infected adults recruited in Kampala, Uganda. Subjects with positive tuberculin skin tests (induration, > or =5 mm) with purified protein derivative (PPD) were randomly assigned to one of four regimens: placebo (464 subjects), isoniazid daily for six months (536), isoniazid and rifampin daily for three months (556), or isoniazid, rifampin, and pyrazinamide daily for three months (462). Subjects with anergy (0 mm induration in reaction to PPD and candida antigens) were randomly assigned to receive either placebo (323 subjects) or six months of isoniazid (395). The medications were dispensed monthly and were self-administered.\n Among the PPD-positive subjects, the incidence of tuberculosis in the three groups that received preventive therapy was lower than the rate in the placebo group (P=0.002 by the log-rank test). The relative risk of tuberculosis with isoniazid alone, as compared with placebo, was 0.33 (95 percent confidence interval, 0.14 to 0.77); with isoniazid and rifampin, 0.40 (0.18 to 0.86); and with isoniazid, rifampin, and pyrazinamide, 0.51 (0.24 to 1.08). Among the subjects with anergy, the relative risk of tuberculosis was 0.83 (95 percent confidence interval, 0.34 to 2.04) with isoniazid as compared with placebo. Side effects were more common with the multidrug regimens, and particularly with the regimen containing pyrazinamide. Survival did not differ among the groups, but the subjects with anergy had a higher mortality rate than the PPD-positive subjects.\n A six-month course of isoniazid confers short-term protection against tuberculosis among PPD-positive, HIV-infected adults. Multidrug regimens with isoniazid and rifampin taken for three months also reduce the risk of tuberculosis."
] |
It is unclear if oral antibiotics (isoniazid, erythromycin, or a combination of isoniazid plus rifampicin) are effective for the resolution of BCG-induced disease. Most non-suppurated lymphadenitis will resolve without treatment in 4 to 6 months. Patients with lymphadenitis abscess might benefit from needle aspiration and possibly local instillation of isoniazid could shorten recovery time. Included studies were generally small and could be better conducted. Further research should evaluate the use of needle aspiration and local instillation of isoniazid in fluctuant nodes. Therapeutic and preventive measures in HIV-infected infants could be important given the higher risk of negative outcomes in this group.
|
CD007612
|
[
"17621203",
"8602477",
"9971865",
"7552649",
"11389408",
"19685848",
"2148221",
"15507794",
"17268258"
] |
[
"Active exercise, education, and cognitive behavioral therapy for persistent disabling low back pain: a randomized controlled trial.",
"Physical performance, pain, pain behavior and subjective disability in patients with subacute low back pain.",
"Lack of effectiveness of bed rest for sciatica.",
"Active treatment programs for patients with chronic low back pain: a prospective, randomized, observer-blinded study.",
"Long-term effects of specific stabilizing exercises for first-episode low back pain.",
"Comparison of short-term response to two spinal manipulation techniques for patients with low back pain in a military beneficiary population.",
"A controlled study on the outcome of inpatient and outpatient treatment of low back pain. Part III. Long-term follow-up of pain, disability, and compliance.",
"Early intervention for the management of acute low back pain: a single-blind randomized controlled trial of biopsychosocial education, manual therapy, and exercise.",
"Multidisciplinary rehabilitation for subacute low back pain: graded activity or workplace intervention or both? A randomized controlled trial."
] |
[
"A randomized controlled trial.\n To determine 1) whether, among patients with persistent disabling low back pain (LBP), a group program of exercise and education using a cognitive behavioral therapy (CBT) approach, reduces pain and disability over a subsequent 12-month period; 2) the cost-effectiveness of the intervention; and 3) whether a priori preference for type of treatment influences outcome.\n There is evidence that both exercise and CBT delivered in specialist settings is effective in improving LBP. There is a lack of evidence on whether such interventions, delivered by trained individuals in primary care, result in improved outcomes.\n The study was conducted in nine family medical practices in East Cheshire, UK. Patients 18 to 65 years of age, consulting with LBP, were recruited; those still reporting LBP 3 months after the initial consultation were randomized between the two trial arms. The intervention arm received a program of eight 2-hour group exercise session over 6 weeks comprising active exercise and education delivered by physiotherapists using a CBT approach. Both arms received an educational booklet and audio-cassette. The primary outcome measures were pain (0-100 Visual Analogue Scale) and disability (Roland and Morris Disability Scale; score 0-24).\n A total of 196 subjects (84%) completed follow-up 12 months after the completion of the intervention program. The intervention showed only a small and nonsignificant effect at reducing pain (-3.6 mm; 95% confidence interval, -8.5, 1.2 mm) and disability (-0.6 score; 95% confidence interval, -1.6, 0.4). The cost of the intervention was low with an incremental cost-effectiveness ratio of pound5000 (U.S. $8650) per quality adjusted life year. In addition, patients allocated to the intervention that had expressed a preference for it had clinically important reductions in pain and disability.\n This intervention program produces only modest effects in reducing LBP and disability over a 1-year period. The observation that patient preference for treatment influences outcome warrants further investigation.",
"The aim of this paper was to study the physical performance, pain, pain behavior and disability in patients with subacute low back pain (LBP). The patients were blue-collar workers and had been sick-listed for 8 weeks due to subacute low back pain. A total of 103 patients were randomized, 51 of them to the intervention group and the other to a control group. Recordings of physical performance and complaints of LBP were done before and after treatment in the intervention group. The proportion of patients with no complaints of LBP was significantly greater in the intervention group than in the control group at the one-year follow-up. The patients who intra-individually improved their physical performance also intra-individually decreased their complaints of LBP. The intra-individual improvements were suggested to be important for the individual return to work.",
"Bed rest is widely advocated for sciatica, but its effectiveness has not been established. To study the effectiveness of bed rest in patients with a lumbosacral radicular syndrome of sufficient severity to justify treatment with bed rest for two weeks, we randomly assigned 183 subjects to either bed rest or watchful waiting for this period. The primary outcome measures were the investigator's and patient's global assessments of improvement after 2 and 12 weeks, and the secondary outcome measures were changes in functional status and in pain scores (after 2, 3, and 12 weeks), absenteeism from work, and the need for surgical intervention. Neither the investigators who assessed the outcomes nor those involved in data entry and analysis were aware of the patients' treatment assignments.\n After two weeks, 64 of the 92 patients in the bed-rest group (70 percent) reported improvement, as compared with 59 of the 91 patients in the control (watchful-waiting) group (65 percent) (adjusted odds ratio for improvement in the bed-rest group, 1.2; 95 percent confidence interval, 0.6 to 2.3). After 12 weeks, 87 percent of the patients in both groups reported improvement. The results of assessments of the intensity of pain, the bothersomeness of symptoms, and functional status revealed no significant differences between the two groups. The extent of absenteeism from work and rates of surgical intervention were similar in the two groups.\n Among patients with symptoms and signs of a lumbosacral radicular syndrome, bed rest is not a more effective therapy than watchful waiting.",
"Several new studies have indicated that an active approach to patients with chronic disabling low back pain (LBP) seems effective. Some of these studies emphasize the importance of dealing with the patient's total situation in comprehensive multidisciplinary programs--the bio-psycho-social model. However, these programs are expensive. The aim of this study was to evaluate the rehabilitation outcome from three different active programs in terms of: (1) return-to-work rate, (2) days of sick leave, (3) health-care contacts, (4) pain and disability scores, and (5) staying physically active. The subjects included 132 patients randomized to the study, of whom 123 started one of the treatment programs. They had all had at least 6 months of chronic LBP. The patients were randomized into one of three programs: group 1--a full-time, intensive 3-week multidisciplinary program, including active physical and ergonomic training and psychological pain management, followed by 1 day weekly for the subsequent 3 weeks; group 2--active physical training, twice a week for 6 weeks, for a total of 24h; group 3--psychological pain management combined with active physical training, twice a week for 6 weeks, also for a total of 24h. The results presented here are based on data collected 4 months following treatment, which shows an 86% response rate. The initial examination and the follow-up evaluation were performed by a blinded observer. The results show that 4 months after treatment, the intensive multidisciplinary program is superior to the less intensive programs in terms of return-to-work rate, health-care contacts, pain and disability scores, and staying physically active.(ABSTRACT TRUNCATED AT 250 WORDS)",
"A randomized clinical trial with 1-year and 3-year telephone questionnaire follow-ups.\n To report a specific exercise intervention's long-term effects on recurrence rates in acute, first-episode low back pain patients.\n The pain and disability associated with an initial episode of acute low back pain (LBP) is known to resolve spontaneously in the short-term in the majority of cases. However, the recurrence rate is high, and recurrent disabling episodes remain one of the most costly problems in LBP. A deficit in the multifidus muscle has been identified in acute LBP patients, and does not resolve spontaneously on resolution of painful symptoms and resumption of normal activity. Any relation between this deficit and recurrence rate was investigated in the long-term.\n Thirty-nine patients with acute, first-episode LBP were medically managed and randomly allocated to either a control group or specific exercise group. Medical management included advice and use of medications. Intervention consisted of exercises aimed at rehabilitating the multifidus in cocontraction with the transversus abdominis muscle. One year and three years after treatment, telephone questionnaires were conducted with patients.\n Questionnaire results revealed that patients from the specific exercise group experienced fewer recurrences of LBP than patients from the control group. One year after treatment, specific exercise group recurrence was 30%, and control group recurrence was 84% (P < 0.001). Two to three years after treatment, specific exercise group recurrence was 35%, and control group recurrence was 75% (P < 0.01).\n Long-term results suggest that specific exercise therapy in addition to medical management and resumption of normal activity may be more effective in reducing low back pain recurrences than medical management and normal activity alone.",
"To determine whether military health care beneficiaries with low back pain (LBP) who are likely to respond successfully to spinal manipulation experience a difference in short-term clinical outcomes based on the manipulation technique that is used.\n Sixty patients with LBP identified as likely responders to manipulation underwent a standardized clinical examination and were randomized to receive a lumbopelvic (LP) or lumbar neutral gap (NG) manipulation technique. Outcome measures were a numeric pain rating scale and the modified Oswestry Disability Questionnaire.\n Both the LP and NG groups experienced statistically significant reductions in pain and disability at 48 hours postmanipulation. The improvements seen in each group were small because of the short follow-up. There were no statistically significant or clinically meaningful differences in pain or disability between the two groups.\n The two manipulation techniques used in this study were equally effective at reducing pain and disability when compared at 48 hours posttreatment. Clinicians may employ either technique for the treatment of LBP and can expect similar outcomes in those who satisfy the clinical prediction rule (CPR). Further research is required to determine whether differences exist at longer-term follow-up periods, after multiple treatment sessions, or in different clinical populations.",
"The long-term outcome results of inpatient and outpatient treatment of low back pain (LBP) were studied in 476 subjects (aged 35-54, 63% men) randomly assigned to three study groups: inpatients (n = 157), outpatients (n = 159), and controls (n = 160). The study included changes in the severity of low back pain, grade and disability, compliance with self-care, data on disability pensions, and days of sickness allowance during a 2.5-year follow-up period. These variables were used as outcome criteria. Pain and disability had decreased significantly in the two treated groups up to the 3-month follow-up. LBP was still a little slighter in the inpatients at the 1.5-year and 22-month follow-ups, but there were no significant differences between the groups in disability caused by LBP. The refresher programme carried out 1.5 years after the first one did not bring about as clear short-term improvement in pain and disability as the first treatment. During the whole 2.5-year follow-up compliance with self-care was better in the two treated groups, especially in the inpatients. Days of sickness allowance had increased somewhat more in the controls than in the inpatients during the follow-up. No differences between the groups were found in the number of disability pensions granted.",
"A single blind randomized controlled trial comparing two models of care for patients with acute simple low back pain.\n To compare two research-based models of care for acute low back pain and investigate the effect of the timing of physical intervention.\n National guidelines offer conflicting information on the delivery of physical treatment in the management of acute low back pain. The guidelines suggest two different models of care. Direct comparisons between these models are lacking in the literature. The present study aims to compare these approaches to the management of acute low back pain.\n Among 804 referred patients, 102 subjects met the specific admission criteria and were randomly assigned to an \"assess/advise/treat\" group or an \"assess/advise/wait\" group. The intervention consisted of biopsychosocial education, manual therapy, and exercise. Assessment of short-term outcome enables comparison to be made between intervention and advice to stay active. Assessment of long-term outcome enables comparison to be made between early and late intervention. Study outcomes of reported pain (Visual Analogue Scale), functional disability (the Roland and Morris Disability Questionnaire), mood (Modified Zung Self Rated Depression Score, Modified Somatic Perception Questionnaire, State-Trait Anxiety Inventory), general health (Euroqol), and quality of life (Short Form 36) were assessed at baseline, 6 weeks, 3 months, and 6 months.\n At 6 weeks, the assess/advise/treat group demonstrated greater improvements in disability, mood, general health, and quality of life than patients in the assess/advise/wait group (P < 0.05). Disability and pain were not significantly different between the groups at long-term follow up (P > 0.05). However, mood, general health, and quality of life remained significantly better in the assess/advise/treat group (P < 0.05).\n At short-term, intervention is more effective than advice on staying active, leading to more rapid improvement in function, mood, quality of life, and general health. The timing of intervention affects the development of psychosocial features. If treatment is provided later, the same psychosocial benefits are not achieved. Therefore, an assess/advise/treat model of care seems to offer better outcomes than an assess/advise/wait model of care.",
"Population-based randomized controlled trial.\n To assess the effectiveness of workplace intervention and graded activity, separately and combined, for multidisciplinary rehabilitation of low back pain (LBP).\n Effective components for multidisciplinary rehabilitation of LBP are not yet established.\n Participants sick-listed 2 to 6 weeks due to nonspecific LBP were randomized to workplace intervention (n = 96) or usual care (n = 100). Workplace intervention consisted of workplace assessment, work modifications, and case management involving all stakeholders. Participants still sick-listed at 8 weeks were randomized for graded activity (n = 55) or usual care (n = 57). Graded activity comprised biweekly 1-hour exercise sessions based on operant-conditioning principles. Outcomes were lasting return to work, pain intensity and functional status, assessed at baseline, and at 12, 26, and 52 weeks after the start of sick leave.\n Time until return to work for workers with workplace intervention was 77 versus 104 days (median) for workers without this intervention (P = 0.02). Workplace intervention was effective on return to work (hazard ratio = 1.7; 95% CI, 1.2-2.3; P = 0.002). Graded activity had a negative effect on return to work (hazard ratio = 0.4; 95% CI, 0.3-0.6; P < 0.001) and functional status. Combined intervention had no effect.\n Workplace intervention is advised for multidisciplinary rehabilitation of subacute LBP. Graded activity or combined intervention is not advised."
] |
Moderate quality evidence shows that patients with acute LBP may experience small benefits in pain relief and functional improvement from advice to stay active compared to advice to rest in bed; patients with sciatica experience little or no difference between the two approaches. Low quality evidence suggests little or no difference between those who received advice to stay active, exercises or physiotherapy. Further research is very likely to have an important impact on the estimate of effect and is likely to change our confidence in it.
|
CD009689
|
[
"8630191",
"15083439",
"11588740"
] |
[
"Effectiveness of an intensive outpatient rehabilitation program for postacute stroke patients.",
"A randomized controlled comparison of upper-extremity rehabilitation strategies in acute stroke: A pilot study of immediate and long-term outcomes.",
"Comparing stroke rehabilitation outcomes between acute inpatient and nonintense home settings."
] |
[
"The effectiveness of ongoing rehabilitation services for postacute stroke survivors is poorly documented. We designed a randomized control, single-blinded study to demonstrate the effectiveness of intensive outpatient therapy. The treatment intervention consisted of 1 hr each of physical and occupational therapy, four times per week, for 12 wk; therapy focused on neuromuscular facilitation and functional tasks. All subjects were screened before the therapies and after 3 mo and 9 mo. Forty-nine stroke survivors, who were at least l yr (mean, 2.9 yr) poststroke, were randomized with two treated patients to each control (no treatment supplied). All patients had received inpatient rehabilitation at the time of their acute stroke, but no patient had any ongoing therapy within the last 6 mo. The outcome measures included the Functional Independence Measure (FIM), Brunnstrom stages of motor recovery, timed mobility tasks, and the Jebson hand evaluation. We also evaluated the level of depression, self-esteem, and socialization. The treated patients demonstrated an improvement of 6.6 points over the 3 mo of therapy compared with only 1.5 points in the control group in the FIM motor score transformed using Rasch analysis. The change from time 0 to 3 mo was significant in the treated group but not in the controls. Treated patients maintained their gains at the 9-mo follow-up, and controls lost ground. The treated group improved in terms of socialization and self-esteem as evidenced by a lower Sickness Impact Profile, whereas the controls tended to get worse. There was a trend toward less depression, but this did not reach a P = 0.05 level of significance. This study demonstrates that significant functional gains can still be attained in the postacute stroke survivor, despite prior inpatient rehabilitation services.",
"To evaluate the immediate and long-term effects of 2 upper-extremity rehabilitation approaches for stroke compared with standard care in participants stratified by stroke severity.\n Nonblinded, randomized controlled trial (baseline, postintervention, 9mo) design.\n Inpatient rehabilitation hospital and outpatient clinic.\n Sixty-four patients with recent stroke admitted for inpatient rehabilitation were randomized within severity strata (Orpington Prognostic Scale) into 1 of 3 intervention groups. Forty-four patients completed the 9-month follow-up.\n Standard care (SC), functional task practice (FT), and strength training (ST). The FT and ST groups received 20 additional hours of upper-extremity therapy beyond standard care distributed over a 4- to 6-week period.\n Performance measures of impairment (Fugl-Meyer Assessment), strength (isometric torque), and function (Functional Test of the Hemiparetic Upper Extremity [FTHUE]).\n Compared with SC participants, those in the FT and ST groups had significantly greater increases in Fugl-Meyer motor scores (P=.04) and isometric torque (P=.02) posttreatment. Treatment benefit was primarily in the less severe participants, where improvement in FT and ST group Fugl-Meyer motor scores more than doubled that of the SC group. Similar results were found for the FTHEU and isometric torque. During the long term, at 9 months, the less severe FT group continued to make gains in isometric muscle torque, significantly exceeding those of the ST group (P<.05).\n Task specificity and stroke severity are important factors for rehabilitation of arm use in acute stroke. Twenty hours of upper extremity-specific therapy over 4 to 6 weeks significantly affected functional outcomes. The immediate benefits of a functional task approach were similar to those of a resistance-strength approach, however, the former was more beneficial in the long-term.",
"To compare outcomes in stroke survivors who received rehabilitation services in an acute inpatient rehabilitation setting (multidisciplinary rehabilitation team) with outcomes in survivors in a home-based setting (family caregivers, limited team supervision).\n Randomized clinical trial, with mean follow-up after 60 days.\n Inpatient rehabilitation setting and home-based settings.\n Sixty patients (age range, 43-80yr) who had a stroke between 1996 and 1999 and had been referred after medical stabilization, randomly divided into 2 groups: group 1, inpatient rehabilitation; group 2, home-based rehabilitation.\n Group 1: therapeutical and neuromuscular exercises with occupational therapy with professional supervision; group 2: conventional exercises with family caregiver and limited professional supervision.\n Spasticity was evaluated with the Ashworth Scale, motor status with Brunnstrom's stages, functional status with the FIM instrument, and cognitive status with the Mini-Mental State Examination before and after rehabilitation.\n Patients rehabilitated in acute inpatient settings had better motor, functional, and cognitive outcomes (p < .05). Spasticity changes did not differ between the groups.\n Intense inpatient rehabilitation services for stroke survivors provide significantly more favorable functional and cognitive outcomes with relatively low complications than did nonintense rehabilitation efforts in home settings.\n Copyright 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation"
] |
At best there was 'low level' evidence for the effectiveness of outpatient MD rehabilitation in improving active function and impairments following BoNT for upper limb spasticity in adults with chronic stroke. No trials explored the effect of MD rehabilitation on 'passive function' (caring for the affected limb), caregiver burden, or the individual's priority goals for treatment. The optimal types (modalities, therapy approaches, settings) and intensities of therapy for improving activity (active and passive function) in adults and children with post-stroke spasticity, in the short and longer term, are unclear. Further research is required to build evidence in this area.
|
CD000270
|
[
"12898500",
"12236381",
"20008945"
] |
[
"Evaluation of a mental health treatment court with assertive community treatment.",
"Understanding team-based quality improvement for depression in primary care.",
"A randomized trial of medical care management for community mental health settings: the Primary Care Access, Referral, and Evaluation (PCARE) study."
] |
[
"Without active engagement, many adults with serious mental illnesses remain untreated in the community and commit criminal offenses, resulting in their placement in the jails rather than mental health facilities. A mental health treatment court (MHTC) with an assertive community treatment (ACT) model of case management was developed through the cooperative efforts of the criminal justice and mental health systems. Participants were 235 adults with a serious mental illness who were booked into the county jail, and who volunteered for the study. An experimental design was used, with participants randomly assigned to MHTC or treatment as usual (TAU), consisting of adversarial criminal processing and less intensive mental health treatment. Results were reported for 6 and 12 month follow-up periods. Clients in both conditions improved in life satisfaction, distress, and independent living, while participants in the MHTC also showed reductions in substance abuse and new criminal activity. Outcomes are interpreted within the context of changes brought about in the community subsequent to implementation of the MHTC.\n Copyright 2003 John Wiley & Sons, Ltd.",
"To assess the impacts of the characteristics of quality improvement (QI) teams and their environments on team success in designing and implementing high quality, enduring depression care improvement programs in primary care (PC) practices.\n Two nonprofit managed care organizations sponsored five QI teams tasked with improving care for depression in large PC practices. Data on characteristics of the teams and their environments is from observer process notes, national expert ratings, administrative data, and interviews.\n Comparative formative evaluation of the quality and duration of implementation of the depression improvement programs developed by Central Teams (CTs) emphasizing expert design and Local Teams (LTs) emphasizing participatory local clinician design, and of the effects of additional team and environmental factors on each type of team. Both types of teams depended upon local clinicians for implementation.\n The CT intervention program designs were more evidence-based than those of LTs. Expert team leadership, support from local practice management, and support from local mental health specialists strongly influenced the development of successful team programs. The CTs and LTs were equally successful when these conditions could be met, but CTs were more successful than LTs in less supportive environments.\n The LT approach to QI for depression requires high local support and expertise from primary care and mental health clinicians. The CT approach is more likely to succeed than the LT approach when local practice conditions are not optimal.",
"Poor quality of healthcare contributes to impaired health and excess mortality in individuals with severe mental disorders. The authors tested a population-based medical care management intervention designed to improve primary medical care in community mental health settings.\n A total of 407 subjects with severe mental illness at an urban community mental health center were randomly assigned to either the medical care management intervention or usual care. For individuals in the intervention group, care managers provided communication and advocacy with medical providers, health education, and support in overcoming system-level fragmentation and barriers to primary medical care.\n At a 12-month follow-up evaluation, the intervention group received an average of 58.7% of recommended preventive services compared with a rate of 21.8% in the usual care group. They also received a significantly higher proportion of evidence-based services for cardiometabolic conditions (34.9% versus 27.7%) and were more likely to have a primary care provider (71.2% versus 51.9%). The intervention group showed significant improvement on the SF-36 mental component summary (8.0% [versus a 1.1% decline in the usual care group]) and a nonsignificant improvement on the SF-36 physical component summary. Among subjects with available laboratory data, scores on the Framingham Cardiovascular Risk Index were significantly better in the intervention group (6.9%) than the usual care group (9.8%).\n Medical care management was associated with significant improvements in the quality and outcomes of primary care. These findings suggest that care management is a promising approach for improving medical care for patients treated in community mental health settings."
] |
Community mental health team management is not inferior to non-team standard care in any important respects and is superior in promoting greater acceptance of treatment. It may also be superior in reducing hospital admission and avoiding death by suicide. The evidence for CMHT based care is insubstantial considering the massive impact the drive toward community care has on patients, carers, clinicians and the community at large.
|
CD000179
|
[
"12745558",
"16641396",
"16579803",
"21596735",
"3302193"
] |
[
"A randomised, double-blind placebo-controlled trial of ascorbic acid supplementation for the prevention of preterm labour.",
"Vitamins C and E and the risks of preeclampsia and perinatal complications.",
"Randomised trial of vitamin A supplementation in pregnant women in rural Malawi found to be anaemic on screening by HemoCue.",
"Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial.",
"Clinical trial of vitamin A supplementation in infants susceptible to bronchopulmonary dysplasia."
] |
[
"In a previous study from this institution, patients at high risk for preterm labour were screened for the presence of bacterial vaginosis (BV). When BV was present, they were randomised to receive either treatment (metronidazole) or placebo (vitamin C). There were significantly more patients with preterm labour in the metronidazole group. The aim of this double-blind randomised placebo-controlled trial study was to determine whether vitamin C could indeed reduce the recurrence risk of preterm labour. Patients with a history of preterm labour in a preceding pregnancy were randomised to receive 250 mg vitamin C or a matching placebo twice daily until 34 weeks' gestation. They attended a dedicated premature labour clinic. Significantly more women delivered before term in the group that received vitamin C, but there was no difference in the outcome of the babies between the two groups. Supplementation with vitamin C did not prevent premature labour.",
"Supplementation with antioxidant vitamins has been proposed to reduce the risk of preeclampsia and perinatal complications, but the effects of this intervention are uncertain.\n We conducted a multicenter, randomized trial of nulliparous women between 14 and 22 weeks of gestation. Women were assigned to daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or placebo (microcrystalline cellulose) until delivery. Primary outcomes were the risks of maternal preeclampsia, death or serious outcomes in the infants (on the basis of definitions used by the Australian and New Zealand Neonatal Network), and delivering an infant whose birth weight was below the 10th percentile for gestational age.\n Of the 1877 women enrolled in the study, 935 were randomly assigned to the vitamin group and 942 to the placebo group. Baseline characteristics of the two groups were similar. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia (6.0 percent and 5.0 percent, respectively; relative risk, 1.20; 95 percent confidence interval, 0.82 to 1.75), death or serious outcomes in the infant (9.5 percent and 12.1 percent; relative risk, 0.79; 95 percent confidence interval, 0.61 to 1.02), or having an infant with a birth weight below the 10th percentile for gestational age (8.7 percent and 9.9 percent; relative risk, 0.87; 95 percent confidence interval, 0.66 to 1.16).\n Supplementation with vitamins C and E during pregnancy does not reduce the risk of preeclampsia in nulliparous women, the risk of intrauterine growth restriction, or the risk of death or other serious outcomes in their infants. (Controlledtrials.com number, ISRCTN00416244.).\n Copyright 2006 Massachusetts Medical Society.",
"To assess the effects of vitamin A supplementation in women with anaemia during pregnancy.\n Single-centre randomised controlled trial.\n Rural community in southern Malawi, central Africa.\n Seven hundred women with singleton pregnancies at 12-24 weeks measured by ultrasound scan and with haemoglobin <11.0 g/dl by HemoCue screening method. Analysis was by intention to treat. All received iron and folate, and sulphadoxine/pyrimethamine for antimalarial prophylaxis.\n Women were randomised to receive oral supplementation with daily 5000 or 10,000 iu vitamin A, or placebo.\n Anaemia, as assessed by Coulter counter, severe anaemia, iron status and indices of infection.\n Vitamin A deficiency was, in this rural population, less common than predicted. Vitamin A supplementation had no significant impact on anaemia, severe anaemia, iron status and indices of infection. Vitamin A stores were less likely to be depleted at the end of pregnancy in supplemented groups.\n Vitamin A supplementation programmes to reduce anaemia should not be implemented in similar antenatal populations in rural sub-Saharan Africa unless evidence emerges of positive benefit on substantive clinical outcomes. Introducing public health interventions of unknown benefit and with unclear biological mechanisms can divert scarce resources from clinical and social interventions more likely to impact maternal mortality.",
"To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk.\n Randomised, blinded, placebo controlled clinical trial.\n Tertiary public hospital in Mexico City.\n Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery.\n Supplementation with a medical food-bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo-during pregnancy.\n Development of pre-eclampsia/eclampsia.\n 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ(2) = 19.41; P < 0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ(2) = 3.76; P = 0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P = 0.004; absolute risk reduction 0.09, 0.05 to 0.14).\n Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be evaluated in a low risk population to determine the generalisability of the protective effect, and the relative contributions of L-arginine and antioxidant vitamins to the observed effects of the combined treatment need to be determined. Trial registration Clinical trials NCT00469846.",
"We conducted a randomized, double-blind, controlled trial to determine whether vitamin A supplementation from early postnatal life could reduce the morbidity associated with bronchopulmonary dysplasia in very low birth weight (VLBW) neonates. Forty VLBW neonates (700 to 1300 g birth weight, 26 to 30 weeks gestational age), who were oxygen dependent and required mechanical ventilation for at least 72 hours after birth, were given by the intramuscular route either supplemental vitamin A (retinyl palmitate 2000 IU) or 0.9% saline solution on postnatal day 4 and every other day thereafter for a total of 14 injections over 28 days. The study groups were comparable in gestational maturity, clinical characteristics, initial lung disease, and vitamin A status at entry into the trial. Vitamin A administration resulted in significantly higher mean plasma concentrations of vitamin A and retinol-binding protein in treated infants compared with controls. Bronchopulmonary dysplasia was diagnosed in nine of 20 infants given vitamin A supplement and in 17 of 20 control infants (P less than 0.008). Four of 19 infants in the vitamin A group and 11 of 20 in the control group required mechanical ventilation on study day 28 (P less than 0.029). The need for supplemental oxygen, mechanical ventilation, and intensive care was reduced in infants given vitamin A supplement compared with controls. Airway infection and retinopathy of prematurity were less frequent in the vitamin A group. We conclude that vitamin A supplementation at the dosage used in this trial in VLBW neonates not only improves their vitamin A status but also appears to promote regenerative healing from lung injury, as evidenced by a decrease in the morbidity associated with bronchopulmonary dysplasia."
] |
There were few trials, reporting few clinical outcomes and mostly with unclear trial methodology and inadequate follow up. There is not enough evidence to detect clinical benefits of vitamin B6 supplementation in pregnancy and/or labour other than one trial suggesting protection against dental decay. Future trials assessing this and other outcomes such as orofacial clefts, cardiovascular malformations, neurological development, preterm birth, pre-eclampsia and adverse events are required.
|
CD008634
|
[
"1608408",
"16543297",
"20002510",
"15066200"
] |
[
"A randomized trial of a program to reduce the use of psychoactive drugs in nursing homes.",
"Effect of enhanced psychosocial care on antipsychotic use in nursing home residents with severe dementia: cluster randomised trial.",
"An evaluation of an adapted U.S. model of pharmaceutical care to improve psychoactive prescribing for nursing home residents in northern ireland (fleetwood northern ireland study).",
"An outreach intervention to implement evidence based practice in residential care: a randomized controlled trial [ISRCTN67855475]."
] |
[
"Although psychoactive medications have substantial side effects in the elderly, these drugs are used frequently in nursing homes. Few interventions have succeeded in changing this situation, and little is known about the clinical effects of such interventions.\n We studied six matched pairs of nursing homes; at one randomly selected nursing home in each pair, physicians, nurses, and aides participated in an educational program in geriatric psychopharmacology. At base line we determined the type and quantity of drugs received by all residents (n = 823), and a blinded observer performed standardized clinical assessments of the residents who were taking psychoactive medications. After the five-month program, drug use and patient status were reassessed.\n Scores on an index of psychoactive-drug use, measuring both the magnitude and the probable inappropriateness of medication use, declined significantly more in the nursing homes in which the program was carried out (experimental nursing homes) than in the control nursing homes (decrease, 27 percent vs. 8 percent; P = 0.02). The use of antipsychotic drugs was discontinued in more residents in the experimental nursing homes than in the control nursing homes (32 percent vs. 14 percent); the comparable figures for the discontinuation of long-acting benzodiazepines were 20 percent vs. 9 percent, and for antihistamine hypnotics, 45 percent vs. 21 percent. In the experimental nursing homes residents who were initially taking antipsychotic drugs showed less deterioration on several measures of cognitive function than similar residents in the control facilities, but they were more likely to report depression. Those who were initially taking benzodiazepines or antihistamine hypnotic agents reported less anxiety than controls but had more loss of memory. Most other measures of clinical status remained unchanged in both groups.\n An educational program targeted to physicians, nurses, and aides can reduce the use of psychoactive drugs in nursing homes without adversely affecting the overall behavior and level of functioning of the residents.",
"To evaluate the effectiveness of a training and support intervention for nursing home staff in reducing the proportion of residents with dementia who are prescribed neuroleptics.\n Cluster randomised controlled trial with blinded assessment of outcome.\n 12 specialist nursing homes for people with dementia in London, Newcastle, and Oxford.\n Residents of the 12 nursing homes; numbers varied during the study period.\n Training and support intervention delivered to nursing home staff over 10 months, focusing on alternatives to drugs for the management of agitated behaviour in dementia.\n Proportion of residents in each home who were prescribed neuroleptics and mean levels of agitated and disruptive behaviour (Cohen-Mansfield agitation inventory) in each home at 12 months.\n At 12 months the proportion of residents taking neuroleptics in the intervention homes (23.0%) was significantly lower than that in the control homes (42.1%): average reduction in neuroleptic use 19.1% (95% confidence interval 0.5% to 37.7%). No significant differences were found in the levels of agitated or disruptive behaviour between intervention and control homes.\n Promotion of person centred care and good practice in the management of patients with dementia with behavioural symptoms provides an effective alternative to neuroleptics.",
"To test the effect of an adapted U.S. model of pharmaceutical care on prescribing of inappropriate psychoactive (anxiolytic, hypnotic, and antipsychotic) medications and falls in nursing homes for older people in Northern Ireland (NI).\n Cluster randomized controlled trial.\n Nursing homes randomized to intervention (receipt of the adapted model of care; n=11) or control (usual care continued; n=11).\n Residents aged 65 and older who provided informed consent (N=334; 173 intervention, 161 control).\n Specially trained pharmacists visited intervention homes monthly for 12 months and reviewed residents' clinical and prescribing information, applied an algorithm that guided them in assessing the appropriateness of psychoactive medication, and worked with prescribers (general practitioners) to improve the prescribing of these drugs. The control homes received usual care.\n The primary end point was the proportion of residents prescribed one or more inappropriate psychoactive medicine according to standardized protocols; falls were evaluated using routinely collected falls data mandated by the regulatory body for nursing homes in NI.\n The proportion of residents taking inappropriate psychoactive medications at 12 months in the intervention homes (25/128, 19.5%) was much lower than in the control homes (62/124, 50.0%) (odds ratio=0.26, 95% confidence interval=0.14-0.49) after adjustment for clustering within homes. No differences were observed at 12 months in the falls rate between the intervention and control groups.\n Marked reductions in inappropriate psychoactive medication prescribing in residents resulted from pharmacist review of targeted medications, but there was no effect on falls.",
"The aim of this project was to assess whether outreach visits would improve the implementation of evidence based clinical practice in the area of falls reduction and stroke prevention in a residential care setting.\n Twenty facilities took part in a randomized controlled trial with a seven month follow-up period. Two outreach visits were delivered by a pharmacist. At the first a summary of the relevant evidence was provided and at the second detailed audit information was provided about fall rates, psychotropic drug prescribing and stroke risk reduction practices (BP monitoring, aspirin and warfarin use) for the facility relevant to the physician. The effect of the interventions was determined via pre- and post-intervention case note audit. Outcomes included change in percentage patients at risk of falling who fell in a three month period prior to follow-up and changes in use of psychotropic medications. Chi-square tests, independent samples t-test, and logistic regression were used in the analysis.\n Data were available from case notes at baseline (n = 897) and seven months follow-up (n = 902), 452 residential care staff were surveyed and 121 physicians were involved with 61 receiving outreach visits. Pre-and post-intervention data were available for 715 participants. There were no differences between the intervention and control groups for the three month fall rate. We were unable to detect statistically significant differences between groups for the psychotropic drug use of the patients before or after the intervention. The exception was significantly greater use of \"as required\" antipsychotics in the intervention group compared with the control group after the pharmacy intervention (RR = 4.95; 95%CI 1.69-14.50). There was no statistically significant difference between groups for the numbers of patients \"at risk of stroke\" on aspirin at follow-up.\n While the strategy was well received by the physicians involved, there was no change in prescribing patterns. Patient care in residential settings is complex and involves contributions from the patient's physician, family and residential care staff. The project highlights challenges of delivering evidence based care in a setting in which there is a paucity of well controlled trial evidence but where significant health outcomes can be attained."
] |
There is evidence to support the effectiveness of psychosocial interventions for reducing antipsychotic medication in care home residents. However, the review was based on a small number of heterogeneous studies with important methodological shortcomings. The most recent and methodologically most rigorous study showed the most pronounced effect.
|
CD007873
|
[
"22475493"
] |
[
"Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial."
] |
[
"Most previous studies of the use of cervical pessaries were either retrospective or case controlled and their results showed that this intervention might be a preventive strategy for women at risk of preterm birth; no randomised controlled trials have been undertaken. We therefore undertook a randomised, controlled trial to investigate whether the insertion of a cervical pessary in women with a short cervix identified by use of routine transvaginal scanning at 20-23 weeks of gestation reduces the rate of early preterm delivery.\n The Pesario Cervical para Evitar Prematuridad (PECEP) trial was undertaken in five hospitals in Spain. Pregnant women (aged 18-43 years) with a cervical length of 25 mm or less were randomly assigned according to a computer-generated allocation sequence by use of central telephone in a 1:1 ratio to the cervical pessary or expectant management (without a cervical pessary) group. Because of the nature of the intervention, this study was not masked. The primary outcome was spontaneous delivery before 34 weeks of gestation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00706264.\n 385 pregnant women with a short cervix were assigned to the pessary (n=192) and expectant management groups (n=193), and 190 were analysed in each group. Spontaneous delivery before 34 weeks of gestation was significantly less frequent in the pessary group than in the expectant management group (12 [6%] vs 51 [27%], odds ratio 0·18, 95% CI 0·08-0·37; p<0·0001). No serious adverse effects associated with the use of a cervical pessary were reported.\n Cervical pessary use could prevent preterm birth in a population of appropriately selected at-risk women previously screened for cervical length assessment at the midtrimester scan.\n Instituto Carlos III.\n Copyright © 2012 Elsevier Ltd. All rights reserved."
] |
The review included only one well-designed randomised clinical trial that showed beneficial effect of cervical pessary in reducing preterm birth in women with a short cervix. There is a need for more trials in different settings (developed and developing countries), and with different risk factors including multiple pregnancy.
|
CD005003
|
[
"9521264"
] |
[
"Randomized prospective study of early discontinuation of antiepileptic drugs in children with epilepsy."
] |
[
"We studied recurrence rate, risk factors for recurrence, and outcome after recurrence in children after early withdrawal of antiepileptic drugs (AEDs). One hundred sixty-one children with newly diagnosed epilepsy who had become seizure free within 2 months after starting treatment and remained so for 6 months were randomly assigned to immediate withdrawal of AEDs (n = 78) or continuation of treatment for another 6 months followed by withdrawal (n = 83). The probability of remaining seizure free at 24 months after randomization was 51% (95% CI, 40 to 62) in Group A and 52% (41 to 63) in Group B. Significant predictive factors for relapse were partial epilepsy, seizure onset at 12 years or older, defined etiology, and epileptiform EEG before randomization. At the end of follow-up (median, 41.9 months), 129 children (80.6%) had a terminal remission of at least 1 year, 88 without AEDs and 41 with AEDs. No significant difference in outcome was found between Groups A and B. In children with epilepsy and an early response to therapy, AED withdrawal after 6 or 12 months of treatment leads to seizure recurrence in approximately half of all patients regardless of the duration of therapy. More than 60% of those with one or more recurrences reach a terminal remission of at least 1 year after long-term follow-up with or without AEDs."
] |
In view of methodological deficiencies and small sample size, in the solitary study identified, we cannot derive any reliable conclusions regarding the optimal rate of tapering of AEDs. Further studies are needed in adults as well as in children to investigate the rate of withdrawal of AEDs and to study the effects of variables such as seizure types, its aetiology, mental retardation, EEG abnormalities, presence of neurological deficits and other co-morbidities on the rate of tapering.
|
CD008274
|
[
"3440987",
"20101007",
"14597860",
"10888969",
"9080920",
"1925430",
"6466017",
"12409965"
] |
[
"How useful is weight reduction in the management of hypertension?",
"Effects of the DASH diet alone and in combination with exercise and weight loss on blood pressure and cardiovascular biomarkers in men and women with high blood pressure: the ENCORE study.",
"Orlistat in hypertensive overweight/obese patients: results of a randomized clinical trial.",
"Exercise and weight loss reduce blood pressure in men and women with mild hypertension: effects on cardiovascular, metabolic, and hemodynamic functioning.",
"Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The Trials of Hypertension Prevention, phase II. The Trials of Hypertension Prevention Collaborative Research Group.",
"The effect of a weight reduction program on cardiovascular risk factors among overweight hypertensives in primary health care.",
"BP changes in obese hypertensive subjects during rapid weight loss. Comparison of restricted v unchanged salt intake.",
"Orlistat improves blood pressure control in obese subjects with treated but inadequately controlled hypertension."
] |
[
"A group of previously untreated obese hypertensive patients were started on a weight reduction programme supervised by two dietitians working in a general practice surgery. It was stressed from the beginning of the programme that reducing blood pressure was the purpose of the diet. The results of follow-up after six months are presented together with results for a control group of obese hypertensive patients not receiving dietary advice or drug therapy, but being followed by the general practitioner. The weight, systolic blood pressure and diastolic blood pressure of the dieting hypertensive group were significantly lower than those of the non-dieting group after six months. However, the drop-out rate was significantly higher for the dieting group than for the non-dieting group.The results of a separate comparison between a control group of obese normotensive patients following the same dietary programme and the group of dieting obese hypertensive patients are also presented. Attendance rates and weight loss achieved were significantly better for the hypertensive group than for the normotensive group after 12 months.Weight reduction appears to be an effective first-line therapy for approximately 50% of obese patients with mild to moderate hypertension, and raised blood pressure appears to provide motivation for such patients to attend a dietitian's clinic and to lose weight.",
"Although the DASH (Dietary Approaches to Stop Hypertension) diet has been shown to lower blood pressure (BP) in short-term feeding studies, it has not been shown to lower BP among free-living individuals, nor has it been shown to alter cardiovascular biomarkers of risk.\n To compare the DASH diet alone or combined with a weight management program with usual diet controls among participants with prehypertension or stage 1 hypertension (systolic BP, 130-159 mm Hg; or diastolic BP, 85-99 mm Hg).\n Randomized, controlled trial in a tertiary care medical center with assessments at baseline and 4 months. Enrollment began October 29, 2003, and ended July 28, 2008.\n Overweight or obese, unmedicated outpatients with high BP (N = 144).\n Usual diet controls, DASH diet alone, and DASH diet plus weight management.\n The main outcome measure is BP measured in the clinic and by ambulatory BP monitoring. Secondary outcomes included pulse wave velocity, flow-mediated dilation of the brachial artery, baroreflex sensitivity, and left ventricular mass.\n Clinic-measured BP was reduced by 16.1/9.9 mm Hg (DASH plus weight management); 11.2/7.5 mm (DASH alone); and 3.4/3.8 mm (usual diet controls) (P < .001). A similar pattern was observed for ambulatory BP (P < .05). Greater improvement was noted for DASH plus weight management compared with DASH alone for pulse wave velocity, baroreflex sensitivity, and left ventricular mass (all P < .05).\n For overweight or obese persons with above-normal BP, the addition of exercise and weight loss to the DASH diet resulted in even larger BP reductions, greater improvements in vascular and autonomic function, and reduced left ventricular mass.\n clinicaltrials.gov Identifier: NCT00571844.",
"To assess the effect of orlistat plus diet compared with diet alone in promoting weight loss and blood pressure reduction in hypertensive, overweight/obese patients.\n A pragmatic randomized, controlled trial.\n Hypertension clinic of a university hospital.\n Hypertensive patients aged 18-75 years with a body mass index greater than 25 kg/m(2).\n Orlistat 360 mg/day combined with a hypocaloric diet (treatment group), or a calorie-restricted diet alone (control group).\n Primary outcomes were reductions in weight and blood pressure. Secondary outcomes were decreases in lipid and glucose concentrations. A subgroup analysis of the main outcomes among diabetic and non-diabetic patients was also performed.\n A total of 204 patients were included in the intention-to-treat analysis. After 12 weeks the orlistat group lost, on average, 3.7 kg and the control group lost 2.0 kg in weight (P < 0.001). Systolic (SBP) and diastolic (DBP) blood pressures decreased by 15.3 and 11.4 mmHg, respectively, in the group given orlistat plus a hypocaloric diet and by 11.6 and 5.2 mmHg, respectively, in the control group given the calorie-restricted diet alone (P = 0.25 and P = 0.0004, respectively). Fasting glucose (0.82 and 0.17 mmol/l, P = 0.01) and total cholesterol (0.85 and 0.56 mmol/l, P = 0.05) were reduced to a greater extent with orlistat than with diet alone. The mean reduction in triglycerides with orlistat plus the hypocaloric diet was 0.75 mmol/l and that in the control group was 0.30 mmol/l (P = 0.28); the increases in high-density lipoprotein cholesterol were 0.05 and 0.00 mmol/l, respectively, in the two groups (P = 0.17). Treatment improved blood pressure and glucose control in the individuals with diabetes, but not in those without diabetes.\n In both groups there was a reduction in weight, blood pressure and metabolic parameters. The orlistat group performed better in reducing weight, DBP, glucose and cholesterol. Results show that even a small reduction in weight helps to control blood pressure and glucose. The cost-benefit of the use of orlistat should be evaluated for hypertensive obese patients.",
"Lifestyle modifications have been recommended as the initial treatment strategy for lowering high blood pressure (BP). However, evidence for the efficacy of exercise and weight loss in the management of high BP remains controversial.\n One hundred thirty-three sedentary, overweight men and women with unmedicated high normal BP or stage 1 to 2 hypertension were randomly assigned to aerobic exercise only; a behavioral weight management program, including exercise; or a waiting list control group. Before and following treatment, systolic and diastolic BPs were measured in the clinic, during daily life, and during exercise and mental stress testing. Hemodynamic measures and metabolic functioning also were assessed.\n Although participants in both active treatment groups exhibited significant reductions in BP relative to controls, those in the weight management group generally had larger reductions. Weight management was associated with a 7-mm Hg systolic and a 5-mm Hg diastolic clinic BP reduction, compared with a 4-mm Hg systolic and diastolic BP reduction associated with aerobic exercise; the BP for controls did not change. Participants in both treatment groups also displayed reduced peripheral resistance and increased cardiac output compared with controls, with the greatest reductions in peripheral resistance in those in the weight management group. Weight management participants also exhibited significantly lower fasting and postprandial glucose and insulin levels than participants in the other groups.\n Although exercise alone was effective in reducing BP, the addition of a behavioral weight loss program enhanced this effect. Aerobic exercise combined with weight loss is recommended for the management of elevated BP in sedentary, overweight individuals.",
"To provide a firmer basis for preventing high blood pressure (BP), we tested interventions to promote weight loss, dietary sodium reduction, and their combination for lowering diastolic BP, systolic BP, and the incidence of hypertension during a 3- to 4-year period.\n We conducted a randomized, 2 x 2 factorial, clinical trial, with BP levels measured by blinded observers. Nine academic medical centers recruited 2382 men and women (age range, 30-54 years) not taking antihypertensive drugs, with a diastolic BP of 83 to 89 mm Hg, a systolic BP lower than 140 mm Hg, and a body mass index (the weight in kilograms divided by the square of the height in meters) representing 110% to 165% of desirable body weight. Counseling aimed at helping participants achieve their desirable weight or a 4.5-kg or more weight reduction (in the weight loss and combined groups) and/or sodium intake of 80 mmol/d (in the sodium reduction and combined groups) was provided.\n From baseline, participants' weight decreased by 4.3 to 4.5 kg at 6 months and by approximately 2 kg at 36 months in the weight loss and combined groups compared with weight changes in the usual care group (all groups, P < .001). Sodium excretion decreased 50 and 40 mmol/d at 6 and 36 months, respectively, in the sodium reduction group and about 15 mmol/d less at each time point in the combined group compared with the usual care group (all groups, P < .01). Compared with the usual care group, BP decreased 3.7/2.7 mm Hg in the weight loss group, 2.9/1.6 mm Hg in the sodium reduction group, and 4.0/2.8 mm Hg in the combined group at 6 months (all groups, P < .001). At 36 months, BP decreases remained greater in the active intervention groups than in the usual care group (weight loss group, 1.3/0.9 mm Hg; sodium reduction group, 1.2/0.7 mm Hg; combined group, 1.1/0.6 mm Hg). Differences were statistically significant for systolic and diastolic BP in the weight loss group and for systolic BP in the sodium reduction group. Through 48 months, the incidence of hypertension (BP > or = 140 mm Hg systolic or > or = 90 mm Hg diastolic or the use of antihypertensive drugs) was significantly less in each active intervention group than the usual care group (average relative risks, 0.78-0.82).\n In overweight adults with high-normal BP, weight loss and reduction in sodium intake, individually and in combination, were effective in lowering systolic and diastolic BP, especially in the short-term (6 months). Although the effects on average BP declined over time, reductions in hypertension incidence were achieved.",
"The aim of the study was to test the effect of a nonpharmacological weight reduction program on cardiovascular risk factors among overweight hypertensives in a primary health care setting. Forty-nine overweight hypertensive patients completed the 12-month program. The patients were randomly allocated into either intervention or control groups. The examinations included interviews by a nutritionist, pertinent laboratory tests, and a medical examination. The intervention involved an individually planned energy-restricted diet of 1000-1500 kcal per day, weekly discussions, and various leaflets on diet modification and on increase of physical activity. The mean body weight was reduced by 5 kg in the intervention group, but remained unchanged in the control group. The intervention group reduced their fat intake by 14 g/day while the control group increased it by 9 g/day on the average. In the intervention group, the total serum cholesterol decreased, HDL-cholesterol increased and triglycerides decreased significantly. The systolic blood pressure fell by 8 mm Hg and 15 mm Hg in the intervention and control groups, respectively. The diastolic blood pressure fell on average by 11 mm Hg in both groups. The results demonstrate the comprehensive weight reduction program to be effective in the control of cardiovascular risk factors.",
"A controlled prospective study compared two groups of obese hypertensive subjects during 12 weeks of a hypocaloric protein-supplemented fast containing 40 mEq of sodium daily. One group received additional sodium chloride sufficient to maintain baseline sodium intake measured prior to the fast (210 m/Eq/day). Sodium restriction resulted in greater weight loss and slightly greater BP reduction only during the initial week of fasting. Thereafter, despite sodium equilibrium, further substantial weight loss and BP reduction were identical in both groups, the decrement in weight being linear (1.89 kg/wk) and the BP reduction asymptotic. Although the initial reduction in BP during the first week of supplemented fast may be attributable to negative salt and water balance, the further reduction in BP during a period of constant sodium balance must be caused by weight loss per se or by the triggering of other antihypertensive mechanisms associated with weight reduction.",
"To investigate the hypothesis that weight reduction with orlistat plus mild caloric restriction leads to better blood pressure control than diet alone in obese individuals with inadequately controlled hypertension. DESIGN This was a 1-year, prospective, randomized, double-blind, placebo-controlled, multicenter trial of orlistat plus diet versus placebo plus diet in obese hypertensives.\n Participants were randomized to receive either orlistat or placebo; all received a 600 kcal deficient diet with no more than 30% of calories from fat. Weight and blood pressure, lipid levels and fasting glucose and insulin levels were followed.\n Patients on orlistat experienced greater weight loss (-5.4 +/- 6.4 versus -2.7 +/- 6.4 kg, P< 0.001) and greater reduction in body mass index (-1.9 +/- 2.3 versus -0.9 +/- 2.2 kg/m2, P<0.001). Target weight loss, defined as > or= 5% body weight (BW), was obtained in more orlistat-treated patients than in the placebo group (46 versus 23%, P<0.001). Diastolic BP decreased more in orlistat-treated patients than in the placebo group (-11.4 +/- 8.3 versus -9.2 +/- 8.4 mmHg, P = 0.002). A greater percentage of orlistat-treated patients reached goal diastolic blood pressure (BP), defined as final diastolic BP< 90 mmHg or a reduction of at least 10 mmHg (67 versus 53%, P< 0.001). The orlistat-treated group had significantly greater reductions in total cholesterol ( P<0.001), low-density lipoprotein cholesterol (P = 0.001) and non-high-density lipoprotein cholesterol (P< 0.005) and target 30% cardiovascular risk reduction was obtained in more orlistat-treated patients (36.1 versus 24.0%, P< 0.04).\n A weight-loss program with orlistat is more effective than diet alone to lower blood pressure and results in greater cardiovascular risk reduction."
] |
In patients with primary hypertension, weight loss diets reduced body weight and blood pressure, however the magnitude of the effects are uncertain as a result of the small number of patients and studies that could be included in the analyses. It is not known whether weight loss reduces mortality and morbidity. No useful information on adverse effects was reported in the relevant trials.
|
CD002079
|
[
"12944571",
"8618283"
] |
[
"Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer.",
"Five-year followup of a prospective trial of radical cystectomy and neoadjuvant chemotherapy: Nordic Cystectomy Trial I. The Nordic Cooperative Bladder Cancer Study Group."
] |
[
"Despite aggressive local therapy, patients with locally advanced bladder cancer are at significant risk for metastases. We evaluated the ability of neoadjuvant chemotherapy to improve the outcome in patients with locally advanced bladder cancer who were treated with radical cystectomy.\n Patients were enrolled if they had muscle-invasive bladder cancer (stage T2 to T4a) and were to be treated with radical cystectomy. They were stratified according to age (less than 65 years vs. 65 years or older) and stage (superficial muscle invasion vs. more extensive disease) and were randomly assigned to radical cystectomy alone or three cycles of methotrexate, vinblastine, doxorubicin, and cisplatin followed by radical cystectomy.\n We enrolled 317 patients over an 11-year period, 10 of whom were found to be ineligible; thus, 154 were assigned to receive surgery alone and 153 to receive combination therapy. According to an intention-to-treat analysis, the median survival among patients assigned to surgery alone was 46 months, as compared with 77 months among patients assigned to combination therapy (P=0.06 by a two-sided stratified log-rank test). In both groups, improved survival was associated with the absence of residual cancer in the cystectomy specimen. Significantly more patients in the combination-therapy group had no residual disease than patients in the cystectomy group (38 percent vs. 15 percent, P<0.001).\n As compared with radical cystectomy alone, the use of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin followed by radical cystectomy increases the likelihood of eliminating residual cancer in the cystectomy specimen and is associated with improved survival among patients with locally advanced bladder cancer.\n Copyright 2003 Massachusetts Medical Society",
"Chemotherapy is widely used in patients with locally advanced bladder cancer but until now there has been no conclusive evidence that this therapy improves survival. The Nordic Cooperative Bladder Cancer Study Group conducted a randomized phase III study to assess the possible benefit of neoadjuvant chemotherapy in patients with bladder cancer undergoing radical cystectomy after short-term radiotherapy.\n Our trial included 325 patients with locally advanced stage T1 grade 3 or stages T2 to T4aNXM0 bladder cancer allocated randomly into a chemotherapy or no chemotherapy group (control). The chemotherapy schedule consisted of 2 cycles of 70 mg./m.2 cisplatin and 30 mg./m.2 doxorubicin with a 3-week interval between the cycles.\n After 5 years the overall survival rate was 59% in the chemotherapy group and 51% in the control group (p = 0.1). The corresponding cancer specific survival rate was 64 and 54%, respectively. In regard to treatment, no difference was observed for stages T1 and T2 disease, while there was a 15% difference in overall survival for patients with stages T3 to T4a disease (p = 0.03). In a multivariate analysis only chemotherapy and T category emerged as independent prognostic factors. The relative death risk for patients who received chemotherapy was 0.69 (95% confidence interval 0.49 to 0.98) compared to the control group after adjustment for the other tested factors.\n Neoadjuvant chemotherapy seems to improve long-term survival after cystectomy in patients with stages T3 to T4a bladder carcinoma, while no survival benefit was found for stages T1 to T2 disease."
] |
The analysis of this review suggests that there is an overall survival benefit with radical surgery compared to radical radiotherapy in patients with muscle-invasive bladder cancer. However, it must be considered that only three trials were included for analysis, the patients numbers were small and that many patients did not receive the treatment they were randomised to. It must also be noted that many improvements in both radiotherapy and surgery have taken place since the initiation of these trials.
|
CD005374
|
[
"1361594",
"11001866",
"2882288",
"4357135",
"1955002",
"10528036",
"10095821",
"8377957",
"3512282",
"10581660",
"2669218",
"10603129",
"6347108",
"1973472",
"7699528",
"3335948",
"16550943",
"14751699",
"1412112",
"16882819"
] |
[
"Comparison of oral-steroid sparing by high-dose and low-dose inhaled steroid in maintenance treatment of severe asthma.",
"Additive effects of prednisolone and beclomethasone dipropionate in patients with stable chronic obstructive pulmonary disease.",
"Effect of a single oral dose of prednisolone in acute childhood asthma.",
"Substitution of beclomethasone aerosol for oral prednisolone in the treatment of chronic asthma.",
"High-dose beclomethasone: oral steroid-sparing effect in severe asthmatic patients.",
"A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis.",
"The response to inhaled and oral steroids in patients with stable chronic obstructive pulmonary disease.",
"Methotrexate in the management of severe steroid dependent asthma.",
"High-dose inhaled budesonide in treatment of severe steroid-dependent asthma.",
"Steroid reversibility test followed by inhaled budesonide or placebo in outpatients with stable chronic obstructive pulmonary disease. The Danish Society of Respiratory Medicine.",
"Randomised controlled trial comparing prednisolone alone with cyclophosphamide and low dose prednisolone in combination in cryptogenic fibrosing alveolitis.",
"Prolonged versus standard prednisolone therapy for initial episode of nephrotic syndrome.",
"A double-blind, randomized clinical trial of methylprednisolone in status asthmaticus.",
"Randomised, double-blind, placebo-controlled trial of methotrexate in steroid-dependent asthma.",
"A multicenter study of alternate-day prednisone therapy in patients with cystic fibrosis. Cystic Fibrosis Foundation Prednisone Trial Group.",
"Intermittent versus long-term tapering prednisolone for initial therapy in children with idiopathic nephrotic syndrome.",
"Severe nasal polyposis and its impact on quality of life. The effect of a short course of oral steroids followed by long-term intranasal steroid treatment.",
"Doubling the dose of inhaled corticosteroid to prevent asthma exacerbations: randomised controlled trial.",
"Corticosteroids in acute severe asthma: effectiveness of low doses.",
"High-dose inhaled fluticasone does not replace oral prednisolone in children with mild to moderate acute asthma."
] |
[
"It is not clear whether high doses of inhaled steroids have a greater sparing effect than low doses on the requirement for systemic steroids. In a randomised, double-blind, multicentre study, we compared the effects of high-dose (1500 micrograms/day) and low-dose (300 micrograms/day) inhaled beclomethasone dipropionate (BDP) in patients with severe asthma requiring a daily oral prednisolone dose of 10-40 mg. During a 3-month run-in period, we tried to achieve optimum asthma control by means of oral steroid and inhaled BDP 300 micrograms/day. The patients were then allocated to high-dose (n = 71) or low-dose (n = 72) treatment by an independent observer who took into account various prognostic factors. BDP was administered by means of an aerosol inhaler with a spacer device. The dose of systemic steroid was reduced as much as possible during the 6-month study period while keeping the peak expiratory flow (PEF) constant and asthma clinically stable. There was no difference between the low-dose and high-dose treatment groups in the mean reduction in oral prednisolone dose achieved by the end of the study (5.2[ SD 7.9] vs 5.0 [9.4] mg/day). The maximum response to inhaled steroid was seen, however, only after several months' therapy in both groups. There were no differences between the groups in use of on-demand beta-agonist inhalations or in asthma symptoms, and PEF values were constant throughout the study. Both doses of BDP were well tolerated. High doses of inhaled steroid offer no further benefit over low doses in the maintenance treatment of severe steroid-dependent asthma when the inhaled steroid is administered with a spacer device.",
"It remains unclear whether inhaled corticosteroids can produce the maximum benefits of corticosteroids in patients with chronic obstructive pulmonary disease (COPD). To assess the additive effects of 30 mg/day prednisolone to high-dose, inhaled beclomethasone dipropionate (BDP), we conducted a randomised double-blind, placebo-controlled cross-over trial. The study population consisted of 21 men with stable COPD. The mean age of the patients was 69.1 +/- 6.8 years, and FEV(1)was 0.86 +/- 0.28 l. Seventeen out of the 21 patients (81%) were considered susceptible to steroids in a previous trial (FEV(1)increased at least 15% from baseline after receiving 14 days of 30 mg/day prednisolone). All of the patients had been on 1600 microg/day BDP for more than 3 months. Spirometry was performed before the entry, and at the end of 3-week placebo and prednisolone periods. The peak expiratory flow (PEF), symptoms, and Guyatt's Chronic Respiratory Disease Questionnaire (CRQ) as a disease specific health-related quality of life over the last seven days of each period were also evaluated. Although a marginal increase in PEF was found during the prednisolone period, no significant differences in FEV(1), FVC, symptoms or CRQ scores were observed between the two treatment periods. We conclude that the therapeutic effects of steroid therapy may be achieved by the long-term use of high-dose, inhaled corticosteroid in some patients with stable COPD.\n Copyright 2000 Academic Press.",
"140 children of 184 with acute asthma entered a randomised double-blind trial of oral prednisolone (n = 67) compared with placebo (n = 73) administered soon after admission. The dose of prednisolone was 30 mg in children under 5, otherwise 60 mg. All children also received salbutamol. All had moderate or severe dyspnoea. Initial evaluation was similar for both groups. On reassessment after a few hours 20 children in the prednisolone group were fit for discharge compared with only 2 in the placebo group. There were no early reattendances. Children remaining in hospital had a shorter median duration of stay and were less likely to require further steroid therapy if they had initially received prednisolone. In acute asthma the prompt use of a single dose of oral prednisolone can reduce morbidity and the need for hospital care.",
"In a double-blind study 10 patients with chronic asthma received beclomethasone dipropionate 400 mug daily in a Freon propellant from a pressurized dispenser, and 10 patients received the Freon propellant alone. At the start of the trial each patient was receiving long-term maintenance treatment with oral prednisolone in a dose of 7.5 to 15 mg daily. The daily dose of prednisolone was reduced by 1 mg every four weeks and the patient's progress followed by regular clinical assessment and studies of pituitary-adrenal function. The trial was continued until the dose of prednisolone was reduced to zero or until asthmatic symptoms increased to an unacceptable level.In the 10 patients who received beclomethasone the mean maintenance dose of oral prednisolone was reduced by 5.6 mg/day but in only two cases could this drug be withdrawn completely. In the placebo group the mean reduction in dose was only 1.3 mg, thus there was a significant difference between the two groups (P <0.01). Studies of pituitary-adrenal function showed that a normal adrenal response to tetracosactrin stimulation returned only in the two patients from whom prednisolone was withdrawn.Hence the addition of beclomethasone dipropionate by inhalation to systemic corticosteroid therapy allows useful reductions to be made in the oral maintenance doses of corticosteroid. Reductions must be made with caution since there is wide individual variation in response to beclomethasone and in only a minority of patients can oral treatment by completely withdrawn.",
"One hundred and twenty four patients with severe asthma requiring maintenance treatment with oral corticosteroids were included in a multicentre, double-blind, randomized study comparing the effects of inhaled beclomethasone dipropionate (BDP) (250 micrograms.puff-1), beginning with 1,000 micrograms daily, vs placebo (P). Pulmonary function was assessed and dosage of prednisone and BDP (or P) were adjusted every 15 days according to a clinical score. Our results showed, after 3 months: 1) A greater drop-out rate in the P group than in the BDP group (36 vs 6%, respectively, p less than 0.01); 2) A total weaning from prednisone in 76% of patients in the BDP group (mean BDP dosage = 1,270 +/- 340 micrograms.day-1, mean +/- SD), vs 34% in the P group (p less than 0.001). The mean daily dosage of prednisone was reduced from 17 +/- 7.5 mg to 3.1 +/- 7.4 mg in the BDP group vs 15.6 +/- 7.7 mg to 9.1 +/- 9.4 mg in the P group (p less than 0.001) without any relationship between the steroid-sparing effect and the initial dosage of prednisone; 3) Mean change in forced expiratory volume in one second (FEV1) was +7 +/- 21% from the initial value in the BDP group vs -6 +/- 20% in the P group; p less than 0.01. Thus, in patients with severe asthma requiring oral corticosteroids, high-dose BDP has an important oral steroid-sparing effect not related to the initial dosage of oral steroids and allows a better control of airway obstruction than oral corticosteroids alone.",
"Patients with idiopathic pulmonary fibrosis have progressive scarring of the lung and usually die within four to five years after symptoms develop. Treatment with oral glucocorticoids is often ineffective. We conducted an open, randomized trial of treatment with a combination of interferon gamma-1b, which has antifibrotic properties, and an oral glucocorticoid. We studied 18 patients with idiopathic pulmonary fibrosis who had not had responses to glucocorticoids or other immunosuppressive agents. Nine patients were treated for 12 months with oral prednisolone alone (7.5 mg daily, which could be increased to 25 to 50 mg daily), and nine with a combination of 200 microg of interferon gamma-1b (given three times per week subcutaneously) and 7.5 mg of prednisolone (given once a day).\n All the patients completed the study. Lung function deteriorated in all nine patients in the group given prednisolone alone: total lung capacity decreased from a mean (+/-SD) of 66+/-8 percent of the predicted value at base line to 62+/-6 percent at 12 months. In contrast, in the group receiving interferon gamma-1b plus prednisolone, total lung capacity increased (from 70+/-6 percent of the predicted value at base line to 79+/-12 percent at 12 months, P<0.001 for the difference between the groups). In the group that received interferon gamma-1b plus prednisolone, the partial pressure of arterial oxygen at rest increased from 65+/-9 mm Hg at base line to 76+/-8 mm Hg at 12 months, whereas in the group that received prednisolone alone it decreased from 65+/-6 to 62+/-4 mm Hg (P<0.001 for the difference in the change from baseline values between the two groups); on maximal exertion, the value increased from 55+/-6 to 65+/-8 mm Hg in the group that received combined treatment and decreased from 55+/-6 mm Hg to 52+/-5 mm Hg in the group given prednisolone alone (P<0.001). The side effects of interferon gamma-1b, such as fever, chills, and muscle pain, subsided within the first 9 to 12 weeks.\n In a preliminary study, 12 months of treatment with interferon gamma-1b plus prednisolone was associated with substantial improvements in the condition of patients with idiopathic pulmonary fibrosis who had had no response to glucocorticoids.",
"A significant minority of patients with COPD have favourable response to corticosteroid treatment. In addition, the benefit of corticosteroid treatment may be outweighed by the side-effects. Long-term administration of inhaled steroids is a safe means of treatment. However, only a few studies have addressed the role of inhaled steroids in patients with COPD, with conflicting results.\n Forty-four patients with stable COPD were defined as 'responders to bronchodilators' (increase in FEV1 > or = 20% following administration of beta 2-agonist) (group A), and 124 as 'non-responders to bronchodilators' (group B). All patients were randomized to receive a 6-week course of either a daily dose of 800 micrograms of inhaled budesonide or placebo, separated by 4 weeks when no medication was taken; were randomized again to receive a 6-week course of either 1600 micrograms day-1 of inhaled budesonide, or 800 micrograms day-1 of inhaled budesonide plus placebo; and were randomized once again to receive a 6-week course of either 40 mg day-1 of prednisone or placebo. All stages were performed in a double-blind cross-over design.\n Following administration of 800 micrograms day-1 of inhaled budesonide, there was an increase in the mean FEV1 from 1.40 +/- 0.20 to 1.92 +/- 0.22 L (P < 0.001) and a significant decrease in inhaled beta 2 agonist consumption in group A. These changes remained almost stable during the increased dose of inhaled budesonide or during prednisone treatment. The mean FEV1 did not change during the placebo period, or in group B in either treatments.\n Treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about one-quarter of patients with stable COPD, and this rate increased to about three-quarters in patients who responded to beta 2-agonist inhalation. There was no additional benefit in using a higher dose of inhaled budesonide or prednisone.",
"This study was designed to assess the efficacy of low dose methotrexate, 15 mg weekly, as a steroid-sparing agent in asthmatic patients requiring long-term oral prednisone treatment.\n The study was a randomised, double blind, placebo controlled, cross over study of 48 weeks duration. Eleven patients with severe steroid-dependent asthma were included. A successful outcome was defined as a reduction in mean prednisone requirements of 7 mg daily compared to baseline requirements, during active treatment.\n Two patients were required to be withdrawn owing to methotrexate-related adverse effects. The mean prednisone dose for patients who completed the study was 14.4 mg per day (95% CI; 13.6, 15.1) during active treatment, and 12.9 mg per day (95% CI: 12.2, 13.6) during placebo treatment (NS). Only one patient reduced his individual dose requirements by more than 7 mg per day, whereas in three patients prednisone requirements actually increased during active treatment. There were no significant differences in symptom scores, pulmonary function data, and exacerbations between active and placebo treatments.\n No significant steroid-sparing effect was obtained using low dose methotrexate in this study. This negative outcome may be attributable to the small population of patients studied, low baseline FEV1, and the omission of a steroid minimisation run-in period. Our results highlight the importance of careful patient selection and a painstaking approach in the management of patients with steroid-dependent asthma.",
"Forty-five steroid-dependent asthmatic outpatients were treated twice daily for 51 weeks with a new inhalation steroid, budesonide (BUD), using a 750 ml spacer. During the initial 15 weeks the prednisone-sparing effects of a high daily dose (1600 micrograms) and a conventional dose (400 micrograms per day) were compared in a double-blind randomized trial including 50 patients. During the remaining 36 weeks 45 patients were treated openly with 1600 micrograms daily. All patients used other antiasthmatic drugs which were maintained throughout the study, except for inhalations of beta-2 agonists that could be used whenever needed. All patients but 2 were able to reduce the daily dose of oral prednisone. The mean daily dose decreased from 13.9 mg to 5.3 mg. Eighteen patients (40%) were able to discontinue oral prednisone. Adrenal gland function improved considerably as prednisone intake decreased. Oropharyngeal thrush frequency showed no change. No severe side effects were observed.",
"The aim of this study was evaluate the predictive value of a 2 week course of prednisolone on the effect of 6 months treatment with inhaled budesonide in patients with stable chronic obstructive pulmonary disease (COPD). Forty patients with stable COPD entered the study, and received prednisolone (37.5 mg o.d.) for 2 weeks. They were subsequently divided into steroid-irreversible and steroid-irreversible, using 15% of baseline as a dividing point. In each group patients were randomized to receive budesonide 400 micrograms b.i.d. or placebo for 6 months. During treatment with prednisolone, three patients dropped out because of side effects. Of the remaining 37, only two patients (5%) were reversible with prednisolone forced expiratory volume in 1s [(FEV1) > 15% of baseline], and among the steroid-irreversible, 26 patients were evaluated after 6 months treatment with either placebo or budesonide. No significant differences in spirometry values, symptoms, or number of exacerbations were found between these two groups. Reversibility with prednisolone is rarely seen in COPD. In outpatients with stable COPD and no signs of asthma or atopy, 2 weeks treatment with prednisolone seems to be of no value in choosing subsequent long-term therapy.",
"In a randomised, controlled study alternate day prednisolone with an initial high dose phase (\"prednisolone only series\") has been compared with cyclophosphamide plus alternate day low dose prednisolone (\"cyclophosphamide-prednisolone series\") in 43 patients with previously untreated fibrosing alveolitis (five patients had received prednisolone in minimal dosage). In the prednisolone only series prednisolone 60 mg daily was given for one month and then reduced by 5 mg a week to 20 mg on alternate days or the minimum dose to maintain early improvement. Patients in the cyclophosphamide-prednisolone series received 100, 110, or 120 mg cyclophosphamide daily (depending on body weight) plus 20 mg prednisolone on alternate days. Treatment was continued indefinitely, or changed to the alternative regimen if the patient deteriorated, failed to improve, or developed drug toxicity. For response to treatment (as judged by change in breathlessness score, radiographic appearance, and lung function) patients were classified as improved, stable, or deteriorating. Deaths from cryptogenic fibrosing alveolitis were also analysed. Improvement had occurred at one or more assessments in seven of the 22 patients in the prednisolone only series and in five of the 21 patients in the cyclophosphamide-prednisolone series. At three years, however, only two of the 22 patients in the prednisolone only series were still improved and three stable, compared with one and seven of the 21 patients in the cyclophosphamide-prednisolone series (three of the seven had stopped treatment because of toxicity). Life table analysis suggested better survival in patients in the cyclophosphamide-prednisolone series but this was not significant. At three years 10 of 22 patients in the prednisolone only series had died compared with three of 21 patients in the cyclophosphamide-prednisolone series. With death or failure of first treatment regimen as outcome there was a significant advantage to the patients having cyclophosphamide-prednisolone. This advantage was explained in part by the better lung volumes in this group on admission. After allowance had been made for total lung capacity (TLC), no other factor was predictive of outcome. Analyses of subgroups according to TLC on admission showed that patients with a TLC below 60% predicted did badly and those with a TLC of 80% or more predicted did well with both regimens. Patients with an initial TLC of 60-79% predicted did better with the cyclophosphamide-prednisolone regimen. Side effects were uncommon in both series and those due to cyclophosphamide resolved when treatment was stopped. The combination of cyclophosphamide with prednisolone may be an alternative to prednisolone alone with an initial high dose phase. Many patients, however, failed to respond to either treatment.",
"We have examined, in a prospective randomized controlled trial, the effect of 8- and 16-week initial steroid treatment on the course of idiopathic nephrotic syndrome (INS). Patients with a first episode of INS were randomized to receive standard 8-week prednisolone (2 mg/kg daily for 4 weeks, then 1.5 mg/kg on alternate days for 4 weeks) or prolonged 16-week prednisolone treatment (2 and 1.5 mg/kg daily each for 4 weeks, then 1.5 and 1 mg/kg on alternate days each for 4 weeks). Relapses were treated with prednisolone, 2 mg/kg daily for 2 weeks, then 1.5 mg/kg on alternate days for 4 weeks. Of 45 patients, 23 received standard therapy and 22 prolonged therapy. The mean duration of follow-up was 29.2 and 27.3 months in the standard and prolonged treatment groups, respectively. The time to first relapse was longer in the prolonged treatment (mean 222.2 days, median 120.0 days) than the standard group (mean 134.3 days, median 96.5 days). The percentage of patients with no relapse at 6 and 12 months after prednisolone withdrawal was 40.9% and 27.3% in the prolonged treatment and 21.7% and 8.7% in the standard groups, respectively. The inability to show statistically significant differences between the two groups was probably related to the small number of patients studied. Prolonged therapy did not affect the subsequent relapse rates and proportion of patients with frequent relapses and steroid dependence. The mean dose of prednisolone received, for the initial episode and relapses during the next year, was higher and associated with significant steroid toxicity in the prolonged treatment group. Our findings suggest that 16-week prednisolone treatment for the initial episode of INS may delay occurrence of the first relapse, but results in significant side effects. Prolongation of initial therapy may be useful in developing countries where frequent infections often induce early relapses.",
"Twenty-five consecutive patients admitted with status asthmaticus were blindly randomized to receive intravenous (IV) methylprednisolone every six hours for three days at one of the following dosages: (1) low, 15 mg; (2) medium, 40 mg; or (3) high, 125 mg. All other therapy, including IV and inhaled bronchodilators, was kept constant. We measured forced expiratory volume in 1 s (FEV1) to quantitate response. The high-dose group improved significantly by the end of the first day, the medium-dose group improved by the middle of the second day, but the low-dose group did not improve significantly in three days. Together, the high- and medium-dose groups were significantly improved (FEV1 greater than 50% of predicted) compared with the low-dose group. No serious steroid side effects were encountered. We conclude that the greater benefit of higher doses of steroids, such as 125 mg of methylprednisolone every six hours, justifies their use in severe asthma.",
"69 patients with steroid-dependent asthma (mean daily prednisolone dose 14.2 [SD 6.1] mg) took part in a randomised, double-blind, placebo-controlled study of 24 weeks' treatment with methotrexate 15 mg weekly. The patients were seen every 4 weeks by the same physician, who reduced the daily prednisolone dose by 2.5 mg if the daily diary card variables and measurements of lung function were unchanged or improved. All other treatment remained unchanged. After 24 weeks of treatment the prednisolone dose had been reduced by a significantly greater proportion in the methotrexate than in the placebo group (50% vs 14%) and the reduction was not sustained after the study treatment stopped. There were substantial abnormalities in liver function tests in 5 of the 38 patients taking methotrexate.",
"The purpose of this study was to evaluate the efficacy and safety of alternate-day prednisone therapy in treating patients with mild-to-moderate cystic fibrosis during a 4-year period. In 15 North American cystic fibrosis centers, we screened 320 patients and enrolled 285 patients from April 1986 to December 1987. Patients were randomly assigned to take prednisone, 1 mg/kg per dose or 2 mg/kg per dose, or a matching placebo given on alternate days. Lung function, clinical status, hospitalizations, growth, and steroid side effects were monitored. During the first 24 months the percentage of the predicted forced vital capacity was greater in the 1 mg/kg group (p < 0.0001) and the 2 mg/kg group (p < 0.01) when each was compared with placebo. Patients in the 1 mg/kg group had a higher percentage of predicted forced vital capacity than placebo patients during the entire 48 months (p < 0.0025), but only in the group of patients who were colonized with Pseudomonas aeruginosa at baseline. For 48 months, the 1 mg/kg group had a higher percentage of predicted forced expiratory volume in 1 second than patients given placebo (p < 0.02). The prednisone-treated groups had a reduction in serum IgG concentrations (1 mg/kg vs placebo, p < 0.007; 2 mg/kg vs placebo, p < 0.003). From 6 months onward, height z scores fell in the 2 mg/kg group compared with those given placebo (p < 0.001). For the 1 mg/kg group, height z scores were lower from 24 months. An excess of abnormalities in glucose metabolism was seen in the 2 mg/kg group compared with the placebo group (p < 0.005). Our findings suggest a role for alternate-day prednisone therapy at a dose of 1 mg/kg in patients with mild to moderate cystic fibrosis. The benefit of improved lung function appears to outweigh the potential for adverse effects when the treatment period is less than 24 months.",
"Forty-six children with steroid-responsive nephrotic syndrome were randomly allocated to receive two different prednisolone regimens for initial therapy. Twenty-nine children (group 1) received an intermittent regimen (60 mg/m2/day for 4 weeks, followed by 40/mg/m2/day on 3 days a week for 4 weeks); 17 children (group 2) had a long-term regimen (60 mg/m2/day for 4 weeks, followed by the same dose on alternate days for 4 weeks and the doses tapered by 10 mg/m2, given on alternate days every 4 weeks for 5 months). There was no difference between the two groups in the regimen used to treat relapses, steroid responsiveness, number of patients with relapses, and frequency of toxic reactions to steroids. However, the number of patients with a relapse within 6 months after initial therapy and the number of those with frequent relapses or steroid dependence were significantly higher in group 1 than in group 2 (P less than 0.05 for both). The data indicate that the long-term tapering regimen appears to be both safe and preferable to the intermittent regimen for initial therapy in children with idiopathic nephrotic syndrome.",
"Nasal polyposis is not a life-threatening disorder but has a great impact on the quality of life. Steroids constitute the first line of treatment of nasal polyps. The aims of this study were to evaluate the quality of life in nasal polyp patients after: (1) a short course of oral steroids; and (2) a long-term treatment with intranasal steroids.\n Patients with severe nasal polyps received either oral prednisone (n = 60) or no steroid treatment (control group, n = 18) for 2 weeks. Patients treated with steroids were also followed-up and evaluated after 12, 24, and 48 additional weeks with intranasal budesonide treatment.\n Patients with nasal polyps showed worse scores on all SF-36 domains, except for physical functioning, compared to the Spanish general population. After two weeks, patients treated with oral prednisone demonstrated a significant improvement (p < 0.05) in all impaired QoL domains compared to both control group and baseline. The mental component summary (51.0 +/- 1.2, p < 0.05) and physical component summary (51.0 +/- 0.9, p < 0.05) were improved compared to both control group and baseline. The improvement of all SF-36 domains was sustained by intranasal budesonida (p < 0.05) after 12, 24, and 48 weeks. Nasal obstruction, sense of smell, and polyp size also improved after both the oral short course and the intranasal long-term steroids treatment (p < 0.05).\n These results suggest that the treatment with a short-course of oral steroids improves the quality of life of patients with severe nasal polyps and that this effect is maintained by a long-term treatment with intranasal steroids.",
"Asthma self-management plans that include doubling the dose of inhaled corticosteroid when the condition deteriorates improve asthma control. Whether doubling the dose of corticosteroid in isolation is effective is unknown. We undertook a randomised controlled trial to investigate the effects of doubling the dose of inhaled corticosteriods when asthma deteriorates.\n 390 individuals with asthma who were at risk of an exacerbation monitored their morning peak flow and asthma symptoms for up to 12 months. When peak flow or symptoms started to deteriorate, participants added an active or placebo corticosteroid inhaler to their usual corticosteroid for 14 days to produce a doubling or no change in dose. The primary outcome was the number of individuals starting oral prednisolone in each group.\n During 12 months, 207 (53%) started their study inhaler and 46 (12%) started prednisolone--22 (11%) of 192 and 24 (12%) of 198 in the active and placebo groups, respectively. The risk ratio for starting prednisolone was therefore 0.95 (95% CI 0.55-1.64, p=0.8).\n We recorded little evidence to support the widely recommended intervention of doubling the dose of inhaled corticosteroid when asthma control starts to deteriorate.",
"Although the need for corticosteroids in acute severe asthma is well established the appropriate dose is not known.\n The response to intravenous hydrocortisone 50 mg (low dose), 100 mg (medium dose), and 500 mg (high dose), administered every six hours for 48 hours and followed by oral prednisone, was compared in patients with acute asthma in a double blind randomised study. After initial emergency treatment with bronchodilators subjects received oral theophylline or intravenous aminophylline and nebulised salbutamol four hourly. Patients were given low, medium, or high doses of intravenous hydrocortisone and then 20, 40, or 60 mg/day respectively of oral prednisone with a reducing regimen over the following 12 days. Beclomethasone dipropionate, 400 micrograms twice daily by metered dose inhaler, was also started. Peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and visual analogue dyspnoea scores (VAS) were recorded daily in hospital and PEF and VAS twice daily after discharge for a total of 12 days.\n The 66 subjects (40 female) who completed the study had a mean (SD) age of 31(14) years. On presentation mean (SD) FEV1% predicted in the low (n = 22), medium (n = 20), and high dose (n = 24) groups was 17(13), 19(12), and 19(11) and after emergency bronchodilator treatment 32(20), 30(12), and 36(13). After 24 hours of treatment the respective post-bronchodilator FEV1% predicted values were 62(22), 62(23), and 65(28) compared with 71(24), 69(22), and 71(24) after 48 hours. No significant difference between the groups was detected. PEF and VAS improved with treatment over the 12 days but was not influenced by steroid dose.\n Hydrocortisone 50 mg intravenously four times a day for two days followed by low dose oral prednisone is as effective in resolving acute severe asthma as 200 or 500 mg of hydrocortisone followed by higher doses of prednisone.",
"Inhaled corticosteroids are not as effective as oral corticosteroids in school-aged children with severe acute asthma. It is uncertain how inhaled corticosteroids compare with oral corticosteroids in mild to moderate exacerbations.\n The purpose of this work was to determine whether there is a significant difference in the percentage of predicted forced expiratory volume in 1 second in children with mild to moderate acute asthma treated with either inhaled fluticasone or oral prednisolone.\n This was a randomized, double-blind controlled trial conducted between 2001 and 2004 in a tertiary care pediatric emergency department. We studied a convenience sample of 69 previously healthy children 5 to 17 years of age with acute asthma and forced expiratory volume in 1 second at 50% to 79% predicted value; 41 families refused participation. Albuterol was given in the emergency department and salmeterol was given after discharge to all patients, as well as either 2 mg of fluticasone via metered dose inhaler and valved holding chamber in the emergency department plus 500 microg twice daily via Diskus for 10 doses after discharge (fluticasone group, N = 35) or 2 mg/kg of oral prednisolone in the emergency department plus 5 daily doses of 1 mg/kg of prednisolone after discharge (prednisolone group, N = 34). We measured a priori defined absolute change in percent predicted forced expiratory volume in 1 second from baseline to 4 and 48 hours in the 2 groups. RESULTS. At 240 minutes, the forced expiratory volume in 1 second increased by 19.1% +/- 12.7% in the fluticasone group and 29.8% +/- 15.5% in the prednisolone group. At 48 hours, this difference was no longer significant (estimated difference: 4.0 +/- 3.4; P = .14). The relapse rates by 48 hours were 12.5% and 0% in the fluticasone group and prednisolone group, respectively.\n Airway obstruction in children with mild to moderate acute asthma in the emergency department improves faster on oral than inhaled corticosteroids."
] |
There is no evidence to support the long-term use of oral steroids at doses less than 10-15 mg prednisolone though some evidence that higher doses (≥ 30 mg prednisolone) improve lung function over a short period. Potentially harmful adverse effects e.g.. diabetes, hypertension, osteoporosis would prevent recommending long-term use at these high doses in most patients.
|
CD003162
|
[
"16549410",
"16446892",
"16151355",
"19410397"
] |
[
"Short-term efficacy of Epley's manoeuvre: a double-blind randomised trial.",
"Posture restrictions do not interfere in the results of canalith repositioning maneuver.",
"Effectiveness of treatments for benign paroxysmal positional vertigo of the posterior canal.",
"Are postural restrictions after an Epley maneuver unnecessary? First results of a controlled study and review of the literature."
] |
[
"Benign paroxysmal positional vertigo of the posterior canal (PC-BPPV) is a common vestibular disorder and can be easily treated with Epley's manoeuvre. Thus far, the short-term efficacy of Epley's manoeuvre for treatment of PC-BPPV is unknown.\n To evaluate the efficacy of Epley's manoeuvre for treatment of PC-BPPV 24 h after applying the manoeuvre.\n The short-term efficacy of Epley's manoeuvre was compared with a sham procedure in 66 patients with PC-BPPV by using a double-blind randomised study design.\n 24 h after treatment, 28 of 35 (80%) patients in the Epley's manoeuvre group had neither vertigo nor nystagmus on positional testing compared with 3 of 31 (10%) patients in the sham group (p<0.001).\n Epley's manoeuvre is shown to resolve PC-BPPV both effectively and rapidly.",
"Benign Paroxysmal Positional Vertigo (BPPV) is a frequent cause of dizziness and despite of the excellent results with its treatment, there is some controversy about management.\n To assess the efficacy of Epley Maneuver with and without post-maneuver restrictions.\n Prospective randomized.\n Fifty patients presenting BPPV of the posterior semicircular canal, treated with Epley Maneuver and divided into two groups: study group--23 patients--with post-maneuver restrictions, and control group--27 patients--without post-maneuver restrictions.\n No significant difference was found between the studied and the control group.\n Post-maneuver restrictions do not influence the efficacy of Epley Maneuver for BPPV management.",
"To determine which common, nonpharmacological, nonsurgical treatments are most effective for treatment of benign paroxysmal positional vertigo (BPPV).\n Prospective, randomized, sham-controlled.\n Patients (n = 124) with BPPV of the posterior semicircular canal.\n Tertiary care center.\n Random assignment to one of five groups: modified canalith repositioning maneuver (CRP), modified liberatory maneuver (LM), sham maneuver, Brandt and Daroff's exercise, and vertigo habituation exercises. Subjects received a standard educational lecture about BPPV and the purpose of the intervention. No vestibular-suppressant medication or special instructions for head positioning were used. Post-tests were given at 1 week after treatment and at approximately 3 months and 6 months later.\n Vertigo intensity and frequency.\n Multilevel analyses showed that vertigo decreased significantly after LM, CRP, and Brandt-Daroff exercise; those three groups did not differ significantly. The habituation group did not differ from sham, Brandt-Daroff, LM, or CRP groups. Changes in scores were maintained throughout the 6-month follow-up period.\n LM, CRP, and exercises are all effective interventions; patient education plus the sham maneuver, however, had some beneficial effect. These results support two possible mechanisms of BPPV: displaced otoconia and a neural mechanism affecting interpretation of semicircular canal signals.",
"Postural restrictions after canalith repositioning maneuvers (CRM) for benign paroxysmal positional vertigo of the posterior semicircular canal (p-BPPV) have no proven value and therefore most physicians regard them as unnecessary. The aim of this study was to assess the short-term efficacy of head and body movement limitations after a single Epley maneuver. A review of the literature was performed to assess the current level of evidence for the efficacy of postural restrictions.\n Sixty-four patients, median age 59 years (range 37-82 years), with p-BPPV, were allocated either to instructions for movement restrictions or free movements for 48 h after a single Epley maneuver. The minimization method was used for allocation to treatment. This procedure 'minimizes' the differences in the distribution of pre-specified prognostic factors (e.g. sex and age) between the two groups of treatment. Minimization was preferred over randomization which is not as effective in balancing baseline characteristics when the number of participants is small. Outcome was assessed by physician and patient reported measures (Dix-Hallpike test, subjective vertigo intensity in a 10-point scale, patient's assessment of improvement) within 1 week after treatment by an independent investigator. The level of statistical significance was 0.05.\n More patients with movement restrictions reported a subjective improvement after treatment (p=0.007). Ninety percent of patients with movement restrictions and 74.2% of patients with free movements had a negative follow up Dix-Hallpike test but the difference was not significant (p=0.108). The mean pre-treatment vertigo intensity was reduced from 6.07 and 5.97 to 1.18 and 2.86, respectively but the difference was not significant (p=0.122).\n Postural restrictions do not increase the efficacy of the canal-repositioning maneuver despite the fact that patients report a subjective improvement after post-procedural instructions. In the review of the literature, all studies except one conclude that postural restrictions are unnecessary. However, a number of methodological issues such as inadequate sample size are not addressed and more conclusive evidence is required. Based on current evidence, the use of postural restrictions after the canal-repositioning maneuver is unjustified."
] |
There is evidence that the Epley manoeuvre is a safe, effective treatment for posterior canal BPPV, based on the results of five mostly small randomised controlled trials with relatively short follow up. There is no good evidence that the Epley manoeuvre provides a long-term resolution of symptoms. There is no good evidence comparing the Epley manoeuvre with other physical, medical or surgical therapy for posterior canal BPPV.
|
CD005430
|
[
"16547328"
] |
[
"Randomised controlled trial of topical ciclosporin A in steroid dependent allergic conjunctivitis."
] |
[
"To evaluate the efficacy, safety, and therapeutic effect of topical ciclosporin A 0.05% as a steroid sparing agent in steroid dependent allergic conjunctivitis.\n Prospective, randomised, double masked, placebo controlled trial comparing signs, symptoms, and the ability to reduce or stop concurrent steroid in steroid dependent atopic keratoconjunctivitis and vernal keratoconjunctivitis using 0.05% topical ciclosporin A compared to placebo. Steroid drop usage per week (drug score), symptoms, and clinical signs scores were the main outcome measures.\n The study included an enrolment of 40 patients, 18 with atopic keratoconjunctivitis and 22 with vernal keratoconjunctivitis. There was no statistical significant difference in drug score, symptoms, or clinical signs scores between the placebo and ciclosporin group at the end of the treatment period. No adverse reactions to any of the study formulations were encountered.\n Topical ciclosporin A 0.05% was not shown to be of any benefit over placebo as a steroid sparing agent in steroid dependent allergic eye disease."
] |
There are no good quality randomized trials evaluating the effects of adjunct use of topical corticosteroids in bacterial keratitis. The only randomized trial we identified in the literature suffered from major methodological inadequacies.
|
CD002782
|
[
"288179",
"782777",
"11455374",
"16856902",
"3476237",
"11553111",
"10226723",
"3910338",
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"11029829",
"1756217",
"284065",
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"281356",
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"7005653",
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"4400348",
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"1790403",
"380773",
"12117087",
"7562728",
"9758424",
"1451289",
"9835826",
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"1059514",
"9692071",
"12502122",
"17394893",
"2403486",
"15857065",
"2589311",
"19298572",
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"3922338",
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"12889718",
"1623700",
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"4382492",
"6754242",
"16315637",
"8646872",
"15927814",
"9314656",
"295702",
"10640840",
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"6594021",
"15528909",
"16512765",
"16739545",
"11720074",
"1890532",
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"4405216",
"7822059",
"20653477",
"9087151",
"11908358",
"9555794"
] |
[
"Effect of flouride varnish (Duraphat) treatment every six months compared with weekly mouthrinses with 0.2 per cent NaF solution on dental caries.",
"Clinical study of an amine fluoride gel and acidulated phosphate fluoride gel.",
"Effects of combined application of antimicrobial and fluoride varnishes in orthodontic patients.",
"Benefit of \"one-stage full-mouth disinfection\" is explained by disinfection and root planing within 24 hours: a randomized controlled trial.",
"Effect of fluoride containing dentifrice, mouthrinsing, and varnish on approximal dental caries in a 3-year clinical trial.",
"Relative anti-caries efficacy of 1100, 1700, 2200, and 2800 ppm fluoride ion in a sodium fluoride dentifrice over 1 year.",
"Fluorosis risk in grade 2 students residing in a rural area with widely varying natural fluoride.",
"Three-year caries increments after fluoride rinses or topical applications with a fluoride varnish.",
"Effect of stannous fluoride treatments on the progression of initial lesions in approximal surfaces of permanent posterior teeth.",
"[Reduction of dental caries after two years with a combination of mouthwashes and topical fluorides].",
"Fluoride-releasing elastomerics--a prospective controlled clinical trial.",
"[The caries-protective efficacy of 2 fluoride varnishes in a 2-year controlled clinical trial].",
"The caries-preventive effect of amine fluorides and inorganic fluorides in a mouthrinse or dentifrice after 30 months of use.",
"Fluoride release and cariostatic ability of a compomer and a resin-modified glass ionomer cement used for orthodontic bonding.",
"Observations on dental caries in primary teeth after frequent fluoride toplications in a program involving other preventives.",
"A comparative study of fluoride-releasing composite resin and glass ionomer materials used as fissure sealants.",
"Randomized trial on fluorides and sealants for fissure caries prevention.",
"Albany topical fluoride study.",
"Prevalence and determinants of enamel fluorosis in Flemish schoolchildren.",
"Topical 5-fluorouracil has no additional benefit in treating common warts with cryotherapy: a single-centre, double-blind, randomized, placebo-controlled trial.",
"Risk factors for enamel fluorosis in a nonfluoridated population.",
"Three-year study of the effect of fluoride varnish (Duraphat) on proximal caries progression in teenagers.",
"Risk factors associated with fluorosis in a non-fluoridated population in Norway.",
"Effect of high-concentration ammonium and sodium fluoride rinses on dental caries in schoolchildren.",
"A 3-year clinical trial into the effect of fluoride content and toothpaste abrasivity on the caries inhibitory properties of a dentifrice.",
"Combined effects of a fluoride dentifrice and mouthrinse on the incidence of dental caries.",
"Caries-preventive effect of two concentrations of stannous fluoride mouthrinse.",
"[Double-blind randomized clinical study on treatment of warts with a fluorouracil-containing topical preparation (author's transl)].",
"Effect on caries of different fluoride prophylactic programs in preschool children. A two year clinical study.",
"Fluocinonide in an adhesive base for treatment of oral lichen planus. A double-blind, placebo-controlled clinical study.",
"In vivo inhibition of demineralization around orthodontic brackets.",
"One-week treatment with 0.5% fluorouracil cream prior to cryosurgery in patients with actinic keratoses: a double-blind, vehicle-controlled, long-term study.",
"[Cariostatic effect of Fluocaril; controlled clinical research].",
"Clinical cariostatic effectiveness of a NaF rinse in a low prevalence child population.",
"MFP versus stannous fluoride mouthrinses for prevention of decalcification in orthodontic patients.",
"Fluorides in community programs; a study of four years of various fluorides applied topically to the teeth of children in fluoridated communities.",
"Risk factors for enamel fluorosis in a fluoridated population.",
"Incremental rates of dental caries after repeated topical sodium fluoride applications in children with lifelong consumption of fluoridated water.",
"A randomized trial of sodium fluoride as a treatment for postmenopausal osteoporosis.",
"Flunisolide nasal spray for perennial rhinitis in children.",
"Evaluation of the efficacy and tolerability of 0.5% fluorouracil cream and 5% fluorouracil cream applied to each side of the face in patients with actinic keratosis.",
"Risk factors for dental fluorosis in pediatric dental patients.",
"Fluorosis risk from early exposure to fluoride toothpaste.",
"Topical fish oil in psoriasis--a controlled and blind study.",
"Reversal of incipient and radiographic caries through the use of sodium and stannous fluoride dentifrices in a clinical trial.",
"The anticaries effect of single and combined topical fluoride systems in school children.",
"Caries preventive effect of a fluoride-containing varnish (Duraphat) after 1 year's study.",
"Fluoride salts are no better at preventing new vertebral fractures than calcium-vitamin D in postmenopausal osteoporosis: the FAVOStudy.",
"Randomized trial evaluating a new 0.5% fluorouracil formulation demonstrates efficacy after 1-, 2-, or 4-week treatment in patients with actinic keratosis.",
"The prevalence of dental fluorosis in relation to water or salt fluoridation and reported use of fluoride toothpaste in school-age children.",
"Caries-preventive effect of fluoride dentifrices with and without anticalculus agents: a 3-year controlled clinical trial.",
"Amine fluoride/stannous fluoride and chlorhexidine mouthwashes as adjuncts to single-stage dental implants: a comparative study.",
"Risk of enamel fluorosis associated with fluoride supplementation, infant formula, and fluoride dentifrice use.",
"Long-term study of fluticasone propionate aqueous nasal spray in acute and maintenance therapy of nasal polyposis.",
"Cariostatic effect of daily use of a fluoride-containing lozenge compared to fortnightly rinses with 0.2% sodium fluoride.",
"Role of débridement and trifluridine (trifluorothymidine) in herpes simplex dendritic keratitis.",
"Effective treatment of actinic keratosis with 0.5% fluorouracil cream for 1, 2, or 4 weeks.",
"Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis.",
"A clinical investigation of the efficacy of three different treatment regimens for the control of plaque and gingivitis.",
"[Treatment of condyloma acuminatum with 0.5% 5-fluorouracil-solution, A double-blind clinical trial].",
"Use of topical ascorbic acid and its effects on photodamaged skin topography.",
"Slow-release sodium fluoride in the management of postmenopausal osteoporosis. A randomized controlled trial.",
"Dental fluorosis in permanent incisor teeth in relation to water fluoridation, social deprivation and toothpaste use in infancy.",
"Five-year double-blind fluoridated milk study in Scotland.",
"Effects of a chlorhexidine-fluoride-strontium rinsing program on caries, gingivitis and some salivary bacteria among Finnish schoolchildren.",
"Risk factors for enamel fluorosis in optimally fluoridated children born after the US manufacturers' decision to reduce the fluoride concentration of infant formula.",
"Treatment of periodontal disease in diabetics reduces glycated hemoglobin.",
"Clinical and radiographic effects of enamel matrix derivative in the treatment of intrabony periodontal defects: a 12-month longitudinal placebo-controlled clinical trial in adult periodontitis patients.",
"Caries clinical trial of fluoride rinses in a Danish Public Child Dental Service.",
"Comparative study of calcipotriene (MC 903) ointment and fluocinonide ointment in the treatment of psoriasis.",
"Efficacy and safety of a new triple-combination agent for the treatment of facial melasma.",
"Caries development after termination of a fluoride rinsing program.",
"The caries-preventive effects of full- and half-strength topical acidulated phosphate fluoride.",
"Prevalence of dental fluorosis in children from non-water-fluoridated Halmstad, Sweden: fluoride toothpaste use in infancy.",
"Clinical anticaries effect of repeated topical sodium fluoride applications by mouthpieces.",
"Comparative unsupervised clinical trial on caries inhibition effect of monofluorophosphate and amine fluoride dentifrices after 3 years in Strasbourg, France.",
"[Prevalence of dental fluorosis and additional sources of exposure to fluoride as risk factors to dental fluorosis in schoolchildren of Campeche, Mexico].",
"Efficacy and safety of fluticasone propionate 0.005% ointment in the treatment of psoriasis.",
"A novel method to control the balance of skin microflora Part 2. A study to assess the effect of a cream containing farnesol and xylitol on atopic dry skin.",
"The relationship between reported toothpaste usage in infancy and fluorosis of permanent incisors.",
"Effect of fluoride varnish (Duraphat) in preschool children.",
"Dystrophic psoriatic fingernails treated with 1% 5-fluorouracil in a nail penetration-enhancing vehicle: a double-blind study.",
"Fluoride varnish versus acidulated phosphate fluoride gel: a 3-year clinical trial.",
"The caries-preventive effect of a fluoride varnish in the fissures of the first permanent molar.",
"The relative anticaries effectiveness of three fluoride-containing dentifrices in Puerto Rico.",
"Periodontal debridement with povidone-iodine in periodontal treatment: short-term clinical and biochemical observations.",
"Fluoride dentifrice ingestion and fluorosis of the permanent incisors.",
"Skin benefits from continuous topical administration of a zinc oxide/petrolatum formulation by a novel disposable diaper.",
"Effectiveness of fortnightly tooth brushing with amine fluorides in caries-prone subjects.",
"A double-blind, vehicle-controlled paired comparison of halobetasol propionate cream on patients with plaque psoriasis.",
"A 24-month study comparing sealant and fluoride varnish in caries reduction on different permanent first molar surfaces.",
"Effects of daily rinsing and ingestion of fluoride solutions upon dental caries and enamel fluoride.",
"Enamel opacities and dental caries in children who used a low fluoride toothpaste between 2 and 5 years of age.",
"Efficacy of topical N-acetylcysteine in the treatment of meibomian gland dysfunction.",
"Fluticasone propionate aqueous nasal spray in the treatment of nasal polyposis.",
"A randomized clinical trial of the desensitizing efficacy of three dentifrices.",
"A randomized trial of acidified nitrite cream in the treatment of tinea pedis."
] |
[
"Recent studies have shown a high fluorine uptake in the enamel and a considerable caries reduction following the application of varnished containing fluoride. As the application is easy to carry out it may in certain situations serve as an alternative to other topical fluoride school programmes. The aim of the present study, therefore, was to compare the caries increment in schoolchildren exposed to a fluoride varnish (Duraphat) every six months and in children receiving the conventional weekly fluoride mouthrinsing programme with 0.2 per cent sodium fluoride over a two-year period. Two hundred 14-year-old children, divided into one test and one control group took part in the study. They were clinically and radiographically examined every year. Preexperimental data revealed no differences between the groups. During the experimental period the children in the fluoride varnish group developed a statistically significant lower number of new carious lesions compared with those in the mouthrinsing group. The difference in caries increment was about 30 per cent. Further clinical studies to compare the effects of various topical fluoride programmes are recommended.",
"This study compared caries inhibition in children by an amine fluoride and an acidulated phosphate fluoride when administered in a topically applied gel. In addition, the effects of applying amine fluoride daily and weekly were compared. Four hundred and sixty-eight children, ages 6 to 13, were randomly assigned to one of five treatment groups and received a total of five, 5-minute treatments. The treatment and interval between each of the five treatments were as follows:(A)acidulated phosphate fluoride daily, (B) amine fluoride daily, (C) amine fluoride weekly, (D) placebo daily, and (E) placebo weekly. When the children were examined for total Decayed, Missing, and Filled Surfaces (DMFS) increments 2 years later, no significant differences were observed. However, when the data were examined for effects of DMFS for specific tooth surface, significant restriction (61%) of occlusal increment was shown in the group which was treated with amine fluoride daily for 5 consecutive days as compared with the control group.",
"A randomized prospective clinical study, with 220 patients scheduled for fixed orthodontic therapy, was conducted to test the hypothesis that application of an antimicrobial varnish in combination with a fluoride varnish (group 1) is significantly more efficient in reducing white spot lesions on the labial surfaces than application of the fluoride varnish alone (group 2). The effects of the antimicrobial varnish on the occurrence of gingivitis and plaque formation were also studied. A third aim was to investigate whether white spot lesion development could be predicted early during treatment. The antimicrobial varnish significantly reduced the number of mutans streptococci in plaque during the first 48 weeks of treatment. This effect did not result in significantly less development of white spot lesions on the labial surfaces compared with the group receiving only the fluoride varnish application. There was however a clear trend that the combination of the antimicrobial and fluoride varnishes more effectively reduced the increments of new lesions on the maxillary incisors. It was speculated that this could be due partly to an inhibiting effect of the antimicrobial varnish in an area with low oral clearance (with low pH and loss of fluoride) and partly to an inhibiting effect of the varnish on mutans streptococci. No significant differences between the groups with respect to gingivitis and plaque were found. Lesion development was difficult to predict early after bonding, despite a number of caries-relevant parameters of orthodontic importance. The best predictors for white spot lesions at debonding were visible plaque and mutans streptococci (eg, the level of oral hygiene and thus the cariogenic challenge) around the appliance shortly after bonding.",
"The beneficial effects of the one-stage, full-mouth disinfection remain controversial in the scientific literature. This might be due to the fact that an entire mouth disinfection with the use of antiseptics has been confused with a full-mouth scaling and root planing. This parallel, single blind RCT study aimed to compare several full-mouth treatment strategies with each other.\n Seventy-one patients with moderate periodontitis were randomly allocated to one of the following treatment strategies: scaling and root planing, quadrant by quadrant, at two-week intervals (negative control, NC), full-mouth scaling and root planing within 2 consecutive days (FRP), or three one-stage, full-mouth disinfection (FM) protocols within 2 consecutive days applying antiseptics to all intra-oral niches for periopathogens using as antiseptics: chlorhexidine (FMCHX) for 2 months, amine fluoride/stannous fluoride for 2 months (FMF), or chlorhexidine for 2 months followed by amine fluoride/stannous fluoride for another 6 months (FMCHX+F). At baseline and after 2, 4, and 8 a series of periodontal parameters were recorded.\n All treatment strategies resulted in significant (p<0.05) improvements of all clinical parameters over the entire duration of the study. Inter-treatment differences were often encountered. The NC group nearly always showed significant smaller improvements than the two CHX groups. The differences between the FRP or FM groups, and the two CHX groups only sporadically reached a statistical significance.\n These observations indicate that the benefits of the \"OSFMD\" protocol are partially due to the use of the antiseptics and partially to the completion of the therapy in a short time.",
"The purpose of this study was to evaluate the separate effect of fluoride dentifrice, fluoride mouthrinsing and fluoride varnish on approximal dental caries. All 252 13-14-yr-old children at an elementary school were selected at random and divided among four groups for a 3-yr longitudinal study. Group 1 received a fluoride dentifrice for home care and a fluoride mouthrinse once a week. Group 2 received a fluoride dentifrice for home care and a placebo mouthrinse once a week. Group 3 received a fluoride dentifrice for home care and a fluoride varnish once every 3 months. Group 4 received a placebo dentifrice for home care and a fluoride rinse once a week. Fluoride rinsing did not give any additional effect compared with placebo-rinsing when a fluoride dentifrice was used for home care. Fluoride varnish gave a significant caries reduction compared with fluoride rinsing.",
"There is limited evidence from clinical trials on the dose response of sodium fluoride dentifrices at concentrations above 1100 ppm fluoride ion, with respect to caries efficacy. This randomized, double-blind study examined the anti-caries effectiveness of sodium fluoride dentifrices containing 1700 ppm, 2200 ppm and 2800 ppm fluoride ion relative to an 1100 ppm fluoride ion control. A population of 5439 elementary schoolchildren, aged 6-15 years, was recruited from an urban central Ohio area with a low fluoride content water supply (<0.3 ppm). Subjects were examined by visual-tactile and radiographic examination at baseline and after 1, 2, and 3 years of using the sodium fluoride dentifrices. Subjects were stratified according to gender, age and baseline DMFS scores derived from the visual-tactile baseline examination and randomly assigned to one of four treatment groups: 0.243% sodium fluoride (1100 ppm fluoride ion), 0.376% sodium fluoride (1700 ppm fluoride ion), 0.486% sodium fluoride (2200 ppm fluoride ion), and 0.619% sodium fluoride (2800 ppm fluoride ion). All products were formulated with the same fluoride compatible silica abrasive. Results after 1 year provided evidence of a positive sodium fluoride dose response. Compared to the 1100 ppm fluoride treatment group, the 1700 ppm fluoride treatment group had an 11.0% reduction in DMFS that was not statistically significant, while the 2200 ppm and 2800 ppm fluoride treatment groups showed statistically significant (P<0.05) reductions of 18.6% and 20.4%, respectively. The reductions in caries delivered by the higher fluoride dentifrices were present across all tooth surface types, but were most pronounced for occlusal surfaces. Results at years 2 and 3 were confounded by a concurrent fluoride rinse program, which involved portions of the study population. While the trends for the higher fluoride dentifrices observed at year 1 remained at years 2 and 3, the difference observed between treatments were substantially less and failed to reach statistical significance (P<0.05). Collectively, the data demonstrate that the 2200 ppm and the 2800 ppm fluoride treatments delivered statistically significantly greater caries efficacy than the 1100 ppm fluoride treatment. This large-scale clinical trial provides evidence of a positive statistically significant dose relationship between dental caries and sodium fluoride in a dentifrice at levels above 1100 ppm fluoride at year 1.",
"This pilot study was performed to determine the prevalence of dental fluorosis and the association between fluorosis and a number of risk factors in a group of second grade students in a rural, non-fluoridated area of Ontario, Canada.\n Of 1739 students screened during routine health surveillance, 1367 had erupted maxillary central incisors. Fluorosis was scored on these children using the Tooth Surface Index of Fluorosis (TSIF). A fluoride exposure questionnaire and water sample vial was sent home from school with each child.\n Valid responses were obtained for 752 children (55%). The prevalence of fluorosis in respondents was 23.3%, with 4.9% scoring TSIF of 2 or more. In bivariate analysis, several variables were significantly associated with the prevalence and/or severity of fluorosis. These included: water fluoride concentration, breast-feeding duration, professionally applied topical fluoride, fluoride supplement use, bottle-feeding, fluoridated mouthwash use, and early parental toothbrushing with toothpaste. In logistic regression analysis limited to children living at the current residence for 4 years or more, only four variables had significant independent effects. These were water fluoride concentration, breast-feeding duration, fluoride supplement use, and fluoridated mouthwash use.\n These findings indicate that fluorosis is an important concern in non-fluoridated areas. Fluoride supplements should not be recommended unless an independent home water test is performed. Breast-feeding for 6 months or more may protect children from developing dental fluorosis in the permanent incisors.",
"251 9-12-yr-old children completed a 3-yr, double-blind, clinical trial of two caries preventive fluoride programs. Caries increments and progression patterns were compared in two groups of children who rinsed every fortnight with a 0.2% NaF solution or received biannual topical applications with a fluoride varnish (Fluor-Protector). Clinically recorded mean DFS increments were 3.3 +/- 0.2 (SE) in the rinse group and 3.5 +/- 0.2 in the varnish group. In both groups nearly half of these increments were recorded in the occlusal surfaces of second molars. The mean incremental DFS recorded radiographically on approximal surfaces of posterior teeth were 1.1 +/- 0.2 and 1.5 +/- 0.2 in the rinse and varnish group, respectively. None of the inter-group differences were statistically significant (P greater than 0.05). Detailed analyses of the radiographic scores revealed a similar and extremely slow caries progression in the two study groups and they strengthened the conclusion of equal clinical efficacy of the two treatments. None of the fluoride programs had been able to change preestablished patterns of caries development among the children.",
"Bite-wing radiographs were used to determine the effect of three forms of topical SnF2 therapy on the progression of initial lesions in the approximal surfaces of permanent posterior teeth. Radiographs were taken annually over a four-year period. The subjects were schoolchildren, aged 12-14 yr, living in a low fluoride area. The professional application of a 10% SnF2 solution for 30 s, semi-annually for two yr, had no discernible effect on the development of the initial lesions. However, the home use of a SnF2 dentifrice did inhibit caries progression appreciably at all but one of the four time intervals in the study. The professional application of a 10% SnF2 solution for 30 s, semi-annually for two yr, combined with the home use of a SnF2 dentifrice, was the most effective treatment in retarding lesion development. Even without topical fluoride therapy, the rate of progression of initial approximal lesions was generally quite slow. In view of these findings, it would seem sound clinical practice to treat all initial lesions in approximal surfaces with topical fluoride therapy and delay placement of restorations until there is radiographic evidence of lesions reaching dentin.",
"The study's purpose was to evaluate the reduction of dental caries incidence by the association of two preventive methods. 246 students of both sexes aged from 7 to 11 years registered in \"Escola de Educação Básica da Universidade Federal de Uberlândia\" and living in the urbana area of Uberlândia, state of Minas Gerais, were examined. The sample was distributed into two groups: children from Group 1, which received a semestral topical application of Acidulated Fluor Phosphate at 1.23% and children from Group II, that besides the topical application above related (Group I) also received weekly mouthwashes of sodium fluoride aquesus solution at 0.2%. After two years of study DMFS index were tabled and statistically analysed. It was verified a reduction of 33.97% in the incidence of dental caries (in the permanent dentition). The difference between the Groups was significant at 5% level of confidence.",
"A prospective controlled clinical trial was undertaken to evaluate the effectiveness of stannous fluoride-releasing elastomeric modules (Fluor-I-Ties) and chain (Fluor-I-Chain) in the prevention of enamel decalcification during fixed appliance therapy. Forty-nine patients (782 teeth) were included in the experimental group, where the fluoride-releasing elastomerics were used. Forty-five patients (740 teeth) who received non fluoride-releasing elastomerics formed the control group. All patients had their elastomerics replaced at each visit. Enamel decalcification incidence and distribution were recorded using an index by direct clinical observation. In the control group enamel decalcification occurred in 73 per cent of patients and in 26 per cent of all teeth. In the experimental group the corresponding incidence was 63 and 16 per cent, respectively. The overall reduction in score per tooth produced by the fluoride-releasing elastomerics was 49 per cent, a highly significant difference (P < 0.001). A significant difference was seen in all but the occlusal enamel zones. The majority (over 50 per cent) of lesions occurred gingivally. The teeth most severely affected were the maxillary lateral incisors and mandibular second premolars. There was no difference in treatment duration between groups.",
"The aim of this randomized, double-blind study was to measure the cariostatic effect of Bifluorid 12 (VOCO GmbH), containing 6% sodium fluoride and 6% calcium fluoride and Laweflour-Schüttellack (LAW), containing 5% sodium fluoride in comparing of placebo varnish. The caries study included 400 schoolchildren, aged 12-14 years. The tests according to the DMFS were carried out by two independent examiners. The 400 children were divided into 3 test and 1 placebo group, each group consisting of 100 subjects. After two years there was a significant inhibition of caries increment in all test groups compared to placebo group. Percentage caries reduction ranged from 25 to 30%. The highest effect was stated at proximal surfaces.",
"The study groups using a dentifrice and mouthrinse both containing fluorides, a dentifrice containing stannous fluoride and a mouthrinse containing sodium fluoride, or a mouthrinse containing sodium fluoride with a placebo dentifrice had a 20.7% to 29.0% lower DMF increment than the control group after 30 months. These differences were significant. The study groups using a dentifrice containing amine fluorides and a placebo mouthrinse, a mouthrinse containing amine fluorides and a placebo dentifrice, or a dentifrice containing stannous fluoride and a placebo mouthrinse had a 13.6% to 22.4% lower DMF increment than the control group. These differences were not statistically significant. There was no significant difference in effectiveness against caries between the use of the organic or inorganic fluoride products.",
"The aims of this study were to compare the local and systemic uptake of fluoride released from a compomer material (Dyract Ortho) and a resin-modified glass ionomer cement (Vitremer) with that of a conventional resin adhesive (Right-On) and to compare the cariostatic ability of each of the test materials with that of the resin control.\n Twenty six patients were randomly allocated to have a bracket bonded to a premolar on one side of the arch with one of the test materials and on the opposite side with the control material. Premolars destined for extraction as part of an orthodontic treatment plan were selected for bonding. A non-fluoride toothpaste was used by all participants for 4 weeks prior to bracket bonding and throughout the 4 week trial period. Fluoride release was measured in saliva, plaque and urine samples taken pre-bonding and 4 weeks post-bonding. Enamel demineralisation was assessed by scoring the buccal surface of each extracted tooth using a caries index.\n Neither Vitremer nor Dyract Ortho altered salivary or urinary fluoride concentration significantly 4 weeks post-bonding but plaque fluoride concentration increased significantly around premolars bonded with Vitremer. The test materials as a combined group were associated with significantly less demineralisation than the control material but there was no significant difference in cariostatic ability detected between either Dyract Ortho or Vitremer when each group was compared separately with the control.\n Fluoride released from Dyract Ortho or Vitremer is likely to exert a local and not a systemic effect. In a 4-week clinical study, the cariostatic ability of the fluoride-releasing cements, as a combined group, was superior to that of the non-fluoride releasing control but there was no significant difference in cariostatic ability between the two test materials when each test group was compared separately with the control.",
"The anticaries effect of repeated toplications with APF gel was assessed in the primary dentition of 2-6-year-olds after 8, 18 and 28 months. Frequent, but less than daily, topical fluoride therapy appeared to have little effect in pre-school children consuming water-borne fluoride and receiving other traditionally recommended modalities of prevention.",
"The objectives of the study were to investigate the clinical use of two fluoride-releasing fissure sealants and to study fluoride release under laboratory conditions.\n In the clinical part of the study the two materials, FluroShield and Baseline, were applied to matched contralateral caries-free first permanent molars in 86 children aged 7-8 years. In the laboratory study fluoride release from each material was measured using a model cavity system.\n After 3 years FluroShield was intact on 70% of teeth. Retention was significantly better on lower molars than upper molars. Baseline was lost from all except two teeth within 6 months. After 3 years, caries had affected four teeth sealed with FluroShield and 24 teeth sealed with Baseline; this difference was highly significant. The laboratory study showed that FluroShield released twice as much fluoride over 9 days than did Baseline. Long term studies using FluroShield showed a small steady fluoride release over 6 months.\n The conclusion of the study was that FluroShield was a much more effective fissure sealant than Baseline. The clinical performance of FluroShield was comparable to that of other inert composite resin sealants and superior to that of fluoride-releasing sealants used previously.",
"To investigate the effectiveness of topical fluorides in preventing fissure caries, we conducted a randomized controlled trial with parallel groups. In total, 501 children (1,539 molars, 3,078 sites), mean age 9.1 years, who had at least one sound permanent first molar with deep fissures or fissures with signs of early caries were recruited. They were randomly allocated among four groups: (1) resin sealant, single placement; (2) 5% NaF varnish, semi-annual application; (3) 38% silver diamine fluoride (SDF) solution, annual application; and (4) placebo control. Follow-up examinations were conducted every 6 months by a masked examiner. After 24 months, 485 children (97%) were examined. Proportions of pit/fissure sites with dentin caries in the sealant, NaF, SDF, and control groups were 1.6%, 2.4%, 2.2%, and 4.6%, respectively. A multi-level logistic regression analysis accounting for the effects of data clustering and confounding factors showed that fissures in any of the three treatment groups had significantly lower risks of carious cavity development into dentin than did controls (p < 0.05). We concluded that placement of resin sealant, semi-annual application of NaF varnish, and annual application of SDF solution are all effective in preventing pit and fissure caries in permanent molars (ClinicalTrials.gov number CT01446107).",
"nan",
"As part of an epidemiological study on the oral health of Flemish schoolchildren, fluoride use was studied together with risk factors (medical history, tap water fluoride concentration, use of fluoride supplements, toothpaste and brushing habits). Fluorosis was scored according to the Thylstrup-Fejerskov index (TFI) in children aged 11 years (4,128 children examined). Explanatory variables were recorded yearly, starting at the age of 7. Earliest toothpaste use was reported at the age of 1. By age 7, 99.7% of the children reported the use of toothpaste (90% fluoride-containing), but only 13.9% reported using a pea-sized amount. At age 7, 66% of the children had received systemic fluoride supplements during at least part of their childhood. At 11 years, 92% of the children used a fluoride-containing toothpaste and 6% still received systemic fluoride supplements. Fluorosis was present in about 10% of all the children examined, mainly TFI score 1 (7.3% in upper central incisors). Logistic regression established tooth brushing frequency and fluoride supplement use, in addition to tap water fluoride concentrations above 0.7 mg/l, as significant risk factors when the presence of fluorosis on at least one tooth was used as outcome variable. Children having fluorosis had a lower risk of caries, both in the primary (median dmft 1, range 0-10 vs. 2, range 0-12) and permanent dentition (median DMFT 0, range 0-5 vs. 0, range 0-11).\n Copyright 2004 S. Karger AG, Basel",
"The role of topical 5-fluorouracil (5-FU) in treating common warts is not well defined. We tried to evaluate the efficacy and adverse effects of combination cryotherapy and topical 5% 5-FU ointment in the treatment of common warts. The study was a single-centre, double-blind randomized placebo-controlled trial. In the study, 80 patients with common warts were randomized into two groups and underwent two 10-second freeze/thaw cycles of cryotherapy with liquid nitrogen once every three weeks for a maximum of five treatments. Between treatments, patients applied either topical 5% 5-FU ointment (group A) or placebo aqueous cream (group B) twice daily. The mean +/- SD reduction in wart area was 58.57 +/- 0.06% in group A and 65.29 +/- 0.06% in group B. In total, 19 patients in group A and 24 patients in group B had wart size reduced by 75% or more (P = 0.50), while 12 patients in group A and 17 patients in group B had clearance of their warts (P = 0.245). Logistic regression with age, sex, smoking status, immune status, site, duration and number of warty lesions, history of previous treatment, and treatment group found that only a history of previous treatment and acral lesions were significant adverse predictors of improvement. There was no significant difference in the number of adverse events between the two groups, although there was a trend towards more pain and blistering associated with topical 5-FU. We concluded that topical 5-FU has no added benefit in treating common warts with cryotherapy.",
"The purpose of this case-control investigation was to investigate the possible association between mild-to-moderate enamel fluorosis and exposure during early childhood to fluoride supplements, fluoride toothpaste, and/or infant formula use in nonfluoridated communities. Analysis was performed on 460 10- to 13-year-old children, born after 1979, who were residents of six nonfluoridated communities in Massachusetts and Connecticut. The fluorosis status of the subjects was determined on the basis of a clinical dental examination using the Fluorosis Risk Index (FRI). Risk factor exposure was ascertained via a mailed questionnaire with a response rate of 90% and a questionnaire reliability of 87%. Logistic regression analyses revealed a moderate association between mild-to-moderate enamel fluorosis on early forming (FRI classification I) enamel surfaces and both fluoride supplement use (odds ratio (OR) = 2.25, 95% confidence interval (CI) 1.08-4.69) and early toothbrushing habits (OR = 2.56, 95% CI 1.34-4.88). There was a strong association between mild-to-moderate fluorosis on later forming (FRI classification II) enamel surfaces and both supplement use (OR = 7.97, 95% CI 2.98-21.33) and early toothbrushing habits (OR = 4.23, 95% CI 1.72-10.41). Infant formula was not found to be associated with fluorosis on either FRI classification I or II surfaces.",
"The effect of sodium fluoride varnish (Duraphat) applications on proximal caries progression was studied during a 3-yr period in 87 teenagers and compared to a control group (n = 107). In the fluoride varnish group the children were treated with fluoride varnish every third month during the experimental period. Caries lesions on the mesial surfaces of first premolars to the mesial surfaces of second molars were recorded annually on radiographs and an individual progression value was calculated. The study showed that topical application of fluoride varnish every third month significantly (P less than 0.05) reduced the progression of proximal caries lesions in premolars and molars. The most obvious reduction of caries progression was observed among children who developed between two and eight new proximal lesions during the test period. In the children with the highest caries activity (greater than nine new proximal lesions) Duraphat treatments did not significantly reduce proximal caries progression in premolars and molars.",
"In Norway, there is no water fluoridation and little naturally occurring fluoride in drinking water. Fluoride toothpaste is used by 95% of the population and there is a long tradition of fluoride supplement use. The purpose of this study was to record the prevalence and severity of dental fluorosis in 8-year-old children and relate this to systemic fluoride exposure (supplements and toothpaste). All children (n = 551, born 1988) in a municipality in Norway were invited to participate. Dental fluorosis on the buccal surface of the upper permanent incisors was recorded according to the Thylstrup-Fejerskov index (TF). Parents provided data on use of supplements and toothpaste. Complete data were obtained from 383 children. Sixty-seven percent of the children had used fluoride supplements regularly during childhood. At 8 months or earlier, the teeth of 26% of the children, and at age 14 months or earlier the teeth of 82%, were being brushed. Among children who used fluoride supplements regularly, periodically, seldom and not at all, 45%, 21%, 10% and 0%, respectively, had dental fluorosis. The dental fluorosis was mild (TF = 1) in 87% of the cases. Bivariate and multivariate analyses showed that, in addition to use of fluoride supplements, starting toothbrushing at an early age was associated with higher prevalence of dental fluorosis. The child's birth weight and liking for or swallowing of toothpaste did not influence the prevalence of fluorosis. Risk factors for fluorosis were use of toothpaste before the age of 14 months and regular use of fluoride supplements during childhood.",
"A double-blind clinical trial was conducted in a non-fluoridated community to determine the effect on enamel fluoride and caries experience of daily rinsing in school with 1,000 parts/10(6) solutions of ammonium fluoride or sodium fluoride at pH 4.4. Subjects were 10- to 12-year-old children (n approximately equal to 200/group at baseline), about one-half of whom reported the usage of fluoride supplements. Dental caries (DFS index) and enamel fluoride (in vivo biopsy) were evaluated at baseline, 12 months, and 24 months. Supplement users had higher enamel fluoride levels and less caries experience initially, as well as generally lower caries increments over the study. In year 1, the overall caries reductions (supplement users and non-users combined) were 23 % (ammonium fluoride) and 33 % (sodium fluoride), P less than 0.01. For year 2, treatment effects were significantly greater: 54 % (ammonium fluoride) and 47 % (sodium fluoride). In newly erupted teeth, the effects of the ammonium fluoride (70 % DFS reduction) was significantly greater (P = 0.013) than that of the sodium fluoride (48 % DFS reduction). Enamel fluoride levels at the end of 2 years were 3,124 parts/10(6) (ammonium fluoride), 2,771 parts/10(6) (sodium fluoride), and 2,603 parts/10(6) (placebo), P = 0.025.",
"The effect of reducing the abrasivity of toothpaste on dental caries was observed in a 3-year clinical trial involving 1106 11-13-year-old Berkshire schoolchildren were divided into three groups; Group 1 were allocated a low abrasivity paste containing 0.8% sodium monofluorophosphate, Group 2 a paste of conventional abrasivity also containing 0.8% sodium monofluorophosphate and Group 3 a low abrasivity non-fluoride paste. After 3 years the net DMFS increments (clinical and radiographic scores combined) were 4.22 in Group 1, 4.72 in Group 2 and 6.43 in Group 3. The differences between Groups 1 and 3 and between Groups 2 and 3 were highly significant (P less than 0.001). The mean increment in Group 1 was lower than in Group 2 but did not reach statistical significance. Reducing the abrasivity of the toothpaste had no meaningful effect on the standard of oral hygiene and prevalence of gingivitis as measured by the Gingival and Plaque Indices.",
"751 14- and 15-year old children completed a 3-year, double-blind, caries preventive program. The effects of daily, supervised toothbrushing with an 0.76% sodium monofluorophosphate dentifrice, rinsing with a 0.05% sodium fluoride mouthrinse, and the combined effects of the two treatments were investigated. Both the dentifrice and mouthrinse reduced the incidence of dental caries, but their combined use at the same time had no greater effect than either used alone.",
"The effectiveness of a stannous fluoride mouthrinse, when used once each school day, was investigated in a 3-year study. Effervescent stannous fluoride tablets of two concentrations were dissolved in 20 ml of water, giving solutions of 100 parts/10(6)F- and 200 parts/10(6)F- respectively. Approximately 1,200 children, with a mean age of 10 years, were divided on a random basis into three groups. Two of the groups rinsed with the two strengths of solution and the third group rinsed with a placebo. Examinations were carried out at the commencement of the study, and at yearly intervals thereafter. The final series was carried out a year after the rinsing procedures were terminated. There were significant reductions in the numbers of new caries in each of the two experimental groups as compared with the controls. The concentration of the solutions appeared to have little influence on the results. More dramatic reductions were noted in the teeth which erupted during the course of the study. A residual effect was demonstrated a year after the rinsing procedures were terminated.",
"In a double blind trial 60 patients were treated with a salicylic acid-containing product against warts (Verrumal) on basis fluorouracil in comparison to placebo. The trial demonstrated a statistically significantly better result for the verum preparation than for the placebo without fluorouracil and without salicylic acid. This product against warts is, therefore, indicated if operative methods are not applicable or refused by the patient.",
"376 three-year old children were divided into four experimental groups and exposed to different combinations of preventive programs for a period of two years. All the groups were given the same basic prophylactic information. Additionally Group I received fluoride tablets (FLUDENT) for daily sucking twice a day plus a placebo dentifrice free of fluoride. Group II was given a fluoride dentifrice containing 0.025% F, (ACTA). Group III was given a placebo dentifrice plus fluoride varnish (Duraphat) twice a year. Group IV a fluoride dentifrice containing 0.025% F (ACTA) plus fluoride varnish (Duraphat) twice a year. No statistically significant difference in caries increment during the two experimental years was found between the groups. A tendency to lower caries increment was found in Group IV, i.e. in the children using the low fluoride dentifrice and treated twice a year with fluoride varnish.",
"Patients with symptomatic oral lichen planus frequently require therapy to reduce signs and symptoms. For this purpose, corticosteroids are often applied topically. In a randomized, double-blind, placebo-controlled study, the efficacy of the topical application of 0.025% fluocinonide was evaluated. Forty consecutive patients with oral lichen planus diagnosed on the basis of histopathologic and immunofluorescence findings participated in this study. All patients were followed for 3 to 17 months. No adverse effects were noted during follow-up period. In the group of 20 patients that received the drug, 4 patients (20%) showed a complete remission, and 12 patients (60%) had a good or partial response to topical treatment. In the placebo-group, these figures were 0 and 6 (30%), respectively. The majority of the placebo-group (70%) did not respond at all with regard to signs (Xt2 = 10.4; p = 0.0013) and symptoms (Xt2 = 6.97, p = 0.008). The results from this study suggest that topical application of fluocinonide in an adhesive base is a safe and effective drug to reduce signs and symptoms in oral lichen planus.",
"Demineralization around orthodontic appliances is a problem. Suboptimal oral hygiene, long intervals between appointments, and potentially poor patient cooperation with using fluoride dentifrices and mouth rinses necessitate a compliance-free means of preventing tooth decay. The hypothesis of this study was that fluoride released by glass ionomer cement inhibits the formation of carious lesions around orthodontic brackets in vivo. Brackets were bonded on 2 first premolars in 21 randomized, consecutively selected patients 11 to 18 years old. Eleven test-group subjects were bonded with fluoride-releasing glass ionomer cement, and 10 control subjects were bonded with composite resin (no fluoride). The teeth were extracted after 4 weeks, sectioned, and evaluated quantitatively by cross-sectional microhardness testing. Fluoride levels in patient saliva were measured by the Taves diffusion method in samples taken at days 0 (baseline), 1, 2, 3, 7, 14, 21, and 28 to determine whether fluoride from the glass ionomer cement influenced the overall intraoral fluoride levels. The results demonstrated significantly more demineralization around the brackets of the control patients (P <.01, Wilcoxon signed rank test). For whole-mouth salivary fluoride levels, no significant overall difference between the groups (P >.05) and no noticeable trend within groups (P >.05) were found. These results indicate that using fluoride-releasing glass ionomer cement for bonding orthodontic brackets successfully inhibited caries in vivo. This cariostatic effect was localized to the area around the brackets and was statistically significant after 4 weeks.",
"Topical fluorouracil is currently approved for the treatment of actinic keratosis (AK) and is often used prior to or following cryosurgery as interval therapy in patients with severe AK lesions. No randomized, controlled studies are available to confirm anecdotal evidence suggesting pretreatment with fluorouracil is beneficial. This prospective, randomized, double-blind, vehicle-controlled study evaluated the effect of pretreatment with 0.5% fluorouracil cream (FC; Carac) or a vehicle cream (VC) once daily for 7 days to the face plus scalp, ears, neck, and/or lips in patients with > or = 5 visible or palpable AKs on the face prior to cryosurgery. Efficacy was determined by evaluating AK reduction and clearance (complete lack of AK lesions in the treatment area) at 4 weeks follow-up. Statistically significant decreases from baseline number of AKs were observed on all treatment areas in both groups. However, the mean number of facial AKs was significantly lower in the FC group at each treatment cycle (p = .011). No serious adverse events were considered related to treatment.",
"A controlled, double-blind trial on 42 children showed that a dentrifrice containing 0,25% fluorine clearly prevented caries when used continuously for 2 years. This effects was greater than that of a similar toothpaste containing fluorine. Tolerance was excellent.",
"Epidemiologic studies in which oral health in schoolchildren in the nonfluoridated city of The Hague has been monitored, have revealed a substantial decrease in caries prevalence since 1969 in groups of all socioeconomic status (SES). Because of a still significantly higher caries activity in children of lower socioeconomic classes, in 1981 a weekly fluoride mouthrinsing program in these children was started. The purpose of the present study was to investigate the cariostatic effectiveness of a weekly 0.2% neutral NaF rinse in children with low caries prevalence. A sample of 29 schools stratified according to SES and randomly assigned to two groups was selected. One group of schools (14) performed weekly rinsing and the other group (15) served as controls. After 3 yr the number of children available for re-examination had dropped from 501 to 333, of which 62.2% had written parental consent for radiographic examination. Statistical analysis of the data showed that fluoride rinsing could establish a reduction in caries incidence only in children who did not use fluoride tablets. The results of this study are of special interest for health authorities in planning and implementing public dental health measures.",
"Twenty-two orthodontic patients in the eleven to fifteen-year age-group participated in a one-year fluoride rinsing program. A 0.1 percent SnF2 solution was compared to a MFP solution containing an equivalent amount of fluoride. A laboratory study evaluated the enamel solubility reducing capacities of the two solutions. Enamel solubility reduction by a two-minute treatment with 0.1 percent SnF2 was 77.8 percent; that for MFP solution was only 13.1 percent. Rinsing daily with SnF2 prevented decalcification completely in twelve patients; two of ten patients rinsing with MFP developed new decalcification during orthodontic treatment. Thus, SnF2 was more effective than MFP in both the laboratory and clinical phases of the study. These results support the requirement for frequent applications, if patients are at advanced risk, and suggest that the method of treatment is at least as important as the choice of specific fluoride.",
"nan",
"The purpose of this case-control investigation was to investigate the possible association between mild-to-moderate enamel fluorosis and exposure during early childhood to infant formula, fluoride toothpaste, and/or fluoride supplements. Analysis was performed on 401 residents of fluoridated communities in Connecticut, who were 12-16 years old and born prior to 1980. The case and control subjects for this study were selected on the basis of a clinical examination given in 1991. Subject fluorosis status was determined using the Fluorosis Risk Index. Risk factor exposure was ascertained via a mailed questionnaire with a response rate of 89% and a questionnaire reliability of 87%. Logistic regression analyses, which adjusted for confounding variables, revealed that mild-to-moderate enamel fluorosis on early forming (Fluorosis Risk Index (FRI) classification I) enamel surfaces was strongly associated with both milk-based (odds ratio (OR) = 3.34, 95% confidence interval (CI) 1.38-8.07) and soy-based (OR = 7.16, 95% CI 1.35-37.89) infant formula use, as well as with frequent brushing (OR = 2.80, 95% CI 1.15-6.81). A very strong association was observed with inappropriate fluoride supplement use (OR = 23.74, 95% CI 3.43-164.30). Respectively similar associations were observed between mild-to-moderate enamel fluorosis on later forming (FRI classification II) enamel surfaces and frequent brushing and fluoride supplement use, but not with infant formula use.",
"nan",
"The anti-fracture efficacy of sodium fluoride (NaF) was evaluated in 84 postmenopausal white women with spinal osteoporosis. The dose of NaF used was 75 mg/day and all patients in this prospective, randomized, double-blind, placebo-controlled clinical trial received calcium supplements (carbonate salt) 1500 mg/day in addition to participating in a structured physical therapy program. For each of the outcome measures (change in stature, change in cortical bone mass in the forearm and development of new vertebral fractures determined by change in vertebral morphometry and by scintigraphy) there was no significant difference between the fluoride or placebo treated groups. Side effects, predominantly gastrointestinal symptoms and the development of the painful lower extremity syndrome, occurred significantly more frequently in the fluoride group (P less than 0.05). Peripheral fractures were not more frequent in the fluoride group. We conclude that, in the dose and manner used in this study, NaF is no more effective than placebo in retarding the progression of spinal osteoporosis. There is no role for NaF in the treatment of osteoporosis outside the confines of clinical research.",
"Twenty-seven children with perennial rhinitis entered a double-blind cross-over study comparing nasal sprays of flunisolide---a new topical corticosteroid---and placebo. Symptoms were assessed over two consecutive monthly periods with each treatment. Weekly diary cards, monthly clinical assessments, and end-of-trial preferences all favoured the active drug. At the end of the trial 20 patients preferred the treatment month with flunisolide, four preferred the placebo month, and two rated the periods equally. Side effects were mild, the commonest being transient nasal stinging. Seventeen children who derived benefit from flunisolide continued with the treatment for a six-month open-study period. Many reduced the dosage from three times to twice or once daily without losing benefit. The effect of flunisolide on the pituitary-adrenal axis was assessed in seven children by measuring the 0900 blood cortisol concentrations at two-month intervals over the six months. No effect was observed. The results show that flunisolide is effective and safe for the treatment and prophylaxis of perennial rhinitis in children.",
"A new 0.5% fluorouracil cream has been developed that provides an alternative to the more highly concentrated topical formulations of fluorouracil that are currently available.\n This was a comparison of the tolerability and efficacy of the 0.5% and 5% fluorouracil creams in the treatment of actinic keratosis (AK).\n During this single-blind, randomized study, patients with > or =6 AK lesions were treated for 4 weeks with the 0.5% (once daily) and 5% (twice daily) fluorouracil creams applied to opposite sides of the face. After the end of treatment, patients were followed for an additional 4 weeks. Efficacy variables included absolute and percent reductions in AK lesions from baseline and total clearance of AK lesions. A questionnaire was used to evaluate patients' treatment preferences. Tolerability was evaluated through continuous monitoring of adverse events.\n Treatment with 0.5% fluorouracil cream reduced the number of AK lesions from 11.3 at baseline to 2.5 at the end of the 4-week follow-up phase, compared with a reduction from 10.3 to 4.2 lesions after treatment with 5% fluorouracil cream. The reduction was significantly greater with the 0.5% cream compared with the 5% cream (P = 0.044). The 0.5% cream was as effective as the 5% cream in terms of the percent reduction in AK lesions from baseline (67% and 47%, respectively) and in achieving total clearance of AK lesions (both treatments, approximately 43% of patients). Both treatments were associated with similar degrees of investigator-rated irritation; however, patients preferred the 0.5% cream because they felt it was more tolerable (P = 0.003), easier to apply, and had a once-daily application schedule. Although all patients experienced facial irritation in association with both creams, fewer patients treated with the 0.5% cream reported symptoms of facial irritation.\n In this study, 0.5% fluorouracil cream once daily was at least as effective as 5% fluorouracil cream twice daily in terms of the percent reduction in AK lesions and total clearance of AK lesions; it was more effective than the 5% cream in reducing the absolute number of AK lesions from baseline. Patients preferred the 0.5% cream to the 5% cream.",
"Concerns have been raised recently about whether a substantial amount of dental fluorosis is resulting from the increased use of fluoride from various sources. The purposes of this study were to determine the prevalence and severity of dental fluorosis in a sample of pediatric patients seeking dental treatment in a university pediatric dental clinic and to evaluate sources of fluoride as risk factors for dental fluorosis.\n A convenience sample of 157 children aged 8 to 17 years were examined for dental fluorosis using the Tooth Surface Index of Fluorosis (TSIF). Fluoride history questionnaires assessing previous exposure to fluoride during the first eight years of life were completed by the children's parents. Fluoride exposures were compared among 54 cases and 54 matched controls using a case-control retrospective design.\n Fluorosis was found in 72 percent of the children, but was generally quite mild. The risk of fluorosis was significantly greater for children who had greater exposure to fluoridated water and who used larger amounts of fluoridated toothpaste up to age eight.\n This study provided evidence that increased use of fluoride toothpaste may be a risk factor for dental fluorosis. The results suggest prudent use of dentifrice by young children to minimize the risk of fluorosis.",
"Swallowed fluoride toothpaste in the early years of life has been postulated to be a risk factor for fluorosis, but the epidemiological evidence is weakened by the fact that most of the relevant studies were done in developed countries where an individual is exposed to multiple sources of fluoride.\n To quantify the risk of fluorosis from fluoride toothpaste in a population whose only potential source of fluoride was fluoride toothpaste.\n Case-control analyses were conducted to test the hypothesis that fluoride toothpaste use before the age of 6 years increased an individual's risk of fluorosis. Data came from a cross-sectional clinical dental examination of schoolchildren and a self-administered questionnaire to their parents. The study was conducted in Goa, India. The study group consisted of 1189 seventh grade children with a mean age of 12.2 years.\n The prevalence of fluorosis was 12.9% using the TF index. Results of the crude, stratified, and logistic regression analyses showed that use of fluoride toothpaste before the age of 6 years was a risk indicator for fluorosis (OR 1.83, 95% CI 1.05-3.15). Among children with fluorosis, beginning brushing before the age of 2 years increased the severity of fluorosis significantly (P<0.001). Other factors associated with the use of fluoride toothpaste, such as eating or swallowing fluoride toothpaste and higher frequency of use, did not show a statistically significant increased risk for prevalence or severity of fluorosis.\n Fluoride toothpaste use before the age of 6 years is a risk indicator for fluorosis in this study population.",
"Omega-3 polyunsaturated fatty acids compete with arachidonic acid as substrates for lipoperoxidases, which transform them into leukotrienes with low biological activity. As this process, in skin, may benefit psoriatic patients, a randomized controlled single blind-study was carried out on a sample of 25 patients. In the study fish oil (FO) was compared with liquid paraffin (LP); both were topically applied and administered daily for 6 h under an occlusive dressing over a 4-week period. Evaluations were performed weekly assessing erythema, scaling, plaque thickness (induration) and itching. The results showed statistically significant improvement in erythema and scaling for both treatments compared to basal values; significant differences between treatments were achieved in scaling but not in erythema. Compared to baseline, FO significantly improved plaque thickness while LP did not. After 4 weeks, FO proved to be significantly better than LP. All patients accepted the treatment despite its unpleasant smell. Irritation and a burning sensation were reported in the FO treated plaque of one patient. This adverse effect reverted after completing the treatment. These findings demonstrate that topical FO shows a better performance than LP under an occlusive dressing.",
"Experimental evidence has clearly demonstrated that the early stages of lesion formation (enamel demineralization) are reversible following exposure to saliva and/or fluoride. Clinical evidence for remineralization has also been reported extensively in the literature. However, the literature is lacking with respect to data from well-controlled clinical studies regarding the quantitative contribution of remineralization to arrestment and reversal of caries. Retrospective analysis of an existing clinical trial database provided an opportunity to examine the incidence of clinical lesion reversals in a placebo-controlled, double-blinded caries clinical study. The clinical study examined three treatment groups: 1) 0.243% sodium fluoride/silica dentifrice, 2) 0.4% stannous fluoride/calcium pyrophosphate (positive control) dentifrice and 3) non-fluoridated placebo/calcium pyrophosphate (negative control) dentifrice. Clinical measures in this study included both radiographic and visual-tactile assessments of caries. Examination of all subjects revealed a statistically greater frequency for caries reversals in the sodium fluoride group as compared to the placebo group at Year 3, for both total and radiographic caries. In contrast, while caries reversals in the stannous fluoride group occurred with greater frequency than in the placebo group at Year 3, for both total and radiographic caries, the differences were not statistically significant. When only subjects who were \"at risk\" for potential reversals (i.e., those with a minimum of one carious lesion at baseline) were examined, a statistically greater frequency in caries reversals was observed in both the sodium fluoride (total, incipient, and radiographic caries) and stannous fluoride (total and radiographic caries) groups as compared to the placebo group at Year 3. Collectively, these data confirm the ability of both 0.243% sodium fluoride/silica and 0.4% stannous fluoride/calcium pyrophosphate dentifrices to clinically reverse caries. The results suggest that sodium fluoride may deliver a greater frequency of caries reversals than stannous fluoride, although these treatments were not found to be significantly different.",
"nan",
"The caries prophylactic effect of semi-annual applications of a fluoride-containing varnish (Duraphat) was tested in 121 15-year-old children. The children were divided into a test (60 subjects). The teeth of the children in the test group were coated with fluoride varnish at the beginning of the experimental period and again 6 months later. A clinical and radiographic examination of all children was performed immediately prior to the first application of varnish and 1 year later. The mean caries increment was 0.9 new DMFS in the test group and 4.0 in the control group. The difference was statistically significant at the 0.1% level. The caries prophylactic effect on different tooth surfaces was statistically significant both on proximal and on occlusal surfaces at the 0.1% level. Analyzing the material with respect to the caries prophylactic effect against the background of caries prevalence at the start of the investigation showed a better effect in the group of children with low and medium initial DMFS values.",
"Although fluoride salts have been shown to be capable of linearly increasing spinal bone mineral density (BMD) in postmenopausal osteoporosis, the effects of this gain in density on the vertebral fracture rate remain controversial. We conducted a 2-year multicenter, prospective, randomized, double-masked clinical trial in 354 osteoporotic women with vertebral fractures (mean age 65.7 years). They received either fluoride (208 patients), given as sodium fluoride (50 mg/day) or as monofluorophosphate (200 mg/day or 150 mg/day), or a placebo (146 patients). All patients received daily supplements of 1 g of calcium (Ca) and 800 IU of vitamin D2 (D). A 1-year open follow-up on Ca-D was obtained in 124 patients. After 2 years the fluoride group and the Ca-D group had increased their lumbar BMD by 10.8% and 2.4% respectively (p = 0.0001). However, the rate of patients with at least one new vertebral fracture, defined by semiquantitative assessment and evaluable on an intention-to-treat basis in 89% of patients, was similar in the fluoride groups and the Ca-D group. No difference between the three fluoride regimens was found. The percentage of patients with nonvertebral fractures was not different in the fluoride and Ca-D groups (1.9% and 1.4% respectively for hip fractures). A lower limb pain syndrome occurred more frequently in the fluoride groups. In the 124 patients followed for 1 year after cessation of fluoride therapy, the percentage of patients with at least one new vertebral fracture after 36 months was identical to the percentages in the previous fluoride group and the Ca-D group. We conclude that fluoride-Ca-D regimen was no more effective that Ca-D supplements for the prevention of new vertebral fractures in women with postmenopausal osteoporosis.",
"The efficacy and safety of a new 0.5% fluorouracil topical cream were compared with vehicle control for the treatment of actinic keratosis (AK). Active treatment applied once daily for 1, 2, or 4 weeks was more effective than vehicle control in achieving reduction from baseline in lesion counts and lesion clearance. Active treatment also resulted in significantly better global assessments of overall improvement. Treatment was effective regardless of the number of baseline lesions. Although longer treatment duration correlated with greater efficacy, treatment for 1, 2, or 4 weeks was effective. This new microsphere-based fluorouracil formulation was generally well tolerated; adverse events were primarily limited to facial irritation that resolved quickly after treatment. This new treatment provides a safe alternative to the topical fluorouracil formulations currently available for the 1-, 2-, or 4-week treatment of AK.",
"To compare prevalence of dental fluorosis (DF) in permanent teeth in children whose domestic water supply was fluoridated since birth with that in a community where fluoridated salt was available. A second aim was to analyse the relationship between DF prevalence and reported use of fluoride toothpaste in early childhood.\n Cross-sectional study.\n A representative, random sample of 12-year-old children was examined in water fluoridated Dublin (Ireland) and non-water fluoridated Freiburg (Germany), where fluoridated salt was available. DF was recorded using the Dean's Index. The child's early experience of toothpaste use was recorded using a questionnaire.\n 377 children in Dublin and 322 children in Freiburg were examined. In Dublin 11.7% of the whole sample had a 'Questionable' level of DF, 9.8% had 'Very Mild', 3.7% had 'Mild' and 0.3% had 'Moderate' fluorosis. The corresponding percentages in Freiburg for all children were 10.9%, 4.0%, 3.4% and 0%. The results suggest that children in Dublin started brushing their teeth at an older age than in Freiburg, but no difference in DF levels was found between 'early' and 'late' users.\n Fisher's test revealed that the difference in DF levels between the two populations was statistically significant (p=0.03).\n The prevalence of aesthetically important DF ('Mild' and 'Moderate') was low and similar in both communities and considerably lower than the expected level at water fluoridation concentrations of 1 ppm. However, the prevalence of 'Very Mild' fluorosis was twice as frequent in Dublin than in Freiburg.",
"A 3-year, double-blind, randomized caries trial was conducted to evaluate the relative anticaries efficacy of four sodium fluoride dentifrices containing 250 ppm fluoride, 1,000 ppm fluoride in combination with 1% disodium 1-hydroxyethylidene-1.1-bisphosphonate (HEBP), and 1,000 ppm fluoride in combination with 1% disodium azacycloheptylidene-2.2-bisphosphonate (AHBP). As a positive control, a monofluorophosphate dentifrice (1,000 ppm fluoride) was used. At outset 1,161 Icelandic children, 11 and 12 years of age, were randomly assigned to one of the five treatment groups and 1,035 subjects completed the trial. After 3 years of unsupervised brushing, the dentifrice containing 250 ppm fluoride was significantly less effective in controlling the caries increment. The combination of sodium fluoride and AHBP was significantly more effective than the positive control.",
"The growing popularity of non-submerged dental implants in recent years requires a greater emphasis on microbial plaque control. Chlorhexidine (CHX), the most commonly used mouthwash in implant surgery, is sometimes associated with tooth staining and alteration in taste perception. Amine fluoride/stannous fluoride (AmF/SnF2) mouthwash has been shown to have anti-infective properties; however, it has not been tested as an adjunct anti-infective means in non-submerged dental implants. The purpose of this trial was to compare AmF/SnF2 and CHX mouthwashes as adjuncts to single-stage dental implants.\n Thirty-three patients aged 34 to 79 (mean 54.30 +/- 8.69 SD) requiring dental implants were accepted into the study. Following comprehensive periodontal therapy patients received one to three non-submerged dental implants (maxilla: 17; mandible: 45; anterior: 3, posterior: 59). After surgery patients were given analgesics and antibiotics as well as 2,400 ml of coded mouthwash bottles previously randomized between the two above mentioned formulations. Clinical and radiographic parameters were recorded at baseline and 3 and 12 months post-surgery.\n Twelve-month survival rates were 100% and 92.9% for the AmF/SnF2 and CHX groups, respectively. Compliance was slightly higher in the AmF/SnF2 group (84.35% +/- 3.39% versus 78.15% +/- 4.59% SE) but statistically similar. There was no statistically significant difference between the AmF/SnF2 and CHX groups in staining index at 3 months (1.519 +/- 0.22 versus 1.457 +/- 0.24 SE) and patient subjective evaluation of the mouthwashes. Radiographic bone loss was 0.79 +/- 0.23 and 1 +/- 0.13 SE at 3 months and 1.06 +/- 0.13 and 1.27 +/- 0.25 at 12 months for the CHX and AmF/SnF2 groups, respectively; the difference was statistically insignificant (P = 0.388 and 0.504, respectively).\n Both CHX and AmF/SnF2 mouthwashes can be used post-surgically after one-stage implant surgery.",
"Eight hundred fifty 11- to 14-year-old residents of nonfluoridated communities in Massachusetts and Connecticut, who were born between 1972 and 1975, were investigated in a case-control study of the possible association between enamel fluorosis and exposure to fluoride supplements, infant formula, and/or fluoride dentifrice. The effect of median household income, an indicator of socioeconomic status, was also examined. Clinical examination, using the Fluorosis Risk Index, a fluorosis index developed for this project, allowed cases and controls to be identified based upon the specific time period of exposure to the various sources of ingested fluoride. Risk factor exposure was assessed via a mailed questionnaire with a response rate of 80%. Mild-to-moderate enamel fluorosis was strongly associated with fluoride supplementation during the first six years of life (odds ratio = 4.0) and with median household income (odds ratio = 6.6). Subjects in the middle median household income group who had used fluoride supplements through the first six years of life had a 28-fold increase in the risk of fluorosis compared with unexposed subjects in the lower median household income group. An odds ratio of 1.7 associated with infant formula use was suggestive of an increased risk of enamel fluorosis as was an odds ratio of 2.9 associated with fluoride dentifrice use.",
"Topical steroids are first-line medication to control nasal polyposis (NP), a disease with long-term clinical course.\n The aim of this study was to evaluate the efficacy and safety of fluticasone propionate aqueous nasal spray (FPANS) 200 microg twice a day (bd) after 1 month of treatment, and to compare FPANS 200 microg bd and FPANS 200 microg once a day (od) in maintenance and long-term treatment.\n Double-blind, placebo-controlled, 8-month study with three treatment periods (1-month acute period followed with 1-month maintenance period and 6-month follow-up period) was carried out. Group 1 received FPANS 200 microg bd, during acute, maintenance and follow-up periods, Group 2 received FPANS 200 microg bd during acute period and FPANS 200 microg od during maintenance and follow-up periods, and Group 3 received placebo during acute and maintenance periods and FPANS 200 microg bd during follow-up period. Endpoints were change from baseline in clinic peak nasal inspiratory flow (PNIF), domiciliary evening PNIF, intensity of symptoms and polyposis grade.\n After acute period and maintenance periods, FPANS 200 microg bd was significantly more effective than placebo on all endpoints and more effective than FPANS 200 microg od after 1-month maintenance period on clinic PNIF, evening PNIF, obstruction, percentage of days with no sense of smell and percentage of nights with no disturbances. The two doses were similar on other endpoints. After the 6-month follow-up period, there was no difference between the two doses of FPANS at all efficacy endpoints. The safety profile of FPANS did not highlight any new or unanticipated adverse events.\n The study demonstrated the efficacy of FPANS 200 microg bd in acute treatment and FPANS 200 microg od as a sufficient dose to maintain a long-term efficacy in the treatment for NP.",
"nan",
"Thirty-four patients with herpes simplex dendritic keratitis were randomized into three treatment categories: Group A had débridement alone; group B, trifluridine (trifluorothymidine) alone; and group C, débridement and trifluridine. Patients treated with débridement alone had a statistically higher failure rate than did the other two groups. No statistically significant difference was observed between trifluridine treatment alone and débridement combined with trifluridine treatment, with regard to healing time. Our results suggest that débridement alone is suboptimal therapy for herpes simplex dendritic keratitis and that débridement combined with trifluridine appears to offer no advantage over trifluridine alone.",
"New therapeutic options would benefit patients with actinic keratosis (AK), a precancerous condition that is a significant health concern. The efficacy and safety of a microsphere-based formulation of 0.5% fluorouracil cream were evaluated in a randomized, double-blind, multicenter, parallel-group study. Patients (N= 177) were randomized to receive 0.5% fluorouracil or vehicle once daily for 1, 2, or 4 weeks. Efficacy was assessed by lesion counts and clearance. Safety was evaluated by monitoring adverse events, including facial irritation. Significant improvements were seen from baseline to posttreatment follow-up in all efficacy variables for all fluorouracil regimens compared with vehicle. Patients treated for one week experienced significant improvements compared with vehicle, although efficacy increased with increasing treatment duration. Most patients experienced mild to moderate facial irritation of predictable onset and duration. Once-daily administration of 0.5% fluorouracil cream for 1, 2, or 4 weeks is safe and effective for the treatment of AKs.",
"Although fluoride increases bone mass, the newly formed bone may have reduced strength. To assess the effect of fluoride treatment on the fracture rate in osteoporosis, we conducted a four-year prospective clinical trial in 202 postmenopausal women with osteoporosis and vertebral fractures who were randomly assigned to receive sodium fluoride (75 mg per day) or placebo. All received a calcium supplement (1500 mg per day). Sixty-six women in the fluoride group and 69 women in the placebo group completed the trial. As compared with the placebo group, the treatment group had increases in median bone mineral density of 35 percent (P less than 0.0001) in the lumbar spine (predominantly cancellous bone), 12 percent (P less than 0.0001) in the femoral neck, and 10 percent (P less than 0.0001) in the femoral trochanter (sites of mixed cortical and cancellous bone), but the bone mineral density decreased by 4 percent (P less than 0.02) in the shaft of the radius (predominantly cortical bone). The number of new vertebral fractures was similar in the treatment and placebo groups (163 and 136, respectively; P not significant), but the number of nonvertebral fractures was higher in the treatment group (72 vs. 24; P less than 0.01). Fifty-four women in the fluoride group and 24 in the placebo group had side effects sufficiently severe to warrant dose reduction; the major side effects were gastrointestinal symptoms and lower-extremity pain. We conclude that fluoride therapy increases cancellous but decreases cortical bone mineral density and increases skeletal fragility. Thus, under the conditions of this study, the fluoride-calcium regimen was not effective treatment for postmenopausal osteoporosis.",
"The objective of this examiner-blind clinical study was to investigate the efficacy of three oral hygiene regimens for the control of gingivitis and supragingival plaque.\n Following a baseline examination for gingivitis and supragingival plaque, qualifying adult male and female subjects from the San Francisco, California area were stratified into three treatment groups, which were balanced for plaque. The groups were then randomly assigned to one of three oral hygiene regimens: 1) twice-daily tooth brushing with Colgate Total Toothpaste, accompanied by once-daily flossing after brushing; 2) twice-daily tooth brushing with Colgate Total Toothpaste without flossing; and 3) twice-daily tooth brushing with a sodium fluoride toothpaste, accompanied by once-daily flossing after brushing. All subjects were given a complete oral prophylaxis, and dispensed their assigned treatment product(s), along with a soft-bristled adult toothbrush for home use. All dentifrice products were supplied in the original packaging to which overwrapping had been applied. Subjects were instructed to brush their teeth for one minute twice daily (morning and evening) using only the dentifrice provided, and to refrain from using anything other than their assigned oral hygiene products for the duration of the study. In addition, subjects were instructed to refrain from any routine dental treatment (except emergency) during the course of the study. There were no restrictions regarding diet or smoking habits over the course of the study. Examinations for gingivitis and supragingival plaque, and oral soft tissue assessments were repeated after three months, and again after six months of product use.\n One-hundred fourteen (114) subjects complied with the protocol and completed the six-month examinations. Statistical analyses showed similar results for both whole-mouth and interproximal scoring sites after six months of product use. Although not statistically significant, subjects using Colgate Total Toothpaste accompanied by the use of dental floss had numerically lower six-month scores for gingivitis and supragingival plaque formation when compared to the scores of subjects using Colgate Total Toothpaste without the use of dental floss. Relative to the sodium fluoride toothpaste accompanied by the use of dental floss, subjects using Colgate Total Toothpaste, both with and without the use of dental floss, exhibited statistically significant reductions in gingivitis and supragingival plaque formation after six months of product use.\n The results of this clinical study support the conclusion that the use of Colgate Total Toothpaste, both with and without the use of dental floss, provided statistically significant improvements over the sodium fluoride toothpaste plus flossing regimen with respect to the control of gingivitis and supragingival plaque formation. Although not statistically significant, numerically lower six-month scores for gingivitis and supragingival plaque were associated with Colgate Total Toothpaste accompanied by the use of dental floss, when compared with Colgate Total Toothpaste without the use of dental floss.",
"30 males and 29 females with condyloma acuminatum took part in a double-blind randomized trial with 0,5% 5-fluorouracil (5-FU) salicylic acid containing varnish for warts versus the varnish without 5-FU. The females were treated twice weekly at the clinic, the males were treated once daily at home by themselves. The 5-FU solution was found significantly superior to placebo (P less than 0,01). 60% of the 5-FU treated patients were healed with a median healing time of two weeks in the males and three weeks in the females. In the placebo group 27,6% healed with a median healing time of 2,5 weeks (males) an 3,5 weeks (females). Blood tests obtained before and after the trial were normal. Patch tests with 0,5% 5-FU revealed no sensitization after the therapy.",
"To determine the efficacy of topical ascorbic acid application in treating mild to moderate photodamage of facial skin using an objective, computer-assisted image analysis of skin surface topography and subjective clinical, photographic, and patient self-appraisal questionnaires.\n A 3-month, randomized, double-blind, vehicle-controlled study.\n Facial plastic surgery private practice.\n Nineteen evaluable volunteer sample patients aged between 36 and 72 years with Fitzpatrick skin types I, II, and III who were in good physical and mental health with mild to moderately photodamaged facial skin were considered for analysis.\n Coded, unmarked medications were randomly assigned to the left and right sides of each subject's face, one containing the active agent, topical ascorbic acid (Cellex-C high-potency serum; Cellex-C International, Toronto, Ontario), the other, the vehicle serum (Cellex-C International). Three drops (0.5 mL) of each formulation were applied daily to the randomly assigned hemifaces over the 3-month study period. Treatment assignments were not disclosed to subjects, clinicians, or personnel involved in analyzing skin replicas.\n Specific clinical parameters were evaluated and graded on a 0- to 9-point scale (0, none; 1-3, mild; 4-6, moderate; and 7-9, severe). Reference photographs were used to standardize grading criteria. Overall investigator scores were compared with baseline and graded as excellent (much improved), good (improved), fair (slightly improved), no change, or worse. Patient self-appraisal questionnaires rated the degree of improvement (much improved, improved, slightly improved, no change, or worse) and reported adverse effects (burning, stinging, redness, peeling, dryness, discoloration, itching, and rash). Standard photographs were taken at baseline, including anteroposterior and left and right oblique views to facilitate subsequent clinical evaluations, and at the end of therapy for comparison. Optical profilometry analysis was performed on the skin surface replicas of the lateral canthal (crow's feet) region, comparing baseline to end-of-study specimens. Using this computer-based system, the resulting image was digitally analyzed, and numeric values were assigned to reflect surface features. The parameters obtained included Rz, Ra, and shadows. These values provided objective data that document pretreatment and posttreatment texture changes proportional to the degree of wrinkling, roughness, and other surface irregularities.\n Optical profilometry image analysis demonstrated a statistically significant 73.7% improvement in the Ra and shadows north-south facial axis values with active treatment greater than vehicle control, as well as a trend for improvement in the Rz north-south facial axis parameter, showing a 68.4% greater improvement of active treatment vs vehicle control. Clinical assessment demonstrated significant improvement with active treatment greater than control for fine wrinkling, tactile roughness, coarse rhytids, skin laxity/tone, sallowness/yellowing, and overall features. Patient questionnaire results demonstrated statistically significant improvement overall, active treatment 84.2% greater than control. Photographic assessment demonstrated significant improvement, active treatment 57.9% greater than control.\n A 3-month daily regimen of topical ascorbic acid provided objective and subjective improvement in photodamaged facial skin. Skin replica optical profilometry is an objective method for quantification of the skin surface texture changes.",
"To test whether intermittent treatment with slow-release sodium fluoride and continuous calcium citrate supplementation inhibits vertebral fractures without causing fluoride complications.\n A placebo-controlled, randomized trial.\n Outpatient setting of specialty clinics in Dallas and Temple, Texas.\n Slow-release sodium fluoride (25 mg twice daily) in repeated 14-month cycles (12 months on treatment followed by 2 months off treatment) compared with placebo. Both groups took calcium citrate (400 mg calcium twice daily) continuously.\n 110 patients with postmenopausal osteoporosis were randomly assigned to two groups. In the slow-release sodium fluoride group, 48 of 54 patients completed more than 1 cycle of treatment (mean, 2.44 cycles/patient), whereas 51 of 56 patients in the placebo group completed at least 1 cycle (mean, 2.14 cycles/patient) in this interim analysis.\n Vertebral fracture rate and lumbar bone mineral content. Vertebral fractures were quantified from yearly radiographs. Bone mass was determined annually by densitometry.\n In the sodium fluoride group, the mean L2 to L4 bone mineral content increased by 4% to 6% in each cycle and the mean femoral neck bone density increased by 4.1% and 2.1% during the first two cycles, but the radial bone density did not change. The placebo group showed no statistical change in bone mass at any site. Compared with the placebo group, the sodium fluoride group had a lower individual new vertebral fracture rate (0.057/patient cycle compared with 0.204/patient cycle, P = 0.017), a higher fracture-free rate (83.3% compared with 64.7%, P = 0.042), and a lower group fracture rate (0.085/patient cycle compared with 0.239/patient cycle, P = 0.006). The side-effect profile was similar for the two groups; no patient developed microfractures, hip fractures, or blood loss anemia.\n Intermittent slow-release sodium fluoride plus continuous calcium citrate, administered for about 2.5 years, inhibits new vertebral fractures, increases the mean spinal bone mass without decreasing the radial shaft bone density, and is safe to use.",
"To determine the prevalence and severity of fluorosis in permanent incisor teeth in young children in a fluoridated and a fluoride-deficient community and to establish what relationship, if any, there was between the occurrence of dental fluorosis and the reported use of fluoride toothpaste in childhood.\n A prevalence study of children aged 8-9 years who had been continuous residents in fluoridated Newcastle or fluoride-deficient Northumberland.\n The permanent maxillary central incisor teeth were examined clinically and photographically by one examiner using the Thylstrup-Fejerskov index; the photographs were read blind to child identity and clinical score. A closed-response questionnaire enquired into the child's early experiences of toothbrushing and use of fluoride toothpastes. Social deprivation was measured by a Jarman score. The study took place in 1998.\n Prevalence of dental fluorosis measured by the Thylstrup-Fejerskov index.\n Complete data were available for 78% (n = 409) and 79% (n = 403) of eligible sampled children in the two areas, respectively. Clinical and photographic results agreed closely and had high reproducibility. The prevalence of fluorosis was 54% in the fluoridated area and 23% in the fluoride-deficient area when all grades (> 0) of fluorosis were included; percentage prevalence of mild to moderate fluorosis (> or = 3) was 3% and 0.5% in the two areas, respectively. Multivariate analysis indicated that area of residence (odds ratio = 4.5), Jarman score (odds ratio = 0.99 per Jarman unit) and type of toothpaste (odds ratio = 1.6) were statistically significantly related to presence or absence of fluorosis: the risk factors were--fluoridated area, affluence, and use of adult toothpaste.\n The prevalence of aesthetically important dental fluorosis was low, although higher in the fluoridated area. Use of a child's toothpaste (with lower fluoride concentration) could decrease risk in a fluoridated area. Adherence to the guidelines published by the British Society of Paediatric Dentistry is recommended.",
"A 5-yr double-blind fluoridated milk study has been completed and, following baseline stratification, 94 children aged 4 1/2/5 1/2 yr were allocated to the test group and 93 to the control. Each subject received 200 ml school milk daily, identification between the test and control plastic packs being by colour-coding alone with the former containing 1.5 mgF- giving a potential topical benefit of approximately 7 ppmF- per school day. After 5 yr, 50 of the test children remained and 56 of the controls. While the mean DMFT incremental data relating to permanent teeth was always in favour of the test group, it was not until the fourth year that a significant difference was obtained (P less than 0.01) between the fluoridated group (mean, 1.65) and the non-fluoridated group (mean, 2.56). For permanent teeth which were unerupted at baseline, the mean DMFS differences increased to 39.6% at the same time and to 48.0% by the fifth year. No benefit was noted for previously erupted primary teeth. Cavitation was less in the test group throughout the study. When the third, fourth and fifth year DMFT reductions obtained were compared with previously published artificial water fluoridated data where children were of comparable age at the onset of water adjustment, similar caries inhibition data were noted.",
"In order to find out if it is possible to prevent caries and gingivitis by periodical use of chlorhexidine-fluoride mouthrinses with or without strontium, and to find out what effects they have on salivary mutans streptococci and lactobacilli counts, a total of 243 schoolchildren aged 11 yr with high DMFS scores were randomly divided into four groups. One group (C) served as a basic control. Subjects in the second group (CXF) rinsed their mouths twice a day every third week with a rinsing solution containing 0.05% chlorhexidine gluconate and 0.04% NaF. In the third group (CXFS) the rinsing solution contained 500 ppm Sr during the first and second year and 15 ppm during the last 6 months, in addition to chlorhexidine and fluoride. In the fourth group (CX) the solution contained only 0.05% chlorhexidine gluconate. All the rinsing solutions had pH 5.8 buffered with succinic acid-NaOH buffer. After 2 yr and 9 months, the mean DMFS (SD) increments in the C, CXF, CXFS, and CX groups were 3.8 (5.7), 2.5 (3.2), 3.5 (4.8), and 3.4 (5.5), respectively. The percentage of subjects with bleeding gingival units had decreased from initial to final values as follows: C, 81-38; CXF, 88-42; CXFS, 89-56; CX, 89-37. The number of lactobacilli and mutans streptococci in saliva remained virtually unchanged throughout the study. For caries increment and gingival bleeding, the differences between groups were not statistically significant. The chlorhexidine-fluoride combination tended to prevent caries, but the effect on gingival bleeding and salivary counts of mutans streptococci and lactobacilli was negligible.",
"This case-control study investigated risk factors for enamel fluorosis in optimally fluoridated children, born after the US infant formula industry voluntarily reduced the fluoride content of their products. Analysis was performed on 233 children, aged 10-14 years. Case-control status was determined using the Fluorosis Risk Index (FRI). Risk factor exposure was ascertained via a mailed questionnaire. Logistic regression analyses revealed a strong association between mild-to-moderate enamel fluorosis on early forming (FRI classification I) enamel surfaces and both fluoride supplement use (odds ratio (OR)=5.95, 95% confidence interval (CI) 1.06-33.53), and early fluoride toothpaste use (OR=6.35, 95% CI 1.21-33.40). The authors found a suggestive, but nonsignificant, association between fluorosis on these enamel surfaces and infant formula in the form of powdered concentrate (OR=4.33, 95% CI 0.73-25.66). There was a strong association between mild-to-moderate fluorosis on later forming (FRI classification II) enamel surfaces and infant formula use in the form of powdered concentrate (OR=10.77, 95% CI 1.89-61.25), fluoride supplement use (OR=10.83, 95% CI 1.90-61.55), and early fluoride toothpaste use (OR=8.37, 95% CI 1.68-41.72). No association was observed between the use of ready to feed infant formula and enamel fluorosis.",
"Periodontal disease is a common infection-induced inflammatory disease among individuals suffering from diabetes mellitus. The purpose of this study was to assess the effects of treatment of periodontal disease on the level of metabolic control of diabetes. A total of 113 Native Americans (81 females and 32 males) suffering from periodontal disease and non-insulin dependent diabetes mellitus (NIDDM) were randomized into 5 treatment groups. Periodontal treatment included ultrasonic scaling and curettage combined with one of the following antimicrobial regimens: 1) topical water and systemic doxycycline, 100 mg for 2 weeks; 2) topical 0.12% chlorhexidine (CHX) and systemic doxycycline, 100 mg for 2 weeks; 3) topical povidone-iodine and systemic doxycycline, 100 mg for 2 weeks; 4) topical 0.12% CHX and placebo; and 5) topical water and placebo (control group). Assessments were performed prior to and at 3 and 6 months after treatment and included probing depth (PD), clinical attachment level (CAL), detection of Porphyromonas gingivalis in subgingival plaque and determination of serum glucose and glycated hemoglobin (HbA1c). After treatment all study groups showed clinical and microbial improvement. The doxycycline-treated groups showed the greatest reduction in probing depth and subgingival Porphyromonas gingivalis compared to the control group. In addition, all 3 groups receiving systemic doxycycline showed, at 3 months, significant reductions (P < or = 0.04) in mean HbA1c reaching nearly 10% from the pretreatment value. Effective treatment of periodontal infection and reduction of periodontal inflammation is associated with a reduction in level of glycated hemoglobin. Control of periodontal infections should thus be an important part of the overall management of diabetes mellitus patients.",
"This randomized, double-masked, placebo-controlled clinical trial evaluated the effect of enamel matrix derivative (EMD) on clinical and radiographic parameters of periodontal intrabony defects.\n A split-mouth design was used in 16 chronic periodontitis patients who had similar defects (> or =6 mm of probing depth). Both groups underwent scaling and root planing and were acid-etched with EDTA. The test sites received the EMD solution and the controls a placebo. Clinical examinations of all 16 patients and radiographs of 14 patients were available at baseline and 6 and 12 months after surgery. Clinical outcomes included probing depth (PD) and clinical attachment level (CAL); radiographic analysis was performed using computerized linear measurements. Intergroup comparisons were performed by paired samples t test, and over time comparisons were made by general linear model (alpha = 0.05).\n A statistically significant improvement over time for PD and CAL and a decrease of the vertical component of the defect was detected in both groups. Comparisons between groups revealed at baseline a mean+/-SD value of CAL of 12.93+/-2.00 and 13.47+/-2.93 for test and control groups, respectively. These values decreased to 10.92+/-1.92 and 11.31+/-1.86 after 12 months for test and control. No statistically significant differences could be observed between groups. PD displayed similar results from 7.57+/-1.02 and 7.38+/-1.16 for test and control groups at baseline to 3.40+/-1.82 and 2.99+/-1.07 after 12 months. If the data are divided into smokers and non-smokers, no differences are observed.\n Use of EMD did not result in more improvement in clinical and radiographic parameters compared to the placebo.",
"365 2nd through 4th graders completed a 3-yr clinical trial on the caries-preventive effect of rinsings every second week during the school year with 10 ml of an 0.2% neutral solution of sodium fluoride. All children received regular dental examinations and treatment in clinics established by the municipality in which the study took place. The trial was performed under double-blind conditions. The caries increment on teeth erupted at baseline was 1.75 DMFS in the fluoride group and 1.83 DMFS in the placebo group (P greater than 0.05; 95% confidence limits for percentage caries reduction: -20.7% and 29.5%). The caries increment on teeth erupting during the trial was 0.73 DMFS in the fluoride group and 0.99 DMFS in the placebo group (P greater than 0.05; 95% confidence limits for percentage caries reduction: 1.0% and 51.6%).",
"The topical vitamin D analogue calcipotriene has been reported to be an effective treatment for patients with psoriasis. Comparative studies with topical steroids are informative in judging this new therapy.\n The purpose of this study was to evaluate the efficacy and safety of calcipotriene ointment 0.005% versus fluocinonide ointment 0.05% in the treatment of plaque psoriasis.\n This study was a randomized, double-blind, parallel-group, active-controlled trial in adults who had at least mild overall disease severity and plaque elevation of at least moderate severity. Treatments were applied twice daily for 6 weeks, and subjects were evaluated at weeks 0, 2, 4, and 6. Subjects were graded on a 9-point scale (0 to 8) for scaling, erythema, plaque elevation, and for overall disease severity. A physician's global assessment of improvement/worsening was performed at every visit.\n A total of 114 subjects were enrolled at six study sites. Ninety-nine subjects completed the trial. Mean scores for signs of scaling and plaque elevation in calcipotriene-treated subjects were significantly lower by week 2 than in the fluocinonide-treated subjects. These scores continued to be significantly lower than fluocinonide through week 6 (p < 0.05). Mean scores for erythema in calcipotriene-treated subjects were significantly lower than those in fluocinonide-treated subjects at weeks 4 and 6 (p < 0.05). Both the physician's global assessment and overall disease severity showed statistically significant treatment differences in favor of calcipotriene at week 4 (p < 0.05). This superior efficacy continued through week 6. Treatment-related adverse events were observed in 12 calcipotriene-treated subjects and 5 fluocinonide-treated subjects; all were considered minor.\n Calcipotriene was superior to fluocinonide in the treatment of plaque psoriasis.",
"Treatment of melasma, a hyperpigmentation disorder, remains a challenge. The primary objective of two 8-week, multicenter, randomized, investigator-blind studies was to compare the efficacy and safety of a hydrophilic cream formulation containing tretinoin 0.05%, hydroquinone 4.0%, and fluocinolone acetonide 0.01% (RA+HQ+FA) with the dual-combination agents tretinoin plus hydroquinone (RA+HQ), tretinoin plus fluocinolone acetonide (RA+FA), and hydroquinone plus fluocinolone acetonide (HQ+FA). All agents had the same drug concentration and vehicle. A total of 641 adult patients, predominantly female, with moderate to severe melasma and Fitzpatrick skin types I through IV, were randomized to the various treatment groups. Due to the similarity of the study designs, the results of the 2 studies were combined and are reported here. The primary efficacy analysis involved the proportion of intent-to-treat patients in each treatment group whose condition had completely cleared by week 8. The results of the combined clinical trials demonstrated that significantly more of the patients treated with RA+HQ+FA (26.1%) experienced complete clearing compared with the other treatment groups (4.6%) at the end of week 8 (P<.0001). In addition, at week 8, a 75% reduction in melasma/pigmentation was observed in more than 70% of patients treated with RA+HQ+FA compared with 30% in patients treated with the dual-combination agents. The most common adverse reactions seen with all treatment groups were erythema, skin peeling, burning, and/or stinging sensation. The majority of treatment-related adverse events were of mild severity.",
"In a municipality near Copenhagen, Denmark, where fortnightly fluoride rinses with 0.2% neutral sodium fluoride had been performed for more than a decade, 1306 children from kindergarten through 6th grade were stratified by school and grade and randomly distributed into two groups. One group continued the fluoride rinses, the other group had the fluoride solution replaced with distilled water. Both solutions were slightly flavored. 1083 children completed the 3-yr trial. Caries was recorded clinically by the dentists in the municipal dental service using the diagnostic criteria for the Child Dental Health Services, and on bitewing radiographs by one of the authors applying the criteria developed by GRONDAHL et al. Permanent molars and premolars were included in the study. Clinically, caries increment in the two groups was the same with pits and fissures containing 94% of the DMFS. According to the radiographs, caries progression in the water group was higher than in the fluoride group. This difference was statistically significant for the surfaces erupting during the study (P less than 0.05).",
"nan",
"To determine the prevalence and severity of dental fluorosis in children aged 7-9 years from non-water-fluoridated Halmstad, Sweden, and to relate the results to their reported fluoride exposure history during infancy.\n In Spring 2002, a questionnaire distributed to a cluster random sample of 1039 parents enquired into their child's early oral health behaviors and included a \"photographic toothpaste menu\". The permanent upper anterior teeth (13-23) were examined clinically (+10% repeats) using a modified Thylstrup-Fejerskov Index.\n Complete data were available for 53% (n=548) of the sampled children. The prevalence offluorosis at any level was 49% (95% CI: 45-54%), and of fluorosis with esthetic concern (TF score > or =3) 4% (95% CI: 3-6%). Based on repeat observations, reliability was good (kappa = 0.82). There was no statistically significant increased risk of dental fluorosis prevalence associated with any of the fluoride exposure risk factors examined, including reported usage of (1000 ppm) fluoride toothpaste from time of first deciduous tooth eruption.\n While there were low levels of dental fluorosis of esthetic concern, half the children had some degree of dental fluorosis. The prevalence of dental fluorosis was not explained by the risk factors, including fluoride toothpaste usage as explored in this study.",
"nan",
"A randomized, double blind clinical trial of the caries inhibition effects of dentifrices containing respectively monofluorophosphate and amine fluoride was performed. A third control group used a toothpaste without fluoride. A total number of 2008 schoolchildren ranging in age from 6 to 8 years and living in Strasbourg (France) participated in this study. After a baseline examination three groups were constructed with the block randomization technic. The caries inhibition effects of the three dental pastes were compared after 3 years of unsupervised use. The monofluorophosphate dentifrice showed a reduction of 7.02% for DMFT, 5.17% for DMFS and 25.26% for the df rate. The reduction of amine fluoride dentifrice caries was respectively 21.62% for DMFT, 20.94% for DMFS and 48.66% for the df rate.",
"To determine the prevalence and severity of dental fluorosis, and to evaluate supplementary fluoride sources as potential risk factors to fluorosis in school children aged 6-9.\n A cross-sectional study was carried out in 320 children attending elementary schools protected by a public preventive dental program in the city of Campeche, Mexico. A self-administered questionnaire directed to the mothers was delivered through the schools and collected in the same way. The examiners were trained and calibrated (kappa > 0.90) in modified Dean's Index. The fluorosis community index (FCI) was calculated. Bivariate analyses were made with Chi2 test; odds ratios (OR) and 95% confidence intervals were calculated. Logistic regression was used in the final model.\n Fluorosis prevalence was 56.3%, with very mild fluorosis present in 45% of children, mild in 10%, and severe in just 1.3%. The FCI was 0.7. The multivariate model showed that the effect of the supplementary fluoride sources was different between children that started brushing with toothpaste before two years of age (OR = 6.15; IC 95% = 2.03-18.67) and after (OR = 2.14; IC 95% = 1.16-3.94).\n Fluorosis prevalence was high for mild modalities, and low for more severe levels. According to FCI the dental fluorosis constitute a public health problem in the studied sample. Exposure to diverse fluoride sources -above and beyond the fluoridated salt program- was a risk factor for dental fluorosis in this community. Results suggest that toothpaste use in children two years of age and younger should be cautious, limited to follow current guidelines, and supervised by parents to minimize the risk of dental fluorosis.",
"Two multicenter, double-blind, randomized, vehicle-controlled parallel-group trials involving 388 patients were conducted to compare the efficacy and safety of fluticasone propionate 0.005% ointment to those of its vehicle in the treatment of moderate-to-severe psoriasis. The study medication (up to 100 gm/week) was applied topically to the affected target areas of the body twice daily for up to four consecutive weeks. Efficacy and safety were evaluated after one, two, three, and four weeks of treatment. In both studies, fluticasone ointment was clearly shown to be superior to vehicle throughout the four weeks of treatment. At the end of the treatment period, the superiority of fluticasone ointment was statistically significant for all efficacy measures. At the end of study 1, the skin of ten of eighty-eight patients (11%) who received fluticasone were rated as cleared by the investigators and fifty (57%) were rated as excellent or good. Of those who received vehicle, the skin of one of ninety (1%) was rated cleared and twenty-five (28%) were rated excellent or good. In study 2, the skin of three of 105 (3%) patients who received fluticasone were rated as cleared and sixty-nine (66%) were rated as excellent or good at the end of the study. Of those who were treated with vehicle, no patient's skin was rated cleared and thirty of 100 (30%) were rated excellent or good. Adverse events were few and mild. The most common drug-related adverse events were burning and pruritus at the site of application, which occurred in 6% of both the fluticasone-treated patients and those who received vehicle. These findings support the conclusion that fluticasone, 0.005%, ointment is clinically superior to its vehicle in the treatment of psoriasis.",
"It is recognized that colonization by Staphylococcus aureus (SA) on the skin is one of the factors that can worsen atopic dermatitis (AD). Antibiotics and germicides are not the best choice to remove bacteria from the skin of AD patients, because of problems of irritation to the skin and bacterial resistance. We therefore turned our attention to the biofilm of SA with the aim of removing only SA from the skin surface of AD patients. We found that xylitol (X) and farnesol (F) synergistically inhibited biofilm formation by SA and dissolved biofilm formed in vivo (Part 1).\n To test whether application of AD for 1 week with FX cream can reduce SA without affecting Staphylococcus epidermidis.\n A randomized, double-blind, placebo-controlled right-and-left comparison study was performed. The arms of 17 patients with dry-type AD were applied with skin-care cream including/or not including a 0.02% F and 5% X combination for 1 week. The clinical response, biophysical assessment of the skin surface and counts of skin microflora were recorded before and after 1 week of therapy.\n The ratio of SA in total bacteria at sites to which FX cream had been applied was significantly decreased after 1 week (P = 0.007), compared with before application and with placebo sites (P = 0.045). The mean skin conductance (a parameter indicating the state of hydration of the skin surface) of FX cream sites was increased significantly compared with the conductance before application (P = 0.0001) and at placebo sites (P = 0.002).\n This study provides evidence supporting the idea that cream containing F and X is a useful skin-care agent for atopic dry skin colonized by SA.",
"To examine a possible relationship between reported toothbrushing habits in infancy and fluorosis of permanent maxillary incisors at age 8-9 years.\n Comparison of clinical findings with retrospective survey data.\n Five primary schools in the City of Birmingham where the water is fluoridated at 1.0 mg F/l.\n Results of clinical examinations were compared with historical data collected via parental questionnaires. Maxillary central incisors of 325 consecutive children were examined for fluorosis clinically and photographically according to the criteria of the Modified Thylstrup and Fejerskov Index. 112 children had fluorosis and 213 did not. Information concerning toothbrushing habits in infancy was obtained via a questionnaire to parents who were also asked to add paste to a brush in a similar way to when the children were small. From a combination of questionnaire replies and paste weights the amount of fluoride that each child may have ingested from toothpaste each day was then estimated.\n Highly significant associations were found between estimated fluoride ingestion from toothpaste and fluorosis. The mean DMF score of the fluorosis group was half that of the fluorosis-free children. The prevalence of fluorosis among children in ACORN group A-C was significantly greater than in groups D-F.\n The results of the study suggest that toothpaste swallowing may be a factor in the production of fluorosis.",
"The caries-preventive effect of semiannual applications of a fluoride varnish (Duraphat) was tested for 2 years in 225 3-year-old children; 113 children served as a control group. At the baseline examination, 69% of the children in the test group and 75% in the control group were caries-free. The results after 2 years showed an average caries increment of 2.1 surfaces in the test group and 3.7 in the control group. The difference is statistically significant. Thirty-eight percent of the children in the test group and 27% in the control group were still caries-free. The caries reduction was 44%.",
"Topically applied nail therapeutics need to permeate the nail plate to reach the nail bed or nail matrix and exert their potential beneficial effect at these locations to obtain a therapeutic benefit. So far only topically applied 5-fluorouracil on affected nails of psoriatic patients has been shown to produce a notable clearance. Vehicle formulations enhancing nail permeation processes are thought to increase the concentration of the active agent and therefore therapeutic efficacy, possibly enabling the use of a low concentration of the active agent thereby lowering the incidence of adverse effects.\n This study was designed to verify whether a recently developed nail penetration enhancer in a lotion formulation, Belanyx((R)) (urea, propylene glycol), improves the efficacy of a low concentration of 5-fluorouracil (1%) in psoriatic fingernail lesions.\n In a randomised, double-blind, left-right study the efficacy of 1% 5-fluorouracil in the Belanyx vehicle was compared to the vehicle preparation Belanyx in dystrophic fingernails of 57 psoriatic patients. Both preparations were applied in a once daily regimen for 12 weeks. Responses and adverse effects of one selected target nail were recorded at screening, at baseline and at weeks 2, 4, 8 and 12 of treatment with a final assessment at week 16: 4 weeks after the end of treatment. As parameter of efficacy was chosen the total nail area severity (NAS) score, consisting of the separate parameters nail pitting area, number of nail pits, subungual keratosis, onycholysis, oil spots and the various scores of overall improvement.\n The efficacy of 1% 5-fluorouracil in lotion and that of the vehicle in suppressing the parameters of dystrophy were shown to be similar at the end of treatment (p = 0.063) or follow-up (p = 0.130). Both preparations produced statistically significant improvements (p </= 0.05) for almost all assessed parameters after 12 weeks of treatment and after the 4 weeks of follow-up. For Belanyx lotion this applied to the nail pitting area, the number of nail pits, subungual keratosis, onycholysis and oil spots. The investigators' and patients' opinion of overall improvement of severity as well as the total NAS score of one target nail likewise showed a statistically significant improvement at the end of treatment and at the end of the observation period (p </= 0.05). With the 1% 5-fluorouracil lotion the same statistically significant improvements were obtained in all of the assessed symptoms with the exception of the number of pits and onycholysis at week 12 and week 16. Possible treatment-related adverse effects were established in 6 patients showing inflammation and infection (3 patients) or discoloration (5 patients); 3 patients on 5-fluorouracil lotion showed onycholysis.\n Addition of 1% 5-fluorouracil to the nail permeation enhancer Belanyx does not increase the efficacy of the active agent in psoriatic nail dystrophy of this study population. The obtained results also suggest that Belanyx lotion can be used in this indication since it has shown a favourable efficacy-safety ratio.\n Copyright (R) 2000 S. Karger AG, Basel",
"The aim of this trial was to compare the caries-preventive effect of sodium fluoride varnish and acidulated phosphate fluoride (APF) gel. A total of 254 children aged 12-13 years with high past caries experience were randomly divided into two groups. The participants received semi-annual applications of either fluoride varnish or APF gel for 3 years. During the study, the mean (+/- SD) total DMFS increments of the varnish and gel groups were 6.8 +/- 5.6 and 7.7 +/- 6.4, respectively, when initial caries was included, and 3.1 +/- 3.7 and 3.6 +/- 4.6 when initial caries was excluded. The difference was most evident on the approximal surfaces (varnish: 1.4 +/- 2.4; gel: 1.9 +/- 3.1). However, this difference was not statistically significant. Although larger studies are needed for firm conclusions about the comparative effect of the two fluoride measures, the results suggest that fluoride varnish is as effective as fluoride gel at least in preventing approximal caries. Taking into account the shorter treatment time, using fluoride varnish for professional applications seems justified.",
"The aim of the present study was to assess the caries-preventive effect of topical application of Duraphat on the occlusal surface of newly erupted first permanent molars. A base-line examination was performed on children aged 5 years and 9 months. The children were randomly divided into a Duraphat group and a control group. In accordance with the anatomy of the fissure system, the molars were divided into shallow and deep fissures, respectively. From the time of eruption, 381 molars were examined every 3rd month during 24 months. Duraphat was applied every 6th month, altogether four times. The results showed that in the Duraphat group 35% of the fissures were decayed compared with 80% in the control group. Caries reduction amounted to 56%, and the caries-preventive effect was found in molars with shallow and deep fissures.",
"The objective of this research was to evaluate the anticaries effectiveness of a low-dose (500 ppm F, low-NaF) sodium fluoride dentifrice, a high-dose (2,800 ppm F, high-NaF) sodium fluoride dentifrice and an experimental 0.454% stabilized stannous fluoride (1,100 ppm F) with sodium hexametaphosphate (SnF2-HMP) dentifrice, each relative to a standard 1,100 ppm F sodium fluoride positive control dentifrice. Subjects (n = 955, with approximately 239 per group) with a mean age of 10.6 (approximately 9-12 years) were randomly assigned to one of four dentifrice treatments. Two calibrated examiners independently measured visual-tactile caries as DMFS that was supplemented with a radiographic examination at baseline, 12 months and 24 months for each subject. Generally similar results were independently observed by both examiners at the conclusion of the 2-year study period. Considering all subjects that attended at least 60% of the supervised brushing sessions, statistically significantly less caries was observed in the high-NaF group compared to the control group. Similarly, statistically significantly less caries was observed in the SnF2-HMP group as compared to the control group. Differences in caries increments between the low-NaF and control groups were not statistically significant. One of the examiners observed these same statistically significant differences after 1 year. In conclusion, the results of this clinical trial indicated that while no difference in caries increments was observed between the low-NaF and control groups, both the high-NaF and the SnF2-HMP groups experienced significantly fewer lesions than the control group.\n 2004 S. Karger AG, Basel.",
"The aim of the present study was to evaluate the clinical effects of one-stage periodontal debridement with an ultrasonic instrument, associated with 0.5% povidone (pvp)-iodine irrigation in patients with chronic periodontitis.\n Forty-five patients were randomly assigned into three groups: the control group (CG) received quadrant root planing at 1-week intervals over four consecutive sessions; the periodontal debridement plus pvp-iodine group (PD-PIG) received a 45-minute full-mouth debridement with an ultrasonic instrument, associated with 0.5% pvp-iodine irrigation; and the periodontal debridement group (PDG) received a 45-minute full-mouth periodontal debridement with an ultrasonic instrument, associated with NaCl irrigation.\n At the 3-month evaluation, the mean probing depth (PD) reduction in CG was 2.51+/-0.52 mm, 2.53+/-0.50 mm in PD-PIG, and 2.58+/-0.60 mm in PDG (P<0.05). The clinical attachment level (CAL) analysis showed a statistically significant gain in all groups compared to baseline (1.87+/-0.56 mm [CG], 1.94+/-0.70 mm [PD-PIG], and 1.99+/-0.92 mm [PDG]). Intergroup analysis of PD and CAL at 1 and 3 months showed no differences (P>0.05). The N-benzoyl-L-arginine-p-nitroanilide (BAPNA) test showed a significant reduction in trypsin activity only during the first month (P<0.05); at 3 months there were no differences compared to baseline (P=0.80).\n This study provides no evidence that pvp-iodine is effective as an adjunct for one-stage periodontal debridement.",
"Fluoride dentifrice is a primary means of preventing childhood caries, but it is also an important risk factor for fluorosis. The authors examine the influence of fluoride dentifrice ingestion on fluorosis of the permanent incisors.\n Participants in the Iowa Fluoride Study received questionnaires at regular intervals concerning fluoride sources. The authors assessed fluorosis using the fluorosis risk index. They estimated daily fluoride ingestion from dentifrice, diet and fluoride supplements and divided the amount by kilograms of body weight. The statistical analysis related fluoride ingestion to fluorosis in the permanent incisors.\n In bivariate analyses, mild fluorosis was significantly related to ingestion of fluoride dentifrice at ages 24 and 36 months (P = .02 for both). After the authors adjusted for fluoride ingested from dietary sources, logistic regression showed a significant association between fluorosis and dentifrice ingestion at age 24 months (P = .04).\n The study results suggest that fluorosis of the permanent incisors is influenced by ingestion of fluoride dentifrice during the first three years of life. Further research is needed to assess total intake of fluoride as a risk factor for fluorosis.\n These results support recommendations that young children use only a pea-sized amount of dentifrice. Parents should supervise young children as they brush their teeth with fluoride dentifrice.",
"Diaper dermatitis is a common childhood affliction. Aiming to help reduce the prevalence of this problem, we have advanced in our development of a novel diaper that delivers dermatological formulations to help protect the skin from over-hydration and irritation.\n To determine the clinical benefits of a novel disposable diaper designed to deliver a zinc oxide and petrolatum-based formulation continuously to the skin during use.\n All studies were independent, blinded, randomized clinical trials. Study A was conducted to confirm transfer of the zinc oxide/petrolatum (ZnO/Pet) formulation from the diaper to the child's skin during use. Children wore a single diaper for 3 h or multiple diapers for 24 h. After the use period, stratum corneum samples were taken from each child and analysed for ZnO/Pet. Study B evaluated the prevention of skin irritation and barrier damage from a standard skin irritant (SLS) in an adult arm model. Study C evaluated skin erythema and diaper rash in 268 infants over a 4-week usage period. One half of the infants used the ZnO/Pet diaper, while the other half used a control diaper that was identical except for the absence of the ZnO/Pet formulation.\n The ointment formulation and ZnO transferred effectively from the diaper to the child's skin during product use. Transfer of ZnO increased from 4.2 microg/cm2 at 3 h to > 8 microg/cm2 at 24 h. Exposure to the formulations directly on adult skin prior to an irritant challenge was associated with up to a 3.5 reduction in skin barrier damage and skin erythema. Greatest reductions were seen for the ZnO containing formulations. Wearing of the formulation treated diaper was also associated with a significant reduction in skin erythema and diaper rash compared to the control product.\n The results demonstrated the clinical benefits associated with continuous topical administration of a zinc oxide/petrolatum-based formulation by this novel diaper.",
"The aim of this study was to assess the caries incidence and plaque accumulation in schoolchildren at caries risk, after brushing the teeth fortnightly with gels containing 0, 0.4% F, 1.25% F as amine fluoride (AmF) or the common amine fluoride toothpaste containing 0.125% F. The study was conducted double blind over an 18-month period, and after 6 months discontinuation of brushing. Only the group that brushed with the 1.25% AmF gel showed a significant decrease in caries development compared to the group that brushed with the 0.125% AmF toothpaste. During the 6-month discontinuation period, the incidence of caries increased in all groups; the differences in caries development between all groups were not significant. Plaque indices were significantly lower in the AmF-treated groups. The highest fluoride concentration in the gel reduced the development of caries to zero, probably due to increased fluoride levels in the oral milieu of caries risk children. In order to maintain a positive effect of fluoride over an extended time period, caries-prone subjects should continue an initiated fluoride programme.",
"The efficacy and safety of halobetasol propionate 0.05% cream, an ultra high-potency corticosteroid preparation, was evaluated in a double-blind, vehicle-controlled, paired comparison study. Patients' psoriatic lesions were evaluated before treatment and after 1 and 2 weeks of twice-daily treatment with halobetasol propionate and vehicle. Response measures (plaque elevation, erythema, scaling, and pruritus) were evaluated with a 4-point severity scale whereby the sum provided a total score. Patient self-assessment measures were obtained at the 2-week visit by categorizing his or her global responses to queries about each treatment's \"effectiveness\" and \"overall rating.\" All efficacy parameters, as judged by the physician, showed statistically significant (p = 0.0001) treatment differences favoring halobetasol propionate at both week 1 and week 2 evaluations. Patient global responses for \"effectiveness\" and \"overall rating\" favored halobetasol propionate 0.05% cream over vehicle after 2 weeks of use. No systemic adverse drug effects were reported during the study. No patient was discontinued from the study because of an adverse event, and there was no evidence of skin atrophy after 2 weeks of treatment with either agent. Patient reports of \"stings\" or \"burns\" were equally distributed between the active and vehicle treatment groups. This trial demonstrates that halobetasol propionate 0.05% cream is clinically beneficial and without evidence of significant risk in the treatment of plaque psoriasis.",
"The aim of this study was to determine the separate effects of dental sealants and fluoride varnish on dental caries in fissured and nonfissured surfaces of permanent first molars.\n A clinical trial was conducted with three groups of 6- to 8-year-old schoolchildren: a sealant group (n = 100), in which Delton was applied to first molars; a varnish group (n = 98), in which Duraphat was applied to first molars; and a control group (n = 116), which had no intervention as part of the study. Absolute and percent caries reductions were compared at 24 months.\n Compared to the controls, sealants resulted in a 68 percent and 87 percent reduction on fissured and nonfissured surfaces, respectively. The corresponding figures for varnish were 38 percent and 66 percent.\n Sealant and fluoride varnish are effective in preventing caries in both fissured and nonfissured surface.",
"nan",
"A recent clinical trial investigated the cariostatic effectiveness of a low (550 ppm) fluoride toothpaste in comparison with a standard (1050 ppm) control paste in pre-school children who were 2-years-old at the start of the 3-year trial. The present study has investigated the prevalence of enamel opacities in permanent incisor teeth and of caries in children who had taken part. As well as children from test and control groups, a third group of non-trial children were included in the sample. A total of 1,523 children were examined in schools and had photographs taken of their upper permanent incisor teeth. The latter were scored using the Thylstrup and Fejerskov (TF) index for fluorosis and the modified Developmental Defects of Enamel (DDE) index. Differences between the groups were small in real terms but using the TF index the child and tooth prevalence of opacities were significantly lower in the children who had used the test paste with a lower fluoride content; the same trend was seen in diffuse defects scored using the modified DDE index. There was no significant difference in the prevalence of caries in either primary or permanent teeth although the trend in both cases was for slightly more disease in children who had used the test paste.",
"To evaluate the efficacy of topical N-acetyl-cysteine (NAC) therapy in patients with meibomian gland dysfunction (MGD).\n Twenty patients with MGD were prospectively randomized and assigned into 2 groups. The patients were instructed to use either NAC 5% or preservative-free artificial tear topically 4 times a day for a month. All patients were instructed to apply lid hygiene once daily. Preservative-free artificial tears treated group served as control. Paired sample Student's t-tests were used to detect differences between the baseline and 1 month after treatment initiation in mean ocular symptoms, fluorescein break-up time (FBUT) values, and Schirmer scores in each group. Difference in mean ocular symptoms, Schirmer's test scores, and FBUT values between the baseline and 1 month after treatment initiation were compared between the groups using Mann-Whitney U test.\n One month of topical NAC therapy provided statistically significant improvements in FBUT and Schirmer scores as compared with the initial study visit. The average Schirmer increase rate was significantly better in the NAC group than in the control group. Significant improvements for the symptoms of ocular burning, foreign body sensation, and intermittent filmy or blurred vision were noted in both groups; and only NAC-treated group showed improvement for the symptom of itching, at 1 month as compared with 1 day. NAC provided significantly better improvement in itching symptom when compared with controls.\n Topical administration of NAC is thought to be effective and well tolerated in patients with MGD.",
"Topical glucocorticoids are the medical treatment of choice in a majority of patients suffering from nasal polyposis. Fluticasone propionate is a fluorinated steroid reported to be highly effective when used topically in the nose for seasonal and perennial allergic and nonallergic rhinitis.\n To evaluate the efficacy and tolerability of intranasal fluticasone propionate in the treatment of long-standing polyposis.\n Fifty-five patients with long-standing nasal polyposis were treated over a 26-week period with fluticasone propionate aqueous nasal spray 200 micrograms bid, beclomethasone dipropionate aqueous nasal spray 200 micrograms bid or placebo, administered intranasally in an aqueous spray in a double-blind, placebo-controlled parallel-group design at a single center. The primary efficacy endpoint was the physicians' assessment of symptoms and polyp score. Peak nasal inspiratory flow was performed twice daily and on every visit to evaluate the effect of the corticosteroids on nasal air flow.\n A significant difference in the primary efficacy endpoint between fluticasone propionate aqueous nasal spray and beclomethasone dipropionate aqueous nasal spray compared with placebo was seen after 14 weeks of treatment. This was further verified by the peak nasal inspiratory flow results. There was some evidence of earlier onset in the fluticasone propionate aqueous nasal spray group compared with the beclomethasone dipropionate aqueous nasal spray group after 4 weeks in terms of the primary efficacy endpoint. From the daily record cards patients receiving fluticasone propionate aqueous nasal spray had a significantly higher percentage of days on which they required no rescue medication (P < .009) and a higher percentage of days with an overall nasal blockage score on waking of < 2 (P < .013) when compared with placebo-treated patients. No other statistically significant results were found between the two active compounds.\n Fluticasone propionate aqueous nasal spray 200 micrograms bid and beclomethasone dipropionate aqueous nasal spray 200 micrograms bid are effective in treating the symptoms of nasal polyps, with some evidence that fluticasone propionate aqueous nasal spray has a faster onset of action and is tolerated at least as well as beclomethasone dipropionate aqueous nasal spray at the same dose.",
"The effect on dentinal hypersensitivity from the use of a new dentifrice containing 5.0% potassium nitrate and 0.454% stannous fluoride in a silica base (Colgate Sensitive Maximum Strength Toothpaste, Colgate-Palmolive Co.) over an 8-week period was compared to a commercially available dentifrice containing 5.0% potassium nitrate and 0.243% sodium fluoride in a silica base (positive control [Sensodyne Fresh Mint Toothpaste, Block Drug Company, Inc.]) and to a commercially available nondesensitizing dentifrice containing 0.243% sodium fluoride in a silica base (negative control [Colgate Winterfresh Gel, Colgate-Palmolive Co.]). A total of 120 participants were stratified into 3 balanced groups according to baseline mean air blast (thermal) and tactile (Yeaple Probe) sensitivity scores, gender, and age. Participants brushed their teeth twice daily (morning and evening) for 1 minute. Dentinal hypersensitivity examinations were conducted at baseline, 4 weeks, and 8 weeks by the same dental examiner. After 4- and 8-weeks' use of their assigned products, participants in the new dentifrice group demonstrated statistically significant improvements (p < 0.05) in tactile and air blast sensitivity, as compared to those using the positive and negative control dentifrices.",
"Nitric oxide is continually released from normal skin and has antimicrobial effects. An acidified nitrite cream releases supraphysiologic concentrations of nitric oxide and is fungicidal in vitro.\n The purpose of this study was to assess the efficacy of an acidified nitrite cream as treatment for tinea pedis.\n Sixty patients were recruited with both a clinical diagnosis of tinea pedis and hyphae identified on direct microscopy; they were randomly placed into an active group treated with twice-daily application of a mixture of 3% salicylic acid in aqueous cream and 3% nitrite in aqueous cream for 4 weeks and a control group treated with 3% salicylic acid in aqueous cream and aqueous cream alone. Nineteen patients completed the trial in the active group and 16 patients in the control group. Mycologic cure (negative results on microscopy and culture) and clinical improvement were measured at 0, 2, and 4 weeks and after a 2-week interval with no treatment.\n At the end of the treatment period, 18 of the 19 patients in the active group were mycologically cured as were 11 of 16 in the control group (p = 0.042). Two weeks after the cessation of treatment, 13 of 19 patients in the active group were mycologically cured and 5 of 16 in the control group (p = 0.028). The initial clinical scores in the active and control groups were 8.1 and 8.19 (two-tailed p = 0.95). At 4 weeks they were 1.66 and 6.0 (two-tailed p = 0.002) and after 2 weeks with no treatment 1.45 and 7.4 (two-tailed p < 0.0002).\n Acidified nitrite is effective therapy for tinea pedis."
] |
The benefits of topical fluorides have been firmly established on a sizeable body of evidence from randomized controlled trials. While the formal examination of sources of heterogeneity between studies has been important in the overall conclusions reached, these should be interpreted with caution. We were unable to reach definite conclusions about any adverse effects that might result from the use of topical fluorides, because data reported in the trials are scarce.
|
CD006528
|
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"22302951",
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"12702891",
"12920411",
"8739664",
"10565799",
"17846258",
"16415711",
"2236455",
"11030486",
"11476127",
"16816220",
"8912401",
"15811165",
"9671343",
"12927007",
"7622801",
"18368615",
"14658972",
"12547477"
] |
[
"A multicentre, double-blind, amitriptyline-controlled study of mirtazapine in patients with major depression.",
"Double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients.",
"Comparison of the effects of mirtazapine and fluoxetine in severely depressed patients.",
"A randomized, double-blind, 24-week study comparing the efficacy and tolerability of mirtazapine and paroxetine in depressed patients in primary care.",
"Mirtazapine orally disintegrating tablet versus sertraline: a prospective onset of action study.",
"A double-blind multicentre comparison of mirtazapine and amitriptyline in elderly depressed patients.",
"Efficacy and tolerability of mirtazapine versus citalopram: a double-blind, randomized study in patients with major depressive disorder. Nordic Antidepressant Study Group.",
"Treatment of post-myocardial infarction depressive disorder: a randomized, placebo-controlled trial with mirtazapine.",
"Mirtazapine orally disintegrating tablets versus venlafaxine extended release: a double-blind, randomized multicenter trial comparing the onset of antidepressant response in patients with major depressive disorder.",
"Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder.",
"Mirtazapine compared with paroxetine in major depression.",
"Mirtazapine versus venlafaxine in hospitalized severely depressed patients with melancholic features.",
"A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: a STAR*D report.",
"A double-blind, fixed blood-level study comparing mirtazapine with imipramine in depressed in-patients.",
"Comparison of mirtazapine and fluoxetine in the treatment of major depressive disorder: a double-blind, randomized trial.",
"Mirtazapine: efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder. Mirtazapine-Fluoxetine Study Group.",
"A double-blind, randomized, group-comparative study of the tolerability and efficacy of 6 weeks' treatment with mirtazapine or fluoxetine in depressed Chinese patients.",
"Mirtazapine is more effective than trazodone: a double-blind controlled study in hospitalized patients with major depression.",
"A placebo-controlled trial of mirtazapine for the management of methamphetamine withdrawal.",
"Comparative effects of mirtazapine and fluoxetine on sleep physiology measures in patients with major depression and insomnia.",
"Mirtazapine vs. placebo in posttraumatic stress disorder: a pilot trial."
] |
[
"Background: the efficacy and tolerability of the new antidepressant mirtazapine were evaluated in a multicentre, randomized, double-blind, amitriptyline-controlled, 5 week clinical study. Method: 156 patients with a DSM-III diagnosis of major depressive episode and 21-item Hamilton Psychiatric Rating Scale for Depression (HPRSD) score ≥ 18, were randomized to treatment with either mirtazapine 20-60 mg/day or amitriptyline 75-225 mg/day. Results: mirtazapine and amitriptyline were equally effective in reducing depressive symptoms, as assessed by the 17-item HPRSD and MADRS scales. Mirtazapine was better tolerated than amitriptyline, with fewer drop-outs due to adverse events and lower incidences of adverse events both at the beginning and at the end of the trial. Conclusion: this study shows that mirtazapine is as effective as amitriptyline in treating major depression, while at the same time better tolerated.",
"Authors studied the efficacy and tolerability of mirtazapine and paroxetine in elderly patients with major depression during an acute phase (8 weeks) and an extension phase (16 weeks).\n Patients with major depression and without dementia, at least 65 years old, were eligible; they were randomized to mirtazapine or paroxetine once daily, with doses increasing over 42 days. Efficacy was assessed with the Ham-D and Clinical Global Impressions Scale, and tolerability was assessed from adverse events.\n Of 255 patients randomized, 126 on mirtazapine and 120 on paroxetine were included in the efficacy analysis. Differences favoring mirtazapine were observed for the mean change from baseline in Ham-D-17 score. Other significant differences were in the proportion of patients classified as responders (50% decrease from baseline Ham-D-17 scores) at Day 14 and in remission (Ham-D-17 score of 7 or less) at Day 42. The median time to response was 26 days in the mirtazapine group and 40 days in the paroxetine group. The mirtazapine group also showed more reduction in Ham-D Factor I (Anxiety/Somatization) and Factor VI (Sleep Disturbance) scores. Efficacy of both drugs was maintained during the extension phase. Patients on paroxetine were more likely to discontinue therapy in the acute phase because of adverse events.\n During the first weeks of treatment, antidepressant effects were more pronounced in the mirtazapine group, suggesting that mirtazapine has an earlier onset of action. Mirtazapine also demonstrated a better tolerability profile and represents a valuable option for the treatment of depression in elderly patients.",
"Depression is a major global problem associated with large medical, sociological and economic burdens. Mirtazapine (Remeron, Organon NV, The Netherlands) is an antidepressant with a unique mechanism of action that has similar or superior efficacy to TCAs and SSRIs in moderate-to-severe depression. However, this agent has not yet been tested in patients with severe depression alone.\n To compare the antidepressant efficacy and tolerability of mirtazapine and fluoxetine and their effects on anxiety and quality of life in patients with severe depression (> or = 25 points on the first 17 items of the Hamilton Depression Rating Scale [HDRS-17]).\n In this double-blind study, 297 severely depressed patients were randomised to receive mirtazapine 15-60 mg/day (n = 147) or fluoxetine 20-40 mg/day (n = 152) for 8 weeks. 294 subjects were actually treated and 292 included in the intent-to-treat population. Symptom severity was measured by the HDRS-17, Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) rating scale. Quality of life was self-assessed by patients using the Leeds Sleep Evaluation Questionnaire and the Quality of Life, Enjoyment and Satisfaction Questionnaire. Adverse events were recorded throughout the study.\n No statistically significant differences were noted between the two groups in change from baseline HDRS-17 score at any time point; both treatments were associated with large (approximately 15 points) decreases by study end. However, more mirtazapine-treated patients tended to exhibit a > or = 50% decrease in HDRS score (significant at day 7; 9.0% vs 0.7%, p = 0.002). Significant differences in favour of mirtazapine were also observed at day 14 for changes in MADRS scores (-10.9 vs -8.5, p = 0.006) and the proportion of patients with > or = 50% decrease in MADRS score (21.4% vs 10.9%, p = 0.031). On the CGI, the proportion of 'much/very much improved' patients tended to be greater with mirtazapine (significant at day 7; 9.7% vs 3.4%, p = 0.032). No significant between-group differences were observed for the majority of quality-of-life measures. However, mirtazapine produced significantly better improvements on 'sleeping assessment 1' (14.9 +/- 5.2 vs 13.7 +/- 5.4, p = 0.028) and 'sleeping assessment 2' (p = 0.013) than fluoxetine. Both agents were generally well tolerated but mirtazapine-treated patients experienced a mean weight gain of 0.8 +/- 2.7 kg compared with a mean decrease in weight of 0.4 +/- 2.1 kg for fluoxetine-treated patients (p < 0.001).\n Mirtazapine is as effective and well tolerated as fluoxetine in the treatment of patients with severe depression.",
"Primary care patients with a major depressive disorder and 17-item Hamilton Rating Scale for Depression (17-HAM-D) score >18 were randomized to 24 weeks of treatment with mirtazapine 30-45 mg/day (n=99) or paroxetine 20-30 mg/day (n=98). Both treatments were efficacious in improving depressive symptomatology, as assessed by group mean 17-HAM-D scores, percentages of HAM-D responders and remitters and Clinical Global Improvement responders. The mirtazapine group showed statistically significantly larger decreases from baseline in group mean 17-HAM-D scores at weeks 1, 2 and 4, and the difference with the paroxetine group reached the level of clinical relevance at weeks 2 and 4. Antidepressant efficacy was maintained throughout both the acute and continuation phase of treatment. Both treatments were well tolerated. The only adverse event with a statistically significantly higher incidence in the mirtazapine group was fatigue. Statistically significantly more paroxetine-treated patients complained of increased sweating, headache and nausea. The results demonstrate that both mirtazapine and paroxetine were efficacious and well tolerated when used for 24 weeks in depressed patients treated in primary care. An observed difference in efficacy favouring mirtazapine between weeks 1 and 4 indicates that mirtazapine patients had improved earlier compared to those on paroxetine, and corroborates similar findings in other comparisons of mirtazapine versus selective serotonin reuptake inhibitors.",
"This multinational, randomized, double-blind study was specifically designed to prospectively compare the onset of antidepressant efficacy of mirtazapine orally disintegrating tablets and sertraline at dosages commonly used in clinical practice. A total of 345 patients with major depressive episode (DSM-IV) received mirtazapine (30-45 mg/d) or sertraline (50-150 mg/d) for 8 weeks. Mirtazapine was administered in the newly developed fast dissolving, orally disintegrating tablet formulation. Assessments were performed at baseline and on days 4, 7, 10, 14, 28, 42, and 56. The primary efficacy variable (mean absolute change from baseline in the Hamilton Depression Rating Scale [HAMD] total score [17 items]) showed that mirtazapine was significantly (P < 0.05) more effective than sertraline at all assessments during the first 2 weeks of the study. After this time, HAMD total scores were similar in both groups. These findings were supported by analysis of the HAMD response rate (ie, > or =50% reduction in HAMD total score from baseline), HAMD remission rate (HAMD total score of < or =7), and the Montgomery-Asberg Depression Rating Scale (MADRS). Both treatments were well tolerated. In addition, mirtazapine had a greater effect than sertraline on sexual functioning. In conclusion, this first prospective onset of action study using the orally disintegrating tablet indicates that mirtazapine has a faster onset of therapeutic effect than sertraline. The orally disintegrating tablet formulation of mirtazapine used in this study is known to enhance the convenience and compliance by the patient.",
"A total of 115 elderly patients (60-85 years of age) with DSM III diagnosis of major depressive episode were randomly assigned to 6 weeks of treatment with either mirtazapine, 15-45 mg/day, or amitriptyline, 30-90 mg/day. Efficacy was assessed biweekly, using the Hamilton Rating Scale for Depression (HRSD) and Montgomery and Asberg Depression Rating Scale (MADRS) as primary outcome variables. The treatment with both drugs resulted in a similar reduction of total HRDS and MADRS scores, with no statistically significant differences between treatment groups at any assessment point or at endpoint. Statistically significant differences favouring amitriptyline were present according to CGI-Global Improvement Scale at endpoint, HRDS cognitive disturbance factor at weeks 2, 4 and 6 and endpoint and retardation factor at week 6. Adverse events were reported by a similar number of patients in both treatment groups. Additional research is needed to assess further the efficacy and tolerability of mirtazapine among elderly depressed patients.",
"We aimed to compare the antidepressant and anxiolytic effects, tolerability and effects on quality of life of mirtazapine and citalopram in a randomized, double-blind, multicentre, 8-week study. Patients with a Major Depressive Episode (DSM-IV) and a baseline score of > or = 22 on the Montgomery-Asberg Depression Rating Scale (MADRS) were randomized to 8 weeks treatment with either mirtazapine (n = 137, 15-60 mg/day) or citalopram (n = 133, 20-60 mg/day). Efficacy was evaluated by the MADRS, Hamilton Anxiety Scale (HAM-A), Clinical Global Impression scales (CGI), the Leeds Sleep Evaluation Questionnaire (LSEQ) and Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ). The efficacy analyses were performed on the Intent-To-Treat Group using the Last Observation Carried Forward method. Vital signs and laboratory variables are measured and adverse events recorded at each weekly visit. The magnitude of reduction from baseline in group mean MADRS scores was large in both groups, reaching after 8 weeks of treatment mean scores of 9.1 in the mirtazapine group and 8.9 in the citalopram group. Both treatments also resulted in a substantial improvement in anxiety symptoms, sleep disturbances and quality of life, and high percentage of responders. However, at day 14, statistically significantly larger magnitudes of change favouring mirtazapine were present in the group mean MADRS, HAM-A and CGI-Severity of illness and Quality of life scores. A difference of 2.3 points on MADRS favouring mirtazapine is considered indicative for a clinically relevant superiority between two proven antidepressants. Mirtazapine treatment was also related to faster improvement of sleep, quality of sleep and improved alertness following awakening, as shown by statistically significant differences on the self-rating LSEQ at various time points. There were no differences between two treatment groups on self-rating QLSEQ. Both drugs were well tolerated, with a low number of patients in either group prematurely terminating the study due to adverse events (mirtazapine: 3.6%, citalopram, 3.0%). Sweating and nausea were statistically significantly more frequent in the citalopram group and increased appetite and complaints of weight increase in the mirtazapine group. There were no clinically relevant changes in laboratory parameters and vital sign variables with either treatment, except for clinically relevant increase in body weight, occurring more frequently in mirtazapine patients. In this study, mirtazapine and citalopram were equally effective in reducing symptoms of depression and anxiety, and well tolerated. However, mirtazapine was significantly more effective than citalopram after 2 weeks of treatment on the MADRS, HAM-A and CGI Severity of illness and Quality of life scales. This finding, consistently present at all major efficacy variables, suggests potentially faster onset of efficacy of mirtazapine over citalopram.",
"To examine the antidepressant efficacy of a dual-acting antidepressant (mirtazapine) in patients with post-myocardial infarction (MI) depressive disorder. Antidepressants used in post MI trials with a randomized, double-blind, placebo-controlled design have been restricted to selective serotonin reuptake inhibitors (SSRIs). Antidepressant effects have been limited.\n In a prospective multicenter study, 2177 patients with MI were evaluated for depressive disorder during the first year post MI. Ninety-one patients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for major or minor depressive disorder were randomized to a 24-week, double-blind, placebo-controlled trial. Antidepressant efficacy was tested using last-observation-carried-forward procedure and repeated measurements analysis using the SPPS mixed models approach, with as primary outcome reduction in depressive symptomatology on the 17-item Hamilton-Depression Rating Scale (Ham-D), and secondary outcomes the Beck Depression Inventory (BDI) and depression subscale of the Symptom Check List 90 items (dSCL-90) as well as the Clinical Global Impression (CGI) scale.\n Using the \"last observation carried forward\" (LOCF) method, mirtazapine did not show to be superior to placebo on the Ham-D, but did on the BDI, dSCL-90, and CGI scale over the acute treatment phase of 8 weeks (n = 91). Using mixed models analysis over the entire 24 weeks of treatment (n = 40), we did find a significant difference favoring mirtazapine to placebo on the Ham-D, BDI, and CGI, but on the dSCL-90, this difference was not significant.\n This trial shows efficacy of mirtazapine on primary and secondary depression measures. Mirtazapine seems to be safe in the treatment of post-MI depression.",
"This randomized, multicenter, double-blind study was designed to compare specifically the onset of antidepressant action of mirtazapine orally disintegrating tablets (ODT) with venlafaxine extended-release (XR) formulation in outpatients with major depression. Both treatments were administered in a rapidly escalating dosing regimen. Target doses (mirtazapine ODT, 45 mg OD; venlafaxine XR, 225 mg OD) were reached by day 6 of treatment. On the primary efficacy parameter [the average of the change in HAM-D (17-item) total score on days 5, 8, 11, and 15], mirtazapine ODT was significantly superior to venlafaxine XR (P = 0.008). In addition, calculating the HAM-D score without the sleep items resulted in significant reductions in favor of mirtazapine ODT on days 8 (P = 0.006) and 11 (P = 0.037). The proportion of responders (HAM-D decrease of > or =50% from baseline) was higher in the mirtazapine ODT group on all assessment days, being significant on days 8 (P = 0.002), 11 (P = 0.004), and 22 (P = 0.027). More patients in the mirtazapine ODT group achieved remission (HAM-D total score of < or =7) up to day 29, and the difference was statistically significant on day 15 (P = 0.016). Significant differences in favor of mirtazapine ODT were evident in the CGI of change on days 8 (P = 0.019), 11 (P = 0.004), and 15 (P = 0.031), and the CGI of severity on days 8 (P = 0.014) and 11 (P = 0.033). Both treatments were well tolerated. These results indicate that mirtazapine ODT has a faster onset of antidepressant efficacy than venlafaxine XR in patients with major depressive disorder, and that this effect is independent of its sleep-improving properties.",
"Patients (n = 150) were randomized to a 6-week, double-blind study to evaluate the relative efficacy and safety of mirtazapine, amitriptyline, and placebo in the treatment of major depressive disorder symptoms. Average daily modal doses were mirtazapine, 18 mg; amitriptyline, 111 mg; and placebo, 4.6 capsules. Mirtazapine- and amitriptyline-treated patients had statistically significantly greater mean Hamilton Rating Scale for Depression (HAM-D) score reductions (weekly visits 1, 2, 4, and endpoint) compared to placebo. These findings were supported by the Montgomery-Asberg Depression Rating Scale (MADRS); the Zung Self-rating Depression Scale (SDS); and the Clinical Global Impressions (CGI) scales. Somnolence and weight gain were the only adverse clinical experiences (ACEs) reported substantially more often by mirtazapine-treated patients than by those in the placebo group. However, more amitriptyline-treated patients reported decreased visual accommodation, dry mouth, dyspepsia, constipation, tachycardia, hypertension, hypotension, discoordination, dizziness, and tremor than mirtazapine- or placebo-treated patients. Results of this study indicate that mirtazapine is more effective than placebo in the treatment of these patients, and superior to amitriptyline in respect to anticholinergic and cardiovascular effects.",
"The aim was to compare the efficacy and tolerability of mirtazapine with those of paroxetine.\n 275 outpatients with a diagnosis of major depressive episode (DSM-IV) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) were randomly assigned to 6 weeks of treatment with mirtazapine (15-45 mg/day) or paroxetine (20-40 mg/day). Efficacy was assessed by the HAM-D-17, Hamilton Rating Scale for Anxiety (HAM-A), and Clinical Global Impressions scales (Severity and Improvement), and analyses were performed on the intent-to-treat sample (127 mirtazapine-treated patients and 123 paroxetine-treated patients).\n Mean daily doses were 32.7 mg of mirtazapine and 22.9 mg of paroxetine. Thirty patients in the mirtazapine group and 33 in the paroxetine group dropped out. Both drugs were equally effective in reducing symptoms of depression. At week 1, the mean HAM-D-17 total score was significantly lower in mirtazapine- than paroxetine-treated patients (16.5 vs. 18.8, p = .0032). Similarly, significantly more mirtazapine-treated patients were HAM-D-17 responders (> or = 50% decrease from baseline) at weeks 1 (23.2% vs. 8.9%, p = .002) and 4 (58.3% vs. 44.5%, p = .04). Both treatments were equally effective in reducing anxiety. However, the reduction in mean HAM-A total score was significantly greater with mirtazapine than with paroxetine at week 1 (-5.1 vs. -3.5, p = .0435). Tolerability of both treatments was good, with more nausea, vomiting, tremor, and sweating in the paroxetine group and more weight increase and influenza-like symptoms in the mirtazapine group.\n Mirtazapine and paroxetine were equally effective after 6 weeks of therapy and were both well tolerated. A potentially faster onset of overall therapeutic efficacy of mirtazapine was suggested by significant differences between treatments after 1 week of therapy that were due to slightly larger improvements of several core symptoms of depression as well as distinct prevention of treatment-emergent worsening of anxiety and physical components of depression.",
"The aim of this multicenter, randomized, double-blind, 8-week study was to compare the antidepressant efficacy and tolerability of mirtazapine and venlafaxine in the treatment of hospitalized patients with DSM-IV diagnosis of severe depressive episode with melancholic features. Patients with a baseline score of > or = 25 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) were randomly assigned to receive treatment with either mirtazapine (N = 78, 15-60 mg/day) or venlafaxine (N = 79, 75-375 mg/day, twice a day) in a rapid up-titration schedule. Efficacy was assessed with the Montgomery-Asberg Depression Rating Scale (MADRS), HAM-D-17, and Clinical Global Impression scale, and quality of life was assessed with the Quality of Life, Enjoyment, and Satisfaction Questionnaire and Quality of Life in Depression Scale. Tolerability was assessed with the Utvalg for Kliniske Undersogelser (UKU) side effect scale and by reporting adverse events. Both drugs were effective in reducing overall symptoms of depression, showing substantial reductions in group mean MADRS scores (-20.1 for mirtazapine and -17.5 for venlafaxine) and HAM-D-17 scores (-17.1 for mirtazapine and -14.6 for venlafaxine) at the end of the treatment. Although not statistically significant, at all assessment times higher percentages of patients treated with mirtazapine were classified as responders (> or =50% reduction) on the HAM-D (at endpoint, 62% vs. 52%) and MADRS (at endpoint: 64% vs. 58%). Likewise were the percentages of remitters (HAM-D score < or =7; MADRS score < or =12) also higher in the mirtazapine group. A statistically significant difference favoring mirtazapine was found on the HAM-D Sleep Disturbance factor at all assessment points (p < or = 0.03). Both treatments were well tolerated. Although slightly more subjects treated with mirtazapine reported at least one adverse event, a statistically significantly higher percentage of patients treated with venlafaxine (15.3%) than mirtazapine (5.1%) dropped out because of adverse events (p = 0.037). Quality of life improved in both treatment groups. In this study, treatment with mirtazapine resulted in a trend toward more responders and remitters than treatment with venlafaxine and in significantly fewer dropouts as a result of adverse events.",
"Few controlled studies have addressed the issue of which antidepressant medications should be recommended for outpatients who have not responded to multiple treatment trials. This study compared the efficacy of switching to mirtazapine to that of switching to a tricyclic antidepressant (nortriptyline) following two prospective, consecutive, unsuccessful medication treatments for nonpsychotic major depressive disorder.\n Following lack of remission or an inability to tolerate an initial trial of citalopram for up to 12 weeks (first step) and a second trial with either monotherapy involving another antidepressant or augmentation of citalopram with bupropion or buspirone (second step), adult outpatients (N=235) with nonpsychotic major depressive disorder were randomly assigned to 14 weeks of treatment with mirtazapine (up to 60 mg/day) (N=114) or nortriptyline (up to 200 mg/day) (N=121). The primary outcome, symptom remission, was defined a priori as a total exit score of </=7 on the 17-item Hamilton Rating Scale for Depression. The 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR(16)), obtained at treatment visits, provided secondary outcomes of remission (score </=5 at exit) and response (>/=50% reduction in score from baseline).\n For mirtazapine, remission rates were 12.3% and 8.0% per the Hamilton and QIDS-SR(16) scores, respectively. For nortriptyline, remission rates were 19.8% and 12.4%, respectively. QIDS-SR(16) response rates were 13.4% for mirtazapine and 16.5% for nortriptyline. Neither response nor remission rates statistically differed by treatment, nor did these two treatments differ in tolerability or adverse events.\n Switching to a third antidepressant monotherapy regimen after two consecutive unsuccessful antidepressant trials resulted in low remission rates (<20%) among patients with major depressive disorder.",
"Antidepressant effects of mirtazapine and imipramine were compared in a randomized, double blind, fixed blood-levels study with in-patients in a single centre. Patients with a DSM-III-R diagnosis of major depression and a Hamilton (17-item) score of > or = 18 were selected. After a drug-free and a placebo-washout period of 7 days in total, 107 patients still fulfilling the HRSD criterion of > or = 18, started on active treatment. The dose was adjusted to a predefined fixed blood level to avoid suboptimal dosing of imipramine. Concomitant psychotropic medication was administered only in a few cases because of intolerable anxiety or intolerable psychotic symptoms. Eight patients dropped out and two were excluded from analyses because of non-compliance; 97 completed the study. According to the main response criterion (50% or more reduction on the HRSD score) 11/51 (21.6%) patients responded on mirtazapine and 23/46 (50%) on imipramine after 4 weeks' treatment on the predefined blood level. Such a dramatic difference in efficacy between antidepressants has not often been reported before. The selection of (severely ill) in-patients, including those with suicidal or psychotic features, may have significance in this respect. Optimization of treatment with the reference drug imipramine through blood level control, exclusion of non-compliance for both drugs, exclusion of most concomitant medication and a low drop-out rate may also have contributed. It is concluded that imipramine is superior to mirtazapine in the patient population studied.",
"Depression is an international public health problem. The aim of this study was to compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Iranian patients suffering major depressive disorder.\n Thirty-six inpatients and outpatients with a diagnosis of major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders-IV) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) were randomly assigned to 6 weeks of treatment with mirtazapine (30 mg/day) or fluoxetine (20 mg/day). Efficacy was assessed by HAM-D-17. Information about adverse events was obtained by questioning of participants and/or their examination. Assessments were performed at weeks 0, 1, 2, 3, 4 and 6.\n Sixteen of mirtazapine-treated patients and fifteen of fluoxetine-treated patients completed the 6-week study period. Both treatment groups were well matched at baseline with respect to demographic and disease characteristics. Both drugs showed a significant improvement over the 6 weeks of treatment (P < 0.001). There was no statistically significant difference between the mean +/- SEM HAM-D scores of two groups at weeks 1, 2, 3, 4, and at the end point. There were no significant differences between two groups in terms of response to treatment (> or = 50% decrease from baseline in HAM-D-17 total score) and remission (HAM-D-17 score of < or = 7). None of the differences in reported adverse events was statistically significant.\n In this study, mirtazapine and fluoxetine were equally effective and well tolerated after 6 weeks of treatment in patients with major depressive disorder.",
"To compare the efficacy and tolerability of mirtazapine and fluoxetine in depressed inpatients and outpatients.\n Patients with a major depressive episode (DSM-III-R), a baseline score of > or=21 on the 17-item Hamilton Rating Scale for Depression (HAM-D), and > or=2 on HAM-D Item 1 (depressed mood) were randomly assigned to a 6-week treatment with either mirtazapine (N=66, 15-60 mg/day) or fluoxetine (N=67, 20-40 mg/day). The upper limit of the mirtazapine dose range was above the dose range approved in the United States (15-45 mg/day). Efficacy was evaluated by the HAM-D, Clinical Global Impressions, the Visual Analogue Mood Rating Scale (VAMRS), and the Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ). The efficacy analyses were performed on the intent-to-treat group using the last-observation-carried-forward method.\n Mean total 17-item HAM-D scores at baseline were 26.0 for the mirtazapine- and 26.1 for the fluoxetine-treated group. The decrease from baseline on the HAM-D was larger in the mirtazapine than in the fluoxetine group throughout the treatment period, reaching statistical significance at days 21 and 28. At assessments from day 21 and onward, the absolute difference between the 2 study groups favoring mirtazapine ranged from 3.7 to 4.2 points, the magnitude of difference usually seen between an efficacious antidepressant drug and placebo. Mean dosages at weeks 1-4 were 36.5 mg/day for mirtazapine and 19.6 mg/day for fluoxetine; the respective dosages at weeks 5-6 were 56.3 mg and 35.8 mg. Similar numbers of patients dropped out due to adverse events; tolerability profiles were comparable except for changes in body weight from baseline which were statistically significantly more pronounced in the mirtazapine group compared to the fluoxetine group.\n We found that mirtazapine was as well tolerated as fluoxetine and significantly more effective after 3 and 4 weeks of therapy.",
"To compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Chinese patients suffering moderate-to-severe depression.\n 133 patients with a diagnosis of major depressive episode (DSM-IV) and scoring 15 or more on the 17-item Hamilton Rating Scale for Depression (HAM-D) were randomly assigned to receive 6 weeks of treatment with either mirtazapine (15-45 mg/day) or fluoxetine (20-40 mg/day). Efficacy was assessed using the HAM-D and Clinical Global Impressions scale, with analyses performed on the intent-to-treat sample using the last-observation-carried-forward method. Safety analysis was based on the all-subjects-treated group.\n Mean daily doses were 34.1 mg for mirtazapine (N = 66) and 30.7 mg for fluoxetine (N = 66). Thirty patients in the mirtazapine group and 22 in the fluoxetine group dropped out. Both drugs proved equally effective for reduction of the overall symptoms of depression throughout the treatment period. At day 42, the mean reductions in HAM-D total score (compared with baseline) were 11.8 and 10.6 for the mirtazapine and fluoxetine groups, respectively; however, the changes were not statistically significant. Both treatments were well tolerated, with more nausea and influenza-like symptoms observed for the fluoxetine group, and greater weight increase and somnolence for the mirtazapine analog.\n Both mirtazapine and fluoxetine were indistinguishable in effectiveness for treatment of depressive symptoms, and both were well tolerated by our population of depressed Chinese patients. In line with analogous Western reports, the safety of mirtazapine and fluoxetine was comparable for our depressed Chinese patients; however, slightly different side effect profiles were noted for the 2 drugs in our study.",
"Two hundred hospitalized patients with DSM-III diagnosis of moderate to severe major depressive episode were randomized to receive mirtazapine or trazodone for 6 weeks in a double-blind trial. The dosages were 24-72 mg/day for mirtazapine and 150-450 mg/day for trazodone. The improvement on all depression rating scales used was generally greater for mirtazapine, with statistically significant differences over trazodone in the Hamilton Psychiatric Rating Scale for Depression total score and two subscores (the Bech melancholia factor and retardation factor), the Brief Psychiatric Rating Scale total score, the General Psychiatric Impression Global Assessment Scale, the Beck score and responder rates. Mirtazapine was well tolerated, while the trazodone-treated patients experienced somnolence more frequently, particularly during the first 2 weeks of treatment. Furthermore, postural symptoms were a clinical problem in 6% of the trazodone-treated patients. In this trial, mirtazapine showed significant clinical advantages over trazodone in terms of overall efficacy and tolerability.",
"As an antidepressant with sedative and anxiolytic properties, mirtazapine may be an appropriate pharmacotherapy for methamphetamine withdrawal. This study sought to examine whether mirtazapine improves retention and alleviates methamphetamine withdrawal symptoms in an out-patient setting.\n An out-patient double-blind, randomised placebo-controlled trial of mirtazapine for the treatment of methamphetamine withdrawal was conducted (15 mg nocte for 2 days, 30 mg nocte for 12 days). Both groups were offered narrative therapy counselling. Measures recorded on days 0, 3, 7, 14 and 35 included: treatment retention, Amphetamine Cessation Symptoms Assessment, the Athens Insomnia Scale, the Brief Symptom Inventory, the Depression-Anxiety-Stress Scale (DASS), Severity of Dependence scale and the Opiate Treatment Index Drug Use subscale.\n Thirty-one participants were recruited (18 placebo, 13 mirtazapine) and 52% completed the 2-week medication phase. No significant differences between the mirtazapine and placebo groups in retention, or any symptom measure were observed, except greater DASS-anxiety and longer sleep duration were measured at baseline among the mirtazapine group.\n Results suggest that mirtazapine does not facilitate retention or recruitment in out-patient methamphetamine withdrawal treatment, although recruitment may have been insufficient to identify a significant treatment effect. The potential role of narrative therapy for methamphetamine dependent patients deserves further exploration.",
"Sleep complaints are common in patients with major depressive disorder (MDD). Both MDD and antidepressant drugs characteristically alter objective sleep measures. This study compares the effects of mirtazapine and fluoxetine on sleep continuity measures in DSM-IV MDD patients with insomnia.\n Patients (N = 19) received initial baseline polysomnography evaluations over 2 consecutive nights. Subjects were randomly assigned to either fluoxetine (20-40 mg/day) or mirtazapine (15-45 mg/day) treatment for an 8-week, double-blind, double-dummy treatment trial. Single-night polysomnograms were conducted at weeks 1, 2, and 8, with depression ratings assessed at baseline and weeks 1, 2, 3, 4, 6, and 8. Statistical analysis was performed by repeated-measures analysis of variance followed by Dunnet's post hoc analyses.\n Patients receiving mirtazapine (N = 8) had significant improvement in objective sleep physiology measures at 8 weeks. Improvements in sleep latency, sleep efficiency, and wake after sleep onset were significant after only 2 weeks of mirtazapine treatment. No significant changes in sleep continuity measures were observed in the fluoxetine group (N = 11). Both groups improved clinically in mood and subjective sleep measures from baseline, with no differences between groups.\n These data demonstrate the differential effects of mirtazapine and fluoxetine, with significant improvement in favor of mirtazapine, on objective sleep parameters in MDD patients with insomnia.",
"Based on an earlier pilot study, as well as a theoretical consideration of its mechanism of action, we undertook a placebo-controlled, double-blind trial of mirtazapine in posttraumatic stress disorder.\n Twenty-nine patients were randomized to receive drug up to 45 mg/day or placebo double-blind on a 2:1 ratio for 8 weeks, with data being available for analysis in 26. Primary outcome measures comprised the Short Posttraumatic Stress Disorder Rating Interview (SPRINT) Global Improvement item and total score. Secondary measures comprised the Davidson Trauma Scale, Structured Interview for Posttraumatic Stress Disorder and Hospital Anxiety Depression Scale. Adverse events were also measured.\n On the Short Posttraumatic Stress Disorder Rating Interview Global Improvement measure, rates of response were 64.7% and 20.0% for mirtazapine and placebo. Treatment effects in favor of mirtazapine were noted on the Short Posttraumatic Stress Disorder Rating Interview global, Structured Interview for Posttraumatic Stress Disorder, and Hospital Anxiety Depression Scale anxiety subscale scores. The drug was well tolerated.\n Mirtazapine was more effective than placebo on some measures in posttraumatic stress disorder and general anxiety symptoms."
] |
Some statistically significant and possibly clinically meaningful differences between mirtazapine and other antidepressive agents were found for the acute-phase treatment of major depression. Mirtazapine is likely to have a faster onset of action than SSRIs during the acute-phase treatment. Dropouts occur similarly in participants treated with mirtazapine and those treated with other antidepressants, although the adverse event profile of mirtazapine is unique.
|
CD002142
|
[
"8412266",
"15908042",
"8648387",
"7851558",
"11597795"
] |
[
"Adjuvant chemotherapy for completely resected stage III non-small-cell lung cancer. Results of a randomized prospective study. The Japan Clinical Oncology Group.",
"A randomised controlled trial of pre-operative chemotherapy followed, if feasible, by resection versus radiotherapy in patients with inoperable stage T3, N1, M0 or T1-3, N2, M0 non-small cell lung cancer.",
"Effect of ABVD chemotherapy with and without mantle or mediastinal irradiation on pulmonary function and symptoms in early-stage Hodgkin's disease.",
"A randomized trial of postoperative adjuvant chemotherapy in non-small cell lung cancer (the second cooperative study). The Study Group of Adjuvant Chemotherapy for Lung Cancer (Chubu, Japan).",
"Randomized trial addressing risk features and time factors of surgery plus radiotherapy in advanced head-and-neck cancer."
] |
[
"Two hundred nine patients with completely resected stage III non-small-cell lung cancer were randomized to receive postoperative cisplatin and vindesine chemotherapy or no further treatment. Before randomization, patients were stratified by the histologic characteristics of their tumors (squamous versus nonsquamous cell carcinoma). Prognostic variables such as histology, performance status, extent of operation, and tumor and nodal status of the eligible patients in chemotherapy (n = 90) and control groups (n = 91) were equally distributed. There was no statistically significant difference in disease-free and overall survival between the two groups. The 3-year disease-free survivals of the chemotherapy and control groups were 37% and 42%, respectively. The median survival times (5-year survival) were 31 months (35%) in the chemotherapy group and 37 months (41%) in the control group. These was no different pattern in the first site of recurrence (local versus systemic) between the two groups. This study failed to demonstrate the therapeutic benefits of postoperative cisplatin and vindesine chemotherapy.",
"The majority of patients with stage T3, N1, M0 or T1-3, N2, M0 non-small cell lung cancer are considered inoperable, and receive radical radiotherapy. This randomised trial aimed to assess whether, in this group of inoperable patients, a policy of neo-adjuvant chemotherapy (with mitomycin, ifosfamide and cisplatin (MIC) or mitomycin, vinblastine and cisplatin (MVP)) followed, if feasible, by surgery (CT-S), would result in better outcomes than radical radiotherapy (RT). The trial closed due to poor accrual, with only 48 patients randomised in 3 years. Only 4 of the 24 patients in the CT-S group had a complete resection, and of these, the 2 patients who had a pneumonectomy both died 12 days after surgery. There was no evidence of an improved survival in the CT-S group (median survival 13.8 months, compared with 11.3 months for the RT group), but because the trial failed to recruit we were unable to reach any reliable conclusions about these two treatment options.",
"To evaluate the effect of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy alone and of ABVD with mantle or mediastinal irradiation (RT) on the pulmonary function of patients with early-stage Hodgkin's disease.\n Between 1989 and 1993, 60 patients with clinical stage I to IIIA HD enrolled onto randomized trials at Memorial Sloan-Kettering Cancer Center (MSKCC) underwent prospective evaluation of pulmonary function. All patients received six cycles of ABVD, and 30 patients received mantle or mediastinal RT. Pulmonary function tests (PFTs) and symptom evaluation were conducted before, during, and after completion of chemotherapy and RT, and at various intervals thereafter. The median follow-up time was 30 months.\n During chemotherapy, symptoms of cough and dyspnea on exertion developed in 32 of 60 patients (53%) and declines in pulmonary function occurred in 22 of 60 patients (37%). Discontinuation of bleomycin was necessary in 14 of 60 patients (23%). Following chemotherapy, there was a significant decline in median forced vital capacity (FVC) and diffusing capacity of carbon monoxide (DLCO). In patients who received mantle or mediastinal RT, there was a further decline in FVC following radiation therapy. At the most recent follow-up evaluation, five of 29 patients (18%) who received ABVD alone and nine of 30 (30%) who received ABVD and RT reported persistent mild pulmonary symptoms (P = .36), which did not significantly affect normal daily activity.\n ABVD chemotherapy induced acute pulmonary toxicity that required bleomycin dose modification in a substantial number of patients. The addition of RT resulted in a further decrease in FVC; however, this did not significantly affect the functional status of patients.",
"A prospective randomized trial (the second cooperative study) was conducted from July 1985 to December 1987 to investigate the benefits of postoperative adjuvant chemotherapy in patients for whom non-small cell lung cancer had been resected completely. Patients were randomly assigned either to a chemotherapy group (group A) treated postoperatively with CDDP (66 mg/m2 x 1), ADM (26 mg/m2 x 1) and UFT (8 mg/kg/day) during 6 months, or to a control group (group B) which had undergone surgery only. Three hundred and thirty-three resected cases were registered. Among them, 24 cases (7.2%) were excluded, because of incomplete resection (15), pathologically benign tumour (3), small cell lung cancer (2) and other factors (4). Three hundred and nine cases were eligible: 155 cases in group A (p-Stage I 93, II 19, III 43) and 154 in group B (I 109, II 10, III 35). The 5-year survival rate in group A was 61.8%, and that in group B 58.1%. The 5-year disease-free survival rate for each group was 61.8% and 57.4%, respectively. There were no significant differences in the 5-year survival between the two groups. However, since a significant difference was observed between the two groups regarding pathological lymph node metastasis (pN), the prognostic factors were adjusted using Cox's proportional hazard model. Thereafter the adjusted survival rate and disease-free survival rate for group A became significantly higher than for group B (P = 0.044 and P = 0.036, respectively). Thus, from these results, it is concluded that the role of surgery for non-small cell lung cancer still remains of primary importance, and postoperative adjuvant chemotherapy is effective to improve the results of surgery and prolong life of patients with non-small cell lung cancer.",
"A multi-institutional, prospective, randomized trial was undertaken in patients with advanced head-and-neck squamous cell carcinoma to address (1) the validity of using pathologic risk features, established from a previous study, to determine the need for, and dose of, postoperative radiotherapy (PORT); (2) the impact of accelerating PORT using a concomitant boost schedule; and (3) the importance of the overall combined treatment duration on the treatment outcome.\n Of 288 consecutive patients with advanced disease registered preoperatively, 213 fulfilled the trial criteria and went on to receive therapy predicated on a set of pathologic risk features: no PORT for the low-risk group (n = 31); 57.6 Gy during 6.5 weeks for the intermediate-risk group (n = 31); and, by random assignment, 63 Gy during 5 weeks (n = 76) or 7 weeks (n = 75) for the high-risk group. Patients were irradiated with standard techniques appropriate to the site of disease and likely areas of spread. The study end points were locoregional control (LRC), survival, and morbidity.\n Patients with low or intermediate risks had significantly higher LRC and survival rates than those with high-risk features (p = 0.003 and p = 0.0001, respectively), despite receiving no PORT or lower dose PORT, respectively. For high-risk patients, a trend toward higher LRC and survival rates was noted when PORT was delivered in 5 rather than 7 weeks. A prolonged interval between surgery and PORT in the 7-week schedule was associated with significantly lower LRC (p = 0.03) and survival (p = 0.01) rates. Consequently, the cumulative duration of combined therapy had a significant impact on the LRC (p = 0.005) and survival (p = 0.03) rates. A 2-week reduction in the PORT duration by using the concomitant boost technique did not increase the late treatment toxicity.\n This Phase III trial established the power of risk assessment using pathologic features in determining the need for, and dose of, PORT in patients with advanced head-and-neck squamous cell cancer in a prospective, multi-institutional setting. It also revealed the impact of the overall treatment time in the combination of surgery and PORT on the outcome in high-risk patients and showed that PORT acceleration without a reduction in dose by a concomitant boost regimen did not increase the late complication rate. These findings emphasize the importance of coordinated interdisciplinary care in the delivery of combined surgery and RT."
] |
PORT is detrimental to patients with early stage completely resected non-small cell lung cancer and should not be used in the routine treatment of such patients. The role of PORT in the treatment of N2 tumours is not clear and may justify further research.
|
CD000950
|
[
"2122630",
"2122016",
"7844680",
"6406654",
"3936908",
"9713029"
] |
[
"Parenteral nutrition in preterm neonates with and without carnitine supplementation.",
"Effect of intravenous L-carnitine on growth parameters and fat metabolism during parenteral nutrition in neonates.",
"Effects of parenteral L-carnitine supplementation on fat metabolism and nutrition in premature neonates.",
"Carnitine deficiency in premature infants receiving total parenteral nutrition: effect of L-carnitine supplementation.",
"The metabolic effects of oral L-carnitine administration in infants receiving total parenteral nutrition with fat.",
"Randomised controlled trial of L-carnitine as a nutritional supplement in preterm infants."
] |
[
"The effects of carnitine supplementation on fat and glucose metabolism and carnitine balance were studied in 12 preterm neonates receiving full or partial parenteral nutrition (PN) for 5 to 21 days. The gestational age ranged from 27 to 32 weeks and the birth weight from 790 to 2090 g. The neonates were assigned at random to receive either L-carnitine 10 mg/kg (n = 6) or saline (n = 6). In the carnitine group, increased concentrations in plasma of total and free carnitine were observed. Less than 50% of the given dose was recovered in urine. In the placebo group no changes in the total plasma carnitine concentration were seen. In all neonates plasma triglycerides, free fatty acids, glycerol, alanine, 3-hydroxybutyrate (BOB), glucose and lactate were measured at predetermined intervals. The only significant difference between the groups was higher BOB-concentrations in the carnitine group 2 days after the start of parenteral nutrition. Elevated BOB concentrations are an indicator of improved fatty acid oxidation in the carnitine group. In this study, only a temporary effect of the carnitine supplementation was found.",
"To determine whether intravenous carnitine can improve nutritional indices, neonates requiring parenteral nutrition were randomized into carnitine treatment (n = 23) and control (n = 20) groups. Observed plasma lipid indices, carnitine and nitrogen balances, and plasma carnitine concentrations were not different in the prestudy period. Under standardized, steady-state conditions, 0.5 g/kg Intralipid was administered intravenously over 2 hr prior to carnitine administration, after infants received 7 days of 50 mumol/kg/day, and after a second 7 days of 100 mumol/kg/day of continuous intravenous L-carnitine as part of parenteral nutrition. Triglyceride (TGY), free fatty acid (FFA), acetoacetate (AA), beta-hydroxybutyrate (BOB), and plasma carnitine concentrations were measured prior to and at 2, 4, and 6 hr after the initiation of the lipid bolus. Twenty-four-hour urine collections for nitrogen and carnitine balance were obtained on days 7 and 14. Neonates receiving carnitine had significantly greater concentrations of plasma carnitine on days 7 and 14 (p less than 0.001). Greater nitrogen (p less than 0.05) and carnitine (p less than 0.001) balances and weight gain (week 2, p less than 0.05) were found in the carnitine-supplemented group when compared with controls. On day 14, (BOB + AA)/FFA ratios were significantly higher (p less than 0.05), and peak TGY concentrations and 6-hr FFA concentrations were significantly lower (p less than 0.05) in the treatment group. Carnitine supplementation was associated with modest increases in growth and nitrogen accretion possibly by enhancing the neonate's ability to utilize exogenous fat for energy.",
"The effects of parenteral L-carnitine supplementation on fat metabolism, nutrient intake, and plasma and erythrocyte carnitine concentrations were studied in 43 very low birth weight infants. Infants were randomly assigned to control or carnitine-supplemented (50 mumol/kg per day) groups within two weight categories: group 1, 750 to 1000 gm, and group 2, 1001 to 1500 gm. Plasma total, free, and acyl carnitine levels, erythrocyte carnitine levels, serum beta-hydroxybutyrate and triglyceride levels, and total fat intake were monitored weekly until 50% of total caloric intake was met enterally. Neonates receiving carnitine had higher plasma carnitine levels than control groups (total carnitine: group 1, 75.2 +/- 22.9 vs 9.6 +/- 2.7 mmol/ml; group 2, 61.6 +/- 31.2 vs 13.0 +/- 9.2 nmol/ml). Levels of beta-OH-butyrate decreased from baseline in control neonates (group 1, 0.12 +/- 0.06 to 0.03 +/- 0.02 mmol/L; group 2, 0.11 +/- 0.03 to 0.05 +/- 0.02 mmol/L); they remained unchanged in supplemented groups. Thus ketogenesis appeared less impaired in infants receiving supplements. Supplemented group 2 tolerated more fat than control group 2; triglyceride levels remained acceptable in all groups. Carnitine group 2 had greater weight gain than control group 2 during the first 2 weeks of life. We conclude that very low birth weight infants requiring prolonged parenteral nutrition have carnitine deficiency with impaired ketogenesis. Parenteral administration of carnitine appears to alleviate this metabolic disturbance.",
"To investigate whether L-carnitine supplementation may correct nutritional carnitine deficiency and associated metabolic disturbances in premature infants receiving total parenteral nutrition, an intravenous fat tolerance test (1 gm/kg Intralipid over four hours) was performed in 29 premature infants 6 to 10 days of age (15 receiving carnitine supplement 10 mg/kg . day L-carnitine IV, and 14 receiving no supplement). Total carnitine plasma values were normal or slightly elevated in supplemented but decreased in nonsupplemented infants. In both groups, fat infusion resulted in an increase in plasma concentrations of triglycerides, free fatty acids, D-beta-hydroxybutyrate, and short-chain and long-chain acylcarnitine, but total carnitine values did not change. After fat infusion, the free fatty acids/D-beta-hydroxybutyrate ratios were lower and the increase of acylcarnitine greater in supplemented infants of 29 to 33 weeks' gestation than in nonsupplemented infants of the same gestational age. This study provides evidence that premature infants of less than 34 weeks' gestation requiring total parenteral nutrition develop nutritional carnitine deficiency with impaired fatty acid oxidation and ketogenesis. Carnitine supplementation improves this metabolic disturbance.",
"beta-Oxidation, an important pathway in the metabolism of free fatty acids, occurs within the mitochondria in mammals. L-Carnitine is an essential cofactor in the transfer of long-chain fatty acids across the inner mitochondrial membrane. Maintenance of normal carnitine concentrations in whole blood and tissues, either through diet or biosynthesis, would appear necessary for adequate utilization of fat as an energy source. Infants, especially premature ones, without an exogenous dietary source of carnitine, have decreased plasma carnitine levels compared with infants receiving carnitine-supplemented feedings. To determine the importance of carnitine supplementation in a total parenteral nutrition program in infants in which a fat emulsion serves as a major calorie source, the following study was undertaken. Twelve infants receiving total parenteral nutrition (TPN) with fat for seven days were divided into two treatment groups. Group 1 was orally supplemented for seven days with carnitine (70 mumol/l/kg/24 h in 24 mL of 5% dextrose), while the second group received seven days of placebo supplementation (dextrose 5%, 24 cc/24 h). Plasma carnitine levels in the carnitine-supplemented group were significantly higher (29 +/- 8 nmol/mL) than in the control group (12.4 +/- 3.5 nmol/mL) after seven days of treatment. However, clearance of serum triglycerides and free fatty acids was not significantly different between the two groups. Baseline triglyceride levels in the carnitine-supplemented group were 96 +/- 42 mg/dL, increased to 242 +/- 101 mg/dL after the lipid challenge and decreased to 121 +/- 47 mg/dL two hours after the lipid infusion.(ABSTRACT TRUNCATED AT 250 WORDS)",
"To evaluate the effect of L-carnitine supplementation (25 mg/kg/d) on the growth and incidence of hypoglycaemia in preterm infants.\n A double blind, placebo controlled randomised trial, stratified for gestational age, was conducted of 86 preterm infants between 28 and 34 gestational weeks. The median gestational ages in the carnitine group and placebo groups were 30.7 weeks (range 28.0 to 33.6) and 31.4 weeks (range 28.0 to 33.9), respectively. The median birthweights were 1.557 kg (range 0.944 to 2.275) and 1.645 kg (range 0.885 to 2.545), respectively.\n Mean plasma free carnitine concentrations were below values for normal term infants in both groups on day 1 (carnitine group 44.8 mumol/l, placebo group 25.5 mumol/l) in the placebo group on day 7 (50.7 mumol/l), but in neither group on days 14 and 28. Total, free, and acylcarnitine concentrations were significantly increased in both urine and blood in the L-carnitine group. There was no significant difference between the placebo and carnitine supplemented groups in growth rate, as assessed by weight, length, skinfold thickness and head circumference measurements, or in the incidence of episodes of hypoglycaemia.\n The addition of carnitine as a nutritional supplement at a dose of 25 mg/kg/day did not improve growth in our group of preterm infants nor protect them from episodes of hypoglycaemia."
] |
We found no evidence to support the routine supplementation of parenterally fed neonates with carnitine.
|
CD003665
|
[
"2881038",
"6407714",
"2777499",
"676731",
"2179850",
"6673482",
"2911997",
"12819167",
"6546416",
"7029275",
"16641396",
"3981321",
"19263337",
"10379020",
"2654350",
"11124916",
"16616557",
"2587133",
"15695996"
] |
[
"Vitamin E supplementation reduces frequency of periventricular haemorrhage in very preterm babies.",
"Protective effect of vitamin E (DL-alpha-tocopherol) against intraventricular haemorrhage in premature babies.",
"Vitamin E and selenium in preterm infants: lack of effect on clinical patency of ductus arteriosus.",
"Vitamin E requirements of preterm infants.",
"Effect of intramuscular vitamin E on mortality and intracranial hemorrhage in neonates of 1000 grams or less.",
"The effect of vitamin E on erythrocyte hemolysis and lipid peroxidation in newborn premature infants.",
"Vitamin E supplementation in very-low-birth-weight infants: long-term follow-up at two different levels of vitamin E supplementation.",
"Effects of vitamin E supplementation during erythropoietin treatment of the anaemia of prematurity.",
"Retrolental fibroplasia and vitamin E in the preterm infant--comparison of oral versus intramuscular:oral administration.",
"Retrolental fibroplasia: efficacy of vitamin E in a double-blind clinical study of preterm infants.",
"Vitamins C and E and the risks of preeclampsia and perinatal complications.",
"Vitamin E status in preterm infants fed human milk or infant formula.",
"Vitamin E levels during early iron supplementation in preterm infants.",
"Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network.",
"Effect of sustained pharmacologic vitamin E levels on incidence and severity of retinopathy of prematurity: a controlled clinical trial.",
"Randomised controlled trial of oral vitamin A supplementation in preterm infants to prevent chronic lung disease.",
"Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial.",
"Maternal administration of vitamin K does not improve the coagulation profile of preterm infants.",
"Vitamin C and E supplementation in women at high risk for preeclampsia: a double-blind, placebo-controlled trial."
] |
[
"231 babies, born at less than or equal to 32 weeks' gestation were enrolled in a randomised, controlled trial to assess the efficacy of vitamin E (dl-alpha-tocopherol acetate) in the prevention of periventricular haemorrhage. Daily supplementation with 20 mg/kg vitamin E intramuscularly during the first 3 days of life was associated with a rise in plasma vitamin E concentration and a reduction in hydrogen peroxide haemolysis of red blood cells in vitro. Among babies without haemorrhage on entry to the trial (n = 210), supplemented babies had a lower frequency of intraventricular haemorrhage than controls (8.8% v 34.3%; p less than 0.005) and a lower combined frequency of intraventricular and parenchymal haemorrhage (10.8% v 40.7%; p less than 0.0001) on the final ultrasound brain scan. This protective effect was observed in both inborn and referred babies but was stronger in the former. Supplementation had no effect on mortality, but among survivors fewer supplemented babies than controls had intraventricular or parenchymal haemorrhage (10.7% v 32.6%; p less than 0.001). Possibly, vitamin E scavenges free radicals generated during ischaemic injury of the subependymal region and thereby limits tissue damage and the extent of periventricular haemorrhage on reperfusion.",
"Forty four babies, of less than 32 weeks' gestation, were either randomly given 25 mg/kg vitamin E (DL-alpha-tocopherol acetate) intramuscularly after birth (day 0) and on days 1, 2, and 3 or served as controls. Frequent real time ultrasound examinations of the brain were made in each baby during the first week and less frequently thereafter. In babies under 32 weeks' gestation the incidence of intraventricular haemorrhage was lower in supplemented babies (18.8%) compared with the controls (56.3%). On days 0, 1, 2, and 3 median plasma vitamin E concentrations in babies without haemorrhage and in those with subependymal haemorrhage only were similar. Babies with intraventricular haemorrhage had lower median concentrations on day 1 (p less than 0.002) and day 2 (p less than 0.05) compared with those with subependymal haemorrhage and lower concentrations on day 0 (p less than 0.02) and day 1 (p less than 0.05) compared with those without haemorrhage. These findings suggest that in premature babies vitamin E, an antioxidant, protects endothelial cell membranes from oxidative damage and disruption and limits the magnitude of haemorrhage and its spread from the subependyma into the ventricles.",
"Levels of antioxidant defenses, which include vitamin E and Se-dependent GSH-Px, are generally relatively low in the fetus and neonate. Se-dependent GSH-Px and vitamin E are known to modulate biosynthesis of eicosanoids and therefore could have the potential for affecting patency or closure of the ductus arteriosus after birth. We evaluated some indices of antioxidant defense in sick LBW infants in relationship to one another as well as to clinical PDA, and investigated the effects of producing a rapid rise in serum vitamin E levels in some of these infants. Twenty-nine sick preterm infants (B. W. 750-1750 g) were randomized into control and vitamin E supplemented groups; the latter received dl-alpha-tocopherol IM., commencing within 12 hours of birth, to a total dosage of 175 mg/kg over four weeks. Most E-supplemented infants attained serum tocopherol levels greater than 0.50 mg/dl (12 mumol/l) within 24 hours of the first dose. Vitamin E supplementation did not influence clinical patency or closure of the ductus arteriosus, and no correlation could be established between serum levels of alpha-tocopherol, Se, GSH-Px or NPS and PDA. At 4 weeks vitamin E-supplemented infants had serum levels of the other antioxidant indices that were not significantly different from the non-supplemented babies.",
"Differences between feeding practices in earlier investigations prompted the present study of iron and vitamin E supplementation in breast milk fed preterm infants. A new and highly sensitive technique for quantitation of alpha-tocopherol in serum was used. Studies on 34 infants with a birth weight below 2000 g or gestational age less than or equal to 35 weeks showed that supplementation with 16.5 mg tocopheryl acetate/day from 10 days of age resulted in a significantly higher haemoglobin concentration and lower reticulocyte count at 8-10 weeks than supplementation with 1.5 mg/day (p is less than 0.05). Studies on 23 infants with a birth weight of 2000-2499 g revealed subnormal alpha-tocopherol levels in 2 of the infants given 1.5 mg tocopheryl acetate/day but there was no effect on the haemoglobin concentration at 8-10 weeks. There were no untoward effects of an early iron supplementation with 2-3 mg Fe++ (as ferrous succinate)/kg/day. It is concluded that extra supplementation with vitamin E is advisable also in breast milk fed preterm infants. A low dosage iron supplementation from 3 weeks of age is safe.",
"A randomized, double-blind study to determine the effect of intramuscular vitamin E on mortality and intracranial hemorrhage (ICH) was performed. One hundred forty-nine neonates with birth weights less than or equal to 1000 g and less than or equal to 24 hours of age were grouped by weight (501 to 750 g and 751 to 1000 g) and randomized to treatment or control. The treatment group received intramuscular injections of vitamin E (dl-alpha-tocopherol) on days 1, 2, 4, and 6 of life. The control group received intramuscular injections of placebo on the same schedule. All neonates initially received oral vitamin E (100 mg/kg/day dl-alpha-tocopheryl acetate), which was subsequently adjusted to keep serum levels at 0.5 to 3.5 mg/dL. Ultrasonographic examinations of the head were performed as possible on days 1, 5 to 7, and 12 to 14. Hemorrhage was defined as mild if less than or equal to grade II ICH, or severe if grade III or IV. No significant differences in neonatal or total hospital mortality between groups were found. However, all ICH, as well as severe ICH, were significantly less in the vitamin E-treated 501 to 750-g subgroup (all ICH: 60% vs 29%; severe ICH: 32% vs 4%). When survivors were analyzed separately, a significant decrease in severe ICH was seen in the vitamin E-treated neonates (25% vs 5%). Necrotizing enterocolitis and sepsis did not occur more frequently in the neonates treated with intramuscular injections of vitamin E. Other than two cases of mild induration at injection sites, no deleterious side effects of treatment were identified. Vitamin E may have a role in the prevention of severe ICH in premature neonates weighing between 501 and 750 g.",
"The biochemical effect of vitamin E supplementation to mothers with threatened premature delivery and to premature infants after birth has been studied. Although a weak correlation was found between maternal and cord blood vitamin E levels at birth, cord blood levels were not significantly higher in the infants from supplemented mothers than those from unsupplemented mothers. Furthermore, maternal vitamin E treatment did not prevent either erythrocyte hemolysis or lipid peroxide formation in the premature infants after birth. On the other hand, intramuscular vitamin E to infants after birth produced a marked biochemical effect, with both zero erythrocyte hemolysis and low lipid peroxide formation when serum vitamin E increased above 2 mg/100 ml. We conclude that intramuscular vitamin E immediately after birth is necessary to achieve a biochemical effect of vitamin E in the early neonatal period. (No cases of retrolental fibroplasia occurred in the present study.)",
"This study evaluates the need of vitamin E supplementation in very-low-birth-weight infants by long-term follow-up of plasma vitamin E status during the first 15 mo of life, with two different levels of supplementation. The subjects were 51 newborn infants with birth weights less than or equal to 1520 g. During hospitalization the infants were fed human milk. On the third day of life oral vitamin E supplementation of less than or equal to 10 mg/d was started in all infants. In addition, 23 infants selected at random were given intramuscular vitamin E (20 mg/kg/d) during the first 3 d. The data indicate that the 10 mg/d supplement resulted in an adequate plasma concentration of vitamin E. After cessation of supplementation at age 3 mo, the risk of low plasma vitamin E levels increased. Although intramuscular administration resulted in long-lasting increments in mean plasma vitamin E values, some later levels in these infants were marginal.",
"To evaluate the effects of vitamin E supplementation on haemoglobin concentration and the requirement for transfusion in premature infants treated with erythropoietin and iron.\n Randomised, double blind, placebo controlled trial. Thirty infants </=32 weeks gestation and </=1250 g birth weight, who were defined as stable based on minimal requirements for respiratory support and phlebotomy, and absence of major congenital anomalies were enrolled. All were treated with erythropoietin and iron, and were randomised to receive, in addition, either vitamin E 50 IU/day or placebo for eight weeks or until discharge, whichever came first.\n Despite higher vitamin E (alpha-tocopherol) levels in the experimental group in weeks 3 (49.0 v 28.1 micro mol/l) and 8 (66.2 v 38.5 micro mol/l), there were no differences in haemoglobin, reticulocyte count, iron concentration, or transfusion requirement.\n Oral vitamin E supplementation at 50 IU/day does not increase the response of preterm infants to erythropoietin and iron. Vitamin E obtained through standard nutrition may have been sufficient or higher doses may be required.",
"To evaluate the efficacy of four early intramuscular injections of vitamin E given in addition to continuous minimal oral vitamin E supplementation, 168 very low-birth-weight infants (less than or equal to 1,500 g) have enrolled in a randomized, double-masked, clinical study. All infants received vitamin E orally, 100 mg/kg/d. In addition, on days 1, 2, 4, and 6, seventy-nine infants received vitamin E intramuscularly, 15, 10, 10, and 10 mg/kg, respectively. On the same days, 89 control infants received placebo intramuscular injections. Multivariate analysis of the 135 infants who survived greater than or equal to 10 weeks showed no significant difference in the development of severe retrolental fibroplasia between these two supplementation schedules (P = .86). Plasma vitamin E levels never exceeded a mean of 3.3 mg/100 mL, and no toxicity was observed. Ultrastructural analyses of seven pairs of whole eye donations from infants receiving IM vitamin E demonstrated identical kinetics of gap junction formation between adjacent spindle cells as compared with 13 pairs of whole eye donations from control infants (P greater than .3). Therefore, oral vitamin E supplementation affords retinal protection against the development of severe retrolental fibroplasia when initiated on the first day of life and maintained continuously until retinal vascularization is complete.",
"We performed a double-blind study in 101 preterm infants who weighed less than or equal to 1500 g at birth, who had respiratory distress, and who survived for at least four weeks, to evaluate the efficacy of oral vitamin E in preventing the development of retrolental fibroplasia. Weekly indirect ophthalmologic examinations begun when the infants were three weeks old revealed a significant decrease in the incidence of retrolental fibroplasia greater than or equal to Grade III (P less than 0.03) and greater than or equal to Grade II (P less than 0.05) (McCormick classification) in the 50 infants given 100 mg of vitamin E per kilogram of body weight per day as compared with 51 given 5 mg per kilogram per day (controls). When multivariate analysis was applied to the controls, five risk factors were identified: gestational age, level and duration of administration oxygen, intraventricular hemorrhage, sepsis, and birth weight. When multivariate analysis was applied to both control and treatment groups, the severity of retrolental fibroplasia was found to be significantly reduced in infants given 100 mg of vitamin E (P = 0.012).",
"Supplementation with antioxidant vitamins has been proposed to reduce the risk of preeclampsia and perinatal complications, but the effects of this intervention are uncertain.\n We conducted a multicenter, randomized trial of nulliparous women between 14 and 22 weeks of gestation. Women were assigned to daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or placebo (microcrystalline cellulose) until delivery. Primary outcomes were the risks of maternal preeclampsia, death or serious outcomes in the infants (on the basis of definitions used by the Australian and New Zealand Neonatal Network), and delivering an infant whose birth weight was below the 10th percentile for gestational age.\n Of the 1877 women enrolled in the study, 935 were randomly assigned to the vitamin group and 942 to the placebo group. Baseline characteristics of the two groups were similar. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia (6.0 percent and 5.0 percent, respectively; relative risk, 1.20; 95 percent confidence interval, 0.82 to 1.75), death or serious outcomes in the infant (9.5 percent and 12.1 percent; relative risk, 0.79; 95 percent confidence interval, 0.61 to 1.02), or having an infant with a birth weight below the 10th percentile for gestational age (8.7 percent and 9.9 percent; relative risk, 0.87; 95 percent confidence interval, 0.66 to 1.16).\n Supplementation with vitamins C and E during pregnancy does not reduce the risk of preeclampsia in nulliparous women, the risk of intrauterine growth restriction, or the risk of death or other serious outcomes in their infants. (Controlledtrials.com number, ISRCTN00416244.).\n Copyright 2006 Massachusetts Medical Society.",
"Vitamin E status was assessed in 36 infants with birth weights less than 1500 gm who were assigned randomly to receive one of three sources of nutrition: milk obtained from mothers of preterm infants (preterm milk), mature human milk, or infant formula. Infants in each dietary group were further assigned randomly to receive iron supplementation (2 mg/kg/day) beginning at 2 weeks or to receive no iron supplementation. All infants received a standard multivitamin, providing 4.1 mg alpha-tocopherol daily. Serum vitamin E concentrations at 6 weeks were significantly related both to type of milk (P less than 0.0001) and to iron supplementation (P less than 0.05). Infants fed preterm milk had significantly higher serum vitamin E levels than did infants fed mature human milk, and both groups had significantly higher levels than did those fed formula. Ratios of serum vitamin E/total lipid were also significantly greater for infants fed human milks than for those fed formula. The addition of iron to all three diets resulted in significantly lower serum vitamin E levels at 6 weeks (P less than 0.05); however, only in the group fed formula was there evidence of vitamin E deficiency. Preterm milk with routine multivitamin supplementation uniformly resulted in vitamin E sufficiency in VLBW infants whether or not iron was administered.",
"On the basis of preliminary data, this larger bi-institutional continuation trial evaluating the efficacy and safety of early iron supplementation in preterm infants calls attention to the levels of vitamin E, a marker of antioxidant activity, during iron treatment. A total of 116 preterm infants were randomly assigned to receive at 2 or 4 weeks of age ( N = 62, N = 54, respectively) 5 mg/kg/d of nonionic iron polymaltose complex concomitantly with a daily dose of 25 IU vitamin E (as dl-alpha-tocopherol acetate) from 2 weeks of age. Vitamin E (alpha-tocopherol) levels, iron, ferritin, hemoglobin concentration, and reticulocyte count were recorded from 2 to 8 weeks of age. The morbidities of prematurity associated with free radicals formation were also documented. A gradual increase of alpha-tocopherol levels within physiological range (0.8 to 3.5 mg/dL) was found in the 2-week and 4-week groups during the study period with no difference among the groups ( P > 0.05 for all comparisons). At 8 weeks of age, iron and ferritin levels, hemoglobin concentration, and reticulocyte count were higher in the 2-week group. No correlation was observed between timing of both iron and vitamin E supplement and hemolysis or morbidities associated with prematurity. Thus, treatment of iron with vitamin E supplement at 2 weeks of age is, in our experience, an efficacious and safe treatment for improving anemia in preterm infants.",
"Vitamin A supplementation may reduce the risk of chronic lung disease and sepsis in extremely-low-birth-weight infants. The results of our pilot study suggested that a dose of 5000 IU administered intramuscularly three times per week for four weeks was more effective than the lower doses given in past trials.\n We performed a multicenter, blinded, randomized trial to assess the effectiveness and safety of this regimen as compared with sham treatment in 807 infants in need of respiratory support 24 hours after birth. The mean birth weight was 770 g in the vitamin A group and 769 g in the control group, and the respective gestational ages were 26.8 and 26.7 weeks.\n By 36 weeks' postmenstrual age, 59 of the 405 infants (15 percent) in the vitamin A group and 55 of the 402 infants (14 percent) in the control group had died. The primary outcome - death or chronic lung disease at 36 weeks' postmenstrual age - occurred in significantly fewer infants in the vitamin A group than in the control group (55 percent vs. 62 percent; relative risk, 0.89; 95 percent confidence interval, 0.80 to 0.99). Overall, 1 additional infant survived without chronic lung disease for every 14 to 15 infants who received vitamin A supplements. The proportions of infants in the vitamin A group and the control group who had signs of potential vitamin A toxicity were similar. The proportion of infants with serum retinol values below 20 microg per deciliter (0.70 micromol per liter) was lower in the vitamin A group than in the control group (25 percent vs. 54 percent, P<0.001).\n Intramuscular administration of 5000 IU of vitamin A three times per week for four weeks reduced biochemical evidence of vitamin A deficiency and slightly decreased the risk of chronic lung disease in extremely-low-birth-weight infants.",
"The incidence and severity of retinopathy of prematurity (ROP) as affected by vitamin E prophylaxis at pharmacologic serum levels (5 mg/dl) were evaluated in a double-masked clinical trial of infants with a birth weight less than or equal to 2000 gm or a gestational age less than or equal to 36 weeks. The infants were enrolled by age 5 days and randomly assigned to receive parenterally administered, and later orally administered, free alpha-tocopherol (vitamin E) or its placebo. Study medication was continued until retinal vascularization was complete or active ROP had subsided, except in infants with a diagnosis of severe disease, in whom vitamin E was substituted for study medication. Acute ROP data were collected on 755 infants. Logistic regression analysis, with control for immaturity, oxygen exposure, and other illness risk factors, showed a decrease in incidence of ROP in vitamin E-treated infants (p = 0.003, all infants; p = 0.035, infants weighing less than or equal to 1500 gm at birth). Among the 424 infants weighing less than or equal to 1500 gm at birth, the age at enrollment influenced treatment effect (age day 0 to 1, p = 0.006 (n = 288) vs age day 2 to 5, p greater than 0.1 (n = 136]. Overall, 77.6% of infants with ROP had mild disease. Moderate to severe ROP was confined to infants weighing greater than or equal to 1500 gm at birth (25 given placebo, 25 given vitamin E), with progression to severe disease in nine placebo-treated versus three vitamin E-treated infants (p = 0.048). The incidence of severe ROP per se was not significantly decreased (all birth weights, p = 0.086; less than or equal to 1500 gm birth weight, p = 0.080); the sample size was too small, however, to assess this end point adequately. An increased incidence of sepsis and late-onset necrotizing enterocolitis was found among vitamin E-treated infants weighing less than or equal to 1500 gm at birth who received study medication for greater than or equal to 8 days (p = 0.006). Because most ROP is mild in degree and regresses completely, the risk/benefit ratio of pharmacologic prophylaxis for ROP is unfavorable. Treatment of moderate and severe ROP with vitamin E above physiologic serum levels (greater than 3 mg/dl) appears promising and should be further investigated. The interpretation of cicatricial outcome was confounded by the small number of patients involved and by subsequent treatment of severe ROP in placebo-treated infants with vitamin E.",
"Intramuscular supplementation with vitamin A in large doses may reduce the incidence of chronic lung disease.\n To investigate whether oral supplementation with vitamin A would reduce the incidence of chronic lung disease in a group of extremely low birthweight infants.\n Infants with birth weight < 1000 g were randomised at birth to receive oral vitamin A supplementation (5000 IU/day) or placebo for 28 days. The primary outcome was oxygen dependency at 28 days of age or death.\n A total of 154 infants were randomised; 77 received vitamin A (median birth weight (interquartile range) 806 (710-890) g), and 77 received placebo (median birth weight (interquartile range) 782 (662-880) g). Plasma vitamin A concentrations in the supplemented group were significantly higher at 24 hours of age but did not differ significantly at birth, 12 hours of age, 7 days, or 28 days of life. There were no significant differences in the proportion of infants who survived, required oxygen at 28 days, required oxygen at 36 weeks postmenstrual age, survived without chronic lung disease at 36 weeks, survived without significant retinopathy, or who survived without significant intraventricular haemorrhage.\n Oral supplementation with 5000 IU vitamin A in extremely low birthweight infants does not significantly alter the incidence of chronic lung disease. However, this dose may have been inadequate to achieve optimal serum retinol concentrations.",
"Oxidative stress could play a part in pre-eclampsia, and there is some evidence to suggest that vitamin C and vitamin E supplements could reduce the risk of the disorder. Our aim was to investigate the potential benefit of these antioxidants in a cohort of women with a range of clinical risk factors.\n We did a randomised, placebo-controlled trial to which we enrolled 2410 women identified as at increased risk of pre-eclampsia from 25 hospitals. We assigned the women 1000 mg vitamin C and 400 IU vitamin E (RRR alpha tocopherol; n=1199) or matched placebo (n=1205) daily from the second trimester of pregnancy until delivery. Our primary endpoint was pre-eclampsia, and our main secondary endpoints were low birthweight (<2.5 kg) and small size for gestational age (<5th customised birthweight centile). Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 62368611 .\n Of 2404 patients treated, we analysed 2395 (99.6%). The incidence of pre-eclampsia was similar in treatment placebo groups (15% [n=181] vs 16% [n=187], RR 0.97 [95% CI 0.80-1.17]). More low birthweight babies were born to women who took antioxidants than to controls (28% [n=387] vs 24% [n=335], 1.15 [1.02-1.30]), but small size for gestational age did not differ between groups (21% [n=294] vs 19% [n=259], 1.12 [0.96-1.31]).\n Concomitant supplementation with vitamin C and vitamin E does not prevent pre-eclampsia in women at risk, but does increase the rate of babies born with a low birthweight. As such, use of these high-dose antioxidants is not justified in pregnancy.",
"The effect of maternal administration of vitamin K1 on cord blood prothrombin time, activated partial thromboplastin time, activity of factors II, VII, and X, and antigen levels of factors II and X in infants less than 35 weeks' gestation was evaluated. Pregnant women in preterm labor were randomly assigned to receive 10 mg of vitamin K1 intramuscularly or no injection. If delivery did not occur in 4 days, the dose of vitamin K1 was repeated. Women who continued their pregnancy 4 days beyond the second dose received 20 mg of vitamin K1 orally daily until the end of the 34th week of gestation. The birth weights of infants ranged from 370 to 2550 g and gestational age ranged from 22 to 34 weeks. The prothrombin time, activated partial thromboplastin time, factors II, VII, and X activity, and factors II and X antigen levels were not statistically different in either group of infants. Intraventricular hemorrhage occurred in 25 of 51 control infants and 25 of 47 vitamin K-treated infants. More control infants had grade III intraventricular hemorrhage on day 1 (P = .032), but on day 3 and 14 of life, the severity of intraventricular hemorrhage was comparable in both groups. Infants in whom an intraventricular hemorrhage developed were significantly smaller, younger, and more critically ill than infants without intraventricular hemorrhage. Administration of vitamin K1 to pregnant women at less than 35 weeks' gestation does not improve the hemostatic defects nor does it reduce the incidence or severity of intraventricular hemorrhage in their infants.",
"We sought to determine the effect of supplemental antioxidant vitamins C and E on the rate of preeclampsia in high-risk pregnant women.\n Women at risk for preeclampsia (previous preeclampsia, chronic hypertension, pregestational diabetes, or multifetal gestation) were recruited at 14 to 20 weeks' gestation and randomly assigned to receive either 1000 mg of vitamin C and 400 IU of vitamin E or placebo daily in addition to their regular prenatal vitamins. The primary outcome was the occurrence of preeclampsia. An estimated sample size of 220 women in each arm was determined to be necessary to demonstrate a 50% reduction in the rate of preeclampsia.\n Funding was terminated after 109 women had been recruited; 9 were lost to follow-up or withdrew. We analyzed data from the remaining 100 women to look for differences in outcome and to estimate the required sample size for future studies. The rate of preeclampsia was not different: 17.3% in women who received supplemental vitamins C and E, versus 18.8% in the placebo group. Assuming a baseline rate of preeclampsia in the placebo group between 15% and 20%, we can estimate that 500 to 950 women in each arm will be required to show a clinically important reduction in the rate of preeclampsia.\n The potential benefit of vitamin C and E supplementation to prevent preeclampsia in women with clinical risk factors is smaller than we estimated. Future studies of antioxidant vitamin supplementation in this population will require more than 500 women in each arm."
] |
Vitamin E supplementation in preterm infants reduced the risk of intracranial hemorrhage but increased the risk of sepsis. In very low birth weight infants, vitamin E increased the risk of sepsis, and reduced the risk of severe retinopathy and blindness among those examined. Evidence does not support the routine use of vitamin E supplementation by intravenous route at high doses or aiming at serum tocopherol levels greater than 3.5 mg/dl.
|
CD007316
|
[
"15231554",
"6691783",
"19455296",
"11086269"
] |
[
"Psychotherapy alone and combined with pharmacotherapy in the treatment of depression.",
"Cognitive therapy and pharmacotherapy. Singly and together in the treatment of depression.",
"[Interpersonal psychotherapy and pharmacotherapy for post-stroke depression. Feasibility and effectiveness].",
"Randomised controlled trial of non-directive counselling, cognitive-behaviour therapy and usual general practitioner care in the management of depression as well as mixed anxiety and depression in primary care."
] |
[
"The relative efficacy of psychotherapy and combined therapy in the treatment of depression is still a matter of debate.\n To investigate whether combined therapy has advantages over psychotherapy alone.\n A 6-month randomised clinical trial compared Short Psychodynamic Supportive Psychotherapy (n=106) with combined therapy (n=85) in ambulatory patients with mild or moderate major depressive disorder diagnosed using DSM-IV criteria. Antidepressants were prescribed according to a protocol providing four successive steps in case of intolerance or inefficacy: venlafaxine, selective serotonin reuptake inhibitor, nortriptyline and nortriptyline plus lithium. Efficacy was assessed using the 17-item Hamilton Rating Scale for Depression, the Clinical Global Impression of Severity and of Improvement, and the depression sub-scale of the Symptom Checklist.\n The advantages of combining antidepressants with psychotherapy were equivocal. Neither the treating clinicians nor the independent observers were able to ascertain them, but the patients experienced them clearly.\n The advantages of combining antidepressants with psychotherapy are equivocal.",
"Eight-seven moderately to severely depressed psychiatric outpatients were randomly assigned to 12 weeks of cognitive therapy (CT) (n = 24), pharmacotherapy (n = 24), CT plus pharmacotherapy (n = 22), or CT plus active placebo (n = 17). Seventy patients completed the treatment protocol. Seventeen dropped out before the end of the treatment period. Patients who completed treatment showed significant improvement in mean scores on two common measures of severity of depression (the Beck Depression Inventory and the Hamilton Rating Scale for Depression) between evaluation and termination. Improvement did not differ as a function of the different treatment modalities. Inclusion of dropout patients' end-point scores did not alter these results. Treatment gains in all groups were maintained at one-month follow-up assessment. A portion of this study replicated an earlier study. While the results were not identical, they indicated that either CT or antidepressant drug treatment can be effective in treating outpatients with primary, nonbipolar depression of moderate or greater severity. Combining treatments did not lead either to additive effects or negative interactions.",
"Only few studies investigated the effectiveness of psychotherapy in post-stroke depression (PSD). The aim of this feasibility study was to compare interpersonal psychotherapy, pharmacotherapy, and their combination regarding depression and rehabilitation outcome.\n Post-stroke depression was found in 35% of 485 stroke patients examined. Seventy-four PSD patients were randomised to one of three treatment conditions. Severity of depression was measured by the Hamilton Depression Rating Scale and the Hospital Anxiety and Depression Scale. The Barthel Index and a questionnaire for health-related quality of life were used as measurements of rehabilitation outcome.\n There were no significant differences between the three groups in patient mood or rehabilitation outcome. Concerning the severity of depression, quality of life, and social support, all patients showed benefits from antidepressive treatment. In addition a correlation was found between rehabilitation outcome and depression.\n In this feasibility study all antidepressive treatments were successfully implemented in the rehabilitation of post-stroke depressed patients. Combination therapy (interpersonal psychotherapy plus medication) was as effective as one of those elements alone. Because of the small sample size however, further randomized trials are required.",
"The aim of this study was to determine both the clinical and cost-effectiveness of usual general practitioner (GP) care compared with two types of brief psychological therapy (non-directive counselling and cognitive-behaviour therapy) in the management of depression as well as mixed anxiety and depression in the primary care setting.\n The design was principally a pragmatic randomised controlled trial, but was accompanied by two additional allocation methods allowing patient preference: the option of a specific choice of treatment (preference allocation) and the option to be randomised between the psychological therapies only. Of the 464 patients allocated to the three treatments, 197 were randomised between the three treatments, 137 chose a specific treatment, and 130 were randomised between the psychological therapies only. The patients underwent follow-up assessments at 4 and 12 months.\n The study was conducted in 24 general practices in Greater Manchester and London.\n A total of 464 eligible patients, aged 18 years and over, were referred by 73 GPs and allocated to one of the psychological therapies or usual GP care for depressive symptoms.\n The interventions consisted of brief psychological therapy (12 sessions maximum) or usual GP care. Non-directive counselling was provided by counsellors who were qualified for accreditation by the British Association for Counselling. Cognitive-behaviour therapy was provided by clinical psychologists who were qualified for accreditation by the British Association for Behavioural and Cognitive Psychotherapies. Usual GP care included discussions with patients and the prescription of medication, but GPs were asked to refrain from referring patients for psychological intervention for at least 4 months. Most therapy sessions took place on a weekly basis in the general practices. By the 12-month follow-up, GP care in some cases did include referral to mental healthcare specialists.\n The clinical outcomes included depressive symptoms, general psychiatric symptoms, social function and patient satisfaction. The economic outcomes included direct and indirect costs and quality of life. Assessments were carried out at baseline during face-to-face interviews as well as at 4 and 12 months in person or by post.\n At 4 months, both psychological therapies had reduced depressive symptoms to a significantly greater extent than usual GP care. Patients in the psychological therapy groups exhibited mean scores on the Beck Depression Inventory that were 4-5 points lower than the mean score of patients in the usual GP care group, a difference that was also clinically significant. These differences did not generalize to other measures of outcome. There was no significant difference in outcome between the two psychological therapies when they were compared directly using all 260 patients randomised to a psychological therapy by either randomised allocation method. At 12 months, the patients in all three groups had improved to the same extent. The lack of a significant difference between the treatment groups at this point resulted from greater improvement of the patients in the GP care group between the 4- and 12-month follow-ups. At 4 months, patients in both psychological therapy groups were more satisfied with their treatment than those in the usual GP care group. However, by 12 months, patients who had received non-directive counselling were more satisfied than those in either of the other two groups. There were few differences in the baseline characteristics of patients who were randomised or expressed a treatment preference, and no differences in outcome between these patients. Similar outcomes were found for patients who chose either psychological therapy. Again, there were no significant differences between the two groups at 4 or 12 months. Patients who chose counselling were more satisfied with treatment than those who chose c"
] |
There is not enough evidence available to support or refute the effectiveness of combined psychological therapy and pharmacotherapy compared to either of these interventions alone. Further large randomised controlled trials are urgently required.
|
CD004767
|
[
"10606851",
"17156002",
"15183850",
"16780480"
] |
[
"Molluscum contagiosum effectively treated with a topical acidified nitrite, nitric oxide liberating cream.",
"A prospective randomized trial comparing the efficacy and adverse effects of four recognized treatments of molluscum contagiosum in children.",
"Essential oil of Australian lemon myrtle (Backhousia citriodora) in the treatment of molluscum contagiosum in children.",
"Double-blind, randomized, placebo-controlled trial of the use of topical 10% potassium hydroxide solution in the treatment of molluscum contagiosum."
] |
[
"A double-blind, group-sequential clinical trial of acidified nitrite was performed to demonstrate the efficacy of this nitric oxide donor in treating molluscum contagiosum. Subjects received either 5% sodium nitrite co-applied with 5% salicylic acid under occlusion, or identical cream with 5% salicylic acid, omitting sodium nitrite. Active and control treatment groups were well matched for the number and duration of lesions and made a similar number of applications. We found a 75% cure rate in the active treatment group and 21% cure with control treatment (P = 0.01). The mean time to cure was 1.83 months. Staining of the skin and irritation were frequent side-effects but did not prevent successful treatment.",
"Molluscum contagiosum is a common viral disease of childhood presenting as small, firm, dome-shaped umbilicated papules. Although benign and generally self-limited, this condition is contagious and can lead to complications such as inflammation, pruritus, dermatitis, bacterial superinfection, and scars. No consensus has been established concerning the management of this condition. We conducted a prospective randomized study comparing four common treatments for molluscum contagiosum in 124 children aged 1 to 18 years. One group was treated with curettage, a second with cantharidin, a third with a combination of salicylic acid and lactic acid, and a fourth with imiquimod. Patients needing, respectively, one, two, or three visits for treatment of their mollusca were: 80.6%, 16.1%, and 3.2% for curettage, 36.7%, 43.3%, and 20.0% for cantharidin, 53.6%, 46.4%, and 0% for salicylic acid and glycolic acid, and 55.2%, 41.4%, and 3.4% for imiquimod. The rate of side effects was 4.7% for group 1, 18.6% for group 2, 53.5% for group 3, and 23.3% for group 4. Curettage was found to be the most efficacious treatment and had the lowest rate of side effects. It must be performed with adequate anesthesia and is a time-consuming procedure. Cantharidin is a useful bloodless alternative particularly in the office setting, but has moderate complications due to blisters and necessitated more visits in our experience. The topical keratolytic used was too irritating for children. Topical imiquimod holds promise but the optimum treatment schedule has yet to be determined. Finally, we believe that the ideal treatment for mollusca depends on the individual patient preference, fear, and financial status, distance from the office, and whether they have dermatitis or blood-borne infections.",
"Molluscum contagiosum is a common viral illness of childhood and is increasingly found as a sexually transmitted disease in sexually active young adults. Current treatment options are invasive, requiring tissue destruction and attendant discomfort. Thirty-one children (mean age 4.6 +/- 2.1 years) with the diagnosis of molluscum contagiosum (mean length of time with condition 8.6 +/- 5.3 months) were treated with once daily topical application of a 10% solution (v/v) of essential oil of Australian lemon myrtle (Backhousia citriodora) or vehicle (olive oil). At the end of 21 days, there was greater than 90% reduction in the number of lesions in 9/16 children treated with lemon myrtle oil, while 0/16 children met the same criteria for improvement in the vehicle group (P < 0.05). No adverse events were reported.",
"Molluscum contagiosum is a common viral infection of the skin that frequently affects children. Lesions take between 6 and 18 months to resolve spontaneously and are a source of great embarrassment to both caretakers and children, often affecting attendance at school and limiting social activity. Treatment options to date have been poorly tolerated by children but recent studies have suggested that potassium hydroxide may be beneficial. This double-blind, randomized, placebo-controlled study compared 10% potassium hydroxide with placebo (normal saline). Twenty patients, aged 2 to 12 years, were recruited. Parents applied a solution twice daily to lesional skin until signs of inflammation appeared. Children were examined by the same observer on days 0, 15, 30, 60, and 90. Seventy percent of children receiving topical potassium hydroxide cleared, compared with 20% in the placebo group. Further dosing studies are required to identify whether weaker concentrations of potassium hydroxide are as efficacious, with less irritancy."
] |
No single intervention has been shown to be convincingly effective in the treatment of molluscum contagiosum. The update identified six new studies, most of them reporting on interventions not included in the original version. However, the conclusions of the review did not change.
|
CD004518
|
[
"11679026"
] |
[
"Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam."
] |
[
"Passionflower (Passiflora incarnata) is a folk remedy for anxiety. A double-blind randomized trial compared the efficacy of Passiflora incarnata extract with oxazepam in the treatment of generalized anxiety disorder.\n The study was performed on 36 out-patients diagnosed with GAD using DSM IV criteria. Patients were allocated in a random fashion: 18 to the Passiflora extract 45 drops/day plus placebo tablet group, and 18 to oxazepam 30 mg/day plus placebo drops for a 4-week trial.\n Passiflora extract and oxazepam were effective in the treatment of generalized anxiety disorder. No significant difference was observed between the two protocols at the end of trial. Oxazepam showed a rapid onset of action. On the other hand, significantly more problems relating to impairment of job performance were encountered with subjects on oxazepam.\n The results suggest that Passiflora extract is an effective drug for the management of generalized anxiety disorder, and the low incidence of impairment of job performance with Passiflora extract compared to oxazepam is an advantage. A large-scale trial is justified."
] |
RCTs examining the effectiveness of passiflora for anxiety are too few in number to permit any conclusions to be drawn. RCTs with larger samples that compare the effectiveness of passiflora with placebo and other types of medication, including antidepressants, are needed.
|
CD004429
|
[
"12382151",
"8145910",
"8247075",
"11506402"
] |
[
"A randomised controlled trial of intravenous immunoglobulin in IgM paraprotein associated demyelinating neuropathy.",
"Intravenous immunoglobulin treatment in patients with motor neuron syndromes associated with anti-GM1 antibodies: a double-blind, placebo-controlled study.",
"A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis.",
"Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy."
] |
[
"This multicentre randomised double blind crossover trial tested the short term efficacy of intravenous immunoglobulin (IVIg) 2.0 g/kg given over 24 or 48 hours in patients with paraproteinaemic demyelinating neuropathy (PDN). Twenty-two patients were randomised and completed the trial. After 2 weeks, the overall disability grade decreased during both IVIg treatment and placebo but neither change was significant nor was the mean difference between the treatment effects. After 4 weeks the overall disability decreased by a mean of 0.55 [0.67] grades during the IVIg period (p = 0.001) while it was substantially unmodified during the placebo period. The mean difference between the treatment effects was significant (p = 0.05). Overall during the IVIg period 10 patients improved and 11 were stable and one got worse. During the placebo period 4 patients improved, 4 deteriorated and 14 were stable. Many secondary outcome measures, including Rankin scale, time to walk 10 metres, grip strength, sensory symptoms score were significantly better during IVIg treatment. Two serious adverse events occurred during the trial, both during placebo treatment. In conclusion the trial showed some short-term benefit of IVIg in about half of the patients confirming previous observation.",
"We studied the effects of intravenous immunoglobulin (IVIg) in 12 patients with motor neuron syndromes associated with high titers of anti-GM1 antibodies. Five of the patients had conduction blocks. The study design was a double-blind, placebo-controlled, crossover trial with IVIg (0.4 g/kg body weight per day injected for 5 consecutive days). We evaluated the patients before and 5, 28, and 56 days after drug administration using a computerized analyzer for muscle strength, the Norris scale for disability, motor nerve conduction velocities for patients with conduction blocks, and measurements of immunologic markers. Compared with placebo, IVIg induced a significant increase in muscle strength only in the patients with conduction blocks.",
"Dermatomyositis is a clinically distinct myopathy characterized by rash and a complement-mediated microangiopathy that results in the destruction of muscle fibers. In some patients the condition becomes resistant to therapy and causes severe physical disabilities.\n We conducted a double-blind, placebo-controlled study of 15 patients (age, 18 to 55 years) with biopsy-proved, treatment-resistant dermatomyositis. The patients continued to receive prednisone (mean daily dose, 25 mg) and were randomly assigned to receive one infusion of immune globulin (2 g per kilogram of body weight) or placebo per month for three months, with the option of crossing over to the alternative therapy for three more months. Clinical response was gauged by assessing muscle strength, neuromuscular symptoms, and changes in the rash. Changes in immune-mediated muscle abnormalities were determined by repeated muscle biopsies.\n The eight patients assigned to immune globulin had a significant improvement in sores of muscle strength (P < 0.018) and neuromuscular symptoms (P < 0.035), whereas the seven patients assigned to placebo did not. With crossovers a total of 12 patients received immune globulin. Of these, nine with severe disabilities had a major improvement to nearly normal function. Their mean muscle-strength scores increased from 74.5 to 84.7, and their neuromuscular symptoms improved. Two of the other three patients had mild improvement, and one had no change in his condition. Of 11 placebo-treated patients, none had a major improvement, 3 had mild improvement, 3 had no change in their condition, and 5 had worsening of their condition. Repeated biopsies in five patients of muscles whose strength improved to almost normal showed an increase in muscle-fiber diameter (P < 0.04), an increase in the number and a decrease in the diameter of capillaries (P < 0.01), resolution of complement deposits on capillaries, and a reduction in the expression of intercellular adhesion molecule 1 and major-histocompatibility-complex class I antigens.\n High-dose intravenous immune globulin is a safe and effective treatment for refractory dermatomyositis.",
"This multicenter, randomized, double-blind, crossover trial compared a six week course of oral prednisolone tapering from 60 mg to 10 mg daily with intravenous immunoglobulin (IVIg) 2.0 g/kg given over one to two days for treating chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Twenty-four of the thirty-two randomized patients completed both treatment periods. Both treatments produced significant improvements in the primary outcome measure, change in an 11-point disability scale two weeks after randomization. There was slightly, but not significantly, more improvement after IVIg than with prednisolone, the mean difference between the groups in change in disability grade being 0.16 (95% CI = -0.35 to 0.66). There were also slightly, but not significantly, greater improvements favoring IVIg in the secondary outcome measures: time to walk 10 meters after two weeks and improvement in disability grade after six weeks. Results may have been biased against IVIg by the eight patients who did not complete the second arm of the trial. A serious adverse event (psychosis) attributable to treatment occurred in one patient while on prednisolone and in none with IVIg."
] |
Limited evidence from randomised controlled trials shows that intravenous immunoglobulin has a beneficial effect on strength. There was a non-significant trend towards improvement in disability. More research is needed to discover whether intravenous immunoglobulin improves disability and is cost-effective.
|
CD002305
|
[
"10665619",
"2679483",
"15602113",
"7912819",
"16816304",
"1681680"
] |
[
"A randomized controlled trial of cognitive-behavioral therapy for persistent symptoms in schizophrenia resistant to medication.",
"Antidepressants in 'depressed' schizophrenic inpatients. A controlled trial.",
"Negative symptoms of schizophrenia are improved by the addition of paroxetine to neuroleptics: a double-blind placebo-controlled study.",
"Clinical, EEG mapping and psychometric studies in negative schizophrenia: comparative trials with amisulpride and fluphenazine.",
"Outcomes of an effectiveness trial of cognitive-behavioural intervention by mental health nurses in schizophrenia.",
"Zuclopenthixol decanoate and haloperidol decanoate in chronic schizophrenia: a double-blind multicentre study."
] |
[
"Research evidence supports the efficacy of cognitive-behavioral therapy in the treatment of drug-refractory positive symptoms of schizophrenia. Although the cumulative evidence is strong, early controlled trials showed methodological limitations.\n A randomized controlled design was used to compare the efficacy of manualized cognitive-behavioral therapy developed particularly for schizophrenia with that of a nonspecific befriending control intervention. Both interventions were delivered by 2 experienced nurses who received regular supervision. Patients were assessed by blind raters at baseline, after treatment (lasting up to 9 months), and at a 9-month follow-up evaluation. Patients continued to receive routine care throughout the study. An assessor blind to the patients' treatment groups rated the technical quality of audiotaped sessions chosen at random. Analysis was by intention to treat.\n Ninety patients received a mean of 19 individual treatment sessions over 9 months, with no significant between-group differences in treatment duration. Both interventions resulted in significant reductions in positive and negative symptoms and depression. At the 9-month follow-up evaluation, patients who had received cognitive therapy continued to improve, while those in the befriending group did not. These results were not attributable to changes in prescribed medication.\n Cognitive-behavioral therapy is effective in treating negative as well as positive symptoms in schizophrenia resistant to standard antipsychotic drugs, with its efficacy sustained over 9 months of follow-up.",
"Fifty-eight actively psychotic inpatients who initially met criteria for long-standing schizophrenia and subsequently met Research Diagnostic Criteria for a current episode of schizoaffective disorder (mainly schizophrenic) with a depressive syndrome, and who scored at least 30 (mean = 55, SEM = 1.6) on the Brief Psychiatric Rating Scale and 17 (mean = 23, SEM = 0.7) on the Hamilton Rating Scale for Depression, were treated for 5 weeks with haloperidol hydrochloride and benztropine. Haloperidol and benztropine treatment was continued, while those patients who consistently scored greater than 17 on the Hamilton Rating Scale for Depression were randomly assigned to the following double-blind treatment groups for 4 weeks: adjunctive amitriptyline hydrochloride, desipramine hydrochloride, or placebo. Adjunctive desipramine or amitriptyline showed no significant therapeutic advantage, when compared with haloperidol and placebo, on the Brief Psychiatric Rating Scale or the Hamilton Rating Scale for Depression. After 4 weeks of combine therapy, patients receiving adjunctive amitriptyline or desipramine, as compared with those receiving adjunctive placebo, tended to score higher on the Brief Psychiatric Rating Scale hallucinatory behavior item and on the thinking disturbance factor than patients receiving placebo. These results suggest that adjunctive antidepressants are not indicated for the treatment of depressive symptoms in actively psychotic schizophrenic inpatients. Adjunctive antidepressants may retard the rate of resolution of psychosis in this population.",
"Despite the availability of atypical antipsychotics, the treatment of negative symptoms in schizophrenia remains a challenge. This study was designed to confirm the positive effect observed in our pilot study with paroxetine as augmentation to antipsychotics in the treatment of negative symptoms in chronic schizophrenia. Twenty-nine patients with chronic schizophrenia, as defined by DSM-IV, who scored at least 20 points on the negative subscale of the Positive and Negative Syndrome Scale (PANSS) were randomized for treatment with 30 mg paroxetine or placebo in a double-blind, placebo-controlled study for 12 weeks. Ratings included the PANSS, the Hamilton Rating Scale for Depression (HAM-D) and scales for extrapyramidal side-effects. An intention-to-treat analysis was based on the 25 patients who were available for at least one follow-up assessment. The last observation carried forward principle was applied. The mean score of the negative subscale of the PANSS decreased in both groups. Using an analysis of covariance, there was a significant treatment effect with paroxetine compared to placebo with respect to negative symptoms (-4.53; 95% confidence interval -9.054 to -0.015). The mean HAM-D scores remained almost constant. The study suggests the efficacy of paroxetine with respect to the treatment of negative symptoms in chronic schizophrenia.",
"Based on recent quantitative EEG findings of increased slow activity in negative schizophrenia indicating organicity, it was hypothesized that neuroleptics decreasing delta/theta activity should be beneficial for schizophrenics with predominantly negative symptoms. Thus, a double-blind, clinical, psychometric and neurophysiological study was carried out in 40 hospitalized patients with unproductive schizophrenia (mean age: 31 years; ICD diagnoses: 295.0, 295.1 and 295.6) who were treated randomly either with the benzamide amisulpride (AMI; n = 19) or low doses of fluphenazine (FLU; n = 21). In the first 2 weeks the daily doses were 50 mg AMI or 2 mg FLU, respectively, from the third week on up to the sixth week 100 mg AMI and 4 mg FLU. Clinical evaluations, psychometry and EEG mapping were performed on day 1 (hours 0 and 4--acute effect), on day 14 (hour 0--subacute effect) and on day 42 (hours 0 and 4--chronic and superimposed effects). Three AMI patients discontinued therapy prematurely because of productive symptoms (days 14, 28 and 35), while in the FLU group 2 patients dropped out due to depressive symptoms (days 21, 28), 1 due to productive symptoms (day 35), 1 due to ineffectiveness (day 28), and 1 because of an akinetic crisis (day 6). Statistical evaluation demonstrated a significant improvement in the AMDP apathy and Andreasen SANS score in both groups with the patients remaining severely ill as rated by the CGI. FLU-treated patients needed significantly more anticholinergic medication than the AMI-treated group. Psychometric evaluation showed in regard to the noopsyche significant improvement after subacute, chronic and superimposed AMI, while FLU-treated patients showed significant improvement only after subacute treatment. AMI was significantly superior to FLU at the hours 0 and 4 of day 42. The thymopsyche improved after subacute, chronic and superimposed administration of both compounds with a significant superiority of AMI on days 14 and 42 (4 h postdrug). EEG mapping showed a decrease of delta/theta and increase of beta activity as well as an acceleration of the centroid after acute and superimposed AMI on day 42 as compared with baseline; FLU patients exhibited a decrease of delta/theta activity and an acceleration of the total centroid too, while alpha activity was augmented and beta activity tended to be reduced. Our study demonstrated that, in addition to the new benzamide AMI, FLU in low doses may also be regarded as a neuroleptic with activating properties and may be utilized in the treatment of schizophrenics with predominantly negative symptoms.",
"Little is known about the medium-term durability of cognitive-behavioural therapy (CBT) in a community sample of people with schizophrenia.\n To investigate whether brief CBT produces clinically important outcomes in relation to recovery, symptom burden and readmission to hospital in people with schizophrenia at 1-year follow-up.\n Participants (336 of 422 randomised at baseline) were followed up at a mean of 388 days (s.d. = 53) by raters masked to treatment allocation (CBT or usual care).\n At 1-year follow-up, participants who received CBT had significantly more insight (P = 0.021) and significantly fewer negative symptoms (P = 0.002). Brief therapy protected against depression with improving insight and against relapse; significantly reduced time spent in hospital for those who did relapse and delayed time to admission. It did not improve psychotic symptoms or occupational recovery, nor have a lasting effect on overall symptoms or depression at follow-up.\n Mental health nurses should be trained in brief CBT for schizophrenia to supplement case management, family interventions and expert therapy for treatment resistance.",
"Zuclopenthixol decanoate (ZPT-D) and haloperidol decanoate (HAL-D) were compared in the maintenance treatment of chronic schizophrenic patients. All patients were treated with either ZPT-D or HAL-D for at least 3 months and were then randomly allocated to treatment with either ZPT-D (100-600 mg every 4 weeks) or HAL-D (38-200 mg every 4 weeks) for 9 months. Sixty-four patients entered the study. Three patients were only assessed at baseline. Four patients in the HAL-D group were withdrawn because of deterioration. One patient in the ZPT-D group committed suicide. Fifty-six patients completed the trial. The assessment programme comprised Clinical Global Impressions by psychiatrists and nurses, the Brief Psychiatric Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), UKU Side Effect Scale and Simpson-Angus Scale, Ratings were made at baseline and after 12, 24 and 36 weeks of treatment. The severity of illness scores remained almost constant. The only between-group difference was recorded at month 6 in favour of ZPT-D. The BPRS total scores were reduced significantly in both groups with no between-group differences. The depression scores on the MADRS were very low. Both treatments caused few and mild side effects according to the UKU Side Effect Scale and the Simpson-Angus scale, and there were no significant differences between the groups. Both ZPT-D and HAL-D seem to be effective in the maintenance treatment of chronic schizophrenic patients and cause few side effects. The injections of ZPT-D and HAL-D can be given at 4-week intervals."
] |
Overall, the literature was of poor quality, and only a small number of trials made useful contributions. Though our results provide some evidence to indicate that antidepressants may be beneficial for people with depression and schizophrenia, the results, at best, are likely to overestimate the treatment effect, and, at worst, could merely reflect selective reporting of statistically significant results and publication bias.
At present, there is no convincing evidence to support or refute the use of antidepressants in treating depression in people with schizophrenia. We need further well-designed, conducted and reported research to determine the best approach towards treating depression in people with schizophrenia.
Note: the 71 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.
|
CD002071
|
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"1558344",
"11666130",
"9581724",
"7697845",
"7798505",
"2857803",
"1987387",
"1936509",
"18456558",
"10458714",
"9299856",
"6371535",
"7849445",
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"10975769"
] |
[
"Cilostazol reduces restenosis after endovascular therapy in patients with femoropopliteal lesions.",
"Batroxobin plus aspirin reduces restenosis after angioplasty for arterial occlusive disease in diabetic patients with lower-limb ischemia.",
"[A clinical trial of using antiplatelet therapy to prevent restenosis following peripheral artery angioplasty and stenting].",
"Low-molecular-weight heparin for prevention of restenosis after femoropopliteal percutaneous transluminal angioplasty: a randomized controlled trial.",
"Failure of aspirin plus dipyridamole to prevent restenosis after carotid endarterectomy.",
"Potential use of a low-molecular-weight heparin to prevent restenosis in patients with extensive wall damage following peripheral angioplasty.",
"Effect of high dose verapamil on restenosis after peripheral angioplasty.",
"Comparison of effects of high-dose and low-dose aspirin on restenosis after femoropopliteal percutaneous transluminal angioplasty.",
"Frequent reocclusion of patent infarct-related arteries between 4 weeks and 1 year: effects of antiplatelet therapy.",
"Drug-induced inhibition of platelet function delays progression of peripheral occlusive arterial disease. A prospective double-blind arteriographically controlled trial.",
"Antiplatelet drugs in femoropopliteal vein bypasses: a multicenter trial.",
"Indobufen versus placebo in the prevention of restenosis after carotid endarterectomy: a double-blind pilot study.",
"Cilostazol as an alternative to aspirin after ischaemic stroke: a randomised, double-blind, pilot study.",
"Acute platelet inhibition with abciximab does not reduce in-stent restenosis (ERASER study). The ERASER Investigators.",
"Antiplatelet agents in thrombotic thrombocytopenic purpura (TTP). Results of a randomized multicenter trial by the Italian Cooperative Group for TTP.",
"Membranoproliferative glomerulonephritis. A prospective clinical trial of platelet-inhibitor therapy.",
"Controlled trial of high- versus low-dose aspirin treatment after percutaneous transluminal angioplasty in patients with peripheral vascular disease.",
"Preservation from left ventricular remodeling by front-integrated revascularization and stem cell liberation in evolving acute myocardial infarction by use of granulocyte-colony-stimulating factor (FIRSTLINE-AMI).",
"Prevention of postcoronary angioplasty restenosis by omega-3 fatty acids: main results of the Esapent for Prevention of Restenosis ITalian Study (ESPRIT).",
"Efficacy of pantoprazole in the prevention of peptic ulcers, induced by non-steroidal anti-inflammatory drugs: a prospective, placebo-controlled, double-blind, parallel-group study."
] |
[
"Despite the recent development of endovascular therapy (EVT), a high incidence of restenosis remains as an unsolved issue in patients presenting with femoropopliteal lesions. We investigated whether cilostazol reduces restenosis after successful EVT for de novo femoropopliteal lesions.\n This study was designed as a prospective, randomized, open-label, blinded end point study in a single institution. Between March 2004 and June 2005, we randomized 127 patients who were successfully treated with EVT for de novo femoropopliteal lesions to receive cilostazol (200 mg/d, n = 63) or ticlopidine (200 mg/d, n = 64) in addition to aspirin (100 mg/d). Antiplatelet medications were started at least 1 week before EVT and were continued until the end of follow-up. Patency was defined by duplex ultrasound imaging with peak systolic velocity ratio >2.4.\n There were no significant differences in the patients and lesion characteristics. Sixteen patients dropped out of the study protocol, six of whom were withdrawn due to adverse drug effects (cilostazol, n = 5; ticlopidine, n = 1; P = .09). Ten patients died (cilostazol, n = 4; ticlopidine, n = 6; P = .53) during the follow-up period. Patency rates at 12, 24, and 36 months were 87%, 82%, and 73% in the cilostazol group and 65%, 60%, and 51% in ticlopidine group by intention-to-treat analysis (P = .013) and were 87%, 82%, and 73% in the cilostazol group and 64%, 57%, and 48% in the ticlopidine group (P = .0088) by as-treated analysis. Freedom from target lesion revascularization and all adverse events (restenosis, amputation, and death) was significantly higher in cilostazol group than in ticlopidine group (P = .036, P = .031). No acute, subacute, or chronic thrombotic occlusion was encountered, and bleeding complication rates were similar between the two groups.\n Cilostazol significantly reduces restenosis after EVT in femoropopliteal lesions.",
"Aspirin is routinely given to reduce vascular events after angioplasty. Batroxobin has been shown to effectively prevent thrombosis after angioplasty via inhibition of the fibrinogen concentration. In this randomized clinical trial, the hypothesis that batroxobin plus aspirin is more effective than aspirin alone in reducing the incidence of restenosis/reocclusion in patients with diabetes undergoing angioplasty for lower-limb ischemia.\n Patients with diabetes and symptomatic arterial obstructions (N = 129) were randomized to receive aspirin 100 mg/d plus batroxobin 5 IU every other day for six doses (n = 58) or aspirin alone (n = 71). The primary outcome was restenosis documented by magnetic resonance (MR) angiography or duplex imaging at 12 months. Secondary outcomes included amputation above the ankle, death, and cumulative rate of amputation or death. Kaplan-Meier analysis was used to evaluate limb salvage and survival rates.\n After 12 months, restenosis had occurred in 43.1% and 29.7% of patients in the control and batroxobin groups, respectively (P = .0018). MR angiography and duplex imaging revealed an improved restenosis rate for infrapopliteal lesions and for lesions longer than 10 cm (P = .0016). The primary and cumulative secondary outcomes indicated significant improvements in restenosis rate, symptom relief, and amputation rates in the batroxobin group compared with the aspirin-only group. Kaplan-Meier analysis showed limb salvage and survival rates of 78.3% in the aspirin-only group and 92.2% in the batroxobin group 12 months after angioplasty (log-rank test, P = .0414).\n Batroxobin plus aspirin reduced the rate of restenosis after arterial angioplasty, particularly in lesions located below the knee and in those longer than 10 cm, with better clinical symptom relief and improved rate of limb salvage.\n Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.",
"To evaluate the clinical effect and restenosis rate of antiplatelet therapy following peripheral artery angioplasty and stenting.\n After successful placement of peripheral artery stents to 103 patients with peripheral arterial occlusive disease (PAOD) in were randomized assigned to 2 groups: antiplatelet therapy group receiving clopidogrel 75 mg plus aspirin 100 mg (n = 56) and control group (n = 47) receiving anticoagulation therapy low molecular weight heparin (LWMH) for 7 d plus long-term warfarin. The patients were followed up 1 day, and 1, 6, 12, and 18 months after the operation to undergo color Doppler ultrasonography, and examinations of blood routine, bleeding time, coagulation time, and ankle-brachial Index. The primary endpoint events included major bleeding rate, and composite rate of restenosis and reocclusion. The secondary endpoint events included cardiovascular events, death, and adverse drug reaction.\n There were no significant differences in the baseline data between these two groups. The thrombotic occlusion rate was 1.8% in the antiplatelet group and 0% in control group, and the restenosis rate was 14.3% in the antiplatelet group and 25.5% in control group (both P > 0.05). The bleeding complication rate of the antiplatelet group was 1.8%, significantly lower than that of the anticoagulation group (19.1%, P < 0.01). There were not significant differences in cardiovascular event rate and mortality 18 months after operation between these two groups.\n Antiplatelet therapy combined with clopidogrel plus aspirin is effective and safe in preventing restenosis following peripheral artery angioplasty and stenting.",
"Restenosis after angioplasty is essentially due to intimal hyperplasia. Low-molecular-weight heparins (LMWHs) have experimentally been shown to have antiproliferative effects in addition to their antithrombotic properties. Their potential in reducing restenosis remains to be established. Therefore, we wanted to test the hypothesis that LMWH plus aspirin is more effective than aspirin alone in reducing the incidence of restenosis/reocclusion in patients undergoing percutaneous transluminal angioplasty (PTA) of femoropopliteal arteries. Further, different effects of LMWH in patients treated for critical limb ischemia (CLI) or claudication only should be investigated.\n After successful PTA, 275 patients with symptomatic peripheral arterial disease (claudication or critical limb ischemia) and femoropopliteal obstructions were randomized to receive either 2500 IU of dalteparin subcutaneously for 3 months plus 100 mg of aspirin daily (n = 137), or 100 mg aspirin daily alone (n = 138). The primary end point was restenosis or reocclusion documented by duplex ultrasonography imaging at 12 months.\n Restenosis/reocclusion occurred in 58 patients (44%) in the dalteparin group and in 62 patients (50%) in the control group (P = .30). In a subgroup analysis according to the severity of peripheral arterial disease, we found that in patients treated for claudication, restenosis/reocclusion developed in 43 (43%) in the dalteparin group, and in 35 (41%) in the control group (P = .70); in patients treated for CLI, restenosis/reocclusion was significantly lower in the dalteparin group (15, 45%) than in the control group (27, 72%; P = .01). No major bleeding events occurred in either group.\n Treatment with 2500 IU dalteparin subcutaneously given for 3 months after femoropopliteal PTA failed to reduce restenosis/reocclusion at 12 months. However, dalteparin may be beneficial in the subgroup of patients with CLI at 12 months follow-up.",
"To evaluate therapy with aspirin plus dipyridamole in reducing restenosis after carotid endarterectomy.\n A total of 163 patients having 175 surgical carotid endarterectomies.\n Eighty-three patients (90 endarterectomies) were randomly assigned to receive oral aspirin, 325 mg, plus dipyridamole, 75 mg, beginning 12 hours preoperatively, followed by a second dose administered within 8 hours after the operation, and given three times daily thereafter for 1 year. Eighty patients (85 endarterectomies) received placebo medication that was identical in appearance to the study drugs.\n After the adequacy of the surgical procedure was confirmed by intraoperative angiography, restenosis at the endarterectomy sites was evaluated using serial duplex ultrasound studies before hospital discharge and at 3-month intervals postoperatively for 1 year.\n Based on the time for developing identifiable restenosis and on efficacy analysis, greater than 50% restenosis developed in 11 operated vessels (16%) in the treated group and in 10 arteries (14%) in the placebo group, yielding an observed risk increase of 14% (95% CI, -52% to 167%; P greater than 0.2). By intention-to-treat analysis, greater than 50% restenosis developed in 16 of 90 operated vessels in treated patients and in 10 of 85 arteries in patients receiving placebo (26% for the treated group and 12% for the placebo group; P = 0.18, Mantel-Haenszel statistic), representing an observed risk increase of 110% (CI, -5% to 365%). Similar differences were observed for greater than 20% restenosis and for the comparison of patients rather than operated vessels by either intention-to-treat or efficacy analyses.\n Because therapy not only failed to reduce carotid restenosis but may have actually increased its frequency, treatment with aspirin plus dipyridamole probably has no clinically important benefit on restenosis in patients having carotid endarterectomy.",
"The long-term outcome of primary successful percutaneous transluminal angioplasty (PTA) for patients with peripheral occlusive arterial disease (POAD) is frequently compromised by the development of restenosis, especially when extensive dissections result from the angioplastic procedure. Unfortunately, prevention of the occlusive process by means of drugs such as antithrombotics, anticoagulants, thrombolytics, corticosteroids, lipid reducers, or cytostatics has not been demonstrated convincingly. The authors sought to clarify whether such patients could benefit from the postsurgical administration of low-molecular-weight heparin. A total of 172 POAD patients with extensive dissections after PTA in the pelvic or upper leg regions were randomized for 7-day post-PTA intravenous treatment with either full heparinization or nadroparin calcium followed by adjunctive oral aspirin for 6 months. The primary outcome measure was the degree of stenosis (normal findings; stenosis < 50%, > 50%, > 80%, occlusion) before and after angioplasty, as well as 3 weeks and 3 and 6 months after dilation; secondary efficacy criteria included changes in the Fontaine stage and in the crurobrachial ratio. No significant treatment-related differences were found at the 3 post-PTA follow-up examinations with regard to the degree of stenosis. This was also the case for the subgroup of patients (n = 62) who had undergone angioplasty in the pelvic region. By contrast, when angioplasty was performed in the superficial femoral artery (n = 110), the degree of restenosis was significantly lower (p<0.01) among patients receiving nadroparin calcium compared to those given heparin at week 3, month 3, and month 6. No intergroup differences emerged for secondary outcome measures in the long term or for safety parameters. These preliminary results indicate that patients with extensive dissections after PTA treatment for POAD in the upper leg region might benefit from a reduction in the rate of restenosis by administration of 7-day weight-adjusted nadroparin calcium.",
"We sought to determine whether treatment with high dose verapamil prevents restenosis in patients at high risk for reoccurrence after successful percutaneous transluminal coronary angioplasty (PTCA).\n Restenosis is the major limitation of PTCA. Calcium antagonists have demonstrated some potential as inhibitors of this process.\n A total of 98 patients with peripheral occlusive arterial disease (POAD), stable angina pectoris, mild hypertension and at least one additional risk factor increasing the likelihood of restenosis after angioplasty were selected for this placebo-controlled, double-blind, randomized trial. Verapamil (240 mg twice daily) or placebo was taken for 6 months. Efficacy variables assessed before and after angioplasty and at 6 weeks and 6 months after PTCA included thickness of the intima/media complex degree of stenosis, interventricular septal thickness, crurobrachial pressure ratios of dorsalis pedis and posterior tibial arteries, distance to claudication and total vessel diameter.\n No significant intergroup differences emerged before or immediately after PTCA. Six weeks after angioplasty, a significant thickening of the intima/media complex in the treated vascular segment of 14.3% occurred in the placebo group versus 0% among verapamil patients (p < 0.01). At 6 months, the intima/media thickness was 35.7% greater in the placebo group but had decreased by 14.3% in the verapamil group (p < 0.001). At 6 months, a marked reduction in septal thickness was observed in the verapamil group versus that in the placebo group (p < 0.001). The rate of restenosis was also significantly lower in the verapamil group (p < 0.001). Few minor side effects were reported.\n In patients with POAD at increased risk for restenosis, the administration of high dose verapamil prevented recurrent stenosis for 6 months after successful peripheral angioplasty and was well tolerated.",
"Long-term treatment with aspirin is recommended in patients with large-vessel peripheral arterial disease since these patients have a high risk of death from cardiovascular causes. Recent studies have demonstrated the prophylactic effect of low-dose aspirin in reducing the risk of cardiovascular events. Since aspirin is also recommended for prevention of late recurrence after peripheral angioplasty, the present study was undertaken to compare the effects of high-dose (1000 mg/d) and low-dose (100 mg/d) aspirin on long-term patency after femoropopliteal angioplasty.\n Two hundred sixteen patients treated successfully by percutaneous transluminal angioplasty for femoropopliteal lesions were randomly allocated to therapy with either 1000 or 100 mg aspirin daily. The follow-up was 24 months. The long-term results were analyzed using the Kaplan-Meier method, and differences between curves of cumulative patency were determined with the Wilcoxon and log-rank statistics. Complete follow-up information (patency after 24 months, restenosis, and death) was obtained in 207 patients. During the 2-year follow-up period, 72 patients--36 in the high-dose and 36 in the low-dose aspirin group, respectively--developed angiographically verified reobstruction within the recanalized segment. By intention-to-treat analysis, the cumulative patency rates at 24 months were 62.5% in the high-dose and 62.6% in the low-dose aspirin group (Wilcoxon, P = .97; log-rank, P = .97). The cumulative survival at 24 months of follow-up was 86.6% in the high-dose and 87.7% in the low-dose aspirin group. The number of patients discontinuing therapy was 30 in the high-dose and 11 in the low-dose aspirin group (P < .01). Fewer patients receiving 100 mg of aspirin discontinued therapy because of gastrointestinal symptoms (4 versus 20).\n The data indicate that 100 mg aspirin is no less effective in the prevention of restenosis after femoropopliteal PTA than a 1000-mg dose and has fewer side effects.",
"This study assessed the effect of the combination of aspirin and dipyridamole on patency of the infarct-related artery between 4 weeks and 1 year after myocardial infarction.\n Patency of the infarct-related artery is an important determinant of prognosis after myocardial infarction. The incidence of late reocclusion and the effects of antiplatelet therapy are unknown.\n To investigate the importance of antiplatelet therapy for the prevention of late reocclusion, 215 patients who had a patent infarct-related artery 4 weeks after myocardial infarction were randomized in a double-blind manner to receive either a combination of 25 mg of aspirin and 200 mg of dipyridamole twice daily or placebo. One hundred fifty-four patients underwent further coronary arteriography 1 year later.\n At 1 year, 38 (25%) of 154 patients had reocclusion of the infarct-related artery; 18 (23%) of 79 patients receiving aspirin and dipyridamole had late reocclusion versus 20 (27%) of 75 who received placebo (p = NS). The rate of reocclusion was related to the severity of the residual coronary artery stenosis at 4 weeks (< 50% stenosis 9.2%; 50% to 69% stenosis 11.6%; 70% to 89% stenosis 30.4%; > or = 90% stenosis 70%, p < 0.01). The majority of reocclusions were silent, and only 17 (45%) of 38 were clinically associated with further infarction. There were no differences for a hierarchic end point of cardiac death, myocardial infarction or revascularization (14.8% aspirin and dipyridamole vs. 17.8% placebo).\n Late reocclusion of the patent infarct-related artery is a frequent event, occurring in 25% of patients. Antiplatelet therapy with the combination of aspirin and dipyridamole does not alter the overall rate of late reocclusion. Other strategies are required to reduce late reocclusion.",
"240 patients were admitted to a double-blind study to determine the effect of long-term treatment with platelet-function inhibiting agents on occlusive arterial disease in the lower extremities. Patients were randomised into 1 of 3 treatment groups: aspirin 330 mg; dipyridamole 75 mg and aspirin 330 mg; or matching placebo 3 times daily. The duration of treatment was 2 years. Arteriography was carried out at the beginning of the study and 2 years later or before if deterioration was observed. 199 patients completed the study according to the trial protocol. The serial arteriograms were assessed in pairs qualitatively, by means of simple comparative viewing, and semiquantitatively with Bollinger's score system. Progression of the disease was most pronounced in the placebo-treated group, less so in the aspirin-treated group, and least of all in the dipyridamole-and-aspirin group. Patients who smoke and those with hypertension may benefit most from treatment with the 2 preparations under investigation.",
"To evaluate the influence of antiplatelet drugs on patency in femoropopliteal vein bypasses, 48 vascular surgeons recruited 549 patients to a randomized double-blind trial of aspirin (300 mg) + dipyridamole (150 mg) or placebo twice daily starting 2 days before surgery and continuing indefinitely. Graft occlusion measured objectively by independent coordinators and cardiovascular events (myocardial infarction or stroke) were studied, expressed by life table, and analyzed statistically by log rank and confidence intervals (95% CI). Randomization achieved comparable groups with 60% of grafts inserted for rest pain or gangrene. Operative complications on aspirin plus dipyridamole included 18 reoperations for bleeding and 12 hematomas compared with 9 and 14, respectively, on placebo (NS). Most of the 172 graft failures occurred early with failure rates of 43/1000 patient-months in the first 3 months, reducing to 17/1000 at 6 to 12 months, and under 10/1000 in subsequent years. Cumulative graft patency on placebo was 72%, 62%, and 60% at 1, 2, and 3 years, respectively, compared with 78%, 70%, and 61% on aspirin plus dipyridamole. The difference in patency of 6.1% (95% CI, -3% to 15.5%) at 1 year and 8.0% (95% CI, -5% to 21%) at 2 years failed to achieve significance (p = 0.43). On mean follow-up of 34 months, 53 (132/1000 patient-years) cardiovascular events (myocardial infarction or cerebrovascular accident) occurred in patients on placebo compared with only 35 (73/1000) on aspirin plus dipyridamole, a significant difference of 59/1000 (p = 0.004). Antiplatelet therapy had little influence on femoropopliteal vein patency, but subsequent myocardial infarction and stroke was reduced in these patients with peripheral vascular disease.",
"A randomized clinical trial was undertaken to assess the efficacy of indobufen in inhibiting platelet adhesiveness in carotid thromboendarterectomy. The patients were treated under double-blind conditions with indobufen and with placebo, and were then assessed by means of scintigraphy with labelled platelets, ultrasonic tomography and angiography for a minimum follow-up period of 6 months. Haematological and clinical assessments were also performed. The results of the study suggest that platelet accumulation in carotid endarterectomy may be an early sign of restenosis; anti-aggregant treatment with indobufen carried out at an early stage prior to surgery inhibited platelet accumulation. The final result showed that anti-aggregant treatment had a positive influence on the short- and medium-term outcome of carotid endarterectomy.",
"Most patients who have had a stroke are given aspirin; however, aspirin-related cerebral haemorrhage is a complication that is currently of concern, particularly in China where there is a high incidence of cerebral haemorrhage in secondary prevention programmes and within the community. Cilostazol, a phosphodiesterase 3 (PDE3) inhibitor, is an alternative to aspirin that works through a different mechanism. This trial aimed to compare the efficacy and safety of cilostazol with that of aspirin for the long-term prevention of the recurrence of ischaemic stroke.\n 720 patients (mean age 60.2 years, SD 9.86) who had had an ischaemic stroke within the previous 1-6 months were enrolled consecutively in a prospective, multicentre, double-blind, randomised trial. 360 patients were randomly assigned to receive cilostazol and 360 patients to receive aspirin. Analysis was by intention to treat. Patients in both groups took the medication for 12-18 months. The primary endpoint was any recurrence of stroke (ischaemic stroke, haemorrhagic stroke, or subarachnoid haemorrhage) during the trial period. All patients had MRI with T1 MRI, T2 MRI, diffusion-weighted imaging (DWI), T2 fluid-attenuated inversion recovery (FLAIR), and T2 gradient echo imaging (T2*) at the beginning and the end of the study. This trial is registered with ClinicalTrials.gov, number NCT00202020.\n The average duration of treatment was 740 person-years, and 719 patients were analysed (360 in the cilostazol group and 359 in the aspirin group). The primary endpoint was reported in 12 patients in the cilostazol group and in 20 patients in the aspirin group. The estimated hazard ratio, calculated with Kaplan-Meier curves (risk of primary endpoint in cilostazol group vs aspirin group), was 0.62 (95% CI 0.30-1.26; p=0.185). Symptomatic cerebral haemorrhage was reported in six patients: one in the cilostazol group and five in the aspirin group. Asymptomatic cerebral haematoma was found in four patients in the aspirin group and one patient in the cilostazol group. Brain bleeding events were significantly more common in the aspirin group than in the cilostazol group (7 vs 1, p=0.034). All of the six patients with symptomatic haemorrhage had previous cerebral microbleeds in the area where the haematoma was located.\n The results of this pilot study showed no significant difference in the rate of recurrence of stroke between patients with ischaemic stroke who were randomly assigned to take either cilostazol or aspirin. The lower rates of ischaemic and haemorrhagic stroke in the cilostazol group suggest that cilostazol might be a more effective and safer alternative to aspirin for Chinese patients with ischaemic stroke; however, a larger phase III trial is required to confirm this.\n National Health Ministry of the People's Republic of China; Otsuka Pharmaceutical.",
"Although stents reduce restenosis compared with balloon angioplasty, their long-term efficacy is limited by neointimal hyperplasia. Platelet and alpha(v)beta(3) integrin receptor inhibition limits neointimal proliferation in animal models of arterial injury.\n We tested whether the dual beta(3) integrin blocking agent abciximab, administered for 12 or 24 hours at the same intravenous dose as that shown to reduce adverse clinical events (death, infarction, and revascularization) after angioplasty, would reduce restenotic tissue volume, as measured by intravascular ultrasound at 6 months. Two hundred twenty-five patients were randomly allocated to placebo or abciximab before coronary intervention. Of the 215 patients who received stents and study drug, 191 (88.8%) returned for late (>/=4 months) coronary evaluation. Tissue volume, expressed as a percentage of stent volume, did not differ: 25+/-15%, 27+/-15%, and 29+/-14% for the patients in the placebo and the 12- and 24-hour abciximab groups, respectively. Lack of abciximab benefit was confirmed by quantitative coronary angiography (dichotomous restenosis: 11.6%, 18. 9%, and 19.4%; loss index: 0.33, 0.52, and 0.47, respectively, P=NS).\n Potent platelet inhibition with abciximab, as administered in this study, does not reduce in-stent restenosis. The interrelationship between stents, platelets, and neointimal proliferation requires further study.",
"Antiplatelet agents are often included in plasma exchange-based regimens for thrombotic thrombocytopenic purpura (TTP) patients; however, the opportuneness of their use in TTP is still controversial. The italian Cooperative Group for TTP carried out a randomized trial to investigate their actual effectiveness, both in acute TTP and as maintenance treatment.\n Seventy-two TTP patients were randomized to receive plasma exchange and steroids with (group B) or without (group A) aspirin and dipyridamole. Treatment efficacy was evaluated after 15 days and salvage treatments were also considered for non-responders. Upon disease remission, the patients already treated with antiplatelet agents received ticlopidine for one year.\n Regarding the treatment of acute phase TTP, similar overall response rates were observed in the two groups (91.4% in group B vs. 75.6% in group A), but lower mortality rates were observed at 15 days in the patients treated with antiplatelet agents; as a matter of fact, 5 patients from arm A died in the first 15 days (13.5%) versus only one in arm B (2.8%). These figures, while not statistically significant, seem to suggest that antiplatelet agents might be useful in preventing deaths in acute TTP; moreover, bleeding did not worsen in antiplatelet agent-treated patients. As for the role of maintenance treatment, our results support the efficacy and safety of one-year ticlopidine therapy since the current relapse rate is significantly higher in non-treated patients; as a matter of fact, 6 patients (21.4%) in the non-ticlopidine group and only 2 (6.25%) in the ticlopidine group relapsed (P = .0182 in favor of maintenance treatment).\n Our results suggest the usefulness of antiplatelet agents in the treatment of acute phase TTP patients. Moreover, one-year ticlopidine maintenance therapy appears to be beneficial in preventing TTP relapses; however, only the completion of an adequate follow-up for all patients will definitively confirm this observation.",
"Forty patients with Type I membranoproliferative glomerulonephritis were treated for one year with dipyridamole, 225 mg per day, and aspirin, 975 mg per day, in a prospective, randomized, double-blind, placebo-controlled study. At the base line, the half-life of 51Cr-labeled platelets was reduced in 12 of 17 patients. The platelet half-life became longer and renal function stabilized in the treated group, as compared with the placebo group, suggesting a relation between platelet consumption and the glomerulopathy. The glomerular filtration rate, determined by iothalamate clearance, was better maintained in the treated group (average decrease, 1.3 ml per minute per 1.73 m2 of body-surface area per 12 months) than in the placebo group (average decrease, 19.6). Fewer patients in the treated group than in the placebo group had progression to end-stage renal disease (3 of 21 after 62 months as compared with 9 of 19 after 33 months). The data suggest that dipyridamole and aspirin slowed the deterioration of renal function and the development of end-stage renal disease.",
"Percutaneous transluminal angioplasty of aortoiliac and femoropopliteal atherosclerotic lesions can provide long-lasting hemodynamic improvement. High-dose aspirin is commonly prescribed as reocclusion prophylaxis, but low doses would be preferable because of fewer adverse effects. We performed a double-blind, randomized, controlled clinical trial in patients with peripheral vascular disease with lesions appropriate for angioplasty. We compared the efficacy and side effects of two doses of aspirin (50 mg vs. 900 mg daily) during a period of 12 months after angioplasty. A total of 359 patients were evaluated: 175 were randomly assigned to treatment with 900 mg aspirin daily and 184 to 50 mg aspirin daily. Thirty-nine patients developed restenosis at the angioplasty site; the cumulative percentage of event-free survival after 1 year (patency rate) was 85% in 900 mg group and 84% in 50 mg group. An equivalence test showed the two groups equivalent with respect to restenosis rates (P = 0.0003 for an equivalence region of < 10% difference. Nine patients (5%) in the 900 mg group had serious gastrointestinal side effects (peptic ulcer, 8; erosive gastritis requiring transfusion, 1) compared to two ( peptic ulcer) in the 50 mg group (P = 0.03). The results of our study show that a dose of 50 mg aspirin a day is as effective as 900 mg for the prevention of restenoses after lower limb angioplasty, and that severe gastrointestinal side effects are less frequent.",
"Considering experimental evidence that stem cells enhance myocardial regeneration and granulocyte colony-stimulating factor (G-CSF) mediates mobilization of CD34+ mononuclear blood stem cells (MNCCD34+), we tested the impact of G-CSF integrated into primary percutaneous coronary intervention (PCI) management of acute myocardial infarction in man.\n Fifty consecutive patients with ST-segment elevation myocardial infarction were subjected to primary PCI stenting with abciximab and followed up for 6 months; 89+/-35 minutes after successful PCI, 25 patients were randomly assigned in this pilot study (PROBE design) to receive subcutaneous G-CSF at 10 microg/kg body weight for 6 days in addition to standard care, including aspirin, clopidogrel, an ACE inhibitor, beta-blocking agents, and statins. By use of CellQuest software on peripheral blood samples incubated with CD45 and CD34, mobilized MNCCD34+ were quantified on a daily basis. With homogeneous demographics and clinical and infarct-related characteristics, G-CSF stimulation led to mobilization of MNCCD34+ to between 3.17+/-2.93 MNCCD34+/microL at baseline and 64.55+/-37.11 MNCCD34+/microL on day 6 (P<0.001 versus control); there was no indication of leukocytoclastic effects, significant pain, impaired rheology, inflammatory reactions, or accelerated restenosis at 6 months. Within 35 days, G-CSF and MNCCD34+ liberation led to enhanced resting wall thickening in the infarct zone of between 0.29+/-0.22 and 0.99+/-0.32 mm versus 0.49+/-0.29 mm in control subjects (P<0.001); under inotropic challenge with dobutamine (10 microg.kg(-1).min(-1)), wall motion score index showed improvement from 1.66+/-0.23 to 1.41+/-0.21 (P<0.004 versus control) and to 1.35+/-0.24 after 4 months (P<0.001 versus control), respectively, coupled with sustained recovery of wall thickening to 1.24+/-0.31 mm (P<0.001 versus control) at 4 months. Accordingly, resting wall motion score index improved with G-CSF to 1.41+/-0.25 (P<0.001 versus control), left ventricular end-diastolic diameter to 55+/-5 mm (P<0.002 versus control), and ejection fraction to 54+/-8% (P<0.001 versus control) after 4 months. Morphological and functional improvement with G-CSF was corroborated by enhanced metabolic activity and 18F-deoxyglucose uptake in the infarct zone (P<0.001 versus control).\n G-CSF and mobilization of MNC(CD34+) after reperfusion of infarcted myocardium may offer a pragmatic strategy for preservation of myocardium and prevention of remodeling without evidence of aggravated restenosis.",
"Previous trials of omega-3 fatty acids (omega-3 FA) for restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA) have yielded conflicting results. We tested the hypothesis that long-term administration of omega-3 FA before PTCA may have significant effects on restenosis.\n We randomized 339 patients in a double-blind, placebo-controlled study of omega-3 FA (as an ethyl ester preparation given as 6 1-g capsules providing 3 g eicosapentaenoic acid and 2.1 g docosahexaenoic acid/d started 1 month before PTCA and given for 1 month thereafter, then continued at half-dose for 6 months) versus an olive oil placebo. Of these, 257 patients (125 on omega-3 FA, 132 on placebo) well matched for risk factors underwent successful balloon-only PTCA (280 total lesions) and were evaluable at 6 months with repeat angiography. Restenosis was defined at quantitative angiography as a recurrence of >50% diameter stenosis in the dilated vessel (Definition I) and as >50% loss of the short-term gain immediately after PTCA (Definition II).\n Restenosis rates per vessel were 29.4% and 31.6% in the omega-3 FA group, and 39.6% and 35.4% in the placebo group according to Definitions I (P =.04) and II (P = not significant), respectively. Restenosis rates per patient were 31.2% and 33.6% in the omega-3 FA group, and 40.9% and 37.1% in the placebo group according to Definitions I (P =.05) and II (P = not significant), respectively.\n With a long treatment before PTCA, omega-3 FA produced a small but significant decrease in the restenosis rate compared with placebo.",
"To evaluate the efficacy of pantoprazole in preventing gastrointestinal lesions in patients with rheumatic diseases receiving continuous, long-term treatment with non-steroidal anti-inflammatory drugs.\n This was a prospective, randomised, double-blind, unbalanced, placebo-controlled, parallel group study. Outpatients (n= 104, age range 22-80 years, mean age 59.5) with rheumatoid arthritis or osteoarthritis, requiring chronic intake of NSAIDs (at least 8 weeks prior to the start of the study), were randomised and enrolled to receive either 40 mg pantoprazole (n=70) or placebo (n=34) once daily, for 12 weeks. Patients had endoscopically confirmed gastric and duodenal lesions grade 0, 1 or 2 (Lanza classification grade 0: normal to hyperaemic mucosa; grade 1: 1 to 3 erosions, submucosal haemorrhage or petechiae, grade 2: 4 to 10 erosions, submucosal haemorrhages or petechiae). Clinical and endoscopic evaluations were performed at baseline, after 4, and 12 weeks. The primary end-point of the study was the incidence of gastric or duodenal ulcers after 4 and 12 weeks of treatment.\n Patients (n=95) were evaluated: 65 in the pantoprazole group and 30 in the placebo group. When considering all patients (those with Lanza score grade 0, 1, 2 at baseline), the overall proportion of patients in remission was 82% and 77% after 4 weeks, and 72% and 59% after 12 weeks in pantoprazole and placebo groups, respectively (cumulative survival analysis according to Kaplan-Meier). The difference between the treatment groups was even more marked when only those patients with normal mucosa at baseline (grade 0) were considered. After 12 weeks, the proportion of patients in remission was 82% (95% confidence limits 70% - 94% in the pantoprazole and 55% (95% confidence limits 33% - 77%) in the placebo treatment group, p=O.036. Adverse events were reported in 4% and 6% of patients in pantoprazole and placebo treatment groups, respectively\n Pantoprazole 40 mg once daily was well tolerated and is more effective than placebo in the prevention of peptic ulcers in patients with rheumatic diseases who require continuous, long-term, treatment with NSAIDs."
] |
There is limited evidence suggesting that restenosis/reocclusion at six months following peripheral endovascular treatment is reduced by use of antiplatelet drugs compared with placebo/control, but associated information on bleeding and gastrointestinal side effects is lacking. There is also some evidence of variation in effect according to different drugs with cilostazol reducing reocclusion/restenosis at 12 months compared with ticlopidine and both LMWH and batroxobin combined with aspirin appearing beneficial compared with aspirin alone. However, available trials are generally small and of variable quality and side effects of drugs are not consistently addressed. Further good quality, large-scale RCTs, stratified by severity of disease, are required.
|
CD002898
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[
"[Comparison of the effectiveness of acyclovir and vidarabine in superficial herpes keratitis].",
"Acyclovir and vidarabine in the treatment of ulcerative herpes simplex keratitis.",
"A double-blind, multicenter clinical trial of acyclovir vs idoxuridine for treatment of epithelial herpes simplex keratitis.",
"A randomised double-blind clinical trial of acyclovir (Zovirax) and adenine arabinoside in herpes simplex corneal ulceration.",
"Combination therapy for dendritic keratitis with acyclovir and vidarabine.",
"[Acyclovir and trifluorothymidine in herpetic kerato-uveitis. A comparative clinical study. Indications for corticoid therapy].",
"Randomised double-blind trial of acyclovir and idoxuridine in dendritic corneal ulceration.",
"Ganciclovir ophthalmic gel (Virgan; 0.15%) in the treatment of herpes simplex keratitis.",
"Ganciclovir ophthalmic gel, 0.15%: a valuable tool for treating ocular herpes.",
"Treatment of herpes simplex keratitis: comparison of acyclovir and vidarabine.",
"[Superficial herpes simplex keratitis. Double-blind comparative trial of acyclovir and idoxuridine (author's transl)].",
"Combination therapy for dendritic keratitis with acyclovir and alpha-interferon.",
"Acyclovir and idoxiuridine treatment of herpes simplex keratitis--a double blind clinical study.",
"Oral acyclovir (Zovirax) in herpes simplex dendritic corneal ulceration.",
"Comparative study of acyclovir and 5 I.D.U. in the management of viral corneal ulcer.",
"A comparison of acyclovir and idoxuridine as treatment for ulcerative herpetic keratitis.",
"A double-controlled evaluation of acyclovir and vidarabine for the treatment of herpes simplex epithelial keratitis.",
"Efficacy of four antiviral agents in the treatment of uncomplicated herpetic keratitis.",
"A comparison between acyclovir and trifluorothymidine ophthalmic ointment in the treatment of epithelial dendritic keratitis. A double blind, randomized parallel group trial.",
"Combination therapy of recombinant human alpha 2 interferon and acyclovir in the treatment of herpes simplex keratitis.",
"Trifluorothymidine versus adenine arabinoside in the treatment of herpes simplex keratitis.",
"Acyclovir and debridement in the treatment of ulcerative herpetic keratitis.",
"Vidarabine therapy of simple and IDU-complicated herpetic keratitis.",
"Combination therapy for dendritic keratitis with human leukocyte interferon and acyclovir.",
"Acyclovir in the treatment of herpetic keratitis.",
"Randomized controlled trial of oral ganciclovir versus oral acyclovir after induction with intravenous ganciclovir for long-term prophylaxis of cytomegalovirus disease in cytomegalovirus-seropositive liver transplant recipients.",
"Randomised double-blind trial of acyclovir (Zovirax) and adenine arabinoside in herpes simplex amoeboid corneal ulceration.",
"Double--blind clinical trial of adenine arabinoside and idoxuridine in herpetic corneal ulcers.",
"A randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for cytomegalovirus prophylaxis in high-risk kidney transplant recipients.",
"High-dose acyclovir compared with short-course preemptive ganciclovir therapy to prevent cytomegalovirus disease in liver transplant recipients. A randomized trial.",
"Oral acyclovir in the management of dendritic herpetic corneal ulceration.",
"Prevention of primary cytomegalovirus disease in organ transplant recipients with oral ganciclovir or oral acyclovir prophylaxis.",
"A prospective randomized trial comparing sequential ganciclovir-high dose acyclovir to high dose acyclovir for prevention of cytomegalovirus disease in adult liver transplant recipients.",
"A comparative randomised study of valacyclovir vs. oral ganciclovir for cytomegalovirus prophylaxis in renal transplant recipients.",
"Comparison of intravenous ganciclovir followed by oral acyclovir with intravenous ganciclovir alone for prevention of cytomegalovirus and Epstein-Barr virus disease after liver transplantation in children.",
"A prospective randomized study of acyclovir versus ganciclovir plus human immune globulin prophylaxis of cytomegalovirus infection after solid organ transplantation.",
"A comparison of ganciclovir and acyclovir to prevent cytomegalovirus after lung transplantation.",
"Failure of high-dose oral acyclovir with or without immune globulin to prevent primary cytomegalovirus disease in recipients of solid organ transplants.",
"Oral acyclovir prophylactic treatment of herpes simplex infection after bone marrow transplantation.",
"A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group.",
"Bromovinyldeoxyuridine and interferon treatment in ulcerative herpetic keratitis: a double masked study.",
"Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients.",
"Multicenter collaborative trial of intravenous acyclovir for treatment of mucocutaneous herpes simplex virus infection in the immunocompromised host.",
"Treatment of herpetic keratitis.",
"Valacyclovir for cytomegalovirus prophylaxis reduces the risk of acute renal allograft rejection.",
"A controlled trial of oral acyclovir for the prevention of stromal keratitis or iritis in patients with herpes simplex virus epithelial keratitis. The Epithelial Keratitis Trial. The Herpetic Eye Disease Study Group.",
"Oral acyclovir in herpes zoster ophthalmicus.",
"Epidermal growth factor in the topical treatment of herpetic corneal ulcers.",
"Randomised comparison of ganciclovir and high-dose acyclovir for long-term cytomegalovirus prophylaxis in liver-transplant recipients.",
"Efficacy of oral ganciclovir in prevention of cytomegalovirus infection in post-kidney transplant patients.",
"Prophylaxis of cytomegalovirus infection in liver transplantation: a randomized trial comparing a combination of ganciclovir and acyclovir to acyclovir. NIDDK Liver Transplantation Database.",
"Oral acyclovir therapy for mucocutaneous herpes simplex virus infections in immunocompromised marrow transplant recipients.",
"Three- or four- versus two-drug antiretroviral maintenance regimens for HIV infection.",
"Randomised trial of efficacy and safety of oral ganciclovir in the prevention of cytomegalovirus disease in liver-transplant recipients. The Oral Ganciclovir International Transplantation Study Group [corrected].",
"Combination therapy for dendritic keratitis. High-titer alpha-interferon and trifluridine.",
"A prospective, 96-week study of the impact of Trizivir, Combivir/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral-naive patients: effect of sex and ethnicity.",
"Once-daily intravenous acyclovir for prophylaxis of herpes simplex virus reactivation after marrow transplantation.",
"Valacyclovir versus acyclovir for HSV prophylaxisin neutropenic patients.",
"Double controlled comparison of IDU and trifluorothymidine in thirty-three patients with superficial herpetic keratitis.",
"Oral acyclovir for prevention of herpes simplex virus reactivation after marrow transplantation.",
"Clinical evaluation of adenine arabinoside and trifluorothymidine in the treatment of corneal ulcers caused by herpes simplex virus.",
"Antioxidant therapy for chronic hepatitis C after failure of interferon: results of phase II randomized, double-blind placebo controlled clinical trial.",
"Viral prophylaxis in combined pancreas-kidney transplant recipients.",
"Oral acyclovir prophylaxis against herpes simplex virus in non-Hodgkin lymphoma and acute lymphoblastic leukaemia patients receiving remission induction chemotherapy. A randomised double blind, placebo controlled trial.",
"Acyclovir given as prophylaxis against oral ulcers in acute myeloid leukaemia: randomised, double blind, placebo controlled trial.",
"Controlled trial of prophylactic versus therapeutic use of ganciclovir after liver transplantation in adults.",
"[Double-blind treatment of ocular herpes simplex: Vira-A and acyclovir].",
"Prophylactic oral ganciclovir compared with deferred therapy for control of cytomegalovirus in renal transplant recipients."
] |
[
"In a double-blind clinical trial 28 patients with primary and recurrent herpetic corneal ulcerations were treated either with 3% Acyclovir eye ointment or 3% Adenosine Arabinoside eye ointment. In 11 out of 14 (78%) patients treated with Acyclovir and 8 out of 14 (57%) patients treated with Adenosine Arabinoside the ulcerations healed within a treatment period of 6.5 days and 8 days respectively (no statistical significance). However, the results revealed that Acyclovir was more effective. Both drugs were well tolerated.",
"In a masked controlled study, we treated 41 patients who had active herpes simplex corneal ulcers with either 3% acyclovir of 3% vidarabine ointment five times daily for 14 days. There was no statistically significant difference between the two drugs with reference to mean healing time, efficacy of healing, development of stromal keratitis or iritis, post-treatment visual acuity, or adverse reaction.",
"Thirty patients randomized to the Acyclovir (ACV) group (26 with dendritic lesions, 4 geographic lesions) and 34 patients randomized to the idoxuridine (IDU) treatment group (26 dendritic lesions, 8 geographic lesions) with epithelial herpetic keratitis were evaluated for efficacy and adverse reactions in a multi-center, double-masked, randomized, stratified trial. Patients were treated with either 3% acyclovir ophthalmic ointment or 0.5% idoxuridine ophthalmic ointment five times a day for 14 days. The results of the trial indicated no significant difference between ACV and IDU as antiviral agents in the treatment of epithelial herpetic keratitis. The overall healing patterns of ACV and IDU adjusted for lesion type and prognostic factors, including presenting condition (initial or recurrent disease), duration of symptoms, prior ophthalmic steroid use, and positive pretreatment herpesvirus culture, as well as, the healing patterns within each lesion type adjusted for these factors, were not significantly different between the two treatment groups. There was no significant difference between the two groups in the frequency of development of deeper involvement. The only significant difference (P less than 0.01) in the frequency of development of adverse reactions was found in the incidence of development of superficial punctate epitheliopathy (IDU-42%, ACV-11%).",
"A double-blind clinical trial of 3% acyclovir (Zovirax) and 3% adenosine arabinoside (ara-A, Vidarabine) in 93 patients with herpetic corneal ulceration is presented. Ulcers in 45 (94%) of acyclovir-treated patients and 37 (82%) ara-A-treated patients healed within 14 days. Patients treated with acyclovir healed more rapidly than those treated with ara-A (p less than 0.01). No serious adverse effects were observed.",
"We treated 32 patients with dendritic keratitis with a combination of acyclovir 3% ointment and vidarabine 3% ointment or acyclovir and placebo. Patients with acyclovir alone healed in an average time of 7.7 days, while patients on the combination healed in an average of 6 days. Only one patient in the acyclovir and vidarabine group had a healing time longer than 7 days, whereas six patients in the acyclovir and placebo group had healing times longer than 7 days. By the median test, this difference in healing times was statistically significant (p = 0.035), and the combination prevented cases of prolonged ulceration.",
"The relative efficacy of aciclovir (ACV) and trifluorothymidine (TFT) was evaluated in a randomized, open clinical trial of 37 patients with herpetic kerato-uveitis. Twenty-one patients were treated with ACV and 16 with TFT. Topical steroids were withheld as long as the degree of inflammation permitted. Although both drugs were effective in healing the herpetic corneal ulcers, TFT had a significantly shorter healing time than ACV. However, ACV was more effective in treating the iridocyclitis than TFT. In 5 cases the keratouveitis responded to ACV alone, while only one case was successfully managed with TFT alone. Both drugs seemed to prevent steroid-induced epithelial complications and no significant side-effects were observed with either drug. The treatment of herpetic keratouveitis with single agents such as ACV and TFT is dependent upon rapidly instituting therapy and minimizing the use of topical steroids. The apparently good intraocular penetration of ACV and TFT may decrease the need for adjunctive steroid therapy and thereby minimize the risks of facilitated viral replication and steroid-dependence.",
"The results of a randomised double-blind clinical trial of 3% acyclovir and 0.5% idoxuridine (IDU) ophthalmic ointments in 60 patients with corneal dendritic ulceration are presented. Ulcers in all 30 patients treated with acyclovir healed compared with 22 (76%) of 29 patients treated with IDU (P < 0.01). Patients treated with acyclovir healed more rapidly (average 4.4 days) than those who received IDU (average 9.2 days) (P < 0.01). No serious side effects were observed, though transient stinging was recorded in 8 patients receiving acyclovir and in 2 patients receiving IDU. Other side effects in the IDU treated group were watering in 2 patients and superficial punctate erosions in 6 patients.",
"Ganciclovir is a broad-spectrum virustatic agent. Its efficacy and safety after ocular application have been demonstrated in studies of herpetic keratitis in rabbits. Two strengths of ganciclovir gel (0.05 and 0.15%) were compared with 3% acyclovir ointment in the treatment of superficial herpes simplex keratitis in humans.\n Two multicenter randomized clinical trials were carried out in Africa (Trial 1) and Europe (Trial 2). Sixty-seven patients (Trial 1) and 37 patients (Trial 2) from herpetic ulceration were recruited.\n The results showed no statistically significant difference between the treatment groups, although the healing rates tended to be better in the group receiving 0.15% ganciclovir gel, with healing rates of 85% (Trial 1) and 83% (Trial 2) as compared with 72% (Trial 1) and 71% (Trial 2) in the group receiving acyclovir ointment. Local tolerance was found to be superior with the gel formulation of ganciclovir with fewer complaints of discomfort (stinging, burning) or blurred vision after application of the drug. Systemic absorption of the drug was low. No hematologic changes were detected.\n These findings support the efficacy of ganciclovir gel in the treatment of ulcerative herpes simplex keratitis and demonstrate its superior local tolerance when compared with acyclovir ointment.",
"Ocular herpes simplex virus (HSV) infection remains a major cause of corneal blindness. Several topical and oral antiviral medications have been used to treat herpetic keratitis. Advances in topical ophthalmic antivirals have been made over the past several decades. The first antivirals that were discovered were cytotoxic, while the antivirals developed more recently, such as acyclovir and ganciclovir, have exceeded these drugs in both efficacy and tolerability. Commercially available outside of the US since 1996, ganciclovir ophthalmic gel, 0.15% (GCV 0.15%, European tradename: Virgan((R))) is sold in more than 30 countries and has become the standard of care in treating acute herpetic keratitis. GCV 0.15% has been studied in animal models of ocular herpes, in healthy volunteers, and in several clinical studies. It has been found to be safe and effective at treating acute superficial herpetic keratitis. Previous preclinical studies of ganciclovir have shown activity against several common adenovirus strains and one recent clinical study demonstrated clinical effect against adenoviral conjunctivitis. This review is intended to provide a comprehensive overview of the GCV 0.15%, including a brief summary of the etiology and available treatments for ocular HSV, an explanation of GCV 0.15% mechanism of action, a compendium of preclinical and clinical GCV 0.15% studies, and an introduction into new areas of interest involving this drug.",
"At three university centres 66 patients presenting with herpetic dendritic or geographic ulcers participated in a double-blind comparative study of 3% acyclovir and 3% vidarabine ointment. There was healing in 31 (97%) of the 32 patients treated with acyclovir, in a mean time of 6.3 days, and in 30 (88%) of the 34 treated with vidarabine, in a mean time of 7.1 days. The two medications were statistically equally effective, no difference being demonstrated in the healing rate, in the frequency of punctate epithelial keratitis or stromal keratitis, or in the final visual acuity.",
"In a double-blind, randomized trial 52 patients with superficial herpes simplex keratitis were treated with a new antiviral compound, acylclovir (ACV) 3% ointment, or with idoxuridine (IDU) 0.5% ointment. No statistically significant difference was found in the number of patients cured with either drug, but healing was achieved more rapidly with ACV than with IDU.",
"Fifty-nine patients with superficial herpetic keratitis were treated with 3% acyclovir ointment five times a day in combination with alpha-interferon (30 million IU/mL) or albumin-placebo once a day in a stratified double-masked clinical trial. All patients had minimal wiping of the superficial lesion to isolate virus. The healing time of the corneal ulcers was substantially lower with the combination of acyclovir and interferon than with the combination of acyclovir and placebo. Only minor toxic effects were observed. The combination of acyclovir and interferon appears to be the best presently known treatment for dendritic keratitis.",
"38 patients with herpes simplex keratitis were treated in double blind clinical trial. 18 patients (10 with pure epithelial and 8 with accompanying stromal affection) were treated with 3% acyclovir (ACV) eye ointment, and 20 patients (10 with pure epithelial and 10 with accompanying stromal affection) were treated with 0.5% idoxiuridine (IDU). The cure rate was 94% in the ACV group compared to 70% in the IDU group. This was significantly higher in the ACV group. Only minor adverse reactions were recorded.",
"Sixty patients with simple dendritic corneal ulceration were randomly assigned to double blind treatment with either acyclovir tablets (400 mg) or acyclovir ophthalmic ointment administered five times daily. There was no significant difference in the proportions of patients healed in either treatment group (88.9% on oral acyclovir and 96.6% on acyclovir ointment). The median healing time was five days in both groups. No systemic or significant local side effects were noted in either treatment group. Trough levels of acyclovir in the tear fluid of those who received the oral preparation were within or above the range of mean in-vitro ID50 levels for herpes simplex virus type 1. We conclude that oral administration of acyclovir (400 mg, five times daily) may be an effective alternative to topical therapy in selected patients.",
"Thus, we found that the role of Acyclovir in the treatment of viral corneal ulcer is definitely better and quicker. It takes less time for healing of corneal ulcer and as a result less hospitalisation is needed.",
"Sixty patients were treated with either acyclovir 2% ointment or idoxuridine 1% ointment 5 times a day in a stratified randomised double-blind clinical trial. The 2 antiviral agents were equally effective.",
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"To evaluate the efficacy of four antiviral agents--1% idoxuridine ointment (group 1), 2% trifluorothymidine ointment (group 2), 3% acyclovir ointment (group 3) and 1% bromovinyldeoxyuridine (BVDU) ointment (group 4)--in herpes simplex keratitis.\n Randomized double-blinded clinical trial.\n Tertiary care institution in New Delhi.\n Eighty patients with uncomplicated herpes simplex keratitis of recent onset who had not previously received antiviral treatment.\n Cure rate, frequency and severity of side effects.\n Cure rates of 60%, 90%, 90% and 95% were obtained in groups 1, 2, 3 and 4 respectively. The average healing time was 13.4, 8.9, 8.5 and 7.5 days respectively. Side effects (follicular conjunctivitis, epithelial keratopathy and stinging) were more frequent in group 1 than in the other groups.\n BVDU has a more pronounced therapeutic effect than idoxuridine, trifluorothymidine and acyclovir in uncomplicated epithelial herpetic disease of recent onset that has not previously been treated.",
"This report presents the results of a double blind randomized study comprising 50 patients with epithelial herpes simplex keratitis. Twenty-five patients received 3% acyclovir ophthalmic ointment, the other 25 patients 2% trifluorothymidine (TFT) ophthalmic ointment. The mean duration of treatment in the 2 study groups before healing of the epithelial ulceration was obtained was 6.7 days and 5.9 days, respectively (no statistically significant difference). Two patient (8%) in the acyclovir group and 1 patient (4%) in the TFT group failed to heal within 14 days of treatment. No clinically significant adverse effects were recorded.",
"No statistical difference was found in both partial and complete healing time in acute epithelial herpetic keratitis between the ACV-recombinant human alpha 2 IFN (both \"eyedrops\" and \"eyerods\") and Buffy coat human leucocyte alpha IFN. A highly significant difference was found in both partial and complete healing time between the ACV-IFN combination versus the ACV-Placebo combination. The combination of ACV and recombinant human alpha 2 arg IFN is a potent anti-herpetic treatment.",
"Trifluorothymidine (TFT) and adenine arabinoside (ara-A) are effective antiviral drugs with a very low toxicity for the cornea. In our study no difference between these 2 drugs in antiviral activity was noted. The average healing time for TFT was 11-14 days and for ara-A 10-54 days. These data differ markedly from those of other studies. This was the result of the use of additional criteria for healing of the lesion. Not only absence of fluorescein staining of the cornea but also the absence of oedema and cystic changes in the epithelium over the previous ulcer were considered criteria for healing. In addition to clearly defined healing criteria and the healing time we found the interval between the first symptoms and the commencement of the therapy of greatest importance in the clinical evaluation of antiviral drug efficacy. An effort was made to approximate this relationship for TFT and ara-A mathematically.",
"We treated 25 patients with dendritic keratitis with debridement and 3% acyclovir ointment and another 25 with acyclovir alone. The patients were randomly assigned to the two treatment groups. There were only minimal adverse effects in both groups. The combination of debridement and acyclovir produced a significantly more rapid healing rate than did acyclovir alone. Factors associated with prolonged healing time were duration of symptoms (longer than one week), length of the epithelial defect (greater than 4 mm), proximity of the defect to the corneoscleral limbus (less than 2 mm), and the presence of stromal inflammation.",
"Large scale, multiclinic evaluations of vidarabine (Ara-A, Vira A, adenine arabinoside) for treating herpetic keratitis have been conducted as double-blind studies (169 patients) in comparison with IDU and open studies (146 patients). In the open studies, the disease in the majority of patients had been refractory to IDU. The effects of vidarabine and IDU were approximately the same in improvement of symptoms (lacrimination, photophobia, sensitivity) and percent of and time for corneal reepithelialization. With vidarabine, significantly more patients had improved distant visual acuity than did with IDU. In the open studies, vidarabine also was effective. Of 116 patients whose ulcers had not responded to IDU, 91 (78%) had reepithelialization within four weeks of treatment with vidarabine. On the basis of results from these studies, vidarabine appears to be a safe and effective drug for treating herpes simplex keratitis.",
"We treated 45 patients with virologically verified dendritic keratitis with a combination of interferon and acyclovir 3% or with placebo and acyclovir 3% in a double-masked study. One drop of human leukocyte interferon (30 X 10(6) IU/ml) or albumin-placebo was administered daily. Acyclovir ointment was applied five times daily. The mean healing time of the corneal ulcers in 24 patients treated with interferon and acyclovir was 3.9 days and the mean healing time in 21 patients treated with placebo and acyclovir was seven days. The difference was significant (P less than .001).",
"Fourty-three eyes with active dendritic keratitis, nearly one third of which had failed to respond to other antiviral agents, were treated with acyclovir with or without preceding debridement. The patients were randomly selected. No statistical difference could be demonstrated between the 2 groups in terms of rate of healing or in efficacy of cure. Acyclovir also seemed to be effective in stromal corneal lesions. There were only minor side effects.",
"Without effective antiviral prophylaxis, cytomegalovirus (CMV) disease is a common cause of morbidity and mortality after liver transplantation. In this randomized, controlled trial, we compared the efficacy and safety of oral ganciclovir with oral acyclovir after induction with intravenous (IV) ganciclovir for long-term prophylaxis of CMV disease in CMV-seropositive liver transplant recipients.\n Patients were initially administered IV ganciclovir at a dose of 6 mg/kg per day from day 1 to day 14 after transplantation followed by either oral ganciclovir (1 g every 8 hr) or oral acyclovir (800 mg every 6 hr) from day 15 to day 100 after transplantation.\n CMV disease occurred in only 1 of 110 patients (0.9%) receiving ganciclovir compared with 8 of 109 patients (7.3%) receiving acyclovir within the first year after transplantation (P =0.019). There was one case of CMV colitis in the ganciclovir group, whereas four cases of CMV syndrome, three cases of CMV pneumonia, and one case of CMV hepatitis developed in the acyclovir group. The only death from CMV disease occurred in an acyclovir-treated patient with CMV pneumonia. Both oral ganciclovir and oral acyclovir were generally well tolerated. Reversible leukopenia (decline in white blood cell count to <3.0 x 10(9)/L) was more common with oral ganciclovir (38/110 patients, 35%) than with oral acyclovir (20/109 patients, 18%) (P =0.009). The emergence of ganciclovir-resistant strains of CMV was not found during the study.\n A prophylactic regimen of 2 weeks of IV ganciclovir followed by an additional 12 weeks of oral ganciclovir is superior to a similar regimen of IV ganciclovir followed by oral acyclovir and almost completely eliminates CMV disease after liver transplantation. This superior protection against CMV disease extends up to 1 year after transplantation and is not associated with ganciclovir resistance.",
"Fifty-one patients were treated in a dual-centre, double-blind comparison of acyclovir and adenine arabinoside in herpetic amoeboid (geographic) corneal ulceration. Twenty-four of the 25 patients receiving acyclovir healed in a mean time of 12.2 days, while 24 of the 26 patients treated with adenine arabinoside healed in a mean time of 11.0 days. There was no statistically significant difference between the two groups in terms of healing. A second analysis, excluding any patients who had received antiviral treatment immediately prior to entry into the study, showed that 18 of the 19 who received acyclovir healed in an average of 11.7 days and 18 of the 19 recipients of adenine arabinoside healed in a mean time of 11.2 days. Again the difference was not statistically significant.",
"The results are reported of a fully controlled randomized double-blind clincial trial of adenine arabinoside and idoxuridine ointment in sixty patients with herpetic ulceration of the cornea. Although both antivirals showed a trend towards superiority over placebo, the therapeutic effect did not reach statistical significance in spite of the known efficacy in laboratory animals. Further studies in rabbits are reported; these indicate that systemic immunity may play a role in combating virus proliferation in recurrent disease, and it is considered this disguises the efficacy of topical antiviral therapy in clinical trials, thus necessitating an estimated requirement for approximately fifty patients per treatment group to obtain significant effects. It is concluded that an antiviral is valuable in the treatment of ulcerative herpetic keratitis, particularly in primary disease and in the presence of systemic and local immunosuppression after the use of topical adrenocorticosteroid. In recurrent disease, where a trigger factor is known, experience has shown that therapy can be profitably administered before the onset of clinical disease.",
"Posttransplantation cytomegalovirus (CMV) infection remains a significant cause of morbidity in kidney transplant recipients. We performed a randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for CMV prophylaxis in a group of renal allograft recipients considered at high risk for CMV disease due to the use of OKT3 induction therapy.\n A total of 101 recipients of cadaveric (83) and zero haplotype-matched live donor (18) kidney transplants were entered into the trial. A total of 22 D-R- patients received no prophylaxis. Twenty-seven D+R-, 29 D+R+, and 23 D-R+ patients were randomized to receive 3 months of either oral acyclovir (800 mg q.i.d.) or oral ganciclovir (1000 mg t.i.d.). Doses were adjusted according to the level of renal function. The D+R- patients were also given CMV immune globulin biweekly for 16 weeks. Surveillance blood cultures were obtained at transplantation, at months 1, 2, 3, and 6, and when clinically indicated. The primary study end points were time to CMV infection and disease the first 6 months after transplantation.\n The mean follow up was 14.4 months. Both agents were well tolerated, and no drug interruptions for toxicity occurred. CMV was isolated in 14 of 39 (35.9%) acyclovir-treated and 1 of 40 (2.5%) ganciclovir-treated recipients by 6 months (P=0.0001). Symptomatic CMV disease occurred in 9 of 14 (64%) of the acyclovir patients, two with tissue-invasive disease. Infection rates for acyclovir vs. ganciclovir, respectively, stratified by CMV serology were: D+R-, 54 vs. 0%, P=0.0008; D+R+, 43 vs. 6.6%, P=0.01; D-R+, 8.3 vs. 0%, P=NS. No patient developed CMV infection while taking oral ganciclovir, however three delayed infections occurred 2-7 months after finishing therapy. Each patient had been previously treated for acute rejection.\n Oral acyclovir provides effective CMV prophylaxis only for recipients of seronegative donor kidneys. Oral ganciclovir is a superior agent providing effective CMV prophylaxis for recipients of seropositive donor kidneys. Recipients who are treated for acute rejection are at risk for delayed CMV infection during the first posttransplantation year.",
"To assess the efficacy of high-dose oral acyclovir therapy compared with preemptive, short-course ganciclovir therapy (administered only if cytomegalovirus [CMV] shedding occurred) to prevent CMV disease in liver transplant recipients.\n A randomized controlled trial.\n Liver transplant center at a university-affiliated Veterans Affairs Medical Center.\n 47 consecutive patients having liver transplantation.\n Patients were stratified by their CMV antibody status and the CMV antibody status of the donor and were randomly assigned to one of two treatment groups. Surveillance cultures for CMV (buffy coat and urine) were done every 2 to 4 weeks for 24 weeks in all patients. One group received high-dose oral acyclovir (800 mg four times daily). The experimental group received no acyclovir, but if surveillance cultures were positive, ganciclovir (5 mg/kg intravenously twice daily) was administered for 7 days.\n Cytomegalovirus shedding and CMV disease were measured in the two groups.\n Cytomegalovirus shedding before the onset of CMV disease occurred in 25% (6 of 24) of patients in the acyclovir group compared with 22% (5 of 23) in the experimental group. Cytomegalovirus disease developed in 29% (7 of 24) of the acyclovir group and in 4% (1 of 23) of the experimental group (P < 0.05). No hematologic toxicity occurred with ganciclovir.\n Oral acyclovir is ineffective prophylaxis against CMV in liver transplant recipients. Preemptive, short-course ganciclovir therapy in patients with CMV shedding was well tolerated and provided effective prophylaxis against subsequent CMV disease; this protocol targets the patients at risk for CMV disease and minimizes toxicity and expense.",
"A controlled trial of oral acyclovir in herpetic dendritic corneal ulcers was carried out on 31 patients. All patients received minimal wiping debridement of the ulcer, following which they were randomly allocated to receive either oral acyclovir or placebo for 7 days. At the end of treatment 67% of dendritic ulcers in patients receiving acyclovir had healed compared with 43% in placebo recipients. The proportion of ulcers healed in the 2 groups at 7 days showed no significant difference (p = 0.18), but the rate of healing was significantly faster in acyclovir group (p = 0.03).",
"Optimal prophylaxis against cytomegalovirus (CMV) disease for organ transplant patients at risk for primary infection (donor seropositive, recipient seronegative, D+R-) remains to be determined. We hypothesized that prolonged oral ganciclovir therapy following intravenous therapy would provide increased protection.\n A total of 155 evaluable D+R- organ transplant recipients from 13 transplant centers were entered into the study: all received intravenous ganciclovir (5 mg/kg/day) for 5-10 days and then either oral acyclovir (400 mg tid) or oral ganciclovir (1 g tid) for an additional 12 weeks. Patients were assigned to their treatment groups at a central randomization site, with a separate randomization scheme for each of the organs transplanted (kidney, heart, or liver). In the case of kidney transplants, the patients were stratified according to source of the kidney (living related vs. cadaveric donor). The primary endpoint was the incidence of CMV disease in the first six months post-transplant.\n Treatment with oral ganciclovir was associated with a significant decrease in the incidence of symptomatic disease or viremia when compared with the oral acyclovir group (32% vs. 50%, P<0.05). This difference was most marked in terms of tissue invasive disease: only 3 of 15 symptomatic patients in the ganciclovir group vs. 10 of 21 in the acyclovir group developed tissue-invasive infection (P<0.05). There was a significant difference in the time to CMV disease or viremia in the two groups: mean time 212+/-17 days post-transplant for the acyclovir group vs. 291+/-13 days for the ganciclovir group (P<0.001). The incidence of allograft rejection was 34% in the ganciclovir group and 46% in the acyclovir group (P=NS). Leukopenia was more common in the ganciclovir group (P<0.05), but in no case did it require drug discontinuation. Ganciclovir resistance did not develop in this study.\n Prophylaxis with oral ganciclovir following a brief course of intravenous ganciclovir provides useful protection against primary CMV disease.",
"Cytomegalovirus disease is an important cause of morbidity following liver transplantation. To date there has not been an effective prophylaxis for CMV disease after liver transplantation. One hundred forty-three patients were randomized to receive either high dose oral acyclovir (800 mg 4 times a day) alone for 3 months after transplantation (acyclovir group) or intravenous ganciclovir (5 mg/kg twice a day) for 14 days followed by high dose oral acyclovir to complete a 3-month regimen (ganciclovir group). Of 139 patients available for evaluation, 43 of 71 (61%) patients from the acyclovir group developed CMV infection compared with 16 of 68 (24%) from the ganciclovir group (relative risk, 3.69; 95% confidence interval, 2.07-6.56; P < 0.00001). Of those randomized, CMV disease was seen in 20 (28%) of the acyclovir group compared with 6 (9%) of the ganciclovir group (relative risk, 5.11; 95% confidence interval, 2.05-12.75; P = 0.0001). The median time to onset of CMV infection was 45 days in the acyclovir group compared with 78 days in the ganciclovir group (P = 0.004). The median time to onset of CMV disease was 40 days in the acyclovir group compared with 78 days in the ganciclovir patients (P = 0.02). With respect to primary CMV infection, there was no difference in the rates in the 2 groups, but tissue invasive disease and recurrent CMV disease were less frequent in the ganciclovir group. It is concluded that a course of 2 weeks of ganciclovir immediately after transplantation followed by high dose oral acyclovir for 10 weeks is superior to a 12-week course of high dose oral acyclovir alone for prevention of both CMV infection and CMV disease after liver transplantation. However, the lack of significant effect in seronegative recipients who received grafts from seropositive donors suggests that other strategies are needed to prevent CMV infection in this high risk population.",
"An open, prospective, randomised study was conducted to compare the safety and efficacy of valacyclovir vs. oral ganciclovir for cytomegalovirus (CMV) prophylaxis in renal transplant recipients. Eighty-three renal transplant recipients were assigned randomly to receive valacyclovir (n=43) or oral ganciclovir (n=40) for the first 3 months after transplantation. Both groups were similar in terms of demographics, primary renal disease, graft source, HLA matching, immunosuppressive therapy and donor-recipient CMV antibody status. CMV infection was diagnosed by detection of virus DNA in plasma with the Amplicor CMV Test. CMV disease was observed in only one patient belonging to the ganciclovir group, who developed enterocolitis 6 months post-transplantation. No difference was observed between the two treatment groups with respect to detection of CMV DNA, virus infections other than CMV, acute rejection episodes, and serum creatinine levels at 3 and 6 months following transplantation. An increased number of bacterial infections was noted in the ganciclovir group (p 0.003). No adverse reactions with either treatment were reported. The estimated cost of valacyclovir treatment was 20% higher than that of ganciclovir treatment. Overall, both valacyclovir and oral ganciclovir were found to be effective and safe for CMV prophylaxis in renal transplant recipients. Decisions regarding prophylactic regimens should include additional criteria, such as cost or possible development of resistance.",
"A randomized trial was performed to compare the sequential use of 2 weeks of intravenous ganciclovir (10 mg/[kg.d]) followed by 50 weeks of high-dose oral acyclovir (800 mg/m2 four times daily) with 2 weeks of intravenous ganciclovir alone as prophylaxis for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) disease after pediatric liver transplantation. CMV disease was diagnosed for seven of 24 patients treated with ganciclovir followed by high-dose oral acyclovir compared with two of 24 children treated with ganciclovir alone (P = .048). Similarly, the rate of CMV disease among high-risk patients (CMV-positive donor/CMV-negative recipient) treated with the combination regimen was higher than that among high-risk patients treated with ganciclovir alone (four [57%] of seven vs. zero of five, respectively; vs P < .05). The rate of EBV disease among patients treated with the combination regimen (eight [33%] of 24) was similar to that among patients treated with ganciclovir alone (five [21%] of 24; P = not significant). We conclude that sequential prophylaxis with 2 weeks of intravenous ganciclovir followed by 50 weeks of high-dose oral acyclovir did not decrease the frequency of CMV or EBV disease after pediatric liver transplantation when compared with 2 weeks of intravenous ganciclovir alone.",
"Cytomegalovirus disease occurs frequently after solid organ transplantation and has been associated with decreased patient and allograft survival. We hypothesized that CMV transmission or reactivation begins immediately or soon after transplantation, and that a short-duration ganciclovir (GCV)-based regimen would obviate the need for long-term antiviral agent administration, perhaps serving to interdict CMV infection and disease as well as, or perhaps even more effectively than, a more prolonged, oral acyclovir (ACV)-based form of prophylaxis. A total of 311 patients were stratified according to allograft type, age, and presence or absence or diabetes mellitus, and were then randomized to receive either long-duration ACV prophylaxis (800 mg orally or 400 mg i.v. q.i.d. for 12 weeks after transplantation or 6 weeks after any antirejection therapy) versus short-duration GCV (5 mg/kg/12 hr i.v. for 7 days after transplant or after any antirejection therapy) plus human immune globulin (HIg; Sandoglobulin or Minnesota CMV immune globulin) 100 mg/kg i.v. administered on days 1, 4, and 7 after transplant or after any antirejection therapy. A total of 266 patients (ACV, n = 133; GCV+HIg, n = 133) completed the protocol and were available for follow-up. CMV disease occurred in fewer patients (n = 28, 21.0%) in the ACV group, while significantly more patients (n = 42, 31.6%) in the GCV + HIg group developed group developed CMV disease slightly later (2.83 +/- 0.70 months) than those who received GCV/HIg (2.15 +/- 0.21 months, P > 0.01). Multivariate analysis demonstrated (2.15 +/- 0.21 months, P > 0.1). Multivariate analysis demonstrated that receiving antirejection therapy, a liver transplant, or a donor organ from a CMV-seropositive individual if the recipient was CMV seronegative were major risk factors for the development of CMV disease (P < 0.001), while the difference between ACV versus GCV + HIg prophylaxis was also significant (P = 0.054). No differences in actuarial patient or allograft survival, however, were noted between the 2 prophylaxis groups. Overall, ACV prophylaxis appeared to be more effective in reducing the incidence of posttransplant CMV disease, although this effect was diminished in high-risk groups of patients. Our findings indicate that CMV transmission or reactivation may best be prevented by long-term antiviral agent administration, and that the primary morbidity of CMV disease is the need for rehospitalization when either prolonged ACV or short-duration GCV + HIg prophylaxis is used in this patient population.",
"In an attempt to modify the sequelae of cytomegalovirus (CMV) infections after lung transplantation, 25 allograft recipients were randomized to either ganciclovir 5 mg/kg once a day 5 d/wk (Group G) or acyclovir 800 mg four times a day (Group A). All subjects received ganciclovir during postoperative Weeks 1 through 3, and they were then given either A or G regimens until Day 90. At termination of study enrollment, the cumulative incidence of all CMV infections (including seroconversions) was increased in Group A compared with that in Group G (75% versus 15%, p < 0.01), as was the incidence of overt CMV shedding and/or pneumonitis (50% versus 15%, p < 0.043). In comparison with those in Group G, subjects in Group A were also afflicted with an increased prevalence of obliterative bronchiolitis (OB) during the first year after transplantation (54% versus 17%, p < 0.033). Intravenous catheters for ganciclovir administration resulted in four complications among three of the subjects in Group G (23%). The short-term benefits of ganciclovir were ultimately limited, moreover, in that cumulative rates of CMV and prevalence of OB are now similar in both treatment groups after approximately 2 yr of observation. We conclude that prolonged ganciclovir prophylaxis decreases the early incidence of CMV and OB among lung transplant recipients, but these effects are of finite duration. Although CMV prevention appears to have considerable potential value in this population, definitive viral prophylaxis will require development of protracted or repeated treatment regimens, or longer-acting agents.",
"To assess the efficacy of acyclovir and intravenous immune globulin (IVIG) for cytomegalovirus (CMV) prophylaxis in high-risk recipients of solid organ transplants.\n We randomized 21 CMV-seronegative organ transplant recipients with seropositive donors (D+R-) to receive oral acyclovir, 800 mg four times daily, or, in addition to acyclovir, IVIG, 300 mg/kg, every 2 weeks for six doses. Patients were followed closely for the development of CMV infection and disease.\n All but one prophylactically treated patient (95%) developed CMV infection. Fifteen of 21 patients (71%) who received prophylaxis fulfilled criteria for CMV disease. Disease onset was delayed in those who received IVIG, but this did not reach statistical significance. Ganciclovir was used for treatment in 15 of the 21 patients (71%).\n Acyclovir, with or without IVIG, did not prevent primary CMV infection or disease in D+R- solid organ transplant recipients at our institution. Moreover, most patients were treated with ganciclovir despite the use of prophylaxis. Given the ready availability of ganciclovir to treat CMV disease, we recommend a reappraisal of the role of CMV prophylaxis by these means in the solid organ transplant population.",
"In a double-blind controlled study, oral acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD); there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation.",
"Despite the use of vidarabine, herpes simplex virus (HSV) infection in neonates continues to be a disease of high morbidity and mortality. We undertook a controlled trial comparing vidarabine with acyclovir for the treatment of neonatal HSV infection.\n Babies less than one month of age with virologically confirmed HSV infection were randomly and blindly assigned to receive either intravenous vidarabine (30 mg per kilogram of body weight per day; n = 95) or acyclovir (30 mg per kilogram per day; n = 107) for 10 days. Actuarial rates of mortality and morbidity among the survivors after one year were compared overall and according to the extent of the disease at entry into the study (infection confined to the skin, eyes, or mouth; encephalitis; or disseminated disease).\n After adjustment for differences between groups in the extent of disease, there was no difference between vidarabine and acyclovir in either morbidity (P = 0.83) or mortality (P = 0.27). None of the 85 babies with disease confined to the skin, eyes, or mouth died. Of the 31 babies in this group who were treated with vidarabine and followed for a year, 88 percent (22 of 25) were judged to be developing normally after one year, as compared with 98 percent (45 of 46) of the 54 treated with acyclovir (95 percent confidence interval for the difference, -4 to 24). For the 71 babies with encephalitis, mortality was 14 percent with vidarabine (5 of 36) and with acyclovir (5 of 35); of the survivors, 43 percent (13 of 30) and 29 percent (8 of 28), respectively, were developing normally after one year (95 percent confidence interval for the difference, -11 to 39). For the 46 babies with disseminated disease, mortality was 50 percent (14 of 28) with vidarabine and 61 percent (11 of 18) with acyclovir (95 percent confidence interval for the difference, -20 to 40); of the survivors, 58 percent (7 of 12) and 60 percent (3 of 5), respectively, were judged to be developing normally after one year (95 percent confidence interval for the difference, -40 to 50). Both medications were without serious toxic effects.\n In this multicenter, randomized, blinded study there were no differences in outcome between vidarabine and acyclovir in the treatment of neonatal HSV infection. The study lacked statistical power to determine whether there were sizable differences within the subgroups of those with localized HSV, encephalitis, or disseminated disease.",
"Bromovinyldeoxyuridine is a potent and safe antiherpes compound that in combination with a placebo treatment promoted the partial and complete healing of herpetic epithelial disease in 22 patients in average times of 4-6 days and 8.5 days respectively. However, when BVDU was combined with 1.5 X 10(6) IU of recombinant a 2C interferon, partial and complete healing times for keratitis in 19 patients were reduced to 2-6 days and 4-6 days respectively. No toxic effects of the medications were observed in any patient.",
"We compared the efficacy and safety of valganciclovir with those of oral ganciclovir in preventing cytomegalovirus (CMV) disease in high-risk seronegative solid organ transplant (SOT) recipients of organs from seropositive donors (D+/R-). In this randomised, prospective, double-blind, double-dummy study, 364 CMV D+/R- patients received valganciclovir 900 mg once daily or oral ganciclovir 1000 mg three times a day (tid) within 10 days of transplant and continued through 100 days. CMV disease, plasma viremia, acute graft rejection, graft loss and safety were analyzed up to 6 and 12 months post-transplant. Endpoint committee-defined CMV disease developed in 12.1% and 15.2% of valganciclovir and ganciclovir patients, respectively, by 6 months, though with a difference in the relative efficacy of valganciclovir and ganciclovir between organs (i.e. an organ type-treatment interaction). By 12 months, respective incidences were 17.2% and 18.4%, and the incidence of investigator-treated CMV disease events was comparable in the valganciclovir (30.5%) and ganciclovir (28.0%) arms. CMV viremia during prophylaxis was significantly lower with valganciclovir (2.9% vs. 10.4%; p=0.001), but was comparable by 12 months (48.5% valganciclovir vs 48.8% ganciclovir). Time-to-onset of CMV disease and to viremia were delayed with valganciclovir; rates of acute allograft rejection were generally lower with valganciclovir. Except for a higher incidence of neutropenia with valganciclovir (8.2%, vs 3.2% ganciclovir) the safety profile was similar for both drugs. Overall, once-daily oral valganciclovir was as clinically effective and well-tolerated as oral ganciclovir tid for CMV prevention in high-risk SOT recipients.",
"Intravenous acyclovir was evaluated in the treatment of 97 immunocompromised patients with mucocutaneous herpes simplex virus infection in a randomized, double-blind, placebo-controlled trial. Acyclovir recipients had significantly shorter periods of virus shedding (p less than 0.0002) and lesion pain (p less than 0.01), and more rapid lesion scabbing (p less than 0.004) and lesion healing (p less than 0.04). The most common adverse reaction was a low incidence of peripheral vein irritation; no serious toxicity could be definitely attributed to acyclovir treatment even in these seriously ill patients. Intravenous acyclovir offers both safe and effective treatment for mucocutaneous herpes simplex virus infection in the immunocompromised host.",
"Idoxuridine which was first used in 1960 (Kaufman et al., 1962), has been for many years the only antiviral agent available in the treatment of herpetic keratitis. It is however no more successful than is mechanical removal of diseased epithelium (Patterson & Jones, 1967), and furthermore it may give rise to serious toxic side effects. The search for an alternative medication is therefore a pressing one. Trifluorothymidine (F3T) has, in recent years, been shown to be more effective than IDU and to be free from significant toxicity. Both of these drugs are pyrimidine nucleosides. Adenine Arabinoside or Arabinoside-A (Ara-A) is, by contrast, a purine nucleoside. It is thought to exert its antiviral effect by blocking DNA polymerase and ribonucleotide reductase.",
"Both oral ganciclovir and valacyclovir decrease the incidence of cytomegalovirus (CMV) disease after renal transplantation. Moreover, valacyclovir has been shown to reduce the risk of acute rejection. Our study was designed to compare the efficacy and safety of oral ganciclovir and valacyclovir in the prophylaxis of CMV disease after renal transplantation.\n A total of 83 patients were prospectively randomized to 3-month treatment with oral ganciclovir (3 g/day, n=36, GAN) or oral valacyclovir (8 g/day, n=35, VAL). A control group (DEF, n=12) was managed by deferred therapy.\n No differences were found in demography, immunosuppression, or donor/recipient CMV serology. The 12-month incidence of CMV disease was 67% in the DEF group compared with 6% in the GAN group and 3% in the VAL group (P<0.001 GAN or VAL vs. DEF; P=0.575 GAN vs. VAL). The biopsy-confirmed acute rejection rate at 12 months was 12% in the VAL group compared with 34% in the GAN group (P=0.030) and 58% in the DEF group (P<0.001). The difference between the GAN and DEF groups was not significant (P=0.087). The average CMV-associated costs per patient were $3,072, $2,906, and $4,906 in the GAN, VAL, and DEF groups, respectively.\n Valacyclovir and oral ganciclovir are equally effective in the prevention of CMV disease after renal transplantation. Both regimens are cost-effective. Valacyclovir is associated with a significantly reduced risk of acute rejection compared with both ganciclovir prophylaxis and deferred therapy.",
"To evaluate the efficacy of oral acyclovir in preventing stromal keratitis or iritis in patients with epithelial keratitis caused by herpes simplex virus (HSV).\n Patients with HSV epithelial keratitis of 1-week or less duration were treated with topical trifluridine and were randomly assigned to receive a 3-week course of oral acyclovir, 400 mg 5 times a day (hereafter referred to as the acyclovir group), or placebo (hereafter referred to as the placebo group). The development of HSV stromal keratitis or iritis was assessed during 12 months of follow-up.\n Stromal keratitis or iritis developed in 17 (11%) of the 153 patients in the acyclovir group and in 14 (10%) of the 134 patients in the placebo group. Compared with the placebo group, the adjusted rate ratio for the development of stromal keratitis or iritis in the acyclovir group was 1.16 (95% confidence interval, 0.56-2.43). The development of stromal keratitis or iritis was more frequent in patients with a history of HSV stromal keratitis or iritis than in those without such a history (23% vs 9%; P = .01).\n For patients with HSV epithelial keratitis treated with topical trifluridine, no apparent benefit of a 3-week course of oral acyclovir in preventing HSV stromal keratitis or iritis was seen during the subsequent year. The 1-year rate of development of stromal keratitis or iritis was lower than previously reported in the literature, except in patients with a history of HSV stromal keratitis or iritis.",
"46 patients with acute herpes zoster ophthalmicus of less than 72 hours duration were recruited into a placebo controlled trial to assess the efficacy of oral acyclovir, 800 mg 5 times daily, in preventing or modifying ocular complications and pain. Fewer acyclovir recipients developed intraocular complications and these were less severe but neither difference was statistically significant. However, active ocular disease was significantly less common in the acyclovir group (p = 0.01) at 6 months. Pain was significantly less severe in the acyclovir group between 2 and 6 months. The proportion of patients with pain scores greater than 0 was significantly lower in the acyclovir group between 2 and 3 months. Oral acyclovir appears to modify the disease process in herpes zoster ophthalmicus, to reduce the severity and incidence of postherpetic pain and especially to protect against long-term ocular complications.",
"The tolerability and efficacy of epidermal growth factor (EGF) in the topical treatment of herpetic corneal ulcers in addition to topical acyclovir have been evaluated in a double-blind, placebo-controlled, randomized study in two groups of patients. The time required for complete reepithelialization of the cornea was recorded, and the data obtained were analyzed statistically. In the EGF group, the reepithelialization was significantly faster than in the control group. Tolerability of EGF was always excellent. These results indicate that EGF is safe and effective in reducing the healing time of herpetic corneal ulcers.",
"Despite current approaches to prophylaxis, cytomegalovirus (CMV) continues to be a common cause of infection and disease in solid-organ-transplant patients. Thus, we conducted a controlled trial comparing long-term administration of ganciclovir with high-dose acyclovir for prevention of CMV infection and disease in liver transplant recipients. At the time of transplant, patients were randomised to receive either ganciclovir (6 mg/kg body weight per day intravenously from postoperative day 1 to day 30, then 6 mg/kg per day Monday through Friday until day 100) or acyclovir (10 mg/kg intravenously every 8 h from postoperative day 1 to day of discharge, then 800 mg orally four times a day until day 100). Patients were followed for development of CMV infection, CMV disease, and drug-related toxicity by frequent cultures, serological tests, laboratory measurements, and tissue biopsies. During the first 120 days after transplant, CMV infection occurred in 48 of 126 (38%) acyclovir patients but in only 6 of 124 (5%) ganciclovir patients (p < 0.0001). Similarly, symptomatic CMV disease developed in 12 of 126 (10%) acyclovir patients but in only 1 of 124 (0.8%) ganciclovir patients (p = 0.002). Ganciclovir reduced the incidence of CMV infection in both CMV antibody positive (37 vs 4%, p = 0.001) and negative patients (42 vs 11%, p = 0.06). In a multivariate analysis of donor-recipient CMV antibody status and other risk factors, prophylactic ganciclovir was the most significant factor protecting against CMV infection (p < 0.0001) and disease (p = 0.001). Ganciclovir and acyclovir were generally well-tolerated. Incidences of leukopenia, thrombocytopenia, renal failure, and other adverse events were similar in the two groups. CMV can be eliminated almost completely as a significant pathogen in liver transplant recipients by the long-term administration of prophylactic ganciclovir. In addition, the treatment is safe.",
"Unlike parenteral gancicovir, the efficacy of oral ganciclovir in the prevention and treatment of cytomegalovirus (CMV) infection in kidney transplantation has not been well documented. This study prospectively evaluated the episodes of CMV infection within the first nine months after transplantation in renal transplant recipients treated prophylactically with oral ganciclovir (750 mg twice a day) over a period of 3 months (oral ganciclovir, N = 22), compared with patients randomly assigned as controls (controls, N = 22) who did not receive any anti-viral prophylaxis. Diagnosis of CMV infection at presentation included serological determination of CMV-specific immunoglobulin M antibodies, CMV immunofluorescence assay [standard culture tube and shell vial] (blood) and virus isolation (urine and tissue). CMV infection occurred in one patient (5%) in the oral ganciclovir group and 6 patients (27%) in the control group (p < 0.05). The episodes of biopsy proven allograft rejections were 5% (1/21) and 18% (4/22) in the oral ganciclovir and control groups, respectively. Except for one, none of these patients developed CMV infection either before or after rejection(s). Controlling for the reason (induction or treatment of rejection) for using cytolytic antibody therapies, we found that prophylactic oral ganciclovir was protective against CMV infection (adjusted risk reduction 0.83; 95% confidence interval, 0.33-0.98; p < 0.05). Neither, the CMV status of donors and recipients nor the treatment for acute rejection had any significant impact on the occurrence of CMV infections. Our results show that oral ganciclovir is an effective and well tolerated therapy in the prevention of CMV infection in renal transplant patients.",
"The optimal prophylactic regimen to prevent cytomegalovirus (CMV) infection and disease in orthotopic liver-transplant patients remains to be established. We tested whether a combination of intravenous ganciclovir (GCV) followed by high dosages of oral acyclovir (ACV) for 4 months provided a higher degree of protection from CMV than oral ACV alone.\n One hundred sixty-seven liver-transplant recipients were randomized to receive 120 days of antiviral treatment starting at the time of transplantation consisting of either ACV 800 mg orally four times daily (n=84) or 14 days of GCV 5 mg/kg intravenously every 12 hr followed by oral ACV 800 mg four times daily (n=83). Prospective laboratory and clinical surveillance was performed to determine primary endpoints (onset of CMV infection and CMV disease) and secondary endpoints (rates of fungal and bacterial infection, allograft rejection, and survival after transplantation). One-year event rates are presented as cumulative percentages.\n During the first year after transplantation, CMV infection developed in 57% of patients treated with ACV and in 37% of patients treated with GCV + ACV (P=0.001). CMV disease developed in 23% of patients treated with ACV and in 11% of patients treated with GCV + ACV (P=0.03). In seronegative recipients of allografts from CMV-seropositive donors (D+/R-), CMV disease developed in 58% of patients treated with ACV and in 25% of patients treated with GCV + ACV (P=0.04). In the D+/R- group, 54% of patients treated with ACV and 17% of patients treated with GCV + ACV developed infection with Candida albicans (P=0.05).\n Prophylaxis of CMV infection in liver-transplant patients with 14 days of intravenous GCV followed by high-dosage oral ACV is more effective than high-dosage oral ACV alone at reducing CMV infection and disease, even for patients in the D+/R- CMV serological group.",
"In a randomized, double-blinded, placebo-controlled trial, we compared the therapeutic effect of oral acyclovir (400 mg five times daily for 10 days) with that of placebo in patients with marrow transplants and culture-proven recurrent mucocutaneous herpes simplex. Twelve patients received acyclovir and nine received placebo. Acyclovir treatment significantly shortened the median duration of viral shedding, new lesion formation, and time to first decrease in pain, resolution of pain, 50% healing, and total healing. These results compared favorably with those previously obtained with intravenous or topical acyclovir preparations. Oral acyclovir is highly effective for the treatment of recurrent mucocutaneous infections caused by herpes simplex virus in immunocompromised patients.",
"Combination antiretroviral therapy administered to HIV-infected individuals has been shown to improve immunologic function and delay the progression of HIV infection. However, because patient adherence to complicated combination-therapy antiretroviral regimens is difficult and because of concerns regarding cumulative toxicity of antiretroviral drugs, regimens that utilize fewer antiretroviral agents are desirable.\n To compare the use three- or four- versus two-drug antiretroviral maintenance regimens following successful induction therapy for HIV infection.\n The following electronic databases were searched for relevant randomized trials or reviews: 1. MEDLINE for the years 1982-1999 using the search terms human immunodeficiency virus, antiretroviral therapy, maintenance therapy, zidovudine, lamivudine, indinavir, stavudine, saquinivir, nelfinavir, didanosine, zalcitabine, ritonovir, AIDS, anti-HIV agents, HIV infection and HIV seropositivity 2. AIDSLINE for the years 1982-1999 using the search terms antiretroviral therapy, maintenance therapy, zidovudine, lamidvudine, indinavir, stavudine, saquinivir, nelfinavir, didanosine, zalcitabine, ritonovir, anti-HIV agents 3. The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness and the Cochrane Clinical Trials Register in the Cochrane Library, Issue 2, 1999. 4. The specialist register of trials maintained by the Cochrane Collaborative Review Group on HIV Infection and AIDS 5. AIDSTRIALS, a specialist registry of current and completed trials maintained by the U.S. National Library of Medicine The abstracts of relevant conferences, including the International Conferences on AIDS, the Conference on Retroviruses and Opportunistic Infections, the Infectious Disease Society of America annual meeting and the Interscience Conference on Antimicrobial Agents and Chemotherapy, as indexed by AIDSLINE, were also reviewed. All reference lists of all review articles and primary articles identified were searched.\n Randomized controlled trials in which HIV-infected adults who had successfully completed three- or four-drug antiretroviral induction therapy were randomized to maintenance therapy with three or four drugs or maintenance therapy with two drugs. Successful induction therapy was defined by a plasma viral load of less than 500 copies/ml.\n Two reviewers assessed eligibility and trial quality. Attempts were made to contact the authors of the included abstract. Data on the number of patients experiencing loss of viral suppression were abstracted by two reviewers. The data were pooled, where appropriate, to yield odds ratios, using random effects models.\n Four trials were identified including three published studies and one abstract. Compared to three- or four-drug maintenance therapy, maintenance therapies including fewer drugs were associated with a higher risk of virologic failure (loss of HIV suppression to non-detectable levels). Combining the results of all four studies yielded an odds ratio of 5.55 (95% confidence interval, 3.14 - 9.80). Similar results were obtained when the one abstract was excluded (odds ratio, 5.48; 95% confidence interval, 2.82 - 10.65). Performing subgroup analyses of studies using the same induction and maintenance regimens gave similar results. Maintenance regimens of zidovudine and lamivudine compared to maintenance regimens with zidovuine, lamivudine and indinavir, were associated with significantly higher rates of virologic failure (odds ratio, 4.57; 95% confidence interval, 1.80 - 11.58). Similarly, maintenance regimens that discontinued one or more protease inhibitor after including them in induction therapy were also associated with a significantly higher risk of virologic failure (odds ratio, 6.15; 95% confidence interval, 3.40 -11.10). (ABSTRACT TRUNCATED)",
"Cytomegalovirus (CMV) disease is a frequent cause of serious morbidity after solid-organ transplantation. The prophylactic regimens used to prevent CMV infection and disease have shown limited benefit in seronegative recipients. We studied the safety and efficacy of oral ganciclovir in the prevention of CMV disease following orthotopic liver transplantation.\n Between December, 1993, and April, 1995, 304 liver-transplant recipients were randomised to receive oral ganciclovir 1000 mg or matching placebo three times a day. Seronegative recipients of seronegative livers were excluded. Study drug was administered as soon as the patient was able to take medication by mouth (no later than day 10) until the 98th day after transplantation. Patients were assessed at specified times throughout the first 6 months after surgery for evidence of CMV infection, CMV disease, rejection, opportunistic infections, and possible drug toxicity.\n The Kaplan-Meier estimate of the 6-month incidence of CMV disease was 29 (18.9%) of 154 in the placebo group, compared with seven (4.8%) of 150 in the ganciclovir group (p < 0.001). In the high-risk group of seronegative recipients (R-) of seropositive livers (D+), incidence of CMV disease was 11 (44.0%) of 25 in the placebo group, three (14.8%) of 21 in the ganciclovir group (p = 0.02). Significant benefit was also observed in those receiving antibodies to lymphocytes, where the incidence of CMV disease was 12 (32.9%) of 37 in the placebo group and two (4.6%) of 44 in the ganciclovir group (p = 0.002). Oral ganciclovir reduced the incidence of CMV infection (placebo 79 [51.5%] of 154; ganciclovir 37 [24.5%] of 150; p < 0.001) and also reduced symptomatic herpes-simplex infections (Kaplan-Meier estimates: placebo 36 [23.5%] of 154; ganciclovir five [3.5%] of 150; p < 0.001).\n Oral ganciclovir is a safe and effective method for the prevention of CMV disease after orthotopic liver transplantation.",
"Previous studies showed that the combination of trifluridine with human leukocyte interferon in the treatment of dendritic keratitis is effective, and that the best results were obtained with the highest titer then available (30 X 10(6) IU/mL). The present study was undertaken to see if an even higher titer (100 X 10(6) IU/mL) would be more effective. A statistically significant greater effectiveness of the higher titer could not be verified.",
"To compare the lipid and metabolic effects, efficacy, and safety of twice-daily regimens of Trizivir (abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg triple nucleoside tablet; TZV), Combivir (lamivudine 150 mg/zidovudine 300 mg combination tablet; COM)+nelfinavir (NFV), and stavudine (d4 T)+lamivudine (3TC)+NFV.\n An international, phase 4, open-label, parallel-group, 34-centre study was conducted in 254 non-diabetic, antiretroviral-naive, HIV-infected out-patients with an HIV-1 RNA level of >1000 HIV-1 RNA copies/mL and < or =200,000 copies/mL and a CD4 cell count of >50 cells/microL.\n Patients were randomized 1 : 1 : 1 to TZV twice daily (n = 85), COM/NFV 1250 mg twice daily (n = 88), or d4T 40 mg+3TC 150 mg+NFV 1250 mg twice daily (n = 81) for 96 weeks. Treatments were compared using analysis of covariance (ANCOVA) with regard to changes from baseline in fasting lipids in the total population and in sex and ethnic subgroups. The proportions of patients achieving HIV-1 RNA <50 and <400 copies/mL were compared using a 95% confidence interval (CI) on the difference between proportions.\n The study population was diverse (50% female, 40% black and 37% Hispanic). Mean baseline low-density lipoprotein (LDL) cholesterol was 99 mg/dL, HIV-1 RNA was 4.43 log10 copies/mL and CD4 cell count was 355 cells/microL. At week 96, fasting LDL cholesterol changed minimally in the TZV group [least square mean (LSM) change from baseline, -8 mg/dL], but increased with d4T/3TC/NFV and COM/NFV (+29 and +19 mg/dL, respectively; P < 0.001 versus TZV). Week 96 LDL-cholesterol levels were significantly lower in the TZV group than in the other two treatment groups in women and men and lower than in the d4T/3TC/NFV group in Hispanic and black patients. In black patients, the week-96 LSM change from baseline in LDL cholesterol was significantly less with TZV than with d4T/3TC/NFV (+1 vs+39 mg/dL; P = 0.003). Total cholesterol >200 mg/dL occurred in a smaller proportion of patients receiving TZV (30%) compared with COM/NFV (50%) or d4T/3TC/NFV (60%; P = 0.005 vs TZV). High-density lipoprotein (HDL) cholesterol did not change markedly with any treatment. Although triglycerides increased, they changed least in women and Hispanic patients receiving TZV. Virological and CD4 responses to the treatments were similar in the total population and in the subgroups. Diarrhoea was reported more often in the NFV arms and nausea in the ZDV arms.\n Over 96 weeks, TZV twice daily has significantly less effect on LDL cholesterol than COM/NFV or d4T/3TC/NFV twice daily, especially in women and black patients, and is associated with similar virological and CD4 responses.",
"To determine the most convenient and least expensive regimen for prevention of recurrent herpes simplex virus (HSV) infection after marrow transplantation, we conducted a randomized, double-blind comparison of intravenous acyclovir 250 mg/m2 and placebo given once daily for four weeks. Six of 14 acyclovir and nine of 13 placebo recipients shed HSV during prophylaxis. All nine culture-positive placebo recipients developed associated lesions during prophylaxis compared to four of six acyclovir recipients. Median time to first culture-positive lesion was significantly delayed by acyclovir compared to placebo (33 days after transplant vs. 10; P = 0.05). Acyclovir-resistant HSV was recovered from one acyclovir recipient while receiving prophylactic acyclovir, and from two placebo recipients during subsequent administration of therapeutic acyclovir. Once-daily intravenous acyclovir can significantly delay time to appearance of culture-positive HSV lesions after marrow transplant, but virological and clinical breakthrough may occur and optimal prevention will require administration of intravenous acyclovir more than once daily.",
"It is common practice to administer acyclovir as prophylaxis to patients with hematologic malignancies during neutropenia; however, effective therapy requires frequent dosing, which is difficult in this setting. Valacyclovir has greater oral bioavailability and requires less frequent dosing.\n To evaluate the efficacy and safety of valacyclovir compared with acyclovir.\n Patients who had been treated with chemotherapy or stem-cell transplantation were randomized to receive acyclovir 400 mg orally 3 times daily (n = 51), valacyclovir 500 mg orally twice daily (n = 48), or valacyclovir 250 mg orally twice daily (n = 52) during neutropenia.\n Clinical success, defined as the absence of an active herpes simplex virus (HSV) lesion or asymptomatic viral shedding, was similar between the 3 groups (acyclovir 96%, valacyclovir 500 mg 95%, valacyclovir 250 mg 100%). The overall rates of adverse events were similar in the 3 groups.\n Prophylactic treatment with valacyclovir is an effective and safe alternative to acyclovir for the prevention of HSV reactivation in patients with hematologic malignancies.",
"Thirty-three patients were followed in a double controlled study to test the efficacy of IDU and TFT on superficial epithelial herpes simplex virus infection. Sixteen received TFT and 17, IDU. There were four failures in patients on IDU therapy and no failures in the 16 patients using TFT. These results indicate a trend for greater efficacy of TFT than IDU. In those patients who healed with IDU and with TFT, there was no difference in the number of days to heal in each group.",
"Oral acyclovir was found to be safe and effective for the prevention of herpes simplex virus reactivation after marrow transplantation in a double-blind, placebo-controlled trial. Acyclovir or placebo was administered to 49 patients for 5 weeks beginning 1 week before transplantation: 5 of 24 patients receiving acyclovir developed herpes simplex virus infection during prophylaxis, compared to 17 of 25 patients receiving placebo (p less than 0.01). The median time to first virus reactivation was significantly longer among patients receiving acyclovir (78 days versus 9 days after transplant, p = 0.006). The effect was even more pronounced when the analysis was adjusted for drug compliance: Among patients taking a minimum of 40% of their prescribed drug, acyclovir was 96% virologically effective and 100% clinically effective during the period of administration. Acyclovir use was also associated with significantly more rapid marrow engraftment in patients receiving methotrexate. No virus resistant to acyclovir was isolated. Oral acyclovir provides effective prophylaxis against reactivation of herpes simplex virus among severely immunosuppressed patients able to take orally administered drugs.",
"One hundred two unselected patients with ulceration of the cornea due to herpes simples virus were treated with either adenine arabinoside or trifluorothymide; the trial was double-blind, stratified, and radomized. The two drugs were given topically five times per day, and the rate of healing was observed and recorded. The series included 87 patients with dendritic ulcers and 15 with amoeboid ulcers. Dendritic ulcers of the cornea can be accurately measured, and the healing process can be easily followed. In this situation no statistically significant difference between the efficacy of adenine arabinoside and that of trifluorothymidine was demonstrated. Amoeboid ulcers are more difficult to evaluate than dendritic ulcers, and their responses to treatment vary considerably; however, data from this small group of patients suggest that trifluorothymodine may be more effective than adenine arabinoside for the treatment of amoeboid ulcers.",
"To assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus (HCV) infection.\n One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone. Primary end points were liver enzymes, HCV-RNA levels and histology.\n Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo (P = 0.05). Histology activity index (HAI) score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo (P = 0.21). HCV-RNA levels decreased by 1-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo (P = NS). In part II of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points.\n Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients.",
"The purpose of this study was to analyze different regimens of viral prophylaxis after combined pancreas-kidney transplantation (PKT). Over a 4-year period, we performed 82 PKTs with quadruple immunosuppression with OKT3 induction. Four regimens of prophylaxis were studied. The first 30 patients received standard intravenous immunoglobulin (IVIG; 0.5 g/kg) for 6 doses and oral acyclovir for 3 months. The next 34 recipients received intravenous ganciclovir (2.5 mg/kg) twice daily for 2 weeks followed by oral acyclovir for 3 months. In the third group, patients were randomized to 5 doses over 2 months of either standard IVIG (n = 9) or CMV hyperimmune globulin (Cytogam; n = 9; 100-150 mg/kg) plus 2 weeks of i.v. ganciclovir followed by 3 months of oral acyclovir. The 4 groups were similar with respect to clinical, demographic, and immunologic variables, including donor and recipient CMV serologic status and blood transfusions. All patients were monitored for viral infections in the first 6 months after PKT. The regimens of prophylaxis resulted in (1) no major non-CMV (including no EBV) viral infections; (2) 3 cases of minor non-CMV viral infections (shingles); and (3) no differences in the incidence, timing, or severity of symptomatic CMV infections in the 4 groups. No death or graft loss was due to viral infection. Prophylaxis is effective in reducing the incidence of non-CMV viral infections and may reduce the severity of symptomatic CMV infection. However, we could not show any added benefit of either Cytogam or standard IVIG when used in combination with other antiviral agents. For economic as well as efficacy reasons, we recommended that IVIG preparations not be used routinely with antilymphocyte therapy but only in high-risk situations such as primary CMV exposure.",
"Forty-one patients receiving remission induction chemotherapy with vincristine, adriamycin and prednisolone (VAP) for high grade lymphoma or acute lymphoblastic leukaemia were entered into a double blind, placebo controlled trial of oral acyclovir prophylaxis against herpes simplex virus (HSV) infection. The dose of acyclovir was 200 mg four times daily for the duration of chemotherapy (six weeks). Of the 40 evaluable patients, 20 were randomised to each arm. Prophylactic oral acyclovir significantly reduced the incidence of clinical HSV infection from 60% on placebo to 5% acyclovir (P less than 0.001), and the incidence of viral isolates from 70% on placebo to 5% on acyclovir (P less than 0.001).",
"To evaluate (a) the prophylactic effect of the antiherpetic drug acyclovir on oral ulcers in patients with acute myeloid leukaemia receiving remission induction chemotherapy and thus (b), indirectly, the role of herpes simplex virus in the aetiology of these ulcers.\n Randomised, double blind, placebo controlled trial.\n 74 herpes simplex virus seropositive patients aged 18-84. Thirty seven patients received acyclovir (800 mg by mouth daily) and 37 placebo. The patients were examined daily for 28 days.\n Occurrence of herpes labialis, intraoral ulcers, and acute necrotising ulcerative gingivitis.\n The two populations were comparable in age, sex, type of antineoplastic treatment, and history of herpes labialis. Acute oral infections occurred in 25 of the acyclovir treated patients and 36 of the placebo treated patients (relative risk 0.69 (95% confidence interval 0.55 to 0.87)). This difference was due to a reduction in the incidence of herpes labialis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)), intraoral ulcers excluding the soft palate (one case versus 13 cases; relative risk 0.08 (0.01 to 0.56)), and acute necrotising ulcerative gingivitis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)). However, ulcers on the soft palate were diagnosed with similar frequency in the two groups. Isolation of herpes simplex virus type 1 in saliva was reduced from 15 cases in the placebo group to one case in the acyclovir group (relative risk 0.07 (0.01 to 0.48)).\n Intraoral ulcers excluding the soft palate are most often due to infection with herpes simplex virus, whereas ulcers on the soft palate have a non-herpetic aetiology. The findings suggest that acute necrotising ulcerative gingivitis may also be due to herpes simplex virus. Prophylaxis with acyclovir should be considered for patients with acute myeloid leukaemia during remission induction therapy.",
"The potential of prophylactic ganciclovir for the control of cytomegalovirus (CMV) infection was evaluated in a prospective controlled trial of 65 patients after liver transplantation. A group of 33 patients received ganciclovir (10 mg/kg/day) during the third and fourth weeks after transplantation, while 32 patients were randomised to receive ganciclovir (10 mg/kg/day) only when clinical CMV disease was diagnosed. Eight patients (25%) in the latter group received ganciclovir and included the only death attributed to CMV infection in the study. Prophylactic ganciclovir was associated with a lower incidence of serologically diagnosed secondary infection and the development of the IgM anti-CMV antibody. However, the frequency of clinical infections was similar in the two groups (9/33 vs. 11/32). Liver function tests during the second month after transplantation were not significantly better in the patients receiving prophylactic ganciclovir. Leucopaenia was not seen in patients receiving prophylactic ganciclovir.",
"nan",
"Treatment with prophylactic oral acyclovir, intravenous ganciclovir, or immunoglobulins to prevent cytomegalovirus (CMV) infection and disease in renal transplantation is associated with variable efficacy and significant expense. We studied control of CMV in renal transplant recipients using either prophylactic oral ganciclovir or deferred therapy with intensive monitoring with polymerase chain reaction (PCR) analysis.\n Forty-two recipients were followed for 6 months after transplantation. Ganciclovir (1000 mg p.o. t.i.d.; n=19) or acyclovir (200 mg p.o. b.i.d.; n=23) was begun at transplantation and continued for 12 weeks. PCR for CMV was performed on buffy-coat specimens every week for 15 weeks and at months 5 and 6.\n No patients in the ganciclovir group, compared with 14 of 23 patients (61%) in the deferred-therapy group (P<0.0001), developed CMV disease during the first 12 weeks. In the ganciclovir group, 4 of 19 patients (21%) subsequently experienced 5 episodes, whereas 14 patients in the deferred-therapy group experienced 18 episodes (P=0.013 for subjects and P=0.026 for episodes). The time to disease was also delayed in the ganciclovir group compared with the deferred-therapy group (133+/-17 days vs. 51+/-7 days; P<0.0001). Oral ganciclovir also prevented CMV viremia during prophylaxis (2/19 patients [11%] vs. 23/23 patients [100%]). Time to CMV viremia was delayed in the ganciclovir group; however, 13/19 patients (68%) ultimately showed PCR evidence for CMV viremia (P=0.005).\n An initial 12-week course of oral ganciclovir prevents CMV disease and infection in renal transplant recipients during prophylaxis, and the benefits persist after discontinuation."
] |
Trifluridine and acyclovir are more effective than idoxuridine or vidarabine and similar in therapeutic effectiveness. Brivudine and ganciclovir are at least as effective as acyclovir. While not improving outcome, the combination of interferon and an antiviral agent may speed healing. The effectiveness of corneal epithelial débridement is improved by an antiviral agent.
|
CD002971
|
[
"16061595",
"8694013",
"3373407",
"3761107",
"10565448"
] |
[
"Randomized trial of donor human milk versus preterm formula as substitutes for mothers' own milk in the feeding of extremely premature infants.",
"Randomized outcome trial of human milk fortification and developmental outcome in preterm infants.",
"Improved bone mineralization and growth in premature infants fed fortified own mother's milk.",
"Growth, biochemical status, and mineral metabolism in very-low-birth-weight infants receiving fortified preterm human milk.",
"Changes in growth and metabolism in very low birthweight infants fed with fortified breast milk."
] |
[
"Compared with preterm formula (PF), mother's milk (MM) is associated with lower rates of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) among premature infants. Because not all mothers of premature infants produce sufficient milk to supply their infants throughout hospitalization, we reasoned that pasteurized donor human milk (DM) would be a suitable alternative.\n Extremely premature infants (<30 weeks of gestation) whose mothers intended to breastfeed were assigned randomly to receive either pasteurized DM or PF if the supply of their own MM became insufficient during the study (birth to 90 days of age or hospital discharge). Infection-related events (LOS, NEC, meningitis, presumed sepsis, or urinary tract infection) that occurred after the attainment of a milk intake of 50 mL/kg, dietary intake, growth, skin-to-skin contact, and duration of hospital stay were compared. The primary analysis compared groups DM and PF on an intent-to-treat basis. If no differences were noted, then these groups were combined and compared with the reference group, group MM. If differences were noted, then the subsequent analyses compared each group with group MM.\n Of 243 infants, 70 (29%) received only MM; group DM included 81 infants and group PF included 92 infants. Because of poor weight gain, 17 infants (21%), all in group DM, were switched to PF. There were no differences in birth weight, gestational age, multiple births, and age at attainment of feeding of 50 mL/kg among groups. There were no differences between group DM and group PF in LOS and/or NEC, other infection-related events, hospital stay, or number of deaths. Group DM received a greater intake of milk and more nutritional supplements but had a slower rate of weight gain, compared with group PF. Compared with groups DM and PF, group MM had fewer episodes of LOS and/or NEC and total infection-related events and a shorter duration of hospital stay. Group MM also had fewer Gram-negative organisms isolated from blood cultures than did the other groups.\n In this randomized, blinded trial of feeding of extremely premature infants, we found that, as a substitute for MM, DM offered little observed short-term advantage over PF for feeding extremely premature infants. Advantages to an exclusive diet of MM were observed in terms of fewer infection-related events and shorter hospital stays.",
"Despite potential benefits, human milk may fail to meet preterm infants' nutrient requirements. We tested the hypothesis that fortified breast milk, fed alone or with preterm formula, would improve neurodevelopment and growth at 18-mo follow-up without adverse short-term clinical or biochemical consequences. Two hundred seventy-five preterm infants from two medical centers (birth weight < 1850 g; mean gestation 29.8 +/- 2.7 wk) whose mothers chose to provide breast milk were randomly assigned to receive for a mean of 39 d a multinutrient fortifier or control supplement containing phosphate and vitamins. Breast milk comprised 47.6% and 46.4% of enteral intake in fortified and control groups, respectively; preterm formula supplements were used when insufficient breast milk was available. Overall, there were no significant growth advantages with fortification; although, when breast milk exceeded 50% of intake, fortification promoted faster weight gain (an advantage of 1.6 g.kg-1.d-1; 95% CI: 0.1, 3.1; P < 0.05). Compared with control infants, the fortified group showed 1) higher plasma urea from week 2 (P = 0.04), 2) higher plasma calcium (mean 2.34 +/- 0.01 compared with 2.27 +/- 0.02 mmol/L; P = 0.003), 3) a greater rise in alkaline phosphatase by week 6 (P = 0.04), 4) more clinical infections (suspected plus proven; 43% compared with 31%, P = 0.04), 5) a nonsignificantly increased incidence of necrotizing enterocolitis (5.8% compared with 2.2%, P = 0.12), and 6) higher white cell and platelet counts. Developmental scores at 18 mo were slightly but not significantly higher in the fortified group. This study confirmed that breast milk fortifiers can improve short-term growth (when breast milk intakes are high); but beneficial effects on long-term development remained unproven. Future research is required to evaluate potential adverse consequences and explore more optimal fortification strategies.",
"\"Preterm\" human milk fortified with protein (0.85 gm/dL), calcium (90 mg/dL), and phosphorus (45 mg/dL) was compared with unfortified preterm human milk as a feeding for low birth weight infants. Additionally, a special formula for low birth weight infants (Similac Special Care (SC), 20 cal/oz), was compared with a standard 20 cal/oz formula (Similac). Bone mineral content (BMC), as measured by photon absorptiometry, improved in the study groups fed fortified human milk and Similac SC formula during the first 6 weeks of full oral feedings. Even though the intakes of calcium in the groups fed fortified human milk and Similac SC formula approached the intrauterine requirement for Ca during the third trimester of pregnancy (150 mg/kg/d), the values for BMC in these two groups (37 to 39 mg/cm) at the completion of the study were still considerably less than the intrauterine values for radial BMC at 36 to 37 weeks gestational age (72.6 +/- 14.1 mg/cm). Furthermore, the relative phosphorus deficiency (as determined by increased urinary Ca excretion and increased renal tubular reabsorption of phosphate) in the human milk groups occurred with or without supplements of Ca and P. Rate of weight gain in the fortified human milk group was greater than that of the unfortified human milk group and was comparable to that of infants fed Similac SC formula. Rate of weight gain for the unfortified human milk group was similar to that of infants fed Similac formula containing 20 cal/oz. However, none of the four feeding groups exceeded the 50th percentile for weight at the time of discharge (36 to 37 weeks postconceptional age). The results suggest that fortifying preterm human milk with Ca, P, and protein for low birth weight infants will improve bone mineralization and rate of growth to levels comparable to those achieved with a special formula containing high amounts of protein, Ca, and P.",
"We compared the growth, biochemical status, and mineral status of 30 very-low-birth-weight infants randomly assigned to receive preterm human milk (Group I, 10 infants) from their own mothers, fortified preterm human milk (Group II, 8 infants), or a high-caloric-density premature formula (Group III, 12 infants). Added to the infant's own mother's milk, a human milk fortifier at full strength provided additional protein (60:40 whey/casein, 0.7 g/dl), calories (4 kcal/oz), and minerals. Volume of intake, feeding tolerance, and complications were similar in the three groups. Infants receiving fortified preterm human milk showed growth, biochemical status, and mineral status similar to those receiving high-caloric-density formula, but infants receiving fortified preterm human milk grew faster (12.0 +/- 3.2 vs. 8.9 +/- 1.1 days/300 g, p less than 0.05), had higher serum protein (4.6 +/- 0.5 vs. 4.2 +/- 0.2 g/dl, p less than 0.05), and tended to have better mineral status (higher serum calcium, lower alkaline phosphatase, and higher serum phosphorus, none individually significant) than infants receiving preterm human milk alone. This study supports previous observations that fortified preterm human milk provides nutritional advantages for very-low-birth-weight infants.",
"Human milk is often inadequate nutritionally for preterm infants. We investigated the effect of adding a commercially prepared milk fortifier to human (maternal or bank) milk and measured changes in lower leg length velocity (LLLvel) using knemometry, weight gain and biochemical indices of nutrition. Babies were allocated to one of three feed groups, in a semi-randomized fashion, to receive human milk alone (group I), fortified human milk (group II) or a preterm formula (group III). The birthweights (median and R) and birth gestations (median and R) of the three groups were as follows: group I 1099 g (654-1248 g) and 28 wk (26-32 wk); group II 838 g (742-1340g) and 31 wk (28-36); group III 1136g (624-1552g) and 32 wk (27-36 wk). All babies who received fortified milk either showed significant (p = 0.0004) acceleration in LLLvel during the period studied, or maintained their pre-study period velocity. This increase in LLLvel was comparable to that achieved by a group of babies given a standard preterm infant formula (p < 0.001). By comparison, the control group's change in LLLvel was more modest (p = 0.04). Babies who received human milk with the fortifier added had the lowest serum levels of alkaline phosphatase at the end of the study period when compared to the other two groups. Other biochemical indices were similar in the three feed groups. No adverse clinical events were encountered which could be attributed to the use of the breast milk fortifier."
] |
In preterm and low birth weight infants, feeding with formula milk compared with donor breast milk results in a higher rate of short-term growth but also a higher risk of developing necrotising enterocolitis. There are only limited data on the comparison of feeding with formula milk versus nutrient-fortified donor breast milk. This limits the applicability of the findings as nutrient fortification of breast milk is now a common practice in neonatal care. Future trials may compare growth, development and adverse outcomes in infants who receive formula milk versus nutrient-fortified donor breast milk given as a supplement to maternal expressed breast milk or as a sole diet.
|
CD007776
|
[
"18411239"
] |
[
"Randomized efficacy trial of early preconception counseling for diabetic teens (READY-girls)."
] |
[
"To develop and assess the feasibility of an early preconception counseling program for adolescents called READY-Girls (Reproductive-health Education and Awareness of Diabetes in Youth for Girls).\n A total of 53 adolescent females with type 1 diabetes between 16 and 19.9 years of age were randomized into groups receiving a CD-ROM, a book, or standard care (control) and given one comprehensive session. Outcomes were assessed at baseline, immediately after, and at 3 months.\n Teens who received the CD and those who received the book demonstrated significant (P < or = 0.05) sustained improvement (over 3 months) in knowledge, perceived benefits of both receiving preconception counseling and using effective family planning, and perceived more support with reproductive health issues.\n Clinical feasibility of the program was demonstrated. Both the CD and the book appeared to be efficacious formats for the short term. Future studies should examine repeated boosters of a CD and a book, which are not meant to replace but rather to reinforce and supplement health professional education."
] |
Little evidence is available to recommend for or against preconception care for women with pre-existing diabetes. Further large, high-quality randomised controlled trials are needed to evaluate the effect of different protocols of preconception care for women with pre-existing diabetes.
|
CD006899
|
[
"14681639",
"16799184",
"7618707",
"1920650",
"18190557",
"15877756"
] |
[
"Randomized trial and local biological effect of autologous platelets used as adjuvant therapy for chronic venous leg ulcers.",
"A prospective, randomized, controlled trial of autologous platelet-rich plasma gel for the treatment of diabetic foot ulcers.",
"Autologous platelet-rich plasmapheresis: risk versus benefit in repeat cardiac operations.",
"A prospective randomized trial of autologous platelet-derived wound healing factors for treatment of chronic nonhealing wounds: a preliminary report.",
"Use of platelet gel with connective tissue grafts for root coverage: a randomized-controlled trial.",
"Does platelet-rich plasma promote remodeling of autologous bone grafts used for augmentation of the maxillary sinus floor?"
] |
[
"Platelet products have been proposed as adjuvant therapy for wound healing. We undertook this study to determine the healing effect of topically applied frozen autologous platelets (FAP) on chronic venous ulcers, compared with effect of placebo, and whether use of topical FAP modifies local expression of vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF), interleukin 8 (IL-8), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in wound fluid.\n This randomized, placebo-controlled, double-blind trial was carried out in institutional practice, with ambulatory patients with proved chronic venous leg ulcers. In all patients, whole venous blood was drawn for preparation of FAP. FAP or normal saline solution was applied three times per week for up to 12 weeks, together with hydrocolloids and standardized compression bandages. Leg ulcer surface was assessed with numerical pictures. IL-8, VEGF, KGF, and TIMP-1 levels were determined (enzyme-linked immunosorbent assay) in wound fluid after each 4 weeks of treatment.\n Fifteen patients were randomized into two groups with comparable leg ulcer characteristics. Mean percent reduction in ulcer area was 26.2% in the FAP group versus 15.2% in the placebo group (P =.94). One ulcer in each group was completely healed at study end. Levels of TIMP-1 increased significantly during FAP treatment. IL-8 concentration was significantly lower in wound fluid of healing ulcers than in the fluid of nonhealing ulcers, in both FAP and placebo groups. Growth factor levels were not modified with FAP treatment.\n Topical autologous platelets have no significant adjuvant effect on healing of chronic venous leg ulcers and increased wound fluid TIMP-1 concentration. Ulcer healing is associated with a decrease in wound fluid IL-8.",
"Nonhealing diabetic foot ulcers are a common cause of amputation. Emerging cellular therapies such as platelet-rich plasma gel provide ulcer management options to avoid loss of limb. The purpose of this prospective, randomized, controlled, blinded, multicenter clinical study was to evaluate the safety and efficacy of autologous platelet-rich plasma gel for the treatment of nonhealing diabetic foot ulcers. One hundred, twenty-nine (129) patients were screened; 72 completed a 7-day screening period and met the study inclusion criteria. Patients were randomized into two groups - the standard care with platelet-rich plasma gel or control (saline gel) dressing group - and evaluated biweekly for 12 weeks or until healing. Healing was confirmed 1 week following closure and monitored for another 11 weeks. An independent audit led to the exclusion of 32 patients from the final per-protocol analysis because of protocol violations and failure to complete treatment. In this group, 13 out of 19 (68.4%) of the platelet-rich plasma gel and nine out of 21 (42.9%) of the control wounds healed. After adjusting for wound size outliers (n = 5), significantly more platelet-rich plasma gel (13 out of 16, 81.3%) than control gel (eight out of 19, 42.1%) treated wounds healed (P = 0.036, Fisher's exact test). Kaplan-Meier time-to-healing also was significantly different between groups (log-rank, P = 0.0177). No treatment-related serious adverse events were reported and bovine thrombin used in the preparation of PRP did not cause Factor V inhibition. When used with good standards of care, the majority of nonhealing diabetic foot ulcers treated with autologous platelet-rich plasma gel can be expected to heal.",
"Preoperative platelet-rich plasmapheresis has been suggested as a means of reducing homologous blood transfusions in cardiac surgical patients. The current study evaluated this technique in patients undergoing repeat cardiac operations. Fifty-two patients undergoing repeat myocardial revascularization and/or valve replacement were evaluated in a prospective randomized controlled study design. Autologous platelet-rich plasma (PRP) was harvested after the induction of anesthesia in the experimental group. After reversal of heparin, each patient received his or her autologous plasma. Patients in the control group did not have plasmapheresis and received standard transfusion therapy if coagulation variables were abnormal and a coagulopathy was clinically evident. Routine coagulation tests, thromboelastography (TEG), perioperative bleeding, and transfusion requirements were compared in the two groups. Forty-four patients completed the study. A significantly larger volume of packed red blood cells (PRBCs) was transfused in the PRP group than in the control group (P = 0.03). Platelet and fresh frozen plasma (FFP) transfusions did not differ between the two groups. Mediastinal tube drainage did not differ between the two groups. During PRP infusion, 60% of the patients required treatment for moderate hypotension (mean arterial pressure [MAP] < 60 mm Hg). Only 16% of control patients required treatment for hypotension during the comparable time period (P < 0.05). No patient who completed the study returned to the operating room for postoperative bleeding. These data suggest that PRP did not reduce postbypass bleeding or transfusion requirements in repeat cardiac surgical patients. Moreover, the incidence of hypotension during PRP reinfusion introduces a potential risk to the procedure in the absence of any obvious benefit.",
"Previous studies have suggested that topically applied platelet-derived wound healing factors (PDWHF) accelerate wound healing by stimulating angiogenesis, fibroblast proliferation, and collagen synthesis. To assess the ability of platelet factors to facilitate healing of chronic cutaneous ulcers we performed a randomized, prospective, double-blind, placebo-controlled study of topical PDWHF in 18 patients with 26 lower extremity wounds refractory to conventional therapy. Wounds were present for at least 8 weeks (mean, 5.5 +/- 4.3 months). They were extensively debrided initially and were measured and photographed at weekly intervals for 12 weeks. Eight patients with nine wounds were treated with placebo solution (controls), and 10 patients with 17 wounds were treated with PDWHF (treatment group). Seventy-eight percent of patients had diabetes mellitus, 72% had occlusive peripheral vascular disease, and 28% had venous disease; distribution of these disorders was equivalent in both groups. Ankle-brachial indexes, which were often spuriously elevated, averaged 0.93 +/- 0.54 in controls and 1.04 +/- 0.56 in patients treated with PDWHF (p greater than 0.5). Mean transcutaneous oxygen tension was 37.8 +/- 11.9 mmHg in controls and 37.1 +/- 9.1 mmHg in patients treated with PDWHF. Initial wound area was larger in controls than in the patients treated with PDWHF (28.9 +/- 45.2 cm2 vs 13.0 +/- 4.4 cm2), but this difference was not statistically significant (p = 0.19). Three (33%) wounds (in two patients) healed in controls, and four (24%) wounds (in three patients) healed in the PDWHF group (p greater than 0.5). The rate of healing in controls was 1.9 +/- 2.7 cm2/week.(ABSTRACT TRUNCATED AT 250 WORDS)",
"Platelet-rich plasma (PRP) was speculated to be a promoter of periodontal regeneration. There are only a few clinical comparative studies using PRP in the treatment of gingival recession. Aim: The aim of the present study was to compare connective tissue graft (CTG)+PRP with CTG alone in the treatment of gingival recession.\n Forty patients with Miller I/II recessions were included. Each recession was randomly treated with either CTG+PRP or CTG. Clinical variables were recorded at baseline and at 6 weeks, 6 and 12 months. Root coverage (RC) and attachment gain (AG) were also calculated.\n Probing depth, recession depth, clinical attachment level, keratinized tissue width and recession width (RW) were improved in both study groups. However, no difference was observed between groups, except RW. RW in the control group was statistically lower than the test group at all follow-up periods.\n Treatment of recession with CTG or a CTG-PRP combination resulted in favourable clinical outcomes. However, no difference could be found between CTG and CTG+PRP. Whether much longer follow-up studies with higher statistical power may change these results remains questionable.",
"The aim of this study was to evaluate the effect of platelet-rich plasma (PRP) on remodeling of autologous bone grafts used for augmentation of the floor of the maxillary sinus. In five edentulous patients suffering from insufficient retention of their upper denture related to a severely resorbed maxilla, the floor of both maxillary sinus was augmented with an autologous bone graft from the iliac crest. Randomly, PRP was added to the bone graft used to augment the floor of the left or right sinus (split-mouth design). Three months after the reconstruction, bone biopsies were taken with a trephine from the planned implant sites (N=30). Subsequently, three implants were placed in the left and right posterior maxilla. Microradiograms were made of all biopsies (N=30), whereafter the biopsies were processed for light microscopic examination. In addition, clinical parameters were scored. Wound healing was uneventful, clinically no difference was observed between the side treated with PRP or not. Also microradiographical and histomorphological examination of the biopsies revealed no statistical difference between the PRP- and non-PRP side. One implant placed in the PRP side of the graft was lost during the healing phase. Implant-retained overdentures were fabricated 6 months after implantation. All patients functioned well (follow-up 20.2+/-4.3 months). In this study, no beneficial effect of PRP on wound healing and bone remodeling was observed. It is posed that PRP has no additional value in promoting healing of grafted non-critical size defects."
] |
There is currently no evidence to suggest that autologous PRP is of value for treating chronic wounds. However, current evidence is based on a small number of RCTs, most of which are either at high or unclear risk of bias. Well-designed and adequately powered clinical trials are needed.
|
CD006106
|
[
"12414003",
"12066096",
"11132739",
"7677537",
"8829939",
"16962532"
] |
[
"Transcervical intrauterine topical local anesthetic at hysterosalpingography: a prospective, randomized, double-blind, placebo-controlled trial.",
"A randomized trial of postoperative wound irrigation with local anesthetic for pain after cesarean delivery.",
"Non-steroidal anti-inflammatory drugs in treatment of postoperative pain after cardiac surgery.",
"Influence of steroids on complement and cytokine generation after cardiopulmonary bypass.",
"Intramuscular NSAIDS reduce post-operative pain after minor outpatient anaesthesia.",
"A randomized comparison of suturing techniques for episiotomy and laceration repair after spontaneous vaginal birth."
] |
[
"To assess whether transcervical intrauterine topical instillation of a local anesthetic agent reduces pain at hysterosalpingography.\n Prospective, randomized, double-blind, placebo-controlled study.\n Department of reproductive medicine at a university teaching hospital.\n One hundred ten women undergoing hysterosalpingography (HSG).\n Subjects were randomized to receive either 2 mL of 2% plain lignocaine or 2 mL of 0.9% sodium chloride solution (placebo) topically into the uterine cavity before the HSG was performed.\n The degree of lower abdominal pain experienced both during the injection of contrast media at HSG and 10 minutes after the procedure using a 20-cm visual analogue scale (VAS) and a four-point verbal descriptor scale (VDS).\n There was no difference in pain scores between lignocaine and placebo during the HSG. However, at 10 minutes after the HSG, subjects receiving lignocaine experienced more pain than those on placebo.\n Transcervical intrauterine topical instillation of 2 mL of 2% plain lignocaine does not reduce pain during HSG and may lead to increased pain immediately after the procedure.",
"The purpose of this study was to investigate the efficacy of continuous local anesthetic infusion system for pain control after cesarean delivery.\n This was a randomized prospective double-blind study. Patients who underwent cesarean delivery had a pain system implanted subcutaneously after closure of the fascia. Patients were randomized to receive an infusion of either 0.25% bupivacaine (n = 20) or normal saline solution (n = 16) into the wound for 48 hours. Postoperative pain (determined with a visual analog scale) and postoperative morphine use were assessed at 12, 24, and 48 hours.\n There were no significant differences in patient demographics or visual analog pain scores at any time interval between the bupivacaine versus the placebo group. However, narcotic requirements to produce this amount of pain relief were significantly less in patients who received bupivacaine infusion rather than normal saline solution at all time intervals.\n The continuous local anesthetic infusion system appears to be effective in reducing postoperative morphine use after cesarean delivery.",
"Non-steroidal anti-inflammatory drugs (NSAIDs) are used as analgesic in postoperative pain to reduce opioid side effects, such as drowsiness and nausea. However, NSAIDs have not been used extensively in cardiac surgical patients due to the fear of untoward effects on gastric, renal, and coagulation parameters. This study will evaluate the efficacy and safety of three NSAIDs for pain control in CABG patients.\n One hundred and twenty patients scheduled for elective CABG surgery were enrolled in randomized, double blind, controlled study. Standardized fast track cardiac anesthesia was used. One dose of drug (75 mg diclofenac, 100 mg ketoprofen, 100 mg indomethacin, or placebo) was given pr one hour before tracheal extubation and a second dose 12 hr later. Pain was treated with morphine iv and acetaminophen po. Visual analogue pain scores were recorded at baseline, 3, 6, 12 and 24 hr after the first dose of drug.\n There were no differences among the groups in pain scores. Only patients who received diclofenac required less morphine than patients in the control group (P < 0.05). When the total amounts of pain medications were computed to morphine equivalents, only patients in the diclofenac group received less pain medications than the placebo group (P < 0.05). Proportion of patients with postoperative increase of creatinine level (20% and over) did not differ between placebo and drug groups.\n Non-steroidal anti-inflammatory drugs may be used for analgesia management post CABG surgery in selected patients. Diclofenac appears to have the best analgesic effects by reducing the morphine and other analgesic requirement postoperatively.",
"It is recognized that the inflammatory mediators complement and cytokines are generated during cardiopulmonary bypass as an endogenous response to extracorporeal circulation.\n Nineteen randomized patients (10 steroid/9 nonsteroid) entered an institutional review board-approved protocol to measure complement and interleukin level generation before and after elective coronary revascularization. The steroid regimen involved 1 g of methylprednisolone sodium succinate intravenously before bypass and 4 mg of dexamethasone every 6 hours for four doses during the first 24 hours of recovery. Complement and interleukin levels were measured before bypass, immediately after bypass, and at 24, 48 and 72 hours of recovery.\n In the nonsteroid group, there was a significant elevation in all inflammatory mediators relative to the steroid group. The predominant changes occurred at 24 hours after operation.\n Steroids produced a dramatic reduction in complement and interleukin levels. The number of patients was clearly too small to document a clinical consequence of steroid administration.",
"Two hundred healthy patients scheduled for elective minor gynaecological surgery under general anaesthesia were randomly allocated to one of four groups who received either diclofenac 75 mg intramuscularly (i.m.), ketorolac 30 mg i.m., diclofenac 50 mg orally, or 2 mL NaCl i.m. The drugs were administered 10-20 min prior to a standard anaesthetic. All surgery was uneventful. The patients were discharged after a mean of 110 +/- 30 min with no differences between the groups. Complaints about pain and need for post-operative analgesics were significantly less frequent in the two groups of patients receiving an intramuscular non-steroidal anti-inflammatory drug (NSAID), as compared to placebo. The patients who received 50 mg diclofenac orally, administered shortly before the procedure, had the same pain course as the placebo patients.",
"To compare the continuous knotless technique of perineal repair with the interrupted method after spontaneous vaginal birth\n A randomized controlled trial.\n Canadian Task Force Classification I.\n This study was undertaken in a university hospital with more than 2200 deliveries per year. The static population of this district includes a wide range of socioeconomic classes and is predominately white.\n From May 1 to November 19, 2003, 214 primiparous women with a second-degree perineal tear or episiotomy were randomly allocated to either the continuous knotless technique (CKT; n=107) or the interrupted technique (IT; n=107) suturing method.\n The interrupted technique (IT) involves placing 3 layers of sutures whereas the continuous knotless technique (CKT) involves reapproximating vaginal trauma, perineal muscles, and skin with a loose, continuous, nonlocking technique.\n The primary outcomes of the study were perineal pain (evaluated by visual analogue scale) at 48 hours and day 10 and dyspareunia 3 months after delivery. Secondary outcomes included suture removal, wound dehiscence, analgesia use up to 48 hours, and satisfaction with repair established at 3 and 12 months after childbirth. At day 10, 19 women had dropped out of the study. Significantly fewer women reported pain at 10 days with the CKT than with the IT (32.3% vs 60.4%; p<.001). Analgesia use up to 48 hours postpartum was less in the CKT group than in the IT group (33.6% vs 54.2%; p<.05). No difference was found in superficial dyspareunia at 3 months for the CKT versus the IT group.\n The use of a continuous knotless technique for perineal repair is associated with less short-term pain than techniques with interrupted sutures."
] |
There is little evidence of benefit in terms of pain relief of any of the interventions considered in this study during or immediately after HSG. However, there is limited evidence of pain reduction 30 minutes after the procedure. Further RCTs should consider the role of non steroidal antiinflammatories (NSAIDs) and intrauterine anaesthetic during HSG.
|
CD005937
|
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[
"[Puerperal inhibition of lactation with metergoline or bromocriptine].",
"Lactation suppression with bromocriptine.",
"Lactation inhibition by the dopamine agonist CV 205-502.",
"Lactation inhibition by a single injection of a new depot-bromocriptine.",
"Serum prolactin and the suppression of lactation.",
"Inhibition of lactation by cyclofenil and bromocriptine.",
"Inhibition of puerperal lactation. A double blind study of bromocriptine and placebo.",
"Study of the suppression of lactation and the influence on blood clotting with bromocriptine (CB 154) (Parlodel): a double blind comparison with diethylstilboestrol.",
"The combined oral contraceptive pill versus bromocriptine to suppress lactation in puerperium: a randomized double blind study.",
"Suppression of lactation. A comparison of bromocriptine and prostaglandin E2.",
"Inhibition of puerperal lactation: evaluation of bromocriptine and placebo.",
"Puerperal lactation suppression and prolactin.",
"Inhibition of puerperal lactation: A comparative study of bromocriptine and pyridoxine.",
"Bromocriptine in an injectable retard form for puerperal lactation suppression: comparison with Estandron prolongatum.",
"Cabergoline versus bromocriptine in suppression of lactation after cesarean delivery.",
"Effects of bromocriptine mesylate on the composition of the mammary secretion in non-breast-feeding women.",
"Metergoline versus bromocriptine in the prevention of puerperal lactation. A double-blind clinical trial.",
"Effect of bromocriptine and chlorotrianisene on inhibition of lactation and serum prolactin. A comparative double-blind study.",
"Suppression of puerperal lactation using jasmine flowers (Jasminum sambac).",
"Prevention of breast pain and milk secretion with bromocriptine after second-trimester abortion.",
"Controlled trial of bromocriptine, quinoestrol, and placebo in suppression of puerperal lactation.",
"[Cabergoline for inhibition of lactation].",
"Bromocriptine, methyl testosterone and placebo for inhibition of physiological lactation: a controlled study.",
"[Treatment of pain due to unwanted lactation with a homeopathic preparation given in the immediate post-partum period].",
"Effects of hormonal contraceptives on milk volume and infant growth. WHO Special Programme of Research, Development and Research Training in Human Reproduction Task force on oral contraceptives.",
"French multicenter randomized double-blind placebo-controlled trial on nebulized amiloride in cystic fibrosis patients. The Amiloride-AFLM Collaborative Study Group.",
"Effects of lisuride and bromocriptine on inhibition of lactation and on serum prolactin levels: comparative double-blind study.",
"Combined behavioral and individualized drug therapy versus individualized drug therapy alone for urge urinary incontinence in women.",
"Prevention of puerperal lactation by a single oral administration of the new prolactin-inhibiting drug, cabergoline.",
"The suppression of puerperal lactation with bromocriptine.",
"A prospective, double-blind, randomized, placebo-controlled clinical trial of bromocriptine in clomiphene-resistant patients with polycystic ovary syndrome and normal prolactin level.",
"Effect of hyoscine-N-butyl bromide rectal suppository on labor progress in primigravid women: randomized double-blind placebo-controlled clinical trial.",
"Randomised trial of one versus two doses of prostaglandin E2 for induction of labour: 1. Clinical outcome.",
"Hormonal suppression treatment or dietary therapy versus placebo in the control of painful symptoms after conservative surgery for endometriosis stage III-IV. A randomized comparative trial.",
"Effectiveness of lactational amenorrhoea in prevention of pregnancy in Manila, the Philippines: non-comparative prospective trail.",
"Effects of a dietary and environmental prevention programme on the incidence of allergic symptoms in high atopic risk infants: three years' follow-up.",
"Prospective, randomized, double-blind study of the efficacy and tolerability of the extended-release formulations of oxybutynin and tolterodine for overactive bladder: results of the OPERA trial.",
"Effects of moderate-dose treatment with varenicline on neurobiological and cognitive biomarkers in smokers and nonsmokers with schizophrenia or schizoaffective disorder.",
"Prospective, randomized, parallel-group trial to evaluate the effects of lactulose and polyethylene glycol-4000 on colonic flora in chronic idiopathic constipation.",
"Suppression of lactation with high doses of pyridoxine.",
"Cluster randomised trial of an active, multifaceted educational intervention based on the WHO Reproductive Health Library to improve obstetric practices.",
"A short-term, multicenter, randomized double-blind dose titration study of the efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence.",
"Behavioral therapy to enable women with urge incontinence to discontinue drug treatment: a randomized trial.",
"Efficacy of bromocriptine and chlorotrianisene in preventing postpartum lactation.",
"Intracervical versus intravaginal PGE2 for induction of labor at term in patients with an unfavorable cervix.",
"Urodynamic changes associated with behavioral and drug treatment of urge incontinence in older women.",
"Double-blind comparison of bromocriptine and placebo in cocaine withdrawal.",
"PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial.",
"Bromocriptine for cocaine dependence. A controlled clinical trial.",
"A prospective randomised trial to compare the efficacy and safety of hemabate and syntometrine for the prevention of primary postpartum haemorrhage.",
"A prospective study on the effects on hemostasis of two oral contraceptives containing drospirenone in combination with either 30 or 20 microg ethinyl estradiol and a reference containing desogestrel and 30 microg ethinyl estradiol.",
"The efficiency of prostaglandin E2 vaginal suppositories versus intracervical prostaglandin gel for induction of labor in patients with unfavorable inducibility prospects.",
"Randomized, placebo-controlled trial of Lactobacillus rhamnosus GG as treatment of atopic dermatitis in infancy.",
"Oral nicardipine versus intravenous magnesium sulfate for the treatment of preterm labor.",
"No effects of probiotics on atopic dermatitis in infancy: a randomized placebo-controlled trial.",
"Dry mouth with conventional and controlled-release oxybutynin in urinary incontinence. The Ditropan XL Study Group."
] |
[
"In a controlled, randomised, prospective, clinical study, the effect of prolactin suppression and clinical course of the lactation suppressors Bromocriptine and Metergoline were investigated. During 7 months 150 patients were studied. 81 of those patients, who did not nurse, were treated by Bromocriptine (primary lactation suppression: n = 62, secondary suppression: n = 19) and 69 of the patients were treated by Metergoline (primary suppression: n = 54, secondary suppression: n = 15). The drugs were administrated orally to all subjects, dosed 2 x 2.5 mg/d of Bromocriptine for 14 days and 3 x 4 mg/d of Metergoline for 10 days, starting in average after 13 hours. Puerperal suppression of prolactine were compared with randomised breast feeding subjects (n = 30). In Bromocriptine treated women the average plasma prolactin level decreased from 78.4 +/- 22 ng/ml to 17.0 +/- 3.3 ng/ml during five days of treatment. In Metergoline treated women the plasma prolactin level decreased from 129.7 +/- 15.1 ng/ml to 56.9 +/- 10.0 ng/ml during the first days of treatment. Prolactin level of breast feeding subjects decreased from 233.6 +/- 21.4 ng/ml to 185.8 +/- 23.7 ng/ml during the same period (p < 0.05). There is no statistical significancy of clinical difference of both drugs, but a statistical trend was seen. With Bromocriptine treated women were suppressed efficiently in 71 of 81 cases, 10 refused. Refusals were divided in two quality levels, level I with subjects with moderate complaints and little puerperal lactation, level II with subjects with considerable complaints including strong puerperal lactation. With Metergoline suppressed women, treatment was efficiently in 51 of 69 cases, but refusals of level I were observed in 11 cases and refusals of level II were observed in 7 cases. The results show that Bromocriptine and Metergoline are effective on suppression of lactation. Under the current drug dose of Metergoline an advantage of Bromocriptine were observed. Only further studies could investigate, whether an adaptation of drug dose would improve the clinical efficiency of Metergoline.",
"The efficacy and acceptability of bromocriptine in suppressing postpartum lactation was determined in a double blind study in which bromocriptine 2.5 mg twice daily for 14 days was compared with a placebo. Forty women who decide during the antenatal period not to breast feed entered the study. The bromocriptine treated group had significantly less mammary secretion and breast engorgement than the control group and also required less analgesia. The most noticeable side effects during the trial were dizziness, headache and abdominal pain. The only statistical difference between the two groups was a higher incidence of dizziness in the bromocriptine treated group.",
"In an open pilot study with a parallel group design 30 bottle feeding women were randomly assigned in a two to one ratio to receive either the new dopamine agonist CV 205-502 or bromocriptine for lactation inhibition. Ten women who intended to breast feed served as normal controls. All treated women reached prepregnant prolactin levels within 72 h with once-daily 0.075 mg of CV 205-502 or twice-daily 2.5 mg of bromocriptine, at starting doses of 0.05 mg and 2.5 mg respectively. Fifteen of the 20 women treated with CV 205-502 reported breast symptoms, 50% occurring on days 3 and 4 of treatment. Three of the 10 women treated with bromocriptine had breast symptoms between days 2 and 28. Overall efficacy and tolerance in the two groups was very good. Side effects did not differ between the groups, with the exception of pulse rate in the standing position, which was significantly higher in the bromocriptine treated group than in either the CV 205-502 group (P = 0.02) or the breast feeding group (P less than 0.01). The coagulation tests (fibrinogen, AT III, PTT and APTT) showed no significant differences between the three groups.",
"Recently, long-acting injectable forms of bromocriptine have become available for the prevention of lactation. The first developed depot-form was very effective, but had the disadvantage of a slowly metabolized carrier. we investigated the pharmacokinetics, efficacy, tolerance and safety of 40 and 50 mg of a new rapidly eliminated depot-form in 61 postpartum women. Bromocriptine rapidly increased after injection and prolactin was effectively suppressed during the study-period of 60 days. Overall efficacy was very good or good in 98% and no rebound lactation occurred. Sixteen women experienced side effects. Tolerance at the injection site was good and safety tests did not show abnormalities. There were no differences between the two dosages. We conclude that this new depot-bromocriptine is a safe, well tolerated and effective drug in the suppression of prolactin and the prevention of post-partum lactation.",
"Bromocriptine (2 bromo-alpha-ergocryptine), stilboestrol, clomiphene citrate, testosterone propionate and a placebo were given to 75 postpartum women for the suppression of puerperal lactation. An additional 15 women who breast-fed their babies served as a control group. Blood samples were taken for the determination of serum prolactin levels by a specific homologous double antibody radioimmunoassay. Concurrently, the clinical effectiveness of the various treatments was assessed. High levels of prolactin were found at the time of delivery. Bromocriptine effectively reduced serum prolactin and prevented lactation; stilboestrol increased serum prolactin and partially suppressed lactation; clomiphene citrate and testosterone propionate both lowered serum prolactin levels and partially suppressed lactation. The placebo showed almost no effect on serum prolactin. It appeared that bromocriptine was the drug of choice in the suppression of puerperal lactation.",
"In a double blind controlled study of the inhibition of lactation 13 women received 300 mg of cyclofenil and 11 women 2.5 mg of bromocriptine twice daily for 14 days. Lactation was effectively inhibited by both drugs, but with bromocriptine there was a significantly higher frequency of relapse. The plasma concentration of prolactin, which decreased rapidly with bromocriptine, returned to the pretreatment level the day after drug treatment stopped, but with cyclofenil it remained low. Plasma oestradiol followed a similar pattern. Plasma FSH increased more rapidly with bromocriptine than with cyclofenil. There was no significant difference between the treatment groups at any stage for haematology, coagulation or liver function tests. The more sustained effect of cyclofenil on prolactin secretion with a reduced frequency of relapse, and the lower oestradiol level, which might indicate a reduced risk of thromboembolism, suggest that this drug has some advantage over bromocriptine in the inhibition of postpartum lactation.",
"Bromocriptine and placebo were randomly allocated for three weeks to 52 postpartum patients requiring lactation suppression. Bromocriptine significantly lowered plasma prolactin levels and suppressed breast milk, breast pain and engorgement quicker than placebo. No side-effects were noted and rebound lactation did not occur. Menstruation appeared to re-start sooner when Bromocriptine was given.",
"Inhibition of lactation was studied in 38 puerperal women in a double blind trial to assess the effect of bromocriptine in comparison with diethylstilboestrol (DS). Simultaneously the influence of both compounds on blood clotting was studied, along with a control group of 20 women not receiving any medication. Bromocriptine was given in a daily dose of 5 mg for 14 days and DS in a daily dose of 20 mg for 7 days followed by a placebo for a further 7 days. The first doses were not later than 8 hours after delivery. Both compounds showed an inhibitory effect on the onset of lactation and mammary congestion. This inhibitory effect on both parameters was significantly in favour of bromocriptine during the last days of the treatment due to rebound in the DS group. The bromocriptine doses used (5 mg daily for 2 weeks) caused no objective side effects and no subjective restraint. Treatment with bromocriptine caused no untoward effect on the blood clotting, while in the DS group a slower return to normal antithrombin III could be observed. Also in this group one case of thrombophlebitis occurred. Bromocriptine can be administered to puerperal women for the suppression of lactation.",
"A randomised double blind comparative study of 230 HIV infected mothers who had a normal delivery at 37-42 weeks' gestation were divided into two groups; 116 combined pill users and 114 bromocriptine users to suppress lactation. There were 33 cases (28.5%) of combined pills users and 29 cases (25.4%) of bromocriptine users who had breast engorgement without statistical difference. All of them had mild breast engorgement without any treatment except one case (0.9%) in the bromocriptine group had severe breast engorgement with puerperal fever and needed an analgesic drug. There were no side effects of the drugs. This study showed that combined pills were beneficial to suppress lactation in HIV infected mothers to prevent postnatal mother-to-child transmission because of low risk and low cost.",
"Women in the puerperium who requested lactation suppression were randomly allocated to receive bromocriptine from puerperal day 1 to 14 or prostaglandin E2 from day 3 or 4 for 24 hours. Subjectively, lactation suppression was satisfactory in all cases. Objective measurements showed a trend toward more-effective early suppression with bromocriptine. After discharge from the hospital, 3 of the 21 women who received prostaglandin E2 complained of mild breast tenderness, whereas 10 of the 22 who received bromocriptine reported severe \"rebound\" breast tenderness.",
"Bromocriptine and placebo were randomly allocated to 50 patients who wished to suppress lactation. Patients on bromocriptine suffered no subjective symptoms such as breast pain and engorgement, and lactation was significantly reduced compared with patients on the placebo with or without breast binding. No side-effects were noted, and rebound lactation was seen in only 3 patients. In most patients contraceptives were commenced once the drug therapy ceased on the fourteenth day.",
"Five methods for puerperal lactation inhibition were assessed in a randomized fashion. The 90 women were divided into five groups. Four of these received a pharmacologic treatment: oral stilbestrol (15 mg dd for 5 days), a diuretic compound (bendroflumethazide 15 mg dd for 5 days) by mouth, oral bromocriptine (5 mg dd for 14 days), or an intramuscular injection containing estradiol (10 mg and testosterone (200 mg) esters administered immediately after delivery. To the women in the remaining group only physical methods were applied (breast support and local infra-red waves) and they served as controls. Prolactin plasma concentrations were determined daily for five consecutive days and showed a correlation with the clinical effectiveness of the various treatment schedules. While bromocriptine reduced and stilbestrol augmented prolactin levels, both types of treatment were equally effective in preventing lactation during the observation period. Treatment with a diuretic compound or with an injection of steroids, though less effective than the first two regimens, was nevertheless significantly more efficacious than physical treatment.",
"Ninety-seven patients requiring suppression of lactation in the postpartum period were treated on a double-blind basis with bromocriptine and pyridoxine--49 patients received bromocriptine and 48 pyridoxine. A statistically significant difference between the two groups was noted, beginning after 1 day of treatment. Bromocriptine was superior to pyridoxine in the parameters measured. At the end of therapy the clinician, the midwife and the patient assessed the therapeutic efficacy of the trial drug. There was a statistically significant difference in favour of bromocriptine. Two patients treated with bromocriptine reported mild side-effects, but medication was not discontinued. In 1 patient receiving pyridoxine side-effects were so severe that medication was discontinued--however, the patient was already receiving the inactive tablets at this stage.",
"Intramuscular injection of a single 50-mg dose of long-acting bromocriptine microspheres was compared with a single intramuscular dose of an estradiol/testosterone ester combination in a single-blind, randomized study of 54 subjects. Bromocriptine was significantly more effective than the steroid drug in preventing milk flow, and rebound lactation was not observed in any bromocriptine-treated patients. Neither group showed deleterious side effects or significant biologic changes in coagulation parameters. There were no blood pressure or electrocardiographic alterations. Postpartum prolactin suppression was more intense after bromocriptine administration than after steroid therapy.",
"We evaluated the efficacy of cabergoline, a new ergoline derivative, in blocking puerperal lactation in a group of women delivered by cesarean section. In a single-blind controlled trial 36 women were randomly allocated to treatment with cabergoline 1 mg in a single dose p.o. (n = 18) or bromocriptine 5 mg/day p.o. for 14 days (n = 18). Treatment was started about 50 h after delivery. Clinical assessment of breast signs and determination of serum prolactin were performed just before treatment and at 3, 5, 7 and 14 days. In the cabergoline-treated group milk secretion was inhibited in 17 women (94.4%). Maximum decrease of serum prolactin was -89.7% at 5 days, and the prolactin-lowering effect of cabergoline was still present at 14 days. In the bromocriptine group milk secretion was inhibited in 16 women (88.9%). Maximum prolactin decrease (-86.9%) was reached at 3 days. Persistent side effects were comparable in the two groups. This study demonstrates that a single oral dose of 1 mg cabergoline is as effective in suppressing puerperal lactation as a full treatment with bromocriptine, even in women delivered by cesarean section.",
"A double-blind trial was performed on 26 women, who had elected not to breast-feed their infants, to determine the effect of bromocriptine mesylate (2.5 mg twice daily for 14 days postpartum) on the composition of the mammary secretion during lactogenesis. Mammary secretion (less than 5.0 ml) was collected from each breast of each woman at daily intervals during the 14-day treatment period and the progressive changes in the concentration of the milk constituents, lactose, alpha-lactalbumin, serum albumin, total protein, lactoferin, IgA, IgG, sodium and potassium were determined. The degree of milk leakage and breast engorgement were also assessed. Both the subjective assessments and the changes in the concentration of the milk constituents demonstrated that lactogenesis occurred between about Day 2 and Day 5 postpartum in the placebo group (in the absence of the suckling stimulus) but was suppressed in the bromocriptine-treated group.",
"In a double blind study of the prevention of puerperal lactation, the clinical efficacy of two antiprolactin drugs was compared: metergoline 4 mg tid and bromocriptine 2.5 mg bid were both given for 7 days. An additional 7 days of treatment was administered to 16 patients in whom mammary activity was still present or appeared in the following 3 days. The first 7 day period of treatment was effective in 16/20 women receiving metergoline and in 7/20 on bromocriptine (p less than 0.02); the second period of treatment was effective in all remaining patients. These data indicate that metergoline acts rapidly to arrest puerperal lactation, possibly by a mechanism different from that of bromocriptine.",
"A double-blind study to compare the effect of 2-Br-alpha-ergocryptine (bromocriptine, CB 154, Sandoz) an ergot alkaloid with chlorotrianisene (Tace, Mer-National) on the inhibition of postpartum lactation was carried out in 38 women. At the dosages selected bromocriptine was more effective than chlorotrianisene in inhibiting lactation. Furthermore, bromocriptine significantly reduced serum prolactin levels to low normal values by the seventh day of treatment, whereas chlorotrianisene did not alter the normal progressive reduction in prolactin post-partum. Neither drug had significant toxic effects.",
"The efficacy of jasmine flowers (Jasminum Sambac) applied to the breasts to suppress puerperal lactation was compared that of Bromocriptine. Effectiveness of both regimens was monitored by serum prolactin levels, clinical evaluation of the degree of breast engorgement and milk production and the analgesic intake. While both bromocriptine and jasmine flowers brought about a significant reduction in serum prolactin, the decrease was significantly greater with bromocriptine. However, clinical parameters such as breast engorgement, milk production and analgesic intake showed the 2 modes of therapy to be equally effective. The failure rates of the 2 regimens to suppress lactation were similar; however, rebound lactation occurred in a small proportion of women treated with bromocriptine. Jasmine flowers seem to be an effective and inexpensive method of suppressing puerperal lactation and can be used as an alternative in situations where cost and nonavailability restrict the use of bromocriptine.",
"Within 24 hours after abortion, 62 patients with a mean gestational age of 19 weeks, who had either induced (n = 50) or spontaneous (n = 12) abortions were randomly allocated to three groups: Group 1, bromocriptine 2.5 mg twice daily for 2 weeks; Group 2, placebo tablets 1 tablet twice daily for 2 weeks; Group 3, no treatment. Fifty-two patients completed the study (bromocriptine n = 18, placebo n = 18 and no treatment n = 16). Placebo had no apparent influence on breast symptoms. In both the placebo group and the untreated group, breast pain and milk secretion peaked on days 3 to 7, and milk secretion often continued for 3 weeks. Only 3/34 (9%) of untreated and placebo treated patients were free of breast symptoms. Compared with placebo, bromocriptine caused a significant reduction in the objective assessment score of breast tenderness (p less than 0.05) and milk secretion (p less than 0.01), in serum prolactin (PRL) (p less than 0.001) and in the subjective assessment score of breast pain (p less than 0.01) and milk secretion (p less than 0.01). Alleviation of breast pain and prevention of milk secretion appears to be indicated after second-trimester abortion, and treatment with bromocriptine is efficacious.",
"2-bromo-alpha-ergocryptine (bromocriptine) in a dosage of 2-5 mg twice daily caused a rapid fall in plasma prolactin. It was more effective than either a single dose of 4 mg quinoestrol or a placebo in suppressing puerperal lactation, as judged by milk flow and the relief of breast pain and congestion. Patients who received quinoestrol were more comfortable than those who received placebo.",
"Despite advances in prevention inhibition of lactation, only administration of estrogens or these combined with androgens show variable effectiveness and are indirectly associated with high percentage for lactation rebound, thrombosis, or pulmonary embolism or both of the later during puerperium; in addition, bromocriptine, also used indirectly for inhibition of lactation, is associated with lactation, rebound in 18-40%. Cabergolin is a new ergoline with efficient and durable prolactin reducer effect with fewer adverse effects.\n Which will the smallest cabergolin dosage be to inhibit lactation?\n To demonstrate clinical effectiveness with smallest cabergolina dosage in lactation inhibition.\n We carried on a the Service Clinical test on patients hospitalization with an indication to inhibit lactation as the Hospital of Gynecology and Obstetrics, Infantil Maternal Institute of the State of Mexico (IMIEM). The study was done 80 patients to who we administered oral 0.5 mg cabergoline to 40 patients and another group of 40 whom we administered 1.0 mg of cabergoline orally at random and blinded by means of out-patient consultation. We studied correlation between dose and inhibition of lactation as well as presence of adverse effects.\n In the group of patients to whom administered 0.5 mg, we found 65% (n = 26) with lactation inhibition; adverse effects in this group appeared in 32.5% (n = 13) the second group with a dose of 1.0 mg; 95% with adverse effects in 25% P < 0.001.\n Inhibition of lactation with unique dose of 1.0 has satisfactory clinical effectiveness, this being the smaller dose to inhibit lactation at a suitable percentage.",
"Lactation occurs when the fully developed breast is released from the inhibitory influence which oestrogen and progesterone exert upon the action of prolactin. The use of oestrogens to suppress lactation depends on a continuation of the peripheral, that is, mammary, inhibition of prolactin. Androgens are also believed to act by inhibition of the action of prolactin on the mammary gland epithelium. Bromocriptine, when compared in a double-blind trial with orally administered methyl testosterone and placebo, gave almost complete relief of breast discomfort and congestion, though a small amount of milk production was seen. Methyl testosterone, in the dosage used in this study, was quite ineffective in suppressing lactation or breast symptoms.",
"Dopaminergic agonists, such as Parlodel((R)), are now widely used to inhibit lactation. However, some countries, such as the United States, no longer use these drugs in this indication because of their sometimes serious adverse effects. In this context, the authors tested a homeopathic treatment designed for parturients unable or not wanting to breastfeed. The APIS MELLIFICA 9 CH and BRYONIA 9 CH combination was chosen for its anti-inflammatory and analgesic effects. 71 patients were included in this double-blind placebo-controlled study. All received basic treatment comprising naproxen and fluid restriction. A significant improvement of lactation pain (main criterion of the study) was observed in parturients treated with homeopathy (p<0.02 on D2 and p<0.01 on D4). A similar effect (p<0.05 on D4) was observed for breast tension and spontaneous milk flow. No significant difference was observed for the other criteria of the study. The homeopathic combination studied was therefore effective on the pain of lactation and should be integrated into the therapeutic armamentarium.",
"WHO conducted a three-centre study in Hungary and Thailand to evaluate the effects of hormonal contraception on lactation and infant growth. Women choosing oral contraceptives were randomly assigned to a combined oral contraceptive containing 30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel (N = 86) or a progestin-only preparation containing 75 micrograms dl-norgestrel (N = 85). Identical packaging and treatment schedules allowed double-blind observation. One-hundred-and-eleven women using no contraception or non-hormonal methods acted as controls. In the two Thai centres 59 women using depot-medroxyprogesterone acetate formed an additional comparison group. All subjects were healthy women with normal deliveries, whose infants had normal birth weights and satisfactory growth in the neonatal period. Breast milk volume was determined by pump expression using standardized procedures. Information was obtained on nursing frequency and supplementation, infant growth and morbidity. Pretreatment observations at 6 weeks post-partum were used as a baseline, and subjects were followed-up at 9, 12, 16, 20 and 24 weeks post-partum. Women using combined oral contraceptives had a decline in milk volume within 6 weeks of initiating treatment, whereas no significant decrease was observed in the other treatment groups. After 18 weeks of treatment, combined oral contraceptive users experienced a 41.9% decline in milk volume, compared to 12.0% with progestin-only minipills and 6.1% in the non-hormonal controls. The prevalence of complementary feeding and withdrawals due to inadequate milk supply were comparable in the four treatment groups. However, data were not available on the daily amounts of complementary feeds. There were no significant differences in growth of infants between treatment groups. Thus, women may have compensated for declines in milk volume by more supplementary feeding or by more prolonged and intense suckling episodes. We conclude that 30 micrograms estrogen-containing combined oral contraceptives impair milk secretion, but in the selected healthy group of mothers and children studied with the prevailing level of supplementary feeding, this did not adversely affect infant growth.",
"The effect of amiloride, a sodium channel blocker, has been evaluated in a multicenter randomized double-blind placebo-controlled trial in cystic fibrosis patients more than 5-years-old (n = 137) whose forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV(1)), and forced mid-expiratory flow (FEF(25-75)) were not below 50%, 50%, and 30% of reference values, respectively. Patients were randomly allocated to two parallel groups. Sixty-four patients were chronically colonized with Pseudomonas aeruginosa; they received either amiloride or placebo as a nebulized solution three times daily for 6 months. Routine treatments were continued. Patients chronically colonized with Pseudomonas received nebulized colimycine twice a day for a month during the third and sixth months of treatment. Bronchopulmonary exacerbations were treated in the usual way. The effects of the amiloride treatment were assessed at the end of the 6-month treatment period. The effects on FVC and secondarily on FEV(1), FEF(25-75), the number of days on antibiotic therapy, the Shwachman score, a nutritional index (weight/height(2)), the change in sputum bacterial flora, and nocturnal cough were assessed. For the patients not chronically colonized with Pseudomonas, the effect of the treatment was also evaluated by counting chronic colonizations with pathogens appearing during the trial period. The present study failed to demonstrate any significant benefit of amiloride over placebo on FVC, FEV(1), and the other secondary endpoints in the studied population. Neither the chronically colonized, nor the noncolonized patients benefited. The confidence intervals of the differences between treatment groups indicated small differences that were most likely of no clinical significance. Complementary analyses taking into account the gender, the type of mutation, the subpopulations whose FVC and FEV(1) were below 80% of normal values at the beginning of the study, and also patients less than 10 years old, did not show any statistically or clinically significant improvements following amiloride therapy.\n Copyright 2000 Wiley-Liss, Inc.",
"The effects of lisuride (Schering) and bromocriptine (Parlodel, Sandoz), two dopaminergic drugs, on the inhibition of puerperal lactation were compared in a double-blind study. At the dosages selected, lisuride was as effective as bromocriptine for the inhibition of lactation but bromocriptine was more effective in lowering serum prolactin levels.",
"We tested whether individualized drug therapy enhanced with behavioral training would result in better outcomes than individualized drug therapy alone.\n Participants were community dwelling women with urge predominant incontinence. Using a randomized clinical trial design women were randomized to 8 weeks (4 visits) of drug therapy alone (32) or drug therapy plus behavioral training (32). Drug therapy was individually titrated, extended release oxybutynin with proactive management of side effects. Behavioral training included pelvic floor muscle training and urge suppression techniques. The primary outcome measure was reduction in frequency of incontinence episodes on bladder diary at 8 weeks (with followup at 6 and 12 months). Secondary outcomes included patient satisfaction, global perception of improvement, Urogenital Distress Inventory and Incontinence Impact Questionnaire.\n In intent to treat analysis frequency of incontinence was reduced a mean of 88.5% in the drug alone group and 78.3% in the combined therapy group (p = 0.16). Outcomes were not significantly different between the groups in the analysis of completers (91.5% vs 86.2%, p = 0.34), or in either analysis at 6 or 12 months. The groups also did not differ significantly on secondary outcomes at any point. Participants in the drug alone group tended to be taking higher doses of oxybutynin at 8 weeks but the final dose did not differ significantly between the groups. Based on a conditional power calculation the trial was stopped early for futility.\n When drug therapy is implemented with frequent individualized dose titration, daily bladder diaries and careful management of side effects, initiating concurrent behavioral training does not enhance outcomes for urge incontinence in women.\n Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.",
"To evaluate the efficacy of a single oral administration of the new ergot derivative Cabergoline in the prevention of post-partum lactation, we compared the effects of three different doses of the drug with those of placebo in 32 puerperal women. In a controlled, double-blind trial, the subjects were randomly allocated to four treatment groups receiving either placebo or 400, 600, or 800 micrograms Cabergoline (N = 8 in each group) within 24 hours after delivery. Treatment efficacy was assessed clinically by physical examination before (day 0) and at one, two, three, four, and 14 days after treatment. Plasma prolactin (PRL) concentrations were measured in blood samples collected before and at one, two, three, and four days after treatment. Lactation was prevented in four of the eight subjects (50%) who received 400 micrograms Cabergoline and in all subjects who received 600 or 800 micrograms Cabergoline. By contrast, only one of the eight subjects (12.5%) receiving placebo showed no signs of spontaneous lactation within the 14 days after delivery. No effects of placebo administration on plasma PRL levels were observed. Plasma PRL concentrations were significantly reduced starting from one day after Cabergoline administration, however, and the amount of inhibition of PRL secretion induced by different doses of the drug was not statistically different. These preliminary data demonstrate that Cabergoline has a dose-related effect in the prevention of postpartum lactation, and milk secretion can be prevented completely by a single oral administration of 600 or 800 micrograms of the drug.",
"nan",
"To evaluate the effects of administration of bromocriptine combined with clomiphene citrate (CC) in CC-resistant patients with polycystic ovary syndrome (PCOS) and normal prolactin (PRL) level.\n Prospective double-blind, placebo-controlled, randomized.\n Referral university hospitals.\n One hundred women with PCOS and normal PRL who failed to ovulate with a routine protocol of CC.\n Treatment group received 150 mg of CC from day 5 to 9 and 7.5 mg bromocriptine continuously, with hCG 10,000 units on day 16 or 17. Control group received the same protocol of CC combined with placebo.\n Follicular development, hormonal changes, ovulation rate, pregnancy rate.\n Follicular development (follicular size greater than 15 mm) was observed in 12 (25.5%) and 8 (15.1%) women in the treatment and placebo group, respectively (p = 0.29). The serum prolactin level was within normal limits in all patients before treatment. After 3 and 6 months of treatment with bromocriptine, there was a significant decrease in serum level of prolactin (p = 0.000001). No significant differences were seen in ovulation, pregnancy rate, or serum levels of FSH, LH, DHEAS, and progesterone between treatment and placebo groups after treatment.\n The only significant effect of long-term bromocriptine therapy in CC-resistant women with PCOS was to lower the serum PRL concentration. It is also concluded that 10%-15% of patients with PCOS experienced occasional ovulatory cycles and pregnancy whether or not they were on treatment.",
"To determine the effects of hyoscine-N-butyl bromide (HBB) rectal suppository on labor progress in primigravid women.\n A randomized double-blind placebo-controlled clinical trial was carried out on 130 primigravid women admitted for spontaneous labor. The women were recruited based on the inclusion and exclusion criteria and randomized into the experimental (n=65) and control group (n=65). In the beginning of the active phase of labor, 20 mg of HBB rectal suppository was administered to the experimental group, while a placebo suppository was administered to the control group. Cervical dilatation and duration of active phase and second stage of labor were recorded.\n The rate of cervical dilatation was 2.6 cm/h in the experimental and 1.5 cm/h in the control group (P<0.001). The active phase and the second stage of labor were significantly shorter in the experimental group (P=0.001 and P<0.001, respectively). There was no significant difference between the two groups in the fetal heart rate, maternal pulse rate, blood pressure, and the APGAR score 1 and 5 minutes after birth.\n Use of HBB rectal suppository in the active management of labor can shorten both the active phase and second stage of labor without significant side-effects.",
"To compare the outcome of induction of labour using a single versus two doses of prostaglandin E2 vaginal gel.\n Prospective randomised trial comparing a single dose of prostaglandin E2 2 mg vaginal gel in the evening with two doses of prostaglandin E2 (2 mg), the second being given after six hours if labour had not started or the cervix was still unripe. Amniotomy and oxytocin titration were performed when necessary for both protocols. Nulliparae and multiparae were analysed separately by treatment intention.\n A maternity unit in a district general hospital annually delivering > 6000 women.\n Nine-hundred and ninety-five women with viable singleton pregnancies and cephalic presentation at term without previous history of caesarean section who were advised to have labour induced with prostaglandins.\n Need for formal amniotomy and oxytocin augmentation, use of epidural analgesia, rate of intrapartum interventions, mode of delivery and neonatal condition at birth.\n For multiparae two prostaglandin doses resulted in a significant reduction in the need for formal amniotomy (15% vs 30%) and oxytocin augmentation (28% vs 38%) compared with those receiving a single dose; there was no significant difference for nulliparae. Other interventions during labour, length of labour, and mode of delivery were similar in both protocols. Failed induction occurred only in nulliparae and was similar in both protocols (1%). There was no discernible difference in fetal or neonatal outcome although passage of meconium was more common in labour if two doses had been given, as was neonatal admission to the special care baby unit.\n There was little clinical benefit from inducing labour with two doses of prostaglandin E2 at a six-hour interval, compared with a single dose. There may be financial advantages with a two-dose regimen.",
"To evaluate the effectiveness for the outcomes of endometriosis-related pain and quality of life of conservative surgery plus placebo compared with conservative surgery plus hormonal suppression treatment or dietary therapy.\n Randomized comparative trial.\n University hospital.\n Two hundred twenty-two consecutive women who underwent conservative pelvic surgery for symptomatic endometriosis stage III-IV (r-AFS).\n Six months of placebo (n = 110) versus GnRH-a (tryptorelin or leuprorelin, 3.75 mg every 28 days) (n = 39) or continuous estroprogestin (ethynilestradiol, 0.03 mg plus gestoden, 0.75 mg) (n = 38) versus dietary therapy (vitamins, minerals salts, lactic ferments, fish oil) (n = 35).\n Painful symptoms (visual analogue scale score) and quality-of-life endometriosis-related symptoms (SF-36 score) at 12 months' follow-up.\n Patients treated with postoperative hormonal suppression therapy showed less visual analogue scale scores for dysmenorrhoea than patients of the other groups. Hormonal suppression therapy and dietary supplementation were equally effective in reducing nonmenstrual pelvic pain. Surgery plus placebo showed significative decrease in dyspareunia scores. Postoperative medical and dietary therapy allowed a better quality of life than placebo.\n Postoperative hormonal suppression treatment or dietary therapy are more effective than surgery plus placebo to obtain relief of pain associated with endometriosis stage III-IV and improvement of quality of life.",
"To determine the contraceptive efficacy of the lactational amenorrhoea method.\n Non-comparative prospective trial.\n Urban Manila, the Philippines.\n 485 lower income, educated women with extensive experience of breast feeding.\n Women were offered all available contraceptives for use after birth. Those who chose the lactational amenorrhoea method were taught the method, screened for the study, and followed for 12 months to determine the risk of pregnancy when the method was used.\n Life table pregnancy rates during correct and incorrect use of the method, censored monthly in the event of sexual abstinence or the use of another contraceptive method.\n The lactational amenorrhoea method was 99% effective when used correctly (that is, during lactational amenorrhoea and full or nearly full breast feeding for up to six months). At 12 months the effectiveness during amenorrhoea dropped to 97%.\n The lactational amenorrhoea method provided as much protection from pregnancy as non-breast feeding women experience with non-medicated intrauterine devices and barrier methods. The contraceptive effect of lactation cannot be attributed to lactational or postpartum abstinence.",
"A prospective case-control study is presented to assess an allergy prevention programme in children up to 36 months of age. Infants born at three maternity hospitals were followed from birth: 279 infants with high atopic risk (intervention group) were compared with 80 infants with similar atopic risk but no intervention (non-intervention group). The intervention programme included dietary measures (exclusive and prolonged milk feeding diet followed by a hypoantigenic weaning diet) and environmental measures (avoidance of parental smoking in the presence of the babies, day care > 2 years of life). Mothers in this group who had insufficient breast milk were randomly assigned to one of two coded formulas: either a hydrolysed milk formula (Nidina HA, Nestlé) or a conventional adapted formula (Nan, Nestlé). Other environmental measures remained the same as for the breastfeeding mothers. The non-intervention group were either breastfed or received the usual Italian milk feeding and weaning diet, without environmental advice. The main outcome measures were anthropometric measurements and allergic disease manifestations. Normal anthropometric data were observed both in the intervention group and in the non-intervention group. The incidence of allergic manifestations was much lower in the intervention group than in the non-intervention group at 1 year (11.5 versus 54.4%, respectively) and at 2 years (14.9 versus 65.6%) and 3 years (20.6 versus 74.1%). Atopic dermatitis and recurrent wheezing were found in both the intervention group and the non-intervention group from birth up to the second year of life, while urticaria and gastrointestinal disorders were only present in the non-intervention group in the first year of life. Conjunctivitis and rhinitis were present after the second year in both the intervention group and the non-intervention group. Relapse of the same allergic symptom was less in the intervention group (13.0%) than in the non-intervention group (36.9%). In comparison to the non-intervention group, there were fewer intervention group cases with two or more different allergic symptoms (8.7 versus 32.6%), and they were more likely to avoid steroid treatment (0 versus 10.8%) and hospital admission (0 versus 6.5%). Babies in the non-intervention group fed with adapted formula were more likely to develop allergies than breastfed babies in the same group. In the intervention group the breastfed infants had the lowest incidence of allergic symptoms, followed by the infants fed the hydrolysed formula (ns). Infants in the intervention group fed the adapted formula had significantly more allergies than the breastfed and hydrolysed milk fed infants, although less than their counterparts in the non-intervention group. Of the affected subjects in the intervention group, 80.4% were RAST and/or Prick positive to food or inhalant allergens. Total serum IgE values detected at birth in the intervention group were not predictive, but at 1 and 2 years of age, IgE values more than 2 SD above the mean in asymptomatic babies were found to predictive for later allergy. In breastfed babies the total IgE level at 1 and 2 years of age was lower than in the other two feeding groups. Of the various factors tested in the non-intervention group, the following were the most important in the pathogenesis of allergic symptoms: (i) formula implementation begun in the first week of life; (ii) early weaning (< 4 months); (iii) feeding beef (< 6 months); (iv) early introduction of cow's milk (< 6 months); and (v) parental smoking in the presence of the babies and early day care admission (< 2 years of life). All the preventive measures used in this study (exclusive breastfeeding and/or hydrolysed milk feeding, delayed and selective introduction of solid foods, and environmental advice) were effective at the third year of follow-up, greatly reducing allergic manifestations in high atopic risk babies in comparison with those not receiving these interventions",
"To compare the efficacy and tolerability of extended-release formulations of oxybutynin chloride and tolterodine tartrate in women with overactive bladder.\n The OPERA (Overactive bladder: Performance of Extended Release Agents) trial was a randomized, double-blind, active-control study performed at 71 US study centers from November 21, 2000, to October 18,2001. Extended-release formulations of oxybutynin at 10 mg/d or tolterodine at 4 mg/d were given for 12 weeks to women with 21 to 60 urge urinary incontinence (UUI) episodes per week and an average of 10 or more voids per 24 hours. Episodes of UUI (primary end point), total (urge and nonurge) incontinence, and micturition were recorded in 24-hour urinary diaries at baseline and at weeks 2, 4, 8, and 12 and compared. Adverse events were also evaluated.\n Improvements in weekly UUI episodes were similar for the 790 women who received extended-release formulations of oxybutynin (n = 391) or tolterodine (n = 399). Oxybutynin was significantly more effective than tolterodine in reducing micturition frequency (P = .003), and 23.0% of women taking oxybutynin reported no episodes of urinary incontinence compared with 16.8% of women taking tolterodine (P = .03). Dry mouth, usually mild, was more common with oxybutynin (P = .02). Adverse events were generally mild and occurred at low rates, with both groups having similar discontinuation of treatment due to adverse events.\n Reductions in weekly UUI and total incontinence episodes were similar with extended-release formulations of oxybutynin and tolterodine. In the oxybutynin group, micturition frequency was significantly lower, and the percentage of women reporting no urinary incontinence episodes was significantly higher compared with the tolterodine group. Dry mouth was more common with oxybutynin, but tolerability was otherwise comparable, including adverse events involving the central nervous system.",
"The administration of nicotine transiently improves many neurobiological and cognitive functions in schizophrenia and schizoaffective disorder. It is not yet clear which nicotinic acetylcholine receptor (nAChR) subtype or subtypes are responsible for these seemingly pervasive nicotinic effects in schizophrenia and schizoaffective disorder.\n Because α4β2 is a key nAChR subtype for nicotinic actions, we investigated the effect of varenicline tartrate, a relatively specific α4β2 partial agonist and antagonist, on key biomarkers that are associated with schizophrenia and are previously shown to be responsive to nicotinic challenge in humans.\n A double-blind, parallel, randomized, placebo-controlled trial of patients with schizophrenia or schizoaffective disorder to examine the effects of varenicline on biomarkers at 2 weeks (short-term treatment) and 8 weeks (long-term treatment), using a slow titration and moderate dosing strategy for retaining α4β2-specific effects while minimizing adverse effects.\n Outpatient clinics.\n A total of 69 smoking and nonsmoking patients; 64 patients completed week 2, and 59 patients completed week 8. Intervention Varenicline.\n Prepulse inhibition, sensory gating, antisaccade, spatial working memory, eye tracking, processing speed, and sustained attention.\n A moderate dose of varenicline (1) significantly reduced the P50 sensory gating deficit in nonsmokers after long-term treatment (P = .006), (2) reduced startle reactivity (P = .02) regardless of baseline smoking status, and (3) improved executive function by reducing the antisaccadic error rate (P = .03) regardless of smoking status. A moderate dose of varenicline had no significant effect on spatial working memory, predictive and maintenance pursuit measures, processing speed, or sustained attention by Conners' Continuous Performance Test. Clinically, there was no evidence of exacerbation of psychiatric symptoms, psychosis, depression, or suicidality using a gradual titration (1-mg daily dose).\n Moderate-dose treatment with varenicline has a unique treatment profile on core schizophrenia-related biomarkers. Further development is warranted for specific nAChR compounds and dosing and duration strategies to target subgroups of schizophrenic patients with specific biological deficits.",
"Although lactulose and polyethylene glycol are osmotic laxatives widely used in the treatment of chronic constipation, no study has been conducted to compare their actions on the colonic bacterial ecosystem, which has an important influence on host health.\n To assess the effects of lactulose and polyethylene glycol on the composition and metabolic indices of the faecal flora in patients with chronic idiopathic constipation.\n Sixty-five patients with chronic idiopathic constipation were included in this controlled, multi-centre, randomized, parallel-group study. Participants received lactulose (Duphalac) or polyethylene glycol-4000 (Forlax) powders for the first week at a fixed dosage at night (20 g/day); in the second week, patients were given the option to vary the dose according to efficacy and tolerance (10-30 g/day); for the last 2 weeks, treatment was administered at a fixed dosage based on the results of the second week (10-30 g/day). Stools were recovered for bacteriological analysis at days -1, 21 and 28.\n Clinical efficacy and tolerance were similar with both treatments. In the lactulose group, an increase in faecal bifidobacteria counts (P = 0.04) and beta-galactosidase activity (P < 0.001) was observed from day -1 to day 28, whereas, in the polyethylene glycol group, there was a decrease in total short-chain fatty acids (P = 0.02), butyrate (P = 0.04), acetate (P = 0.02) and faecal bacterial mass (P = 0.001). No differences were observed in stools with regard to the following parameters: counts of Lactobacillus, clostridial spores, Bacteroides and enterobacteria, pH, biliary acids and neutral sterol concentrations.\n Both lactulose and polyethylene glycol are efficacious and well tolerated. However, although lactulose can be considered as a pre-biotic in constipated patients, polyethylene glycol produces signs of decreased colonic fermentation in the stool.",
"Administration of high doses of vitamins B6, B1 and B12 successfully inhibited lactation without any untoward side-effects or discomfort in 96% of patients who had not yet established lactation, compared with 76,5% of control patients who received placebo.",
"We conducted a trial to evaluate the effect of an active, multifaceted educational strategy to promote the use of the WHO Reproductive Health Library (RHL) on obstetric practices.\n Cluster randomised trial. The trial was assigned the International Standardised Randomised Controlled Trial Number ISRCTN14055385.\n Twenty-two hospitals in Mexico City and 18 in the Northeast region of Thailand.\n The intervention consisted primarily of three interactive workshops using RHL over a period of 6 months. The focus of the workshops was to provide access to knowledge and enable its use. A computer and support for using both the computer and RHL were provided at each hospital. The control hospitals did not receive any intervention.\n The main outcome measures were changes in ten selected clinical practices as recommended in RHL starting approximately four to six months after the third workshop. Clinical practice data were collected at each hospital from 1000 consecutively delivered women or for a 6-month period whichever was reached sooner.\n The active, multifaceted educational intervention we employed did not affect the ten targeted practices in a consistent and substantive way. Iron/folate supplementation, uterotonic use after birth and breastfeeding on demand were already frequently practiced, and we were unable to measure external cephalic version. Of the remaining six practices, selective, as opposed to routine episiotomy policy increased in the intervention group (difference in adjusted mean rate = 5.3%; 95% CI -0.1 to 10.7%) in Thailand, and there was a trend towards an increased use of antibiotics at caesarean section in Mexico (difference in adjusted mean rate = 19.0%; 95% CI: -8.0 to 46.0%). There were no differences in the use of labour companionship, magnesium sulphate use for eclampsia, corticosteroids for women delivering before 34 weeks and vacuum extraction. RHL awareness (24.8-65.5% in Mexico and 33.9-83.3% in Thailand) and use (4.8-34.9% in Mexico and 15.5-76.4% in Thailand) increased substantially after the intervention in both countries.\n The multifaceted, active strategy to provide health workers with the knowledge and skills to use RHL to improve their practice led to increased access to and use of RHL, however, no consistent or substantive changes in clinical practices were detected within 4-6 months after the third workshop.",
"We compared the short-term efficacy, safety and tolerability of transdermal versus oral oxybutynin in adults with urge urinary incontinence.\n Volunteers with detrusor instability currently responding to oral immediate release oxybutynin were enrolled in our study. Those patients presenting with recurrence of incontinent symptoms after a 2-week washout underwent confirmatory cystometrogram with subsequent randomization to transdermal or oral treatment. Matching active and placebo medications included matrix patches applied twice weekly and capsules taken 2 or 3 times daily. Dose titration was based on anticholinergic symptoms. Outcome measures included comparison of baseline to 6 week changes in incontinence episodes on a 3 day urinary diary, a visual analog scale for efficacy and anticholinergic symptoms reported on a questionnaire. Safety monitoring included adverse events and skin tolerability of the transdermal system.\n A total of 76 patients were enrolled and 74 completed at least 4 weeks of treatment. Mean age in the transdermal and oral groups was 64 and 63 years, and 87% and 97% were female, respectively. Daily incontinent episodes decreased in the transdermal and oral groups (7.3 to 2.4 [66%] and 7.4 to 2.6 [72%], respectively, p = 0.39). The visual analog scale reduction in urinary leakage improved from washout in both groups (p <0.0001) with no difference between them (p = 0.9). Dry mouth occurred in significantly fewer patients in the transdermal (38%) compared with those in the oral group (94%, p <0.001). Of the patients in the transdermal group 67% noticed a reduction in dry mouth severity compared with previous oral treatment, and 90% had none or mild skin erythema.\n Transdermal delivery of oxybutynin resulted in comparable efficacy and a significantly improved anticholinergic side effect profile compared with oral administration in adults with urge urinary incontinence.",
"Women with urge urinary incontinence are commonly treated with antimuscarinic medications, but many discontinue therapy.\n To determine whether combining antimuscarinic drug therapy with supervised behavioral training, compared with drug therapy alone, improves the ability of women with urge incontinence to achieve clinically important reductions in incontinence episodes and to sustain these improvements after discontinuing drug therapy.\n 2-stage, multicenter, randomized clinical trial conducted from July 2004 to January 2006.\n 9 university-affiliated outpatient clinics.\n 307 women with urge-predominant incontinence.\n 10 weeks of open-label, extended-release tolterodine alone (n = 153) or combined with behavioral training (n = 154), followed by discontinuation of therapy and follow-up at 8 months.\n The primary outcome, measured at 8 months, was no receipt of drugs or other therapy for urge incontinence and a 70% or greater reduction in frequency of incontinence episodes. Secondary outcomes were reduction in incontinence, self-reported satisfaction and improvement, and scores on validated questionnaires measuring symptom distress and bother and health-related quality of life. Study staff who performed outcome evaluations, but not participants and interventionists, were blinded to group assignment.\n 237 participants completed the trial. According to life-table estimates, the rate of successful discontinuation of therapy at 8 months was the same in the combination therapy and drug therapy alone groups (41% in both groups; difference, 0 percentage points [95% CI, -12 to 12 percentage points]). A higher proportion of participants who received combination therapy than drug therapy alone achieved a 70% or greater reduction in incontinence at 10 weeks (69% vs. 58%; difference, 11 percentage points [CI, -0.3 to 22.1 percentage points]). Combination therapy yielded better outcomes over time on the Urogenital Distress Inventory and the Overactive Bladder Questionnaire (both P <0.001) at both time points for patient satisfaction and perceived improvement but not health-related quality of life. Adverse events were uncommon (12 events in 6 participants [3 in each group]).\n Behavioral therapy components (daily bladder diary and recommendations for fluid management) in the group receiving drug therapy alone may have attenuated between-group differences. Assigned treatment was completed by 68% of participants, whereas 8-month outcome status was assessed on 77%.\n The addition of behavioral training to drug therapy may reduce incontinence frequency during active treatment but does not improve the ability to discontinue drug therapy and maintain improvement in urinary incontinence. Combination therapy has a beneficial effect on patient satisfaction, perceived improvement, and reduction of other bladder symptoms.",
"nan",
"In a randomized double-blind study we evaluated the effects on cervical ripening and labor induction of 0.5 mg PGE2 in gel given intracervically and 2.0 mg PGE2 given as a vaginal suppository. All patients were at term with unfavorable cervical scores. The indications for induction were toxemia, diabetes mellitus, Rh-immunization, or intrauterine growth retardation. Significantly better results for both cervical priming and labor induction were obtained after intracervical PGE2-gel application than after treatment with placebo or vaginal suppositories. Eleven out of 19 patients (58%) were delivered within 24 h after intracervical PGE2-gel compared to two out of 19 patients given placebo (p less than 0.01). In patients not delivered 24 h after the start of treatment, the mean cervical score had changed from 3.7 to 6.0 (p less than 0.05) after PGE2-gel application compared to a change from 3.9 to 4.3 after placebo treatment (n.s.). The outcome after treatment with PGE2 suppositories did not differ significantly from that with placebo treatment. In a subsequent study 25 patients were given 0.5 mg PGE2-gel intracervically. The results were consistent with those obtained in patients receiving PGE2-gel intracervically in the double-blind study. Few side effects were noted. No patient complained of gastro-intestinal discomfort but increased myometrial activity was observed in two patients; one after placebo and the other after active intracervical PGE2-gel treatment. The hyperactivity was readily countered with the beta 2-agonist, terbutaline. All infants were born in good condition with Apgar scores of 7 or more within 5 min. At pediatric examinations at 1 week and at 6 months of age all children seemed healthy.",
"To describe changes in bladder function and voiding frequency associated with behavioral and drug treatment for urge incontinence and to examine whether these variables mediate the positive effects of treatment on the frequency of incontinence.\n Randomized, double-blinded, placebo-controlled, clinical trial. Eligible patients were stratified according to type of incontinence (urge only vs mixed urge and stress) and severity of incontinence (frequency of accidents as documented in bladder diary).\n University-based outpatient geriatric medicine clinic.\n One hundred five ambulatory, nondemented, community-dwelling women; mean age 67.0 (range 55-91); 98% white, 2% African American.\n Four sessions (over 8 weeks) of biofeedback-assisted behavioral training, drug treatment with individually-titrated oxybutynin chloride, or a placebo control condition.\n Two-channel cystometry was performed to determine threshold volumes for first desire to void (FDV), strong desire to void (SDV), bladder capacity, and the volume at which detrusor instability (DI) or leakage occurred, before randomization and after completion of treatment. Two-week bladder diaries were used before and after treatment to document episodes of incontinence and voiding frequency.\n Bladder capacity increased by 68.9 mL in the oxybutynin group (P <.001) and 17.3 mL in the behavior group and decreased 6.0 mL in the control group. SDV increased 69.9 mL in the oxybutynin group (P <.001), 40.5 in the behavior group (P <.05), and 7.8 mL in the control group. FDV increased by 44.4 mL in the oxybutynin group (P <.001), 18.8 mL in the behavior group, and 8.9 mL in the control group. One of seven patients who presented with DI (12.0%) resolved in the behavior group, seven of eight (87.5%) resolved in the oxybutynin group, and seven of 12 (58.3%) resolved in the control group. These differences were not statistically significant. Voiding frequency was significantly reduced after treatment in both the behavior and the oxybutynin group. Behavioral training resulted in a mean 82.3% reduction in frequency of accidents, oxybutynin (final doses 2.5 mg daily to 5 mg three times a day) resulted in a mean 78.3% reduction, and the control condition resulted in a mean 51.5% reduction (P =.002). Although oxybutynin and behavioral treatment were both effective, and oxybutynin increased SDV and bladder capacity, the structural equation modeling did not demonstrate that the clinical improvement was mediated through the effects of these treatments on urodynamic or voiding frequency measures.\n Studies using more-complex urodynamics and studies with larger sample sizes are needed to better characterize changes in bladder function and explore other urodynamic changes that may accompany treatment. In addition, other factors, both physiological and behavioral, need to be explored as mechanisms by which conservative therapies improve urge incontinence.",
"Twenty-nine cocaine-dependent male veterans without other drug dependence completed a double-blind controlled, randomly-assigned study examining the efficacy of bromocriptine versus placebo in the management of cocaine abstinence symptomatology. Serum prolactin (PL) and growth hormone (GH) levels were obtained prior to and after the study was completed. Patients were seen daily and completed several self-report questionnaires, including the Symptom Checklist-90-Revised, the Beck Depression Inventory, and a Cocaine Craving Report. The patients were also asked to rate a variety of cocaine withdrawal symptoms. Overall, there did not appear to be any advantage to receiving bromocriptine versus placebo during the first 3 weeks following cocaine use cessation with the possible exception of changes in activity and appetite level. The placebo group showed a statistically significant increase in activity level during the first week in treatment and a significant increase in appetite throughout the study. Patients in both groups showed significant improvement in the other areas assessed, with improvement appearing to progress according to length of treatment. Hyperprolactinemia or abnormal GH levels were not found in this patient sample as a group. Thirty-four of the original 63 patients dropped out of the study. Seventeen received bromocriptine, and 17 received placebo. There was no significant difference between drug groups in incidence of retaining patients in treatment. The high dropout rate may reflect the difficulty incurred in retaining cocaine-dependent patients in treatment.",
"Recently, polyethylene glycol (PEG 3350) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation. However, no large randomised controlled trials exist evaluating the efficacy of either laxative.\n To compare PEG 3350 (Transipeg: polyethylene glycol with electrolytes) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects.\n One hundred patients (aged 6 months-15 years) with paediatric constipation were included in an eight week double blinded, randomised, controlled trial.\n After faecal disimpaction, patients <6 years of age received PEG 3350 (2.95 g/sachet) or lactulose (6 g/sachet) while children > or =6 years started with 2 sachets/day. Primary outcome measures were: defecation and encopresis frequency/week and successful treatment after eight weeks. Success was defined as a defecation frequency > or =3/week and encopresis < or =1 every two weeks. Secondary outcome measures were side effects after eight weeks of treatment.\n A total of 91 patients (49 male) completed the study. A significant increase in defecation frequency (PEG 3350: 3 pre v 7 post treatment/week; lactulose: 3 pre v 6 post/week) and a significant decrease in encopresis frequency (PEG 3350: 10 pre v 3 post/week; lactulose: 8 pre v 3 post/week) was found in both groups (NS). However, success was significantly higher in the PEG group (56%) compared with the lactulose group (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at defecation than children using lactulose. However, bad taste was reported significantly more often in the PEG group.\n PEG 3350 (0.26 (0.11) g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate with fewer side effects. PEG 3350 should be the laxative of first choice in childhood constipation.",
"On the basis of the dopamine depletion theory, bromocriptine has been tested to treat cocaine withdrawal and dependence. The authors conducted a 6-week study with 1 week of pretreatment observation and 5 weeks of a randomized, double-blind, placebo-controlled clinical trial of bromocriptine for DSM-III-R-defined cocaine dependence in methadone-maintained male patients. The bromocriptine group (n = 24) did not differ from the placebo group (n = 26) in self-reported cocaine use, proportion of positive urine toxicology samples, craving for cocaine, resistance to cocaine use, or mood symptoms between the pretreatment baseline and the last week of the clinical trial. Both groups showed significant reduction in self-reported frequency of cocaine use, resistance to craving, and mood symptoms during participation in the protocol. The results of this study are consistent with recent clinical and laboratory findings in primary cocaine users. Despite initially promising pilot studies, recent evidence does not support the efficacy of bromocriptine to reduce cocaine use or craving.",
"In a prospective, open-label, assessor-blind, randomised parallel group study the efficacy and safety of Hemabate (Pharmacia-Upjohn Pharmaceuticals, Milton Keynes, Buckinghamshire) an analogue of 15-methyl-prostaglandin (PGF2alpha) analogue was compared with Syntometrine (Alliance Pharmaceuticals, Chippenham, Wilts) the standard combination of ergometrine and syntocinon used for the active management of the third stage of labour and the prevention of primary postpartum haemorrhage (PPH). The study was set in a district general hospital with approximately 4,000 deliveries annually. The study was discontinued at the time of the interim analysis because of unacceptable gastrointestinal side effects. At the time of the interim analysis, a total of 529 women had completed the study with 263 randomised to receive PGF2alpha and 266 to receive ergometrine and syntocinon. In a pre-specified subgroup analysis, women delivered vaginally were further subdivided into those considered to be at high or low risk of primary PPH. The measured blood loss and incidence of PPH was similar in both treatment groups whether delivered by caesarean section or vaginally independent of whether women were considered to be at high or low risk. Adverse gastrointestinal events were recorded more often in the Hemabate group. The most common symptom was diarrhoea which occurred in 21% of women who received Hemabate compared to only 0.8% of Syntometrine users. PGF2alpha is as effective as Syntometrine in the prophylaxis of primary PPH in all groups studied but there was a statistically significantly increased risk of diarrhoea among users of PGF2alpha.",
"In this open-label, randomized study, we assessed the effects on hemostasis of two combined oral contraceptives containing drospirenone (DRSP) as progestogen component.\n Three milligrams of DRSP, a progestogen with antimineralocorticoid activity, was combined with either 30 or 20 microg ethinyl estradiol (EE) (DRSP/30EE; DRSP/20EE) and compared with a preparation containing 150 microg desogestrel (DSG) and 30 microg ethinyl estradiol (DSG/30EE). A total of 75 healthy female volunteers aged 18-35 years were enrolled. The hemostasis variables were measured in the medication-free precycle (baseline); in the first, third and sixth treatment cycle; and in the follow-up phase. The target variables for comparison were the relative changes from baseline to Cycle 6.\n Data of 25 volunteers in each group were valid for the per-protocol evaluation. Most changes in hemostasis variables were similar in the three treatment groups. All procoagulatory variables and the anticoagulatory variable protein C antigen increased slightly, while protein S antigen and activity decreased. For fibrinogen and protein S activity, the changes were statistically significant: less pronounced with DRSP/20EE compared to DSG/30EE at Cycle 6. There were no statistically significant differences in the changes of antifibrinolytic variables, the global clotting tests and D-dimer. All pairwise comparisons of DRSP/30EE vs. DSG/30EE yielded nonsignificant results; however, there was a trend of a lower impact of DRSP/20EE on nearly all hemostatic parameters compared to the 30EE products. All three study treatments were safe and well tolerated by the volunteers and provided adequate contraceptive reliability.\n The changes in the hemostatic variables for DRSP/20EE were less pronounced compared to DSG/30EE and DRSP/30EE. The results were in accordance with previous reports on effects of similar OCs.",
"Two different applications of prostaglandin E2 for induction of labor were randomly used in 113 women with an unripe cervix; 57 women were given prostaglandin suppositories each containing 2.5 mg PGE2 in a basis of Witepsol S55 (Dynamit Nobel), another 56 women were treated with intracervical gel containing 1 mg PGE2 in 5 g hydroxypropylmethyl cellulose. The treatment was repeated after 4 h if the cervix was still unripe, and the procedure was repeated the following day if the cervix was still unfavorable. Cesarean sections was performed within 48 h after the start of induction and before the second stage of labor in 8 women in the suppository group and 7 women in the intracervical gel group. Of the remaining 98 women, 73% (34/48 women) in the suppository group and 36% (18/50 women) in the cervical gel group had delivered within 24 h (p less than 0.01). After 48 h, 88% (42/48 women) in the suppository group and 74% of the women (37/50 women) in the cervical gel group had delivered (p greater than 0.05). The induction-delivery interval in the suppository group was half that found in the cervical gel group. There was no significant difference between the two groups in the use of instrumental vaginal deliveries and cesarean sections nor was there any difference with regard to fetal distress. The post-delivery condition of the newborn was similar in the two groups. No side-effects were reported in either of the two groups.",
"Some studies have suggested that supplementation of food with lactobacilli may prevent or improve atopic dermatitis in children. This study was designed to investigate the therapeutic effect of Lactobacillus rhamnosus GG (LGG) as a food supplement in infants suffering from atopic dermatitis.\n Infants aged 3-12 months suffering from mild-to-moderate atopic dermatitis (severity scoring of atopic dermatitis or SCORAD index of 15-40) without current antiinflammatory treatment were randomized to receive LGG (5 x 10(9) colony forming units b.i.d.) or placebo as a food supplement for 12 weeks. Severity scoring of atopic dermatitis index and use of hydrocortisone 1% ointment as rescue medication (2 points per application) were recorded at 4, 8, and 12 weeks of treatment and combined as symptom load (SL).\n Fifty-four infants (LGG group, mean +/- SD SCORAD index 24.6 +/- 8.8) and 48 infants (placebo group, SCORAD index 23.6 +/- 7.8) were randomized and completed the treatment period (intention-to-treat analysis). Symptom load generally improved over time at 4 weeks (LGG vs placebo, 23.8 +/- 12.4 vs 20.6 +/- 9.9), 8 weeks (22.5 +/- 14.6 vs 17.9 +/- 13.1), and 12 weeks (19.6 +/- 15.4 vs 15.1 +/- 12.1), without statistically significant group differences. When stratified for age, eczema severity or use of rescue medication, no statistically significant group differences, in improvement, were found. No significant group differences were found for the use of rescue medication (0.8 +/- 45.0 g vs 3.5 +/- 29.8 g), increase in mean logarithmic total serum IgE (0.17 +/- 0.30 kU/l vs 0.26 +/- 0.45 kU/l), and newly developed allergic sensitization against hen's egg or cow's milk (18.8%vs 10.0%).\n This placebo-controlled trial showed no therapeutic effect of LGG against mild-to-moderate atopic dermatitis in infancy.",
"The aim of this study was to compare the efficacy and safety of oral nicardipine in acute therapy for preterm labor with those of parenteral magnesium sulfate.\n Patients between 24 and 34 weeks' gestation with documented preterm labor were randomly assigned to receive oral nicardipine (n = 57) or intravenous magnesium sulfate (n = 65) as initial tocolytic therapy. Patients in the nicardipine group received a 40-mg loading dose and then 20 mg every 2 hours as needed to stop contractions (total 80 mg). Patients in the magnesium sulfate group received a 6-g bolus followed by 2 to 4 g/h to provide uterine quiescence. Patients could be switched to another tocolytic regimen if they continued to have contractions after 6 hours of therapy. The main outcome variables examined were time to uterine quiescence, time gained in utero, recurrence of preterm labor, failure of tocolysis, and pertinent maternal and neonatal outcomes.\n There were no significant differences in maternal demographic characteristics between the groups. Among patients who responded with uterine quiescence within 6 hours, there was a significant decrease in the time to uterine quiescence in the nicardipine group (P <.01). Patients in the magnesium sulfate group were more likely to have recurrence of preterm labor necessitating further tocolytic attempts (P =.048). The patients in the magnesium sulfate group had more adverse side effects, mainly nausea and vomiting (P =.004). There were no differences in birth weight, estimated gestational age at delivery, or neonatal complications between the 2 groups.\n Oral nicardipine is an effective, safe, and well-tolerated tocolytic agent. In this prospective clinical trial patients randomly assigned to receive oral nicardipine had arrest of preterm labor more rapidly than did those randomly assigned to receive parenteral magnesium sulfate. Patients who received magnesium sulfate were more likely to have adverse medication effects and recurrent preterm labor.",
"Studies have been performed suggesting that administration of probiotics may have therapeutic and/or preventive benefits in the development of sensitization and atopic disease, particularly in infants with atopic dermatitis (AD).\n The purpose of this study was to evaluate the clinical and immunological effects of supplementation of a hydrolysed formula with two probiotic strains of bacteria on symptoms of AD in infancy.\n We conducted a randomized, double-blind, placebo-controlled study. After 4-6 weeks of baseline and double-blind, placebo-controlled challenges for diagnosis of cow's milk allergy (CMA), infants less than 5 months old with AD received a hydrolysed whey-based formula as placebo (n = 17), or supplemented with either Lactobacillus rhamnosus (n = 17) or Lactobacillus GG (n = 16) for 3 months. Before, during and after intervention, the clinical severity of AD was evaluated using SCORing index Atopic Dermatitis (SCORAD). Allergic sensitization was evaluated by measurement of total IgE and a panel of food-specific IgEs as well as skin prick testing for cow's milk. Inflammatory parameters were blood eosinophils, eosinophil protein X in urine, fecal alpha-1-antitrypsin and production of IL-4, IL-5 and IFN-gamma by peripheral blood mononuclear cells after polyclonal stimulation.\n No statistically significant effects of probiotic supplementation on SCORAD, sensitization, inflammatory parameters or cytokine production between groups were found. Only four infants were diagnosed with CMA.\n We found no clinical or immunological effect of the probiotic bacteria used in infants with AD. Our results indicate that oral supplementation with these probiotic bacterial strains will not have a significant impact on the symptoms of infantile AD.",
"To compare the efficacy and safety of controlled-release oxybutynin with conventional, immediate-release oxybutynin and determine rates of dry mouth.\n Patients (n = 226) who were known to be responsive to anticholinergic therapy and who had seven or more urge incontinence episodes per week were randomized to receive controlled-release oxybutynin or immediate-release oxybutynin. After an initial placebo run-in period, dosing in each began at 5 mg per day and increased weekly by 5 mg per day to a maximum of 20 mg per day or when a balance between improvement of incontinence symptoms and tolerability of side effects was achieved. Rates of urge incontinence and dry mouth were compared. Post hoc Kaplan-Meier survival analysis was used to describe elimination of incontinence episodes by dose and to analyze dry mouth risk by dose.\n Reductions in urge urinary incontinence episodes from baseline to the end of treatment were 18.6 to 2.9 per week (83% mean decrease) and 19.8 to 4.4 per week (76% mean decrease) in the controlled- and immediate-release oxybutynin groups (P =.36), respectively. At equal doses, comparable proportions of patients in both groups reported the absence of urge incontinence (P =.85). The incidence of dry mouth increased with dose in both groups, but there was no difference in dry mouth rates between the groups: 47.7% and 59.1% for the controlled- and immediate-release oxybutynin (P =.09), respectively. However, Kaplan-Meier analysis to examine first report of dry mouth at a given dose revealed that a significantly lower proportion of patients taking controlled-release oxybutynin had moderate to severe dry mouth (P =.007) or any dry mouth (P =.003) compared with those taking immediate-release oxybutynin.\n At the same daily dose, controlled- and immediate-release oxybutynin demonstrated comparable efficacy in reduction of urge incontinence episodes. The incidence of dry mouth was dose dependent but equal in both groups; first report of moderate to severe dry mouth was significantly lower in the controlled-release group."
] |
There is weak evidence that some pharmacologic treatments (most of which are currently unavailable to the public) are better than no treatment for suppressing lactation symptoms in the first postpartum week. No evidence currently exists to indicate whether non-pharmacologic approaches are more effective than no treatment. Presently, there is insufficient evidence to address the side effects of methods employed for suppressing lactation. When women desire treatment, bromocriptine may be considered where it is registered for lactation suppression in those without predisposition to its major side effects of public concerns. Many trials did not contribute data that could be included in analyses. Large randomised trials are needed to compare the effectiveness of pharmacologic (especially bromocriptine) and non-pharmacologic methods with no treatment. Such trials should consider the acceptability of the intervention and lactation symptoms of concern to women and be large enough to detect clinically important differences in major side effects between comparison groups.
|
CD009051
|
[
"1320740",
"8158817",
"17947390",
"11798728",
"8182270",
"6754845"
] |
[
"A controlled trial of a formalin-inactivated hepatitis A vaccine in healthy children.",
"Protection against hepatitis A by an inactivated vaccine.",
"Hepatitis A vaccine versus immune globulin for postexposure prophylaxis.",
"[Further survey on efficacy of attenuated live hepatitis A vaccines].",
"Safety, tolerability, and immunogenicity of an inactivated hepatitis A vaccine: effects of single and booster injections, and comparison to administration of immune globulin.",
"Pre-exposure prophylaxis with immune serum globulin for prevention of viral hepatitis in army recruits."
] |
[
"Although inactivated hepatitis A vaccine is known to be well tolerated and immunogenic in healthy children and adults, its efficacy has yet to be established.\n To evaluate the efficacy of the hepatitis A vaccine in protecting against clinically apparent disease, we conducted a double-blind, placebo-controlled trial in an Hasidic Jewish community in upstate New York that has had recurrent outbreaks of hepatitis A. At the beginning of a summer outbreak, 1037 healthy seronegative children 2 to 16 years of age were randomly assigned to receive one intramuscular injection of a highly purified, formalin-inactivated hepatitis A vaccine or placebo. A case was defined by the presence of typical signs and symptoms, a diagnostic increase in IgM antibody to hepatitis A, and a serum concentration of alanine aminotransferase at least twice the upper limit of normal. Cases occurring greater than or equal to 50 days after the injection were included in the evaluation of efficacy. The children were followed for a mean of 103 days.\n A total of 519 children received vaccine, and 518 received placebo. The vaccine was well tolerated, with no serious adverse reactions. From day 50 after the injection, 25 cases of clinically apparent hepatitis A occurred in the placebo group and none in the vaccine group (P less than 0.001), confirming that the vaccine had 100 percent protective efficacy. Before day 21, seven cases occurred in the vaccine group and three cases in the placebo group. After that time, there were no cases among vaccine recipients and 34 cases among placebo recipients.\n The inactivated purified hepatitis A vaccine that we tested is well tolerated, and a single dose is highly protective against clinically apparent hepatitis A.",
"To evaluate the safety and efficacy of a new inactivated hepatitis A vaccine.\n Double-blind randomized controlled trial stratified by community.\n Community-based in Thailand.\n A total of 40,119 children, aged 1 to 16 years, attending 148 primary schools: 38,157 (95%) entered surveillance a mean of 138 days after receiving vaccine dose 1; 33,586 (84%) completed the controlled trial of 532 days; and 31,075 (81%) received crossover vaccine and remained under surveillance until day 844.\n Participants received hepatitis A vaccine or control hepatitis B vaccine starting January 7, 1991 (doses in months 0, 1, and 12), and crossed over to the alternate vaccine 18 months later.\n Cases of hepatitis A (symptoms, alanine aminotransferase levels of 45 U/L or higher, and IgM to hepatitis A virus) were identified by evaluating school absences of 2 or more days.\n There were no serious adverse reactions despite administration of more than 109,000 doses of hepatitis A vaccine. Among initially seronegative recipients of two doses of hepatitis A vaccine, the proportion with 20 mIU/mL or more of antibody to hepatitis A virus before and 5 months after a 1-year booster was 94% and 99%, respectively. Of 6976 episodes of illness during the controlled trial, there were 40 cases of hepatitis A; 38 were in the control group. Of the 40 cases, six, all in controls, occurred after the 1-year booster dose. Following two doses of hepatitis A vaccine (days 138 through 386), protective efficacy was 94% (95% confidence interval, 79% to 99%); cumulative efficacy including the postbooster period (days 138 to 532) was 95% (95% confidence interval, 82% to 99%). The two hepatitis A vaccine recipients who had symptomatic infections (257 and 267 days after dose 1) appeared to have been partially protected since their illnesses were brief and associated with only slight increases in alanine aminotransferase.\n Inactivated hepatitis A vaccine is safe; when administered in two doses, it protects against hepatitis A for at least 1 year.",
"Hepatitis A vaccine administered to persons after exposure to the hepatitis A virus has not been compared directly with immune globulin, which is known to be highly effective in preventing hepatitis A when given within 2 weeks after exposure to the virus.\n We randomly assigned household and day-care contacts, 2 to 40 years of age, in Almaty, Kazakhstan, to receive one standard age-appropriate dose of hepatitis A vaccine or immune globulin within 14 days after exposure to patients with hepatitis A. Instances of laboratory-confirmed, symptomatic hepatitis A infection occurring between 15 and 56 days after exposure were then assessed during active follow-up of all susceptible contacts.\n Of 4524 contacts who underwent randomization, 1414 (31%) were susceptible to hepatitis A virus and 1090 were eligible for the per-protocol analysis. Among these contacts, 568 received hepatitis A vaccine and 522 received immune globulin. Most contacts were children (average age, 12 years), and most received prophylaxis during the second week after exposure (average interval after exposure, 10 days). The baseline characteristics of the contacts were similar in the two groups. Symptomatic infection with hepatitis A virus was confirmed in 25 contacts receiving vaccine (4.4%) and in 17 contacts receiving immune globulin (3.3%) (relative risk, 1.35; 95% confidence interval, 0.70 to 2.67).\n Low rates of hepatitis A in both groups indicate that hepatitis A vaccine and immune globulin provided good protection after exposure. Although the study's prespecified criterion for noninferiority was met, the slightly higher rates of hepatitis A among vaccine recipients may indicate a true modest difference in efficacy and might be clinically meaningful in some settings. Vaccine has other advantages, including long-term protection, and it may be a reasonable alternative to immune globulin for postexposure prophylaxis in many situations. (ClinicalTrials.gov number, NCT00139139 [ClinicalTrials.gov].).\n Copyright 2007 Massachusetts Medical Society.",
"To further survey the protective efficacy of the standard attenuated live hepatitis A vaccines (H(2) strain).\n Randomized and controlled trials were performed in Fucheng county, Hebei province. A total of 12 036 children were assigned into vaccine group (5 551) and control group (6 485) by cluster sampling. The morbidity of hepatitis A was observed and the blood was collected once hepatitis A showed epidemic to detect anti-HAV IgG and IgM.\n During the period of the first 7 months after vaccination, hepatitis A was sporadic, the morbidity of hepatitis A was 0.55/100 000, and only 1 case occurred in the control group and no case in the vaccine group. From January to August 1998, hepatitis A showed epidemic in a township of this county. The morbidities were 0.37% and 6.69% for vaccine group and control group, respectively. The protective efficacy of the vaccine was 94.47%. The ratios of clinical cases to subclinical infections were 1 to 11 and 1 to 1 for vaccine and control groups, respectively (P < 0.05).\n The H(2) strain vaccine has a very good protective efficacy, and obviously decreases the attack rate, new infection rate and clinical cases by HAV infection.",
"Hepatitis A virus (HAV) infection in adults is often symptomatic and disabling. The present article summarizes our experience with phase 2 studies of an inactivated hepatitis A virus vaccine. Pre- and post-exposure prophylaxis with immune globulin (IG) is only effective for 4-6 months. We compared the safety, tolerability, and immunogenicity of a single i.m. injection of IG with single and booster doses of an inactivated hepatitis A virus vaccine (iHAV) in adults. A total of 75 healthy volunteers (aged 18-50 years) were evaluated in two separate studies. The first included 15 volunteers who received 25 units iHAV i.m. at 0 and 24 weeks. The second, a randomly controlled study, consisted of three groups receiving 25 units iHAV i.m. at 0, 1, and 6 months, or at 0, 2, and 6 months, or 0.06 ml/kg IG i.m. given once. Anti-HAV seroconversion was measured by radioimmunoassay (RIA). After IG injection, anti-HAV seroconversion occurred in 100% of recipients at week 1, declining to 10% at week 12, and 0% by week 20. In contrast, after a single 25-unit dose, RIA seropositivity in iHAV vaccines was 73% by week 2, reaching 100% by week 5, and persisted in all up to week 24, at which time anti-HAV geometric mean titers (GMT) were 2-fold higher than those seen at week 1 after IG. Administration of a booster dose given 1 or 2 months after primary immunization did not significantly improve the quantitative anti-HAV response at 6 months as compared to the effect of the primary dose.(ABSTRACT TRUNCATED AT 250 WORDS)",
"A controlled trial with pre-exposure immune serum globulin was undertaken in Israel Defence Forces (IDF) recruits, an indigenous population living in a hyperendemic area for hepatitis A. The objective was to examine whether the prevailing IDF policy of postexposure administration of immune serum globulin prophylaxis should be modified to further reduce the incidence of infectious hepatitis in the IDF. Altogether 23 447 recruits were systematically allocated on their first day of service into an intervention group and a control group. Over the 18-month follow-up period 18 cases of non-B viral hepatitis were identified among the 10 943 vaccinees and 41 among the 12 504 non-immunised group. Protection over six months was about 85%, and over the entire 18 months 50%. Protection was evident until about 40 weeks' follow-up and may have persisted for longer. Rates in the non-immunised were lower than expected, alluding to the possibility of herd immunity. IDF immunisation policy was successfully altered after this trial."
] |
Hepatitis A vaccines are effective for pre-exposure prophylaxis of hepatitis A in susceptible individuals. This review demonstrated significant protection for at least two years with the inactivated HAV vaccine and at least five years with the live attenuated HAV vaccine. There was evidence to support the safety of the inactivated hepatitis A vaccine. More high quality evidence is required to determine the safety of live attenuated vaccines.
|
CD001999
|
[
"1847026",
"10436448",
"17208082",
"12853587",
"19121589"
] |
[
"Efficacy of low-molecular-weight heparin in the management of intermittent claudication.",
"Venographic comparison of subcutaneous low-molecular weight heparin with oral anticoagulant therapy in the long-term treatment of deep venous thrombosis.",
"Self-managed long-term low-molecular-weight heparin therapy: the balance of benefits and harms.",
"Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.",
"A randomised open-label trial comparing long-term sub-cutaneous low-molecular-weight heparin compared with oral-anticoagulant therapy in the treatment of deep venous thrombosis."
] |
[
"Treating chronic arterial occlusive disease with heparin is controversial because of the risks associated with long-term anticoagulant therapy. Low molecular weight (LMW) heparin (mw about 5000 Dalton), which selectively inhibits the Xa factor with minimal risk of hemorrhage, seems to offer new possibilities in the prevention and treatment of both venous and acute arterial thromboembolism. Therefore, 44 patients with intermittent claudication were recruited to a randomized, double-blind, controlled study. Twenty-two were treated for six months with a single daily subcutaneous dose (15,000 UaXa) of LMW heparin and 22 with placebo administered in the same way over the same period of time. After six months, LMW heparin treatment not only improved walking capacity (by lengthening the pain-free walking time by 25%) but also significantly modified the hemorrheologic pattern (by reducing fibrinogen concentrations and whole blood viscosity at low shear rates). LMW heparin also exerted an antithrombotic and profibrinolytic effect by significantly increasing both the anti-Xa factor and plasminogen activity without markedly modifying activated partial thromboplastin time (+20%). No LMW heparin-treated patient hemorrhaged or reported other noteworthy side effects. These results suggest LMW heparin might be a useful drug in the long-term treatment of chronic arterial occlusive disease of the limbs.",
"The primary objective of this study was to evaluate with venography the rate of thrombus regression after a fixed dose of low-molecular weight heparin (LMWH) per day for 3 months compared with oral anticoagulant therapy for deep venous thrombosis (DVT). Secondary endpoints were the comparisons of the efficacy and safety of both treatments.\n This study was designed as an open randomized clinical study in a university hospital setting. Of the 165 patients finally enrolled in the study, 85 were assigned LMWH therapy and 80 were assigned oral anticoagulant therapy. In the group randomized to oral anticoagulant therapy, the patients first underwent treatment in the hospital with standard unfractionated heparin and then coumarin for 3 months. Doses were adjusted with laboratory monitoring to maintain the international normalized ratio between 2.0 and 3.0. Patients in the LMWH group were administered subcutaneous injections of fixed doses of 40 mg enoxaparin (4000 anti-Xa units) every 12 hours for 7 days, and after discharge from the hospital, they were administered 40 mg enoxaparin once daily at fixed doses for 3 months without a laboratory control assay. A quantitative venographic score (Marder score) was used to assess the extent of the venous thrombosis, with 0 points indicating no DVT and 40 points indicating total occlusion of all deep veins. The rate of thrombus reduction was defined as the difference in quantitative venographic scores after termination of LMWH or coumarin therapy as compared with the scores obtained on the initial venographic results. The efficacy was defined as the ability to prevent symptomatic extension or recurrence of venous thromboembolism (documented with venograms or serial lung scans). The safety was defined as the occurrence of hemorrhages.\n After 3 months of treatment, the mean Marder score was significantly decreased in both groups in comparison with the baseline score, although the effect of therapy was significantly better after LMWH therapy (49.4% reduction) than after coumarin therapy (24.5% reduction; P <.001). LMWH therapy and male gender were independently associated with an enhanced resolution of the thrombus. A lower frequency of symptomatic recurrent venous thromboembolism was also shown in patients who underwent treatment with LMWH therapy (9.5%) than with oral anticoagulant therapy (23.7%; P <.05), although this difference was entirely a result of recurrence of DVT. Bleeding complications were significantly fewer in the LMWH group than in the coumarin group (1. 1% vs 10%; P <.05). This difference was caused by minor hemorrhages. Coumarin therapy and cancer were independently associated with an enhanced risk of complications. Subcutaneous heparin therapy was well tolerated by all patients.\n The patients who were allocated to undergo enoxaparin therapy had a significantly greater improvement in their quantitative venographic score, a significantly lower recurrence rate of symptomatic venous thromboembolism, and a significantly lower incidence of bleeding than patients who underwent treatment with coumarin. LMWH can be used on an outpatient basis as a safer and more effective alternative to classical oral anticoagulant therapy for the secondary prophylaxis of selected patients with DVT.",
"A substantial clinical need exists for an alternate to vitamin K antagonists for treating deep vein thrombosis in many patients. Long-term low-molecular-weight heparin (LMWH), body-weight adjusted, avoids anticoagulant monitoring and may be associated with less bleeding. We evaluated the effectiveness and safety of long-term LMWH compared with vitamin K antagonist therapy in a broad spectrum of patients with proximal vein thrombosis.\n We performed a multicenter, randomized, open-label clinical trial using objective outcome measures comparing therapy for 3 months. Outcomes were assessed at 3 and 12 months.\n Of 737 patients, 18 of 369 receiving tinzaparin (4.9%) had recurrent venous thromboembolism at 3 months compared with 21 of 368 (5.7%) receiving usual care (absolute difference, -0.8%, 95% confidence interval -4.1-2.4). Hemorrhagic complications occurred less frequently in the LMWH group largely because of less minor bleeding: 48 of 369 patients (13.0%) versus 73 of 368 patients (19.8%) receiving usual-care anticoagulation (absolute difference -6.8%; P = .011; risk ratio = 0.66). New major bleeding events ceased early (by day 23, P = .034) for patients receiving LMWH but persisted throughout the study treatment interval for patients receiving vitamin K antagonist therapy. No mortality advantage was shown for LMWH.\n Our study shows that LMWH is similar in effectiveness to the usual-care vitamin K antagonist treatment for preventing recurrent venous thromboembolism in a broad spectrum of patients. It causes less harm and enhances the clinicians' therapeutic options for patients with proximal deep vein thrombosis. Our findings reported here suggest the possibility of a broader role for long-term LMWH in selected patients.",
"Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer.\n Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months).\n During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group.\n In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding.\n Copyright 2003 Massachusetts Medical Society",
"To evaluate whether low-molecular-weight heparin (LMWH) could be equally (or more) effective than oral anti-vitamin-K agents (AVK) in the long-term treatment of deep venous thrombosis (DVT).\n A randomised, open-label trial.\n In this trial, 241 patients with symptomatic proximal DVT of the lower limbs confirmed by duplex ultrasound scan were included. After initial LMWH, patients received 6 months of treatment with full therapeutic dosage of tinzaparin or acenocoumarol. The primary outcome was the 12-month incidence of symptomatic recurrent venous thrombo-embolism (VTE). Duplex scans were performed at 6 and 12 months.\n During the 12-month period, six patients (5%) of 119 who received LMWH and 13 (10.7%) of 122 who received AVK had recurrent VTE (p=0.11). In patients with cancer, recurrent VTE tended to be lower in the LMWH group (two of 36 [5.5%]) vs. seven of 33 [21.2%]; p=0.06). One major bleeding occurred in the LMWH group and three in the AVK group. Venous re-canalisation increased significantly at 6 months (73.1% vs. 47.5%) and at 12 months (91.5% vs. 69.2%) in the LMWH group.\n Tinzaparin was more effective than AVK in achieving re-canalisation of leg thrombi. Long-term tinzaparin was at least as efficacious and safe as AVK for preventing recurrent VTE, especially in patients with cancer."
] |
No benefit of heparin, LMWHs or oral anticoagulants has been established for intermittent claudication. An increased risk of major bleeding events has been observed especially with oral anticoagulants. The use of anticoagulants for intermittent claudication cannot be recommended at this stage.
|
CD009528
|
[
"20963843"
] |
[
"Randomized trial of biofilm testing to select antibiotics for cystic fibrosis airway infection."
] |
[
"In cystic fibrosis (CF), conventional antibiotic susceptibility results correlate poorly with clinical outcomes. We hypothesized that biofilm testing would more accurately reflect the susceptibilities of bacteria infecting CF airways.\n A multicenter randomized pilot trial was conducted to assess the efficacy and safety of using biofilm susceptibility testing of Pseudomonas aeruginosa sputum isolates to guide antibiotic regimens for chronic airway infections in clinically stable adolescent and adult CF patients. Thirty-nine participants were randomized to biofilm or conventional treatment groups; 14-day courses of two antibiotics were selected according to an activity-based algorithm using the corresponding susceptibility results.\n Of the agents tested, meropenem was most active against biofilm-grown bacteria, and was included in regimens for about half of each study group. For 19 of 39 randomized participants, randomization to the other study group would not have changed the antibiotic classes of the assigned regimen. Study groups were comparable at baseline, and had similar mean decreases in bacterial density, measured in log(10) colony forming units per gram of sputum (biofilm, -2.94 [SD 2.83] vs. conventional, -3.27 [SD 3.09]), and mean increases in forced expiratory volume in 1 sec, measured in liters (0.18 [SD 0.20] vs. 0.12 [SD 0.22]).\n In this pilot study, antibiotic regimens based on biofilm testing did not differ significantly from regimens based on conventional testing in terms of microbiological and clinical responses. The predictive value of biofilm testing may nonetheless warrant evaluation in an adequately powered clinical trial in younger CF patients or those experiencing acute pulmonary exacerbation.\n Copyright © 2011 Wiley-Liss, Inc."
] |
The current evidence is insufficient to recommend choosing antibiotics based on biofilm antimicrobial susceptibility testing rather than conventional antimicrobial susceptibility testing in the treatment of Pseudomonas aeruginosa pulmonary infections in people with cystic fibrosis. Future randomized clinical trials on this topic may shed further light on this question.
|
CD003778
|
[
"1674105",
"10419922"
] |
[
"A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group.",
"Low-dose methotrexate is ineffective in primary biliary cirrhosis: long-term results of a placebo-controlled trial."
] |
[
"In primary biliary cirrhosis the hepatic lesions may result, at least in part, from the intracellular accumulation of potentially toxic endogenous bile acids. Preliminary work suggests that the administration of ursodiol (also called ursodeoxycholic acid), a hydrophilic bile acid without hepatotoxicity, leads to improvement in the condition of patients with primary biliary cirrhosis.\n We conducted a two-year, multicenter, double-blind trial to compare the efficacy of ursodiol with that of placebo. Patients with biopsy-proved primary biliary cirrhosis were randomly assigned to receive either ursodiol (13 to 15 mg per kilogram of body weight per day) (n = 73) or placebo (n = 73). Treatment failure was defined as a doubling of bilirubin levels to more than 70 mumol per liter or the occurrence of a severe complication (ascites or variceal bleeding) or an adverse reaction.\n Treatment failed in 6 patients in the ursodiol group, as compared with 13 in the placebo group (P less than 0.01 by Cox regression model). A single patient in each group withdrew because of minor adverse effects. After two years of treatment, the proportion of patients with clinically overt disease decreased only in the ursodiol group (P less than 0.02). The patients treated with ursodiol had significant improvements in serum levels of bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, cholesterol, and IgM (all P less than 0.001); the antimitochondrial-antibody titer (P less than 0.01); and the Mayo risk score (P less than 0.001). Follow-up analysis of 95 liver-biopsy specimens showed a significant improvement in the mean histologic score (P less than 0.002) and in all the characteristic histologic features except fibrosis only in the group given ursodiol.\n Ursodiol is a safe and effective treatment for primary biliary cirrhosis.",
"New treatments for primary biliary cirrhosis (PBC) need to be evaluated. We conducted a single-center double-blind, randomized trial of methotrexate, 7.5 mg/wk (n = 30), vs. placebo (n = 30) for up to 6 years in PBC.\n Methods included three monthly symptom assessment and liver function tests and liver biopsy and gastroscopy at baseline, after 2 years, and after 4-6 years.\n Patients randomized to methotrexate had, compared with patients randomized to placebo, (1) significantly lower on-treatment serum alkaline phosphatase, gamma-glutamyltransferase, immunoglobulin (Ig) M, IgG, and (after 24 months) aspartate aminotransferase and alanine aminotransferase levels (P < 0.02-0.001 by analysis of covariance to adjust for baseline differences); (2) a nonsignificant trend toward lower on-treatment pruritus scores; (3) similar on-treatment Knodell inflammatory scores but nonsignificant trends toward lower Knodell fibrosis score and less ductopenia; (4) a trend toward greater increases in serum bilirubin level and Mayo score with time (both significant after 5 years of follow-up); and (5) a 2.9-fold (95% confidence interval, 0.85-10.25-fold) increase the rate of death or liver transplantation as a result of liver disease during or after the trial (P = 0.09) in a Cox multivariate regression analysis compared with patients randomized to placebo.\n These results do not support the clinical use of low-dose methotrexate in PBC."
] |
There is insufficient data to support or reject the use of glucocorticosteroids for patients with primary biliary cirrhosis. It may be appropriate to consider a large prospective randomised clinical trial on this topic.
|
CD004722
|
[
"8114833",
"9855069",
"9054280",
"12045777",
"8864674"
] |
[
"Transdermal nicotine for active ulcerative colitis.",
"Outcome of ulcerative colitis after treatment with transdermal nicotine.",
"Transdermal nicotine for mildly to moderately active ulcerative colitis. A randomized, double-blind, placebo-controlled trial.",
"Distal ulcerative colitis refractory to rectal mesalamine: role of transdermal nicotine versus oral mesalamine.",
"Transdermal nicotine compared with oral prednisolone therapy for active ulcerative colitis."
] |
[
"Ulcerative colitis is largely a disease of nonsmokers. Because anecdotal reports suggest that smoking and nicotine may improve the symptoms of the disease, we examined the effect of nicotine as a supplemental treatment for ulcerative colitis.\n We treated 72 patients with active ulcerative colitis with either transdermal nicotine patches or placebo patches for six weeks in a randomized, double-blind study. Incremental doses of nicotine were given; most patients tolerated doses of 15 to 25 mg per 24 hours. All the patients had been taking mesalamine, and 12 were receiving low doses of glucocorticoids; these medications were continued without change during the study. Clinical, sigmoidoscopic, and histologic assessments were made at base line and at the end of the study; symptoms were recorded daily on a diary card, and the clinician made a global assessment. Side effects and plasma nicotine and cotinine concentrations were monitored throughout the study.\n Seventeen of the 35 patients in the nicotine group had complete remissions, as compared with 9 of the 37 patients in the placebo group (P = 0.03). The patients in the nicotine group had greater improvement in the global clinical grade of colitis (P < 0.001) and the histologic grade (P = 0.03), lower stool frequency (a difference of 1.6 stools daily; P = 0.008), less abdominal pain (P = 0.05), and less fecal urgency (P = 0.009). More patients in the nicotine group had side effects (23, vs. 11 in the placebo group; P = 0.002), the most common of which were nausea, lightheadedness, headache, and sleep disturbance. Withdrawals due to ineffective therapy were more common in the placebo group (3 vs. 8, P = 0.12).\n The addition of transdermal nicotine to conventional maintenance therapy improves symptoms in patients with ulcerative colitis.",
"Transdermal nicotine appears to be of benefit in the short-term treatment of patients with ulcerative colitis. The aim of this study was to determine its long-term effects.\n A randomized, comparative study.\n Patients with mild to moderate clinical relapses of left-sided ulcerative colitis during maintenance treatment with mesalamine 1 g b.i.d. were allocated to an additional treatment with either transdermal nicotine or prednisone for 5 weeks. The first consecutive 15 patients per group, with clinical and endoscopic signs of remission, were followed up for 6 months, while continuing mesalamine maintenance treatment.\n Relapses of active colitis were observed in 20% of patients formerly treated with nicotine and in 60% of patients in the prednisone group (P = 0.027). Relapses occurred earlier in the latter group.\n Our results confirm that nicotine is useful in cases of ulcerative colitis with mild or moderate activity and suggest that remissions induced by nicotine may last longer than those obtained with oral corticosteroids.",
"Ulcerative colitis is predominantly a disease of nonsmokers. Transdermal nicotine may help control clinical manifestations of this condition.\n To determine the efficacy of transdermal nicotine for controlling clinical disease activity in active ulcerative colitis.\n Randomized, double-blind, placebo-controlled, single-center clinical trial.\n Multispecialty group serving as an academic tertiary referral center.\n 64 nonsmoking patients with mildly to moderately active ulcerative colitis despite the use of medication.\n Patients were stratified on the basis of smoking history, extent of disease, and concomitant medical therapy. After stratification, patients were randomly assigned to daily treatment with transdermal nicotine (n = 31) at the highest tolerated dose (11 mg for 1 week and then < or = 22 mg for 3 weeks) or placebo (n = 33).\n Clinical features were assessed at baseline and 4 weeks by endoscopy, physician assessment, and a patient diary of daily symptoms. Serum concentrations of nicotine were determined by using gas chromatography and mass spectrometry, and plasma concentrations of cotinine were measured by using high-performance liquid chromatography.\n At 4 weeks, 12 of 31 patients (39%) who received nicotine showed clinical improvement compared with 3 of 33 patients (9%) who received placebo (P = 0.007). Four patients receiving nicotine discontinued therapy because of side effects (contact dermatitis [n = 2], nausea [n = 1], and acute pancreatitis [n = 1]). At week 4, the nicotine group had a mean (+/-SD) trough serum nicotine concentration of 11.3 +/- 8.4 ng/mL and a mean trough plasma cotinine concentration of 192 +/- 95 ng/mL.\n Transdermal nicotine administered at the highest tolerated dosage (< or = 22 mg/d) for 4 weeks is efficacious for controlling clinical manifestations of mildly to moderately active ulcerative colitis.",
"Distal ulcerative colitis usually responds to treatment with rectal mesalamine, but the management of refractory cases is poorly defined.\n To evaluate the possible therapeutic benefit of transdermal nicotine versus oral mesalamine.\n Thirty patients with left-sided ulcerative colitis unresponsive to treatment with a mesalamine 4 g enema at bedtime were randomly allocated to additional therapy with either transdermal nicotine 15 mg daily or oral mesalamine 800 mg tid for four weeks. Clinical remission was evaluated by Rachmilewitz's activity index and confirmed by sigmoidoscopy.\n Remission was observed in 12 of 15 patients receiving additional treatment with nicotine and in five of 15 patients receiving additional treatment with oral mesalamine (P=0.027).\n The addition of transdermal nicotine to treatment with mesalamine enemas is significantly superior to combined therapy with oral and rectal mesalamine in patients with distal ulcerative colitis refractory to rectal mesalamine alone.",
"Ulcerative colitis is largely a disease of non-smokers. Previous controlled trials have shown benefit with transdermal nicotine when given with 5-aminosalicylic acid in active disease but not when given alone as maintenance therapy.\n To examine nicotine alone compared with prednisolone in active disease.\n Sixty-one patients with active ulcerative colitis were treated with either transdermal nicotine patches or 15 mg prednisolone for 6 weeks in a randomized, double-blind study. Incremental doses of nicotine were given for the first 9 days; patients tolerated between 15 and 25 mg daily. Most patients were taking mesalazine at entry which was discontinued at day 10; a few were taking topical steroids which were discontinued at the onset. Clinical, sigmoidoscopic and histological assessments were made at baseline and 6 weeks, or at premature withdrawal. Symptoms were recorded on a diary card, and the clinician made a global clinical assessment. Side effects and serum nicotine and cotinine concentrations were monitored throughout the study.\n Forty-three patients completed the 6-week trial; of these, 6 of 19 in the nicotine group achieved full sigmoidoscopic remission compared with 14 of 24 with prednisolone (P = 0.08). In those who completed the 6-week study, there was significant improvement within both the nicotine and prednisolone group for the St Mark's score (P < 0.05 and P < 0.01, respectively), Global Clinical Grade (P < 0.01 for both), blood in the stool (P < 0.05 and P < 0.01), abdominal pain (P < 0.05 and P < 0.01) and sigmoidoscopic score (P < 0.01 and P < 0.001); differences between groups tend to favour prednisolone, but none reach statistical significance. However, on intention-to-treat analyses there is little clear evidence of improvement in either group apart from sigmoidoscopic score in which prednisolone was associated with a significantly greater improvement than nicotine (P < or = 0.05). The nicotine group had more withdrawals than the prednisolone group, 11 versus 7, respectively (P = 0.23), both for deterioration (6 vs. 5) and side effects (5 vs. 2, P = 0.15). Side effects were more frequently reported in the nicotine group (average 1.47 episodes per person) than the prednisolone group (average 0.61; P = 0.03), the most common of which were nausea, light-headedness and tremor.\n In those who managed to complete the 6-week study, nicotine alone appeared to be of only very modest benefit in acute colitis and was not as effective as 15 mg of prednisolone daily."
] |
The results of this review provide evidence that transdermal nicotine is superior to placebo for the induction of remission in patient's with ulcerative colitis. The review did not identify any significant advantage for transdermal nicotine therapy compared to standard medical therapy. Adverse events associated with transdermal nicotine are significant and limit its use in some patients.
|
CD006529
|
[
"12204314",
"11354236",
"15200743",
"2569214",
"7846195",
"9517912",
"1821700",
"9871816",
"9421348",
"9690979"
] |
[
"A randomised, double-blind comparison of milnacipran and imipramine in the treatment of depression.",
"Antidepressant efficacy and tolerability of milnacipran, a dual serotonin and noradrenaline reuptake inhibitor: a comparison with fluvoxamine.",
"A comparative study of milnacipran and imipramine in the treatment of major depressive disorder.",
"Controlled comparison of two doses of milnacipran (F 2207) and amitriptyline in major depressive inpatients.",
"Controlled comparison of milnacipran and fluoxetine in major depression.",
"Double-blind study of the efficacy and safety of milnacipran and imipramine in elderly patients with major depressive episode.",
"Interest of a loading dose of milnacipran in endogenous depressive inpatients. Comparison with the standard regimen and with fluvoxamine.",
"Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice.",
"Long-term efficacy and safety of milnacipran compared to clomipramine in patients with major depression.",
"A double-blind comparison of the efficacy and safety of milnacipran and fluoxetine in depressed inpatients."
] |
[
"This multicentre, double-blind, randomised trial in 109 patients compared the efficacy and tolerance of the novel selective serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressant milnacipran (50 mg twice daily, n=53) with the established tricyclic agent imipramine (75 mg twice daily, n=56) over a period of 6 weeks, in patients with major depression (Montgomery-Asberg depression rating score (MADRS) > or =25). Initiation of antidepressant medication was conducted during a 2-week period of hospitalisation, after a 3- to 7-day washout period. Concomitant psychiatric medication was limited to lorazepam, cyamemazine, chloral hydrate and long-term uncomplicated lithium therapy. Assessment for efficacy using the MADRS and Hamilton rating scales of depression, a visual analogue scale and global evaluation revealed both agents to be highly effective (P=0.0001) in this group of patients. Milnacipran was found to be of similar efficacy to imipramine. Tolerance, assessed by physiological and biochemical examinations with routine inventory and spontaneous report of adverse events, revealed a clear advantage for milnacipran. The incidence of anticholinergic events with milnacipran was about half that with imipramine and the overall incidence of adverse events by either reporting method was markedly lower with milnacipran than with imipramine. Furthermore, the patient drop-out rate with imipramine was double that experienced with milnacipran. Milnacipran appears to possess equal antidepressant efficacy to imipramine but with markedly superior tolerance. Therefore, milnacipran constitutes an important new treatment option in major depression.",
"The antidepressant efficacy and tolerability of milnacipran, a dual action serotonin-noradrenaline reuptake inhibitor, were compared with those of the selective serotonin reuptake inhibitor, fluvoxamine, in 113 patients with moderate to severe major depression. Treatment with milnacipran, 50 mg b.d. for 6 weeks, produced a significantly greater reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores than fluvoxamine, 100 mg b.d. (P = 0.007; 65.4% versus 49.9%, respectively); significantly greater decreases were also seen on days 7 (P = 0.04) and 28 (P = 0.03). The response rate (the proportion of patients showing a decrease in MADRS scores of at least 50%) was 78.9% in patients receiving milnacipran, compared with 60.7% in fluvoxamine-treated patients (P = 0.04). Milnacipran also produced greater improvements in 24-item Hamilton Depression Rating Scale scores (P = 0.05). On the Clinical Global Impression Improvement scale, 77.2% of milnacipran-treated patients were rated as considerably or markedly improved, compared with 60.7% of patients receiving fluvoxamine (P = 0.06 chi-squared). Both treatments were well tolerated; the only significant difference between the two groups was a higher incidence of tremor and drowsiness in patients treated with fluvoxamine. It is concluded that milnacipran may offer some advantages over selective serotonin reuptake inhibitors, such as fluvoxamine, in the treatment of moderate to severe major depression.",
"The antidepressant efficacy and safety of milnacipran, a dual action antidepressant drug which inhibits the reuptake of serotonin and noradrenaline, was compared with that of the tricyclic antidepressant, imipramine, in a multi-centre, double-blind, randomised, parallel group, comparative trial in 5 hospital centres in Spain. One hundred patients hospitalised with a diagnosis of major depressive disorder according to the Diagnostic and Statistical Manual of the American Psychiatry Association (third revision), with a minimum score of 25 on the Montgomery and Asberg Depression Rating Scale were treated for 6 weeks with milnacipran (100 mg/day) or imipramine (150 mg/day). Both treatments showed similar efficacy in reducing depressive symptoms. The frequency of most adverse events in the milnacipran-treated patients was lower than that observed in the imipramine group, particularly those related to anticholinergic symptoms. Dysuria and shivering, however, were more common with milnacipran. The results of this study support others which have demonstrated that milnacipran has equivalent efficacy but superior tolerability to a tricyclic antidepressant such as imipramine.",
"A multicenter study compared the antidepressant efficacy and the tolerance of two doses of milnacipran (50 mg and 100 mg/day) and amitriptyline (150 mg/day) in three parallel groups of 45 major depressive inpatients defined by Research Diagnostic Criteria. After a wash-out period of 4-7 days on placebo with lorazepam and/or nitrazepam if necessary, patients were randomly assigned to a daily dose of milnacipran 50 mg, milnacipran 100 mg or amitriptyline 150 mg reached on the 5th day and then stable over a 4-week period, with weekly assessments by means of the Montgomery and Asberg depression scale, the Hamilton depression scale, the Clinical Global Impressions (CGI) and the Target Emergent Signs and Symptoms. Results showed significant superiority of both milnacipran 100 mg/day and amitriptyline over milnacipran 50 mg/day at the end of the treatment period. However, amitriptyline induced a nonsignificant trend toward more rapid improvement after 2 weeks of treatment, mainly based on items related to insomnia, supporting more sedative properties of amitriptyline as compared to milnacipran. Anticholinergic side-effects were significantly lower with milnacipran than with amitriptyline, explaining why milnacipran 100 mg exhibited at the end of the treatment period, a nonsignificantly better efficacy index on the CGI. Moreover, in contrast to milnacipran, amitriptyline was responsible for a significant decrease in blood pressure and a significant weight gain.",
"The efficacy and the tolerance of milnacipran (100 mg/day), a second generation antidepressant which equipotently inhibits both noradrenaline and serotonin reuptake, was compared to fluoxetine (20 mg/day), a selective serotonin reuptake inhibitor, in two parallel groups of, respectively, 97 and 93 major depressive outpatients. The duration of the study was 6 weeks, with assessments every 2 weeks by means of the Montgomery and Asberg depression scale (MADRS), the Hamilton depression scale, the clinical global impressions (CGI), and a checklist of symptoms and side-effects. Results showed significant superiority of fluoxetine over milnacipran on most rating instruments: MADRS (P = 0.01) including five individual items, Hamilton depression scale (P = 0.002) including ten individual items, CGI of severity (P = 0.01) and therapeutical index (P = 0.002). On visual analogue scales assessing the clinical profile of the compounds, fluoxetine was rated as exhibiting more psychostimulating activity than milnacipran (P = 0.0008). The tolerance of the two antidepressants was very similar, with the exception of symptoms of dizziness which were more frequently reported with milnacipran (P = 0.01). These differences in efficacy favoring fluoxetine could result from the selection of a dose of milnacipran below the optimal therapeutic dose for this type of psychiatric patients or to the administration of the compounds in single daily intakes, whereas milnacipran possesses a plasma elimination half-life of only 7 h.",
"The novel antidepressant agent milnacipran is a dual and equipotent serotonin and noradrenaline reuptake inhibitor. The aim of this double-blind study was to compare the efficacy and safety of milnacipran (50 mg twice daily) with that of imipramine (50 mg twice daily) in elderly patients with major depressive episode. A total of 219 patients were randomly assigned to 8 weeks of double-blind treatment with either milnacipran or imipramine; 72 patients withdrew from the study. At the end of treatment no significant differences were found between milnacipran and imipramine in antidepressant efficacy. A significantly greater number of side-effects, particularly anticholinergic effects, was observed in the imipramine group. Milnacipran may be preferable to imipramine in elderly depressed patients, as it provides the same antidepressant activity as imipramine with a lower incidence of side-effects, and does not impair cognitive ability.",
"A multicenter controlled study was designed to test the hypothesis that a loading dose of an antidepressant could shorten the latency of its clinical efficacy. Three parallel groups of about 40 endogenous depressive inpatients received either a loading dose of milnacipran (300 mg daily for 2 weeks and 150 mg daily during the 2 following weeks), the standard regimen of milnacipran in severe depression (200 mg daily for 4 weeks), or fluvoxamine (200 mg daily for 4 weeks). The duration of the study was 4 weeks, with assessments at baseline and after 4, 9, 14, 21, and 28 days of therapy by means of Montgomery and Asberg depression scale (MADS), the Hamilton depression scale, the Clinical Global Impressions (CGI), and a checklist of symptoms and side-effects. Results showed very similar evolution in the 3 treatment groups. In addition, the level of side-effects did not exhibit significant differences among the treatment groups, except for excitement-nervousness and akathisia which were more frequently reported with fluvoxamine. These results do not support the usefulness of a loading dose of an antidepressant such as milnacipran. They demonstrate however that milnacipran can be given at a 300 mg daily dose from the very first day of treatment with an excellent tolerance.",
"The enhanced sensitivity of the elderly to the side effects produced by tricyclic antidepressants (TCAs), and the frequency and type of adverse events, have made the treatment of depression in this group difficult. The selective serotonin reuptake inhibitors (SSRIs) have been reported to produce significantly fewer undesirable side effects and display better tolerance than TCAs. We compared the therapeutic actions and side effects produced by citalopram, the most selective SSRI available, with amitriptyline in a group of elderly patients (aged 65 and older) diagnosed with major depression. In a double-blind, double-dummy, parallel-group, multicenter comparison of citalopram (20 or 40 mg/day) and amitriptyline (50 or 100 mg/day), patients who did not respond to placebo during a 1-week single-blind phase were randomly assigned to receive citalopram or amitriptyline for 8 weeks. Efficacy measures included the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Scale (HAMD), and Clinical Global Impressions. Both drug treatments produced equivalent time-related declines in severity of depression, so that by 8 weeks slightly more than 50% of the patients in each group experienced marked recovery, defined as MADRS scores < or = 12. Amitriptyline produced a greater overall incidence of adverse events, including a significantly higher (P < 0.001) percentage of patients reporting dry mouth (34% vs. 7%), as well as a significantly higher (P < 0.02) incidence of somnolence. Constipation and fatigue also occurred more frequently in the amitriptyline than in the citalopram group. For only one event (nausea) did the citalopram group report a significantly greater (P = 0.012) incidence (12.8% vs. 4.8%). On the basis of these results, it was concluded that citalopram is as effective an antidepressant as amitriptyline in the treatment of the depressed elderly. Because of its low incidence and low magnitude of side effects, citalopram seems especially useful in private practice.",
"Milnacipran is a new antidepressive drug, a combined noradrenaline/serotonin (NA/5-HT) reuptake inhibitor, which has been suggested to be as effective as and better tolerated than tricyclic antidepressants. Since long-term studies are lacking, we compared the efficacy, safety and tolerability of milnacipran and clomipramine in a double-blind, randomized, parallel-group study setting during 26 weeks of treatment in patients with major depression. A total of 107 patients were treated with either milnacipran (n=52) or clomipramine (n=55). Due to active treatment of duration less than 12 days in four patients and protocol deviation in one patient, in total 47 milnacipran-treated patients were eligible for efficacy analysis. Nine patients in the clomipramine group continued on active treatment for less than 12 days. Thus 46 clomipramine-treated patients were finally included in the efficacy analysis. After 1 week of dose escalation, there was a fixed dosage regimen of either milnacipran (200 mg daily) or clomipramine (150 mg daily) during weeks 2 to 10, followed by flexible dosing of milnacipran (100, 150 or 200 mg daily) or clomipramine (75, 100 or 150 mg daily) during weeks 11 to 26. A total of 53 patients (49%) completed the 26-week study period; 21% (11/52) of the patients in the milnacipran group and 38% (21/55) of the patients in the clomipramine group discontinued their medication prematurely due to adverse events, whereas 19% (10/52) of those on milnacipran and 7% (4/55) of those on clomipramine treatment withdrew due to either lack of efficacy or clinical deterioration. The mean change (+/-SD) in the Hamilton Depression Rating Scale (HAMD) score between the baseline and the last rating ranged from 23.7+/-3.1 to 12.0+/-9.5 in the milnacipran-treated patients and from 23.1+/-3.5 to 8.0+/-8.5 in the clomipramine-treated patients, revealing a significant difference in favour of clomipramine. In total 58% of the milnacipran-treated patients vs. 72% of the clomipramine-treated patients showed a > or = 50% reduction in their baseline HAMD scores and 45% vs. 63% had an HAMD score of < or = 7 at the last rating, respectively. Moreover, the time to the onset of the antidepressant action (defined as > or = 50% reduction of the baseline HAMD score) showed a significant difference in favour of clomipramine. In addition, clomipramine was significantly more efficacious in patients with a baseline HAMD score of > or = 24 as evidenced by the analysis of the HAMD score at week 6 and at the last rating. The Montgomery Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI) scale did not show significant differences between the treatment groups. The safety analysis did not reveal any differences of clinical significance in cardiovascular variables between the study drugs. Dry mouth was significantly less frequently reported by the milnacipran-treated patients during the early and later phases (weeks 6 to 26) of the study, while insomnia was more common in the milnacipran group during weeks 1 to 6. In conclusion, milnacipran appeared to be less effective than clomipramine in the long-term treatment of depression. The side-effects of the drugs differed to a certain extent, and milnacipran tended to be somewhat better tolerated than clomipramine.",
"This double-blind, randomised, multicentre study compared the antidepressant efficacy and safety of two doses of milnacipran (100 mg/day and 200 mg/day) and fluoxetine (20 mg/day) in 289 inpatients with endogenous depression. After a placebo washout period of 4-7 days, assessments were performed weekly during the first 4 weeks, and then after 6, 8 and 12 weeks, using the 17-item Hamilton Depression Rating Scale (HDRS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI). HDRS total score was reduced by a mean of 14.8 in the milnacipran 100 mg/day group, 12.9 in the milnacipran 200 mg/day group and 12.1 in the fluoxetine 20 mg/day group. MADRS total score decreased by 17.4, 15.8 and 14.6, respectively. No significant difference could be shown between the three treatment groups for either the HDRS or MADRS total scores. However, the time-by-time change showed a trend in favour of milnacipran 100 mg/day, which was found significantly superior to fluoxetine at day 28 for several converging parameters (MADRS, CGI-3). Overall, efficacy ratings for all parameters were highest for milnacipran 100 mg/day, followed by milnacipran 200 mg/day and fluoxetine 20 mg/day. Side-effect profiles were not significantly different between groups except for a significantly greater frequency of dose-related increase in heart rate > or = 100 bpm in milnacipran recipients and a significantly greater weight loss in fluoxetine recipients."
] |
Currently, there is inadequate evidence to conclude whether milnacipran is superior, inferior or the same as other antidepressive agents in terms of efficacy, acceptability and tolerability in the acute phase treatment of major depression. However, there is some evidence in favour of milnacipran over TCAs in terms of dropouts due to adverse events (acceptability) and the rates of experiencing adverse events (tolerability). Information about other clinically meaningful outcomes such as cost-effectiveness and social functioning, including the ability to return to work, is lacking. Further study is needed to answer whether milnacipran would be the better choice of antidepressant for acute major depression.
|
CD003956
|
[
"9686822",
"1735830",
"10103305",
"11134431"
] |
[
"Administration of recombinant human granulocyte-colony stimulating factor to septic neonates induces neutrophilia and enhances the neutrophil respiratory burst and beta2 integrin expression. Results of a randomized controlled trial.",
"Randomized trial of granulocyte transfusions versus intravenous immune globulin therapy for neonatal neutropenia and sepsis.",
"A randomized, controlled trial of prophylactic granulocyte-macrophage colony-stimulating factor in human newborns less than 32 weeks gestation.",
"A randomized trial of granulocyte-macrophage colony-stimulating factor in neonates with sepsis and neutropenia."
] |
[
"The objective of this study was to investigate the effect of treatment with recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the neutrophil count and function of preterm neonates with documented sepsis. For this purpose 62 preterm neonates with proven sepsis and 19 healthy preterm ones were studied. Of the 62 patients, 27 septic neonates had an absolute neutrophil count (ANC) > 5000/mm3 (group A) and were scheduled not to receive rhG-CSF and 35/62 had an ANC < 5000/mm3 (n=35) and were randomly assigned either to receive rhG-CSF (group B) or not to receive it (group C). rhG-CSF (10 microg/kg) was administered for 3 consecutive days (0, 1, 2). The ANC, plasma levels of G-CSF (ELISA), neutrophil respiratory burst activity (NRBA) and neutrophil expression of CD11a, CD11b and CD11c (flow cytometry) were measured in all septic neonates on days 0 (onset of sepsis), 1, 3 and 5 and in the healthy neonates once within the first 2 days of life. We found that on day 0, G-CSF levels of all groups of septic neonates were significantly higher than those of the healthy ones. The highest levels were observed in group A. NRBA was diminished only in groups B and C and the expression of CD11a and CD11c was reduced in all groups of septic neonates. Administration of rhG-CSF resulted in a rapid and significant increase in ANC, NRBA and CD11a, CD11b and CD11c expression that persisted throughout the follow up. CONCLUSION; The administration of granulocyte colony stimulating factor to septic neonates significantly increases the absolute granulocyte count and enhances the neutrophil respiratory burst and beta2 integrin expression.",
"We prospectively studied newborn infants with sepsis and neutropenia who were randomly selected to receive standard supportive care and either adjuvant granulocyte transfusions or intravenous immune globulin (IVIG) infusions; 21 infants received granulocyte transfusions and 14 received IVIG infusions. Half of the patients were premature (gestational age less than or equal to 32 weeks); the average postnatal age was 5 days (range 3 to 8 days). All infants had neutropenia by the criteria of Manroe et al., and the mean average bone marrow neutrophil storage pool ranged between 35% and 37%. There were no significant differences with respect to serum IgG, IgA, IgM, and total hemolytic complement values between treatment groups or between survivors and nonsurvivors. Clinical severity as defined by hypoxia, acidosis, and hypotension was similar between treatment groups. Group B streptococcus was the most common organism identified and accounted for almost 33% of all bacterial isolates. There was a significantly different survival rate in the group receiving polymorphonuclear leukocyte transfusions (100%, 21/21) compared with the group receiving IVIG infusions (64%, 9/14; p = less than 0.03). There were no significant complications in either treatment group with respect to fluid overload, secondary infection, blood group sensitization, pulmonary complications, or graft-versus-host disease. This pilot study suggests a possible benefit of granulocyte transfusions compared with 'IVIG therapy in the adjuvant treatment of neonatal neutropenia and overwhelming bacterial sepsis.",
"Preterm neonates undergoing intensive care have high morbidity from sepsis. These infants also frequently develop neutropenia, and when this is associated with sepsis, mortality is high. This study investigates the potential for granulocyte-macrophage colony-stimulating factor (GM-CSF) to effect a clinically relevant increase in neutrophil number when used prophylactically in high-risk preterm neonates, and assesses its safety in this population.\n In an open, randomized, controlled study, 75 neonates (25 small for gestational age) <32 weeks gestation were randomized to receive GM-CSF (10 microg/kg/d) by subcutaneous injection for 5 days from <72 hours after birth, or to a control group. The primary outcome measure was the neutrophil count during 14 days from study entry. The infants were monitored for potential toxicity. Clinical outcomes, sepsis, and mortality, were recorded, but this initial study was not designed to address clinical benefit.\n Prophylactic GM-CSF therapy completely abolished neutropenia in treated infants, when both well and septic, throughout the period of study. Neutropenia (</=1.7 x 10(9)/L) developed in 16 of 39 control infants. Five control infants experienced an acute decrease in neutrophil count coincident with the onset of sepsis. There was no evidence of hematologic, respiratory, or gastrointestinal toxicity in treated infants. Treated infants had a trend to fewer symptomatic, blood culture positive septic episodes than controls during 2 weeks from study entry (11/36 vs 18/39).\n Five-day prophylactic GM-CSF completely abolishes postnatal neutropenia and sepsis-induced neutropenia in preterm neonates at high risk of sepsis, and so removes an important risk factor for sepsis and sepsis-related mortality.GM-CSF, preterm neonates, neutropenia, sepsis.",
"To determine whether adjunctive therapy with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) could reverse sepsis-associated neonatal neutropenia and improve neonatal survival and to assess its safety compared with conventional therapy in a control group.\n This prospective, randomized, controlled trial was performed in 60 infants with neutropenia and clinical signs of sepsis. A subcutaneous injection of rhGM-CSF (5 microgram/kg/day) was administered to 30 of the patients for 7 consecutive days. Hematologic parameters (absolute neutrophil, eosinophil, monocyte, lymphocyte counts, and platelet number) and outcome were compared with 30 conventionally treated (control) patients.\n Twenty-five patients from the GM-CSF-treated group and 24 from the conventionally treated group had early-onset sepsis (</=3 days' postnatal age), and the other 11 patients had late-onset sepsis (>3 days' postnatal age). There was no difference between groups in terms of birth weight; gestational age; gender; maturity; maternal age; and incidence of prolonged rupture of membranes, maternal hypertension, or severity of sepsis. All neonates tolerated GM-CSF well with no adverse reactions. The absolute neutrophil count on day 7 was significantly increased in the GM-CSF-treated group compared with the conventionally treated group: 8088 +/- 2822/mm(3) versus 2757 +/- 823/mm(3). The mean platelet count was significantly higher on days 14 in the GM-CSF-treated group compared with conventionally treated group: 266 867 +/- 55 102/mm(3) versus 229 200 +/- 52 317/mm(3). Hematologic parameters were otherwise similar between groups before treatment and on day 28. Twenty-seven neonates in the rh-GMCSF group and 21 in the control group survived to hospital discharge. The mortality rate in the rhGM-CSF group (10%) was significantly lower than in the conventionally treated group (30%).\n Treatment with rhGM-CSF is associated with an increase in absolute neutrophil, eosinophil, monocyte, lymphocyte, and platelet counts and decreased mortality in critically ill septic neutropenic neonates. These results suggest that rhGM-CSF may be effective in the treatment of neonatal sepsis with neutropenia, and further randomized trials are needed to confirm its beneficial effects."
] |
Currently, there is inconclusive evidence from randomised controlled trials (RCTs) to support or refute the routine use of granulocyte transfusions in neutropenic, septic neonates. Researchers are encouraged to conduct adequately powered multi-centre trials of granulocyte transfusions in neutropenic septic neonates.
|
CD003504
|
[
"11094034"
] |
[
"Endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal angioplasty : results of a prospective randomized study."
] |
[
"Inasmuch as endovascular brachytherapy (BT) has gained recent interest because of its inhibitory effect on mechanisms leading to restenosis after percutaneous transluminal angioplasty (PTA), we performed this randomized study to determine its efficacy for prophylaxis of restenosis after femoropopliteal PTA.\n One hundred thirteen patients (63 men, 50 women; mean age 71 years) with de novo or recurrent femoropopliteal lesions were included in this randomized trial comparing the restenosis rate after PTA plus BT (57 patients, PTA+BT group) versus PTA (56 patients, PTA group) without stent implantation. The mean treated length was 16.7 cm (PTA+BT group) versus 14.8 cm (PTA group). In patients randomized to PTA plus BT, a dose of 12 Gy was applied by an (192)Ir source 3 mm from the source axis. Follow-up examinations included measurement of the ankle-brachial index, color-flow duplex sonography, and angiography. The primary end point of the study was patency after 6 months. The overall recurrence rate after 6 months was 15 (28.3%) of 53 in the PTA+BT group versus 29 (53.7%) of 54 in the PTA group (chi(2) test, P<0.05). The cumulative patency rates at 12 months of follow-up were 63.6% in the PTA+BT group and 35.3% in the PTA group (log-rank test, P<0.005).\n This is the first randomized study to demonstrate the efficacy of endovascular BT for prophylaxis of restenosis after femoropopliteal PTA. The value of this approach should now be improved by modification of the BT procedure and by combination with stent implantation."
] |
Results from the only trial available would suggest that IVBT is effective at improving the patency of femoropopliteal arteries undergoing PTA in the short-term, particularly in non-diabetics with long occlusions (>10cm).
|
CD006338
|
[
"3924221",
"355879",
"15239532",
"3907510",
"20927359"
] |
[
"Chest physiotherapy in primary pneumonia.",
"Efficacy of chest physiotherapy and intermittent positive-pressure breathing in the resolution of pneumonia.",
"[Indications of conventional chest physiotherapy in acute bronchiolitis].",
"Chest physiotherapy in acute bronchiolitis.",
"Effectiveness of chest physiotherapy in infants hospitalized with acute bronchiolitis: a multicenter, randomized, controlled trial."
] |
[
"One hundred and seventy one patients with primary pneumonia entered a single blind, placebo controlled trial of physiotherapy. Treatment was allocated at random, physiotherapy consisting of postural drainage, external help with breathing, percussion, and vibration and the controls receiving advice on expectoration, deep breathing, and how to exercise to avoid thrombosis. Principles of pharmaceutical management were the same in the two groups. There was no objective evidence that daily physiotherapy helped during the acute phase of the disease. On the contrary, in younger patients, smokers, and patients with interstitial pneumonia physiotherapy appeared to prolong the duration of fever as well as the hospital stay. It is concluded that chest physiotherapy is at best useless in patients with primary infectious pneumonia.",
"We undertook a randomized clinical trial to evaluate the efficacy of chest physiotherapy and intermittent positive-pressure breathing in the treatment of pneumonia. The diagnosis of pneumonia required a compatible clinical history and x-ray confirmation. A total of 54 patients were assigned to treatment and control groups and were similar in age, smoking history, underlying lung disease and prior antibiotic treatment. Antibiotic therapy, guided by Gram stain and sputum and blood cultures, was similar in both groups. Chest physiotherapy, consisting of postural drainage, percussion and vibration, was given concurrently with intermittent positive-pressure breathing with use of racemic epinephrine every four hours. There was no statistically significant difference in duration of fever, extent of radiographic clearing, duration of hospital stay and mortality between the control and treated groups. Chest physiotherapy and intermittent positive-pressure breathing do not hasten the resolution of pneumonia.",
"To evaluate the benefits of conventional chest physiotherapy in acute bronchiolitis, 32 patients were allocated in a randomized controlled trial, 16 were given twice daily chest physiotherapy compared with 16 controls who were not given chest physiotherapy. The treatment group showed a mean clinical score for respiratory disability at admission of 5.56 (+/- 1.96), and 3.25 (+/- 1.27) when discharged. The control group presented a score of 5.75 (+/- 1.61) and 3.12 (+/- 1.30), p=0.77 and p=0.76 respectively. The mean length of illness in hospital in the treatment group was 4.00 (+/- 2.00) vs 3.87 (+/- 1.30) in the control group, p=0.84. Chest physiotherapy does not produce clinically important benefits in the treatment of acute bronchiolitis.",
"Forty four children with acute bronchiolitis were given twice daily chest physiotherapy in addition to standard supportive measures and were compared with 46 controls who were not given physiotherapy. There was no clinically discernable benefit on the course of their illness.",
"Acute bronchiolitis treatment in children and infants is largely supportive, but chest physiotherapy is routinely performed in some countries. In France, national guidelines recommend a specific type of physiotherapy combining the increased exhalation technique (IET) and assisted cough (AC). Our objective was to evaluate the efficacy of chest physiotherapy (IET + AC) in previously healthy infants hospitalized for a first episode of acute bronchiolitis.\n We conducted a multicenter, randomized, outcome assessor-blind and parent-blind trial in seven French pediatric departments. We recruited 496 infants hospitalized for first-episode acute bronchiolitis between October 2004 and January 2008. Patients were randomly allocated to receive from physiotherapists three times a day, either IET + AC (intervention group, n=246) or nasal suction (NS, control group, n=250). Only physiotherapists were aware of the allocation group of the infant. The primary outcome was time to recovery, defined as 8 hours without oxygen supplementation associated with minimal or no chest recession, and ingesting more than two-thirds of daily food requirements. Secondary outcomes were intensive care unit admissions, artificial ventilation, antibiotic treatment, description of side effects during procedures, and parental perception of comfort. Statistical analysis was performed on an intent-to-treat basis. Median time to recovery was 2.31 days, (95% confidence interval [CI] 1.97-2.73) for the control group and 2.02 days (95% CI 1.96-2.34) for the intervention group, indicating no significant effect of physiotherapy (hazard ratio [HR]=1.09, 95% CI 0.91-1.31, p=0.33). No treatment by age interaction was found (p=0.97). Frequency of vomiting and transient respiratory destabilization was higher in the IET + AC group during the procedure (relative risk [RR]=10.2, 95% CI 1.3-78.8, p=0.005 and RR=5.4, 95% CI 1.6-18.4, p=0.002, respectively). No difference between groups in bradycardia with or without desaturation (RR=1.0, 95% CI 0.2-5.0, p=1.00 and RR=3.6, 95% CI 0.7-16.9, p=0.10, respectively) was found during the procedure. Parents reported that the procedure was more arduous in the group treated with IET (mean difference=0.88, 95% CI 0.33-1.44, p=0.002), whereas there was no difference regarding the assessment of the child's comfort between both groups (mean difference=-0.07, 95% CI -0.53 to 0.38, p=0.40). No evidence of differences between groups in intensive care admission (RR=0.7, 95% CI 0.3-1.8, p=0.62), ventilatory support (RR=2.5, 95% CI 0.5-13.0, p=0.29), and antibiotic treatment (RR=1.0, 95% CI 0.7-1.3, p=1.00) was observed.\n IET + AC had no significant effect on time to recovery in this group of hospitalized infants with bronchiolitis. Additional studies are required to explore the effect of chest physiotherapy on ambulatory populations and for infants without a history of atopy.\n ClinicalTrials.gov NCT00125450."
] |
Based on current limited evidence, chest physiotherapy might not be recommended as routine additional treatment for pneumonia in adults.
|
CD000209
|
[
"8601552",
"7914238",
"9627740",
"9455695",
"11248360",
"19494439",
"12892048",
"15086477",
"15930443"
] |
[
"A double-blind placebo-controlled study of vitamin E treatment of tardive dyskinesia.",
"Vitamin E in the treatment of tardive dyskinesia.",
"Long-term treatment effects of vitamin E for tardive dyskinesia.",
"Vitamin E improves the aminotransferase status of patients suffering from viral hepatitis C: a randomized, double-blind, placebo-controlled study.",
"Vitamin E as treatment for chronic hepatitis B: results of a randomized controlled pilot trial.",
"Vitamin E paradox in Alzheimer's disease: it does not prevent loss of cognition and may even be detrimental.",
"Vitamin E treatment for tardive dyskinesia. Veterans Affairs Cooperative Study #394 Study Group.",
"Effects of vitamin E on cardiovascular outcomes in people with mild-to-moderate renal insufficiency: results of the HOPE study.",
"Daily supplementation with (n-3) PUFAs, oleic acid, folic acid, and vitamins B-6 and E increases pain-free walking distance and improves risk factors in men with peripheral vascular disease."
] |
[
"This study was designed to determine if vitamin E is effective in reducing the severity of abnormal movements in patients with tardive dyskinesia (TD).\n Thirty-five patients completed a double-blind placebo-controlled parallel-group study of vitamin E. Seventeen of the patients were randomly assigned to receive 800 IU b.i.d. of vitamin E and 18 were assigned to placebo for 2 months. Twenty-nine patients had a diagnosis of schizophrenia and 6 of mood disorder. Patients were assessed using modified versions of the Abnormal Involuntary Movement Scale (mAIMS), Simpson-Angus Scale for extrapyramidal side effects, and Brief Psychiatric Rating Scale. Additionally, a subgroup of 23 patients were assessed using instrumental measurements of dyskinesia.\n There was a significant reduction of dyskinesia in the vitamin E group, but not the placebo group, on both the mAIMS and the instrumental assessments. The overall reduction in mAIMS in the active group was 24%, with 5 (29%) of 17 patients demonstrating greater than 33% reduction in score. There was a greater reduction in mean mAIMS score (35%) with vitamin E in the subgroup of patients with TD for 5 years or less compared with the reduction (11%) in patients with TD for greater than 5 years. No change was observed in parkinsonism. In the patients with schizophrenia, there was a reduction in positive symptoms after vitamin E.\n Vitamin E appears to be effective in reducing the severity of TD, especially in patients who have had TD for 5 years or less.",
"In a double-blind placebo controlled trial, the efficacy of Vitamin E in the treatment of tardive dyskinesia (TD) was studied in 32 patients. After a two week wash-out phase a baseline (0 week) TD rating was assessed on the tardive dyskinesia rating scale (TDRS). Subsequently, the patients entered a four week treatment phase during which 17 patients received capsules of vitamin E (600 mg) and 15 patients received identical placebo capsules. In the first week the patients received 1 capsule daily which was then increased to two capsules per day from the second to the fourth week. All patients were rated on the TDRS at the end of each week. The baseline TDRS score in the vitamin E group was significantly higher than the placebo group. This was hence adjusted and the results were then subjected to analysis of co- variance. The TDRS score after four weeks treatment was significantly lower in the vitamin E group as compared to the placebo group (p = 0.03).",
"Several studies have found that alpha-tocopherol (vitamin E) can effectively treat tardive dyskinesia (TD). A limitation of these trials is their short treatment durations (maximum of 12 weeks), which do not allow us to address the effects of long-term treatment.\n To participate, patients had to have TD and be on stable oral medications. The study enrolled 40 patients who received up to 36 weeks of treatment with d-vitamin E (1600 IU per day) or placebo.\n Using the Abnormal Involuntary Movements Scale (AIMS) score (sum of items #1-7) to measure TD severity, the study found a significant difference (3 points) in mean AIMS scores, in favor of vitamin E, starting at 10 weeks of treatment and continuing through the full 36 weeks. We used linear mixed-effects regression to quantify the impact of several covariates, and found that treatment assignment. TD duration, and chlorpromazine equivalents had significant effects on decreasing the AIMS score.\n The study's finding that vitamin E is effective in treating TD agrees with results from prior studies and provides evidence that the effect may extend to treatment of up to 36 weeks. These findings are in direct contrast to those of VA Cooperative Study #394, a much larger, long-term, multi-site study, conducted by many of the same investigators, in which Vitamin E was not superior to placebo.",
"Vitamin E has been shown to protect against liver damage induced by oxidative stress in animal experiments. Based on our previous findings of diminished vitamin E levels in patients suffering from viral hepatitis, we treated 23 hepatitis C patients refractory to alpha-interferon therapy with high doses of vitamin E (2 x 400 IU RRR-alpha-tocopherol/day) for 12 weeks. Study design: pro-spective randomized double-blind crossover design. Clinical parameters including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined for monitoring the disease state, in parallel vitamin E plasma levels and plasma lipids were determined. The plasma levels of the alpha-tocopherol were increased about 2-fold in all 23 patients. In 11 of 23 patients the clinical parameters indicative of liver damage were improved during the phase of vitamin E treatment (48% responders). ALT levels in responders were lowered by 46% and AST levels were lowered by 35% after 12 weeks of vitamin E treatment. Cessation of vitamin E treatment was followed by a rapid relapse of ALT and AST elevation, whereas retreatment led to a reproducible ALT decrease by 45% and AST decrease of 37% after a 6 months followup. Since vitamin E is non-toxic even at elevated doses ingested over extended periods, we suggest the treatment of patients refractory to alpha-interferon therapy suffering from hepatitis C with vitamin E as a supportive therapy.",
"Interferon-alpha treatment has been the treatment of choice for chronic hepatitis with unpredictable results. Recently, Lamivudine has been licensed for use against HBV infection with good results. Unfortunately, recurrence of viremia after lamivudine withdrawal is common and prolonged treatment can induce the emergence of resistant mutant strains. It has been shown that vitamin E can increase the host immune response, and this may provide protection against infectious diseases.\n We evaluated vitamin E supplementation as therapy for chronic hepatitis B in a pilot study including 32 patients. Patients were randomly allocated to receive vitamin E at the dose of 300 mg twice daily for 3 months (15 patients) or no treatment (17 patients). They were seen monthly during the first 3 months and thereafter quarterly for additional 12 months.\n The two groups were comparable at enrollment. At the end of the study period, alanine aminotransferase (ALT) normalization was observed in 7 (47%) patients in vitamin E group and only in 1 (6%) of the controls (P=0.011); HBV-DNA negativization was observed in 8 (53%) patients in the vitamin E group as compared to 3 (18%) in the control group, respectively (P=0.039). A complete response (normal ALT and negative HBV-DNA) was obtained in 7 (47%) patients taking vitamin E and in none of the controls (P=0.0019).\n Vitamin E supplementation might be effective in the treatment of chronic hepatitis B.",
"There is controversy as to whether vitamin E is beneficial in Alzheimer's disease (AD). In this study, we tested if vitamin E prevents oxidative stress and loss of cognition in AD. Fifty-seven AD patients were recruited and divided in two groups: placebo or treated with 800 IU of vitamin E per day for six months. Of these 57 patients, only 33 finished the study. We measured blood oxidized glutathione (GSSG) and used the following cognitive tests: Mini-Mental State Examination, Blessed-Dementia Scale, and Clock Drawing Test. Of those patients treated with vitamin E, we found two groups. In the first group, \"respondents\" to vitamin E, GSSG levels were lower after the treatment and scores on the cognitive tests were maintained. The second group, \"non-respondents\", consisted of patients in which vitamin E was not effective in preventing oxidative stress. In these patients, cognition decreased sharply, to levels even lower than those of patients taking placebo. Based on our findings, it appears that vitamin E lowers oxidative stress in some AD patients and maintains cognitive status, however, in those in which vitamin E does not prevent oxidative stress, it is detrimental in terms of cognition. Therefore, supplementation of AD patients with vitamin E cannot be recommended without determination of its antioxidant effect in each patient.",
"Several short-term, controlled trials have documented the efficacy of vitamin E in treating tardive dyskinesia. However, the persistent nature of the disease prompted us to perform a multicenter, longer-term trial of vitamin E.\n The study was a prospective, randomized, 9-site trial of up to 2 years of treatment with d-vitamin E (1600 IU/d) vs matching placebo. One hundred fifty-eight subjects with tardive dyskinesia who were receiving neuroleptic medications were enrolled. The blinded assessments performed were clinical (Abnormal Involuntary Movements Scale, Barnes Akathisia Scale, and Modified Simpson-Angus [for Extrapyramidal Symptoms] Scale) and electromechanical assessments of movement disorders, psychiatric status (Brief Psychiatric Rating Scale), and functioning (Global Assessment of Functioning). There were no significant differences in baseline demographic characteristics or in study assessments between the group that received vitamin E and the group that received placebo.\n Vitamin E was well tolerated and subject compliance with medication was good and similar between treatment groups. One hundred seven subjects (70% of those receiving vitamin E and 66% of subjects receiving placebo) completed at least 1 year of treatment. There were no significant effects of vitamin E on total scores or subscale scores for the AIMS, electromechanical measures of dyskinesia, or scores from the other 4 scales.\n This long-term, randomized trial of vitamin E vs placebo found no evidence for efficacy of vitamin E in the treatment of tardive dyskinesia.",
"A controlled trial reported cardiovascular benefits of vitamin E in terminal renal insufficiency. There are no data for renal insufficiency before the stage of terminal renal failure. We evaluated effects of vitamin E supplementation on cardiovascular and renal outcomes in 993 people with a serum creatinine > or =1.4 to 2.3 mg/dL.\n Post-hoc analysis of a randomized trial that compared treatment with natural source vitamin E (400 IU/day) to placebo in 9541 people, 993 of which had renal insufficiency. Participants had either known cardiovascular disease or diabetes and at least one additional coronary risk factor. Exclusion criteria included a serum creatinine > 2.3 mg/dL and dipstick-positive proteinuria. The primary study outcome after an average of 4.5 years was the composite of myocardial infarction, stroke, or cardiovascular death. Secondary outcomes included revascularizations, total mortality, and clinical proteinuria.\n In renal insufficiency, vitamin E supplementation had a neutral effect on the primary study outcome, on each component of the composite primary outcome, and on all secondary outcomes. Two hundred twenty-four primary outcomes, 23% of the vitamin E group and 22.1% of the placebo group, relative risk 1.03 (95% CI, 0.79-1.34; P= 0.82), were observed, and 585 secondary outcomes, including death in 17% and 18.8% of the vitamin E and placebo groups, respectively (RR 0.88, 95% CI, 0.66-1.18; P= 0.40). There was no effect of vitamin E on progression of proteinuria.\n In people with mild-to-moderate renal insufficiency at high cardiovascular risk, vitamin E at a dose of 400 IU/day had no apparent effect on cardiovascular outcomes.",
"A number of nutrients are known to be effective in preventing cardiovascular disease (CVD). We investigated the possible effects of a daily intake of low amounts of these nutrients on risk factors and clinical parameters in patients with peripheral vascular disease and intermittent claudication (PVD-IC). Male PVD-IC patients (n = 60) were randomly allocated into 2 groups. The supplement (S) group consumed 500 mL/d of a fortified dairy product containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), oleic acid, folic acid, and vitamins A, B-6, D, and E. The control (C) group consumed 500 mL/d of semiskimmed milk with added vitamins A and D. The patients received lifestyle and dietary recommendations, and they were instructed to consume the products in addition to their regular diet. Blood extractions and clinical explorations were performed after 0, 3, 6, 9, and 12 mo. Plasma concentrations of EPA, DHA, oleic acid, folic acid, and vitamins B-6 and E increased after treatment with supplements (P < 0.05). Plasma total cholesterol and ApoB concentrations decreased in the S group, and total homocysteine decreased in those patients with high initial concentrations. Walking distance before the onset of claudication increased in the S group (P < 0.001), and ankle-brachial pressure index values increased (P < 0.05). The inclusion in the everyday diet of certain nutrients known to promote cardiovascular health improved clinical outcomes while reducing a variety of risk factors in men with PVD-IC, providing new evidence of the potential role of nutrition in the reduction of PVD-IC symptoms."
] |
Small trials of limited quality suggest that vitamin E may protect against deterioration of TD. There is no evidence that vitamin E improves symptoms of this problematic and disfiguring condition once established. New and better trials are indicated in this under-researched area, and, of the many adjunctive treatments that have been given for TD, vitamin E would be a good choice for further evaluation.
|
CD002825
|
[
"9692071",
"9652994",
"7599447",
"2407957",
"3111669",
"8135445",
"9207281",
"1790403",
"8695970",
"6276746",
"9552083"
] |
[
"Fluoride salts are no better at preventing new vertebral fractures than calcium-vitamin D in postmenopausal osteoporosis: the FAVOStudy.",
"The effect of sodium monofluorophosphate plus calcium on vertebral fracture rate in postmenopausal women with moderate osteoporosis. A randomized, controlled trial.",
"Monofluorophosphate increases lumbar bone density in osteopenic patients: a double-masked randomized study.",
"Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis.",
"The effect of fluoride and calcium on spinal bone mineral content: a controlled, prospective (3 years) study.",
"Slow-release sodium fluoride in the management of postmenopausal osteoporosis. A randomized controlled trial.",
"Etidronate versus fluoride for treatment of osteopenia in primary biliary cirrhosis: preliminary results after 2 years.",
"A randomized trial of sodium fluoride as a treatment for postmenopausal osteoporosis.",
"Treatment of postmenopausal vertebral osteopenia with monofluorophospate: a long-term calcium-controlled study.",
"Effect of the fluoride/calcium regimen on vertebral fracture occurrence in postmenopausal osteoporosis. Comparison with conventional therapy.",
"A four-year randomized controlled trial of hormone replacement and bisphosphonate, alone or in combination, in women with postmenopausal osteoporosis."
] |
[
"Although fluoride salts have been shown to be capable of linearly increasing spinal bone mineral density (BMD) in postmenopausal osteoporosis, the effects of this gain in density on the vertebral fracture rate remain controversial. We conducted a 2-year multicenter, prospective, randomized, double-masked clinical trial in 354 osteoporotic women with vertebral fractures (mean age 65.7 years). They received either fluoride (208 patients), given as sodium fluoride (50 mg/day) or as monofluorophosphate (200 mg/day or 150 mg/day), or a placebo (146 patients). All patients received daily supplements of 1 g of calcium (Ca) and 800 IU of vitamin D2 (D). A 1-year open follow-up on Ca-D was obtained in 124 patients. After 2 years the fluoride group and the Ca-D group had increased their lumbar BMD by 10.8% and 2.4% respectively (p = 0.0001). However, the rate of patients with at least one new vertebral fracture, defined by semiquantitative assessment and evaluable on an intention-to-treat basis in 89% of patients, was similar in the fluoride groups and the Ca-D group. No difference between the three fluoride regimens was found. The percentage of patients with nonvertebral fractures was not different in the fluoride and Ca-D groups (1.9% and 1.4% respectively for hip fractures). A lower limb pain syndrome occurred more frequently in the fluoride groups. In the 124 patients followed for 1 year after cessation of fluoride therapy, the percentage of patients with at least one new vertebral fracture after 36 months was identical to the percentages in the previous fluoride group and the Ca-D group. We conclude that fluoride-Ca-D regimen was no more effective that Ca-D supplements for the prevention of new vertebral fractures in women with postmenopausal osteoporosis.",
"Fluoride is effective in increasing trabecular bone mineral density (BMD) in the spine, but its efficacy in reducing vertebral fracture rates and its effect on BMD at cortical sites are controversial.\n To study the effect of low-dose fluoride (sodium monofluorophosphate [MFP]) plus a calcium supplement over 4 years on vertebral fractures and BMD at the lumbar spine and total hip in postmenopausal women with moderately low BMD of the spine.\n Randomized, double-blind, controlled clinical trial.\n Outpatient clinic for osteoporosis at a university medical center.\n 200 postmenopausal women with osteoporosis (according to the World Health Organization definition) and a T-score less than -2.5 for BMD of the spine.\n Women were randomly assigned (100 patients per group) to continuous daily treatment for 4 years with 1) oral MFP (20 mg of equivalent fluoride) plus 1000 mg of calcium (as calcium carbonate) or 2) calcium only.\n Lateral spine radiographs were taken at enrollment and at each year of follow-up for detection of new vertebral fractures (defined as a reduction > or =20% and > or =4 mm from baseline in any of the heights of a vertebral body). Nonvertebral fractures were also recorded. All analyses were done with the intention-to-treat approach.\n Radiologic follow-up was possible for 164 of 200 patients (82%). The rate of new vertebral fractures during the 4 years of the study was lower in the MFP-plus-calcium group (2 of 84 patients; 2.4% [95% CI, 0.3% to 8.3%]) than in the calcium-only group (8 of 80 patients; 10% [CI, 4.4% to 18.8%]). The difference between the groups was 7.6 percentage points (CI, 0.3 to 15 percentage points) (P = 0.05). A moderate but progressive increase in BMD of the spine (10.0% +/- 1.5% at 4 years) was found for MFP plus calcium compared with calcium only (P < 0.001), whereas the more modest increase in BMD of the total hip seen with MFP plus calcium (1.8% +/- 0.6%) did not differ from the increase seen with calcium only.\n Low-dose fluoride (20 mg/d) given continuously with calcium for prolonged periods can decrease vertebral fracture rates compared with calcium alone in patients with mild to moderate osteoporosis.",
"To assess the efficacy of combined sodium monofluorophosphate and calcium therapy (FC) in increasing lumbar bone mineral density (BMD) in patients with low bone mass, we conducted a prospective double-masked randomized study in 94 patients aged 50-70 years. Patients were selected on the basis of a lumbar BMD at least 2 standard deviations (SD) below the young adult mean (T-score) but without evidence of previous vertebral fracture (severe osteopenia). They were randomly assigned to receive for 2 years, twice a day, either FC (13.2 mg F-, i.e. 100 mg sodium monofluorophosphate, and 500 mg Ca2+) or C (500 mg Ca2+). Vertebral BMD was measured by dual photon absorptiometry from L2 to L4. Comparison at final assessment in the 76 eligible patients (Student's t-test) showed a statistically significant difference between the two groups in the mean BMD increase in favour of FC. Furthermore, Student's t-test showed a significantly greater increase in lumbar BMD in FC-treated patients at 1 year, at 18 months and after 2 years (mean increase of 7.1%/year). These results were confirmed by ANOVA at 1 year, at 18 months and after 2 years of treatment. Of the FC-treated patients, 71.4% were considered to have responded (i.e. they showed an increase in lumbar BMD of more than 0.034 g/cm2). The dosage of 26.4 mg fluoride ion/day (i.e. 200 mg monofluorophosphate/day) therefore appears to be safe and to increase the BMD effectively in patients with low bone mass prior to vertebral fracture.",
"Although fluoride increases bone mass, the newly formed bone may have reduced strength. To assess the effect of fluoride treatment on the fracture rate in osteoporosis, we conducted a four-year prospective clinical trial in 202 postmenopausal women with osteoporosis and vertebral fractures who were randomly assigned to receive sodium fluoride (75 mg per day) or placebo. All received a calcium supplement (1500 mg per day). Sixty-six women in the fluoride group and 69 women in the placebo group completed the trial. As compared with the placebo group, the treatment group had increases in median bone mineral density of 35 percent (P less than 0.0001) in the lumbar spine (predominantly cancellous bone), 12 percent (P less than 0.0001) in the femoral neck, and 10 percent (P less than 0.0001) in the femoral trochanter (sites of mixed cortical and cancellous bone), but the bone mineral density decreased by 4 percent (P less than 0.02) in the shaft of the radius (predominantly cortical bone). The number of new vertebral fractures was similar in the treatment and placebo groups (163 and 136, respectively; P not significant), but the number of nonvertebral fractures was higher in the treatment group (72 vs. 24; P less than 0.01). Fifty-four women in the fluoride group and 24 in the placebo group had side effects sufficiently severe to warrant dose reduction; the major side effects were gastrointestinal symptoms and lower-extremity pain. We conclude that fluoride therapy increases cancellous but decreases cortical bone mineral density and increases skeletal fragility. Thus, under the conditions of this study, the fluoride-calcium regimen was not effective treatment for postmenopausal osteoporosis.",
"Daily treatment with 30 mg of sodium fluoride (NaF) and 1 g of calcium over a 3-year period increased the bone mineral content (BMC) in the spines of women (n = 25) with osteoporosis. Determination of the BMC was followed with dual photon absorptiometry (137Cs-241Am) in the third lumbar vertebra. No increase in BMC was found with only 10 mg sodium fluoride in combination with calcium (n = 25), with calcium alone (n = 25), or with placebo (n = 25). No serious side effects were registered. There was, however, minor gastrointestinal distress in one-fifth of the patients taking 30 mg NaF daily.",
"To test whether intermittent treatment with slow-release sodium fluoride and continuous calcium citrate supplementation inhibits vertebral fractures without causing fluoride complications.\n A placebo-controlled, randomized trial.\n Outpatient setting of specialty clinics in Dallas and Temple, Texas.\n Slow-release sodium fluoride (25 mg twice daily) in repeated 14-month cycles (12 months on treatment followed by 2 months off treatment) compared with placebo. Both groups took calcium citrate (400 mg calcium twice daily) continuously.\n 110 patients with postmenopausal osteoporosis were randomly assigned to two groups. In the slow-release sodium fluoride group, 48 of 54 patients completed more than 1 cycle of treatment (mean, 2.44 cycles/patient), whereas 51 of 56 patients in the placebo group completed at least 1 cycle (mean, 2.14 cycles/patient) in this interim analysis.\n Vertebral fracture rate and lumbar bone mineral content. Vertebral fractures were quantified from yearly radiographs. Bone mass was determined annually by densitometry.\n In the sodium fluoride group, the mean L2 to L4 bone mineral content increased by 4% to 6% in each cycle and the mean femoral neck bone density increased by 4.1% and 2.1% during the first two cycles, but the radial bone density did not change. The placebo group showed no statistical change in bone mass at any site. Compared with the placebo group, the sodium fluoride group had a lower individual new vertebral fracture rate (0.057/patient cycle compared with 0.204/patient cycle, P = 0.017), a higher fracture-free rate (83.3% compared with 64.7%, P = 0.042), and a lower group fracture rate (0.085/patient cycle compared with 0.239/patient cycle, P = 0.006). The side-effect profile was similar for the two groups; no patient developed microfractures, hip fractures, or blood loss anemia.\n Intermittent slow-release sodium fluoride plus continuous calcium citrate, administered for about 2.5 years, inhibits new vertebral fractures, increases the mean spinal bone mass without decreasing the radial shaft bone density, and is safe to use.",
"Because osteopenia increases morbidity of primary biliary cirrhosis (PBC), the effects of cyclical etidronate vs. sodium fluoride on bone mass were compared in patients with PBC.\n Thirty-two women with PBC were randomly assigned to receive etidronate (400 mg/day during 14 days every 3 months) or fluoride (50 mg/day, enteric-coated tablets). Bone mineral density of the lumbar spine and proximal femur were measured initially and every 6 months. Bone fractures were also evaluated.\n Sixteen patients were allocated into each group, which were comparable with respect to the severity of PBC and osteopenia. Thirteen patients with etidronate and 10 patients with fluoride completed 2 years in the study. In the etidronate group, bone mineral density increased in the lumbar spine (P = 0.02) and did not change in the proximal femur. In the fluoride group, lumbar bone mineral density did not change but femoral bone mass decreased, particularly in the Ward's triangle. Two patients in the fluoride and none in the etidronate group developed new vertebral fractures, and the number of new nonvertebral fractures was similar in both groups. Neither treatment impaired liver function or cholestasis.\n Cyclical etidronate is more effective and better tolerated than sodium fluoride in preventing bone loss in PBC.",
"The anti-fracture efficacy of sodium fluoride (NaF) was evaluated in 84 postmenopausal white women with spinal osteoporosis. The dose of NaF used was 75 mg/day and all patients in this prospective, randomized, double-blind, placebo-controlled clinical trial received calcium supplements (carbonate salt) 1500 mg/day in addition to participating in a structured physical therapy program. For each of the outcome measures (change in stature, change in cortical bone mass in the forearm and development of new vertebral fractures determined by change in vertebral morphometry and by scintigraphy) there was no significant difference between the fluoride or placebo treated groups. Side effects, predominantly gastrointestinal symptoms and the development of the painful lower extremity syndrome, occurred significantly more frequently in the fluoride group (P less than 0.05). Peripheral fractures were not more frequent in the fluoride group. We conclude that, in the dose and manner used in this study, NaF is no more effective than placebo in retarding the progression of spinal osteoporosis. There is no role for NaF in the treatment of osteoporosis outside the confines of clinical research.",
"The aim of the present study was to assess the effects of the new fluorine pro-drug monofluorophosphate (MFP) in postmenopausal women with vertebral osteopenia and high bone turnover. We enrolled postmenopausal women (PMW, 43-59 years) who had had a natural menopause 2-5 years before the study, had vertebral bone mineral density (BMD) < 1 SD from the premenopausal mean, and had at least one of the biochemical markers of bone remodeling > 1 SD over the mean for premenopausal women. Patients were randomly divided into two treatment groups (group 1, 500 mg/day of oral calcium; group 2, MFP at the dose of 20 mg F-equivalents + 600 mg calcium/day) for 2 years (n = 21 in each group). The lumbar vertebral (L2-4) BMD and total body bone mineral (TBBM) were measured by dual-energy X-ray absorptiometry (Lunar DPX, Lunar Corporation, USA). Urinary hydroxyproline excretion (OH-P/Cr), plasma bone Gla protein (BGP) and serum alkaline phosphatase (AP) were assayed. In group 1 the markers of bone turnover and vertebral BMD did not show any significant modification, while TBBM showed a significant (p < 0.05) decrease after 24 months. In group 2 a significant (p < 0.05) decrease in OH-P/Cr (-23.9 +/- 2.0%), and an increase in both BGP (+19.4 +/- 2.6%) and AP (+10.3 +/- 2.6%) levels were observed after 24 months of MFP administration. In this group, both vertebral BMD (+5.01 +/- 0.9%, p < 0.01) and TBBM (+4.0 +/- 0.6%, p < 0.05) showed a significant increase after 24 months. Present results suggest that, in osteopenic PMW, MFP administration induces a significant increase in vertebral BMD without impairment of cortical bone, with a reduction in bone resorption and an increase in bone formation rate.",
"We assessed the rates of vertebral fracture in patients with postmenopausal osteoporosis. Forty-five patients were not treated (91 person-years of observation); 59 were treated conventionally, with calcium (alone or combined with estrogen) or vitamin D or both (218 years); and 61 were treated with sodium fluoride combined with conventional therapy (251 years). The fracture rate (per thousand person-years) was 834 in untreated patients, 419 in those given calcium with or without vitamin D, 304 in those given fluoride and calcium with or without vitamin D, 181 in those given estrogen and calcium with or without vitamin D, and 53 in those given fluoride, estrogen, and calcium with or without vitamin D. It was reduced in all treatment groups (P less than 0.001 for calcium and P less than 1 x 10(-6) for other combinations); fluoride (one years of treatment) and estrogen (but not vitamin D) independently reduced the rate from that observed with calcium alone (P less than 0.001). The combination of calcium fluoride, and estrogen was more effective than any other combination (P less than 0.001). These results provide grounds for optimism about the efficacy of combinations of available agents with sodium fluoride for fracture in postmenopausal osteoporosis.",
"Hormone replacement therapy (HRT) with estrogen and treatment with bisphosphonates have been shown to increase bone mineral density (BMD) in postmenopausal women. This 4-year prospective randomized study was carried out to assess the effectiveness of the combined HRT plus etidronate on BMD in postmenopausal women with established osteoporosis.\n Seventy-two postmenopausal women (mean age 64.9+/-0.5 years) attending metabolic bone disease outpatient clinics with established osteoporosis were randomly allocated into one of four treatment groups and monitored for 4 years. All patients enrolled in this study including the control group (n=18) received 1.0 g elemental calcium and 400 units vitamin D per day. The HRT group (n=18) received cyclical estrogen and progesterone; the etidronate group (n=17) received intermittent cyclical etidronate; and the combined therapy group (n=19) received both HRT and etidronate. BMD was measured in the lumbar spine and the hip before treatment and at 2 and 4 years after treatment. Changes in height were recorded, and the occurrence of new vertebral fractures were documented in comparison with the baseline radiographic evaluation. In 40 patients (10 patients per group), analysis of bone histomorphometry was carried out after 4 years of treatment.\n In patients who received the combined therapy, BMD increased in the lumbar spine by 10.4% (P <0.001) and in the hip by 7.0% (P <0.001) at 4 years. For patients treated with ICE, these increases were 7.3% (P <0.001) and 0.9% (P <0.05), and with HRT, the increases were 7.0% (P <0.001) and 4.8% (P <0.01) in the vertebrae and femora, respectively. The group treated with calcium and vitamin D lost 2.5% (P <0.05) and 4.4% (P <0.01) of BMD in the vertebrae and femora, respectively, after 4 years. Patients who received combined therapy had significantly higher BMD in both the vertebrae and in the femora (P <0.05) in comparison with patients who were treated with HRT or etidronate alone after 4 years. In comparison with patients in the control group, there was a trend toward a lower rate of new vertebral fractures in the treatment groups. Height loss was significantly less in all three active treatment groups (HRT [P <0.001], etidronate [P <0.02], and combined therapy group [P <0.0001]), in comparison with the control group. The combined therapy group did not have a significant height loss, in comparison with the HRT (P <0.02) and the etidronate (P <0.001) groups. None of the patients had histomorphometric evidence of osteomalacia.\n This 4-year randomized study showed an additive effect of etidronate and HRT on hip and spine BMD in postmenopausal women with established osteoporosis."
] |
Although fluoride has an ability to increase BMD at lumbar spine, it does not result in a reduction of vertebral fractures. In increasing the dose of fluoride, one increases the risk of non-vertebral fracture and gastrointestinal side effects without any effect on the vertebral fracture rate.
|
CD004058
|
[
"10515020",
"11458140",
"11224865",
"8929263",
"10957696",
"9414052",
"9106321",
"8127332"
] |
[
"Randomized trial of radiofrequency lumbar facet denervation for chronic low back pain.",
"Radiofrequency facet joint denervation in the treatment of low back pain: a placebo-controlled clinical trial to assess efficacy.",
"Randomized controlled trial of percutaneous intradiscal radiofrequency thermocoagulation for chronic discogenic back pain: lack of effect from a 90-second 70 C lesion.",
"Percutaneous radio-frequency neurotomy for chronic cervical zygapophyseal-joint pain.",
"Psychological predictors of the effectiveness of radiofrequency lesioning of the cervical spinal dorsal ganglion (RF-DRG).",
"Resolution of psychological distress of whiplash patients following treatment by radiofrequency neurotomy: a randomised, double-blind, placebo-controlled trial.",
"Local and remote sustained trigger point therapy for exacerbations of chronic low back pain. A randomized, double-blind, controlled, multicenter trial.",
"Lack of effect of intraarticular corticosteroids for chronic pain in the cervical zygapophyseal joints."
] |
[
"A prospective double-blind randomized trial in 31 patients.\n To assess the clinical efficacy of percutaneous radiofrequency denervation of the lumbar zygapophysial joints in reducing pain, functional disability, and physical impairment in patients with back pain originating from the lumbar zygapophysial joints.\n Chronic low back pain is a major health problem in the industrialized world. A treatment option is percutaneous radiofrequency denervation of the lumbar zygapophysial joints. Its clinical efficacy has never been formally tested in a controlled trial.\n Thirty-one patients with a history of at least 1 year of chronic low back pain were selected on the basis of a positive response to a diagnostic nerve blockade and subsequently randomly assigned to one of two treatment groups. Each patient in the radiofrequency treatment group (15 patients) received an 80 C radiofrequency lesion of the dorsal ramus of the segmental nerve roots L3, L4, and L5. Patients in the control group (n = 16) underwent an the same procedure but without use of a radiofrequency current. Both the treating physician and the patients were blinded to the group assignment. Before treatment, physical impairment, rating of pain, the degree of disability, and quality of life were assessed by a blinded investigator.\n Eight weeks after treatment, there were 10 success patients in the radiofrequency group (n = 15) and 6 in the sham group (n = 16). The unadjusted odds ratio was 3.3 (P = 0.05, not significant), and the adjusted odds ratio was 4.8 (P < 0.05, significant). The differences in effect on the visual analog scale scores, global perceived effect, and the Oswestry disability scale were statistically significant. Three, 6, and 12 months after treatment, there were significantly more success patients in the radiofrequency group compared with the sham group.\n Radiofrequency lumbar zygapophysial joint denervation results in a significant alleviation of pain and functional disability in a select group of patients with chronic low back pain, both on a short-term and a long-term basis.",
"A prospective double-blind randomized controlled trial was performed.\n To assess the efficacy of percutaneous radiofrequency articular facet denervation for low back pain.\n Uncontrolled observational studies in patients with low back pain have reported some benefits from the use of facet joint radiofrequency denervation. Because the efficacy of percutaneous radiofrequency had not been clearly shown in previous studies, a randomized controlled trial was conducted to assess the efficacy of the technique for improving functional disabilities and reduce pain.\n For this study, 70 patients with low back pain lasting of more than 3 months duration and a good response after intraarticular facet injections under fluoroscopy were assigned randomly to receive percutaneous radiofrequency articular facet denervation under fluoroscopic guidance or the same procedure without effective denervation (sham therapy). The primary outcomes were functional disabilities, as assessed by the Oswestry and Roland-Morris scales, and pain indicated on a visual analog scale. Secondary outcomes included spinal mobility and strength.\n At 4 weeks, the Roland-Morris score had improved by a mean of 8.4% in the neurotomy group and 2.2% in the placebo group, showing a treatment effect of 6.2% (P = 0.05). At 4 weeks, no significant treatment effect was reflected in the Oswestry score (0.6% change) or the visual analog pain score (4.2% change). At 12 weeks, neither functional disability, as assessed by the Roland-Morris scale (2.6% change) and Oswestry scale (1.9% change), nor the pain level, as assessed by the visual analog scale (-7.6% change), showed any treatment effect.\n Although radiofrequency facet joint denervation may provide some short-term improvement in functional disability among patients with chronic low back pain, the efficacy of this treatment has not been established.",
"A prospective double-blind randomized trial in 28 patients.\n To assess the clinical effect of percutaneous intradiscal radiofrequency thermocoagulation for reducing pain, functional disability, and physical impairment in patients with chronic discogenic low back pain.\n Chronic discogenic low back pain is a challenging problem in western countries. A treatment option is radiofrequency heating of the affected disc. Its clinical efficacy has never been formally tested in a controlled trial.\n Twenty-eight patients with a history of at least 1 year of chronic low back pain were selected on the basis of a diagnostic anesthetization of the lower intervertebral discs. Only patients with one putative painful level were selected and randomly assigned to one of two treatment groups. Each patient in the radiofrequency treatment group (n = 13) received a 90-second 70 C lesion of the intervertebral disc. Patients in the control group (n = 15) underwent the same procedure, but without use of radiofrequency current. Both the treating physician and the patients were blinded to the group assignment. Before treatment, physical impairment, rating of pain, the degree of disability, and quality of life were assessed by a blinded investigator.\n Eight weeks after treatment, there was one success in the radiofrequency group (n = 13) and two in the control group (n = 15). The adjusted and unadjusted odds ratio was 0.5 and 1.1, respectively (not significant). Also, visual analog scores for pain, global perceived effect, and the Oswestry disability scale showed no differences between the two groups.\n Percutaneous intradiscal radiofrequency thermocoagulation (90 seconds, 70 C) is not effective in reducing chronic discogenic low back pain.",
"Chronic pain in the cervical zygapohyseal joints is a common problem after whiplash injury, but treatment is difficult. Percutaneous radiofrequency neurotomy can relieve the pain by denaturing the nerves innervating the painful joint, but the efficacy of this treatment has not been established.\n In a randomized, double-blind trial, we compared percutaneous radio-frequency neurotomy in which multiple lesions were made and the temperature of the electrode making the lesions was raised to 80 degrees C with a control treatment using an identical procedure except that the radio-frequency current was not turned on. We studied 24 patients (9 men and 15 women; mean age, 43 years) who had pain in one or more cervical zygapophyseal joints after an automobile accident (median duration of pain, 34 months). The source of their pain had been identified with the use of double-blind, placebo-controlled local anesthesia. Twelve patients received each treatment. The patients were followed by telephone interviews and clinic visits until they reported that their pain had returned to 50 percent of the preoperative level.\n The median time that elapsed before the pain returned to at least 50 percent of the preoperative level was 263 days in the active-treatment group and 8 days in the control group (P=0.04). At 27 weeks, seven patients in the active-treatment group and one patient in the control group were free of pain. Five patients in the active-treatment group had numbness in the territory of the treated nerves, but none considered it troubling.\n In patients with chronic cervical zygapophyseal-joint pain confirmed with double-blind, placebo-controlled local anesthesia, percutaneous radio-frequency neurotomy with multiple lesions of target nerves can provide lasting relief.",
"In this study, 54 patients suffering from chronic cervicobrachialgia (mean pain duration 7 years) were treated with radiofrequency lesioning of the cervical spinal dorsal root ganglion (RF-DRG). The aim of the study was to investigate whether psychological variables would be predictive for the changes in pain intensity after medical treatment. The following psychological aspects were measured: pain cognitions, negative self-efficacy and catastrophizing, physical and psychosocial dysfunction, and overall distress. The level of catastrophizing before treatment appeared to predict 10% of the changes in pain intensity after treatment. Changes in pain intensity after RF-DRG were positively correlated with changes in psychosocial dysfunction and negative self-efficacy.\n Copyright 2000 European Federation of Chapters of the International Association for the Study of Pain.",
"It is well recognised that patients with chronic pain, in particular, chronic whiplash-associated neck pain, exhibit psychological distress. However, debate continues as to whether the psychological distress precedes and causes the chronic pain or, conversely, the psychological distress is a consequence of chronic pain. Using cervical zygapophysial joint pain as a model for chronic pain, the effect of a definitive neurosurgical treatment on the associated psychological distress was studied. Seventeen patients with a single painful cervical zygapophysial joint participated in a randomised, double-blind, placebo-controlled trial of percutaneous radiofrequency neurotomy. Their pain and psychological status were evaluated pre-operatively and 3 months post-operatively by medical interview and examination, a visual analogue pain scale, the McGill Pain Questionnaire, and the SCL-90-R psychological questionnaire. All patients who obtained complete pain relief exhibited resolution of their pre-operative psychological distress. In contrast, all but one of the patients whose pain remained unrelieved continued to suffer psychological distress. Because psychological distress resolved following a neurosurgical treatment which completely relieved pain, without psychological co-therapy, it is concluded that the psychological distress exhibited by these patients was a consequence of the chronic somatic pain.",
"A randomized, double-blind, controlled, multicenter trial was conducted.\n To assess the efficacy of neuroreflexotherapy in the management of low back pain.\n Neuroreflexotherapy consists of temporary implantation of epidermal devices in trigger points in the back and referred tender points in the ear.\n The rheumatology and rehabilitation departments of three teaching hospitals in Madrid recruited 78 patients with chronic low back pain. These patients were randomly assigned to the control group (37 patients) or to the treatment group (41 patients). Patients in the treatment group underwent one neuroreflexotherapeutic intervention. The control group received sham treatment consisting of placement of the same number of epidermal devices within a 5-cm radius of the target zones. Patients from both groups were allowed to continue drug treatment as previously prescribed. The use of medications during the trial was recorded.\n Patients underwent clinical evaluations on three occasions: within 5 minutes before intervention, within 5 minutes after intervention, and 45 days later. The preintervention assessment was carried out by the physician from each hospital department who included the patient in the study. Each of the two follow-up assessments were carried out independently by two of three physicians who had no connection with the research team. Patients in the treatment group showed immediate lessening of pain compared with the results in patients in the control group. The pain relief was clinically relevant and statistically significant, and it persisted up to the end of the trial.\n Neuroreflexotherapy intervention seems to be a simple and effective treatment for rapid amelioration of pain episodes in patients with chronic low back pain. At this time, the duration of pain relief beyond 45 days has not been evaluated.",
"Chronic pain in the cervical zygapophyseal joints is a common problem after a whiplash injury. Treatment with intraarticular injections of corticosteroid preparations has been advocated, but the value of this approach has not been established. We compared the efficacy of a depot injection of a corticosteroid preparation with the efficacy of an injection of a local anesthetic agent in patients with painful cervical zygapophyseal joints.\n Sixteen men and 25 women with pain in one or more cervical zygapophyseal joints after automobile accidents (mean age, 43 years; median duration of pain, 39 months) were randomly assigned to receive an intraarticular injection of either bupivacaine (0.5 percent) or betamethasone (5.7 mg) under double-blind conditions. The patients were followed by means of regular telephone contact and clinic visits until they reported a return to a level of pain equivalent to 50 percent of the preinjection level. The time from treatment to a 50 percent return of pain was compared in the two groups with the use of a survival analysis.\n Less than half the patients reported relief of pain for more than one week, and less than one in five patients reported relief for more than one month, irrespective of the treatment received. The median time to a return of 50 percent of the preinjection level of pain was 3 days in the 21 patients in the corticosteroid group and 3.5 days in the 20 patients in the local-anesthetic group (P = 0.42).\n Intraarticular injection of betamethasone is not effective therapy for pain in the cervical zygapophyseal joints after a whiplash injury."
] |
The selected trials provide limited evidence that radiofrequency denervation offers short-term relief for chronic neck pain of zygapophyseal joint origin and for chronic cervicobrachial pain; conflicting evidence on the short-term effect of radiofrequency lesioning on pain and disability in chronic low-back pain of zygapophyseal joint origin; and limited evidence that intradiscal radiofrequency thermocoagulation is not effective for chronic discogenic low-back pain. There is a need for further high-quality RCTs with larger patient samples and data on long-term effects, for which current evidence is inconclusive. Furthermore, RCTs are needed in non-spinal indications where radiofrequency denervation is currently used without any scientific evidence.
|
CD002750
|
[
"6705752",
"2731086",
"2496577",
"3301560",
"3042126",
"7936231",
"2731087",
"1957968",
"1547765",
"1909241"
] |
[
"Double-blind placebo-controlled trial of flunarizine as add-on therapy in epilepsy.",
"Double-blind cross-over placebo controlled study of flunarizine in patients with therapy resistant epilepsy.",
"Double-blind placebo-controlled evaluation of flunarizine as adjunct therapy in epilepsy with complex partial seizures.",
"Flunarizine as add-on therapy in epilepsy. Crossover study vs placebo.",
"Double-blind placebo-controlled trial with flunarizine in therapy-resistant epileptic patients.",
"Flunarizine for treatment of partial seizures: results of a concentration-controlled trial.",
"Flunarizine as a supplementary medication in refractory childhood epilepsy: a double-blind crossover study.",
"Double-blind placebo-controlled trial of flunarizine as add-on therapy in refractory childhood epilepsy.",
"Nifedipine for epilepsy? A double-blind, placebo-controlled trial.",
"Nimodipine in refractory epilepsy: a placebo-controlled, add-on study."
] |
[
"In a therapy-resistant epileptic population with partial complex seizures with or without secondary generalization, addition of flunarizine to existing therapy was accompanied by a significant reduction in complex partial and tonic-clonic seizures. This result did not appear to be due to serial effects or changes in the plasma levels of the co-medication. Side effects were rare. The serum flunarizine levels (13.8 ng/ml; range, 3-32.5 ng/ml) were lower than previously reported on a daily dose of 10 mg. This may reflect increased metabolism due to induction of liver enzymes by the co-medication. Given this finding, together with the low incidence of side effects, a further study is required to determine whether higher blood levels would give an improved degree and incidence of seizure reduction.",
"Twenty-five patients with long-standing therapy resistant epilepsy were studied in an eight-month double-blind cross-over add-on trial with a daily dose of 15 mg flunarizine. In five patients the seizure frequency decreased 50% or more. The mean seizure frequency reduction in the patients on flunarizine was 35%. Particularly the control of secondary generalized seizures improved. Flunarizine did not significantly alter the plasma levels of the regular anticonvulsant drugs. Minimal adverse side effects were reported equally in the flunarizine and the placebo group. In three patients depressive symptoms improved and two patients became free of postictal headaches. Flunarizine appears to be a safe adjuvant anticonvulsant.",
"Flunarizine was compared to placebo in a double-blind cross-over trial of 2 16-week treatment periods separated by a 4-week wash-out period. The patients had epilepsy with complex partial seizures with or without secondary generalised seizures. Twenty-nine patients entered the trial, but 7 dropped out. Of the 22 patients completing the trial, 13 were women; the median was 39 years (range 15-58) and the median duration of epilepsy 23 years (range 4-55). There was no statistically significant difference between flunarizine 15 mg daily and placebo as adjunct therapy in total seizure frequency, neuropsychological tests, and patient's preferences. No interactions with concomitant antiepileptic drugs and no laboratory abnormalities were registered.",
"The anticonvulsive effect of flunarizine was studied in a multicenter trial, by means of a randomized, double-blind, single crossover design. The subjects who entered the study were 51 males and 39 females, aged 15 to 73 years. They were epileptic patients who suffered from at least two generalized seizures per month or more than 4 partial seizures per month. The patients were already being treated with major antiepileptic drugs. Flunarizine was administered in a single evening dose of 10 mg/die in patients who weighed less than 70 kg and of 15 mg/die in patients who weighed more 70 kg. Our results show that flunarizine, given as add-on therapy, produced a slight but significant decrease in the number of monthly seizures at the end of a 3-month period, while placebo did not significantly change the seizures frequency.",
"The anticonvulsant efficacy and side-effect liability of flunarizine (15 mg/day) was investigated in a randomized, double-blind, placebo-controlled, crossover design in 30 outpatients with drug-resistant complex partial seizures. Flunarizine or placebo was added to the preexisting medication and each patient was followed up for 10 months. At the end of the study data from 22 patients were available for evaluation. In patients taking first flunarizine and then placebo, plasma levels of flunarizine were still detectable at the end of the 4 months' placebo phase. In the group of 13 patients starting therapy with placebo, a significant seizure frequency reduction was observed during the flunarizine period in 11 patients, whereas one patient showed no change and seizure frequency increased in another patient. Two patients had a 50% reduction in seizure frequency. Flunarizine was well tolerated and few side effects were noted.",
"The National Institutes of Health sponsored a randomized, double-blind, multicenter, placebo-controlled trial of flunarizine (FNR) in epileptic patients receiving concomitant phenytoin (PHT) or carbamazepine (CBZ). Because of FNR's long half-life (up to 7 weeks), a parallel rather than crossover design was used. Each patient received an individualized loading dose and maintenance dosage targeted at a 60-ng/ml plasma FNR concentration. Of 93 patients randomized, 92 provided seizure data for the full 25-week treatment period; one placebo-treated patient dropped out for personal reasons. Fifty-four patients received CBZ only, nine received PHT only, and 30 received both CBZ and PHT. Eighty-seven patients had a history of complex partial seizures, and 60 had secondarily generalized seizures. Eight patients discontinued FNR prematurely, all because of adverse neurologic or psychiatric signs or symptoms; depression was the specific cause in three cases. Calculated maintenance dosages, based on single-dose pharmacokinetic profiles, ranged from 7 to 138 mg/day (mean, 40 mg/day). Plasma FNR concentrations generally exceeded the target, with the highest concentrations observed immediately after loading; excluding the first three treatment weeks and all concentrations after a FNR dosage change, the median plasma FNR concentration was 71.7 ng/ml. The percent reduction from baseline seizure rate was statistically greater (p = 0.002) in the FNR-treated group (mean, 24.4%) than in the placebo-treated group (mean, 5.7%).",
"We report a double blinded cross-over study involving Flunarizine versus placebo in the treatment of refractory childhood epilepsy. The patients studied were between the ages of 2 and 18; and were having more than 4 seizures per month not responsive to regular anticonvulsant medications. Of the 34 patients treated, 8 had a 50% decrease in their seizures during the placebo phase, 5 had a 50% decrease during the Flunarizine phase, and 1 patient had a 50% increase in seizures while taking Flunarizine. The remaining 25 patients showed no change in seizure activity in either phase. Patients having partial seizures with secondary generalization tended to do better on Flunarizine than those with other seizure types. Monitoring serum Flunarizine levels showed no significant difference between patients having improved seizure control and those who were unimproved. No significant side effects were noted with this medication, nor were any significant drug interactions noted.",
"Flunarizine (FLN) has been suggested as an add-on treatment in drug-resistant epilepsy patients. In view of the discordant experiences and of the paucity of controlled trials in children, we studied its effectiveness in 20 patients aged 6 to 18 years (10 males and 10 females), affected by drug-resistant epilepsy. 14 had symptomatic generalized epilepsy (the Lennox-Gastaut syndrome in 10; other forms in 4); 3 had cryptogenic generalized epilepsy (the Lennox-Gastaut syndrome in 2; myoclonic absences epilepsy in 1); 3 had symptomatic partial epilepsy (temporal lobe epilepsy). 7 of them were withdrawn: only 1 because of side effects. An initial four-month baseline pretrial period was followed by two four-month periods of administration of FLN or a placebo, under double blind conditions, in a randomized sequence. Preexisting antiepileptic (AEDs) medication was maintained at a constant dose throughout the study. FLN was administered as drops in a single evening dose of 5 mg (patients less than 10 years) or 10 mg. (patients greater than 10 years). During the pretrial phase, after phase 1 and phase 2, a waking EEG was recorded and blood samples were taken for hematology, hepatic-function tests, and AED serum levels. The evaluation of the activity of FLN was based on the total number of seizures. A 30-60% reduction in seizure frequency was found in 5 out of the 13 patients completing the trial (no changes occurred in the remainders). This result did not appear to be due to changes in the plasma levels of the AEDs. No significant differences were seen in the EEG paroxysmal activity in the three phases of the study. Side effects were rare. The serum FLN levels ranged between 16.4 and 109 ng/ml. It seems that the antiepileptic properties of FLN need further validation, particularly in childhood.",
"The movement of calcium into neurons may be the common denominator for the triggering and propagation of seizure activity. We report results of the first double-blind, placebo-controlled, crossover trial with the dihidropyridine calcium antagonist nifedipine (NFD) as adjuvant therapy in refractory epilepsy. Twenty-two students (12 male, 10 female, age 17-22 years) attending Lingfield Hospital School received NFD retard and matched placebo for 8 weeks in 2 doses (20 and 40 mg b.i.d. each for 4 weeks) with a washout period of 8 weeks between treatment phases. In the 20 students who completed the trial, fewer partial seizures (p less than 0.05) were documented during the first 2 weeks of NFD administration. Similarly, fewer seizure days (p less than 0.05) were reported in the first month of active treatment. This response was not sustained into the second month of the trial. Blind scoring of EEGs suggested a small improvement with NFD (p less than 0.05). More patients reported headache when receiving NFD (p less than 0.02) than placebo, but heart rate and erect and supine blood pressure remained unaffected. Mean maximum NFD concentrations were 13.1 +/- 10.4 ng/ml. A weak correlation was noted between total (p less than 0.05) and partial (p = 0.025) seizure numbers and NFD concentrations following 8 weeks of treatment. This study does not support important anticonvulsant efficacy for NFD as adjuvant therapy for refractory epilepsy at doses appropriate for the treatment of angina or hypertension. Further trials are recommended using higher doses of NFD in less severely affected patients.",
"Twenty-two patients (8 male, 14 female) with refractory epilepsy entered a balanced, double-blind, placebo-controlled crossover trial of nimodipine as adjunctive therapy. Treatment periods of 12 weeks (nimodipine 30 mg tds, 60 mg tds, 90 mg tds each for 4 weeks and matched placebo) were followed by wash-out intervals of 4 weeks. Five patients withdrew (2 side-effects, 1 intercurrent illness, 2 non-compliance). Median values (placebo vs. nimodipine) did not vary for total (17 vs. 18), partial (14 vs. 18) and generalised tonic-clonic seizures (2 vs. 5) or seizure days (13 vs. 13). Monthly analysis also failed to uncover any benefit for nimodipine. Side-effects were reported no more frequently with nimodipine than with placebo and pulse and blood pressure did not alter significantly. Antiepileptic drug levels were not affected by nimodipine treatment but circulating nimodipine concentrations were low. In this trial, nimodipine did not fulfil the promise of its success in animal models of epilepsy. Enzyme induction by concurrent antiepileptic therapy may provide an explanation."
] |
Flunarizine may have a weak effect on seizure frequency but had a significant withdrawal rate, probably due to adverse effects, and should not be recommended for use as an add-on treatment. Similarly, there is no convincing evidence to support the use of nifedipine or nimodipine as add-on treatments for epilepsy.
|
CD009008
|
[
"11920415",
"18955452",
"18029237",
"17547760",
"12701945",
"17825697",
"19681881",
"15920210",
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"19000234",
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"17697903",
"19724045",
"11340683",
"12196367",
"11730399",
"16670387",
"11313301",
"19854395",
"1858154",
"11562416",
"16137357",
"19252352",
"12677565",
"22013492",
"6767295",
"20624806",
"12789464",
"9301350",
"15746793",
"18161613",
"16110136",
"12161081",
"17140647",
"7853047",
"17506789",
"18362256",
"11769996",
"11830308",
"11980553",
"16793995",
"11596162",
"1490692",
"8334888",
"16084254",
"15834740",
"16926184",
"8721797",
"9014639",
"19901314",
"19574328",
"11591548",
"17452988",
"12356708",
"3896460",
"19042837"
] |
[
"Secular changes in the quality of published randomized clinical trials in rheumatology.",
"Evolution of the randomized controlled trial in oncology over three decades.",
"The reporting quality of randomised controlled trials in surgery: a systematic review.",
"Implementing a guideline for the treatment of type 2 diabetics: results of a cluster-randomized controlled trial (C-RCT).",
"Publication bias and meta-analyses: a practical example.",
"The quality of reporting of randomized controlled trials of traditional Chinese medicine: a survey of 13 randomly selected journals from mainland China.",
"CONSORT adoption and quality of reporting of randomized controlled trials: a systematic analysis in two dermatology journals.",
"The quality of randomized controlled trials in major anesthesiology journals.",
"Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer.",
"The quality of reporting of randomized controlled trials in solid organ transplantation.",
"Quality of reporting of randomized controlled trials in general endocrinology literature.",
"Comparison of extended-release metformin in combination with a sulfonylurea (glyburide) to sulfonylurea monotherapy in adult patients with type 2 diabetes: a multicenter, double-blind, randomized, controlled, phase III study.",
"Comparison of registered and published primary outcomes in randomized controlled trials.",
"Efficacy of once-daily tobramycin monotherapy for acute pulmonary exacerbations of cystic fibrosis: a preliminary study.",
"Informing breast cancer patients about clinical trials: a randomized clinical trial of an educational booklet.",
"Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses.",
"Reporting of randomized controlled trials in Hodgkin lymphoma in biomedical journals.",
"Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis.",
"Quality of reporting in randomized trials published in high-quality surgical journals.",
"A randomized prospective trial comparing cyclosporine monotherapy with triple-drug therapy in renal transplantation.",
"Long-term results of a randomized study comparing three immunosuppressive schedules with cyclosporine in cadaveric kidney transplantation.",
"High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669].",
"Quality of reports on randomized controlled trials conducted in Japan: evaluation of adherence to the CONSORT statement.",
"Randomized controlled trials in pediatric surgery: could we do better?",
"Triple-target treatment versus low-frequency electrostimulation for anal incontinence: a randomized, controlled trial.",
"Controlled trial of intermittent aerosol therapy with sodium 2-mercaptoethane sulphonate in cystic fibrosis.",
"Assessment of risk of bias among pediatric randomized controlled trials.",
"Randomized phase III trial of postoperative radiochemotherapy +/- amifostine in head and neck cancer. Is there evidence for radioprotection?",
"Randomised controlled trial of inhaled corticosteroids (fluticasone propionate) in cystic fibrosis.",
"Randomized prospective trial of early steroid withdrawal compared with low-dose steroids in renal transplant recipients using serial protocol biopsies to assess efficacy and safety.",
"Quality of reporting of key methodological items of randomized controlled trials in clinical ophthalmic journals.",
"Therapeutic efficacy by recombinant human granulocyte/monocyte-colony stimulating factor on mucositis occurring in patients with oral and oropharynx tumors treated with curative radiotherapy: a multicenter open randomized phase III study.",
"The reporting of methodological factors in randomized controlled trials and the association with a journal policy to promote adherence to the Consolidated Standards of Reporting Trials (CONSORT) checklist.",
"Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial.",
"Cumulative meta-analysis of clinical trials builds evidence for exemplary medical care.",
"Aromatherapy in childbirth: a pilot randomised controlled trial.",
"Treatment success in cancer: new cancer treatment successes identified in phase 3 randomized controlled trials conducted by the National Cancer Institute-sponsored cooperative oncology groups, 1955 to 2006.",
"Steroids, carbogen or placebo for sudden hearing loss: a prospective double-blind study.",
"Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial.",
"Abstracts of randomized controlled trials presented at the society for pediatric research meeting: an example of publication bias.",
"Evidence of improving quality of reporting of randomized controlled trials in subfertility.",
"Comparison of high-frequency chest wall oscillation and oscillating positive expiratory pressure in the home management of cystic fibrosis: a pilot study.",
"Efficacy of 6 months monotherapy with glucosidase inhibitor Acarbose versus sulphonylurea glibenclamide on metabolic control of dietary treated type II diabetics (NIDDM).",
"A multicenter comparative trial of triphasic and monophasic, low-dose combined oral contraceptives.",
"Combination antibiotic susceptibility testing to treat exacerbations of cystic fibrosis associated with multiresistant bacteria: a randomised, double-blind, controlled clinical trial.",
"Chlorhexidine and silver-sulfadiazine coated central venous catheters in haematological patients--a double-blind, randomised, prospective, controlled trial.",
"Combination therapy with sulfasalazine and methotrexate is more effective than either drug alone in patients with rheumatoid arthritis with a suboptimal response to sulfasalazine: results from the double-blind placebo-controlled MASCOT study.",
"Assessing the quality of reports of randomized clinical trials: is blinding necessary?",
"Randomization is important in studies with pain outcomes: systematic review of transcutaneous electrical nerve stimulation in acute postoperative pain.",
"Undisclosed changes in outcomes in randomized controlled trials: an observational study.",
"Quality of randomised trials in COPD.",
"Application and validation of a computerized cough acquisition system for objective monitoring of acute cough: a meta-analysis.",
"What is the quality of reporting in weight loss intervention studies? A systematic review of randomized controlled trials.",
"Educational strategies to promote evidence-based community pharmacy practice: a cluster randomized controlled trial (RCT).",
"Participants in prospective, randomized clinical trials for resected non-small cell lung cancer have improved survival compared with nonparticipants in such trials.",
"A pilot phase II randomized, cross-over, double-blinded, controlled efficacy study of octreotide versus hyoscine hydrobromide for control of noisy breathing at the end-of-life."
] |
[
"To assess the quality of published randomized clinical trials (RCTs) in rheumatology and to determine whether there has been improvement in quality between 2 time periods, 1987-1988 and 1997-1998.\n Using MEDLINE and a hand search of selected rheumatology journals, we identified RCTs of adult rheumatic diseases published in English in 1987-1988 or 1997-1998. We examined trial quality with an expanded version of the Jadad scale, which assesses the adequacy of reported random sequence generation, allocation concealment, blinding, and analysis. All trials were read by 1 reviewer, with prior standardization using a random sample read by 2 reviewers. We also evaluated \"high\"- versus \"low\"-impact journals based on citation index.\n Two hundred forty RCTs (1987-1988 119 RCTs, 1997-1998 121 RCTs) were assessed. Results showed improvement in the quality of the trials, but the rates of reported random sequence generation, allocation concealment, power, and intent-to-treat analyses were persistently low. Low rates of reports of random sequence generation, allocation concealment, and intent-to-treat analyses were present even in the high-impact journals.\n There has been improvement in the quality of reporting of RCTs in rheumatology between 1987-1988 and 1997-1998. However, methodologic problems such as lack of allocation concealment, inadequate random sequence generation, lack of reporting of power, and lack of intent-to-treat analyses remain common. Many of these problems are established sources of bias in RCTs and are easily rectifiable.",
"The randomized controlled trial (RCT) is the gold standard for establishing new therapies in clinical oncology. Here we document changes with time in design, sponsorship, and outcomes of oncology RCTs.\n Reports of RCTs evaluating systemic therapy for breast, colorectal (CRC), and non-small-cell lung cancer (NSCLC) published 1975 to 2004 in six major journals were reviewed. Two authors abstracted data regarding trial design, results, and conclusions. Conclusions of authors were graded using a 7-point Likert scale. For each study the effect size for the primary end point was converted to a summary measure.\n A total of 321 eligible RCTs were included (48% breast, 24% CRC, 28% NSCLC). Over time, the number and size of RCTs increased considerably. For-profit/mixed sponsorship increased substantially during the study period (4% to 57%; P < .001). There was increasing use of time-to-event measures (39% to 78%) and decreasing use of response rate (54% to 14%) as primary end point (P < .001). Effect size remained stable over the study period. Authors have become more likely to strongly endorse the experimental arm (P = .017). A significant P value for the primary end point and industry sponsorship were each independently associated with endorsement of the experimental agent (odds ratio [OR] = 19.6, 95% CI, 8.9 to 43.1, and OR = 3.5, 95% CI, 1.6 to 7.5, respectively).\n RCTs in oncology have become larger and are more likely to be sponsored by industry. Authors of modern RCTs are more likely to strongly endorse novel therapies. For-profit sponsorship and statistically significant results are independently associated with endorsement of the experimental arm.",
"In order to examine the reporting quality of urological RCTs, the initial objectives of this study were to evaluate the degree to which RCTs involving urological surgical techniques (as the intervention) published in the years 2000-2003 complied with the CONSORT statement, and to assess trends and patterns of compliance. Following our initial findings in urology, we extended the methodology to a number of other specialties to assess whether our findings in urology could be generalised to other surgical disciplines.\n The Royal Society of Medicine (RSM) Library was commissioned to search the Medline and Cochrane databases for RCTs in compliance with the study inclusion criteria below. Additional analyses of five other specialties (non-urological trials: cardiovascular, gastrointestinal, hepatic, orthopaedic and vascular) were also made. For the non-urological trials, 15 English language trials (from each specialty) were randomly picked from a blast search conducted by the RSM for the year 2003. The RCTs were given a score out of 22, reflecting how many of the 22 CONSORT items were complied with (with each item being given equal weighting), this score was termed the \"CONSORT score\".\n Urology trials: In total 122 RCT abstracts were identified which met the inclusion criteria for this study. From these, 32 were excluded as they were follow-up studies, involved a virtual procedure or were a cost analysis, leaving 90 RCTs published across 35 different journals which were analysed (68.2%, 90/122). The average score of 11.1 for urological trials indicates that RCTs in our sample do not comply with the CONSORT statement. No trials reported how they implemented their randomisation process. Only 46% of RCTs stated that they had permission from an ethics review board, 20% had declared their sources of funding, 14% stated whether there were any conflicts of interest and only 1.1% stated their trial registry number. For non-urological studies, an average CONSORT score of 11.2 was obtained.\n Clinical research teams conducting RCTs in urology and other surgical disciplines demonstrate poor compliance with the CONSORT statement. We would recommend that trials should be registered at their outset and that urological and other surgical journals to consider supporting the CONSORT statement and to have compliance 'hard-wired' into their submission, editorial and peer-review processes. Since it seems the best researchers are unable to produce an RCT results which enable surgical techniques to be critically assessed, there is a need for education about the CONSORT statement and its importance at all levels of surgical training. We believe that an open debate is needed on the possible role of other research designs, such as tracker studies. Whether this study actually raises the question of how appropriate RCTs are to surgical techniques, we leave to the reader.",
"In Italy many diabetics still lack adequate care in general practice. We assessed the effectiveness of different strategies for the implementation of an evidence-based guideline for the management of non-complicated type 2 diabetes among General Practitioners (GPs) of Lazio region.\n Three-arm cluster-randomised controlled trial with GPs as units of randomisation (clusters). 252 GPs were randomised either to an active strategy (training module with administration of the guideline), or to a passive dissemination (administration of the guideline only), or to usual care (control). Data on prescriptions of tests and drugs were collected by existing information systems, whereas patients' data came from GPs' databases. Process outcomes were measured at the cluster level one year after the intervention. Primary outcomes concerned the measurement of glycosilated haemoglobin and the commissioning of micro- and macrovascular complications assessment tests. In order to assess the physicians' drug prescribing behaviour secondary outcomes were also calculated.\n GPs identified 6395 uncomplicated type 2 patients with a high prevalence of cardiovascular risk factors. Data on GPs baseline performance show low proportions of glycosilated haemoglobin assessments. Results of the C-RCT analysis indicate that the active implementation strategy was ineffective relating to all primary outcomes (respectively, OR 1.06 [95% IC: 0.76-1.46]; OR 1.07 [95% IC: 0.80-1.43]; OR 1.4 [95% IC:0.91-2.16]. Similarly, passive dissemination of the guideline showed no effect.\n In our region compliance of GPs with guidelines was not enhanced by a structured learning programme. Implementation through organizational measures appears to be essential to induce behavioural changes.\n ISRCTN80116232.",
"Publication bias is widely appreciated, but considerable time and effort are needed to locate and obtain data from unpublished randomized controlled trials (RCTs), those published in non-English language journals or those reported in the gray literature; for this publication, we will call this collection of trials the \"gray+literature.\" However, excluding such trials from systematic reviews could introduce bias and give rise to misleading conclusions.\n We aimed to explore and quantify the impact of inclusion of gray+ literature on the results of all completed individual patient data (IPD) reviews coordinated by our group (13 meta-analyses). For each IPD review, results were calculated for RCTs fully published in English language journals and RCTs fully published in English language journals and the gray+literature.\n The IPD meta-analyses based only on RCTs that were fully published in English language journals tended to give more favorable results than those that included RCTs from the gray+literature. Although in most cases the addition of gray+data gave less encouraging results, moving the estimated treatment effect toward a null result, the direction of effect was not always predictable.\n We recommend that all systematic reviews should at least attempt to identify trials reported in the gray+literature and, where possible, obtain data from them.",
"The number of randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) is increasing. However, there have been few systematic assessments of the quality of reporting of these trials. Objective: This study was undertaken to evaluate the quality of reporting of RCTs in TCM journals published in mainland China from 1999 to 2004.\n Thirteen TCM journals were randomly selected by stratified sampling of the approximately 100 TCM journals published in mainland China. All issues of the selected journals published from 1999 to 2004 were hand-searched according to guidelines from the Cochrane Centre. All reviewers underwent training in the evaluation of RCTs at the Chinese Centre of Evidence-based Medicine. A comprehensive quality assessment of each RCT was completed using a modified version of the Consolidated Standards of Reporting Trials (CONSORT) checklist (total of 30 items) and the Jadad scale. Disagreements were resolved by consensus.\n Seven thousand four hundred twenty-two RCTs were identified. The proportion of published RCTs relative to all types of published clinical trials increased significantly over the period studied, from 18.6% in 1999 to 35.9% in 2004 (P < 0.001). The mean (SD) Jadad score was 1.03 (0.61) overall. One RCT had a Jadad score of 5 points; 14 had a score of 4 points; and 102 had a score of 3 points. The mean (SD) Jadad score was 0.85 (0.53) in 1999 (746 RCTs) and 1.20 (0.62) in 2004 (1634 RCTs). Across all trials, 39.4% of the items on the modified CONSORT checklist were reported, which was equivalent to 11.82 (5.78) of the 30 items. Some important methodologic components of RCTs were incompletely reported, such as sample-size calculation (reported in 1.1% of RCTs), randomization sequence (7.9%), allocation concealment (0.3 %), implementation of the random-allocation sequence (0%), and analysis of intention to treat (0%).\n The findings of this study indicate that the quality of reporting of RCTs of TCM has improved, but remains poor.",
"CONSORT (Consolidated Standards for Reporting Trials) guidelines were constructed to ensure optimal reporting quality of randomized controlled trials (RCTs).\n To determine the effect of the adoption of CONSORT on the reporting quality of RCTs, we performed a systematic evaluation of RCTs published in two dermatology journals pre- and post-CONSORT adoption.\n The journals selected for the study were the Journal of the American Academy of Dermatology and the British Journal of Dermatology. We selected RCTs published in 1997 and 2006 using both Medline and hand searching. The following critical CONSORT criteria were recorded: sample size, type of disease studied, type of control, single-centre or multicentre study, type of funding, blinding, methods and type of randomization, definition of a primary endpoint, justification for sample size selection and power calculation, population for analysis, and adequacy of group comparison. A multivariable analysis was conducted to determine factors associated with optimal reporting quality.\n In total, 98 studies were included. Improvement in reporting quality was evident for the specification of the randomization method (20% in 1997 vs. 45% in 2006, P < 0.01) and for the justification of sample size (22% in 1997 vs. 43% in 2006, P = 0.027). The percentage of studies with optimal reporting quality increased from 11% in 1997 to 28% in 2006 (P = 0.03). Factors significantly associated with a good methodological quality were pharmaceutical industry funding and publication in 2006 vs. 1997.\n There is a need to improve the reporting quality of RCTs published in dermatology journals.",
"Increased attention has been directed at the quality of randomized controlled trials (RCTs) and how they are being reported. We examined leading anesthesiology journals to identify if there were specific areas for improvement in the design and analysis of published clinical studies. All RCTs that appeared between January 2000 and December 2000 in leading anesthesiology journals (Anesthesiology,Anesthesia & Analgesia,Anaesthesia, and Canadian Journal of Anaesthesia) were retrieved by a MEDLINE search. We used a previously validated assessment tool, including 14 items associated with study quality, to determine a quality score for each article. The overall mean weighted quality score was 44% +/- 16%. Overall average scores were relatively high for appropriate controls (77% +/- 7%) and discussions of side effects (67% +/- 6%). Scores were very low for randomization blinding (5% +/- 2%), blinding observers to results (1% +/- 1%), and post-beta estimates (16% +/- 13%). Important pretreatment clinical predictors were absent in 32% of all studies. Significant improvement in the reporting and conduct of RCTs is required and should focus on randomization methodology, the blinding of investigators, and sample size estimates. Repeat assessments of the literature may improve the adoption of guidelines for the improvement of the quality of randomized controlled trials.",
"To demonstrate the efficacy of radiochemotherapy (RCT) as the first choice of treatment for advanced unresectable head-and-neck cancer. To prove an expected benefit of simultaneously given chemotherapy, a two-arm randomized study with hyperfractionated accelerated radiochemotherapy (HF-ACC-RCT) vs. hyperfractionated accelerated radiotherapy (HF-ACC-RT) was initiated. The primary endpoint was 1-year survival with local control (SLC).\n Patients with Stage III and IV (UICC) unresectable oro- and hypopharyngeal carcinomas were randomized for HF-ACC-RCT with 2 cycles of 5-FU (600 mg/m(2)/day)/carboplatinum (70 mg/m(2)) on days 1--5 and 29--33 (arm A) or HF-ACC-RT alone (arm B). In both arms, there was a second randomization for testing the effect of prophylactically given G-CSF (263 microg, days 15--19) on mucosal toxicity. Total RT dose in both arms was 69.9 Gy in 38 days, with a concomitant boost regimen (weeks 1--3: 1.8 Gy/day, weeks 4 and 5: b.i.d. RT with 1.8 Gy/1.5 Gy). Between July 1995 and May 1999, 263 patients were randomized (median age 56 years; 96% Stage IV tumors, 4% Stage III tumors).\n This analysis is based on 240 patients: 113 patients with RCT and 127 patients with RT, qualified for protocol and starting treatment. There were 178 oropharyngeal and 62 hypopharyngeal carcinomas. Treatment was tolerable in both arms, with a higher mucosal toxicity after RCT. Restaging showed comparable nonsignificant different CR + PR rates of 92.4% after RCT and 87.9% after RT (p = 0.29). After a median observed time of 22.3 months, l- and 2-year local-regional control (LRC) rates were 69% and 51% after RCT and 58% and 45% after RT (p = 0.14). There was a significantly better 1-year SLC after RCT (58%) compared with RT (44%, p = 0.05). Patients with oropharyngeal carcinomas showed significantly better SLC after RCT (60%) vs. RT (40%, p = 0.01); the smaller group of hypopharyngeal carcinomas had no statistical benefit of RCT (p = 0.84). For both tumor locations, prophylactically given G-CSF was a poor prognostic factor (Cox regression), and resulted in reduced LRC (log-rank test: +/- G-CSF, p = 0.0072).\n With accelerated radiotherapy, the efficiency of simultaneously given chemotherapy may be not as high as expected when compared to standard fractionated RT. Oropharyngeal carcinomas showed better LRC after HF-ACC-RCT vs. HF-ACC-RT; hypopharyngeal carcinomas did not. Prophylactic G-CSF resulted in an unexpected reduced local control and should be given in radiotherapy regimen only with strong hematologic indication.",
"Randomized controlled trials (RCTs) of interventions provide the highest level of evidence about efficacy but their value either alone or within a meta-analysis is dependent on its methodological quality. For this reason recent RCTs in organ transplantation were assessed for quality. RCTs published between 2004 and 2006 (n = 332) were assessed, after excluding duplicate and nonEnglish reports. Quality was evaluated using the Jadad score plus allocation concealment and intention to treat analysis. We noted journal type, journal author instructions, funding source, sample size and number and location of study centres. Around one-third of RCTs had a Jadad score of 3 or greater (indication of a methodologically good quality trial) and the other two parameters were satisfied in just over one third. Although the majority of trials were published in speciality journals the quality of those published in general journals was superior. Commercially sponsored trials were of better quality as were multicentre trials in contrast to single centre trials. Overall quality of reporting of RCTs in organ transplantation is poor and as RCTs provide the highest level of evidence in evaluations of interventions there needs to be a concerted effort within the transplant community to improve the standards of RCTs.",
"The reporting quality of randomized controlled trials (RCTs) is poor in general medicine and several areas of specialization but unknown in endocrinology.\n Our aim was to assess the reporting quality of RCTs in general endocrinology. A secondary objective was to identify predictors for better reporting quality.\n We systematically reviewed RCTs published in three general endocrinology journals between January 2005 and December 2006.\n We included parallel-design RCTs that addressed a question of treatment or prevention. Article selection and data abstraction were conducted by two reviewers independently, and disagreements were resolved by consensus.\n There were two main outcomes: 1) a 15-point overall reporting quality score (OQS) based on the Consolidated Standards for Reporting Trials (CONSORT); and 2) a 3-point key score, based on allocation concealment, blinding, and use of intention-to-treat analysis.\n Eighty nine RCTs were included. The median OQS was 10 (interquartile range = 2). Allocation concealment, blinding, and analysis by intention to treat were reported in 10, 20, and 16 of the 89 RCTs, respectively. A multivariable regression analysis showed that complete industrial funding [incidence rate ratio (IRR) = 1.014; 95% confidence interval (CI), 1.010-1.018], journal of publication (IRR = 1.068; 95% CI, 1.007-1.132), and sample size (IRR = 1.048; 95% CI, 1.026-1.070) were significantly associated with a slightly better OQS.\n The quality of RCT reporting in general endocrine literature is suboptimal. We discuss our results, highlight the areas where improvements are needed, and provide some recommendations.",
"Metformin is widely used in the management of type 2 diabetes, either as monotherapy or in combination with other oral antihyperglycemic agents such as sulfonylureas and thiazolidinediones. Combination treatment with metformin and sulfonylurea in patients who failed monotherapy has been reported to be effective in maintaining glycemic control.\n The purpose for this study was to compare the efficacy and tolerability of extended-release metformin (MER) administered with a sulfonylurea (glyburide) to sulfonylurea monotherapy in patients with type 2 diabetes.\n This multicenter, double-blind, randomized, controlled study enrolled adult patients with type 2 diabetes who were either drug naive or previously treated with oral diabetic medications and who had not achieved glycemic control. Patients were stabilized on sulfonylurea (10 mg/d for 2 weeks, then 15 mg/d for 4 weeks) then randomly assigned at base line to receive MER (1500 mg QD, 1000 mg BID, or 2000 mg QD) plus sulfonylurea (MER+S) or sulfonylurea monotherapy for 24 weeks. Patients were evaluated every 1 to 2 weeks during sulfonylurea stabilization and initial metformin treatment, and then every 4 weeks until study end. The primary efficacy end point was glycemic control as determined by changes in glycosylated hemoglobin (HbA(1c)) from baseline to study end between those receiving combination MER+S treatment and those receiving sulfonylurea monotherapy. Adverse events (AEs) were recorded throughout the study by direct questioning, self-reporting by patients, and from the results of physical examinations and clinical laboratory tests.\n A total of 741 patients were enrolled. Of these, 134 patients were stabilization failures, 607 patients were randomized, 575 patients received treatment and were included in the intent-to-treat population, and 417 patients completed the study per protocol. There were no significant differences between treatment groups for any demographic or baseline characteristics (all patients: mean [SD] age, 53.0 [10.6] years; male sex, 54.6% [314/575]; race, white, 58.8% [338/575], Hispanic, 28.5% [164/575]; mean [SD] weight, 97.0 [22.2] kg; obese [body mass index > or =30 kg/m(2)], 69.4% [399/575] ). There were significant decreases from baseline in mean fasting plasma glucose (FPG) levels by the end of week 1 and in mean HbA(1c) levels by week 8 in each MER+S group (both, P < 0.001). The mean (95% CI) changes from baseline to study end in the combined MER+S groups (HbA(1c), -0.74% [-0.85% to -0.64%]; FPG, -12.9 [-17.1 to -8.7] mg/dL) were significantly different from the sulfonylurea monotherapy group (HbA(1c), 0.08% [-0.08% to 0.25%]; FPG, 15.5 [8.2 to 22.8] mg/dL; P < 0.001). Among patients treated with MER+S, the mean (SEM) change in HbA(1c) was -1.26% (-1.44% to -1.07%) for drugnaive patients and -0.59% (-0.46% to 0.71%) for patients previously treated with metformin. There was a significant difference between treatment groups with regard to the prevalence of hypoglycemia (MER+S groups, 11.6% vs sulfonylurea monotherapy group, 4.2%; P = 0.007), but no significant difference was observed for gastrointestinal events. The most common gastrointestinal AEs were diarrhea and nausea (8.6% and 3.9%, respectively, in the combined MER+S groups; 2.8% and 1.4%, respectively, in the sulfonylurea monotherapy group).\n The combination of QD or BID treatment with MER+S was significantly more effective in lowering HbA(1c) and glucose levels than sulfonylurea monotherapy in these adult patients with type 2 diabetes. However, a significant increase in the prevalence of hypoglycemia was observed in the MER+S treatment groups compared with the sulfonylurea monotherapy group.",
"As of 2005, the International Committee of Medical Journal Editors required investigators to register their trials prior to participant enrollment as a precondition for publishing the trial's findings in member journals.\n To assess the proportion of registered trials with results recently published in journals with high impact factors; to compare the primary outcomes specified in trial registries with those reported in the published articles; and to determine whether primary outcome reporting bias favored significant outcomes.\n MEDLINE via PubMed was searched for reports of randomized controlled trials (RCTs) in 3 medical areas (cardiology, rheumatology, and gastroenterology) indexed in 2008 in the 10 general medical journals and specialty journals with the highest impact factors.\n For each included article, we obtained the trial registration information using a standardized data extraction form.\n Of the 323 included trials, 147 (45.5%) were adequately registered (ie, registered before the end of the trial, with the primary outcome clearly specified). Trial registration was lacking for 89 published reports (27.6%), 45 trials (13.9%) were registered after the completion of the study, 39 (12%) were registered with no or an unclear description of the primary outcome, and 3 (0.9%) were registered after the completion of the study and had an unclear description of the primary outcome. Among articles with trials adequately registered, 31% (46 of 147) showed some evidence of discrepancies between the outcomes registered and the outcomes published. The influence of these discrepancies could be assessed in only half of them and in these statistically significant results were favored in 82.6% (19 of 23).\n Comparison of the primary outcomes of RCTs registered with their subsequent publication indicated that selective outcome reporting is prevalent.",
"Our objective was to compare the efficacy, safety, and microbiology of once-daily intravenous (IV) tobramycin with conventional 8-hourly tobramycin/ceftazidime IV therapy for acute Pseudomonas aeruginosa (PA) pulmonary exacerbations in cystic fibrosis (CF). CF patients with PA-induced pulmonary exacerbations were allocated to receive either once-daily tobramycin (Mono) or conventional therapy with tobramycin/ceftazidime given 8-hourly (Conv). The two longitudinal groups received therapy in a double-blind, randomized manner over a period of 2 years. Tobramycin doses were adjusted to achieve a daily area under the time-concentration curve of 100 mg x hr/L in both groups. Results were assessed for both short-term changes (efficacy and safety after 10 days of IV antibiotics during acute exacerbations) and long-term changes (efficacy, safety, and sputum microbiology between study entry and exit). Pulmonary function tests (PFTs) on admission were similar in both groups. After 10 days of IV antibiotics, absolute mean improvements in percent of predicted PFTs were 12.8, 12.1, and 13.7 for forced expiratory volume in 1 sec (FEV(1)), forced vital capacity (FVC), and forced expired flow between 25--75% of FVC (FEF(25--75%)) in the Conv group (n = 51 admissions) compared to 10.6, 9.9, and 10.6 in the Mono group (n = 47)(P<0.05 for all). Sixteen percent in the Conv group and 15% of patients in the Mono group did not respond to therapy by day 10. Long-term PFT patterns were similar for the Conv and Mono groups. The time between admissions did not differ. The Mono group showed a significant increase in tobramycin minimum inhibitory concentrations (MICs) against PA from study entry to study exit (P = 0.02, n = 27 strains); this failed to reach significance in the Conv group (P = 0.08, n = 25). There was no significant increase in the number of isolates, with MIC> or =8 mg/L in both groups. No short- or long-term changes in audiology or serum creatinine were found in either group. After 10 days of IV therapy, the urinary enzyme N-acetyl-beta-d-glucosaminidase/creatinine ratios increased in both groups (P0.05). This increase was greater in the Conv compared to the Mono group (P < 0.05). We conclude that this pilot study indicates once-daily tobramycin therapy to be as effective and safe as conventional 8-hourly tobramycin/ceftazidime therapy. Combination antibacterial therapy appears to offer no clinical advantage over once-daily tobramycin monotherapy. Tobramycin once-daily monotherapy is a potential alternative to conventional IV antibacterial therapy which deserves further investigation, including the impact on susceptibility of PA to tobramycin.\n Copyright 2001 Wiley-Liss, Inc.",
"To evaluate the impact of an educational booklet on women's knowledge of and willingness to participate in a randomized clinical trial of treatment for breast cancer.\n Women undergoing surgery for newly diagnosed early stage breast cancer were randomized to receive, or not, an information booklet explaining the need for and manner in which randomized trials are conducted.\n Eighty-three women with newly diagnosed early stage breast cancer completed a questionnaire assessing attitudes to random clinical trials (RCTs) and were randomized to receive usual information treatment options provided from their oncologist, or the educational booklet in addition to usual information from their oncologist (42 usual information, 41 booklet). Fewer women who received the clinical trials booklet (40% versus 47%) would consider participating in the hypothetical clinical trial (P = 0.6). Mean knowledge scores increased for both groups; moreover, women who did not receive the booklet showed similar improvements to women who received the booklet [mean difference 0.09, 95% confidence interval (CI) -0.66 to 0.83]. In a multivariate analysis women who would consider participating in the clinical trial were more anxious [odds ratio (OR) 5.9, P = 0.02] had involved lymph nodes (OR 5.8, P = 0.02) and were less influenced by negative aspects of clinical trials (OR 7.7, P = 0.0001). After adjustment for these variables women who received the educational booklet were significantly less likely to consider trial participation (OR 0.22, P = 0.05).\n Educating women about clinical trials in this manner appears ineffective in improving recruitment to RCTs. Women appear to be more influenced by their perception of risk than understanding. This finding has ethical implications for communication of information about RCTs.",
"To explore whether reported methodologic quality affects estimated intervention effects in randomized trials and contributes to discrepancies between the results of large randomized trials and small randomized trials in meta-analyses.\n Meta-analyses of randomized trials that included at least one large trial (>/=1000 participants) were included, regardless of the therapeutic area. Eligible meta-analyses were identified through electronic searches and bibliographies of relevant articles.\n Full-length randomized trials.\n Methodologic quality was assessed according to reported randomization, double blinding, and follow-up as separate components and by using the Jadad composite scale.\n Fourteen meta-analyses involving 190 randomized trials from eight therapeutic areas were included. Compared with large trials, intervention effects were exaggerated in small trials with inadequate allocation sequence generation (ratio of odds ratios, 0.46 [95% CI, 0.25 to 0.83]; P = 0.011), inadequate allocation concealment (ratio of odds ratios, 0.49 [CI, 0.27 to 0.86]; P = 0.014), and no double blinding (ratio of odds ratios, 0.52 [CI, 0.28 to 0.96]; P = 0.01). Large trials did not differ significantly from small trials with adequate generation of the allocation sequence, adequate allocation concealment, or adequate double blinding. No association was seen between reported follow-up and intervention effects. The Jadad scale provided no additional information because the scale and the quality components overlapped substantially.\n Inadequate generation of the allocation sequence, allocation concealment, and double blinding lead to exaggerated estimates of intervention benefit and may contribute to discrepancies between the results of large randomized trials and small randomized trials in meta-analyses.",
"Randomized controlled trials (RCTs) are the best tool to evaluate the effectiveness of clinical interventions. The Consolidated Standards for Reporting Trials (CONSORT) statement was introduced in 1996 to improve reporting of RCTs. We aimed to determine the extent of ambiguity and reporting quality as assessed by adherence to the CONSORT statement in published reports of RCTs involving patients with Hodgkin lymphoma from 1966 through 2002.\n We analyzed 242 published full-text reports of RCTs in patients with Hodgkin lymphoma. Quality of reporting was assessed using a 14-item questionnaire based on the CONSORT checklist. Reporting was studied in two pre-CONSORT periods (1966-1988 and 1989-1995) and one post-CONSORT period (1996-2002).\n Only six of the 14 items were addressed in 75% or more of the studies in all three time periods. Most items that are necessary to assess the methodologic quality of a study were reported by fewer than 20% of the studies. Improvements over time were seen for some items, including the description of statistics methods used, reporting of primary research outcomes, performance of power calculations, method of randomization and concealment allocation, and having performed intention-to-treat analysis.\n Despite recent improvements, reporting levels of CONSORT items in RCTs involving patients with Hodgkin lymphoma remain unsatisfactory. Further concerted action by journal editors, learned societies, and medical schools is necessary to make authors even more aware of the need to improve the reporting RCTs in medical journals to allow assessment of validity of published clinical research.",
"Cyclosporine has been effective in patients with steroid-refractory attacks of ulcerative colitis (UC). We investigated the effects of intravenous (IV) cyclosporine as single IV therapy (without glucocorticosteroids) for severe UC and compared these with the response to glucocorticosteroids.\n Patients with a severe attack of UC were randomized to treatment with IV cyclosporine, 4 mg x kg(-1) x day(-1), or with methylprednisolone, 40 mg/day, in a randomized, double-blind, controlled trial. After 8 days, patients who had a response received the same medication orally in combination with azathioprine. Patients were followed up clinically, endoscopically, and by scintigraphy. Renal function was assessed using urinary inulin clearances. Endpoints were clinical improvement, discharge from the hospital, and remission up to 12 months after intravenous therapy.\n Thirty patients were included. After 8 days, 8 of 15 patients (53%) who received methylprednisolone had a response to therapy vs. 9 of 14 (64%) receiving cyclosporine. In nonresponders, 3 of 7 methylprednisolone patients and 1 of 3 cyclosporine patients improved when both treatments were combined. No serious drug-related toxicity was observed with either treatment. At 12 months, 7 of 9 patients (78%) initially controlled with cyclosporine maintained their remission vs. 3 of 8 (37%) initially treated with methylprednisolone. No clinically significant decrease of renal function was observed.\n Cyclosporine monotherapy is an effective and safe alternative to glucocorticosteroids in patients with severe attacks of UC.",
"Randomized controlled trials (RCTs) in surgery can provide valuable evidence of the efficacy of interventions if they are well-designed, appropriately executed, and adequately reported. Adequate reporting of methodology in surgical RCTs is known to be poor, and adverse-event reporting in surgical research is inconsistent. The Consolidated Standards of Reporting Trials (CONSORT) statement is a framework to help authors report their findings in a transparent manner. Extensions to the CONSORT statement have been published recently to address deficiencies in adverse-event reporting and in reporting of specific criteria related to nonpharmacologic treatments. The aim of this study was to assess the quality of reporting of trial methodology and adverse events in a sample of general surgical RCTs published in high-quality surgical journals using the criteria specified in the CONSORT statements.\n We used impact factor to identify the top three ranked surgical journals in 2004. We then obtained information on all RCTs published in these journals in the 2005 calendar year. We assessed quality of reporting using Jadad score, compared the quality of RCTs from CONSORT-endorsing journals with nonendorsers, and assessed the number of RCTs adequately reporting key generic methodologic, adverse-event-related, and specific nonpharmacologic criteria.\n Of 42 RCTs analyzed, only 40% (17 of 42) had a Jadad score > or = 3. There was no significant difference in the number of high-quality RCTs published in CONSORT-endorsing journals compared with nonendorsers (p = 0.3). The median percentage of RCTs adequately reporting generic methodologic, adverse-event-related, and specific nonpharmacologic criteria was 32.5%, 17%, and 36.5%, respectively.\n Quality of reporting of generic methodologic, adverse-event-related, and specific nonpharmacologic criteria in surgical RCTs is poor. Increased attention to quality of reporting of surgical RCTs is required if studies are to meet published criteria.",
"In a prospective trial 151 recipients of renal transplants were randomly assigned to treatment with CsA alone (74 patients) and to low dose of AZA, prednisolone, and CsA (77 patients). At two years, graft survival was 84% for the monotherapy and 90% for the triple therapy. This difference was not statistically significant. The number of rejection episodes was similar in the two groups, but the severity of rejection was significantly worse among the patients on monotherapy. More kidneys were lost because of rejection (6 versus 3), and a higher number of methylprednisolone pulses was used for treating rejection (5.2 +/- 2.3 versus 4.3 +/- 2.9; P = 0.0077). CsA nephrotoxicity episodes were more frequent among patients on monotherapy (23 versus 7; P less than 0.02). Infectious episodes were equally distributed between the two groups. Creatinine clearance was poorer in the monotherapy-treated patients at the third month (42 +/- 16 ml/min versus 48 +/- 15 ml/min; P = 0.02), but no differences were observed between the two groups since the sixth month after transplantation. Many patients on monotherapy required changes in maintenance therapy. In fact, one patient was switched to conventional immunosuppression because of Cremophor-induced anaphylaxis. Another patient who developed Kaposi's sarcoma 4 months after surgery was switched to steroids alone. Excluding 5 patients who lost their grafts a few days after transplantation, only 30 of 74 patients (40%) could be kept without steroids. We conclude that both the therapeutic protocols can give good results in renal allotransplantation; however, monotherapy could create some problems in keeping the balance between drug toxicity and significant immunosuppression. On the contrary, triple therapy is easier to handle, especially in the early posttransplant period when the differential diagnosis between acute rejection and CsA-related nephrotoxicity can be difficult even for a skilled clinician.",
"In this randomized controlled trial started in October 1990, 354 cadaveric kidney transplant recipients were assigned to receive either cyclosporine (CsA) monotherapy (115 patients), CsA + steroids (117 patients), or CsA + steroids + azathioprine (122 patients). The median follow-up was 85.1 mo. Thirty-one deaths occurred (infection, 12; cardiovascular disease, 11; neoplasia, 4; and others, 4), and 65 grafts were lost, mostly due to acute (15) or chronic rejection (50). The cumulative graft half-life was 18.1 yr. According to the \"intention-to-treat,\" the 9-yr actuarial patient and graft survival were 94.0% and 73.3%, respectively, in monotherapy, 87.3% and 65.9% in dual therapy, and 87% and 72.2% in triple therapy (P = 0.647). At the last follow-up, the percentage of patients who remained with the original treatment was 51.2% in monotherapy, 81.7% in dual therapy, and 63.3% in triple therapy. At the seventh year, the mean creatinine clearances were 54.9 +/- 17.6 ml/min in monotherapy, 57.9 +/- 23.4 in dual therapy, and 60.6 +/- 20.7 in triple therapy (P = 0.375). Cataracts (P = 0.000), osteoporosis (P = 0.000), and cardiovascular complications (P = 0.000) were more frequent in dual or triple therapy than in monotherapy. Actuarial graft survival at 9 yr in patients on monotherapy who had to have steroids added was similar to that of the other two groups (62.2% versus 69.3%, P = 0.134). In conclusion, actuarial patient and graft survivals did not differ among the three schemes. The long-term renal function and survival were not affected in the patients on monotherapy who needed the addition of steroids. Monotherapy was associated with a lower incidence of extrarenal complications than the other two regimens.",
"To compare the safety and efficacy of high frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CV) for early intervention in adult respiratory distress syndrome (ARDS), a multi-centre randomized trial in four intensive care units was conducted.\n Patients with ARDS were randomized to receive either HFOV or CV. In both treatment arms a priority was given to maintain lung volume while minimizing peak pressures. CV ventilation strategy was aimed at reducing tidal volumes. In the HFOV group, an open lung strategy was used. Respiratory and circulatory parameters were recorded and clinical outcome was determined at 30 days of follow up.\n The study was prematurely stopped. Thirty-seven patients received HFOV and 24 patients CV (average APACHE II score 21 and 20, oxygenation index 25 and 18 and duration of mechanical ventilation prior to randomization 2.1 and 1.5 days, respectively). There were no statistically significant differences in survival without supplemental oxygen or on ventilator, mortality, therapy failure, or crossover. Adjustment by a priori defined baseline characteristics showed an odds ratio of 0.80 (95% CI 0.22-2.97) for survival without oxygen or on ventilator, and an odds ratio for mortality of 1.15 (95% CI 0.43-3.10) for HFOV compared with CV. The response of the oxygenation index (OI) to treatment did not differentiate between survival and death. In the HFOV group the OI response was significantly higher than in the CV group between the first and the second day. A post hoc analysis suggested that there was a relatively better treatment effect of HFOV compared with CV in patients with a higher baseline OI.\n No significant differences were observed, but this trial only had power to detect major differences in survival without oxygen or on ventilator. In patients with ARDS and higher baseline OI, however, there might be a treatment benefit of HFOV over CV. More research is needed to establish the efficacy of HFOV in the treatment of ARDS. We suggest that future studies are designed to allow for informative analysis in patients with higher OI.",
"The Consolidated Standards for Reporting of Trials (CONSORT) statement was developed to improve the quality of randomized controlled trial (RCT) reports. We assessed the quality of current Japanese RCT reports by conducting a cross-sectional study to examine the extent to which they adhere to the CONSORT statement.\n Reports of RCTs conducted in Japan that were published in medical journals between January and March 2004 were sampled from MEDLINE. The proportion of adherence to each item in the CONSORT checklist was evaluated for each report. Additionally, information on ethics reporting and funding sources was collected.\n A total of 98 RCT reports from Japan were evaluated, and adherence to the CONSORT statement was found to be suboptimal. Only 6 of 29 items in the checklist were described in more than 80% of reports. Adherence to key methodological items of the CONSORT statement was as follows: 23% for sample size determination, 39% for random sequence generation, 17% for allocation concealment, 29% for blinding, 53% for numbers analyzed, and 6% for inclusion of a flow diagram. Adherence to additional items was 82% for ethics committee approval, 92% for receiving informed consent, and 20% for disclosing funding sources.\n Our study on adherence of recent RCT reports from Japan to the CONSORT statement reveals that there is a significant need for improvement. Further investigation on the quality of RCT reports and ways to improve reporting quality is required.",
"Randomized controlled trials (RCTs) are accepted as the gold standard for assessing the effectiveness of clinical interventions but are rarely reported in pediatric surgery. Have RCTs submitted to the British Association of Paediatric Surgeons (BAPS) Annual Congress during the last 5 years been adequately designed and large enough to produce a valid result?\n Abstracts accepted by the Annual BAPS Congress meetings between 1996 and 2000 were examined in collaboration with a senior health services researcher. The quality of the design, methodology, statistical analysis and conclusions, and the adequacy of the sample size were assessed for all identifiable clinical RCTs.\n From 760 accepted abstracts, there were only 9 RCTs (1%) of clinical interventions. In only 4 trials was the relevant primary end-point specified at the outset of the study, and none documented the method of randomization. Only one abstract mentioned blinding with respect to the intervention or outcome measure. Sample sizes were inadequate to detect even large clinical differences. To date, only one of these RCTs has been published in an English-language, peer-reviewed journal.\n Clear guidelines exist for the conduct of RCTs, yet compliance with these standards was rarely documented in abstracts of pediatric surgical RCTs presented at BAPS. Sample sizes were inadequate. RCTs in pediatric surgery are difficult to perform, but the specialty would benefit from well-designed, carefully conducted, multicentre, clinical RCTs to advance evidence-based practice.\n Copyright 2003, Elsevier Science (USA). All rights reserved.",
"In the nonsurgical treatment of anal incontinence, the combination of amplitude-modulated medium-frequency stimulation and electromyographic biofeedback (EMG-BF), known as triple-target treatment (3T), is superior to EMG-BF alone. The aim of this trial is to compare 3T with the standard treatment, low-frequency stimulation (LFS).\n 80 patients with anal incontinence of Grade I or higher who presented to physicians or centers specialized in coloproctology were enrolled in this multicenter randomized trial with blinded observer. The trial had an open parallel-group design. Randomization was performed centrally by telephone. The primary endpoint was the Cleveland Clinic Score (CCS) after self-training at home with either 3T or LFS in two 20-minute sessions per day for 6 months. The secondary endpoints included the proportion of patients regaining continence, and the patients' quality of life (QoL). On completion of the trial as planned, the results were evaluated with an intention-to-treat analysis. Study registration: DRKS00000138 (http://register.germanctr.de).\n 39 patients were randomized to 3T, and 41 to LFS. After 6 months of treatment, the CCS (mean ± standard deviation) was 3.1 ± 4.2 in the 3T group and 9.6 ± 3.9 in the LFS group. The median improvement in the CCS at 6 months compared to baseline was 7 points greater in the 3T group than in the LFS group (95% CI: 5-9, p<0.001). Anal continence was regained by 54% of the 3T patients, but none of the LFS patients (95% CI for the difference: 37.18% - 69.91%, p<0.001). QoL scores were higher in all dimensions in the 3T group than in the LFS group. No major adverse effects occurred in either group.\n 3T is superior to LFS in the treatment of anal incontinence. The available evidence suggests that the success of 3T is based on the combined effect of biofeedback and medium-frequency stimulation. LFS of the type applied in this trial has no effect. 3T should be used in routine clinical practice instead of LFS.",
"Twenty-seven patients with cystic fibrosis completed a controlled trial comparing the effects of an inhaled mucolytic drug, sodium-2-mercaptoethane sulphonate (Mistabron, UCB Pharmaceutical Division, Brussels, Belgium), with inhaled iso-osmolar hypertonic saline. As a group the 22 patients with chronic sputum production showed small but statistically significant improvement in pulmonary function tests after Mistabron therapy, both when compared with a control period, and with iso-osmolar saline results. Subjective measurements by diary card failed to show any changes. No significant changes were found in five patients with no measurable sputum production. The inhalations were given after physiotherapy and were well tolerated. There were no significant side effects. The results suggest that Mistabron has a beneficial therapeutic effect unrelated to its high osmolality, and the intermittent inhalation of Mistabron may have a role in the treatment of selected patients with cystic fibrosis.",
"The goal was to assess the risk of bias among pediatric, randomized, controlled trials (RCTs) reported in 8 high-impact journals.\n We searched PubMed for all pediatric RCTs reported between July 1, 2007, and June 30, 2008, in 8 journals with high impact factors. Using Cochrane Collaboration methods for risk assessment, we evaluated all reports for risk of bias according to domain (ie, randomized sequence generation, allocation concealment, masking, incomplete outcome data, selective outcome reporting, and other). We used multiple logistic regression to test for associations between the presence of a high risk of bias according to domain and funding source, intervention type, trial registration, and multicenter status.\n Industry-funded RCTs were more likely to show a high risk of bias for sequence generation, compared with government-funded RCTs (adjusted odds ratio [aOR]: 6.1 [95% confidence interval [CI]: 1.70- 21.89]), and behavioral/educational trials were more likely to show a high risk of bias for sequence generation (aOR: 2.8 [95% CI: 1.06-7.36]) and allocation concealment (aOR: 4.09 [95% CI: 1.69-9.90]), compared with drug trials. Registered trials were less likely to have a high risk of bias for sequence generation, compared with nonregistered trials (aOR: 0.33 [95% CI: 0.15-0.71]).\n Overall, we found a large proportion of pediatric RCT reports with a high risk of bias for sequence generation and allocation concealment. Factors associated with a high risk of bias included industry funding and assessment of behavioral/educational interventions, whereas trial registration was associated with a lower risk of bias.",
"Experimental and clinical data suggest a reduction of radiation-induced acute toxicity by amifostine (A). We investigated this issue in a randomized trial comparing radiochemotherapy (RT + CT) versus radiochemotherapy plus amifostine (RC + CT + A) in patients with head and neck cancer.\n 56 patients with oro-/hypopharynx or larynx cancer (T1-2 N1-2 G3, T3-4 N0-2 G1-3) were randomized to receive RC + CT alone or RC + CT + A. Patients were irradiated up to 60 Gy (R0) or 70 Gy (R1/2) and received chemotherapy (70 mg/m(2) carboplatin, day 1-5 in week 1 and 5 of radiotherapy). 250 mg amifostine were applied daily before each radiotherapy session. Acute toxicity was evaluated according to the Common Toxicity Criteria (CTC). As for acute xerostomia, patients with laryngeal cancer were excluded from evaluation.\n 50 patients were evaluable (25 patients in the RC + CT, 25 patients in the RC + CT + A group). Clinical characteristics were well balanced in both treatment groups. Amifostine provided reduction in acute xerostomia and mucositis but had no obvious influence on Karnofsky performance status, body weight, cutaneous side effects, and alopecia. The differences between both groups were statistically significant for acute xerostomia and nonsignificant, but with a trend for mucositis.\n According to our results, there is a radioprotective effect on salivary glands and a potential effect on oral mucosa by amifostine in postoperative radiotherapy combined with carboplatin. To improve the radio- and chemoprotective effects of amifostine in clinical practice, the application of a higher dose (> 250 mg) seems to be necessary.",
"Controlling lung inflammation may be the key to improving morbidity and mortality in cystic fibrosis.\n To assess the effects of inhaled corticosteroids on lung inflammation in cystic fibrosis.\n Double blind placebo controlled randomised sequence crossover trial. Fluticasone propionate (400 micrograms/day) was given as a dry powder inhaler for six weeks with a four week washout period before crossover.\n Sputum inflammatory markers (interleukin-8, tumour necrosis factor-alpha (TNF-alpha) and neutrophil elastase-both free and bound to alpha 1-antiprotease), sputum interleukin-10, lung function, and symptomatology.\n Twenty three children from a regional cystic fibrosis centre were enrolled into the study, with mean age 10.3 years (range 7 to 17 years) and mean baseline forced expiratory volume in one second (FEV1) of 64% (range 21% to 102%) predicted for sex and height. One patient was excluded for non-compliance to the study protocol.\n No significant benefit was shown for the use of fluticasone propionate in any of the outcomes. For sputum interleukin-8 there was an estimated true treatment median difference of 142 pg/ml (95% confidence interval (CI) 8 to 2866 pg/ml) in favour of placebo; while for maximal expiratory flow at 25% (MEF25%) remaining forced vital capacity predicted for sex and height there was a 15 percentage points (pp) (95% CI 4 to 26 pp) mean treatment difference in favour of placebo. Sputum interleukin-10 was undetected in any samples and unaffected by fluticasone propionate. Neither atopic status, baseline FEV1, nor concomitant DNase therapy had any effect on response to treatment.\n Lack of benefit from fluticasone propionate was most likely due to failure of the drug to penetrate the viscid mucus lining the airways. It is suggested a large multicentre trial with higher doses given for a longer time by a different delivery system is required to assess efficacy.",
"Corticosteroid therapy after renal transplantation is associated with many adverse effects. Newer immunosuppressive agents may allow for safe and effective reductions in dose or early steroid withdrawal.\n In this prospective, single-center clinical trial, 60 patients were randomized into 2 groups: control patients (n = 28), who received low doses of prednisone throughout, and study patients (n = 32), who were withdrawn from steroids 7 days posttransplant. Patients received a limited course of rabbit antilymphocyte globulin (rALG) induction therapy, tacrolimus (TAC), and mycophenolate mofetil (MMF). Patients were followed for clinical outcomes and renal function. Protocol biopsies were performed at 1, 6, and 12 months.\n Clinical rejections occurred in 11% of controls and 13% of study patients. Renal function was well maintained and equivalent in both groups. In all, 111 protocol biopsies were performed without complications. Subclinical rejection was noted in only 2 protocol biopsies, and borderline changes were seen in 12 biopsies, all of which were distributed equally between both groups. Unsuspected acute TAC toxicity was seen in 8 biopsies. Protocol biopsies led to changes in therapy in 10% of patients. In both groups, serial protocol biopsies demonstrated increased allograft fibrosis over time, which was significant at 1 year in the steroid withdrawal group.\n The immunosuppressive combination of rALG, TAC, and MMF prevents subclinical rejection and the need for high doses of steroids after transplantation. However, continual low-dose steroid therapy may aid in preventing chronic allograft fibrosis. Protocol biopsies help define the short-term and long-term risks of steroid withdrawal therapy.",
"To evaluate the reporting quality of key methodological items in randomized controlled trials (RCTs) in four general clinical ophthalmology journals.\n The reporting of 11 key methodological items in RCTs published in American Journal of Ophthalmology, Archives of Ophthalmology, British Journal of Ophthalmology and Ophthalmology in the year 2005 was assessed.\n Sixty-seven eligible RCTs were assessed and the mean number of items reported was 6.3 per RCT. No significant difference in the mean number of items reported was found between the four journals (P=0.20). The most frequently reported item was ethics approval and informed consent (97.0%), followed by masking status (85.1%), description of withdrawals (76.1%), adverse events (73.1%), and intention-to-treat analysis (71.6%). Details on sequence generation, randomization restriction, allocation concealment, allocation implementation, patient flow diagrams, and sample size calculation were reported in <50% of the RCTs assessed. Both sample size and page length of the RCTs correlated with the number of methodological items reported (P=0.024 and P=0.008, respectively).\n Similar to other specialties, rooms for improvement exist in the reporting of key methodological items of RCTs in clinical ophthalmic journals. Stricter adoption of the CONSORT statement might enhance the reporting quality of RCTs in ophthalmic journals.",
"Previous studies suggested granulocyte-macrophage-colony stimulating factor (GM-CSF) might be beneficial for radiotherapy-induced mucositis. This trial examined the efficacy of GM-CSF in reducing mucositis of the oral cavity and/or oropharynx compared with conventional treatment.\n Mucositis, documented by a five-grade scale, was defined in patients with tumors of the head-neck. Centers were allowed to use their own preferred fractionation regimen. Randomization to treatment was decided before radiotherapy. Treatment with GM-CSF 4 microg/kg/d subcutaneous, started when patients displayed a mucositis score > or = 1.5.\n Ninety-two patients entered the study according to intention-to-treat principle. Twenty did not reach a mucositis index of 1.5. Sixty-one patients were included in the statistical analysis. Forty-five percent of the patients randomized to receive GM-CSF had a significant reduction of the mucositis more than one grade compared to 9% of the conventional treated.\n In severe mucositis, GM-CSF is more effective than conventional treatment.",
"The \"Consolidated Standards of Reporting Trials\" (CONSORT) was developed to improve the suboptimal reporting of randomized controlled trials (RCTs). However, little is known about the quality of reporting since this publication. We undertook an observational study to determine the quality of reporting key methodological factors in RCTs since the publication of the CONSORT statement and if a journal policy to promote adherence to the CONSORT checklist was associated with superior reporting. We recorded the reporting of 11 key methodological factors in 105 RCTs from 29 medical journals published subsequent to the CONSORT statement. We examined the quality of reporting in relation to whether a journal was a \"CONSORT promoter\" as defined by inclusion of the CONSORT checklist in a journal's \"information to authors\" section or a requirement that authors, manuscript reviewers, or copy editors complete the CONSORT checklist. Multivariate analysis controlled for journal impact factor, study outcome, and time of publication. Six of the 11 methodological factors were reported <50% of the time. The number of methodological factors reported was greater in CONSORT promoters than in journals not promoting CONSORT in both unadjusted (6.0 and 5.1, respectively, p-value = 0.03) and adjusted (6.4 and 4.8 of the 11 methodological factors, respectively, p-value = 0.0001) analyses. While journals that promote CONSORT demonstrate superior reporting of RCTs, persistent inadequacies in reporting remain. Until these inadequacies are resolved health-care providers will remain limited in their ability to make informed inferences about the validity of the studies upon which they base their clinical practice.",
"More evidence is needed on which to base recommendations for treatment of mild-moderate persistent asthma in school-aged children.\n The Pediatric Asthma Controller Trial (PACT) compared the effectiveness of 3 regimens in achieving asthma control.\n A total of 285 children (ages 6-14 years) with mild-moderate persistent asthma on the basis of symptoms, and with FEV(1) >or= 80% predicted and methacholine FEV(1) PC(20) <or= 12.5 mg/mL, were randomized to 1 of 3 double-blind 48-week treatments: fluticasone 100 microg twice daily (fluticasone monotherapy), fluticasone 100 microg/salmeterol 50 microg in the morning and salmeterol 50 mug in the evening (PACT combination), and montelukast 5 mg in the evening. Outcomes included asthma control days (primary outcome), exacerbations, humanistic measurements, and pulmonary function measurements.\n Fluticasone monotherapy and PACT combination were comparable in many patient-measured outcomes, including percent of asthma control days, but fluticasone monotherapy was superior for clinic-measured FEV(1)/forced vital capacity (P = .015), maximum bronchodilator response (P = .009), exhaled nitric oxide (P < .001), and PC(20) (P < .001). Fluticasone monotherapy was superior to montelukast for asthma control days (64.2% vs 52.5%; P = .004) and for all other control outcomes. Growth over 48 weeks was not statistically different (fluticasone, 5.3 cm; PACT combination, 5.3 cm; montelukast, 5.7 cm).\n Both fluticasone monotherapy and PACT combination achieved greater improvements in asthma control days than montelukast. However, fluticasone monotherapy was superior to PACT combination in achieving other dimensions of asthma control. Growth was similar in all groups.\n Therefore, of the regimens tested, the PACT study findings favor fluticasone monotherapy in treating children with mild-moderate persistent asthma with FEV(1) >or= 80% predicted, confirming current guideline recommendations.",
"Cumulative meta-analysis of clinical trials (a Bayesian interpretation for accumulating evidence) will profoundly affect medical care by summarizing evidence in the assessment of technology innovations. Application of the technique to the randomized control trials (RCTs) of streptokinase treatment of acute myocardial infarction, reduction of peri-operative mortality by antibiotic prophylaxis, and prevention of death from bleeding peptic ulcers has revealed efficacy years before it was suspected by any other means. Arrangement of the trials according to event rate in the controls, effect sizes, quality of the trials or according to covariables of interest has supplied unique information. If carried out prospectively the technique supplies invaluable information regarding indications for another trial, the number of patients necessary to determine the validity of past trends, and the type of patients who might be benefitted. Careful examination in a cumulative manner of the prior trials can reduce the need for future large trials.",
"We aimed to determine the feasibility of conducting a randomised controlled trial (RCT) on the use of aromatherapy during labour as a care option that could improve maternal and neonatal outcomes.\n RCT comparing aromatherapy with standard care during labour.\n District general maternity unit in Italy.\n Two hundred and fifty-one women randomised to aromatherapy and 262 controls.\n Participants randomly assigned to administration of selected essential oils during labour by midwives specifically trained in their use and modes of application.\n Intrapartum outcomes were the following: operative delivery, spontaneous delivery, first- and second-stage augmentation, pharmacological pain relief, artificial rupture of membranes, vaginal examinations, episiotomy, labour length, neonatal wellbeing (Apgar scores) and transfer to neonatal intensive care unit (NICU).\n There were no significant differences for the following outcomes: caesarean section (relative risk [RR] 0.99, 95% CI: 0.70-1.41), ventouse (RR 1.5, 95% CI: 0.31-7.62), Kristeller manoeuvre (RR 0.97, 95% CI: 0.64-1.48), spontaneous vaginal delivery (RR 0.99, 95% CI: 0.75-1.3), first-stage augmentation (RR 1.01, 95% CI: 0.83-1.4) and second-stage augmentation (RR 1.18, 95% CI: 0.82-1.7). Significantly more babies born to control participants were transferred to NICU, 0 versus 6 (2%), P = 0.017. Pain perception was reduced in aromatherapy group for nulliparae. The study, however, was underpowered.\n This study demonstrated that it is possible to undertake an RCT using aromatherapy as an intervention to examine a range of intrapartum outcomes, and it provides useful information for future sample size calculations.",
"The evaluation of research output, such as estimation of the proportion of treatment successes, is of ethical, scientific, and public importance but has rarely been evaluated systematically. We assessed how often experimental cancer treatments that undergo testing in randomized clinical trials (RCTs) result in discovery of successful new interventions.\n We extracted data from all completed (published and unpublished) phase 3 RCTs conducted by the National Cancer Institute cooperative groups since their inception in 1955. Therapeutic successes were determined by (1) assessing the proportion of statistically significant trials favoring new or standard treatments, (2) determining the proportion of the trials in which new treatments were considered superior to standard treatments according to the original researchers, and (3) quantitatively synthesizing data for main clinical outcomes (overall and event-free survival).\n Data from 624 trials (781 randomized comparisons) involving 216 451 patients were analyzed. In all, 30% of trials had statistically significant results, of which new interventions were superior to established treatments in 80% of trials. The original researchers judged that the risk-benefit profile favored new treatments in 41% of comparisons (316 of 766). Hazard ratios for overall and event-free survival, available for 614 comparisons, were 0.95 (99% confidence interval [CI], 0.93-0.98) and 0.90 (99% CI, 0.87- 0.93), respectively, slightly favoring new treatments. Breakthrough interventions were discovered in 15% of trials.\n Approximately 25% to 50% of new cancer treatments that reach the stage of assessment in RCTs will prove successful. The pattern of successes has become more stable over time. The results are consistent with the hypothesis that the ethical principle of equipoise defines limits of discoverability in clinical research and ultimately drives therapeutic advances in clinical medicine.",
"There is no consensus regarding treatment modalities for idiopathic sudden sensorineural hearing loss (SNHL). In order to evaluate the effectiveness of steroid or carbogen inhalation therapies, a prospective double-blind placebo controlled study was designed. All 41 patients enrolled in the study had unilateral SNHL with no prior history of SNHL, otological pathological history or otoscopic findings. Patients were assigned to four treatment groups: prednisone tablets, placebo tablets, carbogen inhalation or room air inhalation. All were treated for 5 days. The audiometric data at admission was compared to that at day 6 and to data collected at follow-up (average 33 days). Results revealed no significant difference between the groups for early or late audiometric outcome. Age, time from onset of symptoms to initiation of treatment, tinnitus, audiogram configuration, and the presence of vertigo at onset did not significantly affect the outcome. The discrimination scores that were poor in all patient groups on admission improved within days in all groups. These findings suggest that steroids or carbogen inhalation have no therapeutic advantage over placebo. Also, regardless of treatment modality, hearing continued to improve for at least a month after treatment was stopped.",
"To evaluate the benefits and the drawbacks of post-operative radiotherapy in completely resected Stage I (a and b) non-small cell lung cancer (NSCLC).\n Patients with pathological Stages Ia and Ib NSCLC have been randomized into two groups: Group 1 (G1) received adjuvant radiotherapy, Group 0 (G0) the control group did not receive any adjuvant therapy. Local control, toxicity and survival have been evaluated.\n Between July 1989 and June 1997, 104 patients with pathological stage I NSCLC have been enrolled in this study. Fifty-one patients were randomized to G1 and 53 to G0. Six patients have been excluded from the study due to incomplete follow-up data. Regarding local control, one patient in the G1 group had a local recurrence (2.2%) while in the G0 12 local recurrences have been observed (23%). Seventy-one percent of patients are disease-free at 5 years in G1 and 60% in G0 (P=0.039). Overall 5-year survival (Kaplan-Meier) showed a positive trend in the treated group: 67 versus 58% (P=0.048). Regarding toxicity in G1, six patients experienced a grade 1 acute toxicity. Radiological evidence of long-term lung toxicity, with no significant impairment of the respiratory function, has been detected in 18 of the 19 patients who have been diagnosed as having a post-radiation lung fibrosis.\n Adjuvant radiotherapy gave good results in terms of local control in patients with completely resected NSCLC with pathological Stage I. Overall 5-year survival and disease-free survival showed a promising trend. Treatment-related toxicity is acceptable.",
"Publication bias toward studies that favor new therapies has been known to occur for the past 40 years, yet its implications are not well studied in child health. The increased interest in meta-analyses has highlighted the need to identify the totality of evidence when addressing treatment questions.\n To measure the percentage of randomized controlled trials (RCTs) presented at a major pediatric scientific meeting that were subsequently published as full-length articles, to investigate factors associated with publication, and to describe the variables that change from abstract to manuscript form.\n The scientific proceedings from the Society for Pediatric Research were hand searched for RCTs (1992-1995). Subsequent publication was ascertained through a search of various electronic databases. Quality of abstracts and manuscripts was measured, and data were extracted using a structured form.\n A total of 264 (59.1%) of 447 abstracts were subsequently published. Almost 64% of RCTs that were subsequently published favored new therapy compared with 43.5% of studies that were never published (P<.001). Mean effect size for published vs unpublished RCTs was 0.74 vs 0.05 (P<.001). Median sample size was larger in published (n = 45) vs unpublished (n = 34) RCTs (P =.02). Quality was significantly lower for abstracts vs published RCTs (P<.001). For 5% of abstracts that were subsequently published, the conclusion regarding treatment efficacy changed.\n Publication bias is a serious threat to assessing the effectiveness of interventions in child health, as little more than half of RCTs presented at a major scientific meeting are subsequently published. There is a need to institute an international registry of RCTs in children so that the totality of evidence can be accessed when assessing treatment effectiveness.",
"The quality of randomized controlled trials (RCTs) in subfertility and their suitability for inclusion in meta-analyses have been assessed in the past and found to be insufficient. Our aim was to assess whether this quality has improved over time, particularly since the publication of the Consolidated Standards of Reporting Trials (CONSORT) statement, and to assess what proportion of trials could be included in the meta-analyses of pregnancy outcomes such as those included in Cochrane Reviews.\n A selection of subfertility trials published in 1990, 1996 and 2002 was collected from the Cochrane Menstrual Disorder and Subfertility Group (MDSG) database. Only trials published in English as full journal articles, claiming to be randomized and reporting on pregnancy outcomes, were included.\n One hundred and sixty-four trials met our inclusion criteria. Twenty-four (15%) were found not to be randomized, despite claims, and only 10 trials (6%) provided adequate details on the methods of randomization and allocation concealment. Of these, only three had sufficient details extractable to allow for an intention-to-treat analysis of the outcome 'live birth'.\n Although an improvement in some subfertility-specific issues was observed, the quality of reporting of RCTs still needs to improve to make them suitable for inclusion in meta-analyses such as those in the Cochrane Library.",
"Enhanced airway clearance is thought to result in better-maintained pulmonary function in cystic fibrosis (CF). Postural drainage, percussion, and vibration (PDPV) have been the primary airway clearance technique (ACT) employed in CF for over 40 years. Two new airway clearance modalities are high-frequency chest wall oscillation (HFCWO) and oscillating positive expiratory pressure (OPEP). This pilot study was undertaken to evaluate the efficacy of these techniques during home use, assess patient satisfaction with them as compared to PDPV, and assess the feasibility of performing a definitive comparative trial. The prospective, randomized, multicenter crossover trial was conducted at three urban academic CF Care Centers. Twenty-nine CF patients, 9-39 years of age, participated. Subjects performed 4 weeks each of HFCWO and OPEP following 2-week lead-in/washout periods. Spirometry, lung volumes, National Institutes of Health and Petty Scores, and a satisfaction survey were performed at baseline and after each treatment period. An ACT preference survey was completed at the conclusion of the study. Twenty-four subjects completed both therapies. There were no statistically significant differences between therapies for spirometry, lung volumes, or clinical scores. No significant safety issues arose during the study period. Compliance between therapies was similar. Significant differences among therapies existed in patient satisfaction. Given a choice of therapy, 50% of subjects chose HFCWO, 37% OPEP, and 13% PDPV. This study suggests that HFCWO and OPEP are safe and as effective as patients' routine therapies when used for airway clearance in a home setting. Patient satisfaction and preference differ among ACTs and should be considered when prescribing home therapy. A definitive, multi-center, comparative study evaluating long-term efficacy of these techniques is feasible.\n Copyright 2001 Wiley-Liss, Inc.",
"Six months monotherapy with Acarbose vs. glibenclamide led to a marked improvement of BG and HbA1 in NIDDM, insufficiently controlled with diet. Beneficial effects of these distinct principles of action were statistically not different.",
"A comparative multicenter clinical trial of two combined oral contraceptives (OCs) was conducted at clinics located in the Sudan, Sri Lanka, Chile, the Dominican Republic and Ecuador. The trial was designed to determine if there were differences in efficacy, safety and acceptability between a triphasic and a low-dose monophasic OC. This report includes analysis of 1088 women. At each center, subjects were randomly allocated to one of the two OCs. Follow-up visits were scheduled at 1, 4, 8 and 12 months after admission. There were two accidental pregnancies attributed to user failure reported during the study period; one in the triphasic group and one in the monophasic group. Adverse experiences were mainly minor with headaches and dizziness being the most common complaints; frequency of reports was similar in both groups. Cycle control was good in both groups with women in the triphasic group reporting fewer complaints of intermenstrual bleeding. Both OCs were safe and effective.",
"We did a randomised, double-blind, controlled clinical trial to prospectively assess whether use of combination antibiotic susceptibility testing improved clinical outcomes in patients with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria.\n 251 patients with cystic fibrosis who were chronically infected with multiresistant gram negative bacteria gave sputum at 3-month intervals for conventional culture and sensitivity tests and for combination antibiotic susceptibility tests using multiple combination bactericidal antibiotic testing (MCBT). Patients who developed an exacerbation of pulmonary disease were randomised to receive a 14-day course of any two blinded intravenous antibiotics chosen on the basis of either results from conventional sputum culture and sensitivity testing or the result of MCBT. The primary outcome was time from randomisation until the patient's next pulmonary exacerbation. Analysis was by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN60187870.\n 132 patients had a pulmonary exacerbation and were randomised during the 4.5-year study period. The time to next pulmonary exacerbation was not prolonged in the MCBT-treated group (hazard ratio 0.86 in favour of the conventionally-treated group, 95% CI 0.60-1.23, p=0.40). There was no difference between the groups in treatment failure rate. After 14 days of intravenous antibiotic therapy, changes in lung function, dyspnoea, and sputum bacterial density were similar in both groups.\n Antibiotic therapy directed by combination antibiotic susceptibility testing did not result in better clinical and bacteriological outcomes compared with therapy directed by standard culture and sensitivity techniques. The non-bactericidal effects of antibiotic therapy might play an important part in determining improvement in patients with cystic fibrosis pulmonary exacerbations.",
"Central venous catheters (CVCs) are essential for the intensive care of patients with haematological illness. Catheter-related infections (CRI) are an important problem in modern medicine, which may lead to life-threatening situations, to prolonged hospitalisation and increased cost. In immunocompromised patients suffering from haemato-oncological diseases, CRI is a significant factor for adverse outcome. Several clinical studies have shown that CVCs coated with antiseptics such as chlorhexidine and silver-sulfadiazine (CHSS) reduce the risk of catheter-related bacteraemia. Most studies, however, were performed on intensive care patients not suffering from chemotherapy-induced immunosuppression.\n A prospective double-blind, randomised, controlled trial was performed to investigate the effectiveness of CHSS-coated catheters in haemato-oncological patients. A total number of 184 catheters (median duration of placement, 11 days) were inserted into 184 patients (male 115, female 69), of which 90 were antiseptically coated. After removal, all catheters were investigated for bacterial growth.\n Catheters coated with CHSS were effective in reducing the rate of significant bacterial growth on either the tip or subcutaneous segment (26%) compared to control catheters (49%). The incidence of catheter colonisation was also significantly reduced (12% coated vs 33% uncoated). Data obtained show a significant reduction of catheter colonisation in CHSS catheters. There was no significant difference in the incidence of catheter-related bacteraemia (3% coated vs 7% uncoated). However, due to the overall low rate of CRI, we could not observe a significant reduction in the incidence of catheter-related bacteraemia.\n Our data show that the use of CHSS catheters in patients with haematological malignancy reduces the overall risk of catheter colonisation and CRI, although the incidence of catheter-related bacteremia was similar in both groups.",
"Optimal use of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis is vital if progression of disease is to be reduced. Methotrexate (MTX) and sulfasalazine (SASP) are widely used inexpensive DMARDs, recently often combined despite no firm evidence of benefit from previous studies. Aim: To establish whether a combination of SASP and MTX is superior to either drug alone in patients with rheumatoid arthritis with a suboptimal response to 6 months of SASP.\n A randomised controlled study of step-up DMARD treatment in early rheumatoid arthritis. In phase I, 687 patients received SASP for 6 months. Those with a disease activity score (DAS) > or =2.4 were offered additional treatment in phase II (SASP alone, MTX alone or a combination of the two). The primary outcome measure was change in DAS.\n At 6 months, 191 (28%) patients had a DAS <2.4, 123 (18%) were eligible but did not wish to enter phase II, 130 (19%) stopped SASP because of reversible adverse events and 165 (24%) entered phase II. DAS at 18 months was significantly lower in those who received combination treatment compared with those who received either SASP or MTX: monotherapy arms did not differ. Improvement in European League Against Rheumatism and American College of Rheumatology 20, 50 and 70 scores favoured combination therapy.\n In this \"true-to-life\" study, an inexpensive combination of DMARDs proved more effective than monotherapy in patients with rheumatoid arthritis with a suboptimal response to SASP. There was no increase in toxicity. These results provide an evidence base for the use of this combination as a component of tight control strategies.",
"It has been suggested that the quality of clinical trials should be assessed by blinded raters to limit the risk of introducing bias into meta-analyses and systematic reviews, and into the peer-review process. There is very little evidence in the literature to substantiate this. This study describes the development of an instrument to assess the quality of reports of randomized clinical trials (RCTs) in pain research and its use to determine the effect of rater blinding on the assessments of quality. A multidisciplinary panel of six judges produced an initial version of the instrument. Fourteen raters from three different backgrounds assessed the quality of 36 research reports in pain research, selected from three different samples. Seven were allocated randomly to perform the assessments under blind conditions. The final version of the instrument included three items. These items were scored consistently by all the raters regardless of background and could discriminate between reports from the different samples. Blind assessments produced significantly lower and more consistent scores than open assessments. The implications of this finding for systematic reviews, meta-analytic research and the peer-review process are discussed.",
"We set out to examine the evidence for the importance of randomization of transcutaneous electrical nerve stimulation (TENS) in acute postoperative pain. Controlled studies were sought; randomization and analgesic and adverse effect outcomes were summarized. Forty-six reports were identified by searching strategies. Seventeen reports with 786 patients could be regarded unequivocally as randomized controlled trials (RCT) in acute postoperative pain. No meta-analysis was possible. In 15 of 17 RCT, we judged there to be no benefit of TENS compared with placebo. Of the 29 excluded trials, 19 had pain outcomes but were not RCT; in 17 of these 19 TENS studies, the authors concluded that TENS had a positive analgesic effect. No adverse effects were reported. Non-randomized studies overestimated treatment effects.",
"We wanted to investigate the frequency of undisclosed changes in the outcomes of randomized controlled trials (RCTs) between trial registration and publication.\n Using a retrospective, nonrandom, cross-sectional study design, we investigated RCTs published in consecutive issues of 5 major medical journals during a 6-month period and their associated trials registry entries. Articles were excluded if they did not have an available trial registry entry, did not have analyzable outcomes, or were secondary publications. The primary outcome was the proportion of publications in which the primary outcome of the trial was, without disclosure, changed between that recorded in the trial registry and that reported in the final publication. The secondary outcome was the proportion of publications in which the secondary outcome was changed without disclosure.\n We reviewed 158 reports of RCTs and included 110 in the analysis. In 34 (31%), a primary outcome had been changed, and in 77 (70%), a secondary outcome had been changed.\n There are substantial and important undisclosed changes made to the outcomes of published RCTs between trial registration and publication. This finding has important implications for the interpretation of trial results. Disclosure and discussion of changes would improve transparency in the performance and reporting of trials.",
"Randomised trials can provide high-level evidence to inform treatment decisions. Since their quality in respiratory medicine is largely unknown, we assessed the quality of a large set of chronic obstructive pulmonary disease (COPD) trials. As a marker of trial quality, we assessed the procedure and concealment of random allocation, and the conduct of an intention-to-treat-analysis in 344 randomised trials published between 1957 and 2006. We used ordered logistic regression to assess the association between trial quality and type of intervention, type of journal, journal impact factor and year of publication. 257 (75%) trials assessed pharmacological and 87 (25%) assessed nonpharmacological interventions. The generation of appropriate randomisation was reported in 27.0% of the trials, concealment of random allocation in 11.6% and an intention-to-treat analysis in 21.8% of trials. Significantly higher quality was found in trials on nonpharmacological interventions (OR 2.49, 95% CI 1.56-3.99), and in trials published in general medical journals (versus specialised journals; OR 2.25, 95% CI 1.30-3.90) and after 2000 (versus 1957-2000; OR 2.28, 95% CI 1.45-3.58). The association of quality with a high impact factor was of borderline significance (p = 0.06). The quality of many COPD trials is low but tends to become better since the adoption of the CONSORT (Consolidated Standards of Reporting Trials) statement.",
"The purpose of the meta-analysis was to understand the antitussive effect of treatment with dextromethorphan hydrobromide, 30 mg, vs placebo over a 3-h treatment period in patients with cough due to uncomplicated upper respiratory tract infection (URTI), and to show that the computerized system for acquisition and analysis of cough sound was consistent and reproducible across the individual studies.\n The six studies used for the meta-analysis were randomized, double-blind, parallel-group, single-dose, placebo-controlled studies with a 3-h postdose cough evaluation period.\n One study was conducted in Durban, South Africa, and five studies were conducted in Bombay, India. Four studies took place in clinics, and two studies were in-home studies.\n Seven hundred ten adult patients with cough due to uncomplicated URTI who were otherwise healthy and who satisfied the inclusion/exclusion criteria for the meta-analysis. Measurements and results: For each patient, a standard baseline was calculated pretreatment, then a 3-h continuous cough recording was made after treatment was initiated. Five efficacy variables were measured in 30-min intervals: cough bouts, cough components, cough effort, cough intensity, and cough latency. The meta-analysis showed consistent results across most of the studies for each of the efficacy variables. It demonstrated significantly greater overall reductions in cough bouts, cough components, and cough effort, and an increase in cough latency for patients treated with dextromethorphan hydrobromide, 30 mg, vs those treated with placebo.\n The results of a meta-analysis of the six clinical studies show that the antitussive effect of a single dose of dextromethorphan hydrobromide, 30 mg, has been established. The consistent nature of the results shows that the computerized cough acquisition and analysis system is a valid and reproducible methodology for evaluating cough associated with URTI.",
"Despite the large number of randomized controlled trials (RCTs) assessing weight loss interventions, no study has assessed the quality of reporting in these trials.\n To assess the quality of reporting of RCTs of weight loss interventions and to identify predictors of reporting quality.\n The RCTs assessed were derived from a published systematic review of trials investigating the efficacy of weight loss interventions. For our study, two reviewers independently rated the quality of reporting in these trials, based on the Consolidated Standards for Reporting of Trials (CONSORT) Statement. We describe the quality of reporting using number (percent) of studies satisfying each of the 44 CONSORT criteria. We use generalized estimating equations (GEE) to fit a multivariable regression model to determine factors that are associated with the overall quality reporting score.\n We assessed 63 RCTs, of which 25 were dietary-lifestyle trials, 22 were pharmacological trials and 16 were behavior-cognitive, exercise-lifestyle, or surgical trials. Less than half (46%) of the trials defined the primary outcome of the study; about 10% provided the description of the method of allocation concealment. Multivariable GEE results showed that the sample size, type of intervention (non-pharmacologic trials having lower scores than pharmacologic trials), and publication time relative to the CONSORT Statement publication in 1996 (publications after 1996 having higher scores) were strong predictors of the quality reporting score. Reporting a statistically significant result on the primary outcome was not significantly associated with the quality score.\n While the overall quality in reporting seemed to have improved since the publication of the revised CONSORT Statement in 1996, the reporting of some key methodologic aspects, such as clear description of primary outcome and method of allocation concealment, still requires improvements. Factors that are significantly associated with the overall quality reporting score can be used as surrogates in the review of protocols to enhance the quality of the final reports.",
"Community pharmacists have increasing involvement in the self-management of minor illness as a result of the availability of a wider range of over-the-counter (OTC) medicines. We undertook a randomized controlled trial (RCT) to assess the effectiveness and efficiency of educational strategies to implement evidence-based guidelines for the sale of OTC anti-fungals in the community pharmacy setting.\n The aim of the study was to compare the effectiveness and efficiency of two guideline dissemination strategies in community pharmacy settings.\n A 2 x 2 factorial, cluster RCT was conducted with 60 community pharmacies in the Grampian region of Scotland. The interventions included dissemination of an evidence-based guideline for OTC management of vulvovaginal candidiasis (thrush) by postal dissemination (control), educational outreach visit or attendance at a continuing professional education session. Pre- and post-intervention simulated patient visits were made to participating pharmacies. The simulated patients completed assessment forms following each visit. The primary outcome was the appropriateness (based upon the guidelines) of sale or no sale of OTC anti-fungals.\n There were no significant differences in the proportion of appropriate outcomes following educational outreach [odds ratio (OR) = 1.1; 95% confidence interval (CI) 0.52 to 2.45] or continuing professional education (OR = 0.88; 95% CI 0.41 to 1.91).\n Neither strategy was effective in improving the appropriateness of OTC management of vulvovaginal candidiasis by community pharmacy staff. Further research is needed to identify barriers to guideline implementation and evidence-based practice in this setting.",
"The survival of 78 patients with resected non-small cell lung cancer entered in prospective, randomized investigational trials is compared to that of a population-based group of control patients not included in such trials. The survival of trial patients is significantly better than that of controls (P less than 0.001). This survival advantage for trial participants is most apparent among late Stage I patients, and is observed after matching for known prognostic factors (i.e., primary tumor size, nodal status, tumor histology) and after adjusting in the analysis for age, sex, and the administration of radiation therapy. Several explanations for the improved outcome for trial patients are explored, including differences in preoperative evaluation, staging, surgical technique, placebo effects, and patient motivation. These results suggest the possibility that inclusion in these controlled cancer trials may have had an inherent advantage for all participants.",
"Noisy breathing at the end of life (noisy breathing (\"NB\") occurs in up to 90% of people. Interventions have not been systematically evaluated. There has been clinical observation coupled with a proposed mechanism of effect that supports a role for octreotide in management of NB. The aim of this phase II study was to assess ten completed participants for the feasibility of an adequately powered phase III study. This randomized, double-blind, crossover pilot trial recruited participants from an inpatient palliative unit. Participants while well and their proxies simultaneously provided written informed consent. If NB were encountered, people were randomized to 200 mcg octreotide or 400 mcg hyoscine hydrobromide subcutaneously. If subsequent treatment was needed, the other medication was administered. A five point categorical scale documented the nurses' assessment of secretions over six hours. Eighty participants were consented of whom 10 (3 females, 7 males; median age 79, all with advanced cancer) received medication, five in each arm. There was no difference in the median time to administration of the second medication (3 hours). Two participants in each arm had a 2 category reduction of intensity after the second medication. Although feasible to consent and study this population in a way that respects autonomy and dignity even in the terminal hours of life, this pilot study suggests reconsideration of the pharmacological interventions (choice of agents, dosing, timing of dosing and pharmacokinetic profiles), standardizing of non-pharmacological care; and ways to measure directly family distress before further randomized studies for this symptom."
] |
There is insufficient evidence from RCTs to support the decision as to whether to initiate sulphonylurea monotherapy. Data on patient-important outcomes are lacking. Therefore, large-scale and long-term randomised clinical trials with low risk of bias, focusing on patient-important outcomes are required.
|
CD003670
|
[
"2396618",
"2189428",
"9264888",
"7921089",
"6993111",
"331941",
"3890463",
"319653"
] |
[
"Gowning on a postpartum ward fails to decrease colonization in the newborn infant.",
"A randomized controlled trial of a nursery ritual: wearing cover gowns to care for healthy newborns.",
"Does routine gowning reduce nosocomial infection and mortality rates in a neonatal nursery? A Singapore experience.",
"Gowning does not affect colonization or infection rates in a neonatal intensive care unit.",
"Effect of antiseptic cord care on bacterial colonization in the newborn infant.",
"Staphylococcal and streptococcal colonization of the newborn infant: effect of antiseptic cord care.",
"Bacterial colonization and neonatal infections. Effects of skin and umbilical disinfection in the nursery.",
"Group B beta-hemolytic streptococcal colonization. Acquisition, persistence, and effect of umbilical cord treatment with triple dye."
] |
[
"We conducted a randomized study to evaluate the effect of gowning by visitors and hospital personnel on a postpartum ward on nose and umbilical colonization and disease in healthy newborn infants. Cultures were obtained in infants assigned to the gowning and nongowning groups within 6 hours of birth from the anterior part of the nares and the base of the umbilicus and at the time of discharge from the nursery. There were 102 infants in the gowning group and 100 infants in the nongowning group. No significant differences were noted between the two groups with respect to sex, length of stay, mode of delivery, weight, or status of nursery admission culture results. The use of gowns on a postpartum ward failed to decrease nose or umbilical colonization when compared with infants in the nongowning group. Seventy (68.6%) of 102 infants in the gowning group and 65 (65%) of 100 infants in the nongowning group had negative umbilical cord cultures on admission to the nursery that became positive at discharge. On follow-up, no differences were noted between the two groups with respect to their health. Only one infant in each group had an infection develop in the first 4 weeks of life. We conclude that the routine use of cover gowns on postpartum units in healthy full-term infants is ineffective and costly. It may discourage health care providers from examining patients and providing care.",
"The routine wearing of individual cover gowns by nurses and visitors for direct care of healthy newborns was usual practice on the maternity ward of a regional referral center. We conducted a randomized trial in which cover gowns were not provided for care of infants in the experimental group (n = 222), but were maintained for control infants (n = 230). The principal outcome measured was Staphylococcus aureus colonization of the newborn nares or umbilicus on day 3 or day of discharge. Twenty percent (n = 51) of the experimental group (no gown) had a positive culture compared with 21 percent (n = 47) of the controls. Of the infants with positive cultures, two in each group exhibited symptoms of overt S. aureus infection. Experimental infants were similar to controls with respect to feeding method, route of delivery, amount of time spent rooming-in, and average number of visitors per day. In the group of positively cultured infants, the mothers experienced longer labor, and more vaginal examinations in labor, and the number of males undergoing circumcision was higher. We concluded that routine use of cover gowns was unwarranted, and we have altered the ward policy accordingly. This also has had a positive economic effect.",
"A 1 year prospective study on routine gowning before entering a neonatal unit was conducted in a maternity hospital in Singapore. This study was done based on previous work by Donowitz, Haque and Chagla and Agbayani et al., as there have been no known studies done in Singapore. The aim of the study was to test the hypothesis that routine gowning before entering a neonatal nursery does not reduce nosocomial infection and mortality rate. A total of 212 neonates from the neonatal intensive care unit (NICU) and 1694 neonates from the neonatal special care unit (NSCU) were studied. Neonates admitted during the 1 year study were assigned to the gowning (control) and no routine gowning (trial) group on every alternate 2 months. The hospital infection control nurse provided data on nosocomial infection. The overall nosocomial infection rate in the NICU was 24% (25 of 104 admissions) during gowning periods compared to 16.6% (18 of 108 admissions) when plastic aprons were not worn before entry. In the NSCU, the overall infection rate was 1.5% (12 of 800 admissions) during gowning periods compared to 2.1% (19 of 894 admissions) when no gown was worn before entry. Results of the study found no significant differences in the incidences of nosocomial infection and mortality in the neonates. The cost of gowns used during the no routine gowning periods was S$2012.8 compared to S$3708 used during the routine gowning procedure. The investigators recommend that routine gowning before entering a neonatal unit is not essential and cost effective for the purpose of reducing infection. Rather the focus should be on adequate handwashing by all hospital personnel and visitors before handling neonates.",
"To study the effect of gowning in a neonatal intensive care unit on colonization patterns, necrotizing enterocolitis, respiratory syncytial virus and other infections, mortality, and traffic and handwashing patterns.\n Alternate 2-month gowning and no-gowning cycles were established in a 24-bed level III neonatal intensive care unit for 8 months, with respiratory site, umbilical, and stool surveillance cultures done weekly on all patients. Traffic flow and handwashing compliance were evaluated by direct observation.\n Demographic data did not differ between periods. There were no significant differences between the gowning and no-gowning periods in the rates of bacterial colonization, any type of infection, or mortality. There was no effect on traffic flow or handwashing compliance.\n Gowning in the neonatal intensive care unit is an unnecessary custom without benefit in neonatal colonization, infection rates, mortality, traffic patterns, and handwashing behavior.",
"A randomized controlled study was undertaken to compare the effectiveness of three umbilical cord treatment regimens in controlling neonatal bacterial colonization. The regimens studied included daily application of castile soap, triple dye and silver sulfadiazine. The triple dye and silver sulfadiazine regimens inhibited bacterial colonization. Staphylococcal colonization was inhibited most effectively by triple dye treatment. Group B streptococcal colonization was equally inhibited by triple dye and silver sulfadiazine. Silver sulfadiazine was more effective in controlling colonization with gram-negative microorganisms.",
"A randomized controlled study was undertaken to compare the effectiveness of three umbilical cord treatment regimens in controlling neonatal bacterial colonization. The three regimens studied included castile soap, triple dye, and silver sulfadiazine. The triple dye and silver sulfadiazine application inhibited bacterial colonization. Staphylococcal colonization was inhibited by both treatment regimens but most effectively by triple dye. Group B streptococcal colonization was inhibited most effectively by silver sulfadiazine while triple dye application to the umbilicus promoted colonization with this microorganism. Silver sulfadiazine was more effective in controlling colonization with Gram-negative microorganisms.",
"In a prospective randomized study different regimens for skin and umbilical disinfection in newborn infants were tested: daily whole body soap wash (control group), daily whole body soap wash and umbilical cleansing with (i) benzine solution, or (ii) 0.05% chlorhexidine, and daily whole body wash and umbilical cleansing with a 4% chlorhexidine detergent solution (Hibiscrub). Bacterial cultures were taken from the nose and umbilical area at discharge. Clinical infections were registered in the nursery, and after discharge until 6 weeks of age. Cultures were taken from infected areas. In the control group a high colonization rate was found for S. aureus (91%), E. coli (39%), and group B streptococci (GBS) (20%). The colonization rates were influenced by the Hibiscrub regimen (colonization rate for S. aureus 59%, E. coli 23%, and GBS 10%), but not by the other regimens. Infections (pemphigus, paronychia, conjunctivitis, umbilical infection) occurred in 12.9% of the infants, of whom 65% got infection after discharge from the nursery. 96% of the infections were caused by S. aureus, and 87% caused by strains colonizing the infants in the nursery. None of the tested regimens reduced the rate of infections during the first 6 weeks of life.",
"Following an outbreak of group B beta-hemolytic streptococcal neonatal infection (GBS), a prevalence survey of GBS colonization was performed on 238 infants. No important differences were noted in the prevalence of colonization when the infants were grouped according to age. Follow-up of 24 colonized babies for three months disclosed that most had persistence of GBS at the rectum and pharynx. Local umbilical cord care with triple dye (TD) or hexachlorophene skin cleanser was compared with untreated controls with respect to rates of GBS colonization. At birth the colonization rates of the three groups were similar. The rate of acquisition of colonization with GBS was 1.0% in the TD group, 6.3% in the hexachlorophene group, and 8.3% in the control group. Triple dye was much more effective than no specific cord care or hexachlorophene in preventing acquisition of GBS colonization."
] |
There is no evidence from this systematic review and meta-analysis to demonstrate that overgowns are effective in limiting death, infection or bacterial colonisation in infants admitted to newborn nurseries.
|
CD008743
|
[
"17365766",
"15586837",
"19398690",
"21287886",
"18465176",
"9932067",
"20675426",
"6527988",
"18333706",
"11945214",
"11802453"
] |
[
"Provider feedback to improve 5A's tobacco cessation in primary care: a cluster randomized clinical trial.",
"Results of a randomized controlled trial of intervention to implement smoking guidelines in Veterans Affairs medical centers: increased use of medications without cessation benefit.",
"An electronic health record-based intervention to improve tobacco treatment in primary care: a cluster-randomized controlled trial.",
"A demonstration project for using the electronic health record to identify and treat tobacco users.",
"A computerized aid to support smoking cessation treatment for hospital patients.",
"Tools to improve documentation of smoking status. Continuous quality improvement and electronic medical records.",
"Do faxed quitline referrals add value to dental office-based tobacco-use cessation interventions?",
"Effects of physician counseling on the smoking behavior of asbestos-exposed workers.",
"Care coordination to increase referrals to smoking cessation telephone counseling: a demonstration project.",
"The feasibility of paper-based Tracking Codes and electronic medical record systems to monitor tobacco-use assessment and intervention in an Individual Practice Association (IPA) Model health maintenance organization (HMO).",
"[The effect of smoking cessation counseling at health checkup]."
] |
[
"The electronic health record (EHR) may be an effective tool to help clinicians address tobacco use more consistently. To evaluate the impact of EHR-generated practice feedback on rates of referral to a state-level tobacco quitline, we conducted a cluster randomized clinical trial (feedback versus no feedback) within 19 primary care clinics in Oregon. Intervention clinics received provider-specific monthly feedback reports generated from EHR data. The reports rated provider performance in asking, advising, assessing, and assisting with tobacco cessation compared with a clinic average and an achievable benchmark of care. During 12 months of follow-up, EHR-documented rates of advising, assessing, and assisting were significantly improved in the intervention clinics compared with the control clinics (p<.001). A higher case-mix index and presence of a clinic champion were associated with higher rates of referral to a state-level quitline. EHR-generated provider feedback improved documentation of assistance with tobacco cessation. Connecting physician offices to a state-level quitline was feasible and well accepted.",
"The AHRQ Clinical Practice Guideline for Treating Tobacco Use and Dependence recommends screening and treatment of all tobacco users. Effective methods to implement recommendations are needed because simple guideline dissemination does not necessarily result in changes in practice.\n The Guideline Implementation for Tobacco (GIFT) study tested an organizational intervention to improve Guideline implementation.\n GIFT randomized 20 Veterans Affairs medical centers to intervention or control conditions. We trained prime movers at each site to improve identification of smoking status, promote primary care interventions and increase availability of smoking cessation medications. Sites and patients were evaluated before and after intervention.\n GIFT included 20 Veterans Affairs medical centers and 5678 subjects.\n Data regarding smoking status, delivery of treatment, medication use, and smoking cessation were collected from participant surveys, medical record review, survey of site leaders, and Pharmacy Benefits Management.\n The intervention did not increase participant report of being asked about smoking status or receipt of counseling. It did increase the rate of identification of smoking status in the medical record (P = 0.0001) but did not increase the rate of counseling to stop smoking. Site level data showed no increase in the number of patients receiving smoking cessation medications or dollars spent on medications. Individual smoker data showed a significant increase in the use of medications for smoking cessation in intervention sites (odds ratio = 6.89, P < 0.0001); however, only a small minority of smokers received medication even after the intervention. There was no difference in smoking cessation rates between participants at the intervention and treatment sites.\n We conclude that improvements in smoking cessation rates are likely to require more intensive intervention in this population.",
"To improve the documentation and treatment of tobacco use in primary care, we developed and implemented a 3-part electronic health record enhancement: (1)smoking status icons, (2) tobacco treatment reminders, and (3) a Tobacco Smart Form that facilitated the ordering of medication and fax and e-mail counseling referrals.\n We performed a cluster-randomized controlled trial of the enhancement in 26 primary care practices between December 19, 2006, and September 30, 2007. The primary outcome was the proportion of documented smokers who made contact with a smoking cessation counselor. Secondary outcomes included coded smoking status documentation and medication prescribing.\n During the 9-month study period, 132 630 patients made 315 962 visits to study practices. Coded documentation of smoking status increased from 37% of patients to 54% (+17%) in intervention practices and from 35% of patients to 46% (+11%) in control practices (P < .001 for the difference in differences). Among the 9589 patients who were documented smokers at the start of the study, more patients in the intervention practices were recorded as nonsmokers by the end of the study (5.3% vs 1.9% in control practices; P < .001). Among 12 207 documented smokers, more patients in the intervention practices made contact with a cessation counselor (3.9% vs 0.3% in control practices; P < .001). Smokers in the intervention practices were no more likely to be prescribed smoking cessation medication (2% vs 2% in control practices; P = .40).\n This electronic health record-based intervention improved smoking status documentation and increased counseling assistance to smokers but not the prescription of cessation medication.",
"While the majority of smokers visit a primary care physician each year, only a small proportion of them receive evidence-based tobacco dependence treatment. The electronic health record (EHR) provides an opportunity to prompt clinicians to deliver tobacco dependence treatment in primary care.\n Over 1 year, Dean Health Systems worked with the University of Wisconsin School of Medicine and Public Health to modify the existing Dean EHR system (Epic Systems Corp, Verona, Wisconsin) to improve identification and treatment of adult smokers visiting primary care clinics. Modifications included evidence-based prompts that helped guide medical assistants to identify smokers and clinicians to deliver a brief tobacco cessation intervention (medication and Wisconsin Tobacco Quit Line referral). Eighteen primary care clinics provided data 1 year before and 1 year after implementing the EHR modifications.\n A higher percentage of adult patients had their tobacco use status identified after EHR modification compared to pre-implementation (71.6% versus 78.4%, P < .001). During the post-implementation year, 6.3% of adult smokers were prescribed tobacco cessation medication, 2.5% of adult smokers had documentation of counseling, and 1.5% of adult smokers had counseling billed (pre-implementation data not available).\n This demonstration project showed that a large health care system can increase the delivery of tobacco dependence treatment interventions (increased identification of smokers and relatively high rates of delivering specific tobacco dependence clinical interventions) building on an existing EHR platform. The project demonstrated that brief, evidence-based tobacco dependence interventions can be incorporated into primary care, especially when the EHR is used to improve clinic workflow.",
"Hospital-based interventions promote smoking cessation after discharge. Strategies to deliver these interventions are needed, especially now that providing smoking cessation advice or treatment, or both, to inpatient smokers is a publicly reported quality-of-care measure for US hospitals.\n To assess the effect of adding a tobacco order set to an existing computerized order-entry system used to admit Medicine patients to 1 hospital.\n Pre-post study.\n Proportion of admitted patients who had smoking status identified, a smoking counselor consulted, or nicotine replacement therapy (NRT) ordered during 4 months before and after the change. In 4 months after implementation, the order set was used with 76% of Medicine admissions, and a known smoking status was recorded for 81% of these patients. The intervention increased the proportion of admitted patients who were referred for smoking counseling (0.8 to 2.1%) and had NRT ordered (1.6 to 2.5%) (p < .0001 for both). Concomitantly, the hospital's performance on the smoking cessation quality measure improved.\n Adding a brief tobacco order set to an existing computerized order-entry system increased a hospital's provision of evidence-based tobacco treatment and helped to improve its performance on a publicly reported quality measure. It provides a model for US hospitals seeking to improve their quality of care for inpatients.",
"Despite the deleterious effects of smoking on the nation's health and evidence that smoking cessation advice by family practice physicians is cost-effective, self-sustaining office systems to identify smokers in primary care clinics have been difficult to establish. We worked on a continuous quality improvement project group, aided by an electronic medical record, to design a system to document and periodically update smoking status in a consistent place in the medical record.\n Using the continuous quality improvement plan-do-study-act cycle, a 7-member group worked with nursing staff to define roles, routines and responsibilities for medical assistants to screen for and document 1 of 4 categories of smoking status in the major problem list of the electronic medical record for at least 80% of patient appointments. Screening rate was tracked monthly by means of the electronic medical record and feedback was given to staff.\n The screening rate rose from 18.4% to 80.3% within 2 weeks after the system was implemented and was maintained for 19 months. An additional benefit was an increased rate of smoking cessation counseling documented by providers, from a baseline rate of 17.1% to 48.3%.\n A continuous quality improvement group process aided by an electronic medical record is useful to develop a self-sustaining office system to screen, document, and periodically update smoking status in a consistent place in the medical record. Although screening for and documenting smoking status are only the first step toward helping patients stop smoking, it is an important one.",
"The Ask, Advise, Refer (AAR) model of intervening with patients who use tobacco promotes a brief office-based intervention plus referral to a tobacco quitline. However, there is little evidence that this model is effective. The primary aim of this study was to evaluate the effects on patients' tobacco use of two levels of a dental office-based intervention compared with usual care.\n The authors randomly assigned 68 private dental clinics to one of three conditions: 5 As (Ask, Advise, Assess, Assist, Arrange); 3 As (AAR model); or usual care, and they enrolled 2,160 participants.\n At the 12-month assessment, compared with those in usual care, participants in the two intervention conditions combined were more likely to report cessation of tobacco use, as measured by nine-month prolonged abstinence (3 percent versus 2 percent; F(1,66) = 3.97, P < .10) and 12-month point prevalence (12 percent versus 8 percent; F(1,66) = 7.32, P < .01). There were no significant differences between participants in the clinics using the 5 As and 3 As strategies.\n The results of this study are inconclusive as to whether referrals to a quitline add value to brief dental office-based interventions. Patients receiving telephone counseling quit tobacco use at higher rates, but only a small percentage of those proactively referred actually received counseling.\n The results confirm those of previous research: that training dental practitioners to provide brief tobacco-use cessation advice and assistance results in a change in their behavior, and that these practitioners are effective in helping their patients to quit using tobacco.",
"Physician antismoking advice has been shown to increase smoking cessation, particularly among patients who have medical problems or perceive themselves to be at risk. The present study tested three hypotheses: (a) providing 3 to 5 min of behavioral counseling regarding a cessation strategy would be more effective than simply warning the smoker to quit smoking; (b) smokers with abnormal pulmonary function would be more likely to comply with medical advice than would smokers with normal pulmonary function; and (c) that smokers with abnormal pulmonary function who receive behavioral counseling would be the group most likely to achieve prolonged abstinence. Asbestos-exposed smoking men undergoing screening in a mandated program for naval shipyard workers were categorized as having normal or abnormal pulmonary status on the basis of chest X ray and pulmonary function tests (PFT). They were then randomly assigned within PFT categories to receive either a simple warning or 3 to 5 min of behavioral cessation counseling from the physician who gave them the results of their pulmonary tests. Subjects' smoking status was evaluated at 3- and 11-month intervals following the physician intervention. Smokers who received behavioral counseling were more likely to quit and remain abstinent over the 11-month period (8.4% abstinent) than were smokers given a minimal warning (3.6% abstinent). Prolonged abstinence rates among abnormal PFT subjects (3.7%) did not differ from those of normals (5.9%). The group with normal PFT who received behavioral counseling achieved the highest level of abstinence (9.5%). Maintaining adequate physician compliance with the counseling protocol proved difficult; implications of this for future efforts are discussed.",
"To test the effectiveness of a care coordination program for telephone counseling in raising referral and treatment rates for smoking cessation.\n A demonstration project implementing a smoking cessation care coordination program offering telephone counseling and medication management to patients referred from primary care.\n The study was performed at 18 Veterans Health Administration (VA) sites in California. Participants were VA patients receiving primary care. We randomly allocated 10 of 18 sites to receive the Telephone Care Coordination Program, which included simple 2-click referral, proactive care coordination, medication management, and 5 follow-up telephone calls. Each patient received a 30- to 45-minute counseling session from the California Smokers' Helpline. Patients at control sites received usual care.\n During 10 months, we received 2965 referrals. We were unable to reach 1156 patients (39%), despite at least 3 attempts. We excluded 73 patients (3%), and 391 patients (13%) were not interested. We connected the remaining 1345 patients (45%) to the Helpline. At 6-month followup, 335 patients (11% of all referrals and 25% of participating patients) were abstinent. Providers at intervention sites reported referring many more patients to telephone counseling than providers at control sites (15.6 vs 0.7 in the prior month).\n The program generated a large number of referrals; almost half of the patients referred were connected with the Helpline. Long-term abstinence was excellent. These results suggest that managed care organizations may be able to improve tobacco control by implementing a similar system of care coordination.",
"Despite evidence of its effectiveness, tobacco cessation is not systematically addressed in routine healthcare settings. Its measurement is part of the problem. A pilot study was designed to develop and implement two different tobacco tracking systems in two independent primary care offices that participated in an IPA Model health maintenance organization in Portland, Oregon. The first clinic, which utilized a paper-based charting system, implemented CPT-like tracking codes to measure and report tobacco-cessation activities, which were eventually included in the managed-care organization's (MCO) claims database. The second clinic implemented an electronic tracking system based on its computerized electronic medical record (EMR) charting system. This paper describes the pilot study, including the processes involved in building provider acceptance for the new tracking systems in these two clinics, the barriers and successes encountered during implementation, and the resources expended by the clinics and by the MCO during the pilot. The findings from the 3-month implementation period were that documentation of tobacco-use status remained stable at 42-45% in the paper-based clinic and increased from 79% to 88% in the EMR clinic. This pilot study demonstrated that Tracking Codes are a feasible preventive-care tracking system in paper-based medical offices. However, high levels of effort and support are needed, and a critical mass of insurers and health plans would need to adopt Tracking Codes before widespread use could be expected. Results of the EMR-based tracking system are also reviewed and discussed.",
"Smoking cessation counseling is an important element of tobacco control in the workplace, but it is not easy to persuade workers to stop smoking. We performed a controlled intervention trial to evaluate the effectiveness of a new cessation program developed by Nakamura et al., which consisted of one brief individual counseling session and 4 follow-up telephone calls. Two hundred and twenty-eight smokers who visited our center for an annual health checkup were randomly divided into two group: 117 were assigned to the intervention group, and 111 were controls. Smoking status questionnaires were administered to assess the smoking habit of each subject and to evaluate their stages of change toward smoking cessation before the counseling session. Stage-matched cessation counseling was then provided to the intervention group by nurses who had completed training courses for this program. During the counseling session, carbon monoxide in expired air and nicotine metabolites in urine were measured to enhance self-perception of smoking. Only those clients who set a quit date during their counseling sessions received follow-up telephone calls. It was easy to implement this program (15 to 20 minutes long) during a health checkup. No significant differences were observed in the baseline characteristics of the two groups. The cross-sectional smoking cessation rates at 6 months and 1 year of follow-up were 6.2 times higher in the intervention group than in the control group. The continuous smoking cessation rate at 1 year of follow-up was 7.6 times higher in the intervention group than in the control group. In the intervention group, the lower level of nicotine metabolites in urine and higher smoking stage were related to cessation success, but other baseline characteristics were similar in those who quit smoking and those who did not. The effectiveness and easy applicability of this cessation program was proved in the present study. Further examinations in various settings are expected to clarify the effectiveness of this program."
] |
At least in the short term, documentation of tobacco status and increased referral to cessation counseling do appear to increase following the introduction of an expectation to use the EHR to record and treat patient tobacco use at medical visits. There is a need for additional research to further understand the effect of EHRs on smoking treatment in healthcare settings.
|
CD006602
|
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[
"Cost effectiveness of palivizumab for RSV prevention in high-risk children in the Netherlands.",
"Economic evaluation of possible prevention of RSV-related hospitalizations in premature infants in Germany.",
"Economic evaluation of palivizumab in children with congenital heart disease: a Canadian perspective.",
"Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease.",
"Cost-effectiveness analysis of palivizumab as respiratory syncytial virus prophylaxis in preterm infants in Sweden.",
"Palivizumab for immunoprophylaxis of respiratory syncytial virus (RSV) bronchiolitis in high-risk infants and young children: a systematic review and additional economic modelling of subgroup analyses.",
"Cost effectiveness of palivizumab for respiratory syncytial virus prophylaxis in high-risk children: a UK analysis.",
"Economic analysis of palivizumab in infants with congenital heart disease.",
"[Methodological aspects of economic evaluation in pediatrics: illustration by RSV infection prophylaxis in the French setting].",
"Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. The IMpact-RSV Study Group.",
"Cost-effectiveness of respiratory syncytial virus prophylaxis in various indications.",
"Cost effectiveness of palivizumab in children with congenital heart disease in Germany.",
"Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: a noninferiority trial.",
"Palivizumab for respiratory syncytial virus prophylaxis in high-risk infants: a cost-effectiveness analysis.",
"Cost effectiveness of palivizumab in Spain: an analysis using observational data.",
"Cost-effectiveness of respiratory syncytial virus prophylaxis among preterm infants.",
"Cost-effectiveness analysis of palivizumab in premature infants without chronic lung disease.",
"Cost-effectiveness of palivizumab for respiratory syncytial virus infection in high-risk children, based on long-term epidemiologic data from Austria.",
"The cost-effectiveness of palivizumab for respiratory syncytial virus prophylaxis in premature infants with a gestational age of 32-35 weeks: a Canadian-based analysis .",
"A randomized controlled trial of motavizumab versus palivizumab for the prophylaxis of serious respiratory syncytial virus disease in children with hemodynamically significant congenital heart disease.",
"[The efficiency (cost-effectiveness) of palivizumab as prophylaxis against respiratory syncytial virus infection in premature infants with a gestational age of 32-35 weeks in Spain].",
"Cost-utility analysis of palivizumab in Italy: results from a simulation model in the prophylaxis of respiratory syncytial virus infection (RSV) among high-risk preterm infants.",
"Cost-effectiveness of palivizumab in infancy.",
"Cost-effectiveness of palivizumab against respiratory syncytial viral infection in high-risk children in Austria.",
"Cost-effectiveness analysis of the use of palivizumab in the prophylaxis of preterm patients in Mexico.",
"Cost-effectiveness of palivizumab in New Zealand.",
"The cost effectiveness of palivizumab in term Inuit infants in the Eastern Canadian Arctic.",
"Changing costs and the impact on RSV prophylaxis.",
"Cost-effectiveness analysis of palivizumab among pre-term infant populations covered by Medicaid in the United States.",
"Use of surfactant for prophylaxis versus rescue treatment of respiratory distress syndrome: experience from an Italian-Bulgarian trial.",
"Safety, tolerability, pharmacokinetics, and immunogenicity of motavizumab, a humanized, enhanced-potency monoclonal antibody for the prevention of respiratory syncytial virus infection in at-risk children.",
"The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome."
] |
[
"Respiratory syncytial virus (RSV) is a common pathogen that is the leading cause of lower respiratory tract infections in young children. High-risk children are at risk of severe infection, which may require hospitalisation. RSV is also associated with a high risk for respiratory morbidity and mortality, which may have long-term clinical and economic consequences.\n To assess the cost effectiveness of palivizumab, a humanised monoclonal antibody, used as prevention against severe respiratory syncytial virus (RSV) infection requiring hospitalisation, in the indication of preterm infants and infants with preterm/bronchopulmonary dysplasia and in the second indication of children with congenital heart disease in the Dutch healthcare setting.\n A decision-tree model was used to estimate the cost effectiveness of palivizumab, used as a preventative treatment against severe respiratory syncytial virus (RSV) infection, in high-risk groups of children in the Netherlands. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. Data sources included published literature, the palivizumab pivotal trials, official price/tariff lists and national population statistics. The study was conducted from the perspective of society in the Netherlands.\n The use of palivizumab results in undiscounted incremental cost-effectiveness ratios of €12,728/QALY and €4,256/QALY in preterm/bronchopulmonary dysplasia and congenital heart disease indications, respectively. Inclusion of indirect costs leads to even more favourable cost-effectiveness outcomes. The study is limited by a number of conservative assumptions. It was assumed that palivizumab only affects the occurrence of RSV hospitalisation and does not influence the severity of the RSV infection. Another assumption was that international clinical trial data and data on utilities could be applied to the Dutch healthcare setting.\n Palivizumab provides cost-effective prophylaxis against RSV in high-risk infants. The use of palivizumab in these children results in positive short- and long-term health-economic benefits.",
"Palivizumab (Synagis, MedImmune Inc./Abbott Laboratories) has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in premature infants. The cost-effectiveness ratio of this prophylaxis, however, has not been evaluated in the German health-care system to date. The aim of the study was to assess the costs and benefits of Palivizumab among premature infants </=35 weeks with different risk factors. Projecting a societal perspective, we used decision analysis to compare the strategies of a prophylaxis with and without Palivizumab. Probabilities and costs of hospitalization were derived from a retrospective, population-based cohort study on 1,103 prematurely born infants primarily admitted to nine neonatologic care units in southern Germany between November 1998 and October 1999. Costs of prophylaxis were based on hospital sources. Efficacy of prophylaxis and estimates of RSV mortality were derived from the literature. Effectiveness was defined as the number of averted hospitalizations. The cost-effectiveness ratio of Palivizumab varied strongly among the different risk groups. While demonstrating no net cost savings related to RSV prophylaxis for any of the risk groups analyzed, Palivizumab showed the best cost-effectiveness ratio among male infants with chronic lung disease, discharge from primary neonatal care between October and December, and the presence of siblings visiting a day-care group. One averted hospitalization in this high-risk group was associated with costs of Euro 6,639 (number needed to treat (NNT): 4). For infants in other risk groups, the ratios varied from Euro 25,288 (NNT: 8) to Euro 204,684 (NNT: 54) per hospitalization averted. The cost-effectiveness ratios were sensitive to varying assumptions about probabilities and costs of rehospitalization, efficacy, and costs of Palivizumab prophylaxis.\n The results of this cost-effectiveness analysis do not justify the widespread use of Palivizumab among preterm infants. Lowering the costs of prophylaxis would be the most direct way to improve the cost-effectiveness ratio of Palivizumab.",
"Respiratory syncytial virus (RSV) is a common cause of bronchiolitis in infants. In children with congenital heart disease (CHD), it is associated with significant morbidity and mortality. Palivizumab is a monoclonal antibody that reduces the number of RSV-associated hospitalizations in children with CHD. We sought to assess cost savings and cost-effectiveness of palivizumab in children < 2 years old with hemodynamically significant CHD in a provincially administered RSV prophylaxis program.\n A cohort of children who received palivizumab (N = 292) from 2003-2007 was compared to a historical cohort of children (N = 412) from 1998-2003 who met the eligibility criteria for palivizumab prior to initiation of the prophylaxis program. Direct and indirect costs and benefits were determined.\n The direct and indirect costs in the historical cohort were $838 per patient season compared to $9130 per patient season in the palivizumab cohort. Risk of admission was reduced by 42%, and days in hospital were reduced by 83%. The incremental cost of the RSV prophylaxis program was $8292 per patient for 1 RSV season. The incremental cost to prevent 1 day of hospitalization was $15,514. The cost of palivizumab accounted for 87.9% of the cost of prophylaxis.\n Palivizumab is clinically effective; however, the cost was exceptionally high relative to the outcomes in this population. Given the financial constraints in a public health care setting, more strict criteria for patient selection or reduced drug costs would improve the cost-effectiveness of RSV prophylaxis.\n Copyright © 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.",
"To evaluate the safety, tolerance, and efficacy of palivizumab in children with hemodynamically significant congenital heart disease (CHD).\n A randomized, double-blind, placebo-controlled trial included 1287 children with CHD randomly assigned 1:1 to receive 5 monthly intramuscular injections of 15 mg/kg palivizumab or placebo. Children were followed for 150 days. The primary efficacy end point was antigen-confirmed respiratory syncytial virus (RSV) hospitalization.\n Palivizumab recipients had a 45% relative reduction in RSV hospitalizations (P=.003), a 56% reduction in total days of RSV hospitalization per 100 children (P=.003), and a 73% reduction in total RSV hospital days with increased supplemental oxygen per 100 children (P=.014). Adverse events were similar in the treatment groups; no child had drug discontinued for a related adverse event. Serious adverse events occurred in 55.4% of palivizumab recipients and 63.1% of placebo recipients (P<.005); none were related to palivizumab. Twenty-one children (3.3%) in the palivizumab group and 27 (4.2%) in the placebo group died; no deaths were attributed to palivizumab. The rates of cardiac surgeries performed earlier than planned were similar in the treatment groups.\n Monthly palivizumab (15 mg/kg IM) was safe, well-tolerated, and effective for prophylaxis of serious RSV disease in young children with hemodynamically significant CHD.",
"To investigate the cost-effectiveness of palivizumab vs. no prophylaxis for respiratory syncytial virus (RSV) infection in preterm infants in Sweden.\n A probabilistic Markov model was populated using a nationwide register linkage and data from the literature. Cost-effectiveness was investigated from a societal perspective over a lifetime for infants born at <29 weeks of gestation. Palivizumab was modelled using assumptions for its direct effect on RSV hospitalization risk and an indirect effect (via decreased RSV hospitalization) on subsequent asthma and mortality during the epidemic. Costs and effects were discounted by 3%.\n In the base case, prophylaxis resulted in an additional 0.102 quality-adjusted life-year (QALY) at a cost of 20,000 SEK relative to no prophylaxis (incremental cost-effectiveness ratio [ICER] 195,000 SEK/QALY). The probability of prophylaxis being cost-effective was 99% at a willingness-to-pay of 500,000 SEK/QALY. Assumptions about a causal association between RSV infection and subsequent asthma had a moderate impact, while exclusion of the indirect prophylaxis effect on mortality increased the ICER to 492,000 SEK/QALY. When excluding both of these, prophylaxis was not cost-effective.\n Based on a willingness-to-pay of 500,000 SEK/QALY, palivizumab was found to be cost-effective compared with no prophylaxis for infants born at <29 weeks if severe RSV infection was assumed to increase subsequent asthma or mortality risk.\n © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.",
"Respiratory syncytial virus (RSV) is a seasonal infectious disease, with epidemics occurring annually from October to March in the UK. It is a very common infection in infants and young children and can lead to hospitalisation, particularly in those who are premature or who have chronic lung disease (CLD) or congenital heart disease (CHD). Palivizumab (Synagis®, MedImmune) is a monoclonal antibody designed to provide passive immunity against RSV and thereby prevent or reduce the severity of RSV infection. It is licensed for the prevention of serious lower respiratory tract infection caused by RSV in children at high risk. While it is recognised that a policy of using palivizumab for all children who meet the licensed indication does not meet conventional UK standards of cost-effectiveness, most clinicians feel that its use is justified in some children.\n To use systematic review evidence to estimate the cost-effectiveness of immunoprophylaxis of RSV using palivizumab in different subgroups of children with or without CLD or CHD who are at high risk of serious morbidity from RSV infection.\n A systematic review of the literature and an economic evaluation was carried out. The bibliographic databases included the Cochrane Library [Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] and five other databases, from inception to 2009. Research registries of ongoing trials including Current Controlled Trials metaRegister, Clinical Trials.gov and the National Institute for Health Research Clinical Research Network Portfolio were also searched.\n Searches were conducted for prognostic and hospitalisation studies covering 1950-2009 (the original report searches conducted in 2007 covering the period 1950-2007 were rerun in August 2009 to cover the period 2007-9) and the database of all references from the original report was sifted to find any relevant studies that may have been missed. The risk factors identified from the systematic review of included studies were analysed and synthesised using stata. The base-case decision tree model developed in the original HTA journal publication [Health Technol Assess 2008;12(36)] was used to derive the cost-effectiveness of immunoprophylaxis of RSV using palivizumab in different subgroups of pre-term infants and young children who are at high risk of serious morbidity from RSV infection. Cost-effective spectra of prophylaxis with palivizumab compared with no prophylaxis for children without CLD/CHD, children with CLD, children with acyanotic CHD and children with cyanotic CHD were derived.\n Thirteen studies were included in this analysis. Analysis of 16,128 subgroups showed that prophylaxis with palivizumab may be cost-effective [at a willingness-to-pay threshold of £30,000/quality-adjusted life-year (QALY)] for some subgroups. For example, for children without CLD or CHD, the cost-effective subgroups included children under 6 weeks old at the start of the RSV season who had at least two other risk factors that were considered in this report and were born at 24 weeks gestational age (GA) or less, but did not include children who were > 9 months old at the start of the RSV season or had a GA of > 32 weeks. For children with CLD, the cost-effective subgroups included children < 6 months old at the start of the RSV season who were born at 28 weeks GA or less, but did not include children who were > 21 months old at the start of the RSV season. For children with acyanotic CHD, the cost-effective subgroups included children < 6 months old at the start of the RSV season who were born at 24 weeks GA or less, but did not include children who were > 21 months old at the start of the RSV season. For children with cyanotic CHD, the cost-effective subgroups included children < 6 weeks old at the start of the RSV season who were born at 24 weeks GA or less, but did not include children who were > 12 months old at the start of the RSV season.\n The poor quality of the studies feeding numerical results into this analysis means that the true cost-effectiveness may vary considerably from that estimated here. There is a risk that the relatively high mathematical precision of the point estimates of cost-effectiveness may be quite inaccurate because of poor-quality inputs.\n Prophylaxis with palivizumab does not represent good value for money based on the current UK incremental cost-effectiveness ratio threshold of £30,000/QALY when used unselectively in children without CLD/CHD or children with CLD or CHD. This subgroup analysis showed that prophylaxis with palivizumab may be cost-effective (at a willingness-to-pay threshold of £30,000/QALY) for some subgroups. In summary, the cost-effective subgroups for children who had no CLD or CHD must contain at least two other risk factors apart from GA and birth age. The cost-effective subgroups for children who had CLD or CHD do not necessarily need to have any other risk factors. Future research should be directed towards conducting much larger, better powered and better reported studies to derive better estimates of the risk factor effect sizes.\n This report was funded by the HTA programme of the National Institute for Health Research.",
"To assess the cost effectiveness of palivizumab (a preventative treatment against severe respiratory syncytial virus [RSV] infection) in children at high risk of hospitalisation, i.e. preterm infants < or = 35 weeks gestation, children with bronchopulmonary dysplasia (BPD) and children with congenital heart disease (CHD).\n A decision tree model was developed employing data sources from the published literature, palivizumab clinical trials, official UK price/tariff lists and national population statistics. The comparator was no prophylaxis. The primary perspective of the study was that of the UK NHS. In a societal perspective scenario analysis, the future lost productivity of a child resulting from RSV-related mortality (indirect costs) was also included. The cost of administration of palivizumab, hospital care for RSV infections and the cost of asthma treatment were included. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. The primary efficacy outcome in the palivizumab clinical trials was the number of RSV hospitalisations avoided, which was extrapolated to effectiveness outcomes, i.e. number of life-years gained and number of QALYs. Costs and effects were discounted by 3.5%.\n In preterm infants and children with BPD, prophylaxis with palivizumab compared with no prophylaxis had an incremental cost-effectiveness ratio (ICER) of 7042 pounds/QALY without discounting outcomes, increasing to 16,720 pounds/QALY after discounting. In babies with CHD, the use of palivizumab resulted in an ICER of 2427 pounds/QALY without discounting outcomes and 6664 pounds/QALY after discounting. One-way sensitivity analyses and probabilistic sensitivity analyses confirmed the robustness of the model. A scenario analysis showed that the inclusion of indirect costs leads to further improvement in the cost-effectiveness outcomes for palivizumab.\n This study suggests that palivizumab prophylaxis against severe RSV infection in children at high risk may be cost effective from the NHS perspective (vs no prophylaxis), and that the positive clinical and economic benefits may persist beyond one RSV season.",
"Palivizumab has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations by 45% in children with congenital heart disease (CHD). The American Academy of Pediatrics has recommended that infants with hemodynamically significant CHD be considered for palivizumab. However, the economic implications of palivizumab prophylaxis in the CHD population have not been evaluated. In the present study, we sought to examine the cost savings and cost utility of RSV prophylaxis with palivizumab in children with CHD.\n Probabilities of hospitalization and efficacy of prophylaxis were based on published results. Costs of hospitalization were derived from a published analysis of bronchiolitis hospitalization costs from a consortium of children's hospitals. A hypothetical cohort of 10,000 CHD patients (half of whom would receive palivizumab) was created to calculate cost-savings and cost-utility. To assess cost utility, we assumed that by reducing hospitalization, palivizumab would reduce RSV-related hospital mortality, generally reported to be 3% in CHD patients. Sensitivity analysis was performed.\n On the basis of a protocol of 5 monthly doses of palivizumab, the cost of prophylaxis for 1 RSV season was calculated as 6160 dollars per patient. After accounting for impact on direct and indirect costs of hospitalization, administration of palivizumab to 5000 CHD patients would result in a net loss of 20,415,753 dollars. If one assumes that palivizumab confers a survival benefit, then the cost of life-year saved is 100,338 dollars and cost of quality-adjusted life-year saved is 114,337 dollars.\n The cost of palivizumab prophylaxis was high relative to benefits realized. Given the large number of CHD patients who might be considered candidates for RSV prophylaxis (>6000 patients per year in United States) routine use of palivizumab in young children with hemodynamically significant CHD needs to be evaluated further.",
"The methodological approach of the economic evaluation of drugs in pediatrics is illustrated by the case study of the prophylaxis for RSV infections using palivizumab in the French setting. The indications for the reimbursement of this treatment have been restricted to premature children with bronchopulmonary dysplasia (BPD) or hemodynamically significant congenital-heart disease. A model was developed primarily using the results of the pivotal clinical studies on palivizumab. Unit costs were estimated (2006 values) in both societal and payer's perspectives. An assumption was made and discussed on the benefits of the prophylaxis on mortality. Based on the different data available and the estimated costs and benefits, different cost-effectiveness ratios (CERs) were estimated from both the society's and payer's points of view. A discount rate of 3% was applied to benefit. The CER obtained in the most unfavorable case is considered acceptable for the innovative-medical technologies in the French-healthcare system. Some of the parameters used by the model will be illustrated from the EPIPAGE study data from 2 of the 9 regions involved in this study: this evaluation suggests that the children not having an RSV infection during their 1st year of life will continue to require significantly fewer hospitalizations in the following years. These additional evaluations also suggest that the model overestimates the costs of the treatment with regard to the true medical situation. This could be explained by the model not using the children's exact weight or the real number of injections because the children had been discharged from the maternity ward based on their date of birth and the epidemic period. In spite of these factors, RSV prophylaxis using palivizumab in premature children with BPD or hemodynamically significant congenital-heart disease can be considered cost-effective in France.",
"To determine the safety and efficacy of prophylaxis with palivizumab in reducing the incidence of hospitalization because of respiratory syncytial virus (RSV) infection in high-risk infants.\n A randomized, double-blind, placebo-controlled trial was conducted at 139 centers in the United States, the United Kingdom, and Canada. During the 1996 to 1997 RSV season, 1502 children with prematurity (less than or equal to 35 weeks) or bronchopulmonary dysplasia (BPD) were randomized to receive 5 injections of either palivizumab (15 mg/kg) or an equivalent volume of placebo by intramuscular injection every 30 days. The primary endpoint was hospitalization with confirmed RSV infection. Children were followed for 150 days (30 days from the last injection). Those with hospitalization as a result of RSV infection were evaluated for total number of days in the hospital, total days with increased supplemental oxygen, total days with moderate or severe lower respiratory tract illness, and incidence and total days of intensive care and mechanical ventilation. The incidence of hospitalization for respiratory illness not caused by RSV and the incidence of otitis media were also evaluated. The placebo and palivizumab groups were balanced at entry for demographics and RSV risk factors. Ninety-nine percent of children in both groups completed the protocol and approximately 93% received all five scheduled injections.\n Palivizumab prophylaxis resulted in a 55% reduction in hospitalization as a result of RSV (10.6% placebo vs 4.8% palivizumab). Children with prematurity but without BPD had a 78% reduction in RSV hospitalization (8.1% vs 1.8%); children with BPD had a 39% reduction (12.8% vs 7.9%). When gender, entry age, entry weight, BPD, and gestational age were included in a logistic regression model, the effect of prophylaxis with palivizumab remained statistically significant. The palivizumab group had proportionally fewer total RSV hospital days, fewer RSV hospital days with increased oxygen, fewer RSV hospital days with a moderate/severe lower respiratory tract illness, and a lower incidence of intensive care unit admission. Palivizumab was safe and well tolerated. No significant differences were observed in reported adverse events between the two groups. Few children discontinued injections for related adverse events (0.3%). Reactions at the site of injection were uncommon (1.8% placebo vs 2.7% palivizumab); the most frequent reaction was mild and transient erythema. Mild or moderate elevations of aspartate aminotransferase occurred in 1.6% of placebo recipients and 3.6% of palivizumab recipients; for alanine aminotransferase these percentages were 2.0% and 2.3%, respectively. Hepatic and renal adverse events related to the study drug were similar in the two groups.\n Monthly intramuscular administration of palivizumab is safe and effective for prevention of serious RSV illness in premature children and those with BPD.",
"To evaluate the cost-effectiveness of immunoprophylaxis against respiratory syncytial virus (RSV) infections with palivizumab based on actual cost and observed incidence rates in various pediatric risk groups.\n Decision tree analysis comparing children with various combinations of the following indications: chronic lung disease, congenital heart disease, or prematurity (≤32 weeks gestation), and children with none of these indications. One-way sensitivity analyses and Monte Carlo simulations were used to quantify parameter uncertainty.\n Florida during the 2004-2005 RSV season.\n A total of 159,790 Medicaid-eligible children aged 0 to 2 years.\n Palivizumab prophylaxis compared with no prophylaxis. OUTCOMES MEASURE: Incremental cost (2010 US dollars) per hospitalization for RSV infection avoided.\n The mean cost of palivizumab per dose ranged from $1661 for infants younger than 6 months of age to $2584 for children in their second year of life. Among preterm infants younger than 6 months of age without other indications, immunoprophylaxis with palivizumab cost $302,103 (95% confidence interval, $141,850-$914,798) to prevent 1 RSV-related hospitalization. Given a mean cost of $8910 for 1 RSV-related hospitalization in this subgroup, palivizumab would be cost-neutral at a per-dose cost of $47. Incremental cost-effectiveness ratios for the other subgroups ranged from $361,727 to more than $1.3 million per RSV-related hospitalization avoided in children up to 2 years of age with chronic lung disease and no additional risk factors. Younger age and multiple indications were associated with improvements in the incremental cost-effectiveness ratio.\n The cost of immunoprophylaxis with palivizumab far exceeded the economic benefit of preventing hospitalizations, even in infants at highest risk for RSV infection.",
"To assess the cost effectiveness of palivizumab, a humanised monoclonal antibody, used as prevention against severe respiratory syncytial virus (RSV) infection requiring hospitalisation, in infants with haemodynamically significant congenital heart disease (CHD) in the German healthcare setting.\n A decision-tree model was used to estimate the cost effectiveness of palivizumab for a hypothetical cohort of patients. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. Data sources included published literature, the palivizumab pivotal trials, official price/tariff lists and national population statistics. The study was conducted from the perspective of society (primary analysis) and the healthcare purchaser (secondary analysis).\n From the societal perspective, use of palivizumab results in an incremental cost-effectiveness ratio (ICER) of €2,615 per quality-adjusted life-year (QALY) without discounting, which increases to €9,529/QALY after discounting. From the perspective of the German healthcare purchaser, use of palivizumab results in an ICER of €4,576/QALY without discounting, which increases to €16,673/QALY after discounting. Probabilistic sensitivity analyses confirmed the robustness of the model. The study is limited by a number of conservative assumptions. It was assumed that palivizumab only affects the occurrence of RSV hospitalisation and does not influence the severity of the RSV infection. Another assumption was that international clinical trial data and data on utilities could be applied to the German healthcare setting.\n This analysis showed that palivizumab represents a cost-effective means of prophylaxis against severe RSV infection requiring hospitalisation in infants with haemodynamically significant CHD.",
"Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by approximately 50% compared with placebo. We compared the efficacy and safety of motavizumab, an investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies, with palivizumab.\n This randomized, double-blind, multinational, phase 3, noninferiority trial assessed safety and RSV hospitalization in 6635 preterm infants aged <or=6 months at enrollment or children aged <or=24 months with chronic lung disease of prematurity who received 15 mg/kg palivizumab or motavizumab monthly. Secondary end points included outpatient medically attended lower respiratory tract infections (MALRIs), RSV-specific LRIs, otitis media, antibiotic use, development of antimotavizumab antibodies, and motavizumab serum concentrations.\n Motavizumab recipients had a 26% relative reduction in RSV hospitalization compared with palivizumab recipients, achieving noninferiority. Motavizumab was superior to palivizumab for reduction of RSV-specific outpatient MALRIs (50% relative reduction). Overall, adverse events (AEs) were not significantly different between groups. Cutaneous events were reported in 2 percentage points more motavizumab recipients (7.2% vs 5.1%); most were mild, but 0.3% resulted in dosing discontinuation. Antidrug antibodies (ADA) were detected in 1.8% of motavizumab recipients. Patients with anti-drug antibody reported 6 RSV events and 17 cutaneous events.\n Children receiving prophylaxis with motavizumab or palivizumab had low rates of RSV hospitalization; motavizumab recipients experienced 50% fewer RSV MALRIs than palivizumab recipients. AEs were similar in both groups, although cutaneous AEs were higher for motavizumab recipients. Motavizumab may offer an improved alternative in prophylaxis for serious RSV disease in infants and children at high risk.",
"Prophylactic therapy with palivizumab, a humanized monoclonal antibody, has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in preterm infants. The cost-effectiveness of this therapy has not been evaluated from the provider's perspective using cost data.\n The objectives of this study were to determine the cost per RSV infection episode avoided by using prophylactic palivizumab therapy in a high-risk infant population and to determine whether certain subgroups of infants derived greater benefit from prophylactic therapy.\n A decision-analytic model simulating an RSV infection episode was developed to evaluate the cost-effectiveness of palivizumab prophylaxis from the perspective of the health care system (provider). Data to populate the model were gathered from the medical literature (identified through a MEDLINE search of studies on the incidence of RSV infection) and the IMpact-RSV clinical trial. Data included incidence of RSV infection and the associated health care resource use and costs. Costs to the provider were determined using a university-affiliated hospital cost-accounting system. Cost-effectiveness ratios were calculated over a range of RSV infection incidence rates in a control population. Sensitivity analyses were performed for the cost of palivizumab therapy, the cost of RSV-related hospitalization, and the number of emergency department, physician office, and home health care visits. For the subgroup analysis, infants were classified by gestational age (<32 and > or = 32 weeks) and stratified by severity of chronic lung disease.\n The cost per additional RSV infection episode avoided ranged from dollars 0 (cost savings) to dollars 39,591 for palivizumab prophylaxis costs of dollars 2500 and from dollars 2702 to dollars 79,706 for palivizumab prophylaxis costs of dollars 4500. The model was insensitive to changes in the number of emergency department, physician office, and home health care visits. The difference in RSV incidence between the treatment and control groups was greater among infants > or = 32 weeks' gestational age than among infants <32 weeks' gestational age. onclusions: The incremental cost-effectiveness of palivizumab compared with no prophylactic therapy was sensitive to changes in the incidence of RSV infection in control infants, the average cost of RSV hospitalization, and the cost of palivizumab. Clinicians may use this information along with additional factors to determine whether palivizumab is cost-effective in their clinical setting and geographic area.",
"To assess the cost effectiveness of palivizumab for prevention of severe respiratory syncytial virus (RSV) disease in high-risk infants in Spain, incorporating country-specific observational hospitalisation data.\n An existing decision tree model, designed using data from a large international clinical trial of palivizumab versus no prophylaxis, was updated to include Spanish observational hospitalisation data. The analysis was performed for preterm children born at or before 32 weeks gestational age, who are at high risk of developing severe RSV disease requiring hospitalisation. Data sources included published literature, official price/tariff lists and national population statistics. The primary perspective of the study was that of the Spanish National Health Service in 2006.\n The base-case analysis included the direct medical costs associated with palivizumab prophylaxis and hospital care for RSV infections. Use of palivizumab produces an undiscounted incremental cost-effectiveness ratio (ICER) of euro6,142 per quality-adjusted life-year (QALY), and a discounted ICER of euro12,814/QALY.\n Palivizumab provides a cost-effective method of prophylaxis against severe RSV disease requiring hospitalisation among preterm infants in Spain.",
"To evaluate the costs and benefits of two new agents, respiratory syncytial virus immune globulin (RSVIG) and palivizumab, to prevent respiratory syncytial virus (RSV) infection among premature infants discharged from the neonatal intensive care unit (NICU) before the start of the RSV season. Method. Decision analysis was used to compare the projected societal cost-effectiveness of three strategies-RSVIG, palivizumab, and no prophylaxis-among a hypothetical cohort of premature infants. Probabilities and costs of hospitalization were derived from a cohort of 1721 premature infants discharged from six Kaiser Permanente-Northern California NICUs. Efficacies of prophylaxis were based on published trials. Costs of prophylaxis were derived from published sources. Mortality among infants hospitalized for RSV was assumed to be 1.2%. Future benefits were discounted at 3%.\n Palivizumab was both more effective and less costly than RSVIG. Cost-effectiveness varied widely by subgroup. Palivizumab appeared most cost-effective for infants whose gestational age was </=32 weeks, who required >/=28 days of oxygen in the NICU, and who were discharged from the NICU from September through November. In this subgroup, palivizumab was predicted to cost $12,000 per hospitalization averted (after taking into account savings from prevention of RSV admissions) or $33,000 per life-year saved, and the number needed to treat to avoid one hospitalization was estimated at 7.4. However, for all other subgroups, ratios ranged from $39,000 to $420,000 per hospitalization averted or $110,000 to $1,200,000 per life-year saved, and the number needed to treat extended from 15 to 152. The results were sensitive to varying assumptions about the cost and efficacy of prophylaxis, as well as the probability of hospitalization, but were less sensitive to the cost of hospitalization.\n In our model, the cost of prophylaxis against RSV for most subgroups of preterm infants was high relative to the benefits realized. Lower costs might permit the benefits of prophylaxis to be extended to additional groups of preterm infants.",
"To evaluate the cost-effectiveness of palivizumab as respiratory syncytial virus prophylaxis in premature infants without chronic lung disease and to evaluate the impact on cost-effectiveness of a potential reduction in risk of asthma following respiratory syncytial virus infection among infants receiving palivizumab.\n Two decision analytic models were designed, one with and the other without accounting for increased risk of asthma following respiratory syncytial virus infection.\n A hypothetical community or university hospital.\n Hypothetical cohorts of infants without chronic lung disease born at 26 to 32 weeks' gestation.\n Palivizumab prophylaxis vs no prophylaxis.\n Expected costs and incremental cost-effectiveness ratio expressed as cost per quality-adjusted life-year.\n The expected costs were higher for palivizumab prophylaxis as compared with no prophylaxis. The incremental cost-effectiveness ratios were high for all gestations and are not considered cost-effective by today's standards (<$200 000 per quality-adjusted life-year). Both models were sensitive to variation in the cost of palivizumab. The model that included asthma was sensitive to variation in quality of life for children with asthma. In instances where asthma was considered severe with profound worsening in quality of life compared with life without asthma, some infants had an incremental cost per quality-adjusted life-year that was less than $200 000.\n Our model supports implementing more restrictive guidelines for palivizumab prophylaxis. Palivizumab was cost-effective for some infants in an analysis that accounted for increased risk of severe asthma following respiratory syncytial virus infection.",
"To assess the cost-effectiveness of palivizumab, a monoclonal antibody against respiratory syncytial virus (RSV), in infants at high risk for severe RSV lower respiratory tract infection, such as premature infants, infants with bronchopulmonary dysplasia, and those with congenital heart disease, based on long-term epidemiologic data from Austria.\n A decision-tree model was used, and the analysis was based on a lifetime follow-up investigating cost-effectiveness of palivizumab versus no RSV infection prevention. The primary perspective of the study was that of the healthcare system, the second that of society. Cost and effects were discounted by 5%. The base case analysis included only direct medical costs, and a scenario analysis included various indirect costs.\n Analyses were based on epidemiologic data on a total of 1579 children hospitalized because of RSV lower respiratory tract infection during 16 seasons. The incremental cost-effectiveness ratio for the first outcome measure (life years gained) amounted to discounted costs of €34,956 (for all preterm infants), €35,056 (for < 33 weeks' gestational age [wGA] infants), €35,233 (for 33-35 wGA infants), €35,611 (for infants with bronchopulmonary dysplasia), and €8956 (for infants with congenital heart disease). Use of palivizumab compared with no prophylaxis had an incremental cost-utility ratio of €26,212, €26,292, €24,392, €24,654, and €8484, respectively, per quality-adjusted life years. Results from the society perspective were more cost-effective in all study populations. An additional scenario analysis with 7 injections for the 33 to 35 wGA group revealed cost-effectiveness as well.\n Our results based on nationwide long-term epidemiologic data suggest that palivizumab is cost-effective in prevention of RSV disease in high-risk infants.",
"Prophylactic therapy with palivizumab, a humanized monoclonal antibody, has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in preterm infants, including those in the 32-35 weeks' gestational age (GA) subgroup. The cost-effectiveness of this therapy in Canada is unknown.\n To evaluate the cost-effectiveness of palivizumab as respiratory syncytial virus prophylaxis in premature infants born at 32-35 weeks' GA. Design: A decision analytic model was designed to compare both direct and indirect medical costs and benefits of prophylaxis in this subgroup of premature infants. Sensitivity analyses were performed to ascertain the robustness of the model for five point estimates: mortality rate, discounting rates, health-utility values, degree of vial-sharing and administration costs. A probabilistic sensitivity analysis (PSA) was also conducted.\n Canadian publicly funded health-care system (Ministry of Health payer perspective) for base-case analysis. Societal perspective, accounting for future lost productivity, was adopted for a secondary analysis. Participants: Canadian infants born at 32-35 weeks' GA without chronic lung disease. Interventions: Palivizumab prophylaxis versus no prophylaxis. Main outcome measures: Expected costs and incremental cost-effectiveness ratio expressed as cost per life-year gained (LYG) and quality-adjusted life-year (QALY) using 2007 Canadian dollars. Results: The expected costs were higher for palivizumab prophylaxis as compared with no prophylaxis. The incremental cost-effectiveness ratio (ICER) for the base-case scenario was $20 924 per QALY after discounting, which is considered cost-effective in Canada. When the uncertainty of the input parameter assumptions was tested through sensitivity analyses assessing several data sources for five key parameters, no substantial differences were found from the base-case results. The PSA indicated a 0.99 probability that the ICER for palivizumab was less than $50 000/QALY. Sub-analyses that varied the number of risk factors found that for infants with two or more risk factors, or at least moderate risk, palivizumab had incremental costs per QALY that indicated moderate-to-strong evidence for adoption (range: $808-81 331, per QALY).\n Palivizumab was cost-effective and the authors' model supports prophylaxis for infants born at 32-35 weeks' GA, particularly those with more than two risk factors or at least a moderate level of risk according to a risk scoring tool.",
"Children with hemodynamically significant congenital heart disease (CHD) are at risk for serious respiratory syncytial virus (RSV) disease. This study was designed to assess the safety and tolerability of motavizumab versus palivizumab in children with CHD and was not powered for efficacy. Patients (n = 1236) aged ≤24 mo were randomized to receive five monthly doses (15 mg/kg) of motavizumab or palivizumab during the RSV season. Adverse events (AEs) and serious AEs (SAEs) were recorded through 30 d after the last dose. RSV hospitalizations and RSV outpatient medically attended lower respiratory tract infections (MALRI; season 2) were summarized. Approximately 93 and 50% of patients reported an AE or SAE, respectively. Skin events occurred in 19.3% of motavizumab recipients and 16.2% of palivizumab recipients. Rates of hospitalizations and RSV MALRI were similar between treatment groups [relative risk (RR): 0.75; 95% CI, 0.34-1.59 and RR: 0.49; 95% CI, 0.10-1.99, respectively; both p > 0.05]. Motavizumab and palivizumab had similar safety profiles in children with hemodynamically significantly CHD; with the exception of skin events which were increased in motavizumab recipients. Safety and efficacy were consistent with another study comparing motavizumab with palivizumab in premature infants without CHD.",
"To evaluate the efficiency (cost-effectiveness) of palivizumab in preventing severe respiratory syncytial virus (RSV) infection in premature infants with a gestational age of 32-35 weeks (GA 32-35) and two or more risk factors (RF) in Spain.\n Design: decision tree model using data from the scientific literature and the FLIP I and FLIP II studies (cohort of 326 infants with GA 32-35 and two or more RF who received palivizumab) sponsored by the Spanish Society of Neonatology. Main effectiveness measure: quality-adjusted life years (QALY) gained. Perspectives: the national health service (NHS), which includes direct costs (administration of palivizumab and hospital admissions), and the societal perspective, which also includes indirect costs (the child's future lost productivity). Discount: 3 % annually for effectiveness and indirect costs. Sensitivity analysis: construction of 37 scenarios modifying variables related to effectiveness and costs.\n Prophylaxis with palivizumab in premature infants with GA 32-35 and two or more RF produced an incremental cost-effectiveness ratio (ICER) of 13,849 euro/QALY from the NHS perspective, and an ICER of 4,605 euro/QALY from the societal perspective. In the sensitivity analysis, from the NHS perspective the ICER ranged from 5,351 euro/QALY (most favorable scenario) to 23,276 euro/QALY (least favorable scenario).\n Palivizumab is a cost-effective therapy as prophylaxis against RSV in infants with GA 32-35 and two or more RF. Its use is efficient from the NHS perspective, since the cost of a QALY, even in the least favorable scenarios, is lower than the threshold of 30,000 Euro/QALY considered socially acceptable in Spain.",
"The aim of this study was to assess the cost-utility of palivizumab versus no prophylaxis in the prevention of respiratory syncytial virus infection among high-risk preterm infants.\n We used and adapted a pre-existent model in which two cohorts of patients received palivizumab or no prophylaxis. The patients were followed for their expected lifetimes. The economic evaluation was conducted from the perspective of the Italian National Health Service. We considered Life-Years Gained (LYGs), Quality-Adjusted Life-Years (QALYs) and direct medical costs (pharmacological treatment, hospitalization, recurrences for wheezing, etc.). LYGs and QALYs were based on the results of a double blind cohort study with prospective follow-up and direct medical costs were based on Italian treatment patterns. Benefits and costs were discounted at 3%. Costs were assessed in 2007 Euros. Sensitivity and threshold analysis on key clinical and economic parameters were performed.\n For the two cohorts, the expected life-years (per patient) with palivizumab versus no prophylaxis were 29.842 and 29.754 years, respectively. Quality-adjusted life years (per patient) with palivizumab were 29.202, and for no prophylaxis were 29.043. The expected cost (per patient) was euro 6,244.20 with palivizumab and euro 4,867.70 with no prophylaxis. We calculated for palivizumab versus no prophylaxis the incremental cost per LYG and per QALY gained. It was euro 15,568.65 and euro 8,676.74, respectively.\n This study suggests that, compared with no prophylaxis, palivizumab is cost-effective in the prevention of respiratory syncytial virus infection among high risk preterm infants.",
"Respiratory syncytial virus is the most common cause of bronchiolitis, a lower respiratory tract infection occurring in infancy. It is responsible for several rehospitalizations, substantial morbidity and occasional deaths in the UK every year. Palivizumab is a recombinant monoclonal antibody that has been shown to reduce hospitalizations in infected infants. It is licensed for high-risk infants, primarily those born pre-term or with chronic pulmonary or cardiac conditions. Palivizumab is expensive, but several economic analyses have determined highly discrepant costs. This article reviews the limitations of the available efficacy and economic data, and highlights problems in interpretation and extrapolation. We also present the results of a cost-effectiveness analysis relevant to populations of high-risk infants in the UK.",
"The aim of this study was to estimate the cost-effectiveness of palivizumab, a monoclonal antibody against severe respiratory syncytial virus infection, in high-risk infants in Austria.\n A decision tree model was developed to determine cost-effectiveness in infants born prematurely (<or=35 weeks' gestational age), those with bronchopulmonary dysplasia (BPD), and children with congenital heart disease (CHD). The primary perspective of the analysis was that of the compulsory health insurance fund. The societal perspective was also considered.\n From the health insurance fund perspective, including the costs associated with asthma, the incremental cost-effectiveness ratio (cost per quality-adjusted life year [QALY] gained) without discounting was estimated to be euro 4484 (2006 euros) in preterm infants, euro 6719 in children with BPD, and euro 2668 in the CHD population. When discounted, these figures increased to euro 14,439, euro 21,672, and euro 9754, respectively. The results from the societal perspective were substantially more cost-effective in all populations. The undiscounted cost per QALY was euro 1435 in preterm infants, euro 4881 in children with BPD, and euro 251 in the CHD group. Discounted figures were euro 4623, euro 15,741, and euro 917, respectively. Sensitivity analyses confirmed the robustness of the model, and scenario analyses found that the inclusion of indirect costs led to further improvement in the cost-effectiveness outcomes for palivizumab.\n Use of palivizumab was cost-effective compared with no prophylaxis in high-risk infants and children in Austria.",
"The study evaluated the incremental cost-effectiveness ratio (ICER) of the prophylaxis of palivizumab, for the reduction of complications associated to the respiratory syncytial virus in preterm patients in Mexico.\n A decision tree was developed in preterm groups [<29 and 29-32 weeks of gestational age (wGA)], by using epidemiological and cost local data; the effectiveness was obtained with a systematic review. Patients were evaluated according to their life expectancy. Mexican Health System perspective was used. Effectiveness measures employed were LYG and QALYs. The costs are reported in USD 2009.\n ICERs per LYG resulted on values of USD $25,029 and USD $29,637 for <29 wGA and 29-32 wGA respectively, whereas ICERs per QALYs obtained in the model accounted for USD $17,532 and USD $20,760.\n Palivizumab prophylaxis for preterm newborn patients ≤32 weeks of age resulted in a cost-effective alternative.",
"To establish the preterm infant hospitalization risks from respiratory syncytial virus (RSV) in New Zealand and the net cost per hospitalization averted by palivizumab.\n The 437 infants born < 32 weeks' gestation in 1997 and treated at five major neonatal units were identified. Subsequent admissions during the next 2 years for bronchiolitis, pneumonia and croup were tracked, and information collected on RSV tests performed. Data on the length of stay and hospital costs were used to calculate the potential net cost per hospitalization averted associated with the use of palivizumab and the number needed to treat (NNT) to prevent one hospitalization.\n Estimated RSV readmission risk before 1 year corrected age in infants < 32 weeks' gestation discharged home on oxygen, and those \" 28 weeks' gestation, or between 29 and 31 weeks' gestation with or without chronic lung disease was 42%, 23%, 19%, 10% and 8%, respectively. The NNT with palivizumab to prevent one hospitalization ranged from six to 26 across subgroups. Mean (range) net cost per hospitalization averted was 60,000 New Zealand dollars ($28,000-$166,700). In no subgroup would prophylaxis result in net cost saving. Prophylaxis for all NZ infants \" 28 weeks' gestation would cost approximately $1,090,000 net and prevent 29 hospitalizations annually, being equivalent to $37,000 net per hospitalization averted, with eight infants treated to prevent one hospitalization. Alternative assumptions about cost and efficacy failed to alter these findings.\n If value is placed on preventing morbidity, the priority groups for palivizumab prophylaxis are preterm infants discharged home on oxygen, followed by preterm infants of 28 weeks' gestation or less.",
"Canadian, Inuit, full term infants have the highest rate of respiratory syncytial virus (RSV) infection globally, which results in substantial costs associated hospitalisation.\n Decision-analytical techniques were used to estimate the incremental cost-effectiveness ratio (ICER) for palivizumab compared to no prophylaxis for Inuit infants of all gestational age. The time horizon was that of life-time follow-up, and costs and effectiveness were discounted at 5% per year. Costs (2007 CAD$) for palivizumab, hospitalisation (including medical evacuation, intensive care unit [ICU]), physician visits, and transportation were calculated based on the Canadian payer's perspective. Benefits on decreasing RSV hospitalisation were expressed as quality-adjusted life-years (QALYs). One-way and probabilistic sensitivity analysis (PSA) were conducted, varying: mortality rates, utilities, length of stay in hospital and ICU.\n For all of Baffin Island infants (<1 year), the ICER was $39,435/QALY. However, when infants were grouped by age and area of residence, those residing in Iqaluit (<1 year) had an ICER of $152,145/QALY, while those residing in rural areas (outside of Iqaluit) had an ICER of $24,750/QALY. Prophylaxis was a dominant strategy (cost saving) for rural infants under 6 months of age, with the PSA demonstrating that it was dominant 98% of the time.\n The ICERs suggested that palivizumab is a cost-effective option for the prevention of RSV for Inuit infants on Baffin Island compared to no prophylaxis. Palivizumab is highly cost effective in Arctic infants <1 year of age specifically residing outside of Iqaluit and is a dominant strategy for those under 6 months of age in rural areas. However, palivizumab is not cost effective compared to no treatment for infants of all ages residing in Iqaluit.",
"Acquisition costs of palivizumab have increased in Canada since 2007. This analysis aims to re-evaluate the cost effectiveness of palivizumab in Canada for premature infants born between 32 and 35 weeks' gestational age using updated 2010 healthcare costs compared to those used in a 2007 decision analytic model.\n New costs (CAN$) were acquired from the same Health Canada and Ontario Ministry of Health sources that were utilized in the previously published 2007 model. Palivizumab prices were acquired from Abbott Laboratories Ltd., current as of August 2010.\n Incremental cost-effectiveness ratios (ICERs) rose by $742, going from $30,618/QALY to $31,360/QALY. ICER changes increased from a range of $801,297 to $820,701 for infants with zero risk factors to a decrease from $808 to $192 for infants with four or more risk factors.\n Palivizumab ICERs remained fairly stable from 2007 to 2010. The original recommendation stating that palivizumab is cost effective in infants born between 32 and 35 weeks' GA with two or more risk factors, or who are at moderate-to-high risk based on a risk assessment model, does not change. Analyses founded on evolving country-specific variables are needed in order to accurately reassess the cost effectiveness of interventions as costs change worldwide.\n There are a limited number of publications reporting mortality in premature Canadian infants with RSV as a primary outcome. In addition, conclusions drawn from this analysis are country-specific and limited to premature infants dwelling in Canada.",
"Medicaid infants are at high risk of severe respiratory syncytial virus (RSV) disease. The study objective was to estimate the cost-effectiveness of palivizumab in a Medicaid population.\n A societal cost-utility analysis was conducted of prophylaxis with palivizumab vs no prophylaxis among four groups of premature infants: (1) <32 weeks gestational age (wGA) and ≤ 6 months chronologic age (CA); (2) 32-34 wGA, ≤ 3 months CA with 2009 American Academy of Pediatrics (AAP) risk factors (RF); (3) 32-35 wGA, ≤ 6 months CA with 2006 AAP RF; and (4) 32-35 wGA, ≤ 6 months CA with ≤ 1 RF. Full dosing of palivizumab was assumed throughout the RSV season (consistent with the FDA-approved label). All costs were in 2010 US dollars. The societal public payer spend for palivizumab was estimated using Medicaid reimbursement methodologies for the top 10 palivizumab-using states in 2010 minus mandatory manufacturer rebates. This study reports the incremental cost-effectiveness ratios (ICERs) in cost per quality-adjusted life-year (QALY) gained. Sensitivity and probabilistic analyses were also conducted.\n Palivizumab saved costs and improved QALYs among infants <32 wGA. Palivizumab was cost-effective in infants 32-34 wGA with 2009 AAP RF ($16,037 per QALY) and in infants 32-35 wGA with 2006 AAP RF ($38,244 per QALY). The ICER for infants 32-35 wGA with ≤ 1 RF was $281,892 per QALY. Influential variables in the sensitivity analysis included the background rate of RSV hospitalization, the cost of palivizumab, and the efficacy of palivizumab. KEY LIMITATIONS: These results are not generalizable to commercially insured infants or infants outside of the US.\n This is the first cost-utility analysis of palivizumab in a Medicaid population. Palivizumab, when dosed consistent with the FDA-approved labeling, was either cost-saving or cost-effective among current guideline-eligible infants in the Medicaid population. Palivizumab did not demonstrate cost-effectiveness in 32-35 wGA infants with ≤ 1 RF.",
"To show if surfactant applied in different social-sanitary realities as prophylaxis of respiratory distress syndrome (RDS) is equally useful and able to reduce mortality and incidence of 3-4 radiological grade RDS.\n Two neonatal intensive care units (NICU) in Italy, one NICU in Bulgaria and one NICU in Romania were involved in a randomized controlled clinical trial of prophylaxis vs rescue treatment of RDS. Babies with gestational age 26-30 wks were randomized before birth to prophylaxis in the delivery-room with 200 mg/kg of porcine surfactant (prophylaxis) or to routine assistance (control). Subsequently the babies developing RDS requiring mechanical ventilation and fraction of inspired oxygen (FiO2) > or = 0.4 to maintain PaO2 about 50 mmHg were allowed to be treated rescue with 200 mg/kg of the same surfactant. To reach end-points of reducing mortality by 40% and incidence of radiological grade 3-4 RDS a total number of 174 patients were required.\n Due to logistic, practical and social-political problems the study was interrupted after enrollment of 93 babies (61 in Italy and 32 in Bulgaria). The Romanian centre did not start the study because it was impossible in the scheduled times to equip it for mechanical ventilation of the newborn infants. Analysis done on an intention to treat basis did not show significant reductions of mortality and 3-4 radiological grade RDS, even if there was a trend towards a reduction in the babies given prophylaxis. A significantly lower number of babies given prophylaxis required a subsequent rescue treatment compared to controls (p < 0.001). There was no difference in other complications such as intraventricular haemorrhage, air-leak syndromes and infections between prophylaxis and control infants. As regards pulmonary gas exchange, the PaO2/FiO2 ratio was significantly improved in the babies given prophylaxis for the first 12 hours of life vs the controls.\n Even if the study was terminated before term, the analysis of the data shows that prophylaxis with surfactant is equally effective in different social-clinical conditions to improve pulmonary gas-exchange, especially in the first critical hours of life of premature babies.",
": Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children. Motavizumab is an investigational humanized monoclonal antibody for RSV prophylaxis.\n : A dose-escalation study was conducted followed by assessment of safety, tolerability, serum concentrations, and immunogenicity during a second consecutive RSV season. In season 1, premature infants aged < or =6 months or children < or =24 months with chronic lung disease of prematurity received monthly motavizumab (3 or 15 mg/kg). In season 2, children who received > or =3 motavizumab doses in season 1 were randomized to receive monthly motavizumab or palivizumab 15 mg/kg.\n : Of 217 children enrolled in season 1, 211 (97.2%) received motavizumab 15 mg/kg and 205 (94.5%) patients completed the study through 90 days after the final dose. In season 2, 136 children were randomized to receive motavizumab (n = 66) or palivizumab (n = 70). The most commonly reported related adverse event was transient injection site erythema. In season 1, mean trough motavizumab concentrations were 7.9 and 50.2 microg/mL after the 3- and 15-mg/kg doses, respectively. Trough concentrations increased with repeated motavizumab dosing; a similar pattern was seen in season 2. Antimotavizumab reactivity occurred infrequently (3.3%) in season 1. In season 2, no treatment group-specific antidrug antibody was detected through 90 to 120 days after dosing with either product.\n : The pharmacokinetic profile of motavizumab was similar to that of other IgG1 antibodies. Increased adverse reactions or immunogenicity were not observed during and after a second season of treatment with motavizumab. Safety findings from these studies supported the continued development of motavizumab.",
"To compare the hospital course and clinical outcome of preterm infants with respiratory distress syndrome treated with surfactant and managed with high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CV) as their primary mode of ventilator support.\n A prospective randomized clinical trial.\n Three community-based level III neonatal intensive care units.\n A total of 125 neonates who were 35 weeks or less estimated gestation requiring intubation and assisted ventilation for respiratory distress syndrome with arterial to alveolar oxygen ratio less than .50.\n Patients were randomized to continue CV (61 patients) or be changed to HFOV (64 patients) after exogenous surfactant administration (100 mg/kg). HFOV was used in a strategy to promote lung recruitment and maintain lung volume. Protocol respiratory care guidelines were followed; otherwise routine care was provided by each neonatal intensive care unit.\n No differences were noted in demographic features between the two study groups. The study population birth weight was 1.51 +/- .47 kg (mean +/- SD), gestational age was 30.9 +/- 2.5 weeks, and study entry age was 2 to 3 hours. Patients randomized to HFOV demonstrated the following significant findings compared with CV-treated patients: vasopressor support was less intensive; surfactant redosing was not as frequent; oxygenation improved more rapidly and remained higher during the first 7 days; fewer infants required prolonged supplemental oxygen or ventilator support; treatment failure was reduced; more patients survived without chronic lung disease at 30 days; need for continuous supplemental oxygen at discharge was less; frequency of necrotizing enterocolitis illness was lower; there were fewer abnormal hearing tests; and hospital costs were decreased. No differences were seen between the two study groups in the frequency or severity of patent ductus arteriosus, air leak, retinopathy of prematurity, or intraventricular hemorrhage. Length of hospital stay and survival to discharge were similar for HFOV- and CV-treated infants.\n When used early with a lung recruitment strategy, HFOV after surfactant replacement resulted in clinical outcomes consistent with a reduction in both acute and chronic lung injury. Benefit was evident for preterm infants both less than or equal to 1 kg and more than 1 kg. In addition, early HFOV treatment may have had a more global effect on patient health throughout the hospitalization, resulting in reduced morbidity and decreased health care cost."
] |
There is evidence that palivizumab prophylaxis is effective in reducing the frequency of hospitalisations due to RSV infection, i.e. in reducing the incidence of serious lower respiratory tract RSV disease in children with chronic lung disease, congenital heart disease, or those born preterm.
Results from economic evaluations of palivizumab prophylaxis are inconsistent across studies, ranging from highly cost-effective to not cost-effective, implying that economic findings must be interpreted with caution. The availability of low-cost palivizumab would reduce its inequitable distribution, so that RSV prophylaxis would be available to the poorest countries where children are at greatest risk.
|
CD002817
|
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"1559090",
"17119004",
"15774435",
"18295614",
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"18441040",
"10945420",
"10960936",
"11009194",
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"17055767"
] |
[
"Efficacy of a physical therapy program in patients with Parkinson's disease: a randomized controlled trial.",
"Circuit class therapy versus individual physiotherapy sessions during inpatient stroke rehabilitation: a controlled trial.",
"A comparison of two physiotherapy treatment approaches to improve walking in multiple sclerosis: a pilot randomized controlled study.",
"Balance and mobility following stroke: effects of physical therapy interventions with and without biofeedback/forceplate training.",
"Effect of a physical therapeutic intervention for balance problems in the elderly: a single-blind, randomized, controlled multicentre trial.",
"Randomised trial of a brief physiotherapy intervention compared with usual physiotherapy for neck pain patients: outcomes and patients' preference.",
"Physiotherapy intervention late after stroke and mobility.",
"A randomised controlled trial of a home based exercise programme to reduce the risk of falling among people with Parkinson's disease.",
"Comparison of Bobath based and movement science based treatment for stroke: a randomised controlled trial.",
"Whole body vibration versus conventional physiotherapy to improve balance and gait in Parkinson's disease.",
"A randomized, controlled pilot study of a home-based exercise program for individuals with mild and moderate stroke.",
"Short- and long-term outcome of constraint-induced movement therapy after stroke: a randomized controlled feasibility trial.",
"Bobath or motor relearning programme? A comparison of two different approaches of physiotherapy in stroke rehabilitation: a randomized controlled study.",
"Use of visual feedback in retraining balance following acute stroke.",
"The role of sensory cues in the rehabilitation of parkinsonian patients: a comparison of two physical therapy protocols.",
"Randomised controlled trial of physiotherapy compared with advice for low back pain.",
"Effectiveness of physiotherapy in Parkinson's disease: the feasibility of a randomised controlled trial."
] |
[
"To investigate the effects of a physical therapy (PT) program in groups of people with Parkinson's disease (PD).\n Randomized controlled trial with a crossover design.\n Two outpatient rehabilitation clinics in Boston and Amsterdam, respectively.\n Sixty-eight subjects diagnosed with typical, idiopathic PD, Hoehn and Yahr stage II or III, and stable medication use.\n Group A received PT and medication therapy (MT) for the first 6 weeks, followed by MT only for the second 6 weeks. Group B received only MT for the first 6 weeks and PT and MT for the second 6 weeks.\n The Sickness Impact Profile (SIP-68), the mobility portion of the SIP-68, the Unified Parkinson's Disease Rating Scale (UPDRS), and comfortable walking speed (CWS) at baseline, 6-week, 12-week, and 3-month follow-up.\n At 6 weeks, differences between groups were significant for the SIP mobility ( P =.015; effect size [ES]=.55), for CWS ( P =.012; ES=.49), for the activities of daily living (ADL) section of the UPDRS ( P =.014; ES=.45), and for the total UPDRS ( P =.007; ES=.56). The total SIP and the mentation and motor sections of the UPDRS did not differ significantly between groups. Significant differences were found at 3 months compared with baseline for CWS, the UPDRS ADL, and total scores.\n People with PD derive benefits in the short term from PT group treatment, in addition to their MT, for quality of life related to mobility, CWS, and ADLs; long-term benefits were found in CWS, UPDRS ADL, and total scores but varied between groups.",
"To compare the effectiveness of circuit class therapy and individual physiotherapy (PT) sessions in improving walking ability and functional balance for people recovering from stroke.\n Nonrandomized, single-blind controlled trial.\n Medical rehabilitation ward of a rehabilitation hospital.\n Sixty-eight persons receiving inpatient rehabilitation after a stroke.\n Subjects received group circuit class therapy or individual treatment sessions as the sole method of PT service delivery for the duration of their inpatient stay.\n Five-meter walk test (5MWT), two-minute walk test (2MWT), and the Berg Balance Scale (BBS) measured 4 weeks after admission. Secondary outcome measures included the Iowa Level of Assistance Scale, Motor Assessment Scale upper-limb items, and patient satisfaction. Measures were taken on admission and 4 weeks later.\n Subjects in both groups showed significant improvements between admission and week 4 in all primary outcome measures. There were no significant between group differences in the primary outcome measures at week 4 (5MWT mean difference, .07m/s; 2MWT mean difference, 1.8m; BBS mean difference, 3.9 points). A significantly higher proportion of subjects in the circuit class therapy group were able to walk independently at discharge (P=.01) and were satisfied with the amount of therapy received (P=.007).\n Circuit class therapy appeared as effective as individual PT sessions for this sample of subjects receiving inpatient rehabilitation poststroke. Favorable results for circuit classes in terms of increased walking independence and patient satisfaction suggest this model of service delivery warrants further investigation.",
"To use a pilot study to compare two physiotherapy approaches to improve walking in patients with gait disturbance due to multiple sclerosis (MS).\n Patients were assessed and then randomly assigned to one of two groups using a block randomization technique. They were treated by the research physiotherapist for a minimum of 15 treatments over a 5-7-week period and then reassessed by an independent therapist one week after treatment.\n Both assessment and treatment were undertaken at a specialist rehabilitation centre.\n Outpatients with clinically stable MS (chronic progressive or relapsing-remitting types) who were referred for physiotherapy to improve their mobility.\n Comparison was between a facilitation (impairment-based) approach and a task-oriented (disability-focused) approach.\n Mobility was assessed using four measures: the 10-metre timed walk, the Rivermead Mobility Index, stride length and the Rivermead Visual Gait Assessment. Balance was assessed using the Berg Balance Test.\n Twenty-three patients were entered, and 10 in each group completed the study. The groups were similar on all measured items both before and after treatment. There was no significant difference in improvement between the two approaches. Following treatment, patients in both groups showed a significant overall improvement (p < 0.05) in both impairment and disability measures.\n No significant differences in effectiveness between the two methods were demonstrated. Both a task-oriented approach and a facilitation approach to the treatment of MS outpatients were associated with improved mobility.",
"Visual biofeedback/forceplate systems are often used for treatment of balance disorders. In this study, the researchers investigated whether the addition of visual biofeedback/forceplate training could enhance the effects of other physical therapy interventions on balance and mobility following stroke.\n The study included a sample of convenience of 13 outpatients with hemiplegia who ranged in age from 30 to 77 years (mean=60.4, SD=15.4) and were 15 to 538 days poststroke.\n Subjects were assigned randomly to either an experimental group or a control group when the study began, and their cognitive and visual-perceptual skills were tested by a psychologist. Subjects were also assessed using the Berg Balance Scale and the Timed \"Up & Go\" Test before and after 4 weeks of physical therapy. Both groups received physical therapy interventions designed to improve balance and mobility 2 to 3 times per week. The experimental group trained on the NeuroCom Balance Master for 15 minutes of each 50-minute treatment session. The control group received other physical therapy for 50 minutes.\n Following intervention, both groups scored higher on the Berg Balance Scale and required less time to perform the Timed \"Up & Go\" Test. These improvements corresponded to increased independence of balance and mobility in the study population. However, a comparison of mean changes revealed no differences between groups.\n Although both groups demonstrated improvement following 4 weeks of physical therapy interventions, no additional effects were found in the group that received visual biofeedback/forceplate training combined with other physical therapy.",
"To establish the effect of a short, individualized exercise programme on balance dysfunction in the elderly.\n A single-blind, randomized, controlled, multicentre trial.\n Physical and recreational therapy departments from two rehabilitation centres.\n Ninety-four subjects of >75 years with functional balance problems living independently or in a residential care facility. Seventy-seven subjects completed the intervention period and four-week follow-up. At a one-year follow-up 49 subjects were evaluated on balance functioning.\n Twelve sessions of an individualized balance training programme (experimental group) or 12 sessions of an individualized extra attention programme (control group) given in 4-6 weeks.\n Berg Balance Scale and the Dynamic Gait Index to establish balance functioning, a visual analogue scale to establish fear of falling in daily life and the Hospital Anxiety Depression Scale to verify feelings of anxiety and depression.\n Subjects in the experimental group improved significantly more on the Berg Balance Scale and the Dynamic Gait Index than those in the control group (p f 0.001, p f 0.001, respectively). However the effect disappeared at a one-year follow-up on the Berg Balance Scale. No prognostic factors could be identified to determine who would benefit most from the individualized exercise programme. Results on the other response variables revealed no effect of the intervention.\n A short individualized exercise programme can improve functional balance in people aged 75 years and older. This improvement was maintained at least for one month but had worn off by one year.",
"Firstly, to compare the effectiveness of a brief physiotherapy intervention with \"usual\" physiotherapy for patients with neck pain. Secondly, to evaluate the effect of patients' preferences on outcome.\n Non-inferiority randomised controlled trial eliciting preferences independently of randomisation.\n Physiotherapy departments in a community setting in Yorkshire and north Lincolnshire.\n 268 patients (mean age 48 years) with subacute and chronic neck pain, who were referred by their general practitioner and randomly assigned to a brief physiotherapy intervention (one to three sessions) using cognitive behaviour principles to encourage self management and return to normal function or usual physiotherapy, at the discretion of the physiotherapist concerned.\n The Northwick Park neck pain questionnaire (NPQ), a specific measure of functional disability resulting from neck pain. Also, the short form 36 (SF-36) questionnaire, a generic, health related, quality of life measure; and the Tampa scale for kinesophobia, a measure of fear and avoidance of movement.\n At 12 months, patients allocated to usual physiotherapy had a small but significant improvement in NPQ scores compared with patients in the brief intervention group (mean difference 1.99, 95% confidence interval 0.45 to 3.52; P = 0.01). Although the result shows a significant inferiority of the intervention, the confidence interval shows that the effect could be in the non-inferiority range for the brief intervention (below 1.2 points of NPQ score). Patients who preferred the brief intervention and received this treatment had similar outcomes to patients receiving usual physiotherapy.\n Usual physiotherapy may be only marginally better than a brief physiotherapy intervention for neck pain. Patients with a preference for the brief intervention may do at least as well with this approach. Additional training for the physiotherapists in cognitive behaviour techniques might improve this approach further.",
"To determine whether the intervention of a physiotherapist improved mobility in patients seen more than one year after stroke.\n Randomised crossover trial comparing two groups offered intervention by a physiotherapist, one immediately after entry into the trial and the other after a delay of three months. The intervention consisted of identifying problems and offering advice and help to solve the problems.\n Patients' homes in Oxfordshire.\n Patients who had reduced mobility due to a stroke more than one year before entry; 60 were recruited from a community stroke register and 34 in other ways.\n Standard measures of mobility including gait speed, functional ambulation categories, the Nottingham extended activities of daily living index, and individual items from the Barthel activities of daily living index and the Frenchay activities index. Measures of manual dexterity, depression, and anxiety were used as controls.\n 94 patients entered the trial and 49 were randomised to immediate and 45 to delayed physiotherapy; 89 were compared at the crossover point. At randomisation the two groups were comparable. At three months the group given early therapy showed an improvement in gait speed whereas the untreated group had declined (differences of -3.9 v 6.4 s to walk 10 m; p less than 0.01); between three and six months the group given delayed therapy showed improvement and the previously treated group declined (differences of 6.5 v -3.9 s to walk 10 m; p less than 0.01). A 9% (95% confidence interval 0% to 18%) decrease in time taken to walk 10 m was associated with treatment and a 12% (2% to 19%) increase when patients were untreated. Other measures did not change significantly.\n Intervention of an experienced physiotherapist late after stroke specifically improves mobility, albeit by a small amount, but the effects do not seem to be maintained, perhaps because there is an underlying decline in mobility in these patients. Gait speed offers a simple and sensitive measure of outcome.",
"To evaluate the effectiveness of a personalised home programme of exercises and strategies for repeat fallers with Parkinson's disease (PD).\n Patients with a confirmed diagnosis of idiopathic PD, independently mobile, living at home in the community, experiencing more than one fall in the previous 12 months and with intact gross cognitive function were invited to participate in this randomised controlled trial. Usual care was compared with a personalised 6 week, home based exercise and strategy programme. The primary outcomes were rates of falling at 8 weeks and 6 months. Whether participants had repeat fallen, nearly fallen or experienced injurious falls were also examined. Functional Reach, the Berg Balance Test, PD Self-assessment Scale and the Euro Quol were rated by a blinded assessor.\n Participants were randomised to the exercise (n = 70) and control (n = 72) groups. There was a consistent trend towards lower fall rates in the exercise group at both 8 weeks and 6 months and lower rates of injurious falls needing medical attention at 6 months. Lower rates of repeat near falling were evident for the exercise group at 8 weeks (p = 0.004) and 6 months (p = 0.007). There was a positive effect of exercises at 6 months on Functional Reach (p = 0.009) and quality of life (p = 0.033). No significant differences were found on other secondary outcomes measures.\n There was a trend towards a reduction in fall events and injurious falls with a positive effect of exercises on near falls and quality of life.",
"Bobath based (BB) and movement science based (MSB) physiotherapy interventions are widely used for patients after stroke. There is little evidence to suggest which is most effective. This single-blind randomised controlled trial evaluated the effect of these treatments on movement abilities and functional independence.\n A total of 120 patients admitted to a stroke rehabilitation ward were randomised into two treatment groups to receive either BB or MSB treatment. Primary outcome measures were the Rivermead Motor Assessment and the Motor Assessment Scale. Secondary measures assessed functional independence, walking speed, arm function, muscle tone, and sensation. Measures were performed by a blinded assessor at baseline, and then at 1, 3, and 6 months after baseline. Analysis of serial measurements was performed to compare outcomes between the groups by calculating the area under the curve (AUC) and inserting AUC values into Mann-Whitney U tests.\n Comparison between groups showed no significant difference for any outcome measures. Significance values for the Rivermead Motor Assessment ranged from p = 0.23 to p = 0.97 and for the Motor Assessment Scale from p = 0.29 to p = 0.87.\n There were no significant differences in movement abilities or functional independence between patients receiving a BB or an MSB intervention. Therefore the study did not show that one approach was more effective than the other in the treatment of stroke patients.",
"To compare the effects of whole body vibration (WBV) and conventional physiotherapy (PT) on levodopa-resistant disturbances of balance and gait in idiopathic Parkinson's disease (PD).\n Randomized controlled rater-blinded trial comparing 2 active interventions, final follow-up assessment 4 weeks after termination of active intervention.\n Specialized referral center, hospitalized care.\n Patients with PD and dopa-resistant imbalance on stable dopamine replacement medication (N=27) were randomized (intent-to-treat population) to receive WBV (n=13) or conventional PT (controls, n=14). Twenty-one patients (per protocol population) completed follow-up (14 men, 7 women; mean age, 73.8 y; age range, 62-84 y; mean disease duration, 7.2 y; mean dopa-equivalent dose, 768 mg/d).\n Subjects were randomized to receive 30 sessions (two 15-min sessions a day, 5 days a week) of either WBV on an oscillating platform or conventional balance training including exercises on a tilt board. Twenty-one subjects (10 with WBV, 11 controls) were available for follow-up 4 weeks after treatment termination.\n The primary measure was Tinetti Balance Scale score. Secondary clinical ratings included stand-walk-sit test, walking velocity, Unified Parkinson's Disease Rating Scale (section III motor examination) score, performance in the pull test, and dynamic posturography.\n The Tinetti score improved from 9.3 to 12.8 points in the WBV group and from 8.3 to 11.7 in the controls. All secondary measures, except posturography, likewise improved at follow-up compared with baseline in both groups. Quantitative dynamic posturography only improved in patients with WBV (1937-1467 mm) whereas there was no significant change in controls (1832-2030 mm).\n Equilibrium and gait improved in patients with PD receiving conventional WBV or conventional PT in the setting of a comprehensive rehabilitation program. There was no conclusive evidence for superior efficacy of WBV compared with conventional balance training.",
"BACKGROUND and\n Many stroke survivors have minimal to moderate neurological deficits but are physically deconditioned and have a high prevalence of cardiovascular problems; all of these are potentially modifiable with exercise. The purposes of this randomized, controlled pilot study were (1) to develop a home-based balance, strength, and endurance program; (2) to evaluate the ability to recruit and retain stroke subjects; and (3) to assess the effects of the interventions used.\n Twenty minimally and moderately impaired stroke patients who had completed inpatient rehabilitation and who were 30 to 90 days after stroke onset were randomized to a control group or to an experimental group that received a therapist-supervised, 8-week, 3-times-per-week, home-based exercise program. The control group received usual care as prescribed by the patients' physicians. Baseline and postintervention assessments included the Fugl-Meyer Motor Assessment, the Barthel Index of Activities of Daily Living (ADL), the Lawton Scale of Instrumental ADL, and the Medical Outcomes Study-36 Health Status Measurement. Functional assessments of balance and gait included a 10-m walk, 6-Minute Walk, and the Berg Balance Scale. Upper extremity function was evaluated by the Jebsen Test of Hand Function.\n Of 22 patients who met study criteria, 20 completed the study and 2 refused to participate. The experimental group tended to improve more than the control group in motor function (Fugl-Meyer Upper Extremity: mean change in score, 8. 4 versus 2.2; Fugl-Meyer Lower Extremity: 4.7 versus -0.9; gait velocity: median change, 0.25 versus .09 m/s; 6-Minute Walk: 195 versus 114 ft; Berg Balance Score: 7.8 versus 5; and Medical Outcomes Study-36 Health Status Measurement of Physical Function: 15. 5 versus 9). There were no trends in differences in change scores by the Jebsen Test of Hand Function, Barthel Index, and Lawton Instrumental ADL Scale.\n This study demonstrated that a randomized, controlled clinical trial of a poststroke exercise program is feasible. Measures of neurological impairments and lower extremity function showed the most benefit. Effects of the intervention on upper extremity dexterity and functional health status were equivocal. The lasting effects of the intervention were not assessed.",
"Constraint-induced movement therapy (CIMT) is a method to improve motor function in the upper extremity following stroke. The aim of this trial was to determine the effect and feasibility of CIMT compared with traditional rehabilitation in short and long term.\n A randomized controlled trial.\n An inpatient rehabilitation clinic.\n Thirty patients with unilateral hand impairment after stroke.\n Six hours arm therapy for 10 consecutive weekdays, while using a restraining mitten on the unaffected hand.\n The patients were assessed at baseline, post-treatment and at six-month follow-up using the Wolf Motor Function Test as primary outcome measure and the Motor Activity Log, Functional Independence Measure and Stroke Impact Scale as secondary measurements.\n The CIMT group (n=18) showed a statistically significant shorter performance time (4.76 seconds versus 7.61 seconds, P= 0.030) and greater functional ability (3.85 versus 3.47, P= 0.037) than the control group (n=12) on the Wolf Motor Function Test at post-treatment assessment. There was a non-significant trend toward greater amount of use (2.47 versus 1.97, P= 0.097) and better quality of movement (2.45 versus 2.12, P=0.105) in the CIMT group according to the Motor Activity Log. No such differences were seen on Functional Independence Measure at the same time. At six-month follow-up the CIMT group maintained their improvement, but as the control group improved even more, there were no significant differences between the groups on any measurements.\n CIMT seems to be an effective and feasible method to improve motor function in the short term, but no long-term effect was found.",
"To examine whether two different physiotherapy regimes caused any differences in outcome in rehabilitation after acute stroke.\n A double-blind study of patients with acute first-ever stroke. Sixty-one patients were consecutively included, block randomized into two groups, and stratified according to gender and hemiplegic site. Group 1 (33 patients) and group 2 (28 patients) had physiotherapy according to Motor Relearning Programme (MRP) and Bobath, respectively. The supplemental treatment did not differ in the two groups.\n The Motor Assessment Scale (MAS), the Sødring Motor Evaluation Scale (SMES), the Barthel ADL Index and the Nottingham Health Profile (NHP) were used. The following parameters were also registered: length of stay in the hospital, use of assistive devices for mobility, and the patient's accommodation after discharge from the hospital.\n Patients treated according to MRP stayed fewer days in hospital than those treated according to Bobath (mean 21 days versus 34 days, p = 0.008). Both groups improved in MAS and SMES, but the improvement in motor function was significantly better in the MRP group. The two groups improved in Barthel ADL Index without significant differences between the groups. However, women treated by MRP improved more in ADL than women treated by Bobath. There were no differences between the groups in the life quality test (NHP), use of assistive devices or accommodation after discharge from the hospital.\n The present study indicates that physiotherapy treatment using the MRP is preferable to that using the Bobath programme in the acute rehabilitation of stroke patients.",
"Visual feedback related to weight distribution and center-of-pressure positioning has been shown to be effective in increasing stance symmetry following stroke, although it is not clear whether functional balance ability also improves. This study compared the relative effectiveness of visual feedback training of center-of-gravity (CoG) positioning with conventional physical therapy following acute stroke.\n Forty-six people who had strokes within 80 days before the study, resulting in unilateral hemiparesis, and who were in need of balance retraining participated.\n Initially, subjects were randomly assigned to visual feedback or conventional physical therapy groups for balance retraining until 16 subjects per group were recruited. The next 14 subjects were assigned to a control group. All subjects received physical therapy and occupational therapy (regular therapy) 2 hours a day, and subjects in the 2 experimental groups received additional balance training 30 minutes a day until discharge. The visual feedback group received information about their CoG position as they shifted their weight during various activities. The conventional therapy group received verbal and tactile cues to encourage symmetrical stance and weight shifting. Static (postural sway) and activity-based measures of balance (Berg Balance Scale, gait speed, and the Timed \"Up & Go\" Test) were contrasted across the 3 groups at baseline, at discharge, and at 1 month following discharge using an analysis of variance for repeated measures.\n All groups demonstrated marked improvement over time for all measures of balance ability, with the greatest improvements occurring in the period from baseline to discharge. No between-group differences were detected in any of the outcome measures.\n Visual feedback or conventional balance training in addition to regular therapy affords no added benefit when offered in the early stages of rehabilitation following stroke.",
"We devised a single-blind study to assess the role of providing external sensory cues in the rehabilitation of patients with idiopathic Parkinson's disease (PD). Twenty stable, nondemented patients with PD entered a 6-week rehabilitation program and were randomly assigned to two balanced protocols which were differentiated by the use of external sensory cues (\"non-cued\" vs \"cued\"). Patients were evaluated by a neurologist, who was blind to group membership, with the Unified Parkinson's Disease Rating Scale (UPDRS) at baseline, end of treatment, and after 6 weeks. Patient groups were comparable for age, disease duration, and severity. A significant reduction of UPDRS scores (activities of daily living and motor sections) was present after the rehabilitation phase in both groups. However, at follow up, while this clinical improvement had largely faded in the \"non-cued\" group, mean UPDRS scores of the \"cued\" group were still significantly lower than baseline values. The incorporation of external sensory cues in the rehabilitation protocol can extend the short-term benefit of physical therapy in moderately disabled patients with PD, possibly as a result of the learning of new motor strategies. \"Cued\" physical therapy for PD should be targeted to compensate for the defective physiological mechanisms.",
"To measure the effectiveness of routine physiotherapy compared with an assessment session and advice from a physiotherapist for patients with low back pain.\n Pragmatic, multicentre, randomised controlled trial.\n Seven British NHS physiotherapy departments.\n 286 patients with low back pain of more than six weeks' duration.\n Routine physiotherapy or advice on remaining active from a physiotherapist. Both groups received an advice book.\n Primary outcome was scores on the Oswestry disability index at 12 months. Secondary outcomes were scores on the Oswestry disability index (two and six months), scores on the Roland and Morris disability questionnaire and SF-36 (2, 6 and 12 months), and patient perceived benefit from treatment (2, 6, and 12 months).\n 200 of 286 patients (70%) provided follow up information at 12 months. Patients in the therapy group reported enhanced perceptions of benefit, but there was no evidence of a long term effect of physiotherapy in either disease specific or generic outcome measures (mean difference in change in Oswestry disability index scores at 12 months -1.0%, 95% confidence interval -3.7% to 1.6%). The most common treatments were low velocity spinal joint mobilisation techniques (72%, 104 of 144 patients) and lumbar spine mobility and abdominal strengthening exercises (94%, 136 patients).\n Routine physiotherapy seemed to be no more effective than one session of assessment and advice from a physiotherapist.",
"To study the feasibility of a large randomised controlled trial (RCT) evaluating the effectiveness of physiotherapy in Parkinson's disease (PD), 173 patients were asked to participate in a study with random allocation to best practice physiotherapy, or to no physiotherapy. The primary outcome measures were the Parkinson's disease questionnaire-39, the Parkinson activity scale, and a patient preference outcome scale (PPOS). Only 14% of the patients could be included in the study. The PPOS showed the largest effect size (0.74) with a significant group effect (p<0.05). Specific alterations to the study design to ensure successful RCTs in this field are recommended."
] |
Benefit for physiotherapy was found in most outcomes over the short-term (i.e. < three months), but was only significant for velocity, two- or six-minute walk test, step length, Timed Up & Go, Functional Reach Test, Berg Balance Scale and clinician-rated UPDRS. Most of the observed differences between the treatments were small. However, for some outcomes (e.g. velocity, Berg Balance Scale and UPDRS), the differences observed were at, or approaching, what are considered minimally clinical important changes.
The review illustrates that a wide range of approaches are employed by physiotherapists to treat PD. However, there was no evidence of differences in treatment effect between the different types of physiotherapy interventions being used, though this was based on indirect comparisons. There is a need to develop a consensus menu of 'best-practice' physiotherapy, and to perform large well-designed randomised controlled trials to demonstrate the longer-term efficacy and cost-effectiveness of 'best practice' physiotherapy in PD.
|
CD006391
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[
"Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol.",
"Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder.",
"Efficacy of risperidone versus olanzapine in patients with schizophrenia previously on chronic conventional antipsychotic therapy: a switch study.",
"Ethyl-eicosapentaenoic acid in first-episode psychosis: a randomized, placebo-controlled trial.",
"Antidepressants in 'depressed' schizophrenic inpatients. A controlled trial.",
"Lithium augmentation fails to reduce symptoms in poorly responsive schizophrenic outpatients.",
"Pharmacotherapy of impaired affect in recovering schizophrenic patients.",
"Cognition, functioning and quality of life in schizophrenia treatment: results of a one-year randomized controlled trial of olanzapine and quetiapine.",
"The efficacy of olanzapine for decreasing cue-elicited craving in individuals with schizophrenia and cocaine dependence: a preliminary report.",
"A double-blind study of combination of clozapine with risperidone in patients with schizophrenia: effects on cognition.",
"A 12-week, double-blind, placebo-controlled trial of donepezil adjunctive treatment to risperidone in chronic and stable schizophrenia.",
"Shared decision making and long-term outcome in schizophrenia treatment.",
"Efficacy and safety of donepezil in patients with schizophrenia or schizoaffective disorder: significant placebo/practice effects in a 12-week, randomized, double-blind, placebo-controlled trial.",
"Neuropsychological change in patients with schizophrenia after treatment with quetiapine or haloperidol.",
"Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms.",
"[Adjuvant treatment of schizophrenic illness with carbamazepine].",
"Comparative effectiveness of second-generation antipsychotics and haloperidol in acute schizophrenia.",
"Educating physicians to reduce benzodiazepine use by elderly patients: a randomized controlled trial.",
"Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepines.",
"Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment.",
"Randomized, placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia.",
"Lamotrigine in treatment-resistant schizophrenia: a randomized placebo-controlled crossover trial.",
"Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia."
] |
[
"Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder. This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large, controlled clinical trial.\n Patients with first-episode psychosis (N=263) were randomly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks. Domains measured included psychopathology, psychosocial variables, neurocognitive functioning, and brain morphology and metabolism. This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase.\n Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity, which did not differ significantly in last-observation-carried-forward analyses. However, in a mixed-model analysis, olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Asberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating. Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain, compared with the haloperidol-treated patients. Overall, significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study (67% versus 54%).\n As expected on the basis of previous studies, both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis. However, olanzapine had several relative advantages in therapeutic response. Although the nature of adverse events differed between the two agents, retention in the study was greater with olanzapine. Retention in treatment is important in this patient population, given their risk of relapse. Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia.",
"Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community. Finding appropriate treatment of violent behaviors is of primary importance.\n To compare the efficacy of 2 atypical antipsychotic agents, clozapine and olanzapine, with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder.\n Randomized, double-blind, parallel-group, 12-week trial. Physically assaultive subjects with schizophrenia or schizoaffective disorder who were inpatients in state psychiatric facilities were randomly assigned to treatment with clozapine (n = 37), olanzapine (n = 37), or haloperidol (n = 36).\n Number and severity of physical assaults as measured by the Modified Overt Aggression Scale (MOAS) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score. Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS).\n Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score. Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures. There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales.\n Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior. This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications.",
"The objective of the study was to examine whether patients with schizophrenia who were judged to be stable on long-term treatment with conventional antipsychotic medications would further benefit from a switch to an atypical antipsychotic drug. Thirty-six subjects with schizophrenia spectrum disorder, on conventional antipsychotic medication therapy for at least 2 years, were randomized in double-blind fashion to risperidone versus olanzapine. Patients were titrated up to 6 mg risperidone or 15 mg olanzapine as tolerated, followed by tapering and discontinuation of conventional antipsychotic medication. Atypical antipsychotic agents were then administered alone (monotherapy) for 12 weeks. Efficacy and tolerability were assessed using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale, and Simpson Angus Scale. Body weight was measured at each visit. Both treatment groups exhibited marked and similar improvement in the total PANSS score from baseline to study endpoint (22 weeks) [risperidone: baseline=59.3 (SE 3.1), 22 weeks=44.3 (SE 2.3) (p<0.001); olanzapine: baseline=55.9 (SE 3.3), 22 weeks=46.9 (SE 3.2) (p<0.001). Both groups also exhibited significant reductions in PANSS factor scores for positive and negative symptoms and disorganized thoughts. Only risperidone-treated patients exhibited significant decreases in uncontrolled hostility/excitement and anxiety and depression. Of note, while positive factor scores exhibited the majority of change within the first 10 weeks, negative factor scores continued to decline significantly in both treatment groups throughout the study. Tolerability assessments did not differ between groups. The results indicate that both atypical antipsychotic medications provided significant additional improvement in symptom severity in patients with schizophrenia previously on conventional antipsychotic agents.",
"To investigate if ethyl-eicosapentaenoic acid (E-EPA) augmentation improves antipsychotic efficacy and tolerability in first-episode psychosis (FEP).\n We performed a 12-week, randomized, double-blind, placebo-controlled trial of 2-g E-EPA augmentation in 80 FEP patients. Sixty-nine patients were eligible for analysis; a post hoc analysis was computed for a subgroup of nonaffective FEP patients (N = 53). The first participant was included in November 2000 and the last participant completed the trial in August 2003. Primary outcome measures were symptom change scores and time to first response, while tolerability measures and cumulative antipsychotic dose were secondary outcome measures.\n Analysis of covariance controlling for baseline symptoms found no significant mean difference between E-EPA and placebo at week 12 for symptom change scores. Cox regression analysis revealed a significant treatment by diagnosis interaction (p = .024) for time to first response favoring E-EPA in nonaffective psychosis. Post hoc analysis for cumulative response rates further confirmed a higher response rate at week 6 (42.9% [15/35] vs. 17.6% [6/34] for all participants, p = .036; 54.2% [13/24] vs. 17.2% [5/29] for the nonaffective psychosis subset, p = .008); however, the difference at week 12 was no longer significant. Analysis of secondary outcome measures revealed that E-EPA-augmented participants needed 20% less antipsychotic medication between weeks 4 through 6 (p = .03), had less extrapyramidal side effects in the initial 9 weeks (p < .05 for all participants and for all timepoints), and reported less constipation (p = .011) and fewer sexual side effects (p = .016) than those treated with antipsychotic medication alone.\n The findings suggest that E-EPA may accelerate treatment response and improve the tolerability of antipsychotic medications. However, it was not possible to demonstrate a sustained symptomatic benefit of E-EPA in early psychosis, possibly due to a ceiling effect, since a high proportion of first-episode patients already achieve symptomatic remission with antipsychotic medication alone. Further controlled trials in nonaffective early psychosis seem warranted.\n Australian Clinical Trials Registry identifier 12605000267651 (http://actr.org.au).",
"Fifty-eight actively psychotic inpatients who initially met criteria for long-standing schizophrenia and subsequently met Research Diagnostic Criteria for a current episode of schizoaffective disorder (mainly schizophrenic) with a depressive syndrome, and who scored at least 30 (mean = 55, SEM = 1.6) on the Brief Psychiatric Rating Scale and 17 (mean = 23, SEM = 0.7) on the Hamilton Rating Scale for Depression, were treated for 5 weeks with haloperidol hydrochloride and benztropine. Haloperidol and benztropine treatment was continued, while those patients who consistently scored greater than 17 on the Hamilton Rating Scale for Depression were randomly assigned to the following double-blind treatment groups for 4 weeks: adjunctive amitriptyline hydrochloride, desipramine hydrochloride, or placebo. Adjunctive desipramine or amitriptyline showed no significant therapeutic advantage, when compared with haloperidol and placebo, on the Brief Psychiatric Rating Scale or the Hamilton Rating Scale for Depression. After 4 weeks of combine therapy, patients receiving adjunctive amitriptyline or desipramine, as compared with those receiving adjunctive placebo, tended to score higher on the Brief Psychiatric Rating Scale hallucinatory behavior item and on the thinking disturbance factor than patients receiving placebo. These results suggest that adjunctive antidepressants are not indicated for the treatment of depressive symptoms in actively psychotic schizophrenic inpatients. Adjunctive antidepressants may retard the rate of resolution of psychosis in this population.",
"Nearly one third of patients suffering from schizophrenia do not fully respond to antipsychotic medication. Safe, effective, and cost-efficient methods to reduce symptoms are clearly needed; therefore, lithium as an adjunct to fluphenazine decanoate was tested in a placebo-controlled trial in outpatients who were part of the Treatment Strategies of Schizophrenia (TSS) study.\n Forty-one patients with DSM-III schizophrenia or schizoaffective disorder were assigned to either adjunctive lithium or placebo after at least 6 months of fluphenazine decanoate treatment to stabilize symptoms had failed. The trial was designed for 8 weeks of treatment, and patients assigned to placebo could afterward be administered lithium in an 8-week, open-label study.\n Assessment of the intent-to-treat analysis revealed no significant differences in demographic variables between the lithium and placebo groups. Although both groups showed significant (p = .00135) improvement as measured by total scores on the Brief Psychiatric Rating Scale (BPRS), there were no significant differences in response between the lithium and placebo groups. Patients originally treated with placebo added to neuroleptic did not have significantly greater improvement when receiving open-label adjunctive lithium.\n Although success with lithium augmentation therapy for persistent psychosis has been reported in the past, this study of well-characterized patients showed no benefit for this common strategy, thus indicating that care be used in utilizing lithium augmentation.",
"Prominent and persistent anxiety, depression, and/or negative features characterize a substantial minority of recovered or residually psychotic schizophrenic outpatients and contribute to poor outcome. Because extrapyramidal side effects of typical neuroleptic medications often resemble such features, we first systematically studied the contribution of extrapyramidal side effects to these problems and their treatment. For patients who remained distressed, controlled trials of supplemental thymoleptics were undertaken.\n In trial 1, 92 distressed (depressed and/or anxious) patients and 36 patients in a defect state (patients with negative symptoms) participated in a double-blind, intramuscular challenge that compared centrally acting benztropine mesylate with peripherally acting glycopyrrolate. In trial 2, 57 distressed patients and 22 patients in a defect state were randomly assigned to a double-blind, neuroleptic medication dose-reduction group. In trial 3, 57 chronically distressed patients who were maintained on a low dose of fluphenazine decanoate were randomly assigned to a supplemental desipramine hydrochloride, lithium carbonate, or placebo group under double-blind conditions for 12 weeks.\n For patients who were already maintained on antiparkinsonian medication, impaired affect was not resolved by additional benztropine. Only distressed patients with a family history of severe mental disorder (often affective) showed improvement with neuroleptic medication dose reduction. Patients in the defect-state group reported less dysphoria on a reduced neuroleptic medication dose, but negative symptoms persisted. Desipramine improved diverse aspects of mood and residual psychoticism, possibly as a prophylaxis against minor affective exacerbations. Depression improved in women only. Lithium positively affected multiple indexes of anxiety and anxious depression.\n Most often, persistent affective impairments are neither resistant extrapyramidal side effects nor characterological traits. Thymoleptics improve the nonphasic, chronic types of anxiety and depression in contrast to the acute, episodic forms, for which little support can be found in the literature.",
"Cognitive deficits are recognized as a critical determinant of functional outcomes in schizophrenia; and second generation antipsychotic drugs have been touted for their potential to enhance cognitive functioning and community tenure.\n The study examined the relative merits of olanzapine and quetiapine in improving cognitive deficits and enhancing psychosocial functioning in a sample of community dwelling adults previously treated with first generation antipsychotic drugs for schizophrenia.\n In a prospective, rater-blinded study, 86 participants were randomized to receive either olanzapine or quetiapine, and assessed at baseline and after 3, 6, 9 and 12 months. Outcome measures included, besides symptoms and side effects rating scales, the subjective scale to investigate cognition in schizophrenia (SSTICS), a computer-assisted cognitive test battery (COGLAB), the sickness impact profile (SIP), the global assessment of functioning (GAF) scale, and the drug attitude inventory (DAI).\n Both olanzapine and quetiapine were equally effective in improving symptom severity and decreasing the neurological side effects. Quetiapine was significantly better tolerated (p=0.002), improved self-rated cognitive dysfunction (p=0.002) and subjects' performance on selected neurocognitive tasks (p=0.01). Olanzapine use was associated with greater symptom stability, fewer drop outs (p=0.01) and frequent metabolic aberrations (p=0.001). The accrued benefits of drug therapy, however, were not reflected as significant gains in daily functioning and quality of life.\n Quetiapine is noted to have specific cognition enhancing properties in schizophrenia that warrants further exploration. The observed clinical and cognitive benefits associated with quetiapine may likely be attributable to its loose binding to, and fast dissociation from the dopamine receptors. Olanzapine has proved to be a reliable antipsychotic drug with a greater liability to cause metabolic abnormalities.",
"Although a growing body of research suggests that atypical neuroleptic medications are efficacious in the treatment of cocaine addiction among individuals with schizophrenia, more rigorously controlled trials are needed. To extend this research, we performed a 6-week double-blind study comparing olanzapine to haloperidol with the primary objective of reducing cue-elicited cocaine craving and the secondary aims of decreasing substance use, improving psychiatric symptoms, and determining an effect size for future studies.\n Thirty-one subjects with cocaine dependence and schizophrenia were randomized to olanzapine or haloperidol, underwent a cue-exposure procedure, and completed psychiatric and substance abuse ratings.\n Individuals in the olanzapine group who completed the study had a significant reduction on the energy subscale of the Voris Cocaine Craving Scale at study completion compared with individuals in the haloperidol group. The olanzapine-treated group also had lower, but not statistically significant, PANSS General Psychopathology Subscale scores and fewer positive urine toxicology screens compared with those in the haloperidol group.\n This small, but rigorously controlled, pilot trial provides additional evidence for the use of atypical antipsychotics for the treatment of individuals with co-occurring schizophrenia and cocaine dependence. Reductions in craving were associated with medium to large effect sizes.",
"Atypical antipsychotic drugs produce improvement in some domains of cognition as well as psychopathology in patients with schizophrenia. However, the effect of combinations of atypical antipsychotic drugs on cognitive function is unknown. The aim of this study was to compare the effect of risperidone or placebo on cognitive function in patients with schizophrenia who were previously treated with clozapine monotherapy.\n This prospective, randomized, double-blind, placebo-controlled, 6-week study included 30 patients with DSM-IV schizophrenia. Patients whose psychopathology was no more than partially responsive to clozapine treatment were randomly assigned to receive adjunctive treatment with risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Cognitive test scores for verbal learning and memory, verbal fluency, attention, executive function, verbal working memory, and motor function were the primary outcome measures. Secondary outcome measures included assessment of psychopathology, extrapyramidal side effects, and global functioning. Data were collected between November 2001 and July 2003.\n Significant improvement was found in both treatment groups in a variety of cognitive measures, but there was significantly greater improvement in the placebo-augmented group on measures of initial learning acquisition and attention. The improvement in cognition was not correlated with improvement in psychopathology. There were significant correlations between improvement in verbal working memory, verbal learning and memory, and attention and quality of life and global functioning in the placebo-augmented but not the risperidone-augmented group.\n Adjunctive treatment with risperidone for 6 weeks in patients with schizophrenia who had received chronic treatment with clozapine does not significantly improve cognitive function.",
"There is considerable incentive to develop new treatment strategies that effectively target cognitive deficits in schizophrenia. One of the theoretically promising novel treatment candidates is acetylcholinesterase inhibitors that increase the synaptic levels of cholinergic, nicotinic, and muscarinic receptor activity. The purpose of this study was to assess the efficacy of donepezil as an adjuvant agent in the treatment of chronic schizophrenia in particular for cognitive impairments. This investigation was a 12-week, double-blind study of parallel groups of patients with stable chronic schizophrenia. Thirty patients were recruited from inpatient and outpatient departments, age ranging from 22 to 44 years. All participants met DSM-IV-TR. diagnostic criteria for schizophrenia. To be eligible, patients were required to have been treated with a stable dose of risperidone as their primary antipsychotic treatment for a minimum period of 8 weeks. The subjects were randomized to receive donepezil (10 mg/day) or placebo, in addition to risperidone (4-6 mg/day). Clinical psychopathology was assessed with Positive and Negative Syndrome Scale (PANSS). Cognition was measured by a cognitive battery. Patients were assessed by a psychiatrist at baseline and after 8, and 12 weeks after the medication started. The PANSS scores and cognitive performance were used as the outcome measures. The donepezil group had significantly greater improvement in the negative symptoms over the 12-week trial. There were no differences between the donepezil and placebo groups on any neurocognitive assessments at endpoint (week 12). The present study indicates donepezil as a potential adjunctive treatment strategy for negative symptoms of chronic schizophrenia.",
"Compliance with antipsychotic medication is a major issue in schizophrenia treatment, and noncompliance with antipsychotic treatment is closely related to relapse and rehospitalization. An enhanced involvement of patients with schizophrenia in treatment decisions (\"shared decision making\") is expected to improve long-term compliance and reduce rehospitalizations. The aim of the present analysis was to study whether shared decision making (SDM) in antipsychotic drug choice would influence long-term outcome.\n From February 2003 to January 2004, psychiatric state hospital inpatients with a diagnosis of schizophrenia (ICD-10; N = 107) were recruited for the trial using a cluster-randomized controlled design. An SDM program on antipsychotic drug choice consisting of a decision aid and a planning talk between patient and physician was compared with routine care with respect to long-term compliance and rehospitalizations (6-month and 18-month follow-up).\n On the whole, we found high rates of noncompliance and rehospitalization. There were no differences between intervention and control groups in the univariate analyses. However, when controlling for confounding factors in a multivariate analysis, there was a positive trend (p = .08) that patients in the SDM intervention had fewer rehospitalizations. Additionally, a higher desire of the patient for autonomy and better knowledge at discharge were associated with higher hospitalization rates.\n The intervention studied showed a positive trend but no clear beneficial effect on long-term outcomes. A more thorough implementation of SDM (e.g., iterative administration of decision aid) might yield larger effects. Those patients with higher participation preferences are at higher risk for poor treatment outcomes and therefore require special attention. Strategies to match these patients' needs might improve compliance and long-term outcomes.",
"Altered expression of central muscarinic and nicotinic acetylcholine receptors in hippocampal and cortical regions may contribute to the cognitive impairment exhibited in patients with schizophrenia. Increasing cholinergic activity through the use of a cholinesterase inhibitor (ChEI) therefore represents a possible strategy for cognitive augmentation in schizophrenia. We examined the efficacy and safety of the ChEI donepezil as cotreatment for mild to moderate cognitive impairment in schizophrenia or schizoaffective disorder in a prospective, 12-week, placebo-controlled, double-blind, parallel-group study. In total, 250 patients (18-55 years) with schizophrenia or schizoaffective disorder who were clinically stabilized on risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole, alone or in combination, were enrolled at 38 outpatient psychiatric clinics in the United States. Patients were randomized to donepezil 5 mg q.d. for 6 weeks then 10 mg q.d. for 6 weeks, or placebo administered as oral tablets. The primary outcome measure was the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) neurocognitive battery composite score. In the intent-to-treat sample (donepezil, n=121; placebo, n=124), both treatments showed improvement in the composite score from baseline to week 12. At week 12, cognitive improvement with donepezil was similar to that with placebo (last-observation-carried-forward effect size, 0.277 vs 0.411; p=0.1182) and statistically significantly inferior for the observed-cases analysis (0.257 vs 0.450; p=0.044). There was statistically significant improvement in the Positive and Negative Syndrome Assessment Scale negative symptoms score for placebo compared with donepezil, while total and positive symptom scores were similar between both treatments. Statistically significant improvements in positive symptoms score and Clinical Global Impression-Improvement for donepezil compared with placebo were noted at Week 6. Treatment-emergent adverse events (AEs) were observed for 54.5% of donepezil- and 61.3% of placebo-treated patients; most AEs were rated as mild to moderate in severity. Donepezil was safe and well-tolerated but was not effective compared with placebo as a cotreatment for the improvement of cognitive impairment in this patient population. A significant and surprisingly large placebo/practice effect was observed among placebo-treated patients, and is a serious consideration in future clinical trial study designs for potential cognitive enhancing compounds in schizophrenia.",
"To assess the efficacy of quetiapine, a recently introduced second generation antipsychotic medication, in reducing cognitive impairment in patients with schizophrenia.\n Prospective, randomized, double-blind clinical trial.\n 25 patients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, (DSM-IV) criteria for schizophrenia were recruited from 3 Canadian hospitals. INTERVENTION AND OUTCOME MEASURES: After a 48-hour washout period, 25 patients with schizophrenia were randomly assigned to double-blind treatment with quetiapine or haloperidol for 6 months and evaluated with rating scales for psychotic symptoms, mood and extrapyramidal side effects, as well as standardized neuropsychological measures sensitive to 6 cognitive domains: fine motor skill, attention span, verbal reasoning and fluency, visuospatial construction and fluency, executive skills and visuomotor tracking, and immediate recall of verbal and nonverbal materials. The measures were repeated 8 weeks and 6 months after treatment was initiated.\n Quetiapine improved psychosis and mood without inducing extrapyramidal symptoms. Quetiapine also had beneficial effects on cognitive skills, particularly verbal reasoning and fluency skills and immediate recall, with additional improvements on executive skills and visuomotor tracking and on the average of the 6 cognitive domains with sustained treatment. Patients taking haloperidol showed improvements in general clinical status, but no specific improvements on the positive syndrome, the negative syndrome, depression ratings or cognitive skills.\n These preliminary results support the potential value of quetiapine for improving cognitive impairment in patients with schizophrenia and emphasize the importance of further research with this promising atypical antipsychotic.",
"Most disability produced by psychotic illnesses, especially schizophrenia, develops during the prepsychotic period, creating a case for intervention during this period. However, only recently has it been possible to engage people in treatment during this phase.\n A randomized controlled trial compared 2 interventions in 59 patients at incipient risk of progression to first-episode psychosis. We termed this group ultra-high risk to emphasize the enhanced risk vs conventional genetic high-risk studies. Needs-based intervention was compared with specific preventive intervention comprising low-dose risperidone therapy (mean dosage, 1.3 mg/d) and cognitive behavior therapy. Treatment was provided for 6 months, after which all patients were offered ongoing needs-based intervention. Assessments were performed at baseline, 6 months, and 12 months.\n By the end of treatment, 10 of 28 people who received needs-based intervention progressed to first-episode psychosis vs 3 of 31 from the specific preventive intervention group (P=.03). After 6-month follow-up, another 3 people in the specific preventive intervention group became psychotic, and with intention-to-treat analysis, the difference was no longer significant (P=.24). However, for risperidone therapy-adherent patients in the specific preventive intervention group, protection against progression extended for 6 months after cessation of risperidone use.\n More specific pharmacotherapy and psychotherapy reduces the risk of early transition to psychosis in young people at ultra-high risk, although their relative contributions could not be determined. This represents at least delay in onset (prevalence reduction), and possibly some reduction in incidence.",
"Very few controlled clinical trials have been assessing the interaction of antipsychotics and antiepileptics. However, schizophrenic patients frequently receive a combination therapy consisting of haloperidol and carbamazepine. The data for this treatment strategy are contradictory and may depend on the initial plasma concentration of the antipsychotic. There is convincing evidence that after addition of carbamazepine the plasma concentration of neuroleptics drops due to hepatic enzyme induction. In this study, we treated 18 schizophrenic patients either with haloperidol alone or in combination with carbamazepine. The use of carbamazepine was associated with a dramatic fall in haloperidol plasma levels and a worse clinical outcome compared to the monotherapy group. These results, together with a review of the literature, lead us to the conclusion that there are no obvious advantages of carbamazepine co-medication in schizophrenia compared to an optimized neuroleptic monotherapy.",
"There is little information on the comparative effectiveness of second-generation antipsychotic agents.\n To determine if any of five second-generation antipsychotics or haloperidol is more effective in treating acutely ill patients with schizophrenia, schizoaffective disorder or schizophreniform disorder.\n A sample of 327 newly admitted patients were randomised to open-label treatment with aripiprazole, haloperidol, olanzapine, quetiapine, risperidone or ziprasidone for a minimum of 3 weeks. Measures of effectiveness were improvement in mental status so that the patient no longer required acute in-patient care, and changes in Brief Psychiatric Rating Scale (BPRS) scores.\n By the first measure, haloperidol (89%), olanzapine (92%) and risperidone (88%) were significantly more effective than aripiprazole (64%), quetiapine (64%) and ziprasidone (64%). Changes in BPRS ratings were not significant among treatments.\n Haloperidol, olanzapine and risperidone are superior to aripiprazole, quetiapine and ziprasidone for the acute treatment of psychosis in hospitalised patients with schizophrenia, schizoaffective disorder or schizophreniform disorder.",
"Benzodiazepine use by elderly patients is associated with adverse outcomes including increased risk of falls and fractures, motor vehicle accidents and cognitive impairment. Recent studies suggest that individualized feedback and education to physicians may improve drug prescribing. In this study, we evaluated an intervention to address the inappropriate prescribing of benzodiazepines for elderly patients.\n We identified 1624 primary care physicians who wrote at least 10 prescriptions for the target drugs in a 2-month period and randomly assigned these physicians to the intervention group or the control group. We obtained data from the Ontario Drug Benefit claims database, which covers all Ontario residents aged 65 years and over for drugs selected from a minimally restrictive formulary. Every 2 months for 6 months, confidential profiles of benzodiazepine prescription use coupled with evidence-based educational bulletins were mailed to the intervention group. The control group received feedback and educational bulletins about first-line antihypertension drug prescribing for elderly patients. Our main outcome measures were reductions in the proportion of each physician's total benzodiazepine prescriptions for long-acting agents, combinations of benzodiazepines with other psychoactive medications (including other benzodiazepines) and long-term benzodiazepine therapy.\n After randomization, 168 physicians agreed to be in the intervention group and 206 in the control group. Their demographic and prescribing characteristics were similar. Although the proportion of long-acting benzodiazepine prescriptions decreased by 0.7% in the intervention group between the baseline period and the end of the intervention period (from 20.3%, or a mean of 29.5 prescriptions, to 19.6%, or a mean of 27.7 prescriptions) and increased by 1.1% in the control group (from 19.8%, or a mean of 26.4 prescriptions, to 20.9%, or a mean of 27.7 prescriptions) (p = 0.036), this difference was not clinically significant. There was no significant difference over the study period in either combination prescribing of benzodiazepines or in prescriptions for long-term benzodiazepine therapy.\n We did not find that a program of confidential feedback and educational material offered to Ontario primary care physicians had a clinically significant impact on their benzodiazepine prescribing.",
"A 5-week randomized, placebo-controlled, double-blind study was carried out to investigate the efficacy of kava-kava special extract WS1490 in non-psychotic nervous anxiety, tension and restlessness states. During the first treatment week, the study dose drug was increased from 50 mg to 300 mg per day and pretreatment with benzodiazepines was tapered off over 2 weeks. These dosage adjustments were followed by 3 weeks of monotherapy with WS1490 or placebo. Outcome measures were the differences between baseline and end of treatment on the Hamilton Anxiety Scale (HAMA) and on a subjective well-being scale (Bf-S), as well as the benzodiazepine withdrawal symptoms. Changes in the Erlanger Anxiety, Tension and Aggression Scale (EAAS) and Clinical Global Impressions (CGI) were analyzed as secondary measures. Treatment safety was checked by interviews, adverse event reports and laboratory investigations. Forty patients (2x20) were included into the study. WS1490 was superior to placebo regarding the HAMA (P=0.01) and Bf-S (P=0.002) total scores and all secondary efficacy measures. The tolerance of WS1490 was not inferior to placebo. The study confirms the anxiolytic efficacy and good tolerance of WS1490 and shows that a further symptom reduction is possible after a change-over from benzodiazepine treatment.",
"When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation.\n Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]).\n Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation.\n For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.",
"The study investigated the efficacy and tolerability of ethyl-eicosapentaenoic acid (E-EPA) as add-on treatment in chronic, severe schizophrenia.\n A randomized, parallel-group, double-blind, placebo-controlled, fixed-dose, add-on study was conducted over 12 weeks. Forty patients with persistent symptoms after at least 6 months of stable antipsychotic treatment received E-EPA or placebo, in addition to their existing treatment.\n At 12 weeks, the E-EPA group had significantly greater reduction of Positive and Negative Syndrome Scale total scores and of dyskinesia scores than the placebo group.\n EPA may be an effective and well-tolerated add-on treatment in schizophrenia.",
"There is no evidence from randomized, controlled trials that demonstrate effectiveness for any pharmacological treatment in clozapine-resistant schizophrenia. Since the introduction of chlorpromazine, all antipsychotics with proven efficacy on positive symptoms have been dopamine antagonists, but recent experimental data suggest that ketamine-induced positive schizophreniform symptoms in healthy subjects can be controlled by a glutamate antagonist lamotrigine. The hypothesis tested was that lamotrigine is more effective than placebo in the treatment of positive schizophrenic symptoms when combined with clozapine.\n Thirty-four hospitalized treatment-resistant patients having chronic schizophrenia participated in a double-blind, placebo-controlled, 14-week, crossover trial where 200 mg/day lamotrigine was gradually added to their ongoing clozapine treatment. Clinical assessments were made by the Positive and Negative Syndrome Scale at the beginning and end of each treatment period.\n In intention-to-treat analysis, lamotrigine treatment was more effective in reducing positive (effect size.7, p =.009) and general psychopathological (effect size.6, p =.030) symptoms, whereas no improvement was observed in negative symptoms.\n These results provide the first evidence from a randomized controlled trial of an effective pharmacological treatment with an anticonvulsant agent in treatment-resistant schizophrenia and indicate that both positive and general psychopathological symptoms in patients with schizophrenia can be controlled by a drug that is not a dopamine antagonist. The results are in line with previous experimental data suggesting that excessive glutamate neurotransmission contributes to the positive symptoms of schizophrenia.",
"The focus of this study was the systematic evaluation of the clinical effects of glycine as an adjunct to the atypical antipsychotic clozapine in the treatment of schizophrenia.\n In a double-blind, placebo-controlled study, 19 patients with chronic, treatment-resistant schizophrenia who were maintained on optimal doses of clozapine (400-1200 mg/day) were administered either 30 g/day of glycine (N=9) or placebo (N=10) for 12 weeks. Clinical evaluations with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, and the Simpson-Angus movement scale were completed biweekly.\n The use of glycine as an adjunct to clozapine was not effective in decreasing positive or negative symptoms. In contrast, the patients treated with clozapine without glycine had a 35% reduction in positive symptoms.\n These preliminary data suggest that glycine may interfere with the antipsychotic efficacy of atypical neuroleptics such as clozapine."
] |
There is currently no convincing evidence to confirm or refute the practise of administering benzodiazepines as monotherapy or in combination with antipsychotics for the pharmacological treatment of schizophrenia and schizophrenia-like psychosis. Low-quality evidence suggests that benzodiazepines are effective for very short-term sedation and could be considered for calming acutely agitated people with schizophrenia. Measured by the overall attrition rate, the acceptability of benzodiazepine treatment appears to be adequate. Adverse effects were generally poorly reported. High-quality future research projects with large sample sizes are required to clarify the evidence of benzodiazepine treatment in schizophrenia, especially regarding long-term augmentation strategies.
|
CD008511
|
[
"19015968",
"22735897",
"15679185",
"21949005",
"20058059"
] |
[
"Parent-assisted social skills training to improve friendships in teens with autism spectrum disorders.",
"Randomized controlled trial: Multimodal Anxiety and Social Skill Intervention for adolescents with autism spectrum disorder.",
"A social adjustment enhancement intervention for high functioning autism, Asperger's syndrome, and pervasive developmental disorder NOS.",
"Learning through interaction in children with autism: preliminary data from asocial-communication-based intervention.",
"A randomized controlled study of parent-assisted Children's Friendship Training with children having autism spectrum disorders."
] |
[
"This study examines the efficacy of a manualized parent-assisted social skills intervention in comparison with a matched Delayed Treatment Control group to improve friendship quality and social skills among teens 13-17 years of age with autism spectrum disorders. Targeted skills included conversational skills, peer entry and exiting skills, developing friendship networks, good sportsmanship, good host behavior during get-togethers, changing bad reputations, and handling teasing, bullying, and arguments. Results revealed, in comparison with the control group, that the treatment group significantly improved their knowledge of social skills, increased frequency of hosted get-togethers, and improved overall social skills as reported by parents. Possibly due to poor return rate of questionnaires, social skills improvement reported by teachers was not significant. Future research should provide follow-up data to test the durability of treatment.",
"Anxiety is common among adolescents with autism spectrum disorders (ASD) and may amplify the core social disability, thus necessitating combined treatment approaches. This pilot, randomized controlled trial evaluated the feasibility and preliminary outcomes of the Multimodal Anxiety and Social Skills Intervention (MASSI) program in a sample of 30 adolescents with ASD and anxiety symptoms of moderate or greater severity. The treatment was acceptable to families, subject adherence was high, and therapist fidelity was high. A 16 % improvement in ASD social impairment (within-group effect size = 1.18) was observed on a parent-reported scale. Although anxiety symptoms declined by 26 %, the change was not statistically significant. These findings suggest MASSI is a feasible treatment program and further evaluation is warranted.",
"This paper reports the findings of a 20-week social adjustment enhancement curriculum for boys aged 8-12. The curriculum was designed to address three areas hypothesized to be deficient in persons with HFA, AS, and PDDNOS: emotion recognition and understanding; theory of mind; and executive functions/real life type problem solving. Parents attended a semi-structured concurrent psychoeducational training meeting during children's sessions. Statistically significant improvements in facial expression recognition, and problem solving were reported for intervention group children compared to waiting list control group children. For the intervention group (the only group for whom data were available), older and less cognitively able boy's scores on a depression inventory decreased significantly more than younger children's. Mother's depression scores tended to decrease and there were significant reductions in child problem behaviors reported. Results are discussed in the context of individual differences in participant cognitive levels and profiles, symptom severity, and affect-related variables.",
"The study evaluates a social-communication-based approach to autism intervention aimed at improving the social interaction skills of children with autism spectrum disorder. We report preliminary results from an ongoing randomized controlled trial of 51 children aged 2 years 0 months to 4 years 11 months. Participants were assigned to either a target treatment or community treatment group. Families in the target treatment group were given 2 hours of therapy and coaching each week in an intervention emphasizing social-interaction and the parent-child relationship. Children in the community treatment group received a variety of services averaging 3.9 hours per week. After 12 months, outcomes were measured to determine changes in the groups in social interaction and communication. In addition, a regression analysis was conducted to determine whether changes in social interaction skills were associated with language development. Results suggest that children in the treatment group made significantly greater gains in social interaction skills in comparison to the community treatment group, but no between-group differences were found for standard language assessments. Initiation of joint attention, involvement, and severity of language delay were found to be significantly associated with improvement of language skills in children with autism. Finally caregiver skills targeted by the intervention were found to be significantly associated with changes in children's interaction skills.",
"This study evaluated Children's Friendship Training (CFT), a manualized parent-assisted intervention to improve social skills among second to fifth grade children with autism spectrum disorders. Comparison was made with a delayed treatment control group (DTC). Targeted skills included conversational skills, peer entry skills, developing friendship networks, good sportsmanship, good host behavior during play dates, and handling teasing. At post-testing, the CFT group was superior to the DTC group on parent measures of social skill and play date behavior, and child measures of popularity and loneliness, At 3-month follow-up, parent measures showed significant improvement from baseline. Post-hoc analysis indicated more than 87% of children receiving CFT showed reliable change on at least one measure at post-test and 66.7% after 3 months follow-up."
] |
There is some evidence that social skills groups can improve social competence for some children and adolescents with ASD. More research is needed to draw more robust conclusions, especially with respect to improvements in quality of life.
|
CD003752
|
[
"18155755",
"7558945"
] |
[
"Comparison of outcome measures in patients with advanced squamous cell carcinoma of the vulva treated with surgery or primary chemoradiation.",
"A prospective randomized study of chemotherapy adjunctive to definitive radiotherapy in advanced nasopharyngeal carcinoma."
] |
[
"To review outcome measures including overall survival (OS), progression free survival (PFS), and patterns of recurrence in patients with advanced vulvar cancer managed by primary surgery (PS) or primary chemoradiation (PCRT) as well as population characteristics for the two groups.\n Patients diagnosed with stage III and IV squamous cell carcinoma of the vulva from 1990 to 2006 were identified for retrospective analysis at a single institution. Charts were abstracted for clinical and pathologic findings, treatment modalities, complications, recurrence, and follow-up. Kaplan-Meier method was used to determine PFS and OS.\n Sixty-three patients with stage III (n=47) and IV (n=16) carcinoma of the vulva were identified; 30 patients were treated with PS, and 33 patients had tumor that was unresectable by vulvectomy and underwent PCRT. Patients treated with PCRT were younger (61 vs. 72 years; p=0.09), had less metastasis to lymph nodes (54% vs. 83%, p=0.01), and larger tumors (6 vs. 3.5 cm, p=0.0001) compared to patients treated with PS. Despite these differences, OS for the PS and PCRT groups was 69% and 76% (NS), respectively, with median follow-up at 31 months. There were no differences in PFS or recurrence rates between the two groups. By multivariate analysis, age was the only significant predictor of OS or PFS.\n Patients with advanced vulvar cancer that are managed with PS tend to be older patients that have smaller lesions but positive lymph nodes, whereas patients requiring PCRT are younger and have larger volume disease but fewer lymph node metastases. Despite these differences, patients treated with PS and PCRT have no differences in OS, PFS, or recurrence rates. Age is the most powerful predictor of survival when size, lymph node status, stage and treatment are accounted for.",
"A prospective randomized trial was conducted to compare chemoradiotherapy against radiotherapy alone in the treatment of locoregionally advanced nasopharyngeal carcinoma.\n Eighty-two patients with histologically proven nasopharyngeal carcinoma who had either Ho's N3 staging or any N stage with a nodal diameter of > or = 4 cm were entered. Seventy-seven patients were evaluated for tumor response and survival. The patients were randomized to receive two cycles of cisplatin 100 mg/m2 Day 1,5-fluorouracil 1000 mg/m2 24-h infusion Days 2, 3, and 4 before radical radiotherapy, and four cycles of postradiotherapy chemotherapy (37 patients) or radiotherapy alone (40 patients). All patients received radical radiotherapy to the nasopharynx and neck. The nasopharynx and upper neck were treated to 66 Gy by conventional fractionation and the lower neck to 58 Gy. Booster radiotherapy (7.5 Gy/two fractions/week) was given to any residual nodes after standard radiotherapy.\n The patient characteristics, including staging, were similar in both arms. The overall response rate to neoadjuvant chemotherapy was 81% (19% complete response, 62% partial response). The rates of radiotherapy for boosting parapharyngeal disease or residual lymph nodes were not significantly different in the two arms. The overall complete response rate to chemoradiotherapy was 100%, and to radiotherapy alone, 95%. Toxicities in the chemoradiotherapy arm were mainly myelosuppression, nephrotoxicity, and nausea and vomiting. The degree of mucositis was not significantly different in the two arms. There was no treatment-related death. The median follow up was 28.5 months. The 2-year overall survival was 80% in the chemoradiotherapy arm and 80.5% in the radiotherapy arm. The 2-year disease-free survival was 68% in the chemoradiotherapy arm and 72% in the radiotherapy arm, without significant difference between the two arms. The locoregional relapse rate, distant metastatic rate, and median time to relapse were also not significantly different between the two arms.\n Despite promising tumor response rates from Phase II trials, this prospective randomized trial has demonstrated no benefit from adjunctive chemotherapy to radiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma."
] |
Women with advanced vulval tumours showed no significant difference in overall survival or treatment-related adverse events when chemoradiation (primary or neoadjuvant) was compared with primary surgery.
The retrospective studies had a high risk of bias as the entry criteria for primary chemoradiation was based on inoperability or tumour requiring exenteration.The radiochemotherapy regimens varied widely. There was no data on QoL.
There is no standard terminology for 'operable and inoperable vulval cancer', and for 'primary and neoadjuvant chemoradiation'. Stratification according to unresectability of the primary tumour and/or lymph nodes is needed, for good quality comparison.
|
CD000435
|
[
"7359242",
"3748681",
"678328",
"6773022",
"7070890",
"11483805",
"7721525",
"6402753"
] |
[
"Heat balance in premature infants: comparative effects of convectively heated incubator and radiant warmer, with without plastic heat shield.",
"Energy metabolism and substrate utilization in low birth weight neonates under radiant warmers.",
"Minimal oxygen consumption in infants cared for under overhead radiant warmers compared with conventional incubators.",
"Oxygen consumption and insensible water loss in premature infants under radiant heaters.",
"Relative efficacy of an incubator and an open warmer in producing thermoneutrality for the small premature infant.",
"A clinical comparison of radiant warmer and incubator care for preterm infants from birth to 1800 grams.",
"Comparison of heated water-filled mattress and space-heated room with infant incubator in providing warmth to low birthweight newborns.",
"A double-walled incubator alters the partition of body heat loss of premature infants."
] |
[
"Insensible water loss, oxygen consumption, and carbon dioxide production were measured in eight premature infants under four different conditions: in conventional single-walled incubator with and without plastic heat shield, and under radiant warmer with and without heat shield. IWL was greater under the radiant warmer (3.40 +/- 1.50 ml/kg/hour, mean +/- SD) than in the incubator (2.37 +/- 1.15 ml/kg/hour) when both were compared without heat shield. Addition of the heat shield reduced IWL in the incubator (2.13 +/- 0.76 ml/kg/hour) but not under the radiant warmer (3.37 +/- 0.94 ml/kg/hour). There were no significant differences in VO2 or respiratory quotient between any two of the four study conditions.",
"We evaluated the metabolic response to the thermal demands of an open radiant warmer device, as distinct from convection incubator, in 13 healthy premature infants (1.395 +/- 169 g, 28 +/- 12 days of age, mean +/- SD). Metabolic rate was 10% higher for infants under the radiant warmer than in the incubator (2.60 +/- 0.4 v 2.36 +/- 0.3 kcal/kg/h; P less than .05). The radiant warmer also induced a small (4%), but significant, increase in nonprotein respiratory quotient (0.94 +/- 0.1 v 0.90 +/- 0.1; P less than .05) and a 13% increase in carbon dioxide production (8.26 +/- 1.1 v 7.31 +/- 1.1 mL/kg/min; P less than .05). Subcutaneous fat accumulation (estimated from 60-second skin-fold thickness measurements) was greater under the radiant warmer than in the incubator (0.08 +/- 0.05 v 0.04 +/- 0.04 mm/d; P less than .05). Under the warmer, the infant's mean skin temperatures and core temperatures were normal and similar to those found in the incubator, but the foot temperature was on average 0.6 degrees C cooler. The average rate of weight gain (18 g/kg/d) was the same in the radiant environment. The pattern of the elevated metabolic rate, shift of respiratory quotient coupled with the accumulation of subcutaneous fat, and cool extremities of infants under the radiant warmer may represent a physiologic adaptive response to thermal stress. However, the reasons for the elevated metabolic rate are unclear, because activation of the sympathetic nervous system with the release of catecholamines is not apparently involved.(ABSTRACT TRUNCATED AT 250 WORDS)",
"Infants under radiant warmers have large increases in insensible water loss compared with infants in single wall incubators. To answer the question of whether or not a minimal rate of oxygen consumption could be achieved under overhead radiant warmers, we measured oxygen consumption, carbon dioxide production, and abdominal skin, cheek, rectal, thigh, and environmental temperature in ten healthy newborn infants in incubators and radiant warmers, using each infant as his/her own control. The minimal VO2 ranged from 4.41 to 8.87 and from 4.35 to 9.06 cc/kg/minute in the incubator and radiant warmer, respectively. The differences were clearly not significant (paired Student t-test, P greater than 0.60). There were no significant differences between the respiratory quotients, VCO2, or abdominal skin, check, rectal or environmental temperatures. These data support the hypothesis that a thermoneutral environment can be provided with a radiant warmer and imply that large increases in insensible water loss can occur without affecting minimal oxygen consumption.",
"Oxygen consumption ((Vo2), carbon dioxide production (Vco2), and insensible water loss (IWL) were measured simultaneously in nine nondistressed, appropriately grown, premature infants less than 2 weeks old, nursed in a conventional, blow-warmed incubator, and were compared with measurements made on the same infants under a radiant heater. The infants had a pronounced increase (148% on average) in IWL when under the radiant heater (P < .001) whereas Vo2 increased by only 4.6% (P = .073). Abdominal skin temperature (servocontrolled to maintain 36.5 C) and esophageal temperature were the same under both conditions, but ambient air temperature was 0.7 C higher in the incubator (P < 05). Although a positive correlation was found between the increase in IWL and the change in Vo2 (r = .75, P < .01), the large increase in IWL (and, therefore, evaporative heat loss) under the radiant heater is out of proportion to, and cannot be accounted for, by the change in metabolic heat production. The heat transfer processes involved in maintaining body temperature constant under these conditions require further study.",
"To determine which warming system more closely approximates a neutral thermal environment, the oxygen consumption of 16 premature babies, weighing less than 1,500 gm each, was measured in a convectively heated incubator and under an open radiant warmer. Both systems were controlled to maintain a skin temperature of 36 C. The oxygen consumption of the infants was significantly higher under the radiant warmer. This result is in agreement with published data for this group of premature infants.",
"The objective of this study was to compare radiant warmer and incubator care for preterm infants from birth with respect to temperature control and weight gain.\n Sixty preterm infants <33 weeks' gestation were randomized at birth to radiant warmer or incubator care. The initial goal was to maintain abdominal temperature at 36.8 degrees C in both groups and axillary temperature at 36.8 to 37.3 degrees C; air servocontrol was used for incubator infants. Infants in both groups received added humidity for 5 days if their weight was <1000 g and for 3 days if they weighed between 1000 and 1249 g. During a 3-hour period on days 1 to 7, recordings of abdominal, forehead, and foot temperatures were obtained. The percentage of the recording time during which the abdominal temperature was in the target range of between 36 degrees C and 37.5 degrees C was determined as an indicator of temperature control. Weight gain from birth to 1800 g was compared. Secondary outcomes included fluid balance and clinical events.\n There were 30 infants in each group; 48 were <1500 g (of whom 17 were <1000 g). There were no significant differences in birth weight, gestation, gender, or illness severity scores in the 2 groups. Significant differences in temperature control were noted on day 1. Although admission temperatures were similar, lower abdominal temperatures were noted in the first 2 hours of life in the incubator group (medians were 36.6 degrees C and 35.9 degrees C in the radiant warmer and incubator groups, respectively). Similarly, mean abdominal temperatures during the 3-hour recording on day 1 were lower in the incubator group, and infants in this group spent a significantly greater percentage of the recording time with temperatures outside the target range (17.3% compared with 0.88%). Other temperature recordings from the forehead and foot were not significantly different in the groups. Fluid intakes were higher for infants under radiant warmer on days 2, 3, and 4, and the difference amounted to a mean of 12.8 mL/kg/d. Maximum sodium levels in the first week were similar in the 2 groups. Mean weight gain was 17.4 g/kg/d for the radiant warmer group and 17.1 g/kg/d for the incubator group; days to regain birth weight and length of hospital stay were not significantly different. Greater numbers of infants in the radiant warmer group required phototherapy, and adverse events (which included death, necrotizing enterocolitis, chronic lung disease, grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, or retinopathy requiring laser treatment) were less frequent in the radiant warmer group (1 infant compared with 8 in the incubator group; relative risk 0.1; 95% confidence intervals: 0.01-0.82).\n This study has shown differences in abdominal temperatures on day 1 and outcome, although the latter finding should be viewed with caution because of the sample size. The results indicate benefits for the initial use of the radiant warmer after birth. Although fluid requirements were higher in the radiant warmer group for days 2 through 4, the increased fluid volumes were given without apparent adverse effect.",
"Prevention of excessive heat loss is fundamental to survival of low birthweight (LBW) newborns. The use of infant incubators (INC) is beyond the resources of developing countries, and the space-heated room (SHR) has been the only feasible means of providing thermal protection to LBW newborns. Recently a thermostatically controlled, heated, water-filled mattress (HWM) has been developed as a potentially simpler and affordable alternative.\n In a neonatal care ward of a referral hospital in Addis Ababa, 62 < 1 week old newborns, weighing 1000-1999 g, who were well enough to breathe comfortably in room air and tolerate oral feeds, were randomly allocated to INC, HWM or SHR and followed for 3 weeks. The level of cold stress as assessed by core-to-skin temperature gradient and the rate of weight gain were the main outcome measures.\n The level of cold stress was lowest in the INC, intermediate in the HWM and highest in the SHR. Relative to the INC group, the HWM group exhibited a modest increase in the occurrence of clinically important hyperthermic or hypothermic deviations in core temperature (rate ratio (RR) = 2.3; 95% CI: 0.9, 5.6), and the SHR displayed a definite increase (RR = 4.0; 95% CI: 1.7, 9.3). During the first week, the rate of weight gain was highest in the INC group (3.6 g/kg/day), lowest in the SHR group (-2.3 g/kg/day, P < 0.05 versus INC) and intermediate in the HWM group (1.6 g/kg/day, P > 0.1 versus INC).\n Care in the SHR produced clinically significant thermal stresses and was associated with deficient early neonatal growth, but the use of HWM may constitute a feasible and clinically acceptable alternative in providing warmth to LBW newborns during the neonatal period.",
"Partitional calorimetry was used to assess the influence of a double-walled incubator (Air-Shields C-86 Isolette) on the body heat loss of eight premature newborn infants (birth weights 1.44-1.89 kg, ages 6-19 days). Each infant was studied in the same incubator with and without the inner wall. Incubator heater output was regulated by servocontrol to maintain the abdominal skin temperature at 36.5 degrees C. Operative environmental temperature was the same (mean 33.0 degrees C) in both incubators. There were no differences in body temperatures, oxygen consumption, carbon dioxide production, respiratory quotient, or evaporative water and heat losses. The double-walled incubator reduced radiant heat loss but increased convective heat loss, so that the total rate of body heat loss was unchanged."
] |
Radiant warmers result in increased IWL compared to incubators. This needs to be taken into account when calculating daily fluid requirements. The results of this review do not provide sufficient evidence concerning effects on important outcomes to guide clinical practice. Further randomised controlled trials are required to assess the effects of radiant warmers versus incubators in neonatal care on important short and long term outcomes, with particular attention to extremely low birthweight infants in the early neonatal period.
|
CD006792
|
[
"19505878",
"16291357",
"17710485",
"10379017",
"8881815",
"8625660"
] |
[
"Steroid-sparing properties of sargramostim in patients with corticosteroid-dependent Crohn's disease: a randomised, double-blind, placebo-controlled, phase 2 study.",
"Clinical impact of corticosteroid-induced adrenal suppression during treatment for acute lymphoblastic leukemia in children: a prospective observational study using the low-dose adrenocorticotropin test.",
"Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization.",
"Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group.",
"Budesonide prolongs time to relapse in ileal and ileocaecal Crohn's disease. A placebo controlled one year study.",
"Effects of long-term treatment with corticosteroids in COPD."
] |
[
"Although treatment with corticosteroids induces remission in Crohn's disease, prolonged exposure to corticosteroids is undesirable. This randomised clinical trial evaluated the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (sargramostim), an activator of innate immunity, in corticosteroid-dependent patients with Crohn's disease.\n Patients were randomised in a 2:1 ratio, to sargramostim 6 microg/kg subcutaneously once daily or placebo for up to 22 weeks. The study consisted of (1) an adjunctive phase (weeks 1-4) in which patients received study drug plus corticosteroid therapy; (2) a forced corticosteroid tapering phase (weeks 4-14); and (3) an observation phase (4 weeks) in which patients received study drug plus prednisone < or =7.5 mg. The primary endpoint was corticosteroid-free remission (Crohn's Disease Activity Index (CDAI) < or =150) 4 weeks after corticosteroid elimination. Secondary endpoints were corticosteroid-free response (CDAI decreased by > or =100) and induction of remission in patients who reduced the dose of corticosteroid to 2.5-7.5 mg.\n Eighty-seven patients were randomised to sargramostim and 42 to placebo. Significantly more sargramostim-treated patients than placebo patients achieved corticosteroid-free remission (18.6% vs 4.9%; p = 0.03). Similar differences were seen for corticosteroid-free response and in patients who tapered corticosteroids to 2.5-7.5 mg/day. Sargramostim treatment was also associated with significant improvements in health-related quality of life. Patients who received sargramostim were more likely to experience musculoskeletal pain, injection site reactions and dyspnoea.\n Sargramostim was more effective than placebo for inducing corticosteroid-free remission in patients with Crohn's disease with corticosteroid dependence. Sargramostim may provide significant benefit in this population if these findings are confirmed.",
"To investigate how frequently adrenal function fails to recover after corticosteroid therapy in children with acute lymphoblastic leukemia and to explore the clinical impact of slow adrenal recovery without steroid substitution.\n Low-dose (1 microg) adrenocorticotropic hormone tests were performed before and after steroid courses and during infectious episodes in 24 children. Test results were not available during the study.\n All 13 patients tested before treatment had normal adrenal responses. Adrenal suppression was found in 8 (47%) of 17 patients 5 days after discontinuation of a 5-week induction course of prednisolone and in 1 (20%) of 5 patients 7 days after a 3-week intensification course of dexamethasone, both courses being tapered over 9 days, as well as in all 13 patients tested 2 days after a 1-week prednisolone course. Clinically significant manifestations of adrenal suppression were noted in 3 (12%) patients. Of 204 scheduled tests, 131 were performed.\n High-dose glucocorticoid therapy may cause adrenal suppression lasting more than 1 week in children with acute lymphoblastic leukemia, even after tapering the dose. We suggest steroid replacement during stress episodes within 1 to 2 weeks after discontinuation and thereafter testing adrenal function selectively in accordance with symptoms.",
"Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia.\n The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia (CAP) requiring hospitalization.\n An open label, prospective, randomized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan.\n Thirty-one adult CAP patients who required hospitalization were enrolled.\n Fifteen patients received 40 mg of prednisolone intravenously for 3 days (steroid group). Sixteen patients did not receive prednisolone (control group). Both groups were also evaluated for their adrenal function. The primary endpoint was length of hospital stay. Secondary endpoints were duration of intravenous (IV) antibiotics and time required to stabilize vital signs. Both groups demonstrated similar baseline characteristics and length of hospital stay, and yet a shorter duration of IV antibiotics was observed in the steroid group (p < 0.05). In addition, vital signs were stabilized earlier in the steroid group (p < 0.05). These differences were more prominent in the moderate-severe subgroup but not as significant in the mild-moderate subgroup. The prevalence of relative adrenal insufficiency (RAI) in both groups was high (43%), yet there was no difference in baseline characteristics between patients, with or without RAI. In multiple regression models, RAI seemed to have no influence on clinical courses.\n In moderate-severe CAP, administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy.",
"Although their clinical efficacy is unclear and they may cause serious adverse effects, systemic glucocorticoids are a standard treatment for patients hospitalized with exacerbations of chronic obstructive pulmonary disease (COPD). We conducted a double-blind, randomized trial of systemic glucocorticoids (given for two or eight weeks) or placebo in addition to other therapies, for exacerbations of COPD. Most other care was standardized over the six-month period of follow-up. The primary end point was treatment failure, defined as death from any cause or the need for intubation and mechanical ventilation, readmission to the hospital for COPD, or intensification of drug therapy.\n Of 1840 potential study participants at 25 Veterans Affairs medical centers, 271 were eligible for participation and were enrolled; 80 received an eight-week course of glucocorticoid therapy, 80 received a two-week course, and 111 received placebo. About half the potential participants were ineligible because they had received systemic glucocorticoids in the previous 30 days. Rates of treatment failure were significantly higher in the placebo group than in the two glucocorticoid groups combined at 30 days (33 percent vs. 23 percent, P=0.04) and at 90 days (48 percent vs. 37 percent, P=0.04). Systemic glucocorticoids (in both groups combined) were associated with a shorter initial hospital stay (8.5 days, vs. 9.7 days for placebo, P=0.03) and with a forced expiratory volume in one second that was about 0.10 liter higher than that in the placebo group by the first day after enrollment. Significant treatment benefits were no longer evident at six months. The eight-week regimen of therapy was not superior to the two-week regimen. The patients who received glucocorticoid therapy were more likely to have hyperglycemia requiring therapy than those who received placebo (15 percent vs. 4 percent, P=0.002).\n Treatment with systemic glucocorticoids results in moderate improvement in clinical outcomes among patients hospitalized for exacerbations of COPD. The maximal benefit is obtained during the first two weeks of therapy. Hyperglycemia of sufficient severity to warrant treatment is the most frequent complication.",
"To evaluate the efficacy and safety of the topical corticosteroid budesonide, given in an oral controlled release formulation for maintenance of remission in patients with ileal and ileocaecal Crohn's disease (CD).\n Out of 176 patients with active CD who had achieved remission (CD activity index score < or = 150) after 10 weeks' treatment with either budesonide or prednisolone, 90 were randomised to continue with once daily treatment of 6 mg budesonide, or 3 mg budesonide or placebo for up to 12 months in a double blind, multicentre trial. Time to symptomatic relapse was calculated using Kaplan-Meier estimates. Morning plasma cortisol was measured at clinic visits and a corticotropin stimulation test was performed after three months of treatment.\n Thirty two patients were allocated to the 6 mg budesonide group, 31 to the 3 mg group, and 27 to the placebo group. After three months, 19 per cent of the patients in the 6 mg group had relapsed, compared with 45 per cent in the 3 mg group and 44 per cent in the placebo group (p = 0.047). The corresponding results after 12 months was 59 per cent in the 6 mg budesonide group, 74 per cent in the 3 mg group, and 63 per cent in the placebo group (p = 0.44). The median time to relapse or discontinuation was 258 days in the 6 mg group, 139 days in the 3 mg group, and 92 days in the placebo group (p = 0.021). Mean morning plasma cortisol values increased from entry in all three groups with no statistically significant differences at 12 months. All 13 patients remaining in the placebo group after three months had a normal corticotropin stimulation response, compared with 18 of 23 patients in the 6 mg, and 19 of 21 in the 3 mg budesonide groups (p = 0.14). Acne and moon face were slightly more common in the budesonide groups.\n 6 mg budesonide once daily is significantly more efficacious than placebo in prolonging time to relapse in CD, and causes only minor systemic side effects.",
"To determine the effectiveness of treatment with corticosteroids in patients with COPD.\n In this study, we investigated the effect of a 2-year treatment with corticosteroids on clinical symptoms and the decline of lung function in 58 nonallergic patients with COPD. Subjects were treated in a double-blind, randomized, placebo-controlled, parallel way with inhaled budesonide (bud), 1,600 micrograms/d; inhaled budesonide, 1,600 micrograms/d, plus oral prednisolone, 5 micrograms/d (bud + pred); or placebo (plac). Clinical assessment (history, physical examination, and spirometry) was carried out every 2 months. The rate of decline in FEV1 was assessed by calculating individual regression co-efficients from linear regression of FEV1 on time for each subject.\n Eleven patients dropped out. The number of withdrawals due to pulmonary problems was significantly higher in the plac group (n = 5 out of 18) than in the actively treated groups (n = 2 out of 40). Treatment with corticosteroids significantly reduced pulmonary symptoms. Median decline of FEV1 was 60 mL/yr in the plac group, 40 mL/yr in the bud + pred group, and 30 mL/yr in the bud group. Variation was large and differences were not statistically significant. No treatment effect was found on frequency or duration of exacerbations, possibly because of the high number of withdrawals due to pulmonary deterioration in the plac group. Treatment with a combination of inhaled plus oral corticosteroids was not more effective than inhaled corticosteroids alone. Morning plasma cortisol levels remained within the normal range in all three groups.\n Our study shows beneficial effects of long-term daily treatment with inhaled corticosteroids in patients with COPD with regard to symptoms and drop out due to pulmonary problems. Lung function decline tends to decrease during treatment with inhaled corticosteroids. The observed effects are limited but warrant further studies on the effectiveness of corticosteroids in larger numbers of patients with COPD."
] |
Corticosteroids are effective for induction of remission in patients with CD, particularly when used for more than 15 weeks. Although corticosteroids cause more adverse events than either placebo or low-dose 5-ASA, these adverse events did not lead to increased study withdrawal in the included studies. Further information is required to determine the optimal duration of treatment and tapering protocol to maximize the efficacy of treatment with corticosteroids. Additionally, further study is required to determine whether corticosteroids are more effective in patients with certain phenotypes or when administered intravenously.
|
CD006920
|
[
"16600232",
"16600225",
"16966110",
"17091416",
"11802511",
"15280133",
"12118641",
"11937123",
"17261096"
] |
[
"Acupuncture on the day of embryo transfer significantly improves the reproductive outcome in infertile women: a prospective, randomized trial.",
"Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer.",
"A randomized controlled trial of acupuncture for initiation of labor in nulliparous women.",
"Acupuncture administered after spontaneous rupture of membranes at term significantly reduces the length of birth and use of oxytocin. A randomized controlled trial.",
"Acupuncture for cervical ripening and induction of labor at term--a randomized controlled trial.",
"Acupuncture plus moxibustion to resolve breech presentation: a randomized controlled study.",
"Acupuncture treatment during labour--a randomised controlled trial.",
"Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy.",
"The effects of acupuncture during labour on nulliparous women: a randomised controlled trial."
] |
[
"To evaluate the effect of acupuncture on reproductive outcome in patients treated with IVF/intracytoplasmic sperm injection (ICSI). One group of patients received acupuncture on the day of ET, another group on ET day and again 2 days later (i.e., closer to implantation day), and both groups were compared with a control group that did not receive acupuncture.\n Prospective, randomized trial.\n Private fertility center.\n During the study period all patients receiving IVF or ICSI treatment were offered participation in the study. On the day of oocyte retrieval, patients were randomly allocated (with sealed envelopes) to receive acupuncture on the day of ET (ACU 1 group, n = 95), on that day and again 2 days later (ACU 2 group, n = 91), or no acupuncture (control group, n = 87).\n Acupuncture was performed immediately before and after ET (ACU 1 and 2 groups), with each session lasting 25 minutes; and one 25-minute session was performed 2 days later in the ACU 2 group.\n Clinical pregnancy and ongoing pregnancy rates in the three groups.\n Clinical and ongoing pregnancy rates were significantly higher in the ACU 1 group as compared with controls (37 of 95 [39%] vs. 21 of 87 [26%] and 34 of 95 [36%] vs. 19 of 87 [22%]). The clinical and ongoing pregnancy rates in the ACU 2 group (36% and 26%) were higher than in controls, but the difference did not reach statistical difference.\n Acupuncture on the day of ET significantly improves the reproductive outcome of IVF/ICSI, compared with no acupuncture. Repeating acupuncture on ET day +2 provided no additional beneficial effect.",
"To evaluate the effects of acupuncture on clinical pregnancy rates for women undergoing ET.\n Single-blind, randomized controlled trial using a noninvasive sham acupuncture control.\n Repromed, The Reproductive Medicine Unit of The University of Adelaide.\n Women undergoing IVF.\n Women were randomly allocated to acupuncture or noninvasive sham acupuncture with the placebo needle. All women received three sessions, the first undertaken on day 9 of stimulating injections, the second before ET, and the third immediately after ET.\n The primary outcome was pregnancy. Secondary outcomes were implantation, ongoing pregnancy rate at 18 weeks, adverse events, and health status.\n Two hundred twenty-eight subjects were randomized. The pregnancy rate was 31% in the acupuncture group and 23% in the control group. For those subjects receiving acupuncture, the odds of achieving a pregnancy were 1.5 higher than for the control group, but the difference did not reach statistical significance. The ongoing pregnancy rate at 18 weeks was higher in the treatment group (28% vs. 18%), but the difference was not statistically significant.\n There was no significant difference in the pregnancy rate between groups; however, a smaller treatment effect can not be excluded. Our results suggest that acupuncture was safe for women undergoing ET.",
"To evaluate the utility of outpatient acupuncture for labor stimulation.\n Nulliparous women at 39 4/7 weeks or greater with a singleton gestation and Bishop score of less than 7 were randomized to usual medical care (control group) versus usual care and three outpatient acupuncture treatments (acupuncture group). Each treatment consisted of eight needles applied to bilateral points LI4, SP6, UB31, and UB32. The primary outcome was time elapsed from the time of randomization to delivery. Secondary outcomes included rates of cesarean section and induction of labor. Medical records were abstracted for maternal demographic, medical, and delivery outcome data. A priori sample size calculation revealed that 56 women were required to detect a 72-hour difference in delivery time with a power of 83% and an alpha of 0.05. Student's t-test, Chi-square, and Kaplan-Meier statistics were used to compare groups.\n Fifty-six women were randomized and completed the study procedures. Race, age, gestational age, and cervical Bishop score were similar in both groups. Mean time to delivery occurred 21 hours sooner in the acupuncture group, but this difference did not reach statistical significance (p = 0.36). Compared to controls, women in the acupuncture group tended to be more likely to labor spontaneously (70% vs. 50%, p = 0.12) and less likely to deliver by cesarean section (39% vs. 17%, p = 0.07). Of women who were not induced, those in the acupuncture group were more likely to be delivered than the controls at any point after enrollment (p = 0.05).\n Acupuncture is well tolerated among term nulliparous women and holds promise in reducing interventions that occur in post-term pregnancies.",
"The objective was to investigate whether acupuncture could be a reasonable option for augmentation in labor after spontaneous rupture of membranes at term and to look for possible effects on the progress of labor.\n In a randomized controlled trial 100 healthy parturients, with spontaneous rupture of membranes at term, were assigned to receive either acupuncture or no acupuncture. The main response variables were the duration of active labor, the amount of oxytocin given, and number of inductions.\n Duration of labor was significantly reduced (mean difference 1.7 h, p=0.03) and there was significant reduction in the need for oxytocin infusion to augment labor in the study group compared to the control group (odds ratio 2.0, p=0.018). We also discovered that the participants in the acupuncture group who needed labor induction had a significantly shorter duration of active phase than the ones induced in the control group (mean difference 3.6 h, p=0.002). These findings remained significant also when multiple regression was performed, controlling for potentially confounding factors like parity, epidural analgesia, and birth weight.\n Acupuncture may be a good alternative or complement to pharmacological methods in the effort to facilitate birth and provide normal delivery for women with prelabor rupture of membranes.",
"The aim of this study was to evaluate whether acupuncture at term can influence cervical ripening, induce labor and thus reduce the need for postdates induction.\n On the estimated date of confinement (EDC) women were prospectively randomized to an acupuncture group (AG) or a control group (CG). Data of 45 women were evaluated (AG, n = 25; CG, n = 20). Inclusion criteria were as follows: confirmed EDC, uncomplicated course of pregnancy, singleton pregnancy in cephalic presentation. Exclusion criteria were as follows: cervical dilation > 3 cm, active labor, premature rupture of membranes, previous cesarean section, pathologies in mother or fetus. Women were examined at 2-day intervals. The cervical length was measured with vaginal ultrasonography, cervical mucus was obtained for a fetal Fibronectin test and the cervical status was assessed according to the Bishop score. In the AG, the points Hegu (Large Intestine 4) and Sanyinjiao (Spleen 6) were pierced on both sides every second day. If women were not delivered 10 days after EDC, labor was induced by administering vaginal prostaglandin tablets.\n The cervical length in the AG was shorter than that in the CG on day 6 and day 8 after EDC (P = 0.04 for both). In the AG the time period from the first positive Fibronectin test to delivery was 2.3 days, while that in the CG was 4.2 days (P = 0.08). The time period from EDC to delivery was on average 5.0 days in the AG and 7.9 days in the CG (P = 0.03). Labor was induced in 20% of women in the AG (n = 5) and in 35% in the CG (n = 7) (P = 0.3). Overall duration of labor, and first and second stage of labor were not different in the two groups. In 56% of women who underwent acupuncture (n = 14) and in 65% of controls (n = 13), Oxytocin was used to augment labor. (P = 0.54).\n Acupuncture at points LI4 and SP 6 supports cervical ripening at term and can shorten the time interval between the EDC and the actual time of delivery.",
"In many Western countries breech presentation is an indication for elective Cesarean section. In order to correct fetal presentation, the stimulation of the acupoint BL67 by moxibustion, acupuncture or both has been proposed. Since no studies had previously been carried out on Western populations, pregnant Italian women at 33-35 weeks gestational age carrying a fetus in breech presentation were enrolled in a randomized, controlled trial involving an active BL67 point stimulation and an observation group.\n A total of 240 women at 33-35 weeks of gestation carrying a fetus in breech presentation were randomized to receive active treatment (acupuncture plus moxibustion) or to be assigned to the observation group. Bilateral acupuncture plus moxibustion was applied at the BL67 acupoint (Zhiyin). The primary outcome of the study was fetal presentation at delivery.\n Fourteen cases dropped out. The final analysis was thus made on 226 cases, 114 randomized to observation and 112 to acupuncture plus moxibustion. At delivery, the proportion of cephalic version was lower in the observation group (36.7%) than in the active-treatment group (53.6 %) (p = 0.01). Hence, the proportion of Cesarean sections indicated for breech presentation was significantly lower in the treatment group than in the observation group (52.3% vs. 66.7%, p = 0.03).\n Acupuncture plus moxibustion is more effective than observation in revolving fetuses in breech presentation. Such a method appears to be a valid option for women willing to experience a natural birth.",
"To investigate acupuncture treatment during labour with regard to pain intensity, degree of relaxation and outcome of the delivery.\n Randomised controlled trial.\n Delivery ward at a tertiary care centre hospital in Sweden.\n Ninety parturients who delivered during the period April 12, 1999 and June 4, 2000.\n Forty-six parturients were randomised to receive acupuncture treatment during labour as a compliment, or an alternative, to conventional analgesia.\n Assessments of pain intensity and degree of relaxation during labour, together with evaluation of delivery outcome.\n Acupuncture treatment during labour significantly reduced the need of epidural analgesia (12% vs 22%, relative risk [RR] 0.52, 95% confidence interval [CI] 0.30 to 0.92). Parturients who received acupuncture assessed a significantly better degree of relaxation compared with the control group (mean difference -0.93, 95% CI -1.66 to -0.20). No negative effects of acupuncture given during labour were found in relation to delivery outcome.\n The results suggest that acupuncture could be a good alternative or complement to those parturients who seek an alternative to pharmacological analgesia in childbirth. Further trials with a larger number of patients are required to clarify if the main effect of acupuncture during labour is analgesic or relaxing.",
"To evaluate the effect of acupuncture on the pregnancy rate in assisted reproduction therapy (ART) by comparing a group of patients receiving acupuncture treatment shortly before and after embryo transfer with a control group receiving no acupuncture.\n Prospective randomized study.\n Fertility center.\n After giving informed consent, 160 patients who were undergoing ART and who had good quality embryos were divided into the following two groups through random selection: embryo transfer with acupuncture (n = 80) and embryo transfer without acupuncture (n = 80).\n Acupuncture was performed in 80 patients 25 minutes before and after embryo transfer. In the control group, embryos were transferred without any supportive therapy.\n Clinical pregnancy was defined as the presence of a fetal sac during an ultrasound examination 6 weeks after embryo transfer.\n Clinical pregnancies were documented in 34 of 80 patients (42.5%) in the acupuncture group, whereas pregnancy rate was only 26.3% (21 out of 80 patients) in the control group.\n Acupuncture seems to be a useful tool for improving pregnancy rate after ART.",
"Acupuncture is as an ancient system of diagnosis and treatment. It is regarded as a complementary tool for pain management.\n To assess the effects of acupuncture on nulliparous women during labour with respect to pain, labour duration and maternal acceptability.\n One hundred and forty-four healthy nulliparous women in active phase were randomised into the study and control group, receiving real and minimal acupuncture, respectively. Visual analogue scale was used to assess pain. Objectives were to evaluate acupuncture effect on pain and labour duration and patients' willingness to receive acupuncture for subsequent pregnancies.\n Visual analogue scale pain score in the study group was lower after two hours. Active phase duration and the oxytocin units administered were lower in the study group. Study group patients had greater willingness to receive acupuncture again. No adverse effects were detected.\n Acupuncture could reduce pain experience, active phase duration and oxytocin units. Patients were satisfied and no adverse effects were noted."
] |
Acupuncture performed on the day of ET shows a beneficial effect on the live birth rate; however, with the present evidence this could be attributed to placebo effect and the small number of women included in the trials. Acupuncture should not be offered during the luteal phase in routine clinical practice until further evidence is available from sufficiently powered RCTs.
|
CD004805
|
[
"7490154",
"2207419",
"1747217"
] |
[
"Combinations of potassium, calcium, and magnesium supplements in hypertension.",
"Efficacy of potassium and magnesium in essential hypertension: a double-blind, placebo controlled, crossover study.",
"Calcium treatment of essential hypertension in elderly patients evaluated by 24 H monitoring."
] |
[
"Dietary intakes of potassium, calcium, and magnesium have each been reported to lower blood pressure, but the extent of blood pressure reduction in epidemiological studies and clinical trials has tended to be small and inconsistent. We hypothesized that combinations of these mineral supplements would lower blood pressure and that the reductions would be greater than that usually reported in studies of each cation alone. One hundred twenty-five patients 82 men and 43 women) with untreated mild or borderline hypertension were randomly assigned to daily treatment with one of the following four regimens: 60 mmol potassium and 25 mmol (1000 mg) calcium, 60 mmol potassium and 15 mmol (360 mg) magnesium, calcium and magnesium, or placebo. Standardized clinic blood pressure measurements were obtained on 3 days at baseline and after 3 and 6 months of treatment. At baseline, systolic and diastolic blood pressures (mean +/- SD) were 139 +/- 12 and 90 +/- 4 mm Hg, respectively, and dietary intakes of potassium, calcium, and magnesium were 77 +/- 32, 19 +/- 13, and 12 +/- 52 mmol/d, respectively. The mean differences (with 95% confidence intervals) of the changes in systolic and diastolic blood pressures between the treatment and placebo groups were not significant: -0.7 (-4.3 to +2.9) and -0.4 (-2.9 to +2.1) for potassium and calcium, -1.3 (-4.4 to +1.8) and 0.4 (-2.5 to +3.3) for potassium and magnesium, and +2.1 (-1.8 to +6.0) and +2.2 (-1.0 to +5.4) for calcium and magnesium. In conclusion, this trial provides little evidence of an important role of combinations of cation supplements in the treatment of mild or borderline hypertension.",
"To evaluate the antihypertensive activity of potassium given alone or in combination with magnesium in patients with mild hypertension.\n A double blind, randomised, placebo controlled, crossover trial of 32 weeks' duration.\n Cardiology outpatient department, Sassoon General Hospitals, Pune, India.\n 37 Adults with mild hypertension (diastolic blood pressure less than 110 mm Hg).\n Patients received either placebo or potassium 60 mmol/day alone or in combination with magnesium 20 mmol/day in a crossover design. No other drug treatment was allowed.\n Blood pressure and heart rate assessed at weekly intervals and biochemical parameters at monthly intervals.\n Potassium alone or in combination with magnesium produced a significant reduction in systolic and diastolic blood pressures (p less than 0.001) and a significant reduction in serum cholesterol concentration (p less than 0.05); other biochemical variables did not change. Magnesium did not have an additional effect. Urinary potassium excretion increased significantly in the groups who received potassium alone or in combination with magnesium. The drug was well tolerated and compliance was satisfactory.\n Potassium 60 mmol/day lowers arterial blood pressure in patients with mild hypertension. Giving magnesium as well has no added advantage.",
"We used 24-h monitoring of blood pressure (BP) to evaluate the effect of calcium supplementation on mild to moderate essential hypertension in elderly hospitalized patients for the first time in a controlled crossover study. The mean systolic and diastolic BP over a period of 24 h declined by 13.6 mm Hg (P less than .005) and 5.0 mm Hg (P less than .05) respectively in patients whose diet was supplemented with 1 g of elemental calcium in the form of oystershell electrolysate (AA calcium). Serum ionized calcium and urinary calcium and sodium excretion increased (serum Ca2+ 0.16 +/- 0.03 mEq/L, P less than .05; FECa 0.5 +/- 0.2%, P less than .05; FENa 0.4 +/- 0.1%, P less than .05) and plasma parathyroid hormone was suppressed (12.2 +/- 2.3 pg/mL, P less than .005). These data suggest that supplementation of dietary calcium may contribute to a reduction of BP in elderly patients with essential hypertension."
] |
We found no robust evidence that supplements of any combination of potassium, magnesium or calcium reduce mortality, morbidity or BP in adults. More trials are needed to investigate whether the combination of potassium & magnesium is effective.
|
CD005953
|
[
"2783342",
"2865674",
"19097907",
"8090293",
"7121779",
"2728855",
"9719328",
"9270646",
"17947936",
"9882786",
"18662624",
"10421111",
"6152311",
"16365207",
"1682845",
"1375987",
"12458242",
"11093490"
] |
[
"Clinical results of extracranial-intracranial bypass surgery in patients with hemodynamic cerebrovascular disease.",
"Failure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke. Results of an international randomized trial. The EC/IC Bypass Study Group.",
"STA-MCA bypass for symptomatic carotid occlusion and haemodynamic impairment.",
"[Spinal cord electric stimulation vs. femoro-distal bypass in critical ischemia of the legs. Preliminary results in a randomized prospective study].",
"Overall management of vascular lesions considered treatable with extracranial-intracranial bypass: part 1. Internal carotid occlusion.",
"Long-term clinical and neurophysiological effects of reconstructive vascular surgery for cerebral ischemia.",
"Randomized study of carotid angioplasty and stenting versus carotid endarterectomy: a stopped trial.",
"Cerebral dysfunction after coronary artery bypass grafting done with mild or moderate hypothermia.",
"Risk of retinal microembolism after off-pump and on-pump coronary artery bypass surgery.",
"A randomized trial of intraoperative autotransfusion during aortic surgery.",
"Neuropsychologic and quality-of-life outcomes after coronary artery bypass surgery with and without cardiopulmonary bypass: a prospective randomized trial.",
"Effects of hypothermic and normothermic cardiopulmonary bypass on brain oxygenation.",
"Long-term follow-up in 257 ICA occlusion: comparison between EIAB-treated and untreated patients.",
"Retinal and cerebral microembolization during coronary artery bypass surgery: a randomized, controlled trial.",
"Comparison of the clinical results of STA-MCA anastomosis and the medical treatment in the cerebral low perfusion patients with viable brain tissue.",
"STA-MCA bypass surgery for internal carotid artery occlusion--comparative follow-up study.",
"Assessment of neurocognitive impairment after off-pump and on-pump techniques for coronary artery bypass graft surgery: prospective randomised controlled trial.",
"Off-pump coronary bypass operations significantly reduce S100 release: an indicator for less cerebral damage?"
] |
[
"The importance of hemodynamic factors in the pathogenesis and treatment of cerebrovascular disease remains uncertain. The extracranial-intracranial (EC-IC) bypass trial has been criticized for failing to identify and separately analyze those patients with chronic reduction in regional cerebral perfusion pressure (rCPP) who might be most likely to benefit from surgery. Positron emission tomography (PET) measurements of regional cerebral blood flow (rCBF) and blood volume (rCBV) were performed on 29 patients with symptomatic occlusion or intracranial stenosis of the carotid arterial system prior to undergoing EC-IC bypass surgery. Twenty-four patients had evidence of reduced rCPP (increased rCBV/rCBF ratio) distal to the arterial lesion. Of 21 patients who survived surgery without stroke, three suffered ipsilateral ischemic strokes during the 1st postoperative year. A nonrandomized control group of 23 nonsurgical patients' with similar clinical, arteriographic, and PET characteristics experienced no ipsilateral ischemic strokes during the 1st year following PET. Based on these results in 44 patients, the probability that successful surgery reduces the occurrence of ipsilateral ischemic stroke 1 year later was calculated. This probability ranged from 0.045 for a 50% reduction to 0.168 for a 10% reduction. Thus, there was little evidence to suggest that measurements of cerebral hemodynamics can identify a group of patients who would benefit from EC-IC bypass surgery.",
"To determine whether bypass surgery would benefit patients with symptomatic atherosclerotic disease of the internal carotid artery, we studied 1377 patients with recent hemisphere strokes, retinal infarction, or transient ischemic attacks who had atherosclerotic narrowing or occlusion of the ipsilateral internal carotid or middle cerebral artery. Of these, 714 were randomly assigned to the best medical care, and 663 to the same regimen with the addition of bypass surgery joining the superficial temporal artery and the middle cerebral artery. The patients were followed for an average of 55.8 months. Thirty-day surgical mortality and major stroke morbidity rates were 0.6 and 2.5 per cent, respectively. The postoperative bypass patency rate was 96 per cent. Nonfatal and fatal stroke occurred both more frequently and earlier in the patients operated on. Secondary survival analyses comparing the two groups for major strokes and all deaths, for all strokes and all deaths, and for ipsilateral ischemic strokes demonstrated a similar lack of benefit from surgery. Separate analyses in patients with different angiographic lesions did not identify a subgroup with any benefit from surgery. Two important subgroups of patients fared substantially worse in the surgical group: those with severe middle-cerebral-artery stenosis (n = 109, Mantel-Haenszel chi-square = 4.74), and those with persistence of ischemic symptoms after an internal-carotid-artery occlusion had been demonstrated (n = 287, chi-square = 4.04). This study thus failed to confirm the hypothesis that extracranial-intracranial anastomosis is effective in preventing cerebral ischemia in patients with atherosclerotic arterial disease in the carotid and middle cerebral arteries.",
"Patients with carotid artery occlusion and haemodynamic insufficiency have a high risk of stroke. Cerebral revascularization surgery improves cerebral blood flow, but it remains unclear whether this reduces the risk of stroke. This study assesses the long-term outcome of patients undergoing superficial temporal artery to middle cerebral artery (STA-MCA) bypass for symptomatic carotid occlusion. The long-term clinical follow-up and haemodynamic reserve, measured by (99)Technetium single photon emission computed tomography (Tc99 SPECT) scan with acetazolamide challenge, were reviewed for 19 consecutive patients before and after STA-MCA bypass. The stroke rate after bypass surgery was 8% per year. In patients waiting for surgery, the stroke rate was 18% per year. Cerebral perfusion assessed with SPECT scan improved in 88% of patients. These results are consistent with the high risks of haemodynamic infarction in untreated patients and a benefit from revascularization surgery. The percentage annual stroke risk compares favourably with an 18% rate reported for patients with internal carotid artery occlusion and impaired cerebrovascular reserve.",
"In the last few years the development of new and improved surgical procedures caused a more aggressive approach, by femoro-distal bypass, to the limb affected by critical ischaemia. A good surgical result is related to the crural vessel patency, the presence of an adequate autologous vein and the possibility to visualize inframalleolar and foot arteries by selective angiograms. Should all these conditions not be present, an outflow procedure might be at high risk for failure. On the other hand, several studies show that SCS relieves rest pain and improves trophic lesion healing although there is no evident increase in peripheral blood flow, but these studies refer to heterogeneous non-randomized patients. In order to evaluate the effectiveness of SCS compared to distal arterial reconstruction, we started this prospective and randomized study. In a period of 15 months, 12 patients affected by critical limb ischaemia at 4th stage of Fontaine with angiographic multilevel distal lesions were randomised for SCS (7 cases: group A) and distal bypass (5 cases: group B). The result of the therapy was judged as good or fair when either complete or evident pain regression and trophic lesion healing were obtained; otherwise the result was considered as poor. Actually the study is in progress, the follow-up is partial (3-12 months), the results are preliminary. In the patients of group A the results were good or fair in 5 cases (72%) and poor in 2 (28%). In the patients of group B the results were good or fair in 2 cases (40%) and poor in 3 (60%).(ABSTRACT TRUNCATED AT 250 WORDS)",
"From 1973 to 1979, 49 patients with internal carotid occlusion were evaluated and treated. Eighteen of 49 (37%) presented with transient ischemic attack/prolonged reversible ischemic neurological deficit, 14 of 49 (29%) presented with mild completed stroke, 13 of 49 (27%) presented with severe completed stroke, and 4 of 49 (8%) were asymptomatic. Surgical treatment consisting of extracranial-intracranial (EC-IC) bypass, internal carotid stump reconstruction and endarterectomy to open the occlusion, contralateral endarterectomy for carotid stenosis opposite the occlusion, and iatrogenic carotid occlusion with EC-IC bypass was carried out on 22 (45%) patients considered at risk for ischemia based on angiographic evidence of poor collateral circulation and potential sources of emboli. Medical treatment consisting of anticoagulants or anti-platelet aggregation agents was used in 27 (55%) patients with good collateral circulation. By 6 weeks after the initiation of treatment, 10 of 49 (20%) reached end points of new strokes and death. By an average of 3 years after treatment began, 30 of 49 (61%) reached the same end points. The results suggest that new ischemic events in the distribution of the occluded carotid artery occur infrequently if the angiographic study shows adequate collateral circulation to the ischemic territory at risk. Surgical revascularization should be reserved for patients with (a) recurrent ischemic events after the diagnosis of carotid occlusion or (b) poor collateral circulation.",
"In a series of patients with unilateral supratentorial ischemia, clinical scores and parameters derived from computer analysis of the EEG and from measurement of the CBF were determined in the first several weeks after the stroke. Seventeen of these patients underwent a carotid-endarterectomy and 15 a STA-MCA bypass operation. Matched control patients were selected from the remaining cases. All patients, including the controls, were eligible for vascular surgery. The measurements were repeated respectively 3 months and 3 years after the first examination. Clinical improvement occurred in all groups. The degree of these clinical changes was similar for operated and non operated cases. EEG changes indicated more improvement in the cases without surgery. Finally, the CBF was remarkably stable in all patients. The overall effects of reconstructive vascular surgery on the recovery after cerebral ischemia appeared to be negligible.",
"Carotid angioplasty (CA) has been suggested to be a safer and more cost-effective alternative to carotid endarterectomy (CEA) in the management of symptomatic severe internal carotid artery (ICA) disease.\n The study was conducted as a prospective consecutive randomized trial of CEA versus CA for symptomatic severe ICA disease in a university teaching hospital. All patients were assessed before and after surgery by a neurologist. The study consisted of 23 patients with focal carotid territory symptoms and severe ICA stenosis (> 70%) who were randomized to either CEA or CA. However, only 17 had received their allocated treatment before trial suspension. CEA with patching or CA with stenting were used as interventions. The main outcome measures were death or disabling or nondisabling stroke within 30 days.\n All 10 CEA operations proceeded without complication, but 5 of the 7 patients who underwent CA had a stroke (P=.0034), 3 of which were disabling at 30 days.\n After referral, the Data Monitoring Committee invoked the stopping rule and the trial was suspended. The investigators and the Ethics Committee subsequently concluded that the trial could not be restarted--even in an amended format-primarily because of problems with informed consent. We review many of the ethical dilemmas encountered in the performance of this study. If future trials do suggest a selected role for CA, it is essential that both the inclusion and the exclusion criteria are fully documented.",
"Ninety-nine patients undergoing elective coronary artery bypass grafting were enrolled in a prospective, randomized study to evaluate the incidence of cerebral dysfunction after \"mild\" or \"moderate\" hypothermia during cardiopulmonary bypass.\n Patients were evaluated before and after operation before hospital discharge and in some cases at follow-up at least 6 weeks later with a complete neurologic examination (85 patients) and a battery of standard neuropsychometric tests (86 patients).\n Postoperative changes detected by neurologic examination consisted of the appearance of new primitive reflexes in both groups. No statistically significant differences in incidence were found. The neuropsychometric performances of the two groups were statistically similar by either event-rate or group-rate analysis.\n There is no detectable difference in postoperative cerebral dysfunction in patients undergoing coronary artery bypass grafting who are supported by cardiopulmonary bypass with either mild or moderate hypothermia.",
"In order to investigate the neuroprotective efficacy of off-pump coronary artery bypass surgery (OPCAB) over conventional on-pump coronary artery bypass surgery (CCAB), we have performed a prospective randomized study evaluating retinal circulation changes after OPCAB and CCAB.\n Twenty patients were randomized to OPCAB or CCAB. Retinal fluorescein angiography and 60 degrees black-and-white as well as color fundus photographs of both eyes of each patient were taken 1 to 24 h before and 5 to 6 days after the operation.\n Patients undergoing OPCAB had more severely stenosed carotid arteries (P=0.075), higher incidence of slightly diseased ascending aorta (P=0.087) and higher Northern New England Cardiovascular Study Group stroke risk score (P=0.075). Neither stroke nor transient ischemic attack occurred postoperatively in these patients. Inferotemporal retinal arterial embolization and microinfarction was detected in one patient after CCAB, but in none of the OPCAB group.\n The risk of retinal embolism can be minimized by the use of OPCAB and, most likely, by adequate epiaortic ultrasound scanning of the ascending aorta and avoiding clamping in case of severely diseased aorta.",
"The net benefit of routine intraoperative autotransfusion (IAT) in patients undergoing elective infrarenal aortic surgery was studied.\n One hundred patients undergoing abdominal aortic aneurysm (AAA) repair (n = 50) or aortofemoral bypass (AFB) for occlusive disease (n = 50) were randomized to IAT and control groups. This experience accounted for 58% of patients undergoing aortic surgery during the 16-month study period.\n IAT and control groups were balanced for preoperative demographics, disease (50:50 split of AFB:AAA in each group), and risk factors. There were no significant differences between patients randomized to IAT and control patients in estimated blood loss (EBL), allogeneic blood transfusion (units administered intraoperatively, postoperatively, and total), proportion of patients not receiving allogeneic blood (34% of patients randomized to IAT and 28% of control patients), postoperative hemoglobin/hematocrit levels, and complications. IAT did not reduce allogeneic blood transfusion among all patients undergoing aortic surgery nor in any subgroups that might be more likely to benefit, such as those undergoing AAA repair, those with 1000 mL or more EBL, and those receiving larger volumes of IAT-processed blood.\n We could find no net benefit of IAT in patients undergoing elective, infrarenal aortic surgery.",
"The objective of this study was to compare neuropsychologic and quality-of-life outcomes of patients undergoing off-pump coronary artery bypass surgery to those undergoing coronary artery bypass graft surgery using conventional cardiopulmonary bypass.\n A prospective randomized trial of coronary artery bypass graft surgery with and without the use of cardiopulmonary bypass.\n A cardiothoracic surgery unit at a tertiary hospital.\n Sixty-six patients undergoing coronary artery bypass graft surgery and a control group of 50 participants not undergoing cardiac surgery.\n Patients were randomized to receive coronary artery bypass graft surgery with cardiopulmonary bypass or randomized to coronary artery bypass graft surgery without the use of cardiopulmonary bypass.\n The proportions of neuropsychologic deficits and improvement in quality-of-life were comparable regardless of whether patients were randomized to receive off-pump coronary artery bypass graft surgery or conventional coronary artery graft surgery with cardiopulmonary bypass.\n Patients receiving coronary artery bypass grafts without cardiopulmonary bypass did not show fewer cognitive deficits or greater improvement in quality of life.",
"In this study, we assessed the effects of normothermia and hypothermia during cardiopulmonary bypass (CPB) both on internal jugular venous oxygen saturation (SjvO2) and the regional cerebral oxygenation state (rSO2) estimated by near infrared spectroscopy (NIRS).\n Thirty patients scheduled for elective coronary artery bypass graft surgery (CABG) were randomly divided into two groups. Group 1 (n = 15) underwent surgery for normothermic (> 35 degrees C) CPB, and group 2 (n = 15) underwent surgery for hypothermic (30 degrees C) CPB, and alpha-stat regulation was applied. A 4.0-French fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to continuously monitor the SjvO2 value. To estimate the rSO2 state, a spectrophotometer probe was attached to the mid-forehead. SjvO2 and rSO2 values were then collected simultaneously using a computer.\n Neither the cerebral desaturation time (duration during SjvO2 value below 50%), nor the ratio of the cerebral desaturation time to the total CPB time significantly differed (normothermic group: 18+/-6 min, 15+/-6%; hypothermic group: 17+/-6 min, 13+/-6%, respectively). The rSO2 value in the normothermic group decreased during the CPB period compared with the pre-CPB period. The rSO2 value in the hypothermic group did not change throughout the perioperative period.\n These findings suggest that near infrared spectroscopy might be sensitive enough to detect subtle changes in regional cerebral oxygenation.",
"The purpose of this paper is to estimate the real value of the Extra-Intracranial Arterial Bypass (EIAB) in preventing or reducing further and more catastrophic ischaemic events in patients suffering from an Internal Carotid Artery (ICA) occlusion. 257 patients, suffering from ICA occlusion, are considered retrospectively: 122 of them submitted to EIAB and 135 medically treated or untreated. In both groups, homogeneous by sex, age, neurological grading distribution and length of follow-up, the following parameters were considered: the incidence of ischaemic recurrences during the follow-up period; the characters of the recurrences with particular reference to the fatal stroke; the rate of ischaemic events per year. The comparison between the outcome in surgically treated patients and in \"untreated\" ones indicates that the EIAB can be effective in preventing or reducing the ischaemic recurrences and the frequency of fatal stroke in TIA-, RIND, or stroke-patients suffering from ICA occlusion.",
"We sought to compare the effects on ophthalmic function of coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) and off-pump (OPCAB) grafting and to investigate whether retinal microvascular damage is associated with markers of cerebral injury.\n Retinal microvascular damage was assessed by fluorescein angiography and color fundus photography. Ophthalmic function was tested by the logarithm of the minimum angle of resolution visual acuity (VA), and cerebral injury, by transcranial Doppler ultrasound-detected emboli and S100 protein values. Twenty patients were randomized. Fluorescein angiography and postoperative VA could not be obtained for 1 CABG-CPB patient. Retinal microvascular damage was detected in 5 of 9 CABG-CPB but in none of 10 OPCAB patients (risk difference, 55%; 95% confidence interval [CI], 23% to 88%; P=0.01). Color fundus photography detected microvascular damage in 1 CABG-CPB patient but in no OPCAB patients; this lesion was associated with a field defect, which remained after 3 months of follow-up. There was no difference in postoperative VA. Doppler high-intensity transient signals (HITS) were 20.3 times more frequent in the CABG-CPB than in the OPCAB group (95% CI, 9.1 to 45; P<0.0001). Protein S100 levels were higher in the CABG-CPB than in the OPCAB group 1 hour after surgery (P<0.001). HITS were 14.7 times more frequent (95% CI, 3.5 to 62; P=0.001) and S100 level 2.1 times higher (95% CI, 1.3 to 3.5; P=0.005) when retinal microvascular damage was present.\n The relative frequency of retinal microvascular damage between groups shows the extent to which the risk of cerebral injury is reduced with OPCAB. Imaging of part of the cerebral circulation provides evidence to validate markers of cerebral injury.",
"The long-term clinical results of STA-MCA anastomosis as well as the medical treatments were compared in cases that were confined as having a focal cerebral perfusion deficit with viable brain tissue, based on either the drug induced EEG and evoked potential test (DEE test) and/or by positron emission tomography (PET). The criteria for viable cerebral tissue was determined by the following four conditions: (1) functional reversibility could be confirmed by the DEE test; (2) a haemodynamic process could be found in the DEE test; (3) a haemodynamic compromise could be confirmed in the PET study; (4) misery perfusion could be confirmed in the PET study. From 1975 to 1989, 55 cases were confirmed as having viable brain tissue according to the DEE test and the PET study. Of the 55 cases, bypass surgery was performed on 35. Conservative treatment was given to the other 20 cases. There were 3 cases of perioperative neurological deterioration. One was permanent and the other 2 were transient. Results of the long-term follow up are as follows, Ipsilateral attack: 1 case (2.0%) received surgery, and 7 cases (35%) received conservative treatment. Re-attack in the contralateral or posterior circulation: 6 cases (17.2%) received surgery, and 1 case (5%) received conservative treatment. Seventy-seven per cent of the surgical cases improved or had no change in the final functional status, while only 55% of the conservative group either improved or showed no change. The incidence of ipsilateral cerebral ischaemia was significantly low in the surgical group. Contralateral and/or posterior circulation ischaemia tended to be high in this group, however.(ABSTRACT TRUNCATED AT 250 WORDS)",
"Sixty-three patients with internal carotid artery occlusion manifesting as transient ischemic attack or minor stroke received superficial temporal artery-middle cerebral artery bypass surgery and medical treatment (n = 27) or medical treatment only (n = 36). Long-term follow-up showed that there was no significant difference in the outcomes. However, positron emission tomography studies suggested that patients with misery perfusion in the chronic stage benefited from extracranial-intracranial bypass surgery.",
"To assess neurocognitive impairment after the off-pump and on-pump techniques for coronary artery bypass graft surgery in patients with triple vessel disease.\n Randomised controlled trial.\n University Hospital of Wales, Cardiff. Participants: 60 patients undergoing coronary artery bypass graft surgery for triple vessel disease prospectively randomised to the off-pump or on-pump technique.\n Change in scores in nine standard neuropsychometric tests administered preoperatively and at 1 and 10 weeks postoperatively.\n The on-pump group showed a significantly greater deterioration in scores for two and three tests at 1 week and 10 weeks postoperatively, respectively, than the off-pump group. The on-pump group also showed a significantly higher incidence of major deterioration in one of the tests both 1 week and 10 weeks postoperatively. The incidence of neurocognitive impairment at 1 week postoperatively was 27% (8 out of 30) in the off-pump group and 63% (19 out of 30) in the on-pump group (P=0.004); and at 10 weeks postoperatively was 10% (3 out of 30) in the off-pump group and 40% (12 out of 30) in the on-pump group (P=0.017).\n Off-pump coronary artery bypass graft surgery results in less neurocognitive impairment than the on-pump technique.",
"Cardiac operations using extracorporeal circulation bear a risk of cerebral complications. The aim of our study was to investigate if off-pump operations without heart-lung machines can reduce cerebral injury.\n S100, a protein specific for cerebral tissue, was used as a marker for cerebral impairment in 108 randomized patients undergoing coronary bypass operation: 67 patients (group A) were operated on with extracorporeal circulation and cardioplegic cardiac arrest, and 41 patients (group B) underwent off-pump beating heart revascularization. Both groups were similar regarding age, sex, ejection fraction, and number of anastomoses. S100 levels were measured from induction of anesthesia until 24 hours after the operation.\n Data collection was 100% complete. There was no in-hospital death. Nonfatal myocardial infarctions occurred in 2 patients in group A, and 1 patient in group B required resternotomy for bleeding. There was no neurologic deficit in either group. S100 levels increased only slightly in the off-pump patients (group B), whereas in group A there was a sharp rise in S100 concentration during extracorporeal circulation, only returning to baseline 6 hours after the end of the operation. Peak S100 levels were four times higher in group A than in group B (2.1 microg/L versus 0.5 microg/L; p < 001).\n The results of our study suggest that perioperative cerebral impairment is reduced in cardiac operations without the use of extracorporeal circulation. Further large-scale studies are needed to show whether this result is reflected by fewer neurologic deficits."
] |
EC/IC bypass surgery in patients with sCAO disease was neither superior nor inferior to medical care alone. However, most studies included patients irrespective of their cerebral haemodynamics. Participation in an ongoing RCT, which is restricted to patients with impaired haemodynamics, is recommended as these patients might benefit from bypass surgery.
|
CD003362
|
[
"17321310",
"17321311",
"16231970"
] |
[
"Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial.",
"Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial.",
"Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial."
] |
[
"Male circumcision could provide substantial protection against acquisition of HIV-1 infection. Our aim was to determine whether male circumcision had a protective effect against HIV infection, and to assess safety and changes in sexual behaviour related to this intervention.\n We did a randomised controlled trial of 2784 men aged 18-24 years in Kisumu, Kenya. Men were randomly assigned to an intervention group (circumcision; n=1391) or a control group (delayed circumcision, 1393), and assessed by HIV testing, medical examinations, and behavioural interviews during follow-ups at 1, 3, 6, 12, 18, and 24 months. HIV seroincidence was estimated in an intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, with the number NCT00059371.\n The trial was stopped early on December 12, 2006, after a third interim analysis reviewed by the data and safety monitoring board. The median length of follow-up was 24 months. Follow-up for HIV status was incomplete for 240 (8.6%) participants. 22 men in the intervention group and 47 in the control group had tested positive for HIV when the study was stopped. The 2-year HIV incidence was 2.1% (95% CI 1.2-3.0) in the circumcision group and 4.2% (3.0-5.4) in the control group (p=0.0065); the relative risk of HIV infection in circumcised men was 0.47 (0.28-0.78), which corresponds to a reduction in the risk of acquiring an HIV infection of 53% (22-72). Adjusting for non-adherence to treatment and excluding four men found to be seropositive at enrollment, the protective effect of circumcision was 60% (32-77). Adverse events related to the intervention (21 events in 1.5% of those circumcised) resolved quickly. No behavioural risk compensation after circumcision was observed.\n Male circumcision significantly reduces the risk of HIV acquisition in young men in Africa. Where appropriate, voluntary, safe, and affordable circumcision services should be integrated with other HIV preventive interventions and provided as expeditiously as possible.",
"Ecological and observational studies suggest that male circumcision reduces the risk of HIV acquisition in men. Our aim was to investigate the effect of male circumcision on HIV incidence in men.\n 4996 uncircumcised, HIV-negative men aged 15-49 years who agreed to HIV testing and counselling were enrolled in this randomised trial in rural Rakai district, Uganda. Men were randomly assigned to receive immediate circumcision (n=2474) or circumcision delayed for 24 months (2522). HIV testing, physical examination, and interviews were repeated at 6, 12, and 24 month follow-up visits. The primary outcome was HIV incidence. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, with the number NCT00425984.\n Baseline characteristics of the men in the intervention and control groups were much the same at enrollment. Retention rates were much the same in the two groups, with 90-92% of participants retained at all time points. In the modified intention-to-treat analysis, HIV incidence over 24 months was 0.66 cases per 100 person-years in the intervention group and 1.33 cases per 100 person-years in the control group (estimated efficacy of intervention 51%, 95% CI 16-72; p=0.006). The as-treated efficacy was 55% (95% CI 22-75; p=0.002); efficacy from the Kaplan-Meier time-to-HIV-detection as-treated analysis was 60% (30-77; p=0.003). HIV incidence was lower in the intervention group than it was in the control group in all sociodemographic, behavioural, and sexually transmitted disease symptom subgroups. Moderate or severe adverse events occurred in 84 (3.6%) circumcisions; all resolved with treatment. Behaviours were much the same in both groups during follow-up.\n Male circumcision reduced HIV incidence in men without behavioural disinhibition. Circumcision can be recommended for HIV prevention in men.",
"Observational studies suggest that male circumcision may provide protection against HIV-1 infection. A randomized, controlled intervention trial was conducted in a general population of South Africa to test this hypothesis.\n A total of 3,274 uncircumcised men, aged 18-24 y, were randomized to a control or an intervention group with follow-up visits at months 3, 12, and 21. Male circumcision was offered to the intervention group immediately after randomization and to the control group at the end of the follow-up. The grouped censored data were analyzed in intention-to-treat, univariate and multivariate, analyses, using piecewise exponential, proportional hazards models. Rate ratios (RR) of HIV incidence were determined with 95% CI. Protection against HIV infection was calculated as 1 - RR. The trial was stopped at the interim analysis, and the mean (interquartile range) follow-up was 18.1 mo (13.0-21.0) when the data were analyzed. There were 20 HIV infections (incidence rate = 0.85 per 100 person-years) in the intervention group and 49 (2.1 per 100 person-years) in the control group, corresponding to an RR of 0.40 (95% CI: 0.24%-0.68%; p < 0.001). This RR corresponds to a protection of 60% (95% CI: 32%-76%). When controlling for behavioural factors, including sexual behaviour that increased slightly in the intervention group, condom use, and health-seeking behaviour, the protection was of 61% (95% CI: 34%-77%).\n Male circumcision provides a degree of protection against acquiring HIV infection, equivalent to what a vaccine of high efficacy would have achieved. Male circumcision may provide an important way of reducing the spread of HIV infection in sub-Saharan Africa. (Preliminary and partial results were presented at the International AIDS Society 2005 Conference, on 26 July 2005, in Rio de Janeiro, Brazil.)."
] |
There is strong evidence that medical male circumcision reduces the acquisition of HIV by heterosexual men by between 38% and 66% over 24 months. Incidence of adverse events is very low, indicating that male circumcision, when conducted under these conditions, is a safe procedure. Inclusion of male circumcision into current HIV prevention measures guidelines is warranted, with further research required to assess the feasibility, desirability, and cost-effectiveness of implementing the procedure within local contexts.
|
CD003418
|
[
"10068412",
"1406860",
"9972673",
"1499473",
"16513202",
"1936482",
"17403126",
"1523352",
"12716810",
"12610040",
"2507265",
"17714824",
"16456680",
"10323055",
"15111525",
"9444449",
"16021649",
"16732007",
"12351462",
"15545844"
] |
[
"Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomized, controlled trial.",
"Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus.",
"Efficacy of combined treatments in NIDDM patients with secondary failure to sulphonylureas. Is it predictable?",
"Comparison of combined therapies in treatment of secondary failure to glyburide.",
"Efficacy of conversion from bedtime NPH insulin to morning insulin glargine in type 2 diabetic patients on basal-prandial insulin therapy.",
"Treatment of NIDDM patients with secondary failure to glyburide: comparison of the addition of either metformin or bed-time NPH insulin to glyburide.",
"A randomized controlled trial examining combinations of repaglinide, metformin and NPH insulin.",
"Combination daytime chlorpropamide-metformin/bedtime insulin in the treatment of secondary failures in non insulin dependent diabetes.",
"Intensive replacement of basal insulin in patients with type 1 diabetes given rapid-acting insulin analog at mealtime: a 3-month comparison between administration of NPH insulin four times daily and glargine insulin at dinner or bedtime.",
"Randomized cross-over trial of insulin glargine plus lispro or NPH insulin plus regular human insulin in adolescents with type 1 diabetes on intensive insulin regimens.",
"Efficacy of bedtime NPH insulin with daytime sulfonylurea for subpopulation of type II diabetic subjects.",
"Safety and efficacy of repaglinide in combination with metformin and bedtime NPH insulin as an insulin treatment regimen in type 2 diabetes.",
"Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study.",
"Comparison of bedtime NPH insulin or metformin combined with glibenclamide in secondary sulphonylurea failure in obese type II (NIDDM) patients.",
"Insulin detemir offers improved glycemic control compared with NPH insulin in people with type 1 diabetes: a randomized clinical trial.",
"Efficacy of insulin lispro in combination with NPH human insulin twice per day in patients with insulin-dependent or non-insulin-dependent diabetes mellitus. Multicenter Insulin Lispro Study Group.",
"A randomized multicentre trial of insulin glargine compared with NPH insulin in people with type 1 diabetes.",
"A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes.",
"Repaglinide versus metformin in combination with bedtime NPH insulin in patients with type 2 diabetes established on insulin/metformin combination therapy.",
"A comparison of bedtime insulin glargine with bedtime neutral protamine hagedorn insulin in patients with type 2 diabetes: subgroup analysis of patients taking once-daily insulin in a multicenter, randomized, parallel group study."
] |
[
"Compared with other insulin regimens, combination therapy with oral hypoglycemic agents and bedtime insulin produces similar improvement in glycemic control but induces less weight gain.\n To determine whether bedtime insulin regimens differ with respect to their effects on weight gain in patients with type 2 diabetes.\n Randomized, controlled trial.\n Four outpatient clinics at central hospitals.\n 96 patients (mean age, 58 +/- 1 years; mean body mass index, 29 +/- 1 kg/m2) whose type 2 diabetes was poorly controlled with sulfonylurea therapy (mean glycosylated hemoglobin value, 9.9% +/- 0.2%; mean fasting plasma glucose level, 11.9 +/- 0.3 mmol/L [214 +/- 5 mg/dL]).\n Random assignment to 1 year of treatment with bedtime intermediate-acting insulin plus glyburide (10.5 mg) and placebo, metformin (2 g) and placebo, glyburide and metformin, or a second injection of intermediate-acting insulin in the morning. Patients were taught to adjust the bedtime insulin dose on the basis of fasting glucose measurements.\n Body weight, biochemical and symptomatic hypoglycemias, and indices of glycemic control.\n At 1 year, body weight remained unchanged in patients receiving bedtime insulin plus metformin (mean change, 0.9 +/- 1.2 kg; P < 0.001 compared with all other groups) but increased by 3.9 +/- 0.7 kg, 3.6 +/- 1.2 kg, and 4.6 +/- 1.0 kg in patients receiving bedtime insulin plus glyburide, those receiving bedtime insulin plus both oral drugs, and those receiving bedtime and morning insulin, respectively. The greatest decrease in the glycosylated hemoglobin value was observed in the bedtime insulin and metformin group (from 9.7% +/- 0.4% to 7.2% +/- 0.2% [difference, -2.5 +/- 0.4 percentage points] at 1 year; P < 0.001 compared with 0 months and P < 0.05 compared with other groups). This group also had significantly fewer symptomatic and biochemical cases of hypoglycemia (P < 0.05) than the other groups.\n Combination therapy with bedtime insulin plus metformin prevents weight gain. This regimen also seems superior to other bedtime insulin regimens with respect to improvement in glycemic control and frequency of hypoglycemia.",
"Insulin is widely used to improve metabolic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), but there is no consensus about the optimal regimen of insulin treatment.\n We treated 153 patients with NIDDM for three months with five regimens: (1) oral hypoglycemic drug therapy plus NPH insulin given at 7 a.m. (the morning-NPH group), (2) oral hypoglycemic drug therapy plus NPH insulin given at 9 p.m. (the evening-NPH group), (3) NPH and regular insulin (ratio, 70 units to 30 units) given before breakfast and dinner (the two-insulin-injection group), (4) NPH insulin at 9 p.m. and regular insulin before meals (the multiple-insulin-injection group), and (5) continued oral hypoglycemic drug therapy (the control group).\n The mean (+/- SE) value for glycosylated hemoglobin decreased similarly in all four insulin-treatment groups (1.7 +/- 0.3, 1.9 +/- 0.2, 1.8 +/- 0.3, and 1.6 +/- 0.3 percent, respectively). The decrease was significantly greater in these four groups than in the control group (0.5 +/- 0.2 percent; P < 0.001 vs. all insulin-treated groups). Weight gain was significantly less (1.2 +/- 0.5 kg) in the evening-NPH group than in the other insulin-treatment groups (2.2 +/- 0.5 kg in the morning-NPH group, 1.8 +/- 0.5 kg in the two-insulin-injection group, and 2.9 +/- 0.5 kg in the multiple-injection group; P < 0.05). In addition, the increment in the mean diurnal serum free insulin concentration was 50 to 65 percent smaller in the evening-NPH group than in the other insulin-treatment groups. Subjective well-being improved significantly more in the insulin-treatment groups than in the control group (P < 0.001).\n In patients with NIDDM who are receiving oral hypoglycemic drug therapy, the addition of NPH insulin in the evening improves glycemic control in a manner similar to combination therapy with NPH insulin in the morning, a two-insulin-injection regimen, or a multiple-insulin-injection regimen, but induces less weight gain and hyperinsulinemia. The data thus suggest that patients with NIDDM do not benefit from multiple insulin injections and that nocturnal insulin administration appears preferable to daytime administration.",
"The treatment of NIDDM patients with secondary failure to sulphonylurea is a common problem. We performed a crossover study in 50 NIDDM patients with secondary failure to glibenclamide by comparing the addition to sulphonylurea of either a low-dose bedtime NPH insulin or a t.i.d. oral metformin and by analyzing treatment efficacy in relation to patient and disease characteristics. Both combined therapies clearly improved glycaemic control. HbA1 c were similarly reduced by the addition of either bedtime NPH insulin (7.6+/-0.34 vs 8.7+/-0.35, p<0.01) or metformin (7.6+/-0.22 vs 8.6+/-0.31, p<0.01). Also fasting plasma glucose (FPG) and post-prandial plasma glucose (PPPG) significantly decreased (p<0.01) with both treatments. Bed-time NPH insulin was more effective on FPG reduction than metformin (-36+/-2% vs -25+/-2%, p<0.01); in contrast, metformin addition was more effective on PPPG reduction than bedtime NPH insulin addition (-30+/-2% vs 20+/-3%, p<0.01). Serum cholesterol was marginally but significantly decreased after metformin (5.49+/-0.19 vs 5.91 +/-0.18 mM, p<0.05) but not after NPH insulin. Body weight increase was significantly greater after insulin addition than after metformin (1.47+/-0.25 Kg vs 0.64+/-0.17 p=0.02). All patients preferred the addition of metformin rather than NPH insulin. None of the measured clinical and metabolic variables (before treatment FPG and PPPG, HbA1 c, post-glucagon C-peptide levels, insulin sensitivity, patient age, BMI and diabetes duration) significantly correlated to the efficacy of the two combined treatments studied. In conclusion, in NIDDM patients with secondary failure to sulphonylureas the addition of either low-dose bedtime NPH insulin or t.i.d. metformin is similarly effective in improving glycaemic control. Metformin is better accepted by patients and provides a modest advantage in terms of body weight and cholesterol levels. The most common clinical and metabolic variables are not useful for predicting the efficacy of these two combined treatments.",
"To compare the effectiveness of alternative combined treatments in patients with non-insulin-dependent diabetes mellitus (NIDDM) with secondary failure to sulfonylureas.\n A crossover study was carried out by randomly assigning 16 NIDDM patients to a combined treatment with the addition of either a single low-dose bedtime injection of 0.2 U/kg body wt NPH insulin or an oral three times a day administration of 1.5 g/day metformin to the previously ineffective glyburide treatment.\n Both combined therapies significantly (P less than 0.01) reduced fasting plasma glucose (FPG), postprandial plasma glucose (PPPG) and percentage of HbA1. The addition of metformin was more effective than the addition of insulin (P less than 0.01) in improving PPPG in the 8 patients with higher post-glucagon C-peptide levels. In contrast, the efficacy of neither combined therapy was related to patient age, age of diabetes onset, duration of the disease, percentage of ideal body weight, and FPG. The addition of insulin but not metformin caused a significant (P less than 0.01) increase of mean body weight. Neither combined treatment caused changes in serum cholesterol and triglyceride levels. No symptomatic hypoglycemic episode was reported in any of the 16 patients.\n The addition of bedtime NPH insulin or metformin was effective in improving the glycemic control in most NIDDM patients with secondary failure to glyburide. The combination of metformin and sulfonylurea was more effective in reducing PPPG and did not induce any increase of body weight.",
"In normal subjects, approximately half of the daily insulin requirement constitutes basal insulin. We investigated whether increasing the dose of insulin glargine up to half of the total insulin requirement could lead to better glycemic control in type 2 diabetic patients who were treated on basal-prandial insulin therapy. A total of 62 patients with type 2 diabetes on mealtime rapid-acting insulin analogue and bedtime NPH were randomized to either continuation of bedtime NPH (n=31) or morning glargine (n=31) for 6 months while continuing the aspart/lispro at each meal. The two groups were matched for age, sex, diabetes duration, BMI, HbA(1C), endogenous insulin secretion, and proportion of numbers using aspart/lispro and using oral hypoglycemic agents. The dose of insulin glargine was increased by 2-4 units to meet the target fasting blood glucose, whereas the dose of NPH was principally unchanged as a control group. Mean HbA(1C) at baseline was similar between patients with glargine and NPH (7.2% versus 6.9%). The percentage of glargine dose increased significantly (31% at baseline to 48% at 6 months) without any significant changes in total insulin dose. Mean HbA(1C) at 3 months was 6.6% with glargine and 7.0% with NPH (P<0.0001, adjusted mean change between-treatment difference 0.6% [95% CI 0.3-0.9]), and the values at 6 months were 6.6% and 6.9%, respectively (P=0.007). Frequency of hypoglycemia did not differ between the groups. Increasing the dose of glargine without changing the total daily insulin dose resulted in significantly better glycemic control in type 2 diabetic patients on basal-prandial insulin therapy. Conversion from bedtime NPH to morning glargine appears efficacious with no increase in frequency of hypoglycemia.",
"In this study we compared, in 12 NIDDM patients with secondary failure to glyburide, the effect of adding either a single, low-dose bed time NPH insulin injection (0.2 U/Kg) or an oral metformin administration (500 mg x 3) to the previously ineffective sulfonylurea treatment. The addition of both insulin and metformin treatment significantly improved fasting plasma glucose, post-prandial plasma glucose and %HbA1. The effect of both combined therapies was already evident and maximal after 2 weeks of treatment. The addition of bed-time NPH insulin caused a greater decrease of fasting plasma glucose, although the difference with the addition of metformin was not significant. In contrast, the average post-prandial plasma glucose decrease was significantly greater after metformin addition. The addition of bed-time NPH insulin caused a significant increase in average body weight, while after metformin addition, average body weight was unchanged; no change in the average cholesterol and triglyceride level was observed after either combined therapies.",
"To compare combination use of repaglinide, metformin and bedtime Neutral Protamine Hagedorn (NPH) insulin with conventional approaches of insulin initiation in patients with Type 2 diabetes (T2DM).\n Eighty-two patients with T2DM with suboptimal glycaemic control on oral glucose-lowering agents were randomized to one of three treatment regimens for 4 months. Group 1 received metformin and twice daily biphasic 30/70 human insulin mixture (n = 27), group 2 metformin and bedtime NPH insulin (n = 26) and group 3 metformin, bedtime NPH insulin and mealtime repaglinide (n = 25).\n Seventy-five patients completed the study. Baseline and end-point mean HbA1c levels fell from 9.0 +/- 1.1 to 7.9 +/- 1.1% in group 1, 10.0 +/- 2.2 to 9.2 +/- 1.4% group 2 and 10.0 +/- 1.7 to 8.1 +/- 1.5% in group 3, respectively. All groups showed improvements in HbA1c. There was no significant difference between groups in the proportions of patients experiencing hypoglycaemia (29.6, 25.0 and 16.7%, respectively; P = 0.55) or in mean weight gain (2.9, 0.7 and 2.2 kg, respectively; P = 0.06). By 4 months, insulin doses were 0.63 +/- 0.32 IU/kg in group 1, 0.58 +/- 0.21 IU/kg in group 2 and 0.37 +/- 0.22 IU/kg in group 3 (group 3 vs. groups 1 and 2: P < 0.002).\n The approach using repaglinide, metformin and NPH insulin improved glycaemic control with a similar safety profile to conventional insulin initiation in T2DM and produced final glycaemic control similar to metformin and a twice daily biphasic insulin mixture.",
"To determine the effectiveness of the combination therapy with daytime chlorpropamide-metformin and bedtime NPH insulin in the treatment of secondary failures in NIDDM and to study its effects on insulin secretion.\n Non randomized open study with a duration of two months. The patients were followed six months after ending the study. INSTITUTION: Department of Diabetes and Lipid Metabolism. Instituto Nacional de la Nutrición \"Salvador Zubirán\", Mexico City. CHARACTERISTICS OF THE PATIENTS: Nine patients (seven women and two men) were included. All had NIDDM and secondary failure to antidiabetic oral drugs. Their fasting plasma glucose was 14.5 +/- 2 mM/L and their HbA1c 13.37 +/- 2.9%. At the entry and at the end of the study a 5h-OGTT was done with assays of plasma glucose and C-peptide.\n Chlorpropamide (375 mg/day) plus metformin (1200 mg/day) and bedtime insulin (0.1 U/kg/day).\n After two months on combination therapy, fasting plasma glucose and HbA1c levels were remarkably improved (decreases of 7.3 +/- 0.6 and 9.1 +/- 1.02 respectively, p less than 0.002). The insulin dose was small (6.77 +/- 2.09 U/day). Side effects were minimal and infrequent. During the 5h-OGTT, the mean glucose area under the curve also decreased. The insulin secretion did not change but the C-peptide/glucose ratio increased. At the end of the study, the insulin dose was tapered off and stopped when possible. The four patients with the best glycemic control during the study were able to suspend the bedtime insulin and maintain a good control six months after the insulin suspension.\n The combination therapy is useful in the treatment of secondary failures in NIDDM: Its advantages are the very low mean daily insulin dose needed, the low incidence of side effects and, if a HbA1c less than 8.7% is achieved, the restoration of oral antidiabetic drugs efficacy. The very low insulin dose used in this study could be explained by complementary effects of metformin and bedtime insulin on hepatic glucose output and a putative decrease in peripheral resistance attributable both to sulfonylurea and metformin.",
"To establish differences in blood glucose between different regimens of optimized basal insulin substitution in type 1 diabetic patients given lispro insulin at meals, i.e., NPH injected four times a day versus glargine insulin once daily at dinner or at bedtime.\n A total of 51 patients with type 1 diabetes on intensive therapy (NPH four times/day and lispro insulin at each meal) were randomized to three different regimens of basal insulin substitution while continuing lispro insulin at meals: continuation of NPH four times/day (n = 17), once daily glargine at dinnertime (n = 17), and once daily glargine at bedtime (n = 17) for 3 months. Blood glucose targets were fasting, preprandial, and bedtime concentrations at 6.4-7.2 mmol/l and 2 h after meals at 8.0-9.2 mmol/l. The primary end point was HbA(1c).\n Mean daily blood glucose was lower with dinnertime glargine (7.5 +/- 0.2 mmol/l) or bedtime glargine (7.4 +/- 0.2 mmol/l) versus NPH (8.3 +/- 0.2 mmol/l) (P < 0.05). A greater percentage of blood glucose values were at the target value with glargine at dinner and bedtime versus those with NPH (P < 0.05). HbA(1c) at 3 months did not change with NPH but decreased with glargine at dinnertime (from 6.8 +/- 0.2 to 6.4 +/- 0.1%) and glargine at bedtime (from 7.0 +/- 0.2 to 6.6 +/- 0.1%) (P < 0.04 vs. NPH). Total daily insulin doses were similar with the three treatments, but with glargine there was an increase in basal and a decrease in mealtime insulin requirements (P < 0.05). Frequency of mild hypoglycemia (self-assisted episodes, blood glucose < or =4.0 mmol/l) was lower with glargine (dinnertime 8.1 +/- 0.8 mmol/l, bedtime 7.7 +/- 0.9 mmol/l) than with NPH (12.2 +/- 1.3 mmol/l) (episodes/patient-month, P < 0.04). In-hospital profiles confirmed outpatient blood glucose data and indicated more steady plasma insulin concentrations at night and before meals with glargine versus NPH (P < 0.05). There were no differences between glargine given at dinnertime and at bedtime.\n Regimens of basal insulin with either NPH four times/day or glargine once/day in type 1 diabetic patients both result in good glycemic control. However, the simpler glargine regimen decreases the HbA(1c) level and frequency of hypoglycemia versus NPH. In contrast to NPH, which should be given at bedtime, insulin glargine can be administered at dinnertime without deteriorating blood glucose control.",
"To compare blood glucose control and incidence of nocturnal hypoglycemia in adolescents with type 1 diabetes on multiple injection regimens managed with either an insulin analog combination or NPH insulin plus regular human insulin.\n In a randomized cross-over study, 28 adolescents with type 1 diabetes on multiple injection therapy received either insulin glargine prebedtime plus lispro preprandially (LIS/GLAR) or NPH insulin prebedtime plus regular human insulin preprandially (R/NPH). During each 16-week treatment arm, subjects completed home blood glucose profiles, and at the end of each treatment arm, they were admitted for an overnight metabolic profile. A total of 25 subjects completed the study.\n Compared with R/NPH therapy, LIS/GLAR was associated with lower mean blood glucose levels (LIS/GLAR versus R/NPH): fasting (8.0 vs. 9.2 mmol/l, P < 0.0001), 2 h postbreakfast (8.1 vs. 10.7 mmol/l, P < 0.0005), prelunch (8.9 vs. 10.1 mmol/l, P < 0.01), and 2 h postlunch (8.0 vs. 9.5 mmol/l, P < 0.002). However, there was no difference in mean blood glucose levels before or after the evening meal. Incidence of nocturnal hypoglycemia on overnight profiles was 43% lower on LIS/GLAR compared with R/NPH therapy; however, there was no difference in rates of self-reported symptomatic hypoglycemia. Total insulin dose required to achieve target blood glucose control was lower on LIS/GLAR (1.16 IU/kg) compared with R/NPH therapy (1.26 IU/kg, P < 0.005), but there was no significant difference in HbA(1c) levels (LIS/GLAR versus R/NPH: 8.7 vs. 9.1%, P = 0.13).\n Combination therapy with insulin glargine plus lispro reduced the incidence of nocturnal hypoglycemia and was at least as effective as R/NPH insulin therapy in maintaining glycemic control in adolescents on multiple injection regimens.",
"Although insulin and sulfonylureas often have additive clinical effects when used in combination for type II (non-insulin-dependent) diabetes, these results are variable and a clinical role for this approach is not yet established. This study tests the efficacy of a specific combined regimen for a subpopulation of patients with a randomized double-masked placebo-controlled crossover design and under conditions similar to those of clinical practice. Twenty subjects with limited duration (less than 15 yr) type II diabetes who were moderately obese (less than 160% ideal wt) and proved imperfectly controlled on 10 mg glyburide twice daily completed two 4-mo crossover protocols, comparing a single injection of NPH insulin in the evening plus 10 mg glyburide in the morning with insulin plus placebo. Insulin dose was adjusted by experienced endocrinologists seeking the best glycemic control consistent with safety. All subjects had glycosylated hemoglobin values less than or equal to 150% of the control mean on combined therapy, and combined therapy was superior to insulin alone (fasting plasma glucose 8.0 +/- 0.3 vs. 11.1 +/- 0.6 mM, P less than .01; glycosylated hemoglobin 9.8 +/- 0.1 vs. 10.6 +/- 0.2%, P less than .01). Despite greater weight gain on combined therapy, blood pressure and plasma lipid concentrations were the same on the two regimens. These results suggest this simple regimen offers another option, besides multiple injections of insulin, for patients of this kind who are unsuccessful with a sulfonylurea or a single injection of insulin alone.",
"To evaluate the efficacy and safety of the association of repaglinide, metformin and bedtime NPH insulin compared to two classic regimens: metformin plus NPH and two doses of NPH in patients with poorly controlled type 2 diabetes despite two or more oral antidiabetic drugs (OADs).\n Random, parallel and open study of 24 weeks with 37 patients randomized into three therapeutic groups: group A (n=12) (repaglinide/metformin/NPH), group B (n=12) (metformin/NPH) and group C (n=13) (NPH/NPH). The insulin was adjusted in the visits to obtain a basal blood glucose <110 mg/dl. The endpoint criteria included HbA1c, blood glucose profile, hypoglycemias and body weight.\n At the end of the study, group A presented HbA1c (mean+/-standard deviation) 7.2+/-0.7%, which was significantly less than B (8.8+/-0.1%) and C (8.4+/-1.2%). In terms of absolute reduction, there were only differences (p=0.01) between group A (-2.4+/-1.1%) and B (-0.7+/-1.2%). Group A presented lower postprandial blood glucose values (p<0.01). Nor were there any significant differences in weight gain and incidence of hypoglycemia.\n The combination of repaglinide, metformin and bedtime NPH is safe and effective and it provides better postprandial blood glucose control. The association of metformin and a dose of NPH does not obtain suitable control in patients with a long evolution who have already received two or more OADs.",
"In type 2 diabetic patients we compared 9 months of combination therapy with insulin glargine and metformin with 9 months of NPH insulin combined with metformin. The primary focus was changes in HbA(1c); secondary focus was diurnal glucose profiles and symptomatic hypoglycaemia.\n In this investigator-initiated open, parallel-group clinical trial involving seven centres, 110 insulin-naive type 2 diabetic patients with poor glycaemic control (HbA(1c) >or=8.0%) on oral hypoglycaemic agents (90% using sulfonylurea plus metformin) were randomised to receive bedtime insulin glargine with metformin (G+MET) or bedtime NPH with metformin (NPH+MET) for 36 weeks. The patients were taught how to self-adjust their insulin dose and use a modem to send the results of home glucose monitoring to treatment centres. The goal was to achieve a fasting plasma glucose (FPG) of 4.0 to 5.5 mmol/l in both groups.\n During the last 12 weeks, FPGs averaged 5.75+/-0.02 and 5.96+/-0.03 mmol/l (p<0.001) and insulin doses were 68+/-5 and 70+/-6 IU/day (0.69+/-0.05 and 0.66+/-0.04 IU kg(-1) day(-1), NS) in the G+MET and NPH+MET groups, respectively. At 36 weeks, mean HbA(1c) was 7.14+/-0.12 and 7.16+/-0.14%, respectively (NS). Symptomatic, but not confirmed symptomatic, hypoglycaemia was significantly lower during the first 12 weeks in the G+MET group (4.1+/-0.8 episodes/patient-year) than in the NPH+MET group (9.0+/-2.3 episodes/patient-year, p<0.05), but not significantly different thereafter. Glucose levels before dinner were higher in the NPH+MET group (10.1+/-0.3 mmol/l) than in the G+MET group (8.6+/-0.3 mmol/l, p=0.002) throughout the 36-week study. With regard to baseline characteristics such as initial glycaemia or C-peptide, there was no difference between patients who achieved good glycaemic control (HbA(1c) <7.0%) and those who did not. Differences were seen in the following: between study centres, weight gain during the run-in period and insulin therapy, and FPG during the last 12 weeks (5.7+/-0.2 vs 6.7+/-0.3 mmol/l for patients reaching vs those not reaching target, p<0.01).\n Good glycaemic control can be achieved with both G+MET and NPH+MET. Use of G+MET reduces symptomatic hypoglycaemia during the first 12 weeks and dinner time hyperglycaemia compared with NPH+MET.",
"To compare the effects of bedtime NPH Insulin vs Metformin combined with Glibenclamide in patients who are obese and had secondary failure to sulphonylurea treatment.\n Prospective, randomized, comparative study of patients having type-II diabetes, without complications with associated obesity and secondary failure to sulphonylureas. Thirty-six obese patients who continued to have blood glucose values of fasting > 150 mg/dl and/or random > 220 mg/dl, after 8 weeks of intensive dietary and drug therapy.\n For the 20 weeks of study, the patients were randomised in two equal groups, one receiving 20 to 40 units of NPH Insulin at bed time and the second group, Metformin upto a maximum dose of 3 grams, along with Sulphonylureas.\n Both the groups showed, a significant reduction in the blood glucose values, with an average decrease of 50 mg/dl. The other monitored parameters, such as, serum cholesterol, triglycerides and blood pressure values, also demonstrated a similar downwards trend. However, the drop out rate was high in the Insulin treated group and the remainder group did show slight increase in weight and BMI, while the reverse, stood true, for the metformin group, with 100% compliance rate.\n Metformin, in obese, type II diabetics, with secondary failure to Sulphonylureas, is an effective, safe and well tolerated treatment, which not only improves the metabolic control but also favourably modifies other parameters such as weight, total cholesterol and triglyceride values.",
"Insulin detemir is a soluble long-acting basal insulin analog designed to overcome the limitations of conventional basal insulin formulations. Accordingly, insulin detemir has been compared with NPH insulin with respect to glycemic control (HbA1c, prebreakfast glucose levels and variability, and hypoglycemia) and timing of administration.\n People with type 1 diabetes (n = 408) were randomized in an open-label, parallel-group trial of 16-week treatment duration using either insulin detemir or NPH insulin. Insulin detemir was administered twice daily using two different regimens, either before breakfast and at bedtime (IDet(morn+bed)) or at a 12-h interval (IDet(12h)). NPH insulin was administered before breakfast and at bedtime. Mealtime insulin was given as the rapid-acting insulin analog insulin aspart.\n With both insulin detemir groups, clinic fasting plasma glucose was lower than with NPH insulin (IDet(12h) vs. NPH, -1.5 mmol/l [95% CI -2.51 to -0.48], P = 0.004; IDet(morn+bed) vs. NPH, -2.3 mmol/l (-3.32 to -1.29), P < 0.001), as was self-measured prebreakfast plasma glucose (P = 0.006 and P = 0.004, respectively). The risk of minor hypoglycemia was lower in both insulin detemir groups (25%, P = 0.046; 32%, P = 0.002; respectively) compared with NPH insulin in the last 12 weeks of treatment, this being mainly attributable to a 53% reduction in nocturnal hypoglycemia in the IDet(morn+bed) group (P < 0.001). Although HbA1c for each insulin detemir group was not different from the NPH group, HbA1c for the pooled insulin detemir groups was significantly lower than for the NPH group (mean difference -0.18% [-0.34 to -0.02], P = 0.027). Within-person between-day variation in self-measured prebreakfast plasma glucose was lower for both detemir groups (both P < 0.001). The NPH group gained weight during the study, but there was no change in weight in either of the insulin detemir groups (IDet(12h) vs. NPH, -0.8 kg [-1.44 to -0.24], P = 0.006; IDet(morn+bed) vs. NPH, -0.6 kg [-1.23 to -0.03], P = 0.040).\n Overall glycemic control with insulin detemir was improved compared with NPH insulin. The data provide a basis for tailoring the timing of administration of insulin detemir to the individual person's needs.",
"A common treatment regimen for patients with either insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM) is a combination of rapid-acting insulin and intermediate-acting insulin administered twice each day. It is usually recommended that regular human insulin be injected 30 to 45 minutes before a meal. In practice, patients often inject regular human insulin closer to mealtime, causing a higher post-prandial serum glucose level and an increased potential for hypoglycemia in the postabsorptive period. Insulin lispro, a rapid-acting insulin analogue, is best injected just before a meal because of its more rapid absorption and shorter duration of action. In 707 randomized patients, 379 with IDDM and 328 with NIDDM, we studied the effect of twice-daily insulin lispro or regular human insulin in combination with NPH human insulin (isophane insulin) on premeal, 2-hour postprandial, and bedtime glycemic control. Assessments were based on the results of a seven-point blood glucose profile, the insulin dose (by formulation and time of administration), the incidence and frequency of hypoglycemic episodes, and the glycated hemoglobin value. Treatment with insulin lispro resulted in lower postprandial glucose levels and smaller increases in glucose level after the morning and evening meals compared with treatment with regular human insulin. Overall glycemic control, frequency of hypoglycemic events, and total insulin dose were not different between the two groups. Insulin lispro in combination with NPH human insulin in a twice-per-day regimen allows injection closer to mealtime and improves post-prandial glycemic control without increasing the risk of hypoglycemia.",
"To compare insulin glargine with NPH human insulin for basal insulin supply in adults with type 1 diabetes.\n People with type 1 diabetes (n = 585), aged 17-77 years, were randomized to insulin glargine once daily at bedtime or NPH insulin either once- (at bedtime) or twice-daily (in the morning and at bedtime) according to their prior treatment regimen and followed for 28 weeks in an open-label, multicentre study. Both groups continued with pre-meal unmodified human insulin.\n There was no significant difference between the two insulins in change in glycated haemoglobin from baseline to endpoint (insulin glargine 0.21 +/- 0.05% (mean +/- standard error), NPH insulin 0.10 +/- 0.05%). At endpoint, self-monitored fasting blood glucose (FBG) had decreased similarly in each group (insulin glargine -1.17 +/- 0.12 mmol/L, NPH insulin -0.89 +/- 0.12 mmol/L; p = 0.07). However, people on >1 basal insulin injection per day prior to the study had a clinically relevant decrease in FBG on insulin glargine versus NPH insulin (insulin glargine -1.38 +/- 0.15 mmol/L, NPH insulin -0.72 +/- 0.15 mmol/L; p < 0.01). No significant differences in the number of people reporting >or=1 hypoglycaemic episode were found between the two groups, including severe and nocturnal hypoglycaemia. Insulin glargine was well tolerated, with a similar rate of local injection and systemic adverse events versus NPH insulin.\n A single, bedtime, subcutaneous dose of insulin glargine provided a level of glycaemic control at least as effective as NPH insulin, without an increased risk of hypoglycaemia.\n Copyright (c) 2005 John Wiley & Sons, Ltd.",
"To assess efficacy and tolerability of insulin detemir or NPH insulin added to oral therapy for type 2 diabetes in a treat-to-target titration protocol.\n Individuals (n = 476) with HbA(1c) (A1C) 7.5-10.0% were randomized to addition of twice-daily insulin detemir or NPH insulin in a parallel-group, multicenter trial. Over 24 weeks, insulin doses were titrated toward prebreakfast and predinner plasma glucose targets of < or =6.0 mmol/l (< or =108 mg/dl). Outcomes assessed included A1C, percentage achieving A1C < or =7.0%, risk of hypoglycemia, and body weight.\n At 24 weeks, A1C had decreased by 1.8 and 1.9% (from 8.6 to 6.8 and from 8.5 to 6.6%) for detemir and NPH, respectively (NS). In both groups, 70% of participants achieved an A1C </= 7.0%; [corrected] there was a trend towards [corrected] the proportion achieving this without hypoglycemia being [corrected] higher with insulin detemir than with NPH insulin (34% [corrected] vs. 25[corrected]%, P = 0.052[corrected]). Compared with NPH insulin, the risk for all hypoglycemia with insulin detemir was reduced by 47% (P < 0.001) and nocturnal hypoglycemia by 55% (P < 0.001). Mean weight gain was 1.2 kg with insulin detemir and 2.8 kg with NPH insulin (P < 0.001), and the difference in baseline-adjusted final weight was -1.58 (P < 0.001).\n Addition of basal insulin to oral drug therapy in people with suboptimal control of type 2 diabetes achieves guideline-recommended A1C values in most people with aggressive titration. Insulin detemir compared with NPH insulin achieves this with reduced hypoglycemia and less weight gain.",
"To compare the effect on glycemic control and weight gain of repaglinide versus metformin combined with bedtime NPH insulin in patients with type 2 diabetes.\n A total of 80 subjects treated with 850 or 1,000 mg t.i.d. metformin combined with bedtime NPH insulin were randomized to 13 weeks of open-label treatment with 4 mg t.i.d. repaglinide (n = 39) or metformin (dose unchanged) (n = 41). Insulin dose was titrated at the clinician's discretion, aiming for a fasting blood glucose (FBG) < or =6.0 mmol/l.\n Baseline age, diabetes duration, insulin requirement, weight, BMI, FBG, and HbA(1c) (Diabetes Control and Complications Trial-aligned assay, normal range 4.6-6.2%) were similar. Glycemic control improved (nonsignificantly) with insulin/metformin by (mean) 0.4%, from 8.4 to 8.1% (P = 0.09) but deteriorated with insulin/repaglinide by (mean) 0.4%, from 8.1 to 8.6% (P = 0.03; P = 0.005 between groups). Weight gain was less with insulin/metformin: 0.9 +/- 0.4 kg (means +/- SE) (P = 0.01) versus 2.7 +/- 0.4 kg (P < 0.0001) (P = 0.002 between groups). The Diabetes Treatment Satisfaction Questionnaire score (potential range 0 [minimum] to 36 [maximum]) increased from 32.4 +/- 0.8 to 34.1 +/- 0.5 (P = 0.01) with insulin/metformin but decreased from 32.5 +/- 0.9 to 29.1 +/- 1.3 (P < 0.002) with insulin/repaglinide.\n Combined with bedtime NPH insulin, metformin provides superior glycemic control to repaglinide with less weight gain and improved diabetes treatment satisfaction.",
"Basal insulin is frequently administered once daily. This subgroup analysis of a multicenter, randomized, parallel study compared insulin glargine (Lantus Aventis Pharmaceuticals, Bridgewater, NJ) with neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes, evaluating only patients treated previously with once-daily NPH insulin.\n Patients received bedtime insulin glargine or NPH insulin, with preprandial regular insulin. One hundred patients (mean age, 57.9 years; mean glycohemoglobin, 8.4%; mean fasting blood glucose, 167 mg/dL) were treated for up to 28 weeks.\n Patients treated with insulin glargine (n = 52) and NPH insulin (n = 48) achieved similar reductions from baseline in glycohemoglobin (-0.41% versus -0.46%) and fasting blood glucose (-22 mg/dL versus -22 mg/dL) at week 28. The proportion of patients reaching target fasting blood glucose (<120 mg/dL) at 28 weeks was 34.2% with insulin glargine and 24.4% with NPH insulin. Similar proportions of patients achieved glycohemoglobin less than 7% and less than 8% in both groups. Baseline and week-28 mean daily doses of insulin glargine (27.3 IU versus 36.4 IU) were similar to NPH insulin doses (25.5 IU versus 30.2 IU). However, significantly fewer patients reported one or more episodes of hypoglycemia with insulin glargine (46.2%) versus NPH insulin (60.4%; P < 0.05). Significantly fewer patients also reported one or more symptomatic episodes confirmed by blood glucose less than 50 mg/dL with insulin glargine (17.3%) versus NPH insulin (31.3%; P < 0.005).\n Bedtime insulin glargine is as effective as bedtime NPH insulin in improving glycemic control, with significantly less hypoglycemia."
] |
Bedtime NPH insulin combined with oral hypoglycaemic agents provides comparable glycaemic control to insulin monotherapy and is associated with less weight gain if metformin is used.
|
CD005028
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[
"Efficacy of topical treatment in psoriasis with MC903, a new vitamin D analogue.",
"A double-blind, vehicle-controlled paired comparison of halobetasol propionate cream on patients with plaque psoriasis.",
"Intermittent corticosteroid maintenance treatment of psoriasis: a double-blind multicenter trial of augmented betamethasone dipropionate ointment in a pulse dose treatment regimen.",
"Calcitriol ointment and clobetasol propionate cream: a new regimen for the treatment of plaque psoriasis.",
"Topical paricalcitol (19-nor-1 alpha,25-dihydroxyvitamin D2) is a novel, safe and effective treatment for plaque psoriasis: a pilot study.",
"Comparing clobetasol propionate 0.05% spray to calcipotriene 0.005% betamethasone dipropionate 0.064% ointment for the treatment of moderate to severe plaque psoriasis.",
"Evaluation of halobetasol propionate ointment in the treatment of plaque psoriasis: report on two double-blind, vehicle-controlled studies.",
"Intra-individual comparison of the cutaneous safety and efficacy of calcitriol 3 microg g(-1) ointment and calcipotriol 50 microg g(-1) ointment on chronic plaque psoriasis localized in facial, hairline, retroauricular or flexural areas.",
"Rationale for use and clinical responsiveness of hexafluoro-1,25-dihydroxyvitamin D3 for the treatment of plaque psoriasis: a pilot study.",
"A multicentre, parallel-group comparison of calcipotriol ointment and short-contact dithranol therapy in chronic plaque psoriasis.",
"A double-blind study of topical 1 alpha,25-dihydroxyvitamin D3 in psoriasis.",
"A study of the safety and efficacy of calcipotriol and betamethasone dipropionate scalp formulation in the long-term management of scalp psoriasis.",
"Calcipotriol plus betamethasone dipropionate gel compared with tacalcitol ointment and the gel vehicle alone in patients with psoriasis vulgaris: a randomized, controlled clinical trial.",
"Comparative study of calcipotriene (MC 903) ointment and fluocinonide ointment in the treatment of psoriasis.",
"Cyclosporine for plaque-type psoriasis. Results of a multidose, double-blind trial.",
"Efficacy, safety and quality of life of calcipotriol/betamethasone dipropionate (Dovobet) versus calcipotriol (Daivonex) in the treatment of psoriasis vulgaris: a randomized, multicentre, clinical trial.",
"An intra-individual randomized safety and efficacy comparison of clobetasol propionate 0.05% spray and its vehicle in the treatment of plaque psoriasis.",
"Calcipotriene ointment 0.005% for psoriasis: a safety and efficacy study. Calcipotriene Study Group.",
"Vitamin B(12) cream containing avocado oil in the therapy of plaque psoriasis.",
"Efficacy and safety of a new combination of calcipotriol and betamethasone dipropionate (once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis vulgaris: a randomized, double-blind, vehicle-controlled clinical trial.",
"The efficacy and tolerability of clobetasol propionate foam 0.05% in the treatment of mild to moderate plaque-type psoriasis of nonscalp regions.",
"Comparison of calcipotriol monotherapy and a combination of calcipotriol and betamethasone valerate after 2 weeks' treatment with calcipotriol in the topical therapy of psoriasis vulgaris: a multicentre, double-blind, randomized study.",
"A comparison of tazarotene 0.1% gel once daily plus mometasone furoate 0.1% cream once daily versus calcipotriene 0.005% ointment twice daily in the treatment of plaque psoriasis.",
"Calcitriol shows greater persistence of treatment effect than betamethasone dipropionate in topical psoriasis therapy.",
"Topical calcitriol in the treatment of chronic plaque psoriasis: a double-blind study.",
"Management of psoriasis vulgaris with methotrexate 0.25% in a hydrophilic gel: a placebo-controlled, double-blind study.",
"Clobetasol propionate followed by calcipotriol is superior to calcipotriol alone in topical treatment of psoriasis.",
"Comparative efficacy of calcipotriol (MC903) cream and betamethasone 17-valerate cream in the treatment of chronic plaque psoriasis. A randomized, double-blind, parallel group multicentre study. Calcipotriol Study Group.",
"Highly purified omega-3-polyunsaturated fatty acids for topical treatment of psoriasis. Results of a double-blind, placebo-controlled multicentre study.",
"Topical fish oil in psoriasis--a controlled and blind study.",
"Once daily treatment of psoriasis with tacalcitol compared with twice daily treatment with calcipotriol. A double-blind trial.",
"A double-blind, randomized, placebo-controlled trial of n-3 fatty acid based lipid infusion in acute, extended guttate psoriasis. Rapid improvement of clinical manifestations and changes in neutrophil leukotriene profile.",
"Topical PTH (1-34) is a novel, safe and effective treatment for psoriasis: a randomized self-controlled trial and an open trial.",
"0.3% Tacrolimus gel and 0.5% Tacrolimus cream show efficacy in mild to moderate plaque psoriasis: Results of a randomized, open-label, observer-blinded study.",
"Betamethasone dipropionate ointment in the treatment of psoriasis and atopic dermatitis: a double-blind study.",
"Randomized controlled trial using vitamins E and D supplementation in atopic dermatitis.",
"Topical tacrolimus is not effective in chronic plaque psoriasis. A pilot study.",
"The safety and efficacy of tazarotene gel, a topical acetylenic retinoid, in the treatment of psoriasis.",
"Dietary supplementation with very long-chain n-3 fatty acids in patients with atopic dermatitis. A double-blind, multicentre study.",
"A randomized, double-blind, placebo-controlled study of clobetasol propionate 0.05% foam in the treatment of nonscalp psoriasis.",
"Topical maxacalcitol for the treatment of psoriasis vulgaris: a placebo-controlled, double-blind, dose-finding study with active comparator.",
"Clobetasol propionate emollient 0.05 percent: hypothalamic-pituitary-adrenal-axis safety and four-week clinical efficacy results in plaque-type psoriasis.",
"Long-term management of atopic dermatitis in infants with topical pimecrolimus, a nonsteroid anti-inflammatory drug.",
"Efficacy and tolerability of a cosmetically acceptable coal tar solution in the treatment of moderate plaque psoriasis: a controlled comparison with calcipotriene (calcipotriol) cream.",
"Once-daily treatment of psoriasis with topical glucocorticosteroid ointments.",
"Clobetasol propionate lotion in the treatment of moderate to severe plaque-type psoriasis.",
"Double-blind, placebo-controlled, randomized, right-left study comparing calcipotriol monotherapy with a combined treatment of calcipotriol and diflucortolone valerate in chronic plaque psoriasis.",
"Treatment of psoriasis with topical sirolimus: preclinical development and a randomized, double-blind trial.",
"Treatment of psoriasis vulgaris with topical calcipotriol has no short-term effect on calcium or bone metabolism. A randomized, double-blind, placebo-controlled study.",
"Topical becocalcidiol for the treatment of psoriasis vulgaris: a randomized, placebo-controlled, double-blind, multicentre study.",
"Treatment of psoriasis with topical NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthesis.",
"Comparative study of calcipotriol (MC 903) ointment and betamethasone 17-valerate ointment in patients with psoriasis vulgaris.",
"Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children.",
"Long-term safety and tolerability of pimecrolimus cream 1% and topical corticosteroids in adults with moderate to severe atopic dermatitis.",
"Tazarotene gel, a new retinoid, for topical therapy of psoriasis: vehicle-controlled study of safety, efficacy, and duration of therapeutic effect.",
"Efficacy and safety of calcipotriol (MC 903) ointment in psoriasis vulgaris. A randomized, double-blind, right/left comparative, vehicle-controlled study.",
"Efficacy and tolerance of topical calcitriol 3 microg g(-1) in psoriasis treatment: a review of our experience in Poland.",
"Efficacy of once-daily treatment regimens with calcipotriol/betamethasone dipropionate ointment and calcipotriol ointment in psoriasis vulgaris.",
"Calcitriol 3 microg/g ointment in the management of mild to moderate plaque type psoriasis: results from 2 placebo-controlled, multicenter, randomized double-blind, clinical studies.",
"Efficacy and safety of calcipotriene 0.005% foam for the treatment of plaque-type psoriasis: results of two multicenter, randomized, double-blind, vehicle-controlled, phase III clinical trials.",
"Improvement of psoriasis by a topical vitamin D3 analogue (MC 903) in a double-blind study.",
"Management of psoriasis with Aloe vera extract in a hydrophilic cream: a placebo-controlled, double-blind study.",
"Remission of ordinary psoriasis following a short clearance course of cyclosporin.",
"Evaluation of the efficacy of methotrexate and cyclosporine therapies on psoriatic nails: a one-blind, randomized study.",
"Use of topical ascorbic acid and its effects on photodamaged skin topography.",
"Efficacy and safety of topical calcitriol (1,25-dihydroxyvitamin d3) for the treatment of psoriasis.",
"One-minute dithranol therapy in psoriasis: a placebo-controlled paired comparative study.",
"A comparative study of calcipotriol ointment and tar in chronic plaque psoriasis.",
"Efficacy results of a 52-week, randomised, double-blind, safety study of a calcipotriol/betamethasone dipropionate two-compound product (Daivobet/Dovobet/Taclonex) in the treatment of psoriasis vulgaris.",
"Efficacy and safety of ustekinumab in Japanese patients with moderate-to-severe plaque-type psoriasis: long-term results from a phase 2/3 clinical trial.",
"Betamethasone valerate foam for treatment of nonscalp psoriasis.",
"A new calcipotriol/betamethasone dipropionate formulation (Daivobet) is an effective once-daily treatment for psoriasis vulgaris.",
"Calcipotriene-induced improvement in psoriasis is associated with reduced interleukin-8 and increased interleukin-10 levels within lesions.",
"A double-blind, vehicle-controlled study of clobetasol propionate 0.05% (Temovate) scalp application in the treatment of moderate to severe scalp psoriasis.",
"A comparative clinical evaluation of a new topical steroid 'halcinonide' and hydrocortisone in steroid-responsive dermatoses.",
"Calcipotriol plus betamethasone dipropionate gel compared with its active components in the same vehicle and the vehicle alone in the treatment of psoriasis vulgaris: a randomised, parallel group, double-blind, exploratory study.",
"A comparison of two regimens of topical corticosteroids in the treatment of patients with bullous pemphigoid: a multicenter randomized study.",
"Dystrophic psoriatic fingernails treated with 1% 5-fluorouracil in a nail penetration-enhancing vehicle: a double-blind study.",
"Comparison of cutaneous tolerance and efficacy of calcitriol 3 microg g(-1) ointment and tacrolimus 0.3 mg g(-1) ointment in chronic plaque psoriasis involving facial or genitofemoral areas: a double-blind, randomized controlled trial.",
"A comparison of treatment with dithranol and calcipotriol on the clinical severity and quality of life in patients with psoriasis.",
"Safety and efficacy of combined high-dose treatment with calcipotriol ointment and solution in patients with psoriasis.",
"Low-dose short-term cyclosporine versus etretinate in psoriasis: improvement of skin, nail, and joint involvement.",
"1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone in the treatment of intertriginous psoriasis: a double-blind, randomized controlled study.",
"Safety and efficacy of early intervention with pimecrolimus cream 1% combined with corticosteroids for major flares in infants and children with atopic dermatitis.",
"Betamethasone dipropionate in optimized vehicle. Intermittent pulse dosing for extended maintenance treatment of psoriasis.",
"A randomized, multicenter study of calcipotriene ointment and clobetasol propionate foam in the sequential treatment of localized plaque-type psoriasis: short- and long-term outcomes.",
"A double-blind comparison of 0.1% dithranol in a 17% urea base (\"Psoradrate\") and base alone in the treatment of active chronic psoriasis.",
"Pimecrolimus cream in the long-term management of atopic dermatitis in adults: a six-month study.",
"Lack of efficacy of topical mycophenolic acid in psoriasis vulgaris.",
"Left-right comparison study of the combination of fluticasone propionate and UV-A vs. either fluticasone propionate or UV-A alone for the long-term treatment of vitiligo.",
"A multicenter study of topical azelaic acid 15% gel in combination with oral doxycycline as initial therapy and azelaic acid 15% gel as maintenance monotherapy.",
"Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial.",
"Early onset of action and efficacy of a combination of calcipotriene and betamethasone dipropionate in the treatment of psoriasis.",
"Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris.",
"Comparative effects of calcipotriol ointment (50 micrograms/g) and 5% coal tar/2% allantoin/0.5% hydrocortisone cream in treating plaque psoriasis.",
"A randomized double-blind comparison of the effects on systemic calcium homeostasis of topical calcitriol (3 micrograms/g) and calcipotriol (50 micrograms/g) in the treatment of chronic plaque psoriasis vulgaris.",
"A phase II placebo-controlled study of photodynamic therapy with topical hypericin and visible light irradiation in the treatment of cutaneous T-cell lymphoma and psoriasis.",
"Fluocinolone acetonide topical oil for scalp psoriasis.",
"Tacrolimus ointment is effective for facial and intertriginous psoriasis.",
"Evaluation of the efficacy of topical caffeine in the treatment of psoriasis vulgaris."
] |
[
"In 10 in-patients with chronic plaque psoriasis, the antipsoriatic effect of MC903, a new synthetic analogue of vitamin D was evaluated. In each patient two symmetrical located psoriatic plaques were selected for the study. Topical treatment with MC903 cream (containing 1.2 mg MC903 per g cream) was compared with placebo cream in a double-blind, controlled, left-right, randomized way during 6 weeks of therapy. Compared with baseline, the clinical (erythema, scaling and infiltration) improvement was significant after 1 week of therapy with MC903 cream, while lateral comparison showed MC903 cream significantly better than cream base after 4 weeks of therapy (p less than 0.05). Measurements of skin blood flow by the laser Doppler technique in evaluating the disease activity was not superior to the clinical assessments. In 3 patients the psoriatic lesions treated with MC903 cream cleared completely during 6 weeks of therapy. No essential adverse reactions were observed. MC903 has a potent effect on cell proliferation and cell differentiation, but has minimal effect on calcium metabolism. It is concluded that this synthetic vitamin D analogue is potentially useful in the treatment of psoriasis.",
"The efficacy and safety of halobetasol propionate 0.05% cream, an ultra high-potency corticosteroid preparation, was evaluated in a double-blind, vehicle-controlled, paired comparison study. Patients' psoriatic lesions were evaluated before treatment and after 1 and 2 weeks of twice-daily treatment with halobetasol propionate and vehicle. Response measures (plaque elevation, erythema, scaling, and pruritus) were evaluated with a 4-point severity scale whereby the sum provided a total score. Patient self-assessment measures were obtained at the 2-week visit by categorizing his or her global responses to queries about each treatment's \"effectiveness\" and \"overall rating.\" All efficacy parameters, as judged by the physician, showed statistically significant (p = 0.0001) treatment differences favoring halobetasol propionate at both week 1 and week 2 evaluations. Patient global responses for \"effectiveness\" and \"overall rating\" favored halobetasol propionate 0.05% cream over vehicle after 2 weeks of use. No systemic adverse drug effects were reported during the study. No patient was discontinued from the study because of an adverse event, and there was no evidence of skin atrophy after 2 weeks of treatment with either agent. Patient reports of \"stings\" or \"burns\" were equally distributed between the active and vehicle treatment groups. This trial demonstrates that halobetasol propionate 0.05% cream is clinically beneficial and without evidence of significant risk in the treatment of plaque psoriasis.",
"Ninety psoriasis patients, who were either completely cleared of or manifested only a minimal presence of disease signs following 3-4 weeks of twice daily treatment with augmented betamethasone dipropionate (ABD) ointment 0.05%, were enrolled in this multicenter, double-blind, placebo-controlled study. The study was designed to determine if an intermittent pulse dose regimen of ABD ointment could safely and effectively maintain a remission disease status when treatment was applied in three consecutive applications 12 h apart, once a week for a maximum treatment period of 6 months. The disease of 60% of the patients in the active treatment group was successfully controlled for 6 months, while 80% of the placebo-treated patients experienced exacerbation of disease signs. No serious local or systemic treatment-related adverse experiences were reported. ABD ointment 0.05%, when applied using the intermittent treatment regimen described here, was shown to be a clinically beneficial and well-tolerated method of long-term (up to 6 months) maintenance therapy for psoriasis patients.",
"For psoriasis therapy, topical derivatives of vitamin D3 represent a versatile option: they can be used either alone or in combination with other agents such as topical corticosteroids. In this two-phase parallel-group study, the naturally occurring vitamin D3 analogue, calcitriol, was compared with the vitamin D analogue calcipotriol in 125 patients with chronic plaque-type psoriasis. The proposed treatment regimen was an initial bitherapy for 2 or 4 weeks, with clobetasol propionate 0.05% cream, a super potent topical corticosteroid applied in the morning and either calcitriol 3 mug/g ointment or calcipotriol 50 mug/g ointment applied in the evening, followed by monotherapy with either calcitriol or calcipotriol applied twice daily until endpoint week 12. Efficacy evaluations (global assessment of improvement, PASI and body surface area (BSA) affected) showed no significant differences between the two regimen groups at the primary endpoints (week 2 and week 12) or at any interim points. At week 2 the investigator's global assessment showed clinical success (psoriasis markedly improved, almost clear or clear) for more than 50% of the patients in both groups and for 48 (79%) and 56 (88%) patients, respectively in the calcitriol and calcipotriol regimen group at week 12. Least-square means analysis of PASI indicated the calcitriol regimen to be equivalent to the calcipotriol regimen. There were no significant differences between the two groups with regards to cutaneous safety or to incidence of adverse events. The present study shows that for the treatment of mild to moderate plaque psoriasis calcitriol 3 mug/g ointment can provide a safe and effective alternative to calcipotriol 50 mug/g ointment while being administered within a regimen based on a bitherapy with corticosteroids followed by a vitamin D3 maintenance monotherapy.",
"There continues to be a need to develop new pharmacological approaches for treating psoriasis. Topical active vitamin D compounds have proven to be both safe and effective for treating psoriasis. Paricalcitol (19-nor-1 alpha,25-dihydroxyvitamin D(2)) is a novel vitamin D analogue which has been developed for the prevention of secondary hyperparathyroidism in patients with chronic renal failure.\n To investigate the efficacy and safety of 12 weeks' therapy with a once-daily application of paricalcitol ointment (15 microg g(-1)) in comparison with placebo ointment.\n This pilot double-blinded self-controlled study was initiated in 11 patients with moderate plaque psoriasis. To characterize the biological effects further and to evaluate the efficacy of topical paricalcitol treatment in psoriasis, we have analysed immunohistochemically the expression of one of the markers for epidermal differentiation (transglutaminase K) in paricalcitol-treated skin as compared with placebo treatment.\n Treatment with paricalcitol was superior to placebo treatment beginning at week 1. The global severity score for erythema, plaque elevation and scaling was improved significantly more by paricalcitol ointment than by placebo (P < 0.001). Similar results were obtained for assessments of scaling, erythema and plaque elevation. No symptoms of local skin irritation were noted. Laboratory parameters including serum calcium, phosphorus, parathyroid hormone and urinary calcium/creatinine ratio did not reveal any changes of clinical relevance during treatment. The immunoreactivity of transglutaminase K changed after 12 weeks of paricalcitol treatment almost completely to the pattern characteristic for nonlesional psoriatic skin.\n Once-daily application of paricalcitol ointment was safe and effective for the treatment of plaque psoriasis.",
"Topical corticosteroids are widely used in the treatment of psoriasis. This study was conducted to compare the efficacy and safety of clobetasol propionate (CP) 0.005% spray to calcipotriene 0.005%-betamethasome diproprionate 0.064% (C-BD) ointment in patients with moderate to severe plaque psoriasis. Assessments were made at baseline, week 2, week 4 (end of treatment) and week 8 (4 weeks posttreatment). An assessment for Overall Disease Severity (ODS) found that 75% of CP spray-treated patients achieved a rating of clear or almost clear after 4 weeks of treatment compared to 45% of C-BD ointment-treated patients (P=.003). Adverse events were reported by less than one-third of patients from each treatment group (31% for CP spray and 33% for C-BD ointment).",
"The results of two studies are presented that reveal the efficacy and safety of 0.05% halobetasol ointment in the treatment of patients with plaque psoriasis of at least moderate severity. Both multicenter studies were randomized, double-blind, and vehicle controlled, and study medications were applied twice daily for 2 weeks. One study was a paired-comparison (PC); the other study was of parallel-group (PG) design. Both studies called for evaluations at entry (week 0) and after 1 and 2 weeks of treatment. The PC study enrolled 100 patients; the PG study enrolled 110 patients; 204 patients provided efficacy data over both studies. In the PC study, plaque elevation, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistical (p less than or equal to 0.0003) and clinical significance (all greater than 1-unit difference on the rating scale) favoring 0.05% halobetasol ointment over vehicle. Pruritus (initially mild) and total score also showed statistically significant treatment differences favoring halobetasol at the final evaluation. Patient global responses for \"effectiveness\" and \"overall rating\" favored 0.05% halobetasol ointment over vehicle. In the PG study, induration, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistically and clinically significant differences favoring 0.05% halobetasol ointment over vehicle. Physician's global evaluation favored 0.05% halobetasol ointment over vehicle after 2 weeks of use. No patients were released from either study because of adverse events. No systemic adverse events or findings of skin atrophy were reported in these studies. Reports of \"stings\" or \"burns\" were equally divided between halobetasol and its vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)",
"Psoriasis involving sensitive skin areas remains difficult to treat because of the side-effects of topical corticosteroids and the irritancy potential of vitamin D3 derivatives. Several clinical trials have demonstrated that calcitriol, the naturally occurring and hormonally active form of vitamin D3, is effective and safe at the dose of 3 microg g(-1) for the treatment of psoriasis affecting the trunk and limbs.\n We compared the safety and efficacy of calcitriol 3 microg g(-1) ointment and calcipotriol 50 microg g(-1) ointment in a multicentre, randomized, investigator-blinded, left-right comparison in mild to moderate chronic plaque psoriasis affecting sensitive areas, defined as being the face, hairline, retroauricular and flexural areas. One pair of symmetrical and bilateral target lesions was selected from each area and assessed for perilesional erythema, oedema, and stinging/burning. Global assessment of local tolerability and global improvement were rated by the investigator, and the subjects were asked to evaluate the tolerability and efficacy of each product and to express their global preference.\n In the 75 subjects, calcitriol and calcipotriol both led to clearing of at least one target lesion in 21 (28%) of the subjects each. Perilesional erythema (P < 0.001), perilesional oedema (P < 0.02) and stinging/burning (P < 0.001) were all significantly less severe with calcitriol than with calcipotriol. The subjects' evaluation of local tolerability was significantly (P < 0.0001) in favour of calcitriol. Ten treatment-related dermatological events occurred in eight subjects, including one subject who experienced skin discomfort on both sides. All other events occurred only on the calcipotriol-treated side (irritant dermatitis, six subjects; contact dermatitis, one subject). Global assessment of improvement from baseline by the investigators was significantly greater for the calcitriol-treated lesions (P < 0.02). The subjects' global preference was significantly in favour of calcitriol (P < 0.02).\n In the present study, calcitriol ointment was found to be better tolerated and would appear to be more effective than calcipotriol ointment in the treatment of psoriasis in sensitive areas.",
"Vitamin D analogues are useful in topical therapy of psoriasis.\n To evaluate the effect of hexafluoro-1,25-dihydroxyvitamin D3 (F6-1,25(OH)2D3) in treatment of psoriasis.\n Fifteen patients with plaque-type psoriasis were enrolled in a single centre double-blind, right/left comparison, placebo-controlled study, and received 0.1 g of petrolatum containing 5 microg of F6-1,25(OH)2D3 or 0.1 g of petrolatum (placebo) for 3 months. After completion of this double-blind study, a subset of these patients (n = 12) applied F6-1,25(OH)2D3 ointment (50 microg g-1 of petrolatum) to all their lesions (total area, 100-5000 cm2, mean area: 3300 m2) for 2 months as a single application at night.\n The mean severity score in the right/left-sided controlled topical F6-1,25(OH)2D3 (50 microg g-1) therapy group showed a decrease of 85%. In contrast, the mean severity score for the placebo-treated areas showed a decrease of 45% (P < 0.001). In the 12 patients who subsequently applied F6-1,25(OH)2D3 (50 microg g-1) ointment to all of their lesions, 91.6% showed moderate to excellent improvement. The mean Psoriasis Area and Severity Index score decreased by 44.9% (from 33.6 +/- 15 to 18.5 +/- 13). No effect on calcium homeostasis was noted. Adverse events included mild irritation in two patients that resolved during therapy.\n Topical F6-1,25(OH)2D3 is a safe and effective once a day treatment for psoriasis.",
"Short-contact treatment with dithranol (anthralin) is a widely used treatment for chronic plaque psoriasis. Although effective, it causes staining and irritation, and is therefore inconvenient. Calcipotriol is a recently developed vitamin D analogue which is effective and easy to use. To evaluate the relative efficacy, safety and acceptability of these treatments a multicentre, open, randomized, parallel-group comparison was performed. Four hundred and seventy-eight patients with chronic plaque psoriasis were randomized to use one of the two treatments for 8 weeks. One group applied calcipotriol ointment (50 micrograms/g) twice daily. The other used a single application for 30 min each day of Dithrocream in the highest concentration tolerated. Severity of psoriasis was assessed by modified PASI score at baseline, and after 2, 4, and 8 weeks of treatment. A five-point scale was used by subjects and by investigators as an additional assessment of overall response, and a similar scale was used by subjects to grade acceptability. Total serum calcium was monitored at baseline and after 2 and 8 weeks on treatment. The mean PASI score fell from 9.1 to 4.7 after 8 weeks on dithranol (P < 0.001), and from 9.4 to 3.4 on calcipotriol (P < 0.001). The difference between the two treatments was significant in favour of calcipotriol at 2 weeks (P < 0.001), and remained so at subsequent assessments. At 8 weeks the difference between mean improvements in scores for the two groups was 1.6 (95% confidence interval 0.5-2.7). Efficacy grading by subjects and investigators, and acceptability grading by subjects, were all significantly better for calcipotriol.(ABSTRACT TRUNCATED AT 250 WORDS)",
"Several open studies with active forms of vitamin D3 have been reported to be effective in the treatment of psoriasis. We report a double-blind study of 1 alpha,25-dihydroxycholecalciferol in psoriasis using 0.5 microgram of active substance applied topically twice daily. In contrast to previous studies, the present investigation does not provide evidence of clinical efficacy for the drug at that dosage and with the vehicle that was used.",
"Effective and safe products are needed for long-term management of scalp psoriasis. This study investigated the long-term safety and efficacy of a two-compound formulation (calcipotriol 50 microg/g plus betamethasone dipropionate 0.5 mg/g) for scalp psoriasis.\n In this 52-week, international, double-blind study, 869 patients with moderate-to-severe scalp psoriasis were randomized to either a two-compound scalp formulation (n = 429) or calcipotriol (n = 440).\n Adverse drug reactions were less frequent in the two-compound group compared with the calcipotriol group (17.2 vs. 29.5%; p < 0.001). Incidences of adverse events possibly associated with long-term corticosteroid use were low in both the two-compound (2.6%) and the calcipotriol (3.0%) groups. Disease was satisfactorily controlled in 92.3% of visits in the two-compound group versus 80.0% in the calcipotriol group (p < 0.001).\n The two-compound scalp formulation demonstrated a high level of safety and efficacy in long-term management of scalp psoriasis.\n 2008 S. Karger AG, Basel.",
"To establish the efficacy and safety of once daily treatment of Daivobet®/Dovobet® gel in patients with psoriasis vulgaris, relative to tacalcitol ointment and the gel vehicle alone.\n 458 patients with at least moderately severe disease were randomized in 3 treatment arms for an 8-week period. Treatment was investigator blinded, and treatment success was defined as patients with an Investigator's Global Assessment of 'clear' or 'almost clear' at week 8.\n The proportion of patients who were 'clear or almost clear' was significantly higher in the 2-compound gel group (39.9%) compared with 17.9% in the tacalcitol group and 5.5% in the gel vehicle group: p < 0.001 in both comparisons. The proportion of patients with at least 1 adverse drug reaction was significantly lower in the 2-compound gel group compared to the other 2 treatment groups.\n Once-a-day treatment with the 2-compound Daivobet/Dovobet gel is a safe and efficacious therapeutic regimen for individuals with psoriasis on the body.\n Copyright © 2011 S. Karger AG, Basel.",
"The topical vitamin D analogue calcipotriene has been reported to be an effective treatment for patients with psoriasis. Comparative studies with topical steroids are informative in judging this new therapy.\n The purpose of this study was to evaluate the efficacy and safety of calcipotriene ointment 0.005% versus fluocinonide ointment 0.05% in the treatment of plaque psoriasis.\n This study was a randomized, double-blind, parallel-group, active-controlled trial in adults who had at least mild overall disease severity and plaque elevation of at least moderate severity. Treatments were applied twice daily for 6 weeks, and subjects were evaluated at weeks 0, 2, 4, and 6. Subjects were graded on a 9-point scale (0 to 8) for scaling, erythema, plaque elevation, and for overall disease severity. A physician's global assessment of improvement/worsening was performed at every visit.\n A total of 114 subjects were enrolled at six study sites. Ninety-nine subjects completed the trial. Mean scores for signs of scaling and plaque elevation in calcipotriene-treated subjects were significantly lower by week 2 than in the fluocinonide-treated subjects. These scores continued to be significantly lower than fluocinonide through week 6 (p < 0.05). Mean scores for erythema in calcipotriene-treated subjects were significantly lower than those in fluocinonide-treated subjects at weeks 4 and 6 (p < 0.05). Both the physician's global assessment and overall disease severity showed statistically significant treatment differences in favor of calcipotriene at week 4 (p < 0.05). This superior efficacy continued through week 6. Treatment-related adverse events were observed in 12 calcipotriene-treated subjects and 5 fluocinonide-treated subjects; all were considered minor.\n Calcipotriene was superior to fluocinonide in the treatment of plaque psoriasis.",
"Severe plaque-type psoriasis has been successfully treated with orally administered cyclosporine, but there has been no comparative, controlled evaluation of various dosages and their efficacy and side effects.\n In a 16-week, double-blind trial, we randomly assigned 85 patients with severe psoriasis to receive 3, 5, or 7.5 mg of cyclosporine per kilogram of body weight per day or a placebo consisting of the vehicle for the drug. After eight weeks the dose could be adjusted to improve safety or efficacy while maintaining blinding.\n The psoriasis improved in a dose-dependent fashion. After eight weeks of fixed-dose therapy, 36, 65, and 80 percent of the patients receiving 3, 5, and 7.5 mg of cyclosporine per kilogram per day, respectively, were rated as being clear or almost clear of psoriasis; each group had significant improvement (P less than 0.0001) as compared with the group receiving vehicle, in which none of the patients were rated as clear or almost clear. The patients who received 5 mg per kilogram were the least likely to require dosage adjustments because of side effects or a lack of efficacy. The glomerular filtration rate, measured in a subgroup of 34 patients receiving cyclosporine, decreased by a median of 16 percent. Higher doses of cyclosporine had greater adverse effects on systolic blood pressure, glomerular filtration rate, and serum levels of creatinine, uric acid, bilirubin, and cholesterol. Delayed-type hypersensitivity reactions to skin-test antigens were reduced by cyclosporine administration. Cyclosporine appears to become concentrated in skin.\n Cyclosporine therapy leads to a rapid and thorough clearing of psoriasis; an initial dose of 5 mg per kilogram per day seems to be appropriate. However, the safety of cyclosporine for the long-term treatment of psoriasis remains to be determined.",
"A clinical trial was performed to evaluate the efficacy, speed of response, side effects and quality of life of patients treated with calcipotriol/betamethasone dipropionate (Dovobet) for 4 weeks followed by maintenance with calcipotriol for 8 weeks (group A) versus calcipotriol (Daivonex) alone for 12 weeks (group B) for the treatment of psoriasis.\n A total of 150 patients were enrolled and randomized to groups A and B. PASI and Skindex-29 were considered the outcome measures.\n Ninety-six patients completed the trial. At weeks 2 and 4, both groups showed a significant clinical improvement compared to baseline; group A demonstrated a higher clinical response compared with group B (p< 0.001). Treatment with calcipotriol was associated with a gradual improvement in group B and maintenance of the results in group A. Similarly, the quality of life assessment showed a marked improvement in terms of Skindex-29 in both groups at weeks 2 and 4 compared to baseline. Both treatments were safe and well tolerated.\n Our results demonstrate a higher efficacy and more rapid onset of action with the two-compound ointment compared with calcipotriol cream alone in short-term treatment. However, sequential application of calcipotriol allows maintenance of the results.",
"Plaque psoriasis affects about 2% of the US population. A new and unique spray formulation of clobetasol propionate (CP) 0.05% was developed to provide advantages over the currently available treatment formulations.\n To evaluate the efficacy and safety of CP 0.05% spray compared to its vehicle in the treatment of moderate to severe plaque psoriasis.\n A 4-week, single-center, randomized, double-blind, vehicle-controlled, intra-individual study in subjects with plaque psoriasis. Each of 2 target lesions per subject were randomized to receive either CP 0.05% spray or its vehicle twice daily over 4 weeks. Efficacy parameters included overall target plaque severity score, scaling, erythema, and plaque elevation at all visits. Adverse events were reported throughout the study.\n A total of 27 subjects were enrolled in the study. At all visits there was a significant intra-individual treatment effect for the overall target plaque severity (P < .001) in favor of CP spray. Throughout the study, results for scaling, erythema, and plaque elevation were significantly (P < .001) in favor of CP spray. After 4 weeks of treatment, all intra-individual response measures, with the exception of erythema, showed an average difference in severity scores of more than 4 points (based on a 9-point scale) between the lesions treated with CP 0.05% spray and the lesions treated with vehicle. No serious adverse event occurred during the course of the study. One local adverse event at the application site (5%) was considered probably related to study medication.\n CP 0.05% spray was effective and safe in reducing overall plaque severity, scaling, erythema, and plaque elevation from the first week of treatment continuing throughout the trial.",
"Plaque psoriasis of mild to moderate severity is routinely treated with topical steroids and coal tar along with emollients. A safe and convenient new treatment modality would be of value to most patients with psoriasis.\n Our purpose was to evaluate the safety and efficacy of a new vitamin D3 analogue, calcipotriene, for the treatment of plaque psoriasis.\n Twice-daily dosing of calcipotriene was compared with its vehicle, for up to 8 weeks, in a double-blind study of 277 patients at 10 study centers in the United States. Two hundred forty-seven patients completed the trial. The clinical characteristics of plaque elevation, erythema, scaling, and overall disease severity were evaluated at baseline and after 1, 2, 4, 6, and 8 weeks of treatment. A Physician's Global Assessment of improvement or worsening of the disease was performed after 1, 2, 4, 6, and 8 weeks of treatment. Blood and urine samples, for routine clinical laboratory tests, were collected at baseline and after 1, 2, 4, and 8 weeks of treatment.\n As early as the week 1 evaluation, patients treated with calcipotriene ointment 0.005% had significantly lower mean scores (p = 0.043) than the vehicle-treated patients for the disease characteristics of plaque elevation, erythema, and scaling. This trend continued through week 8 of treatment when 70% of the calcipotriene-treated patients showed 75% or more improvement compared with only 19% of vehicle-treated patients. Only minor treatment-related adverse events were observed. There were no abnormal laboratory results judged related to treatment and the rare instances of elevated serum calcium values were equally distributed between active and vehicle treatments.\n This study provides evidence that calcipotriene is a safe, effective, and promising new agent for the treatment of moderately severe plaque psoriasis.",
"There are already many effective topical therapies available for use in the treatment of chronic plaque psoriasis. Unfortunately, these treatments are often associated with a rather significant risk of undesirable effects.\n In this randomized, prospective clinical trial, the effects of the vitamin D(3) analog calcipotriol were evaluated against those of a recently developed vitamin B(12) cream containing avocado oil in an intraindividual right/left-side comparison. The trial population consisted of 13 patients, 10 men and 3 women, with chronic plaque psoriasis. The observation period was 12 weeks; the effects of therapy were assessed on the basis of a PASI score adapted to the right/left-side comparison technique, the subjective evaluations of the investigator and patients and the results of 20-MHz sonography.\n There was a more rapid development of beneficial effects with the use of calcipotriol in the initial 8 weeks, although differences in effects were significant only at the time point of therapy week 8 (p < 0.05). After 12 weeks, neither the PASI score nor 20-MHz sonography showed significant differences between the two treatments. While the efficacy of the calcipotriol preparation reached a maximum in the first 4 weeks and then began to subside, the effects of the vitamin B(12) cream containing avocado oil remained at a constant level over the whole observation period. This would indicate that the vitamin B(12) preparation containing avocado oil may be suitable for use in long-term therapy, a hypothesis further supported by the fact that the investigator and the patients assessed the tolerability of the vitamin B(12) cream containing avocado oil as significantly better in comparison with that of calcipotriol.\n The results of this clinical trial provide evidence that the recently developed vitamin B(12) cream containing avocado oil has considerable potential as a well-tolerated, long-term topical therapy of psoriasis.\n Copyright 2001 S. Karger AG, Basel",
"Calcipotriol and betamethasone dipropionate are both widely used, effective treatments for psoriasis. Vitamin D analogues and topical corticosteroids have different mechanisms of action in the treatment of psoriasis. A new vehicle has been developed in order to contain both calcipotriol (50 micro g g-1) and betamethasone dipropionate (0.5 mg g-1) in an ointment form. By using calcipotriol and a corticosteroid together, greater efficacy may be achieved than by using either compound alone.\n The present study was conducted in order to compare the clinical efficacy and safety of the combined ointment formulation used once daily with the vehicle ointment used twice daily, calcipotriol ointment used twice daily and the combined formulation used twice daily in psoriasis vulgaris.\n This was an international, multicentre, prospective, randomized, double-blind, vehicle-controlled, parallel group, 4-week study in patients with psoriasis vulgaris amenable to topical treatment. Patients were randomized to one of four treatment groups: combined formulation once daily, combined formulation twice daily, calcipotriol twice daily or vehicle twice daily. Efficacy and safety were assessed.\n There was no statistically significant difference in the mean percentage change in the Psoriasis Area and Severity Index (PASI) from baseline to end of treatment between the two combined formulation groups, but the difference in PASI reduction was significantly higher in the combined formulation groups (68.6% once daily, 73.8% twice daily) than in both the twice daily calcipotriol group (58.8%) and the vehicle group (26.6%). Safety data showed the frequency of adverse events to be less in the combined formulation groups than in both the calcipotriol group and the vehicle group. The proportion of patients with lesional/perilesional adverse reactions was less in the combined formulation groups and vehicle group than in the calcipotriol group (9.9% combined formulation once daily, 10.6% combined formulation twice daily, 19.8% calcipotriol, 12.5% vehicle).\n No statistically significant nor clinically relevant difference in efficacy was seen between the combined formulation used once daily and twice daily. When compared to vehicle ointment or calcipotriol ointment alone, the combined formulation was shown to be clearly more efficacious.",
"Clobetasol propionate foam 0.05% (Connetics Corporation, Palo Alto, CA) is approved by the United States Food and Drug Administration for the treatment of corticosteroid-responsive scalp dermatoses, but there is only limited data available for its efficacy and tolerability in treating dermatoses which affect nonscalp sites.\n The efficacy and tolerability of clobetasol propionate foam (clobetasol foam) in treating psoriatic lesions at nonscalp sites was evaluated in a multicenter, randomized, double-blinded, placebo-controlled study of 279 patients with mild to moderate plaque-type psoriasis.\n The patients applied clobetasol foam or placebo to the psoriatic lesions twice daily for two weeks. In addition to receiving clinical evaluations, the study patients completed a questionnaire evaluating various characteristics of the foam formulation, including their preference for its use and their projected likelihood to comply with similar therapy in a nonstudy environment.\n At Week 2 (or end of treatment), 68% (94/139) of patients who received clobetasol foam had a Physician's Static Global Assessment score of 0 (clear, except for minor residual discoloration) or 1 (majority of lesions have individual scores for plaque thickness, erythema, and scaling that averages 1). This was significantly more than the 21% (30/140) observed in the placebo group (P < 0.0001). Similar results were obtained for the Patient's Global Assessment score at Week 2 and in changes (from Baseline to Week 2) in the scores for the signs of psoriasis at a target lesion and for pruritus. Adverse effects were generally limited to mild and transient burning or other application site reactions in only a few patients in each treatment group. In the patient's poststudy questionnaire (completed at Week 2, or end of treatment) a majority of patients rated the characteristics of the foam formulation very highly. The patients ranked the foam formulation as superior to other topical formulations based on factors impacting their quality of life and indicated they would be more likely to comply with a recommended course of therapy with the foam formulation than with other topical formulations.\n Clobetasol propionate foam 0.05% is safe and effective for the treatment of plaque-type psoriasis on scalp and nonscalp areas, when applied twice daily for two weeks. As it is understood that patient dissatisfaction with select topical formulations affects their compliance with therapy, which necessarily affects the effectiveness of the therapy, the results of the patient's poststudy questionnaire suggest that there are multiple and integrated benefits for the use of clobetasol foam in the treatment of psoriasis of nonscalp sites.",
"A clinical study was conducted to determine whether, in the topical treatment of psoriasis, a combination of calcipotriol and betamethasone valerate after previous treatment with calcipotriol alone was more effective than the continuation of the monotherapy with calcipotriol, especially in 'low responders'. Patients (n = 169) with the clinical diagnosis 'chronic plaque-type psoriasis' were treated twice daily for 2 weeks with calcipotriol, followed by a 4-week treatment with calcipotriol monotherapy in 87 patients or combined calcipotriol/betamethasone valerate in 82 patients; all patients were followed for 8 weeks. The psoriasis area and severity index (PASI) was used to compare the two treatment groups. The overall therapeutic result was also assessed by the investigators and patients. The combination therapy was more effective, as assessed by all evaluated variables; moreover, patients showing insufficient response to calcipotriol alone after 2 weeks showed a regression of psoriatic lesions using the combination regimen. Thus, the combination of calcipotriol and topical steroids is recommended as the therapy of first choice for patients who do not respond well to treatment with 2 weeks of calcipotriol alone. Furthermore, this combination reduces the hazards associated with the long-term use of topical corticosteroids (atrophy and rebound) as well as the irritation associated with calcipotriol.",
"Both tazarotene (a retinoid prodrug) and calcipotriene (a synthetic analog of vitamin D3) are effective in the treatment of plaque psoriasis, but no reports in the literature directly compare the efficacy and tolerability of these 2 drugs. Tazarotene is commonly used in conjunction with a topical corticosteroid. In this study, tazarotene was used with mometasone furoate (a synthetic corticosteroid), and the 2-drug regimen was compared with calcipotriene monotherapy.\n This study was conducted to compare the efficacy and tolerability of tazarotene 0.1% gel once daily plus mometasone furoate 0.1% cream once daily with those of calcipotriene 0.005% ointment twice daily in the treatment of plaque psoriasis.\n In this multicenter, investigator-blinded, parallel-group study, adult patients with chronic, stable plaque psoriasis affecting 5% to 20% of their body surface area were randomly allocated to receive up to 8 weeks of treatment with either tazarotene 0.1% gel once daily (in the evening) plus mometasone furoate 0.1% cream once daily (in the morning) or calcipotriene 0.005% ointment twice daily. Patients were assessed at baseline and at weeks 2, 4, and 8 of treatment. Patients who demonstrated complete clearance of plaque psoriasis after 2 or 4 weeks of treatment and those whose psoriasis had improved > or = 50% after 8 weeks of treatment entered a 12-week posttreatment follow-up phase during which they applied only moisturizer. Patients were reassessed after 4, 8, and 12 weeks of posttreatment follow-up. Physician-rated measures of efficacy included global improvement, plaque elevation, scaling, erythema, and percentage of body surface area involvement. Patient-rated assessments included efficacy of study treatment compared with previous therapies, comfort of treated skin, outlook for long-term control of psoriasis, and overall impression of treatment.\n Of 120 patients with moderate to severe psoriasis enrolled from 3 centers, 106 (88%) completed the study. No significant differences in baseline clinical variables were observed between the 2 groups. Twenty-seven patients (45%) in the tazarotene plus cortico-steroid group achieved marked improvement (> or = 75% global improvement) after 2 weeks of treatment compared with 15 patients (26%) in the calcipotriene group (P < or = 0.05). Between-group comparisons of the percentage of patients achieving complete or almost complete clearance (> or = 90% global improvement) did not reach statistical significance at any time point. When compared with the calcipotriene regimen, the tazarotene plus corticosteroid regimen resulted in significantly greater efficacy on trunk lesions in reducing plaque elevation (at the end of treatment and at week 4 of the posttreatment phase, P < or = 0.05), scaling (week 4 of treatment and week 4 of the posttreatment phase, P < or = 0.05), erythema (week 4 of treatment and at the end of treatment, P < or = 0.05), and percentage of body surface area involvement (weeks 2 and 4 of treatment, P < or = 0.01). In addition, the tazarotene plus corticosteroid regimen was significantly more effective in reducing the percentage of body surface area involvement in upper limb lesions (weeks 2 [P < or = 0.05] and 4 [P < or = 0.01] of treatment). Forty-two of 55 patients (76%) in the tazarotene plus corticosteroid group rated their medication as more or much more effective than previous therapies compared with 30 of 52 patients (58%) in the calcipotriene group (P < or = 0.05). Although adverse events (burning, pruritus, irritation, and erythema) occurred in a significantly greater proportion of patients who received tazarotene plus corticosteroid than in those who received calcipotriene (P < or = 0.05), 47 of 55 patients (85%) in both groups rated the comfort of their treated skin as \"somewhat comfortable\" or better and both groups had similar discontinuation rates due to treatment-related adverse events (3% and 5%, respectively). CONCL",
"To establish the efficacy and duration of remission post-treatment of calcitriol 3 micro g/g ointment in comparison with betamethasone dipropionate 0.05% ointment.\n A randomized, multicentre trial was conducted in 258 adult patients with chronic plaque psoriasis. Calcitriol 3 microg/g ointment or betamethasone dipropionate 0.05% ointment was applied twice daily for 6 weeks or until complete clearance of lesions. Patients whose psoriasis cleared or were significantly improved and did not require treatment continuation at treatment endpoint were contacted over the following 8 weeks to determine whether relapse had occurred.\n Both treatments were efficacious; improvement in psoriasis or clearance of lesions (residual erythema was allowed) was recorded for 79% and 82% of patients receiving calcitriol or betamethasone dipropionate, respectively. Global improvement and global severity scores at treatment endpoint showed statistically significant differences in favour of betamethasone dipropionate (p<0.05); however, the absolute reduction in mean PASI (psoriasis area and severity index) was comparable between the groups. A statistically significantly (p<0.01) higher proportion of responders remained in remission (no worsening of the disease warranting new treatment) following calcitriol therapy (48%) than betamethasone therapy (25%). This is of potential importance to patients, physicians and healthcare suppliers.\n Twice-daily applications of either calcitriol 3 microg/g ointment or betamethasone dipropionate 0.05% ointment can be used to good effect in the treatment of chronic plaque psoriasis. However, the beneficial effect is likely to persist for longer following calcitriol treatment.",
"A randomized, double-blind, left-right, vehicle-controlled study to assess the therapeutic efficacy and safety of twice daily application of 15 micrograms/g calcitriol ointment for a period of 6 weeks was performed in 32 patients suffering from bilateral, symmetrical, severe chronic plaque psoriasis. Twice daily 15 micrograms/g calcitriol ointment significantly improved erythema, induration, scaling and global severity of psoriatic plaques, and was much more effective than vehicle ointment. The difference in overall clinical efficacy between calcitriol and vehicle was statistically significant from week 1 onwards, and was maintained over the entire study. On completion of the study, clearance of psoriatic lesions was found in 47% of calcitriol-treated sides and in 13% of vehicle-treated sides. Skin histopathology of calcitriol-treated sides revealed a return to normal keratinization, with decreased inflammatory cell infiltration in the dermis and disappearance of the inflammatory infiltrate from the epidermis. Three patients had asymptomatic hypercalcaemia during the study. Mean serum levels of total calcium, albumin-adjusted total calcium, phosphorus, 25-hydroxyvitamin D and calcitriol did not show statistically significant changes in the baseline/end-point comparisons.",
"Methotrexate has been used as one of the first and systemic therapies for psoriasis. In general, 70% of patients with psoriasis prefer topical therapy as the treatment of choice.\n The purpose of this placebo-controlled double-blind study was to evaluate the clinical efficacy and tolerability of methotrexate 0.25% incorporated in a hydrophilic gel (hydroxyethylcellulose 1%) to treat patients afflicted with psoriasis vulgaris.\n Sixty patients (37M/23F) ranging between 18 and 70 years of age, with slight to moderate chronic plaque-type psoriasis and PASI (Psoriasis Area and Severity Index) scores between 5.3 and 17.5 joined the study. The mean duration of the disease at entry was 9.6 years (range 1-24 years). The diagnosis of psoriasis was established by clinical and histopathologic methods. Patients were sequentially randomized into two parallel groups. Each patient was allocated a precoded 100-g tube (active or placebo) with instructions on how to self-administer the trial medication topically (without occlusion) to their lesions two times daily for 5 consecutive days per week. The study lasted for 12 weeks with 4 weeks of active treatment. Patients were examined on a weekly basis and those showing total clearing or remission of lesions were considered effectively treated.\n By the end of the treatment, breaking the code disclosed that methotrexate 0.25% gel had significantly treated more patients than placebo (83.3% vs. 6.7%; p < 0.0001), reduced the PASI score to a mean of 2.2, and cleared more plaques (82.2% vs. 4.3%; p < 0.0001). Laboratory evaluations, including CBC with differential and platelet count, renal function, liver chemistry [SGOT (aspartate transaminase) and SGPT (alanine transaminase)], and serum creatinine, were within the normal limits. The treatment was well-tolerated by all the patients, with no adverse drug-related symptoms and no dropouts. The study was followed up for 12 months from the first day of the treatment; two cured patients had relapsed after 8 months.\n The findings of this study demonstrate that methotrexate 0.25% in a hydrophilic gel is well tolerated and significantly more effective than placebo as a patient-applied topical medication to treat psoriasis vulgaris.",
"Although potent, topical corticosteroids offer effective and rapid healing of psoriatic lesions. Their long term use is limited because of the risk of side effects. Calcipotriol is safe for long-term treatment, but its initial efficacy is lower than with topical corticosteroids.\n To investigate whether 2 weeks of treatment with clobetasol propionate 0.05% ointment bd followed by 4 weeks of treatment with calcipotriol 50 microg/g bd would offer therapeutic advantages over 6 weeks of continuous treatment with calcipotriol.\n Forty-nine patients with moderate to severe plaque psoriasis were recruited from five centres in Norway. In a randomised, double-blind, right- versus left-side comparison, ointments were applied to two symmetrically-located areas.\n Two weeks of treatment with clobetasol propionate produced a significantly greater decrease in total symptom score (combined scores of erythema, induration and scaling) than calcipotriol treatment (P < 0.0001). This improvement on the clobetasol propionate-treated side of the body was maintained throughout a subsequent 4-week treatment period when calcipotriol was applied to both sides of the body (P < 0.0001). The superiority of the clobetasol propionate followed by calcipotriol treatment was maintained during a 4-week, treatment-free, observation period. Treatments were well tolerated with no rebound effect.\n Clobetasol propionate ointment bd for 2 weeks followed by treatment with calcipotriol ointment bd for 4 weeks was superior to calcipotriol ointment alone in the treatment of plaque psoriasis.",
"The efficacy, safety and tolerability of calcipotriol cream was compared with betamethasone 17-valerate cream in the treatment of plaque-type psoriasis in a multicentre double-blind, parallel group study. Patients with stable mild-to-moderate chronic disease were randomized to treatment with either calcipotriol, 50 micrograms/g, in a cream formulation (210 patients) or betamethasone 17-valerate cream, 1 mg/g (211 patients). After a wash-out period of 2 weeks, the treatment was applied twice daily, without occlusion, for 8 weeks or to complete clearing. The severity of psoriasis was assessed using the PASI at baseline and after 4 and 8 weeks treatment. The mean percentage reduction of PASI from baseline to end of treatment was 47.8% in the calcipotriol group and 45.4% in the betamethasone group. The reduction from baseline was highly significant in both groups, but the difference between the groups was not significant. There was a difference in the reduction in thickness of the lesions in favour of calcipotriol. The investigator's as well as the patient's overall assessment of treatment response at end of treatment showed no difference between the two treatment groups. Treatment-related adverse events were more frequent with calcipotriol than betamethasone. Lesional/perilesional irritation was reported in 16% and 9% (P = 0.03), and facial irritation in 10% and 0.5% (P < 0.001), respectively. No change was found in serum levels of calcium. Calcipotriol in a cream formulation was effective, safe, well-tolerated, and equal in effect to betamethasone valerate cream.",
"We report the results of a multicentre, double-blind, placebo-controlled study of topical therapy with omega-3-polyunsaturated fatty acids (omega-3-PUFA) in 52 patients suffering from moderate plaque-type psoriasis. In each patient, two similar stable psoriatic plaques served as indicator lesions for the study. One indicator lesion was randomly assigned to treatment with topical preparations of highly purified omega-3-PUFA in one of two concentrations (1 or 10%), and the other was treated with placebo. Efficacy assessment was based on changes in local psoriasis severity index, area involved, erythema, desquamation, induration and pruritus. After 8 weeks of treatment, all indicator lesions had improved significantly, compared with baseline. However, no statistically or clinically relevant differences between the omega-3-PUFA-treated and the placebo-treated lesions were found. Therapy was well tolerated and, apart from one patient who developed perilesional eczema, no clinically relevant adverse events occurred. In conclusion, topical omega-3-PUFA were not effective in a randomized, placebo-controlled, double-blind setting. Results of non-blind trials should be (re-)considered with caution.",
"Omega-3 polyunsaturated fatty acids compete with arachidonic acid as substrates for lipoperoxidases, which transform them into leukotrienes with low biological activity. As this process, in skin, may benefit psoriatic patients, a randomized controlled single blind-study was carried out on a sample of 25 patients. In the study fish oil (FO) was compared with liquid paraffin (LP); both were topically applied and administered daily for 6 h under an occlusive dressing over a 4-week period. Evaluations were performed weekly assessing erythema, scaling, plaque thickness (induration) and itching. The results showed statistically significant improvement in erythema and scaling for both treatments compared to basal values; significant differences between treatments were achieved in scaling but not in erythema. Compared to baseline, FO significantly improved plaque thickness while LP did not. After 4 weeks, FO proved to be significantly better than LP. All patients accepted the treatment despite its unpleasant smell. Irritation and a burning sensation were reported in the FO treated plaque of one patient. This adverse effect reverted after completing the treatment. These findings demonstrate that topical FO shows a better performance than LP under an occlusive dressing.",
"Once daily topical treatment of psoriasis with tacalcitol ointment (4 micrograms/g) was compared with twice daily treatment with calcipotriol ointment (50 micrograms/g) in a double-blind, randomized study over a treatment period of 8 weeks. The severity of pruritus, erythema, infiltration and scaling was scored on a scale from 0 to 4. These features were scored at the initiation of treatment, after 2, 4, 6 and 8 weeks of treatment, and at 4 weeks after discontinuation of treatment. The sum score was the total score for erythema, infiltration and scaling. Serum levels of calcium, phosphate, ionized calcium and intact parathyroid hormone were used as safety parameters. Two hundred and eighty-seven adults with stable plaque psoriasis participated and were treated at least once. Both tacalcitol and calcipotriol ointments effectively reduced the severity of psoriasis. The mean reduction in the sum score in the intention-to-treat population of 287 patients was 4.03 in the group treated with tacalcitol compared with 5.05 in the group treated with calcipotriol. The mean baseline sum scores were 7.64 and 7.15, respectively. The acceptability of both ointments was excellent, and none of the patients had adverse effects in terms of increased serum calcium or other alterations in calcium metabolism. Although less effective than calcipotriol ointment used twice daily, tacalcitol ointment is an effective and useful once daily treatment of chronic plaque psoriasis.",
"Twenty patients hospitalized for acute psoriasis guttata with a minimum 10% of body surface area involvement (range 10-90%) completed a 10-day trial in which they were randomly allocated to receive daily infusions with either an n-3 fatty acid based lipid emulsion [100 ml/day with 2.1 g eicosapentaenoic (EPA) and 21 g docosahexaenoic acid (DHA)] or a conventional n-6 lipid emulsion (EPA + DHA < 0.1 g/100 ml). The severity of disease was evaluated by scoring daily erythema, infiltration, and desquamation and by a subjective scoring of clinical manifestations offered by the patients. Leukotriene (LT) and platelet-activating factor (PAF) generation were investigated in ionophore-stimulated neutrophils obtained on days 0, 1, 3, 5, 10, and 40. Moderate improvement in clinical manifestations was noted in the n-6 group (changes in score systems between 16-25% from baseline within 10 days). In contrast, the severity of disease markedly decreased in all patients of the n-3 group, with improvements in all score systems ranging between 45% and 76% within 10 days (P < 0.05 for each variable). The difference in response to the two regimens was evident within 4-7 days after onset of lipid infusion. A more than ten fold increase in neutrophil EPA-derived 5-lipoxygenase product formation (LTB5, its omega-oxidation products, non-enzymatic degradation products of LTA5 and 5-hydroxyeicosapentaenoic acid) was noted in the n-3 group but not in the n-6 group. Neutrophil PAF generation increased in the n-6 group but decreased in the n-3 group. In conclusion, modulation of eicosanoid metabolism by intravenous n-3 fatty acid supplementation appears to exert a rapid beneficial effect on inflammatory skin lesions in acute guttate psoriasis.",
"There continues to be a need to develop new pharmacological approaches for treating the common skin disease psoriasis. Human skin produces parathyroid hormone related peptide. This peptide is a potent inhibitor of epidermal cell growth.\n A programme was initiated to determine whether an agonist of this peptide's receptor, PTH (1-34), could be developed as a drug to treat psoriasis.\n PTH (1-34) was formulated in Novasome A cream. Fifteen adult patients with chronic plaque psoriasis who had failed to respond to at least one standard treatment were enrolled in a randomized double-blinded placebo self-controlled trial. The patients topically applied to a 25-cm2 psoriatic lesion 0.1 g of either Novasome A cream or Novasome A cream that contained 20 microg of PTH (1-34) twice a day for 2 months. At the end of the double-blind study, patients were enrolled in an open large area study. Ten patients applied PTH (1-34) (50 microg per 0.1 g) once daily to their psoriatic lesions. The patients were evaluated for their global improvement and calcium metabolism.\n Novasome A cream enhanced the percutaneous absorption of PTH (1-34) in human skin in comparison with formulations in propylene glycol or normal saline. Psoriatic lesions treated with PTH (1-34) showed marked improvement in scaling, erythema and induration. There was a 67.3% improvement in the global severity score for the lesion treated with PTH (1-34) compared with the placebo-treated lesion, which only showed a 17.8% improvement. Ten patients topically applied PTH (1-34) on all of their lesions in a stepwise manner. A Psoriasis Area and Severity Index score analysis of all the patients revealed improvement of 42.6% (P < 0.02). None of the patients experienced hypercalcaemia or hypercalciuria or developed any side-effect to the medication.\n Patients who were resistant to at least one standard therapy for psoriasis had a remarkable improvement in their psoriasis when they applied PTH (1-34) to their lesion(s). No untoward toxicity was observed in any of the subjects. This pilot study suggests that topical PTH (1-34) is a safe and effective novel therapy for psoriasis.",
"The efficacy and safety of 0.3% tacrolimus gel and 0.5% tacrolimus cream compared with calcipotriol ointment were evaluated in adults (n = 124) with mild to moderate plaque psoriasis. Treatment was twice daily for a maximum of 12 weeks. Clinical efficacy was assessed by the percentage change in the local psoriasis severity index of a target lesion between baseline and week 12. By week 12, the median percentage changes in local psoriasis severity index of the target lesions in the tacrolimus gel, tacrolimus cream and calcipotriol groups were 55.6%, 50.0% and 58.6%, respectively (no statistically significant differences). Clinical improvement was observed after one week and increased throughout the study. Tacrolimus-treated patients experienced more application site skin burning (tacrolimus gel and cream both 31.0% versus 7.5% for calcipotriol; p = 0.011). Skin burning was mostly mild in intensity and decreased substantially after 1 week of treatment. There were no differences in the nature and incidence of infections and no clinically relevant changes in laboratory values.",
"This report describes the use of a new corticosteroid ointment in the treatment of psoriasis and atopic dermatitis. It further summarizes the results of treatment with the active medication versus the vehicle alone in these two disease categories. In the group with psoriasis 13 of 17 patients (76.4%) treated with the active drug showed either excellent or good clinical response (50% to 100% improvement) in three weeks. Five of 16 patients (31.2%) treated with the placebo showed excellent or good response. In the group with atopic dermatitis 16 of 17 patients (94.1%) treated with the active drug showed either excellent or good clinical response (50% to 100% improvement) in three weeks. Two of 16 (12.5%) treated with the placebo showed excellent or good response.",
"Atopic dermatitis is a chronically relapsing, highly pruritic and inflammatory skin disease. This study was done to assess the effects of vitamins D and E supplementation on the clinical manifestation of atopic dermatitis.\n Forty-five atopic dermatitis patients were included in a randomized, double-blind, placebo-controlled trial. They were randomly divided into four groups and treated for 60 days: group P (n = 11), vitamins D and E placebos; group D (n = 12), 1600 IU vitamin D(3) plus vitamin E placebo; group E (n = 11), 600 IU synthetic all-rac-α-tocopherol plus vitamin D placebo; and group DE (n = 11), 1600 IU vitamin D(3) plus 600 IU synthetic all-rac-α-tocopherol. Serum 25(OH) vitamin D and plasma α-tocopherol were determined before and after the trial. The clinical improvement was evaluated with SCORing Atopic Dermatitis (SCORAD). Data were analyzed by analysis of variance (ANOVA) and Kruskal-Wallis tests.\n SCORAD was reduced after 60 days in groups D, E and DE by 34.8%, 35.7% and 64.3%, respectively (p = 0.004). Objective SCORAD also showed significant improvement. There was a positive correlation between SCORAD and intensity, objective, subjective and extent (p < 0.001). We found a significant negative association between plasma α-tocopherol and SCORAD, intensity, objective and extent (p = 0.02).\n This study supports the contributing and beneficial effects of vitamins D and E in the treatment of atopic dermatitis.",
"Cyclosporine for the treatment of psoriasis constitutes a new approach. Alternative systemic cyclosporine derivatives have been studied to find an immunosuppressive drug with fewer adverse effects. Tacrolimus is one of these new immunosuppressive drugs. Systematically, it has been proven effective in treating psoriasis. A topical formulation of tacrolimus is attractive because it has fewer adverse effects and is useful for a large group of patients. We report for the first time on the efficacy of nonocclusive topical tacrolimus in the treatment of psoriasis.\n After a washout phase of 2 weeks, patients were randomized to receive 0.005% calcipotriol ointment twice daily, placebo ointment once daily, or 0.3% tacrolimus ointment once daily. One psoriatic plaque was treated with a surface area of 40 to 200 cm2. Efficacy was estimated using the local psoriasis severity index. The reduction in the local psoriasis severity index score after 6 weeks was 62.5% in the calcipotriol group, 33.3% in the tacrolimus group, and 42.9% in the placebo group.\n There was no statistically significant difference between the efficacy of tacrolimus and placebo ointment (P = .77). Calcipotriol ointment, applied twice daily, had a better effect than tacrolimus ointment and placebo ointment once daily.",
"To determine the safety and efficacy of topically applied tazarotene gel in the treatment of mild to moderate psoriatic plaques.\n Two multicenter, double-blind, randomized studies of 6- and 8-week duration, with an 8-week follow-up in the second study.\n Medical center outpatient dermatology services.\n One hundred fifty-three adults with 2 bilateral target plaques on the trunk, legs, or arms.\n Vehicle gel or 0.01% and 0.05% tazarotene gel administered twice daily to 45 patients (study A), or 0.05% and 0.1% tazarotene gel administered either once or twice daily to 108 patients (study B).\n Treatment success and plaque elevation, scaling, and erythema vs time.\n The 0.01% tazarotene gel showed minimal efficacy. Applications of 0.05% and 0.1% tazarotene gels administered once or twice daily, resulted in significant improvements in plaque elevation, scaling, erythema, and overall clinical severity as early as 1 week. Treatment success rates (defined as > 75% improvement from baseline) were 45% with 0.05% tazarotene gel vs 13% with vehicle gel after 6 weeks of treatment (P < .05; study A) and ranged from 48% to 63% with the various tazarotene treatment regimens after 8 weeks of treatment (study B). These improvements were evident at the 8-week follow-up. Treatment-related adverse effects were generally limited to mild or moderate local irritation and were less frequent with the treatment regimen administered once daily.\n The 0.05% and 0.1% tazarotene gels demonstrated significant efficacy in the treatment of mild to moderate psoriatic plaques that persisted after cessation of treatment.",
"The purpose of this study was to investigate whether fish oil and/or corn oil had a beneficial effect on the clinical state of atopic dermatitis, and to evaluate the dietary intake of nutrients in this group of patients. In a double-blind, multicentre study lasting 4 months, during wintertime, 145 patients with moderate to severe atopic dermatitis were randomly assigned to receive either 6 g/day of concentrated n-3 fatty acids, or an isoenergetic amount of corn oil. As local treatment, only an emollient cream or hydrocortisone cream was allowed. The fatty acid pattern in serum phospholipids, and the dietary intake of nutrients were monitored in a subgroup of patients, and the results were compared with a group of patients with psoriasis. The overall clinical score, as evaluated by the physicians, improved during the trial by 30% in the fish oil (P < 0.001) and 24% in the corn oil group (P < 0.001). This was also consistent with the results from a selected skin area, and it was further confirmed by the total subjective clinical score reported by the patients. There were no significant differences in the clinical scores between the two groups at baseline, and at the end of the study. In the fish oil group, the amount of n-3 fatty acids in serum phospholipids was significantly increased at the end of the trial, compared with pretreatment values (P < 0.001), whereas the level of n-6 fatty acids was decreased (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)",
"Topical corticosteroids are the primary treatment for mild to moderate psoriasis. Foam preparations of corticosteroids offer potential cosmetic and pharmacodynamic advantages over cream and ointment vehicles. A clobetasol propionate foam product is as effective as clobetasol propionate solution in the treatment of scalp psoriasis.\n To evaluate the safety and efficacy of clobetasol propionate foam in the treatment of psoriasis involving sites other than the scalp.\n Eighty-one subjects with mild to moderate psoriasis were randomized in a 3 : 1 ratio to receive clobetasol propionate foam vs. placebo foam treatment in this double-blind study of psoriasis involving nonscalp sites. The investigator's and subject's global assessment of the response at week 2 (or at the end of treatment) and at week 4 (follow-up) and the severity of erythema, scaling, and plaque thickness were assessed. Safety was assessed from reported adverse events.\n After 2 weeks of treatment, there was significantly greater improvement with clobetasol propionate foam compared with placebo foam in both investigator's and subject's global assessment of the response (P < 0.0005). The improvement with clobetasol propionate foam was still present at the 4-week follow-up visit. Adverse effects were generally limited to mild to moderate application site reactions. No subjects withdrew because of adverse events.\n Clobetasol propionate foam is more effective than placebo in the treatment of nonscalp psoriasis. Twice-daily applications are well tolerated, compliance exceeds 90%, cosmetic characteristics are acceptable, and the medication may eliminate the need for separate scalp and body prescriptions.",
"1alpha, 25-Dihydroxy-22-oxacalcitriol (maxacalcitol) is a vitamin D3 analogue which displays approximately 10 times greater efficacy at suppressing keratinocyte proliferation in vitro than calcipotriol and tacalcitol. To determine clinical efficacy, a phase II double-blind, randomized, left vs. right, concentration-response study was performed with once-daily topical maxacalcitol in patients with mild to moderate chronic plaque psoriasis. Primary efficacy parameters were psoriasis severity index (PSI) based on sum of scores for erythema, scaling and induration and investigators' overall assessment of patients' response to therapy at 8 weeks of treatment. One hundred and forty-four patients participated. All concentrations of maxacalcitol ointment (6, 12.5, 25 and 50 microg/g) were significantly more effective at reducing PSI than placebo (P < 0.01), with greatest effect noted for maxacalcitol 25 microg/g. Calcipotriol ointment 50 microg/g once daily as active comparator had a similar effect. Marked improvement or clearance of psoriasis was greatest for maxacalcitol 25 microg/g (55% of subjects) which compared favourably with calcipotriol (46%). Improvement continued throughout the study period, with no plateau at week 8. Investigators' and patients' side preference (secondary efficacy parameters) rated maxacalcitol more effective than placebo and 25 microg/g maxacalcitol better than calcipotriol (P < 0.05 for investigators' assessment). Twelve patients withdrew from the study due to adverse events, of which four were judged to be due to study medication. This study indicates that once-daily maxacalcitol ointment is effective in the management of plaque psoriasis, with greatest effect noted at 25 microg/g. As no response plateau was noted at 8 weeks, these data suggest that further benefit might be obtained if maxacalcitol ointment were applied for longer. Finally, investigators' overall assessment and side preference suggest that maxacalcitol 25 microg/g may be more effective than once-daily calcipotriol.",
"Two clinical trials were conducted to evaluate the safety and antipsoriatic efficacy of a new 0.05 percent emollient formulation of clobetasol propionate (CP). In a crossover study of hypothalamic-pituitary-adrenal (HPA)-axis effects in 12 patients with psoriasis or eczema, 1.5 gm of CP emollient, applied to lesions twice daily for seven consecutive days, resulted in fewer patients with serum cortisol concentrations < 10 micrograms/100 mL than CP cream 0.05 percent (1vs 4); such concentrations were seen in two other patients during both treatment phases. A double-blind, randomized, parallel-group clinical trial in patients with moderate to severe plaque-type psoriasis showed that four weeks' treatment with CP emollient 0.43 to 0.5 gm twice daily (n = 35) was significantly more effective than emollient vehicle (n = 39) in reducing total signs/symptoms and scaling by Day 4, erythema and skin thickening by Day 8, and pruritus by Day 15. CP emollient was rated superior to vehicle by Day 4 in physician's gross assessment ratings and by Day 15 in patient's self-assessment ratings. In all assessments, CP emollient continued to be superior to vehicle during the remainder of the treatment period and two-week posttreatment period. No significant differences were observed in tolerability or serum cortisol effects during the course of the study.",
"Pimecrolimus cream 1% (Elidel, SDZ ASM 981), a nonsteroid selective inhibitor of inflammatory cytokines, is effective in the treatment of atopic dermatitis (AD). In this study we compared early intervention with pimecrolimus cream with treatment with a vehicle control.\n The purpose of this investigation was to assess whether early treatment in infants of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares.\n In this 1-year, double-blind controlled study, 251 infants aged 3 to 23 months with AD were randomized 4:1 to a pimecrolimus-based regimen (n = 204) or a conventional treatment regimen (n = 47). Both groups used emollients for dry skin. Early AD signs and symptoms were treated either with pimecrolimus cream to prevent flares or, in the control group, with vehicle. Vehicle was used to maintain blinding conditions. In the event of flares, moderately potent corticosteroid was permitted in both groups. The primary efficacy end point was the incidence of flares at 6 months.\n Pimecrolimus significantly reduced the incidence of flares compared with control treatment (P <.001), with 67.6% versus 30.4% of patients completing 6 months with no flare and 56.9% versus 28.3% completing 12 months with no flare. Overall corticosteroid use was substantially lower in the pimecrolimus group: 63.7% versus 34.8% of patients did not use corticosteroids at all during the study. Pimecrolimus was also more effective than control treatment in the long-term control of pruritus and the signs of AD. There were no clinically significant differences in incidence of adverse events between the 2 treatment groups.\n Treatment with pimecrolimus of early signs and symptoms significantly modified the disease course in infants by reducing the incidence of flares and improving overall control of AD. Pimecrolimus was safe and well tolerated.",
"Topical coal tar is a well known and effective treatment for psoriasis, but the messiness, staining, odor, and inconvenience associated with its use make patient satisfaction and compliance a challenge.\n To determine the efficacy, patient tolerability, and cosmetic acceptability of a new topical liquor carbonis distillate (LCD) 15% solution compared with calcipotriene (calcipotriol) cream in patients with moderate, chronic plaque psoriasis.\n A randomized, single-blind, active-controlled, parallel-group, clinical trial consisting of a 12-week treatment phase and a 6-week post-treatment follow-up phase.\n Outpatient dermatology research unit in an academic hospital.\n Sixty adults with moderate, chronic plaque psoriasis (3-15% body surface area affected) not receiving other psoriasis therapies.\n Patients were randomized to apply either an LCD 15% solution (Psorent) or a commercially available calcipotriene 0.005% cream (Dovonex) to their psoriasis areas (excluding the head) twice daily at home for 12 weeks.\n A blinded investigator evaluated the patients' psoriasis using a modified Psoriasis Area and Severity Index (PASI) that excluded the head, and a Physician's Global Assessment (PGA) scale at weeks 0 (baseline), 2, 4, 8, and 12 (end of treatment), and 18 (6 weeks after treatment was withdrawn). Patients assessed their psoriasis symptoms and quality of life and completed a cosmetic acceptability survey about their medication.\n The changes in the baseline PASI scores after 12 weeks of treatment were compared between LCD and calcipotriene groups. Additional comparisons were performed for success rates during treatment (PASI 75 and PASI 50), changes in PGA scores, patient-reported psoriasis symptom scores, patients' quality-of-life scores, and recurrence rates during post-treatment follow-up.\n Both treatment groups showed improvement in psoriasis severity and quality of life. However, the LCD group had greater mean reductions in PASI scores: 58% vs 37% in the calcipotriene group (p < 0.05) at week 12. Additionally, the LCD group had more patients (14/27) with absent or minimal psoriasis on the PGA scale than the calcipotriene group (6/28) by the end of treatment (p < 0.05). LCD-treated patients also maintained their improvement better than calcipotriene-treated patients through week 18 after treatment was withdrawn for 6 weeks. Both treatments were well tolerated and cosmetically acceptable to patients.\n The newly formulated LCD solution, applied twice daily at home for 12 weeks, was more effective and as well tolerated and cosmetically acceptable as the calcipotriene cream over 12 weeks of treatment and 6 weeks of follow-up. The LCD solution is a patient-accepted and effective corticosteroid-sparing treatment alternative for psoriasis patients.",
"A double-blind, vehicle-controlled comparison of two glucocorticosteroid ointments demonstrated that once-daily therapy for psoriasis was effective. After 3 weeks of once-daily therapy, psoriasis subjects treated with betamethasone dipropionate (BD) ointment or diflorasone diacetate (DD) ointment showed statistically significant (p less than 0.01) improvement compared to subjects using vehicle alone.",
"Owing to its anti-inflammatory, antipruritic, vasoconstrictive, and immune-modulating properties, clobetasol propionate is used to treat psoriasis. This study was conducted to evaluate the efficacy, safety, and cosmetic acceptability of clobetasol propionate lotion compared with its vehicle and with clobetasol propionate cream in the treatment of moderate to severe plaque-type psoriasis. A total of 222 patients were treated. After 4 weeks of treatment, clobetasol propionate lotion was more efficient than vehicle lotion and of equivalent efficacy as clobetasol propionate cream. Cosmetic acceptability was significantly better with clobetasol propionate lotion than with clobetasol propionate cream. Clobetasol propionate lotion was efficient, safe, and well tolerated and offers a significantly higher cosmetic advantage in the treatment of moderate to severe plaque-type psoriasis compared with clobetasol propionate cream.",
"A double-blind, randomized clinical study was conducted to compare the efficacy and tolerability of twice-daily topical calcipotriol treatment with a combination treatment of calcipotriol once a day in the morning and diflucortolone valerate in the evening. Sixty-three patients with a clinical diagnosis of chronic plaque psoriasis and comparable psoriatic lesions on both sides of the body were included. After a washout phase of 1 week, psoriatic lesions were treated for 4 weeks with calcipotriol ointment twice daily on one side of the body and a combination of calcipotriol and diflucortolone valerate ointment on the other side. The treatment period was followed by a period of 4 weeks without any treatment. The psoriasis area and severity index (PASI) was used to compare the 2 groups. Furthermore, the overall therapeutic results were assessed independently by the investigators and by the patients. Both treatment regimens showed a significant, nearly identical, reduction in PASI. The mean PASI for calcipotriol alone was 5.7 at baseline, 1.9 after 4 weeks of treatment and 3.8 at the end of the follow-up period. For combination therapy, these values were 5.7, 1.8 and 3.8, respectively. There was a statistically significant advantage in favor of combined calcipotriol and diflucortolone valerate treatment at weeks 1 and 2 (p < 0.05); however, at the end of the treatment phase the difference between the 2 therapies was not significant. Subjective evaluation of efficacy by both the investigators and the patients revealed no difference between the 2 treatments. The frequency of side effects (e.g. irritation) was low in both groups. In conclusion, both therapies were effective for the treatment of chronic plaque-type psoriatic lesions. The combination of calcipotriol and a topical steroid appeared to produce a more rapid clinical response and was shown to be as effective as calcipotriol therapy alone.",
"Systemically administered sirolimus has demonstrated efficacy in psoriasis in a multicentre European study.\n To determine the efficacy and safety of topically applied sirolimus in treating psoriasis.\n In vitro studies were followed by a pilot study designed to determine if sirolimus penetrates human skin, and by a randomized, double-blind, left-right comparative, dose-ranging study consisting of treatment with 2.2% sirolimus for 6 weeks and 8% sirolimus for an additional 6 weeks in 24 patients with stable, chronic plaque psoriasis. The primary outcome measure was clinical score. Secondary measures were ultrasound plaque thickness, plaque erythema, and computerized image analysis of immunohistochemical stains for immunocytes and proliferating cells. Pharmacokinetics and blood chemistry monitoring for safety were also performed.\n A significant reduction in the clinical score (P = 0.03) (mean score 9.1 following sirolimus vs. 11.2 in control) was achieved with topical sirolimus. Measurements of plaque thickness and erythema did not show significant improvement with treatment. Computerized image analysis of biopsies showed a significant reduction in CD4+ cells (P = 0.0054) and proliferating cells (stained by Ki-67) in the epidermis (P = 0.0153) with sirolimus treatment compared with control.\n Topically applied sirolimus penetrates normal skin and may have some antipsoriatic and immunosuppressive activity.",
"The purpose of this double-blind, placebo-controlled study was to examine whether the vitamin D analogue calcipotriol, topically applied to psoriatic skin lesions, had any effect on calcium or bone metabolism. Thirty-four outpatients with psoriasis vulgaris were randomized to treatment with either calcipotriol ointment (50 micrograms/g) or vehicle ointment twice daily for 3 weeks. The patients were put on a calcium energy fixed diet and examined once weekly. The mean amount of calcipotriol ointment used was 40.3 g/week (range 8.2-95.4 g/week). The results of biochemical markers on calcium and bone metabolism showed no significant differences between the two groups. No correlation was found between the amount of ointment used and changes in parameters on calcium and bone metabolism during the 3-week treatment. It is concluded that calcipotriol ointment (50 micrograms/g), applied in doses of 8.2-95.4 g/week for 3 weeks to psoriatic skin lesions, has no effect on calcium or bone metabolism.",
"Becocalcidiol is a vitamin D(3) analogue which has not caused hypercalcaemia or significant irritation in preclinical trials.\n To evaluate the efficacy and safety of two dosing regimens of becocalcidiol ointment (low dose = 75 microg g(-1) once daily for 8 weeks; high dose = 75 microg g(-1) twice daily for 8 weeks) in the treatment of plaque-type psoriasis.\n One hundred and eighty-five subjects with chronic plaque-type psoriasis affecting 2-10% of their body surface area took part in a multicentre, double-blind, parallel-group, vehicle-controlled, randomized controlled trial comparing topical application of placebo, becocalcidiol 75 microg g(-1) once daily (low dose) or becocalcidiol twice daily (high dose) for 8 weeks. Main outcomes included Physician's Static Global Assessment of Overall Lesion Severity (PGA) score; Psoriasis Symptom Severity (PSS) score; adverse events; and laboratory assessment.\n In the intent-to-treat population at week 8, high-dose becocalcidiol was statistically superior to vehicle [P = 0.002; 95% confidence interval (CI) 6.7-32.2], with 16 of 61 (26%) subjects achieving a PGA score of clear or almost clear. Greater improvement in PSS score was seen with high-dose becocalcidiol than with vehicle, but this result did not quite achieve statistical significance (P = 0.052; 95% CI -16.2 to 0.1). In all groups, therapy was safe and well tolerated, with fewer subjects experiencing irritation than is reported in studies using calcipotriol.\n Treatment with high-dose topical becocalcidiol for 8 weeks led to almost or complete clearing of moderate plaque-type psoriasis in over a quarter of patients. Therapy was safe and well tolerated.",
"A double blind left, right comparative study was carried out in 17 psoriatic subjects to examine the influence of a topically applied inhibitor of nitric oxide (NO) synthesis on the pathogenic events of psoriasis. The inhibitor NG-monomethyl-L-arginine (L-NMMA) in aqueous cream BP was applied to one plaque while aqueous cream BP alone served as control. Compared with the control, the L-NMMA-treated side showed significant (77%) inhibition of NO production and a reduction in blood flow, confirming its bioavailability. L-NMMA significantly reduced staining for endothelial cells and intercellular adhesion molecule 1, while CD1a-positive Langerhans cells and CD8-positive suppressor cytotoxic T cells increased. CD4-positive lymphocytes and epidermal proliferation, as indicated by Ki-67 staining, were unaffected by this degree of inhibition of NO synthesis, and correspondingly significant clinical improvement was not found.",
"Topical vitamin D analogues have been reported to be an effective treatment in patients with psoriasis. Comparative studies with existing treatments are required.\n Our purpose was to compare the effectiveness of calcipotriol (50 micrograms/gm) and betamethasone 17-valerate (1 mg/gm) ointments twice daily in the treatment of stable plaque psoriasis.\n This study was a randomized, double-blind comparison over 6 weeks in 409 patients. Efficacy, as measured by the Psoriasis Area and Severity Index (PASI), and safety were assessed at 2, 4, and 6 weeks.\n Reduction of PASI was statistically significant at all time points for both treatments but there were no significant between-treatment differences. At the completion of 6 weeks of treatment, the mean PASI reduction was 5.50 for calcipotriol and 5.32 for betamethasone (95% confidence interval [CI] -0.40 to 0.78). Analysis of patient assessment at 6 weeks showed clearance or marked improvement in 61.2% of the calcipotriol patients and 50.5% with betamethasone (95% CI 1.4 to 20.8). Calcipotriol produced significantly more local side effects (19.5% compared with 3.9%, p less than 0.001); however, these were minimal leading to withdrawal in only 3 of 205 patients.\n Calcipotriol ointment was as effective as betamethasone 17-valerate ointment as measured by the PASI and superior as measured by self-assessment in patients with stable plaque psoriasis. Both treatments were well tolerated.",
"Pimecrolimus cream (SDZ ASM 981), a nonsteroid inhibitor of inflammatory cytokines, is effective in atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares.\n Early intervention with pimecrolimus was compared with a conventional AD treatment strategy (ie, emollients and topical corticosteroids). In this 1-year, controlled, double-blind study, 713 AD patients (2-17 years) were randomized 2:1 to a pimecrolimus-based or conventional regimen. Both groups used emollients for dry skin. Early AD signs/symptoms were treated with pimecrolimus cream or, in the conventional treatment group, vehicle to prevent progression to flares. If flares occurred, moderately potent topical corticosteroids were mandated. The primary efficacy endpoint was ranked flares at 6 months. Safety was monitored clinically, and a skin recall-antigen test was performed at study completion.\n BASELINE CHARACTERISTICS OF THE PATIENTS: The mean age for both groups was approximately 8 years, and the majority of patients had moderate disease at baseline. PATIENT FOLLOW-UP AND EXPOSURE TO STUDY MEDICATION: The mean duration of follow-up (+/-standard error) was 303.7 (+/-5.30) days in the pimecrolimus group and 235.2 (+/-9.40) days in the control group. The discontinuation rate was significantly higher in the control group than in the pimecrolimus group (51.5% vs 31.6% at 12 months), and proportionately more patients with severe or very severe disease discontinued in the control group. The main reason for the higher discontinuation rate in the control group was unsatisfactory therapeutic effect (30.4% vs 12.4%). This resulted in a substantially higher mean number of study medication treatment days in the pimecrolimus group compared with the control group: 211.9 (69.8% of study days) versus 156.0 (66.3% of study days). Of those patients who completed 12 months on study, 14.2% and 7.0% of patients in the pimecrolimus and vehicle groups, respectively, used study medication continuously.\n Patients in the pimecrolimus group experienced significantly fewer AD flares than those in the control group, according to the primary efficacy analysis on ranked flares of AD (Van Elteren test). The proportion of patients who completed 6 or 12 months with no flares was approximately twice as high in the pimecrolimus group compared with control (61.0% vs 34.2% at 6 months; 50.8% vs 28.3% at 12 months). Fewer flares were observed in the pimecrolimus group regardless of baseline disease severity, so even severe patients derived benefit from the treatment. The analysis of time to first flare showed that treatment with pimecrolimus was associated with a significantly longer flare-free period (log- rank test). Covariate analysis indicated a statistically significant effect on time to first flare of baseline Eczema Area and Severity Index score, and whether patients had \"severe\" or \"very severe\" disease at baseline according to the Investigators' Global Assessment, although patients in all baseline disease severity subgroups benefited from treatment. Age had no significant effect. Fewer patients in the pimecrolimus group required topical corticosteroid therapy compared with control (35.0% vs 62.9% at 6 months; 42.6% vs 68.4% at 12 months), and patients in the pimecrolimus group spent fewer days on topical corticosteroid therapy (57.4% vs 31.6% [pimecrolimus vs control, respectively] spent 0 days on topical corticosteroid therapy, 17.1% vs 27.5% 1-14 days, and 25.5% vs 41.0% >14 days over the 12 months of the study). This steroid-sparing effect of pimecrolimus was evident despite pimecrolimus-treated patients being on study longer than patients in the control group. The average proportion of study days spent on second-line corticosteroids was 4.08% in the pimecrolimus group and 9.10% in the control group. Analysis of Eczema Area and Severity Index over time showed significantly lower median scores, thus indicating better disease control in the pimecrolimus group compared with the control group. Similar results were obtained from analysis of the Investigators' Global Assessment (not shown). The treatment groups were well balanced with respect to the number of patients using antihistamines during the study (57.2% vs 62.9%, pimecrolimus vs control, respectively).\n There were no appreciable differences between treatment groups in the overall incidence of adverse events. The most frequent adverse events were common childhood infections and ailments, including nasopharyngitis, headache, and cough. The incidence of suspected drug-related adverse events was not significantly different in the pimecrolimus group (24.7% vs 18.7%--pimecrolimus vs control), and the incidence of serious adverse events was low (8.3% vs 5.2%--pimecrolimus vs control). Life-table analysis of incidence of adverse events revealed no significant differences between the treatment groups, except for cough. Local tolerability was good in both treatment groups. The most common application site reaction reported was sensation of burning (10.5% vs 9.3%--pimecrolimus vs control). There were no major differences between treatment groups in the duration or severity of application site reactions, most of which were mild-to-moderate and transient, occurring within the first week of treatment. Skin infections were reported in both groups. There were no between-group differences in the life-table analysis of time to first occurrence of bacterial skin infections nor in the adjusted incidence of bacterial skin infections. Although there were no significant differences between treatment groups in the incidence of individual viral skin infections, the incidence of grouped viral skin infections (12.4% vs 6.3%--pimecrolimus vs control) showed a slightly higher incidence in the pimecrolimus group. Laboratory values and vital signs showed no significant between-group differences. There were no significant differences between treatment groups in response to recall antigens in those patients who remained on study for 12 months.\n Treatment of early AD signs/symptoms with pimecrolimus was effective in preventing progression to flares in more than half the patients, reducing or eliminating the need for topical corticosteroids. The benefits were consistently seen at 6 months across important disease severity subgroups and with respect to the various predefined efficacy endpoints. Furthermore, these benefits were sustained for 12 months, providing evidence that long-term treatment with pimecrolimus leads to better control of AD. Treatment with pimecrolimus was well tolerated and was not associated with clinically relevant adverse events compared with the conventional treatment group. The results reported here offer the prospect of effective long-term management of AD with reduced need for topical corticosteroids.",
"This randomized, double-blind, multi-centre study compared the long-term safety and tolerability of pimecrolimus cream 1% and topical corticosteroids (TCS) in 658 adults with moderate-severe atopic dermatitis (AD).\n Patients applied either pimecrolimus or TCS (i.e. 0.1% triamcinolone acetonide cream and/or 1% hydrocortisone acetate cream) twice daily to all affected areas until complete clearance or for up to 1 year. The study was approved by the institutional review board or ethics committee at each centre.\n A majority of patients treated with either pimecrolimus or TCS used the drug on a continuous basis over 1 year. In patients who had >30% of the body surface involved by AD, the incidence rate of all skin infections was significantly lower in the pimecrolimus group than in the TCS group (95% CI of the treatment difference: -25.3% to -3.4%). The most frequent application site reaction was burning (25.9% of patients on pimecrolimus and 10.9% on TCS), which was transient and mild-moderate in most cases. Three TCS-treated patients reported skin striae. There were no treatment-related serious or clinically significant systemic adverse events. Efficacy was better in patients on continuous TCS therapy, although patients completing the study were similarly well-controlled in both groups. About 42% of the pimecrolimus-treated patients were maintained for 1 year without TCS.\n Pimecrolimus demonstrated a favourable safety profile when used to treat adult patients with moderate-severe AD for up to 1 year. A significant proportion of patients could be maintained without TCS for a year.",
"Topical therapy providing initial improvement and maintenance of effect after treatment of the large majority of patients with limited, mild to moderate psoriasis is not presently available. Previous topical retinoids have generally been either ineffective or too irritating for therapy of psoriasis.\n Our purpose was to evaluate a new topical retinoid, tazarotene, in the treatment of stable plaque psoriasis during treatment and posttreatment periods.\n In a double-blind manner, 324 patients were randomly selected to receive tazarotene 0.1% or 0.05% gel, or vehicle control, once daily for 12 weeks and were then followed up for 12 weeks after treatment.\n Of the total, 318 patients could be evaluated. Tazarotene gels were superior (p < 0.05) to vehicle, often as early as treatment week 1, in all efficacy measures: plaque elevation, scaling, and erythema; treatment response; percentage treatment success (patients with > or = 50% improvement); and time to initial success. Efficacy was equivalent on target lesion sites (trunk or limbs and knees or elbows) and overall. A sustained therapeutic effect was observed for 12 weeks after treatment. Tazarotene gel was cosmetically acceptable. There was low systemic absorption, limiting toxicity to local irritation.\n Once-daily tazarotene was effective and safe as a topical monotherapy for plaque psoriasis, providing rapid reduction of signs and symptoms.",
"The biologically active form of vitamin D3, calcitriol, may offer a new therapeutic approach to psoriasis. Calcipotriol, a new vitamin D3 analogue, is at least 100 times less calcemic than calcitriol.\n Our purpose was to study the efficacy and safety of calcipotriol in the treatment of psoriasis vulgaris.\n In a right/left comparative, double-blind study, treatment with calcipotriol ointment (50 micrograms/gm) twice daily and placebo was given for 4 weeks. The preferred treatment was continued, without opening the code, for another 4 weeks. Efficacy, as measured by the Psoriasis Area and Severity Index and by the investigator's and patient's global assessment, and safety were assessed every 2 weeks.\n The mean Psoriasis Area and Severity Index fell in 4 weeks from 14.2 to 6.3 with calcipotriol and from 14.1 to 9.2 with placebo (p < 0.001; 95% confidence interval for difference: 1.78-->3.94). Local side effects were equally common with calcipotriol and placebo. The mean serum calcium remained unchanged.\n Topical application of up to 50 gm of calcipotriol ointment per week was found to be an effective and safe treatment of psoriasis vulgaris.",
"Although topical vitamin D3 derivatives have been used in the treatment of patients with psoriasis for the past 15 years, questions remain about the indications and limitations of application. Extensive personal experience gained during the development of calcitriol (1alpha25-dihydroxyvitamin D3) is therefore reviewed. Three double-blind, vehicle-controlled trials have revealed that calcitriol 3 microg g(-1) ointment (Silkis ointment, Galderma Laboratories) has very good clinical efficacy. In a left-right comparison with vehicle ointment, complete clearance of psoriatic lesions was achieved in 48% of sites treated with calcitriol and a further 41% showed considerable or definite improvement. The clinical response to calcitriol in another study was as good as, or even better than, that achieved with betamethasone valerate 0.1% ointment. A preparation containing calcitriol 15 microg g(-1) did not show any clinical superiority to the lower dose but was associated with a higher risk of hypercalciuria, particularly when applied to extensive skin lesions. These results suggest that calcitriol 3 microg g(-1) ointment is an effective and safe treatment for chronic plaque psoriasis.",
"A two-compound ointment containing calcipotriol 50 micro g g-1 and betamethasone dipropionate 0.5 mg g-1 has recently been shown to be an effective treatment for psoriasis.\n This study was designed to investigate efficacy and safety of different treatment regimens with the two-compound product (Daivobet/Dovobet; LEO Pharma, Ballerup, Denmark) and calcipotriol 50 micro g g-1 ointment (Daivonex/Dovonex; LEO Pharma).\n In total, 972 patients with psoriasis vulgaris were randomized to one of three treatment regimens: group 1, the two-compound product once daily for 8 weeks followed by calcipotriol ointment once daily for 4 weeks; group 2, the two-compound product once daily for 4 weeks followed by 8 weeks of treatment with calcipotriol ointment once daily on weekdays and the two-compound product once daily at weekends; and group 3, calcipotriol ointment twice daily for 12 weeks. The efficacy was evaluated by Psoriasis Area and Severity Index (PASI) and investigators' global assessments of disease severity. The primary response criteria were percentage reduction in PASI and proportion of patients with absent/very mild disease according to the investigators' global assessments after 8 weeks of treatment.\n The mean reduction in PASI from baseline to the end of 8 weeks of treatment was 73.3% for group 1, 68.2% for group 2 and 64.1% for group 3. The proportion of patients with absent/very mild disease at the end of 8 weeks of treatment was 55.3% for group 1, 47.7% for group 2 and 40.7% for group 3. For both primary response criteria, group 1 was statistically superior to group 3 (P < 0.001), whereas group 2 did not differ significantly from group 3. The difference between group 1 and group 2 was statistically significant with regard to PASI but not regarding the proportion of patients with absent/very mild disease. Patients receiving initial therapy with the two-compound product achieved the fastest treatment response, and the maximum treatment effect for these patients was seen after 5 weeks. This effect was maintained with continued treatment with the two-compound product for up to 8 weeks. After 12 weeks of treatment, no significant differences were seen between the three groups with regard to reduction in PASI, whereas the proportion of patients with absent/very mild disease in group 2 was superior to that in group 3. Patients receiving therapy with the two-compound product experienced fewer lesional/perilesional adverse drug reactions than the calcipotriol-treated patients (P < 0.001): 10.9% in group 1, 11.5% in group 2 and 22.3% in group 3.\n Two different short-term treatment regimens employing a recently developed two-compound product (calcipotriol/betamethasone dipropionate) provided rapid and marked clinical efficacy and were shown to be safe therapies for psoriasis vulgaris.",
"Psoriasis is a chronic skin disorder affecting approximately 2% of the US population. Psoriasis may occur anywhere on the body with initial presentation usually seen between 15 and 30 years of age. Calcitriol 3 microg/g ointment has demonstrated good clinical efficacy as well as topical and systemic safety when used to treat psoriasis.\n To confirm the efficacy and safety of calcitriol 3 microg/g ointment versus its vehicle in the treatment of subjects with mild to moderate chronic plaque psoriasis.\n Suitable subjects were randomized to receive either calcitriol 3 microg/g ointment or its vehicle twice daily for up to 8 weeks in 2 multicenter, randomized, vehicle-controlled, double-blind parallel group studies. Efficacy was evaluated through a Global Severity Score dichotomized in success (clear and minimal) or failure. Erythema, plaque elevation, scaling and dermatologic sum score (sum of the scores for erythema, plaque elevation, and scaling), pruritus, and global improvement were also assessed. Routine safety and clinical laboratory parameters, including calcium homeostasis, were evaluated throughout the study.\n In total, 839 subjects were included in the 2 studies: 419 patients received calcitriol 3 microg/g ointment and 420 received the vehicle. In both studies, calcitriol 3 microg/g ointment was shown to be significantly more effective than its vehicle, with onset of therapeutic effect seen as early as week 2 and sustained at all subsequent visits. Calcitriol 3 microg/g ointment demonstrated good systemic and local safety profile comparable to its vehicle with no effect on calcium homeostasis.\n Calcitriol 3 microg/g ointment applied for 8 weeks is effective and safe in the treatment of mild to moderate psoriasis.",
"Topical calcipotriene is frequently prescribed for the treatment of plaque-type psoriasis. Calcipotriene is currently available in the US as an ointment, a solution, a cream, and in a fixed-dose combination ointment with betamethasone dipropionate. Calcipotriene 0.005% has recently been formulated as a foam using a novel aqueous-based formulation to provide a new topical treatment option for patients with psoriasis.\n The objective of this study was to evaluate the efficacy and safety of topical calcipotriene 0.005% foam for the treatment of mild to moderate plaque-type psoriasis.\n Two identical, randomized, double-blind, vehicle-controlled, 8-week phase III clinical trials.\n Subjects with plaque-type psoriasis affecting 2-20% of the body surface area, with an identifiable target lesion affecting the trunk or extremities, were randomized in a 2:1 ratio to calcipotriene foam (n = 437) or vehicle foam (n = 222). Study medication was applied twice daily for 8 weeks.\n Treatment success was defined as a score of 0 or 1 (clear or almost clear) on the Investigator's Static Global Assessment (ISGA) psoriasis rating scale and a minimum improvement of ISGA score of at least 2 grades from baseline. Predefined target lesions were assessed for erythema, scaling, and plaque thickness. Primary endpoint was the proportion of subjects in each treatment group who achieved treatment success after 8 weeks, analyzed on an intent-to-treat (ITT) basis. In the primary endpoint analysis, subjects missing 8-week outcomes data were classified as treatment failures regardless of their outcomes at earlier evaluations. As part of the sensitivity analysis, a last-observation-carried-forward (LOCF) approach to impute missing 8-week efficacy outcomes also examined treatment. Secondary endpoints included treatment success as a function of baseline ISGA score (mild or moderate), ISGA score of 0 or 1 (clear or almost clear), and effects of treatment on target lesion. Adverse events (AEs) were recorded throughout the study.\n In the ITT population of Study 1, treatment success after 8 weeks was achieved by 14% of subjects in the calcipotriene foam group versus 7% of subjects in the vehicle foam group (p = 0.058). In the LOCF analysis, treatment success was achieved by more subjects with calcipotriene foam than with vehicle foam (15% vs 7%; p = 0.034). In Study 2, treatment success was achieved by more subjects in the calcipotriene foam group for the primary endpoint (27% vs 16%; p = 0.016) and the LOCF analysis (28% vs 16%; p = 0.010). Subjects in the calcipotriene foam group exhibited better response rates than did the vehicle foam group for most of the secondary outcomes. Calcipotriene foam was safe with an overall incidence of AEs similar to those experienced in the vehicle foam group. Application-site reactions were noted in approximately 1-2% of subjects in each group. No AE was reported in more than 2% of subjects in the calcipotriene foam group. Treatment was discontinued because of AEs in approximately 2% of subjects in both groups.\n In two identically designed, phase III clinical trials, calcipotriene 0.005% foam was safe and effective for the treatment of mild to moderate plaque-type psoriasis for up to 8 weeks. Clinical Trial Registration: Registered at clinicaltrials.gov: NCT00688519 and NCT00689481.",
"nan",
"The purpose of this double-blind, placebo-controlled study was to evaluate the clinical efficacy and tolerability of topical Aloe vera extract 0.5% in a hydrophilic cream to cure patients with psoriasis vulgaris. Sixty patients (36M/24F) aged 18-50 years (mean 25.6) with slight to moderate chronic plaque-type psoriasis and PASI (Psoriasis Area and Severity Index) scores between 4.8 and 16.7 (mean 9.3) were enrolled and randomized to two parallel groups. The mean duration of the disease prior to enrollment was 8.5 years (range 1-21). Patients were provided with a precoded 100g tube, placebo or active (with 0.5% Aloe vera extract), and they self-administered trial medication topically (without occlusion) at home 3 times daily for 5 consecutive days per week (maximum 4 weeks active treatment). Patients were examined on a weekly basis and those showing a progressive reduction of lesions, desquamation followed by decreased erythema, infiltration and lowered PASI score were considered healed. The study was scheduled for 16 weeks with 12 months of follow-up on a monthly basis. The treatment was well tolerated by all the patients, with no adverse drug-related symptoms and no dropouts. By the end of the study, the Aloe vera extract cream had cured 25/30 patients (83.3%) compared to the placebo cure rate of 2/30 (6.6%) (P < 0.001) resulting in significant clearing of the psoriatic plaques (328/396 (82.8%) vs placebo 28/366 (7.7%), P < 0.001) and a decreased PASI score to a mean of 2.2. The findings of this study suggest that topically applied Aloe vera extract 0.5% in a hydrophilic cream is more effective than placebo, and has not shown toxic or any other objective side-effects. Therefore, the regimen can be considered a safe and alternative treatment to cure patients suffering from psoriasis.",
"We set out to show that the assumption is incorrect that continuous treatment with cyclosporin is necessary in psoriasis, as this tenet forms a basis for current recommended treatment regimens. Sixty patients with mild to moderate plaque psoriasis were allocated at random to treatment with oral cyclosporin 5 mg/kg/day (30 patients) or topical dithranol and ultraviolet B therapy (30 patients) for up to 16 weeks until clear (median time 6 weeks cyclosporin and 8 dithranol), and the times to relapse compared. The patients were seen monthly for up to 8 months, and the severity and the extent of psoriasis were assessed. Relapse, defined as return of psoriasis to 50% of the area at the start of the trial or patient demand for further treatment, was not significantly different between the groups (hazard ratio 1.11, 95% CI 0.55-2.32). No patients suffered a rebound of severe disease and none relapsed in the first 8 weeks after stopping treatment. The relapse rate was higher following cyclosporin from 8 to 28 weeks after treatment and following dithranol from 28 to 34 weeks. The patients with arthritis had a higher median joint severity score at relapse than prior to treatment with cyclosporin. At the end of 8 months, 5 patients treated with dithranol and 8 patients with cyclosporin remained clear, 75% and 67% having relapsed. We conclude that rapid relapse does not occur after clearance of mild to moderate plaque psoriasis with cyclosporin and the relapse rate was no different from dithranol treatment.",
"Treatment of psoriatic nail is difficult.\n The aim of this study was to evaluate and compare the efficacy and safety of methotrexate and cyclosporine in psoriatic nail.\n Thirty-seven psoriatic patients with nail involvement were randomized to treatment with methotrexate (initial dose, 15 mg per week) or cyclosporine (initial dose, 5 mg per kg of bodyweight per day) for 24 weeks. The primary outcome was the Nail Psoriasis Severity Index (NAPSI). The Psoriasis Area and Severity Index (PASI), doctor and patient global score were also measured. The scores were determined by a blinded observer.\n Seventeen patients completed the study in each group. The mean percentages of reduction of the NAPSI score after methotrexate and cyclosporine treatments were 43.3% and 37.2%, respectively. No significant differences between the treatment groups was found for in the NAPSI, PASI, physician's and patient's global score at the end of the study period. The methotrexate group showed a significant improvement in nail matrix scores and the cyclosporine group in nail bed score.\n Moderate effectiveness on psoriatic nail was found in the two treatment agents and there were no significant differences in efficacy between the groups. A significant improvement was detected in methotrexate group for the nail matrix findings, and in cyclosporine group for the nail bed findings.\n © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.",
"To determine the efficacy of topical ascorbic acid application in treating mild to moderate photodamage of facial skin using an objective, computer-assisted image analysis of skin surface topography and subjective clinical, photographic, and patient self-appraisal questionnaires.\n A 3-month, randomized, double-blind, vehicle-controlled study.\n Facial plastic surgery private practice.\n Nineteen evaluable volunteer sample patients aged between 36 and 72 years with Fitzpatrick skin types I, II, and III who were in good physical and mental health with mild to moderately photodamaged facial skin were considered for analysis.\n Coded, unmarked medications were randomly assigned to the left and right sides of each subject's face, one containing the active agent, topical ascorbic acid (Cellex-C high-potency serum; Cellex-C International, Toronto, Ontario), the other, the vehicle serum (Cellex-C International). Three drops (0.5 mL) of each formulation were applied daily to the randomly assigned hemifaces over the 3-month study period. Treatment assignments were not disclosed to subjects, clinicians, or personnel involved in analyzing skin replicas.\n Specific clinical parameters were evaluated and graded on a 0- to 9-point scale (0, none; 1-3, mild; 4-6, moderate; and 7-9, severe). Reference photographs were used to standardize grading criteria. Overall investigator scores were compared with baseline and graded as excellent (much improved), good (improved), fair (slightly improved), no change, or worse. Patient self-appraisal questionnaires rated the degree of improvement (much improved, improved, slightly improved, no change, or worse) and reported adverse effects (burning, stinging, redness, peeling, dryness, discoloration, itching, and rash). Standard photographs were taken at baseline, including anteroposterior and left and right oblique views to facilitate subsequent clinical evaluations, and at the end of therapy for comparison. Optical profilometry analysis was performed on the skin surface replicas of the lateral canthal (crow's feet) region, comparing baseline to end-of-study specimens. Using this computer-based system, the resulting image was digitally analyzed, and numeric values were assigned to reflect surface features. The parameters obtained included Rz, Ra, and shadows. These values provided objective data that document pretreatment and posttreatment texture changes proportional to the degree of wrinkling, roughness, and other surface irregularities.\n Optical profilometry image analysis demonstrated a statistically significant 73.7% improvement in the Ra and shadows north-south facial axis values with active treatment greater than vehicle control, as well as a trend for improvement in the Rz north-south facial axis parameter, showing a 68.4% greater improvement of active treatment vs vehicle control. Clinical assessment demonstrated significant improvement with active treatment greater than control for fine wrinkling, tactile roughness, coarse rhytids, skin laxity/tone, sallowness/yellowing, and overall features. Patient questionnaire results demonstrated statistically significant improvement overall, active treatment 84.2% greater than control. Photographic assessment demonstrated significant improvement, active treatment 57.9% greater than control.\n A 3-month daily regimen of topical ascorbic acid provided objective and subjective improvement in photodamaged facial skin. Skin replica optical profilometry is an objective method for quantification of the skin surface texture changes.",
"Plaque-type psoriasis has been successfully treated with topical calcitriol, but there has been no long-term follow-up study of the safety and efficacy of this calciotropic hormone. In a single-centre study, patients with plaque or erythrodermic psoriasis were enrolled in a double-blind, right/left comparison, placebo-controlled study, and received 1.5 micrograms of calcitriol (15 micrograms/g of Vaseline) per day, or a placebo consisting of Vaseline alone. A subset of these patients (n = 22), with at least 25% involvement, applied 0.1 g of calcitriol ointment/50 cm2 on an area of from 2,500 to 5,000 cm2. Of the 84 patients enrolled in the double-blind control study, 96.5% responded to topical calcitriol therapy, compared with 15.5% whose lesions improved with Vaseline alone, after 2.4 months. After completion of the double-blind study, 22 patients applied calcitriol ointment (15 micrograms/g Vaseline) to all of their lesions (up to 10 g of calcitriol ointment; 150 micrograms calcitriol lesions showed either excellent or moderate clearing in 90.9% of all cases. The remaining 9.1% of cases showed slight improvement of their lesions. No abnormalities in calcium metabolism were noted in any of the patients using topical calcitriol. None of the patients experienced any local cutaneous side-effects, including six patients who applied calcitriol ointment to the face. Topical calcitriol is safe and effective for the treatment of psoriasis.",
"In a double-blind left-right randomised comparison, 27 patients suffering from chronic plaque-type psoriasis vulgaris were treated for one minute with dithranol 2% ointment, Psoralon (Psoralon MT), on a selected psoriasis plaque on one half of the body and with a placebo ointment on a corresponding plaque on the other. The preparations were applied once daily for 8 weeks. Seventeen patients achieved clearing or considerable improvement with dithranol therapy, as compared with 6 patients with placebo (p = 0.002). Erythema, infiltration, scaling, pruritus and the overall result were assessed. Statistically significant differences in favour of dithranol treatment were seen for all five variables, except for pruritus. The average of these five variables, designated the mean score, was also analysed; dithranol was seen to yield significantly better results (p = 0.001). Staining of clothes and the bathroom was noted by 3 and 5 patients, respectively, but no medical side effects were seen.",
"The antipsoriatic efficacy, tolerability and safety of calcipotriol ointment was compared with tar in a prospective, right/left randomized, investigator-blinded controlled study. Calcipotriol ointment 50 micrograms/g twice daily was applied to one-half of the body. On the opposite side, white soft paraffin was applied in the morning, and coal tar solution BP 15% v/w in aqueous cream in the evening. Thirty patients with stable chronic plaque-type psoriasis were recruited. Assessments were made at 2, 4 and 6 weeks. Three patients were withdrawn from the study. A decrease in PASI score was seen on both sides at 2, 4 and 6 weeks. The differences from baseline between the two treatments were statistically significant in favour of calcipotriol. Improvement with calcipotriol was rapid in the first 2 weeks of treatment. With tar, significant improvement occurred only after 4 weeks of treatment. The differences in the scores for erythema, induration and desquamation from baseline between the two treatments were also statistically significantly in favour of calcipotriol at all evaluation points. Seven patients developed irritation on the calcipotriol-treated side, but there were no adverse effects on the tar-treated side. In two patients, itching associated with psoriasis was reduced by the calcipotriol. Although the mean serum calcium and phosphate levels remained within the normal ranges after 6 weeks' treatment, there were significant changes in their values compared with baseline.",
"The calcipotriol/betamethasone dipropionate two-compound product is safe and effective in the short-term treatment of psoriasis.\n The primary objective was to investigate the safety of two treatment regimens involving use of the two-compound product over 52 weeks. The efficacy results are presented here.\n Six hundred and thirty-four patients were randomised double-blind to treatment (once daily, when required) with either: 52 weeks of two-compound product (two-compound group), 52 weeks of alternating 4-week periods of two-compound product and calcipotriol (alternating group), or 4 weeks of two-compound product followed by 48 weeks of calcipotriol (calcipotriol group).\n There was a trend towards a difference between treatments from the overall treatment effect for the percentage of satisfactory responses for each patient during the study (p = 0.071). This appeared to be due to the comparison of the two-compound and calcipotriol groups (p = 0.025).\n There was a trend towards the efficacy of the two-compound product used for up to 52 weeks being better than that of 4 weeks of the two-compound product followed by 48 weeks of calcipotriol.\n Copyright (c) 2006 S. Karger AG, Basel.",
"This phase 2/3, double-blind, placebo-controlled study was designed to assess the safety and efficacy of ustekinumab in Japanese patients with moderate-to-severe plaque-type psoriasis. Overall, 158 patients were randomized to receive ustekinumab 45 or 90 mg at weeks 0, 4, and every 12 weeks, or placebo with cross-over to ustekinumab at week 12. The primary end-point was the proportion of patients achieving at least 75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 12. Physician's Global Assessment (PGA), Dermatology Life Quality Index (DLQI), Nail Psoriasis Severity Index and joint pain Visual Analog Scale (VAS) were also measured. At week 12, 59.4% and 67.7% of ustekinumab 45 and 90 mg patients achieved PASI 75, respectively, compared with 6.5% in the placebo group (P < 0.0001 each). PASI 75 responses were maintained through week 64 in 65.0% and 78.6% of the ustekinumab-treated patients, respectively. Placebo cross-over patients had similar responses to ustekinumab-treated patients. Significant improvements in PGA, DLQI and VAS scores were observed at week 12 and generally maintained over time. Adverse events during the placebo-controlled period were similar among groups (45 mg, 65.6%; 90 mg, 59.7%; placebo, 65.6%). Serious adverse events were observed in 0%, 4.8% and 6.3% of patients, respectively. Through week 72, similar rates and types of adverse events and serious adverse events were reported in patients receiving 45 and 90 mg. Rates of injection site reactions and antibodies to ustekinumab were low. Ustekinumab was efficacious and generally well-tolerated in Japanese patients with moderate-to-severe plaque-type psoriasis through 72 weeks. These results are consistent with those reported in the global, phase 3 studies.\n © 2011 Japanese Dermatological Association.",
"Although betamethasone valerate (BMV) foam, 0.12% (Luxiq, Connectics Corporation, Palo Alto, CA) is approved by the Food and Drug Administration for the treatment of corticosteroid-responsive scalp dermatoses, no data are available for its use on nonscalp psoriasis.\n We evaluated the safety and efficacy of BMV foam in treating psoriatic lesions at nonscalp sites.\n We conducted a randomized, double-blind, placebo-controlled, paired-comparison, split-body study of 40 patients with mild to moderate plaque-type psoriasis. Patients applied BMV foam and placebo foam twice daily for 12 weeks.\n At the end of the treatment period, 70% of patients had greater than 50% improvement of lesions on their active foam-treated side compared with 24% of patients with similar improvement on their placebo foam-treated side. Adverse effects were limited to temporary stinging, burning, or itching in several patients. Three patients (7.5%) withdrew because of stinging or itching.\n The results indicate that BMV foam is effective against nonscalp psoriasis. Twice-daily applications are well tolerated, compliance exceeds 90%, cosmetic characteristics are acceptable, and the medication may reduce the need for multiple prescriptions.",
"Topical corticosteroids and calcipotriol have been used separately for many years to treat psoriasis. A new combination ointment has been formulated, which contains both calcipotriol and the corticosteroid betamethasone dipropionate.\n To compare the combination ointment with betamethasone dipropionate ointment, calcipotriol ointment and ointment vehicle in patients with psoriasis vulgaris.\n 1,603 patients were randomised to one of the 4 double-blind treatments used once daily for 4 weeks.\n The mean percentage change in the PASI at the end of treatment was -71.3 (combination), -57.2 (betamethasone), -46.1 (calcipotriol) and -22.7 (vehicle). The mean difference of combination minus betamethasone was -14.2 (95% CI: -17.6 to -10.8, p < 0.001), of combination minus calcipotriol -25.3 (95% CI: -28.7 to -21.9, p < 0.001) and of combination minus vehicle -48.3 (95% CI: -53.2 to -43.4, p < 0.001). 6.0% of patients (combination) reported local adverse reactions compared to 4.9% (betamethasone), 11.4% (calcipotriol) and 13.6% (vehicle).\n Calcipotriol/betamethasone dipropionate combination ointment used once daily is well tolerated and more effective than either active constituent used alone.\n Copyright 2002 S. Karger AG, Basel",
"Calcipotriene is a synthetic analogue of 1,25-dihydroxyvitamin D3 established to be effective topically in the treatment of psoriasis. We investigated the early cellular and immunological events induced by calcipotriene in psoriasis. Thirty patients with moderate plaque-type psoriasis were randomly assigned to receive twice daily applications of either calcipotriene ointment 0.005% or matching vehicle for 6 weeks. Skin biopsies (6 mm) were performed from designated plaques at baseline and days 3 and 7. On these days and at weeks 2, 4 and 6, complete clinical evaluations were made in a double-blind fashion. Consistent with previous studies, significant clinical improvement (P < 0.05) in psoriasis was observed in patients receiving calcipotriene vs. those receiving vehicle by day 7 for scale and erythema, and by day 14 for thickness. No significant improvement, however, was seen on day 3. None of the immunohistological markers (CD1a, CD4, CD8, ICAM-1, VCAM-1, E-selectin, HLA-DR) semiquantitatively assessed in psoriatic plaques was significantly changed by calcipotriene treatment for 7 days. In the calcipotriene-treated group, interleukin (IL)-10 levels (pg/microgram of protein) increased by 57% from baseline (0.030 +/- 0.006; mean +/- SEM) to day 3 (0.047 +/- 0.011) (P = 0.05 vs. baseline; n = 10) and remained elevated at day 7 (0.046 +/- 0.012). IL-8 levels (pg/microgram of protein), however, declined by 70% from baseline (0.13 +/- 0.06) to day 3 (0.04 +/- 0.01), and remained low at day 7 (0.03 +/- 0.02) (P < 0.05 vs. baseline; n = 10). Both IL-8 and IL-10 were unaffected by vehicle treatment. Calcipotriene-induced clinical improvement of psoriasis is preceded by an increase in IL-10 and a concomitant decrease in IL-8 levels. The changes in the level of these two cytokines provide further evidence for immunological changes as a significant part of the mechanism of action of calcipotriene in psoriasis.",
"The efficacy and safety of clobetasol propionate 0.05% scalp application was evaluated in 378 patients with moderate to severe scalp psoriasis in a double-blind vehicle-controlled parallel group study. After 2 weeks of twice-daily applications, 81% receiving active drug versus 22% receiving vehicle had clearing of 50% or greater. Complete clearing was seen in 26% with active drug and 1% with vehicle. Local side effects were primarily burning or stinging in 11% and 10% of patients treated on an active or a vehicle regimen, respectively. The morning cortisol levels of 168 patients were checked at baseline and again after 2 weeks of drug therapy. Subnormal morning plasma cortisol values were seen in 5% of the patients receiving active drug and in 5% receiving vehicle; 13% of those taking active drug versus 5% taking vehicle had a 50% or greater decrease in morning cortisol at the 2-week visit compared with baseline values. Clobetasol propionate 0.05% scalp application appears to be a safe and an effective treatment for scalp psoriasis.",
"Fifty patients with symmetrical, bilateral lesions of psoriasis, eczematous dermatitis, atopic dermatitis, or neurodermatitis participated in a double-blind paired comparison study in which 0-1% halcinonide (in a cream formulation containing also neomycin and nystatin) was applied to the lesions on one side of the body and 1% hydrocortisone cream to those on the opposite side for two to three weeks. The number of excellent responses to therapy showed the halcinonide combination to be significantly superior (p less than 0-01) to the control cream in all diagnostic categories if considered collectively, and in psoriasis if the responses were grouped according to diagnosis. No adverse reactions occurred during the trial.",
"A two-compound ointment containing calcipotriol plus betamethasone dipropionate is an effective treatment for psoriasis vulgaris. The same active ingredients have now been combined in a gel formulation. Our objective was to compare the efficacy and safety of once daily treatment of the two-compound gel with the single components in the same gel vehicle and the gel vehicle alone, in patients with psoriasis vulgaris on the trunk and/or limbs. 364 patients received once daily treatment for up to 8 weeks with either the two-compound gel, the single components in the gel vehicle or the gel vehicle alone. The percentage of patients whose disease was clear or very mild and who had at least a two-step improvement in the Investigator's Global Assessment of disease severity at week 8, was significantly higher with calcipotriol plus betamethasone dipropionate (27.2%) than with betamethasone dipropionate (16.9%, p = 0.027), calcipotriol (11.4%, p = 0.006) or gel vehicle (0.0%, p < 0.001). This exploratory study showed that the two-compound gel was safe and more efficacious than its individual ingredients in the treatment of psoriasis vulgaris.",
"Superpotent topical corticosteroids (CS) have been demonstrated to improve bullous pemphigoid (BP) patients' survival. We assessed whether a mild regimen using lower doses of topical CS and a shorter duration could improve the outcome of BP patients even more. Three-hundred and twelve BP patients were included in a multicenter randomized controlled trial and stratified depending on the extent of BP as moderate (n=134) or extensive (n=178). Patients were randomly assigned to the standard regimen (clobetasol propionate cream, 40 g per day initially, with CS tapering over 12 months) or the mild regimen (10-30 g per day), with CS tapering over 4 months. A noninferior rate of BP control was obtained with the mild regimen 156/159 (98%) as compared with the standard regimen 150/150 (100%; P=0.005). Event-free survival, that is, the combined outcome of deaths and life-threatening adverse events did not differ between the two treatment groups (P=0.77). However, upon adjusting through the Cox model for age and Karnofsky score, a strong beneficial effect of the mild regimen was observed in patients with moderate BP, with an almost twofold decrease in the risk of death or life-threatening adverse events relative to the standard regimen (hazard ratio=0.54; 95% confidence interval, 0.30-0.97; P=0.039). This mild regimen allows a 70% reduction of the cumulative doses of CS and improves BP patients' outcome.",
"Topically applied nail therapeutics need to permeate the nail plate to reach the nail bed or nail matrix and exert their potential beneficial effect at these locations to obtain a therapeutic benefit. So far only topically applied 5-fluorouracil on affected nails of psoriatic patients has been shown to produce a notable clearance. Vehicle formulations enhancing nail permeation processes are thought to increase the concentration of the active agent and therefore therapeutic efficacy, possibly enabling the use of a low concentration of the active agent thereby lowering the incidence of adverse effects.\n This study was designed to verify whether a recently developed nail penetration enhancer in a lotion formulation, Belanyx((R)) (urea, propylene glycol), improves the efficacy of a low concentration of 5-fluorouracil (1%) in psoriatic fingernail lesions.\n In a randomised, double-blind, left-right study the efficacy of 1% 5-fluorouracil in the Belanyx vehicle was compared to the vehicle preparation Belanyx in dystrophic fingernails of 57 psoriatic patients. Both preparations were applied in a once daily regimen for 12 weeks. Responses and adverse effects of one selected target nail were recorded at screening, at baseline and at weeks 2, 4, 8 and 12 of treatment with a final assessment at week 16: 4 weeks after the end of treatment. As parameter of efficacy was chosen the total nail area severity (NAS) score, consisting of the separate parameters nail pitting area, number of nail pits, subungual keratosis, onycholysis, oil spots and the various scores of overall improvement.\n The efficacy of 1% 5-fluorouracil in lotion and that of the vehicle in suppressing the parameters of dystrophy were shown to be similar at the end of treatment (p = 0.063) or follow-up (p = 0.130). Both preparations produced statistically significant improvements (p </= 0.05) for almost all assessed parameters after 12 weeks of treatment and after the 4 weeks of follow-up. For Belanyx lotion this applied to the nail pitting area, the number of nail pits, subungual keratosis, onycholysis and oil spots. The investigators' and patients' opinion of overall improvement of severity as well as the total NAS score of one target nail likewise showed a statistically significant improvement at the end of treatment and at the end of the observation period (p </= 0.05). With the 1% 5-fluorouracil lotion the same statistically significant improvements were obtained in all of the assessed symptoms with the exception of the number of pits and onycholysis at week 12 and week 16. Possible treatment-related adverse effects were established in 6 patients showing inflammation and infection (3 patients) or discoloration (5 patients); 3 patients on 5-fluorouracil lotion showed onycholysis.\n Addition of 1% 5-fluorouracil to the nail permeation enhancer Belanyx does not increase the efficacy of the active agent in psoriatic nail dystrophy of this study population. The obtained results also suggest that Belanyx lotion can be used in this indication since it has shown a favourable efficacy-safety ratio.\n Copyright (R) 2000 S. Karger AG, Basel",
"Two nonsteroidal topical agents, calcitriol and tacrolimus, have been reported to be effective and safe for psoriatic lesions on sensitive areas. However, no comparative studies between calcitriol and tacrolimus have been reported.\n To compare the tolerability and efficacy of calcitriol 3 microg g(-1) and tacrolimus 0.3 mg g(-1) ointment in chronic plaque psoriasis affecting facial and genitofemoral regions.\n This is a double-blind, parallel, 6-week study of 50 patients who were randomized in a 1 : 1 ratio to apply calcitriol or tacrolimus twice daily. The primary efficacy variable was the mean reduction of the target area score (TAS), and the secondary efficacy variable was the percentage of patients with the Physician's Global Assessment (PGA) score of 5 (clear) and 4 (almost clear) at the end of the study.\n Both calcitriol and tacrolimus were well tolerated. Although calcitriol induced perilesional erythema in a statistically significant higher proportion of patients than tacrolimus (55% vs. 16% at week 6; P < 0.05), it did not necessitate treatment discontinuation. At the end of the study, tacrolimus was significantly more effective than calcitriol based on a significant reduction of mean TAS (67% vs. 51%; P < 0.05) as well as more patients achieving complete or almost complete clearance by PGA (60% vs. 33%; P < 0.05).\n Both calcitriol 3 microg g(-1) and tacrolimus 0.3 mg g(-1) are safe and well-tolerated therapeutic agents in the treatment of psoriasis in sensitive areas. Tacrolimus demonstrated a more effective clinical outcome compared with calcitriol.",
"In a multicentre, randomized, open study, 306 patients of either sex, over 18 years of age with stable chronic plaque psoriasis > 100 cm2 in surface area, and who gave informed consent, applied Dovonex (calcipotriol) ointment (50 micrograms/g) twice daily or Dithrocream (short-contact dithranol) 0.1-2% for up to 3 months. The number of patients 'cleared' or with 'marked improvement' at the end of treatment were: investigators' assessment--calcipotriol 92 of 153 (60.1%); dithranol 67 of 131 (51.1%); odds ratio 1.44 [95% confidence interval (CI) 0.90, 2.31; P = 0.128]; patients' assessment--calcipotriol 93 of 153 (60.8%); dithranol 65 of 131 (49.6%); odds ratio 1.57 (95% CI 0.98, 2.52; P = 0.059). Significant improvement in patients' quality of life as assessed by the Psoriasis Disability Index (PDI) and the Sickness Impact Profile (SIP) were seen in both treatment groups. Reduction in the total mean score for PDI was 6.5 in the calcipotriol group (95% CI 4.4, 8.6; P = 0.001) and 3.7 in the dithranol group (95% CI 1.1, 6.3; P = 0.005). The reduction in the total mean score for SIP was 2.8 in the calcipotriol group (95% CI 1.4, 4.3; P < 0.001) and 1.7 in the dithranol group (95% CI 0.2, 3.1; P = 0.024). Calcipotriol treatment tended to have advantages over treatment with dithranol in improving quality of life.",
"In the vast majority of psoriatic patients, psoriatic lesions are localised on the body as well as on the scalp. Therefore, safety data on the combined use of calcipotriol in lotion and calcipotriol in ointment are needed.\n This study investigated the effect of high-dose treatment with a combination of calcipotriol ointment and scalp solution on calcium metabolism, indices of bone turnover and PASI in patients with extensive psoriasis.\n Following a 2-week wash-out period, 88 patients were randomised to 4 weeks of treatment with either calcipotriol ointment/scalp solution (80-100 g/week and 30-50 ml/week, respectively; n = 41) or with a dithranol/tar regimen (n = 47). Patients were seen at weeks 1, 2 and 4 during treatment and 1 week following cessation of treatment.\n No significant differences at the end of treatment were found between the 2 groups with respect to 24-hour urinary excretion of calcium (expressed as calcium/creatinine ratio), phosphate or pyridinoline, serum concentrations of calcium (albumin corrected), creatinine, phosphate, parathyroid hormone, 25-hydroxyvitamin D(3), 1,25-dihydroxyvitamin D(3), osteocalcin, alkaline phosphatase (total and bone-specific iso-enzymes) or 1-collagen telopeptide. At the end of treatment, the psoriasis area and severity index had decreased by 57.4% in the calcipotriol group and by 36.1% in the dithranol/tar group (p = 0.004). Investigators' and patients' assessments of overall efficacy also favoured treatment with calcipotriol (p < 0.001).\n The combined use of calcipotriol ointment/scalp solution did not affect the indices of calcium metabolism or bone turnover and was significantly more effective than dithranol/tar in reducing disease severity and extent in patients with extensive psoriasis.\n Copyright 2002 S. Karger AG, Basel",
"High-dose cyclosporine therapy significantly alleviates psoriasis within 2 to 4 weeks but is associated with a high rate of side effects. Reports are conflicting on the frequency and promptness of relapse after discontinuation of cyclosporine therapy.\n Our purpose was to compare the efficacy and safety of low-dose cyclosporine with that of etretinate and the stability of remission after replacing cyclosporine therapy with topical anthralin during tapering of cyclosporine.\n In a multicenter study 210 patients with moderate to severe chronic plaque-type psoriasis were randomly assigned to treatment with cyclosporine or etretinate. The initial dosages were 2.5 mg/kg/day for cyclosporine and 0.5 mg/kg/day for etretinate, which could be individually adjusted to 5.0 and 0.75 mg/kg/day, respectively. After a treatment phase of 10 weeks (phase 1) patients receiving cyclosporine were again randomly assigned to a group in which cyclosporine was replaced by topical dithranol (anthralin), or to another group in which the drug was tapered during the next 12 weeks (phase 2). All patients treated with etretinate discontinued therapy after 10 weeks and used topical dithranol.\n Mean Psoriasis Area and Severity Index decreased by 71% in the cyclosporine group and by 47% in the etretinate group during phase 1. After 10 weeks of treatment 47% of the patients treated with cyclosporine and 10% of those treated with etretinate showed a reduction of more than 80% in skin involvement. Sixty-four percent of the cyclosporine group and 48% of the etretinate group did not require an increase in the initial dosage, resulting in a mean daily dose of 3.0 and 0.53 mg/kg, respectively. There was significant alleviation of nail involvement and joint complaints in both groups. In phase 2 the increase in mean Psoriasis Area and Severity Index and the incidence of relapse were significantly higher in patients in whom cyclosporine was discontinued and replaced by dithranol than in patients in whom cyclosporine was tapered or who were pretreated with etretinate. During treatment four patients from the cyclosporine group and three patients of the etretinate group discontinued the study because of side effects.\n Low-dose short-term cyclosporine therapy for psoriasis is, in comparison with etretinate, highly effective and well tolerated. Individually adjusted cyclosporine therapy allows the majority of patients to continue the low dosage of 2.5 mg/kg/day and still achieve a good clinical response. Remission can be better preserved by tapering the drug than by discontinuing treatment abruptly.",
"During the last decades, management of intertriginous psoriasis (IP) has been unsatisfactory because of the adverse effects associated with long-term corticosteroid application and the lack of alternatives. Recently, both pimecrolimus and tacrolimus have been investigated for this indication and shown to be safe and effective. So far, to our knowledge, a comparison of one of these drugs with standard regimens for IP has not been performed.\n A single-center, 4-week, double-blind, randomized, vehicle-controlled comparison study to assess the safety and efficacy of 1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone valerate in the treatment of IP.\n Dermatologic hospital at Ruhr University of Bochum.\n Eighty adults with IP.\n Treatment of IP with 1% pimecrolimus, 0.005% calcipotriol, 0.1% betamethasone, or the vehicle once daily for 28 days.\n Mean reduction of the Modified Psoriasis Area and Severity Index (M-PASI) score after 28 days of treatment was considered the primary outcome measure, which was analyzed on an intention-to-treat basis. The secondary outcome was a visual analog scale score for itching.\n After 4 weeks of treatment, the 3 active compounds and the vehicle resulted in a significant decrease in mean M-PASI score (86.4% for 0.1% betamethasone, 62.4% for 0.005% calcipotriol, 39.7% for 1% pimecrolimus, and 21.1% for vehicle). The 0.1% betamethasone was significantly more effective than 1% pimecrolimus during the study period (P<.05). No significant difference was found between 0.005% calcipotriol and 0.1% betamethasone and between 0.005% calcipotriol and 1% pimecrolimus. The visual analog scale score for pruritus decreased by 78% for 0.1% betamethasone, 57% for 0.005% calcipotriol, 35% for 1% pimecrolimus, and 43% for the vehicle, again demonstrating a clear advantage for the corticosteroid (P<.05).\n The 1% pimecrolimus was shown to be less potent than 0.1% betamethasone in the treatment of IP. Considering the adverse-effect profile of long-term application of corticosteroids, occasional or intermittent rescue therapy with short-term topical corticosteroids and maintenance with a less potent agent, such as 1% pimecrolimus or 0.005% calcipotriol, might be appropriate for patients with IP in general practice.",
"To assess early intervention with pimecrolimus combined with corticosteroid (CS) for major flares in patients with severe atopic dermatitis (AD).\n In this 6-month, double-blind, multicenter, randomized, vehicle-controlled, parallel-group in 35 US centers, 275 children aged 3 months to 11 years with mild to severe AD applied the study medication twice daily at first signs/symptoms of AD. For major flares not controlled with study medication, a mid-potency CS cream replaced the evening study drug for up to 3 weeks. The percentage of subjects with no major flares was the main outcome measure.\n Pimecrolimus reduced the major flare incidence and prolonged flare-free intervals. Significantly more pimecrolimus subjects (52%) had no major flares compared with vehicle subjects (34%; p = 0.007). Pimecrolimus significantly delayed the first flare (median, 53 days vs 13 days; p<0.001), and increased the time between flares (median, 31 days vs 15 days). Additionally, there was earlier pruritus improvement (median, day 3 vs day 6; p = 0.034) in the pimecrolimus group, as well as a reduced need for CS by 37% (p = 0.020) [corrected] Adverse events (AEs) incidence and type were comparable between groups. Combination therapy with pimecrolimus used at half the recommended dose did not shorten the mean flare duration or alter the AE profile.\n Early treatment of signs/symptoms of AD with pimecrolimus cream 1% provided an effective steroid-sparing option that reduced the incidence of major flares.",
"A study was done of extended maintenance therapy using either betamethasone dipropionate (Diprolene) in optimized vehicle (OV) (ointment) or placebo in patients with psoriasis vulgaris. Of 59 patients originally enrolled in the study, 38 assessable patients achieved clearing of at least 85% improvement from baseline with traditional betamethasone in OV twice a day for two to three weeks before intermittent pulse dosing was attempted. Thereafter, the test medication was used on weekends (three consecutive doses at 12-hour intervals) once a week. Fourteen patients (74%) of the betamethasone in OV group and four patients (21%) of the placebo group maintained a remission status for 12 weeks. Intermittent pulse dosing with betamethasone in OV seems safe and efficacious maintenance therapy in selected psoriatic patients.",
"The merit of topical sequential therapy involving clobetasol foam and calcipotriene ointment has not been experimentally demonstrated.\n We sought to assess the short-term efficacy of twice-daily clobetasol foam plus calcipotriene ointment compared with either agent alone as monotherapy and to compare long-term use of weekday calcipotriene ointment with or without clobetasol foam weekend pulse therapy.\n Eighty-six subjects with plaque-type psoriasis received twice-daily treatment with clobetasol foam plus calcipotriene ointment or either agent as monotherapy for 2 weeks. Subjects in the combination group who achieved remission received weekday calcipotriene plus weekend pulse therapy with either clobetasol foam or vehicle for 6 months.\n After 2 weeks, psoriasis scores were significantly lower (P < .001) in the combination therapy group (adjusted trunk lesion score = 0.67) compared with monotherapy with either agent (lesion scores = 1.40 calcipotriene, 1.13 clobetasol foam). During the follow-up \"weekday-weekend\" phase, after 6 months, weekend pulse clobetasol foam was associated with a trend toward greater maintenance of remission compared with vehicle (92% improvement of trunk lesion vs 62%).\n Small sample size may have hampered the detection of statistical significance during long-term therapy.\n The combination of clobetasol foam and calcipotriene ointment is significantly more effective than monotherapy for short-term treatment. Weekday calcipotriene plus weekend pulse clobetasol foam shows a consistent trend toward greater maintenance of remission.",
"A preliminary double-blind controlled trial was carried out in 8 patients with active chronic psoriasis, whose lesions were more or less bilaterally symmetrical, to assess the efficacy of topical treatment with 0.1% dithranol in a specialized carbamide (17% urea) base. The trial preparation was applied twice daily to one side only over a period of 3 weeks, and lesions on the other side of the body were treated in a similar manner with the base alone. Assessments of clinical improvement, based on severity rating scores, were carried out at weekly intervals. The results showed that, although use of the base alone led to some improvement, the preparation including dithranol was twice as effective, and this finding was supported by the patients' preference. It was easy to apply and remove and was well tolerated, the only side-effects reported being stinging and/or smarting.",
"Pimecrolimus cream (Elidel, SDZ ASM 981), a non-steroid inhibitor of inflammatory cytokines, is effective in the treatment of atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms reduces the need for topical corticosteroids.\n To investigate the efficacy and safety of pimecrolimus cream 1% in the long-term management of adult AD.\n 192 adults with moderate to severe AD were randomised (1:1) for twice daily (b.i.d.) treatment of early signs or symptoms of AD with either pimecrolimus cream 1% or vehicle cream (control group) to prevent progression to flares. Treatment was given as needed for 24 weeks. In the event of flares, a moderately potent corticosteroid (prednicarbate 0.25% cream) was permitted as rescue medication in both groups. The percentage of days on which a topical corticosteroid was used to treat disease flares was the main outcome measure.\n Corticosteroid medication was used on 14.2% (95% confidence interval, CI: 8.3-21.1) of the days of the 24-week treatment period in the pimecrolimus group and on 37.2% (95% CI: 30.4-44.0) of the days in the control group (p < 0.001). In total, 44.8% (43/96) of patients in the pimecrolimus group did not experience a flare compared with 18.8% (18/96) of patients in the control group. The median time to first flare was 144 days in the pimecrolimus group and 26 days in the control group (p < 0.001). Pimecrolimus treatment was also associated with improvement in signs and symptoms of AD, pruritus, patients' self-assessment and quality of life.\n Pimecrolimus cream 1% b.i.d. is an effective, well-tolerated, long-term treatment for AD in adults, substantially reducing the number of flares compared to a conventional therapy and consequently reducing or eliminating the need for corticosteroid treatment.\n Copyright 2002 S. Karger AG, Basel",
"Mycophenolic acid is effective for systemic treatment of psoriasis. However, there is no report about its topical use in this cutaneous disorder so far. We undertook a randomized, placebo-controlled, within subject comparison of mycophenolic acid 1% incorporated in an ointment base and the corresponding vehicle alone (placebo) using the psoriasis plaque test in 7 patients with plaque-type psoriasis over a period of 3 weeks. Scoring of erythema and induration was performed 3 times weekly. After 3 weeks of occlusive treatment there was a reduction of the sum score for erythema and induration in the mycophenolic acid-treated sites of 23% and of 5.7% in the vehicle-treated sites, which was not statistically significant. No adverse advents were noted during the time of study. We conclude that mycophenolic acid is ineffective when applied topically in psoriasis even under occlusion.",
"To compare the efficacy and safety of using a combination of fluticasone propionate (FP) and UV-A with that of either drug used alone in the long-term treatment of vitiligo.\n Prospective, randomized, controlled, left-right comparison study. Repigmentation was judged by a single dermatologist (L.N.-K.) and skin thickness was scored by a pathologist (using biopsy samples), a dermatologist (L.N.-K.) (visually), and patients (using a standard questionnaire).\n Netherlands Institute for Pigmentary Disorders, Amsterdam.\n Patients with lesions on arms, legs, and trunk were treated on 2 symmetrical lesions for 9 months with FP alone and a combination of FP and UV-A (FP group) or with UV-A alone and a combination of FP and UV-A (UV-A group). Fluticasone propionate cream was applied once daily at about bedtime, and UV-A (10 J/cm2) exposure was twice a week. Patients attended the clinic at 3-month intervals.\n One hundred thirty-five patients were included, 96 of whom were evaluable after 9 months. Patients not reaching the end point withdrew because of insufficient repigmentation (n = 23), decreased motivation (n = 11), or protocol violations (n = 5). No patient (irrespective of whether they withdrew) experienced any adverse effects. The FP and UV-A groups were comparable with respect to sex, age, and location of lesions. On average, combination treatment was 3 times more effective than either UV-A or FP treatment alone. In the FP group, no atrophy was seen after 9 months with either treatment. In the UV-A group, a little atrophy was detected twice: as well during UV-A treatment alone as during combination treatment.\n Combination treatment with FP and UV-A is much more effective in reaching complete repigmentation than are FP and UV-A used alone, but large inter-individual differences occur. Fluticasone propionate, UV-A, and a combination of FP and UV-A seem to be safe for long-term treatment of vitiligo.",
"This two-phase, multicenter study was undertaken to examine the safety and efficacy of combination therapy with oral doxycycline and topical azelaic acid (AzA) 15% gel in moderate-to-severe papulopustular rosacea and to determine the effect of subsequent maintenance monotherapy with AzA 15% gel alone. In the initial open-label, non-randomized phase of the study, subjects (n=172) received topical AzA 15% gel and oral doxycycline (100 mg), both twice daily, for < or = 12 weeks. In the second, double-blind study phase, subjects who had initially undergone at least four weeks of combination treatment in phase 1 and who achieved > or = 75% inflammatory lesion count reduction (n=136) were randomized to receive either AzA 15% gel or its vehicle twice daily for an additional 24 weeks. Assessments of efficacy were obtained at four-week intervals throughout both phases of the study and included change in inflammatory lesion count, investigator global assessment (IGA) of rosacea severity, and separate assessments of erythema and telangiectasia severity. At the last visit for each phase of the study, the investigator and participant each rated overall improvement, with the participant rating cosmetic acceptability and the investigator rating treatment as \"success\" or \"failure\" based on IGA score. During the second phase of the trial, the rate of relapse -- defined as either a 50% deterioration in the lesion count improvement from phase 1, an increase in erythema intolerable to the subject or maintenance therapy failure as judged by the investigator and/or the subject -- was obtained. Safety assessments were conducted for both phases of the study and included analysis of adverse events (AEs) and a rating of cutaneous tolerability by the subject. By week 12 of the open-label phase of the study, 81.4% of subjects had reached a 75% or greater reduction in inflammatory lesion count, and 64% of patients achieved treatment success. During the second study phase (maintenance phase), AzA 15% gel consistently provided a better maintenance response than vehicle, with maintenance of remission in 75% of patients over the six-month duration of the maintenance phase. Additionally AzA 15% gel showed a statistically significantly lower deterioration in absolute inflammatory lesion counts than did vehicle after 8, 16, 20 and 24 weeks of maintenance therapy. No serious treatment-related AEs were encountered in the study, and 98.5% of subjects were satisfied with the local tolerability of both AzA gel and vehicle.",
"Therapy with low-dose corticosteroids is commonly used to treat allergic and autoimmune diseases. Long-term use of corticosteroids can lead to loss of bone mineral density and higher risk for vertebral fractures. Calcium and vitamin D3 supplementation is rational therapy for minimizing bone loss, but little evidence for its effectiveness exists.\n To assess 1) the effects of supplemental calcium and vitamin D3 on bone mineral density of patients with rheumatoid arthritis and 2) the relation between the effects of this supplementation and corticosteroid use.\n 2-year randomized, double-blind, placebo-controlled trial.\n University outpatient-care facility.\n 96 patients with rheumatoid arthritis, 65 of whom were receiving treatment with corticosteroids (mean dosage, 5.6 mg/d).\n Calcium carbonate (1000 mg/d) and vitamin D3 (500 IU/d) or placebo.\n Bone mineral densities of the lumbar spine and femur were determined annually.\n Patients receiving prednisone therapy who were given placebo lost bone mineral density in the lumbar spine and trochanter at a rate of 2.0% and 0.9% per year, respectively. Patients receiving prednisone therapy who were given calcium and vitamin D3 gained bone mineral density in the lumbar spine and trochanter at a rate of 0.72% (P = 0.005) and 0.85% (P = 0.024) per year, respectively. In patients receiving prednisone therapy, bone mineral densities of the femoral neck and the Ward triangle did not increase significantly with calcium and vitamin D3. Calcium and vitamin D3 did not improve bone mineral density at any site in patients who were not receiving corticosteroids.\n Calcium and vitamin D3 prevented loss of bone mineral density in the lumbar spine and trochanter in patients with rheumatoid arthritis who were treated with low-dose corticosteroids.",
"Calcipotriene and betamethasone dipropionate are topical treatments for psoriasis vulgaris. Their mode of action is different. Improved risk/benefit may result with concomitant use of the two compounds together. A new vehicle has been created with the objective of obtaining optimal stability of both calcipotriene and betamethasone dipropionate in the combination product.\n We compared the clinical efficacy of a fixed combination of calcipotriene and betamethasone dipropionate in a new vehicle to calcipotriene in the new vehicle, betamethasone in the new vehicle, and the new vehicle alone.\n This was an international, multicenter, prospective, randomized, double-blind, parallel-group, 4-week study in patients with psoriasis vulgaris amenable to topical treatment.\n The mean percentage reduction in PASI from baseline to end of treatment was 73.2% in the combination group (n = 301), 48.8% in the calcipotriene group (n = 308), 63.1% in the betamethasone dipropionate group (n = 312) and 28.8% in the new vehicle group (n = 107), (P < .001). The mean percentage reduction in PASI during the first week was 48.1%, 28.4%, 41.4%, and 21.5%, respectively (P < .001).\n A combination product of calcipotriene 50 microg/g and betamethasone dipropionate 0.5 mg/g in the new vehicle shows superior efficacy with a more rapid onset of action than the new vehicle containing either constituent alone in the treatment of psoriasis vulgaris.",
"The therapeutic efficacy and tolerability of calcipotriol ointment and betamethasone valerate ointment in psoriasis were compared in a multicentre, prospective, randomised, double-blind, right/left trial. 345 inpatients and outpatients with psoriasis vulgaris of symmetrical distribution were treated twice daily for 6 weeks with calcipotriol ointment 50 micrograms/g and betamethasone ointment 0.1% randomly assigned to opposite sides of the body. The main outcome measures--the psoriasis area and severity index (PASI), the investigators' assessments of erythema, thickness, and scaling, and the patients' own assessments of the overall response to treatment--were sought at weeks 2, 4, and 6. Both treatments significantly reduced the PASI scores and the investigator's assessment scores, but at each visit the PASI score was significantly (p less than 0.001) lower with calcipotriol than with betamethasone. At 6 weeks the mean PASI reduction was 68.8% with calcipotriol and 61.4% with betamethasone (95% confidence interval for difference 5.1-9.8, p less than 0.001). The scores for erythema, thickness, and scaling were significantly (p less than 0.001) lower with calcipotriol than with betamethasone at the end of treatment. The patients considered that 82.1% of calcipotriol-treated sides and 69.3% of betamethasone-treated sides had improved greatly or cleared up by the end of treatment (p less than 0.001). 57 adverse events were reported by 52 patients (15.1%). The most common adverse event, lesional/perilesional skin irritation, was slightly but not significantly (p = 0.12) more common with calcipotriol treatment. 15 (4.3%) patients were withdrawn from the study, 3 because of local adverse events. There were no changes in serum calcium during the study. Thus, calcipotriol ointment was superior to betamethasone valerate ointment in psoriasis vulgaris. Though long-term results are not yet available, calcipotriol holds great promise as an antipsoriatic agent.",
"The comparative efficacy, tolerability and acceptability of calcipotriol ointment (50 micrograms/g) and 5% coal tar/2% allantoin/0.5% hydrocortisone cream were determined in 122 patients with chronic plaque psoriasis affecting at least 100 cm2 of skin. Both preparations were applied twice daily for up to 8 weeks. At the end of treatment, investigators considered calcipotriol significantly more effective in the proportion of patients 'cleared' or 'markedly improved' (calcipotriol 72.3%, coal tar/allantoin/hydrocortisone 49.1%: p < 0.02). Calcipotriol was also superior in reducing the total sign score (p = 0.002), and individual scores for scaliness (p < 0.0001) and thickness (p = 0.001). The proportion of patients with less than 100 cm2 of affected skin at the end of treatment was significantly greater in the calcipotriol group (p < 0.05). Patients considered calcipotriol significantly more effective overall (p < 0.02) and in reducing flakiness/scaliness of skin (p = 0.001). Adverse events, most of which were application related and mild to moderate, were recorded in 15 (23.1%) patients using calcipotriol and in 10 (17.5%) patients using coal tar/allantoin/hydrocortisone (n.s.), and contributed to treatment withdrawal in one (1.5%) and three (5.3%) patients, respectively.",
"Calcitriol and calcipotriol are effective treatments for psoriasis, although the two have never been directly compared. We compared the efficacy and toxicity of each agent in 24 patients with moderately extensive chronic plaque psoriasis, who were randomized in double-blind fashion to apply 90 g per week of either calcitriol (3 micrograms/g) ointment or calcipotriol (50 micrograms/g) ointment over an 8-week period. Mean PASI in patients applying calcitriol fell from 13 to 8.8 (p < 0.05) and in patients applying calcipotriol from 14.9 to 4.7 (p < 0.005). The reduction was significantly greater in the calcipotriol-treated group (p < 0.05). There was a small increase in serum ionized calcium in the calcipotriol-treated group (from 1.21 mmol/L to 1.25 mmol/L, p < 0.05) but no effect on calcium homeostasis in the calcitriol group.",
"Hypericin is a known photodynamic agent that has been demonstrated to induce apoptosis in normal and malignant B and T lymphocytes, and has potential to treat benign and malignant disorders of the skin, including psoriasis and cutaneous T-cell lymphoma.\n We wished to test whether topical hypericin was an effective, safe, and well-tolerated therapy for patch or plaque phase mycosis fungoides and for plaque psoriasis.\n We conducted a phase II placebo-controlled clinical study in patients who had either patch or plaque phase mycosis fungoides or plaque type psoriasis vulgaris. Representative lesions were treated twice weekly for 6 weeks with topically applied hypericin or placebo followed 24 hours later by exposure to visible light at 8 to 20 J/cm(2).\n After 6 weeks of twice-weekly therapy, several concentrations of hypericin resulted in the significant improvement of treated skin lesions among the majority of patients with cutaneous T-cell lymphoma and psoriasis whereas the placebo vehicle was ineffective.\n The clinical trial involved a small number of patients.\n Overall, the data from this study support the conclusion that topical hypericin/visible light photodynamic therapy is an effective and well-tolerated alternative to standard psoralen plus ultraviolet A treatment of these disorders.\n Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.",
"Numerous preparations that are available for the treatment of psoriasis of the scalp contain high potency steroids, such as betamethasone dipropionate lotion or clobetasol propionate solution. Of special interest is a currently marketed oil preparation that contains the steroid fluocinolone acetonide (0.01%), classified as low potency (Class 6) steroid. Because the combination of emollients in the vehicle base are present to aid in softening the stratum corneum and allow penetration of the steroid component into the lower skin layer, it was thought this preparation would be an efficient treatment for psoriasis of the scalp. This study was designed to demonstrate the efficacy, tolerance and safety of fluocinolone acetonide 0.01% in oil, compared to its vehicle, for the treatment of scalp psoriasis. This was a randomized, double-blind, vehicle-controlled multi-center study in patients with moderate to severe scalp psoriasis. At the completion of the treatment period (21 days) all signs of psoriasis had improved in both treatment groups, the improvements in the FA group being significantly greater compared to those in the vehicle-treated group. The results of the physician global assessments of improvement in the signs of psoriasis from baseline confirmed the findings. Significantly more patients in the FA group had a good or better improvement from baseline compared to the number in the vehicle-treated group. The results of this study conclusively show that FA in an oil base that aids in the softening of the skin and allows penetration of the steroid into the stratum corneum, is an effective treatment for psoriasis of the scalp. This study also showed that the vehicle alone causes an improvement in the signs of psoriasis, but that the addition of 0.1% of the low potency steroid, fluocinolone acetonide, leads to a significantly better improvement.",
"Intertriginous and facial involvement are manifestations of psoriasis that require a different approach than is used for typical plaque psoriasis on other skin areas. Topical corticosteroids are the primary treatment for psoriasis; however, the side effects of corticosteroids are magnified on intertriginous and facial skin. Topical tacrolimus offers the potential for anti-inflammatory effect without the atrophy or other local side effects associated with the use of topical corticosteroids.\n To determine the efficacy and tolerability of 0.1% tacrolimus ointment for the treatment of facial or intertriginous psoriasis.\n One hundred sixty-seven patients 16 years or older were evaluated in an 8-week, randomized, double-blind, vehicle-controlled, multi-center study. Upon entry into the study, patients were randomized 2:1 to apply the tacrolimus ointment 0.1% or vehicle twice daily to all psoriatic lesions of the face or intertriginous areas for 8 weeks. The physician's global assessment was used to assess improvement from baseline. The inverse psoriasis severity for patients was measured using a 6-point scale from clear to very severe.\n As early as day 8, more patients ( P = .004) had cleared or achieved excellent improvement in the 0.1% tacrolimus ointment group compared to the vehicle group (24.8% vs 5.8%). At the end of the 8-week treatment period 65.2% of the tacrolimus ointment group and 31.5% of the vehicle were clear or almost clear ( P < .0001) based on a Static Severity Score. Adverse events were similar in the 0.1% tacrolimus ointment and vehicle groups. Conclusion Tacrolimus ointment is an effective treatment for psoriasis of the face or intertriginous areas.",
"Psoriasis is a common disease which often requires long-term maintenance therapy. In psoriatic epidermis, the level of cyclic adenosine monophosphate (cAMP) decreases. It has been reported that beta-blockers exacerbate existing psoriatic plaque and decrease the concentration of intracellular cAMP. Caffeine is a methylxanthine that inhibits phosphodiesterase enzyme and results in a higher concentration of intracellular cAMP.\n Evaluation of the efficacy of topical caffeine 10% in the treatment of psoriasis.\n The patients were treated by topical application of 10% caffeine or placebo three times per day on the right or left side of the body (randomly selected by flipping a coin). Thirty-nine patients with stable plaque psoriasis were included in a randomized, double-blind, placebo-controlled, right/left comparison. The patients visited every other week for a period of 8 weeks. Their Psoriatic Area and Severity Index (PASI) scores were assessed at each visit.\n The reductions in PASI scores measured at the four visits for the caffeine-treated group were 2.64+/-2.89, 4.47+/-3.62, 5.73+/-4.16, 6.58+/-4.40 and for the placebo-treated group the values were 1.45+/-2.32, 3.04+/-2.68, 4.02+/-3.36, 4.43+/-3.45, respectively. Comparing the corresponding results of the two groups, p values at the second, fourth, sixth and eighth week were 0.081, 0.083, 0.079 and 0.047, respectively. Based on presented p values, the treatment with caffeine is more effective than with placebo after 8 weeks (p<0.05), and the only side effect of caffeine is mild itching.\n Based on the results of the trial, topical caffeine is an effective, safe and inexpensive treatment for psoriasis, with a delay in action."
] |
Corticosteroids perform at least as well as vitamin D analogues, and they are associated with a lower incidence of local adverse events. However, for people with chronic plaque psoriasis receiving long-term treatment with corticosteroids, there remains a lack of evidence about the risk of skin dermal atrophy. Further research is required to inform long-term maintenance treatment and provide appropriate safety data.
|
CD006060
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[
"Effect of pioglitazone on arteriosclerosis in comparison with that of glibenclamide.",
"Comparison of pioglitazone and gliclazide in sustaining glycemic control over 2 years in patients with type 2 diabetes.",
"Glimepiride versus pioglitazone combination therapy in subjects with type 2 diabetes inadequately controlled on metformin monotherapy: results of a randomized clinical trial.",
"[Six-month effectiveness and tolerability of pioglitazone in combination with sulfonylureas or metformin for the treatment of type 2 diabetes mellitus].",
"Efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component monotherapy in patients with type 2 diabetes.",
"Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: a 6-month randomized placebo-controlled dose-response study. The Pioglitazone 001 Study Group.",
"Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.",
"Long-term therapy with addition of pioglitazone to metformin compared with the addition of gliclazide to metformin in patients with type 2 diabetes: a randomized, comparative study.",
"A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia.",
"Treatment of type 2 diabetes with a combination regimen of repaglinide plus pioglitazone.",
"Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial.",
"Pioglitazone treatment in type 2 diabetes mellitus when combined with portion control diet modifies the metabolic syndrome.",
"Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial.",
"Comparison of the effects of pioglitazone and metformin on insulin resistance and hormonal markers in patients with impaired glucose tolerance and early diabetes.",
"Metabolic efficacy and safety of once-daily pioglitazone monotherapy in patients with type 2 diabetes: a double-blind, placebo-controlled study.",
"A long-term comparison of pioglitazone and gliclazide in patients with Type 2 diabetes mellitus: a randomized, double-blind, parallel-group comparison trial.",
"One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes.",
"Long-term effects on lipids and lipoproteins of pioglitazone versus gliclazide addition to metformin and pioglitazone versus metformin addition to sulphonylurea in the treatment of type 2 diabetes.",
"Efficacy and safety of therapy with metformin plus pioglitazone in the treatment of patients with type 2 diabetes: a double-blind, placebo-controlled, clinical trial.",
"Pioglitazone decreases carotid intima-media thickness independently of glycemic control in patients with type 2 diabetes mellitus: results from a controlled randomized study.",
"Comparison of effect of pioglitazone with metformin or sulfonylurea (monotherapy and combination therapy) on postload glycemia and composite insulin sensitivity index during an oral glucose tolerance test in patients with type 2 diabetes.",
"Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial."
] |
[
"Pioglitazone is an insulin-sensitizing agent that has been reported to have anti-arteriosclerotic effects.\n To investigate the anti-arteriosclerotic effects of pioglitazone in patients with diabetes mellitus using pulse wave velocity (PWV) as an index of efficacy.\n Twenty-seven patients with type 2 diabetes mellitus were randomly assigned to two groups, and pioglitazone (n=13) or glibenclamide (n=14) was administered for 6 months. The TG, TC, LDL-C, and HDL-C, FPG, HbA1c, IRI levels, HOMA-IR, and ba-PWV data were examined before and after administration of each agent.\n FPG and HbA1c were significantly improved in both the groups after treatment, but IRI, HOMA-IR and were improved only in the PIO group. The percent change of ba-PWV from the baseline after treatment in the PIO group improved significantly than that in the GC group (-6.3 +/- 5.6% versus 0.8 +/- 5.7%).\n The findings in this study suggested that pioglitazone has anti-arteriosclerotic effects. We concluded that drugs for the treatment of diabetes mellitus should be selected taking into consideration such endpoints as blood sugar control, and also the risk of complications such as cardiovascular events in the future.",
"The hypothesis that pioglitazone treatment is superior to gliclazide treatment in sustaining glycemic control for up to 2 years in patients with type 2 diabetes was tested.\n This was a randomized, multicenter, double-blind, double-dummy, parallel-group, 2-year study. Approximately 600 patients from 98 centers participated. Eligible patients had completed a previous 12-month study and consented to continue treatment for a further year. To avoid selection bias, all patients from all centers were included in the primary analysis (a comparison of the time-to-failure distributions of the two groups by using a log-rank test) regardless of whether they continued treatment for a 2nd year. By using repeated-measures ANOVA, time course of least square means of HbA(1c) and homeostasis model of assessment (HOMA) indexes (HOMA-%S and HOMA-%B) were analyzed.\n A greater proportion of patients treated with pioglitazone maintained HbA(1c) <8% over the 2-year period than those treated with gliclazide. A difference between the Kaplan-Meier curves was apparent as early as week 32 and widened at each time point thereafter, becoming statistically significant from week 52 onward. At week 104, 129 (47.8%) of 270 pioglitazone-treated patients and 110 (37.0%) of 297 gliclazide-treated patients maintained HbA(1c) <8%. Compared with gliclazide treatment, pioglitazone treatment produced a larger decrease in HbA(1c), a larger increase in HOMA-%S, and a smaller increase in HOMA-%B during the 2nd year of treatment.\n Pioglitazone is superior to gliclazide in sustaining glycemic control in patients with type 2 diabetes during the 2nd year of treatment.",
"To compare the effect of add-on glimepiride or pioglitazone in subjects with type 2 diabetes inadequately controlled on metformin monotherapy.\n Multicenter, randomized, parallel-group, open-label, forcedtitration study involving 203 adults with poorly controlled type 2 diabetes (A1C 7.5-10%) on metformin monotherapy. Subjects were randomized to receive glimepiride or pioglitazone, titrated to the maximum dose for 26 weeks. Subjects were evaluated for A1C changes, fasting plasma glucose (FPG), insulin, C-peptide, and lipid levels. Safety outcomes and diabetes-related healthcare resource utilization were also evaluated.\n Both treatment groups achieved similar and significant mean decreases from baseline to endpoint (week 26) in A1C (p = 0.0001) and FPG (p < 0.05). Glimepiride therapy, however, resulted in a more rapid decline in A1C levels at weeks 6, 12, and 20 vs. pioglitazone (p < 0.05). A mean A1C < or = 7% was reached faster in the glimepiride group (median, 80-90 days vs. 140-150 days [p = 0.024]). Total and LDL cholesterol were significantly higher with pioglitazone treatment than with glimepiride at endpoint (p < 0.05). Glimepiride treatment was associated with an increased risk of hypoglycemia and pioglitazone with higher rate of peripheral edema. Healthcare resource utilization was similar between groups, but total healthcare costs were significantly lower for glimepiride versus pioglitazone over the course of the study, driven largely by drug costs. The use of fasting C-peptide concentration > or = 0.27 nmol/L in the inclusion criteria was a potential limitation as it may have included those patients with an improved probability for glimepiride or pioglitazone response. In addition, a larger patient population would have provided a greater degree of data applicability.\n In patients with type 2 diabetes inadequately controlled on metformin monotherapy, add-on glimepiride or pioglitazone results in similar overall improvements in glycemic control. Compared with pioglitazone, glimepiride is associated with faster glycemic control, lower total and LDL cholesterol levels and reduced short-term healthcare costs.",
"Pioglitazone has been reported to improve common cardiovascular risk factors in addition to glycemic control in patients with type 2 diabetes mellitus (T2DM). The changes in cardiovascular risk profile were evaluated comparatively in large cohorts either treated or not with pioglitazone-containing combinations in the current clinical setting within Spain.\n A nationwide prospective, controlled, observational cohort clinical study was performed in 2294 patients with T2DM who started, at the criterion of the treating physician, oral antihyperglycemic treatment with either pioglitazone plus a sulfonylurea (Pio+SU; n=851), pioglitazone plus metformin (Pio+Met; n=723) or a sulfonylurea plus metformin (SU+Met; n=720) due to inadequate control with previous therapy. Serum cholesterol, blood glucose, hemoglobin A1C, blood pressure and certain anthropometric parameters were measured at baseline and after 6 months of treatment.\n Serum high density lipoprotein-cholesterol increased in average (mg/dl) 2.08 with Pio+SU, 2.06 with Pio+Met and 0.67 with SU+Met; while triglycerides decreased (mg/dl) 26.6, 30.6 and 17.6 in the same cohorts. Inter-group differences were significant (p<0.001 in both parameters). Total cholesterol decreased significantly more with SU+Met than in the pioglitazone cohorts. Mean fasting plasma glucose and hemoglobin A1C reductions were significantly greater in the pioglitazone cohorts than in the SU+Met cohort: 27.74, 28.94 and 23.46 mg/dl (p=0.012); and 0.80, 0.87 and 0.71% (p=0.016) with Pio+SU, Pio+Met and SU+Met, respectively. Slight, but significant variations of body weight were also registered in the Pio+SU (+1.4 kg) and SU+Met (-0.7 kg) groups.\n Treatment with pioglitazone was associated with significant improvements of lipid and glycemic parameters that are linked to insulin resistance and cardiovascular risk in patients with T2DM in their routine clinical care. The non-randomised allocation of patients to treatments, inherent to its observational design, is an important limitation of the present study.",
"The aim of this study was to compare efficacy and tolerability of initial combination therapy with vildagliptin/pioglitazone to component monotherapy.\n This 24-week, multicentre, randomized, double-blind, active-controlled study assessed the effects of the dipeptidyl peptidase-4 inhibitor vildagliptin (100 mg q.d.), pioglitazone (30 mg q.d.) and vildagliptin combined with pioglitazone (100/30 mg q.d. or 50/15 mg q.d.) in 607 drug-naive patients with type 2 diabetes (T2DM). The primary outcome measure was change from baseline in HbA(1c) in patients receiving initial combination therapy compared with pioglitazone monotherapy.\n After 24-week treatment, adjusted mean changes in HbA(1c) from baseline (approximately 8.7%) in patients receiving pioglitazone monotherapy, 50/15 mg combination, 100/30 mg combination and vildagliptin monotherapy were -1.4 +/- 0.1%, -1.7 +/- 0.1%, -1.9 +/- 0.1% and -1.1 +/- 0.1% respectively. Both low-dose and high-dose combinations were significantly more efficacious than pioglitazone alone (p = 0.039 and p < 0.001 respectively). Adjusted mean changes in fasting plasma glucose were -1.9 +/- 0.2, -2.4 +/- 0.2, -2.8 +/- 0.2 and -1.3 +/- 0.2 mmol/l respectively, and both combination groups were significantly more effective than pioglitazone monotherapy (p = 0.022 and p < 0.001 respectively). The overall incidence of adverse events ranged from 45.8% in the low-dose combination to 51.6% in the pioglitazone monotherapy group. The incidence of peripheral oedema was highest in patients receiving pioglitazone monotherapy (9.3%) and lowest in those receiving low-dose combination (3.5%). One mild hypoglycaemic event was reported by one patient receiving high-dose combination and one patient receiving vildagliptin monotherapy.\n First-line treatment with vildagliptin/pioglitazone combination in patients with T2DM provides better glycaemic control than either monotherapy component yet has minimal risk of hypoglycaemia and a tolerability profile comparable with component monotherapy.",
"To evaluate the efficacy and safety of four doses of pioglitazone monotherapy in the treatment of patients with type 2 diabetes.\n There were 408 patients randomized in this multicenter double-blind placebo-controlled clinical trial. Patients who had HbA1c > or = 7.0%, fasting plasma glucose (FPG) > or = 140 mg/dl, and C-peptide > 1 ng/ml were randomized to receive placebo or 7.5, 15, 30, or 45 mg pioglitazone administered once a day for 26 weeks.\n Patients treated with 15, 30, or 45 mg pioglitazone had significant mean decreases in HbA1c (range -1.00 to -1.60% difference from placebo) and FPG (-39.1 to -65.3 mg/dl difference from placebo). The decreases in FPG were observed as early as the second week of therapy; maximal decreases occurred after 10-14 weeks and were maintained until the end of therapy (week 26). In the 15-, 30-, or 45-mg pioglitazone groups, there were significant mean percent decreases in triglycerides, significant mean percent increases in HDL cholesterol, and only small percent changes in total cholesterol and LDL. The subset of patients naive to therapy had greater improvements in HbA1c and FPG (difference from placebo of -2.55% and -79.9 mg/dl for the 45-mg group) compared with previously treated patients. The overall adverse event profile of pioglitazone was similar to that of placebo. There was no evidence of drug-induced hepatotoxicity or drug-induced elevations of alanine aminotransferase levels in this study\n Pioglitazone monotherapy significantly improves HbA1c and FPG while producing beneficial effects on serum lipids in patients with type 2 diabetes with no evidence of drug-induced hepatotoxicity.",
"The efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy were assessed in patients with type 2 diabetes and inadequate glycemic control (glycosylated hemoglobin [HbA(1c)] > or =7% and < or =10%) while receiving a stable dose of pioglitazone.\n This was a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel group study in patients aged > or =18 years (ClinicalTrials. gov NCT00086502). At screening, all patients began a diet/exercise program that continued throughout the study period. Patients taking antihyperglycemic therapy other than pioglitazone underwent a washout of this therapy and entered an 8- to 14-week open-label pioglitazone dose-titration/stabilization period. Patients with an HbA(1c) > or =7% and < or =10% at the end of this period entered a 2-week, single-blind, placebo run-in period (total duration of run-in period, up to 21 weeks). Patients who had been receiving pioglitazone monotherapy (30 or 45 mg/d) and had an HbA(1c) > or =7% and < or =10% entered the 2-week, single-blind, placebo run-in period directly. Thus, at the time of randomization, all patients were receiving ongoing pioglitazone (30 or 45 mg/d). Patients were randomized in a 1:1 ratio to receive sitagliptin 100 mg once daily or placebo for 24 weeks. The primary efficacy end point was the change from baseline in HbA(1c) at week 24. Secondary efficacy end points included the change from baseline in fasting plasma glucose (FPG), insulin, and proinsulin; the Homeostasis Model Assessment beta-cell function and insulin-resistance indexes; the proinsulin/ insulin ratio; the Quantitative Insulin Sensitivity Check Index; the percent changes from baseline in selected lipid parameters; the proportion of patients meeting the American Diabetes Association HbA(1c), goal of <7.0%; the proportion of patients requiring metformin rescue therapy; and the time to the initiation of rescue therapy.\n One hundred seventy-five patients were randomized to receive sitagliptin, and 178 were randomized to receive placebo. The mean (SD) baseline HbAlc value was 8.1% (0.8) in the sitagliptin group and 8.0% (0.8) in the placebo group. After 24 weeks, sitagliptin added to pioglitazone therapy was associated with significant reductions compared with placebo in HbA(1c) (between-treatment difference in least squares [LS] mean change from baseline. -0.70 %; 95 % CI, -0.85 to -0.54; P < 0.001) and FPG (-17.7 mg/dL; 95% CI, -24.3 to -11.0; P < 0.001). Mean HbA(1c) values at end point were 7.2% (0.9) and 7.8% (1.1) in the respective treatment groups, and the proportions of patients reaching a target HbA(1c) of <7.0% were 45.4% and 23.0% (P < 0.001). Significant reductions in fasting serum proinsulin levels and the proinsulin/insulin ratio were seen with sitagliptin treatment compared with placebo (both, P < 0.01). Sitagliptin was generally well tolerated, with no increased risk of hypoglycemia compared with placebo (2 vs 0 patients, respectively).",
"This 52-week, randomized, double-blind study compared the efficacy and safety of metformin plus pioglitazone with the established combination of metformin plus gliclazide in type 2 diabetes mellitus.\n Patients with poorly controlled type 2 diabetes (HbA1c > or = 7.5% to < or =11.0%) received either pioglitazone 15 mg o.d. (titrated up to 45 mg; n = 317) or gliclazide 80 mg o.d. (titrated up to 320 mg; n = 313) and metformin at the pre-study dose. HbA1c, fasting plasma glucose (FPG), insulin, lipids and the urinary albumin/creatinine ratio were measured.\n There were no significant differences in HbA1c (1% decrease in both groups) and FPG between groups. There was a decrease in fasting insulin in the pioglitazone group compared to an increase in the gliclazide group (p < 0.001). There were significantly greater improvements in triglycerides and HDL-cholesterol in the metformin plus pioglitazone group compared to the metformin plus gliclazide group (p < 0.001). Mean LDL-cholesterol decreased with metformin plus gliclazide and increased with metformin plus pioglitazone (p < 0.001); however, this increase was considerably less marked than that in HDL-cholesterol. The mean urinary albumin/creatinine ratio was reduced by 10% in the metformin plus pioglitazone group compared to an increase of 6% in the metformin plus gliclazide group (p = 0.027). The incidence of adverse events was comparable between groups and both combinations were well tolerated.\n Compared to the established combination of metformin plus gliclazide, this study indicates potential benefits of addition of pioglitazone to metformin in terms of improvements in microalbuminuria and specific abnormalities associated with diabetic dyslipidemia.\n Copyright 2004 John Wiley & Sons, Ltd.",
"Published reports suggest that pioglitazone and rosiglitazone have different effects on lipids in patients with type 2 diabetes. However, these previous studies were either retrospective chart reviews or clinical trials not rigorously controlled for concomitant glucose- and lipid-lowering therapies. This study examines the lipid and glycemic effects of pioglitazone and rosiglitazone.\n We enrolled subjects with a diagnosis of type 2 diabetes (treated with diet alone or oral monotherapy) and dyslipidemia (not treated with any lipid-lowering agents). After a 4-week placebo washout period, subjects randomly assigned to the pioglitazone arm (n = 400) were treated with 30 mg once daily for 12 weeks followed by 45 mg once daily for an additional 12 weeks, whereas subjects randomly assigned to rosiglitazone (n = 402) were treated with 4 mg once daily followed by 4 mg twice daily for the same intervals.\n Triglyceride levels were reduced by 51.9 +/- 7.8 mg/dl with pioglitazone, but were increased by 13.1 +/- 7.8 mg/dl with rosiglitazone (P < 0.001 between treatments). Additionally, the increase in HDL cholesterol was greater (5.2 +/- 0.5 vs. 2.4 +/- 0.5 mg/dl; P < 0.001) and the increase in LDL cholesterol was less (12.3 +/- 1.6 vs. 21.3 +/- 1.6 mg/dl; P < 0.001) for pioglitazone compared with rosiglitazone, respectively. LDL particle concentration was reduced with pioglitazone and increased with rosiglitazone (P < 0.001). LDL particle size increased more with pioglitazone (P = 0.005).\n Pioglitazone and rosiglitazone have significantly different effects on plasma lipids independent of glycemic control or concomitant lipid-lowering or other antihyperglycemic therapy. Pioglitazone compared with rosiglitazone is associated with significant improvements in triglycerides, HDL cholesterol, LDL particle concentration, and LDL particle size.",
"The efficacy and safety of combination therapy (repaglinide plus pioglitazone) was compared to repaglinide or pioglitazone in 24-week treatment of type 2 diabetes. This randomized, multicenter, open-label, parallel-group study enrolled 246 adults (age 24-85) who had shown inadequate response in previous sulfonylurea or metformin monotherapy (HbA(1c) > 7%). Prior therapy was withdrawn for 2 weeks, followed by randomization to repaglinide, pioglitazone, or repaglinide/pioglitazone. In the first 12 weeks of treatment, repaglinide doses were optimized, followed by 12 weeks of maintenance therapy. Pioglitazone dosage was fixed at 30 mg per day. Baseline HbA(1c) values were comparable (9.0% for repaglinide, 9.1% for pioglitazone, 9.3% for combination). Mean changes in HbA(1c) values at the end of treatment were -1.76% for repaglinide/pioglitazone, -0.18% for repaglinide, +0.32% for pioglitazone. Fasting plasma glucose reductions were -82 mg/dl for combination therapy, -34 mg/dl for repaglinide, -18 mg/dl for pioglitazone. Minor hypoglycemia occurred in 5% of patients for the combination, 8% for repaglinide, and 3% for pioglitazone. Weight gains for combination therapy were correlated to individual HbA(1c) reductions. In summary, for patients who had previously failed oral antidiabetic monotherapy, the combination repaglinide/pioglitazone had acceptable safety, with greater reductions of glycemic parameters than therapy using either agent alone.",
"Patients with type 2 diabetes are at high risk of fatal and non-fatal myocardial infarction and stroke. There is indirect evidence that agonists of peroxisome proliferator-activated receptor gamma (PPAR gamma) could reduce macrovascular complications. Our aim, therefore, was to ascertain whether pioglitazone reduces macrovascular morbidity and mortality in high-risk patients with type 2 diabetes.\n We did a prospective, randomised controlled trial in 5238 patients with type 2 diabetes who had evidence of macrovascular disease. We recruited patients from primary-care practices and hospitals. We assigned patients to oral pioglitazone titrated from 15 mg to 45 mg (n=2605) or matching placebo (n=2633), to be taken in addition to their glucose-lowering drugs and other medications. Our primary endpoint was the composite of all-cause mortality, non fatal myocardial infarction (including silent myocardial infarction), stroke, acute coronary syndrome, endovascular or surgical intervention in the coronary or leg arteries, and amputation above the ankle. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN NCT00174993.\n Two patients were lost to follow-up, but were included in analyses. The average time of observation was 34.5 months. 514 of 2605 patients in the pioglitazone group and 572 of 2633 patients in the placebo group had at least one event in the primary composite endpoint (HR 0.90, 95% CI 0.80-1.02, p=0.095). The main secondary endpoint was the composite of all-cause mortality, non-fatal myocardial infarction, and stroke. 301 patients in the pioglitazone group and 358 in the placebo group reached this endpoint (0.84, 0.72-0.98, p=0.027). Overall safety and tolerability was good with no change in the safety profile of pioglitazone identified. 6% (149 of 2065) and 4% (108 of 2633) of those in the pioglitazone and placebo groups, respectively, were admitted to hospital with heart failure; mortality rates from heart failure did not differ between groups.\n Pioglitazone reduces the composite of all-cause mortality, non-fatal myocardial infarction, and stroke in patients with type 2 diabetes who have a high risk of macrovascular events.",
"Treatment with thiazolidinediones (TZDs) produces weight gain.\n To test whether a portion control diet could prevent weight gain during treatment with pioglitazone in patients with type 2 diabetes mellitus (T2DM).\n This 16-week randomized, open-label, parallel arm study compared three groups: (i) pioglitazone plus the American Diabetes Association diet (Pio + ADA); (ii) pioglitazone plus a portion control weight loss diet (Pio + PC); (iii) metformin plus the American Diabetes Association diet (Met + ADA). All participants received the same advice about calorie reduction, lifestyle change and exercise.\n Fifty-one men and women with T2DM, naive to TZDs, were randomized to a 16-week study. Pioglitazone (Pio) was titrated to a dose of 45 mg/day and metformin (Met) to a dose of 2 g/day. Fasting blood was collected for lipids, insulin and glycosylated haemoglobin A1c (HbA1c) at baseline and 16 weeks.\n Forty-eight of fifty-one randomized subjects completed the study. Patients treated with Pio + ADA gained 2.15 +/- 1.09 kg (mean +/- SD) compared with a weight loss of 2.59 +/- 1.25 kg (p < 0.05) in the Pio + PC group, and a weight loss of 3.21 +/- 0.7 kg (p < 0.05) in the Met + ADA group. Waist circumference and visceral adipose tissue decreased significantly more in the Pio + PC group than in the Pio + ADA group. High-density lipoprotein cholesterol levels were significantly increased in the Pio + PC group compared with the Met + ADA group. Pioglitazone reduced insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)) more than metformin. No significant differences between groups were seen for glucose, insulin, HbA1c or low-density lipoprotein cholesterol levels.\n Pio + PC, prevented weight gain, reduced waist circumference and visceral fat compared with Pio + ADA diet.",
"Pioglitazone increases the insulin sensitivity of peripheral tissues and may provide an alternative first-line treatment for type 2 diabetes. This study compared metabolic control in drug-naive type 2 diabetes patients given either pioglitazone or metformin. Eleven hundred and ninety-nine patients with poorly controlled type 2 diabetes mellitus [glycosylated hemoglobin (HbA1c), 7.5-11%; normal, 4.3-6.1%] were randomized to receive either pioglitazone (< or =45 mg/d) or metformin (< or =850 mg, three times daily). HbA1c, fasting plasma glucose (FPG), insulin levels, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol, triglycerides, free fatty acids, and urinary albumin/creatinine ratio were measured. Mean HbA1c decreased in both treatment groups from baseline to wk 52 (-1.4% and -1.5%). Significantly greater mean reductions in FPG were observed in the pioglitazone group (-45.0 mg/dl; -2.5 mmol/liter) than in the metformin (-39.6 mg/dl; -2.2 mmol/liter) group (P = 0.016). Favorable changes in triglycerides and HDL-C were more pronounced with pioglitazone. Although low density lipoprotein cholesterol and TC levels increased with pioglitazone, TC/HDL-C ratios decreased similarly with both treatments. The urinary albumin/creatinine ratio was reduced by 19% with pioglitazone treatment, but remained unchanged with metformin therapy (-1%; P = 0.002). There was an increase in body weight of 1.9 kg in the pioglitazone group and a decrease of 2.5 kg in the metformin group. The overall frequency of adverse events was similar between treatment groups, but adverse event profiles were different between treatment groups. HbA1c reduction is similar after pioglitazone and metformin monotherapies, but differences in FPG, plasma lipids, and adverse effects between the two compounds may influence decision-making in individual prescribers.",
"Impaired glucose tolerance (IGT) is associated with cardiovascular risk factors, but the effects of pioglitazone and metformin on IGT are not well described. We tested the hypothesis that each drug would exhibit antiatherogenic and anti-inflammatory effects in subjects with IGT and early diabetes. The study design was a prospective, randomized, open label, cross-over study. Blood tests, including a 75-g oral glucose tolerance test (OGTT), were performed at baseline and after each treatment. Pioglitazone 15 mg/day or metformin 500-750 mg/day was given for 3 months. Biochemical markers to assess insulin resistance as well as lipid, inflammatory, neurohumoral, and hemostatic factors were included. Twenty-five subjects (17 male, 8 female; age [mean+/-SD]: 61+/-9 years; 84% hypertensive) completed the protocol. Of 25 subjects, 14 were diagnosed as IGT and 11 as diabetes with 75-g OGTT. Pioglitazone significantly reduced fasting glucose (p<0.05), and homeostasis model assessment of insulin resistance (HOMA-IR) (p<0.05) and metformin (p<0.01) reduced cholesterol. Both drugs significantly reduced aldosterone (both p<0.05) and von Willebrand factor (vWF) (both p<0.05). Plasma adiponectin was increased only by pioglitazone (p<0.001). Neither drug affected BP levels. In conclusion, pioglitazone was superior to metformin for the improvement of insulin resistance and adiponectin, and both drugs were equally effective in reducing vWF and aldosterone in subjects with IGT and early diabetes. Early intervention with pioglitazone or metformin therapy may reduce the incidence of future cardiovascular disease in subjects with impaired glucose tolerance or early diabetes.",
"Pioglitazone is a novel oral anti-diabetic agent belonging to the thiazolidinedione class. Pioglitazone has been shown to be effective and well tolerated in the treatment of patients with type 2 diabetes, as it reduces insulin resistance and improves glycaemic control and abnormal lipid profiles. This double-blind, randomised, placebo-controlled study was conducted for further evaluation of the efficacy and tolerability of once-daily administration of pioglitazone monotherapy alongside dietary measures in patients with type 2 diabetes. Following a 10-week washout period, 251 patients received one of three treatment regimens for 26 weeks: placebo + diet (n = 84), pioglitazone 15 mg once-daily + diet (n = 89), or pioglitazone 30 mg once-daily + diet (n = 78). Pioglitazone, both 15 and 30 mg/day, in addition to dietary control, was associated with significant reductions (vs. placebo) in mean levels of both glycosylated haemoglobin (HbA 1C ) and fasting blood glucose (FBG). HbA 1C was reduced by 0.92 % and 1.05 %, respectively, and FBG was reduced by 34.3 and 36.0 mg/dl, respectively, compared with the control group. Pioglitazone at 15 and 30 mg/day significantly reduced postprandial blood glucose levels at all visits (- 163 and - 165 mg/dl/hour, respectively) compared with an increase of 47.7 mg/dl/hour on placebo. The profile and frequency of adverse events were similar in all treatment groups. These results indicate that pioglitazone monotherapy together with dietary control is both effective and safe in patients with type 2 diabetes.",
"This study compared the effects of pioglitazone and gliclazide on metabolic control in drug-naive patients with Type 2 diabetes mellitus.\n A total of 1270 patients with Type 2 diabetes were randomized in a parallel-group, double-dummy, double-blind study. Patients with poorly controlled Type 2 diabetes (HbA1c 7.5-11%), despite dietary advice, received either pioglitazone up to 45 mg once daily or gliclazide up to 160 mg two times daily. Primary efficacy endpoint was change in HbA1c from baseline to the end of the study. Secondary efficacy endpoints included change in fasting plasma glucose, fasting plasma insulin and plasma lipids. At selected centres, oral glucose tolerance tests were performed and C-peptide and pro-insulin levels were measured.\n Mean HbA1c values decreased by the same amount in the two treatment groups from baseline to week 52 [pioglitazone: -1.4%; gliclazide: -1.4%; (90% CI: -0.18 to 0.02)]. A significantly greater mean reduction in fasting plasma glucose was observed in the pioglitazone group (2.4 mmol/l) than in the gliclazide group [2.0 mmol/l; treatment difference -0.4 mmol/l in favour of pioglitazone; P = 0.002; (95% CI: -0.7 to -0.1)]. Improvements in high-density lipoprotein cholesterol (HDL-C) and total cholesterol/HDL-C were greater with pioglitazone than with gliclazide (P < 0.001). The frequencies of adverse events were comparable between the two treatment groups, but more hypoglycaemic events were reported for gliclazide, whereas twice as many patients reported oedema with pioglitazone than with gliclazide.\n Pioglitazone monotherapy was equivalent to gliclazide in reducing HbA1c, with specific differences between treatments in terms of mechanism of action, plasma lipids and adverse events.",
"The goal was to assess the 1-year efficacy and safety of the addition of pioglitazone or metformin to existing sulfonylurea (SU) therapy in patients with inadequately controlled type 2 diabetes.\n In this multicenter, double-blind study, patients were randomized to receive either pioglitazone 15 mg (n = 319) or metformin 850 mg (n = 320) and up to 45 mg/day and 2,550 mg/day, respectively. The primary efficacy endpoint was HbA(1c) at week 52. Fasting plasma glucose, insulin, and lipid profiles were also measured.\n HbA(1c) was reduced by 1.20% in the SU plus pioglitazone group and 1.36% in the SU plus metformin group, and fasting plasma glucose was reduced by 2.2 and 2.3 mmol/l in the respective groups. Fasting insulin levels were also reduced (pioglitazone arm -1.3 micro IU/ml; metformin arm -0.8 micro IU/ml). There were no significant between-treatment differences in these three parameters. Pioglitazone addition to SU significantly reduced triglycerides (-16 vs. -9%; P = 0.008) and increased HDL cholesterol (14 vs. 8%; P < 0.001) compared with metformin addition. LDL cholesterol was increased 2% by the addition of pioglitazone and decreased 5% by the addition of metformin to SU (P < 0.001). Urinary albumin-to-creatinine ratio was reduced by 15% in the SU plus pioglitazone group and increased 2% in the SU plus metformin group (P = 0.017). Both combinations were well tolerated with no evidence of hepatic or cardiac toxicity in either group.\n Clinically equivalent improvements in glycemic control were observed for both combinations. Compared with metformin plus SU, addition of pioglitazone to SU resulted in a reduction of the urinary albumin-to-creatinine ratio, a small but significant rise in LDL cholesterol, and significantly greater improvements in triglyceride levels and HDL cholesterol levels. Metformin plus SU was associated with a significant reduction in LDL cholesterol. SU plus pioglitazone is an effective and well-tolerated combination regimen that may provide additional beneficial effects for patients with type 2 diabetes.",
"The aim of this study was to determine the long-term effects of pioglitazone add-on to metformin or sulphonylurea on plasma lipids and lipoproteins.\n The effects of pioglitazone were studied in two clinical trials in patients with inadequately controlled type 2 diabetes (HbA1c > or =7.5 and < or =11%). In the first trial, patients currently receiving metformin were randomised to pioglitazone (15-45 mg/day, n=317) or gliclazide (80-320 mg/day, n=313) add-on therapy. In the second study, pioglitazone (15-45 mg/day, n=319) or metformin (850-2,550 mg/day, n=320) was added to sulphonylurea therapy. Patients were force-titrated to the maximum tolerated dose of add-on therapy, which was maintained to the 2-year endpoint.\n There were no statistically significant differences between the groups with respect to HbA1c reduction from baseline to week 104. Whether added to metformin or sulphonylurea, pioglitazone caused highly significant greater decreases in triglycerides and increases in HDL cholesterol from baseline to week 104 than treatments with gliclazide or metformin add-on therapies (p< or =0.001). The triglyceride reductions noted with pioglitazone were maintained over time, with decreases of 16-18% at 1 year and 17-23% at 2 years. In the pioglitazone groups, the improvement in HDL cholesterol at 1 year was maintained, with 21-22% augmentations at 2 years (p<0.001 between-group difference). Small but statistically significant greater reductions in LDL cholesterol were observed with gliclazide vs pioglitazone add-on to metformin and metformin vs pioglitazone add-on to sulphonylurea (p<0.001 for between-group difference). In the pioglitazone groups, mean LDL cholesterol at 2 years was similar to mean baseline LDL cholesterol.\n After 2 years, highly significant decreases in triglycerides and increases in HDL cholesterol that were sustained over time or even improved were observed when pioglitazone was added to metformin or sulphonylurea therapy. These effects of pioglitazone on lipids may be potentially beneficial in reducing cardiovascular risk in type 2 diabetes.",
"To assess the efficacy and safety of combination therapy with pioglitazone and metformin in Japanese patients with type 2 diabetes.\n During a 12-week observation period 236 patients were treated with metformin 500 or 750 mg/day. 169 patients with a confirmed HbA(1c) level >or= 6.5% were randomized (stratified according to metformin dosage) to receive pioglitazone 15 mg/day for 12 weeks then increased to 30 mg/day for a further 16 weeks (n = 83), or placebo (n = 86). Outcome measures included HbA(1c), fasting blood glucose (FBG), percentage of patients achieving HbA(1c) < 6.5%, lipid profile, and other metabolic parameters.\n Mean HbA(1c) was reduced by 0.67% in patients receiving pioglitazone plus metformin versus an increase of 0.25% in those receiving metformin alone (p < 0.0001). After 8 weeks' treatment and until the end of the study, HbA(1c) was significantly lower with pioglitazone plus metformin and more patients in this group achieved an HbA(1c) < 6.5% (38.6% vs. 8.1%; p < 0.0001). FBG was also reduced by a significantly greater amount in patients receiving pioglitazone plus metformin compared with metformin monotherapy (-20.5 vs. 1.9 mg/dl; p < 0.0001). Combination therapy was associated with significantly increased HDL-cholesterol, total cholesterol, and adiponectin, and significantly decreased levels of fasting insulin, free fatty acids, and homeostasis model assessment insulin resistance (HOMA-R) compared with metformin monotherapy. Overall, combination therapy and monotherapy were equally well tolerated and the incidence of adverse effects 'possibly' related to therapy was 15.7% and 11.6% (p = 0.505), respectively. Edema occurred slightly more often in the combination group (6.0 vs. 1.2%).\n Pioglitazone plus metformin significantly improved glycemic control (HbA(1c) and FBG), and markers associated with increased insulin resistance and cardiovascular risk compared with metformin monotherapy.\n UMIN 000001110.",
"Patients with type 2 diabetes mellitus are at high risk of cardiovascular disease. Carotid intima-media thickness (IMT) is a strong predictor of myocardial infarction and stroke.\n We compared the effects of pioglitazone-based therapy (45 mg/d) and glimepiride-based treatment (2.7+/-1.6 mg/d) for 12 and 24 weeks on metabolic control (HbA1c), insulin resistance (homeostasis model assessment), and carotid IMT (B-mode ultrasonography) in a randomized controlled study in 173 orally treated patients with type 2 diabetes (66 women, 107 men; mean+/-SD age, 62.6+/-7.9 years; body mass index, 31.8+/-4.6 kg/m2; HbA1c, 7.5+/-0.9%). Treatment was generally well tolerated in both groups. Despite similar improvements in metabolic control (HbA1c) after 24 weeks (-0.8+/-0.9% [pioglitazone] versus -0.6+/-0.8% [glimepiride]; P=NS), carotid IMT was reduced only in the pioglitazone group after 12 weeks (-0.033+/-0.052 versus -0.002+/-0.047 mm [glimepiride]; P<0.01 between groups) and 24 weeks (-0.054+/-0.059 versus -0.011+/-0.058 mm [glimepiride]; P<0.005 between groups). Insulin resistance was also improved only in the pioglitazone group (homeostasis model assessment, -2.2+/-3.4 versus -0.3+/-3.3; P<0.0001 between groups). Reduction of IMT correlated with improvement in insulin resistance (r=0.29, P<0.0005) and was independent of improvement in glycemic control (r=0.03, P=0.68).\n We found a substantial regression of carotid IMT, independent of improved glycemic control, after 12 and 24 weeks of pioglitazone treatment. This finding may have important prognostic implications for patients with type 2 diabetes mellitus.",
"Pioglitazone, metformin, and gliclazide lower HbA(1c) and fasting plasma glucose in patients with type 2 diabetes. We compared the effects of these three drugs, used as monotherapy and in combination, on postload glycemia and composite insulin sensitivity index (CISI) in these patients.\n Postload glycemia and CISI were analyzed for 940 patients who had oral glucose tolerance tests (OGTTs) in four multicenter, randomized, double-blind, double-dummy, parallel group clinical trials (pioglitazone versus metformin, pioglitazone versus gliclazide, pioglitazone plus sulfonylurea versus metformin plus sulfonylurea, and pioglitazone plus metformin versus gliclazide plus metformin). Plasma glucose and insulin were determined during the 3-h OGTT performed at baseline and after 1 year of therapy. Incremental area under the curve for glucose was the surrogate for postload glycemia. CISI was calculated using the formula {10,000/ radical of [(fasting glucose x fasting insulin) x (mean glucose x mean insulin)]} during the OGTT.\n In monotherapy, pioglitazone reduced postload glycemia and enhanced CISI more than metformin and gliclazide. In combination therapy, pioglitazone plus sulfonylurea reduced postload glycemia and increased CISI more than metformin plus sulfonylurea. Pioglitazone plus metformin also decreased postload glycemia and increased CISI more than gliclazide plus metformin.\n Pioglitazone improves postload glycemia and CISI more than metformin or gliclazide when used as monotherapy or in combination therapy in patients with type 2 diabetes.",
"Most patients with type 2 diabetes begin pharmacotherapy with metformin, but eventually need additional treatment. We assessed the safety and efficacy of once weekly exenatide, a glucagon-like peptide 1 receptor agonist, versus maximum approved doses of the dipeptidyl peptidase-4 inhibitor, sitagliptin, or the thiazolidinedione, pioglitazone, in patients treated with metformin.\n In this 26-week randomised, double-blind, double-dummy, superiority trial, patients with type 2 diabetes who had been treated with metformin, and at baseline had mean glycosylated haemoglobin (HbA(1c)) of 8.5% (SD 1.1), fasting plasma glucose of 9.1 mmol/L (2.6), and weight of 88.0 kg (20.1), were enrolled and treated at 72 sites in the USA, India, and Mexico. Patients were randomly assigned to receive: 2 mg injected exenatide once weekly plus oral placebo once daily; 100 mg oral sitagliptin once daily plus injected placebo once weekly; or 45 mg oral pioglitazone once daily plus injected placebo once weekly. Primary endpoint was change in HbA(1c) between baseline and week 26. Analysis was by intention to treat, for all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00637273.\n 170 patients were assigned to receive once weekly exenatide, 172 to receive sitagliptin, and 172 to receive pioglitazone. 491 patients received at least one dose of study drug and were included in the intention-to-treat analysis (160 on exenatide, 166 on sitagliptin, and 165 on pioglitazone). Treatment with exenatide reduced HbA(1c) (least square mean -1.5%, 95% CI -1.7 to -1.4) significantly more than did sitagliptin (-0.9%, -1.1 to -0.7) or pioglitazone (-1.2%, -1.4 to -1.0). Treatment differences were -0.6% (95% CI -0.9 to -0.4, p<0.0001) for exenatide versus sitagliptin, and -0.3% (-0.6 to -0.1, p=0.0165) for exenatide versus pioglitazone. Weight loss with exenatide (-2.3 kg, 95% CI-2.9 to -1.7) was significantly greater than with sitagliptin (difference -1.5 kg, 95% CI -2.4 to -0.7, p=0.0002) or pioglitazone (difference -5.1 kg, -5.9 to -4.3, p<0.0001). No episodes of major hypoglycaemia occurred. The most frequent adverse events with exenatide and sitagliptin were nausea (n=38, 24%, and n=16, 10%, respectively) and diarrhoea (n=29, 18%, and n=16, 10%, respectively); upper-respiratory-tract infection (n=17, 10%) and peripheral oedema (n=13, 8%) were the most frequent events with pioglitazone.\n The goal of many clinicians who manage diabetes is to achieve optimum glucose control alongside weight loss and a minimum number of hypoglycaemic episodes. Addition of exenatide once weekly to metformin achieved this goal more often than did addition of maximum daily doses of either sitagliptin or pioglitazone.\n Amylin Pharmaceuticals and Eli Lilly.\n Copyright 2010 Elsevier Ltd. All rights reserved."
] |
Until new evidence becomes available, the benefit-risk ratio of pioglitazone remains unclear. Different therapeutic indications for pioglitazone of the two big U.S. and European drug agencies should be clarified to reduce uncertainties amongst patients and physicians.
|
CD003842
|
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[
"Readiness for surgery after axillary block: single or multiple injection techniques.",
"[Comparison of transarterial and multiple nerve stimulation techniques for axillary block using lidocaine with epinephrine.].",
"Comparison of transarterial and multiple nerve stimulation techniques for an initial axillary block by 45 mL of mepivacaine 1% with adrenaline.",
"A prospective, randomized comparison between ultrasound and nerve stimulation guidance for multiple injection axillary brachial plexus block.",
"Double-injection method using peripheral nerve stimulator is superior to single injection in axillary plexus block.",
"A comparison of three methods of axillary brachial plexus anaesthesia.",
"Efficacy of vertical infraclavicular plexus block vs. modified axillary plexus block: a prospective, randomized, observer-blinded study.",
"A comparison of the vertical infraclavicular and axillary approaches for brachial plexus anaesthesia.",
"Efficacy of ultrasound-guided axillary brachial plexus block: a comparative study with nerve stimulator-guided method.",
"Axillary brachial plexus block using peripheral nerve stimulator: a comparison between double- and triple-injection techniques.",
"Comparison of two neurostimulation techniques for axillary brachial plexus blockade.",
"A comparison of a single-stimulation lateral infraclavicular plexus block with a triple-stimulation axillary block.",
"Comparison of the clinical efficacy of three perivascular techniques for axillary brachial plexus block.",
"Comparison of transarterial and multiple nerve stimulation techniques for axillary block using a high dose of mepivacaine with adrenaline.",
"Axillary plexus block using a peripheral nerve stimulator: single or multiple injections.",
"[Axillary brachial plexus anesthesia. How many nerve stimulation responses do we look for?].",
"Ultrasound guidance improves the success rate of a perivascular axillary plexus block.",
"A comparison of four stimulation patterns in axillary block."
] |
[
"We have assessed prospectively the time to readiness for surgery following axillary block (sum of block performance and latency times) in 80 patients. The brachial plexus was identified using a nerve stimulator, and anaesthetized with 45 mL of mepivacaine 1% with adrenaline 5 micrograms mL-1. In group 1 (single injection) the whole volume of mepivacaine was injected after locating only one of the plexus nerves. In group 2 (multiple injections) at least three plexus nerves were located, and the volume of mepivacaine was divided between them. Sensory block was assessed by a blinded observer every 10 min. Patchy analgesia was supplemented after electrolocating the unblocked nerves after 20, 30 or 40 min. The patient was pronounced ready for surgery when analgesia was present in all areas to be operated upon, which always included the three nerves to the hand. The single injection technique required less time for block performance (mean 5.5 min) than multiple injections (mean 9.5 min), P < 0.0001. However, latency of the block was longer and the requirement for supplemental nerve blocks was greater, after single injections (33 min and 57%) than after multiple injections (15.5 min and 7%, respectively), P < 0.0001. As a result, readiness for surgery was achieved faster in group 2 (25 min), than in group 1 (38.5 min), P < 0.0001. After supplementation, block effectiveness was 100% in group 1 and 98% in group 2 (NS). The frequency of adverse effects (vessel puncture or paraesthesia) was similar in both groups. No neurological sequelae were observed. We conclude that the multiple injection technique takes longer to perform than single injection, but that readiness for surgery is faster because of shorter block latency and better spread of analgesia.",
"High-dose transarterial technique results in highly effective axillary block. The multiple nerve stimulation technique (MNS) requires more time and experience. This prospective study aimed at comparing onset and success rate of multiple-injection axillary brachial plexus block using two methods of nerve location: transarterial or multiple nerve stimulation technique.\n Axillary block was initially induced with 800 mg lidocaine with epinephrine. The transarterial group received deeply injected 30 mL of 1.6% lidocaine with epinephrine, and 20 mL superficially to the axillary artery. For the multiple nerve stimulation group, three terminal motor nerves were electrolocated and blocked with 20 mL, 20 mL and 10 mL. Blockade was considered effective when analgesia was present in all sensory nerves distal to the elbow.\n Onset (8.8 +/- 2.3 min versus 10.2 +/- 2.4 min; p-value = 0.010) was significantly shorter in the transarterial group. Complete sensory block of all four nerves (median, ulnar, radial and musculocutaneus) was achieved in 92.5% versus 83.3% for multiple nerve stimulation group and transarterial group, respectively, without significant difference (p = 0.68). Musculocutaneous nerve was significantly easier to be blocked with the aid of peripheral nerve stimulator (p = 0.034).\n Both MNS technique for axillary block with nerve stimulator (3 injections) and transarterial technique (2 injections) promote similar results. Musculocutaneous nerve is more easily blocked with the aid of peripheral nerve stimulator. MNS technique has required less supplementary blocks and has delayed beginning of surgery.",
"The single-injection axillary block is rapidly performed but gives unpredictable results. Axillary block by multiple nerve stimulation technique (MNS) gives better results, but takes longer to perform. Transarterial (TA) injections of high doses of local anaesthetics are very successful. This double-blind study compared both block effectiveness and anaesthesiologic time consumption in 100 patients, having an axillary block by either TA or MNS techniques.\n 45 mL of 1% mepivacaine with adrenaline 5 microg/mL was used in each patient. Five mL was injected subcutaneously. In the TA group, 20 mL was injected deep to, and 20 mL superficial to the axillary artery. In the MNS group, four terminal motor nerves were electrolocated in the axilla, and injected with 10 mL each. Analgesia was assessed every 10 min and when needed supplemented after 30 min. The block was considered successful when analgesia was present in all sensory nerve areas distal to the elbow.\n MNS group required 10+/-2 min (mean+/-1 SD) for the initial block performance compared with 7+/-2 min for TA group, P<0.001. Latency of the initial block was shorter and the frequency of supplemental analgesia lower in the MNS group (mean 17 min and 12%), than in the TA group (25 min and 38%, respectively), P<0.001. All incomplete blocks were successfully supplemented by electrolocating the unblocked nerves. However, the total time to obtain 100% success rate was shorter in the MNS group (30 min), than in the TA group (38 min), P<0.001. The adverse effects (accidental intravascular injections and axillary haematomas) were fewer in the MNS group.\n In the hands of anaesthetists experienced in nerve electrolocation, the MNS technique of an initial axillary block by four separate injections of 10 mL of mepivacaine produces faster and more extensive block than the TA technique by two separate injections of 20 mL. Hence, the MNS technique requires fewer supplementary blocks and results in faster patient readiness for surgery than the TA technique.",
"This prospective, randomized, blinded study tested the hypothesis that ultrasound guidance can shorten the onset time of axillary brachial plexus block as compared with nerve stimulation guidance when using a multiple injection technique.\n Sixty American Society of Anesthesiology physical status I-III patients receiving axillary brachial plexus block with 20 ml ropivacaine, 0.75%, using a multiple injection technique, were randomly allocated to receive either nerve stimulation (group NS, n = 30), or ultrasound guidance (group US, n = 30) for nerve location. A blinded observer recorded the onset of sensory and motor blocks, the need for general anesthesia (failed block) or greater than 100 microg fentanyl (insufficient block) to complete surgery, procedure-related pain, success rate, and patient satisfaction.\n The median (range) number of needle passes was 4 (3-8) in group US and 8 (5-13) in group NS (P = 0.002). The onset of sensory block was shorter in group US (14 +/- 6 min) than in group NS (18 +/- 6 min) (P = 0.01), whereas no differences were observed in onset of motor block (24 +/- 8 min in group US and 25 +/- 8 min in group NS; P = 0.33) and readiness to surgery (26 +/- 8 min in group US and 28 +/- 9 min in group NS; P = 0.48). No failed block was reported in either group. Insufficient block was observed in 1 patient (3%) of group US and 2 patients (6%) of group NS (P = 0.61). Procedure-related pain was reported in 6 patients (20%) of group US and 14 patients (48%) of group NS (P = 0.028); patient acceptance was similarly good in the two groups.\n Multiple injection axillary block with ultrasound guidance provided similar success rates and comparable incidence of complication as compared with nerve stimulation guidance.",
"Axillary block using a single-injection method does not always provide effective analgesia. This study examined whether a double axillary block injection technique is superior to a single injection axillary block.\n Fifty patients were randomly allocated to two groups. In group I (single injection), the whole volume of local anesthetic (0.7 mL/kg) was injected after locating only one of the median, radial, or ulnar nerves. In group 2 (double injection), half of the volume was injected after locating one nerve and the other half after locating another peripheral nerve. Bupivacaine 0.5% and prilocaine 1% (1:1 volumes) were used as local anesthetic. A peripheral nerve stimulator was used to identify the nerves. Sensory block of seven nerves and motor block of four nerves were tested after 40 minutes.\n Complete sensory and motor block (scores 2 or 3 on scale 0-3) in all four main nerves (median, ulnar, radial, musculocutaneous) was achieved in 3 (12%) versus 20 (80%) patients in groups 1 and 2, respectively (P = .000001). Primary success rate (no need for supplemental nerve block) was 52% in group 1 and 92% in group 2 (P = .0016).\n A double-injection method in axillary block provides excellent analgesia and motor block compared with a single-injection method. Moreover, the need for supplemental nerve blocks is significantly decreased.",
"One hundred patients scheduled for elective outpatient hand surgery had blockade of the axillary brachial plexus by one of three techniques; insertion of a catheter into the brachial plexus sheath (n = 25), use of paraesthesia (n = 50) or use of the nerve stimulator (n = 25) to localise the plexus. Only two patients required general anaesthesia for the planned surgery. Assessment of the dermatomes blocked did not demonstrate a statistical difference between the success rates of the three groups. The more nerves detected in the paraesthesia and the nerve stimulator groups before injection of local anaesthetic the higher the success rate of the block. We advocate use of the nerve stimulator technique in view of the possible risk of neurological damage associated with paraesthesia and the technical difficulties with the catheter technique, for routine brachial plexus blockade.",
"Despite containing severe risks, infraclavicular approaches to the brachial plexus gained increasing popularity. Likewise, the vertical infraclavicular plexus block improved anesthesia compared to the standard axillary approach but contains the risk of pneumothorax. Therefore we modified the standard axillary technique by inserting a proximal directed catheter, referred to as a high axillary plexus block. We prospectively compared quality and onset of neural blockade after vertical infraclavicular plexus block (VIP) and high axillary plexus block (HAP) in two randomized groups (30 patients in each).\n In group VIP the insulated needle was inserted midway between the ventral process of the acromion and the jugular notch. In group HAP, first an axillary needle was placed. Through this a stimulating catheter was inserted in a proximal direction (10-15 cm); correct placement was confirmed by nerve stimulation. All patients received 40 ml ropivacaine 0.75% (300 mg). Discriminating between analgesia and anesthesia, a blinded observer assessed progression of neural blockade every 5 min for 60 min by pin prick. Incomplete blocks were supplemented 60 min after initial injection.\n All patients in both groups demonstrated sufficient surgical anesthesia. No patient needed systemic supplementation or general anesthesia. However, vertical infraclavicular plexus block indicated superior anesthesia compared to high axillary plexus block, regarding musculocutaneous, axillary and radial nerve, which were completely blocked with a higher success rate and in a shorter time interval (P < 0.05).\n While both techniques provide sufficient surgical anesthesia, vertical infraclavicular plexus block demonstrated a partially higher success rate and a faster onset than high axillary plexus block.",
"This prospective, randomized study compared the efficacy of the vertical infraclavicular and axillary approaches using a single injection blockade of the brachial plexus. The primary endpoint was complete blockade in dermatomes C5-Th1, while secondary endpoints included onset time, motor block, block performance time, surgical success rate, patient satisfaction, and side-effects/complications.\n Sixty patients, American Society of Anesthesiologists physical status I or II, scheduled for surgery of the forearm or hand received either a vertical infraclavicular (n = 30) or an axillary block (n = 30). A single injection of 0.5 ml/kg ropivacaine 7.5 mg/ml was made after electrolocalization of nerve fibres corresponding to the median nerve at maximum 0.5 mA (2 Hz, 0.1 ms). Onset and distribution of analgesia and motor block were assessed at 5, 10, 15, 20, 30 and 60 min after the local anaesthetic injection. A complete block was defined as analgesia in all dermatomes (C5-Th1) at 60 min post-injection.\n The vertical infraclavicular approach provided complete blockade in 29 patients (97%) and the axillary approach in 23 patients (77%). Analgesia in C5-C6 dermatomes and corresponding motor block occurred significantly more frequently in the vertical infraclavicular approach, which also had the shortest onset time. Block procedure was quicker in the axillary approach. Side-effects were similar in both groups, and there were no permanent sequelae. Patient satisfaction was equally high in both groups.\n The vertical infraclavicular approach provides a more complete block than the axillary approach when using a single injection technique and equal volumes/doses of local anaesthetic.",
"The aim of this study was to compare the efficacy of axillary brachial plexus block using an ultrasound-guided method with the nerve stimulator-guided method. We also compared the efficacy of ultrasound-guided single-injection with those of double-injection for the quality of the block.\n Ninety patients scheduled for surgery of the forearm or hand were randomly allocated into three groups (n = 30 per group), i.e., nerve stimulator-guided and double-injection (ND) group, ultrasound-guided and double-injection (UD) group, and ultrasound-guided and single-injection (US) group. Each patient received 0.5 ml kg(-1) of 1.5% lidocaine with 5 mg kg(-1) epinephrine. Patients in the ND group received half the volume of lidocaine injected near the median and radial nerves after identification using a nerve stimulator. Patients in the UD group received half the volume of lidocaine injected around the lateral and medial aspects of the axillary artery, while those in the US group were given the entire volume near the lateral aspect of the axillary artery. The extent of the sensory blockade of the seven nerves and motor blockades of the four nerves were assessed 40 min after the performance of axillary brachial plexus block.\n Seventy percent of the patients in the ND and US groups as well as 73% of the patients in the UD group obtained satisfactory sensory and motor blockades. The success rate of performing the block was 90% in patients in the ND and UD groups and 70% in the US group. The incidence of adverse events was significantly higher in the ND group (20%) compared with that in the US group and the UD group (0%; p = 0.03).\n Ultrasound-guided axillary brachial plexus block, using either single- or double-injection technique, provided excellent sensory and motor blockades with fewer adverse events.",
"The multiple-injection technique for axillary block, in which the main 4 nerves of the plexus are located by a nerve stimulator and separately injected, has been shown to produce a high success rate. However, this technique may prove to be more difficult and time-consuming than other methods. Therefore, a simplified technique, with a reduced number of injections, might be desirable. A comparison between 2- and 3-injection techniques was made in the present double-blind study.\n One hundred patients were randomly allocated to 2 groups. In group 3N, the radial, median, and musculocutaneous nerves were located by a nerve stimulator and injections made. In group 2N, the radial and median nerves were located and injections made. Forty milliliters of local anesthetic was used.\n A greater success rate for anesthetizing the musculocutaneous nerve was found in group 3N (98% v 80%; P <.005). No differences between the groups were found in the success rate for blocking the radial, median, and ulnar nerves. The rate of complete block (all the sensory areas distal to the elbow) was 90% in group 3N and 76% in group 2N. The time to perform the block was shorter in group 2N (5 +/- 1 v 6 +/- 1 minutes; P <.001).\n The 2-injection technique offers a success rate in blocking the 3 nerves innervating the hand similar to that obtained with the 3-injection technique. The latter approach should be considered when the musculocutaneous nerve distribution is involved in the surgical area.",
"This prospective, randomized, double-blind study compared two techniques of axillary brachial plexus block using a peripheral nerve stimulator. Both groups received initial musculocutaneous nerve block followed by either a single injection on median nerve stimulation (group 1) or a double injection divided between median and radial nerves (group 2). All 60 patients received a total of 30 ml of lidocaine 15 mg/ml with epinephrine 5 microg/ml. Complete sensory blockade of all six peripheral nerves occurred in 53% and 97% of patients in groups 1 and 2, respectively (P<0.001), with a more rapid onset of blockade occurring in group 2 patients (P<0.001). Complete motor blockade was evident in 30% and 83% of patients in groups 1 and 2, respectively (P<0.001).",
"A single-stimulation infraclavicular brachial plexus block (ICB) is safe and easy to perform, although underused. This technique was compared with a triple-stimulation axillary block (AxB).\n One hundred patients scheduled for hand and forearm surgery were randomly allocated to 2 groups. ICB was performed with the needle inserted above the coracoid process in the upper lateral angle of the infraclavicular fossa and directed vertically until nerve stimulation elicited a distal motor response (median, radial, or ulnar). A single 40-mL bolus of ropivacaine 0.75% was injected. In the AxB group, 3 stimulations were performed to identify median or ulnar, radial, and musculocutaneous nerves, followed by an infiltration near the medial brachial and antebrachial cutaneous nerves. The same 40 mL of ropivacaine 0.75% was injected. Sensory and motor blocks were assessed at 5-minute intervals over 30 minutes.\n The time to block performance was shorter in the ICB than in the AxB group (2.5 +/- 1.9 minutes v 6.0 +/- 2.8 minutes, P <.001). The success rate (complete block in median, radial, ulnar, musculocutaneous, and medial antebrachial cutaneous nerves) was comparable in the 2 groups (90% v 88% in groups ICB and AxB, respectively). Block extension was comparable, except for a higher rate of block completion in the axillary nerve distribution in group ICB and in the medial brachial cutaneous nerve in group AxB. The onset of each nerve block was comparable except for a faster onset for the musculocutaneous nerve in group AxB (8 +/- 3 v 10 +/- 5 minutes).\n A single shot ICB is equally effective as a triple-nerve stimulation AxB.",
"This study compared the efficacy of three perivascular techniques of axillary block.\n In group 1, all of the local anesthetic was injected after advancing the needle through the axillary artery (back of artery, n = 20); in group 2, after withdrawing slightly from the artery (front of artery, n = 20); and in group 3, half of the anesthetic was injected after advancing through and half after withdrawing from the axillary artery (half and half, n = 20). The local anesthetic used for the axillary block was 50 ml of 1.5% mepivacaine with epinephrine 1:200,000.\n The groups did not differ significantly in the incidence of analgesia or anesthesia expected in the median nerve distribution, where there was a significantly lower incidence of anesthesia in the back of the artery group. This group also had a slower onset of anesthesia for the median and the medial antebrachial cutaneous nerves.\n There was no significant difference in the number of patients requiring supplementation, with five patients in the back group (25%), three patients in the front group (15%), and one patient in the half and half group (5%) requiring supplementation for the surgical procedure.",
"High-dose transarterial (TA) technique results in high effectiveness of the axillary block. The technique is fast and simple, but does not produce a satisfactory success rate when using the manufacturer's recommended dose of mepivacaine. The multiple nerve stimulation (MNS) technique requires more time and experience. This double-blind study compared effectiveness, safety and the time used to obtain an effective analgesia in 101 patients, having an axillary block by either TA or MNS techniques.\n Mepivacaine with adrenaline (MEPA), 850 mg, was used for the initial block. Five millilitres of 1% solution was injected subcutaneously. In the TA group, 20 mL of 2% solution was injected deep to, and 20 mL superficial to the axillary artery. In the MNS group, four terminal motor nerves were electrolocated in the axilla, and injected with 10 mL each. Analgesia was assessed every 10 min and, when needed, supplemented after 30 min. The block was effective when analgesia was present in all sensory nerve areas distal to the elbow.\n The MNS group required median 11 min for block performance compared with 8 min for the TA group (P < 0.001). Latency of the initial block was shorter and the frequency of supplemental analgesia lower in the MNS group (median 10 min and 6%) than in the TA group (30 min and 36%, respectively), P < 0.001. All incomplete blocks were successfully supplemented. However, the total time to obtain an effective block was shorter in the MNS group (23 min) than in the TA group (37 min), P < 0.001. Two patients in each group had signs and symptoms of systemic toxicity, the most serious being atrial fibrillation and temporary loss of consciousness in a cardiovascularly medicated patient. The local adverse effects (intravascular injections and haematomas) were fewer in the MNS group, P < 0.001.\n The MNS technique of axillary block by four injections of 10 mL of 2% MEPA produces faster and more extensive block than the TA technique by two injections of 20 mL. Therefore, the MNS technique requires fewer supplementary blocks and results in faster patient readiness for surgery. However, high doses of MEPA may result in dangerous systemic toxic reactions.",
"This prospective, randomized, double-blind study was undertaken to evaluate the success rates of axillary brachial plexus block performed with the help of a peripheral nerve stimulator when either one, two or four of the major nerves of the brachial plexus were located. Seventy-five patients undergoing upper limb surgery were randomly allocated to one of the following five groups according to the nerve and number of nerves to be located; G-1: musculo-cutaneous, radial, median and ulnar nerves; G-2: musculo-cutaneous plus one of the other three nerves; G-3: radial nerve; G-4: median nerve; G-5: ulnar nerve. The sensory block was evaluated before surgery and cutaneous anaesthesia was considered to be present when the needles of a Wartenberg Pinwheel were no longer felt in all the dermatomes of the nerves implicated in the surgical site. Otherwise, the block was considered to need completion before surgery. Only one out of the 15 patients in G-1 and G-2 needed completion of their block before surgery whereas seven out of 15 for G-3 and eight out of 15 for G-4 and G-5 needed completion of their block (P less than 0.01). We conclude that when performing an axillary block with the help of a peripheral nerve stimulator, stimulation of the musculo-cutaneous nerve and one other nerve or stimulation of all four major nerves of the brachial plexus gives a higher success rate than stimulation of only one nerve, whether the stimulated nerve is the median, radial or ulnar.",
"To determine whether axillary block with nerve stimulation involving the location of four motor responses is more effective than other techniques using fewer locations, without increasing patient discomfort or the rate of complications.\n Prospective, randomized single blind study enrolling 100 patients undergoing orthopedic surgery under axillary block with nerve stimulation. Patients were randomly assigned to five groups of 20 patients: in group A, 4 motor responses were located; in group B three were located (musculocutaneous nerve and two more); in group C two responses, the musculocutaneous nerve and one more; in group D two non-musculocutaneous responses; and in group E only one non-musculocutaneous response was located (medial, cubital or radial). We used 40 ml of 1% mepivacaine. Data collected were location of responses, duration of blockade, adverse events occurring during the technique; level of motor and sensory block; tolerance to the tourniquet; level of patient discomfort; and presence of complications.\n A full sensory block was achieved for 100% in group A, 90% in group B, 60% in group C, 75% in group D and 40% in group E. Patient discomfort was similar in all groups. One patient continued to suffer postoperative neurologic dysfunction three months after the block.\n Locating 4 responses gives the greatest degree of assurance of obtaining full sensory block without increasing patient discomfort or rate of complications.",
"Traditional approaches to performing brachial plexus blocks via the axillary approach have varying success rates. The main objective of this study was to evaluate if a specific technique of ultrasound guidance could improve the success of axillary blocks in comparison to a two injection transarterial technique.\n Fifty-six ASA physical status I-III patients presenting for elective hand surgery were prospectively randomized to receive an axillary block performed by either a transarterial technique (Group TA) or an ultrasound-guided perivascular approach (Group US). Both groups received a total of 30 ml of 1.5% lidocaine (225 mg) with 5 microg/ml epinephrine. Patients were then evaluated for block onset in specific nerve distributions and whether or not the block acted as a surgical anesthetic.\n Group TA sustained more failures defined as conversion to general anesthesia or the inability to localize the artery [Group TA eight patients (29%) vs. Group US in which 0 patients required conversion to general anesthesia (0%) P < 0.01]. Group US demonstrated a reduction in performance times vs. Group TA (7.9 +/- 3.9 min vs. 11.1 +/- 5.7 min, P < 0.05). By 30 min post-injection, there were no significant differences between groups TA and US in terms of the proportion of patients demonstrating a complete motor or sensory loss.\n Ultrasonographic guidance improves the overall success rate of axillary blocks in comparison to a transarterial technique.",
"Insufficient spread of the local anesthetic toward the retroarterial region of the neurovascular space may be responsible for inconsistent anesthesia of the upper limb after single-injection axillary block. We hypothesized that injection of the local anesthetic on a single radial-nerve stimulation would produce the same extent of anesthesia as either a single median-nerve stimulation, a double-stimulation technique (radial and musculocutaneous nerves), or a triple-stimulation technique (radial, musculocutaneous, and median nerves).\n One hundred twenty patients were randomly assigned to receive an axillary block by either median-nerve, radial-nerve, radial-nerve plus musculocutaneous-nerve, or triple-nerve stimulation with 40 mL of plain 1.5% mepivacaine. Patients were assessed for sensory block by the pinprick method at 5 and 20 minutes.\n Radial-nerve stimulation produced more extensive anesthesia than did median-nerve stimulation. The rate of anesthesia at 20 minutes in the median-nerve cutaneous distribution was similar after median-nerve stimulation or radial-nerve stimulation. The ulnar nerve was more frequently blocked at 20 minutes after radial-nerve stimulation than after median-nerve stimulation. Extent of anesthesia at 20 minutes after radial-nerve plus musculocutaneous-nerve stimulation was similar to that produced by triple-nerve stimulation, except for lower rates of anesthesia that corresponded to the median nerve. All of the differences were statistically significant.\n Musculocutaneous-nerve stimulation and radial-nerve stimulation play predominant roles in the success of axillary brachial plexus block, although a triple-nerve stimulation technique is still required to produce complete anesthesia of the upper limb."
] |
This review provides evidence that multiple injection techniques using nerve stimulation for axillary plexus block produce more effective anaesthesia than either double or single injection techniques. However, there was insufficient evidence for a significant difference in other outcomes, including safety.
|
CD006005
|
[
"12763375",
"11451173",
"12072596",
"16035063"
] |
[
"A randomized study comparing lamivudine monotherapy after a short course of hepatitis B immune globulin (HBIg) and lamivudine with long-term lamivudine plus HBIg in the prevention of hepatitis B virus recurrence after liver transplantation.",
"Randomized trial of lamivudine versus hepatitis B immunoglobulin for long-term prophylaxis of hepatitis B recurrence after liver transplantation.",
"High sustained response rate in patients with histologically mild (low grade and stage) chronic hepatitis C infection. A randomized, double blind, placebo controlled trial of interferon alpha-2b with and without ribavirin.",
"A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients."
] |
[
"To compare the efficacy in preventing hepatitis B virus (HBV) recurrence of lamivudine vs. lamivudine plus hepatitis B immune globulin (HBIg) after a short course of HBIg and lamivudine in liver transplanted chronic hepatitis B patients.\n Forty-six patients with HBV cirrhosis received lamivudine before liver transplantation and were then randomized to receive lamivudine plus HBIg for 1 month followed by lamivudine or both drugs for 17 months.\n Thirty-two patients were transplanted and 29 were randomized to receive combination therapy (15 cases) or lamivudine monotherapy (14 cases). HBV DNA was undetectable in all cases (17 induced by lamivudine therapy) at the time of liver transplantation. After 18 months of follow-up, all patients survived without HBV recurrence: hepatitis Bs antigen and HBV DNA were negative; however, HBV DNA was detected by polymerase chain reaction in four cases (three with HBIg plus lamivudine and one with lamivudine). Alanine aminotransferase levels were normal except in six cases (one HCV and two HDV coinfections). There were no drug-related adverse events.\n Lamivudine monotherapy after a short course of lamivudine and HBIg is equally as efficacious in preventing HBV recurrence as HBIg plus lamivudine during the first 18 months after liver transplantation. This strategy is more economic and convenient to administer than long-term HBIg plus lamivudine.",
"The long-term prophylaxis of hepatitis B after liver transplantation requires further optimization. In a randomized trial we investigated a regimen where the initially given hepatitis B immunoglobulin (HBIg) is replaced by long-term lamivudine treatment.\n Twenty-four liver transplant recipients (all HBsAg-positive/HBV DNA-negative before transplantation), who had received HBIg for at least 6 months without HBV recurrence, were randomized to receive lamivudine (n = 12) or HBIg (n = 12) for 52 weeks. The efficacy criteria involved seronegativity for HBsAg and undetectable HBsAg/ HBcAg in the liver.\n Twenty-one of 24 patients completed the study without hepatitis B virus (HBV) recurrence (11 on HBIg, ten on lamivudine), while three patients became HBsAg-positive. Amongst those without HBV recurrence HBV DNA was detectable only by polymerase chain reaction, intermittently in serum and lymphocytes, and in liver specimens from six of eight patients receiving HBIg and five of seven receiving lamivudine. YMDD variant was found in four cases with no viral antigen expression. Eight patients continued lamivudine after the study and during an additional 6-22 months remained HBsAg-negative with normal graft function.\n Substitution of HBIg with lamivudine is effective for prevention of HBV recurrence in low-risk liver transplant recipients and offers a convenient and cost-effective alternative for long-term HBV prophylaxis.",
"To evaluate the efficacy and safety of therapy for patients with histologically mild hepatitis C virus (HCV) liver disease.\n A randomized, double blind, placebo controlled trial of interferon alpha-2b with or without ribavirin.\n Regional and university hospitals.\n One hundred and sixteen treatment naive patients with mild chronic HCV infection. Mild HCV infection was defined according to Knodell as a grade score of > or = 1 and < or = 6 and a stage score of < or = 1.\n Interferon alpha-2b (3 MU three times weekly) for 52 weeks in combination with either ribavirin or a matched placebo.\n The study endpoint was the absence of HCV RNA in plasma and liver tissue 26 weeks post-treatment. In addition, liver histology was compared pre- and post-treatment.\n Combination therapy was superior to interferon monotherapy, with a virological sustained response rate of 54% (31/57) and 20% (12/59), respectively, in both serum and liver tissue (P = 0.001). The sustained response rate was higher with combination therapy than monotherapy both in genotype non-1 (81% vs 36%) and in genotype 1 (28% vs 4%). There was a significant improvement in mean grade score in all sustained responders, irrespective of treatment arm.\n Combination therapy with interferon and ribavirin was safe and as effective in patients with histologically mild HCV infection as previously reported for more advanced disease.",
"Chronic hepatitis C is the most common indication for liver transplantation, but viral recurrence is universal and progressive graft injury occurs in most recipients. Our aim was to assess the safety, pharmacokinetics (PK), and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product (HCIG) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter, randomized, open-label, controlled trial conducted at 4 transplant centers in the United States. A total of 18 patients with chronic hepatitis C, who underwent liver transplantation, were randomized to receive low-dose HCIG (75 mg/kg) or high-dose HCIG (200 mg/kg), or no treatment. A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients. Hepatitis C virus levels, liver enzymes, and liver biopsies were obtained serially throughout the study period. PK profiles of HCV antibodies were determined on days 4, 10, and 98. HCIG infusions were safe and tolerated. The infusion rate could not be maximized because of symptoms for 18% to 30% of the doses. The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged. In the high-dose group, serum alanine aminotransferase (ALT) levels normalized in most subjects and no patient developed hepatic fibrosis. However, serum HCV RNA levels were not suppressed at either dose. In conclusion, HCIG, an anti-HCV enriched immune globulin product, appears to be safe in patients with chronic hepatitis C undergoing liver transplantation. Further studies are required to determine whether the drug has beneficial effects in this group of patients."
] |
This review could not derive clear evidence from randomised clinical trials for the treatment of patients with chronic HBV following liver transplantation for preventing recurrence of HBV infection. Large randomised clinical trials comparing long-term combination treatment to each of the monotherapy alone, including the newer antiviral drugs, are needed.
|
CD001538
|
[
"10865316"
] |
[
"Ischemic Optic Neuropathy Decompression Trial: twenty-four-month update."
] |
[
"To describe visual acuity outcomes of patients in the Ischemic Optic Neuropathy Decompression Trial (IONDT) after 24 months of follow-up.\n The IONDT is a single-masked, multicenter, randomized clinical trial.\n Patients were evaluated and followed up at 25 clinical centers located throughout the United States. Data were sent to and analyzed at a central coordinating center.\n Two hundred fifty-eight patients 50 years or older with nonarteritic anterior ischemic optic neuropathy and visual acuity of 20/64 or worse, but better than no light perception, were randomized to either a careful follow-up group (n=131) or an optic nerve decompression surgery (ONDS) group (n=127). Of these, 174 continued participation for at least 24 months, 89 in the careful follow-up group and 85 in the ONDS group.\n Randomized patients underwent a standard visual acuity examination at 3, 6, 12, 18, and 24 months of follow-up. The primary outcome was a change of 3 lines or more of visual acuity, defined as a difference of 0.3 in logMAR scores, between baseline and 6 months of follow-up. A secondary outcome was mean change in visual acuity (in logMAR units) at 3, 6, 12, 18, and 24 months following baseline. These changes were estimated using available data from all randomized patients for whom we had data.\n Of the 258 patients randomized, 143 (55.4%) were male, and 169 (65.5%) were 65 years or older. Mean visual acuity was statistically significantly improved from baseline value at all study visits and for both treatment groups, although visual acuity declined gradually in both groups after the 3-month visit. There were no significant differences between careful follow-up and ONDS in mean change in vision from the baseline and any follow-up time point. At 24 months of follow-up, 31.0% of patients in the careful follow-up group and 29.4% of patients in the ONDS group experienced an increase of 3 or more lines of vision compared with baseline acuity; 21.8% of patients in the careful follow-up group and 20.0% of patients in the ONDS group experienced a decrease of 3 or more lines. In patients who could read at least 1 letter on the Lighthouse chart, there was a gradual decline in mean visual acuity noted over time for both treatment groups, although acuity remained significantly better than at baseline.\n Analysis of visual acuity data from patients enrolled in the IONDT at 24 months of follow-up confirms that there is no benefit of ONDS compared with careful follow-up in patients with nonarteritic anterior ischemic optic neuropathy. Arch Ophthalmol. 2000;118:793-798"
] |
Results from the single trial indicate no evidence of a beneficial effect of optic nerve decompression surgery for NAION. Future research should focus on increasing our understanding of the etiology and prognosis of NAION. New treatment options should be examined in the context of randomized clinical trials.
|
CD003836
|
[
"9971865",
"7546872",
"2945109",
"20054944",
"12131705",
"11933280",
"18410774",
"2662802",
"7823996",
"16563893",
"8173852",
"2864530",
"14720531"
] |
[
"Lack of effectiveness of bed rest for sciatica.",
"Does 48 hours' bed rest influence the outcome of acute low back pain?",
"How many days of bed rest for acute low back pain? A randomized clinical trial.",
"How many days of bed rest for acute low back pain? Objective assessment of trunk function.",
"Bed rest or normal activity for patients with acute low back pain: a randomized controlled trial.",
"Randomised controlled trial of two pressure-relieving systems.",
"Double-blind placebo-controlled trial of amitriptyline for the treatment of irritable bowel syndrome in adolescents.",
"Bed rest and postlumbar puncture headache. The effectiveness of 24 hours' recumbency in reducing the incidence of postlumbar puncture headache.",
"The treatment of acute low back pain--bed rest, exercises, or ordinary activity?",
"Return to full normal activities including work at two weeks after acute myocardial infarction.",
"A randomized controlled study of post-injection rest following intra-articular steroid therapy for knee synovitis.",
"The effects of hospital admission for bed rest on the duration of twin pregnancy: a randomised trial.",
"A randomized placebo-controlled trial of pre-treatment and short- or long-term maintenance therapy with amiodarone supporting DC cardioversion for persistent atrial fibrillation."
] |
[
"Bed rest is widely advocated for sciatica, but its effectiveness has not been established. To study the effectiveness of bed rest in patients with a lumbosacral radicular syndrome of sufficient severity to justify treatment with bed rest for two weeks, we randomly assigned 183 subjects to either bed rest or watchful waiting for this period. The primary outcome measures were the investigator's and patient's global assessments of improvement after 2 and 12 weeks, and the secondary outcome measures were changes in functional status and in pain scores (after 2, 3, and 12 weeks), absenteeism from work, and the need for surgical intervention. Neither the investigators who assessed the outcomes nor those involved in data entry and analysis were aware of the patients' treatment assignments.\n After two weeks, 64 of the 92 patients in the bed-rest group (70 percent) reported improvement, as compared with 59 of the 91 patients in the control (watchful-waiting) group (65 percent) (adjusted odds ratio for improvement in the bed-rest group, 1.2; 95 percent confidence interval, 0.6 to 2.3). After 12 weeks, 87 percent of the patients in both groups reported improvement. The results of assessments of the intensity of pain, the bothersomeness of symptoms, and functional status revealed no significant differences between the two groups. The extent of absenteeism from work and rates of surgical intervention were similar in the two groups.\n Among patients with symptoms and signs of a lumbosacral radicular syndrome, bed rest is not a more effective therapy than watchful waiting.",
"Bed rest is a traditional treatment for back pain, yet only in recent years has the therapeutic benefit of this been questioned.\n The aim of this pilot study was to ascertain whether or not 48 hours' bed rest had an effect on the outcome of acute low back pain.\n The study was conducted as a randomized controlled trial to compare a prescription of 48 hours' strict bed rest with controls; the control subjects were encouraged to remain mobile and to have no daytime rest. Nine general practitioners from practices in the West Midlands recruited patients in the age range 16-60 years who presented with low back pain of less than seven days' duration, with or without pain radiation. The outcome measures assessed were: change in straight leg raise and lumbar flexion after seven days, Oswestry and Roland-Morris disability scores after seven days and 28 days, and time taken from work.\n Forty two patients were recruited: 20 were allocated to bed rest and 22 as controls. Compared with the bed rest group the control group had statistically better Roland-Morris scores at day seven (P < 0.05) but not at day 28. At day seven, there were no statistically significant differences between groups in straight leg raise or lumbar flexion measurements although the control group had a better mean lumbar flexion than the bed rest group. The improvement in disability scores at day seven compared with day one was similar for the two groups but more of the control group had fully recovered (defined as scores of one or zero on the Roland-Morris disability scale and five or less on the Oswestry disability scale) by day seven. Remaining mobile did not appear to cause any adverse effects. The number of days lost from work in both groups was equal. A large number of self-remedies and physical therapies were recorded by subjects from both groups.\n The results of this pilot study did not indicate whether bed rest or remaining mobile was superior for the treatment of acute low back pain; however, the study sample was small. Subjects in the control group possibly fared better as they appeared to have better lumbar flexion at day seven. It appears that 48 hours' bed rest cannot be recommended for the treatment of acute low back pain on the basis of this small study. Large-scale definitive trials are required to detect clinically significant differences.",
"Bed rest is usually recommended for acute low back pain. Although the optimal duration of bed rest is uncertain, a given prescription may directly affect the number of days lost from work or other activities. In a randomized trial, we compared the consequences of recommending two days of bed rest (Group I) with those of recommending seven days (Group II). The subjects were 203 walk-in patients with mechanical low back pain; 78 percent had acute pain (less than or equal to 30 days), and none had marked neurologic deficits. Follow-up data were obtained at three weeks (93 percent) and three months (88 percent). Although compliance with the recommendation of bed rest was variable, patients randomly assigned to Group I missed 45 percent fewer days of work than those assigned to Group II (3.1 vs. 5.6 days, P = 0.01), and no differences were observed in other functional, physiologic, or perceived outcomes. For many patients without neuromotor deficits, clinicians may be able to recommend two days of bed rest rather than longer periods, without any perceptible difference in clinical outcome. If widely applied, this policy might substantially reduce absenteeism from work and the resulting indirect costs of low back pain for both patients and employers.",
"Bed rest is usually considered an efficient treatment for acute low back pain. However, the optimal duration of bed rest is still being discussed. The recommended periods vary from 2 days to 2 weeks. The duration of optimum length is an important topic given the economical and physiological drawbacks of prolonged inactivity. The purpose of this work is to measure objectively the efficacy of two different durations of bed rest through a dynamometric measure of trunk function. Some 51 male patients, students or self-employed, being treated for acute low back pain were randomized into two groups. Group I was prescribed a bed rest period of 3 days and group II, a period of 7 days. We used a multi-axis isoinertial trunk testing dynamometric device (Isostation B200, Isotechnologies, USA). Patients were all assessed on day 1 and also on day 5 for group I or on day 9 for group II. The variables measured in the sagittal plane were isometric torques in flexion and extension, unresisted range of motion, average dynamic torques and average velocities. Patients were also asked to fill in a visual analogue pain scale on both assessment days. The improvement of all performance measures were important and highly significant (P < 0.001) in both groups. The results of the functional testing and the visual analogue pain scale showed no significant differences between the groups. In these relatively young and motivated patients, a duration of bed rest of 3 days resulted in the same objective functional improvement of trunk function and pain rating as a period of 7 days. This shorter duration should be considered as preferable, given the same objective results but important physiological and economical advantages.",
"The management of common low back pain has two principal objectives: to relieve acute pain and to attempt prevention of transition to chronicity. Several studies have shown the ineffectiveness of prolonged periods of bed rest.\n To compare 4 days of bed rest with continued normal daily activity in acute low back pain, taking into account the type of work (physical or sedentary labor).\n This open, comparative multicenter study enrolled 281 ambulatory patients, ages 18 to 65 years, with low back pain (onset < 72 hours). The subjects did not have pain radiating below the buttocks and did not have work-related injuries. They were randomized into two treatment groups: one instructed to continue normal activity (insofar as the pain allowed), and the other prescribed 4 days of bed rest. After inclusion, patients were seen at three visits: on day 6 or 7, after 1 month, and after 3 months.\n On day 6 or 7, pain intensity was similar for both groups, as was the overall judgment of the treatment by patients and physicians. At 1 and 3 months, the groups again had equivalent intensity of back pain, functional disability, and vertebral stiffness. A higher proportion of patients in the bed rest group than in the normal activity group had an initial sick leave (86% vs 52%; P < 0.0001). This difference was greater for the patients whose work was sedentary.\n For patients with acute low back pain, normal activity is at least equivalent to bed rest. The findings of this study indicate that prescriptions for bed rest, and thus for sick leaves, should be limited when the physical demands of the job are similar to those for daily life activities.",
"The primary objective of this randomised controlled trial was to determine whether there were significant differences between two pressure-relieving systems. A secondary aim was to investigate whether the availability of extra pressure-relieving equipment would reduce the incidence of ulcers in an acute hospital setting. A total of 141 patients in a care-of-the-elderly unit, who were assessed to have a high risk of developing pressure ulcers using the Waterlow score, were recruited; 70 were nursed using Huntleigh Nimbus 3 in conjunction with the Aura cushion (Group A), and 71 using the Pegasus Cairwave Therapy System in conjunction with the Proactive 2 Seating cushion (Group B). The main outcome measure was visual assessment, supported by a photographic record. There were three main findings: for non-heel ulcers and overall improvement, there was no statistically significant difference between the two products tested; for heel ulcers there was a significant difference (P = 0.019) with more patients healing in Group A than in Group B. The average length of stay of patients who completed the trial was 21.6 days (Group A) and 21.7 days (Group B) for patients completing a live (range 1-121 days) and for patients who died 29.7 days (Group A) and 24.3 days (Group B). Routine monitoring showed that, before the trial, the incidence of hospital-acquired pressure ulcers (Torrance grade 2+) was 0.2%; during the trial, this dropped to 0.13%. The study showed differences in the efficacy of different mattress products; with a sufficiently large study, it is possible to demonstrate statistically significant results. Provision of extra pressure-relieving equipment can reduce the incidence of pressure ulcers but may not influence length of stay.",
"To determine the efficacy of amitriptyline (AMI) in treating irritable bowel syndrome (IBS) in adolescents.\n Adolescents 12 to 18 years with newly diagnosed IBS were surveyed with a symptom checklist, pain rating scale, visual analog scale, and IBS quality of life (QOL) questionnaire. Subjects were randomized in a double-blinded fashion to receive AMI or placebo, and again completed surveys at 2, 6, 10, and 13 weeks.\n Thirty-three patients (24 female) were enrolled. Patients receiving AMI were more likely to experience improvement from baseline in overall QOL at 6, 10, and 13 weeks (P = .019, .004, and .013). Patients receiving AMI were also more likely to experience a reduction in IBS-associated diarrhea at 6 and 10 weeks (P = .029 for both), a reduction in periumbilical pain at 10 weeks (P = .018), and a reduction in right lower quadrant pain at 6, 10, and 13 weeks (P = .014, .039, and .004).\n AMI significantly improves overall QOL in adolescents with IBS and should be a therapeutic option for adolescents with this disorder.",
"A prospective, blind, randomised trial was undertaken to determine if the incidence of postlumbar puncture headache is significantly altered by 24 hours' recumbency. One hundred and two patients were allocated randomly to rest supine in bed for either 4 or 24 hours after spinal anaesthesia for urological or gynaecological surgery. A standardised spinal anaesthetic technique was applied that incorporated the use of a 22-gauge needle. All patients were followed-up prospectively to determine if there was a difference in the incidence of postlumbar puncture headache between the two groups. Five patients (11.6%) who were recumbent for 4 hours developed postlumbar puncture headache, a result which was not statistically significantly different from the seven patients (11.9%) in the other group who complained of postlumbar puncture headache.",
"Bed rest and back-extension exercises are often prescribed for patients with acute low back pain, but the effectiveness of these two competing treatments remains controversial.\n We conducted a controlled trial among employees of the city of Helsinki, Finland, who presented to an occupational health care center with acute, nonspecific low back pain. The patients were randomly assigned to one of three treatments: bed rest for two days (67 patients), back-mobilizing exercises (52 patients), or the continuation of ordinary activities as tolerated (the control group; 67 patients). Outcomes and costs were assessed after 3 and 12 weeks.\n After 3 and 12 weeks, the patients in the control group had better recovery than those prescribed either bed rest or exercises. There were statistically significant differences favoring the control group in the duration of pain, pain intensity, lumbar flexion, ability to work as measured subjectively, the Oswestry back-disability index, and number of days absent from work. Recovery was slowest among the patients assigned to bed rest. The overall costs of care did not differ significantly among the three groups.\n Among patients with acute low back pain, continuing ordinary activities within the limits permitted by the pain leads to more rapid recovery than either bed rest or back-mobilizing exercises.",
"Patients are generally advised to return to full normal activities, including work, 6 to 8 weeks after acute myocardial infarction (AMI). We assessed the outcomes of early return to normal activities, including work at 2 weeks, after AMI in patients who were stratified to be at a low risk for future cardiac events. Patients were considered for randomization before discharge if they had no angina, had left ventricular ejection fraction >40%, a negative result from a symptom-limited exercise stress test for ischemia (<2 mm ST depression) at 1 week, and achieved >7 METs. Patients with left ventricular ejection fraction <40% were included only if they did not have inducible ventricular tachycardia at electrophysiologic studies. Seventy-two patients were randomized to return to normal activities at 2 weeks and 70 patients to undergo standard cardiac rehabilitation and return to normal activities at 6 weeks after AMI. There were no deaths or heart failure in either group. There was no significant difference in the incidence of reinfarction, revascularization, left ventricular function, lipids, body mass index, smoking, or exercise test results at 6 months. In conclusion, return to full normal activities, including work at 2 weeks, after AMI appears to be safe in patients who are stratified to a low-risk group. This should have significant medical and socioeconomic implications.",
"In order to assess the effect of 24 h observed bed rest following intra-articular steroid injection of the knee joint in patients with an inflammatory arthritis such as RA, AS or colitic arthropathy, 91 patients with inflammatory arthritis of one knee joint were randomized to receive 24 h bed rest in hospital following intra-articular steroid injection or were injected in outpatients. The clinical and laboratory assessments such as pain and stiffness on a 10-cm visual analogue scale, knee circumference (cm), 50 ft walking time (s), CRP and ESR were measured before receiving the steroid injection and at 3, 6, 12 and 24 weeks. Both groups of patients improved clinically and serologically at 3 weeks. By 12 weeks the degree of improvement in the pain score, stiffness score, knee circumference, 50 ft walking time and CRP was better in the rest group and these differences persisted to 24 weeks. For each outcome variable the summary measure of response was significantly better in the rest group compared to the no rest group. Intra-articular steroid injection of the knee joint followed by strict i inpatient bed rest for 24 h results in a greater degree of clinical and serological improvement, compared to routine outpatient injections for up to 6 months. It is therefore possible that 24-h post-injection rest will result in a prolonged duration of clinical response and reduce the need for frequent steroid injections and the risk of complications.",
"212 women with twin pregnancies were randomly allocated either to receive advice to rest in hospital from 32 weeks' gestation until delivery, or to be part of a control group in which hospital admission was offered selectively (and, on average, 5 weeks later). Preterm delivery was more common among women admitted routinely for bed rest than among controls, and this difference was unlikely to have occurred by chance. There is at present no scientifically acceptable evidence that this common, disruptive, and expensive obstetric policy does more good than harm.",
"The efficacy of cardioversion (DCCV) for restoration of sinus rhythm (SR) in persistent atrial fibrillation (AF) is limited by a high relapse rate. Relapse may be reduced by amiodarone but no placebo-controlled trials of efficacy have been performed and the appropriate duration of therapy is unknown.\n In this double-blind study, 161 subjects with persistent AF were randomized to one of three groups-placebo (n=38); amiodarone 400mg BD for 2 weeks prior to DCCV and 200mg daily for 8 weeks followed by placebo for 44 weeks (n=62, short-term amiodarone); amiodarone 400mg BD for 2 weeks then 200mg daily for 52 weeks (n=61, long-term amiodarone). Spontaneous reversion to SR occurred before DCCV in 21% (26/123) patients on amiodarone and none of the 38 patients on placebo (absolute difference 21%, 95% confidence interval (CI): 10 to 29%, P=0.002). At 8 weeks following DCCV, 51% (63/123) patients on amiodarone remained in SR compared to 16% (6/38) taking placebo (difference-35% 95% CI: -48 to -18%, P<0.001). At 1 year, 49% (30/61) patients on long-term amiodarone were in SR compared to 33% (21/62) taking short-term amiodarone (difference-15%, 95% CI: -31 to 2%, P=0.085). There was no difference in adverse event rate or quality of life scores between groups.\n Amiodarone pre-treatment before electrical DCCV for persistent AF allows chemical conversion in one-fifth of patients without altering the efficacy of subsequent DC conversion. Amiodarone is more effective than placebo in the maintenance of SR when continued for 8 weeks following successful DCCV. More patients taking long-term amiodarone remained in SR at 52 weeks, but more had serious adverse effects requiring discontinuation of therapy. Eight weeks of adjuvant therapy with amiodarone following successful DCCV may be the preferred option."
] |
Bed rest ranging from 2 to 12 days appears to be as safe as longer periods of bed rest. The quality of most trials is unsatisfactory. Current bed rest recommendations are not supported by the existing evidence as the optimal duration of bed rest is unknown. The lack of adequate trials is surprising, considering the large size of several studies to compare effectiveness of drugs on people with AMI.
|
CD009077
|
[
"17383291"
] |
[
"A randomized trial of carvedilol after renin-angiotensin system inhibition in chronic Chagas cardiomyopathy."
] |
[
"The objective of this study was to determine the safety and efficacy of renin-angiotensin system (RAS) inhibitors and beta-blockers in chronic Chagas cardiomyopathy.\n Chronic Chagas cardiomyopathy causes substantial morbidity and mortality in Latin America. Whether RAS inhibitors and beta-blockers are safe and beneficial has been challenged because of the lack of formal trials.\n We conducted a double-blind, placebo-controlled, and randomized trial in 42 patients with Trypanosoma cruzi infection and cardiomyopathy. All patients received enalapril (up-titrated to 20 mg BID) and spironolactone (25 mg QD). Subsequently, the patients were randomly assigned to receive placebo (n = 20) or carvedilol up-titrated to 25 mg BID (n = 19). The primary end points were change in left ventricular ejection fraction (LVEF) after RAS inhibition and that after the addition of carvedilol. The secondary end points were changes in other echocardiographic parameters, Framingham score, quality of life (36-item Short-Form Health Survey), New York Heart Association class, radiographic indices, brain natriuretic peptide levels, and chemokines as well as safety end points.\n Optimization of RAS inhibition was safe, hemodynamically well tolerated, and associated with improvements in Framingham score (P = .001) and quality of life as well as reductions in the cardiothoracic index (P = .002), brain natriuretic peptide level (P = .032), and RANTES (regulated on activation, normal T expressed and secreted) level (P = .001). Left ventricular ejection fraction increased by 2.3% (P = .25); in patients with an LVEF < or = 45% at baseline, it increased by 2.8% (P = .017). Treatment with carvedilol was associated with a trend toward an increase in LVEF (absolute difference between groups, 2.3%; P = .094). The addition of carvedilol was safe, hemodynamically well tolerated, and not associated with symptomatic bradycardia.\n In patients with chronic Chagas cardiomyopathy, optimization of treatment with enalapril and spironolactone and subsequent addition of carvedilol were safe and associated with benefits in cardiac function and clinical status. Larger trials are needed to show effects on mortality and/or hospitalization."
] |
This Cochrane review has found a lack of evidence on the effects of carvedilol for treating heart failure in patients with Chagas disease. The two included trials were underpowered and had a high risk of bias. There are no conclusive data to support the use of carvedilol for treating Chagas cardiomyopathy. Unless randomized clinical trials provide evidence of a treatment effect, and the trade off between potential benefits and harms is established, policy-makers, clinicians, and academics should be cautious when recommending and administering carvedilol for treating heart failure in patients with Chagas disease. The efficacy and safety of other pharmacological interventions for treating heart failure in patients with Chagas disease is unknown.
|
CD006015
|
[
"14681504",
"12559281",
"8684407",
"12526285",
"8595647",
"1383816",
"9475762",
"7495111",
"8911291",
"9340898",
"9610579",
"14663474",
"9152564",
"7542109",
"8876706",
"10210385",
"1283370",
"10971268",
"12824459",
"9146609",
"9697781"
] |
[
"The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia.",
"Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial.",
"The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group.",
"Comparison of tamsulosin and finasteride for lower urinary tract symptoms associated with benign prostatic hyperplasia in Korean patients.",
"Efficacy, tolerability, and effect on health-related quality of life of finasteride versus placebo in men with symptomatic benign prostatic hyperplasia: a community based study. CUSP Investigators. Community based study of Proscar.",
"The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group.",
"The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group.",
"Can finasteride reverse the progress of benign prostatic hyperplasia? A two-year placebo-controlled study. The Scandinavian BPH Study Group.",
"Efficacy and safety of finasteride therapy for benign prostatic hyperplasia: results of a 2-year randomized controlled trial (the PROSPECT study). PROscar Safety Plus Efficacy Canadian Two year Study.",
"[Combination of Sabal and Urtica extract vs. finasteride in benign prostatic hyperplasia (Aiken stages I to II). Comparison of therapeutic effectiveness in a one year double-blind study].",
"Long-term effects of finasteride in patients with benign prostatic hyperplasia: a double-blind, placebo-controlled, multicenter study. PROWESS Study Group.",
"A comparison of the efficacy and tolerability of tamsulosin and finasteride in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.",
"Efficacy and tolerability of finasteride in symptomatic benign prostatic hyperplasia: a primary care study. Primary Care Investigator Study Group.",
"Therapeutic effects of finasteride in benign prostatic hyperplasia: a randomized double-blind controlled trial.",
"Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostate hyperplasia: a randomized international study of 1,098 patients.",
"Improvement of pressure flow parameters with finasteride is greater in men with large prostates. Finasteride Urodynamics Study Group.",
"Scandinavian clinical study of finasteride in the treatment of benign prostatic hyperplasia.",
"Combined sabal and urtica extract compared with finasteride in men with benign prostatic hyperplasia: analysis of prostate volume and therapeutic outcome.",
"The influence of finasteride on the development of prostate cancer.",
"Prostate tissue composition and response to finasteride in men with symptomatic benign prostatic hyperplasia.",
"Treatment with finasteride preserves usefulness of prostate-specific antigen in the detection of prostate cancer: results of a randomized, double-blind, placebo-controlled clinical trial. PLESS Study Group. Proscar Long-term Efficacy and Safety Study."
] |
[
"Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown.\n We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia.\n The risk of overall clinical progression--defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection--was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone.\n Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy.\n Copyright 2003 Massachusetts Medical Society",
"To evaluate the efficacy and tolerability of the selective alpha(1)-adrenergic antagonist doxazosin and the 5-alpha-reductase inhibitor finasteride, alone and in combination, for the symptomatic treatment of benign prostatic hyperplasia.\n In a prospective, double-blind, placebo-controlled trial, 1095 men aged 50 to 80 years were randomized to treatment for 52 weeks with doxazosin, finasteride, the combination of doxazosin and finasteride, or placebo. The dose of finasteride (or its matched placebo) was 5 mg/day. Doxazosin (or its matched placebo) was initiated at 1 mg/day, and titrated up to a maximum of 8 mg/day over approximately 10 weeks according to the response of the maximal urinary flow rate (Qmax) and International Prostate Symptom Score (IPSS). The IPSS and Qmax were assessed at baseline and at weeks 10, 14, 26, 39, and 52 or at the endpoint.\n An intent-to-treat analysis of 1007 men showed doxazosin and doxazosin plus finasteride combination therapy produced statistically significant improvements in total IPSS and Qmax compared with placebo and finasteride alone (P <0.05). Finasteride alone was not significantly different statistically from placebo with respect to total IPSS and Qmax. All treatments were generally well tolerated.\n Doxazosin was effective in improving urinary symptoms and urinary flow rate in men with benign prostatic hyperplasia, and was more effective than finasteride alone or placebo. The addition of finasteride did not provide further benefit to that achieved with doxazosin alone.",
"Men with benign prostatic hyperplasia can be treated with alpha 1-adrenergic-antagonist drugs that relax prostatic smooth muscle or with drugs that inhibit 5 alpha-reductase and therefore reduce tissue androgen concentrations. However, the effects of the two types of drugs have not been compared.\n We compared the safety and efficacy of placebo, terazosin (10 mg daily), finasteride (5 mg daily), and the combination of both drugs in 1229 men with benign prostatic hyperplasia. American Urological Association symptom scores and peak urinary-flow rates were determined at base line and periodically for one year.\n The mean changes from base line in the symptom scores in the placebo, finasteride, terazosin, and combination-therapy groups at one year were decreases of 2.6, 3.2, 6.1, and 6.2 points, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). The mean changes at one year in the peak urinary-flow rates were increases of 1.4, 1.6, 2.7, and 3.2 ml per second, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). Finasteride had no more effect on either measure than placebo. In the placebo group, 1.6 percent of the men discontinued the study because of adverse effects, as did 4.8 to 7.8 percent of the men in the other three groups.\n In men with benign prostatic hyperplasia, terazosin was effective therapy, whereas finasteride was not, and the combination of terazosin and finasteride was no more effective than terazosin alone.",
"Tamsulosin (0.2 mg) and finasteride (5 mg) once daily for 24 weeks were compared in a single-blind, randomized study as initial treatments for lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH) in 205 Korean patients. Symptom and quality of life (QOL) assessment by the International Prostatic Symptom Score (I-PSS), maximum urinary flow rate (Qmax) and adverse events were analysed at 4 weeks and 24 weeks. On intention-to-treat analysis, both drugs showed similar efficacy at endpoint (decreased I-PSS, increased Qmax and improved QOL score; 34.7%, 23.9% and 34.1% for tamsulosin, and 30.5%, 22.2% and 23.1% for finasteride, respectively). However, tamsulosin produced significant improvements in I-PSS and Qmax at 4 weeks compared with finasteride (17.6% versus 10.0% and 10.9% versus 3.1%, respectively), and a superior QOL score improvement during the study. Adverse events were observed significantly more frequently among finasteride than tamsulosin patients (23 versus four). Both were equally effective in long-term treatment of urinary outflow obstruction symptoms associated with BPH in Korean patients, but tamsulosin was more effective for short-term treatment, with a better safety profile.",
"This study sought to assess the efficacy, tolerability, and effect of finasteride on health-related quality of life (HRQL) in a diverse population of men with moderate-to-severe symptomatic benign prostatic hyperplasia (BPH). This double-blind study evaluated finasteride and placebo for 12 months in 2342 men with BPH (16.2% black, 14.5% Hispanic, 69.3% Caucasian/other) in a community-based setting. At 3-month intervals, urinary symptoms were measured by use of the American Urologic Association symptom index. HRQL was assessed by use of the BPH impact index (BII), which evaluated degree of bother, worry, physical discomfort, and restriction in activities as a result of urinary symptoms. Additional questions regarding activities of living were administered, and global assessments of change in urologic status were performed by both patients and investigators. Compared with placebo, patients treated with finasteride had a statistically significant decrease in symptom scores when first measured at month 3. Symptom scores continued to improve in finasteride-treated patients throughout the study; at month 12, the mean decrease in symptom scores in the finasteride-treated patients was -4.8 compared with -3.4 for placebo patients ( P = 0.0001). Statistically significant differences in favor of finasteride also were noted at month 12 on the BII (P = 0.0465), and finasteride-treated patients experienced less interference with activities of living (P = 0.0518). Patient and investigator global assessments of urologic status showed that significantly more patients in the finasteride group considered themselves improved and were considered improved by investigators at month 12 (P = 0.000). Finasteride was generally well tolerated. The incidence of drug-related sexual adverse experiences was significantly higher in the finasteride group (P = 0.000), but led to withdrawal in only 1.5% of patients. The demonstrated efficacy and tolerability of finasteride in reducing symptoms and improving quality of life confirm observations of previous trials and make finasteride a highly desirable treatment option for many men with symptomatic BPH.",
"Benign prostatic hyperplasia is a progressive, androgen-dependent disease resulting in enlargement of the prostate gland and urinary obstruction. Preventing the conversion of testosterone to its tissue-active form, dihydrotestosterone, by inhibiting the enzyme 5 alpha-reductase could decrease the action of androgens in their target tissues; in the prostate the result might be a decrease in prostatic hyperplasia and therefore in symptoms of urinary obstruction.\n In a double-blind study, we evaluated the effect of two doses of finasteride (1 mg and 5 mg) and placebo, each given once daily for 12 months, in 895 men with prostatic hyperplasia. Urinary symptoms, urinary flow, prostatic volume, and serum concentrations of dihydrotestosterone and prostate-specific antigen were determined periodically during the treatment period.\n As compared with the men in the placebo group, the men treated with 5 mg of finasteride per day had a significant decrease in total urinary-symptom scores (P less than 0.001), an increase of 1.6 ml per second (22 percent, P less than 0.001) in the maximal urinary-flow rate, and a 19 percent decrease in prostatic volume (P less than 0.001). The men treated with 1 mg of finasteride per day did not have a significant decrease in total urinary-symptom scores, but had an increase of 1.4 ml per second (23 percent) in the maximal urinary-flow rate, and an 18 percent decrease in prostatic volume. The men given placebo had no changes in total urinary-symptom scores, an increase of 0.2 ml per second (8 percent) in the maximal urinary-flow rate, and a 3 percent decrease in prostatic volume. The frequency of adverse effects in the three groups was similar, except for a higher incidence of decreased libido, impotence, and ejaculatory disorders in the finasteride-treated groups.\n The treatment of benign prostatic hyperplasia with 5 mg of finasteride per day results in a significant decrease in symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic volume, but at a slightly increased risk of sexual dysfunction.",
"Finasteride is known to improve urinary symptoms in men with benign prostatic hyperplasia, but the extent to which the benefit is sustained and whether finasteride reduces the incidence of related events, including the need for surgery and the development of acute urinary retention, is not known.\n In this double-blind, randomized, placebo-controlled trial, we studied 3040 men with moderate-to-severe urinary symptoms and enlarged prostate glands who were treated daily with 5 mg of finasteride or placebo for four years. Symptom scores (on a scale of 1 to 34), urinary flow rates, and the occurrence of outcome events were assessed every four months in 3016 men. Prostate volume was measured in a subgroup of the men. Complete data on outcomes were available for 2760 men.\n During the four-year study period, 152 of the 1503 men in the placebo group (10 percent) and 69 of the 1513 men in the finasteride group (5 percent) underwent surgery for benign prostatic hyperplasia (reduction in risk with finasteride, 55 percent; 95 percent confidence interval, 41 to 65 percent). Acute urinary retention developed in 99 men (7 percent) in the placebo group and 42 men (3 percent) in the finasteride group (reduction in risk with finasteride, 57 percent; 95 percent confidence interval, 40 to 69 percent). Among the men who completed the study, the mean decreases in the symptom score were 3.3 in the finasteride group and 1.3 in the placebo group (P<0.001). Treatment with finasteride also significantly improved urinary flow rates and reduced prostate volume (P<0.001).\n Among men with symptoms of urinary obstruction and prostatic enlargement, treatment with finasteride for four years reduces symptoms and prostate volume, increases the urinary flow rate, and reduces the risk of surgery and acute urinary retention.",
"To study if placebo-induced improvement in men with symptomatic benign prostatic hyperplasia (BPH) is maintained over 2 years, and to study the efficacy and safety from intervention with finasteride 5 mg for 24 months.\n This was a multicenter, double-blind, placebo-controlled study involving 707 patients with moderate symptoms of BPH enrolled at 59 centers in five Scandinavian countries. Following enrollment and a 4-week single-blind placebo run-in period, patients were randomized to receive finasteride 5 mg once daily or placebo for 24 months. Urinary symptoms, urinary flow rate, prostate volume, postvoiding residual urinary volume, and serum concentrations of prostate-specific antigen together with laboratory safety parameters were measured at entry and at months 12 and 24. Interim physical and laboratory examinations were performed when indicated clinically.\n In finasteride-treated patients the total symptom score improved throughout the study, with a significant difference between the two groups at 24 months (P < or = 0.01), whereas in placebo-treated patients, there was an initial improvement in the symptom score but no change from baseline at 24 months. The maximum urinary flow rate decreased in the placebo group, but improved in the finasteride group, resulting in a between-group difference of 1.8 mL/s at 24 months (P < or = 0.01). The mean change in prostate volume was +12% in the placebo group versus -19% in the finasteride-treated group (P < 0.01). Finasteride was generally well tolerated throughout the 2-year study period.\n The efficacy of therapy with finasteride 5 mg in improving both symptoms and maximum urinary flow rate and reducing prostate volume has been shown to be maintained during 24 months while patients receiving placebo experienced a return to baseline or deterioration of these parameters during the study. These results demonstrate that finasteride can reverse the natural progression of BPH.",
"To evaluate the efficacy and safety of 2 years' treatment of moderate benign prostatic hyperplasia (BPH) with finasteride.\n Double-blind, parallel-group, placebo-controlled, multicentre, prospective randomized study.\n Outpatient care in 28 centres across Canada.\n Men aged 45 to 80, in good health, with moderate BPH and no evidence of prostate cancer. A total of 613 men were entered into the study; 472 completed the 2 years of treatment.\n After 1 month of receiving a placebo (run-in period), patients were given either finasteride (5 mg/d) or a placebo for 2 years.\n Efficacy: changes from baseline in BPH symptom scores, maximum urinary flow rates and prostate volume. Safety: onset, course and resolution of all adverse events during the treatment period.\n In the efficacy analyses the mean BPH symptom scores decreased 2.1 points (from 15.8 to 13.7) in the finasteride group, as compared with a decrease of 0.7 points (from 16.6 to 15.9) in the placebo group (P < or = 0.01). The maximum urinary flow rate increased by a mean of 1.4 mL/s (from 11.1 to 12.5 mL/s) in the finasteride group, as compared with an increase of 0.3 mL/s (from 10.9 to 11.2 mL/s) in the placebo group (p < or = 0.01). The mean prostate volume decreased by 21% (from a mean volume of 44.1 cm3 at baseline) in the treatment group; it increased by 8.4% (from a mean volume of 45.8 cm3 at baseline) in the placebo group (p < or = 0.01). In the safety analysis, the proportion of patients who experienced any adverse event was similar in the two groups (81.0% in the treatment group and 81.2% in the placebo group). However, the incidence of adverse events related to sexual dysfunction were significantly higher in the finasteride group than in the placebo group (ejaculation disorder 7.7% v. 1.7% and impotence 15.8% v. 6.3%; p < or = 0.01 for both parameters).\n Finasteride is a well-tolerated and effective alternative to watchful waiting in the treatment of moderate BPH.",
"Therapeutic equivalence should be demonstrated in a randomised, reference-controlled multicentric double blind clinical trial with PRO 160/120, a combination of Sabal- and Urtica-Extract, and Finasteride, respectively, in patients suffering from benign prostatic hyperplasia (BPH, Stage I to II according to Aiken). The study involved 543 patients, who were treated for 48 weeks with two capsules of PRO 160/120 or one capsule of Finasteride per day, in a double dummy design. Primary variable was the change of the maximum urinary flow after 24 weeks of therapy in comparison to therapy start. As secondary variables urodynamic parameters such as average urinary flow, miction volume and miction time were monitored. Urinary symptoms were recorded by the International-Prostate-Symptom-Score (I-PSS, Paris 1993). Additionally, the impacts of the symptoms on quality of life had been assessed by a quality of life questionnaire according to The American Urological Association Measurement Committee (1991). An increase of the urinary flow rate could be observed in both treatment groups (1.9 ml/s with PRO 160/ 120; 2.4 ml/s with Finasteride). During the trial, the average urinary flow increased, whereas the miction time decreased in both groups in a similar extent. The miction volume did not show any relevant differences after treatment with either PRO 160/120 or Finasteride. The I-PSS decreased from 11.3 at the therapy start to 8.2 after 24 weeks and 6.5 (week 48) under PRO 160/120 and from 11.8 to 8.0 and 6.2, under Finasteride, respectively. Accordingly, life quality improved between therapy start and therapy end from 7.5 to 4.3 with PRO 160/120 and from 7.7 to 4.1 with Finasteride. In terms of safety aspects less adverse events occurred with the Sabal/Urtica-Extract as with Finasteride. Especially less cases of diminished ejaculation volume, erectile dysfunction and headache have been reported.",
"To compare the long-term effects of finasteride (5 mg/day) and placebo in patients with moderate symptoms of benign prostatic hyperplasia (BPH).\n Patients aged 50 to 75 years, with at least two urinary symptoms indicating moderate BPH, and an enlarged prostate, were followed in a 2-year double-blind, randomized, placebo-controlled multicenter study. The effects of finasteride versus placebo were assessed by total symptom score (modified Boyarsky), obstructive symptom score, maximal urinary flow rate, prostate volume, and urologic end points (acute urinary retention, BPH-related surgical intervention).\n Of the 3270 men enrolled, 3168 contributed data to the safety analysis, and 2902 to the efficacy evaluation. Significantly greater improvement with finasteride compared to placebo was observed at 12 and 24 months for total symptom score (mean -2.9 versus -1.9 at 12 months, P < or =0.001; -3.2 versus -1.5 at 24 months, P < or =0.001), obstructive symptom score (mean -1.9 versus -1.3 at 12 months, P < or =0.001; -2.1 versus -1.1 at 24 months, P < or =0.001), maximal urinary flow rate (mean +1.2 versus +0.6 mL/s at 12 months, P = 0.010; +1.5 versus +0.7 mL/s at 24 months, P = 0.002), and prostate volume (mean -14.2 versus +5.4% at 12 months, P < or =0.01; -15.3 versus +8.9% at 24 months, P < or =0.001). Greater improvements in placebo-adjusted total symptom score occurred in men with large prostates than in men with small prostates (mean -2.4 versus -1.1 at 12 months; -3.2 versus -1.3 at 24 months, placebo-adjusted data, P = 0.053). Fifteen of 1450 men (1.0%) in the finasteride group experienced an acute urinary retention event, compared with 37 of 1452 (2.5%) in the placebo group, and the corresponding figures for surgery were 51 of 1450 (3.5%) and 86 of 1452 (5.9%), respectively. The hazard rate for occurrence, computed using the log-rank statistic, decreased by 57% for acute urinary retention and by 40% for surgery accompanied by finasteride therapy compared to placebo.\n Finasteride causes long-term symptomatic improvement and reduces the risk of acute urinary retention or surgery. Men with enlarged prostates benefit most from finasteride treatment.",
"In this multicentre, double-blind study, patients with LUTS/BPH were randomised to 26 weeks with finasteride 5 mg once daily (n=204) or tamsulosin 0.4 mg once daily (n=199). Double-blind treatment was continued for another 26 weeks (total treatment duration: 1 y). The primary efficacy parameter was the difference in mean change in total Symptom Problem Index (SPI) from baseline to end point at week-26 in the intention-to-treat (ITT) and per protocol (PP) populations. Tamsulosin induced a greater improvement in total SPI (-5.2 points or -37%) compared to finasteride (-4.5 points or -31%) at week-26 (P=0.055 in ITT and P=0.032 in PP). Tamsulosin improved urinary symptoms (particularly the more bothersome storage symptoms) and flow more quickly than finasteride. The difference was statistically significant for the SPI from week-1 (reduction, respectively, -2.5 vs -1.8 points, P=0.043) to week-18 and for Qmax from week-1 (increase, respectively, 2.3 vs 0.7 ml/s, P=0.0007) to week-12. Both treatments were well tolerated with a comparable incidence of adverse events, including urinary retention.",
"Because increasing numbers of men are seeking treatment for benign prostatic hyperplasia (BPH) from primary care physicians, we sought to assess the efficacy and tolerability of finasteride in a primary care setting. In this randomized, double-masked study, 2,112 men with symptomatic BPH received either finasteride (n = 1,589) or placebo (n = 523) for 1 year. At 3, 6, 9, and 12 months, urinary symptoms were measured using the American Urological Association Symptom Index (AUASI). Quality of life was assessed using the BPH Impact Index (BII), which assessed bother, worry, physical discomfort, and restriction in activities. Both patients and investigators assessed overall urologic status. Investigators assessed the effect of the drug on plasma lipids in a subset of patients. Patients treated with finasteride had a statistically significant mean decrease in AUASI scores compared with patients treated with placebo beginning at month 6 and continuing throughout the study. At month 12, adjusted mean decreases in AUASI scores were -4.96 for finasteride versus -3.71 for placebo. Statistically significant differences in favor of finasteride were also noted on BII at months 9 and 12. Patient and investigator overall assessments showed greater improvement in the finasteride group beginning at month 6. The incidence of drug-related sexual adverse experiences was significantly greater in finasteride-treated patients but led to withdrawal in only 2.2% of these patients. Overall lipid profile was not significantly altered in either group. Based on improvement in symptoms and quality of life, and on its favorable tolerability profile, finasteride should be considered by primary care physicians for management of symptomatic BPH.",
"The clinical effects of finasteride, a 5 alpha-reductase inhibitor, in patients with benign prostatic hyperplasia (BPH) were evaluated in a double-blind, placebo-controlled study. Forty-six patients with symptomatic BPH were randomly assigned to 2 groups, the finasteride group and the placebo group. The finasteride group received 5 mg of finasteride daily for 6 months. Prostate volume, urinary flow, urinary symptoms, serum prostate-specific antigen (PSA) and adverse events were determined before and after treatment. After 6 months of treatment the patients treated with 5 mg of finasteride per day had a 30% decrease in their total urinary symptom score, a 14% decrease in prostate volume and a 0.9 ng/dL decrease of PSA. Their maximal urinary flow rate increased by 1.42 mL per second and the mean urinary flow rate increased by 0.64 mL per second. The patients given placebo showed no significant changes in their prostate volume, serum PSA and maximal and mean urinary flow rate. However, the symptom scores in the placebo group also decreased significantly. When compared with the placebo group, those in the finasteride group had significantly lower prostate volume, serum PSA, maximal urinary flow rate and urinary symptoms, but not mean urinary flow rate. The frequency of adverse events was low in both the finasteride and placebo groups. These results show that finasteride may be an effective and safe alternative for the treatment of patients with BPH.",
"Controversy regarding the relative efficacy of treatments for the relief of the symptoms of benign prostatic hyperplasia (BPH).\n This was a 6-month double-blind randomized equivalence study that compared the effects of a plant extract (320 mg Permixon) with those of a 5 alpha-reductase inhibitor (5 mg finasteride) in 1,098 men with moderate BPH using the International Prostate Symptom Score (IPSS) as the primary end-point.\n Both Permixon and finasteride decreased the IPSS (-37% and -39%, respectively), improved quality of life (by 38 and 41%), and increased peak urinary flow rate (+25% and +30%, P = 0.035), with no statistical difference in the percent of responders with a 3 ml/sec improvement. Finasteride markedly decreased prostate volume (-18%) and serum PSA levels (-41%); Permixon improved symptoms with little effect on volume (-6%) and no change in PSA levels. Permixon fared better than finasteride in a sexual function questionnaire and gave rise to less complaints of decreased libido and impotence.\n Both treatments relieve the symptoms of BPH in about two-thirds of patients but, unlike finasteride, Permixon has little effect on so-called androgen-dependent parameters. This suggests that other pathways might also be involved in the symptomatology of BPH.",
"We assess the effect of finasteride, a 5alpha-reductase inhibitor, on objective voiding parameters in men with lower urinary tract symptoms and benign prostatic enlargement on digital rectal examination (known as clinical benign prostatic enlargement) in a double-blind placebo controlled multicenter study using strict standard pressure flow study techniques.\n A modification of the Abrams-Griffiths nomogram was used by 1 reader to ensure that all patients met objective criteria for bladder outlet obstruction at baseline. After performing a pressure flow study patients with obstruction were randomized 2:1 to receive 5 mg. finasteride (81) or placebo (40) daily. A second pressure flow study was performed at month 12. At baseline and month 12 free urinary flow studies and transrectal ultrasound were performed, and International Prostate Symptom Score questionnaires were completed. Patients were treated between May 1994 and July 1996.\n Finasteride caused a significant decrease (-8.1 cm. water) in detrusor pressure at maximum flow (p <0.05 versus placebo p = 0.02), increase (+1.1 ml. per second) in maximum flow rate (p <0.05 versus placebo p = 0.02) and decrease (-22.8%) in prostate volume (p <0.05 versus placebo p <0.001). Men with prostates larger than 40 cc had greater improvement in detrusor pressure at maximum flow (between group difference -14.5 cm. water, 95% confidence interval -26.2 to -2.6, p = 0.02) and maximum flow rate (mean treatment effect +1.6 ml. per second, 95% confidence interval -0.2 to 3.0, p = 0.02) compared to those with prostates 40 cc or less (between group differences not significant).\n Finasteride treatment resulted in improvements in urodynamic parameters, which were greater in men with large prostates.",
"The effects of finasteride, a potent 5 alpha-reductase inhibitor, were assessed in patients with benign prostatic hyperplasia. Patients were treated with finasteride or placebo for 24 weeks in a double-blind multicenter study followed by a 12-month open-extension period. After 24 weeks, finasteride-treated patients, when compared to placebo-treated patients, showed a significant reduction in prostate volume (22.5% median decrease) and prostate significant antigen (32.4% median decrease), a significant increase in maximum urinary flow (1.6 ml/s mean increase from baseline) and a significant improvement in their obstructive symptom scores (two-point decrease from baseline). Finasteride was well tolerated, and the improvements in prostate volume, maximum urinary flow rate and obstructive symptom scores observed in the controlled study were maintained throughout the extension study.",
"To test the hypothesis that in patients with benign prostatic hyperplasia (BPH), the outcome of drug therapy with finasteride may be predictable from the baseline prostate volume and that positive clinical effects might be expected only in patients with prostate volumes of > 40 mL, using a subgroup analysis of results from a previously reported clinical trial of finasteride and phytotherapy.\n A subgroup of 431 patients was analysed from a randomized, multicentre, double-blind clinical trial involving 543 patients with the early stages of BPH. Patients received a fixed combination of extracts of saw palmetto fruit (Serenoa repens) and nettle root (Urtica dioica) (PRO 160/120) or the synthetic 5alpha-reductase inhibitor finasteride. The patients assessed had valid ultrasonographic measurements and baseline prostate volumes of either </= 40 mL or > 40 mL. All 516 patients were included in the safety analysis. The results of the original trial showed equivalent efficacy for both treatments.\n The mean (SD) maximum urinary flow (the main outcome variable) increased (from baseline values) after 24 weeks by 1.9 (5.6) mL/s with PRO 160/120 and by 2.4 (6.3) mL/s with finasteride. There were no statistically significant group differences (P = 0.52). The subgroups with small prostates (</= 40 mL) showed similar improvements, with mean values of 1.8 (5.2) mL/s with PRO 160/120 and 2.7 (7.4) mL/s with finasteride. The mean values for the subgroups with prostates of > 40 mL were similar, at 2.3 (6.1) and 2. 2 (5.3) mL/s, respectively. There were improvements in the International Prostate Symptom Score in both treatment groups, with no statistically significant differences. The subgroup analysis showed slightly better results for voiding symptoms in the patients with prostates of > 40 mL, but there were also improvements in the subgroup with smaller prostates. The safety analysis showed that more patients in the finasteride group reported adverse events and also there were more adverse events in this group than in patients treated with PRO 160/120.\n The present analysis showed that the efficacy of both PRO 160/120 and finasteride was equivalent and unrelated to prostate volume. However, PRO 160/120 had better tolerability than finasteride.",
"Androgens are involved in the development of prostate cancer. Finasteride, an inhibitor of 5alpha-reductase, inhibits the conversion of testosterone to dihydrotestosterone, the primary androgen in the prostate, and may reduce the risk of prostate cancer.\n In the Prostate Cancer Prevention Trial, we randomly assigned 18,882 men 55 years of age or older with a normal digital rectal examination and a prostate-specific antigen (PSA) level of 3.0 ng per milliliter or lower to treatment with finasteride (5 mg per day) or placebo for seven years. Prostate biopsy was recommended if the annual PSA level, adjusted for the effect of finasteride, exceeded 4.0 ng per milliliter or if the digital rectal examination was abnormal. It was anticipated that 60 percent of participants would have prostate cancer diagnosed during the study or would undergo biopsy at the end of the study. The primary end point was the prevalence of prostate cancer during the seven years of the study.\n Prostate cancer was detected in 803 of the 4368 men in the finasteride group who had data for the final analysis (18.4 percent) and 1147 of the 4692 men in the placebo group who had such data (24.4 percent), for a 24.8 percent reduction in prevalence over the seven-year period (95 percent confidence interval, 18.6 to 30.6 percent; P<0.001). Tumors of Gleason grade 7, 8, 9, or 10 were more common in the finasteride group (280 of 757 tumors [37.0 percent], or 6.4 percent of the 4368 men included in the final analysis) than in the placebo group (237 of 1068 tumors [22.2 percent], P<0.001 for the comparison between groups; or 5.1 percent of the 4692 men included in the final analysis, P=0.005 for the comparison between groups). Sexual side effects were more common in finasteride-treated men, whereas urinary symptoms were more common in men receiving placebo.\n Finasteride prevents or delays the appearance of prostate cancer, but this possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high-grade prostate cancer.\n Copyright 2003 Massachusetts Medical Society",
"We sought to quantify prostate tissue changes induced by finasteride and to identify a predictor of finasteride response in men with symptomatic benign prostatic hyperplasia (BPH) via a randomized, placebo controlled, double-blind clinical trial.\n Men with symptomatic BPH (52 to 78 years old) were randomly assigned to 6 months of treatment with finasteride (26) or placebo (15). Outcome measures were clinical (urinary symptom score and flow rate), chemical (serum prostate specific antigen and dihydrotestosterone levels), volumetric (transrectal ultrasound, and magnetic resonance imaging for whole and zonal prostate volumes) and histological (morphometry of prostate sextant biopsies, separated into inner and outer gland segments, to measure the percent epithelium, stroma and glandular lumen).\n In the finasteride group we found a suggestion of decreasing symptom scores and increasing flow rates (not significant) with significant decreases (p < 0.01) in prostate specific antigen (48%), dihydrotestosterone (74%) and prostate volume (21%). Finasteride treatment induced a 55% decrease in inner gland epithelium (p < 0.01) with little effect on stroma or lumina. We also found a linear correlation between pretreatment inner gland epithelial content and prostate volume decrease induced by the drug (tau = 0.58, p = 0.01).\n Finasteride treatment results in a major suppression of prostate epithelium, which is most pronounced in the inner gland. Moreover, a finasteride induced prostate volume decrease was predictable by quantification of epithelial tissues of the inner gland. These data lend additional support to the emerging concept of transition zone primacy in symptomatic BPH.",
"To evaluate prostate cancer detection and prostate-specific antigen (PSA) among men with benign prostatic hyperplasia treated with finasteride.\n Three thousand forty men 45 to 78 years of age with PSA less than 10 ng/mL and no history of prostate cancer were randomized in a double-blind, placebo-controlled trial to finasteride (n = 1524) or placebo (n = 1516) for up to 4 years. A prerandomization biopsy negative for prostate cancer was obtained in 98% of patients with a screening PSA of 4.0 ng/mL or more, and an end-of-study biopsy was requested of all such patients without a recent second negative biopsy or a prostate cancer diagnosis.\n Overall, 644 patients (21%) underwent biopsy and 201 (6.6%) underwent transurethral resection of the prostate. Prostate cancer was diagnosed in 4.7% of men on finasteride and 5.1% on placebo (P = 0.7). Elevated PSA prompted diagnosis in 35% of cases on finasteride and 34% on placebo. The area under the receiver operating characteristic curve for last PSA was 0.84 on finasteride and 0.79 on placebo (P = 0.07). Use of an upper limit of normal for last PSA of 2.0 ng/mL for finasteride and 4.0 ng/mL for placebo yielded similar sensitivity (66% versus 70%, P = 0.6), higher specificity (82% versus 74%, P < 0.0001), and a higher likelihood ratio (3.6 versus 2.7, P < 0.05) for finasteride than for placebo.\n In men treated with finasteride, multiplying PSA by 2 and using normal ranges for untreated men preserves the usefulness of PSA for prostate cancer detection."
] |
Finasteride improves long-term urinary symptoms versus placebo, but is less effective than doxazosin. Long-term combination therapy with alpha blockers (doxazosin, terazosin) improves symptoms significantly better than finasteride monotherapy. Finasteride + doxazosin improves symptoms equally - and clinically - to doxazosin alone. In comparison to doxazosin, finasteride + doxazosin appears to improve urinary symptoms only in men with medium (25 to < 40 mL) or large prostates (≥ 40 mL), but not in men with small prostates (25 mL).
Comparing short to long-term therapy, finasteride does not improve symptoms significantly better than placebo at the short term, but in the long term it does, although the magnitude of differences was very small (from < 1.0 point to 2.2 points). Doxazosin improves symptoms better than finasteride both short and long term, with the magnitude of differences ∼2.0 points and 1.0 point, respectively. Finasteride + doxazosin improves scores versus finasteride alone at both short and long term, with mean differences ∼2.0 points for both time points. Finasteride + doxazosin versus doxazosin improves scores equally for short and long term.
Drug-related adverse effects for finasteride are rare; nevertheless, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder, versus placebo. Versus doxazosin, which has higher rates of dizziness, postural hypotension, and asthenia, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder. Finasteride significantly reduces asthenia, postural hypotension, and dizziness versus terazosin. Finasteride significantly lowers the risk of asthenia, dizziness, ejaculation disorder, and postural hypotension, versus finasteride + terazosin.
|
CD003878
|
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[
"Immediate versus early loading of flapless-placed implants supporting maxillary full-arch prostheses: a randomised controlled clinical trial.",
"Immediate nonocclusal versus early loading of dental implants in partially edentulous patients: 1-year results from a multicenter, randomized controlled clinical trial.",
"Immediate versus early loading of two implants placed with a flapless technique supporting mandibular bar-retained overdentures: a single-blinded, randomised controlled clinical trial.",
"Replacement of mandibular molars with single-unit restorations supported by wide-body implants: immediate versus delayed loading. A randomized controlled study.",
"Immediate loading of Brånemark implants: a 24-month follow-up of a comparative prospective pilot study between mandibular overdentures supported by Conical transmucosal and standard MK II implants.",
"Immediate versus delayed loading of single mandibular molars. One-year results from a randomised controlled trial.",
"Immediate versus early loading of 7-mm-long flapless-placed single implants: a split-mouth randomised controlled clinical trial.",
"Immediate loading of dental implants supporting fixed partial dentures in the posterior mandible: a randomized controlled split-mouth study--machined versus titanium oxide implant surface.",
"Immediate versus delayed loading of dental implants placed in fresh extraction sockets in the maxillary esthetic zone: a clinical comparative study.",
"Vertical bone augmentation versus 7-mm-long implants in posterior atrophic mandibles. Results of a randomised controlled clinical trial of up to 4 months after loading.",
"Early loading of unsplinted implants supporting mandibular overdentures using a one-stage operative procedure with two different implant systems: a 2-year report.",
"Immediate implant placement with transmucosal healing in areas of aesthetic priority. A multicentre randomized-controlled clinical trial I. Surgical outcomes.",
"Early loading of ITI implants supporting a maxillary full-arch prosthesis: 1-year data of a prospective, randomized study.",
"Immediate and early non-occlusal loading of Straumann implants with a chemically modified surface (SLActive) in the posterior mandible and maxilla: interim results from a prospective multicenter randomized-controlled study.",
"Early functional loading of unsplinted roughened surface implants with mandibular overdentures 2 weeks after surgery.",
"Immediate versus early non-occlusal loading of dental implants placed flapless in partially edentulous patients. One-year results from a randomised controlled trial.",
"Implant-retained mandibular overdentures with Brånemark System MKII implants: a prospective comparative study between delayed and immediate loading.",
"Immediate occlusal versus non-occlusal loading of single zirconia implants. A multicentre pragmatic randomised clinical trial.",
"Conventional and early loading of unsplinted ITI implants supporting mandibular overdentures.",
"Restoration of partially edentulous patients using dental implants with a microtextured surface: a prospective comparison of delayed and immediate full occlusal loading.",
"Immediate non-occlusal loading of single implants in the aesthetic zone: a randomized clinical trial.",
"Immediate functional loading of implants in single tooth replacement: a prospective clinical multicenter study.",
"A prospective, randomized controlled clinical trial of anterior lumbar interbody fusion using a titanium cylindrical threaded fusion device.",
"Immediate loading versus immediate provisionalization of maxillary single-tooth replacements: a prospective randomized study with BioComp implants.",
"Clinical and radiographic evaluation of implant-retained mandibular overdentures with immediate loading."
] |
[
"To evaluate the efficacy of flapless placed implants immediately or early loaded at 2 months with full-arch prostheses.\n Thirty patients were randomised: 15 to the immediately loaded group and 15 to the early loaded group. All implants had to be inserted with a minimum torque > 48 Ncm. Outcome measures were prosthesis and implant failures, biological and biomechanical complications, peri-implant marginal bone level changes, patient satisfaction and implant stability quotient (ISQ) assessed with a resonance frequency analysis instrument.\n Ninety implants were placed in the immediately loaded and 87 in the early loaded group. Four localised flaps had to be elevated. Six implants in five patients did not reach the planned insertion torque. Four were immediately replaced by larger diameters ones, one was early loaded and another removed just after placement. After 1 year no drop-out occurred. One implant failed in the immediately loaded group versus three early loaded implants in two patients. There were no statistically significant differences between groups for implant losses, complications, and mean marginal bone level changes. There were borderline significant differences for mean ISQ values, and patients in the immediately loaded group were significantly more satisfied than those early loaded. When comparing mean ISQ values taken 2 months after placement with year 1 data within each group, values increased significantly.\n Maxillary cross-arch prostheses can be successfully loaded the same day of flapless implant placement, increasing patient satisfaction while decreasing treatment time and patient discomfort. No apparent advantages were seen when loading implants at 2 months.",
"To compare the efficacy of immediate nonocclusal loading (test group) versus early loading (control group) in partially edentulous patients.\n Fifty-two patients in 5 Italian private practices were randomized to 1 of the treatments: 25 to the immediately loaded group and 27 to the early loaded group. To be immediately loaded, single implants had to be inserted with a torque of > 30 Ncm, and splinted implants had to be inserted with a torque of > 20 Ncm. Implants in the immediately loaded group were provided with full acrylic resin nonoccluding temporary restorations within 48 hours after placement. After 2 months, full occluding provisional restorations were provided. Implants in the early loading group were not submerged and were loaded after 2 months. At 8 months, provisional restorations were replaced with definitive metal-ceramic prostheses. Outcome measures were prosthesis and implant failures as well as biologic and prosthetic complications recorded by nonblinded assessors. The Fisher exact test was used to compare the proportion of implant failures.\n Fifty-two implants were placed in the immediately loaded group and 52 in the early loaded group. No dropouts or complications occurred up to 14 months postinsertion. One single implant failed in the immediately loaded group 2 months after placement. There was no statistically difference for the tested outcome measures between the 2 procedures (P > .99).\n The results of this randomized controlled clinical trial with 25 patients rehabilitated with immediately restored nonocclusally loaded implant-supported prostheses compared to 27 patients restored 2 months following placement suggest that there are no major clinical differences in implant survival between these 2 protocols. No biologic or prosthetic complications occurred.",
"To evaluate the efficacy of immediate loading versus early loading at 6 weeks of bar-retained mandibular overdentures supported by two implants placed with a flapless technique.\n Sixty patients were randomised: 30 to the immediately loaded group and 30 to the early loaded group. To be immediately loaded, implants had to be inserted with a minimum torque > 48 Ncm. Outcome measures were prosthesis and implant failures, biological and biomechanical complications, patient satisfaction, and Implant Stability Quotient (ISQ) assessed with a resonance frequency analysis instrument.\n Sixty implants were placed in each group. Flaps had to be raised in nine patients to check drill direction or to better visualise the area after multiple teeth extraction. Two implants in two patients did not reach the planned insertion torque and were immediately replaced by larger diameters ones. After 1 year no drop out occurred and two early loaded implants failed in two patients. There were no statistically significant differences between groups for prosthesis failures, implant losses, complications, and mean ISQ values; however, patients in the immediately loaded group were significantly more satisfied than those loaded early. When comparing mean ISQ values taken 6 weeks after placement with 1-year data within each group, values decreased significantly.\n Mandibular overdentures can be successfully loaded the same day of implant placement with a minimally invasive surgery, increasing patient satisfaction while decreasing treatment time and patient discomfort. No apparent advantages were seen when loading the overdentures at 6 weeks.",
"This prospective randomized controlled trial aimed to compare single implant-supported mandibular molar restorations using either an immediate or a delayed loading protocol.\n Thirty subjects requiring single mandibular molar replacement were consecutively treated. One implant was placed in each patient. Fifteen subjects were assigned to delayed loading protocol and 15 to immediate loading protocol according to a randomization table. After insertion, the delayed loaded implants were connected to a healing abutment and restored after 3 to 4 months of healing without loading. The immediately loaded implants were loaded within 24 hours of surgery with a provisional restoration. The interim prosthesis was placed in centric occlusion. All contacts in lateral excursions were eliminated. At implant placement the maximum value of insertion torque was recorded. Radiographic bone level change was measured on periapical radiographs obtained at the time of implant placement and 12 months after loading. Means of the 2 groups were compared by Student t test and analysis of variance (ANOVA). The level of significance was set at .05.\n No implants were lost in the delayed loading group (0/15), whereas 1 implant failed (1/15) in the immediate loading group. No differences were observed in relation to implant length or insertion torque between the groups. The average radiographic bone level change after 1 year of function was 1.2 +/- 0.55 mm (range, 0.5 to 2.6 mm) and 0.77 +/- 0.38 mm (range, 0.29 to 1.23 mm) for the delayed loaded and the immediately loaded implants, respectively. The difference in radiographic bone level change between the delayed and immediate loading groups was statistically significant (P = .022; CI = -0.79 to -0.06; Student t test).\n Immediate loading of wide-diameter implants supporting single restorations in mandibular molar sites seems to be a suitable clinical option. Moreover, the radiographic bone level change observed after 12 months of loading was significantly less for immediately loaded implants.",
"The purpose of this prospective study is to compare the long-term outcome of immediately loaded implant-retained mandibular overdentures supported by four screw-type one-piece transmucosal implants with that of four screw-type two-piece implants inserted in the interforaminal area of the mandible and rigidly connected by a U-shaped curved\n A prospective pilot study was conducted with 10 patients receiving an implant-supported overdenture in the mandible. The patients were randomly assigned to two groups. In the control group (five patients), four standard Brånemark implants (MK II; Nobel Biocare AB, Gothenburg, Sweden), 3.75 mm large and at least 10 mm long, were sited anterior to the mental foramina, and four standard abutments (Nobel Biocare AB) for bar construction were immediately screwed to the implants. In the test group (five patients), four conical transmucosal implants (Nobel Biocare AB), 3.75 mm large and at least 9 mm long in the threaded part, were sited anterior to the mental foramina. Immediately after implant placement, a U-shaped gold or titanium bar was fabricated and implants were immediately loaded (within 24 h) in both groups with an implant-retained overdenture. The patients were followed up for a minimum of 24 months. Implants were evaluated at the time of immediate loading and at 12 and 24 months after prosthetic loading, with the following parameters: modified plaque index (MPI), modified bleeding index (MBI), and probing depth (PD). Periimplant bone resorption was evaluated on panoramic radiographs taken 12 and 24 months after the beginning of prosthetic loading.\n No significant differences were found between the two groups with regard to MPI, MBI, PD, and periimplant bone resorption at 12 and 24 months. The cumulative success rate of implants according to the criteria proposed by Albrektsson and colleagues was 100% in both groups after 2 years of functional loading.\n Results from this study demonstrated that the success rate for immediately loaded mandibular implants is similar to that obtained in cases of delayed loading and that there are no significant differences between results with two-piece implants and one-piece transmucosal implants.",
"To compare the outcome of immediate non-occlusal loading and that of delayed implant loading in the bilateral replacement of single mandibular molars.\n This study was designed as a randomised, controlled, split-mouth trial. Twenty patients with bilaterally missing first mandibular molars had one of the sites to be restored randomly assigned to be treated with immediately or conventionally loaded single implants. A total of 40 implants were bilaterally installed. All the implants were inserted in healed healthy bone with an insertion torque between 35 and 45 Ncm. One molar was restored with a non-occluding temporary crown within 24 h after implant placement, while the contralateral molar was restored with a definitive crown 4 to 5 months later, according to a two-stage procedure. Final restorations were provided 4 to 5 months after implant placement for all implants. Outcome measures were implant survival, complications, radiographic marginal bone-level changes, PPD and BOP.\n No patients dropped out and no implant failed. Only minor prosthetic complications were observed (2 provisional acrylic crown fractures in the immediate loading group and 2 ceramic chipping in the delayed loading group). Mean marginal bone loss was 0.83 ± 0.16 mm (95% CI 0.75 to 0.91) in the immediate loading group and 0.86 ± 0.16 mm (95% CI 0.78 to 0.94) in the conventional loading group and no statistically significant differences between the two groups were observed (P = 0.530). Mean PPD and BOP values were, respectively, 2.76 ± 0.48 (95% CI 2.55 to 2.97) and 1.30 ± 0.73 (95% CI 0.98 to 1.62) in the immediate loading group, and 2.70 ± 0.37 (95% CI 2.54 to 2.86) and 1.40 ± 0.75 (95% CI 1.07 to 1.73) in the conventional loading group. Also, a statistical comparison of BOP and PPD did not show any significant difference (P = 0.163 and P = 0.652, respectively).\n Within the limitations of this study, the present data seem to confirm the hypothesis that the clinical outcome of immediate versus delayed loading of implants in single mandibular molar sites is comparable.",
"To evaluate the efficacy of 7-mm-long flapless placed single implants immediately or early loaded at 6 weeks.\n Thirty patients received two single Nanotite External Hex Biomet 3i implants that were then randomised for immediate or early loading. All implants had to be inserted with a minimum torque >40Ncm. Provisional crowns were put in slight occlusal contact and replaced by definitive crowns 3 months after loading. Outcome measures were implant failures, biological and biomechanical complications, peri-implant marginal bone level changes and patient preference.\n Twenty-nine implants were immediately loaded and 31 early loaded. Thirteen flaps had to be elevated in 12 patients. Eleven implants in ten patients did not reach the planned insertion torque. Eight implants in seven patients were immediately replaced by implants with a larger diameter, two were loaded anyway, and one implant that was randomised to immediate loading was early loaded instead. Nine months after loading, no drop-out occurred. One implant failed in each group. There were no statistically significant differences between groups for implant losses, complications, mean marginal bone level changes, and patient preferences.\n Flapless placed 7-mm-long single implants can be successfully loaded the day of insertion. Longer follow-ups are needed to monitor the long-term prognosis of short implants.",
"A split-mouth study was conducted to compare dental implants with either machined or titanium oxide (TiO) surfaces immediately loaded with fixed partial dentures in the posterior mandible.\n Ten patients with bilateral partial edentulism in the posterior mandible received 42 implants; 20 on the test (TiO) and 22 on the control (machined) side. The implants were loaded within 24 hours postsurgery. At implant placement the maximum insertion torque (IT) was recorded. Implant stability quotient (ISQ) was also evaluated at baseline (day 0) and 1, 2, 4, 12, 24, and 52 weeks following implant placement. The radiographic bone level (RBL) change was measured on periapical radiographs at baseline and 12 months after loading. Means for the 2 groups were compared by paired t test.\n The overall implant success rate was 95%. No implants were lost in the test group; 2 failed in the control group. The difference between the groups in RBL change after 1 year of function was not statistically significant (P = .224). However, average RBL change for machined implants in distal positions was significantly higher than for TiO surface implants in the same position (post-hoc comparison; P = .048). ISQ and peak IT values did not differ between the groups (P = .414 and P = .762, respectively). The high IT necessary to insert the implants did not seem to affect the RBL change (P = .203).\n No significant difference was observed between machined and TiO implant surface in terms of RBL change or ISQ, although TiO implants may provide a lower RBL change compared to machined implants when utilized in the distal position. Immediate loading of implants using fixed partial dentures in posterior mandible may be considered as a treatment option if implants are inserted with IT > or = 20 Ncm and ISQ > or = 60 into nonaugmented bone and loaded with light centric occlusal contact.",
"The aim of this study was to report a clinical comparative assessment of crestal bone level change around single implants in fresh extraction sockets in the esthetic zone of the maxilla either immediately loaded or loaded after a delay.\n Forty patients were included in a prospective, randomized study. All patients required 1 tooth extraction (ie, 1 tooth with a hopeless prognosis) and were randomized into either the test group or the control group. Implants were positioned immediately after tooth extraction and were loaded immediately in the test group (20 implants) and after 3 months in the control group (20 implants). The implant site was prepared, with at least 4 mm of sound apical bone below the implant apex, and the coronal margin of the implant was placed at the buccal level of the bone crest. All implants were 13 mm long; 30 implants had a diameter of 5 mm, and 10 had a diameter of 3.75 mm. Radiographic examinations were made at baseline, at 6 months, and at 24 months. To compare the mean values between test and control group, a paired t test was performed (considered statistically significant at P < .05).\n After a 24-month follow-up period, a cumulative survival rate of 100% was reported for all implants. The control group resulted in a mean mesial bone loss of 1.16 +/- 0.32 mm and a mean distal bone loss of 1.17 +/- 0.41 (mean bone loss, 1.16 +/- 0.51 mm). The test group resulted in a mesial bone loss of 0.93 +/- 0.51 mm and a distal bone loss of 1.1 +/- 0.27 mm (mean bone loss, 1.02 +/- 0.53 mm). No statistically significant difference between control and test groups (P > .05) was found.\n The success rate and radiographic results of immediate restorations of dental implants placed in fresh extraction sockets were comparable to those obtained in delayed loading group.",
"To evaluate whether 7-mm-long implants could be a suitable alternative to longer implants placed in vertically augmented bone for the treatment of atrophic posterior mandibles.\n Sixty partially edentulous patients having 7 to 8 mm of residual crestal height and at least 5.5 mm thickness measured on a computed tomography scan above the mandibular canal were randomised to receive either two to three submerged 7-mm-long NanoTite External Hex implants (Biomet 3i) or 10-mm or longer implants (30 patients per group) placed in vertically augmented bone. Bone was augmented with anorganic bovine bone blocks (Bio-Oss) using a sandwich technique and resorbable barriers. The grafts were left healing for 5 months before placing the implants, which were submerged. Four months after implant placement, provisional acrylic prostheses were delivered. Definitive screw-retained metal-ceramic prostheses were delivered 4 months later. Outcome measures were: prosthesis and implant failures, any complications, and time needed to fully recover mental nerve sensitivity. All patients were followed up to the delivery of the final restorations (4 months after loading).\n No patient dropped out. In two patients of the augmented group, there was not enough space to place 10-mm or longer implants as planned and 7-mm-long implants were used instead. The most likely reason for this is that the Bio-Oss blocks fractured in many pieces at placement. One prosthesis could not be placed when planned in the 7-mm group versus three prostheses in the augmented group, because of failure of one implant in each patient. The difference was not statistically significant. All implants were successfully replaced and final prostheses delivered. Four complications (wound dehiscence) occurred during graft healing in the augmented group (one possibly associated with the failure of one implant) versus none in the 7-mm-long implant group. The difference was not statistically significant. No patient suffered from permanent paraesthesia of the alveolar inferior nerve; however, sensitivity was recovered significantly faster in the short implant group.\n The early results of this study suggest that, when the residual bone height over the mandibular canal is between 7 and 8 mm, 7-mm short implants might be a preferable choice since the treatment is faster, cheaper and associated with less morbidity than vertical bone augmentation. These preliminary results must be confirmed by follow-ups of 5 years or more in order to monitor the performance of short implants over time.",
"Step-wise reduction in loading protocols is necessary to evaluate early loading of implants with mandibular overdentures.\n To compare the success rates of two different dental implant systems following conventional or early loading protocols in patients being rehabilitated with mandibular overdentures.\n Forty-eight edentulous participants were randomly allocated to two different implant systems: one with a machined titanium implant surface (Sterioss, Nobel Biocare, Yorba Linda, California, USA) and the other with a roughened titanium surface (Southern Implants, Irene, South Africa). For each system, the participants were further divided into control groups, in whom mandibular implant overdentures and their respective matrices were inserted following a standard 12-week healing period, and test groups, in whom a 6-week healing period was followed prior to identical loading. Two unsplinted implants to support implant overdentures were placed in the anterior mandible of all participants, using a standardized one-stage surgical procedure. Mobility tests and marginal bone levels, as well as peri-implant parameters, were evaluated at each baseline and 52 and 104 weeks after surgery.\n There was no statistically significant difference in the success rates of the two systems in either control or test groups. At the 2-year evaluation, a success rate was found of 87.5% and 70.8% for the control and test Sterioss groups, respectively, and 83.3% and 100% for the control and test Southern Implants groups were observed. For the Sterioss groups, eight implants were lost at an early stage: seven in the test group and one in the control group. For the Southern Implants control and test groups, no failures were seen at any time interval. There were no significant differences in marginal bone loss, Periotest values, and peri-implant parameters between implant systems or between any of the control or test groups.\n Early loading, with step-wise reductions in loading protocols, of unsplinted machined Sterioss and roughened Southern Implants fixtures with mandibular overdentures is possible for up to 2 years.",
"To compare the clinical outcomes of standard, cylindrical, screw-shaped to novel tapered, transmucosal (Straumann Dental implants immediately placed into extraction sockets. Material and methods: In this randomized-controlled clinical trial, outcomes were evaluated over a 3-year observation period. This report deals with the need for bone augmentation, healing events, implant stability and patient-centred outcomes up to 3 months only. Nine centres contributed a total of 208 immediate implant placements. All surgical and post-surgical procedures and the evaluation parameters were discussed with representatives of all centres during a calibration meeting. Following careful luxation of the designated tooth, allocation of the devices was randomly performed by a central study registrar. The allocated SLA titanium implant was installed at the bottom or in the palatal wall of the extraction socket until primary stability was reached. If the extraction socket was >or=1 mm larger than the implant, guided bone regeneration was performed simultaneously (Bio Oss and BioGide. The flaps were then sutured. During non-submerged transmucosal healing, everything was done to prevent infection. At surgery, the need for augmentation and the degree of wound closure was verified. Implant stability was assessed clinically and by means of resonance frequency analysis (RFA) at surgery and after 3 months. Wound healing was evaluated after 1, 2, 6 and 12 weeks post-operatively.\n The demographic data did not show any differences between the patients receiving either standard cylindrical or tapered implants. All implants yielded uneventful healing with 15% wound dehiscences after 1 week. After 2 weeks, 93%, after 6 weeks 96%, and after 12 weeks 100% of the flaps were closed. Ninety percent of both implant designs required bone augmentation. Immediately after implantation, RFA values were 55.8 and 56.7 and at 3 months 59.4 and 61.1 for cylindrical and tapered implants, respectively. Patient-centred outcomes did not differ between the two implant designs. However, a clear preference of the surgeon's perception for the appropriateness of the novel-tapered implant was evident.\n This RCT has demonstrated that tapered or standard cylindrical implants yielded clinically equivalent short-term outcomes after immediate implant placement into the extraction socket.",
"This prospective, randomized study investigated the safety, feasibility, and reliability of the early loading of implants in edentulous maxillae.\n Twenty-four patients with completely edentulous maxillae were randomized into a test group (n = 16) and a control group (n = 8). All patients received 5 or 6 solid screw-type titanium implants. These were loaded with full-arch prostheses after 9 to 18 days in the test group and after 2.5 to 5.1 months in the control group. Periapical radiographs were taken and routine clinical assessments were made at loading, after 6 months, and after 12 months.\n The implant survival rate 1 year after loading was 100%. Modified Plaque index scores and Sulcus Bleeding index scores were better in the test group than in the control group (P < or = .05). There was a significant difference in peri-implant bone height between the 2 groups (P < .001) and this difference converged with time (P < .001).\n This clinical, prospective, randomized, controlled study fulfilled the criteria for a comparable study. Owing to the small patient sample, the conclusions drawn were based on feasibility analyses of the results. Standard materials and methods were used. Only patients with maxillary bone of sufficient height and width were selected. The use of a single operator in each discipline--maxillofacial surgery, prosthodontics, and dental technology--may have improved the chances of achieving consistent standards and opinions.\n These results indicate that early loading in selected patients was as safe and reliable as delayed loading in this small patient population and may offer a satisfactory alternative to the standard protocol.",
"Immediate and early loading of dental implants can simplify treatment and increase overall patient satisfaction. The purpose of this 3-year prospective randomized-controlled multicenter study was to assess the differences in survival rates and bone level changes between immediately and early-loaded implants with a new chemically modified surface (SLActive). This investigation shows interim results obtained after 5 months.\n Patients > or =18 years of age missing at least one tooth in the posterior maxilla or mandible were enrolled in the study. Following implant placement, patients received a temporary restoration either on the day of surgery (immediate loading) or 28-34 days after surgery (early loading); restorations consisted of single crowns or two to four unit fixed dental prostheses. Permanent restorations were placed 20-23 weeks following surgery. The primary efficacy variable was change in bone level (assessed by standardized radiographs) from baseline to 5 months; secondary variables included implant survival and success rates.\n A total of 266 patients were enrolled (118 males and 148 females), and a total of 383 implants were placed (197 and 186 in the immediate and early loading groups, respectively). Mean patient age was 46.3+/-12.8 years. After 5 months, implant survival rates were 98% in the immediate group and 97% in the early group. Mean bone level change from baseline was 0.81+/-0.89 mm in the immediate group and 0.56+/-0.73 mm in the early group (P<0.05). Statistical analysis revealed a significant center effect (P<0.0001) and a significant treatment x center interaction (P=0.008).\n The results suggested that Straumann implants with an SLActive can be used predictably in time-critical (early or immediate) loading treatment protocols when appropriate patient selection criteria are observed. The mean bone level changes observed from baseline to 5 months (0.56 and 0.81 mm) corresponded to physiological observations from other studies, i.e., were not clinically significant. The presence of a significant center effect and treatment x center interaction indicated that the differences in bone level changes between the two groups were center dependent.",
"Before early functional loading of unsplinted implants with mandibular overdentures can become widespread, more clinical studies are needed to investigate the success of the approach.\n To evaluate the success rates of two types of roughened titanium surface implants with early 2-week functional loading of paired mandibular interforaminal implants with overdentures.\n Random allocation divided 24 strictly selected edentulous participants into two groups, with each group to receive a different implant system (ITI Dental Implant System, Straumann AG, Waldenburg, Switzerland; or Southern Implant System, Southern Implants, Irene, South Africa). Two implants were placed in the anterior mandible of all participants using one-stage standardized surgical procedures. Previously constructed conventional mandibular dentures (opposing maxillary complete dentures) were temporarily relined and worn by the participants for the first 2 weeks; participants used a soft diet. Two weeks after implant surgery and following some mucosal healing, the mandibular dentures had the tissue conditioner removed and the appropriate matrices included for an unsplinted prosthodontic design.\n No implant from either group was lost. Resonance frequency analysis (RFA) indicated higher primary stability at surgery for the Southern group than for the ITI group, with a statistically significant difference between the groups throughout the study period. The drop in RF values between surgery and 6 weeks was significant and was greater for the Southern group. RFA also indicated stabilized osseointegration between 6 to 12 and 12 to 52 weeks, with no participant showing any decrease in those values over time. Participants with type 3 bone showed a significant improvement in RF values between 12 and 52 weeks, eventually matching those of participants with type 2 bone. There were no significant differences in marginal bone loss, periimplant parameters, or prosthodontic maintenance between the groups over the study period.\n Using only strict patient selection criteria, 1-year follow-up data indicate that early functional loading of ITI and Southern implants with mandibular two-implant overdentures is possible as early as 2 weeks after implant surgery.",
"To compare immediate versus early (6 weeks) non-occlusal loading of dental implants placed flapless in partially edentulous patients 1 year after loading.\n Sixty patients were randomised: 30 to the immediately loaded group and 30 to the early loaded group. In order to be immediately loaded, implants were inserted with a minimum torque of > or = 40Ncm. Implants were fully occlusally loaded after 6 months. Outcome measures were prosthesis and implant failures, and biological and biomechanical complications.\n Five implants in five patients randomised to the immediately loaded group did not reach the required primary implant stability. Three of these implants (two prostheses) were not immediately loaded. Two patients who were randomised to the early loaded group were immediately loaded erroneously. Implants in five patients of the early loaded group were conventionally loaded. No patient dropped out and there were no failures. Two complications occurred in the early and one in the immediately loaded group (no statistically significant difference), but were solved.\n The use of a flapless technique for placing dental implants in conjunction with non-occlusal immediate or early loading in selected patients can provide excellent clinical results. No differences were observed when comparing implants that were loaded immediately or early. Therefore, when a high primary implant stability is obtained, it might be preferable to load the implants immediately rather than waiting for a few weeks.",
"This study was designed to compare the results of immediate and delayed loading of implants with implant-retained mandibular overdentures. Ten patients (test group) received 40 Brånemark System MKII implants (4 per patient) placed in the interforaminal area of the mandible. Standard abutments were immediately screwed to the implants, rigidly connected with a bar, and immediately loaded with an overdenture. Ten patients (control group) received the same type and number of implants in the same area, but the implants were left to heal submerged. Four to 8 months later, standard abutments were screwed to the implants and the same prosthetic procedure was applied. Each implant was evaluated at the time of prosthetic loading and at 6, 12, and 24 months after the initial prosthetic load with the following parameters: modified Plaque Index (MPI), modified Bleeding Index (MBI), probing depth (PD), and Periotest. Peri-implant bone resorption was evaluated on panoramic radiographs taken 12 and 24 months after initial prosthetic loading. No significant differences were found between the 2 groups regarding MPI, MBI, Periotest, peri-implant bone resorption, and PD at 6 and 24 months (P > .05). The only difference was found regarding PD values on the mesial and lingual sites at 12 months (P < .05). The cumulative success rate of implants was 97.5% in both groups. Results from this study showed that immediate loading of endosseous implants rigidly connected with a U-shaped bar does not seem to have any detrimental effect on osseointegration. Conversely, this method significantly shortens the duration of treatment with relevant satisfaction for the patients.",
"To evaluate whether immediate non-occlusal loading of single zirconia implants could reduce early failures when compared to immediate occlusal loading.\n Forty partially edentulous patients who received one single zirconia implant (Z-Systems) at least 10 mm long and 3.25 mm wide inserted with a torque of at least 35 Ncm were randomised to immediate occlusal or non-occlusal loading groups. All patients received provisional acrylic crowns the same day of implant placement. Provisional crowns were replaced after 4 to 5 months by definitive full ceramic crowns. Outcome measures were implant success, any complications and peri-implant marginal bone levels.\n One year after loading, no patients had dropped out. Five implants (12.5%) failed early: three occlusally loaded and two non-occlusally loaded. Three complications occurred, all after delivery of the definitive crowns: one crown fractured (occlusal loading), one had to be remade after debridement because of hyperplastic tissues (occlusal loading), and one crown decemented (nonocclusal loading). These differences were not statistically significant. Both groups gradually lost periimplant bone in a highly statistically significant way. One year after loading, patients subjected to non-occlusal loading lost an average of 0.7 mm of peri-implant bone versus 0.9 mm in the occlusal group. This difference in bone loss between groups was not statistically significant. There was an association between immediate post-extractive implants and implant failures (P=0.01). Four of the 10 immediate post-extractive implants (40%) failed versus one out of 30 delayed implants (3%).\n The results of this study do not provide a conclusive answer to whether immediate non-occlusal loading may decrease implant failures. Immediately loaded zirconia implants placed in post-extractive sites had high failure rates.",
"The aim of this study was to compare the success rates after 1 and 2 years of conventionally and early loaded pairs of unsplinted ITI implants supporting mandibular overdentures in edentulous patients. Twenty-four participants (age range 55-80 years) were randomly allocated with maximum concealment to two treatment groups. In the first group, the implants were allowed to heal for 12 weeks before being functionally loaded (control) and the second group had 6 weeks of healing with identical loading. All participants had new conventional complete maxillary and mandibular dentures prior to the study. Two sandblasted large-grit acid-etched (SLA) surface ITI implants were placed in the mandibular interforaminal area, following a standardized nonsubmerged surgical protocol. After 6 or 12 weeks of healing, matrices were processed into the fitting surface of the pre-existing mandibular dentures and the implants loaded. Implant success was determined using mobility tests and radiographs taken at baseline and 52 and 104 weeks after surgery. Clinical peri-implant parameters were also documented. Results showed all implants successfully osseointegrated, according to accepted criteria, after 2 years. Mean loss of crestal bone height after 1 year was 0.35 +/- 0.22 mm (control) vs. 0.27 +/- 0.18 mm (test). After 2 years this reduced to 0.09 +/- 0.06 mm (control) vs. 0.12 +/- 0.17 mm (test). The mean Periotest value after 1 year was -4.9 (control) vs.-3.78 (test). After 2 years, the mean resonance frequency value for the control implants was 6797 Hz [mean implant stability quotient (ISQ) = 64.77] and for the test implants 6670 Hz (mean ISQ = 62.0). Shortened loading periods for these ITI implants did not cause any statistically significant differences in osseointegration or peri-implant parameters. We conclude that pairs of unsplinted SLA-surface ITI implants can be successfully loaded with mandibular overdentures 6 weeks after surgery.",
"The aim of this study was to determine the clinical effectiveness of placing dental implants with microtextured surfaces into full occlusal loading at the time of placement in partially edentulous patients.\n Two demographically similar groups of 14 patients each were treated with a total of 92 Spline Twist Implants (Centerpulse Dental, Carlsbad, CA). Test implants were placed into immediate full occlusal loading, and control implants were restored using a conventional delayed loading procedure. Otherwise, both groups of patients received similar therapy from the same treatment team. Radiographs, periodontal indices, and Periotest values were recorded every 6 months during routine clinical follow-up appointments. The mean loading time for all prostheses was 24 months at the time of this report.\n No implants failed in the test group, and 1 implant failed before loading in the control group. Cumulative implant success was 98.9% for all implants placed (test group = 100%; control group = 92.9%). Periodontal measurements indicated no significant clinical differences between implants placed into immediate full occlusal loading and those loaded via a conventional delayed protocol.\n Immediate full occlusal loading of partial prostheses supported by microtextured implants in partially edentulous patients demonstrated excellent clinical results, with no adverse periodontal effects after 24 months of function. Additional follow-up will provide invaluable information on the long-term effects of this technique.\n Immediate full occlusal loading of partial prostheses supported by microtextured implants can be successfully achieved for 24 months in highly motivated patients with excellent oral hygiene.",
"this study compared the outcome of immediate non-occlusal loading with conventional loading for single implants in the maxillary aesthetic zone. It was hypothesized that immediate non-occlusal loading is not inferior to conventional loading.\n sixty-two patients with a missing maxillary anterior tooth were randomly assigned to be treated with an implant that was either restored with a non-occluding temporary crown within 24 h after implant placement (the \"immediate group\") or was restored according to a two-stage procedure after 3 months (the \"conventional group\"). All implants were installed in healed sites. Follow-up visits were conducted after 6 and 18 months post-implant placement. Outcome measures were radiographic marginal bone-level changes, survival, soft tissue aspects (probing depth, plaque, bleeding, soft tissue level), aesthetics and patient satisfaction.\n no significant differences were found between both study groups regarding marginal bone loss (immediate group 0.91 ± 0.61 mm, conventional group 0.90 ± 0.57 mm), survival (immediate group 96.8%: one implant lost, conventional group 100%), soft tissue aspects, aesthetic outcome and patient satisfaction.\n within the limitations of this study (sample size, follow-up duration), it was demonstrated that, for single implants in the anterior maxilla, the outcome of immediate non-occlusal loading was not less favourable than conventional loading.",
"The aim of the present study was to evaluate the outcome of immediate functional loading of implants in single-tooth replacement using two different installation procedures.\n One hundred and fifty-one subjects, who required single-tooth rehabilitation in the area of 15-25 and 35-45, were enrolled in eight private clinics in Italy. The implant sites were randomly allocated to one of the following treatment groups. In the control group, in which a standard preparation procedure for implant placement and submerged healing of the implant was used, abutment connection and loading of the implants were performed 3 months after installation. In the test group 1, a standard preparation procedure for the implant placement and immediate functional loading of implant was carried out. In the test 2 group, however, a modified implant installation procedure (osteotome technique) was used followed by immediate functional loading of the implant. Clinical and radiographic examinations were performed at 3 and 12 months of follow-up at all sites.\n Three implants (5.5%) from the test 2 group (osteotome preparation) and one (2%) from the test 1 group (conventional drill preparation) failed to integrate and were removed one and three months after implant installation. The mean marginal bone loss assessed at 12 months was 0.31 mm (test 1), 0.25 mm (test 2) and 0.38 mm (control) (no statistically significant differences were found between the three treatment groups.)\n It is suggested that immediate functional loading of implants that are placed with a conventional installation technique and with sufficient primary stability may be considered as a valid treatment alternative in a single-tooth replacement.",
"A prospective, randomized, controlled clinical trial comparing a cylindrical threaded titanium cage to a femoral ring allograft control for anterior lumbar interbody fusion.\n To compare these two implants with regard to arthrodesis. Secondary outcome measures included pain relief, neurological status, and general health status.\n Anterior lumbar interbody fusion is a well-accepted procedure using trapezoidal femoral ring allografts or cylindrical titanium cages. Clinical and biomechanical studies evaluating these two distinct constructs are numerous; however, no prospective, randomized study comparing them has been done.\n A multicenter trial of 140 patients: 78 were randomized to the cylindrical threaded titanium cage device treatment arm and 62 patients randomized into the control group. All had autogenous iliac crest bone graft packed into the device. All patients had a single-level stand-alone anterior lumbar interbody fusion at either the L4-L5 or L5-S1 interspace for symptomatic degenerative disc disease. Radiographic fusion data were collected as well as multiple types of outcome data, including pain/disability scores, neurologic status, and overall health.\n At 12 months, 97% of the cylindrical threaded titanium cage device group and 40% of the control group demonstrated radiographic fusion. At 24 months, 97% of the cylindrical threaded titanium cage group and 52% of the control group showed radiographic fusion. These fusion rate differences are statistically significant (P < 0.001). The Oswestry and neurologic scores were not significantly different between groups.\n This is the first prospective, randomized, multicenter clinical trial that compares fusion cage results to control data.\n Cylindrical threaded titanium cages have a higher fusion rate, comparable improvements in clinical outcome (Oswestry, Low Back Pain Questionnaire, SF-36), and fewer secondary supplemental fixation procedures compared to the femoral ring allograft control.",
"The aim of this prospective randomized study was to evaluate the clinical outcome of immediately loaded solid plasma sprayed (TPS) BioComp (BioComp Industries BV, Vught, The Netherlands) implants versus immediate provisionalized but non-loaded BioComp implants in the anterior and premolar region of the maxilla.\n Forty-eight patients (31 females and 17 males) with a mean age of 42.3+/-13.1 years (range 19 to 78 years) were included in the study. Fifty threaded TPS implants were placed and provisionalized within 24 hours after surgery. The patients were randomly assigned to 2 groups. In the immediate loaded (IL) group (n=24) the occlusion of the provisional was designed with normal contacts in centric relation and at lateral excursions, while in the non-immediate loaded (IP) group (n=24) the provisional restoration was adjusted to clear all occlusal contacts or contacts at lateral excursions. Patients were instructed to eat a soft diet and to avoid placing food in the area of the provisional crown during the first 6 weeks. Regular clinical and radiographic controls were performed and the survival rate and implant stability quotient (ISQ) values were evaluated at delivery of the definitive restoration at 6 months. At 1 year, radiographic coronal bone defects and gingival esthetics between the 2 groups were assessed.\n Of the IL group, 2 fixtures were lost, while 3 implants were lost in the IP group. The failing implants showed increasing mobility at 2 to 3 weeks after insertion, and were removed. The remaining 45 implants were stable at every subsequent follow-up examination, and 6 months after implant placement, ISQ values were measured. The mean ISQ value in the IL group was 63.7+/-5.8 versus 63.2+/-4.3 for the IP group (P=.78). The mean mesial marginal bone loss after 12 months in the IL group was 0.27+/-0.2 mm versus 0.28+/-0.22 mm in the IP group (P=.9). The mean distal marginal bone loss after 12 months in the IL group was 0.19+/-0.15 mm versus 0.2+/-0.11 mm in the IP group (P=.87). All implants of the IL group had an ideal gingival buccal margin, versus 91% of the IP group. Full regeneration of the mesial interdental papilla was observed in 70% of the IL group versus 91% of the IP group, while full regeneration of the distal papilla was observed in 91% of both the IL and IP implants.\n No significant differences in ISQ mean values in radiographic bone loss and gingival esthetics were found between immediate non-loaded provisionalization and immediately loaded BioComp implants in the maxilla.",
"The aim of this study was to evaluate and compare immediate-loaded implant-retained mandibular overdentures and delayed-loaded implant-retained mandibular overdentures.\n Ten completely edentulous male patients received 40 dental implants. Patients were randomly divided into 2 equal groups, 5 patients each. Patients of both groups received conventional maxillary complete denture and had stage 1 surgery for placing 4 dental implant fixtures, 2 on each side anterior to the mental foramina. Group A: One-stage surgical procedure and immediate loading. Patients in this group received mandibular bar-retained overdenture supported by 4 endosseous implants loaded immediately after implant placement. Group B: The original 2-stage concept and delayed loading. Patients in this group received mandibular bar-retained overdenture supported by 4 endosseous implants that remained submerged for a period of 4 months before loading. The patients were evaluated clinically and radiographically immediately after overdenture delivery and after 6 months, 12 months, 18 months, and 24 months.\n The results of clinical evaluation showed no statistical significant difference between the 2 groups regarding the effect of treatment. The radiographic assessment showed no statistical significant difference in mesial and distal alveolar bone loss at the different intervals of the follow-up period, except at the 12-month period, where immediately loaded implants showed a decrease in the amount of alveolar bone loss mesially and distally compared to delayed loaded implants.\n The results suggest that immediate-loaded implants provide promising results compared to delayed-loaded implants and can be a possible alternative procedure in implant dentistry."
] |
Overall there was no convincing evidence of a clinically important difference in prosthesis failure, implant failure, or bone loss associated with different loading times of implants. The quality of the evidence is assessed as very low due to high and unclear risk of bias of primary studies and there is some evidence of reporting bias so clinicians should treat these findings with caution. A high value of insertion torque (at least 35 Ncm) seems to be one of the prerequisites for a successful immediate/early loading procedure. More well-designed RCTs are needed and should be reported according to the CONSORT guidelines (www.consort-statement.org/), and registered with a trials registry.
|
CD005627
|
[
"10232637",
"14709187",
"10675424",
"10870784",
"11810100",
"19775782"
] |
[
"Randomized trial of the short-term effects of dieting compared with dieting plus aerobic exercise on lactation performance.",
"Structured diet and physical activity prevent postpartum weight retention.",
"The effect of weight loss in overweight, lactating women on the growth of their infants.",
"Antenatal exercise and birthweight.",
"Continuing regular exercise during pregnancy: effect of exercise volume on fetoplacental growth.",
"A diet and physical activity intervention for preventing weight retention among Taiwanese childbearing women: a randomised controlled trial."
] |
[
"Limiting postpartum weight retention is important for preventing adult obesity, but the effect of weight loss on lactation has not been studied adequately.\n We evaluated whether weight loss by dieting, with or without aerobic exercise, adversely affects lactation performance.\n At 12+/-4 wk postpartum, exclusively breast-feeding women were randomly assigned for 11 d to a diet group (35% energy deficit; n = 22), a diet plus exercise group (35% net energy deficit; n = 22), or a control group (n = 23). Milk volume, composition, and energy output; maternal weight, body composition, and plasma prolactin concentration; and infant weight were measured before and after the intervention.\n Weight loss averaged 1.9, 1.6, and 0.2 kg in the diet, diet + exercise, and control groups, respectively (P < 0.0001) and was composed of 67% fat in the diet group and nearly 100% fat in the diet + exercise group. Change in milk volume, composition, and energy output and infant weight did not differ significantly among groups. However, there was a significant interaction between group and baseline percentage body fat: in the diet group only, milk energy output increased in fatter women and decreased in leaner women. The plasma prolactin concentration was higher in the diet and diet + exercise groups than in the control group.\n Short-term weight loss (approximately 1 kg/wk) through a combination of dieting and aerobic exercise appears safe for breast-feeding mothers and is preferable to weight loss achieved primarily by dieting because the latter reduces maternal lean body mass. Longer-term studies are needed to confirm these findings.",
"Postpregnancy weight retention contributes to the near-epidemic prevalence of obesity in the United States. This study examines the impact of an individualized, structured diet and physical activity intervention on weight loss in overweight women during the first year postpartum.\n Forty overweight postpartum women were randomized to either a structured (STR) or a self-directed (SELF) intervention. Measurements included body weight, percent body fat, daily caloric intake, habitual physical activity, and cardiorespiratory fitness. Subjects in STR received individualized diet and physical activity prescriptions derived from baseline measurements. They met weekly for the first 12 weeks and kept daily food and activity diaries. Subjects in SELF received a single 1-hour educational session about diet and activity.\n Only 23 of 40 participants remained in the study at 1 year postpartum. Of those, STR (n = 13) had a significant weight loss (7.3 kg, p < 0.01), a significant decrease in percent body fat (6%, p < 0.01), and no change in fat-free mass. SELF (n = 10) had no significant change in weight, percent body fat, or fat-free mass.\n Women who committed to this one class per week for 12 weeks postpartum had a high likelihood of successful weight loss that persisted at 1 year. Women who were overweight before pregnancy were unlikely to lose the pregnancy-related weight without the help of a formal intervention. This suggests that healthcare professionals should strongly encourage postpartum women to enroll in a structured diet and exercise program.",
"The retention of weight gained during pregnancy may contribute to obesity. Lactation should promote weight loss, but weight loss is highly variable among lactating women. The risks associated with the restriction of energy intake during lactation have not been adequately evaluated. The purpose of this study was to determine whether weight loss by women during lactation affects the growth of their infants.\n We randomly assigned 40 breast-feeding women who were overweight (defined as a body-mass index [the weight in kilograms divided by the square of the height in meters] of 25 to 30) at 4 weeks post partum either to restrict their energy intake by 500 kcal per day and to exercise for 45 minutes per day for 4 days per week (the diet-and-exercise group) or to maintain their usual dietary intake and not exercise more than once per week for 10 weeks (the control group). We measured the weight and fat mass of the women and the weight and length of the infants before, during, and at the end of the study period.\n The mean (+/-SD) energy intake decreased by 544+/-471 kcal per day in the diet-and-exercise group. As compared with the control group, the women in the diet-and-exercise group lost more weight (4.8+/-1.7 kg vs. 0.8+/-2.3 kg, P<0.001) and fat mass (4.0+/-2.0 kg vs. 0.3+/-1.8 kg, P<0.001). The gains in weight and length of the infants whose mothers were in the diet-and-exercise group (1925+/-500 g and 7.8+/-2.0 cm, respectively) were not significantly different from those of the infants whose mothers were in the control group (1861+/-576 g and 7.3+/-1.7 cm).\n Weight loss of approximately 0.5 kg per week between 4 and 14 weeks post partum in overweight women who are exclusively breast-feeding does not affect the growth of their infants.",
"Does strenuous antenatal exercise reduce birthweight? Does reducing maternal exercise increase birthweight? What to advise about exercise during pregnancy? We recruited 117 women who intended to exercise 5 or more times weekly during pregnancy to a study of whether reducing the amount of maternal exercise during pregnancy is associated with an increase in birthweight. Only 61/117 (52%) of women agreed to be randomised to either continue or to reduce (to 3 or fewer sessions of exercise weekly) their intended pregnancy exercise program. Most women who refused randomisation did not want to risk being asked to reduce their exercise during pregnancy. Within the randomised trial, there was no statistically significant difference between the mean birthweight of babies born to women who continued and those who reduced their intended exercise program. The high rate of refusal of randomisation limits the power of the study to find a difference in birthweight, limits the generalisability of the results and shows that many women intending to exercise at this level during pregnancy have an uncompromising attitude to exercise.",
"The purpose of this study was to test the null hypothesis that the volume of exercise at different times during pregnancy has no effect on fetoplacental growth.\n Seventy-five women who exercised regularly were evaluated before pregnancy and randomly assigned at 8 weeks' gestation to one of 3 exercise regimens for the remainder of pregnancy. Primary outcome variables included placental growth rate, birth weight, and placental volume at term.\n The offspring of the women who were randomly assigned to a high volume of exercise in mid and late pregnancy were significantly lighter (3.39 kg vs 3.81 kg) and thinner (8.3% fat vs 12.1% fat) than those offspring born of women who were randomly assigned to reduce their exercise volume after the 20th week. Maternal weight gain, fresh placental volumes, and histomorphometric indices of placental function were greater in the high-low group.\n These data indicate that a high volume of moderate-intensity, weight-bearing exercise in mid and late pregnancy symmetrically reduces fetoplacental growth, whereas a reduction in exercise volume enhances fetoplacental growth with a proportionally greater increase in fat mass than in lean body mass.",
"to examine the effect of individual counselling on diet and physical activity from pregnancy to six months post partum, or from birth to six months post partum, on weight retention among Taiwanese women.\n a randomised controlled trial assigned participants to two experimental groups [from pregnancy to six months post partum (EP) and from birth to six months post partum (EPP)] and one comparison group.\n a 3900-bed medical centre in northern Taiwan with around 3000 births annually.\n a sample of 189 women who had regular check-ups during pregnancy and gave birth at the medical centre.\n the comparison group received the routine outpatient department obstetric educational programme. The EP group attended regularly scheduled clinic visits with individualised dietary and physical activity education plans from 16 gestational weeks to six months post partum, and received on brochure. The EPP group received the same educational intervention as the EP group from 24-48 hours after birth to six months post partum.\n body weight, body mass index, health-promoting behaviour and psycho-social variables (self-efficacy, body image, depression and social support).\n average gestational weight gain was 14.02, 15.27 and 16.22 kg in the three EP, EPP and comparison groups respectively, and average weight retention at six months post partum was 2.34, 4.06 and 5.08 kg in the three groups, respectively.\n a diet and physical activity intervention from pregnancy is effective for reducing post-pregnancy weight retention.\n the findings of the present study should be taken into consideration when incorporating significant others and weight-loss maintenance strategies with interventions for a healthier family lifestyle.\n Copyright © 2009 Elsevier Ltd. All rights reserved."
] |
Preliminary evidence from this review suggests that both diet and exercise together and diet alone help women to lose weight after childbirth. Nevertheless, it may be preferable to lose weight through a combination of diet and exercise as this improves maternal cardiorespiratory fitness and preserves fat-free mass, while diet alone reduces fat-free mass. This needs confirmation in large trials. For women who are breastfeeding, more evidence is required to confirm whether diet or exercise, or both, is not detrimental for either mother or baby.
[Note: The 23 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]
|
CD007783
|
[
"16344515",
"9860069"
] |
[
"Double-blind, placebo-controlled study of lamotrigine in primary generalized tonic-clonic seizures.",
"Double-blind, placebo-controlled, crossover study of lamotrigine in treatment-resistant generalised epilepsy."
] |
[
"To evaluate the efficacy and tolerability of adjunctive lamotrigine in primary generalized tonic-clonic (PGTC) seizures in a randomized, double-blind, placebo-controlled trial.\n Patients with a diagnosis of epilepsy with PGTC seizures who were receiving one or two antiepileptic drugs at study entry were eligible. Patients with partial seizures were excluded on the basis of seizure history and screening EEGs. The study comprised a baseline phase, an escalation phase during which study medication was titrated to a target dose, and a 12-week maintenance phase during which doses of lamotrigine/placebo and concomitant antiepileptic drugs were maintained.\n Of the 121 randomized patients ages 2 to 55 years, 117 (58 lamotrigine, 59 placebo) entered the escalation phase and received study medication. During the escalation and maintenance phases combined, median percent reduction in PGTC seizure frequency was 66.5% with lamotrigine compared with 34.2% with placebo (p = 0.006). The corresponding numbers for lamotrigine and placebo were 60.6% and 32.8% (p = 0.038) during the escalation phase and 81.9% and 43.0% (p = 0.006) during the maintenance phase. During the maintenance phase, 72% of lamotrigine-treated patients compared with 49% of placebo-treated patients experienced a > or = 50% reduction in frequency of PGTC seizures (p = 0.014). A similar pattern of results was observed for all generalized seizures. The most common drug-related adverse events were dizziness (5% lamotrigine, 2% placebo), somnolence (5% lamotrigine, 2% placebo), and nausea (5% lamotrigine, 3% placebo).\n Adjunctive lamotrigine is effective in the treatment of primary generalized tonic-clonic seizures and has a favorable tolerability profile.",
"Lamotrigine (LTG) is recognised as effective add-on therapy for focal epilepsies, but this is the first double-blind, placebo-controlled, crossover study in treatment-resistant generalised epilepsy.\n The study consisted of 2 x 8-week treatment periods followed by a 4-week washout period. Patients received doses of either 75 or 150 mg daily, depending on their concomitant antiepileptic drugs (AEDs). Long-term continuation was offered at the end of the study with open-label LTG.\n Five centres in Australia recruited 26 patients who were having absence, myoclonic, or generalized tonic-clonic seizures or a combination of these. Twenty-two patients completed the study. There was a significant reduction in frequency of both tonic-clonic and absence seizure types with LTG. A 350% decrease in seizures was observed for tonic-clonic seizures in 50% of cases and for absence seizures in 33% of evaluable cases. Rash was the only adverse effect causing discontinuation. Twenty-three of 26 opted for open-label LTG, with 20 still receiving LTG for a mean of 26 months. In these 20, 80% had > or =50% seizure reduction and five (25%) were seizure free.\n This study shows that LTG is effective add-on therapy in patients with refractory generalised epilepsies. Statistically significant reduction in seizures in both absence and tonic-clonic seizure types was seen even with low doses of LTG."
] |
Two short term trials indicate that lamotrigine has efficacy against primary generalized tonic-clonic seizures; however, this evidence is insufficient to inform clinical practice and longer term active controlled trials are required.
|
CD005258
|
[
"6195948",
"8549224",
"15457363",
"6998538",
"3672322",
"9161392",
"1702235",
"7717832",
"946507",
"8331703"
] |
[
"Prevention of postoperative deep venous thrombosis and pulmonary emboli with combined modalities.",
"The efficacy of pneumatic compression stockings in the prevention of pulmonary embolism after cardiac surgery.",
"Venous thromboembolism prophylaxis after head and spinal trauma: intermittent pneumatic compression devices versus low molecular weight heparin.",
"Low dose heparin and compression stockings in the prevention of postoperative deep venous thrombosis.",
"Regimen for improved effectiveness of intermittent pneumatic compression in deep venous thrombosis prophylaxis.",
"A randomized, prospective trial of deep venous thrombosis prophylaxis in aortic surgery.",
"Prophylaxis of deep venous thrombosis after acute abdominal operation.",
"Deep vein thrombosis: prevention in stroke patients during rehabilitation.",
"Prevention of venous thrombosis with small, subcutaneous doses of heparin.",
"Efficacy of deep venous thrombosis prophylaxis in trauma patients and identification of high-risk groups."
] |
[
"Worldwide statistics reveal that 25 to 40 per cent of patients who are over the age of 40 years and operated on for 1 or more hours will develop a deep venous thrombosis (DVT). The studies reviewed in this paper were performed to evaluate several modalities and compare their effectiveness in preventing DVT in postoperative patients. In the first study, five modalities plus a control group were evaluated in 562 patients from five surgical specialties. The incidence of DVT in the control group was 35 per cent. Though most of the pharmacologic agents were effective in reducing the incidence of DVT, the antistasis devices (gradient elastic stockings and intermittent pneumatic compression) were most effective. The purpose of the second study was to evaluate the effectiveness of combining a pharmacologic drug with an antistasis modality. Deep venous thrombosis was virtually eliminated in this group of 328 patients. There was only a 1.5 per cent incidence of DVT in the treated population as compared to a 26.8 per cent incidence in the control group. Thus, it seems that combining one antistasis and one pharmacologic agent greatly reduces the incidence of lower extremity thrombi. I-125 fibrinogen scanning was the most sensitive test in detecting DVT and had an accuracy of 97 per cent.",
"Pneumatic compression stocking (PCS) devices have been introduced to decrease the incidence of postoperative deep venous thrombosis (DVT). However, their role in the prophylaxis against pulmonary embolism (PE) remains unclear. This study was undertaken to compare the prophylactic effectiveness of subcutaneous heparin (SCH) alone vs the combined use of PCS and SCH in the prevention of PE following cardiac surgery.\n We studied 2,551 consecutive patients who underwent cardiac surgery over a 10-year period. They were randomly allocated to two groups. Group A included 1,196 patients who were treated with 5,000 U of SCH every 12 h and group B included 1,355 patients treated with a combined prophylactic regimen of PCS and SCH.\n The diagnosis of PE was established in 69 patients by either high-probability ventilation perfusion scan, pulmonary angiogram, or autopsy. The incidence of PE in group A patients was 4% (48/1,196) and in group B was 1.5% (21/1,355). The concomitant use of bilateral PCS and SCH reduced the frequency of postoperative PE in 62% in comparison to the prophylaxis with SCH alone (p < 0.001).\n These data suggest that the combined prophylactic method of bilateral PCS and SCH is superior to SCH alone in the prevention of PE after cardiac surgery.",
"Although there are alternative methods and drugs for preventing venous thromboembolism (VTE), it is not clear which modality is most suitable and efficacious for patients with severe (stable or unstable) head/spinal injures. The aim of this study was to compare intermittent pneumatic compression devices (IPC) with low-molecular-weight heparin (LMWH) for preventing VTE. We prospectively randomized 120 head/spinal traumatized patients for comparison of IPC with LMWH as a prophylaxis modality against VTE. Venous duplex color-flow Doppler sonography of the lower extremities was performed each week of hospitalization and 1 week after discharge. When there was a suspicion of pulmonary embolism (PE), patients were evaluated with spiral computed tomography. Patients were analyzed for demographic features, injury severity scores, associated injuries, type of head/spinal trauma, complications, transfusion, and incidence of deep venous thrombosis (DVT) and PE. Two patients (3.33%) from the IPC group and 4 patients (6.66%) from the LMWH group died, with their deaths due to PE. Nine other patients also succumbed, unrelated to PE. DVT developed in 4 patients (6.66%) in the IPC group and in 3 patients (5%) in the LMWH group. There was no statistically significant difference regarding a reduction in DVT, PE, or mortality between groups ( p = 0.04, p > 0.05, p > 0.05, respectively). IPC can be used safely for prophylaxis of VTE in head/spinal trauma patients.",
"The frequency of deep venous thrombosis (DVT) was studied in 98 patients undergoing major abdominal surgery. All the patients received low dose heparin prophylaxis 5000 i.u. every 12 h for 5-7 days. In each patient, a graduated compression stocking was also worn and randomly allocated to one of the legs and the other leg served as a control. DVT was diagnosed by the 125I-fibrinogen method. Four patients developed bilateral DVT and 8 patients unilateral DVT, all of whom developed it in the control leg. The difference in unilateral DVT between stockinged and control legs was significant (P < 0.004). It is concluded that a combination of low dose heparin and graduated compression stockings is more effective than low dose heparin alone in reducing the frequency of postoperative DVT. It is suggested that this combination of prophylaxis might be of value in high risk patients.",
"The incidence of deep venous thrombosis (DVT) was assessed in a series of 78 patients undergoing major surgical operations to compare the prophylactic effectiveness of intermittent sequential pneumatic compression alone with the simultaneous use of graduated compression stockings and intermittent sequential pneumatic compression. The diagnosis of DVT was determined with the I-125 fibrinogen-uptake test, Doppler ultrasound, maximum venous outflow by strain-gauge plethysmography, and contrast venography. The incidence of DVT in nonstockinged legs was 9% while that in the stockinged legs was 1%. The simultaneous use of graduated elastic compression stockings and intermittent pneumatic compression is more effective than pneumatic compression alone in the prevention of postoperative DVT.",
"To study the incidence of postoperative deep venous thrombosis (DVT) in patients undergoing elective aortic reconstruction and to determine if aggressive DVT prophylaxis would reduce the incidence of DVT in these patients.\n Randomized, prospective trial.\n University hospital and Veterans Affairs hospital.\n One hundred patients undergoing aortic reconstruction for aneurysmal or occlusive disease randomized to receive DVT prophylaxis (treatment group) or no prophylaxis (control group). Exclusion criteria included a history of DVT, long-term anticoagulant use, or a malignant neoplasm. During the study period, 12 patients were ineligible for follow-up. Ninety-eight patients completed the trial, including 50 patients in the treatment group and 48 patients in the control group. Two patients in the control group died postoperatively of unrelated causes.\n Patients in the treatment group received DVT prophylaxis using a combination of low-dose heparin sodium therapy (5000 U every 12 hours) and calf-length intermittent mechanical compression devices. Control patients received no DVT prophylaxis.\n The occurrence of acute lower extremity DVT diagnosed by interval venous duplex ultrasound scan surveillance performed on postoperative days 1, 3, and 7.\n The overall incidence of proximal DVT in this study was 2%. One case of DVT occurred in the treatment group, and the other one occurred in the control group. There was no statistically significant difference (P = .99) in the incidence of DVT between the 2 groups. One patients in the control group had a nonfatal pulmonary embolus (1% of the patients overall).\n The incidence of proximal DVT in patients undergoing elective aortic reconstruction is low compared with patients undergoing other major intraabdominal general surgical procedures. The use of aggressive DVT prophylaxis did not reduce the risk of postoperative proximal DVT in this study. The selective use of DVT prophylaxis in patients undergoing elective aortic surgery should be based on associated concomitant or evolving risk factors.",
"Two hundred and forty-five patients who underwent acute extensive abdominal operations were randomized into three regimens to achieve optimal prophylaxis of postoperative thromboembolic complications. All of the patients were screened by the 125I-fibrinogen uptake test for seven days and if the phlebographic findings were positive. Of 81 patients receiving low dose heparin, 12 had thromboembolism. Of 79 receiving a combination of low dose heparin and graded compression stockings, two had thromboembolism, and of 85 receiving a combination of dextran and graded compression stockings, 13 had this complication. This difference is significant in favor of the second treatment (p = 0.013). It is concluded that the combination of low dose heparin and graded compression stockings is an effective way to prevent thromboembolism after acute abdominal operations.",
"Deep vein thrombosis (DVT) and subsequent pulmonary embolism (PE) is a major source of mortality and morbidity in stroke patients. This study was designed to determine the effectiveness of different prophylactic treatments in the prevention of DVT after a stroke in patients undergoing rehabilitation. An additional objective was the identification of risk factors for DVT in stroke in patients during rehabilitation. Three hundred and sixty patients, over a 3-year period, were randomly assigned to one of four groups: adjusted dose heparin, intermittent pneumatic compression (IPC), functional electrical stimulation (FES), or control. There was no significant difference in the development of DVT by treatment group. Patients with DVT on admission (prevalent, n = 61) were compared with the study patients (n = 360). Time interval (from stroke to admission) and lactic dehydrogenase (LDH) concentration were significant risk factors, as well as predictors, for development of DVT (p < .000). These results suggest that the longer a patient remains without DVT prophylaxis after a stroke, the greater the risk of developing DVT and this supports early prophylaxis before rehabilitation.",
"The effect of low-dose heparin prophylaxis on venous thrombosis and bleeding after major elective surgery was studied in a prospective controlled study of 820 patients. The total incidence of venous thrombosis detected with leg-scanning using fibrinogen labeled with radioactive iodine (125I) was reduced from 16.0% in the control group to 4.2% in treated patients. More important, the incidence of popliteal or femoral vein thrombosis was reduced from 2.9% to 1.0%. Prophylaxis resulted in a slight increase in bleeding-minor wound hematoma, mean volume of blood transfused, and a post-operative hematocrit fall in treated patients. However, increased bleeding was clinically minor, and prophylaxis was well tolerated.",
"The incidence of deep venous thrombosis (DVT) and the efficacy of prophylactic measures were prospectively evaluated in all patients admitted to a level I trauma center during 1991. Patients with Injury Severity Scores (ISS) > 9 who survived a minimum of 48 hours (n = 395) were monitored using venous Doppler and ultrasound studies during hospitalization (total, 1308 studies). Two hundred eighty-one patients (71%) were randomly assigned to low-dose heparin or sequential compression devices. There were 18 cases of lower extremity DVT (4.6%) and four cases (1.0%) of pulmonary emboli (PE), three of which were fatal. Eight patients (2.9%) on prophylaxis and 10 (8.8%) without prophylaxis developed DVT (p < 0.02 by Chi-square). There were two PEs in each group. Fourteen of these 18 patients sustained blunt trauma and included seven spinal fractures or subluxations (four paraplegic) and four severe head injuries. This represented 14.0% of 50 patients admitted with spinal injuries and 4.3% of 92 patients with severe head injuries. Compared with those with no neurologic injury (7 of 253 or 2.7%), the risk of DVT is significantly higher in the spinal injury patients (p < 0.001, Chi-square) and twice as high as in the head injury group, although not statistically significant (p = 0.4, Chi-square). Three of the four patients with penetrating trauma and DVT had venous injuries. We conclude that DVT prophylaxis can significantly reduce the incidence of DVT in trauma patients with ISS > 9. Patients with severe neurologic injuries (particularly spinal cord) are at high risk for DVT and PE and may be considered for a prophylactic Greenfield filter."
] |
Compared with compression alone, combined prophylactic modalities decrease significantly the incidence of venous thromboembolism. Compared with pharmacological prophylaxis alone, combined modalities reduce significantly the incidence of DVT but the effect on PE is unknown. The results of the current review support, especially in high-risk patients, the use of combined modalities. More studies on their role in PE prevention, compared with pharmacological prophylaxis alone, are urgently needed.
|
CD004857
|
[
"19007842",
"16816222",
"19324530"
] |
[
"Bipolar I and II disorder residual symptoms: oxcarbazepine and carbamazepine as add-on treatment to lithium in a double-blind, randomized trial.",
"A double-blind, randomized, placebo-controlled trial of oxcarbazepine in the treatment of bipolar disorder in children and adolescents.",
"Comparative efficacy and safety of oxcarbazepine versus divalproex sodium in the treatment of acute mania: a pilot study."
] |
[
"Bipolar affective disorders often require adjunctive therapy to treat persistent symptoms. In order to evaluate bipolar symptoms inadequately responsive to lithium, we have compared the effects of two structurally related compounds carbamazepine (CBZ) and oxcarbazepine (OXC). We evaluated the efficacy and safety of CBZ and OXC administration in residual symptoms as an adjunctive therapy in Bipolar I (BP I) and Bipolar II (BP II) patients while on lithium maintenance treatment. We selected from 153 bipolar patients in treatment those fulfilling Research Diagnostic Criteria for mania or hypomania, according to the SADS-L and conducted in 52 bipolar patients (27 BP I, 25 BP II) a double-blind, randomized, parallel-group, single centre, clinical trial. Bipolar I and II outpatients, were randomly assigned on a 1:1 ratio to OXC (n=26) or CBZ (n=26) for an 8-week period as add-on treatment to the existing lithium regimen. Outcome measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale 21 items (HDRS-21) and Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impression severity (CGI-S) and improvement illness (CGI-I). These scales were administered at baseline and at the end of weeks 2, 4 and 8. All the fifty-two patients completed the trial. Overall, females were 35 (65%) and mean (S.D.) age was 39.4 (11.9) years; final doses at the end of week 8 in OXC group was 637.7 (210) mg/day and in the CBZ group 673.5 (179) mg/day; lithium plasma levels were 0.73 (0.25) meq/l and 0.71 (0.28) meq/l, respectively. Both OXC and CBZ were effective in reducing bipolar scores from baseline to endpoint (p<0.01). OXC was more effective than CBZ at weeks 4 and 8 on all 5 outcome measures. OXC resulted in greater significant mean reductions in YMRS, HDRS-21, MADRS, CGI-S and CGI-I scores from baseline to week 4 (p<0.05) and from baseline to week 8 (p<0.001), except YMRS (p<0.01). OXC appeared to be significantly more effective and with better tolerability than CBZ as add-on strategy treatment in BP I and BP II patients. This pilot, randomized clinical trial, suggests the potential usefulness of OXC as adjunctive therapy to lithium both in acute and long-term treatment of bipolar disorder. However, further adequately placebo-controlled trials are needed to expand these findings.",
"This multicenter trial examined the efficacy and safety of oxcarbazepine in the treatment of bipolar disorder in children and adolescents.\n A total of 116 outpatients 7 to 18 years of age with bipolar I disorder, manic or mixed, were recruited at 20 centers in the United States and randomly assigned to receive 7 weeks of double-blinded, flexibly dosed treatment with oxcarbazepine (maximum dose 900-2400 mg/day) or placebo. The primary efficacy measure was the mean change from baseline to endpoint in the Young Mania Rating Scale (YMRS), using the last-observation-carried-forward method.\n Oxcarbazepine (mean dose=1515 mg/day) did not significantly improve YMRS scores at endpoint compared with placebo [adjusted mean change: oxcarbazepine, -10.90 (N=55); placebo, -9.79 (N=55)]. Dizziness, nausea, somnolence, diplopia, fatigue, and rash were each reported in at least 5% of the patients in the oxcarbazepine group with an incidence at least twice that of the placebo group. The majority of adverse events were mild to moderate and occurred during the titration period. Eleven patients (19%) in the oxcarbazepine group discontinued the study because of adverse events, compared with two (4%) in the placebo group.\n Oxcarbazepine is not significantly superior to placebo in the treatment of bipolar disorder in youths. While the overall adverse event profile was similar to that reported for patients with epilepsy, the incidence of psychiatric adverse events for both the oxcarbazepine and placebo groups was higher than that reported for the epilepsy population.",
"This study compared the efficacy and safety of oxcarbazepine and divalproex sodium in acute mania patients.\n In this 12 week, randomized, double-blind pilot study, 60 patients diagnosed with acute mania (DSM-IV) and a baseline Young Mania Rating Scale (YMRS) score of 20 or more received flexibly dosed oxcarbazepine (1,000-2,400 mg/day) or divalproex (750-2,000 mg/day). The mean decrease in the YMRS score from baseline was used as the main outcome measure of response to treatment. A priori protocol-defined threshold scores were <or=12 for remission and >or=15 for relapse. Number of patients showing adequate response and the time taken to achieve improvement was compared. Adverse events were systematically recorded throughout the study.\n Over 12 weeks, mean improvement in YMRS scores was comparable for both the groups including the mean total scores as well as percentage fall from baseline. There were no significant differences between treatments in the rates of symptomatic mania remission (90% in divalproex and 80% in oxcarbazepine group) and subsequent relapse. Median time taken to symptomatic remission was 56 days in divalproex group while it was 70 days in the oxcarbazepine group (p=0.123). A significantly greater number of patients in divalproex group experienced one or more adverse drug events as compared to patients in the oxcarbazepine group (66.7% versus 30%, p<0.01).\n Oxcarbazepine demonstrated comparable efficacy to divalproex sodium in the management of acute mania. Also the overall adverse event profile was found to be superior for oxcarbazepine."
] |
Currently, there are insufficient trials of adequate methodological quality on oxcarbazepine in the acute treatment of bipolar disorder to inform us on its efficacy and acceptability. Studies predominantly examine the treatment of mania: there are data from subgroup analysis on mixed affective, hypomania and rapid-cycling states.
From the few studies included in this review, oxcarbazepine did not differ in efficacy compared to placebo in children and adolescents. It did not differ from other active agents in adults. It may have a poorer tolerability profile compared to placebo. No data were found on outcomes relevant to patients and clinicians, such as length of hospital admission.
There is a need for adequately powered randomised controlled trials of good methodological quality to inform us of the therapeutic potential of oxcarbazepine across the spectrum of acute episodes in bipolar disorder.
|
CD005011
|
[
"18496183",
"16788315",
"20838118",
"16102099",
"15734783",
"16035095",
"17686152",
"16269927",
"19546387",
"12105840",
"16442954",
"18480205",
"16096533",
"15480990",
"16035081",
"15569871",
"12734081",
"18393319",
"17906567",
"16757825",
"1913123",
"11573637"
] |
[
"Recombinant factor VIIA in traumatic intracerebral hemorrhage: results of a dose-escalation clinical trial.",
"Elective administration in infants of low-dose recombinant activated factor VII (rFVIIa) in cardiopulmonary bypass surgery for congenital heart disease does not shorten time to chest closure or reduce blood loss and need for transfusions: a randomized, double-blind, parallel group, placebo-controlled study of rFVIIa and standard haemostatic replacement therapy versus standard haemostatic replacement therapy.",
"Results of the CONTROL trial: efficacy and safety of recombinant activated Factor VII in the management of refractory traumatic hemorrhage.",
"Recombinant activated factor VII in treatment of bleeding complications following hematopoietic stem cell transplantation.",
"Use of activated recombinant coagulation factor VII in patients undergoing reconstruction surgery for traumatic fracture of pelvis or pelvis and acetabulum: a double-blind, randomized, placebo-controlled trial.",
"Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation.",
"Safety of rFVIIa in hemodynamically unstable polytrauma patients with traumatic brain injury: post hoc analysis of 30 patients from a prospective, randomized, placebo-controlled, double-blind clinical trial.",
"Control of bleeding in children with Dengue hemorrhagic fever using recombinant activated factor VII: a randomized, double-blind, placebo-controlled study.",
"Safety and efficacy of recombinant activated factor VII: a randomized placebo-controlled trial in the setting of bleeding after cardiac surgery.",
"Safety and efficacy of recombinant factor VIIa in patients with liver disease undergoing laparoscopic liver biopsy.",
"Safety and hemostatic effect of recombinant activated factor VII in cirrhotic patients undergoing partial hepatectomy: a multicenter, randomized, double-blind, placebo-controlled trial.",
"Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage.",
"Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials.",
"Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial.",
"Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease.",
"Safety and feasibility of recombinant factor VIIa for acute intracerebral hemorrhage.",
"Feasibility of adjuvant hepatic arterial infusion of chemotherapy after radiofrequency ablation with or without resection in patients with hepatic metastases from colorectal cancer.",
"Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial.",
"Recombinant activated factor VII in spinal surgery: a multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial.",
"Recombinant activated factor VII for acute intracerebral hemorrhage: US phase IIA trial.",
"Randomized trial of intra-arterial recombinant tissue plasminogen activator, intravenous recombinant tissue plasminogen activator and intra-arterial streptokinase in peripheral arterial thrombolysis.",
"Reduced haemostatic factor transfusion using heparinase-modified thrombelastography during cardiopulmonary bypass."
] |
[
"Intracerebral hemorrhages, whether spontaneous or traumatic (tICH), often expand, and an association has been described between hemorrhage expansion and worse clinical outcomes. Recombinant factor VIIa (rFVIIa) is a hemostatic agent that has been shown to limit hemorrhage expansion and which, therefore, could potentially reduce morbidity and mortality in tICH. This first prospective, randomized, placebo-controlled, dose-escalation study evaluated the safety and preliminary effectiveness of rFVIIa to limit tICH progression.\n Patients were enrolled if they had tICH lesions of at least 2 ml on a baseline computed tomographic scan obtained within 6 hours of injury. rFVIIa or placebo was administered within 2.5 hours of the baseline computed tomographic scan but no later than 7 hours after injury. Computed tomographic scans were repeated at 24 and 72 hours. Five escalating dose tiers were evaluated (40, 80, 120, 160, and 200 microg/kg rFVIIa). Clinical evaluations and adverse events were recorded until Day 15.\n No significant differences were detected in mortality rate or number and type of adverse events among treatment groups. Asymptomatic deep vein thrombosis, detected on routinely performed ultrasound at Day 3, was observed more frequently in the combined rFVIIa treatment group (placebo, 3%; rFVIIa, 8%; not significant). A nonsignificant trend for rFVIIa dose-response to limit tICH volume increase was observed (placebo, 21.0 ml; rFVIIa, 10.1 ml).\n In this first prospective study of rFVIIa in tICH, there appeared to be less hematoma progression in rFVIIa-treated patients (80-200 microg/kg) compared with that seen in placebo treated patients. The potential significance of this biological effect on clinical outcomes and the significance of the somewhat higher incidence of ultrasound-detected deep vein thromboses in the rFVIIa-treated group need to be examined in a larger prospective randomized clinical trial.",
"We investigated the effectiveness of prophylactic administration of recombinant activated factor VII (rFVIIa) for cardiopulmonary bypass surgery in children under 1 year old with congenital heart disease (CHD) in a double-blinded, placebo-controlled study. The rFVIIa dose was 40 microg/kg and all patients also received standard haemostatic replacement therapy. The primary endpoint was the time to chest closure from neutralization of heparin with protamine sulphate as this could be most objectively and accurately measured during surgery. Secondary endpoints were volumes of transfused blood, platelet concentrates and fresh-frozen plasma. All adverse events were recorded. In the intention-to-treat analysis there were 76 patients (40 in rFVIIa group and 36 in placebo group). The demographics and severity of CHD were similar in both groups. No benefit of rFVIIa prophylaxis was found in the time to chest closure, which was significantly prolonged in the rFVIIa group (rFVIIa mean +/- SE, 98.8 +/- 27.27 versus 55.3 +/- 29.15, P = 0.0263). In the 41 patients available for a follow-up visit 6 weeks after discharge, the chest closure time was also prolonged in the rFVIIa group (P = 0.0515). There were no significant differences in the secondary endpoints. Adverse events were similar in both groups.",
"Traumatic coagulopathy contributes to early death by exsanguination and late death in multiple organ failure. Recombinant Factor VIIa (rFVIIa, NovoSeven) is a procoagulant that might limit bleeding and improve trauma outcomes.\n We performed a phase 3 randomized clinical trial evaluating efficacy and safety of rFVIIa as an adjunct to direct hemostasis in major trauma. We studied 573 patients (481 blunt and 92 penetrating) who bled 4 to 8 red blood cell (RBC) units within 12 hours of injury and were still bleeding despite strict damage control resuscitation and operative management. Patients were assigned to rFVIIa (200 μg/kg initially; 100 μg/kg at 1 hour and 3 hours) or placebo. Intensive care unit management was standardized using evidence-based trauma \"bundles\" with formal oversight of compliance. Primary outcome was 30-day mortality. Predefined secondary outcomes included blood products used. Safety was assessed through 90 days. Study powering was based on prior randomized controlled trials and large trauma center databases.\n Enrollment was terminated at 573 of 1502 planned patients because of unexpected low mortality prompted by futility analysis (10.8% vs. 27.5% planned/predicted) and difficulties consenting and enrolling sicker patients. Mortality was 11.0% (rFVIIa) versus 10.7% (placebo) (p = 0.93, blunt) and 18.2% (rFVIIa) versus 13.2% (placebo) (p = 0.40, penetrating). Blunt trauma rFVIIa patients received (mean ± SD) 7.8 ± 10.6 RBC units and 19.0 ± 27.1 total allogeneic units through 48 hours, and placebo patients received 9.1 ± 11.3 RBC units (p = 0.04) and 23.5 ± 28.0 total allogeneic units (p = 0.04). Thrombotic adverse events were similar across study cohorts.\n rFVIIa reduced blood product use but did not affect mortality compared with placebo. Modern evidence-based trauma lowers mortality, paradoxically making outcomes studies increasingly difficult.",
"Bleeding is a common complication following hematopoietic stem cell transplantation (HSCT) and standard hemostatic treatment is often ineffective. We conducted a multicentre, randomized trial of the efficacy and safety of activated recombinant factor VII (rFVIIa, NovoSeven) in the treatment of bleeding following HSCT.\n 100 patients with moderate or severe bleeding (52 gastrointestinal; 26 hemorrhagic cystitis; seven pulmonary; one cerebral; 14 other) were included from days +2 to +180 post-transplant (97 allogeneic; three autologous) to receive seven doses of rFVIIa (40, 80 or 160 microg kg(-1)) or placebo every 6 h. The primary efficacy endpoint was the change in bleeding score between the first administration and 38 h.\n No significant effect of increasing rFVIIa dose was observed on the primary endpoint. A post hoc analysis comparing each rFVIIa dose with placebo showed that 80 microg kg(-1) rFVIIa improved the bleeding score at the 38 h time point (81% vs. 57%, P = 0.021). This effect was not seen at 160 microg kg(-1). There were no differences in transfusion requirements across dose groups. There was no trend in the type or number of severe adverse events observed. Six thromboembolic events were observed in the active treatment groups: three during, and three following the 96-h observation period.\n Despite no overall effect of rFVIIa treatment on primary endpoint, post hoc analysis showed an improvement in the control of bleeding for 80 microg kg(-1) rFVIIa vs. standard hemostatic treatment. The heterogeneity of the population may have contributed to the lack of an increasing effect with increased dose. Further trials should focus upon identifying the patient populations that may benefit from treatment with rFVIIa.",
"Activated recombinant coagulation factor VII (rFVIIa) effectively prevents and controls bleeding in patients with coagulopathy. Data show that rFVIIa may reduce blood loss and eliminate the need for transfusion in patients with normal haemostasis undergoing major surgery. We assessed the efficacy of rFVIIa in patients with normal haemostasis undergoing repair surgery of major traumatic fracture of the pelvis or the pelvis and acetabulum, who were expected to have a large volume of blood loss.\n We performed a double-blind, randomized, placebo-controlled trial involving 48 patients undergoing major pelvic-acetabular surgery. Patients were randomized to receive an i.v. bolus injection of rFVIIa 90 microg kg(-1) or placebo as add-on therapy at the time of the first skin incision. All patients also received intraoperative salvaged red blood cells (RBC).\n There was no significant difference in the total volume of perioperative blood loss, the primary outcome variable, between the rFVIIa and placebo groups. In addition, there were no differences between the two groups in the total volume of blood components, including salvaged RBC transfused, number of patients requiring allogeneic blood components, total volume of fluids infused, total operating time, time taken after entry to the intensive care unit to reach normal body temperature and acid-base status, and time spent in hospital. No adverse events, in particular thromboembolic events, were reported in either group.\n In patients with normal haemostasis undergoing repair surgery of traumatic pelvic-acetabular fracture, the prophylactic use of rFVIIa does not decrease the volume of perioperative blood loss.",
"Patients undergoing orthotopic liver transplantation (OLT) have excessive blood loss during surgery that requires blood transfusions, leading to increased postoperative morbidity and mortality. We studied the efficacy and safety of activated recombinant factor VII (rFVIIa) in reducing transfusion requirements in OLT. This multicenter, randomized, double-blind, placebo-controlled trial enrolled patients undergoing OLT because of cirrhosis (Child-Turcotte-Pugh class B or C). Patients received a repeated intravenous bolus regimen of rFVIIa 60 or 120 microg/kg or placebo. The primary efficacy endpoint was the total number of red blood cell (RBC) units transfused during the perioperative period. A total of 182 patients were analyzed for efficacy and 183 for safety. No significant effect of rFVIIa was observed on the number of RBC units transfused or intraoperative blood loss compared with the placebo group. A significantly higher number of patients in the rFVIIa study groups avoided RBC transfusion. Administration of rFVIIa but not placebo restored the preoperative prolonged prothrombin time to normal value during surgery. Patients receiving rFVIIa and placebo did not experience a significant difference in rate of thromboembolic events. Additionally, there was no statistically significant effect of rFVIIa treatment on hospitalization rate, total surgery time, and the proportion of patients undergoing retransplantation. In conclusion, use of rFVIIa during OLT significantly reduced the number of patients requiring RBC transfusion. There was no increase in thromboembolic events with rFVIIa administration compared with placebo.",
"Trauma is a leading cause of mortality and morbidity, with traumatic brain injury (TBI) and uncontrolled hemorrhage responsible for the majority of these deaths. Recombinant activated factor VIIa (rFVIIa) is being investigated as an adjunctive hemostatic treatment for bleeding refractory to conventional replacement therapy in trauma patients. TBI is a common component of polytrauma injuries. However, the combination of TBI with polytrauma injuries is associated with specific risk factors and treatment modalities somewhat different from those of polytrauma without TBI. Although rFVIIa treatment may offer added potential benefit for patients with combined TBI and polytrauma, its safety in this population has not yet been assessed. We conducted a post hoc sub analysis of patients with TBI and severe blunt polytrauma enrolled into a prospective, international, double-blind, randomized, placebo-controlled study.\n A post hoc analysis of study data was performed for 143 patients with severe blunt trauma enrolled in a prospective, randomized, placebo-controlled study, evaluating the safety and efficacy of intravenous rFVIIa (200 + 100 + 100 microg/kg) or placebo, to identify patients with a computed tomography (CT) diagnosis of TBI. The incidences of ventilator-free days, intensive care unit-free days, and thromboembolic, serious, and adverse events within the 30-day study period were assessed in this cohort.\n Thirty polytrauma patients (placebo, n = 13; rFVIIa, n = 17) were identified as having TBI on CT. No significant differences in rates of mortality (placebo, n = 6, 46%, 90% confidence interval (CI): 22% to 71%; rFVIIa, n = 5, 29%, 90% CI: 12% to 56%; P = 0.19), in median numbers of intensive care unit-free days (placebo = 0, rFVIIa = 3; P = 0.26) or ventilator-free days (placebo = 0, rFVIIa = 10; P = 0.19), or in rates of thromboembolic adverse events (placebo, 15%, 90% CI: 3% to 51%; rFVIIa, 0%, 90% CI: 0% to 53%; P = 0.18) or serious adverse events (placebo, 92%, 90% CI: 68% to 98%; rFVIIa, 82%, 90% CI: 60% to 92%; P = 0.61) were observed between treatment groups.\n The use of a total dose of 400 (200 + 100 + 100) microg/kg rFVIIa in this group of hemodynamically unstable polytrauma patients with TBI was not associated with an increased risk of mortality or with thromboembolic or adverse events.",
"We evaluated the efficacy and safety of recombinant activated factor VII (rFVIIa) in children aged < 18 years old with grade II or grade III Dengue hemorrhagic fever (DHF) who required blood component therapy for controlling bleeding episodes.\n Patients were randomized to the rFVIIa group or placebo group in a ratio of 2:1. rFVIIa or placebo (100 microg/kg body weight) was given by intravenous bolus injection. When bleeding was not effectively controlled, a second dose of rFVIIa or placebo (100 microg/kg) was given 30 min after the first dose.\n Nine and 16 patients received placebo and rFVIIa, respectively. The demographics, bleeding manifestations and grade of DHF were similar for the rFVIIa and placebo groups. Apart from petechiae and ecchymosis, one to four additional bleeding sites were found in each patient, including hematemesis (n = 15), epistaxis (n = 14), gum bleeding (n = 12), melena (n = 7), hypermenorrhea (n = 4), hematochezia (n = 2) and hematuria (n = 2). The mean total dose of rFVIIa (138.4 +/- 50.9 microg/kg) and placebo (145.4 +/- 53.7 microg/kg) were comparable. The efficacy of bleeding control at 2 h after the first dose was completely ceased (rFVIIa 75.0% versus placebo 44.4%), decreased (rFVIIa 18.7% versus placebo 11.2%), and unchanged or worsened (rFVIIa 6.3% versus placebo 44.4%). Some patients with active bleeding received platelet concentrates 3-12 h after the first dose of rFVIIa or placebo. The subsequent efficacy of bleeding control at 6, 12 and 24 h was comparable between the two groups. The cumulative use of red blood cells (rFVIIa 31.3% versus placebo 33.3%) and plasma (rFVIIa 25% versus placebo 22%) during the 24-h period was not significantly different between the two groups. In contrast, platelet concentrate requirement in the rFVIIa group (6.3%) was lower than the placebo (33.3%). No clinical evidence of thromboembolic complications or mortality as a result of bleeding was observed.\n rFVIIa appears to be a useful adjunctive treatment to blood component transfusion for controlling active bleeding in children with DHF especially when platelet concentrate is not readily available.",
"Blood loss is a common complication of cardiac surgery. Evidence suggests that recombinant activated factor VII (rFVIIa) can decrease intractable bleeding in patients after cardiac surgery. Our objective was to investigate the safety and possible benefits of rFVIIa in patients who bleed after cardiac surgery.\n In this phase II dose-escalation study, patients who had undergone cardiac surgery and were bleeding were randomized to receive placebo (n=68), 40 microg/kg rFVIIa (n=35), or 80 microg/kg rFVIIa (n=69). The primary end points were the number of patients suffering critical serious adverse events. Secondary end points included rates of reoperation, amount of blood loss, and transfusion of allogeneic blood. There were more critical serious adverse events in the rFVIIa groups. These differences did not reach statistical significance (placebo, 7%; 40 microg/kg, 14%; P=0.25; 80 microg/kg, 12%; P=0.43). After randomization, significantly fewer patients in the rFVIIa group underwent a reoperation as a result of bleeding (P=0.03) or required allogeneic transfusions (P=0.01).\n On the basis of this preliminary evidence, rFVIIa may be beneficial for treating bleeding after cardiac surgery, but caution should be applied and further clinical trials are required because there is an increase in the number of critical serious adverse events, including stroke, in those patients randomized to receive rFVIIa.",
"Activated recombinant factor VII (rFVIIa) has been shown to be effective in correcting prolonged prothrombin time (PT) in cirrhotic patients. The main objective of this study was to evaluate the effect of 4 (5, 20, 80, and 120 microg/kg) doses of rFVIIa on correction of PT and the time to achieve hemostasis in cirrhotic patients with coagulopathy who are undergoing laparoscopic liver biopsy.\n Seventy-one patients (parts I and II) with advanced liver disease (Child-Turcotte B or C), platelet count > or =60,000/mm3, and PT in the range of 3-15 seconds above normal were included in the study. Efficacy endpoints were normalization of PT and time to hemostasis.\n PT was corrected to normal levels (<13.1 seconds) in the majority of patients. The duration of normalization of PT was longer in patients treated with higher doses of rFVIIa. Forty-eight (74%) of 65 patients (part II) achieved hemostasis within 10 minutes. No correlation between the time to hemostasis and duration of correction of PT was observed. None of the patients required operative intervention or transfusion of blood/blood products to control bleeding. One thrombotic event and one case of disseminated intravascular coagulation were reported, but both events were considered by the investigator as unlikely to be related to treatment with rFVIIa.\n The results of this study suggest that treatment with rFVIIa may offer benefit for patients with liver disease undergoing laparoscopic biopsy.",
"Coagulopathy caused by cirrhosis may contribute to excessive bleeding during hepatectomy. We evaluated the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in cirrhotic patients undergoing partial hepatectomy.\n Patients were randomized to rFVIIa 50 or 100 mug/kg or placebo, administered intravenously 10 minutes before surgery and every second hour during surgery. The primary efficacy end points were the proportion of patients receiving red blood cell (RBC) transfusions and the amount of RBCs transfused. The RBC transfusion trigger was blood loss of 500 mL. Safety end points included thromboembolic and adverse events.\n No statistically significant effect of rFVIIa treatment on efficacy end points was observed. Serious and thromboembolic adverse events occurred at similar incidences in the study groups.\n Using blood loss as a transfusion trigger, the efficacy of rFVIIa in reducing the requirement for RBC transfusion was not established in this study. No safety concerns were identified.",
"Intracerebral hemorrhage is the least treatable form of stroke. We performed this phase 3 trial to confirm a previous study in which recombinant activated factor VII (rFVIIa) reduced growth of the hematoma and improved survival and functional outcomes.\n We randomly assigned 841 patients with intracerebral hemorrhage to receive placebo (268 patients), 20 microg of rFVIIa per kilogram of body weight (276 patients), or 80 microg of rFVIIa per kilogram (297 patients) within 4 hours after the onset of stroke. The primary end point was poor outcome, defined as severe disability or death according to the modified Rankin scale 90 days after the stroke.\n Treatment with 80 microg of rFVIIa per kilogram resulted in a significant reduction in growth in volume of the hemorrhage. The mean estimated increase in volume of the intracerebral hemorrhage at 24 hours was 26% in the placebo group, as compared with 18% in the group receiving 20 microg of rFVIIa per kilogram (P=0.09) and 11% in the group receiving 80 microg (P<0.001). The growth in volume of intracerebral hemorrhage was reduced by 2.6 ml (95% confidence interval [CI], -0.3 to 5.5; P=0.08) in the group receiving 20 microg of rFVIIa per kilogram and by 3.8 ml (95% CI, 0.9 to 6.7; P=0.009) in the group receiving 80 microg, as compared with the placebo group. Despite this reduction in bleeding, there was no significant difference among the three groups in the proportion of patients with poor clinical outcome (24% in the placebo group, 26% in the group receiving 20 microg of rFVIIa per kilogram, and 29% in the group receiving 80 microg). The overall frequency of thromboembolic serious adverse events was similar in the three groups; however, arterial events were more frequent in the group receiving 80 microg of rFVIIa than in the placebo group (9% vs. 4%, P=0.04).\n Hemostatic therapy with rFVIIa reduced growth of the hematoma but did not improve survival or functional outcome after intracerebral hemorrhage. (ClinicalTrials.gov number, NCT00127283 [ClinicalTrials.gov].).\n Copyright 2008 Massachusetts Medical Society.",
"Uncontrolled bleeding is a leading cause of death in trauma. Two randomized, placebo-controlled, double-blind trials (one in blunt trauma and one in penetrating trauma) were conducted simultaneously to evaluate the efficacy and safety of recombinant factor VIIa (rFVIIa) as adjunctive therapy for control of bleeding in patients with severe blunt or penetrating trauma.\n Severely bleeding trauma patients were randomized to rFVIIa (200, 100, and 100 microg/kg) or placebo in addition to standard treatment. The first dose followed transfusion of the eighth red blood cell (RBC) unit, with additional doses 1 and 3 hours later. The primary endpoint for bleeding control in patients alive at 48 hours was units of RBCs transfused within 48 hours of the first dose.\n Among 301 patients randomized, 143 blunt trauma patients and 134 penetrating trauma patients were eligible for analysis. In blunt trauma, RBC transfusion was significantly reduced with rFVIIa relative to placebo (estimated reduction of 2.6 RBC units, p = 0.02), and the need for massive transfusion (>20 units of RBCs) was reduced (14% vs. 33% of patients; p = 0.03). In penetrating trauma, similar analyses showed trends toward rFVIIa reducing RBC transfusion (estimated reduction of 1.0 RBC units, p = 0.10) and massive transfusion (7% vs. 19%; p = 0.08). Trends toward a reduction in mortality and critical complications were observed. Adverse events including thromboembolic events were evenly distributed between treatment groups.\n Recombinant FVIIa resulted in a significant reduction in RBC transfusion in severe blunt trauma. Similar trends were observed in penetrating trauma. The safety of rFVIIa was established in these trauma populations within the investigated dose range.",
"Upper gastrointestinal bleeding (UGIB) is a severe and frequent complication of cirrhosis. Recombinant coagulation factor VIIa (rFVIIa) has been shown to correct the prolonged prothrombin time in patients with cirrhosis and UGIB. This trial aimed to determine efficacy and safety of rFVIIa in cirrhotic patients with variceal and nonvariceal UGIB.\n A total of 245 cirrhotic patients (Child-Pugh < 13; Child-Pugh A = 20%, B = 52%, C = 28%) with UGIB (variceal = 66%, nonvariceal = 29%, bleeding source unknown = 5%) were randomized equally to receive 8 doses of 100 microg/kg rFVIIa or placebo in addition to pharmacologic and endoscopic treatment. The primary end point was a composite including: (1) failure to control UGIB within 24 hours after first dose, or (2) failure to prevent rebleeding between 24 hours and day 5, or (3) death within 5 days.\n Baseline characteristics were similar between rFVIIa and placebo groups. rFVIIa showed no advantage over standard treatment in the whole trial population. Exploratory analyses, however, showed that rFVIIa significantly decreased the number of failures on the composite end point (P = 0.03) and the 24-hour bleeding control end point (P = 0.01) in the subgroup of Child-Pugh B and C variceal bleeders. There were no significant differences between rFVIIa and placebo groups in mortality (5- or 42-day) or incidence of adverse events including thromboembolic events.\n Although no overall effect of rFVIIa was observed, exploratory analyses in Child-Pugh B and C cirrhotic patients indicated that administration of rFVIIa significantly decreased the proportion of patients who failed to control variceal bleeding. Dosing with rFVIIa appeared safe. Further studies are needed to verify these findings.",
"Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however, there has been a limited amount of research into its use in OLT. The purpose of this dose-finding study was to examine the efficacy and safety of rFVIIa in the reduction of bleeding in patients undergoing OLT. In this double-blind trial, patients with end-stage liver disease scheduled for OLT were randomized to 1 of 4 parallel study groups. They received a single intravenous bolus of rFVIIa (20, 40, or 80 microg/kg) or placebo prior to surgery. The primary assessment endpoint was the total number of red blood cell (RBC) units transfused perioperatively. Safety was evaluated by adverse events reported. Eighty-three comparable patients were randomized to receive study product, with 82 ultimately undergoing OLT. There were no significant differences in required RBC units between the placebo and rFVIIa study groups. The number of adverse events was comparable between study groups. In conclusion, rFVIIa has a good safety profile in patients undergoing OLT. However, the doses studied did not have any effect on the number of RBC transfusions required.",
"Hematoma growth occurs in 38% of intracerebral hemorrhage (ICH) patients scanned by computed tomography (CT) within 3 hours of onset. Activated recombinant factor VII (rFVIIa) promotes hemostasis at sites of vascular injury and may minimize hematoma growth after ICH.\n In this randomized, double-blind, placebo-controlled, dose-escalation trial, 48 subjects with ICH diagnosed within 3 hours of onset were treated with placebo (n=12) or rFVIIa (10, 20, 40, 80, 120, or 160 microg/kg; n=6 per group). The primary endpoint was the frequency of adverse events (AEs). Safety assessments included serial electrocardiography (ECG), troponin I and coagulation testing, lower extremity Doppler ultrasonography, and calculation of edema:ICH volume ratios.\n Mean age was 61 years (range, 30 to 93) and 57% were male. At admission, mean National Institutes of Health Stroke Scale (NIHSS) score was 14 (range, 1 to 26), median Glasgow Coma Scale score was 14 (range, 6 to 15), and mean ICH volume was 21 mL (range, 1 to 151). Mean time from onset to treatment was 181 minutes (range, 120 to 265). Twelve serious AEs occurred, including 5 deaths (mortality 11%). Six AEs were considered possibly treatment-related, including rash, vomiting, fever, ECG T-wave inversion, and 2 cases of deep vein thrombosis (placebo and 20-microg/kg groups). No myocardial ischemia, consumption coagulopathy, or dose-related increase in edema:ICH volume occurred.\n This small phase II trial evaluated a wide range of rFVIIa doses in acute ICH and raised no major safety concerns. Larger studies are justified to determine whether rFVIIa can safely and effectively limit ICH growth.",
"The safety of combined hepatic artery infusion chemotherapy (HAI) and radiofrequency ablation (RFA) for liver metastases has not been assessed. We conducted a study to determine the feasibility of using HAI after RFA for colorectal cancer (CRC) liver metastases.\n Between 1996 and 2001, patients with hepatic metastases from CRC were enrolled onto a prospective study of RFA plus HAI consisting of continuous-infusion floxuridine and bolus fluorouracil. Surgical complications, treatment-related toxicities, and patient outcomes were recorded.\n Fifty patients were treated with RFA and HAI with or without resection. A median of two lesions per patient, with a median greatest diameter of 2.0 cm, were treated with RFA. Postoperative complications, including 1 death, occurred in 11 of 50 patients. Toxicity from HAI was relatively mild. At 20 months' median follow-up, 32% of patients remained disease free. Ten percent of patients had recurrences at the site of RFA, 30% developed new liver metastases, and 48% developed extrahepatic disease.\n RFA of CRC liver metastases followed by HAI is feasible and is associated with acceptable complication and toxicity rates. The high rate of disease recurrence in our patients indicates that novel combinations of regional and systemic therapies are needed to improve patient outcomes.",
"A beneficial effect of recombinant activated factor VII (rFVIIa) in Child-Pugh class B and C patients with cirrhosis who have variceal bleeding has been suggested. This randomized controlled trial assessed the efficacy and safety of rFVIIa in patients with advanced cirrhosis and active variceal bleeding. At 31 hospitals in an emergency setting, 256 patients (Child-Pugh > 8; Child-Pugh B = 26%, C = 74%) were randomized equally to: placebo; 600 microg/kg rFVIIa (200 + 4x 100 microg/kg); or 300 microg/kg rFVIIa (200 + 100 microg/kg). Dosing was intravenous at 0, 2, 8, 14, and 20 hours after endoscopy, in addition to standard vasoactive, prophylactic antibiotic, and endoscopic treatment. The primary composite endpoint consisted of failure to control 24-hour bleeding, or failure to prevent rebleeding or death at day 5. Secondary endpoints included adverse events and 42-day mortality. Baseline characteristics were comparable between groups. Administration of rFVIIa had no significant effect on the composite endpoint compared with placebo (P = 0.37). There was no significant difference in 5-day mortality between groups; however, 42-day mortality was significantly lower with 600 microg/kg rFVIIa compared with placebo (odds ratio 0.31, 95% confidence interval = 0.13-0.74), and bleeding-related deaths were reduced from 12% (placebo) to 2% (600 microg/kg). A marked heterogeneity in the failure rate in all treatment groups was observed across participating centers. Adverse events, including overall thromboembolic events, were comparable between groups.\n Treatment with rFVIIa had no significant effect on the primary composite endpoint compared with placebo. Therefore, decision on the use of this hemostatic agent in acute variceal bleeding should be carefully considered, because results of this study do not support the routine use of rFVIIa in this setting. Adverse events were comparable across groups.",
"Randomized, placebo-controlled, double-blind, multicenter, Phase IIa study.\n To assess the safety and efficacy of recombinant-activated Factor VII (rFVIIa) in major spinal surgery.\n Spinal fusion surgery can cause substantial blood loss and blood product transfusions. Recombinant FVIIa is approved for treatment of bleeding in patients with coagulation abnormalities and has been shown to reduce blood loss and transfusion requirements in surgery in patients with no underlying coagulopathy.\n Forty-nine patients undergoing fusion of 3 or more vertebral segments were randomized and treated on losing 10% of their estimated blood volume (with total expected surgical blood loss > or = 20%) and received 3 doses (2-hour intervals) of placebo (n = 13) or 30, 60, or 120 microg/kg rFVIIa (n = 12 per group). The primary endpoint was safety. A priori-defined efficacy endpoints included blood loss and transfusion requirements between placebo and each rFVIIa dose group, adjusted for surgery duration, number of segments fused, and estimated blood volume.\n Serious adverse events did not occur at any greater frequency in any of the treatment groups. One patient (3 x 30 microg/kg rFVIIa) with advanced cerebrovascular disease (undiagnosed, trial exclusion criterion) died 6 days after surgery due to an ischemic stroke. Mean blood loss was as follows: 2270 mL for placebo; 1909, 1262, and 1868 mL for 3 x 30, 3 x 60, and 3 x 120 microg/kg rFVIIa, respectively (differences not statistically significant). Mean adjusted surgical blood loss was as follows: 2536 mL for placebo; 1120, 400, and 823 mL for 3 x 30, 3 x 60, and 3 x 120 microg/kg rFVIIa, respectively (P < or = 0.001). Mean surgical transfusion volume was reduced by 27% to 50% with rFVIIa treatment (not significant). The mean adjusted surgical transfusion volume was reduced by 81% to 95% with rFVIIa treatment (P < or = 0.002).\n No safety concerns were indicated for the use of rFVIIa in patients at all doses tested; rFVIIa reduced adjusted blood loss and adjusted transfusions during spinal surgery.",
"Ultra-early hemostatic therapy may improve outcome after intracerebral hemorrhage (ICH) by preventing rebleeding and hematoma expansion. We conducted this trial to evaluate the safety of activated recombinant factor VII (rFVIIa; NovoSeven) for preventing early hematoma growth in acute ICH.\n In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial, 40 patients diagnosed with ICH by computed tomography within 3 hours of onset were treated with placebo or 5, 20, 40, or 80 microg/kg of rFVIIa ( n = 8 per group). Patients with any history of thromboembolic or vaso-occlusive disease were excluded. The primary endpoint was the frequency of adverse events (AEs).\n Mean age was 65 years (range 34 - 91) and the median admission Glasgow Coma Scale score was 14.5 (range 6 to 15). Mean ICH volume was 17 +/- 19 mL; nearly three-quarters were located in the basal ganglia ( n = 29). The mean interval from onset to treatment was 178 +/- 41 minutes. Thirty-three patients experienced 186 AEs, which occurred with similar frequency in the five groups. There were 10 thromboembolic AEs, including one case of deep vein thrombosis (20 microg g/kg group); one case of cerebral infarction (placebo); two cases of pulmonary embolism (20 and 40 microg g/kg groups); and six instances of ischemic ECG changes or cardiac enzyme elevation (placebo [ n = 2], 20 microg g/kg [ n = 1], 40 microg g/kg [ n = 1], and 80 microg g/kg [ n = 2] groups). No consumption coagulopathy or dose-related increase in edema-to-ICH volume ratio occurred.\n Ultra-early rFVIIa treatment for ICH was associated with a reasonable safety profile in this preliminary study across a wide range of dosages. Further research is warranted to investigate the safety and potential efficacy of rFVIIa for minimizing ICH growth.",
"Sixty patients were recruited into a randomized parallel group comparison of three thrombolytic regimens for acute or subacute peripheral arterial thrombosis. There were no significant differences in age, duration of history, length of occlusion or presence of neurosensory deficit between the groups. Initially successful lysis was significantly greater with intra-arterial (IA) recombinant tissue plasminogen activator (rt-PA) than with either streptokinase (Sk) (P less than 0.04) or intravenous (IV) rt-PA (P less than 0.01). The duration of therapy varied from a median of 35 h with IA rt-PA to 40 h with Sk (P greater than 0.5). The median (confidence interval) increase in ankle:brachial pressure index following IA rt-PA of 0.57 (0.33-0.82) was significantly higher than for either Sk of 0.24 (0-0.57) or for IV rt-PA of 0.18 (0-0.41). Limb salvage at 30 days was achieved in 80, 60 and 45 per cent respectively for IA rt-PA, Sk and IV rt-PA. Haemorrhagic complications occurred in six patients following Sk and in 13 following IV rt-PA; only one minor haemorrhage occurred following a catheter perforation in a patient who received IA rt-PA (P less than 0.05). IA rt-PA provides a more effective, safer fibrinolytic regimen than conventional therapy with Sk. IV rt-PA has not been as successful and carries a significantly higher risk of haemorrhagic complications.",
"We set out to determine if the heparinase-modified thrombelastogram using anticoagulated blood from patients during cardiac surgery could guide treatment with haemostatic components. In 60 patients a simple algorithm predicted a possible 60-80% decrease in the use of haemostatic components. In a second series, 30 patients were allocated to receive components using this intra-operative algorithm and 30 using clinical criteria and laboratory-based tests. Ten patients in the clinical group received a total of 16 units of fresh frozen plasma and nine platelet concentrates compared with five patients transfused with five units of fresh frozen plasma and one platelet concentrate in the algorithm group. Twelve-hour chest tube losses [algorithm group 470 (295-820) ml, clinically managed group 390 (240-820) ml (median, quartile values)] were not different between groups despite the threefold reduction in the use of haemostatic products, showing that intra-operative monitoring of coagulation in the anticoagulated patient can be used to guide treatment."
] |
The effectiveness of rFVIIa as a more general haemostatic drug, either prophylactically or therapeutically, remains unproven. The results indicate increased risk of arterial events in patients receiving rFVIIa. The use of rFVIIa outside its current licensed indications should be restricted to clinical trials.
|
CD008013
|
[
"8824057",
"19596010"
] |
[
"A randomized, controlled trial of amitriptyline in the acute treatment of adolescent major depression.",
"Multicenter, randomized, placebo-controlled trial of amitriptyline in children with functional gastrointestinal disorders."
] |
[
"To determine amitriptyline's (AMI) efficacy in the acute treatment of adolescent major depressive disorder (MDD).\n Subjects aged 12 through 17 years meeting Research Diagnostic Criteria for MDD, diagnosed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), participated in a 2-week placebo-washout followed by an 8-week, randomized, double-blind, parallel-design, placebo-controlled trial of AMI, 5 mg/kg per day. The K-SADS nine-item scale, the Hamilton Depression Rating Scale, and the Clinical Global Impressions rating scale were used as outcome measures.\n Thirty-one subjects were randomized (18 AMI, 13 placebo). Twenty-two subjects were study completers (12 AMI, 10 placebo). AMI's efficacy was suggested by the Clinical Global Impressions but not the K-SADS-derived data. Perhaps the primary limitation of the current study is its small sample size.\n No definitive recommendation can be made regarding the efficacy of tricyclic antidepressants in the treatment of adolescent MDD.",
"There are no prospective, multicenter, double-blind, placebo-controlled, randomized pharmacologic trials for the treatment of pain-predominant functional gastrointestinal disorders in children. The aim of this study was to evaluate the efficacy of amitriptyline in children with pain-predominant functional gastrointestinal disorders.\n In this multicenter placebo-controlled trial, children with irritable bowel syndrome, functional abdominal pain, or functional dyspepsia were randomized to 4 weeks of placebo or amitriptyline (10 mg/d, weight <35 kg; 20 mg/d, weight >35 kg). Assessment of gastrointestinal symptoms, psychological traits, and daily activities occurred before and after intervention. Pain was assessed daily with self-report diaries. The primary outcome was overall response to treatment (child's assessment of pain relief and sense of improvement). Secondary outcomes were effect on psychosocial traits and daily functioning.\n Ninety children were enrolled, and 83 completed the study (placebo, 40 children [30 girls]; drug, 43 children [35 girls]). A total of 63% of patients reported feeling better and 5% feeling worse in the amitriptyline arm compared with 57.5% feeling better and 2.5% feeling worse in the placebo arm (P = .63). Pain relief was excellent in 7% and good in 38% of children receiving placebo compared with excellent in 15% and good in 35% of children treated with amitriptyline (P = .85). Logistic regression analysis of those reporting excellent or good response versus fair, poor, or failed response showed no difference between amitriptyline and placebo (P = .83). Children who had more severe pain at baseline in both groups (P = .0065) had worse outcome. Amitriptyline reduced anxiety scores (P < .0001).\n Both amitriptyline and placebo were associated with excellent therapeutic response. There was no significant difference between amitriptyline and placebo after 4 weeks of treatment. Patients with mild to moderate intensity of pain responded better to treatment."
] |
Clinicians must be aware that for the majority of antidepressant medications no evidence exists that supports their use for the treatment of abdominal pain-related FGIDs in children and adolescents. The existing randomised controlled evidence is limited to studies on amitriptyline and revealed no statistically significant differences between amitriptyline and placebo for most efficacy outcomes. Amitriptyline does not appear to provide any benefit for the treatment of FGIDs in children and adolescents. Studies in children with depressive disorders have shown that antidepressants can lead to substantial, sometimes life-threatening adverse effects. Until better evidence evolves, clinicians should weigh the potential benefits of antidepressant treatment against known risks of antidepressants in paediatric patients.
|
CD001357
|
[
"9519098",
"10836281",
"9696517",
"11032464",
"15076013",
"10200742",
"12442883",
"12464464",
"16528136",
"9068769",
"17113759",
"9682999"
] |
[
"One-year, low-dose neuroleptic study of in-patients with chronic schizophrenia characterised by persistent negative symptoms. Amisulpride v. haloperidol.",
"Long-term safety and efficacy of amisulpride in subchronic or chronic schizophrenia. Amisulpride Study Group.",
"Amisulpride, and atypical antipsychotic, in the treatment of acute episodes of schizophrenia: a dose-ranging study vs. haloperidol. The Amisulpride Study Group.",
"Amisulpride has a superior benefit/risk profile to haloperidol in schizophrenia: results of a multicentre, double-blind study (the Amisulpride Study Group).",
"A double-blind, randomized comparative trial of amisulpride versus olanzapine for 6 months in the treatment of schizophrenia.",
"Improvement of schizophrenic patients with primary negative symptoms treated with amisulpride. Amisulpride Study Group.",
"A double-blind, randomised comparative trial of amisulpride versus olanzapine in the treatment of schizophrenia: short-term results at two months.",
"Amisulpride vs. risperidone in chronic schizophrenia: results of a 6-month double-blind study.",
"Ziprasidone and amisulpride effectively treat negative symptoms of schizophrenia: results of a 12-week, double-blind study.",
"Amisulpride versus placebo in the medium-term treatment of the negative symptoms of schizophrenia.",
"A double-blind randomised comparative trial of amisulpride versus olanzapine for 2 months in the treatment of subjects with schizophrenia and comorbid depression.",
"Amisulpride versus flupentixol in schizophrenia with predominantly positive symptomatology -- a double-blind controlled study comparing a selective D2-like antagonist to a mixed D1-/D2-like antagonist. The Amisulpride Study Group."
] |
[
"Amisulpride is a potent substituted benzamide antipsychotic drug claimed to improve the negative symptoms of schizophrenia, particularly at low dosage.\n Sixty long-term in-patients with schizophrenia and selected for predominant negative symptoms were randomised to receive either haloperidol or amisulpride. Over a year there was systematic dose reduction, as symptoms allowed.\n There were no significant differences between the treatment groups in the proportion receiving low-dose treatment, the control of positive symptoms, or ratings of social behaviour, side-effects or tardive dyskinesia. For negative symptoms, there were consistent but non-significant trends in favour of amisulpride. The amisulpride patients required significantly less anticholinergic medication.\n In chronically-hospitalised in-patients with schizophrenia characterised by persistent negative symptoms, amisulpride was a well-tolerated maintenance antipsychotic medication. The drug had only a limited effect in reducing negative symptoms, which were relatively stable, enduring phenomena in this sample, despite dosage reduction.",
"Amisulpride is an atypical antipsychotic with selective affinity for dopamine D2/3 receptors. In this long-term, open, randomised, multicentre trial, patients with chronic or subchronic schizophrenia received amisulpride (n =370) or haloperidol (n = 118) for 12 months. Dosage regimens were flexible (amisulpride 200-800 mg/day, haloperidol 5-20 mg/day). Improvement in mean Brief Psychiatric Rating Scale total score was significantly greater for amisulpride than haloperidol (17.0 versus 12.8, P = 0.01). Positive symptoms (Positive and Negative Syndrome Scale [PANSS] positive) improved in a similar way in each group but amisulpride caused a significantly better improvement in negative symptoms (PANSS negative) (7.1 versus 3.7, P < 0.0001). Improvements in Global Assessment of Functioning (GAF) and Quality of Life Scale (QLS) scores were also significantly greater in the amisulpride group (GAF -20.1 versus -13.6, P = 0.001; QLS -0.64 versus -0.30, P = 0.02). Adverse events were mainly psychiatric in nature, and occurred with similar frequency in each group (amisulpride 254/370, 69%; haloperidol 82/118, 70%). Extrapyramidal symptoms were more frequent for haloperidol (48/118, 41% versus 96/370, 26% for amisulpride), leading to a greater requirement for antiparkinsonian medication (haloperidol 66/118, 56% versus amisulpride 118/370, 32%). Haloperidol significantly aggravated parkinsonism, akathisia and involuntary movement compared to amisulpride. The overall incidence of endocrine events was comparable between groups (4% for amisulpride, 3% for haloperidol). Maintenance of efficacy was comparable in both treatment groups; 59% of amisulpride patients and 55% of haloperidol patients improved after 1 month of therapy remained improved throughout the study period. Amisulpride is effective following flexible long-term administration and significantly improves social functioning and quality of life.",
"This 4-week, double-blind, randomized study was undertaken to determine the dose-response relationship of amisulpride in 319 patients with acute exacerbation of schizophrenia. Fixed doses of amisulpride (400, 800 and 1200 mg/day) and haloperidol (16 mg/day) were compared to amisulpride, 100 mg/day, as a potentially subtherapeutic dose. Efficacy data (BPRS total score and PANSS positive subscale) in the amisulpride groups generated a bell-shaped dose-response curve, with 400 mg/day and 800 mg/day being the most effective treatments for positive symptoms. Parkinsonism did not increase significantly between baseline and endpoint with amisulpride 400, 800 and 1200 mg/day compared to the amisulpride 100 mg/day group, whereas the difference was significant for haloperidol (P<0.05). It is concluded that amisulpride 400 mg and 800 mg/day is highly effective in treating the positive symptoms of schizophrenia, with less extrapyramidal side-effects than haloperidol 16 mg/day.",
"In a multicentre, double-blind, flexible-dose study, 199 patients with paranoid schizophrenia or schizophreniform disorders received haloperidol (10-30 mg/d) or amisulpride (400-1200 mg/d) for four months. More patients in the haloperidol group withdrew prematurely (44% vs 26%; P = 0.0077) due to a higher incidence of adverse events. Amisulpride was at least as effective as haloperidol in reducing the Brief Psychiatric Rating Scale (BPRS) total score (-27.3 vs -21.9) (non-inferiority test; P < 0.001). The PANSS positive score improved to a similar extent in both groups whilst improvement in the PANSS negative score was significantly greater with amisulpride (-10.5 vs -7.2; P = 0.01). The percentage of responders on the Clinical Global Impression scale was also significantly greater with amisulpride (71% vs 47%; P < 0.001). Both the Quality of Life Scale (QLS) and the Functional Status Questionnaire (FSQ) improved to a significantly greater extent under amisulpride. Haloperidol was associated with a greater incidence in extrapyramidal symptoms and with a greater increase in the Simpson-Angus score than was seen with amisulpride (0.32 vs 0.02; P < 0.001). In conclusion, amisulpride is globally superior to haloperidol in the treatment of acute exacerbations of schizophrenia and significantly improves patients' quality of life and social adjustment.",
"Atypical antipsychotics offer advantages over earlier drugs for the treatment of schizophrenia, although few data exist on the relative merits of different atypical antipsychotics. A multicentre, double-blind, randomized trial was performed to compare amisulpride and olanzapine in the treatment of acute schizophrenia. Adult schizophrenic patients with dominant positive symptomatology received amisulpride (200-800 mg/day) or olanzapine (5-20 mg/day) for 6 months. The primary efficacy variable was change from baseline of the Brief Psychiatric Rating Scale (BPRS) score, assessed with a non-inferiority analysis. The evolution of positive and negative symptomatology, depression, social functioning and quality of life were assessed. Safety evaluation included adverse event reporting, neurological status and body weight. The improvement of BPRS score was 32.7% in the amisulpride group and 33.0% in the olanzapine group; thus, the efficacy of amisulpride was not inferior to that of olanzapine. All other secondary efficacy outcome variables evolved to a similar extent in both groups. Adverse event frequency was similar in both groups. Amenorrhoea was encountered only in the amisulpride group (6.2% of patients), whereas elevations of liver transaminases were more frequent in the olanzapine group (17% versus 3.7% of patients). The incidence and mean extent of clinically relevant weight gain were higher in the olanzapine group (35.1% and 3.9 kg) than in the amisulpride group (20.6% and 1.6 kg). The efficacy of amisulpride is not inferior to that of olanzapine in the treatment of acute schizophrenia. The side-effect profile of the two drugs differed.",
"The goal of this placebo-controlled study was to evaluate the efficacy and safety of low doses of amisulpride, an atypical antipsychotic of the benzamide class with high affinity for D2 and D3 dopamine receptors, in the treatment of schizophrenic patients with predominantly primary negative symptoms.\n After completion of a 4-week washout period, schizophrenic patients with primary negative symptoms participated in a 12-week, multicenter double-blind trial of placebo (N = 83), amisulpride, 50 mg/day (N = 84), or amisulpride, 100 mg/day (N = 75). They were evaluated with the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, the Brief Psychiatric Rating Scale, and the Montgomery-Asberg Depression Rating Scale.\n Both amisulpride treatment groups showed significantly greater improvement in negative symptoms than the placebo group. Positive symptom scores were low at baseline and changed minimally during the study, suggesting that the improvement in negative symptoms was independent of improvement in positive symptoms. The safety of amisulpride was comparable to that of placebo, and extrapyramidal symptoms were infrequent. Comparable efficacy and safety results were observed with either dose of amisulpride.\n These findings confirm and extend those of earlier placebo-controlled studies of low-dose amisulpride in the treatment of patients with predominantly negative symptoms of schizophrenia.",
"To compare the efficacy and safety of the atypical antipsychotics amisulpride and olanzapine in the treatment of acute psychotic exacerbations of schizophrenia.\n A multinational, double-blind randomised clinical trial.\n Three hundred and seventy-seven patients with predominantly positive symptomatology were treated for six months with either amisulpride (200-800 mg/d) or olanzapine (5-20 mg/d).\n Short-term results were analysed after two months of treatment. The primary efficacy measure was the change of score on the Brief Psychiatric Rating Scale (BPRS). Other measures of efficacy and safety were also evaluated.\n Psychotic symptoms, as measured on the BPRS score, improved with both treatments, amisulpride being equivalent to olanzapine. All BPRS factor scores, as well as depressive symptoms, improved to a similar extent with both treatments. Less than five per cent of patients withdrew for adverse events, and there was no evidence for the emergence of extrapyramidal symptoms with either treatment. Statistically significant greater weight gain (2.7 +/- 3.9 kg) was observed during the study in the olanzapine group, compared with the amisulpride group (0.9 +/- 3.2 kg, p < 0.0001).\n Amisulpride and olanzapine show equivalent efficacy at 2 months in the treatment of acute psychotic exacerbations of schizophrenia. Amisulpride offers a significant advantage in preserving body weight.",
"This multicenter, double-blind, randomized study evaluated the efficacy, safety and functional effects of two atypical antipsychotics, amisulpride and risperidone, in patients with chronic schizophrenia (DSM IV) with a recent worsening of symptoms. It was planned as a non-inferiority trial. 309 patients received amisulpride (400-1,000 mg/day) or risperidone (4-10 mg/day) for six months. Amisulpride was demonstrated to be not inferior to risperidone with respect to the decrease in Positive and Negative Syndrome Scale (PANSS) total score from baseline (90% 2-sided confidence interval (-5.6; 4.0)). Symptomatic improvement measured with the Brief Psychiatry Rating Scale (BPRS), the PANSS positive subscale, and the Bech Rafaelsen Melancholia Scale was similar in both groups. Amisulpride was significantly (p <.05) superior to risperidone in terms of response (>/=50% improvement in PANSS and BPRS total scores or \"very much/much improved\" on the Clinical Global Impression Scale) and also demonstrated better functional effects and subjective response. Both treatments were well tolerated and had a similar low incidence of extrapyramidal symptoms; however, amisulpride was associated with less weight gain and endocrine/sexual symptoms.",
"We compared the efficacy of ziprasidone and amisulpride in the treatment of negative symptoms and overall psychopathology in subjects who had chronic schizophrenia with predominantly negative symptoms. This multicentre, 12-week, double-blind study randomly assigned subjects with predominantly negative-symptom schizophrenia [i.e. Positive and Negative Syndrome Scale (PANSS) Negative Subscale score >or=6 points greater than Positive Subscale score] to ziprasidone (40-80 mg b.i.d.; n=60) or amisulpride (50-100 mg b.i.d.; n=63). The primary efficacy variable was the change from baseline in PANSS Negative Subscale score. Secondary efficacy variables included change in scores for PANSS Total, Global Assessment of Functioning, Brief Psychiatric Rating Scale derived from PANSS Total and Core, Clinical Global Impression (CGI)-Severity and CGI-Improvement. For the change in PANSS Negative Subscale score, a ratio to assess the equivalence of the treatment groups was calculated from the least squares mean changes from baseline, with equivalence claimed if the lower limit of the 95% confidence interval of the ratio exceeded 0.60. Mean daily dose, adjusted for differential numbers of subjects and differential days between visits, was 118.0 mg for ziprasidone and 144.7 mg for amisulpride. Mean PANSS Negative Subscale scores improved over the 12-week treatment period for intent-to-treat subjects, evaluable subjects (subjects with >or=4 weeks of double-blind treatment and no protocol deviations) and completers in both treatment groups. Ziprasidone demonstrated efficacy comparable to amisulpride in improving negative symptoms and global psychopathology. The groups demonstrated comparable improvements in secondary efficacy variables. Both agents were generally well tolerated, with comparably low incidences of movement disorders. In subjects with negative symptom-prominent schizophrenia, ziprasidone in mean daily doses of 118 mg was equivalent to amisulpride in mean daily doses of 148 mg in ameliorating negative symptoms and comparable in improving overall psychopathology and global illness severity.",
"Amisulpride is a substituted benzamide with high selectivity for dopamine D2 and D3 receptors. The purpose of the study was to evaluate the effect of 100 mg amisulpride in patients with predominantly negative symptoms of schizophrenia.\n This was a multi-centre, randomised, parallel-group, double-blind study. Patients received either amisulpride (100 mg/day) or placebo over a six-month treatment period.\n A total of 141 patients were included, 69 received amisulpride, 72 placebo. Fifty-eight patients (41%) had received neuroleptic treatment prior to inclusion. The percentage of amisulpride patients completing the study (55%) was significantly higher than that with placebo (32%), and drop-out rates due to lack of efficacy were 27% with amisulpride and 47% with placebo. All efficacy assessments were statistically in favour of amisulpride compared with placebo. The overall incidence of extrapyramidal symptoms was comparable in both groups; only five patients started anti-Parkinsonian treatment during the study (one in the placebo and four in the amisulpride group).\n Amisulpride is effective in the medium-term treatment schizophrenic patients with predominantly negative symptoms.",
"To compare the efficacy and safety of amisulpride and olanzapine in subjects with schizophrenia and comorbid depression in a randomised double-blind trial.\n Eighty-five adult patients fulfilling DSM-IV criteria for schizophrenia and presenting a depressive episode were randomised to amisulpride (200-600 mg/day) or olanzapine (5-15 mg/day) for 8 weeks. Primary efficacy variables were change in Calgary Depression Scale (CDS) score and Clinical Global Impression (CGI) of Change. Safety was monitored by adverse event reporting and determination of extrapyramidal function and metabolic variables.\n The mean change from baseline of CDS score was -6.84 in the amisulpride group and -7.36 in the olanzapine group. 65.9% and 61.5% of subjects, respectively, were considered \"much\" or \"very much\" improved. No significant inter-group difference in effect size was observed. The frequency of adverse events was low and emergence of extrapyramidal symptoms was not seen. Four patients in the olanzapine group developed abnormal triglyceride levels. Mean weight gain was 1.45 and 0.5 kg, respectively, in the olanzapine and amisulpride groups.\n Amisulpride and olanzapine are effective in patients with schizophrenia and comorbid depression. Tolerance of both drugs was acceptable, although use of olanzapine was associated with a trend toward greater metabolic side-effects .",
"The benzamide amisulpride (ASP) is a selective D2-like dopamine antagonist, while flupentixol (FPX), a thioxanthene, blocks D2-like, D1-like and 5-HT2 receptors. To evaluate efficacy and safety of ASP and to investigate the importance of an additional D1-like antagonism for antipsychotic effects and extrapyramidal tolerability, a randomized double-blind multi- center study versus FPX as reference drug was performed for 6 weeks in 132 patients suffering from acute schizophrenia (DSM-III-R) with predominant positive symptomatology. Doses were initially fixed (ASP: 1000 mg/day; FPX: 25 mg/day) but could be reduced by 40% in case of side effects (mean daily doses: ASP: 956 mg; FPX: 22.6 mg). Intention-to-treat evaluation demonstrated significant improvement under both medications. The difference between the mean BPRS decreases of both treatment groups was 5.6 points (95% CI: 0.55; 10.65) in favour of ASP. According to CGI, 62% of patients in either drug group were treatment responders. ANCOVA analysis showed that reductions of BPRS (ASP: -42%; FPX: -32%) and SAPS (ASP: -78%; FPX: -65%) were more pronounced under ASP. Due to adverse events, significantly fewer ASP patients (6%) were withdrawn from the study (FPX: 18%). Extrapyramidal tolerability was better in the ASP group, as demonstrated by smaller increases in the Simpson-Angus Scale, the AIMS, and the Barnes Akathisia Scale in ANCOVA analyses with dosage as covariate. ASP appears to be as effective as FPX with regard to antipsychotic effects on positive schizophrenic symptomatology, while extrapyramidal tolerability is better. These conclusions have to be drawn cautiously, as dosage effects on outcome parameters cannot be entirely ruled out. The present results question the notion that additional blockade of D1-like receptors may be necessary to achieve sufficient antipsychotic effects or to improve extrapyramidal tolerability."
] |
This systematic review confirms that amisulpride is an effective 'atypical' antipsychotic drug for those with schizophrenia. Amisulpride may offer a good general profile, at least compared to high-potency 'typical' antipsychotics. It may also yield better results in some specific outcomes related to efficacy, such as improvement of global state and general negative symptoms. It might be more acceptable and more tolerable than high-potency conventional antipsychotics, especially regarding extrapyramidal side-effects.
Longer term randomised trials are needed to evaluate the comparative value of amisulpride, particularly compared to other expensive atypical antipsychotics. These should focus on important outcomes which have not been sufficiently monitored such as service use, family burden and quality of life.
|
CD008523
|
[
"15161896",
"19724045",
"12213183"
] |
[
"Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles.",
"Comparison of registered and published primary outcomes in randomized controlled trials.",
"Funding source, trial outcome and reporting quality: are they related? Results of a pilot study."
] |
[
"Selective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected, but direct evidence of such bias is currently limited to case reports.\n To study empirically the extent and nature of outcome reporting bias in a cohort of randomized trials.\n Cohort study using protocols and published reports of randomized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg, Denmark, in 1994-1995. The number and characteristics of reported and unreported trial outcomes were recorded from protocols, journal articles, and a survey of trialists. An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta-analysis. Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias. Protocols and published articles were also compared to identify discrepancies in primary outcomes.\n Completeness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes; consistency between primary outcomes defined in the most recent protocols and those defined in published articles.\n One hundred two trials with 122 published journal articles and 3736 outcomes were identified. Overall, 50% of efficacy and 65% of harm outcomes per trial were incompletely reported. Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy (pooled odds ratio, 2.4; 95% confidence interval [CI], 1.4-4.0) and harm (pooled odds ratio, 4.7; 95% CI, 1.8-12.0) data. In comparing published articles with protocols, 62% of trials had at least 1 primary outcome that was changed, introduced, or omitted. Eighty-six percent of survey responders (42/49) denied the existence of unreported outcomes despite clear evidence to the contrary.\n The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocols. Published articles, as well as reviews that incorporate them, may therefore be unreliable and overestimate the benefits of an intervention. To ensure transparency, planned trials should be registered and protocols should be made publicly available prior to trial completion.",
"As of 2005, the International Committee of Medical Journal Editors required investigators to register their trials prior to participant enrollment as a precondition for publishing the trial's findings in member journals.\n To assess the proportion of registered trials with results recently published in journals with high impact factors; to compare the primary outcomes specified in trial registries with those reported in the published articles; and to determine whether primary outcome reporting bias favored significant outcomes.\n MEDLINE via PubMed was searched for reports of randomized controlled trials (RCTs) in 3 medical areas (cardiology, rheumatology, and gastroenterology) indexed in 2008 in the 10 general medical journals and specialty journals with the highest impact factors.\n For each included article, we obtained the trial registration information using a standardized data extraction form.\n Of the 323 included trials, 147 (45.5%) were adequately registered (ie, registered before the end of the trial, with the primary outcome clearly specified). Trial registration was lacking for 89 published reports (27.6%), 45 trials (13.9%) were registered after the completion of the study, 39 (12%) were registered with no or an unclear description of the primary outcome, and 3 (0.9%) were registered after the completion of the study and had an unclear description of the primary outcome. Among articles with trials adequately registered, 31% (46 of 147) showed some evidence of discrepancies between the outcomes registered and the outcomes published. The influence of these discrepancies could be assessed in only half of them and in these statistically significant results were favored in 82.6% (19 of 23).\n Comparison of the primary outcomes of RCTs registered with their subsequent publication indicated that selective outcome reporting is prevalent.",
"There has been increasing concern regarding the potential effects of the commercialization of research.\n In order to examine the relationships between funding source, trial outcome and reporting quality, recent issues of five peer-reviewed, high impact factor, general medical journals were hand-searched to identify a sample of 100 randomized controlled trials (20 trials/journal). Relevant data, including funding source (industry/not-for-profit/mixed/not reported) and statistical significance of primary outcome (favouring new treatment/favouring conventional treatment/neutral/unclear), were abstracted. Quality scores were assigned using the Jadad scale and the adequacy of allocation concealment.\n Sixty-six percent of trials received some industry funding. Trial outcome was not associated with funding source (p=.461). There was a preponderance of favourable statistical conclusions among published trials with 67% reporting results that favored a new treatment whereas 6% favoured the conventional treatment. Quality scores were not associated with funding source or trial outcome.\n It is not known whether the absence of significant associations between funding source, trial outcome and reporting quality reflects a true absence of an association or is an artefact of inadequate statistical power, reliance on voluntary disclosure of funding information, a focus on trials recently published in the top medical journals, or some combination thereof. Continued and expanded monitoring of potential conflicts is recommended, particularly in light of new guidelines for disclosure that have been endorsed by the ICMJE."
] |
Trials published to date lack information on clinically relevant end-points. Existing data is derived from small trials at high risk of bias, which concentrate on physiological measures. Their results are inconclusive. Further large and high quality trials with more appropriate outcomes are warranted.
|
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