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CD004062	[ "11966543", "14572560", "9440631", "15647648", "7904847", "8284627", "8759659" ]	[ "Successful eradication of Helicobacter pylori prevents relapse of peptic ulcer disease.", "Eradication of Helicobacter pylori improves the healing rate and reduces the relapse rate of nonbleeding ulcers in patients with bleeding peptic ulcer.", "One-week antibiotics versus maintenance acid suppression therapy for Helicobacter pylori-associated peptic ulcer bleeding.", "Helicobacter pylori eradication as the sole treatment for gastric and duodenal ulcers.", "Eradication of Helicobacter pylori infection and the recurrence of duodenal ulcers.", "Treatment of Helicobacter pylori reduces the rate of rebleeding in peptic ulcer disease.", "Antimicrobial therapy for Helicobacter pylori infection versus long-term maintenance antisecretion treatment in the prevention of recurrent hemorrhage from peptic ulcer: prospective nonrandomized trial on 125 patients." ]	[ "The NIH consensus conference in 1994 recommended that all patients with peptic ulcers should be tested and treated for Helicobacter pylori. Recent studies have shown that the eradication of H. pylori is associated with a significant reduction in the relapse rate of peptic ulcers, but there are few reports about long-term outcome.\n To evaluate the relapse rate of peptic ulcer in the long-term follow-up of patients after H. pylori eradication therapy.\n Patients infected with H. pylori (445; 88 duodenal ulcer, 357 gastric ulcer) were randomly divided into three groups. In group A, patients received 'conventional treatment' including acid decreasing therapy with a histamine H2-receptor antagonist or proton pump inhibitor (PPI). In group B, patients received 'dual therapy' including one antibiotic plus acid-decreasing therapy. In group C, patients received 'triple therapy' with PPI plus amoxicillin and clarithromycin. Eradication of H. pylori infection was assessed by histology of biopsy specimens from both the antrum and body corpus at 4 weeks, and 6 and 12 months after stopping therapy. Endoscopy was performed at intervals of 6 months for 5 years.\n Intention-to-treat eradication rates for the duodenal ulcer patients were 0% for group A, 46% for group B and 80% for group C; eradication rates for the gastric ulcer patients were 0%, 33% and 83% respectively. No recurrence was noted in the duodenal ulcer patients and only 4% of gastric ulcers recurred after successful eradication during follow-up for 5 years. In contrast, in patients with persistent H. pylori infection all DU and 92% of gastric ulcers recurred.\n Eradication of H. pylori infection changes the natural course of peptic ulcer.", "A causal relationship between Helicobacter pylori (H. pylori) and peptic ulcer complications remains obscure. The aim of this study was to determine the importance of H. pylori and other risk factors for healing rate, ulcer recurrence, and rebleeding in patients with bleeding peptic ulcer.\n A total of 223 patients with H. pylori positive bleeding peptic ulcer were randomly allocated to three treatment groups: 1) quadruple therapy (QT) (88 patients); 2) dual therapy (DT) (88 patients); and 3) omeprazole and placebo therapy (OPl) (47 patients). Endoscopic assessment was performed initially and at 8 and 52 wk. Ulcer healing and eradication rates were assessed; endpoints were ulcer relapse and ulcer rebleeding during 52 wk.\n Results after 8 and 52 wk were available for 211 and 179 patients, respectively. Eradication rate was 100% (95% CI = 96-100%) in the QT, 84% (95% CI = 74-91%) in the DT, and 4% (95% CI = 1-15%) in the OPl group. Ulcer healing rate was 95% (95% CI = 91-98%) in H. pylori negative and 8% (95% CI = 70-91%) in H. pylori positive patients. Ulcer relapses occurred in 2% (95% CI = 0.5-6%) of H. pylori negative and in 38% (95% CI = 24-54%) of H. pylori positive patients, and rebleeding occurred in five patients (three H. pylori positive and two negative).\n Eradication of H. pylori infection enhances healing of bleeding peptic ulcers after endoscopic therapy. H. pylori infection is an important independent risk factor for relapsing of nonbleeding ulcers in patients with bleeding peptic ulcer.", "Bleeding peptic ulcer is the most important cause of upper gastrointestinal bleeding. Our aim was to compare the effect of anti-Helicobacter therapy with maintenance treatment of H2-receptor antagonist in the prevention of relapses of ulcer and bleeding. Patients with bleeding duodenal or gastric ulcers and H. pylori infection were randomized to receive either a one-week course of triple therapy with bismuth subcitrate, metronidazole, and tetracycline plus ranitidine or a six-week course of ranitidine 300 mg/day. After the ulcers healed, the antibiotic-treated patients were not given any medication, whereas the ranitidine-treated patients continued to receive a maintenance dose of 150 mg/day. One hundred twenty-six patients were randomized to receive anti-Helicobacter therapy and 124 patients to receive long-term ranitidine. H. pylori eradication was achieved in 98.2% in those who received triple therapy and 6.1% in those who received ranitidine (P < 0.0001). At the six-week follow-up, ulcer healing was documented in 88.2% in those who received triple therapy and 86.1% in those who received ranitidine (P = 0.639). Recurrent ulcer developed in nine of the ranitidine-treated patients and three of them presented with recurrent upper gastrointestinal bleeding. One patient in the antibiotic group developed recurrent ulcer without rebleeding (P = 0.01). It is concluded that eradication of H. pylori is sufficient for the prevention of recurrent bleeding ulcers.", "It is uncertain whether eradication of Helicobacter pylori--without a prolonged suppression of acid secretion--is sufficient to allow healing of peptic ulcers. We evaluated whether eradication of H. pylori with no following anti-secretory medication then administered is sufficient for treatment of peptic ulcers. We also looked at the impact of non-steroidal anti-inflammatory drug (NSAID) and acetylsalicylic acid (ASA) use on ulcer relapses.\n The effect of eradication on ulcer healing and relapse rate was analysed in 115 patients, randomly allocated to four treatment groups: (1) quadruple therapy (28); (2) dual therapy (n-30); (3) triple therapy (n=27); and (4) lansoprazole and placebo (n=30). Endoscopic assessment was performed at 0, 8, and 52 weeks.\n The ulcer healing rate was 100% [95% confidence interval (CI), 95-100%] in H. pylori-negative and 83% (95% CI, 67-94%) in H. pylori-positive patients (P<0.01). In patients who used NSAIDS or ASA, the healing rates was 100% (95% CI, 73-100%) and 75% (95% CI, 19-99%) in H. pylori-negative (12 patients) and H. pylori-positive patients (four patients) (P = not significant). Ulcer relapses occurred in 5% (95% CI, 1-13%) of H. pylori-negative and in 36% (95% CI, 19-56%) of H. pylori-positive patients (P < 0.01). In H. pylori-negative patients who used NSAIDs or ASA the ulcer relapse rate was 30% (95% CI, 7-65%), whereas the ulcer relapse rate was 2% (95% CI, 0.4-10%) in patients who did not use NSAIDs or ASA (P < 0.05). No difference in ulcer relapse rate in H. pylori-positive patients who used or did not use NSAIDs or ASA was found. The eradication rate of H. pylori was 93% (95% CI, 76-99%) in the quadruple therapy group, 83% (95% CI, 64-94%) in the dual therapy group, 100% (95% CI, 87-100%) in the triple therapy group, and 0% (95% CI, 0-12%) in the lansoprazole and placebo group.\n Eradication treatment for H. pylori-positive gastric or duodenal ulcer is sufficient, with no need to follow it with anti-secretory medication. Cure of the infection reduces ulcer relapses in patients who did not use NSAIDs or ASA.", "The purpose of this study was to compare the performance of different regimens on Helicobacter pylori (H. pylori) eradication and duodenal ulcer recurrence. During a four-week period, 59 patients with duodenal ulcers who were positive for H. pylori infection were randomly treated with one of three regimens. Seventeen patients were treated with ranitidine, 19 with colloidal bismuth subcitrate (CBS), and 23 with triple therapy (CBS, tetracycline and metronidazole). Forty-six patients with healed ulcers after treatment received follow-up for six months without maintenance therapy. The recurrence rates of duodenal ulcers confirmed by endoscopy in these three groups were 64%, 33% and 0% at the third month, and 73%, 67% and 5% at the sixth month, respectively. In the ranitidine therapy group, H. pylori infection was still present at the final follow-up. In the CBS therapy group, H. pylori was suppressed initially, but recurred in all cases. In the triple therapy group, there was only one case in which H. pylori infection persisted and where ulcer recurrence occurred after 3.5 months. The remaining cases were all H. pylori negative and had no recurrence of duodenal ulcers during the six months of follow-up. Overall, 19/27 (70%) patients positive for H. pylori had a recurrence of duodenal ulcers, while none of the 19 patients who were negative for H. pylori had a recurrence of ulcers at the sixth month. This study shows that triple therapy is more effective than the other two regimens in the eradication of H. pylori and in reducing the recurrence of ulcers. H. pylori may play a role in the recurrence of the duodenal ulcer.", "We evaluated whether therapy designed to eradicate Helicobacter pylori infection resulted in a reduction in rebleeding in patients with peptic ulcer disease. Patients presenting because of major upper gastrointestinal hemorrhage from peptic ulcer and whose ulcers healed in a study in which they were randomized to receive ranitidine alone or triple therapy plus ranitidine were followed up regularly with endoscopy. No maintenance anti-ulcer therapy was given after ulcer healing.\n Patients received ranitidine, 300 mg, or ranitidine plus triple therapy. Triple therapy consisted of tetracycline, 2 g; metronidazole, 750 mg; and bismuth subsalicylate, 5 or 8 tablets (151 mg bismuth per tablet), and was administered for the first 2 weeks of treatment; ranitidine therapy was continued until the ulcer had healed or 16 weeks had elapsed. After ulcer healing, no maintenance antiulcer therapy was given. Development of ulcer recurrence with or without recurrent upper gastrointestinal bleeding was evaluated.\n Thirty-one patients with major upper gastrointestinal bleeding from peptic ulcer were studied; 17 received triple therapy and 14 ranitidine alone. Major rebleeding occurred significantly (p = 0.031) more often in those in the ranitidine group (28.6%), compared with none (0%) in the triple therapy group.\n Eradication of H. pylori infection reduces the rate of ulcer recurrence and rebleeding in complicated ulcer disease.", "Our objective was to assess the effectiveness of therapy for Helicobacter pylori (HP) on the prevention of recurrent bleeding in patients with recent upper gastrointestinal hemorrhage from peptic ulcers.\n We performed a prospective follow-up study without randomization on 125 consecutive patients (83 males and 42 females) who had presented with their first major episode of upper gastrointestinal hemorrhage from peptic ulcer (22 gastric and 103 duodenal ulcers). All 125 patients were HP-positive. During the acute phase of bleeding, all patients were treated with standard supportive measures. After the acute bleeding phase, patients were allocated to two treatment groups: 1) antimicrobial therapy-84 patients received one of the following three regimens: 1) amoxicillin 500 mg t.i.d. for 10 days + omeprazole 20 mg b.i.d. for 30 days; 2) clarythromycin 500 mg t.i.d. for 12 days + omeprazole 20 mg b.i.d. for 30 days; or 3) amoxicillin 500 mg t.i.d. for 10 days + metronidazole 500 mg t.i.d. for 10 days + colloidal bismuth subcitrate 240 mg b.i.d. for 30 days. For long-term antisecretion maintenance treatment, 41 patients were allocated to either omeprazole 20 mg once a day or ranitidine 150 mg once a day, for 1 yr.\n During the follow-up period, peptic ulcers recurred in six patients in the antibiotic group (7.14%) and 13 patients in the maintenance group (31.7%) (p < 0.001). The fraction of patients without recurrent bleeding was greater in the antibiotic group than in the maintenance group. Two patients in the antibiotic group (2.3%) and five in the maintenance group (12.1%) had recurrent hemorrhages (p < 0.1).\n Cure of HP infection reduces the recurrence of peptic ulcer and of rebleeding from ulcer disease more effectively than does long-term maintenance therapy." ]	Treatment of H. pylori infection is more effective than antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) in preventing recurrent bleeding from peptic ulcer. All patients with peptic ulcer bleeding should be tested for H. pylori infection, and eradication therapy should be prescribed to H. pylori-positive patients.
CD006930	[ "16076335", "10449846", "17277653", "17698432", "16749570", "12960786", "9171125", "7577282", "9322475", "9566570", "11360058", "17943385", "7611964", "12684804" ]	[ "Randomized, prospective comparison of postoperative pain in low- versus high-pressure pneumoperitoneum.", "Randomized comparison between low-pressure laparoscopic cholecystectomy and gasless laparoscopic cholecystectomy.", "Prospective randomized trial on low-pressure versus standard-pressure pneumoperitoneum in outpatient laparoscopic cholecystectomy.", "Randomized trial of low-pressure carbon dioxide-elicited pneumoperitoneum versus abdominal wall lifting for laparoscopic cholecystectomy.", "Lactate and acid base changes during laparoscopic cholecystectomy.", "Randomized comparison between different insufflation pressures for laparoscopic cholecystectomy.", "Laparoscopic cholecystectomy using abdominal wall retraction. Hemodynamics and gas exchange, a comparison with conventional pneumoperitoneum.", "Conventional pneumoperitoneum compared with abdominal wall lift for laparoscopic cholecystectomy.", "Splanchnic and renal deterioration during and after laparoscopic cholecystectomy: a comparison of the carbon dioxide pneumoperitoneum and the abdominal wall lift method.", "Comparison of N2O and CO2 pneumoperitoneums during laparoscopic cholecystectomy with special reference to postoperative pain.", "Randomized comparison of conventional and gasless laparoscopic cholecystectomy: operative technique, postoperative course, and recovery.", "Laparoscopic cholecystectomy with carbon dioxide pneumoperitoneum is safe even for high-risk patients.", "A simple and effective way to reduce postoperative pain after laparoscopic cholecystectomy.", "Effect of drainage on postoperative nausea, vomiting, and pain after laparoscopic cholecystectomy." ]	[ "Reduced postoperative pain after laparoscopic cholecystectomy (LC) compared to open cholecystectomy (OC) may be able to be further optimized. To reduce pain, focus should be directed on the effects of individual components of pain.\n A double-blind, randomized, controlled trial was carried out in a tertiary care hospital. Fifty-three elective patients with symptomatic gallstones were enrolled into the study. Patients were randomized to low- or high-pressure pneumoperitoneum groups. In all patients, gas pressure was set to 15 mmHg during placement of ports. Later on, in the low-pressure group, the rest of the procedure was performed at 10 mmHg pressure. At 6 and 24 h postoperatively, a short-form McGill Questionnaire (MPQ) was obtained from all patients. Patients were then asked to complete a 10-cm visual analogue scale (VAS) for abdominal pain.\n Pain scores were generally low for both groups. Statistical comparisons of mean cumulative McGill score and VAS abdominal pain scores in both groups did not reach statistical significance at 6 and 24 h after operation.\n There was no correlation between high- and low-pressure laparoscopy and postoperative pain after LC. Peritoneal stretching may be more responsible for shoulder pain but has less effect on intensity of abdominal pain or incisional pain. On the basis of these negative findings, routine use of low-pressure pneumoperitoneum for alleviation of postoperative pain following LC is not recommended.", "Laparoscopic cholecystectomy using low-pressure pneumoperitoneum (8 mmHg) minimizes adverse hemodynamic effects, reduces postoperative pain, and accelerates recovery. Similar claims are made for gasless laparoscopy using abdominal wall lifting. The aim of this study was to compare gasless laparoscopic cholecystectomy to low-pressure cholecystectomy with respect to postoperative pain and recovery.\n Thirty-six patients were randomized to low-pressure or gasless laparoscopic cholecystectomy using a subcutaneous lifting system (Laparotenser).\n The characteristics of the patients were similar in the two groups. The procedure was completed in all patients in the low-pressure group, but two patients in the gasless group were converted to pneumoperitoneum. There were no significant differences in postoperative pain and analgesic consumption, but patients in the gasless group developed shoulder pain more frequently (50% vs 11%, p < 0.05). Gasless operation took longer to perform (95 vs 72.5 min, p = 0.01).\n Gasless and low-pressure laparoscopic cholecystectomy were similar with respect to postoperative pain and recovery. The gasless technique provided inferior exposure and the operation took longer, but the technique may still have value in high-risk patients with cardiorespiratory disease.", "Inpatient low-pressure pneumoperitoneum laparoscopic cholecystectomy (LPLC) has been shown to have less postoperative pain (especially shoulder-tip pain). No report so far has documented the use of lower-pressure pneumoperitoneum in outpatient laparoscopic cholecystectomy (LC). A prospective randomized trial was conducted in Tung Wah Hospital, Day Surgery Centre from January 2004 to December 2004. A total of 40 patients were recruited and 20 of whom were allocated to each arm. Outcome measures included operation time, treatment-related morbidity, mortality, postoperative pain (eg, shoulder-tip pain), consumption of analgesics, and level of satisfaction. All patients in both groups could be discharged on the same day. Patients' demographics and operation time were comparable in both groups. There were no treatment-related morbidity and mortality, nor was there any significant difference in postoperative pain. Less shoulder-tip pain was observed in the LPLC group though without significant difference (5% vs. 20%; P=0.151). Three patients in the LPLC group needed higher insufflation pressure (12 mm Hg) because of inadequate exposure and adhesions, and the operations were successful in all of them. Otherwise, no conversion to open procedure was noted in both groups. The consumption of analgesics was minimal and a high level of satisfaction was achieved in both groups of patients. The present study demonstrated no difference in LPLC and standard-pressure pneumoperitoneum laparoscopic cholecystectomy in the outcomes of outpatient LC. Routine use of lower-pressure pneumoperitoneum in outpatient LC would not be recommended unless in selected straightforward cases.", "Two alternative surgical techniques for elective laparoscopic cholecystectomy (LC), low-pressure insufflation of the peritoneal cavity and abdominal wall lifting (AWL), have been developed over time to minimize the disadvantages associated with CO2-elicited pneumoperitoneum. To the best of our knowledge, the 2 methods have seldom been compared as regards their relative advantages and disadvantages.\n Eighty patients scheduled for elective LC were randomized into either a low-pressure (8 mmHg) CO2 insufflation method (LPLC) group, or a gasless technique using a subcutaneous abdominal wall lifting device (GLC group). The duration of the surgical procedure, the surgical results including level of postoperative pain, and perioperative cardiopulmonary function changes experienced by the members of both groups were compared.\n Laparoscopic surgery was completed for all but 1 patient from each group due to an inadequate surgical-site exposure. There was no mortality for study participants, and no major complications were noted for members of either group. The LPLC group evidenced a shorter surgical duration as compared to the GLC group (77 +/- 28 minutes vs. 98 +/- 27 minutes, respectively; p < 0.01) and a lower incidence of postoperative shoulder pain (2/38 vs. 8/39, respectively; p < 0.05), although significant differences in intraoperative pulmonary function were noted (an increased PaCO2, Pet CO2 and peak-airway pressure and decreased arterial blood pH; p < 0.01) for the LPLC group compared to the GLC group.\n Both alternative methods for this type of surgery appeared feasible and safe for LC. Low-pressure CO2 pneumoperitoneum had a shorter surgical duration and less postoperative shoulder pain compared to the GLC technique, but did not feature any other advantage over the AWL technique with regard to impact on cardiopulmonary function.", "The observation of hemodynamic and metabolic impairment related to CO2 pneumoperitoneum and postoperative mesenteric ischemia reports following laparoscopic procedures have raised concern about local and systemic effects of increase intraabdominal pressure during laparoscopic procedures. The present study aims to evaluate the metabolic and acid base responses of using high pressure versus low pressure pneumoperitonium in patients undergoing laparoscopic cholecystectomy in a prospective randomized clinical trial.\n 20 ASA I-II patients scheduled for elective laparoscopic cholecystectomy were randomly allocated to one of two study groups; high pressure pneumoperitoneum 12-14mmHg (HPP, n=10) versus low pressure pneumoperitoneum 6-8mmHg (LPP, n=10) undergoing laparoscopic cholecystectomy. Arterial blood gases and lactate levels were determined after induction of anesthesia (before pneumoperitonium), then after 10 min, then 30 min after insufflations and at the end of surgery and 1 hour postoperatively. Nurses in recovery unit reported pain assessment starting postoperatively until 3 hours on a 10mm VAS (0-10). Statistical significant was established at P<0.05.\n Bicarbonate was significantly (P>0.0412) lower in high pressure group at 30 min and 60 min after insufflations. In high pressure group lactate levels increased significantly as compared to low pressure group, (at 30 minutes after the establishment of abdominal pneumatic inflation P<0.006 and remained significantly increased (P<0.001) until the end of surgery and one hour thereafter) (P<0.001). The mean postoperative pain score during second hour (VAS) at HPP group was 7.4 +/- 1.17 which is significantly (P < or = 0.006) higher than pain score in LPP group 5.0 +/- 1.886. Shoulder tip pain was reported in 3 patients in the high pressure group and only one patient in the lower pressure group.\n High-pressure pneumoperitonium causes statistically significant elevation in the arterial lactate level intraoperatively until one hour post operatively. It also causes higher pain score and shoulder tip pain.", "Laparoscopy using carbon dioxide insufflation induces adverse effects in both the cardiovascular and the respiratory function. The use of low pressure pneumoperitoneum has been shown to reduce adverse hemodynamic effects. However, its effect on tissue trauma and postoperative pain and recovery remains controversial. The aim of this study was to compare tissue trauma, postoperative pain, and recovery in two groups of patients undergoing laparoscopic cholecystectomy, one at insufflation pressure of 8 (LC8) and the other at 15 mm Hg (LC15). Forty patients were randomized, 20 in each group. The characteristics of the patients were similar in the two groups. The procedure was completed in all patients in the LC15 group, but in 2 patients in the LC8 group the pressure was increased to 15 mm Hg to complete the operation. There were no significant differences in postoperative pain scores, analgesic consumption, and the incidence of nausea, vomiting, and shoulder pain between the two groups. C-reactive protein concentrations and white blood cell count rose significantly after surgery, but the increase was similar in the two groups. The median duration of surgery was similar, 23 minutes (range 15-65) in the LC8 group and 25 minutes (range 15-80) in the LC15 group. Using our technique of laparoscopic cholecystectomy, there were no advantages to tissue damage, postoperative pain, and recovery when a low pressure pneumoperitoneum was used.", "Disadvantages related to CO2 pneumoperitoneum have led to development of the abdominal wall retractor (AWR), a device designed to facilitate laparoscopic surgery without conventional pneumoperitoneum (15 mmHg CO2). We investigated the effects of the AWR on hemodynamics and gas exchange in humans. We also investigated whether the use of an AWR imposed extra technical difficulties for the surgeon. A pilot study revealed that cholecystectomy without low-pressure pneumoperitoneum was technically impossible.\n A prospective randomized controlled trial: Twenty patients undergoing laparoscopic cholecystectomy were randomly allocated into group 1: AWR with low-pressure pneumoperitoneum (5 mmHg), or group 2: conventional pneumoperitoneum (15 mmHg).\n Surgery using the AWR lasted longer, 72 +/- 16 min (mean +/- SD) vs 50 +/- 18 min compared with standard laparoscopic cholecystectomy. There were no differences between the groups with respect to hemodynamic parameters, although a small reduction of the cardiac output was observed using conventional pneumoperitoneum (from 3.9 +/- 0.7 to 3. 2 +/- 1.1 l/min) and an increase during AWR (from 4.2 +/- 0.9 to 5.2 +/- 1.5 l/min). Peak inspiratory pressures were significantly higher during conventional pneumoperitoneum compared to AWR. A slight decrease in pH accompanied by an increase in CO2 developed during pneumoperitoneum and during the use of the AWR. In both groups arterial PO2 decreased.\n The results indicate that the view was impaired during use of the AWR and therefore its use was difficult and time-consuming. Possible advantages of this devices' effects on hemodynamics and ventilatory parameters could not be confirmed in this study.", "We have compared, in a randomized study, conventional carbon dioxide pneumoperitoneum with abdominal wall lift in 25 patients undergoing laparoscopic cholecystectomy. Intra-abdominal pressure (IAP) (11 (SD 2) mm Hg vs 2.7 (9) mm Hg) (P < 0.01) and total amount of carbon dioxide used (40 (23) litre vs 9 (7) litre) (P < 0.001) were significantly less with abdominal wall lift. Pulmonary compliance was significantly greater (P < 0.01) in the abdominal wall lift group throughout operation. During the first 15 min of insufflation, arterial pressures were lower with abdominal wall lift (P < 0.05). In the conventional pneumoperitoneum group, femoral vein pressure increased (P < 0.01) and remained elevated for 3 h in the recovery room. Postoperative drowsiness was of significantly longer duration in the conventional pneumoperitoneum group than in the abdominal wall lift group (98 (46) min vs 13 (34) min) (P < 0.01). Postoperative nausea and vomiting and right shoulder pain occurred more often in patients with conventional pneumoperitoneum (P < 0.05). We conclude that the benefits of abdominal wall lift may be attributed to avoiding excessive carbon dioxide and high IAP.", "Carbon dioxide (CO2) pneumoperitoneum together with an increased intraabdominal pressure (IAP) induces a hemodynamic stress response, diminishes urine output, and may compromise splanchnic perfusion. A new retractor method may be less traumatic. Accordingly, 30 ASA physical status I or II patients undergoing laparoscopic cholecystectomy were randomly allocated to a CO2 pneumoperitoneum (IAP 12-13 mm Hg) (control) or to a gasless abdominal wall lift method (retractor) group. Anesthesia and intravascular fluids were standardized. Direct mean arterial pressure (MAP), urine output, urine-N-acetyl-beta-D-glucosaminidase (U-NAG), arterial blood gases, gastric mucosal PCO2, and intramucosal pH (pHi) were measured. Normoventilation was instituted in all patients. MAP increased (P < 0.001) only with CO2 pneumoperitoneum. Minute volume of ventilation had to be increased by 35% with CO2 insufflation. PaCO2 was significantly higher (P < 0.05) for 3 h postoperatively in the control group. Diuresis was less (P < 0.01) and U-NAG levels (P < 0.01) higher in the control group. The pHi decreased after induction of pneumoperitoneum up to three hours postoperatively and remained intact in the retractor group. We conclude that the retractor method for laparoscopic cholecystectomy ensures stable hemodynamics, prevents respiratory acidosis, and provides protection against biochemical effects, which reveal the renal and splanchic ischemia caused by CO2 insufflation. Implications: A mechanical retractor method (gasless) was compared with conventional CO2 pneumoperitoneum for laparoscopic cholestectomy. The gasless method ensured stable hemodynamics, prevented respiratory acidosis, and provided protection against the renal and splanchnic ischemia seen with CO2 pneumoperitoneum.", "To study the possible benefits of N2O pneumoperitoneum, 40 patients scheduled for laparoscopic cholecystectomy for symptomatic cholelithiasis were randomized into either CO2-induced (n = 20) or N2O-induced (n = 20) pneumoperitoneum groups. The intensity of postoperative pain was assessed by the patients themselves using an visual analogue pain score scale. CO2 insufflation caused respiratory acidosis. The total amount of anesthetic enflurane needed was lower in the N2O than in the CO2 group (p < 0.041). The N2O group experienced less pain 1 hour (p < 0.040) and 6 hours (p < 0.017) postoperatively and the next morning. Serum cortisol and plasma adrenaline concentrations in the N2O group did not differ from those in the CO2 group. Patients with N2O pneumoperitoneum seem to have less pain without the side effects caused by CO2. The N2O pneumoperitoneum is a good alternative to the CO2 pneumoperitoneum, especially for prolonged laparoscopic operations in patients with chronic cardiopulmonary diseases.", "The positive CO2 pneumoperitoneum needed to create the working space for laparoscopic surgery induces cardiovascular, neuroendocrine, and renal changes. Concern about these pathophysiologic changes has led to the introduction of a gasless technique. Fifty consecutive patients with symptomatic gallstones were randomized to conventional (CLC) or gasless laparoscopic cholecystectomy (GLC), with special reference to overall patient satisfaction, technical difficulties, duration of surgery, postoperative pain, and recovery. The overall exposure of the operative field was extremely poor in the GLC group, whereas the duration of surgery, steps involved in the cholecystectomy technique, length of hospital stay, and postoperative pain score did not differ significantly. After discharge, the median time to complete relief of pain tended to be shorter in the gasless group (5 days [range 1 to 15]) vs. the conventional group (8 days [range 1 to 15]). The period to return to normal activity was shorter in the GLC group (6 days [range 1 to 15]) compared to the CLC group (8.5 days [range 1 to 15]) (P = 0.031). No differences were found in terms of fatigue, dizziness and nausea, and overall satisfaction with the outcome. This study demonstrates a significantly shorter convalescence after laparoscopic cholecystectomy by means of the gasless technique compared to the conventional CO2 technique. Exposure of the operative field was less than optimal using the gasless technique.", "Because of absorbed carbon dioxide (CO(2)) and elevated intraabdominal pressure (IAP), CO(2) pneumoperitoneum (CO(2)PP) has potentially harmful intraoperative circulatory and ventilatory effects. Although not clinically significant for healthy patients, these effects are assumed to be deleterious for patients with a high risk for anesthesia (American Society of Anesthesiology [ASA] 3 and 4) and significant cardiopulmonary, renal, or hepatic diseases. The authors assessed CO(2)PP-related adverse effects by comparing ASA 3 and 4 patients who underwent laparoscopic cholecystectomy (LC) with or without CO(2)PP.\n A total of 20 successive ASA 3 and 4 patients who underwent LC were randomized into CO(2)PP (n = 10) and abdominal wall elevator (Laparolift) (n = 10) groups. The parameters for perioperative hemodynamics, ventilation, perfusion of intraabdominal organs, and blood chemistry were recorded periodically from before the induction of the anesthesia until postoperative day 2 and compared between the groups.\n Mean age, height, weight, the proportional number of ASA 3 vs ASA 4 patients, the volume of perioperative fluid loading, and the dose of analgesics did not differ significantly between the groups. The length of the operation was 49.9 +/- 10.6 min for the CO(2)PP group and 50.6 +/- 17.2 min for Laparolift group (nonsignificant difference). The mean central venous pressure (CVP) 30 min after insufflation was higher (12.3 +/- 4.8 vs 7.9 +/- 3.7 mmHg) and the (Gastric Mucosal pH) pHi at the end of the operation was lower (7.29 +/- 0.07 vs 7.35 +/- 0.04) in the CO(2)PP group than in the Laparolift group (p < 0.05). Later, CVP and pHi did not differ significantly. Other parameters of hemodynamics including oxygenation, perfusion, and blood chemistry did not differ significantly.\n For LC for patients with an ASA 3 and 4 risk for anesthesia, no significant adverse effects could be attributed to CO(2 )pneumoperitoneum. For high-risk patients, preoperative preparation and active perioperative monitoring are essential for safe anesthesia for LC with or without CO(2)PP.", "The aims of this study were to see if laparoscopic cholecystectomy is associated with a similar postoperative pain pattern to gynaecological laparoscopy and to see whether the use of a suprahepatic suction drain makes recovery from laparoscopic cholecystectomy more comfortable. After routine laparoscopic cholecystectomy and insertion of a suprahepatic suction drain, patients were randomized to suction or no suction on the drain. The time course of the severity of wound, abdominal and shoulder tip pain was assessed by visual analogue scales administered in the morning and afternoon of the first 3 postoperative days. The control group had a high incidence of shoulder tip pain similar to that after gynaecological laparoscopy. Patients in the treatment group reported significantly less shoulder tip pain than the control group (O.R. 0.16, 95% CI, 0.06-0.40). There was a tendency for the treatment group to report reduced abdominal and, to a lesser extent, wound pain. The authors recommend suprahepatic suction as a simple and more effective way to improve patient comfort after laparoscopic cholecystectomy.", "Laparoscopic cholecystectomy is associated with a high incidence of postoperative pain, nausea, and vomiting. Pneumoperitoneum created during the operation and residual gas after the operation are two of the factors in postoperative pain and nausea. We studied the effects of a subdiaphragmatic gas drain, which is intended to decrease the residual gas, on postoperative pain, nausea, and vomiting after laparoscopic cholecystectomy.\n Seventy patients were randomized into two demographically and clinically comparable groups: drainage and control. Postoperative pain, nausea, and vomiting were measured by verbal grading and visual analog scale 2-72 h postoperatively. Analgesic and antiemetic use and incidence of retching, vomiting and other complaints were also recorded.\n Subdiaphragmatic drain effectively reduced the incidence and amount of subdiaphragmatic gas bubble. The incidence and severity of nausea was lower in the drainage group at 72 h. Although severity of pain was lower at 8 and 12 h in the drainage group, the difference was not significant. There was also no difference between the groups in regard to analgesic and antiemetic use.\n Subdiaphragmatic drain offers only minor, if any, benefit on postoperative pain, nausea, and vomiting after laparoscopic cholecystectomy, and this effect is probably clinically irrelevant." ]	Low pressure pneumoperitoneum appears effective in decreasing pain after laparoscopic cholecystectomy. The safety of low pressure pneumoperitoneum has to be established.
CD002814	[ "20626310", "18647729", "8747817", "21281410" ]	[ "The effectiveness of traditional methods and altered auditory feedback in improving speech rate and intelligibility in speakers with Parkinson's disease.", "Design and methods of a randomized controlled trial on early speech and language therapy in patients with acute stroke and aphasia.", "Comparison of two forms of intensive speech treatment for Parkinson disease.", "Treating disordered speech and voice in Parkinson's disease online: a randomized controlled non-inferiority trial." ]	[ "Communication problems are a frequent symptom for people with Parkinson's disease (PD) which can have a significant impact on their quality-of-life. Deciding on the right management approach can be problematic though, as, with the exception of LSVT, very few studies have been published demonstrating the effectiveness of treatment techniques. The aim of this study was to compare traditional rate reduction methods with altered auditory feedback (AAF) with respect to their effectiveness to reduce speech rate and improve intelligibility in speakers with PD. Ten participants underwent both types of treatments in once weekly sessions for 6 weeks. Outcomes measures were speech rate for passage reading as well as intelligibility on both a passage reading and a monologue task. The results showed that, as a group, there was no significant change in either speech rate or intelligibility resulting from either treatment type. However, individual speakers showed improvements in speech performance as a result of each therapy technique. In most cases, these benefits persisted for at least 6 months post-treatment. Possible reasons for the variable response to treatment, as well as issues to consider when planning to use AAF devices in treatment are discussed.", "Most clinicians would recommend speech and language therapy (SLT) for aphasic patients. The question of when and for how long SLT should be administered still remains controversial. The aim of this trial is to evaluate the efficacy of early SLT in patients with acute stroke and aphasia in a randomized controlled trial. This report will present design and methods and discuss feasibility.\n Consecutive patients with first ever ischemic stroke and aphasia are assessed by the Amsterdam-Nijmegen Everyday Language Test (ANELT) and a short version of the Norsk Grunntest for Afasi. The treatment is language enrichment therapy, and the therapy is given 45 min/day for 15 weekdays. The primary outcome is the difference in the degree of aphasia between the SLT treated group and the control group measured by ANELT at 3 weeks.\n Around 10% of acute consecutive patients with aphasia are included. Of the first 79 included patients, 86% have completed the study according to protocol. We intend to include 125 patients, which provide sufficient statistical power to detect a clinically significant difference in the degree of aphasia.\n It is feasible to conduct a randomized controlled study on very early SLT for acute aphasic patients.", "This study investigated the effect of two forms of intensive speech treatment, (a) respiration (R) and (b) voice and respiration (Lee Silverman Voice Treatment [LSVT]), on the speech and voice deficits associated with idiopathic Parkinson disease. Forty-five subjects with Idiopathic Parkinson disease completed extensive pretreatment neurological, otolaryngological, neuropsychological, and speech assessments. All subjects completed 16 sessions of intensive speech treatment, 4 times a week for 1 month. Pre- and post-treatment measures included intensity and maximum duration during sustained vowel phonation. Intensity, habitual fundamental frequency, fundamental frequency variability, and utterance and pause duration were measured during reading of the \"Rainbow Passage\" and conversational monologue as well. Family and subject self-ratings were completed pre- and post-treatment for the perceptual variables loudness, monotonicity, hoarseness, overall intelligibility, and initiation of conversation. Significant pre- to post-treatment improvements were observed for more variables and were of greater magnitude for the subjects who received the voice and respiration treatment (LSVT). Only subjects who received the LSVT rated a significant decrease post-treatment on the impact of Parkinson disease on their communication. Correlations between descriptive prognostic variables (i.e., stage of disease, speech/voice severity rating, depression, and time since diagnosis) and magnitude of treatment-related change indicated these factors did not significantly predict treatment effectiveness. These findings suggest that intensive voice and respiration (LSVT) treatment, focusing on increased vocal fold adduction and respiration, is more effective than respiration (R) treatment alone for improving vocal intensity and decreasing the impact of Parkinson disease on communication.", "Telerehabilitation may be a feasible solution to the current problems faced by people with Parkinson's disease in accessing speech pathology services.\n To investigate the validity and reliability of online delivery of the Lee Silverman Voice Treatment (LSVT®) for the speech and voice disorder associated with Parkinson's disease.\n Thirty-four participants with Parkinson's disease and mild-to-moderate hypokinetic dysarthria took part in the randomized controlled non-inferiority laboratory trial and received the LSVT® in either the online or the face-to-face environment. Online sessions were conducted via two personal computer-based videoconferencing systems with real-time and store-and-forward capabilities operating on a 128 kbit/s Internet connection. Participants were assessed pre- and post-treatment on acoustic measures of mean vocal sound pressure level, phonation time, maximum fundamental frequency range, and perceptual measures of voice, articulatory precision and speech intelligibility.\n Non-inferiority of the online LSVT® modality was confirmed for the primary outcome measure of mean change in sound pressure level on a monologue task. Additionally, non-significant main effects for the LSVT® environment, dysarthria severity, and interaction effects were obtained for all outcomes measures. Significant improvements following the LSVT® were also noted on the majority of measures. The LSVT® was successfully delivered online, although some networking difficulties were encountered on a few occasions. High participant satisfaction was reported overall.\n Online treatment for hypokinetic dysarthria associated with Parkinson's disease appears to be clinically valid and reliable. Suggestions for future research are outlined.\n © 2010 Royal College of Speech & Language Therapists." ]	Considering the small patient numbers in these trials, there is insufficient evidence to support or refute the efficacy of any form of SLT over another to treat speech problems in patients with Parkinson's disease.
CD010538	[ "17318618", "9269267", "10908688", "16331769", "1954640", "1375648" ]	[ "Choosing between NSAID and arnica for topical treatment of hand osteoarthritis in a randomised, double-blind study.", "Copper-salicylate gel for pain relief in osteoarthritis: a randomised controlled trial.", "A randomized controlled trial comparing topical piroxicam gel with a homeopathic gel in osteoarthritis of the knee.", "Efficacy of topical diclofenac diethylamine gel in osteoarthritis of the knee.", "Treatment of arthritis with topical capsaicin: a double-blind trial.", "Effect of topical capsaicin in the therapy of painful osteoarthritis of the hands." ]	[ "The use of topical preparations for symptom relief is common in osteoarthritis. The effects of ibuprofen (5%) and arnica (50 g tincture/100 g, DER 1:20), as gel preparations in patients with radiologically confirmed and symptomatically active osteoarthritis of interphalangeal joints of hands, were evaluated in a randomised, double-blind study in 204 patients, to ascertain differences in pain relief and hand function after 21 days' treatment. Diagnosis was according to established criteria; primary endpoints were pain intensity and hand function; statistical design was as per current regulatory guidelines for testing topical preparations. There were no differences between the two groups in pain and hand function improvements, or in any secondary end points evaluated. Adverse events were reported by six patients (6.1%) on ibuprofen and by five patients (4.8%) on arnica. Our results confirm that this preparation of arnica is not inferior to ibuprofen when treating osteoarthritis of hands.", "To assess the efficacy and safety of a copper-salicylate gel in osteoarthritis of the hip and knee.\n Randomised, double-blind, placebo-controlled study.\n Rheumatology Clinic of St Vincent's Hospital, Sydney, New South Wales (a tertiary referral hospital), June 1993 to October 1994.\n 116 patients with pain associated with osteoarthritis of the hip and/or knee (diagnosed by criteria of the European League against Rheumatism), drawn from patients attending the Clinic or self-referred after newspaper advertisements.\n Copper-salicylate or placebo gel (1.5 g) applied twice daily to the forearm for four weeks.\n Self-assessment of pain before the trial and after two and four weeks of treatment; patient and investigator assessments of efficacy; additional analgesia required; adverse reactions; and withdrawal rates.\n Pain scores at rest and on movement decreased in both the copper-salicylate and placebo groups by 13%-20%. There was no significant difference between the two groups for decrease in pain score, patient and investigator efficacy ratings, number of patients requiring paracetamol for extra analgesia (active, 77%; placebo, 71%) and average dose of paracetamol (active, 555 mg/day; placebo, 600 mg/day). Significantly more patients in the copper-salicylate group reported adverse reactions (83% versus 52% of the placebo group), most commonly skin reactions, and withdrew from the trial because of these reactions (17% versus 1.7% of the placebo group).\n Copper-salicylate gel applied to the forearm was no better than placebo gel as pain relief for patients with osteoarthritis of the hip or knee, but produced significantly more skin rashes.", ": To evaluate the efficacy and safety of a homeopathic gel vs an NSAID (piroxicam) gel in the treatment of osteoarthritis of the knee.\n : One hundred and eighty-four out-patients with radiographically confirmed symptomatic osteoarthritis of the knee were entered into a pragmatic, randomized, double-blind controlled trial and treated with 1 g of gel three times daily for 4 weeks. Main outcome measures were pain on walking as a Visual Analogue Score (VAS) and a single-joint Ritchie index.\n : One hundred and seventy-two of the 184 enrolled patients had endpoints for the main outcome parameters. The pain reduction was 16.5 mm VAS in the homeopathy group (n = 86) and 8.1 mm in the piroxicam group (n = 86); the difference between treatment groups was 8.4 mm (95% confidence interval 0.8-15.9), and after adjustment for pain at baseline it was 6.8 mm (95% confidence interval -0.3 to 13.8). There was no significant difference between treatment groups in the single-joint Ritchie index (P = 0.78). Adverse events occurred in 28 patients (12 homeopathy group, 5 withdrawn; 16 piroxicam group, 9 withdrawn); 18 of the events involved a local reaction (7 homeopathy group, 2 withdrawn; 11 piroxicam group, 5 withdrawn).\n : The homeopathic gel was at least as effective and as well tolerated as the NSAID gel. The presence of a clinically relevant difference between treatment groups cannot be excluded. The homeopathic gel supplemented by simple analgesics if required may provide a useful treatment option for patients with osteoarthritis.", "To assess the efficacy and safety of topical diclofenac diethylamine gel, 1.16%, 4 g applied qid for 3 weeks to relieve the symptoms of osteoarthritis (OA) of the knee.\n Patients with OA of the knee washed out their OA medications for at least 5 drug half-lives. Patients with adequately high baseline pain scores were randomized to apply either double-blind active or placebo gel for 3 weeks. Acetaminophen (up to 2 g/day) was supplied as rescue medication. In a diary, patients recorded compliance to dosing and use of rescue medication and assessed daily pain on movement, spontaneous pain, and pain relief. At weekly site visits, patients completed the Western Ontario and McMaster (WOMAC) Osteoarthritis Index Questionnaire, which includes assessment of pain, stiffness, and physical function, and assessed pain intensity \"right now.\" At the final visit, a global assessment of treatment efficacy was completed.\n Of 238 randomized patients, 237 were included in the intent to treat efficacy analysis. Treatments differed significantly for daily pain on movement at Day 5, and continued on most days through end of study. Peak differences were achieved in the second week. On the primary outcome, average pain on movement over Days 1-14, diclofenac gel was significantly superior to placebo gel. Scores for all 3 WOMAC indices for diclofenac gel treatment were significantly superior to placebo at Weeks 2 and 3. A significant difference was achieved on pain intensity \"right now\" at all 3 weeks. At the end of the study, patients rated diclofenac gel as significantly more effective in treating the pain of OA of the knee (p = 0.03) compared to placebo. There were no safety issues concerning adverse events or laboratory values.\n Diclofenac gel was effective and safe for relief of symptoms of OA of the knee over 3 weeks of dosing.", "The neuropeptide substance P has been implicated in the pathogenesis of inflammation and pain in arthritis. In this double-blind randomized study, 70 patients with osteoarthritis (OA) and 31 with rheumatoid arthritis (RA) received capsaicin (a substance P depletor) or placebo for four weeks. The patients were instructed to apply 0.025% capsaicin cream or its vehicle (placebo) to painful knees four times daily. Pain relief was assessed using visual analog scales for pain and relief, a categorical pain scale, and physicians' global evaluations. Most of the patients continued to receive concomitant arthritis medications. Significantly more relief of pain was reported by the capsaicin-treated patients than the placebo patients throughout the study; after four weeks of capsaicin treatment, RA and OA patients demonstrated mean reductions in pain of 57% and 33%, respectively. These reductions in pain were statistically significant compared with those reported with placebo (P = 0.003 and P = 0.033, respectively). According to the global evaluations, 80% of the capsaicin-treated patients experienced a reduction in pain after two weeks of treatment. Transient burning was felt at the sites of drug application by 23 of the 52 capsaicin-treated patients; two patients withdrew from treatment because of this side effect. It is concluded that capsaicin cream is a safe and effective treatment for arthritis.", "Topical capsaicin 0.075% was evaluated for the treatment of the painful joints of rheumatoid arthritis (RA) and osteoarthritis (OA) in a 4 week double blind, placebo controlled randomized trial. Twenty-one patients were selected, all of whom had either RA (n = 7) or OA (n = 14) with painful involvement of the hands. Assessments of pain (visual analog scale), functional capacity, morning stiffness, grip strength, joint swelling and tenderness (dolorimeter) were performed before randomization. Treatment was applied to each painful hand joint 4 times daily with reassessment at 1, 2 and 4 weeks after entry. One subject did not complete the study. Capsaicin reduced tenderness (p less than 0.02) and pain (p less than 0.02) associated with OA, but not RA as compared with placebo. A local burning sensation was the only adverse effect noted. These findings suggest that topical capsaicin is a safe and potentially useful drug for the treatment of painful OA of the hands." ]	Although the mechanism of action of the topical medicinal plant products provides a rationale basis for their use in the treatment of osteoarthritis, the quality and quantity of current research studies of effectiveness are insufficient. Arnica gel probably improves symptoms as effectively as a gel containing non-steroidal anti-inflammatory drug, but with no better (and possibly worse) adverse event profile. Comfrey extract gel probably improves pain, and Capsicum extract gel probably will not improve pain or function at the doses examined in this review. Further high quality, fully powered studies are required to confirm the trends of effectiveness identifed in studies so far.
CD006706	[ "7778840", "9220235", "6378236", "9224082", "7767151", "6359995", "6313595", "15512809", "3006228", "7032303", "19668521", "12530483", "16816068", "6375840", "3039882", "6326632", "12523578" ]	[ "Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Collaborative Famciclovir Herpes Zoster Study Group.", "Ganciclovir ophthalmic gel (Virgan; 0.15%) in the treatment of herpes simplex keratitis.", "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.", "Treatment of herpes simplex gingivostomatitis with aciclovir in children: a randomised double blind placebo controlled study.", "Acyclovir given as prophylaxis against oral ulcers in acute myeloid leukaemia: randomised, double blind, placebo controlled trial.", "Acyclovir prophylaxis against herpes simplex virus infection in patients with leukemia. A randomized, double-blind, placebo-controlled study.", "Oral acyclovir prophylactic treatment of herpes simplex infection after bone marrow transplantation.", "Oral valacyclovir as prophylaxis against herpes simplex virus reactivation during high dose chemotherapy for leukemia.", "Acyclovir prophylaxis in bone marrow transplant recipients.", "Acyclovir and vidarabine in the treatment of ulcerative herpes simplex keratitis.", "Ganciclovir ophthalmic gel, 0.15%: a valuable tool for treating ocular herpes.", "Acyclovir suppression to prevent recurrent genital herpes at delivery.", "Valacyclovir prophylaxis to prevent recurrent herpes at delivery: a randomized clinical trial.", "Treatment of herpes simplex keratitis: comparison of acyclovir and vidarabine.", "Prevention of lower respiratory herpes simplex virus infection with acyclovir in patients with the adult respiratory distress syndrome.", "Oral acyclovir for prevention of herpes simplex virus reactivation after marrow transplantation.", "Oral valacyclovir versus intravenous acyclovir in preventing herpes simplex virus infections in autologous stem cell transplant recipients." ]	[ "To document the effects of treatment with famciclovir on the acute signs and symptoms of herpes zoster and postherpetic neuralgia.\n A randomized, double-blind, placebo-controlled, multicenter trial.\n 36 centers in the United States, Canada, and Australia.\n 419 immunocompetent adults with uncomplicated herpes zoster.\n Patients were assigned within 72 hours of rash onset to famciclovir, 500 mg; famciclovir, 750 mg; or placebo, three times daily for 7 days.\n Lesions were assessed daily for as long as 14 days until full crusting occurred and then weekly until the lesions healed. Viral cultures were obtained daily while vesicles were present. Pain was assessed at each of the visits at which lesions were examined and then monthly for 5 months after the lesions healed. Safety was assessed throughout the study.\n Famciclovir was well tolerated, with a safety profile similar to that of placebo. Famciclovir accelerated lesion healing and reduced the duration of viral shedding. Most importantly, famciclovir recipients had faster resolution of postherpetic neuralgia (approximately twofold faster) than placebo recipients; differences between the placebo group and both the 500-mg famciclovir group (hazard ratio, 1.7 [95% CI, 1.1 to 2.7]) and the 750-mg famciclovir group (hazard ratio, 1.9 [CI, 1.2 to 2.9]) were statistically significant (P = 0.02 and 0.01, respectively). The median duration of postherpetic neuralgia was reduced by approximately 2 months.\n Oral famciclovir, 500 mg or 750 mg three times daily for 7 days, is an effective and well-tolerated therapy for herpes zoster that decreases the duration of the disease's most debilitating complication, postherpetic neuralgia.", "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.", "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 examine the efficacy of aciclovir suspension for treating herpetic gingivostomatitis in young children.\n Randomised double blind placebo controlled study.\n Day care unit of a tertiary paediatric hospital.\n 72 children aged 1-6 years with clinical manifestations of gingivostomatitis lasting less than 72 hours; 61 children with cultures positive for herpes simplex virus finished the study.\n Duration of oral lesions, fever, eating and drinking difficulties, and viral shedding.\n Aciclovir suspension 15 mg/kg five times a day for seven days, or placebo.\n Children receiving aciclovir had oral lesions for a shorter period than children receiving placebo (median 4 v 10 days (difference 6 days, 95% confidence interval 4.0 to 8.0)) and earlier disappearance of the following signs and symptoms: fever (1 v 3 days (2 days, 0.8 to 3.2)); extraoral lesions (lesions around the mouth but outside the oral cavity) (0 v 5.5 days (5.5 days, 1.3 to 4.7)); eating difficulties (4 v 7 days (3 days, 1.31 to 4.69)); and drinking difficulties (3 v 6 days (3 days, 1.1 to 4.9)). Viral shedding was significantly shorter in the group treated with aciclovir (1 v 5 days (4 days, 2.9 to 5.1)).\n Oral aciclovir treatment for herpetic gingivostomatitis, started within the first three days of onset, shortens the duration of all clinical manifestations and the infectivity of affected children. Further studies are needed to evaluate the ideal dose and length of treatment.", "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.", "Twenty-nine adult patients with acute leukemia receiving timed sequential chemotherapy participated in a randomized, double-blind, placebo-controlled trial of acyclovir prophylaxis against reactivated herpes simplex virus infection. Patients with pretreatment antibody titers of 1:16 or greater received acyclovir or placebo starting 4 days after their initial chemotherapy. Treatment was given either for 32 days or until the patients were discharged from the hospital or until a culture-positive herpes simplex virus infection was found. Culture-positive herpes simplex virus infection developed in 11 of 15 patients who received placebo. No infection appeared in 14 patients who received acyclovir (p less than 0.00005). No obvious acute drug toxicity was seen. Recurrent infection was seen in 6 of 14 patients after cessation of acyclovir when retreated with chemotherapy, suggesting no effect on viral latency in these 6 patients. Acyclovir provided highly effective prophylaxis against reactivated herpes simplex virus infections in adult patients with acute leukemia receiving timed sequential chemotherapy.", "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.", "Reactivation of herpes simplex virus is a common event in patients undergoing dose-intensive remission induction or consolidation chemotherapy of acute leukemia, for which either intravenous or oral acyclovir provides effective prophylaxis. This drug's short serum half-life and low oral bioavailability make frequent dosing necessary, however, and we therefore sought to determine if the pro-drug valacyclovir, which has improved bioavailability, could be successfully substituted for this indication. Eighty-one patients with leukemia were randomized to receive either 500 mg or 1,000 mg of valacyclovir orally every 8 h and followed clinically, as well as with serial surveillance cultures. Over a total of 1,979 days on study between the groups, and 380 throat cultures, no documented episodes of herpes simplex reactivation were noted. Valacyclovir was tolerated well with no evident drug-related toxicities. We conclude that valacyclovir at either of the two doses studied can be safely substituted for oral or intravenous acyclovir, and that it provides effective prophylaxis against reactivation of herpes simplex virus in this patient population.", "Forty-two patients undergoing bone marrow transplantation were included in a randomised, double-blind and placebo controlled trial of prolonged acyclovir prophylaxis against infections with viruses of the herpes group. Twenty patients were allocated to receive acyclovir and 22 to receive placebo. Acyclovir or placebo was administered i.v. at a dose of 250 mg/m2 twice daily, starting 5 days before transplantation. At 5 weeks after transplantation, administration was changed to tablets, 400 mg three times daily (children less than 6 years, 200 mg three times daily) and continued until 6 months after transplantation. In the placebo group, 10 acute herpes simplex virus (HSV) infections occurred in 7 patients (5 HSV-1 and 2 HSV-2), and another patient repeatedly shed HSV in throat washings. Five patients developed herpes zoster. Among patients receiving acyclovir only one episode of HSV infection occurred and no herpes zoster. The difference in the number of infection episodes and the number of infected patients was strongly significant (p = 0.0002 and 0.0017, respectively). The only acyclovir patient who reactivated HSV was terminally ill, and it is highly likely that she did not absorb a sufficient amount of the orally administered drug to control infection. All HSV and varicella zoster virus (VZV) infections were reactivations, and 9 of 10 patients who developed HSV infections or shed virus had a pre-transplantation HSV IgG titer of greater than 10 000 (ELISA). Acyclovir had no effect on cytomegalovirus (CMV), time of engraftment, or graft versus host disease (GVHD). Apart from a possible allergic reaction (skin rash) to acyclovir tablets, no adverse reactions were seen during this long prophylaxis with acyclovir.", "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.", "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.", "To determine if suppressive acyclovir near term decreased the frequency of clinical recurrences at delivery in women with recurrent genital herpes simplex virus (HSV) infection.\n We conducted a prospective, double-blind, randomized trial in 234 women with recurrent genital herpes. Women with genital infection of any frequency were enrolled. Patients received either suppressive oral acyclovir 400 mg three times daily or an identical placebo after 36 weeks' gestation. Clinical lesions were identified, and HSV cultures were obtained at delivery. The frequencies of clinical and subclinical HSV recurrences at delivery were evaluated.\n Six percent of patients treated with acyclovir, and 14% of patients treated with placebo had clinical HSV at delivery (p = 0.046). No patients in the acyclovir group had positive HSV cultures, compared with 6% of placebo-treated patients (p = 0.029). There was no significant difference in subclinical HSV shedding in the acyclovir group (0%) compared with the placebo-treated group (3%) (p = 0.102).\n Suppressive acyclovir therapy significantly decreased the incidence of clinical genital herpes and the overall incidence of HSV excretion at delivery in patients with previous herpes infection.", "To measure the efficacy of valacyclovir suppression in late pregnancy to reduce the incidence of recurrent genital herpes in labor and subsequent cesarean delivery.\n A total of 350 pregnant women with a history of genital herpes were assigned randomly to oral valacyclovir 500 mg twice a day or an identical placebo from 36 weeks of gestation until delivery. In labor, vulvovaginal herpes simplex virus (HSV) culture and polymerase chain reaction (PCR) specimens were collected. Vaginal delivery was permitted if no clinical recurrence or prodromal symptoms were present. Neonatal HSV cultures and laboratory tests were obtained, and infants were followed up for 1 month after delivery. Data were analyzed using chi2 and Student t tests.\n One hundred seventy women treated with valacyclovir and 168 women treated with placebo were evaluated. Eighty-two percent of the women had recurrent genital herpes; 12% had first episode, nonprimary genital herpes; and 6% had first episode, primary genital herpes. At delivery, 28 women (8%) had recurrent genital herpes requiring cesarean delivery: 4% in the valacyclovir group and 13% in the placebo group (P = .009). Herpes simplex virus was detected by culture in 2% of the valacyclovir group and 9% [corrected] of the placebo group (P =.02). No infants were diagnosed with neonatal HSV, and there were no significant differences in neonatal complications. There were no significant differences in maternal or obstetric complications in either group.\n Valacyclovir suppression after 36 weeks of gestation significantly reduces HSV shedding and recurrent genital herpes requiring cesarean delivery.\n I.", "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.", "Herpes simplex virus (HSV) type I commonly occurs in the lower respiratory tract (LRT) of seriously ill patients, particularly those with the adult respiratory distress syndrome (ARDS), but it is not known whether HSV is a benign mucosal colonizer or a pathogen. The aims of this study were to determine whether the antiviral agent acyclovir could prevent this occurrence, and if so, whether prevention improved the outcome. Forty-five patients with ARDS underwent double-blind randomization into a treatment group (22 subjects) who received prophylactic acyclovir intravenously, 5 mg/kg every 8 h, and a control group (23 subjects). Upper and lower respiratory secretions were examined for the presence of HSV before randomization and twice weekly thereafter. Seven patients were excluded because of HSV detection prior to treatment. There were no significant differences between the remaining 17 acyclovir and 21 control patients in age, sex, distribution of primary diagnostic categories, and severity of primary illness. Only 1 patient (6%) in the acyclovir group developed HSV after treatment compared with 15 (71%) in the control group (p less than 0.001), but there was no improvement in the acyclovir group in the severity of respiratory failure, the duration of ventilator support (acyclovir, 20 +/- 19 days; control, 14 +/- 11 days), or mortality (acyclovir, 8 of 17, 47%; control, 9 of 21, 43%). We conclude that acyclovir is effective in preventing the high incidence of HSV in patients with ARDS, but that this prevention does not improve outcome. Routine prophylaxis of HSV is not recommended.", "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.", "Patients who are seropositive for herpes simplex virus (HSV) and are undergoing autologous marrow or peripheral blood stem cell transplantation require prophylaxis for HSV infection. Most prophylaxis regimens have used intravenous acyclovir (ACY). Oral valacyclovir (VAL), the L-valyl ester of ACY, can be used to achieve plasma concentrations equivalent to levels achieved with intravenous ACY. In this study, adults undergoing autologous stem cell transplantation were randomized to receive ACY, 250 mg/m2 intravenously (IV) every 12 hours from day 0 to engraftment, or VAL, 1 g orally every 12 hours from day 0 to engraftment. The primary study objective was to compare cost of HSV prophylaxis between study groups. Thirty patients were randomized to receive either oral VAL (n = 14) or IV ACY (n = 16) prophylaxis. Mean pharmacy cost of HSV prophylaxis in the patient group randomized to IV ACY was $1080 versus $320 for the group randomized initially to VAL. This study demonstrates the feasibility and significant cost savings of using oral VAL for HSV prophylaxis." ]	There is evidence that aciclovir is efficacious in the prevention and treatment of herpes simplex virus infections. There is no evidence that valaciclovir is more efficacious than aciclovir, or that a high dose of valaciclovir is better than a low dose of valaciclovir. There is evidence that as a prophylaxis, placebo is more efficacious than prostaglandin E. However, in all included trials, risk of bias is unclear.
CD008185	[ "16912578" ]	[ "A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome)." ]	[ "To evaluate the safety and efficacy of recombinant human iduronate-2-sulfatase (idursulfase) in the treatment of mucopolysaccharidosis II.\n Ninety-six mucopolysaccharidosis II patients between 5 and 31 years of age were enrolled in a double-blind, placebo-controlled trial. Patients were randomized to placebo infusions, weekly idursulfase (0.5 mg/kg) infusions or every-other-week infusions of idursulfase (0.5 mg/kg). Efficacy was evaluated using a composite endpoint consisting of distance walked in 6 minutes and the percentage of predicted forced vital capacity based on the sum of the ranks of change from baseline.\n Patients in the weekly and every-other-week idursulfase groups exhibited significant improvement in the composite endpoint compared to placebo (P = 0.0049 for weekly and P = 0.0416 for every-other-week) after one year. The weekly dosing group experienced a 37-m increase in the 6-minute-walk distance (P = 0.013), a 2.7% increase in percentage of predicted forced vital capacity (P = 0.065), and a 160 mL increase in absolute forced vital capacity (P = 0.001) compared to placebo group at 53 weeks. Idursulfase was generally well tolerated, but infusion reactions did occur. Idursulfase antibodies were detected in 46.9% of patients during the study.\n This study supports the use of weekly infusions of idursulfase in the treatment of mucopolysaccharidosis II." ]	The current evidence is limited. While the randomised clinical trial identified was considered to be of good quality, it failed to describe important outcomes. It has been demonstrated that enzyme replacement therapy with idursulfase is effective in relation to functional capacity (distance walked in six minutes and forced vital capacity), liver and spleen volumes and urine glycosaminoglycan excretion in patients with mucopolysaccharidosis type II compared with placebo. There is no available evidence in the included study and in the literature on outcomes such as improvement in growth, sleep apnoea, cardiac function, quality of life and mortality. More studies are needed to obtain more information on the long-term effectiveness and safety of enzyme replacement therapy.
CD002776	[ "2035325", "2587133", "1444522", "9875038", "7780540", "3421279", "16519625", "3601288", "1428134", "8296850", "2585215", "8272312", "8635828" ]	[ "Vitamin K to neonates. Peroral versus intramuscular administration.", "Maternal administration of vitamin K does not improve the coagulation profile of preterm infants.", "Effects of oral and intramuscular vitamin K prophylaxis on vitamin K1, PIVKA-II, and clotting factors in breast fed infants.", "A new mixed micellar preparation for oral vitamin K prophylaxis: randomised controlled comparison with an intramuscular formulation in breast fed infants.", "[Efficacy of oral administration of a micellaar solution of vitamin K during the neonatal period].", "The use of antenatal vitamin K in the prevention of early neonatal intraventricular hemorrhage.", "Maternal antenatal administration of vitamin K1 results in increasing the activities of vitamin K-dependent coagulation factors in umbilical blood and in decreasing the incidence rate of periventricular-intraventricular hemorrhage in premature infants.", "Maternally administered antenatal vitamin K1: effect on neonatal prothrombin activity, partial thromboplastin time, and intraventricular hemorrhage.", "Comparative study of oral versus injectable vitamin K in neonates.", "Antenatal vitamin K therapy of the low-birth-weight infant.", "Maternal-fetal transport of vitamin K1 and its effects on coagulation in premature infants.", "Antepartum vitamin K and phenobarbital for preventing intraventricular hemorrhage in the premature newborn: a randomized, double-blind, placebo-controlled trial.", "Effect of oral water soluble vitamin K on PIVKA-II levels in newborns." ]	[ "In a randomized study of 300 infants, the effect of 1 mg of peroral vitamin K given at birth was compared to the same dose given as an intramuscular injection. The combined activity of coagulation factor II + VII + X taken after 48 and before 72 hours after delivery served as the primary endpoint. Prothrombin (antigen) and PIVKA II (acarboxyprothrombin) were also measured. All infants were observed for events of bleeding until discharge from the hospital, normally on the fifth day. No significant differences between the groups in any of the biochemical markers were observed. The 95% confidence limits of the differences were very narrow for all factors. No cases of bleeding were observed. We conclude that administration of 1 mg peroral vitamin K is as efficient as intramuscular administration of the same dose in the prevention of classical hemorrhagic disease of the newborn.", "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.", "A randomised clinical trial was conducted to establish the effects of oral and intramuscular administration of vitamin K at birth on plasma concentrations of vitamin K1, proteins induced by vitamin K absence (PIVKA-II), and clotting factors. Two groups of about 165 healthy breast fed infants who received at random 1 mg vitamin K1 orally or intramuscularly after birth were studied at 2 weeks and 1 and 3 months of age. Although vitamin K1 concentrations were statistically significantly higher in the intramuscular group, blood coagulability, activities of factors VII and X and PIVKA-II concentrations did not reveal any difference between the two groups. At 2 weeks of age vitamin K1 concentrations were raised compared with reported unsupplemented concentrations and no PIVKA-II was detectable. At 3 months vitamin K1 concentrations were back at unsupplemented values and PIVKA-II was detectable in 11.5% of infants. Therefore, a repeated oral prophylaxis will be necessary to completely prevent (biochemical) vitamin K deficiency beyond the age of 1 month.", "To compare a new oral preparation of vitamin K1 (Konakion MM) containing lecithin and glycocholic acid with a standard intramuscular (IM) preparation during the first 8 weeks of life in exclusively breast fed infants.\n Infants were randomised at birth to the IM group (1 mg vitamin K) or the oral group (2 mg given at birth and repeated at 7 and 30 days of life). Prothrombin time (INR), plasma vitamin K1, and PIVKA II (undercarboxylated prothrombin) were monitored at 14, 30, and 56 days of age.\n Seventy nine infants were randomised to the oral group and 77 to the IM group. Sixty seven infants in each group completed eight weeks of the study. Prothrombin times did not differ between the two groups. Mean (SD) plasma vitamin K1 values (in ng/ml) decreased in both groups over time, but were higher in the oral group at 14 and 56 days: 2.0 (1.6) v 1.3 (1.1) at 14 days; 0.5 (0.3) v 0.5 (0.7) at 30 days; and 0.5 (0.8) v 0.2 (0.2) at 56 days of life. PIVKA II was raised (> or = 0.1 AU/ml) in cord blood in 47% of the infants. By 14 days, only one infant in each group had a raised PIVKA II value and both of these initially had high concentrations of PIVKA II in cord blood. At 30 days, there were no raised PIVKA II values. At 56 days, there were no raised PIVKA II values in the oral group, although three infants in the IM group had raised values.\n Plasma vitamin K concentrations were at least equal or significantly higher in babies given oral vitamin K supplements compared with IM treated babies at the time points measured. Through the first 8 weeks of life, multiple doses of the new oral preparation maintain haemostasis and vitamin K status in breast fed infants at least equal to that of the intramuscular preparation.", "Oral administration of vitamin K to neonates is quite satisfactory for preventing hemorrhagic disease of the newborn. The aim of this study is to test efficacy of a micellar solution of vitamin K at birth.\n Thirty full term infants, exclusively breast-fed during the first month of life, were included in this study. Seven of them (control group Cos) were given oral supplementation with 5 mg vitamin K1, cremophor; 15 other infants were given oral supplementation with 3 mg micellar solution of vitamin K1 (group MMos) and 7 were given an intramuscular injection of 1.5 mg micellar solution of vitamin K1 (group MMim). Prothrombin time activity and plasma vitamin K concentration were measured in the cord blood, 24 +/- 12 hours and 1 month after supplementation.\n No hemorrhage was seen and tolerance to vitamin K was good in the 3 groups. Mean prothrombin time activity was 54% in the cord blood, around 55% and 75%, 24 hrs and 1 month after supplementation, respectively; only one infant had low value (41%) by 1 month despite normal plasma vitamin K concentration. Two infants had low plasma vitamin K1 concentration by the second control despite normal prothrombin time activity; one belonged to the MMos group and the other to the Cos group. Mean values of plasma vitamin K1 concentration were higher by 1 month in the MMos group.\n A unique dose of micellar solution of vitamin K given orally at birth seems effective to prevent hemorrhagic disease.", "To establish the effect of antenatal vitamin K on the incidence and severity of intraventricular hemorrhage, 92 patients destined to deliver infants less than 32 weeks' gestation were, in a prospective fashion, randomly assigned to two groups. Group I received 10 mg of vitamin K1 intramuscularly every 5 days until delivery. Group II received no antenatal vitamin K1 therapy. There were 100 neonates less than 1500 gm, equally divided between groups I and II with respect to gestational age, birth weight, race, sex, presentation, route of delivery, duration of labor, Apgar scores, and arterial umbilical cord acid-base balance. The antenatal use of vitamin K resulted in significant reduction in the prothrombin time (12.7 versus 15.2 seconds) and partial thromboplastin time (42.6 versus 58.9 seconds; p less than 0.05). Furthermore, group I experienced a lower incidence of total (16% versus 36%) and severe (0% versus 11%) grades of intraventricular hemorrhage (p less than 0.05). This study suggests that the antenatal use of vitamin K may result in a reduction and severity of intraventricular hemorrhage in the neonate less than 1500 gm.", "Infants less than 35 weeks' gestation age are susceptible to periventricular-intraventricular hemorrhage (PIVH). This may be partially attributable to low concentrations of vitamin K-dependent coagulation factors. The purposes of this study were: (1) to determine the umbilical blood activity levels of vitamin K-dependent coagulation factors II, VII, IX and X; (2) to investigate the change in activities of these factors in premature infants' umbilical blood after prenatal administration of vitamin K1 to the mothers; and (3) to study the prophylactic effects on PIVH after maternal antenatal supplemental vitamin K1.\n Pregnant women in preterm labor at less than 35 weeks of gestation were randomly selected to receive antenatal vitamin K1 10 mg per day injection intramuscularly or intravenously for 2-7 days (vitamin K1 group, n = 40), or no such treatment (control group, n = 50). At the same period, cord blood samples were collected from thirty full-term neonates to compare the factor levels with those of premature infants. Intracranial ultrasound was performed by the same sonographer to determine the presence and severity of PIVH.\n The activities of vitamin K-dependent coagulation factors in umbilical blood in the control group were: factor II 25.64+/-9.49%, factor VII 59.00+/-17.66%, factor IX 24.67+/-8.88%, and factor X 30.16+/-5.02%. In full-term infants, the respective values were: factor II 36.70+/-4.88%, factor VII 64.54+/-10.62%, factor IX 30.18+/-5.69%, and factor X 34.32+/-12.63%. In vitamin K1 group these factors were: factor II 36.35+/-6.88%, factor VII 69.59+/-16.55%, factor IX 25.71+/-10.88%, and factor X 39.26+/-8.02%. The data suggest the absence of vitamin K-dependent coagulation factors in preterm infants, and antenatal supplement of vitamin K1 may increase the cord blood activity of factor II, VII and factor X (P < 0.001). In addition, the overall rates of PIVH in the vitamin K1 group and in controls were 32.4 and 52.0%, respectively (P = 0.036), and the frequency of severe PIVH was 5.0 and 20.0%, respectively (P = 0.038).\n Administration of vitamin K1 to pregnant women at less than 35 weeks' gestation age may result in improved coagulation and may reduce the incidence as well as the severity degree of PIVH.", "Infants weighing 1500 g or less at birth are susceptible to intraventricular hemorrhage. This may be due in part to low concentrations of vitamin K-dependent clotting factors. Women in labor between 24-34 weeks' gestation were selected, according to their hospital registration number, to receive 10 mg vitamin K1 intramuscularly at least four hours before delivery. Control women received no vitamin K. The study included only infants born of mothers who were in hospital more than four hours before delivery, who weighed 1500 g or less at birth, and were less than 34 weeks' gestation. Twenty vitamin K1 and 33 control infants qualified for the study. Infants in both groups received routine postnatal vitamin K1. On admission, the infant's prothrombin activity and partial thromboplastin time (PTT) were measured. A head ultrasound was done between days 2 and 4 of life. Results demonstrated significantly improved prothrombin activity, a nonsignificant trend toward improved PTT, and a significantly decreased frequency of intraventricular hemorrhage in infants whose mothers had received vitamin K1. The effect of antenatal vitamin K1 on prothrombin activity and PTT appeared to be more pronounced in female infants.", "One hundred term exclusively breast fed babies weighing more than 2.5 kg were evaluated to determine the efficacy of various modes and doses of Vitamin K to prevent hemorrhagic disease of newborn (HDN). The babies were grouped into four categories of 25 each: Group A--1 mg Vitamin K intramuscular (Menadione sodium disulphite) at birth; Group B--0.5 mg Vitamin K intramuscular; Group C--1 mg Vitamin K orally, and group D--no Vitamin K. The prothrombin index was estimated in all babies between 36-72 hours of age. The results revealed a prothrombin index in Groups A, B, C and D as 94.98 +/- 7.64%, 95.08 +/- 9.91%, 92.51 +/- 10.10% and 80.39 +/- 15.90%, respectively. The differences between Groups A, B and C were insignificant. However, Group D, prothrombin index was significantly reduced as compared with the other three groups. It is, therefore, concluded that oral Vitamin K is as effective as injectable Vitamin K and its usage is recommended in our country to reduce complications and costs of parenteral therapy.", "The purpose of our study was to determine whether maternal vitamin K1 administered antenatally improved global coagulation parameters and the levels of specific vitamin K-dependent proteins in low-birth-weight infants.\n Thirty-three preterm mothers admitted in labor were assigned in a prospective, blinded fashion to receive either intramuscular vitamin K1 (17) or placebo (16). At delivery cord blood samples were tested for prothrombin time, activated partial thromboplastin time, factor II and protein C activity, and antigen levels. Statistical analysis was by Student t test.\n No statistically significant differences could be demonstrated with regard to group mean values for global tests (prothrombin time, activated partial thromboplastin time) or specific vitamin K-dependent protein levels (factor II, protein C) in newborns whose mothers received antenatal vitamin K compared with those who did not.\n These results would suggest that antenatal vitamin K1 therapy to mothers < 32 weeks' gestation has no significant effect on the level of vitamin K-dependent factors in the fetus.", "We conducted a prospective study to determine (1) the maternal-fetal vitamin K1 transport in premature infants after vitamin K1 was given to the mothers antenatally and (2) the vitamin K1 effects on blood coagulation in the babies. Women in labor at less than or equal to 34 weeks of gestation were randomly selected to receive antenatal vitamin K1, 5 mg given intramuscularly (vitamin K1 group), or no vitamin K1 (control group). Eight infants, including one set of twins, were in the vitamin K1 group and six in the control group. Vitamin K1 concentrations were higher in the vitamin K1 group than in the control group (p = 0.06). Activated partial thromboplastin time was prolonged, and factor II coagulation activity and factor II antigen were proportionately decreased in cord plasma in both groups. The average ratio of factor II coagulation activity to antigen was not decreased in either group. Protein induced by vitamin K absence-II (PIVKA-II) was not detectable in any cord plasma sample in either group. These findings support previous reports that the decreased vitamin K-dependent coagulation activity in premature infants is the result of reduced synthesis of precursor proteins, rather than the result of vitamin K deficiency, and suggest that additional vitamin K1 is not likely to improve coagulation activity. Among those infants who underwent cranial ultrasonography, all four in the vitamin K1 group and one of five in the control group had mild intraventricular hemorrhage. Studies of a larger number of patients are necessary before it can be established that maternal antenatal administration of vitamin K1 results in improvement of coagulation and the prevention of intraventricular hemorrhage in premature infants.", "To determine whether antepartum phenobarbital and vitamin K reduce the risk of intraventricular hemorrhage in premature newborns.\n Patients at imminent risk for spontaneous or indicated premature delivery between 24-34 weeks' gestation were randomized to receive either placebo or vitamin K and phenobarbital. All patients received betamethasone and antibiotics and were managed uniformly by a single perinatal group in one hospital. All newborns were managed uniformly in the same facility by a single neonatal group.\n There was a nonsignificant reduction in all grades of intraventricular hemorrhage in the treatment group when compared to the placebo group (48.2 versus 38.3%; P > .05). Frequencies were reduced for severe intraventricular hemorrhage (grades 3 and 4) (6.0 versus 2.5%; P > .05) and mild intraventricular hemorrhage (grades 1 and 2) (42.2 versus 35.8%; P > .05).\n Antepartum phenobarbital and vitamin K effected a nonsignificant reduction in both mild and severe intraventricular hemorrhage. The incidence of severe intraventricular hemorrhage in our control group was significantly less than that observed in previous studies.", "Intramuscular administration of vitamin K for prophylaxis against hemorrhagic disease of the newborn has the disadvantage of increased cost, pain, anxiety to parents and risk of transmission of infection. Oral route is a better alternative. Oral absorption of vitamin K has been shown to be equally good using special oral preparations. However, this preparation is not available in India. A prospective study was carried out on 51 full term, healthy breastfed newborns to evaluate if the injectable water soluble preparation of vitamin K (menadione sodium bisulphite) could be as effective. Fourteen babies received 1 mg vitamin K intramuscularly, 24 received 2 mg vitamin K orally while 13 controls did not receive vitamin K at birth. PIVKA-II levels were measured in cord blood and at 72-78 hours of age in all babies as a marker of vitamin K deficiency. The overall PIVKA-II prevalence in cord blood was 64.7%. At 72-78 hours, PIVKA-II was present in 50% of babies in IM group, 58.3% of babies in oral group and in 76.9% of babies in 'no vitamin K' group (p > 0.05). The PIVKA-II levels decreased or did not change at 72-78 hours in 91.6% of babies in oral group versus 92.8% of babies in IM group (p > 0.05). On the other hand, PIVKA-II levels increased in 30.7% of babies who did not receive vitamin K as against in 7.8% of babies receiving vitamin K in either form (p < 0.05). Hence, vitamin K prophylaxis is required for all newborns at birth and injectable vitamin K (menadione sodium bisulphite) given orally to term healthy babies is effective in preventing vitamin K deficiency state." ]	A single dose (1.0 mg) of intramuscular vitamin K after birth is effective in the prevention of classic HDN. Either intramuscular or oral (1.0 mg) vitamin K prophylaxis improves biochemical indices of coagulation status at 1-7 days. Neither intramuscular nor oral vitamin K has been tested in randomized trials with respect to effect on late HDN. Oral vitamin K, either single or multiple dose, has not been tested in randomized trials for its effect on either classic or late HDN.
CD003352	[ "17134849", "9803702", "18164144", "17347121", "20545388", "8122955", "12757964", "12873248", "3276670", "10359461", "15730351", "19874153", "16169160", "12215081", "16040376", "15283944", "12699026", "11754709", "15796645" ]	[ "Safety, tolerability and efficacy of levodopa-carbidopa treatment for cocaine dependence: two double-blind, randomized, clinical trials.", "Superior efficacy of cognitive-behavioral therapy for urban crack cocaine abusers: main and matching effects.", "Levodopa pharmacotherapy for cocaine dependence: choosing the optimal behavioral therapy platform.", "Preliminary feasibility and efficacy of a brief motivational intervention with psychophysiological feedback for cocaine abuse.", "Contingency management and levodopa-carbidopa for cocaine treatment: a comparison of three behavioral targets.", "Psychotherapy and pharmacotherapy for ambulatory cocaine abusers.", "A pilot trial of olanzapine for the treatment of cocaine dependence.", "Pilot randomized double blind placebo-controlled study of dexamphetamine for cocaine dependence.", "Pharmacological and behavioral treatments of cocaine dependence: controlled studies.", "Psychosocial treatments for cocaine dependence: National Institute on Drug Abuse Collaborative Cocaine Treatment Study.", "A placebo-controlled screening trial of tiagabine, sertraline and donepezil as cocaine dependence treatments.", "High-dose naltrexone therapy for cocaine-alcohol dependence.", "A randomized placebo-controlled trial of gabapentin for cocaine dependence.", "A comparison of contingency management and cognitive-behavioral approaches during methadone maintenance treatment for cocaine dependence.", "Use of dopamine agonist pergolide in outpatient treatment of cocaine dependence.", "A pilot trial of topiramate for the treatment of cocaine dependence.", "Treatment responsivity of cocaine-dependent patients with antisocial personality disorder to cognitive-behavioral and contingency management interventions.", "Acupuncture for the treatment of cocaine addiction: a randomized controlled trial.", "Prize reinforcement contingency management for cocaine dependence: integration with group therapy in a methadone clinic." ]	[ "The role of dopamine in cocaine abuse has been long recognized. Cocaine use can profoundly alter dopaminergic functioning through depletion of this monoamine and changes in receptor functioning. Based on these facts, levodopa (L-dopa) pharmacotherapy may be helpful in reducing or abolishing cocaine use.\n The current studies sought to evaluate the safety, tolerability and efficacy of L-dopa as a treatment for cocaine dependence.\n In Study 1, 67 cocaine-dependent subjects were randomized in a 5-week, double-blind, placebo-controlled safety trial. Subjects received either placebo, or 400 mg L-dopa plus 100 mg of the peripheral decarboxylase inhibitor, carbidopa, in a sustained-release preparation (Sinemet CR). In Study 2, 122 cocaine-dependent subjects were enrolled in a 9-week, randomized, double-blind, placebo-controlled trial to compare placebo to 400/100 mg and 800/200 mg L-dopa/carbidopa treatments. Placebo or L-dopa were administered twice daily in both studies.\n L-dopa was well tolerated with similar retention and medication adherence rates compared to placebo. Only two side effects occurred more often in L-dopa-treated patients: nausea and dizziness. L-dopa lowered diastolic blood pressure in a dose-dependent fashion. In these trials, L-dopa had no effect on cocaine use, cocaine craving, or mood.\n These two studies demonstrate the safety and tolerability of L-dopa pharmacotherapy in cocaine-dependent patients. No evidence for greater efficacy of L-dopa compared to placebo was observed. The possibility of enhancing treatment effects by combining L-dopa with other behavioral or pharmacological interventions is discussed.", "This study evaluated the efficacy of cognitive-behavioral therapy (CBT) and 12-step facilitation (12SF) in treating cocaine abuse. Participants (N = 128) were randomly assigned to treatment conditions and assessed at baseline and at Weeks 4, 8, 12, and 26. Treatment lasted for 12 weeks. It was hypothesized that participants treated with CBT would be significantly more likely to achieve abstinence from cocaine than participants treated with 12SF. A series of patient-treatment matching hypotheses was also proposed. Across 2 different outcome variables, it was found that participants in CBT were significantly more likely to achieve abstinence than participants in 12SF. In addition, some support for matching hypotheses was found, suggesting that both psychotherapies may be differentially effective for identified subgroups of persons that abuse cocaine.", "The dopamine precursor levodopa has shown some, albeit relatively weak, promise in treating cocaine dependence. This study sought to identify the most appropriate behavioral therapy platform for levodopa pharmacotherapy by evaluating its effect when administered in combination with behavioral platforms of varying intensities.\n A total of 161 treatment-seeking cocaine dependent subjects received sustained release levodopa/carbidopa (400/100mg bid, Sinemet) or placebo delivered in combination with Clinical Management (ClinMan); ClinMan+cognitive behavioral therapy (CBT); or ClinMan+CBT+voucher-based reinforcement therapy (VBRT) in a 12-week randomized, placebo-controlled, double-blind (for medication condition) trial. Medication compliance was monitored with riboflavin (100mg/capsule) and the Medication Event Monitoring System. Protocol compliance was addressed in weekly, 10-min nurse-delivered ClinMan sessions. Weekly, 1-h CBT sessions focused on coping skills training. VBRT (with escalating reinforcer value) provided cash-valued vouchers contingent on cocaine-negative urine toxicology results. Urine benzoylecgonine assays collected thrice-weekly were analyzed by intention-to-treat criteria using generalized linear mixed models.\n Levodopa main effects were found on all outcome measures of cocaine use. Contrasts testing the levodopa-placebo difference within each behavioral platform found reliable effects, favoring levodopa, only in the VBRT platform. Levodopa treatment with vouchers produced higher proportions of cocaine-negative urines and longer periods of consecutive abstinence compared to other treatment combinations.\n This is the first study to find a significant treatment effect for levodopa and, in doing so, to demonstrate that the magnitude of this effect is dependent upon conditions of the behavioral therapy platform. The data support use of levodopa with abstinence-based reinforcement therapy as one efficacious combination in cocaine dependence disorder treatment.", "Motivational interviewing (MI) with personalized feedback, particularly related to biological markers of risk or harm, has been found effective for alcohol use disorders, but has not been fully investigated in cocaine use disorders. A randomized, controlled pilot study evaluating the feasibility and preliminary efficacy of a brief MI intervention using EEG/ERP graphical feedback for cocaine abusers was conducted. Treatment-seeking cocaine abusers (N = 31) were randomly assigned to a two-session MI intervention or a minimal control condition. All participants received EEG assessments at intake and post-treatment. Results indicated that the MI intervention was feasible and the subjective impact of the EEG feedback was positive. Significant group differences in percentage of cocaine positive urine screens across the study were found, favoring the MI group; 84.9% for the control group and 62.6% in the MI group, p < .05. Further research must determine the specific conditions under which MI is most appropriate and efficacious.", "New data support use of levodopa pharmacotherapy with behavioral contingency management (CM) as one efficacious combination in cocaine dependence disorder treatment. A potential mechanism of the combined treatment effects may be related to dopamine-induced enhancement of the saliency of contingently delivered reinforcers. Evidence to support this mechanism was sought by evaluating levodopa-enhancing effects across distinct CM conditions that varied in behavioral targets. A total of 136 treatment-seeking, cocaine dependent subjects participated in this 12-week, randomized, placebo-controlled trial of levodopa (vs. placebo) administered in combination with one of three behavioral CM conditions. In the CM-URINE condition, subjects received cash-valued vouchers contingent on cocaine-negative urine toxicology results. In the CM-ATTEND condition, the same voucher schedule was contingent on attending thrice weekly clinic visits. In the CM-MEDICATION condition, the same voucher schedule was contingent on Medication Event Monitoring Systems- and riboflavin-based evidence of pill-taking behavior. Primary outcomes associated with each CM target behavior were analyzed using generalized linear mixed models for repeated outcomes. CM responding in the CM-ATTEND and CM-MEDICATION conditions showed orderly effects, with each condition producing corresponding changes in targeted behaviors, regardless of medication condition. In contrast, CM responding in the CM-URINE condition was moderated by medication, with levodopa-treated subjects more likely to submit cocaine-negative urines. These findings specify the optimal target behavior for CM when used in combination with levodopa pharmacotherapy.", "At present, there is no consensus regarding effective treatment for cocaine abuse or the most productive roles for the two major forms of treatment, pharmacotherapy and psychotherapy. We conducted the first randomized clinical trial evaluating psychotherapy and pharmacotherapy, alone and in combination, as treatment for ambulatory cocaine abusers.\n One hundred thirty-nine subjects were assigned to one of four conditions offered over a 12-week abstinence initiation trial: relapse prevention plus desipramine hydrochloride, clinical management plus desipramine, relapse prevention plus placebo, and clinical management plus placebo. All treatments were manual-guided, delivered by experienced therapists, and monitored to promote the integrity of both forms of treatment.\n First, although all groups showed significant improvement, significant main effects for medication or psychotherapy, or their combination, were not found for treatment retention, reduction in cocaine use, or other outcomes at 12 weeks. Second, baseline severity of cocaine use interacted differently with psychotherapy and pharmacotherapy: higher-severity patients had significantly better outcome when treated with relapse prevention than with clinical management, while desipramine was associated with improved abstinence initiation among lower-severity subjects. Third, desipramine was significantly more effective than placebo in reducing cocaine use over 6, but not 12, weeks of treatment. Fourth, depressed subjects had greater reduction in cocaine use than nondepressed subjects and had better response to relapse prevention than to clinical management.\n These findings underscore the significance of heterogeneity among cocaine abusers and the need to develop specialized treatments for clinically distinct subgroups of cocaine abusers.", "Multiple lines of evidence suggest both dopaminergic and serotonergic involvement in the reinforcing effects of cocaine. Medications such as olanzapine, which block dopamine D2 receptors, as well as serotonin receptors 5HT2A and 5HT2C may be able to reduce cocaine use in cocaine dependent patients by reducing the euphoric effects of cocaine and attenuating cocaine craving.\n This was a 12-week, double blind, placebo controlled, pilot trial involving 30 cocaine dependent subjects. Subjects received either olanzapine (10 mg/day) or identical placebo. Outcome measures included treatment retention, qualitative urine benzoylecgonine tests, cocaine craving, clinical global impression scores, and results from the addiction severity index.\n Treatment retention was slightly, but significantly, better in the placebo-treated subjects. Placebo-treated subjects were more likely to be abstinent from cocaine during the trial compared to olanzapine-treated subjects, based on urine benzoylecgonine results. Olanzapine was not superior to placebo in any outcome measure.\n The results of this trial do not support the usefulness of olanzapine for the treatment of cocaine dependence. In fact, olanzapine may worsen cocaine treatment outcome.", "To establish the feasibility of conducting a placebo-controlled clinical trial of dexamphetamine replacement therapy for cocaine dependence and to obtain preliminary data.\n Double-blind randomized placebo-controlled trial.\n Thirty cocaine-dependent injecting drug users.\n Subjects were assigned randomly to receive 60 mg/day dexamphetamine (n = 16) or placebo (n = 14) for 14 weeks.\n Immunoassay and mass spectrometric techniques were used to identify cocaine metabolites in urine. Subjects were screened using the Composite International Diagnostic Interview and DSM-IV. The Opiate Treatment Index, Brief Symptom Inventory, Severity of Dependence Scale and visual analogue craving scales were used to collect pre- and post-self-report data.\n Treatment retention was equivalent between groups; however, outcomes favoured the treatment group with no improvements observed in the placebo control group. The proportion of cocaine-positive urine samples detected in the treatment group declined from 94% to 56% compared to no change in the placebo group (79% positive). While the improvements were not significant between groups, within-group analysis revealed that the treatment group reduced self-reported cocaine use (P = 0.02), reduced criminal activity (P = 0.04), reduced cravings (P < 0.01) and reduced severity of cocaine dependence (P < 0.01) with no within-group improvements found in the placebo group.\n A definitive evaluation of the utility of dexamphetamine in the management of cocaine dependence is feasible and warranted.", "The cocaine epidemic has stimulated novel treatments aimed at reducing relapse to this extremely addicting drug. After detoxification and standard treatment, former cocaine users continue to exhibit strong cocaine craving and physiological changes when presented with cocaine-related stimuli. Because these conditioned responses may increase the risk of relapse, a new treatment has been developed to extinguish such responses. The extinction process, consisting of repeated presentations of cocaine-related stimuli until the stimuli gradually lose their ability to evoke conditioned responses, is integrated into a comprehensive rehabilitation program. Cocaine dependence is often combined with opiate dependence. Desipramine has been added to methadone maintenance in an attempt to reduce dependence on both substances. Methadone impedes catabolism of desipramine so that relatively low doses of desipramine may produce antidepressant effects and possibly reduce the desire to use cocaine. Preliminary evidence from a placebo-controlled study of desipramine in combination with methadone suggests that desipramine produces significant improvements in psychological functioning, but its effects on reduction of cocaine use are less dramatic.", "This was a multicenter investigation examining the efficacy of 4 psychosocial treatments for cocaine-dependent patients.\n Four hundred eighty-seven patients were randomly assigned to 1 of 4 manual-guided treatments: individual drug counseling plus group drug counseling (GDC), cognitive therapy plus GDC, supportive-expressive therapy plus GDC, or GDC alone. Treatment was intensive, including 36 possible individual sessions and 24 group sessions for 6 months. Patients were assessed monthly during active treatment and at 9 and 12 months after baseline. Primary outcome measures were the Addiction Severity Index-Drug Use Composite score and the number of days of cocaine use in the past month.\n Compared with the 2 psychotherapies and with GDC alone, individual drug counseling plus GDC showed the greatest improvement on the Addiction Severity Index-Drug Use Composite score. Individual group counseling plus GDC was also superior to the 2 psychotherapies on the number of days of cocaine use in the past month. Hypotheses regarding the superiority of psychotherapy to GDC for patients with greater psychiatric severity and the superiority of cognitive therapy plus GDC compared with supportive-expressive therapy plus GDC for patients with antisocial personality traits or external coping style were not confirmed.\n Compared with professional psychotherapy, a manual-guided combination of intensive individual drug counseling and GDC has promise for the treatment of cocaine dependence.", "To conduct a preliminary evaluation of the safety and efficacy of tiagabine, sertraline or donepezil versus an unmatched placebo control as a treatment for cocaine dependence.\n A 10-week out-patient study was conducted using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design.\n This study was conducted at the Cincinnati Medication Development Research Unit (MDRU) and at an affiliated site in Dayton, Ohio.\n Participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence. Sixty-seven participants were enrolled with 55 completing final study measures.\n The targeted daily doses of medication were tiagabine 20 mg, sertraline 100 mg and donepezil 10 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis.\n Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression Scale-Observer and self-report of cocaine use. Safety measures included adverse events, ECGs, vital signs and laboratory tests.\n Subjective measures of cocaine dependence indicated significant improvement for all study groups. Generalized estimating equations analysis indicated that the tiagabine group showed a trend toward a significant decrease in urine BE level from baseline to weeks 5-8 (P = 0.10) and non-significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures.\n The present findings suggest that tiagabine may be worthy of further study as a cocaine dependence treatment.", "This randomized, double-blind, placebo-controlled study compared the effects of high-dose (100 mg/d) naltrexone versus placebo in a sample of 87 randomized subjects with both cocaine and alcohol dependence. Medication conditions were crossed with two behavioral therapy platforms that examined whether adding contingency management (CM) that targeted cocaine abstinence would enhance naltrexone effects compared to cognitive behavioral therapy (CBT) without CM. Primary outcome measures for cocaine (urine screens) and alcohol use (timeline followback) were collected thrice-weekly during 12 weeks of treatment. Retention in treatment and medication compliance rates were low. Rates of cocaine use and drinks per day did not differ between treatment groups; however naltrexone did reduce frequency of heavy drinking days, as did CBT without CM. Notably, adding CM to CBT did not enhance treatment outcomes. These weak findings suggest that pharmacological and behavioral interventions that have shown efficacy in the treatment of a single drug dependence disorder may not provide the coverage needed when targeting dual drug dependence.", "In laboratory animals, augmentation of GABA neurotransmission results in inhibition of cocaine self-administration and inhibition of reinstatement to cocaine-seeking behaviors. If parallel effects were observed in humans, GABA-ergic medication should be effective both in the abstinence-induction as well as in the relapse-prevention phase of cocaine dependence treatment. Gabapentin is an anticonvulsant medication that increases human brain GABA levels. We evaluated the safety and efficacy of gabapentin combined with relapse-prevention therapy in the treatment of cocaine-dependent individuals.\n The study involved 129 individuals with cocaine dependence. Of the 99 participants, who were randomized into a double-blind trial 88% were males, 66% were minorities and with an average age of 39 years (range 22-58 years). After 2 weeks of placebo lead-in, participants were randomized to receive either gabapentin 3200 mg (1600 mg bid) or placebo for 12 weeks, followed by 2 weeks of placebo lead-out. Prior to randomization, participants were stratified into four groups based on the principal route of cocaine use (smokers versus intranasal users) and the level of cocaine use during the 2 weeks of lead-in (high level versus low level). Throughout the 16 weeks study, participants received weekly individual relapse-prevention therapy. The outcome measures included: days of cocaine use and a binary indicator of abstinence based on urine toxicology test, self-reported cocaine craving and retention in treatment.\n Forty-nine percent of randomized patients completed 12 weeks of the trial. Retention did not differ by treatment group but cocaine-smokers dropped out of treatment at a significantly faster rate than intranasal users. For the entire sample, odds of cocaine use over the course of the study did not differ between gabapentin- and placebo-treated individuals. There was a significant difference in the odds of cocaine use between high and low-use groups, with the odds in high-use groups decreasing over time and odds in the low-use groups gradually increasing over the course of the study, such that by the end of the study low and high users were similarly likely to use cocaine. In the low-use group, there was a non-significant trend suggesting that gabapentin-treated subjects had more favorable outcome compared to placebo-treated individuals. There was no treatment effect on abstinence rates, craving or other substance use. Gabapentin at 3200 mg/day was very well tolerated in this group of cocaine-dependent participants.\n When combined with weekly individual relapse-prevention therapy, gabapentin 1600 mg bid was no more effective than placebo in the treatment of cocaine dependence. When reviewed in conjunction with other published studies, gabapentin and other GABA enhancing anticonvulsant medications may deserve further study as relapse-preventive agents in cocaine-dependent individuals who achieve abstinence early in treatment.", "This study compared 2 psychosocial approaches for the treatment of cocaine dependence: contingency management (CM) and cognitive-behavioral therapy (CBT).\n Patients with cocaine dependence who were receiving methadone maintenance treatment (n = 120) were randomly assigned to 1 of 4 conditions: CM, CBT, combined CM and CBT (CBT + CM), or treatment as usual (ie, methadone maintenance treatment program only [MMTP only]) (n = 30 per cell). The CM procedures and CBT materials were comparable to those used in previously published research. The active study period was 16 weeks, requiring 3 clinic visits per week. Participants were evaluated during treatment and at 17, 26, and 52 weeks after admission.\n Urinalysis results during the 16-week treatment period show that participants assigned to the 2 groups featuring CM had significantly superior in-treatment urinalysis results, whereas urinalysis results from participants in the CBT group were not significantly different than those from the MMTP-only group. At week 17, self-reported days of cocaine use were significantly reduced from baseline levels for all 3 treatment groups but not for the MMTP-only group. At the 26-week and 52-week follow-up points, CBT participants showed substantial improvement, resulting in equivalent performance with the CM groups as indicated by both urinalysis and self-reported cocaine use data.\n Study findings provide solid evidence of efficacy for CM and CBT. Although the effect of CM is significantly greater during treatment, CBT appears to produce comparable long-term outcomes. There was no evidence of an additive effect for the 2 treatments in the CM + CBT group.", "The dopamine agonist pergolide was evaluated in the treatment of 42 men who manifested cocaine dependence in a single-blind, 4-week-long placebo-controlled study, during 1998-1999 in São Paulo, Brazil. The patients were randomly assigned to two groups: the first group received pergolide (0.05-0.2 mg per day) and the second group received placebo (one to four tablets per day). Urine toxicology screens were obtained. The groups were compared in terms of depressive symptoms, \"craving,\" use of cocaine, side effects of medications, results of urine tests, and retention in treatment. At 3 months' follow-up, the participants were reassessed. No differences were found between the two groups.", "Both GABAergic and glutamatergic neurons appear to be important modulators of the brain reward system and medications that affect GABA and glutamatergic neurotransmission may reduce the rewarding properties of cocaine and reduce cocaine craving. Topiramate, an anticonvulsant, raises cerebral GABA levels, facilitates GABAergic neurotransmission and inhibits glutametergic activity at AMPA/kainite receptors. Thus, it may be useful for treating cocaine dependence.\n The efficacy of topiramate for cocaine dependence was tested in a 13-week, double-blind, placebo-controlled pilot trial (n = 40). Topiramate was titrated gradually over 8 weeks to a dose of 200 mg daily. The primary outcome measure was cocaine abstinence verified by twice weekly urine benzoylecgonine tests (UBT).\n Eighty-two percent of subjects completed the trial. Analysis of the UBT using a GEE model showed that after week 8, when the dose titration was completed, topiramate-treated subjects were more likely to be abstinent from cocaine compared to placebo-treated subjects (Z = 2.67, P = 0.01). Topiramate-treated subjects were also more likely to attain 3 weeks of continuous abstinence from cocaine (chi2 = 3.9, d.f. = 1, P = 0.05).\n Topiramate may be effective for the treatment of cocaine dependence.", "This study compared the efficacy of 2 approaches for the treatment of cocaine dependence among methadone-maintained patients with and without antisocial personality disorder (ASPD). Patients were randomly assigned to 4 study conditions: cognitive-behavioral treatment (CBT), contingency management (CM), CBT with CM, or methadone maintenance. The Structural Clinical Interview for Mental Disorders-IV was administered to 108 patients to assess ASPD. A 2-way analysis of variance showed that patients with ASPD were more likely to abstain from cocaine use during treatment than patients without ASPD. The strong treatment effect for ASPD patients was primarily due to the CM condition. Regression analyses showed that ASPD remained significantly related to CM treatment responsivity while controlling for other factors.", "Auricular acupuncture is widely used to treat cocaine addiction in the United States and Europe. However, evidence from controlled studies regarding this treatment's effectiveness has been inconsistent.\n To investigate the effectiveness of auricular acupuncture as a treatment for cocaine addiction.\n Randomized, controlled, single-blind clinical trial conducted from November 1996 to April 1999.\n Six community-based clinics in the United States: 3 hospital-affiliated clinics and 3 methadone maintenance programs.\n Six hundred twenty cocaine-dependent adult patients (mean age, 38.8 years; 69.2% men); 412 used cocaine only and 208 used both opiates and cocaine and were receiving methadone maintenance.\n Patients were randomly assigned to receive auricular acupuncture (n = 222), a needle-insertion control condition (n = 203), or a relaxation control condition (n = 195). Treatments were offered 5 times weekly for 8 weeks. Concurrent drug counseling was also offered to patients in all conditions.\n Cocaine use during treatment and at the 3- and 6-month postrandomization follow-up based on urine toxicology screens; retention in treatment.\n Intent-to-treat analysis of urine samples showed a significant overall reduction in cocaine use (odds ratio, 1.40; 95% confidence interval, 1.11-1.74; P =.002) but no differences by treatment condition (P =.90 for acupuncture vs both control conditions). There were also no differences between the conditions in treatment retention (44%-46% for the full 8 weeks). Counseling sessions in all 3 conditions were poorly attended.\n Within the clinical context of this study, acupuncture was not more effective than a needle insertion or relaxation control in reducing cocaine use. Our study does not support the use of acupuncture as a stand-alone treatment for cocaine addiction or in contexts in which patients receive only minimal concurrent psychosocial treatment. Research will be needed to examine acupuncture's contribution to addiction treatment when provided in an ancillary role.", "In this study, the authors evaluated a low-cost contingency management (CM) procedure for reducing cocaine use and enhancing group therapy attendance in 77 cocaine-dependent methadone patients. Patients were randomly assigned to 12 weeks of standard treatment or standard treatment with CM, in which patients earned the opportunity to win prizes ranging from $1 to $100 for submitting cocainenegative samples and attending therapy. Patients in the CM condition submitted more cocaine-negative samples and attended more groups than patients in standard treatment. The best predictor of cocaine abstinence at follow-up was duration of abstinence during treatment. On average, patients in the CM condition earned $117 in prizes. Data from this study suggest that some aspects of reinforcement can be implemented in group therapy in community-based clinics.\n Copyright (c) 2005 APA, all rights reserved" ]	Current evidence from randomised controlled trials does not support the use of dopamine agonists for treating cocaine dependence. This absence of evidence may leave to clinicians the alternative of balancing the possible benefits against the potential adverse effects of the treatment.Even the potential benefit of combining a dopamine agonist with a more potent psychosocial intervention which was suggested by the previous Cochrane review (Soares 2003), is not supported by the results of this updated review.
CD005193	[ "10587936", "15282836", "17071020", "11258740", "9513628" ]	[ "Comparing the impact of standard and abbreviated treatment in a therapeutic community. Findings from the district of Columbia treatment initiative experiment.", "Modified TC for MICA offenders: crime outcomes.", "Adapting judicial supervision to the risk level of drug offenders: discharge and 6-month outcomes from a prospective matching study.", "Multisystemic treatment of substance-abusing and dependent delinquents: outcomes, treatment fidelity, and transportability.", "Increasing participation in substance abuse aftercare treatment." ]	[ "This study examines the efficacy of providing Enhanced Abbreviated or Standard Inpatient treatment and Outpatient treatment to drug-abusing clients. The experiment randomly assigned 412 clients to two therapeutic community programs, which differed primarily in planned duration. This study addressed limitations of prior research, as it used random assignment of clients to treatment programs, achieved high follow-up rates and used objective measures of drug use and criminal history. Self-reports and objective measures of criminal activity and substance abuse were collected at pre- and posttreatment interviews. Completing the entire 12-month program (inpatient and outpatient) was more important than duration of inpatient program attended. Regardless of program, completers had substantial reductions in posttreatment drug abuse and arrests. A 12-month course of treatment including at least 6 months in a therapeutic community followed by outpatient treatment can produce marked reductions in drug abuse and crime among persons who complete both phases.", "The study randomly assigned male inmates with co-occurring serious mental illness and chemical abuse (MICA) disorders to either modified therapeutic community (MTC) or mental health (MH) treatment programs. On their release from prison, MICA inmates who completed the prison MTC program could enter the MTC aftercare program. The results, obtained from an intent-to-treat analysis of all study entries, showed that inmates randomized into the MTC group had significantly lower rates of reincarceration compared with those in the MH group. The results also show that differences between the MTC + aftercare and comparison group across a variety of crime outcomes (i.e. any criminal activity, and alcohol or drug related criminal activity) are consistent and significant, and persist after an examination of various threats to validity (e.g. initial motivation, duration of treatment, exposure to risk). This study provides some support for the effectiveness of the prison TC only condition. The findings are encouraging and consonant with other studies of integrated prison and aftercare TC programs for substance abusing non-MICA offenders, although qualified by the possibility that selection bias (i.e. differences in motivation on entry into aftercare) may be operating. Nevertheless, given the available evidence and the need for effective programming for MICA offenders, program and policy makers should strongly consider developing integrated prison and aftercare modified TC programs for MICA offenders.\n Copyright 2004 John Wiley & Sons, Ltd.", "This article reports recent findings from a program of experimental research examining the effects of adapting judicial supervision to the risk level of drug-abusing offenders. Prior studies revealed that high-risk participants with (1) antisocial personality disorder or (2) a history of drug abuse treatment performed significantly better in drug court when they were scheduled to attend frequent, bi-weekly judicial status hearings in court. Low-risk participants performed equivalently regardless of the schedule of court hearings. The current study prospectively matched misdemeanor drug court clients to the optimal schedule of court hearings based upon an assessment of their risk status, and compared outcomes to those of clients randomly assigned to the standard schedule of court hearings. Results confirmed that high-risk participants graduated at a higher rate, provided more drug-negative urine specimens at 6 months post-admission, and reported significantly less drug use and alcohol intoxication at 6 months post-admission when they were matched to bi-weekly hearings as compared to the usual schedule of hearings. These findings yield practical information for enhancing the efficacy and cost-efficiency of drug court services. Directions for future research on adaptive programming for drug offenders are discussed.", "The effectiveness and transportability of multisystemic therapy (MST) were examined in a study that included 118 juvenile offenders meeting DSM-III-R criteria for substance abuse or dependence and their families. Participants were randomly assigned to receive MST versus usual community services. Outcome measures assessed drug use, criminal activity, and days in out-of-home placement at posttreatment (T2) and at a 6-month posttreatment follow-up (T3); also treatment adherence was examined from multiple perspectives (i.e., caregiver, youth, and therapist). MST reduced alcohol, marijuana, and other drug use at T2 and total days in out-of-home placement by 50% at T3. Reductions in criminal activity, however, were not as large as have been obtained previously for MST. Examination of treatment adherence measures suggests that the modest results of MST were due, at least in part, to difficulty in transporting this complex treatment model from the direct control of its developers. Increased emphasis on quality assurance mechanisms to enhance treatment fidelity may help overcome barriers to transportability.", "Increasing the length of participation in alcohol and drug treatment is associated with improved outcomes (1). The present study was designed to increase substance abuse aftercare participation following completion of inpatient treatment. We compared the effect of a 20-minute aftercare orientation session to a minimal treatment condition on aftercare group therapy participation. The orientation session was conducted by an aftercare group therapist, who met with the participant to encourage him to attend aftercare, to explain why aftercare is helpful, and to have him sign an aftercare participation contract. Participants in the minimal treatment condition watched a videotape on motivation to reach goals. Participants were 40 males in an inpatient substance abuse treatment program at a Veterans Affairs Medical Center (VAMC). Ninety percent were alcohol dependent; 35% were cocaine dependent; 10% were marijuana dependent; and 10% were polysubstance dependent. Participants who received the aftercare orientation were more likely to attend aftercare (70%) than those who received the minimal treatment (40%). Additionally, the former group attended more sessions (x = 3.0) than those who were not oriented to aftercare (x = 1.4). The utility and limitations of a brief orientation session on aftercare adherence are discussed." ]	Limited conclusions can be drawn about the effectiveness of drug treatment programmes for drug-using offenders in the courts or the community. This is partly due to the broad range of studies and the heterogeneity of the different outcome measures presented. Therapeutic communities with aftercare show promising results for the reduction of drug use and criminal activity in drug using offenders. Standardisation of outcome measures and costing methodology would help improve the quality of research conducted in the area.
CD000523	[ "18260482", "7675718", "1527129", "2670950" ]	[ "Conservative management of minimally displaced isolated fractures of the ulnar shaft.", "Treatment of ulnar shaft fractures: a prospective, randomized study.", "Isolated ulnar shaft fractures. Comparison of treatment by a functional brace and long-arm cast.", "Operative or conservative treatment for trochanteric fractures of the femur. A randomised epidemiological trial in elderly patients." ]	[ "The purpose of this prospective study was to compare three different ways of conservative management of isolated fractures of the ulnar shaft: immediate mobilisation, below-elbow plaster cast and above-elbow plaster cast immobilisation. Over a 24-month period, 102 minimally displaced isolated fractures of the distal two-thirds of the ulnar shaft were treated on an outpatient basis. Thirty-two fractures were immobilised with an above-elbow plaster cast for 3 weeks and a below-elbow plaster cast for an additional 3 weeks. Thirty-six fractures were immobilised with a below-elbow plaster cast for 6 weeks. The remaining 34 fractures were managed with immediate mobilisation. Radiological healing, range of motion of the wrist, and pain were assessed. Results were good and were comparable in terms of healing, time to healing, pain and range of motion of the wrist.", "The treatment of isolated ulnar shaft fractures is controversial. Previous studies comparing treatment options have been largely retrospective and nonrandomized. In this study, consecutive patients were randomized into treatment groups of long arm plaster immobilization, short arm plaster immobilization, or Ace Wrap bandage, based on the order of hospital admission. Thirty-one patients were followed until radiographic or clinical union, with no significant difference in time to union between groups. Age, sex, fracture pattern, and displacement did not significantly influence time to union or final angulation. Two patients in both the long arm cast group and the short arm cast group lost significant motion at final follow up. Seventy percent of patients in the Ace Wrap group failed treatment secondary to pain and were converted to plaster immobilization. Furthermore, patients in this group demonstrated significantly greater angulation than those treated in a long arm cast. Our results demonstrate that above-elbow plaster immobilization offers no advantage over below-elbow immobilization. We recommend short arm casting for a period of 8 weeks.", "In a prospective study, we randomly allocated 39 patients with isolated fractures of the lower two-thirds of the ulnar shaft to treatment either by a prefabricated functional brace or a long-arm cast. Significantly better wrist function and a higher percentage of satisfied patients were found in the braced group. Thirteen patients returned to employment while still wearing the brace but only one was able to work in a cast.", "All elderly patients with extracapsular hip fractures seen in hospitals in Newcastle upon Tyne over a 12-month period were studied and followed up for six months. At one of the hospitals, patients were randomised to treatment by AO dynamic hip-screw or by traction. Complications specific to the two treatments were low, and general complications, six-month mortality and prevalence of pain, leg swelling and unhealed sores, showed no difference between the two modes of treatment. Operative treatment gave better anatomical results and a shorter hospital stay, but significantly more of the patients treated by traction showed loss of independence six months after injury." ]	There is insufficient evidence from randomised trials to determine which method of treatment is the most appropriate for isolated fractures of the ulnar shaft in adults. Well designed and reported randomised trials of current forms of conservative treatment are recommended.
CD001415	[ "10448830", "8232945", "1907907", "11407953" ]	[ "Gabapentin as add-on therapy in children with refractory partial seizures: a 12-week, multicentre, double-blind, placebo-controlled study. Gabapentin Paediatric Study Group.", "Gabapentin as add-on therapy in refractory partial epilepsy: a double-blind, placebo-controlled, parallel-group study. The US Gabapentin Study Group No. 5.", "Double-blind study of Gabapentin in the treatment of partial seizures.", "A randomized open-label study of gabapentin and lamotrigine in adults with learning disability and resistant epilepsy." ]	[ "To evaluate the efficacy and safety of gabapentin (Neurontin; GBP) as add-on therapy for refractory partial seizures in paediatric patients aged 3-12 years.\n After a 6-week baseline period, 247 patients (54 centres) entered a 12-week double-blind phase and were randomized to receive either GBP (t.i.d., titrated to 23-35 mg/kg/ day) or placebo. Seizure activity and type were recorded daily. Efficacy variables included Response Ratio (RRatio), responder rate, and percentage change in frequency (PCH) for all partial seizures; PCH and RRatio for individual types of partial seizures; and investigator and parent/guardian global assessments of seizure frequency and patient well-being.\n RRatio for all partial seizures was significantly lower (better) for GBP-treated patients (p = 0.0407). Responder rate favored GBP, but the difference between treatment groups was not statistically significant. Median PCH for all partial seizures for the GBP treatment group (-17.0%) was better than that for the placebo group (-6.5%). Median PCH for specific seizure types showed GBP to be most effective in controlling complex partial seizures (-35%) and secondarily generalized seizures (-28%) when compared with placebo (-12%, +13%, respectively). A greater percentage of GBP-treated patients exhibited improvement according to investigator and parent/guardian global assessments, with a statistically significant difference observed in the parent/guardian global assessment of seizure-frequency reduction (p = 0.046). Three GBP patients and one placebo patient were seizure free during the double-blind treatment period. GBP was well tolerated.\n GBP was effective and well tolerated as an add-on therapy for partial seizures in paediatric patients with previously drug-resistant seizures.", "Gabapentin, administered as add-on therapy, was safe and effective in this 12-week, multicenter, placebo-controlled, parallel-group study in 306 patients with refractory partial epilepsy. For patients in each gabapentin treatment group (600, 1,200, or 1,800 mg/d), the mean response ratio was significantly better than that of a placebo group. The percentage of patients achieving at least a 50% reduction in seizure frequency was 8% among placebo-treated patients and ranged from 18% to 26% for patients who received gabapentin. Adverse events were generally mild and transient and occurred at a slightly higher frequency among patients receiving gabapentin than among those receiving placebo. Gabapentin did not affect the serum concentrations of concurrent antiepileptic drugs and was not regularly associated with any deviations in clinical laboratory values. Gabapentin's low inherent toxicity and its lack of drug interactions make it an ideal candidate for use as add-on therapy in patients with refractory partial epilepsy.", "Forty-three patients completed a double-blind, placebo-controlled study of Gabapentin (GBP) as add-on therapy in partial and secondarily generalized seizures. All patients were followed for an initial 3-month baseline period, after which they were randomly allocated to receive either a placebo or 900 or 1,200 mg/day GBP for 3 months. A statistically significant difference in seizure frequency from the baseline to the treatment phase was noted between patients receiving placebo and GBP 1,200 mg, in whom seizure frequency decreased 57%. The GBP dosage of 900 mg appeared to be ineffective. A close relationship was observed between the serum GBP concentrations and the GBP dosage based on the seizure frequency. Serum GBP concentrations greater than 2 micrograms/ml resulted in a lower frequency of seizures. The adverse effects were minor and consisted mainly of transient drowsiness. GBP appears to be effective in the treatment of partial epileptic seizures in a dosage-related manner.", "The aim of this study was to evaluate the efficacy and safety of gabapentin in patients with learning disabilities and resistant epilepsy, comparing the effects of gabapentin with lamotrigine on efficacy, behaviour and mood. An open-label, randomized, parallel group, multicentre add-on study comparing gabapentin with lamotrigine in 109 patients with drug-resistant localization-related epilepsy and learning disabilities was conducted: 39 patients were randomized to gabapentin and 44 to lamotrigine. The study population had a range of learning disabilities and severe partial epilepsy. The percentage of patients achieving a greater than or equal to 50% reduction in seizure frequency on gabapentin was 50%, (mean reduction in seizures was 51%). Compared to 48.6% of lamotrigine patients, no statistically significant treatment differences could be identified. The safety profile of both drugs was consistent with that seen in previous clinical trials. Carer-rated visual analogue scales detected significant improvements (P< 0.05) for the gabapentin-treated patients in seizure severity, attention, general health and sleeping pattern, while for lamotrigine seizure severity improved significantly. For learning disabled patients with resistant epilepsy, gabapentin and lamotrigine provide safe and effective treatment, with positive benefits on behaviour." ]	Gabapentin has efficacy as an add-on treatment in people with drug-resistant partial epilepsy. However, trials reviewed were of relatively short duration, and provide no evidence for the long-term efficacy of gabapentin. Results cannot be extrapolated to monotherapy or people with other epilepsy types.
CD006863	[ "2512486" ]	[ "The effect of protein restriction on the progression of renal insufficiency." ]	[ "Dietary protein intake may be an important determinant of the rate of decline in renal function in patients with chronic renal insufficiency. We conducted a prospective, randomized study of the efficacy of protein restriction in slowing the rate of progression of renal impairment. The study lasted 18 months and included 64 patients with serum creatinine concentrations ranging from 350 to 1000 micromol per liter. The patients were randomly assigned to follow either a regular diet or an isocaloric protein-restricted diet (0.4 g of protein per kilogram of the body weight per day). Blood-pressure levels and the balance between calcium and phosphate were similar in the two groups. End-stage renal failure developed in 9 of the 33 patients (27 percent) who followed the regular diet during the study, as compared with 2 of the 31 patients (6 percent) who followed the protein-restricted diet (P less than 0.05). The mean (+/- SE) glomerular filtration rate, as measured by the clearance of 51Cr bound to EDTA, fell from 0.25 +/- 0.03 to 0.10 +/- 0.05 ml per second (P less than 0.01) in the group on the regular diet, whereas it fell from 0.23 +/- 0.04 to 0.20 +/- 0.05 ml per second (P not significant) in the group on the protein-restricted diet. We conclude that dietary protein restriction is effective in slowing the rate of progression of chronic renal failure." ]	Reducing protein intake does not appear to have significant impact in delaying the progression to ESKD in children.
CD004378	[ "10575581", "16055454", "10966992", "11228214" ]	[ "Clinical outcome of day 2 versus day 3 embryo transfer using serum-free culture media: a prospective randomized study.", "Live birth rate is significantly higher after blastocyst transfer than after cleavage-stage embryo transfer when at least four embryos are available on day 3 of embryo culture. A randomized prospective study.", "Day 5 versus day 3 embryo transfer: a controlled randomized trial.", "A prospective, randomized study comparing day 2 and day 3 embryo transfer in human IVF." ]	[ "The objective was to evaluate whether extending the embryo culture period from 2 to 3 days would yield a more optimal selection of viable embryos, thereby increasing the implantation and live birth rates.\n Patients undergoing in vitro fertilization with at least one oocyte fertilized were prospectively randomized to 2 or 3 days of embryo culture in serum-free media. On the basis of their morphology and cleavage rate, a maximum of three embryos was selected for transfer.\n Embryos transferred on day 2 or day 3 were similar morphologically, however, a higher proportion of retarded embryos was observed on day 3. The implantation rate was 15.8 and 14.3% for day 2 and day 3 transfers, respectively. The increase in live birth rate from 18.5 to 22.6%, possibly suggesting a better embryo selection on day 3, was not statistically significant.\n Extending the embryo culture period from 2 to 3 days had no effect on implantation and live birth rates.", "In a randomized controlled trial, we assessed whether pregnancy outcome would be improved by extending embryo culture to day 5 and transferring a blastocyst in patients with at least four good-quality embryos on day 3.\n Multifollicular ovarian stimulation was performed with a GnRH agonist in 44% of patients and with a GnRH antagonist in 56%. Overall, 164 patients younger than 37 years fulfilled embryo quality criteria (at least four having at least six cells on the morning of day 3, maximum 20% anucleate fragments) on the third day of culture and were randomized to the day 3 (n = 84) or day 5 (n = 80) groups. Equal numbers of embryos (n = 2) were transferred in each group.\n Demographics, stimulation parameters and embryological data were comparable in the two groups. Blastocyst-stage transfer resulted in a significantly higher ongoing pregnancy rate [51.3 versus 27.4%; odds ratio (OR) 2.78, 95% confidence interval (CI) 1.45-5.34] and live birth rate (47.5 versus 27.4%; OR 2.40, 95% CI 1.25-4.59) compared with day-3 embryo transfer. A high twin birth rate was observed in both groups (36.8 versus 30.4%; P > 0.05).\n A threshold of four good embryos on the third day of embryo culture appears to indicate that the patient will benefit from embryo transfer at the blastocyst stage and have a better chance of achieving a live delivery than with cleavage-stage embryo transfer.", "Blastocyst transfer has been suggested to improve implantation rate without affecting pregnancy rate. The aim of this study was to compare the pregnancy and implantation rates of day 3 and 5 transfers in a prospective randomized manner. Patients with four or more zygotes were randomly allocated on day 1 to either day 3 or 5 transfers. Fertilization was achieved through regular IVF or intracytoplasmic sperm injection. Zygotes were kept in Medicult IVF medium for day 3 transfers and transferred into G1.2 and G2.2 on day 1 and 3 respectively for day 5 transfers. The morphologically best two or three embryos or blastocysts were chosen for transfer in both groups. Overall pregnancy rates per embryo transfer were the same (39%) in day 3 and 5 transfers. Implantation rates were 21 and 24% for day 3 and 5 transfers respectively. The pregnancy and implantation rates for day 5 transfers were significantly affected by the availability of at least one blastocyst to transfer and the number of zygotes. The number of good quality embryos on day 3 also significantly affected pregnancy and implantation rates on day 5 transfers. Multiple gestation rate, number of abortions and ongoing pregnancies were similar in both groups. In conclusion, day 3 and 5 transfer had similar pregnancy, implantation and twinning rates. Currently, day 5 transfers have no advantages over day 3 transfers.", "It is believed that delayed transfer of embryos after IVF allows for a better selection of good quality embryos. Hence, the number of embryos and all other prognostic factors being equal, transfer of day 3 embryos should be associated with higher implantation and pregnancy rates than transfer of day 2 embryos. To investigate this hypothesis, a prospective randomized study was carried out to compare implantation and pregnancy rates between day 2 and day 3 transfers. The relationship between the embryo quality score of day 2 and day 3 embryos and their respective implantation rates was also analysed. In a 2 year period all patients undergoing infertility treatment and in whom at least seven normally fertilized oocytes were obtained were included in the study. A minimization procedure was performed taking into account the patient's age and the method of fertilization (IVF or intracytoplasmic sperm injection). By using a uniform policy of embryo transfer, the number of embryos transferred was similar in both groups. The outcome parameters were embryo quality, implantation and pregnancy rates. No difference was observed in implantation and pregnancy rates between transfers on day 2 versus day 3 (23.8 versus 23.8% and 47.9 versus 46.8% respectively). The incidence of embryos of moderate to poor quality was higher in embryos cultured for 3 days compared with those cultured for 2 days. It is concluded that the outcomes of embryo transfer in terms of implantation and pregnancy rates are comparable for day 2 and day 3 embryos, although the overall embryo quality score decreases when embryos are kept in culture till day 3." ]	Although an increase in clinical pregnancy rate with day three embryo transfer was demonstrated, at present there is not sufficient good quality evidence to suggest an improvement in live birth when embryo transfer is delayed from day two to day three.
CD002285	[ "11226090", "11818760", "18679598", "10081532", "16428565", "2181138", "12855628", "18043058" ]	[ "The use of transcutaneous acupoint electrical stimulation for preventing nausea and vomiting after laparoscopic surgery.", "Electroacupuncture prophylaxis of postoperative nausea and vomiting following pediatric tonsillectomy with or without adenoidectomy.", "Evaluation of transcutaneous electroacupoint stimulation with the train-of-four mode for preventing nausea and vomiting after laparoscopic cholecystectomy.", "Effect and placebo effect of acupressure (P6) on nausea and vomiting after outpatient gynaecological surgery.", "Transcutaneous acupoint electrical stimulation with the ReliefBand for the prevention of nausea and vomiting during and after cesarean delivery under spinal anesthesia.", "Postoperative nausea is relieved by acupressure.", "Effect of acupuncture compared with placebo-acupuncture at P6 as additional antiemetic prophylaxis in high-dose chemotherapy and autologous peripheral blood stem cell transplantation: a randomized controlled single-blind trial.", "Monitoring of neuromuscular blockade at the P6 acupuncture point reduces the incidence of postoperative nausea and vomiting." ]	[ "Nonpharmacologic techniques may be effective in preventing postoperative nausea and vomiting (PONV). This sham-controlled, double-blinded study was designed to examine the antiemetic efficacy of transcutaneous acupoint electrical stimulation (TAES) in a surgical population at high risk of developing PONV. We studied 221 outpatients undergoing laparoscopic cholecystectomy with a standardized general anesthetic technique in this randomized, multicenter trial. In the TAES group, an active ReliefBand(Woodside Biomedical, Inc., Carlsbad, CA) device was placed at the P6 acupoint, whereas in the Sham and Placebo groups, an inactive device was applied at the P6 acupoint and at the dorsal aspect of the wrist, respectively. The ReliefBand was applied after completion of electrocautery and remained in place for 9 h after surgery. The incidence of PONV and need for \"rescue\" medication were evaluated at predetermined time intervals. TAES was associated with a significantly decreased incidence of moderate-to-severe nausea as denoted on the Functional Living Index-Emesis score for up to 9 h after surgery (5%-11% for the TAES group vs 16%-38% [P < 0.05] and 15%-26% [P < 0.05] for Sham and Placebo groups, respectively). TAES was also associated with a larger proportion of patients free from moderate to severe nausea symptoms (73% vs 41% and 49% for Sham and Placebo groups, respectively; P < 0.05). However, there were no statistically significant differences among the three groups with regard to incidence of vomiting or the need for rescue antiemetic drugs. We conclude that TAES with the ReliefBand at the P6 acupoint reduces nausea, but not vomiting, after laparoscopic cholecystectomy.\n Transcutaneous acupoint electrical stimulation at the P6 acupoint reduced postoperative nausea, but not vomiting, in outpatients undergoing laparoscopic cholecystectomy procedures.", "Electrical stimulation of acupuncture point P6 reduces the incidence of postoperative nausea or vomiting (PONV) in adult patients. However, acupressure, laser stimulation of P6, and acupuncture during anesthesia have not been effective for reducing PONV in the pediatric population. The authors studied the effect of electrical P6 acupuncture in awake pediatric patients who had undergone surgery associated with a high incidence of PONV.\n Patients aged 4-18 yr undergoing tonsillectomy with or without adenoidectomy were randomly assigned to acupuncture, sham acupuncture, or control groups. Acupuncture needles at P6 and a neutral point were placed while patients were anesthetized, and low-frequency electrical stimulation was applied to these points for 20 min in the recovery room while the patients were awake (P6 Acu group). This treatment was compared with sham needles along the arm at acupuncture points not associated with antiemesis (sham group) and a no-needle control group. The arms were wrapped to prevent identification of treatment group, and anesthetic, analgesic, and surgical technique were standardized. Assessed outcomes were occurrence of nausea, occurrence and number of episodes of vomiting, time to vomiting, and use of antiemetic rescue medication.\n One hundred twenty patients were enrolled in the study, 40 per group. There were no differences in age, weight, sex, or opioid administration between groups. The PONV incidence was significantly lower with P6 acupuncture (25 of 40 or 63%; odds ratio, 0.135; number needed to treat, 3.3; P < 0.001) compared with controls (37 of 40 or 93%). Sham puncture had no effect on PONV (35 of 40 or 88%; P = not significant). Occurrence of nausea was significantly less in P6 Acu (24 of 40 or 60%; odds ratio, 0.121; P < 0.01), but not in the sham group (34 of 40 or 85%) compared with the control group (37 of 40 or 93%). Vomiting occurred in 25 of 40 or 63% in P6 Acu; 35 of 40 or 88% in the sham group, and 31 in 40 or 78% in the control group (P = not significant). Patients receiving sham puncture vomited significantly earlier (P < 0.02) and needed more rescue treatment (33 of 40 or 83%; odds ratio, 3.48; P < 0.02) compared with P6 Acu (23 of 40 or 58%) and the control group (24 of 40 or 60%).\n Perioperative P6 electroacupuncture in awake patients significantly reduced the occurrence of nausea compared with the sham and control groups, but it did not significantly reduce the incidence or number of episodes of emesis or the use of rescue antiemetics. Sham acupuncture may exacerbate the severity but not the incidence of emesis. The efficacy of P6 acupuncture for PONV prevention is similar to commonly used pharmacotherapies. Its appropriate role in prevention and treatment of PONV requires further study.", "To evaluate the efficacy of transcutaneous electroacupoint stimulation with a train-of-four (TOF) mode for the prevention of postoperative nausea and vomiting (PONV) in the patients undergoing laparoscopic cholecystectomy.\n Ninety-six ASA Grade I - II patients scheduled for laparoscopic cholecystectomy were randomized into Neiguan (P6) electroacupoint stimulation group (treated group) and a placebo control group (placement of electrodes without electroacupoint stimulation). The anesthetic regimen was standardized by needling at Neiguan on the left side and connecting the TOF peripheral nerve stimulator. The incidence of nausea, vomiting, severity, antiemetic dosage and the degree of pain were assessed at 0, 60, 120 min, and 24 h after surgery.\n The incidence of nausea and vomiting, the dose of antiemetics and the occurrence of severe nausea were all significantly lower in the treated group compared with the control group and the score for pain was obviously reduced in patients of the treated group at 24 h post-operation (P<0.05 or P<0.01).\n Transcutaneous electroacupoint stimulation at P6 with the TOF mode could reduce the incidence and severity of nausea and vomiting with analgesic effects.", "Acupuncture and acupressure have previously been reported to possess antiemetic effect. We wanted to investigate the \"true\" and placebo effect of acupressure in prevention of postoperative nausea and vomiting (PONV).\n Sixty women undergoing outpatient minor gynaecological surgery were entered into a double-blind and randomised study. One group received acupressure with bilateral stimulation of P6 (A), a second group received bilateral placebo stimulation (P) and a third group received no acupressure wrist band and served as a reference group (R). PONV was evaluated as number of patients with complete response (no PONV), nausea only or vomiting. In addition, the need for rescue antiemetic medication and nausea after 24 h was registered.\n Complete response was obtained in 11, 11 and 9 patients in groups, A, P and R, respectively. Nine, 7 and 6 patients had nausea before discharge home, and 1, 1 and 8 patients were nauseated (8 vs 1 patient: P < 0.05) 24 h after operation in A, P and R groups, respectively. When compared to placebo acupressure (2 patients vomited and 5 needed rescue), significantly (P < 0.05) fewer needed rescue antiemetic medication after acupressure at P6 (no vomiting or rescue medication). When compared to the observation group (5 vomited and 4 needed rescue antiemetics), significantly fewer vomited after acupressure (P < 0.05)\n In patients undergoing brief gynaecological surgery, placebo effect of acupressure decreased nausea after 24 h but vomiting and need of rescue antiemetics was reduced only by acupressure with the correct P6 point stimulation.", "We randomized 94 patients undergoing cesarean delivery with spinal anesthesia to receive transcutaneous acupoint electrical stimulation using the ReliefBand at the P6 point (active group) or an active ReliefBand applied to the dorsum of the wrist (sham control group). The ReliefBand was applied 30-60 min preoperatively and left in place for 24 h. There was no statistically significant difference between the active and sham control groups in the incidence of intraoperative/postoperative nausea (30% versus 43%/23% versus 41%), vomiting (13% versus 9%/26 versus 37%), need for rescue antiemetics (23% versus 18%/34% versus 39%), or complete response (55% versus 57%/51% versus 34%). There was also no difference between the two groups in nausea scores, number of vomiting episodes, or patient satisfaction with postoperative nausea and vomiting management.", "One hundred and sixty-two general surgical patients were prospectively randomized to one of three treatments for postoperative nausea and vomiting: (1) acupressure using elasticated bands containing a plastic button to apply sustained pressure at the P6 (Neiguan) point above the wrist, (2) control dummy bands without the pressure button and (3) antiemetic injections of prochlorperazine with each opiate given and as required. All patients received papaveretum injections as required for pain, and additional prochlorperazine injections were prescribed if nausea was not controlled in groups 1 and 2. The severity of nausea was assessed using a linear analogue scale and was significantly (P = 0.002) reduced by acupressure on both days 1 and 2, in comparison to both controls and drug treated patients. The incidence of postoperative vomiting, and the need for unplanned antiemetic injections was also reduced by acupressure but this was not statistically significant. Acupressure can work and should be investigated in other clinical situations.", "The purpose is to investigate an additional antiemetic effect to ondansetron with needle acupuncture at P6 compared with nonskin-penetrating placebo acupuncture in patients undergoing high-dose chemotherapy and autologous peripheral blood stem cell transplantation.\n Eighty patients who were admitted to hospital for high-dose chemotherapy and autologous peripheral blood stem cell transplantation were included into a randomized placebo-controlled single-blind trial. The patients were randomized to receive acupuncture (n = 41) or noninvasive placebo acupuncture (n = 39) at the acupuncture point P6 30 min before first application of high-dose chemotherapy and the day after. All patients received 8 mg ondansetron/day i.v. as basic antiemetic prophylaxis. The main outcome measure was the rate of patients who either had at least one episode of vomiting or required any additional antiemetic drugs on the first 2 days of chemotherapy.\n The main outcome measure showed no significant difference (P = 0.82): 61% failure in the acupuncture group and 64% in the placebo acupuncture group (95% confidence interval of 3% difference: -18.1 and 24.3%). Comparing nausea, episodes of vomiting or retching and number of additionally required antiemetic drugs did not provide any discrepancy with the main result.\n This study suggests that in combination with ondansetron i.v., invasive needle acupuncture at P6 compared with nonskin-penetrating placebo acupuncture has no additional effect for the prevention of acute nausea and vomiting in high-dose chemotherapy.", "Electrical stimulation of the P6 acupuncture point reduces the incidence of postoperative nausea and vomiting (PONV). Neuromuscular blockade during general anesthesia can be monitored with electrical peripheral nerve stimulation at the wrist. The authors tested the effect of neuromuscular monitoring over the P6 acupuncture point on the reduction of PONV.\n In this prospective, double-blinded, randomized control trial, the authors investigated, with institutional review board approval and informed consent, 220 women undergoing elective laparoscopic surgery anesthetized with fentanyl, sevoflurane, and rocuronium. During anesthesia, neuromuscular blockade was monitored by a conventional nerve stimulator at a frequency of 1 Hz over the ulnar nerve (n = 110, control group) or over the median nerve (n = 110, P6 group) stimulating at the P6 acupuncture point at the same time. The authors evaluated the incidence of nausea and vomiting during the first 24 h.\n No differences in demographic and morphometric data were found between both groups. The 24-h incidence of PONV was 45% in the P6 acupuncture group versus 61% in the control group (P = 0.022). Nausea decreased from 56% in the control group to 40% in the P6 group (P = 0.022), but emesis decreased only from 28% to 23% (P = 0.439). Nausea decreased substantially during the first 6 h of the observation period (P = 0.009). Fewer subjects in the acupuncture group required ondansetron as rescue therapy (27% vs. 39%; P = 0.086).\n Intraoperative P6 acupuncture point stimulation with a conventional nerve stimulator during surgery significantly reduced the incidence of PONV over 24 h. The efficacy of P6 stimulation is similar to that of commonly used antiemetic drugs in the prevention of PONV." ]	This review complements data on post-operative nausea and vomiting suggesting a biologic effect of acupuncture-point stimulation. Electroacupuncture has demonstrated benefit for chemotherapy-induced acute vomiting, but studies combining electroacupuncture with state-of-the-art antiemetics and in patients with refractory symptoms are needed to determine clinical relevance. Self-administered acupressure appears to have a protective effect for acute nausea and can readily be taught to patients though studies did not involve placebo control. Noninvasive electrostimulation appears unlikely to have a clinically relevant impact when patients are given state-of-the-art pharmacologic antiemetic therapy.
CD001427	[ "7903180", "16629429", "2390654" ]	[ "Biochemical and physiological parameters of recovery in acute severe head injury: responses to multisensory stimulation.", "The efficacy of multidisciplinary rehabilitation in stable multiple sclerosis patients.", "Coma arousal procedure: a therapeutic intervention in the treatment of head injury." ]	[ "We investigated the efficacy of applying a programme of multisensory stimulation to patients with severe diffuse traumatic brain injury, during their admission to a tertiary neurosurgical intensive care unit. We attempted to determine the nature and extent of any physiological or biochemical changes occurring as a result of the multisensory stimulation in the initial period of their comatose state. The findings were inconclusive with no significant treatment effect demonstrated.", "To evaluate the short-term efficacy of multidisciplinary, inpatient rehabilitation of multiple sclerosis (MS) patients.\n A double-blind, randomized, parallel group design was used. The intervention group were offered comprehensive, multidisciplinary inpatient rehabilitation at the Haslev MS Hospital for an average of 35.5 days, while the control group received no treatment related to the study. All patients were examined in their homes twice with a 10-week interval. The rehabilitation of the intervention group started 2-3 weeks after the first examination and ended 2-3 weeks before the second examination. Impairment was assessed by the Multiple Sclerosis Impairment Scale and the Expanded Disability Status Scale. Disability was assessed by means of Guy's Neurological Disability Scale. Two specific scales were used to assess upper limb function and ambulation: The Nine-Hole Peg Test and timed 10-metre walking. Patients' own perception of bodily pain, bladder symptoms, spasticity, fatigue, impaired walking and transfers were recorded using visual analogue scales. Finally, quality of life was assessed using the Life Appreciation and Satisfaction Questionnaire and the Functional Assessment in Multiple Sclerosis.\n Two hundred and thirty-three patients were screened and of those 38 were included for treatment and 52 as controls.\n We found no statistically significant differences between the two groups in any of the outcome measures.\n Although the study was underpowered, the negative outcome exposes the difficulties in quantitative analyses of the efficacy of multidisciplinary rehabilitation, which is liable to confounding factors such as variation in the indication for treatment, in the placebo effect, and in the reliability and responsiveness of the outcome measures.", "This study reports on the efficacy of a 'coma arousal procedure'. This procedure involved a programme of vigorous sensory stimulation administered to comatose patients by relatives using Comakits. An experimental group of 12 severely head-injured patients received the coma arousal procedure while a matched control group did not. Total duration of coma and weekly Glasgow Coma Scale Scores were recorded for the two groups. Results indicate that the total duration of coma was significantly shorter and that coma lightened more rapidly for the experimental group." ]	This systematic review indicates that there is no reliable evidence to support, or rule out, the effectiveness of multisensory programmes in patients in coma or vegetative state.
CD000339	[ "11372943", "11886906", "10622478", "11514765", "6368412", "18162669", "1762007", "1592640", "9728307", "15686240", "18669966", "10076936", "2005167", "10232034", "11514766" ]	[ "Extramedullary fixation of 569 unstable intertrochanteric fractures: a randomized multicenter trial of the Medoff sliding plate versus three other screw-plate systems.", "Treatment of reverse oblique and transverse intertrochanteric fractures with use of an intramedullary nail or a 95 degrees screw-plate: a prospective, randomized study.", "Extramedullary fixation of 107 subtrochanteric fractures: a randomized multicenter trial of the Medoff sliding plate versus 3 other screw-plate systems.", "Prospective randomized controlled trial of an intramedullary nail versus dynamic screw and plate for intertrochanteric fractures of the femur.", "Intertrochanteric fractures: a comparison between fixation with a two-piece nail plate and Ender's nails.", "Intramedullary nailing versus fixed angle blade plating for subtrochanteric femoral fractures: a prospective randomised controlled trial.", "Treatment of intertrochanteric fractures: comparison of Ender nails and sliding screw plates.", "[The gamma-nail as a resilient alternative to the dynamic hip screw in unstable proximal femoral fractures in the elderly].", "Treatment of intertrochanteric fracture with the Gamma AP locking nail or by a compression hip screw--a randomised prospective trial.", "The standard Gamma nail or the Medoff sliding plate for unstable trochanteric and subtrochanteric fractures. A randomised, controlled trial.", "A prospective trial comparing the Holland nail with the dynamic hip screw in the treatment of intertrochanteric fractures of the hip.", "Prospective randomized comparison of gliding nail and gamma nail in the therapy of trochanteric fractures.", "Fixation of intertrochanteric fractures of the femur. A randomised prospective comparison of the gamma nail and the dynamic hip screw.", "[Classic nail versus DHS. A prospective randomised study of fixation of trochanteric femur fractures].", "Prospective randomized comparison between a dynamic hip screw and a mini-invasive static nail in fractures of the trochanteric area: preliminary results." ]	[ "We compared the efficacy of the Medoff sliding plate (MSP) with 3 other screw-plate systems for fixation of unstable intertrochanteric fractures in a randomized multicenter trial of 569 elderly patients. The MSP has biaxial dynamic capacity along both the neck and the shaft of the femur unlike the other systems, which lack dynamic capacity along the shaft. 268 fractures were operated on with the MSP, and 301 with the dynamic hip screw (DHS), with or without a trochanteric stabilizing plate (DHS/TSP) or with the dynamic condylar screw (DCS). The MSP had recently been shown to the surgeons. The patients in the groups were similar as regards age, domestic situation, preinjury walking ability and type of fracture. We followed the patients clinically and radiographically for at least 1 year. There was no significant difference in walking ability at follow-up or rate of return to home. Fixation failure occurred in 18/268 fractures operated on with the MSP, in 8/238 with the DHS, in 3/49 with the DHS/TSP and in 1/14 with the DCS. The difference in the rate of fixation failure was not statistically significant when the MSP group was compared to the 3 other groups. In 14 of the 18 fixation failures in the MSP group, the biaxial dynamic capacity of the MSP had not been used due to technical errors by surgeons, unfamiliar with the new method. No selection bias was found regarding fracture types in the 2 subgroups of patients with correct or inadequate biaxial dynamization. Extramedullary fixation of unstable intertrochanteric fractures with these implants showed a low failure rate. When using the MSP, biaxial dynamization must be correctly performed.", "Intertrochanteric fractures are composed of different anatomic patterns that vary in their degree of stability following open reduction and internal fixation. A particularly unstable group is classified as AO/OTA 31-A3, with the fracture pattern described as reverse oblique or transverse. The purpose of this study was to compare the results of intramedullary fixation with those of plate fixation for these intertrochanteric fractures in elderly patients.\n Thirty-nine elderly patients with AO/OTA 31-A3 intertrochanteric fractures of the femur were randomized into two treatment groups and were followed for a minimum of one year. The nineteen patients in Group I were treated with a 95 fixed-angle screw-plate (Dynamic Condylar Screw), and the twenty patients in Group II were treated with an intramedullary nail (Proximal Femoral Nail). The treatment groups were comparable with regard to all demographic and injury variables.\n Patients treated with an intramedullary nail had shorter operative times, fewer blood transfusions, and shorter hospital stays compared with those treated with a 95 screw-plate. Implant failure and/or nonunion was noted in seven of the nineteen patients who had been treated with the 95 screw-plate. Only one of the twenty fractures that had been treated with an intramedullary nail did not heal.\n The results of our study support the use of an intramedullary nail rather than a 95 screw-plate for the fixation of reverse oblique and transverse intertrochanteric fractures in elderly patients.", "We compared the efficacy of a load-sharing device, the Medoff sliding plate (MSP), with that of 3 other load-bearing screw-plate devices for the fixation of subtrochanteric fractures in a randomized multicenter trial of 107 elderly patients. 55 fractures were operated on with the MSP, and 52 with the dynamic hip screw (DHS) with or without a trochanteric stabilizing plate (TSP) or with the dynamic condylar screw (DCS). The patient material in the groups was similar regarding age, domestic situation, preinjury walking ability and fracture types. We followed the patients clinically and radiographically for a minimum of 1 year. There was no significant difference in walking ability or return rate to the home at follow-up. Fixation failure occurred in 1/55 fractures operated on with the MSP, in 3/32 with the DHS, in 3/12 with the DCS and in 2/8 with the DHS/TSR The difference in the rate of fixation failure was statistically significant, when the MSP group was compared to the 3 load-bearing devices in the other group (1 vs 8). On the basis of this experience, we think that the load-sharing principle of the MSP, which seems to facilitate fracture impaction and stability, appears to be a good alternative in extramedullary fixation of subtrochanteric fractures.", "To compare the surgical complications and functional outcome of the Gamma nail intramedullary fixation device versus the Richards sliding hip screw and plate device in intertrochanteric femoral fractures.\n A prospective, randomised controlled clinical trial with observer blinding.\n A regional teaching hospital in the United Kingdom.\n All patients admitted from the local population with intertrochanteric fractured femurs were included. There were 400 patients entered into the study and 399 followed-up to one year or death.\n The devices were assigned by randomization to either a short-type Gamma nail (203 patients) or a Richard's-type sliding hip screw and plate (197 patients).\n The main surgical outcome measurements were fixation failure and reoperation. A functional outcome of pain, mobility status, and range of movement were assessed until one year.\n The requirement for revision in the Gamma nail group was twelve (6%); for Richard's group, eight (4%). This was not statistically different (p = 0.29; odds ratio, 1.48 [0.59-3.7]). A subcapital femoral fracture occurred in the Richard's group. Femoral shaft fractures occurred with four in the Gamma nail group (2%) and none in the Richard's group (p = 0.13). Three required revision to another implant. Lag-screw cut-out occurred in eight patients in the gamma nail group (4%) and four in the Richard's group (2%). This was not statistically significant (p = 0.37; odds ratio, 2.29 [0.6-9.0]). The development of other postoperative complications was the same in both groups. There was no difference between the two groups in terms of early or long-term functional status at one year.\n The use of an intramedullary device in the treatment of intertrochanteric femoral fractures is still associated with a higher but nonsignificant risk of postoperative complications. Routine use of the Gamma nail in this type of fracture cannot be recommended over the current standard treatment of dynamic hip screw and plate.", "The progress of 182 patients who presented with intertrochanteric fractures was followed over a six month period. Eighty-seven patients were treated using Thornton/McLaughlin nail plates and 95 were treated using Ender's intramedullary nails. Each fracture was classified according to radiological position and mechanical stability. The results show that the more unstable fractures are more likely to develop unsatisfactory results. Post operatively, the different mechanical complications have been recorded at various stages. Those fractures fixed with a nail plate tended to develop varus deformity resulting from either bony collapse around the implant or implant failure, whereas those fixed with Ender's nails did not develop deformity at the fracture site but encountered distal migration of the nails at the knee. The use of a classification system in predicting post operative mechanical complications is considered, and the comparative merits and disadvantages of the two fixation systems is discussed, with suggestions for improvement in operative technique.", "To compare closed intramedullary nailing to open reduction and internal fixation using a fixed angle blade plate for the management of subtrochanteric femoral fractures.\n 58 patients were equally randomised to undergo either an intramedullary nailing (IN) or fixed angle blade plating (BP).\n There were no significant differences between the 2 groups with regard to age, time to surgery, operating time, receipt of blood transfusions, duration of hospital stay, or fracture classification. The revision rate was 28% (8/29) in the BP group and none in the IN group; the difference was statistically significant.\n Internal fixation using a fixed angle blade plate for subtrochanteric femoral fractures has higher implant failure and revision rates, compared to closed intramedullary nailing.", "The results of two fixation devices for the treatment of intertrochanteric fractures were compared in 220 patients--163 women and 57 men with a mean age of 81 +/- 10 years. One hundred and one patients were randomized to Ender nailing and 119 to fixation with a sliding screw plate (SSP). The two treatment groups were equal with respect to important preinjury variables. The two methods did not differ in operating time or perioperative blood loss. The proportions of good reduction of the fractures and of good positioning of the internal fixation devices were equal in the two groups. But the complication rate and the reoperation rate were more than twice as high in the Ender group than in the SSP group. The outcome at 1-year follow-up was approximately equal in the two groups.", "In a prospective randomised trial between September 1989 and June 1990 one hundred patients with per- and subtrochanteric fractures were consecutively treated by gamma-nail or DHS. The average age of both groups was about 80 years. The operation time for gamma-nailing was longer than for DHS implantation and also the postoperative blood loss was higher in the gamma-nail group. We found no difference of intraoperative blood loss, of perioperative lethality and in duration of hospital care. 90% of gamma-nail patients and 80% of DHS patients were successfully able to walk four days after operation with full weight bearing on the operated limb. Three patients in the DHS group with unstable fractures got cranial perforation of the cephalic screw mobilisation. Five patients of the gamma-nail group were reoperated, one case because of missed distal locking, one because of cranial perforation of the cephalic screw after varus dislocation of the proximal fragment. One patient suffered intraoperatively a proximal femur shaft fracture which was corrected during operation. In one case a wound hematoma was evacuated, an other patient needed secondary wound closure. Despite technical imperfection of implant and instruments, we conclude that the gamma-nail allows a very high percentage early and full weight bearing immediately after operation. So we consider that in the treatment of unstable pertrochanteric fractures of geriatric patients, the gamma-nail has proven to be more efficient than the DHS.", "The Gamma AP (Asia-Pacific) locking nail (GAPN) is a modification of the standard Gamma locking nail made especially for use in Oriental patients. We made a randomised prospective comparison of the compression hip screw (CHS) and the Gamma AP locking nail for the internal fixation of 60 intertrochanteric fractures of the hip in elderly patients by comparing perioperative details and analysing the radiographic and clinical results. The operation time for the GAPN group was shorter than for the CHS group and the intraoperative blood loss was lower. The Gamma AP nail enabled earlier mobilisation. We found no significant difference in the time to union and the length of sliding of the lag screw between the two groups. The decrease in the neck shaft angle in the Gamma nail group was significantly smaller than in the CHS patients. There were no significant mechanical complications, such as fracture of the femoral shaft or failure of fixation in the Gamma nail group. On the basis of our observations we conclude that the Gamma AP locking nail is more efficient than the CHS in the treatment of intertrochanteric fractures in geriatric patients.", "We studied 217 patients with an unstable trochanteric or subtrochanteric fracture who had been randomly allocated to treatment by either internal fixation with a standard Gamma nail (SGN) or a Medoff sliding plate (MSP, biaxial dynamisation mode). Their mean age was 84 years (65 to 99) and they were reviewed at four and 12 months after surgery. Assessments of outcome included general complications, technical failures, revision surgery, activities of daily living (ADL), hip function (Charnley score) and the health-related quality of life (HRQOL, EQ-5D). The rate of technical failure in patients with unstable trochanteric fractures was 6.5% (6/93) (including intra-operative femoral fractures) in the SGN group and 5.2% (5/96) in the MSP group. In patients with subtrochanteric fractures, there were no failures in the SGN group (n = 16) and two in the MSP group (n = 12). In the SGN group, there were intra-operative femoral fractures in 2.8% (3/109) and no post-operative fractures. There was a reduced need for revision surgery in the SGN group compared with the MSP group (8.3%; 9/108; p = 0.072). The SGN group also showed a lower incidence of severe general complications (p < 0.05) and a trend towards a lower incidence of wound infections (p = 0.05). There were no differences between the groups regarding the outcome of ADL, hip function or the HRQOL. The reduction in the HRQOL (EQ-5D(index) score) was significant in both groups compared with that before the fracture (p < 0.005). Our findings indicate that the SGN showed good results in both trochanteric and subtrochanteric fractures. The limited number of intra-operative femoral fractures did not influence the outcome or the need for revision surgery. Moreover, the SGN group had a reduced number of serious general complications and wound infections compared with the MSP group. The MSP in the biaxial dynamisation mode had a low rate of failure in trochanteric fractures but an unacceptably high rate when used in the biaxial dynamisation mode in subtrochanteric fractures. The negative influence of an unstable trochanteric or subtrochanteric fracture on the quality of life was significant regardless of the surgical method.", "We compared the outcome of patients treated for an intertrochanteric fracture of the femoral neck with a locked, long intramedullary nail with those treated with a dynamic hip screw (DHS) in a prospective randomised study. Each patient who presented with an extra-capsular hip fracture was randomised to operative stabilisation with either a long intramedullary Holland nail or a DHS. We treated 92 patients with a Holland nail and 98 with a DHS. Pre-operative variables included the Mini Mental test score, patient mobility, fracture pattern and American Society of Anesthesiologists grading. Peri-operative variables were anaesthetic time, operating time, radiation time and blood loss. Post-operative variables were time to mobilising with a frame, wound infection, time to discharge, time to fracture union, and mortality. We found no significant difference in the pre-operative variables. The mean anaesthetic and operation times were shorter in the DHS group than in the Holland nail group (29.7 vs 40.4 minutes, p < 0.001; and 40.3 vs 54 minutes, p < 0.001, respectively). There was an increased mean blood loss within the DHS group versus the Holland nail group (160 ml vs 78 ml, respectively, p < 0.001). The mean time to mobilisation with a frame was shorter in the Holland nail group (DHS 4.3 days, Holland nail 3.6 days, p = 0.012). More patients needed a post-operative blood transfusion in the DHS group (23 vs seven, p = 0.003) and the mean radiation time was shorter in this group (DHS 0.9 minutes vs Holland nail 1.56 minutes, p < 0.001). The screw of the DHS cut out in two patients, one of whom underwent revision to a Holland nail. There were no revisions in the Holland nail group. All fractures in both groups were united when followed up after one year. We conclude that the DHS can be implanted more quickly and with less exposure to radiation than the Holland nail. However, the resultant blood loss and need for transfusion is greater. The Holland nail allows patients to mobilise faster and to a greater extent. We have therefore adopted the Holland nail as our preferred method of treating intertrochanteric fractures of the hip.", "In a prospective randomized study, we compared the new intramedullary implant of the gliding nail to the gamma nail in the fixation of 80 unstable trochanteric fractures in elderly patients. The preconditions of both groups were comparable. We found no differences concerning the operation time, blood loss, period of stationary treatment or social situation. Also, the anatomic reconstruction and the long-term function according to the Merle d'Aubigne score were comparable. Regarding postoperative complications, the gliding nail showed a minor tendency of cutting out; this we attribute to the special design of the dynamic blade and regard it as the most favourable advantage of this new implant.", "We have prospectively compared the fixation of 100 intertrochanteric fractures of the proximal femur in elderly patients with random use of either a Dynamic Hip Screw (DHS) or a new intramedullary device, the Gamma nail. We found no difference in operating time, blood loss, wound complications, stay in hospital, place of eventual discharge, or the patients' mobility at final review. There was no difference in failure of proximal fixation: cut-out occurred in three cases with the DHS, and twice with the Gamma nail. However, in four cases fracture of the femur occurred close to the Gamma nail, requiring further major surgery. In the absence of these complications, union was seen by six months in both groups.", "The intramedullary hip screw system Classic-Nail and the Dynamic Hip Screw (DHS) were evaluated in a prospective-randomized clinical trial for operative treatment of trochanteric femur fractures. Hundred and ten geriatric patients (mean age 82 years) were runningly included in the study (56 Classic Nail, 54 DHS). No significant differences between the two study groups were observed with regard to treatment and follow-up data. With the Classic-Nail one complete femur shaft fracture and one incomplete fracture occurred at the tip of the nail intraoperatively and could successfully be fixed with cerclage wires. In the DHS group two patients underwent reoperation for significant loss of reduction early postoperatively. At an average follow-up of 3.7 months all fractures were healed with no difference in functional outcome between the two groups.--Classic Nail and DHS both lead to equally good results in the operative treatment of trochanteric femur fractures.", "This study aimed at comparing the results obtained with a sliding screw plate and an experimental device including a small-diameter nail that can be placed with a mini-invasive approach and provides a stable fixation.\n Randomized prospective study.\n University hospital.\n The study included two groups with thirty fractures of the trochanteric area.\n In both groups, the surgical procedure was carried out on patients placed on a traction table in a supine position, under an x-ray amplifier. Sliding screw plates (THS) were set in place according to the usual open technique. Nails were placed through a twenty-millimeter supratrochanteric cutaneous incision. This experimental system comprised a locked intramedullary nail with two nonparallel seven-millimeter cervicocephalic screws.\n The comparison between the two groups was based on the surgical procedure (time, duration of x-ray irradiation, and total blood loss); the initial postoperative period (complications, duration of hospital stay, and the time before returning home); the time before full weight bearing became effective; the functional and social recovery; mortality; and the quality of immediate and final anatomic restitution and healing.\n Operating time (p < 0.001) and blood loss (p < 0.001) were lower in the nail group, and no blood transfusion was required. Postoperative pain (p < 0.01), time necessary to support full weight bearing (p < 0.02), and time before returning home (p < 0.05) were reduced in the nail group. All fractures healed in the same amount of time, with good anatomic results in the nail group, whereas ten impactions beyond ten millimeters occurred in the plate group. No difference was found between the two groups in walking ability and autonomy recovery, but hip function (p < 0.05) was better in the nail group.\n This preliminary clinical study has shown the advantages of this mini-invasive technique. It could not evaluate all the possible disadvantages inherent in the method. These points will be evaluated in a multicenter study justified by these preliminary results." ]	The markedly increased fixation failure rate of fixed nail plates compared with the SHS is a major consideration and thus the SHS appears preferable. There was insufficient evidence from other comparisons of extramedullary implants or on the use of external fixators to draw definite conclusions.
CD000219	[ "16968847", "17846935", "9821420", "1912887", "12728089", "15930204", "19671372", "11159657", "10819344", "3277153", "15684116", "19434268", "6816006", "17353072" ]	[ "Wait-and-see prescription for the treatment of acute otitis media: a randomized controlled trial.", "Evaluation of phenoxymethylpenicillin treatment of acute otitis media in children aged 2-16.", "A multicenter, randomized, double-blind trial of 5 versus 10 days of antibiotic therapy for acute otitis media in young children.", "Acute red ear in children: controlled trial of non-antibiotic treatment in general practice.", "Antibiotic treatment of acute otorrhea through tympanostomy tube: randomized double-blind placebo-controlled study with daily follow-up.", "Nonsevere acute otitis media: a clinical trial comparing outcomes of watchful waiting versus immediate antibiotic treatment.", "A double-blind randomised placebo-controlled trial of topical intranasal corticosteroids in 4- to 11-year-old children with persistent bilateral otitis media with effusion in primary care.", "Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media.", "Five vs. ten days of antibiotic therapy for acute otitis media in young children.", "Five vs. ten days of therapy for acute otitis media.", "A randomized, double-blind, placebo-controlled noninferiority trial of amoxicillin for clinically diagnosed acute otitis media in children 6 months to 5 years of age.", "Management for the children with otitis media with effusion in the tertiary hospital.", "Penicillin treatment of acute otitis media in children. A study of the duration of treatment.", "Treatment of acute otitis media with probiotics in otitis-prone children-a double-blind, placebo-controlled randomised study." ]	[ "Acute otitis media (AOM) is the most common diagnosis for which antibiotics are prescribed for children. Previous trials that have evaluated a \"wait-and-see prescription\" (WASP) for antibiotics, with which parents are asked not to fill the prescription unless the child either is not better or is worse in 48 hours, have excluded children with severe AOM. None of these trials were conducted in an emergency department.\n To determine whether treatment of AOM using a WASP significantly reduces use of antibiotics compared with a \"standard prescription\" (SP) and to evaluate the effects of this intervention on clinical symptoms and adverse outcomes related to antibiotic use.\n A randomized controlled trial conducted between July 12, 2004, and July 11, 2005. Children with AOM aged 6 months to 12 years seen in an emergency department were randomly assigned to receive either a WASP or an SP. All patients received ibuprofen and otic analgesic drops for use at home. A research assistant, blinded to group assignment, conducted structured phone interviews 4 to 6, 11 to 14, and 30 to 40 days after enrollment to determine outcomes.\n Filling of the antibiotic prescription and clinical course.\n Overall, 283 patients were randomized either to the WASP group (n = 138) or the SP group (n = 145). Substantially more parents in the WASP group did not fill the antibiotic prescription (62% vs 13%; P<.001). There was no statistically significant difference between the groups in the frequency of subsequent fever, otalgia, or unscheduled visits for medical care. Within the WASP group, both fever (relative risk [RR], 2.95; 95% confidence interval [CI], 1.75 - 4.99; P<.001) and otalgia (RR, 1.62; 95% CI, 1.26 - 2.03; P<.001) were associated with filling the prescription.\n The WASP approach substantially reduced unnecessary use of antibiotics in children with AOM seen in an emergency department and may be an alternative to routine use of antimicrobials for treatment of such children.\n clinicaltrials.gov Identifier: NCT00250900.", "To study the clinical recovery from acute otitis media (AOM) in children, 2-16 years of age, managed with or without treatment with phenoxymethylpenicillin (PcV).\n An open, prospective randomized trial. Children aged between 2 and 16 years, presenting with one- or double-sided AOM (without perforation) with symptom duration of less than four days, were included. The children were randomized to PcV for five days or to no primary antibiotic treatment. A health score and compliance were registered on a daily basis for seven days.\n A total of 32 health centres and 72 GPs in south-east Sweden. Subjects. Children aged 2-16 presenting with earache.\n Recovery time, symptom duration, frequency of complications (up to three months) and consumption of healthcare services independent of treatment with or without antibiotics.\n A total of 179 patients carried out the trial; 92 were randomized to PcV, 87 to no primary antibiotic treatment. The median recovery time was four days in both groups. Patients who received PcV had less pain (p <0.001) and used fewer analgesics. There were no significant differences in the number of middle-ear effusions or perforations at the final control after three months. Children randomized to PcV treatment consulted less (p <0.001) during the first seven days.\n Our investigation supports that PcV treatment of AOM does not affect the recovery time or complication rates. PcV provided some symptomatic benefit in the treatment of AOM in otherwise healthy children, aged 2-16 years.", "All but 2 of the 15 published trials have failed to show a difference in efficacy between short (3 to 5 days) and standard (7 to 10 days) antibiotic regimens for acute otitis media (AOM). These studies involved relatively few patients under 2 years of age, who are at a higher risk for treatment failure.\n In a prospective, comparative, double-blind, randomized, multicenter trial, we compared amoxicillin/clavulanate in 3 divided doses for 10 days with an identical 5-day regimen, followed by a 5-day placebo period.\n Between February 1995 and May 1996, 385 children (mean age, 13.3 months) were enrolled, 194 in the 5-day treatment group and 191 in the 10-day treatment group. In the per protocol analysis, clinical success was obtained on days 12 to 14 after the beginning of treatment (main analysis) in 125 (76.7%) of the 163 children receiving the 5-day regimen and 148 (88.1%) of the 168 receiving the 10-day regimen (P = .006). Clinical success persisted on days 28 to 42 among 57 (40.4%) of the 141 assessable patients in the 5-day group and 64 (46%) of the 139 assessable patients in the 10-day group. (P = .34). Multivariate analysis showed that the 10-day course was statistically superior only among children cared for outside their homes (86.8% vs 70.8%; P = .008).\n When assessed on days 12 to 14 after the outset of treatment, a 5-day regimen is not equivalent to a 10-day regimen among young children with AOM.", "To examine the efficacy and safety of conservative management of mild otitis media (\"the acute red ear\") in children.\n Double blind placebo controlled trial.\n 17 group general practices (48 general practitioners) in Southampton, Bristol, and Portsmouth.\n 232 children aged 3-10 years with acute earache and at least one abnormal eardrum (114 allocated to receive antibiotic, 118 placebo).\n Amoxycillin 125 mg three times a day for seven days or matching placebo; 100 ml paracetamol 120 mg/5 ml.\n Diary records of pain and crying, use of analgesic, eardrum signs, failure of treatment, tympanometry at one and three months, recurrence rate, and ear, nose, and throat referral rate over one year.\n Treatment failure was eight times more likely in the placebo than the antibiotic group (14.4% v 1.7%, odds ratio 8.21, 95% confidence interval 1.94 to 34.7). Children in the placebo group showed a significantly higher incidence of fever on the day after entry (20% v 8%, p less than 0.05), mean analgesic consumption (0.36 ml/h v 0.21 ml/h, difference 0.14, 95% confidence interval 0.07 to 0.23; p = 0.0022), mean duration of crying (1.44 days v 0.50 days, 0.94; 0.50 to 1.38; p less than 0.001), and mean absence from school (1.96 days v 0.52 days, 1.45; 0.46 to 2.42; p = 0.0132). Differences in recorded pain were not significant. The prevalence of middle ear effusion at one or three months, as defined by tympanometry, was not significantly different, nor was there any difference in recurrence rate or in ear, nose, and throat referral rate in the follow up year. No characteristics could be identified which predicted an adverse outcome.\n Use of antibiotic improves short term outcome substantially and therefore continues to be an appropriate management policy.", "The role of routine antimicrobial treatment of acute middle-ear infections is under debate, because the efficacy of antimicrobials in the resolution of middle-ear fluid has not been unambiguously proven. Acute tube otorrhea is regarded as evidence of acute otitis media, and for methodologic reasons it was chosen to provide objectivity for diagnostics and outcome assessment. The objective of this study was to assess whether amoxicillin-clavulanate accelerates the resolution of acute tube otorrhea.\n Randomized, double-blind, placebo-controlled study in outpatient setting.\n Volunteer sample of basically healthy 6- to 72-month-old children with a tympanostomy tube. Eligibility required having acute tube otorrhea of <48 hours' of duration and no prior treatment within the last 2 weeks. The mean age of the participants was 25 months; they had a history of 3 episodes of acute otitis media (median), and 99% had manifestations of a concomitant respiratory infection. Of 79 randomized patients, 7 were withdrawn because of adverse events; 66 patients completed the study.\n Amoxicillin-clavulanate (N = 34; 45 mg/kg/d) or matching placebo (N = 32) for 7 days and daily suction of middle-ear fluid through tympanostomy tube.\n Duration of acute tube otorrhea and duration of bacterial growth in middle-ear fluid.\n The median duration of tube otorrhea was significantly shorter in amoxicillin-clavulanate than in the placebo group (3 vs 8 days). At the end of the 7-day medication period, tube otorrhea was resolved in 28 of 34 children receiving amoxicillin-clavulanate compared with 13 of 32 children on placebo (treatment-control difference 41%; 95% confidence interval, 20%-63%; number needed to treat, 2.4). The median duration of bacterial growth in middle-ear fluid was shorter in amoxicillin-clavulanate than in the placebo group (1 vs 8 days).\n Oral antibiotic treatment significantly accelerates the resolution of acute tube otorrhea by reducing bacterial growth in middle-ear fluid.", "The widespread use of antibiotics for treatment of acute otitis media (AOM) has resulted in the emergence of multidrug-resistant pathogens that are difficult to treat. However, it has been shown that most children with nonsevere AOM recover without ABX. The objective of this study was to evaluate the safety, efficacy, acceptability, and costs of a non-ABX intervention for children with nonsevere AOM.\n Children 6 months to 12 years old with AOM were screened by using a novel AOM-severity screening index. Parents of children with nonsevere AOM received an educational intervention, and their children were randomized to receive either immediate antibiotics (ABX; amoxicillin plus symptom medication) or watchful waiting (WW; symptom medication only). The investigators, but not the parents, were blinded to enrollment status. Primary outcomes included parent satisfaction with AOM care, resolution of symptoms, AOM failure/recurrence, and nasopharyngeal carriage of Streptococcus pneumoniae strains resistant to ABX. Secondary outcomes included medication-related adverse events, serious adverse events, unanticipated AOM-related office and emergency department visits and telephone calls, the child's absence from day care or school resulting from AOM, the parent's absence from school or work because of their child's AOM, and costs of treatment. Subjects were defined as failing (days 0-12) or recurring (days 13-30) if they experienced a higher AOM-severity score on reexamination.\n A total of 223 subjects were recruited: 73% were nonwhite, 57% were <2 years old, 47% attended day care, 82% had experienced prior AOM, and 83% had not been fully immunized with heptavalent pneumococcal vaccine. One hundred twelve were randomized to ABX, and 111 were randomized to WW. Ninety-four percent of the subjects were followed to the 30-day end point. Parent satisfaction with AOM care was not different between the 2 treatment groups at either day 12 or 30. Compared with WW, symptom scores on days 1 to 10 resolved faster in subjects treated with immediate ABX. At day 12, among the immediate-ABX group, 69% of tympanic membranes and 25% of tympanograms were normal, compared with 51% of normal tympanic membranes and 10% of normal tympanograms in the WW group. Parents of children in the ABX group gave their children fewer doses of pain medication than did parents of children in the WW group. Subjects in the ABX group experienced 16% fewer failures than subjects in the WW group. Of the children in the WW group, 66% completed the study without needing ABX. Immediate ABX resulted in eradication of S pneumoniae carriage in the majority of children, but S pneumoniae strains cultured from children in the ABX group at day 12 were more likely to be multidrug-resistant than strains from children in the WW group. More ABX-related adverse events were noted in the ABX group, compared with the WW group. No serious AOM-related adverse events were observed in either group. Office and emergency department visits, phone calls, and days of work/school missed were not different between groups. Prescriptions for ABX were reduced by 73% in the WW group compared with the ABX group. Costs of ABX averaged $47.41 per subject in the ABX group and $11.43 in the WW group.\n Sixty-six percent of subjects in the WW group completed the study without ABX. Parent satisfaction was the same between groups regardless of treatment. Compared with WW, immediate ABX treatment was associated with decreased numbers of treatment failures and improved symptom control but increased ABX-related adverse events and a higher percent carriage of multidrug-resistant S pneumoniae strains in the nasopharynx at the day-12 visit. Key factors in implementing a WW strategy were (a) a method to classify AOM severity; (b) parent education; (c) management of AOM symptoms; (d) access to follow-up care; and (e) use of an effective ABX regimen, when needed. When these caveats are observed, WW may be an acceptable alternative to immediate ABX for some children with nonsevere AOM.", "To determine the clinical effectiveness and cost-effectiveness of topical mometasone in children with bilateral otitis media with effusion (OME).\n A double-blind randomised placebo-controlled trial with an intention to treat analysis; the 10.6% of patients lost to follow-up at 1 month were censored in the analysis.\n 76 Medical Research Council General Practice Research Framework practices throughout the UK between 2004 and 2007.\n A sample of 217 children aged 4-11 years was selected from those presenting to their GP with one or more episodes of otitis media or ear-related problems in the previous 12 months whom the research nurse confirmed had bilateral glue ear using microtympanometry (B B or B C2 types using a modified Jerger classification) at randomisation.\n Mometasone 50 micrograms in each nostril or placebo spray once daily for 3 months.\n The primary outcome was the proportions of children cleared of OME assessed by tympanometry at 1 month. Secondary outcomes included clearance at 3 months and 9 months; adverse events; OM8-30 scores (a functional health status responsive disease-specific measure); hearing loss; days with otalgia; cost-effectiveness; and health utilities.\n Of the topical steroid group, 40.6% (39/96) demonstrated tympanometric clearance (C1 or A type) in one or both ears at 1 month, compared with 44.9% (44/98) of the placebo group. The absolute risk reduction at 1 month was -4.3% (95% CI -18.05% to 9.26%); the odds ratio (OR) was 0.84 (95% CI 0.48 to 1.48). Four covariates were pre-specified for inclusion in logistic regression analysis: age as a continuous variable (p = 0.94), season (p = 0.70), atopy (p = 0.61) and clinical severity (p = 0.006). The adjusted OR (AOR) at 1 month for the main outcome was 0.93 (95% CI 0.50 to 1.75). Secondary analysis at 3 months showed 58.1% of the steroid group had resolved and 52.3% of the placebo group, AOR 1.45 (95% CI 0.74 to 2.84). At 9 months 55.6% of the treated group remained clear in at least one ear and 65.3% of the placebo group, AOR 0.82 (95% CI 0.39 to 1.75). Adverse events (although relatively minor) occurred in 7-22% of children and included nasal stinging, epistaxis, dry throat and cough. The OM8-30 scores (p = 0.55) reported hearing difficulty (p = 0.08), and days with otalgia (p = 0.46) were not significantly different between groups at 3 months. The economic evaluation found the active treatment arm to be dominated by placebo, accruing slightly (but not significantly) higher costs and fewer quality-adjusted life-years (QALYs), with a 24.2% probability that topical steroids are a cost-effective use of NHS resources at a ceiling ratio of 20,000 pounds per QALY gained.\n Use of topical intranasal corticosteroids is very unlikely to be a clinically effective treatment for OME (glue ear) in the primary care setting.\n Current Controlled Trials ISRCTN38988331.", "To compare immediate with delayed prescribing of antibiotics for acute otitis media.\n Open randomised controlled trial. Setting: General practices in south west England.\n 315 children aged between 6 months and 10 years presenting with acute otitis media.\n Two treatment strategies, supported by standardised advice sheets-immediate antibiotics or delayed antibiotics (antibiotic prescription to be collected at parents' discretion after 72 hours if child still not improving).\n Symptom resolution, absence from school or nursery, paracetamol consumption.\n On average, symptoms resolved after 3 days. Children prescribed antibiotics immediately had shorter illness (-1.1 days (95% confidence interval -0.54 to -1.48)), fewer nights disturbed (-0.72 (-0.30 to -1.13)), and slightly less paracetamol consumption (-0.52 spoons/day (-0.26 to -0.79)). There was no difference in school absence or pain or distress scores since benefits of antibiotics occurred mainly after the first 24 hours-when distress was less severe. Parents of 36/150 of the children given delayed prescriptions used antibiotics, and 77% were very satisfied. Fewer children in the delayed group had diarrhoea (14/150 (9%) v 25/135 (19%), chi(2)=5.2, P=0.02). Fewer parents in the delayed group believed in the effectiveness of antibiotics and in the need to see the doctor with future episodes.\n Immediate antibiotic prescription provided symptomatic benefit mainly after first 24 hours, when symptoms were already resolving. For children who are not very unwell systemically, a wait and see approach seems feasible and acceptable to parents and should substantially reduce the use of antibiotics for acute otitis media.", "Many publications in recent years have argued in favor of shortened therapy for acute otitis media. However, doubt persists regarding children younger than 2 years, and some authors therefore restrict short course therapy to children older than 2 years.\n In a prospective, comparative, double blind, randomized, multicenter trial we compared cefpodoxime-proxetil, 8 mg/kg/day in two divided doses for 10 days, with an identical 5-day regimen followed by a 5-day placebo period.\n Between October, 1996, and April, 1997, 450 children (mean age, 14.3 months) were enrolled, 227 in the 5-day group and 223 in the 10-day group. In the per protocol analysis clinical success was obtained on Days 12 to 14 after the beginning of treatment (main analysis) in 175 (84.1%) of the 208 children receiving the 5-day regimen and 194 (92.4%) of the 210 children receiving the 10-day regimen (P = 0.009). The superiority of the standard regimen was more marked among children cared for outside their homes (92.5% vs. 81.5%). Clinical success persisted on Days 28 to 42 among 134 (85.4%) of the 157 assessable patients in the 5-day group and 144 (83.7%) of the 172 assessable patients in the 10-day group (P = 0.68).\n The 10-day regimen resulted in a higher success rate at the conclusion of therapy, but there were no differences between the two study groups 4 to 6 weeks after enrollment in the study protocol.", "In a double blind study 175 patients with acute otitis media were randomized into 2 treatment groups: 10 days of therapy with cefaclor or 5 days of therapy followed by 5 days of placebo. The dosage of cefaclor was 40 mg/kg/day administered orally in equally divided doses at 12-hour intervals. Tympanocentesis before treatment yielded specimens that contained Streptococcus pneumoniae or Haemophilus influenzae or both in 55% of specimens. Branhamella catarrhalis was isolated from 21% of specimens. Culture of material from the ear canal of patients with spontaneous perforation of the tympanic membrane of less than 24 hours duration yielded pneumococci or H. influenzae or both in 38% of specimens and staphylococci in 31%. Patients were scheduled for follow-up examinations at 5 or 6, 10, 30, 60 and 90 days. Of the 175 children 151 were evaluable at 10 days. There were 123 patients with both tympanic membranes intact at the time of diagnosis. There were 6 (10%) treatment failures of therapy in the 59 patients assigned to 5 days of therapy and 4 (6%) failures and 1 (2%) early relapse in the 64 assigned to 10 days of therapy (difference not significant). There were 28 evaluable patients with spontaneous perforation. There were 8 (53%) failures in the 15 children assigned to 5 days of therapy and only 1 (8%) failure in the 13 children assigned to receive 10 days of therapy (P = 0.016, Fisher exact test). Rates of reinfection and persistent middle ear effusion at 10, 30, 60 and 90 days follow-up were not significant different in patients assigned to 5 to 10 days of therapy. In patients with acute otitis media with intact tympanic membranes we have not been able to show any advantage of the standard duration of 10 days of therapy over a shortened course of 5 days. A 5-day course of antibiotic therapy does not appear to be sufficient for children with acute otitis media and spontaneous purulent drainage.", "Debate continues with respect to a \"watch and wait\" approach versus immediate antibiotic treatment for the initial treatment of acute otitis media. In this double-blind noninferiority trial, we compared clinical improvement rates at 14 days for children (6 months to 5 years of age) with acute otitis media who were randomly assigned to receive amoxicillin or placebo.\n We enrolled healthy children who presented to clinics or the emergency department with a new episode of acute otitis media during the fall and winter months in Ottawa (from December 1999 to the end of March 2002). The children were randomly assigned to receive amoxicillin (60 mg/kg daily) or placebo for 10 days. Telephone follow-up was performed on each of days 1, 2 and 3 and once between day 10 and day 14. The primary outcome was clinical resolution of symptoms, defined as absence of receipt of an antimicrobial (other than the amoxicillin in the treatment group) at any time during the 14-day period. Secondary outcomes were the presence of pain and fever and the activity level in the first 3 days, recurrence rates, and the presence of middle ear effusion at 1 and 3 months.\n According to clinical scoring, 415 of the 512 children who could be evaluated had moderate disease. At 14 days 84.2% of the children receiving placebo and 92.8% of those receiving amoxicillin had clinical resolution of symptoms (absolute difference -8.6%, 95% confidence interval -14.4% to -3.0%). Children who received placebo had more pain and fever in the first 2 days. There were no statistical differences in adverse events between the 2 groups, nor were there any significant differences in recurrence rates or middle ear effusion at 1 and 3 months.\n Our results did not support the hypothesis that placebo was noninferior to amoxicillin (i.e., that the 14-day cure rates among children with clinically diagnosed acute otitis media would not be substantially worse in the placebo group than the treatment group). Nevertheless, delaying treatment was associated with resolution of clinical signs and symptoms in most of the children.", "Recently, new evidence-based recommendations have been introduced for diagnosing and managing otitis media with effusion (OME) in children. However, there are some difficulties to follow the general guidelines in the tertiary hospitals. The purpose is to evaluate the efficiency of antibiotics or antihistamines for treatment of children with OME in the tertiary hospital with a randomized prospective clinical study.\n Eighty-four children with OME who had been diagnosed in the tertiary hospital were randomized to receive 5 different medications for 2 weeks. We prescribed antibiotics (amoxicillin-clavulanate syrup) in Group I (n=16), antibiotics/steroids (prednisolone) in Group II (n=18), antibiotics/antihistamines (ebastine) in Group III (n=15), antibiotics/steroids/antihistamines in Group IV (n=17), and mucolytics (ivy leaf extract) in Group V (n=17) for control. We followed-up children every 2 weeks and evaluated the state of OME at 3 months.\n Thirty six (42.9%) of 84 children were resolved within average 6.9 weeks after the treatments. Thirty-six (42.9%) were treated with ventilation tube insertion and 12 patients (14.3%) were observed. There was no difference in the resolution rates of OME among the five different protocols (P>0.05). There was no difference in the resolution rates among groups who used steroids, antihistamines, steroids and antihistamines, or other medications to manage 42 children with allergies (P>0.05).\n In the tertiary hospital, the cure rate of children with OME was not as high as well-known, and antibiotics or anti-allergic medications were not more effective than control. We may, therefore, need any other guidelines which are different from the previous evidence-based recommendations, including early operation in the tertiary hospitals.", "Two hundred and ninety-seven children, aged 6 months to 7 years, with AOM were treated with penicillin V. One hundred and forty-eight children were given 25 or 50 mg/kg body weight twice a day for 5 days, and 149 children 25 mg/kg body weight twice a day for 10 days. No differences were found in the rate of healing between the 5- and 10-day groups. The larger penicillin dose, which was given to half the 5-day group, did not lead to improved healing. Treatment with penicillin for 5 days instead of 10 does not mean any increased risk of complications such as SOM, relapses, or therapeutic failure. Nor does the risk of a recurrence of otitis increase either. The investigation showed that the treatment of AOM with penicillin for 10 days, which is the rule in Sweden, can be reduced to 5 days with maintained satisfactory healing and without risk of increasing the number of complications.", "To examine whether probiotics would reduce the occurrence or duration of acute otitis media (AOM), or the nasopharyngeal carriage of otitis pathogens in otitis-prone children.\n During this double-blind, placebo-controlled, randomised, 24-week intervention, 309 otitis-prone children (10 months-6 years) consumed either one probiotic capsule (Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve 99 and Propionibacterium freudenreichii JS) (n=155) or placebo (n=154) daily. Clinical examinations were carried out and nasopharyngeal samples taken three times. Parents recorded the symptoms of upper respiratory infection (URI) in a diary.\n Probiotic treatment did not reduce the occurrence (probiotic vs. placebo: 72% vs. 65%, OR=1.48, 95% CI 0.87-2.52, p=n.s.) or the recurrence ( three) of AOM episodes (18% vs. 17%, OR=1.04, 95% CI 0.55-1.96, p=n.s.). The median duration of AOM episodes was 5.6 (IQR 3.5-9.4) vs. 6.0 (IQR 4.0-10.5) days, respectively (p= n.s.). There was a tendency showing a reduction in the occurrence of recurrent (4 to 6) respiratory infections in the probiotic group (OR for 4 URIs: 0.56, 95%CI 0.31-0.99, p=0.046; OR for 6 URIs: 0.59, 95% CI 0.34 to 1.03, p=n.s.). Probiotics did not affect the carriage of Streptococcus pneumoniae or Haemophilus influenzae, but increased the prevalence of Moraxella catarrhalis (OR=1.79, 95% CI 1.06-3.00, p=0.028).\n Probiotics did not prevent the occurrence of AOM or the nasopharyngeal carriage of otitis pathogens in otitis-prone children. A tendency showing a reduction in recurrent respiratory infections must be confirmed in further studies." ]	Antibiotic treatment led to a statistically significant reduction of children with AOM experiencing pain at two to seven days compared with placebo but since most children (82%) settle spontaneously, about 20 children must be treated to prevent one suffering from ear pain at two to seven days. Additionally, antibiotic treatment led to a statistically significant reduction of tympanic membrane perforations (NNTB 33) and contralateral AOM episodes (NNTB 11). These benefits must be weighed against the possible harms: for every 14 children treated with antibiotics, one child experienced an adverse event (such as vomiting, diarrhoea or rash) that would not have occurred if antibiotics had been withheld. Antibiotics appear to be most useful in children under two years of age with bilateral AOM, or with both AOM and otorrhoea. For most other children with mild disease, an expectant observational approach seems justified. We have no trials in populations with higher risks of complications.
CD006088	[ "21829969", "19434268", "3781700" ]	[ "Antibiotic treatment schemes for very severe community-acquired pneumonia in children: a randomized clinical study.", "Management for the children with otitis media with effusion in the tertiary hospital.", "Possibility of interaction among antibiotics and mucolytics in children." ]	[ "To compare clinical response to initial empiric treatment with oxacillin plus ceftriaxone and amoxicillin plus clavulanic acid in hospitalized children diagnosed with very severe community-acquired pneumonia (CAP).\n A prospective randomized clinical study was conducted among children 2 months to 5 years old with a diagnosis of very severe CAP in the pediatric ward of São Paulo State University Hospital in Botucatu, São Paulo, Brazil, from April 2007 to May 2008. Patients were randomly divided into two groups by type of treatment: an oxacillin/ceftriaxone group (OCG, n = 48) and an amoxicillin/clavulanic acid group (ACG, n = 56). Analyzed outcomes were: time to clinical improvement (fever and tachypnea), time on oxygen therapy, length of stay in hospital, need to widen antimicrobial spectrum, and complications (including pleural effusion).\n The two groups did not differ statistically for age, sex, symptom duration before admission, or previous antibiotic treatment. Time to improve tachypnea was less among ACG patients than OCG patients (4.8 ± 2.2 versus 5.8 ± 2.4 days respectively; P = 0.028), as was length of hospital stay (11.0 ± 6.2 versus 14.4 ± 4.5 days respectively; P = 0.002). There were no statistically significant differences between the two groups for fever improvement time, time on oxygen therapy, need to widen antimicrobial spectrum, or frequency of pleural effusion.\n Both treatment plans are effective in treating very severe CAP in 2-month-to 5-year-old hospitalized children. The only analyzed outcome that favored amoxicillin/clavulanic acid treatment was time required to improve tachypnea.\n ClinicalTrials.gov ID: NCT01166932.", "Recently, new evidence-based recommendations have been introduced for diagnosing and managing otitis media with effusion (OME) in children. However, there are some difficulties to follow the general guidelines in the tertiary hospitals. The purpose is to evaluate the efficiency of antibiotics or antihistamines for treatment of children with OME in the tertiary hospital with a randomized prospective clinical study.\n Eighty-four children with OME who had been diagnosed in the tertiary hospital were randomized to receive 5 different medications for 2 weeks. We prescribed antibiotics (amoxicillin-clavulanate syrup) in Group I (n=16), antibiotics/steroids (prednisolone) in Group II (n=18), antibiotics/antihistamines (ebastine) in Group III (n=15), antibiotics/steroids/antihistamines in Group IV (n=17), and mucolytics (ivy leaf extract) in Group V (n=17) for control. We followed-up children every 2 weeks and evaluated the state of OME at 3 months.\n Thirty six (42.9%) of 84 children were resolved within average 6.9 weeks after the treatments. Thirty-six (42.9%) were treated with ventilation tube insertion and 12 patients (14.3%) were observed. There was no difference in the resolution rates of OME among the five different protocols (P>0.05). There was no difference in the resolution rates among groups who used steroids, antihistamines, steroids and antihistamines, or other medications to manage 42 children with allergies (P>0.05).\n In the tertiary hospital, the cure rate of children with OME was not as high as well-known, and antibiotics or anti-allergic medications were not more effective than control. We may, therefore, need any other guidelines which are different from the previous evidence-based recommendations, including early operation in the tertiary hospitals.", "A controlled clinical trial in children with acute infections of the lower respiratory tract was carried out to see whether or not treatment with ambroxol could bring about faster and better results. One hundred twenty children with acute lower respiratory tract infections were all given antibiotics plus, at random, either ambroxol (1.5-2.0 mg/kg body weight orally) or a placebo. The duration of the trial was ten days. All the patients in both groups were cured clinically. However, remission of the cough, of the chest pathological signs, as well as the improvement of the lung radiographical pictures were significantly more rapid in children treated with ambroxol than in those who received the antibiotic alone. Ambroxol was tolerated perfectly by all the children." ]	There is insufficient evidence to decide whether OTC medications for cough associated with acute pneumonia are beneficial. Mucolytics may be beneficial but there is insufficient evidence to recommend them as an adjunctive treatment for acute pneumonia. This leaves only theoretical recommendations that OTC medications containing codeine and antihistamines should not be used in young children.
CD006380	[ "9212478", "14742379", "12791434", "8665549", "7644238", "9313274", "14594516", "8537695", "11498314", "12370455", "11916808", "14622817", "11376910" ]	[ "Comparison of oral controlled-release morphine with transdermal fentanyl in terminal cancer pain.", "A placebo-controlled randomized crossover trial of the N-methyl-D-aspartic acid receptor antagonist, memantine, in patients with chronic phantom limb pain.", "Efficacy of the NMDA-receptor antagonist memantine in patients with chronic phantom limb pain--results of a randomized double-blinded, placebo-controlled trial.", "Intravenous infusion of the NMDA antagonist, ketamine, in chronic posttraumatic pain with allodynia: a double-blind comparison to alfentanil and placebo.", "Analgesic efficacy and safety of single-dose intramuscular ketorolac for postoperative pain management in children following tonsillectomy.", "Comparative efficacy of patient-controlled administration of morphine, hydromorphone, or sufentanil for the treatment of oral mucositis pain following bone marrow transplantation.", "Comparison of TTS-fentanyl with sustained-release oral morphine in the treatment of patients not using opioids for mild-to-moderate pain.", "Long-term intraspinal infusions of opioids in the treatment of neuropathic pain.", "Evaluation of the safety and efficacy of epidural ketamine combined with morphine for postoperative analgesia after major upper abdominal surgery.", "Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial.", "Perioperative small-dose S(+)-ketamine has no incremental beneficial effects on postoperative pain when standard-practice opioid infusions are used.", "Evaluation of long-term efficacy and safety of transdermal fentanyl in the treatment of chronic noncancer pain.", "'Balanced analgesia' in the perioperative period: is there a place for ketamine?" ]	[ "Controlled-release morphine (MST) given twice daily provides a simpler and more convenient treatment regimen than 4-hourly opioid administration for the control of cancer pain. Recently, a new formulation of transdermal fentanyl (TDF) has been developed which provides a new route for the treatment of cancer pain. The present study was designed to compare the analgesic efficacy, safety and adverse effects of MST and TDF in the management of chronic cancer pain.\n In this open, comparative and randomized study, patients were treated with oral morphine hydrochloride immediate-release (MHIR) in the stabilization phase and then the prescription was switched to MST or TDF for 14 days in the treatment phase. Oral MHIR was provided as rescue medication for breakthrough pain. Assessments of the pain intensity, pain frequency, degree of pain improvement, profile of mood states, quality of sleep, activity status and adverse effects were performed before and after the stabilization phase and before and after the treatment phase.\n Forty of 47 cancer patients completed the study with 20 patients in each group. There were significant (p < 0.05) improvements in pain intensity, pain frequency, mood states and quality of sleep in both groups before and after treatment, while improvement in the activity status was not significant. No specific adverse effects were encountered except for drowsiness which occurred in 6 patients treated with MST and 5 treated with TDF (p < 0.05). Insomnia was significantly improved (p < 0.05) with both regimens compared with that in the period before treatment. There were no significant differences between the two study groups in analgesic efficacy or adverse effects.\n These results suggest that TDF and MSt are safe and effective analgesics for the management of chronic cancer pain. However, TDF provides a simpler and more convenient treatment for those patients with severe nausea, vomiting or dysphagia.", "In the present study we investigated the effect of the N-methyl-D-aspartic acid (NMDA) receptor antagonist memantine (30 mg/d) on the intensity of chronic phantom limb pain (PLP) and cortical reorganization. In 8 patients with chronic PLP, memantine was tested in a placebo-controlled double-blinded crossover trial of 4 wk duration per trial. The intensity of PLP was rated hourly by the patients on a visual analog scale during baseline and both treatment periods. At the same time points, the functional organization of the primary somatosensory cortex (SI) was determined by neuromagnetic source imaging. In comparison to baseline and placebo, the NMDA receptor antagonist had no effect on the intensity of chronic PLP. In none of the periods were significant changes in the functional organization of SI observed. Although the conclusions regarding the clinical effect are limited because of the small sample size, the data indicate that in the studied dosage the NMDA receptor antagonist memantine is ineffective in the treatment of chronic PLP and is also ineffective for the reduction of associated neural plasticity in the primary SI.\n NMDA receptors play a substantial role in central nervous system changes underlying neuropathic pain. In a placebo-controlled double-blinded study we tested the effect of 30 mg memantine on chronic phantom limb pain and pain-associated cortical reorganization.", "Phantom limb pain (PLP) associated neuroplastic changes are partly mediated by excitatory amino acids at NMDA receptor sites. This study was undertaken to deduce if NMDA-receptor antagonists may be effective in patients with chronic PLP. Therefore a four week double-blinded, randomized placebo-controlled trial was performed to evaluate the efficacy of 30 mg memantine/day, an orally administrable NMDA receptor antagonist.Thirty-six patients, 18 per group, with a history of at least 12 months PLP and an average pain of at least 4 on the 11-point numeric rating scale (NRS) were enrolled. The patients completed a standardized questionnaire before the trial. PLP intensity and the level of eight complaints were assessed during the trial. Number needed to treat (NNT) was calculated based on the average PLP during the 3rd week (steady state). In both groups, PLP declined significantly in comparison with the baseline (verum: 5.1 (+/-2.1) to 3,8 (+/-2,3), placebo from 5.1 (+/-2.0) to 3.2 (+/-1,46) NRS) without a re-rising of the PLP during the washout period. Mean pain relief was 47% in the memantine group (10 patients reported more than 50% relief), 40% in the placebo group (6>50%): NNT were 4.5 (KI: 2.1-10.6). Analysis of covariance demonstrated a significant impact only on the prior PLP intensity, but no treatment effect. Two patients have demonstrated long-term pain relief under memantine until now (16 months). The total number of slight adverse events were comparable in both groups, but the overall number of severe events was higher in the memantine group (P<0.05). This trial failed to demonstrate a significant clinical benefit of the NMDA-receptor antagonist memantine in chronic PLP. The administration of a higher dosage is probably not tolerable.", "NMDA antagonists and opioids relieve experimentally produced hyperalgesia in animals and humans, presumably by attenuating a heightened central nervous system response to afferent input. A few small studies in patients have suggested that intravenous boluses or rapid infusions of the N-methyl-D-aspartate (NMDA) antagonist ketamine relieve some neuropathic pains but also produce disturbances of cognition and mood. In a randomized, double-blind, crossover trial, we treated eight patients with chronic posttraumatic pain and widespread mechanical allodynia with 2-h intravenous infusions of the NMDA antagonist ketamine (mean dose, 58 mg), the opioid mu-receptor agonist alfentanil (mean dose, 11 mg), and placebo. The patients were selected because extensive sensory testing suggested that altered central processing contributed to their symptoms. The slow rate of drug infusion was chosen to see if pain relief would precede dose-limiting side effects. Means of the peak effect scores achieved during the 2-h infusion were for pain relief: ketamine, 65%, alfentanil, 46%, and placebo, 22% (p < 0.01 for ketamine and p = 0.08 for alfentanil, each compared to placebo); and for relief of allodynia: ketamine, 71%, alfentanil, 57%, and placebo, 21% (p < 0.01 for both ketamine and alfentanil). Appreciable symptomatic relief developed only after the onset of unpleasant drug side effects. After the infusion was stopped, pain relief disappeared before the side effects resolved. We conclude that NMDA antagonists may have promise for the treatment of neuropathic pain, but strategies are needed to improve their therapeutic ratio, such as intrathecal administration or systemic treatment with more selective drugs.", "The efficacy of ketorolac, a non-steroidal anti-inflammatory drug, in the management of moderate to severe pain in adults, has led us to conduct a trial of this analgesic in children following tonsillectomy. Children were randomized to receive intramuscular (i.m.) ketorolac (1 mg/kg, EXP group, n = 45) or saline (CTL group, n = 42) at the completion of surgery. Intravenous (i.v.) fentanyl (0.5 micrograms/kg/dose) was administered in repeated doses postoperatively. Pain intensity was measured using both the Oucher and the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) to allow for comparison between self-report and behavioral measures of pain intensity. Severity of postoperative bleeding was measured using a 4-point rating scale. The EXP group had a significant reduction in total fentanyl dose (mean: 35.9 micrograms) compared to the CTL group (mean: 48.3 micrograms, t = -2.21, P < 0.03). There was a statistically significant decrease in pre-fentanyl CHEOPS scores in the Post-Anesthesia Care Unit (PACU) in the ketorolac group (F (2, 30) = 5.34, P < 0.01), but not in the saline group (F (2.24) = 2.46, P > 0.05). In the first hour postoperatively, the CHEOPS demonstrated significant decreases in pain intensity scores in response to opioids, in both groups. In the PACU, children were unable to provide a self-report of pain intensity potentially due to a variety of factors (e.g., emergence delirium, agitation, excitement, sedation, and/or pain). However, during the remainder of the postoperative stay, the photographic scale of the Oucher was a more valid measure of pain intensity than the CHEOPS.(ABSTRACT TRUNCATED AT 250 WORDS)", "A total of 119 bone marrow transplant patients suffering from oral mucositis pain were enrolled in a randomized, double-blind, parallel-group trial comparing the efficacy of patient-controlled analgesia with morphine, hydromorphone and sufentanil. Patient ratings of pain and side-effects on visual analog scales were gathered daily from the start of patient-controlled analgesia (PCA) therapy until the discontinuation of opioid treatment either because of resolution of oral mucositis pain, intolerable side-effects, inadequate pain control, or complications related to transplantation. Of the 119 enrolled subjects, 100 met the evaluable criteria of developing oral mucositis and remaining on the study for at least 2 days. Multivariate analysis of the outcome measures indicated that the analgesia achieved in all three opioid groups was nearly equivalent, while measures of side-effects, especially for the combination of sedation, sleep and mood disturbances, were statistically lower in the morphine group than in hydromorphone or sufentanil groups. Patients in the hydromorphone group exhibited the most variability in pain control. Event analysis also indicated significant differences in time to treatment failure between the three groups, with the morphine arm exhibiting clear superiority. The proportion of patients discontinued because of inadequate pain relief was much higher in the sufentanil group (7/36) as compared to the hydromorphone (0/34) or the morphine group (1/30). The daily opioid consumption pattern showed a continual dose escalation during the first week of therapy for all groups, coincident with worsening mucositis. Morphine consumption reached a plateau by day 5, whereas hydromorphone and sufentanil consumption continued to rise until days 7 and 9, respectively. Sufentanil dose requirement increased by approximately 10-fold compared to morphine and hydromorphone, whose requirements increased only 5-fold, suggesting the possibility of development of acute pharmacological tolerance in some patients with this phenylpiperidine opioid. This study provides support for the recommendation that morphine is the opioid of first choice when patient-controlled analgesia is employed for the treatment of severe oropharyngeal pain in bone marrow transplantation (BMT) patients.", "This randomised, multicentre, direct open comparative trial evaluated the efficacy, treatment convenience, tolerability and safety aspects of transdermal therapeutic system (TTS)-fentanyl and sustained-release oral morphine (SRM) in both opioid-naïve patients with moderate-to-severe cancer-related pain and in patients who had already been using opioids for mild-to-moderate pain. The two treatment groups were run in parallel. Special attention was paid to constipation, nausea/vomiting, drowsiness and respiratory depression.\n The 131 enrolled patients started the 4-week treatment at low doses of opioid (25 microg/h TTS-fentanyl for 3 days or 30 mg SRM every 12 h) and were individually titrated. Tolerability, efficacy and safety were assessed throughout the study period. Frequency of constipation was the primary study variable and accordingly the study was powered for this. Both patients and investigators made a global treatment evaluation.\n TTS-fentanyl and SRM were shown to be equally effective. Pain control and sleep quality improved with both treatments. None of the patients developed respiratory depression. Statistically significantly more patients in the SRM treatment group discontinued the trial prematurely (59% vs 27%; p < 0.001), particularly due to adverse events (36% vs 4%; p < 0.001). Fewer patients in the TTS-fentanyl than in the SRM treatment group reported constipation during the trial. This finding was statistically significant after 1 week of treatment (27% vs 57%; p = 0.003). The favourable tolerability profile of TTS-fentanyl was also reflected in both the patient and the investigator global evaluation of the treatment. Patient assessment favoured TTS-fentanyl treatment in terms of a significantly lower rate of troublesome side-effects ('quite a bit' to 'very much' troublesome side-effects in 14% vs 36% of patients; p = 0.003) and less interruption of daily activities (absence of any interruption of daily activities in 88% vs 63% of patients; p = 0.012). Investigators scored TTS-fentanyl as significantly better with respect to 'side-effects' (p = 0.039) and 'overall impression' (p = 0.013). Sub-analyses of opioid-naïve users gave similar results.\n These data indicate that TTS-fentanyl, when used as an opioid of first choice in the treatment of cancer-related pain, is as effective as, but better tolerated than, SRM, including in opioid-naïve patients.", "Long-term intraspinal infusions of opioid drugs are being increasingly utilized in patients with noncancer pain. Despite this, there is a lack of long-term information, including success and failure rates for pain relief and technical problems. During a 5-year period, 18 noncancer patients underwent implantation of programmable infusion pumps for long-term intrathecal opioid infusion. Patients had (a) neuropathic pain, (b) had failed or been ineligible for noninvasive treatments, and (c) obtained greater than 50% pain relief with intrathecal trial infusions of morphine sulfate or sufentanil citrate. A disinterested third-party reviewer evaluated patients at the most recent follow-up. Sixty-one percent (11/18) of patients had good or fair pain relief with mean follow-up 2.4 +/- 0.3 years (0.8-4.7 years). Average numeric pain scores decreased by 39% +/- 4.3%. Five of the 11 responders required lower opioid doses (12-24 mg/day morphine) and the remaining six patients required higher opioid doses (> 34 mg/day morphine). Failure of long-term pain relief occurred in 39% (7/18) despite good pain relief in trial infusions and the use of both morphine and sufentanil. Technical problems developed in 6/18 patients but appeared to be preventable with further experience. Long-term intrathecal opioid infusions can be effective in treatment of neuropathic pain but might require higher infusion doses.", "To evaluate the efficacy of the combination of epidural ketamine and morphine compared with epidural morphine alone for postoperative pain relief following major upper abdominal surgery.\n Prospective, randomized, double-blinded study.\n Tertiary care referral and teaching hospital.\n 46 ASA physical status I and II patients who underwent major upper abdominal procedures.\n Patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 microg/kg whereas patients in Group 2 received epidural ketamine 1 mg/kg combined with 50 microg/kg of morphine postoperatively.\n A blinded observer using a visual analog scale (VAS) for pain assessment followed up patients for 48 hours postoperatively. Top-up dose of epidural morphine was provided when VAS was higher than 4. Analgesic requirements and side effects were compared between the two groups.\n Only 40 patients completed the study. There were no differences between the two groups with respect to age, gender, weight, duration, or type of surgical procedure or intraoperative opioid requirements. Onset of analgesia was faster (p < 0.001) in Group 2 (11 min) than in Group 1 patients (25 min). The time for first requirement of analgesia was significantly (p < 0.01) longer (19.8 +/- 9.8 hours) in Group 2 patients than Group 1 (12.8 +/- 6.2 hours). Total number of supplemental doses of epidural morphine required in the first 48 hours postoperatively was also significantly less (p < 0.005) in Group 2 compared to Group 1. Patients in Group 2 had higher sedation scores than Group I patients for the first 2 hours postoperatively. None of the patients in either group developed hallucinations or respiratory depression. Other side effects such as pruritus, nausea, and vomiting were also similar in both groups.\n The addition of epidural ketamine 1 mg/kg to morphine 50 microg/kg improved analgesia after major upper abdominal surgery without increasing side effects.", "Tricyclic antidepressants (TCA) provide less than satisfactory pain relief for postherpetic neuralgia (PHN), and the role of opioids is controversial.\n To compare the analgesic and cognitive effects of opioids with those of TCA and placebo in the treatment of PHN.\n Seventy-six patients with PHN were randomized in a double-blind, placebo-controlled, crossover trial. Each subject was scheduled to undergo three treatment periods (opioid, TCA, and placebo), approximately 8 weeks' duration each. Doses were titrated to maximal relief or intolerable side effects. The primary outcome measures were pain intensity (0 to 10 scale), pain relief (0 to 100%), and cognitive function. Analyses included patients who provided any pain ratings after having received at least a single dose of a study medication.\n Fifty patients completed two periods, and 44 patients completed all three. Mean daily maintenance doses were morphine 91 mg or methadone 15 mg and nortriptyline 89 mg or desipramine 63 mg. Opioids and TCA reduced pain (1.9 and 1.4) more than placebo (0.2; p < 0.001), with no appreciable effect on any cognitive measure. The trend favoring opioids over TCA fell short of significance (p = 0.06), and reduction in pain with opioids did not correlate with that following TCA. Treatment with opioids and TCA resulted in greater pain relief (38 and 32%) compared with placebo (11%; p < 0.001). More patients completing all three treatments preferred opioids (54%) than TCA (30%; p = 0.02).\n Opioids effectively treat PHN without impairing cognition. Opioids and TCA act via independent mechanisms and with varied individual effect.", "Several studies report that when small-dose racemic ketamine, an N-methyl-D-aspartate receptor antagonist, is administered perioperatively, opioid consumption is reduced postoperatively. S(+)-ketamine has a higher affinity for the N-methyl-D-aspartate receptor and less-serious side effects than racemic ketamine. Thirty patients scheduled for elective arthroscopic anterior cruciate ligament repair were enrolled in this randomized, double-blinded clinical trial designed to determine the preemptive effect of S(+)-ketamine on postoperative analgesia requirements in a setting of clinically relevant perioperative analgesia. Total IV anesthesia was induced and maintained with remifentanil (0.125-1.0 microg x kg(-1) x min(-1)) and a propofol target-controlled infusion (target 2-4 microg/mL). The Ketamine group received a bolus of 0.5 mg/kg S(+)-ketamine before incision, followed by a continuing infusion of 2 microg x kg(-1) x min(-1) until 2 h after emergence from anesthesia. The Control group received NaCl in the same sequence. After IV morphine provided pain relief down to < or =3 on a visual analog scale scored from 0 to 10, patients were connected to a patient-controlled analgesia device. There were no significant differences between the two groups in terms of total morphine consumption or VAS scores, either at rest or with movement. In our study, S(+)-ketamine did not contribute to postoperative pain reduction, possibly because of the clinically routine perioperative opioid analgesia.\n Small-dose S(+)-ketamine had no positive effect on postoperative analgesia when administered perioperatively for elective arthroscopic anterior cruciate ligament repair. Unlike investigations of the racemic mixture of ketamine, our study methods included timely standard-practice perioperative opioid analgesia, which seems to make supplemental analgesia unnecessary.", "The objective of this international, multicenter, open-label trial was to assess the efficacy and safety of up to 12 months of therapy with transdermal therapeutic system (TTS) fentanyl in patients (n = 532) with chronic noncancer pain. The trial was completed by 301 (57%) of the patients. The main outcome measures were pain control assessment, global treatment satisfaction, patient preference for TTS fentanyl, and quality of life. The mean dose of transdermal fentanyl (TDF) increased from 48 to 90 microg/h during a period of 12 months. During treatment, on average 67% of patients within the efficacy analysis group (n = 524) reported very good, good, or moderate pain control. Global satisfaction (very good or good) was also stable at 42%. The majority (86%) of patients reported a preference for TDF over their previous treatment (P < .001, binomial test). Short Form 36 quality-of-life scores improved from baseline for bodily pain. The most frequent treatment-related adverse events were nausea (31%), constipation (19%), and somnolence (18%). With regard to opioid-specific adverse events (respiratory depression [< 1%], adrenal insufficiency [< 1%], drug abuse/dependence [1%], and opioid withdrawal syndrome [3%]), these were extremely rare and, with the exception of opioid withdrawal syndrome, none was considered definitively related to the treatment. Long-term treatment with TDF provided a stable degree of pain control in the majority of patients with moderate to severe chronic noncancer pain. It was preferred by the majority of patients compared with their previous opioid medication. Overall, long-term treatment with TDF was generally well tolerated, particularly in view of the low incidence of potentially serious side effects such as drug abuse/dependence and respiratory depression. However, at present, it is important that patients receiving TDF should still be subject to careful assessment and monitoring.", "We investigated whether intraoperative 'subanesthetic doses' of ketamine have a postoperative anti-hyperalgesic and an analgesic effect and which is the preferential route of administration, either systemic (intravenous, i.v.) or epidural. One hundred patients scheduled for rectal adenocarcinoma surgery under combined epidural/general anesthesia were included. Before skin incision all the patients received an epidural bolus followed by an infusion of continuous bupivacaine/sufentanil/clonidine mixture. They were randomly assigned to receive no ketamine (group 1), i.v. ketamine at the bolus dose of 0.25 mg/kg followed by an infusion of 0.125 mg/kg per h (group 2), 0.5 mg/kg and 0.25 mg/kg per h (group 3), epidural ketamine 0.25 mg/kg and 0.125 mg/kg per h (group 4), or 0.5 mg/kg and 0.25 mg/kg per h (group 5). All i.v. and epidural analgesics were stopped at the end of surgery and patients were connected to an i.v. morphine patient-controlled analgesia (PCA) device. Short-term postoperative analgesia (72 h) was assessed by pain visual analog scale scores at rest, cough, and movements as well as by PCA requirements. Wound mechanical hyperalgesia was evaluated and residual pain was assessed by asking the patients at 2 weeks, and 1, 6, and 12 months. The area of hyperalgesia and morphine PCA requirements were significantly reduced in group 3. These patients reported significantly less residual pain until the sixth postoperative month. These observations support the theory that subanesthetic doses of i.v. ketamine (0.5 mg/kg bolus followed by 0.25 mg/kg per h) given during anesthesia reduce wound hyperalgesia and are a useful adjuvant in perioperative balanced analgesia. Moreover, they show that the systemic route clearly is the preferential route." ]	The short- and long-term effectiveness of opioids, NMDA receptor antagonists, anticonvulsants, antidepressants, calcitonins, and anaesthetics for clinically relevant outcomes that include pain, function, mood, sleep, quality of life, satisfaction and adverse effects remains unclear. Morphine, gabapentin and ketamine demonstrate trends towards short-term analgesic efficacy. Memantine and amitriptyline were ineffective for PLP. Results, however, are to be interpreted with caution as these were based mostly on a small number of studies with limited sample sizes that varied considerably and also lacked long-term efficacy and safety outcomes. The direction of efficacy of calcitonin, anaesthetics and dextromethorphan need further clarification. Larger and more rigorous randomised controlled trials are needed to make stronger recommendations about which medications would be useful for clinical practice.
CD004250	[ "7706955", "12221344", "19674713", "11353937", "19770596", "21303529", "12759322", "19066648", "16949939", "15162353", "10767816", "17768009", "18457329", "16813473", "8976475", "8053797", "15614241", "17413465", "12438988" ]	[ "Phasic exercises for cervical rehabilitation after \"whiplash\" trauma.", "A randomized controlled trial of exercise and manipulative therapy for cervicogenic headache.", "A feasibility study assessing manual therapies to different regions of the spine for patients with subacute or chronic neck pain.", "A pilot randomized clinical trial on the relative effect of instrumental (MFMA) versus manual (HVLA) manipulation in the treatment of cervical spine dysfunction.", "Neck/shoulder exercise for neck pain in air force helicopter pilots: a randomized controlled trial.", "A randomised controlled trial of preventive spinal manipulation with and without a home exercise program for patients with chronic neck pain.", "Active neck muscle training in the treatment of chronic neck pain in women: a randomized controlled trial.", "Immediate effects of inhibitive distraction on active range of cervical flexion in patients with neck pain: a pilot study.", "Immediate effects on neck pain and active range of motion after a single cervical high-velocity low-amplitude manipulation in subjects presenting with mechanical neck pain: a randomized controlled trial.", "A pilot study of a randomized controlled trial to evaluate the effects of progressive resistance exercise training on shoulder dysfunction caused by spinal accessory neurapraxia/neurectomy in head and neck cancer survivors.", "Active treatment of chronic neck pain: a prospective randomized intervention.", "The effectiveness of a work style intervention and a lifestyle physical activity intervention on the recovery from neck and upper limb symptoms in computer workers.", "Effect of exercise on upper extremity pain and dysfunction in head and neck cancer survivors: a randomized controlled trial.", "Effects of a multimodal exercise program for people with ankylosing spondylitis.", "Trunk exercise combined with spinal manipulative or NSAID therapy for chronic low back pain: a randomized, observer-blinded clinical trial.", "Changes in cervicocephalic kinesthesia after a proprioceptive rehabilitation program in patients with neck pain: a randomized controlled study.", "Dose response for chiropractic care of chronic cervicogenic headache and associated neck pain: a randomized pilot study.", "Neck collar, \"act-as-usual\" or active mobilization for whiplash injury? A randomized parallel-group trial.", "Two-year follow-up of a randomized clinical trial of spinal manipulation and two types of exercise for patients with chronic neck pain." ]	[ "To assess whether \"phasic\" exercises, including rapid eye-head-neck-arm movements, can benefit patients with chronic cervical injuries.\n A randomized, controlled, double blind study involving 30 chronic patients, who were allocated to either group 1 or group 2. The study period was for 8 wk.\n The study was conducted in a private practice.\n Thirty chronic motor vehicle accident patients who continued to experience increased pain/soreness/stiffness of the cervical musculature with sports/activities requiring rapid head neck movements were selected for the study.\n Group 1 patients (n = 15) had standard exercises (stretching/isometric/isokinetic) and chiropractic therapy. Group 2 patients (n = 15) had \"phasic\" exercises and chiropractic therapy. Patients in both groups exercised for a minimum of four times weekly, for 8 wk.\n Pre and Post Pain and Disability Index was administered to both groups.\n Group 1, which had standard exercises and chiropractic therapy, improved by 7.4% (p > .05). Group 2, which had \"phasic\" exercises and chiropractic therapy, improved by 48.3% (p > .001). Confounders were identified, which explains the minimal improvement of group 1 and the remarkable results of group 2.\n It would appear that any rehabilitation program for chronic neck-injured patients should involve exercises that address the following: eye-head-neck-arm coordinated movements, coordination of the entire vertebral column,/ and return the \"phasic\" component of the musculature to functional levels. Additional studies will address the effect of these exercises on the strength, range of motion and pain improvement of the cervical spine in normal, acute and chronic patients.", "A multicenter, randomized controlled trial with unblinded treatment and blinded outcome assessment was conducted. The treatment period was 6 weeks with follow-up assessment after treatment, then at 3, 6, and 12 months.\n To determine the effectiveness of manipulative therapy and a low-load exercise program for cervicogenic headache when used alone and in combination, as compared with a control group.\n Headaches arising from cervical musculoskeletal disorders are common. Conservative therapies are recommended as the first treatment of choice. Evidence for the effectiveness of manipulative therapy is inconclusive and available only for the short term. There is no evidence for exercise, and no study has investigated the effect of combined therapies for cervicogenic headache.\n In this study, 200 participants who met the diagnostic criteria for cervicogenic headache were randomized into four groups: manipulative therapy group, exercise therapy group, combined therapy group, and a control group. The primary outcome was a change in headache frequency. Other outcomes included changes in headache intensity and duration, the Northwick Park Neck Pain Index, medication intake, and patient satisfaction. Physical outcomes included pain on neck movement, upper cervical joint tenderness, a craniocervical flexion muscle test, and a photographic measure of posture.\n There were no differences in headache-related and demographic characteristics between the groups at baseline. The loss to follow-up evaluation was 3.5%. At the 12-month follow-up assessment, both manipulative therapy and specific exercise had significantly reduced headache frequency and intensity, and the neck pain and effects were maintained (P < 0.05 for all). The combined therapies was not significantly superior to either therapy alone, but 10% more patients gained relief with the combination. Effect sizes were at least moderate and clinically relevant.\n Manipulative therapy and exercise can reduce the symptoms of cervicogenic headache, and the effects are maintained.", "The purpose of this project was to develop and test protocols for a randomized clinical trial of a combined therapeutic approach (thoracic spine and sacroiliac joint high-velocity, low-amplitude spinal manipulation [HVLA SM] + cervical spine postisometric relaxation) and cervical spine HVLA SM for patients with subacute or chronic neck pain.\n Patients were recruited in the Quad Cities in Iowa and Illinois. After a baseline assessment visit, eligible patients were randomly assigned to cervical spine HVLA SM or to the combined therapeutic approach for 4 treatment visits over 2 weeks. Outcome assessments included the Neck Disability Index, visual analog scale, and posttreatment response questionnaire. Patient outcomes were not aggregated or compared by treatment group.\n It took approximately 8 months of planning, which included the development of forms and protocols, pretesting the forms, and training staff and clinicians in the standardized protocols. Twelve participants were screened, and 6 patients were enrolled and randomly allocated to care over a 6-week period. All patients completed 5 visits. Five of 6 patients had an improvement on the Neck Disability Index. On the visual analog scale, 2 patients improved at 2 weeks, whereas the other 4 got worse. Five patients completed the posttreatment response questionnaire; 2 of the 5 indicated they experienced discomfort or an unpleasant reaction from the study treatments.\n Designing a successful feasibility randomized clinical trial requires considerable planning, development and pretesting of the forms and protocols, and training clinicians and staff for standardized protocols. Patients were willing to be randomized, follow treatment protocols, complete baseline and outcome assessments, and return 83% of the follow-up questionnaires.", "To determine the relative effect of instrument-delivered thrust cervical manipulations in comparison with traditional manual-delivered thrust cervical manipulations in the treatment of cervical spine dysfunction.\n Prospective, randomized, comparative clinical trial.\n Outpatient chiropractic clinic, Technikon Natal, South Africa.\n Thirty patients diagnosed with neck pain and restricted cervical spine range of motion without complicating pathosis for at least 1 month were included in the study.\n The patients were randomized into 2 groups. Those in one group received mechanical force, manually assisted (MFMA) manipulation to the cervical spine, delivered by means of a hand-held instrument (Activator II Adjusting Instrument). Those in the other group received specific contact high-velocity, low-amplitude (HVLA) manipulation consisting of standard Diversified rotary/lateral break techniques to the cervical spine. Each group received only the specific therapeutic intervention, no other treatment modalities or interventions (including medication) being used, until asymptomatic status was achieved or a maximum of 8 treatments had been received. Main Outcome Measures: Both treatment groups were assessed through use of subjective (Numerical Pain Rating Scale 101, McGill Short-Form Pain Questionnaire, and Neck Disability Index) and objective (goniometer cervical range of motion) measurement parameters at specific intervals during the treatment period and at 1-month follow-up. The data were assessed through use of 2-tailed nonparametric paired and unpaired analysis, descriptive statistics, and power analysis of the data.\n The results indicate that both treatment methods had a positive effect on the subjective and objective clinical outcome measures, no significant difference being observed between the 2 groups (P < .025). The subjective data from all 3 questionnaires showed statistically significant changes from initial to final consultations as well as from initial consultation to 1-month follow-up (P < .025). The objective range of motion measures showed statistically significant changes in the MFMA group for left and right rotation and left and right lateral flexion from initial consultation to final consultations and for right rotation and right lateral flexion from initial consultation to 1-month follow-up. The HVLA group showed only the change in left rotation from initial to final consultations and from initial consultation to 1-month follow-up to be statistically significant.\n The results of this clinical trial indicate that both instrumental (MFMA) manipulation and manual (HVLA) manipulation have beneficial effects associated with reducing pain and disability and improving cervical range of motion in this patient population. A randomized, controlled clinical trial in a similar patient base with a larger sample size is necessary to verify the clinical relevance of these findings.", "The study was a randomized, controlled trial with blinded outcome assessment. A 6-week intervention was followed up directly afterwards and after 12 months.\n The purpose was to evaluate the preventive efficacy of a neck/shoulder exercise regimen for neck pain in air force helicopter pilots.\n Neck pain is a significant medical problem in modern military aviation. Research shows neck-muscle dysfunction in subjects with various neck disorders. So far, evidence for neck exercise as prevention or early intervention is sparse, and few trials use randomized controlled design.\n Sixty-eight helicopter pilots on active flying duty with or without neck pain were randomly assigned to a supervised neck/shoulder exercise regimen or a control group receiving no such regimen. The key outcome was change in the prevalence of neck pain cases at the 12-month follow-up, rated for the previous week and the previous 3 months. Secondary outcomes included neck-flexor surface electromyographic activity during active craniocervical flexion and pain-related fear regarding physical activity. In addition, a secondary regression analysis included preintervention predictors that may be associated with change in prevalence of neck-pain cases at the 12-month follow-up.\n Eighty-two percent (56/68) of the participants assigned at random completed the intervention and provided data at month 12. Regression analysis showed a reduction in the prevalence of neck pain cases in the exercise group, which was significant for pain ratings during the previous week, OR = 3.2 (95% CI = 1.3-7.8), and previous 3 months, OR = 1.9 (95% CI = 1.2-3.2). Electromyographic activity at the highest contraction level was significantly reduced in the exercise group, P < 0.05, whereas no between-groups effect emerged for pain-related fear. Results from the secondary analysis showed that general strength training for more than 1 hour per week before the intervention predicted reduction in prevalence of pain at follow-up.\n A supervised neck/shoulder exercise regimen was effective in reducing neck pain cases in air force helicopter pilots. This was supported by improvement in neck-flexor function postintervention in regimen members. However, no effect emerged for pain-related fear. General strength training before the intervention predicted reduction in prevalence of pain at follow-up.", "Evidence indicates that supervised home exercises, combined or not with manual therapy, can be beneficial for patients with non-specific chronic neck pain (NCNP). The objective of the study is to investigate the efficacy of preventive spinal manipulative therapy (SMT) compared to a no treatment group in NCNP patients. Another objective is to assess the efficacy of SMT with and without a home exercise program.\n Ninety-eight patients underwent a short symptomatic phase of treatment before being randomly allocated to either an attention-group (n = 29), a SMT group (n = 36) or a SMT + exercise group (n = 33). The preventive phase of treatment, which lasted for 10 months, consisted of meeting with a chiropractor every two months to evaluate and discuss symptoms (attention-control group), 1 monthly SMT session (SMT group) or 1 monthly SMT session combined with a home exercise program (SMT + exercise group). The primary and secondary outcome measures were represented by scores on a 10-cm visual analog scale (VAS), active cervical ranges of motion (cROM), the neck disability index (NDI) and the Bournemouth questionnaire (BQ). Exploratory outcome measures were scored on the Fear-avoidance Behaviour Questionnaire (FABQ) and the SF-12 Questionnaire.\n Our results show that, in the preventive phase of the trial, all 3 groups showed primary and secondary outcomes scores similar to those obtain following the non-randomised, symptomatic phase. No group difference was observed for the primary, secondary and exploratory variables. Significant improvements in FABQ scores were noted in all groups during the preventive phase of the trial. However, no significant change in health related quality of life (HRQL) was associated with the preventive phase.\n This study hypothesised that participants in the combined intervention group would have less pain and disability and better function than participants from the 2 other groups during the preventive phase of the trial. This hypothesis was not supported by the study results. Lack of a treatment specific effect is discussed in relation to the placebo and patient provider interactions in manual therapies. Further research is needed to delineate the specific and non-specific effects of treatment modalities to prevent unnecessary disability and to minimise morbidity related to NCNP. Additional investigation is also required to identify the best strategies for secondary and tertiary prevention of NCNP.\n ClinicalTrials.gov: NCT00566930.", "Active physical training is commonly recommended for patients with chronic neck pain; however, its efficacy has not been demonstrated in randomized studies.\n To evaluate the efficacy of intensive isometric neck strength training and lighter endurance training of neck muscles on pain and disability in women with chronic, nonspecific neck pain.\n Examiner-blinded randomized controlled trial conducted between February 2000 and March 2002.\n Participants were recruited from occupational health care systems in southern and eastern Finland.\n A total of 180 female office workers between the ages of 25 and 53 years with chronic, nonspecific neck pain.\n Patients were randomly assigned to either 2 training groups or to a control group, with 60 patients in each group. The endurance training group performed dynamic neck exercises, which included lifting the head up from the supine and prone positions. The strength training group performed high-intensity isometric neck strengthening and stabilization exercises with an elastic band. Both training groups performed dynamic exercises for the shoulders and upper extremities with dumbbells. All groups were advised to do aerobic and stretching exercises regularly 3 times a week.\n Neck pain and disability were assessed by a visual analog scale, the neck and shoulder pain and disability index, and the Vernon neck disability index. Intermediate outcome measures included mood assessed by a short depression inventory and by maximal isometric neck strength and range of motion measures.\n At the 12-month follow-up visit, both neck pain and disability had decreased in both training groups compared with the control group (P<.001). Maximal isometric neck strength had improved flexion by 110%, rotation by 76%, and extension by 69% in the strength training group. The respective improvements in the endurance training group were 28%, 29%, and 16% and in the control group were 10%, 10%, and 7%. Range of motion had also improved statistically significantly in both training groups compared with the control group in rotation, but only the strength training group had statistically significant improvements in lateral flexion and in flexion and extension.\n Both strength and endurance training for 12 months were effective methods for decreasing pain and disability in women with chronic, nonspecific neck pain. Stretching and fitness training are commonly advised for patients with chronic neck pain, but stretching and aerobic exercising alone proved to be a much less effective form of training than strength training.", "The purpose of this pilot study was to examine the immediate effects of a manual therapy technique called Inhibitive Distraction (ID) on active range of motion (AROM) for cervical flexion in patients with neck pain with or without concomitant headache. A secondary objective of this study was to see whether patient subgroups could be identified who might benefit more from ID by studying variables such as age, pain intensity, presence of headache, or pre-intervention AROM. We also looked at patients' ability to identify pre- to post-intervention changes in their ability to actively move through a range of motion. Forty subjects (mean age 34.7 years; range 16-48 years) referred to a physical therapy clinic due to discomfort in the neck region were randomly assigned to an experimental and a control group. We used the CROM goniometer to measure pre- and post-intervention cervical flexion AROM in the sagittal plane within a single treatment session. The between-group difference in AROM increase was not statistically significant at P<0.05 with a mean post-intervention increase in ROM of 2.4 degrees (SD 6.2 degrees ) for the experimental group and 1.2 degrees (SD 5.8 degrees ) for the placebo group. We were also unable to identify potential subgroups more likely to respond to ID, although a trend emerged for greater improvement in chronic patients with headaches, lower pain levels, and less pre-intervention AROM. In the experimental group and in both groups combined, subjects noting increased AROM indeed had a significantly greater increase in AROM than those subjects not noting improvement. In conclusion, this study did not confirm immediate effects of ID on cervical flexion AROM but did provide indications for potential subgroups likely to benefit from this technique. Recommendations are provided with regard to future research and clinical use of the technique studied.", "The objective of this study is to analyze the immediate effects on neck pain and active cervical range of motion after a single cervical high-velocity low-amplitude (HVLA) manipulation or a control mobilization procedure in mechanical neck pain subjects. In addition, we assessed the possible correlation between neck pain and neck mobility.\n Seventy patients with mechanical neck pain (25 males and 45 females, aged 20-55 years) participated in this study. The lateral gliding test was used to establish the presence of an intervertebral joint dysfunction at the C3 through C4 or C4 through C5 levels. Subjects were divided randomly into either an experimental group, which received an HVLA thrust, or a control group, which received a manual mobilization procedure. The outcome measures were active cervical range of motion and neck pain at rest assessed pretreatment and 5 minutes posttreatment by an assessor blinded to the treatment allocation of the patient. Intragroup and intergroup comparisons were made with parametric tests. Within-group effect sizes were calculated using Cohen's d coefficient.\n Within-group changes showed a significant improvement in neck pain at rest and mobility after application of the manipulation (P < .001). The control group also showed a significant improvement in neck pain at rest (P < .01), flexion (P < .01), extension (P < .05), and both lateral flexions (P < .01), but not in rotation. Pre-post effect sizes were large for all the outcomes in the experimental group (d > 1), but were small to medium in the control mobilization group (0.2 < d < 0.6). The intergroup comparison showed that the experimental group obtained a greater improvement than the control group in all the outcome measures (P < .001). Decreased neck pain and increased range of motion were negatively associated for all cervical motions: the greater the increase in neck mobility, the less the pain at rest.\n Our results suggest that a single cervical HVLA manipulation was more effective in reducing neck pain at rest and in increasing active cervical range of motion than a control mobilization procedure in subjects suffering from mechanical neck pain.", "Shoulder dysfunction remains a frequent complication after neck dissection procedures for head and neck cancer.\n We conducted a pilot study to evaluate the effects of progressive resistance exercise training (PRET) on shoulder dysfunction caused by spinal accessory neurapraxia/neurectomy in patients with head and neck cancer. Twenty patients (mean age, 61 +/- 7.7 years) were randomly assigned to PRET or standard care intervention. Subjects assigned to the PRET group exercised three times per week for 12 weeks. The goal of the exercise program was to enhance scapular stability and strength of the upper extremity. The resistance-training program was progressive in terms of number of sets and repetitions performed, as well as the amount of weight lifted, depending on performance status.\n The completion rate for the trial was 85% (17 of 20). The exercise group completed 93% of scheduled exercise sessions. Significant improvements were found in favor of the PRET group in active shoulder external rotation (p =.001), shoulder pain (p =.038), and overall score for shoulder pain and disability (p =.045).\n The study results demonstrate a high rate of completion and adherence with our PRET program among patients with head and neck cancer. The preliminary findings, although limited, also suggest a potential therapeutic role for resistance exercise as an adjunct to standard physical therapy treatment.\n Copyright 2004 Wiley Periodicals, Inc. Head Neck 26: 518-530, 2004", "A randomized comparative study with single-blind outcome assessments.\n To compare the efficacy of a multimodal treatment emphasizing proprioceptive training (ACTIVE) with activated home exercises (HOME) and recommendation of exercise (CONTROL) in patients with nonspecific chronic neck pain.\n The efficacy of active exercises and passive physiotherapy for neck trouble has been somewhat disappointing in the previous few studies.\n Seventy-six patients (22 men, 54 women) with chronic, nonspecific neck pain participated. Sixty-two participated the 1-year follow-up. Subjective pain and disability, cervical ranges of motion, and pressure pain threshold in the shoulder region were measured at baseline, at 3 months, and at 12 months. The ACTIVE treatment consisted of 24 sessions of proprioceptive exercises, relaxation, and behavioral support. The HOME regimen included a neck lecture and two sessions of practical training for home exercises and instructions for maintaining a diary of progress. The CONTROL treatment included a lecture regarding care of the neck with a recommendation to exercise.\n The average self-experienced total benefit was highest in the ACTIVE group, and the HOME group rated over the CONTROL group (P < 0.001). Differences between the groups in favor of the ACTIVE treatment were recorded in reduction of neck symptoms and improvements in general health and self-experienced working ability (P < 0.01-0.03). Changes in measures of mobility and pressure pain threshold were minor.\n Regarding self-experienced benefit, the multimodal treatment was more efficacious than activated home exercises that were clearly more efficacious than just advising. No major differences were noted in objective measurements of cervical function between the groups, but the content validity of these assessments in chronic neck trouble can be questioned.", "This study assessed the effectiveness of a single intervention targeting work style and a combined intervention targeting work style and physical activity on the recovery from neck and upper limb symptoms. Computer workers with frequent or long-term neck and upper limb symptoms were randomised into the work style group (WS, n=152), work style and physical activity group (WSPA, n=156), or usual care group (n=158). The WS and WSPA group attended six group meetings. All meetings focused on behavioural change with regard to body posture, workplace adjustment, breaks and coping with high work demands (WS and WSPA group) and physical activity (WSPA group). Pain, disability at work, days with symptoms and months without symptoms were measured at baseline and after 6 (T1) and 12 months (T2). Self-reported recovery was assessed at T1/T2. Both interventions were ineffective in improving recovery. The work style intervention but not the combined intervention was effective in reducing all pain measures. These effects were present in the neck/shoulder, not in the arm/wrist/hand. For the neck/shoulder, the work style intervention group also showed an increased recovery-rate. Total physical activity increased in all study groups but no differences between groups were observed. To conclude, a group-based work style intervention focused on behavioural change was effective in improving recovery from neck/shoulder symptoms and reducing pain on the long-term. The combined intervention was ineffective in increasing total physical activity. Therefore we cannot draw conclusions on the effect of increasing physical activity on the recovery from neck and upper limb symptoms.", "Shoulder pain and disability are well recognized complications associated with surgery for head and neck cancer. This study was designed to examine the effects of progressive resistance exercise training (PRET) on upper extremity pain and dysfunction in postsurgical head and neck cancer survivors.\n Fifty-two head and neck cancer survivors were assigned randomly to PRET (n = 27) or a standardized therapeutic exercise protocol (TP) (n = 25) for 12 weeks. The primary endpoint was change in patient-rated shoulder pain and disability from baseline to postintervention. Secondary endpoints were upper extremity strength and endurance, range of motion, fatigue, and quality of life.\n Follow-up assessment for the primary outcome was 92%, and adherence to the supervised PRET and TP programs were 95% and 87%, respectively. On the basis of intention-to-treat analyses, PRET was superior to TP for improving shoulder pain and disability (-9.6; 95% confidence interval [95% CI], -16.4 to -4.5; P = .001), upper extremity strength (+10.8 kg; 95% CI, 5.4-16.2 kg; P < .001), and upper extremity endurance (+194 repetitions x kg; 95% CI, 10-378 repetitions x kg; P = .039). Changes in neck dissection impairment, fatigue, and quality of life favored the PRET group but did not reach statistical significance.\n The PRET program significantly reduced shoulder pain and disability and improved upper extremity muscular strength and endurance in head and neck cancer survivors who had shoulder dysfunction because of spinal accessory nerve damage. Clinicians should consider the addition of PRET in the rehabilitation of postsurgical head and neck cancer survivors.\n (Copyright) 2008 American Cancer Society.", "Few randomized controlled studies have examined the effects of exercise in patients with ankylosing spondylitis (AS). This study investigated the effects of a 12-week, multimodal exercise program in patients with AS.\n A convenience sample of 30 patients with AS (18 male, 12 female), with a mean age of 34.9 years (SD=6.28), participated in the study. Twenty-six subjects were classified as having stage I AS and 4 subjects were classified as having stage II AS according to the modified New York Criteria.\n This study was a randomized controlled trial. Subjects were assigned to either a group that received an exercise program or to a control group. The exercise program consisted of 50 minutes of multimodal exercise, including aerobic, stretching, and pulmonary exercises, 3 times a week for 3 months. Subjects in both groups received medical treatment for AS, but the exercise group received the exercise program in addition to the medical treatment. All subjects received a physical examination at baseline and at 12 weeks. The examinations were conducted under the supervision of a physician who specialized in physical medicine and rehabilitation and included the assessment of spinal mobility using 2 methods: clinical measurements (chin-to-chest distance, Modified Schober Flexion Test, occiput-to-wall distance, finger-to-floor distance, and chest expansion) and inclinometer measurements (gross hip flexion, gross lumbar flexion, and gross thoracic flexion). In addition, vital capacity was measured by a physiologist, and physical work capacity was evaluated by a doctorally prepared exercise instructor.\n The measurements of the exercise group for chest expansion, chin-to-chest distance, Modified Schober Flexion Test, and occiput-to-wall distance were significantly better than those of the control group after the 3-month exercise period. The spinal movements of the exercise group improved significantly at the end of exercise program, but those of the control group showed no significant change. In addition, the results showed that the posttraining value of gross thoracic flexion of the exercise group was significantly higher than that of the control group. Physical work capacity and vital capacity values improved in the exercise group but decreased in the control group.\n In this study, a multimodal exercise program including aerobic, stretching, and pulmonary exercises provided in conjunction with routine medical management yielded greater improvements in spinal mobility, work capacity, and chest expansion.", "To study the relative efficacy of three different treatment for chronic low back pain (CLBP). Two preplanned comparisons were made: (a) Spinal manipulative therapy (SMT) combined with trunk strengthening exercises (TSE) vs. SMT combined with trunk stretching exercises, and (b) SMT combined with TSE vs. nonsteroidal anti-inflammatory drug (NSAID) therapy combined with TSE.\n Interdisciplinary, prospective, observer-blinded, randomized clinical trial with a 1-yr follow-up period. The trial evaluated therapies in combination only and was not designed to test the individual treatment components.\n Primary contact, college out-patient clinic.\n In total, 174 patients aged 20-60 yr were admitted to the study.\n Patient-rated low back pain, disability, and functional health status at 5 and 11 wk.\n Five weeks of SMT or NSAID therapy in combination with supervised trunk exercise, followed by and additional 6 wk of supervised exercise alone.\n Individual group comparisons after 5 and 11 wk of intervention on all three main outcome measures did not reveal any clear clinically important or statistically significant differences. There seemed to be a sustained reduction in medication use at the 1-yr follow-up. in the SMT/TSE group. Continuance of exercise during the follow-up year, regardless of type, was associated with a better outcome.\n Each of the three therapeutic regimens was associated with similar and clinically important improvement over time that was considered superior to the expected natural history of long-standing CLBP. For the management of CLBP, trunk exercise in combination with SMT or NSAID therapy seemed to be beneficial and worthwhile. The magnitude of nonspecific therapeutic (placebo) effects, cost-effectiveness and relative risks of side effects associated with these types of therapy need to be addressed in future studies.", "Head repositioning accuracy (HRA) after full range active motion was evaluated in 60 cervicalgic patients. The mean angular error was 7.7 degrees +/- 3.3 (mean +/- SD) and 82% were outside a threshold value of 4.5 degrees. After randomization 30 patients followed a rehabilitation program based on eye-head coupling (RG) and 30 served as a control group (CG). At 10 week follow-up, a greater gain in HRA was observed in the RG (2 degrees +/- 2.7, mean +/- SD) than in the CG (0 +/- 2.6, mean +/- SD) (p = 0.005). Clinical parameters (pain, drug intake, range of motion, and self assessed functional improvement) were also more improved in the RG than in the CG. These data emphasize the role of a neck proprioception alteration in chronic neck pain and suggest that a rehabilitation program based on eye-head coupling should be included in most medical management of cervicalgic patients.", "To acquire information for designing a large clinical trial and determining its feasibility and to make preliminary estimates of the relationship between headache outcomes and the number of visits to a chiropractor.\n Randomized, controlled trial.\n Private practice in a college outpatient clinic and in the community.\n Twenty-four adults with chronic cervicogenic headache.\n Patients were randomly allocated to 1, 3, or 4 visits per week for 3 weeks. All patients received high-velocity low-amplitude spinal manipulation. Doctor of Chiropractics could apply up to 2 physical modalities at each visit from among heat and soft tissue therapy. They could also recommend modification of daily activities and rehabilitative exercises. Outcomes included 100-point Modified Von Korff pain and disability scales, and headaches in last 4 weeks.\n Only 1 participant was insufficiently compliant with treatment (3 of 12 visits), and 1 patient was lost to follow-up. There was substantial benefit in pain relief for 9 and 12 treatments compared with 3 visits. At 4 weeks, the advantage was 13.8 ( P = .135) for 3 visits per week and 18.7 (P = .041) for 4 visits per week. At the 12-week follow-up, the advantage was 19.4 (P = .035) for 3 visits per week and 18.1 (P = .048) for 4 visits per week.\n A large clinical trial on the relationship between pain relief and the number of chiropractic treatments is feasible. Findings give preliminary support for the benefit of larger doses, 9 to 12 treatments, of chiropractic care for the treatment of cervicogenic headache.", "Randomized, parallel-group trial.\n To compare the effect of 3 early intervention strategies following whiplash injury.\n Long-lasting pain and disability, known as chronic whiplash-associated disorder (WAD), may develop after a forced flexion-extension trauma to the cervical spine. It is unclear whether this, in some cases disabling, condition can be prevented by early intervention. Active interventions have been recommended but have not been compared with information only.\n Participants were recruited from emergency units and general practitioners within 10 days after a whiplash injury and randomized to: 1) immobilization of the cervical spine in a rigid collar followed by active mobilization, 2) advice to \"act-as-usual,\" or 3) an active mobilization program (Mechanical Diagnosis and Therapy). Follow-up was carried out after 3, 6, and 12 months postinjury. Treatment effect was measured in terms of headache and neck pain intensity (0-10), disability, and work capability.\n A total of 458 participants were included. At the 1-year follow-up, 48% of participants reported considerable neck pain, 53% disability, and 14% were still sick listed at 1 year follow-up. No significant differences were observed between the 3 interventions group.\n Immobilization, \"act-as-usual,\" and mobilization had similar effects regarding prevention of pain, disability, and work capability 1 year after a whiplash injury.", "Randomized clinical trial.\n To compare the effects of spinal manipulation combined with low-tech rehabilitative exercise, MedX rehabilitative exercise, or spinal manipulation alone in patient self-reported outcomes over a two-year follow-up period.\n There have been few randomized clinical trials of spinal manipulation and rehabilitative exercise for patients with neck pain, and most have only reported short-term outcomes.\n One hundred ninety-one patients with chronic neck pain were randomized to 11 weeks of one of the three treatments. Patient self-report questionnaires measuring pain, disability, general health status, improvement, satisfaction, and OTC medication use were collected after 5 and 11 weeks of treatment and 3, 6, 12, and 24 months after treatment. Data were analyzed taking into account all time points using repeated measures analyses.\n Ninety-three percent (178) of randomized patients completed the 11-week intervention phase, and 76% (145) provided data at all evaluation time points over the two-year follow-up period. A difference in patient-rated pain with no group-time interaction was observed in favor of the two exercise groups [F(2141) = 3.2; P= 0.04]. There was also a group difference in satisfaction with care [F(2143) = 7.7; P= 0.001], with spinal manipulation combined with low-tech rehabilitative exercise superior to MedX rehabilitative exercise (P = 0.02) and spinal manipulation alone (P < 0.001). No significant group differences were found for neck disability, general health status, improvement, and OTC medication use, although the trend over time was in favor of the two exercise groups.\n The results of this study demonstrate an advantage of spinal manipulation combined with low-tech rehabilitative exercise and MedX rehabilitative exercise versus spinal manipulation alone over two years and are similar in magnitude to those observed after one-year follow-up. These results suggest that treatments including supervised rehabilitative exercise should be considered for chronic neck pain sufferers. Further studies are needed to examine the cost effectiveness of these therapies and how spinal manipulation compares to no treatment or minimal intervention." ]	Low to moderate quality evidence supports the use of specific cervical and scapular stretching and strengthening exercise for chronic neck pain immediately post treatment and intermediate term, and cervicogenic headaches in the long term. Low to moderate evidence suggests no benefit for some upper extremity stretching and strengthening exercises or a general exercise program. Future trials should consider using an exercise classification system to establish similarity between protocols and adequate sample sizes. Factorial trials would help determine the active treatment agent within a treatment regimen where a standardized representation of dosage is essential. Standardized reporting of adverse events is needed for balancing the likelihood of treatment benefits over potential harms.
CD004424	[ "8780077", "7823066", "10486394", "8601999", "3919805" ]	[ "A randomized, blinded, placebo-controlled trial of divalproex sodium prophylaxis in adults with newly diagnosed brain tumors.", "Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial.", "Comparative double blind clinical trial of phenytoin and sodium valproate as anticonvulsant prophylaxis after craniotomy: efficacy, tolerability, and cognitive effects.", "Randomised comparative monotherapy trial of phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed childhood epilepsy.", "Which drug for the adult epileptic patient: phenytoin or valproate?" ]	[ "Seizures occur after the diagnosis of brain tumors in up to 40% of patients. Prophylactic anticonvulsants are widely advocated despite a lack of convincing evidence of their efficacy in preventing first seizures. We conducted a randomized, double-blind, placebo-controlled study comparing the incidence of first seizures in divalproex sodium- and placebo-treated patients with newly diagnosed brain tumors.\n Patients who had not previously had a seizure were randomized within 14 days of diagnosis of their brain tumor to receive either divalproex sodium or placebo. All patients had at least one supratentorial brain lesion, a Karnofsky Performance Score (KPS) > or = 50%, and no previous anticonvulsant use or other brain disease. Compliance and adequacy of dosing were assessed by pill counts and monthly blood levels.\n Seventy-four of 75 consecutive eligible patients were entered in this study. Median follow-up was 7 months. The drug and placebo groups did not differ significantly in age, sex, KPS, primary tumor type, number or location of brain lesions, frequency of brain surgery, or pretreatment EEG. Thirteen of 37 patients (35%) receiving divalproex sodium and 9 of 37 patients (24%) on placebo had seizures. The odds ratio for a seizure in the divalproex sodium arm relative to the placebo arm was 1.7 (95% CI 0.6 to 4.6; p = 0.3). The hypothesis that anticonvulsant prophylaxis provides a reduction in the frequency of first seizure as small as 30% was rejected (p = 0.05).\n Anticonvulsant prophylaxis with divalproex sodium is not indicated for patients with brain tumors who have not had seizures.", "Recent studies have shown that most newly diagnosed epileptic patients can be satisfactorily treated with a single antiepileptic drug. We therefore undertook a prospective randomised pragmatic trial of the comparative efficacy and toxicity of four major antiepileptic drugs, utilised as monotherapy in newly diagnosed epileptic patients. Between 1981 and 1987 243 adult patients aged 16 years or over, newly referred to two district general hospitals with a minimum of two previously untreated tonic-clonic or partial with or without secondary generalised seizures were randomly allocated to treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform with standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to enter one year remission. The overall outcome with all of the four drugs was good with 27% remaining seizure free and 75% entering one year of remission by three years of follow up. No significant differences between the four drugs were found for either measure of efficacy at one, two, or three years of follow up. The overall incidence of unacceptable side effects, necessitating withdrawal of the randomised drug, was 10%. For the individual drugs phenobarbitone (22%) was more likely to be withdrawn than phenytoin (3%), carbamazepine (11%), and sodium valproate (5%). In patients with newly diagnosed tonic-clonic or partial with or without secondary generalised seizures, the choice of drug will be more influenced by considerations of toxicity and costs.", "To determine the efficacy, tolerability, and impact on quality of life and cognitive functioning of anticonvulsant prophylaxis with phenytoin or sodium valproate in patients after craniotomy.\n A prospective, stratified, randomised, double blind single centre clinical trial was performed, comparing two groups of 50 patients each, who underwent craniotomy for different pathological conditions and who were treated for 1 year after surgery with either 300 mg phenytoin/day or 1500 mg sodium valproate/day. During the study period patients were seen in the outpatient clinic at 1.5, 3, 6, and 12 months, when medical history, adverse events, and drug plasma concentrations were evaluated. Neuropsychological functioning and quality of life were assessed on the last three visits. In cases of a seizure an EEG was performed, drug plasma concentration assessed, and medication subsequently increased.\n Of the 100 included patients 14 (seven in each group) experienced one or more postoperative seizures. Severity of the seizures was comparable in the two groups. In all patients, drug plasma concentrations were in the low or subtherapeutic ranges at the time of the first postoperative seizure. Five patients in the phenytoin group and two in the valproate group had to stop their treatment due to drug related adverse events. Sixty patients completed the 12 month period. Analysis of neuropsychological and quality of life data showed no significant differences.\n For efficacy, tolerability, impact on cognitive functioning, and quality of life, no major differences were found between phenytoin and valproate prophylaxis. Valproate is an alternative for anticonvulsant prophylaxis in patients after craniotomy.", "The medical treatment of childhood epilepsy is largely influenced by clinical trials in adult patients. We know of only one randomised comparative trial (of two drugs) in newly diagnosed childhood epilepsy. We have undertaken a long-term, prospective, randomised, unmasked, pragmatic trial of the comparative efficacy and toxicity of four standard antiepileptic drugs used as monotherapy in children with newly diagnosed epilepsy.\n Between 1981 and 1987, 167 children aged 3-16 years, who had had at least two previously untreated tonic-clonic or partial seizures, with or without secondary generalisation, were randomly allocated treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform to standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to achieving 1-year remission.\n The overall outcome with all four drugs was good. 20% of children remained free of seizures and 73% had achieved 1-year remission by 3 years of follow-up. We found no significant differences between the drugs for either measure of efficacy at 1, 2, or 3 years of follow-up. The overall frequency of unacceptable side-effects necessitating withdrawal of the randomised drug was 9%. This total included six of the first ten children assigned phenobarbitone; no further children were allocated this drug. Of the other three drugs, phenytoin (9%) was more likely to be withdrawn than carbamazepine (4%) or sodium valproate (4%). INTERPRETATION Our data will inform choice of drug and outcome with four of the standard drugs available for newly diagnosed tonic-clonic or partial seizures with or without secondary generalisation in children.", "A series of 140 previously untreated patients with tonic-clonic or partial seizures were randomised to receive either phenytoin or sodium valproate. There was no difference between the treatment groups in pretreatment variables that might influence outcome. Sodium valproate and phenytoin in the treatment of tonic-clonic or partial seizures showed no difference in efficacy as regards time to two year remission or time to first seizure. When the possible prognostic factors were studied, including history and results of clinical examination and investigations before treatment; the only factor which influenced the proportion of patients achieving two year remission was type of seizure. Patients with a clinical history of partial seizures did significantly less well than those with a history of tonic-clonic seizures only. This study showed no major difference in efficacy between sodium valproate and phenytoin in adults with recent onset of epilepsy, irrespective of the type of seizures that the patient suffered." ]	The evidence is neutral, neither for nor against seizure prophylaxis, in people with brain tumors. These conclusions apply only for the antiepileptic drugs phenytoin, phenobarbital, and divalproex sodium. The decision to start an antiepileptic drug for seizure prophylaxis is ultimately guided by assessment of individual risk factors and careful discussion with patients.
CD003906	[ "8813270", "3511382" ]	[ "Plasma-exchange therapy in chronic inflammatory demyelinating polyneuropathy. A double-blind, sham-controlled, cross-over study.", "Plasma exchange in chronic inflammatory demyelinating polyradiculoneuropathy." ]	[ "Eighteen patients with definite, untreated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) of chronic progressive (nine patients) or relapsing course (nine patients) were randomized prospectively to receive 10 plasma-exchange (PE) or sham plasma-exchange (SPE) treatments over 4 weeks in a double-blind trial. After a wash-out period of 5 weeks or when they returned to baseline scores, patients were crossed over to the alternate treatments. Neurological function was assessed serially using a quantitative neurological disability score (NDS), a functional clinical grade (CG) and grip strength (GS) measurements. Electrophysiological studies were done at the beginning and end of each treatment. A primary 'intention to treat' analysis showed significant improvement with PE in all clinical outcome measures: NDS by 38 points, P < 0.001; CG by 1.6 points, P < 0.001; GS by +13 kg, P < 0.003 and in selected electrophysiological measurements, sigma proximal CMAP, P < 0.01; sigma motor conduction velocities, P < 0.006; sigma distal motor latencies, P < 0.01. Fifteen patients completed the trial and of those, 12 patients (80%) improved substantially with PE; i.e. five out of seven patients with chronic progressive course and seven out of eight patients with relapsing CIDP improved. There were three drop-outs; one patient lost venous access; one patient suffered a stroke and one patient left the trial to receive open treatment elsewhere. The improvement in motor functions correlated with the electrophysiological data, i.e. with improved motor conduction velocities and reversal of conduction block. Eight of 12 PE responders (66%) relapsed within 7-14 days after stopping PE. All improved with subsequent open label PE; all but two patients required long-term immunosuppressive drug therapy for stabilization. The PE non-responders improved with prednisone. We conclude that PE is a very effective adjuvant therapy for CIDP of both chronic progressive and relapsing course; concurrent immunosuppressive drug treatment is required. Exchange treatments should be given two to three times per week until improvement is established; the treatment frequency should then be tapered over several months.", "Plasma exchange has been reported to be efficacious in chronic inflammatory demyelinating polyradiculoneuropathy. We performed a prospective double-blind trial in which patients with static or worsening disease were randomly assigned to plasma exchange (n = 15) or to sham exchange (n = 14) for three weeks. After three weeks, we observed statistically significant differences in combined measurements of nerve conduction (total, motor, proximal, velocity, and amplitude) favoring patients who had received plasma exchange. Improvement to a greater degree than for any patient receiving sham exchange was detected in the neurologic-disability score in five patients (P = 0.025) and in subset scores for weakness and reflex in four patients (P less than 0.057). We conclude that for some patients with chronic inflammatory demyelinating polyradiculoneuropathy, plasma exchange has an ameliorating effect on neurologic dysfunction and nerve conduction, but in others no improvement is observed. Because plasma was replaced with normal serum albumin, a humoral factor or factors may have a role in the neurologic deficit of this disorder." ]	Moderate to high quality evidence from two small trials showed that plasma exchange provides significant short-term improvement in disability, clinical impairment and motor nerve conduction velocity in CIDP but rapid deterioration may occur afterwards. Adverse events related to difficulty with venous access, use of citrate and haemodynamic changes are not uncommon. More research is needed to identify agents which will prolong the beneficial action of plasma exchange.
CD006527	[ "18161613", "17416878", "12384193", "12677565" ]	[ "Quality of reporting of key methodological items of randomized controlled trials in clinical ophthalmic journals.", "Studying injury prevention: practices, problems, and pitfalls in implementation.", "In the dark: the reporting of blinding status in randomized controlled trials.", "Randomized controlled trials in pediatric surgery: could we do better?" ]	[ "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.", "This prospective, randomized, controlled trial was conducted to determine feasibility and effectiveness of a chronic care model approach to injury prevention compared with standard anticipatory guidance. Enrolled caregivers of children aged 0 to 5 years received focused counseling from a physician and health assistant, educational handouts, phone follow-up, and access to free safety devices and automobile restraint evaluations. Only 35.1% of eligible parents participated. Home visits were completed at 6 months to observe safety practices. Injuries were gleaned from parent report and medical record review. Safety practices were evaluated in 27 households. Chart review showed no significant difference in the number of medically attended injuries between groups (P = 0.6). The impact of the chronic care model on injury prevention in primary care could not be determined with certainty. Evaluating effectiveness of injury prevention strategies on actual safety practices with direct observation is challenging.", "To determine the quality of reporting of blinding in randomized controlled trials (RCTs), we evaluated 40 consecutive RCTs published in each of five leading journals. We noted whether authors reported the blinding status of participants, health care providers, data collectors, judicial assessors of outcomes, data analysts, and manuscript writers. Explicit reporting of blinding status occurred in <25% of RCTs for all groups. Eighty-three RCTs, reported as double-blind, provided eight combinations of blinded groups. In conclusion, prestigious journals do not currently report blinding status optimally. To do so, journals should abandon the term \"double blind\" and explicitly report the blinding status of the groups involved in RCTs. Until such reporting occurs, clinicians will be left with uncertainty about the validity of RCTs that guide their clinical practice.", "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." ]	The included studies do not provide reliable evidence that educational interventions are effective in preventing eye injuries. There is a need for well-conducted RCTs with adequate allocation concealment and masking (blinding). Studies should have a longer follow-up time and more studies need to be conducted in low and middle-income countries.
CD002195	[ "7931476", "12881382", "3666158", "12488405" ]	[ "First isolated locoregional recurrence following mastectomy for breast cancer: results of a phase III multicenter study comparing systemic treatment with observation after excision and radiation. Swiss Group for Clinical Cancer Research.", "Adjuvant therapy after excision and radiation of isolated postmastectomy locoregional breast cancer recurrence: definitive results of a phase III randomized trial (SAKK 23/82) comparing tamoxifen with observation.", "A trial of human alpha interferon as an adjuvant agent in breast cancer after loco-regional recurrence.", "Randomized adjuvant trial of tamoxifen and goserelin versus cyclophosphamide, methotrexate, and fluorouracil: evidence for the superiority of treatment with endocrine blockade in premenopausal patients with hormone-responsive breast cancer--Austrian Breast and Colorectal Cancer Study Group Trial 5." ]	[ "We performed a randomized phase III multicenter study to compare systemic treatment versus no treatment after complete excision and radiotherapy for isolated first locoregional recurrence in patients with breast cancer.\n One hundred sixty-seven good-risk patients with an estrogen receptor (ER+) positive recurrence or, in case of unknown receptor status, a disease-free interval (DFI) of greater than 12 months and < or = three recurrent tumor nodules each < or = 3 cm in diameter were entered onto the study. They were randomized to observation subsequent to local treatment or to receive tamoxifen (TAM) until disease progression. Seventy-nine percent of the patients were postmenopausal.\n The median observation period for the entire study population was 6.3 years. The median disease-free survival (DFS) duration was 26 months for observation and 82 months for TAM patients (P = .007). This was mainly due to the reduction of further local recurrences, whereas the occurrence of early distant metastases was delayed. A multivariate analysis identified DFI and treatment with TAM as significant prognostic factors for DFS. The 5-year overall survival (OS) rates were 76% and 74%, respectively (P = .77). DFI was also a prognostic factor for OS.\n Systemic therapy with TAM after isolated locoregional recurrence of breast cancer significantly increased 5-year DFS rates from 36% to 59% compared with observation alone and prolonged median DFS by more than 4.5 years in patients with ER+ tumors or in the case of unknown ER status with a DFI of greater than 12 months and minimal tumor burden. Treatment with TAM currently has no significant impact on OS, but the median survival duration of the study population has not yet been reached.", "Adjuvant systemic treatment for patients with isolated locoregional recurrence (ILRR) of breast cancer is based on a single reported randomized trial. The trial, conducted by the Swiss Group for Clinical Cancer Research, compared tamoxifen (TAM) with observation after complete excision of the ILRR and proper radiotherapy. We performed a definitive analysis of treatment outcome at >11 years of follow-up, after the majority of the patients had a subsequent event of interest. Patient and methods One hundred and sixty-seven patients with 'good-risk' characteristics of disease were randomized. 'Good-risk' was defined as estrogen receptor expression in the ILRR, or having a disease-free interval of >12 months and a recurrence consisting of three or less tumor nodules, each </=3 cm in diameter. Seventy-nine percent of the patients were postmenopausal at randomization.\n The median follow-up time of the surviving patients was 11.6 years. The median post ILRR disease-free survival (DFS) was 6.5 years with TAM and 2.7 years with observation (P = 0.053). The difference was mainly due to reduction of further local relapses (P = 0.011). In postmenopausal patients, TAM led to an increase of DFS from 33% to 61% (P = 0.006). In premenopausal women, 5-year DFS was 60%, independent of TAM medication. For the whole study population, the median post-recurrence overall survival (OS) was 11.2 and 11.5 years in the observation and the TAM group, respectively; premenopausal patients experienced a 5-year OS of 90% for observation compared with 67% for TAM (P = 0.175), while the respective figures for postmenopausal patients were both 75%.\n These definitive results confirmed that TAM significantly improves the post-recurrence DFS of patients after local treatment for ILRR. This beneficial effect does not translate into a detectable OS advantage.", "Thirty-two women who had developed loco-regional recurrence of breast carcinoma were entered into a controlled trial of adjuvant alpha-interferon. All patients had histological confirmation of recurrence, local treatment with radiotherapy and negative staging investigations. They were then randomized to either observation alone, or treatment with human alpha interferon 3 x 10(6) units subcutaneously daily for 1 year. There were no differences detected in the rate of local or distant relapse. With this lack of clinically significant efficacy and a high incidence of side effects, it is concluded that alpha interferon is of doubtful value in the adjuvant treatment of breast cancer.", "Effective adjuvant treatment modalities in premenopausal breast cancer patients today include chemotherapy, ovariectomy, and tamoxifen administration. The purpose of Austrian Breast and Colorectal Cancer Study Group Trial 5 was to compare the efficacy of a combination endocrine treatment with standard chemotherapy.\n Assessable trial subjects (N = 1,034) presenting with hormone-responsive disease were randomized to receive either 3 years of goserelin plus 5 years of tamoxifen or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Stratification criteria included tumor stage and grade, number of involved nodes, type of surgery, and steroid hormone receptor content. Relapse-free survival (RFS) was defined as time from randomization to first relapse, local recurrence, or contralateral incidence, and overall survival (OS) as time to date of death.\n With a 60-month median follow-up, 17.2% of patients in the endocrine group and 20.8% undergoing chemotherapy developed relapses. Local recurrences emerged in 4.7% and 8.0%, respectively. RFS and local recurrence-free survival differed significantly in favor of endocrine therapy (P =.037 and P =.015), with a similar trend observed in OS (P =.195).\n Overall, our data suggest that the goserelin-tamoxifen combination is significantly more effective than CMF in the adjuvant treatment of premenopausal patients with stage I and II breast cancer." ]	This systematic review of randomised trials provides insufficient evidence to support systemic treatment in women with loco-regional recurrence of breast cancer. Participation in randomised trials of systemic treatment versus observation is appropriate.
CD003861	[ "12964289", "1356466", "17456554", "12216046", "12712026", "14974959", "7212184", "10085281", "10734596", "16553931" ]	[ "Is tap water a safe alternative to normal saline for wound irrigation in the community setting?", "Comparison between sterile saline and tap water for the cleaning of acute traumatic soft tissue wounds.", "A multicenter comparison of tap water versus sterile saline for wound irrigation.", "Tap water for irrigation of lacerations.", "Wound irrigation in children: saline solution or tap water?", "Bacterial load in relation to vacuum-assisted closure wound therapy: a prospective randomized trial.", "Effect of washing closed head and neck wounds on wound healing and infection.", "Effects of topical honey on post-operative wound infections due to gram positive and gram negative bacteria following caesarean sections and hysterectomies.", "[Modification of postoperative wound healing by showering].", "Combining drinking water treatment and hand washing for diarrhoea prevention, a cluster randomised controlled trial." ]	[ "This double-blind randomised controlled trial compared the effects of tap water and normal saline on the healing and infection rates of acute and chronic wounds.\n The trial was conducted in two metropolitan community health centres in New South Wales, Australia. Thirty-five patients with 49 acute or chronic wounds were randomised to receive wound irrigation with either normal saline or tap water.\n Statistical analysis demonstrated there was no significant difference between the infection and healing rates in wounds irrigated with normal saline or tap water.\n Although the small sample size is a limitation of this study, the researchers conclude that drinkable tap water appears to provide a safe alternative to normal saline for wound cleansing and may be preferred by some patients.", "To find out if there were any differences in infection rates if acute traumatic soft tissue wounds were cleaned with tap water instead of sterile saline.\n Randomised study.\n Emergency department at one city hospital.\n 705 consecutive patient with soft tissue wounds less than six hours old that did not penetrate a viscus, cavity, or joint and could be treated by primary suture.\n Randomly allocated to have the wound cleaned with either sterile saline or tap water in addition to debridement.\n Rate of wound infection, the presence of which was indicated by pus in the wound and prolonged healing.\n The infection rate in wounds cleaned with sterile saline was 10.3% compared with 5.4% in wounds cleaned with tap water (p less than 0.05). Infected wounds were significantly larger than uninfected ones (p less than 0.05) and more likely to be located on a lower extremity (p less than 0.05). There were no microbiological differences between the two groups, and no bacterial species grown from tap water was subsequently grown from an infected wound.\n Sterile saline should be replaced by tap water for the cleaning of acute traumatic superficial soft tissue wounds.", "To compare wound infection rates for irrigation with tap water versus sterile saline before closure of wounds in the emergency department.\n The study was a multicenter, prospective, randomized trial conducted at two Level 1 urban hospitals and a suburban community hospital. Subjects were a convenience sample of adults presenting with acute simple lacerations requiring sutures or staples. Subjects were randomized to irrigation in a sink with tap water or with normal saline using a sterile syringe. Wounds were closed in the standard fashion. Subjects were asked to return to the emergency department for suture removal. Those who did not return were contacted by telephone. Wounds were considered infected if there was early removal of sutures or staples, if there was irrigation and drainage of the wound, or if the subject needed to be placed on antibiotics. Equivalence of the groups was met if there was less than a doubling of the infection rate.\n A total of 715 subjects were enrolled in the study. Follow-up data were obtained on 634 (88%) of enrolled subjects. Twelve (4%) of the 300 subjects in the tap water group had wound infections, compared with 11 (3.3%) of the 334 subjects in the saline group. The relative risk was 1.21 (95% confidence interval = 0.5 to 2.7).\n Equivalent rates of wound infection were found using either irrigant. The results of this multicenter trial evaluating tap water as an irrigant agree with those from previous single institution trials.", "This study was designed to compare the infection rates of simple lacerations irrigated with tap water versus sterile normal saline before repair. Patients with simple lacerations to an extremity that were less than 8 hours from injury were prospectively enrolled. Exclusions from the study were: dog bites, hand lacerations, immunocompromised patients, and those on antibiotics at the time of injury. Patients who qualified were randomized to receive tap water or normal saline for wound irrigation. Before and after irrigation, wound cultures were obtained. After the procedure was complete, patients were scheduled for a 48 hour follow-up wound check. A total of 46 patients were enrolled in the study. Twenty-four patients were randomized to the normal saline group and 21 were assigned to receive tap water irrigation. There were 2 infected lacerations in both the tap water and normal saline groups. The organisms cultured from the wounds in both groups were similar and there was no difference in colony counts when tap water was used. The use of tap water for the irrigation of lacerations does not result in the growth of unusual organisms or increase the colony counts of organisms. Wound infection rates were the same in both groups. This pilot study suggests that the use of tap water for irrigation of wounds may be safe. Further validation is necessary.\n Copyright 2002, Elsevier Science (USA). All rights reserved.", "Irrigation, a critical component of wound management, is commonly performed with sterile normal saline solution. The purpose of this study was to compare the infection rates of wounds irrigated with normal saline solution versus those of wounds irrigated with running tap water.\n A prospective trial was conducted in an urban pediatric emergency department. Tap water pressure and flow rates were measured, and cultures were obtained before the study and at 5 months after study initiation. Patients 1 to 17 years of age presenting to the pediatric ED with a simple laceration were eligible. Exclusion criteria included immunocompromise, complicated lacerations, or current use of or need for antibiotics. Patients were allocated to the running tap water group or the standard normal saline solution irrigation group. Wounds were closed in standard fashion. Patients returned to the pediatric ED in 48 to 72 hours for evaluation.\n Two hundred seventy-one patients were enrolled in the normal saline solution group and 259 in the tap water group. Tap water and normal saline solution pressures and flow rates differed. The groups did not differ in terms of patient demographic characteristics or wound characteristics. However, more wounds were located on the hand in the tap water group (21.3%; 95% confidence interval [CI] 16.3% to 27.1%) compared with those in the normal saline solution group (9.2%; 95% CI 5.9% to 13.4%). The wound infection rates were similar in the 2 groups (normal saline solution group: 2.8% [95% CI 1.1% to 5.7%] versus running tap water group: 2.9% [95% CI 1.2% to 5.9%]).\n There were no clinically important differences in infection rates between wounds irrigated with tap water or normal saline solution. Tap water might be an effective alternative to normal saline solution for wound irrigation in children.", "Vacuum-assisted closure has become a new technique in the challenging management of contaminated, acute, and chronic wounds. Although promising clinical results have been described, scientific proof to substantiate the mechanism of action of this therapy is scarce. In the present study, we examined whether the positive effect on wound healing found in vacuum-assisted closure-treated wounds could be explained by an effect on the bacterial load. Fifty-four patients who needed open wound management before surgical closure were included in this study. Wounds were randomized to either vacuum-assisted closure therapy (n= 29) or treatment by conventional moist gauze therapy (n= 25). Healing was characterized by development of a clean granulating wound bed (\"ready for surgical therapy\") and reduction of wound surface area. To quantify bacterial load, biopsies were collected. No significant difference was found in time needed to reach \"ready for surgical therapy\" comparing both therapies. Wound surface area reduction was significantly larger in vacuum-assisted closure-treated wounds: 3.8 +/- 0.5 percent/day (mean +/- SEM) compared to conventional-treated wounds (1.7 +/- 0.6 percent/day; p < 0.05). The total quantitative bacterial load was generally stable in both therapies. However, nonfermentative gram negative bacilli showed a significant decrease in vacuum-assisted closure-treated wounds (p < 0.05), whereas Staphylococcus aureus showed a significant increase in vacuum-assisted closure-treated wounds (p < 0.05). In conclusion, this study shows a positive effect of vacuum-assisted closure therapy on wound healing, expressed as a significant reduction of wound surface area. However, this could not be explained by a significant quantitative reduction of the bacterial load.", "A group of 100 patients were compared with 100 control patients. Both groups had either traumatic or surgically incised clean wounds of the head and neck. The groups were similar except that the 100 test patients were allowed to wash their head and neck wounds with soap and water within hours after the repair, while the control group kept their wounds dry until all of the sutures were removed. On the basis of this study, we believe that allowing patients to wash their wounds and bathe routinely as early as 8 hours after wound closure hs no effect on wound or infection. We believe that good technique during surgery for incision or laceration closure is much more important than any manipulation of the wound or of the general body systems.", "The possible therapeutic effect of topical crude undiluted honey in the treatment of severe acute postoperative wound infections was studied. Fifty patients having postoperative wound infections following caesarean sections or total abdominal hysterectomies with gram positive or gram negative bacterial infections were allocated in two groups. Twenty-six patients (group A) were treated with 12 hourly application of crude honey and 24 patients (group B) were treated with local antiseptics: spirit (70% Ethanol) and povidone-iodine. Both groups received systemic antibiotics according to culture and sensitivity. Results showed that eradication of bacterial infections was obtained after 6 +/- 1.9 days (mean +/- SD) in group A and after 14.8 +/- 4.2 days in group B (p <0.05). Period for antibiotics use was 6.88 +/- 1.7 days in-group A and 15.45 +/- 4. 37 in-group B (p <0.05). Complete wound healing was evident after 10. 73 +/- 2.5 days in group A and after 22.04 +/- 7.33 in group B (p <0. 05). Size of postoperative scar was 3.62 +/- 1.4 mm after using topical honey and was 8.62 +/- 3.8 mm after local antiseptics (p <0. 05). The mean hospital stay was 9.36 +/- 1.8 days in group A and 19. 91 +/- 7.35 days in group B (p <0.05). After using honey, 22/26 patients (84.4%) showed complete wound healing without wound disruption or need for re-suturing and only 4 patients showed mild dehiscence. In group B, 12/24 patients (50%) showed complete wound healing and 12 patients showed wound dehiscence, six of them needed re-suturing under general anesthesia. We concluded that topical application of crude undiluted honey could (1) faster eradication of bacterial infections, (2) reduce period of antibiotic use and hospital stay, (3) accelerate wound healing, (4) prevent wound dehiscence and need for re-suturing and (5) result in minimal scar formation.", "Usually postoperative wounds are kept dry until the stitches are removed. In a prospective randomized study early water contact was allowed in order to test postoperative wound healing in 817 patients operated on for varicose veins. Regardless of whether the wounds were kept dry or had water contact with or without shower foam from the second postoperative day, no infection was registered.", "To evaluate the effectiveness of point of use water treatment with flocculent-disinfectant on reducing diarrhoea and the additional benefit of promoting hand washing with soap.\n The study was conducted in squatter settlements of Karachi, Pakistan, where diarrhoea is a leading cause of childhood death. Interventions were randomly assigned to 47 neighbourhoods. Households in 10 neighbourhoods received diluted bleach and a water vessel; nine neighbourhoods received soap and were encouraged to wash hands; nine neighbourhoods received flocculent-disinfectant water treatment and a water vessel; 10 neighbourhoods received disinfectant-disinfectant water treatment and soap and were encouraged to wash hands; and nine neighbourhoods were followed as controls. Field workers visited households at least once a week from April to December 2003 to promote use of the interventions and to collect data on diarrhoea.\n Study participants in control neighbourhoods had diarrhoea on 5.2% of days. Compared to controls, participants living in intervention neighbourhoods had a lower prevalence of diarrhoea: 55% (95% CI 17%, 80%) lower in bleach and water vessel neighbourhoods, 51% (95% CI 12%, 76%) lower in hand washing promotion with soap neighbourhoods, 64% lower (95% CI 29%, 90%) in disinfectant-disinfectant neighbourhoods, and 55% (95% CI 18%, 80%) lower in disinfectant-disinfectant plus hand washing with soap neighbourhoods.\n With an intense community-based intervention and supplies provided free of cost, each of the home-based interventions significantly reduced diarrhoea. There was no benefit by combining hand washing promotion with water treatment." ]	There is no evidence that using tap water to cleanse acute wounds in adults or children increases or reduces infection. There is not strong evidence that cleansing wounds per se increases healing or reduces infection. In the absence of potable tap water, boiled and cooled water as well as distilled water can be used as wound cleansing agents.
CD008414	[ "2668784", "8549944", "1638191", "10925979", "7502549", "3319461", "10102971", "11227650" ]	[ "A placebo-controlled, randomized, double-masked, variable dosage, clinical trial of azathioprine with and without methylprednisolone in multiple sclerosis.", "A controlled double blind study of azathioprine in the management of Crohn's disease.", "Randomised controlled trial of azathioprine withdrawal in ulcerative colitis.", "Long-term use of mesalamine (Rowasa) suppositories in remission maintenance of ulcerative proctitis.", "Comparison between high dose 5-aminosalicylic acid and 6-methylprednisolone in active Crohn's ileocolitis. A multicenter randomized double-blind study. German 5-ASA Study Group.", "Double-blind, placebo-controlled evaluation of 5-ASA suppositories in active distal proctitis and measurement of extent of spread using 99mTc-labeled 5-ASA suppositories.", "Is maintenance therapy always necessary for patients with ulcerative colitis in remission?", "[Azathioprine and 5-ASA in the prevention of postoperative recurrence of Crohn's disease]." ]	[ "Ninety-eight patients with multiple sclerosis (MS) in the chronic progression phase entered a 3-year clinical trial to determine if azathioprine (AZ) alone or with adrenal cortical steroids stabilizes the course of MS. In group AM, the patients took AZ throughout and methylprednisolone (MP) for the first 36 weeks. Group AP received AZ and placebo instead of MP. Group PP took placebos for both drugs. We adjusted the AZ to maintain the total white blood cell count within 3,000 to 4,000/mm3; we gave the MP in a fixed dose \"pulse\" and alternate-day regimen. The \"intent-to-treat\" groups had no statistically significant differences in the rates of progression among the 3 treatments. Subgroup analysis suggests that patients in the AM group who completed treatment exactly according to protocol did statistically significantly better than the placebo recipients using the sum of Standard Neurological Examination scores, slightly better using the quantitative neuro-performance tests, but no better using Mickey's Illness Severity Scores or Kurtzke's Disability Status Scale. Also, the AZ-treated groups had half the relapse rate of the placebo-treated group. Adverse reactions to AZ accounted for most withdrawals. Hematologic and hepatic abnormalities were significantly associated with AZ, but serious non-MS abnormalities were uncommon and were equally distributed among the 3 groups. Addition of MP to the AZ slightly improved the efficacy of the treatment, but also increased the adverse effects. The benefits of AZ with or without steroids did not outweigh the risks, and therefore we do not recommend this treatment for patients with chronic progressive MS.", "While immunosuppressive agents are used widely in the management of Crohn's disease, their efficacy has not been well established in randomised controlled trials. This study was designed to examine whether azathioprine increases remission rate when used in conjunction with a diminishing dose regimen of prednisolone over a period of 12 weeks. It further examined whether azathioprine offers any therapeutic advantage over placebo in the maintenance of remission in Crohn's disease over a period of 15 months. Sixty three patients with active Crohn's disease were treated with a 12 weeks diminishing dose of prednisolone and at the same time entered into a randomised, double blind 15 month trial of either azathioprine (2.5 mg/kg) or placebo. Remission rates between the two groups were compared at 12 weeks and at 15 months. There was no significant difference in the proportion of patients who had achieved and maintained remission by week 12 but at 15 months there was a highly significant difference in the proportion of patients in remission (42% receiving azathioprine v 7% receiving placebo), p = 0.001. Using life tables this beneficial effect was reflected as the difference in the median number of days on the trial (p = 0.02). There were significantly greater decreases over the trial period in the median erythrocyte sedimentation rate, C reactive protein, and leucocyte count in the azathioprine group. There were no cases of severe bone marrow suppression or clinical pancreatitis. In conclusion, azathioprine offers a therapeutic advantage over placebo in the maintenance of remission in Crohn's disease.", "To determine whether azathioprine can prevent relapse in ulcerative colitis.\n One year placebo controlled double blind trial of withdrawal or continuation of azathioprine.\n Outpatient clinics of five hospitals.\n 79 patients with ulcerative colitis who had been taking azathioprine for six months or more. Patients in full remission for two months or more (67), and patients with chronic low grade or corticosteroid dependent disease (12) were randomised separately. 33 patients in remission received azathioprine and 34 placebo; five patients with chronic stable disease received azathioprine and seven placebo.\n Rate of relapse. Relapse was defined as worsening of symptoms or sigmoidoscopic appearance.\n For the remission group the one year rate of relapse was 36% (12/33) for patients continuing azathioprine and 59% (20/34) for those taking placebo (hazard rate ratio 0.5, 95% confidence interval 0.25 to 1.0). For the subgroup of 54 patients in long term remission (greater than six months before entry to trial) benefit was still evident, with a 31% (8/26) rate of relapse with azathioprine and 61% (17/28) with placebo (p less than 0.01). For the small group of patients with chronic stable colitis (six were corticosteroid dependent and six had low grade symptoms) no benefit was found from continued azathioprine therapy. Adverse events were minimal.\n Azathioprine maintenance treatment in ulcerative colitis is beneficial for at least two years if patients have achieved remission while taking the drug. Demonstration of the relapse preventing properties of azathioprine has implications for a large number of patients with troublesome ulcerative colitis, who may benefit from treatment with azathioprine.", "The purpose of this study was to evaluate the efficacy and safety of a single nightly 500-mg Rowasa (mesalamine) suppository as maintenance therapy for patients with ulcerative proctitis in remission.\n In this 24-month, multicenter, double-blind trial, 65 patients with ulcerative proctitis in clinical and endoscopic remission were randomized to receive either a single nightly 500-mg rectal mesalamine (Rowasa) suppository or matching placebo as sole therapy. Efficacy was assessed by time to relapse (defined as rectal bleeding or increase in stool frequency for > or =1 wk and active inflammation upon endoscopy).\n Mean time to relapse was 453.4 days for mesalamine-treated patients and 158.0 days for placebo-treated patients. Survival analysis demonstrated that time to relapse was significantly greater for mesalamine-treated patients than for placebo-treated patients (p < 0.001). In addition, at both 12 and 24 months, the proportion of placebo-treated patients (86% at 12 months and 89% at 24 months) who relapsed was significantly (p < or = 0.001) greater than mesalamine-treated patients (32% and 46%, respectively). No statistically significant differences occurred between treatment groups in the reporting of any particular adverse event or the number of patients reporting adverse events.\n The results demonstrate that mesalamine suppositories are efficacious, well tolerated, and safe for the long-term maintenance of remission of ulcerative proctitis.", "The value of 5-aminosalicylic acid (5-ASA) in Crohn's disease (CD) is still under discussion. In a previous study 2 g 5-ASA per day were inferior to a standard glucocorticoid treatment with 6-methylprednisolone (6-MPred) (Can J Gastroenterol 1990; 4: 446-51). In the present study we tested whether in active CD response rates to 4.5 g 5-ASA/day were not different from those to 6-MPred.\n Multicenter randomized double-blind double-dummy trial. 34 patients with active CD (CDAI > 150) were included. 17 patients were in the 5-ASA group (Salofalk, 4.5 g/day), 17 patients in the 6-MPred group (Urbason, initial dose 48 mg/day, weekly tapering). Duration of treatment was 8 weeks. Main outcome measure was remission of CD (CDAI < 150) and decrease of at least 60 points.\n Both groups were comparable with respect to demographic and clinical parameters. The median CDAI decrease in the 5-ASA group was 85, in the 6-MPred group 122 (p = 0.7437). The median AUC of the CDAI in the 5-ASA group was 1027, in the 6-MPred group 950 (p = 0.137). The median AUC of the CDAI per treatment day was 22.94 in the 5-ASA group, and 17.33 in the 6-MPred group (p = 0.0555). On an intention-to-treat basis remission rates after 8 weeks were 40.0% in the 5-ASA group and 56.3% in the 6-MPred group (p = 0.5867).\n Response rates to 5-ASA or 6-MPred were not significantly different although there was a trend towards a higher efficacy of 6-MPred. 5-ASA may be considered as alternative treatment in patients with activer CD who are intolerant to or refuse glucocorticoids.", "Patients with active distal proctitis received either 5-aminosalicylic (5-ASA) acid or identical placebo suppositories, 500 mg t.i.d. for 6 weeks. Activity at 3 and 6 wks was assessed using a Disease Activity Index (DAI), derived from four categories: number of daily evacuations more than usual, evacuations containing blood, sigmoidoscopy appearance, and physician's overall assessment. Each category was graded 0-3. There was thus 0-12 points scored ranging from complete remission to severe disease. A minimum score of 3 from two categories was necessary for study entry. Of 27 patients randomized, 14 received active medication and 13 placebo. Of the 14 patients, with initial mean DAI 7.1 +/- 1.8, 11 were in complete remission at 6 wks (78.6%). Whereas, there was no significant change in the placebo group, with initial mean DAI 7.1 +/- 1.8. An additional 6 patients with inflammatory bowel disease and 6 healthy volunteers were given 99mTc-labelled 5-aminosalicylic acid suppositories. The extent of spread was limited to the rectum, and the suppositories were retained for 3 hours. There was no absorbed radioactivity. 5-ASA suppositories are safe, well-tolerated, and effective treatment for active distal proctitis.", "The efficacy of sulphasalazine and mesalazine in preventing relapse in patients with ulcerative colitis is well known. It is less clear how long such maintenance should be continued, and if the duration of disease remission is a factor that affects the risk of recurrence.\n To determine whether the duration of disease remission affects the relapse rate, by comparing the efficacy of a delayed-release mesalazine (Asacol, Bracco S.p.A., Milan, Italy) against placebo in patients with ulcerative colitis with short- and long-duration of disease remission.\n 112 patients (66 male, 46 female, mean age 35 years), with intermittent chronic ulcerative colitis in clinical, endoscopic and histological remission with sulphasalazine or mesalazine for at least 1 year, were included in the study. Assuming that a lower duration of remission might be associated with a higher relapse rate, the patients were stratified according to the length of their disease remission, prior to randomization into Group A (Asacol 26, placebo 35) in remission from 1 to 2 years, or Group B (Asacol 28, placebo 23) in remission for over 2 years, median 4 years. Patients were treated daily with oral Asacol 1.2 g vs. placebo, for a follow-up period of 1 year.\n We employed an intention-to-treat analysis. In Group A, whilst no difference was found between the two treatments after 6 months, mesalazine was significantly more effective than placebo in preventing relapse at 12 months [Asacol 6/26 (23%), placebo 17/35 (49%), P = 0.035, 95% Cl: 48-2.3%]. In contrast, in Group B no statistically significant difference was observed between the two treatments, either at 6 or 12 months [Asacol 5/28 (18%), placebo 6/23 (26%), P = 0.35, 95% Cl: 31-14%] of follow-up. Patients in group B were older, and had the disease and remission duration for longer, than those in Group A.\n Mesalazine prophylaxis is necessary for the prevention of relapse by patients with ulcerative colitis in remission for less than 2 years, but this study casts doubt over whether continuous maintenance treatment is necessary in patients with prolonged clinical, endoscopic and histological remission, who are at very low risk of relapse.", "Recurrence of Crohn's disease (CD) lesions in the neo-ileum after apparently curative resection frequently occurs after surgery. The most appropriate prophylactic treatment has not been clearly defined. This study evaluated the efficacy of 5-ASA and azathioprine in decreasing postoperative recurrence and analysed the presence of variables associated with recurrence. Thirty-nine patients (mean age 32.8 years, range 18-61) with a history of ileal or ileocecal surgical resection were studied. They received 5-ASA (3 mg/day) or azathioprine (50 mg/day) immediately after the operation and for 2 years thereafter. Patients were followed clinically (Crohn's disease activity index) and serologically every 3 months and by imaging methods every 6 months. The latter included colonoscopy with ileoscopy and if not available, small bowel barium or ultrasonographic study. Laboratory tests included ESR, C-reactive protein, white blood cell and platelet count, fibrinogen and albumin. The end-point evaluated included clinical recurrence (CR), serological recurrence (SR: alteration of at least three of the above-mentioned variables) and morphologic recurrence (MR: endoscopic recurrence > 1 according to Rutgeerts score or radiological or ultrasonographic recurrence). Eighteen patients received azathioprine and 21 received 5-ASA. Thirty-four patients were evaluated. The cumulative proportion of patients with recurrence was 29% (CR), 35% (SR) and 50% (MR). Statistical analysis did not show significant differences between the two groups. Twenty-seven patients completed the 2-year study (11 in the azathioprine group and 16 in the 5-ASA group). Crude relapse rates were 37% (CR), 44% (SR) and 69% (MR) in the 5-ASA group and 36% (CR), 45% (SR) and 64% (MR) in the azathioprine group. No statistically significant differences were observed between groups. No variables associated with recurrence were detected. In conclusion, treatment does not prevent a high percentage of postsurgical recurrence. 5-ASA (3 g/day) and azathioprine (50 mg/day) showed similar efficacy in the prevention of recurrence." ]	The pooled analyses suggest that 5-ASA preparations may be superior to placebo for the maintenance of surgically-induced remission in patients with CD. The results of the pooled analyses should be interpreted with caution because adequately powered studies demonstrated no difference and publication bias (failure to publish negative studies) may be an issue. The potential benefit provided by 5-ASA drugs is modest with a number needed to treat of approximately 16 to 19 patients to avoid one relapse which raises issues about the cost-effectiveness of this therapy. However, 5-ASA drugs are safe and well tolerated. The incidence of adverse events was not different in patients receiving 5-ASA compared with those receiving placebo. There is insufficient evidence to allow any conclusions on how 5-ASA preparations compare with azathioprine or 6-mercaptopurine.
CD001183	[ "2847578", "7606516", "2536255", "2847600", "8412049", "2852903", "2167369", "3027153", "1310834", "9564987", "3036020", "2992839", "9433364", "8265272", "7560663", "8087189", "7930301", "2177889" ]	[ "Effect of nedocromil sodium on exercise-induced bronchoconstriction in children.", "Effect of nedocromil sodium on exercise-induced bronchoconstriction exacerbated by inhalation of cold air.", "Nedocromil sodium in exercise-induced bronchoconstriction in children.", "A comparative study of the effect of three doses of nedocromil sodium and placebo given by pressurized aerosol to asthmatics with exercise-induced bronchoconstriction.", "Nedocromil sodium in the prevention of exercise-induced bronchospasm in athletes with asthma.", "A comparative study of the effects of two different doses of nedocromil sodium and placebo given by pressurised aerosol in exercise-induced bronchoconstriction.", "Attenuation of exercise induced asthma by nedocromil sodium and sodium cromoglycate.", "The preventive effect and duration of action of nedocromil sodium and cromolyn sodium on exercise-induced asthma (EIA) in adults.", "Effects of nedocromil sodium, cromolyn sodium, and a placebo in exercise-induced asthma.", "Combination drug therapy for the prevention of exercise-induced bronchoconstriction in children.", "Nedocromil sodium and exercise induced asthma.", "Attenuation of exercise-induced asthma by pretreatment with nedocromil sodium and minocromil.", "Effect of nedocromil sodium on bronchial hyperreactivity in children with nonatopic asthma.", "Nedocromil sodium vs. sodium cromoglycate pressurized aerosol in the prevention of bronchoconstriction induced by ultrasonic nebulized distilled water in asthmatic children.", "Cromolyn versus nedocromil: duration of action in exercise-induced asthma in children.", "Inhibition of exercise-induced-asthma (EIA) by nedocromil sodium and sodium cromoglycate in children.", "Comparison of the protective effects of cromolyn sodium and nedocromil sodium in the treatment of exercise-induced asthma in children.", "[Study of the protective action of nedocromil sodium with bronchial cold-air provocation in children with bronchial asthma]." ]	[ "A double-blind, placebo-controlled, crossover study investigated the efficacy of nedocromil sodium in reducing bronchoconstriction subsequent to exercise challenge in asthmatic children. Twelve children aged 7-14 years (mean 10.8 years) were pretreated with nedocromil sodium aerosol (2 inhalations; 2 mg/inhalation) or matching placebo, 30 min prior to treadmill running. Lung function was measured at regular intervals postexercise and the mean maximum percentage decrease in PEF and FEV1 compared following nedocromil sodium or placebo pretreatment. Nedocromil sodium significantly reduced the fall in PEF (P less than 0.001) and FEV1 (P less than 0.001) and provided significantly greater protection (P less than 0.001) than placebo. No adverse reactions or unusual symptoms were observed.", "This double-blind placebo-crossover study examined the effect of nedocromil sodium, 4 mg aerosol 30 min before challenge, on exercise-induced bronchoconstriction (EIB) in cold air conditions. Twenty-one asthmatic patients (15-28 years), with methacholine PC20 < or = 8 mg/ml in the absence of significant allergen exposure, were randomized to active and placebo therapy on separate study days. Pulmonary function, measured up to 20 min after exercise, showed significantly less deterioration with nedocromil sodium, which effectively halved the maximum percentage decline in forced expiratory volume in the first second. EIB was increased by cold air, whereas an ancillary study in 15 healthy volunteers (18-19 years) showed no such effects. We conclude that prior inhalation of nedocromil sodium diminished cold air-exacerbated EIB in young adult asthmatic patients.", "Twenty asthmatic children were studied in a double-blind within-patient comparative trial designed to assess the efficacy of nedocromil sodium (4 mg) and placebo in exercise-induced bronchoconstriction. The response to exercise challenge given 30 minutes after treatment showed statistically significant differences in favor of nedocromil sodium. No unusual symptoms were reported.", "The effect of placebo and 1 mg, 4 mg, or 8 mg nedocromil sodium, administered 60 minutes prior to treadmill challenge, was determined in a double-blind study of 12 adult asthmatics with reproducible exercise-induced bronchoconstriction. All nedocromil sodium treatments gave significantly smaller falls in PEFR than placebo. Four and 8 mg gave significantly greater protection than 1 mg.", "The aim of this study was to determine the efficacy of nedocromil sodium in the prevention of exercise-induced bronchospasm (EIB) in 13 top athletes affected by bronchial asthma. At a dose of 4 mg the drug significantly reduced the fall in FEV1 compared with placebo but not with respect to basal values. In 9 athletes, 4 mg nedocromil sodium produced a good protective effect and reduced the mean fall in FEV1 to 4% with respect to baseline values, while in the remaining 4 subjects, the protective effect was not satisfactory. In these 4 \"non responders\" 6 mg nedocromil was effective, and in 2 cases induced prolonged bronchodilatation. In conclusion, the effect of nedocromil sodium in the prevention of EIB may be dose-dependent in relation to the degree of bronchial hyperreactivity or to interference of other factors.", "Fourteen adult subjects with stable asthma were treated using a double-blind crossover, randomised protocol, with either nedocromil sodium (4 mg or 2 mg) or placebo. The agents were administered from matched pressurised aerosol inhalers 30 min before exposure to an exercise regimen which, on a previous screening day, resulted in a 24-53% (mean: 33.9%) decrease in peak expiratory flow (PEF). Both doses of nedocromil sodium were significantly superior to placebo in preventing the exercise-induced decrease in PEF and were without side effects. This study confirms and extends the results of earlier trials with nedocromil sodium and further supports the contention that this new agent may be of benefit in the treatment of reversible obstructive airways disease in the adult patient.", "A randomized double blind cross over trial to compare nedocromil sodium and sodium cromoglycate with placebo in the prevention of exercise induced asthma was conducted. Twenty asthmatics received nedocromil sodium, sodium cromoglycate or placebo via metered dose inhalers on successive days 30 minutes before exercise in a randomized order. Nedocromil sodium and sodium cromoglycate gave sufficient protection (P less than 0.05) compared to placebo as assessed by the reduction in the maximum percentage fall in the forced expiratory volume in 1 second (FEV1). The protective effect of nedocromil sodium and sodium cromoglycate varied in individuals.", "Nedocromil sodium, 4 mg, from a metered-dose inhaler, cromolyn sodium, (cr) 20 mg, from a Spinhaler, and placebo (pl) were compared in their efficacy and duration of action in preventing exercise-induced asthma. Twelve patients with asthma performed treadmill exercise tests 20 minutes, 2 hours, and 4 hours after a single dose of drug in a double-blind, crossover trial. Both active drugs were significantly better than pl at 20 minutes. Two hours after drug administration, only cr was significantly different from pl. The direct comparison between nedocromil and cr demonstrated no significant difference on FEV1, and the only significant difference was with forced expiratory flow between 25% and 75% of vital capacity at 2 hours. It is concluded that at these clinically recommended doses, both drugs are equally effective in preventing exercise-induced asthma with cr possibly having a somewhat longer duration of action.", "The incidence and severity of exercise-induced asthma were determined in nineteen asthmatic patients who performed eight minutes of exercise following four treatments administered in a random order. The treatments were nedocromil sodium, cromolyn sodium, placebo, and no treatment. It was concluded that nedocromil sodium (8 mg) and cromolyn sodium (4 mg) provide equal protection against exercise-induced asthma.", "Sequential administration of a beta-agonist and cromolyn or nedocromil before exercise is recommended for patients whose symptoms are not controlled by beta-agonists alone; however, this practice reduces compliance.\n To evaluate the effectiveness of a new pre-combined aerosol formulation (salbutamol and nedocromil) in preventing exercise-induced bronchoconstriction and to compare it to salbutamol alone.\n Twelve children with asthma were studied in a double-blind, double-dummy, randomized, crossover, placebo-controlled design to compare the protective effect of salbutamol and a new pre-combined salbutamol/nedocromil formulation against exercise-induced bronchoconstriction. The drugs were delivered by a metered-dose inhaler (salbutamol, 200 microg; salbutamol/nedocromil, 200 microg/4 mg; placebo, 2 puffs) 20 minutes before exercise.\n Both active drugs were significantly more protective than placebo but there was no difference between them. Complete protection was obtained in 12/12, 10/12, and 1/12 subjects for the salbutamol/nedocromil combination, salbutamol alone and placebo, respectively.\n Although inhaled beta-agonists alone are highly efficacious in preventing exercise-induced bronchoconstriction, a minority of patients exists for whom a combined treatment with salbutamol and nedocromil is advantageous. This group may represent a subpopulation of subjects who release more, or different, mediators in response to exercise.", "Serial exercise tests were carried out by 12 children with asthma on two study days. After a control exercise test either nedocromil sodium 4 mg or placebo were given double blind by metered dose inhaler. Highly significant inhibition of exercise induced asthma occurred after nedocromil, lasting for over two hours.", "In a group of atopic adult asthmatic patients the effects of two new inhaled antiasthmatic drugs, nedocromil sodium and minocromil were studied in two independent randomized double-blind trials to assess their efficacy in preventing exercise-induced asthma (EIA). Exercise testing consisted of steady state running on an inclined treadmill. Neither drug administered 30 min before exercise significantly altered baseline FEV1. Nedocromil sodium (2 and 4 mg) pre-treatment in nine patients and minocromil (4 mg) in eight patients gave significant protection (P less than 0.001) compared to placebo as assessed by the reduction in the maximum percentage fall in FEV1. There was no significant difference in the inhibitory effect of the two doses of nedocromil sodium. These results indicate that both nedocromil sodium and minocromil can attenuate EIA.", "Although cromones inhibit immediate bronchial responses to both allergen and nonspecific challenge, their effectiveness in treating nonatopic childhood asthma is unknown. We therefore investigated a possible effect of nedocromil sodium on bronchial hyperreactivity and asthmatic symptoms in a group of children receiving this drug for nonatopic asthma.\n A double-blind, placebo-controlled, randomized trial of two parallel groups was carried out in our pediatric respiratory disease clinic. Twenty children with mild, nonatopic asthma hyperreactive to fog-induced challenge were treated with inhaled nedocromil sodium 16 mg each day for 6 weeks (group N) or with a placebo (group P). Five girls and five boys (7 to 13 years of age) were randomly assigned to group N, and three girls and seven boys (aged 6 to 16 years) to group P. Symptoms and bronchodilator use were reported on diary cards. Ultrasonic nebulized distilled water PD10 was measured administering increasing doses of nebulized distilled water (2.5, 5, 10, 20, and 40 L).\n Symptom scores were significantly affected by the active treatment. Baseline lung function was normal and remained unaltered after treatment with nedocromil sodium. Nonspecific reactivity was significantly reduced over time only in the active treatment group.\n Nedocromil sodium can reduce the severity of asthmatic symptoms and nonspecific bronchial hyperreactivity at fog-induced challenge in children with stable, nonatopic asthma.", "To compare the effectiveness of nedocromil sodium (NS) and sodium cromoglycate (SCG), administered by metered dose inhaler (MDI) with a 700 mL holding chamber (Fisonair Fisons UK) in preventing bronchoconstriction induced by inhalation of ultrasonically nebulized distilled water (UNDW), 12 asthmatic children were studied in a randomized, double-blind, placebo-controlled, intrapatient study. Following a baseline challenge with UNDW, the protective effect of NS, SCG, or placebo was evaluated in each subject. Cumulative doses of delivered nebulized water producing a 20% fall in forced expiratory volume in 1 sec (PD20 UNDW) was measured. Mean (+/- SD) PD20 UNDW was 4.83 (+/- 4.84), 10.16 (+/- 7.05), 1.58 (+/- 0.5), and 15.93 (+/- 0.23) respectively, for baseline, and placebo, SCG, and NS-treated groups. A significant (P < 0.05) protection from UNDW induced bronchoconstriction by NS was observed in comparison with placebo, while no such effect was evident when the children were treated with SCG.", "Cromolyn sodium (10 mg), nedocromil sodium (4 mg), and placebo, all delivered by a metered dose inhaler, were compared in their efficacy and duration of action in preventing exercise-induced asthma in children. After a screening test was performed, 13 patients with asthma performed standard exercise tests 20 minutes and 140 minutes after drug inhalation in a randomized, double-blind, crossover study. Both drugs were significantly more protective than placebo after 20 minutes, but no significant difference was seen between cromolyn sodium and nedocromil sodium. No difference between active drugs and placebo was found 140 minutes after inhalation. At these clinically recommended doses both cromolyn sodium and nedocromil sodium provide equal protection against exercise-induced asthma, and the duration of action of both lasts for less than 2 hours.", "Nedocromil sodium (Ned) 4 mg, sodium cromoglycate (SCG) 10 mg, and placebo were compared for their efficacy in preventing exercise-induced asthma. Nineteen asthmatic children aged six to 15 years performed a treadmill exercise test before and 20' after a single dose of drug in a double-blind trial. Both active drugs performed significantly better than placebo; in fact the exercise challenge resulted in a mean maximum fall in FEV1 of 26.1 +/- 14.9% after placebo, but only of 14.6 +/- 11.5% after SCG (P < 0.05), and 11.0 +/- 12.4% after Ned (p < 0.01). Measurements of PEFR gave similar results, while the effect of treatment on FEF 25-75 was significant for Ned alone (p < 0.05). Direct comparison between Ned and SCG at different time points demonstrated significant differences in FEV1 at 1 min (p < 0.05) with a better overall performance of Ned. In individual patients, complete protection was provided in 9 patients with SCG, in 14 patients with Ned and in 2 with placebo. No side effects were observed. This study suggests that at the dosages used there are only slight differences between SCG and Ned activity in the prevention of exercise-induced asthma.", "Seventeen children with asthma were studied in a double-blind, crossover, placebo-controlled study designed to compare the efficacy of cromolyn sodium with that of nedocromil sodium in preventing exercise-induced asthma. All drugs were delivered through a metered-dose inhaler (cromolyn sodium, 10 mg; nedocromil sodium, 4 mg; placebo, two puffs). Nedocromil sodium and cromolyn sodium provided significant, comparable protection from exercise-induced asthma, and both drugs were better than placebo. We conclude that nedocromil sodium and cromolyn sodium administered by a pressurized aerosol provide equal protection against exercise-induced asthma in children.", "12 children with known bronchial hyperreactivity and asthma had isocapnic cold air hyperventilation challenges of their bronchial airways. In a double-blind cross-over study they inhaled either placebo or nedocromil sodium (2 puffs à 2 mg) from a MDI before challenge. 2 subjects were found to be non-responders during the two days of the study. The remainder all reacted on the placebo days, while 5 subjects were completely protected on the nedocromil-days and 5 subjects were partially protected. Nedocromil is a potent agent for the suppression of bronchial hyperresponsiveness." ]	Nedocromil sodium used before exercise reduces the severity and duration of exercise-induced bronchoconstriction. This effect appears to be more pronounced in people with severe exercise-induced bronchoconstriction.
CD000967	[ "11768836", "16267634", "16062094", "16889453", "17728106", "16585435", "16585434", "16797162", "12766921", "11291531" ]	[ "A comparison of the relative safety, efficacy, and tolerability of quetiapine and risperidone in outpatients with schizophrenia and other psychotic disorders: the quetiapine experience with safety and tolerability (QUEST) study.", "Quetiapine has equivalent efficacy and superior tolerability to risperidone in the treatment of schizophrenia with predominantly negative symptoms.", "Risperidone, quetiapine, and fluphenazine in the treatment of patients with therapy-refractory schizophrenia.", "Comparison of quetiapine and risperidone in the treatment of schizophrenia: A randomized, double-blind, flexible-dose, 8-week study.", "Cognition, functioning and quality of life in schizophrenia treatment: results of a one-year randomized controlled trial of olanzapine and quetiapine.", "Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic.", "Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment.", "A double-blind comparison of risperidone, quetiapine and placebo in patients with schizophrenia experiencing an acute exacerbation requiring hospitalization.", "The impact upon extra-pyramidal side effects, clinical symptoms and quality of life of a switch from conventional to atypical antipsychotics (risperidone or olanzapine) in elderly patients with schizophrenia.", "Neuropsychological change in patients with schizophrenia after treatment with quetiapine or haloperidol." ]	[ "The few published direct comparative studies of the tolerability and efficacy of atypical antipsychotic agents were performed in relatively homogeneous populations that may not be typical of patients seen in clinical practice.\n The Quetiapine Experience with Safety and Tolerability (QUEST) study compared the relative safety, tolerability, and efficacy of quetiapine and risperidone in outpatients with a broad range of psychotic symptoms.\n This was a multicenter, 4-month, open-label, randomized clinical trial. Patients were randomized in a 3:1 ratio to receive quetiapine or risperidone. Doses were adjusted to maximize efficacy and to minimize adverse events. Extrapyramidal symptoms (EPS) were assessed with an EPS checklist; adverse events were recorded. Efficacy was assessed using the Clinical Global Impression (CGI) scale, Positive and Negative Symptom Scale (PANSS), and Hamilton Rating Scale for Depression (HAM-D).\n A total of 728 patients were randomized, 553 to quetiapine and 175 to risperidone. Mean prescribed doses over the study period were 253.9 mg/d quetiapine and 4.4 mg/d risperidone. At the end of 4 months, EPS declined in both treatment groups, but quetiapine-treated patients were significantly less likely to require dose adjustment or concurrent anti-EPS medication (P < 0.001). The most common adverse events in the quetiapine and risperidone groups were somnolence (31.3% and 15.4%, respectively), dry mouth (14.5% and 6.9%), and dizziness (12.7% and 6.9%). Overall, tolerance to side effects with the 2 drugs, measured by dropout rates, was comparable. At each visit, a higher percentage of quetiapine-treated patients showed improvement on the CGI scale, but there were no significant between-group differences on the PANSS. At end point, quetiapine-treated patients had significantly lower HAM-D scores (P = 0.028).\n The results of this study suggest that quetiapine is as effective as risperidone for the treatment of psychotic symptoms, is more effective for depressive symptoms, may have a more favorable EPS profile, and has comparable overall tolerability.", "Atypical antipsychotics are generally thought to be more effective than conventional agents in treating the negative symptoms of schizophrenia; however, there have been few direct comparisons among atypicals. We therefore investigated risperidone and quetiapine with respect to their efficacy against negative symptoms in a 12-week,double-blind, comparative pilot study involving 44 patients with schizophrenia with predominantly negative symptoms, as defined by Positive and Negative Syndrome Scale (PANSS) scores. Other efficacy measures included the Scale for the Assessment of Negative Symptoms (SANS) and the Clinical Global Impression (CGI) rating scale. Antipsychotic tolerability was assessed using the Simpson-Angus Scale (SAS) and various laboratory measures. Mean doses were 589.7 mg/ day quetiapine and 4.9 mg/day risperidone (observed cases). Both antipsychotics produced significant decreases in PANSS total, positive and negative scores, and SANS scores. Patients receiving risperidone were significantly more likely to experience extrapyramidal symptoms (EPS) [p <0.05], or to require anticholinergic medication (p <0.05), and had significantly higher prolactin levels (p <0.001) than quetiapine-treated patients. In conclusion, there is no significant difference in efficacy between quetiapine and risperidone in alleviating the negative symptoms of schizophrenia. Quetiapine is also well tolerated, with a lower incidence of EPS and prolactin increase than risperidone.", "This 12-week, double-blind study evaluated the effectiveness of risperidone (4 mg/day), quetiapine (400 mg/day), or fluphenazine (12.5 mg/day) in a stringently defined treatment-resistant population of people with schizophrenia. No differences were noted in total Brief Psychiatric Rating Scale (BPRS) or Clinical Global Impression scores among the drug groups (n = 38). More subjects tended to complete the study on risperidone (69%) or quetiapine (58%) than those treated with fluphenazine (31%; P value not significant). Eighty-nine percent of those who discontinued on fluphenazine (8 of 9) were due to lack of efficacy. Discontinuation due to adverse effects was low, with only 2 subjects (both on quetiapine) stopping due to side effects. Three of 13 risperidone-treated subjects (23%) and 3 of 12 quetiapine-treated subjects (25%) met response criteria (decrease of 20% of total BPRS score), whereas 2 of 13 subjects (15%) responded to fluphenazine. Side effect occurrence was similar among drug groups and EPS ratings on the Simpson Angus Scale improved in all drug groups (quetiapine, 1.64; risperidone, 1.30; fluphenazine, 0.69; P value not significant). Despite the newer class of second-generation antipsychotic medications, this treatment-resistant population remains difficult to treat. Many people have only minimal to modest improvements with antipsychotic treatment and most continue to have residual psychotic symptoms. Treatment with first- and second-generation antipsychotics may demonstrate similar efficacy; however, patients treated with second-generation antipsychotics may be more likely to adhere to treatment.", "To compare the efficacy and tolerability of quetiapine and risperidone in the treatment of schizophrenia.\n In this 8-week, double-blind, multicenter, flexible-dose study, patients with schizophrenia (DSM-IV diagnosis) were randomly assigned to quetiapine (200-800 mg/day) or risperidone (2-8 mg/day). The primary hypothesis was that quetiapine was not inferior to risperidone. The primary efficacy measure was change from baseline in Positive and Negative Syndrome Scale (PANSS) total scores; secondary outcomes included response rate (> or = 40% reduction in PANSS scores), Clinical Global Impression-Change (CGI-C), and cognitive and social functioning. Tolerability assessments included treatment-emergent adverse events and changes in weight, glucose, and prolactin. Patients were recruited from June 2001 to September 2002.\n Patients (N = 673) were randomly assigned to quetiapine (N = 338, mean dose = 525 mg/day) or risperidone (N = 335, mean dose = 5.2 mg/day). The primary analysis demonstrated noninferiority between treatments (p < .05). Improvements with both treatments were comparable on PANSS total, negative, and general psychopathology subscales. Risperidone-treated patients had a significantly (p = .03) greater improvement in PANSS positive subscale score among all patients, but not among completers. Improvements in PANSS response rates, CGI-C, and cognitive function were similar between treatment groups. Changes in serum glucose and weight were minimal and comparable. The rate of extrapyramidal symptom (EPS)-related adverse events was significantly higher with risperidone (22%) than quetiapine (13%; p < .01). Somnolence was more common with quetiapine (26%) than risperidone (20%; p = .04). Prolactin levels increased with risperidone (+35.5 ng/mL), but decreased with quetiapine (-11.5 ng/mL; p < .001).\n Quetiapine and risperidone had broadly comparable clinical efficacy. Both agents improved cognitive and social functioning, and neither had a clinically significant effect on weight or glucose. Somnolence was more common with quetiapine; EPS and elevated prolactin rates were significantly higher with risperidone.", "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.", "In the treatment of schizophrenia, changing antipsychotics is common when one treatment is suboptimally effective, but the relative effectiveness of drugs used in this strategy is unknown. This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic.\n Subjects with schizophrenia (N=444) who had discontinued the atypical antipsychotic randomly assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) investigation were randomly reassigned to double-blind treatment with a different antipsychotic (olanzapine, 7.5-30 mg/day [N=66]; quetiapine, 200-800 mg/day [N=63]; risperidone, 1.5-6.0 mg/day [N=69]; or ziprasidone, 40-160 mg/day [N=135]). The primary aim was to determine if there were differences between these four treatments in effectiveness measured by time until discontinuation for any reason.\n The time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months). Among patients who discontinued their previous antipsychotic because of inefficacy (N=184), olanzapine was more effective than quetiapine and ziprasidone, and risperidone was more effective than quetiapine. There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability (N=168).\n Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic, risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason.", "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.", "This study compared the effects of atypical antipsychotics (risperidone or quetiapine) with placebo and with each other in recently exacerbated patients with schizophrenia requiring hospitalization.\n This international, randomized, double-blind study included a 2-week monotherapy phase followed by a 4-week additive therapy phase. Recently exacerbated patients with schizophrenia or schizoaffective disorder (DSM-IV) were randomized (2:2:1) to risperidone (n = 153), quetiapine (n = 156), or placebo (n = 73). Target doses were 4 or 6 mg/day of risperidone and 400 or 600 mg/day of quetiapine by day 5, with the ability to increase to 600 or 800 mg/day of quetiapine on day 8. The main outcome measures were the total Positive and Negative Syndrome Scale (PANSS) and need for additional psychotropic medications.\n Monotherapy Phase: The combined atypical antipsychotic group (n = 308) reached borderline superiority to placebo (n = 71) at the 2-week endpoint on mean change in total PANSS score (-24.1 +/- 1.2 and -20.2 +/- 2.0, respectively; p = 0.067). The change in the atypical group was driven by the improvement with risperidone (-27.7 +/- 1.5 vs. -20.2 +/- 2.0 with placebo, p < 0.01; and vs. -20.5 +/- 1.5 with quetiapine, p < 0.01); the improvement with quetiapine was similar to placebo, p = 0.879. Results were similar on other efficacy endpoints. Additive Therapy Phase: Additional psychotropics were prescribed to fewer (p < 0.01) risperidone (36%) than quetiapine (53%) or placebo patients (59%). The overall discontinuation rate was 18%, 26%, and 38%, respectively. Risperidone, compared with placebo, was associated with more parkinsonism, akathisia, plasma prolactin changes, and weight gain; while quetiapine was associated with more somnolence, sedation, dizziness, constipation, tachycardia, thyroid dysregulation, and weight gain.\n While the combined atypical antipsychotic group did not experience greater improvements than the placebo group, risperidone, but not quetiapine, was significantly superior in all measured domains to placebo in the management of recently exacerbated hospitalized patients with schizophrenia or schizoaffective disorder, with no unexpected tolerability findings.", "Atypical antipsychotics are commonly used in the management of schizophrenia in late life with evidence suggesting they induce lower rates of motor disturbance, but have similar efficacy to conventional antipsychotics. Trials in the elderly have been either retrospective, small, of short duration or of a single-arm design.\n To demonstrate the effects upon motor side-effects, efficacy, safety and quality of life (QOL) of switching elderly patients with schizophrenia from conventional antipsychotics to olanzapine or risperidone.\n Elderly patients with schizophrenia were randomly allocated to olanzapine or risperidone and followed through an open-label crossover period. Between and within group intention to treat analyses were conducted.\n 66 patients were randomised (mean age 69.6 [SD +/- 6.2]). Four (11.8%) patients on olanzapine and 8 (26.7%) patients on risperidone failed to complete the crossover because of treatment failure [Odds Ratio (OR) = 2.73[0.73-10.2] p = 0.14]. The mean doses upon completion of switching in each arm were 9.9 mg (SD = 4.2) and 1.7 mg (SD = 1.2) for olanzapine and risperidone respectively. In both arms there was improvement in Parkinsonism, though only olanzapine was associated with a reduction in dyskinetic symptoms. The Brief Psychiatric Rating Scale, Scale for the assessment of Negative Symptoms and Montgomery and Asberg Depression Rating Scale scores all improved through the crossover period in both arms with no between group differences. Treatment with olanzapine was associated with a better response over risperidone on the psychological domain of the World Health Organisation-Quality Of Life [Brief] (WHO-QOL-BREF) scale ( p = 0.02). Patients in the olanzapine arm also demonstrated improvement from baseline in the WHO-QOL-BREF physical, psychological and health satisfaction domains, but risperidone had no effect on any Quality of Life (QOL) measure.\n After switching from a conventional antipsychotic, olanzapine and risperidone were associated with improvement in core symptoms of schizophrenia and motor side effects. Subjects switched to olanzapine were more likely to complete the switching process and show an improvement in psychological QOL.\n Copyright 2003 John Wiley & Sons, Ltd.", "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." ]	Quetiapine is effective for the treatment of schizophrenia, but it is not much different from first-generation antipsychotics and risperidone with respect to treatment withdrawal and efficacy. In comparison to first-generation antipsychotics and risperidone, quetiapine has a lower risk of movement disorders but higher risks of dizziness, dry mouth and sleepiness. More clearly reported pragmatic randomised controlled trials should be carried out to determine its position in everyday clinical practice. Studies of medium and long-term effects, including cost-effectiveness, quality of life, social functioning and service utilisation, in comparison with the effects of typical and atypical antipsychotics should be priority areas.
CD008741	[ "19926959" ]	[ "A cluster-randomized trial of enhanced labor ward-based PMTCT services to increase nevirapine coverage in Lusaka, Zambia." ]	[ "Determine whether enhanced labor ward-based services for prevention of mother-to-child transmission of HIV (PMTCT) would improve nevirapine (NVP) coverage.\n Cluster-randomized trial at 12 public-sector delivery centers in Lusaka, Zambia.\n Following a baseline surveillance period, 12 labor wards were randomized, six to offer opt-in HIV testing to women of unknown serostatus (with NVP administration as indicated) and to assess NVP adherence among known HIV-infected women. The six control labor wards provided the standard of care. The NVP coverage endpoint was defined as the proportion of HIV-infected/exposed women/infant pairs with confirmed NVP ingestion. We used generalized estimating equations (GEE) to determine the odds of coverage associated with the intervention and ultimately used the parameters for the estimated GEE model to estimate relative risk.\n Between October 2005 and January 2006, 7664 women gave birth at participating clinics. We collected anonymous-linked blood from 7592 (99%) umbilical cords; tested 7438 (97%) for HIV, 1618 (22%) were seropositive, and of these, 1279 (79%) were tested for NVP. At baseline (preintervention), the probability of HIV-infected/exposed women/infant pairs receiving NVP in treatment clinics (42%) was 0.89 times the probability of being covered in control clinics (53%) whereas during the intervention period the probability of treatment clinic coverage (52%) was 1.22 the probability control clinic coverage (43%), representing a multiplicative effect of 1.37 upon the RR at baseline (ratio of relative risks 1.37, bootstrapped 95% CI, 1.04-1.77).\n Labor ward-based PMTCT programs are feasible and can have a significant, positive impact on NVP coverage." ]	We found only one study suggesting that integrating perinatal PMTCT interventions with other healthcare services in low- and middle-income countries increases the proportion of pregnant women, mothers and infants receiving PMTCT intervention. The weak evidence base does not enable making any inferences for other countries or contexts. The study that met the inclusion criteria assessed only the impact of integrating PMTCT intervention in labour ward on the proportion of mothers and their infants receiving nevirapine. The study showed significant improvement in intervention coverage but it only addressed the labour ward aspect of PMTCT programme. We did not find sufficient evidence to make definitive conclusions about the effectiveness of integration of these interventions with other health services rather than providing them as stand-alone services. Further research is urgently needed to assess the effect of integrating perinatal prevention of mother-to-child HIV transmission interventions with other health services on intervention coverage, service uptake, quality of care and health outcomes and the optimal integration modality.
CD004398	[ "16708003", "12694632", "15466769", "16569189", "19775439", "17034605", "12817353", "17010115", "12358871", "17509808", "8564938", "17623736", "19707060", "15249521", "3892184", "3735627", "18237352", "16412443", "3977198", "9734786", "12677565", "8296253", "11911510", "16808764", "19902034", "10557684", "15066200", "17456241", "16243954", "16629429", "20008582", "10630654", "15596155", "18535027", "14702508", "14521638", "18450604", "9311323", "10551192", "15184205", "20166337", "11490051", "12240812", "12433764" ]	[ "Cluster randomized controlled trial of the effectiveness of audit and feedback and educational outreach on improving nursing practice and patient outcomes.", "Randomised controlled trial of a theoretically grounded tailored intervention to diffuse evidence-based public health practice [ISRCTN23257060].", "A multimethod quality improvement intervention to improve preventive cardiovascular care: a cluster randomized trial.", "Use of an 'evidence-based implementation' strategy to implement evidence-based care of asthma into rural district hospital emergency departments.", "A randomized controlled trial evaluating the impact of knowledge translation and exchange strategies.", "A randomized controlled trial of the effectiveness of pelvic floor therapies for urodynamic stress and mixed incontinence.", "Modifying dyspepsia management in primary care: a cluster randomised controlled trial of educational outreach compared with passive guideline dissemination.", "Cluster randomised trial of an active, multifaceted educational intervention based on the WHO Reproductive Health Library to improve obstetric practices.", "Multifaceted support to improve clinical decision making in diabetes care: a randomized controlled trial in general practice.", "The effects of a shared decision-making intervention in primary care of depression: a cluster-randomized controlled trial.", "A psychoeducational nursing intervention to enhance coping and affective state in newly diagnosed malignant melanoma patients.", "Intravenous immunoglobulin in primary and secondary chronic progressive multiple sclerosis: a randomized placebo controlled multicentre study.", "The tools of an evidence-based culture: implementing clinical-practice guidelines in an Israeli HMO.", "Patient-based outcome results from a cluster randomized trial of shared decision making skill development and use of risk communication aids in general practice.", "A randomized controlled trial of quality assurance in sixteen ambulatory care practices.", "A randomized trial of medical quality assurance. Improving physicians' use of pelvimetry.", "Strategies for improving the quality of health care in maternal and child health in low- and middle-income countries: an overview of systematic reviews.", "Evaluation of a MS specialist nurse programme.", "Expanding patient involvement in care. Effects on patient outcomes.", "Using an office system intervention to increase breast cancer screening.", "Randomized controlled trials in pediatric surgery: could we do better?", "Controlled trial evaluation of an asthma education programme for adults.", "Evaluation of the effectiveness of professionally guided self-care for people with multiple sclerosis living in the community: a randomized controlled trial.", "Primary care clinicians treat patients with medically unexplained symptoms: a randomized controlled trial.", "The impact of pharmaceutical care on the clinical outcome of diabetes mellitus among a rural patient population.", "Can small group education and peer review improve care for patients with asthma/chronic obstructive pulmonary disease?", "An outreach intervention to implement evidence based practice in residential care: a randomized controlled trial [ISRCTN67855475].", "Practice development plans to improve the primary care management of acute asthma: randomised controlled trial.", "A multifaceted intervention according to the Audit Project Odense method improved secondary prevention of ischemic heart disease: a randomised controlled trial.", "The efficacy of multidisciplinary rehabilitation in stable multiple sclerosis patients.", "Randomized controlled trial of anticipatory and preventive multidisciplinary team care: for complex patients in a community-based primary care setting.", "The effect of a respiratory home nurse intervention in patients with chronic obstructive pulmonary disease (COPD).", "Psychosocial interventions for somatizing patients by the general practitioner: a randomized controlled trial.", "Effectiveness of rehabilitation intervention in persons with multiple sclerosis: a randomised controlled trial.", "Drug treatment of stable angina pectoris and mass dissemination of therapeutic guidelines: a randomized controlled trial.", "Randomized controlled trial of education and feedback for implementation of guidelines for acute low back pain.", "A behavioral intervention to improve obstetrical care.", "Determining the effectiveness of a clinical-practice intervention in improving the control of pain in outpatients with cancer.", "Evaluating the effectiveness of 2 educational interventions in family practice.", "Peak flow monitoring for guided self-management in childhood asthma: a randomized controlled trial.", "Improving combined diabetes outcomes by adding a simple patient intervention to physician feedback: a cluster randomized trial.", "Randomized clinical trial of a quality improvement intervention in nursing homes.", "Fetal health surveillance: a community-wide approach versus a tailored intervention for the implementation of clinical practice guidelines.", "Nurse led follow up and conventional medical follow up in management of patients with lung cancer: randomised trial." ]	[ "Current understanding of implementation methods is limited, and research has focused on changing doctors' behaviors.\n Our aim was to evaluate the impact of audit and feedback and educational outreach in improving nursing practice and patient outcomes.\n Using a factorial design, cluster randomized controlled trial, we evaluated 194 community nurses in 157 family practices and 1078 patients with diagnosis of urinary incontinence (UI) for nurses compliance with evidence-linked review criteria for the assessment and management of UI and impact on psychologic and social well-being and symptoms. In the outreach arms, nurses' self-reported barriers informed development of tailored strategies.\n In comparison with educational materials alone, the implementation methods tested did not improve care at 6 months follow-up. Moderate rates of improvement (10-17% of patients) in performance for the assessment of UI and greater rates of improvement (20-30% of patients) for the management of care were found but effects were similar across arms. Improvement in patient outcomes was more consistently positive for educational outreach than for audit and feedback but differences were not significant. Adjustment for caseload size, severity or duration of UI and patients' age did not alter results.\n Printed educational materials alone may be as effective as audit and feedback and educational outreach in improving nurses' performance and outcomes of care for people with UI. Greater understanding of the underlying processes in improving performance within multidisciplinary teams through further, theory-driven studies with \"no intervention\" control groups and longer follow-up are needed.", "Previous studies have shown that Norwegian public health physicians do not systematically and explicitly use scientific evidence in their practice. They work in an environment that does not encourage the integration of this information in decision-making. In this study we investigate whether a theoretically grounded tailored intervention to diffuse evidence-based public health practice increases the physicians' use of research information.\n 148 self-selected public health physicians were randomised to an intervention group (n = 73) and a control group (n = 75). The intervention group received a multifaceted intervention while the control group received a letter declaring that they had access to library services. Baseline assessments before the intervention and post-testing immediately at the end of a 1.5-year intervention period were conducted. The intervention was theoretically based and consisted of a workshop in evidence-based public health, a newsletter, access to a specially designed information service, to relevant databases, and to an electronic discussion list. The main outcome measure was behaviour as measured by the use of research in different documents.\n The intervention did not demonstrate any evidence of effects on the objective behaviour outcomes. We found, however, a statistical significant difference between the two groups for both knowledge scores: Mean difference of 0.4 (95% CI: 0.2-0.6) in the score for knowledge about EBM-resources and mean difference of 0.2 (95% CI: 0.0-0.3) in the score for conceptual knowledge of importance for critical appraisal. There were no statistical significant differences in attitude-, self-efficacy-, decision-to-adopt- or job-satisfaction scales. There were no significant differences in Cochrane library searching after controlling for baseline values and characteristics.\n Though demonstrating effect on knowledge the study failed to provide support for the hypothesis that a theory-based multifaceted intervention targeted at identified barriers will change professional behaviour.", "Research is needed to validate effective and practical strategies for improving the provision of evidence-based medicine in primary care.\n To determine whether a multimethod quality improvement intervention was more effective than a less intensive intervention for improving adherence to 21 quality indicators for primary and secondary prevention of cardiovascular disease and stroke.\n 2-year randomized, controlled clinical trial with the practice as the unit of randomization.\n 20 community-based family or general internal medicine practices in 14 states. All used the same electronic medical record.\n 44 physicians, 17 midlevel providers, and approximately 200 staff members; data from the electronic medical records of 87,291 patients.\n All practices received copies of practice guidelines and quarterly performance reports. Intervention practices also hosted quarterly site visits to help them adopt quality improvement approaches and participated in 2 network meetings to share \"best practice\" approaches.\n The percentage of indicators at or above predefined targets and the percentage of patients who had achieved each clinical indicator.\n Intervention practices improved 22.4 percentage points (from 11.3% to 33.7%) in the percentage of indicators at or above the target; control practices improved 16.4 percentage points (from 6.3% to 22.7%). The 6.0-percentage point absolute difference between the intervention and control group was not statistically significant (P > 0.2). Patients in intervention practices had greater improvements than those in control practices for diagnoses of hypertension (improvement difference, 15.7 percentage points [95% CI, 5.2 to 26.3 percentage points]) and blood pressure control in patients with hypertension (improvement difference, 8.0 percentage points [CI, 0.0 to 16.0 percentage points]).\n The study involved a small number of practices and lacked a pure control group.\n Primary care practices that use electronic medical records and receive regular performance reports can improve their adherence to clinical practice guidelines for cardiovascular disease and stroke prevention.", "To determine if an evidence-based implementation (EBI) could lead to the successful implementation of evidence based care for adult asthma in small rural district hospitals.\n A controlled trial involving eight small rural hospitals (four each in the study and control groups) was conducted. Retrospective pre-intervention audits were conducted at all eight hospitals for 7 months (1 January 2004 to 31 July 2004) and evidence-practice gaps identified. An EBI was then used to implement established guidelines for the management of asthma in the study hospitals. Post-intervention audits were then performed over a period of 7 months (1 October 2004 to 31 April 2005).\n There were 52 presentations of asthma in the study hospitals in the pre-implementation phase and 47 post-implementation. The corresponding numbers for the control hospitals were 46 and 42 respectively. There were no statistically significant differences in the severity between the groups. Following the EBI there were significant improvements at the study hospitals for the documentation of severity (8% to 62%, p <0.001), use of spirometry (12% to 62%, p <0.001) and the use of written short-term asthma plans (9% to 26%, p = 0.05). There was a decrease in use of ipratropium in mild asthma (44% to 30%, p = 0.228), an increase in the use of systemic steroids (61% to 72%, p = 0.255) and no change in prescribing antibiotics for afebrile patients with asthma (21% to 21% p = 0.956). There was no significant change in practice at the control hospitals except for a decrease in the use of systemic steroids (48% to 21%, p = 0.011). For the six clinical indicators aggregate there was a significant increase in compliance with guidelines at the study hospitals (36% to 62%, p < 0.001) but no change at the control hospitals (31% to 31%, p = 0.970).\n The pre-intervention audits demonstrated low levels of compliance with asthma guidelines across six clinical indicators. An EBI significantly improved compliance across these six indicators, and no improvement was noted in the control hospitals. This study demonstrates that an EBI can alter clinical practice in small rural district hospitals.", "Significant resources and time are invested in the production of research knowledge. The primary objective of this randomized controlled trial was to evaluate the effectiveness of three knowledge translation and exchange strategies in the incorporation of research evidence into public health policies and programs.\n This trial was conducted with a national sample of public health departments in Canada from 2004 to 2006. The three interventions, implemented over one year in 2005, included access to an online registry of research evidence; tailored messaging; and a knowledge broker. The primary outcome assessed the extent to which research evidence was used in a recent program decision, and the secondary outcome measured the change in the sum of evidence-informed healthy body weight promotion policies or programs being delivered at health departments. Mixed-effects models were used to test the hypotheses.\n One hundred and eight of 141 (77%) health departments participated in this study. No significant effect of the intervention was observed for primary outcome (p < 0.45). However, for public health policies and programs (HPPs), a significant effect of the intervention was observed only for tailored, targeted messages (p < 0.01). The treatment effect was moderated by organizational research culture (e.g., value placed on research evidence in decision making).\n The results of this study suggest that under certain conditions tailored, targeted messages are more effective than knowledge brokering and access to an online registry of research evidence. Greater emphasis on the identification of organizational factors is needed in order to implement strategies that best meet the needs of individual organizations.\n The trial registration number and title are as follows: ISRCTN35240937 -- Is a knowledge broker more effective than other strategies in promoting evidence-based physical activity and healthy body weight programming?", "To assess the efficacy and cost-effectiveness of pelvic floor muscle therapies (PFMT) in women aged > or = 40 years with urodynamic stress incontinence (USI) and mixed UI.\n In a three-arm randomized controlled trial in Leicestershire and Rutland UK, 238 community-dwelling women aged > or = 40 years with USI in whom previous primary behavioural intervention had failed were randomized to receive either intensive PFMT (79), vaginal cone therapy (80) or to continue with primary behavioural intervention (79) for 3 months. The main outcome measure was the frequency of primary UI episodes, and secondary measures were pad-test urine loss, patient perception of problem, assessment of PF function, voiding frequency, and pad usage. Validated scales for urinary dysfunction, and impact on quality of life and satisfaction were collected at an independent interview.\n All three groups had a moderate reduction in UI episodes after intervention but there was no statistically significant difference among the groups. There were marginal improvements in voiding frequency for all groups, with no statistically significant difference among them.\n In women who have already had simple behavioural therapies (including advice on PFM exercises) for urinary dysfunction, the continuation of these behavioural therapies can lead to further improvement. The addition of vaginal cone therapy or intensive PFMT does not seem to contribute to further improvement. The improvement in pelvic floor function was significantly greater in the PFMT arm than in the control arm although this did not translate into changes in urinary symptoms.", "Quality improvement initiatives in health services rely upon the effective introduction of clinical practice guidelines. However, even well constructed guidelines have little effect unless supported by dissemination and implementation strategies.\n To test the effectiveness of 'educational outreach' as a strategy for facilitating the uptake of dyspepsia management guidelines in primary care.\n A pragmatic, cluster-randomised controlled trial of guideline introduction, comparing educational outreach with postal guideline dissemination alone.\n One-hundred and fourteen general practices (233 general practitioners) in the Salford and Trafford Health authority catchment area in the northwest of England.\n All practices received guidelines by post in July 1997. The intervention group practices began to receive educational outreach three months later. This consisted of practice-based seminars with hospital specialists at which guideline recommendations were appraised, and implementation plans formulated. Seminars were followed up with 'reinforcement' visits after a further 12 weeks. Outcome measures were: (a) the appropriateness of referral for; and (b) findings at, open access upper gastrointestinal endoscopy; (c) costs of GP prescriptions for acid-suppressing drugs, and (d) the use of laboratory-based serological tests for Helicobacter pylori. Data were collected for seven months before and/or after the intervention and analysed by intention-to-treat.\n (a) The proportion of appropriate referrals was higher in the intervention group in the six-month post-intervention period (practice medians: control = 50.0%, intervention = 63.9%, P < 0.05); (b) the proportion of major findings at endoscopy did not alter significantly; (c) there was a greater rise in overall expenditure on acid-suppressing drugs in the intervention as compared with the control group (+8% versus +2%, P = 0.005); and (d) the median testing rate per practice for H pylori in the post-intervention period was significantly greater in the intervention group (four versus O, P < 0.001).\n This study suggests that educational outreach may be more effective than passive guideline dissemination in changing clinical behaviour. It also demonstrates that unpredictable and unanticipated outcomes may emerge.", "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.", "To evaluate the effectiveness of a multifaceted intervention to improve the clinical decision making of general practitioners (GPs) for patients with diabetes. To identify practice characteristics which predict success.\n Cluster randomized controlled trial with 124 practices and 185 GPs in The Netherlands. The intervention group received feedback reports and support from a facilitator; the control group received no special attention. Outcome measures were the compliance rates with evidence-based recommendations pertaining to discussion of body weight control, discussion of problems with medication, blood pressure measurement, foot examination, eye examination, initiating anti-diabetic medication or increasing the dosage in cases of uncontrolled blood glucose, and scheduling a follow-up appointment.\n The GPs reported on their clinical decision making in 1410 consultations with Type 2 diabetic patients at baseline and 1449 consultations after the intervention period. The intervention resulted in statistically significant improvement for two of the seven outcome measures: foot examination (odds ratio 1.68; 95% confidence interval 1.19-2.39) and eye examination (1.52; 1.07-2.16). Discussion of problems with medication showed a near significant trend towards increased benefit for the intervention group (1.52; 0.99-2.32). Practice characteristics were not found to be related to the success of the intervention.\n Feedback reports with support from facilitators appear to increase rates of foot examination and eye examination in general practice. Alternative interventions should be explored to improve the pursuit of metabolic control by GPs.", "Patient-centred depression care approaches should better address barriers of insufficient patient information and involvement in the treatment decision process. Additional research is needed to test the effect of increased patient participation on outcomes. The aim of this study was to assess, if patient participation in decision-making via a shared decision-making intervention leads to improved treatment adherence, satisfaction, and clinical outcome without increasing consultation time.\n Cluster-randomized controlled intervention study based on physician training and patient-centered decision aid compared to usual care in primary care settings in Südbaden region of Germany. Twenty-three primary care physicians treating 405 patients with newly diagnosed depression were enrolled. Patient involvement was measured with the patient perceived involvement in care scale (PICS) and a patient participation scale (MSH-scale). Patient satisfaction was measured by the CSQ-8 questionnaire. Treatment adherence was evaluated by patient and provider self-report. Depression severity and remission outcomes were assessed with the Brief PHQ-D.\n Physician facilitation of patient participation improved significantly and to a greater extent in the intervention compared to the control group. There was no intervention effect for depression severity reduction. Doctor facilitation of patient participation, patient-rated involvement, and physician assessment of adherence improved only in the intervention group. Patient satisfaction at post-intervention was higher in the intervention group compared to the control group. The consultation time did not differ between groups.\n A shared decision-making intervention was better than usual care for improving patient participation in treatment decision-making, and patient satisfaction without increasing consultation time. Additional research is needed to model causal linkages in the decision-making process in regard to outcomes.\n The study results encourage the implementation of patient participation in primary care of depression.", "The primary purpose of this study was to determine if a psychoeducational nursing intervention including (a) health education, (b) stress management, and (c) the teaching of coping skills could enhance the coping behavior and affective state of newly diagnosed Stage I/II malignant melanoma patients. The secondary purpose was to determine if this intervention could be implemented by a nurse and integrated into the overall patient care program. Sixty-one patients were randomized to a control condition or an experimental condition that received and educational manual plus 3 h of individual nurse teaching. Despite randomization, experimental patients had significantly higher baseline distress. By 3 months there was a complete reversal of the baseline trend in Profile of Mood States (POMS) total mood disturbance (TMD), suggesting that the experimental subjects were experiencing less distress over time. Between-group analysis of change scores found significant decreases in experimental subjects for POMS TMD, fatigue, and Brief Symptom Index (BSI) somatization. Within-group analysis found significant experimental decreases for BSI somatization, anxiety, grand total, General Severity Index, and Positive Symptom Distress Index as well as for POMS anxiety, fatigue, confusion, vigor, and TMD. No significant changes were found for controls. Experimental patients were using significantly fewer ineffective passive resignation coping strategies than controls at 3 months.", "In patients with relapsing-remitting multiple sclerosis (MS), IVIG was shown to reduce the relapse rate and progression of disability. In patients with chronic progressive MS, a beneficial effect of IVIG was not documented in placebo controlled studies. This trial investigated the influence of IVIG in primary (PPMS) and secondary (SPMS) chronic progressive MS. Two-hundred and thirty-one patients stratified for PPMS (n=34) and SPMS (n=197) were randomly assigned to IVIG 0.4 g/kg per month or to placebo for 24 months. Primary endpoints were 1) the time to sustained progression of disease identified as worsening of the expanded disability status scale (EDSS) sustained for 3 months, and 2) the improvement of neurological functions defined by a patient's best EDSS score. Secondary endpoints were the proportion of patients with sustained progression, the relapse rate, the assessment of fine motor skills, visual evoked potentials, contrast sensitivity, depression and quality of life. Analysis of the intention-to-treat (ITT) population of combined PPMS and SPMS patients showed that the mean time to sustained progression was 74 weeks in the IVIG compared with 62 weeks in the placebo group (P=0.0406). When PPMS and SPMS patients were analysed separately, the time to sustained progression was also longer in the IVIG group, but the difference was not significant. There was no IVIG-mediated improvement in neurological functions. In the combined per protocol (PP) treated patients, IVIG treatment prolonged time to sustained progression by 13 weeks (P=0.0396). PPMS patients, but not SPMS patients showed a slight favourable IVIG effect on the best EDSS score. In the combined ITT population there were less patients with sustained progression in the IVIG than in the placebo group (P=0.028). The difference was significant in PPMS (P=0.016), but not in SPMS patients. In the combined PP population, there was a trend for a favorable IVIG effect on the rates of patients with sustained progression. In patients with PPMS, this IVIG effect reached significance (P=0.036). Other secondary endpoints did not show significant differences between treatment groups. Eighteen patients with PPMS and 102 patients with SPMS withdrew from the study for various reasons. Treatment was generally well tolerated. It was concluded that monthly IVIG infusion could delay progression of disease in patients with PPMS, and that there was a trend in favour of IVIG treatment in patients with SPMS.", "Although clinical-practice guidelines (CPGs) are implemented on the assumption that they will improve the quality, efficiency, and consistency of health care, they generally have limited effect in changing physicians' behavior. The purpose of this study was to design and implement an effective program for formulating, promulgating, and implementing CPGs to foster the development of an evidence-based culture in an Israeli HMO.\n The authors implemented a four-stage program of stepwise collaborative efforts with academic institutions composed of developing quantitative tools to evaluate prescribing patterns, updating CPGs, collecting MDs' input via focus groups and quantitative surveys, and conducting a randomized controlled trial of a two-stage, multipronged intervention. The test case for this study was the development, dissemination, and implementation of CPG for the treatment of acute uncomplicated cystitis in adult women. Interventions in the form of a lecture at a conference and a letter with personalized feedback were implemented, both individually and combined, to improve physicians' rates of prescribing the first-line drug, nitrofurantoin, and, in the absence of nitrofurantoin, adhering to the recommended duration of three days of treatment with ofloxacin.\n The tools and data-generating capabilities designed and constructed in Stage I of the project were integral components of all subsequent stages of the program. Personalized feedback alone was sufficient to improve the rate of adherence to the guidelines by 19.4% (95% CI = 16.7, 22.1).\n This study provides a template for introducing the component of experimentation essential for cultivating an evidence-based culture. This process, composed of collaborative efforts between academic institutions and a managed care organization, may be beneficial to other health care systems.", "Shared decision-making (SDM) between professionals and patients is increasingly advocated from ethical principles. Some data are accruing about the effects of such approaches on health or other patient-based outcomes. These effects often vary substantially between studies.\n Our aim was to evaluate the effects of training GPs in SDM, and the use of simple risk communication aids in general practice, on patient-based outcomes.\n A cluster randomized trial with crossover was carried out with the participation of 20 recently qualified GPs in urban and rural general practices in Gwent, South Wales. A total of 747 patients with known atrial fibrillation, prostatism, menorrhagia or menopausal symptoms were invited to a consultation to review their condition or treatments. After baseline, participating doctors were randomized to receive training in (i) SDM skills; or (ii) the use of simple risk communication aids, using simulated patients. The alternative training was then provided for the final study phase. Patients were randomly allocated to a consultation during baseline or intervention 1 (SDM or risk communication aids) or intervention 2 phases. A randomly selected half of the consultations took place in 'research clinics' to evaluate the effects of more time for consultations, compared with usual surgery time. Patient-based outcomes were assessed at exit from consultation and 1 month follow-up. These were: COMRADE instrument (principal measures; subscales of risk communication and confidence in decision), and a range of secondary measures (anxiety, patient enablement, intention to adhere to chosen treatment, satisfaction with decision, support in decision making and SF-12 health status measure). Multilevel modelling was carried out with outcome score as the dependent variable, and follow-up point (i.e. exit or 1 month later for each patient), patient and doctor levels of explanatory variables.\n No statistically significant changes in patient-based outcomes due to the training interventions were found: COMRADE risk communication score increased 0.7 [95% confidence interval (CI) -0.92 to 2.32] after risk communication training and 0.9 (95% CI -0.89 to 2.35) after SDM training; and COMRADE satisfaction with communication score increased by 1.0 (95% CI -1.1 to 3.1) after risk communication, and decreased by 0.6 (95% CI 2.7 to -1.5) after SDM training. Patients' confidence in the decision (2.1 increase, 95% CI 0.7-3.5, P < 0.01) and expectation to adhere to chosen treatments (0.7 increase, 95% CI 0.04-1.36, P < 0.05) were significantly greater among patients seen in the research clinics (when more time was available) compared with usual surgery time. Most outcomes deteriorated between exit and 1 month later. There was no interaction between intervention effects.\n Patients can be more involved in treatment decisions, and risks and benefits of treatment options can be explained in more detail, without adversely affecting patient-based outcomes. SDM and risk communication may be advocated from values and ethical principles even without evidence of health gain or improvement in patient-based outcomes, but the resources required to enhance these professional skills must also be taken into consideration. These data also indicate the benefits of extra consultation time.", "A crossover randomized controlled trial of cycles of quality assurance in 16 primary care (8 medical, 8 pediatric) group practices was conducted. Of four medical and four pediatric tasks important to patient outcome, two were randomly assigned to experimental intervention (a quality assurance cycle), and two were also measured and used as blinded controls for each medical or pediatric group practice. Task performance was measured in each group for 12 months prior to, 9 months during, and 9 months after the experimental intervention, using as a performance score the percentage of evaluation criteria failed of those applicable to a case. As a result of quality assurance intervention, quality of performance was significantly improved in two of the tasks (P less than 0.0001, with 6.7, and 9.8 percentage points improvement), and marginally improved in one task (P = 0.06, 5.7 percentage points improvement). Surprisingly, tasks with lower perceived effect on patient health (low physician motivation) had greater improvement in quality. Unimproved tasks were associated with the perceived need for delivery system changes beyond the immediate control of the individual practitioner.", "The capacity of educational programs to improve physician performance remains doubtful despite many evaluative efforts. This is especially true for programs sponsored by the federal government. We tested the efficacy of an educational program conducted by Professional Standards Review Organizations in reducing the inappropriate use of x-ray pelvimetry. This procedure may cause harm to the fetus, and there is little evidence that it is efficacious. We randomly assigned 120 hospitals in six Professional Standards Review Organizations to study and control groups. Physicians with delivery privileges at each study hospital participated in an educational program that discussed acceptable indications for x-ray pelvimetry. Pelvimetry use was similar in study and control hospitals before the program. However, after the program, pelvimetry was performed by physicians at study hospitals less than one third as often as by physicians at control hospitals. We conclude that educational programs can improve physician performance substantially and that such programs can be effectively conducted by federally sponsored physician organizations.", "There are many systematic reviews of continuing education programmes and educational strategies for quality improvement in health care. Most of the reviewed studies are one-off evaluations rather than impact evaluations with long-term follow-up. There are few systematic reviews of organisational, financial and regulatory interventions, and few high-quality studies. These interventions are probably as or more important than educational strategies, although they are less well evaluated. Few studies have been undertaken in low- and middle-income countries (LMIC) or that address maternal and child health (MCH). Thus, the results of the available studies and reviews need to be interpreted cautiously when applied to LMIC. Interactive workshops, reminders and multifaceted interventions can improve professional practice, and they generally have moderate effects. Educational outreach visits consistently improve prescribing but have variable effects on other behaviours. Audit and feedback interventions have variable effects on professional practice, but most often these are small to moderate effects. Mass-media and patient-mediated interventions may change professional practice. Multifaceted interventions that combine several quality-improvement strategies are also effective but may not be more so than single interventions. While all of these strategies are applicable to MCH in LMIC, the applicability of the results to rural settings, in particular, may be limited. Use of these strategies could exacerbate inequalities, and this should be taken into consideration when planning implementation. Scaling up and sustainability may be difficult to achieve in LMIC contexts and need careful consideration. The use of financial interventions has not been well studied; financial incentives and disincentives may be difficult to use effectively and efficiently, although their impact on practice needs to be considered. Organisational interventions are likely to be important, given that there are often underlying organisational or system problems. Regulatory interventions have not been well evaluated, but may sometimes be both inexpensive and effective. There are no 'magic bullets' or simple solutions for ensuring the quality of health care services. Interventions should be selected or tailored to address the underlying reasons for a failure to deliver effective services. Decision-makers should select the most appropriate interventions for specific problems. This requires a governance structure that clearly assigns responsibility for quality-improvement activities, priority setting, selection and design of interventions, and evaluation.", "Specialist nurses are being promoted as a means of improving the health care provided to people with multiple sclerosis (MS).\n To identify the impact of a programme of MS specialist nurses on MS health care provision and on the health and well-being of people with MS.\n A quasi-experimental design comparing an intervention group in which new MS nurse posts were installed with a control group that had no MS nurse posts.\n Six neurological services in four English regions.\n Seven hundred and fifty-three of the 1510 people invited to participate returned completed questionnaires at baseline. Follow-up of participants was 82% with 616 patients participating in the main outcome analysis.\n Data were collected prospectively before the appointment of the MS nurses and then at 12 and 24 months. Data were collected via a postal questionnaire comprising questions related to care processes (information provision and care quality) and health outcome measures, hospital admissions, MS complications, health-related quality of life (SF36) and disease impact (MS Impact Scale-29). Analysis repeated measures in CAT MOD for process variables and ANCOVA to longest follow-up for outcome measures.\n Information provision was higher in the intervention group (68% (n=153) compared to 53% (n=98) at 24 months) but no significant improvement was observed in information provision through time compared to the control group. There was an increase in the availability of a contact person in the intervention group, at 24 months 83% (n=42) had a contact person compared to 44% in the control (p=0.01). The only significant finding in relation to MS complications was a reduction of 17% in the incidence of pressure ulcers in the intervention sites compared to a 3% reduction in the control (p<0.001). In relation to the disease and health-related quality of life measures, the intervention group showed a small but significant (p<0.05) worsening in the physical and symptom scales of the SF36 compared to the control (mean differences: physical function -2.81, CI -5.45 to -0.1; bodily pain -4.09, CI -7.2 to -0.9; general health -5.35, CI -8.1 to -2.5; and energy and vitality -2.82, CI -5.5 to -0.1). No differences were observed in relation to disease impact or psychosocial well-being, although a relative benefit in mental health (with a 7.8 point advantage on the SF36 mental health scale, p=0.04) was observed in some of the intervention sites for people with relapsing/remitting MS.\n The specialist nurse programme was found to impact positively on the provision of MS-related health care. However, there was very limited evidence that the programme led to any improvements in disease-related problems, impact or health-related quality of life, These findings were in part explained by the inherent difficulties of measuring effects in evaluations of complex phenomena such as a nursing role. The deterioration observed in the intervention group on the physical outcome measures was explained by a selection bias in which people with worsening health were more likely to seek contact with a specialist nurse. It is contended that future research in this area may be better directed toward identifying specific interventions that nurses and other health professionals might employ in addressing the many problems confronting people with MS.", "An intervention was developed to increase patient involvement in care. Using a treatment algorithm as a guide, patients were helped to read their medical record and coached to ask questions and negotiate medical decisions with their physicians during a 20-minute session before their regularly scheduled visit. In a randomized controlled trial we compared this intervention with a standard educational session of equal length in a clinic for patients with ulcer disease. Six to eight weeks after the trial, patients in the experimental group reported fewer limitations in physical and role-related activities (p less than 0.05), preferred a more active role in medical decision-making, and were as satisfied with their care as the control group. Analysis of audiotapes of physician-patient interactions showed that patients in the experimental group were twice as effective as control patients in obtaining information from physicians (p less than 0.05). Results of the intervention included increased involvement in the interaction with the physician, fewer limitations imposed by the disease on patients' functional ability, and increased preference for active involvement in medical decision-making.", "To evaluate an innovative approach to continuing medical education, an outreach intervention designed to improve performance rates of breast cancer screening through implementation of office systems in community primary care practices.\n Randomized, controlled trial with primary care practices assigned to either the intervention group or control group, with the practice as the unit of analysis.\n Twenty mostly rural counties in North Carolina.\n Physicians and staff of 62 randomly selected family medicine and general internal medicine practices, primarily fee-for-service, half group practices and half solo practitioners.\n Physician investigators and facilitators met with practice physicians and staff over a period of 12 to 18 months to provide feedback on breast cancer screening performance, and to assist these primary care practices in developing office systems tailored to increase breast cancer screening.\n Physician questionnaires were obtained at baseline and follow-up to assess the presence of five indicators of an office system. Three of the five indicators of office systems increased significantly more in intervention practices than in control practices, but the mean number of indicators in intervention practices at followup was only 2.8 out of 5. Cross-sectional reviews of randomly chosen medical records of eligible women patients aged 50 years and over were done at baseline (n = 2,887) and follow-up (n = 2,874) to determine whether clinical breast examinations and mammography, were performed. Results for mammography were recorded in two ways, mention of the test in the visit note and actual report of the test in the medical record. These reviews showed an increase from 39% to 51% in mention of mammography in intervention practices, compared with an increase from 41% to 44% in control practices (p = .01). There was no significant difference, however, between the two groups in change in mammograms reported (intervention group increased from 28% to 32.7%; control group increased from 30.6% to 34.0%, p = .56). There was a nonsignificant trend (p = .06) toward a greater increase in performance of clinical breast examination in intervention versus control practices.\n A moderately intensive outreach intervention to increase rates of breast cancer screening through the development of office systems was modestly successful in increasing indicators of office systems and in documenting mention of mammography, but had little impact on actual performance of breast cancer screening. At follow-up, few practices had a complete office system for breast cancer screening. Outreach approaches to assist primary care practices implement office systems are promising but need further development.", "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.", "To improve asthma control and reduce readmission rates through increased knowledge and the development of self management skills, a brief (three hour) adult education programme was developed.\n The course was designed to improve inhaler skills and to teach how to adjust drug doses according to peak flow (PEF) measurements and a treatment plan. It was evaluated in a randomised controlled trial in 76 patients admitted to hospital for asthma by using questionnaires, spirometry, and home monitoring of PEF at entry and at five and 10 months after intervention. The questionnaire provided measures of knowledge about asthma, self management behaviour appropriate to asthma control, asthma symptom frequency and severity, and psychosocial disturbance attributable to asthma.\n During the 10 months observation period the readmission rate for the educated group was one seventh that of the control group and attendance at accident and emergency departments also decreased. No consistent differential improvements were observed in spirometric results, average PEF, or mean daily variability of PEF. Both groups showed improvements in measures of asthma knowledge, behaviour, symptoms, and psychosocial disturbances. However, the intervention group showed a significantly greater improvement in some measures of asthma knowledge and self management skills.\n Despite minimal effect on measures of airway function, substantial changes in illness behaviour and use of health care facilities can be achieved by a brief asthma education programme.", "The aim of the study was to assess the efficacy of a patient-focused professionally guided self-care programme for the management of multiple sclerosis (MS) in the community.\n This was a single-blind randomized controlled trial.\n The study was conducted with people with MS living in the community.\n Two hundred and seventy-eight people with MS were invited to take part in the study. One hundred and eighty-nine people consented to take part (68%). Of these 183 began the study and 169 (92.3%) completed it. Seventy-three individuals were in the intervention group and 96 were in the control group.\n The intervention comprised discussion of self-care based on client priorities, using an information booklet about self-care.\n These included the Barthel Index, a measure of mobility, the SF-36, and the Standard Day Dependency Record (SDDR) which measures the need for assistance with daily activities. Assessments were conducted at baseline and again six months later.\n Changes in health status were small. However, at follow-up the intervention group had better SF-36 health scores, in mental health (p = 0.04), and vitality (p = 0.05) and considered help with daily activities to be less essential, as measured by the SDDR (p = 0.04), than the control group. Participants in the intervention group had maintained levels of independence at follow-up (p = 0.62) while the control group showed a significant decrease in independence (p= 0.001).\n This intervention could be a useful aid for health professionals who are supporting people with MS living in the community.", "There is no proven primary care treatment for patients with medically unexplained symptoms (MUS). We hypothesized that a long-term, multidimensional intervention by primary care providers would improve MUS patients' mental health.\n Clinical trial.\n HMO in Lansing, MI.\n Patients from 18 to 65 years old with 2 consecutive years of high utilization were identified as having MUS by a reliable chart rating procedure; 206 subjects were randomized and 200 completed the study.\n From May 2000 to January 2003, 4 primary care clinicians deployed a 12-month intervention consisting of cognitive-behavioral, pharmacological, and other treatment modalities. A behaviorally defined patient-centered method was used by clinicians to facilitate this treatment and the provider-patient relationship.\n The primary endpoint was an improvement from baseline to 12 months of 4 or more points on the Mental Component Summary of the SF-36.\n Two hundred patients averaged 13.6 visits for the year preceding study. The average age was 47.7 years and 79.1% were females. Using intent to treat, 48 treatment and 34 control patients improved (odds ratio [OR]=1.92, 95% confidence interval [CI]: 1.08 to 3.40; P=.02). The relative benefit (relative \"risk\" for improving) was 1.47 (CI: 1.05 to 2.07), and the number needed to treat was 6.4 (95% CI: 0.89 to 11.89). The following baseline measures predicted improvement: severe mental dysfunction (P<.001), severe body pain (P=.039), nonsevere physical dysfunction (P=.003), and at least 16 years of education (P=.022); c-statistic=0.75.\n The first multidimensional intervention by primary care clinicians led to clinically significant improvement in MUS patients.", "To evaluate the impact of pharmaceutical care on the clinical outcomes of patients enrolled in a pharmacist-coordinated diabetes management program in a rural health setup.\n Patients were registered into 'control' and 'intervention' groups by randomization at three primary health centers. The study was an open-label parallel study.\n Medical records were prospectively reviewed. Capillary blood glucose level, blood pressure and demographic data were collected at baseline and at the follow-up visits. Pharmacists gave counseling to the intervention group during every visit and their health-related quality of life (HRQoL) was assessed with the Ferrans and Powers questionnaire.\n Single factor ANOVA and the t-test were used to compare the results using SPSS version 0.9 software and MS Excel worksheets.\n The intervention group (n = 104) showed well-controlled BMI, whereas the control group (n = 50) showed significant increase in the BMI. Mean blood glucose level in the intervention group reduced to 25 units from baseline (P = 0.0001) but was significantly increased in the control group (P = 0.0001). ANOVA showed that from the second follow-up onward there was significant decrease in blood glucose levels. Overall, the HRQoL scores increased by 45% in the intervention group and decreased by 2% in the control group.\n The pharmaceutical care program was effective in improving the clinical outcome and HRQoL of diabetes patients in rural India. Such 'pharmaceutical care' models should be fine-tuned and implemented widely.", "To study the effectiveness of an intensive small group education and peer review programme aimed at implementing national guidelines on asthma/chronic obstructive pulmonary disease (COPD) on care provision by general practitioners (GPs) and on patient outcomes.\n A randomised experimental study with pre-measurement and post-measurement (after one year) in an experimental group and a control group in Dutch general practice.\n Two groups of GPs were formed and randomised. The education and peer review group (17 GPs with 210 patients) had an intervention consisting of an interactive group education and peer review programme (four sessions each lasting two hours). The control group consisted of 17 GPs with 223 patients (no intervention).\n Knowledge, skills, opinion about asthma and COPD care, presence of equipment in practice; actual performance about peakflow measurement, non-pharmacological and pharmacological treatment; asthma symptoms (Dutch Medical Research Council), smoking habits, exacerbation ratio, and disease specific quality of life (QOL-RIQ). Data were collected by a written questionnaire for GPs, by self recording of consultations by GPs, and by a written self administered questionnaire for adult patients with asthma/COPD.\n Data from 34 GP questionnaires, 433 patient questionnaires, and recordings from 934 consultations/visits and 350 repeat prescriptions were available. Compared with the control group there were only significant changes for self estimated skills (+16%, 95% confidence interval 4% to 26%) and presence of peakflow meters in practice (+18%, p < 0.05). No significant changes were found for provided care and patient outcomes compared with the control group. In the subgroup of more severe patients, the group of older patients, and in the group of patients not using anti-inflammatory medication at baseline, no significant changes compared with the control group were seen in patient outcomes.\n Except for two aspects, intensive small group education and peer review in asthma and COPD care do not seem to be effective in changing relevant aspects of the provided care by GPs in accordance with guidelines, nor in changing patients' health status.", "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.", "Our professional development plan aimed to improve the primary care management of acute asthma, which is known to be suboptimal.\n We invited 59 general practices in Grampian, Scotland to participate. Consenting practices were randomised to early and delayed intervention groups. Practices undertook audits of their management of all acute attacks (excluding children under 5 years) occurring in the 3 months preceding baseline, 6-months and 12-months study time-points. The educational programme [including feedback of audit results, attendance at a multidisciplinary interactive workshop, and formulation of development plan by practice teams] was delivered to the early group at baseline and to the delayed group at 6 months. Primary outcome measure was recording of peak flow compared to best/predicted at 6 months. Analyses are presented both with, and without adjustment for clustering.\n 23 consenting practices were randomised: 11 to early intervention. Baseline practice demography was similar. Six early intervention practices withdraw before completing the baseline audit. There was no significant improvement in our primary outcome measure (the proportion with peak flow compared to best/predicted) at either the 6 or 12 month time points after adjustment for baseline and practice effects. However, the between group difference in the adjusted combined assessment score, whilst non-significant at 6 months (Early: 2.48 (SE 0.43) vs. Delayed 2.26 (SE 0.33) p = 0.69) reached significance at 12 m (Early:3.60 (SE 0.35) vs. Delayed 2.30 (SE 0.28) p = 0.02).\n We demonstrated no significant benefit at the a priori 6-month assessment point, though improvement in the objective assessment of attacks was shown after 12 months. Our practice development programme, incorporating audit, feedback and a workshop, successfully engaged the healthcare team of participating practices, though future randomised trials of educational interventions need to recognise that effecting change in primary care practices takes time. Monitoring of the assessment of acute attacks proved to be a feasible and responsive indicator of quality care.", "No single quality improvement instrument has proved consistently effective, but multifaceted interventions are believed to have the greatest impact. However, only little is known regarding what combinations are likely to be successful.\n To evaluate the impact of a multifaceted intervention strategy combining GP registrations, outreach visits and feedback, targeting secondary prevention of ischemic heart disease in general practice.\n A randomised controlled trial including 28 GPs in Ringkjøbing County, Denmark. Half of the GPs received outreach visits and feedback on their prescribing of heart disease drugs. Evaluation was based on registration of consultations with patients suffering from ischemic heart disease.\n The intervention had a statistically significant impact on prescribing of lipid lowering drugs [odds ratio 1.59; 95% confidence interval (CI) 1.00 to 2.53] and acetylsalicylic acid (odds ratio 2.54; 95% CI 1.21 to 5.31).\n An intervention strategy combining outreach visits, feedback and GP registrations is a promising way of improving the quality of preventive treatment in general practice.", "To evaluate the short-term efficacy of multidisciplinary, inpatient rehabilitation of multiple sclerosis (MS) patients.\n A double-blind, randomized, parallel group design was used. The intervention group were offered comprehensive, multidisciplinary inpatient rehabilitation at the Haslev MS Hospital for an average of 35.5 days, while the control group received no treatment related to the study. All patients were examined in their homes twice with a 10-week interval. The rehabilitation of the intervention group started 2-3 weeks after the first examination and ended 2-3 weeks before the second examination. Impairment was assessed by the Multiple Sclerosis Impairment Scale and the Expanded Disability Status Scale. Disability was assessed by means of Guy's Neurological Disability Scale. Two specific scales were used to assess upper limb function and ambulation: The Nine-Hole Peg Test and timed 10-metre walking. Patients' own perception of bodily pain, bladder symptoms, spasticity, fatigue, impaired walking and transfers were recorded using visual analogue scales. Finally, quality of life was assessed using the Life Appreciation and Satisfaction Questionnaire and the Functional Assessment in Multiple Sclerosis.\n Two hundred and thirty-three patients were screened and of those 38 were included for treatment and 52 as controls.\n We found no statistically significant differences between the two groups in any of the outcome measures.\n Although the study was underpowered, the negative outcome exposes the difficulties in quantitative analyses of the efficacy of multidisciplinary rehabilitation, which is liable to confounding factors such as variation in the indication for treatment, in the placebo effect, and in the reliability and responsiveness of the outcome measures.", "T o examine whether quality of care (QOC) improves when nurse practitioners and pharmacists work with family physicians in community practice and focus their work on patients who are 50 years of age and older and considered to be at risk of experiencing adverse health outcomes.\n Randomized controlled trial.\n A family health network with 8 family physicians, 5 nurses, and 11 administrative personnel serving 10 000 patients in a rural area near Ottawa, Ont.\n Patients 50 years of age and older at risk of experiencing adverse health outcomes (N = 241).\n At-risk patients were randomly assigned to receive usual care from their family physicians or Anticipatory and Preventive Team Care (APTCare) from a collaborative team composed of their physicians, 1 of 3 nurse practitioners, and a pharmacist.\n Quality of care for chronic disease management (CDM) for diabetes, coronary artery disease, congestive heart failure, and chronic obstructive pulmonary disease.\n Controlling for baseline demographic characteristics, the APTCare approach improved CDM QOC by 9.2% (P < .001) compared with traditional care. The APTCare intervention also improved preventive care by 16.5% (P < .001). We did not observe significant differences in other secondary outcome measures (intermediate clinical outcomes, quality of life [Short-Form 36 and health-related quality of life scales], functional status [instrumental activities of daily living scale] and service usage).\n Additional resources in the form of collaborative multidisciplinary care teams with intensive interventions in primary care can improve QOC for CDM in a population of older at-risk patients. The appropriateness of this intervention will depend on its cost-effectiveness. TRIAL REGISTRATION NUMBER NCT00238836 (CONSORT).", "Chronic obstructive pulmomary disease (COPD) is associated with substantial mortality, morbidity, and costs to the health care system. With the increasing interest in outreach care programmes it is important to evaluate their impact upon patients and health services, for conditions such as COPD.\n To determine the effectiveness of an outreach respiratory nurse in a shared care approach, with collaboration between general practitioners and hospital services, in the management of patients with severe COPD.\n Patients with severe COPD attending The Queen Elizabeth Hospital, Adelaide participated in a randomised controlled trial of a home based nursing intervention (HBNI) over 12 months with outcome measures including mortality rate, hospital service utilisation, FEV1 and health related quality of life (HRQL) using a modified Dartmouth Primary Care Co-operative Quality of Life questionnaire.\n There were 48 subjects in each study arm, with no differences in mortality rate (eight deaths in the HBNI group and seven in the control group), hospital admissions, length of stay, number of outpatient and Emergency Service visits. The study had inadequate follow-up of FEV1 and HRQL within the control group. Within the HBNI group, a small improvement in HRQL (in three of ten indices measured) was demonstrated, despite a deterioration in FEV1 (11% reduction, p=0.04) compared to baseline. Quality of life of HBNI subjects' carers did not change.\n An increased level of care given by an outreach respiratory nurse in a shared care approach for patients with severe COPD produced small improvements in HRQL but did not result in the prevention of deaths or reduced health care utilisation.", "The objective of this study was to compare the effects of psychosocial interventions based on the modified reattribution model for somatizing patients in general practice (GP) with those of nonspecific psychosocial primary care (PPC) alone.\n Forty-two GPs were randomized, 23 into the intervention group (IG), who were trained in reattribution techniques, and 19 into the control group (CG). One hundred twenty-seven patients were included. Primary outcome measures were somatoform symptoms and quality of life.\n Multilevel modeling revealed a reduction of physical symptoms (P = .007), an improvement in physical functioning (P = .0172), and a reduction of depression (P = .0211) and anxiety (P = .0388) in the IG compared with the CG at the 3-month follow-up. However, results no longer remained significant after controlling for baseline and covariate variables besides a reduction of physical symptoms at 6-month follow-up (P = .029).\n Compared with nonspecific PPC, the effects of reattribution techniques were small and limited to physical symptoms.", "A stratified, randomised, waitlist controlled study over 12 months assessed the effectiveness of rehabilitation in persons with multiple sclerosis (MS) in an Australian community cohort.\n Patients with definite MS (n = 101) recruited from a tertiary hospital database, randomised to a treatment group (n = 49) for individualised rehabilitation programme or a control waitlist group (n = 52). Functional Independence Measure (FIM) was used to assess \"activity\" while the Multiple Sclerosis Impact Scale (MSIS-29) and General Health Questionnaire (GHQ-28) assessed \"participation\" and quality of life (QoL). Assessments were at baseline and 12 months.\n Analysis of data from 98 patients (treatment n = 48, control n = 50) showed reduced disability in the treatment group, with statistically significant differences in post-treatment FIM motor scores for the two groups (p<0.001). There was a clinical and statistically significant improvement in FIM (motor) total scores (p<0.001), and the FIM motor domains of: transfer (p<0.001), locomotion (p<0.001), self-care (p<0.001) and the FIM cognitive subscale (p<0.016). In the treated group, 70.8% improved compared with 13% of controls. Significantly more patients in the control group deteriorated over the study period (58.7% vs 16.7%; p<0.001). There were no differences between the control and treatment group scores on the MSIS-physical (p = 0.18), MSIS-psychological (p = 0.45) or GHQ subscales.\n An individualised rehabilitation programme reduces disability in persons with MS compared with no intervention. The impact of rehabilitation on QoL needs further evaluation. More information on the effectiveness of the various components of the multidisciplinary rehabilitation programmes are now needed. Australian clinical trials registry: Trials registration number: ACTRNO12605000676617.", "Public agencies responsible for implementing health care policies often adapt and disseminate clinical practice guidelines, but the effectiveness of mass dissemination of guidelines is unknown. Aim: To study the effects of guideline dissemination on physicians' prescribing practices for the treatment of stable angina pectoris.\n Randomized controlled trial.\n A sample of 3293 Quebec physicians were randomly assigned to receive a one-page summary of clinical practice guidelines on the treatment of stable angina (in February 1999), to receive the summary and a reminder (in February and March 1999, respectively), or to receive no intervention (controls). The prescribing profiles of participants, as well as sociodemographic characteristics of the physicians and their patients, were examined for June-December 1999.\n The intervention had no effect on prescription rates of beta-blockers, antiplatelet agents, or hypolipaemic drugs. Compared to 1997 data for the same physicians, there was an overall 10% increase in appropriate prescription rates, irrespective of the intervention.\n In-house production and dissemination of clinical practice guidelines may not improve physicians' practice patterns if there is pre-existing substantial scientific consensus on the issue.", "The effect of clinical guidelines on resource utilization for complex conditions with substantial barriers to clinician behavior change has not been well studied. We report the impact of a multifaceted guideline implementation intervention on primary care clinician utilization of radiologic and specialty services for the care of acute low back pain.\n Physician groups were randomized to receive guideline education and individual feedback, supporting patient education materials, both, or neither. The impact on guideline adherence and resource utilization was evaluated during the 12-month period before and after implementation.\n Fourteen physician groups with 120 primary care physician and associate practitioners from 2 group model HMO practices.\n Guideline implementation utilized an education/audit/feedback model with local peer opinion leaders. The patient education component included written and videotaped materials on the care of low back pain.\n The clinician intervention was associated with an absolute increase in guideline-consistent behavior of 5.4% in the intervention group versus a decline of 2.7% in the control group (P =.04). The patient education intervention produced no significant change in guideline-consistent behavior, but was poorly adopted. Patient characteristics including duration of pain, prior history of low back pain, and number of visits during the illness episode were strong predictors of service utilization and guideline-consistent behavior.\n Implementation of an education and feedback-supported acute low back pain care guideline for primary care clinicians was associated with an increase in guideline-consistent behavior. Patient education materials did not enhance guideline effectiveness. Implementation barriers could limit the utility of this approach in usual care settings.", "Implementation of evidence-based obstetrical practices remains a significant challenge. Effective strategies to disseminate and implement such practices are needed.\n We randomly assigned 19 hospitals in Argentina and Uruguay to receive a multifaceted behavioral intervention (including selection of opinion leaders, interactive workshops, training of manual skills, one-on-one academic detailing visits with hospital birth attendants, reminders, and feedback) to develop and implement guidelines for the use of episiotomy and management of the third stage of labor or to receive no intervention. The primary outcomes were the rates of prophylactic use of oxytocin during the third stage of labor and of episiotomy. The main secondary outcomes were postpartum hemorrhage and birth attendants' readiness to change their behavior with regard to episiotomies and management of the third stage of labor. The outcomes were measured at baseline, at the end of the 18-month intervention, and 12 months after the end of the intervention.\n The rate of use of prophylactic oxytocin increased from 2.1% at baseline to 83.6% after the end of the intervention at hospitals that received the intervention and from 2.6% to 12.3% at control hospitals (P=0.01 for the difference in changes). The rate of use of episiotomy decreased from 41.1% to 29.9% at hospitals receiving the intervention but remained stable at control hospitals, with preintervention and postintervention values of 43.5% and 44.5%, respectively (P<0.001 for the difference in changes). The intervention was also associated with reductions in the rate of postpartum hemorrhage of 500 ml or more (relative rate reduction, 45%; 95% confidence interval [CI], 9 to 71) and of 1000 ml or more (relative rate reduction, 70%; 95% CI, 16 to 78). Birth attendants' readiness to change also increased in the hospitals receiving the intervention. The effects on the use of episiotomy and prophylactic oxytocin were sustained 12 months after the end of the intervention.\n A multifaceted behavioral intervention increased the prophylactic use of oxytocin during the third stage of labor and reduced the use of episiotomy. (ClinicalTrials.gov number, NCT00070720 [ClinicalTrials.gov]; Current Controlled Trials number, ISRCTN82417627 [controlled-trials.com].).\n Copyright 2008 Massachusetts Medical Society.", "To determine the effectiveness of a clinical-practice intervention in improving the control of pain in outpatients with cancer.\n Between July 5 and September 30, 1995, a randomized, controlled trial of 510 cancer outpatients and 13 oncologists was conducted at 23 clinics in Indiana. All the patients completed assessments of their pain, their pain regimens, and the degrees of relief received; they were surveyed again by mail four weeks after their clinic visits. The intervention group's clinical charts contained a summary of the completed pain scales; the oncologists who treated these patients were instructed to review the summary sheet prior to an evaluation. This summary was not available for the oncologists treating the patients in the control group. Each patient's pain management index (PMI) was calculated: the patient's pain medication level was rated on a scale of 0 to 3; the patients's pain level was rated on a scale of 0 to 3 and then subtracted from the first rating. A negative PMI was interpreted as representing insufficient treatment. Data were analyzed with several statistical tests.\n In all, only 320 patients who reported cancer-related pain were used in the analysis: 160 to 260 in the control group and 160 of 250 in the intervention group. The groups were similar with respect to demographics, cancer sites, and performance status. A significant difference (p = .0162) in the physicians' prescription patterns was found. In the control group, prescriptions for 86% of the patients did not change, with no decrease in analgesic prescriptions; for 14% of the patients analgesic prescriptions increased. In the intervention group, analgesic prescriptions changed for 25% of the patients, decreasing for 5% and increasing for 20%. A decrease in the incidence of pain described as more than life's usual aches and pains was found for the intervention group (p = .05). No significant difference was found between the groups for the patients undertreated for pain, as measured by PMIs.\n Although analgesic regimens were altered significantly when the physicians understood more about the patient's pain, cancer pain management remains a complex problem. Future studies should focus on the long-term systematic incorporation of simple pain-assessment tools into daily outpatient oncology practices as well as on innovative ways to address other aspects of managing cancer pain.", "Structured feedback of information can produce change in physician behaviour. The objective of this study was to assess the effectiveness of 2 educational interventions for improving the quality of care provided by family physicians in Ontario: the Practice Assessment Report (PAR) and the Continuing Medical Education Plan (CMEP) with a follow-up visit by a mentor.\n The study was a randomized controlled trial. Physicians in the control group received only the PAR, whereas those in the experimental group received the PAR, CMEP and mentor interventions. The participants were 56 family physicians and general practitioners (27 in the PAR group and 29 in the CMEP group) in southern Ontario who agreed to participate in the interventions and provide data. A total of 2395 patients randomly sampled from the practices returned questionnaires and consented to have their medical records abstracted. The outcome measures were global scores in 4 areas--quality of care, charting, prevention and overall use of medications--and patient ratings of satisfaction with care and preventive practices. The measures were applied at the beginning (phase 1) and end (phase 2) of the study.\n The mean global scores at the end of the study for the PAR group were 70.1% for quality of care, 84.7% for prevention, 77.7% for charting and 82.2% for overall use of medications. The corresponding scores for the CMEP group were 68.3%, 82.1%, 76.4% and 83.2%. In the patient satisfaction component, the personal care scores at phase 2 were 93.6% for the PAR group and 94.6% for the CMEP group. Examples of the scores for prevention for the PAR group were 98.3% for children's current immunization, 96.6% for blood pressure measured within the previous 5 years, 79.4% for referral of women of the appropriate age for mammography within the previous 2 years, and 58.4% for discussion about alcohol use. The corresponding scores for the CMEP group were 95.8%, 97.6%, 77.6% and 64.6%. The changes in mean scores between phase 1 and phase 2 ranged from -1.9 to 2.3 points. There were no significant differences between the 2 groups in phase 1 or phase 2 scores or in change in scores. A total of 64.3% of the physicians rated the PAR as useful, 26.5% found the CMEP to be useful, and 41.0% considered the mentor strategy to be a useful form of continuing medical education. Although changes in practice related to the PAR, CMEP or mentor were reported by some physicians, they were not related to chart audit or patient scores.\n Educational interventions based on quality-of-care assessments and directed to global improvements in quality of care did not result in improvements in the outcome measures. Educational interventions may have to be targeted to specific areas of the practice, with physicians being monitored and receiving ongoing feedback on their performance.", "We asked whether the addition of PEF recordings to a symptom-based self-management plan improved outcome in school children with asthma. In an open-randomized, parallel-group, controlled trial, we studied children aged 7-14 years with moderate asthma. After a 4-week run-in, 90 children were randomized to receive either PEF plus symptom-based management or symptom-based management alone for 12 weeks. Thresholds for action based on PEF were 70% of best (for increasing inhaled steroids) and 50% of best (for commencing prednisolone). Children were asked to perform twice-daily spirometry at home (using an electronic recording spirometer that revealed only PEF to the study group alone) and to record a symptom diary. The mean daily symptom score was the main outcome. There were no differences between groups in mean symptom score or in spirometric lung function, PEF, quality of life score, or reported use of health services over 12 weeks. During acute episodes, children responded to changes in symptoms by increasing their inhaled steroids at a mean value of PEF of greater than 70% of best so that overall PEF did not contribute to this important self-management decision. Knowledge of PEF did not enhance self-management even during acute exacerbations.", "Research on synergistic effects of patient targeted interventions combined with physician-targeted interventions has been limited.\n To compare a combined physician-patient intervention to physician feedback alone on a composite outcome of glycemic, lipid and blood pressure control.\n In this cluster study 417 patients with adult-type 2 diabetes from four primary care clinics were randomized to receive either a physician-only intervention or a combined physician-plus-patient intervention. Physicians in all clinics received diabetes-related quality performance feedback during staff meetings. Patients at combined-intervention clinics also received a letter encouraging them to remind their doctors to address essential aspects of diabetes care at the next visit. At 1 year follow-up, outcome measurements included hemoglobin A1c, low density lipoprotein-cholesterol and systolic blood pressure: namely, the proportion of patients with HbA1c 9%, LDL <130 mg/dl and SBP <140 mmHg both as separate outcomes and combined.\n After adjusting for patient characteristics and baseline measures, follow-up levels of HbA1c (7.5% vs. 7.8%, P = 0.09), LDL (104.7 vs. 110.7 mg/dl, P < 0.05) and SBP (135.6 vs. 139.9, P = 0.10) were marginally better for combined-intervention patients compared to physician-only intervention patients. Significantly more patients in the combined-intervention (38.8%) than physician-only intervention (24.2%) met all three targets (HbA1c (9%, LDL (130 mg/dl and SBP <140 mmHg) as a single combined outcome (adjusted odds ratio 2.4, P < .01).\n Compared to physician-feedback alone, a dual intervention combining a patient letter with physician feedback produced modest improvements in glycemic, lipid and blood pressure control individually, but substantial improvement in a combined measure of these three outcomes together. Using composite outcomes may detect meaningful improvements in the management of complex chronic disease.", "The purpose of the study was to determine if simply providing nursing facilities with comparative quality performance information and education about quality improvement would improve clinical practices and subsequently improve resident outcomes, or if a stronger intervention, expert clinical consultation with nursing facility staff, is needed.\n Nursing facilities (n = 113) were randomly assigned to one of three groups: workshop and feedback reports only, workshop and feedback reports with clinical consultation, and control. Minimum Data Set (MDS) Quality Indicator (QI) feedback reports were prepared and sent quarterly to each facility in intervention groups for a year. Clinical consultation by a gerontological clinical nurse specialist (GCNS) was offered to those in the second group.\n With the exception of MDS QI 27 (little or no activity), no significant differences in resident assessment measures were detected between the groups of facilities. However, outcomes of residents in nursing homes that actually took advantage of the clinical consultation of the GCNS demonstrated trends in improvements in QIs measuring falls, behavioral symptoms, little or no activity, and pressure ulcers (overall and for low-risk residents).\n Simply providing comparative performance feedback is not enough to improve resident outcomes. It appears that only those nursing homes that sought the additional intensive support of the GCNS were able to effect enough change in clinical practice to improve resident outcomes significantly.", "The decreased use of electronic fetal monitoring (EFM) for healthy women in labour and the increased provision of professional support to all women in labour is recommended by experts. We evaluated the effectiveness of a community-wide approach to transferring research results to practice using a regional committee, newsletter articles and annual conference presentations compared with an additional tailored hospital intervention involving workshops to enhance self-efficacy for nurses, policy review, multidisciplinary meetings, rounds and unit discussions.\n We compared the proportion of women at low risk who received EFM and the proportion of nurses' time spent providing labour support before and after the intervention within each of 4 hospitals (2 tertiary and 2 secondary). One hospital of either type was randomly selected to receive the tailored intervention. Randomly selected charts (n = 200) were reviewed for the use of EFM at each hospital before (1995) and after (1996) the intervention. Trained observers at randomly selected times recorded the nurses' activities, including time spent providing labour support before and after the intervention.\n At the intervention secondary hospital, there was a large decrease in the use of EFM, from 90.1% before to 41.0% after the intervention (p < 0.001), but no change in nurses' time spent providing labour support. At the intervention tertiary hospital there was no change in EFM rates, but there was a small, statistically significant increase in time spent providing labour support (23.5% to 29.8%, p < 0.001). A negative effect on time spent providing labour support was found at the control secondary hospital (decrease from 19.6% to 12.8%, p < 0.001), with no change in the EFM rate. At the control tertiary hospital there was a small decrease in the use of EFM, from 99.5% to 91.4% (p < 0.001), but no change in time spent providing labour support.\n The results are mixed, and the tailored intervention thus appeared to have limited effects. No association was found between the reduction in the use of EFM and an increase in nurses' time spent providing labour support.", "To assess the effectiveness of nurse led follow up in the management of patients with lung cancer.\n Randomised controlled trial.\n Specialist cancer hospital and three cancer units in southeastern England.\n 203 patients with lung cancer who had completed their initial treatment and were expected to survive for at least 3 months.\n Nurse led follow up of outpatients compared with conventional medical follow up. Outcome measures: Quality of life, patients' satisfaction, general practitioners' satisfaction, survival, symptom-free survival, progression-free survival, use of resources, and comparison of costs.\n Patient acceptability of nurse led follow up was high: 75% (203/271) of eligible patients consented to participate. Patients who received the intervention had less severe dyspnoea at 3 months (P=0.03) and had better scores for emotional functioning (P=0.03) and less peripheral neuropathy (P=0.05) at 12 months. Intervention group patients scored significantly better in most satisfaction subscales at 3, 6, and 12 months (P<0.01 for all subscales at 3 months). No significant differences in general practitioners' overall satisfaction were seen between the two groups. No differences were seen in survival or rates of objective progression, although nurses recorded progression of symptoms sooner than doctors (P=0.01). Intervention patients were more likely to die at home rather than in a hospital or hospice (P=0.04), attended fewer consultations with a hospital doctor during the first 3 months (P=0.004), had fewer radiographs during the first 6 months (P=0.04), and had more radiotherapy within the first 3 months (P=0.01). No other differences were seen between the two groups in terms of the use of resources.\n Nurse led follow up was acceptable to lung cancer patients and general practitioners and led to positive outcomes." ]	The results of this review suggest that when used alone and compared to no intervention, PEMs may have a small beneficial effect on professional practice outcomes. There is insufficient information to reliably estimate the effect of PEMs on patient outcomes, and clinical significance of the observed effect sizes is not known. The effectiveness of PEMs compared to other interventions, or of PEMs as part of a multifaceted intervention, is uncertain.
CD005427	[ "8602477", "2148221", "17268258", "19685848", "17621203", "15131431", "18564952", "15319761", "15507794", "12809196", "19539115" ]	[ "Physical performance, pain, pain behavior and subjective disability in patients with subacute low back pain.", "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.", "Multidisciplinary rehabilitation for subacute low back pain: graded activity or workplace intervention or both? A randomized controlled trial.", "Comparison of short-term response to two spinal manipulation techniques for patients with low back pain in a military beneficiary population.", "Active exercise, education, and cognitive behavioral therapy for persistent disabling low back pain: a randomized controlled trial.", "Mini-intervention for subacute low back pain: two-year follow-up and modifiers of effectiveness.", "A comparison between chiropractic management and pain clinic management for chronic low-back pain in a national health service outpatient clinic.", "A randomized clinical trial comparing chiropractic adjustments to muscle relaxants for subacute low back pain.", "Early intervention for the management of acute low back pain: a single-blind randomized controlled trial of biopsychosocial education, manual therapy, and exercise.", "Intensive group training versus cognitive intervention in sub-acute low back pain: short-term results of a single-blind randomized controlled trial.", "A randomized controlled trial comparing 2 types of spinal manipulation and minimal conservative medical care for adults 55 years and older with subacute or chronic low back pain." ]	[ "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.", "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.", "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.", "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.", "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.", "Randomized controlled trial.\n To Investigate the long-term effectiveness, costs, and effect modifiers of a mini-intervention, provided in addition to the usual care, and the incremental effect of a worksite visit for patients with subacute disabling low back pain (LBP).\n A mini-intervention was earlier proved to be an effective treatment for subacute LBP. Whether the beneficial effect is sustained is not known. Furthermore, modifiers of a treatment effect are largely unknown.\n A total of 164 patients with subacute LBP randomized into a mini-intervention (A, n = 56), a mini-intervention plus a worksite visit (B, n = 51), or the usual care (C, n = 57). Mini-intervention consisted of a detailed assessment of the patients' history, beliefs, and physical findings by a physician and a physiotherapist, followed by recommendations and advice. The usual care patients received the conventional care. Pain, disability, health-related quality of life, satisfaction with care, days on sick leave, and health care consumption and costs were measured during a 24-month follow-up. Thirteen candidate modifiers were tested for each outcome.\n There were no differences between the three treatment arms regarding the intensity of pain, the perceived disability, or the health-related quality of life. However, mini-intervention decreased occurrence of daily (A vs., C, P = 0.01) and bothersome (A vs. C, P < 0.05) pain and increased treatment satisfaction. Costs resulting from LBP were lower in the intervention groups (A 4670 Euros, B 5990 Euros) than in C (C 9510 Euros) (A vs. C, P = 0.04; and B vs. C, not significant). The average number of days on sick leave was 30 in A, 45 in B, and 62 in C (A vs. C, P = 0.03; B vs. C, not significant). The perceived risk for not recovering was the strongest modifier of treatment effect. Mental and mental-physical workers in A and B were less often on sick leave than those in C.\n Mini-intervention is an effective treatment for subacute LBP. Despite lack of a significant effect on intensity of low back pain and perceived disability, mini-intervention, including proper recommendations and advice, according to the \"active approach,\" is able to reduce LBP-related costs. The perceived risk of not recovering was the strongest modifier of treatment effect. In alleviating pain, the intervention was most effective among the patients with a high perceived risk of not recovering.", "To compare outcomes in perception of pain and disability for a group of patients suffering with chronic low-back pain (CLBP) when managed in a hospital by either a regional pain clinic or a chiropractor.\n The study was a pragmatic, randomized, controlled trial.\n The trial was performed at a National Health Service (NHS) hospital outpatient clinic (pain clinic) in the United Kingdom.\n Patients with CLBP (i.e., symptom duration of >12 weeks) referred to a regional pain clinic (outpatient hospital clinic) were assessed and randomized to either chiropractic or pain-clinic management for a period of 8 weeks. The study was pragmatic, allowing for normal treatment protocols to be used. Treatment was administered in an NHS hospital setting.\n The Roland-Morris Disability Questionnaire (RMDQ) and Numerical Rating Scale were used to assess changes in perceived disability and pain. Mean values at weeks 0, 2, 4, 6, and 8 were calculated. The mean differences between week 0 and week 8 were compared across the two treatment groups using Student's t-tests. Ninety-five percent (95%) confidence intervals (CIs) for the differences between groups were calculated.\n Randomization placed 12 patients in the pain clinic and 18 in the chiropractic group, of which 11 and 16, respectively, completed the trial. At 8 weeks, the mean improvement in RMDQ was 5.5 points greater for the chiropractic group (decrease in disability by 5.9) than for the pain-clinic group (0.36) (95% CI 2.0 points to 9.0 points; p = 0.004). Reduction in mean pain intensity at week 8 was 1.8 points greater for the chiropractic group than for the pain-clinic group (p = 0.023). Conclusions: This study suggests that chiropractic management administered in an NHS setting may be effective for reducing levels of disability and perceived pain during the period of treatment for a subpopulation of patients with CLBP.", "The adult lifetime incidence for low back pain is 75% to 85% in the United States. Investigating appropriate care has proven difficult, since, in general, acute pain subsides spontaneously and chronic pain is resistant to intervention. Subacute back pain has been rarely studied.\n To compare the relative efficacy of chiropractic adjustments with muscle relaxants and placebo/sham for subacute low back pain.\n A randomized, double-blind clinical trial.\n Subjects (N = 192) experiencing low back pain of 2 to 6 weeks' duration were randomly allocated to 3 groups with interventions applied over 2 weeks. Interventions were either chiropractic adjustments with placebo medicine, muscle relaxants with sham adjustments, or placebo medicine with sham adjustments. Visual Analog Scale for Pain, Oswestry Disability Questionnaire, and Modified Zung Depression Scale were assessed at baseline, 2 weeks, and 4 weeks. Schober's flexibility test, acetaminophen usage, and Global Impression of Severity Scale (GIS), a physician's clinical impression used as a secondary outcome, were assessed at baseline and 2 weeks.\n Baseline values, except GIS, were similar for all groups. When all subjects completing the protocol were combined (N = 146), the data revealed pain, disability, depression, and GIS decreased significantly (P <.0001); lumbar flexibility did not change. Statistical differences across groups were seen for pain, a primary outcome, (chiropractic group improved more than control group) and GIS (chiropractic group improved more than other groups). No significant differences were seen for disability, depression, flexibility, or acetaminophen usage across groups.\n Chiropractic was more beneficial than placebo in reducing pain and more beneficial than either placebo or muscle relaxants in reducing GIS.", "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.", "To evaluate the short-term effect of physical exercise and a cognitive intervention in low back pain.\n Randomized controlled trial.\n Ninety-three patients sick-listed for 8-12 weeks for sub-acute low back pain were randomized to an exercise regime (n = 30), a cognitive intervention (n = 34) or a control group (n = 29).\n Primary outcome measures were pain, disability, sick-listing and satisfaction with care. Secondary outcome measures were self-efficacy for pain and for function, fear-avoidance beliefs, emotional distress, generic health status and life satisfaction.\n Eighteen percent of subjects dropped out. Drop-out was most frequent in the exercise group. At 18 weeks after inclusion fear-avoidance beliefs were reduced in both intervention groups. The cognitive group demonstrated significant improvement in disability, self-efficacy for pain, emotional distress, general health and life satisfaction. Patients in the exercise group were significantly more satisfied with the treatment, and patients following the exercise protocol reduced pain significantly. No effect on sick-listing was seen.\n Cognitive intervention improved disability and may be feasible for most patients sick-listed in the sub-acute phase. Physical exercise reduced patients' symptoms, but requires high motivation by patients. Despite positive effects in intervention groups on variables considered as negative prognostic factors for long-term disability and sickness absence, interventions had no effect on sick-listing.", "Chiropractic care is used by many older patients for low back pain (LBP), but there are no published results of randomized trials examining spinal manipulation (SM) for older adults. The purpose of this study was to compare the effects of 2 biomechanically distinct forms of SM and minimal conservative medical care (MCMC) for participants at least 55 years old with subacute or chronic nonradicular LBP.\n Randomized controlled trial. The primary outcome variable was low back-related disability assessed with the 24-item Roland Morris Disability questionnaire at 3, 6, 12, and 24 weeks. Participants were randomly allocated to 6 weeks of care including 12 visits of either high-velocity, low-amplitude (HVLA)-SM, low-velocity, variable-amplitude (LVVA)-SM, or 3 visits of MCMC.\n Two hundred forty participants (105 women and 135 men) ages 63.1 +/- 6.7 years without significant comorbidities. Adjusted mean Roland Morris Disability change scores (95% confidence intervals) from baseline to the end of active care were 2.9 (2.2, 3.6) and 2.7 (2.0, 3.3) in the LVVA-SM and HVLA-SM groups, respectively, and 1.6 (0.5, 2.8) in the MCMC group. There were no significant differences between LVVA-SM and HVLA-SM at any of the end points. The LVVA-SM group had significant improvements in mean functional status ranging from 1.3 to 2.2 points over the MCMC group. There were no serious adverse events associated with any of the interventions.\n Biomechanically distinct forms of SM did not lead to different outcomes in older LBP patients and both SM procedures were associated with small yet clinically important changes in functional status by the end of treatment for this relatively healthy older population. Participants who received either form of SM had improvements on average in functional status ranging from 1 to 2.2 over those who received MCMC. From an evidence-based care perspective, patient preference and clinical experience should drive how clinicians and patients make the SM procedure decision for this patient population." ]	Combined chiropractic interventions slightly improved pain and disability in the short-term and pain in the medium-term for acute and subacute LBP. However, there is currently no evidence that supports or refutes that these interventions provide a clinically meaningful difference for pain or disability in people with LBP when compared to other interventions. Future research is very likely to change the estimate of effect and our confidence in the results.
CD004385	[ "10419922", "10535881", "15057894", "770224" ]	[ "Low-dose methotrexate is ineffective in primary biliary cirrhosis: long-term results of a placebo-controlled trial.", "A prospective trial of colchicine and methotrexate in the treatment of primary biliary cirrhosis.", "A randomized controlled trial of colchicine plus ursodiol versus methotrexate plus ursodiol in primary biliary cirrhosis: ten-year results.", "A prospective controlled trial of azathioprine in 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.", "The aim of this study was to determine if colchicine or methotrexate improves blood test results, symptoms, and/or liver histology in patients with primary biliary cirrhosis.\n Patients with histologically confirmed primary biliary cirrhosis whose serum alkaline phosphatase (ALP) levels were at least 2 times above normal and who were not yet candidates for liver transplantation received colchicine or methotrexate and were followed up for 2 years.\n In patients receiving colchicine (n = 43), mean pruritus score decreased from 1.63 to 1.12 (P = 0.04), ALP level from 494 to 355 U/L (P < 0.0001), and alanine aminotransferase (ALT) level from 79 to 61 U/L (P < 0.0001). In patients receiving methotrexate (n = 42), pruritus score decreased from 1.25 to 0.44 (P = 0.0001), ALP from 478 to 235 U/L (P < 0.0001), and ALT from 96 to 61 U/L (P = 0.0001). Methotrexate but not colchicine significantly improved liver histology (P = 0.005) and serum immunoglobulin G levels (P = 0.0002). Methotrexate improved most blood test results more than colchicine. Serum bilirubin levels increased slightly with each drug, and albumin levels decreased slightly.\n Both colchicine and methotrexate improved biochemical test results and symptoms in primary biliary cirrhosis, but the response to methotrexate was greater.", "Primary biliary cirrhosis frequently progresses despite treatment with ursodeoxycholic acid (UDCA), the only approved therapy. Previous studies suggested that colchicine and methotrexate may improve biochemical tests of liver function, symptoms, and liver histology. The aim of the present study was to determine if the addition of colchicine or methotrexate to UDCA would improve survival free of liver transplantation. Eighty-five patients with histologically confirmed primary biliary cirrhosis whose serum alkaline phosphatase levels were at least twice the normal level and who were not yet candidates for liver transplantation were randomly assigned to receive colchicine or methotrexate in a double-blind study. UDCA was administered to all patients after 2 years. The primary end point was survival free of liver transplantation. Patients were followed up for a total of up to 10 years or until treatment failure. Data were analyzed on an intention-to-treat basis. Transplant-free survival was similar in both groups: 0.57 for colchicine plus UDCA and 0.44 for methotrexate plus UDCA, results that are similar to those predicted by the Mayo prognostic model. Significant improvement in liver biochemical tests and liver histology was observed in a subset of patients in both treatment groups who remained in the study for all 10 years. In conclusion, neither colchcine plus UDCA nor methotrexate plus UDCA improved survival beyond that predicted by the Mayo prognostic model. However, clinical, histologic, and biochemical improvement observed among those who remained in the study for 10 years suggests a possible benefit of these drugs in a subset of patients.", "Between 1968 and 1974, azathioprine has been used in a controlled prospective trial to treat patients with symptomatic but precirrhotic primary cirrhosis. Forty-five patients were admitted, of whom 22 were given azathioprine in a dose of 2 mg per kg of body weight. During the 1st year, serum aspartate transaminase levels showed a significant change in favor of the treated group, but improvement did not continue. Throughout the trial, serum alkaline phosphatase, bilirubin, cholesterol, albumin and immunoglobulin M values showed no significant change. Titers of serum mitochondrial antibodies tended to become negative more often in the treated than the untreated. Pruritus cannot be assessed objectively, but seemed less in the treated than in controls. Serial hepatic biopsy specimens showed the development of cirrhosis equally in the two groups. Survival, as judged by the life table method, was similar for the first 5 years of the trial. There was, however, a significant difference in favor of the treated group in the 6th year, although the number of patients available for assessment at that time was extremely small." ]	Methotrexate had no statistically significant effect on mortality in patients with primary biliary cirrhosis nor the need for liver transplantation. Although methotrexate may benefit other outcomes (pruritus score, serum alkaline phosphatase, immunoglobulin M levels), there is no sufficient evidence to support methotrexate for patients with primary biliary cirrhosis.
CD000516	[ "9655655" ]	[ "Randomised comparison of percutaneous angioplasty vs continued medical therapy for hypertensive patients with atheromatous renal artery stenosis. Scottish and Newcastle Renal Artery Stenosis Collaborative Group." ]	[ "Data from randomised studies are lacking on the value of interventional procedures in the management of atheromatous renal artery stenosis. This randomised prospective trial compared the effects on blood pressure (BP) and renal function of percutaneous transluminal angioplasty vs medical therapy in hypertensive patients with both unilateral and bilateral disease.\n A total of 135 eligible patients were identified, of whom 55 (44%) were randomised. Eligible patients had sustained hypertension, with a minimum diastolic BP of 95 mm Hg on at least two anti-hypertensive drugs. Renal artery stenosis was defined by renal angiography as at least 50% stenosis in the affected vessel. All patients were observed during an initial 4-week run-in period on a fixed drug regimen and subsequent changes measured from this 4-week baseline.\n Blood pressure fell during the run-in period in all groups. In patients with bilateral renal artery stenosis randomised to angioplasty, a statistically significant (P<0.05) fall in BP was observed at latest follow-up (range 3-54 months). The mean fall in BP at latest follow-up in the angioplasty group, corrected for the medical group response, was 26/10 mm Hg. In patients with unilateral renal artery stenosis, no statistically significant or clinically important differences in outcome were observed between the two groups. No significant differences or trends in serum creatinine were observed between or within any group during follow-up. Major outcome events (death, myocardial infarction, heart failure, stroke, dialysis) were similar in the angioplasty and medical groups during follow-up. In the 40/135 patients undergoing angioplasty, serious or potentially serious complications attributable to the procedure were observed in 11 patients, bleeding at the arterial site (8 patients) being the most frequent.\n In hypertensive patients with atheromatous renal artery stenosis, percutaneous renal angioplasty results in a modest improvement in systolic BP compared with medical therapy alone. This benefit was confined to patients with bilateral disease. No patient was 'cured', renal function did not improve, and intervention was accompanied by a significant complication rate." ]	There is currently insufficient evidence to assess the effects of percutaneous transluminal angioplasty with or without stenting or primary stenting for vertebral artery stenosis.
CD002933	[ "8671131", "1390143", "2303961" ]	[ "A randomized controlled trial of electromagnetic therapy in the primary care management of venous leg ulceration.", "A portable pulsed electromagnetic field (PEMF) device to enhance healing of recalcitrant venous ulcers: a double-blind, placebo-controlled clinical trial.", "Effect of low frequency pulsing electromagnetic fields on skin ulcers of venous origin in humans: a double-blind study." ]	[ "The aim was to establish the potential efficacy, tolerability and side-effect profile of electromagnetic therapy as an adjunct to conventional dressings in the treatment of venous leg ulcers.\n A prospective, randomized, double blind controlled clinical trial was carried out in a dedicated leg ulcer clinic based in one urban general practice. Nineteen patients with leg ulcers of confirmed venous aetiology were assessed. The main outcome measures were rate and scale of venous leg ulcer healing, changes in patient-reported pain levels, quality of life, degree of mobility, side effect profile and acceptability to patients and staff.\n Sixty-eight per cent of patients attending this dedicated clinic achieved improvements in the size of their ulcer (4, 21%, healed fully) and in reduced pain levels (P < 0.05) during the trial, despite the chronicity of ulcer histories. Patients treated with electromagnetic therapy at 800 Hz were found at day 50 to have significantly greater healing (P < 0.05) and pain control (P < 0.05) than placebo therapy or treatment with 600 Hz. All patients reported improved mobility at the end of the study. The electromagnetic therapy was well tolerated by patients, with no differences between groups in reporting adverse events, and proved acceptable to staff.\n Despite the small numbers in this pilot study, electromagnetic therapy provided significant gains in the healing of venous leg ulcers and reduction in pain.", "A prospective, randomized, double-blind, placebo-controlled multicentre study assessed the clinical efficacy and safety of pulsed electromagnetic limb ulcer therapy (PELUT) in the healing of recalcitrant, predominantly venous leg ulcers. The portable device was used at home for 3 h daily during this 8-week clinical trial as an adjunct to a wound dressing. Wound surface area, ulcer depth and pain intensity were assessed at weeks 0, 4 and 8. At week 8 the active group had a 47.7% decrease in wound surface area vs. a 42.3% increase for placebo (P < 0.0002). Investigators' global evaluations indicated that 50% of the ulcers in the active group healed or markedly improved vs. 0% in the placebo group, and 0% of the active group worsened vs. 54% of the placebo group (P < 0.001). Significant decreases in wound depth (P < 0.04) and pain intensity (P < 0.04) favouring the active group were seen. Patients whose ulcers improved significantly after 8 weeks were permitted to continue double-blind therapy for an additional 4 weeks. Eleven active and one placebo patient continued therapy until week 12, with the active treatment group continuing to show improvement. There were no reports of adverse events attributable to this device. We conclude that the PELUT device is a safe and effective adjunct to non-surgical therapy for recalcitrant venous leg ulcers.", "The effect of an electromagnetic field on the healing of skin ulcers of venous origin in humans has been investigated in a double-blind study. Forty-four patients have been admitted to the study; one-half were exposed to active stimulators (experimental group) and the remaining to dummy stimulators (control group). The stimulation was scheduled to last a maximum of 90 days. The success rate was significantly higher in the experimental group both at day 90 (p less than 0.02) and in the follow-up period (p less than 0.005). The data suggest that the effect of the electromagnetic field lasts even when the stimulation is over. No ulcers worsened in the experimental group, while four worsened in the control group. Twenty-five percent of the patients in the experimental group and 50% in the control group experienced recurrence of the ulcer. It is concluded that stimulation with an electromagnetic field is a useful adjunctive therapy in the management of these patients." ]	There is no high quality evidence that electromagnetic therapy increases the rate of healing of venous leg ulcers, and further research is needed.
CD009244	[ "20729710" ]	[ "A double-blind, randomized controlled trial of the use of imiquimod cream for the treatment of anal canal high-grade anal intraepithelial neoplasia in HIV-positive MSM on HAART, with long-term follow-up data including the use of open-label imiquimod." ]	[ "To determine whether imiquimod was more effective than placebo for the treatment of high-grade anal canal intraepithelial neoplasia (HG-ACIN).\n Double-blind, randomized placebo-controlled clinical trial.\n Sixty-four HIV-positive patients were randomized to self-application of imiquimod cream or matched placebo into the anal canal three times a week for 4 months. Response was assessed by cytology, high-resolution anoscopy and biopsy 2 months after therapy. All patients who failed to resolve were offered treatment with open-label imiquimod for a further 4 months.\n Fifty-three patients completed the study, of which 28 patients were on active drug and 25 patients on placebo. In the imiquimod group, four patients resolved and eight patients downgraded to low-grade squamous intraepithelial lesion (LSIL) with a median follow-up of 33 months. In the placebo group, one patient resolved. Imiquimod was significantly associated with a positive outcome (P = 0.003). Only one patient discontinued owing to side effects. Twenty-one patients entered a second open-label phase of treatment. Five of these patients cleared their anal canal intraepithelial neoplasia (ACIN) and four patients downgraded to LSIL. The overall mean duration of follow-up was 36 months. During this extended follow-up period, 61% have exhibited sustained absence of high-grade squamous intraepithelial lesion (HSIL).\n This study demonstrates the effectiveness of imiquimod for the treatment of ACIN, and the benefit of prolonged or repeated treatments. This form of therapy is likely to be especially valuable for patients with widespread multifocal ACIN who are otherwise difficult to treat, and should be considered as an adjunct to ablative therapy." ]	The included trial failed to demonstrate any statistically significant efficacy of imiquimod in the management of anal intraepithelial neoplasia (AIN). The absence of reliable evidence for any of the interventions used in AIN precludes any definitive guidance or recommendations for clinical practice. Prospective cohort studies and retrospective studies have not been included in this review as they are considered to provide lower quality evidence. Well designed RCTs are needed.
CD008224	[ "1892197", "2659132", "16765169", "3382883", "11023726", "7806870", "12174159", "6244414" ]	[ "Effectiveness of antibiotic prophylaxis in preventing bacteriuria after multichannel urodynamic investigations: a blind, randomized study in 124 female patients.", "Are prophylactic antibiotics necessary during extracorporeal shockwave lithotripsy?", "Effectiveness of ciprofloxacin prophylaxis in preventing bacteriuria caused by urodynamic study: a blind, randomized study of 192 patients.", "Is antibiotic prophylaxis necessary for routine urodynamic investigations? A controlled study in 100 patients.", "Could the incidence of postoperative urinary tract infection be reduced by reversing the sequence of vaginal cleansing and urethral catheterization?", "Antibiotic prophylaxis for urodynamic testing in patients with spinal cord injury: a preliminary study.", "Value of urinary prophylaxis with methenamine in gynecologic surgery.", "Prophylaxis of bacteriuria during intermittent catheterization of the acute neurogenic bladder." ]	[ "One hundred twenty-four women with chronic, persistent lower urinary tract symptoms who had been scheduled for elective urodynamic investigations at Mount Sinai's Urodynamic Investigative Unit were divided into two blind, randomized groups, receiving either a placebo or prophylactic antibiotic. At the time of urodynamic testing, the rate of unsuspected urinary tract infection was 8.1%. There was no statistically significant decrease in postinstrumentation infection rate in the group who received prophylactic antibiotics. We conclude that, given in the fashion described in the study, prophylactic antibiotics are not effective in preventing urinary tract infections caused by urodynamic testing.", "A randomised clinical study was carried out on patients admitted for ESWL treatment in order to establish the requirement for prophylactic treatment with antibiotics during this procedure. Patients with clinical signs of urinary tract infection, evidence of infectious stones or a positive urine culture were excluded. All other patients were consecutively randomised into 3 groups which were given either trimethoprim + sulphamethoxazole or mecillinam (Group A), methenamine hippurate (Group B), or no treatment at all (Group C). Evaluation with respect to clinical signs of infection was done immediately after the treatment and 4 weeks later. In addition, a urine culture was performed 2 weeks after ESWL, i.e. 1 week after completing treatment with antibiotics and methenamine hippurate. With respect to infectious complications there were no differences between Groups A and C, between Groups B and C or between Group A and B+C, whereas an unexplained slightly higher infectious rate was recorded for Group B compared with Group A. In all patients the occurrence of bacteriuria was low (6.7%) despite the fact that almost 30% of patients had a ureteric catheter during the ESWL procedure. Patients with ureteric catheters did not present with more infectious complications than those without. All patients had a bladder catheter during ESWL. It was concluded that prophylactic treatment with antibiotics during ESWL treatment is unnecessary in all situations where an infectious aetiology is unlikely.", "To determine the efficacy of prophylactic ciprofloxacin in preventing urinary tract infections caused by urodynamic study (UDS).\n A total of 210 patients presenting for UDS during a 16-month period were offered enrollment in the study. A clean-catch midstream urine sample was taken 24 hours before and 48 to 72 hours after the procedure and after microscopic examination and culture were done. All patients underwent a standard UDS. The 192 patients who had sterile urine before intervention were included in the study. Randomly, 98 of the 192 patients were orally given 500 mg of ciprofloxacin 1 hour before the urodynamic intervention and 94 were not given anything. The patients who were found to have significant bacteriuria after UDS were followed up and treated properly.\n Eighteen patients (8.6%) who had significant bacteriuria in the urine culture before UDS were excluded from the study. The rate of significant bacteriuria in the urine culture after UDS was 7.3% overall, 1% in the prophylaxis group, and 14% in the controls, a significant difference (P = 0.002). The most common uropathogen was Escherichia coli (57%). Three independent risk factors were identified: not giving antibiotic prophylaxis before UDS; antibiotic use in the preceding month; and the presence of pyuria before UDS.\n Urinary tract infections after UDS decreased from 14% to 1% with a single dose of ciprofloxacin 500 mg orally before UDS. We recommend antibiotic prophylaxis for patients undergoing a UDS.", "The value of a prophylactic antibiotic before a routine cystometrogram has been assessed in a controlled trial of 100 patients. The infection rate was low and not statistically different in both groups. Subsequent symptoms of dysuria and haematuria had a mechanical aetiology.", "Postoperative urinary tract infection (UTI) is a common hospital infection after gynaecological operations. A prospective randomized study was performed to examine whether the incidence of UTI could be reduced by reversing the sequence of vaginal cleansing and urethral catheterization. Subjects were randomly allocated to: (1) urethral catheterization before vaginal cleansing; and (2) urethral catheterization after vaginal cleansing. Urine cultures were performed immediately after the procedures as the baseline, on the day of catheter removal, and two days after catheter removal. Patients were examined daily after the operation for any urinary symptoms and fever. The incidences of preoperative asymptomatic bacteriuria were similar in both groups, seven of 84 in group 1 vs. eight of 83 in group 2. Among those with negative urine culture before the operation, 77 in group 1 and 75 in group 2, there was no significant difference in postoperative bacteriuria at catheter removal (23 vs. 22) and two days later (35 vs. 42). No significant difference was noted in the incidence of UTI (5 vs. 10, P = 0.25), with a trend towards less UTI in group 1. Voiding discomfort was more common, and fever less common in group 1. There were significant associations between urine culture results at three different occasions. Bacteriuria at catheter removal is associated with a 7.2 times risk of bacteriuria two days later, 2.4 times risk of urinary symptoms and 3.2 times risk of UTI. Routine surveillance at catheter removal is not cost-effective. We conclude that postoperative bacteriuria and UTI are common. Reversing the sequence of the procedures cannot reduce the incidence. There is no evidence to change the status quo.", "This study was performed in order to: (i) determine the incidence of symptomatic urinary tract infection (UTI) in patients with spinal cord injury after urodynamic testing; (ii) evaluate the role of antibiotic prophylaxis for such a procedure; and (iii) investigate whether pre-existing bacteriuria predisposes to the development of symptomatic UTI after urodynamic testing. Forty patients were prospectively randomized in a double-blind fashion to receive a 3-day oral course of either ciprofloxacin (18 patients) or placebo (22 patients), beginning 2 days prior to the urodynamic procedure. None of 18 (0%) patients who received ciprofloxacin developed symptomatic UTI within 5 days after the procedure compared with three of 22 (14%) subjects randomized to the placebo group; the protective efficacy of antibiotic prophylaxis, however, did not attain statistical significance (P = 0.24). None of the three bacterial isolates that were responsible for symptomatic infection were grown in corresponding urine cultures prior to the procedure. These findings may serve as a pilot for a larger study.", "There is a high risk of postoperative bacteriuria and urinary tract infection after gynecologic surgery. Postoperative asymptomatic bacteriuria often disappears without treatment, but 15-20% of patients still require treatment for postoperative urinary tract infection. This study was carried out to assess the value of prophylactic treatment with methenamine hippurate after routine gynecologic surgery.\n This was a prospective, randomized, double-blind, placebo-controlled clinical trial comprising 145 patients undergoing routine gynecologic laparotomy or vaginal plastic surgery using a Foley catheter for 24 h. Antibiotics were not used. Subjects received 1 g Hiprex or placebo twice daily for 5 days. Urine was cultured preoperatively, at catheter removal, and 2 days later. Patients with positive cultures were not given antibiotics unless they were symptomatic. The follow-up period was 1 month.\n The chi-square test, Fisher exact test, and t-test were used with level of significance at 0.05, and odds ratios with 95% confidence intervals were calculated.\n Asymptomatic bacteriuria was diagnosed in 36 cases (50.0%) in the placebo group and 22 cases (30.1%) in the methenamine group (p = 0.02). Urinary tract infection was diagnosed in 10 cases (13.9%) in the placebo group and two cases (2.7%) in the methenamine group (p = 0.03). There were few adverse events.\n Prophylactic treatment with methenamine hippurate significantly reduces the incidence of postoperative bacteriuria and urinary tract infection.", "A randomized prospective study of bacteriuria control during early intermittent bladder catheterization was performed on a spinal cord injury service. The 64 male subjects underwent 16,620 catheterizations and had 83 significant episodes of infection. The infection rates among various groups were compared: 1) control patients, 2) patients treated with intravesical neomycin/polymyxin-B, 3) patients given low dose daily macrocrystals of nitrofurantoin and 4) patients given intravesical treatment and oral nitrofurantoin. There was significant reduction in infection rates when oral and intravesical antibiotics were used." ]	Prophylactic antibiotics did reduce the risk of bacteriuria after urodynamic studies but there was not enough evidence to suggest that this effect reduced symptomatic urinary tract infections. There was no statistically significant difference in the risk of fever, dysuria or adverse reactions. Potential benefits have to be weighed against clinical and financial implications, and the risk of adverse effects.
CD001361	[ "3788652", "1681680", "3322467", "1684310" ]	[ "Haloperidol decanoate and flupenthixol decanoate in schizophrenia. A long-term double-blind cross-over comparison.", "Zuclopenthixol decanoate and haloperidol decanoate in chronic schizophrenia: a double-blind multicentre study.", "Haloperidol decanoate v. fluphenazine decanoate as maintenance therapy in chronic schizophrenic in-patients.", "Minimal effective dose and relapse--double-blind trial: haloperidol decanoate vs. placebo." ]	[ "Thirty-two schizophrenic patients, previously treated with antipsychotics, were treated with haloperidol decanoate and flupenthixol decanoate in a double-blind cross-over study. The drugs were given for 24 weeks each at an individually adapted dose. The last three injections of either drug were given at fixed 4-week intervals. The mean dose over the two treatment periods changed from 131 mg (start) to 151 mg (week 24) in the haloperidol decanoate group and from 56 mg to 66 mg in the flupenthixol decanoate group, the inter-drug ratio being 2.3:1. During the first study period, the patients' condition remained rather stable with both drugs. After crossing-over, the symptoms were further reduced with haloperidol decanoate but increased with flupenthixol decanoate. Side effects of the two drugs were comparable and were generally few and mild. It was concluded that 4-week intramuscular administration of haloperidol decanoate provides appropriate control of schizophrenic symptoms, but that flupenthixol decanoate should be dosed at shorter intervals.", "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.", "In a double-blind study of 38 chronic schizophrenic in-patients, haloperidol decanoate was compared with fluphenazine decanoate as maintenance therapy over 60 weeks. Both drugs were given by injection at 4-week intervals. Haloperidol and fluphenazine were assumed to be equipotent; the mean starting dose of the former was 127 mg and of the latter 106 mg. The number of withdrawals over 60 weeks was similar in both groups but relapses, strictly defined, were significantly more frequent in the haloperidol group. When patients were switched to haloperidol, Parkinsonism diminished more quickly than in the fluphenazine group, but after 60 weeks there was no difference in severity in the two drug groups. The higher relapse rate and the quicker reduction in Parkinsonism in the haloperidol group might be due to a misjudgement in equivalent doses of the two drugs. Plasma haloperidol steady state levels were reached in most patients by 8-12 weeks. Plasma neuroleptic and prolactin levels, week-by-week systemic drug availability and Parkinsonism showed less variation between injections with haloperidol than with fluphenazine.", "Fifty-six chronic schizophrenic patients were randomized into haloperidol decanoate (HD) or placebo groups for 48 weeks of double-blind treatment. The double-blind trial was preceded by a 15-week single-blind run-in period, during which all patients were treated with 60 mg of HD (approximately corresponding to 3.6 mg orally/day) every fourth week (except for the second injection, which was given after 3 weeks). Eight relapses occurred during the run-in period, and seven other patients refused further participation. The remaining 41 patients were then treated double blind, either with HD, 60 mg/4 weeks (18 patients), or with placebo (23 patients). Two patients (11%) in the HD group and 16 (69%) in the placebo group relapsed during the 48-week double-blind period. The plasma concentrations of haloperidol were measured every fourth week in both groups. Steady state was reached after 11 weeks. The mean steady-state level was 6.3 nmol/L. In the placebo group, a 50% decrease in the mean haloperidol plasma concentration was seen 8 weeks after withdrawal of haloperidol. The haloperidol plasma concentration was a predictor of relapse. There was no statistical difference between the treatment groups regarding extrapyramidal symptoms. More biperiden, however, was used in the HD group, while the placebo patients took more sedatives. The results of this study show that the relatively low and fixed dose of 60 mg of HD every fourth week was superior to placebo in preventing relapse in schizophrenia.(ABSTRACT TRUNCATED AT 250 WORDS)" ]	Haloperidol decanoate may have a substantial effect in improving the symptoms and behaviour associated with schizophrenia in comparison to placebo, but data are remarkably sparse. There are no discernible differences between the depot form of haloperidol and its oral equivalent. For those needing and willing to take the drug, the means of administration is then a matter of individual choice and clinical judgement. As there are no clear differences between haloperidol decanoate and other depots, the choice of depot medication could also be individually tailored and patient preference exercised. Well-conducted and reported randomised trials are needed comparing haloperidol decanoate with other depots but the comparison of haloperidol decanoate to oral antipsychotics is a priority.
CD004501	[ "9580172" ]	[ "Administration of antibiotics to patients with rupture of membranes at term: a prospective, randomized, multicentric study. Collaborative Group on PROM." ]	[ "To assess whether antibiotic administration changes the rate of materno-fetal infectious morbidity in premature rupture of membranes occurring later than 35 weeks of gestation.\n A prospective, randomized and multicentric study in the Perinatology Units of eleven hospitals in Spain. Women were randomized to either antibiotic administration or control group. All were induced, if labor had not started spontaneously after 12 hours of ruptured membranes. Main outcome measures were maternal infection (chorioamnionitis and endometritis) and neonatal infectious morbidity (neonatal sepsis, meningitis and bronchopneumonia).\n Seven hundred and thirty-three patients were enrolled in the study, 371 in the antibiotics group and 362 in the control group. The incidence of chorioamnionitis and puerperal endometritis were reduced but the differences are statistically nonsignificant. However, the incidence of neonatal sepsis was significantly lower in newborns to mothers who had received antibiotics, 1 vs. 7 cases (Fisher's exact test, p<0.007).\n The study strongly suggests that prophylactic use of antibiotics in premature rupture of membranes occurring at 36 or more weeks of gestation reduces the risk of neonatal sepsis and probably maternal endometritis." ]	There is inadequate evidence from randomised trials in favour of any particular antibiotic regimen for the treatment of suspected late onset neonatal sepsis. The available evidence is not of high quality. Although suspected sepsis and antibiotic use is common, quality research is required to specifically address both narrow and broad spectrum antibiotic use for late onset neonatal sepsis. Future research also needs to assess cost effectiveness and the impact of antibiotics in different settings such as developed or developing countries and lower gestational age groups.
CD003729	[ "16754835", "11982448", "12900300" ]	[ "Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder.", "A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia.", "Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol." ]	[ "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.", "An intramuscular (IM) formulation of olanzapine has been developed because there are no rapid-acting IM atypical antipsychotic drugs currently available in the United States for treating acute agitation in patients with schizophrenia.\n Recently hospitalized acutely agitated patients with schizophrenia (N = 270) were randomized to receive 1 to 3 IM injections of olanzapine (2.5, 5.0, 7.5, or 10.0 mg), haloperidol (7.5 mg), or placebo within 24 hours. A dose-response relationship for IM olanzapine in the reduction of agitation was assessed by measuring the reduction in Positive and Negative Syndrome Scale Excited Component (PANSS-EC) scores 2 hours after the first injection. Safety was assessed by recording adverse events and with extrapyramidal symptom scales and electrocardiograms at 24 hours after the first injection.\n Olanzapine exhibited a dose-response relationship for reduction in agitation (F(1,179)= 14.4; P<.001). Mean PANSS-EC reductions 2 hours after the first injection of olanzapine (2.5 mg = -5.5; 5.0 mg = -8.1; 7.5 mg = -8.7; 10.0 mg = -9.4) were superior to those with placebo (-2.9; P =.01 vs olanzapine at 2.5 mg; P<.001 for each other olanzapine dose) but not with haloperidol (-7.5). A dose of 5.0, 7.5, or 10.0 mg of olanzapine caused a greater reduction in agitation than placebo 30 minutes after the first injection. There were no differences between treatment groups for hypotension, the most frequently reported adverse event, or for clinically relevant changes in the QTc interval. There was a greater incidence of treatment-emergent parkinsonism during treatment with IM haloperidol (16.7%) than with 2.5 (P =.03), 5.0 (P =.03), or 7.5 mg (P =.01) of IM olanzapine (0%) or with placebo (0%) (P =.01).\n Intramuscular olanzapine at a dose of 2.5 to 10.0 mg per injection exhibits a dose-response relationship in the rapid treatment of acute agitation in patients with schizophrenia and demonstrates a favorable safety profile.", "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." ]	Data relevant to the effects of olanzapine IM are taken from some studies that may not be considered ethical in many places, all are funded by a company with a pecuniary interest in the result. These studies often poorly report outcomes that are difficult to interpret for routine care. Other important outcomes are not recorded at all. Nevertheless, olanzapine IM probably has some value in helping manage acute aggression or agitation, especially where it is necessary to avoid some of the older, better, known treatments. Olanzapine causes fewer movement disorders than haloperidol and more than lorazepam. The value of the oro-dipersable velotab preparation is untested in trials. There is a need for well designed, conducted and reported randomised studies in this area. Such studies are possible and, we argue, should be designed with the patient groups and clinicians in mind. They should report outcomes of relevance to the management of people at this difficult point in their illness.
CD006117	[ "9832348", "21869697", "9413414", "11579351", "11147927", "17196045", "11074227", "16160624", "8263318", "10982198", "17647298", "16259546", "11910265", "11343529", "7775364", "12359680", "9547134", "16889454", "2258378", "10572324", "12680747", "12691786", "15960563", "12927001", "10363731", "16509835", "11206600", "11729017", "10770145", "10221945", "10732656", "12169073", "10784465", "11352337", "12232543", "2258379", "12724503", "11106136", "21206792", "8792754", "12777339", "10438693", "17288677" ]	[ "Double-blind, multicenter comparative study of sertraline and amitriptyline in hospitalized patients with major depression.", "Faster onset of antidepressant effects of citalopram compared with sertraline in drug-naïve first-episode major depressive disorder in a Chinese population: a 6-week double-blind, randomized comparative study.", "A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression.", "Effect of sertraline on the recovery rate of cardiac autonomic function in depressed patients after acute myocardial infarction.", "Double-blind, multicenter comparative study of sertraline versus amitriptyline in outpatients with major depression.", "A randomized, double-blind, active-control study of sertraline versus venlafaxine XR in major depressive disorder.", "Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline.", "Sertraline versus fluvoxamine in the treatment of elderly patients with major depression: a double-blind, randomized trial.", "Double-blind study of the efficacy and safety of sertraline versus fluoxetine in major depression.", "A double-blind comparison of sertraline and fluoxetine in depressed elderly outpatients.", "Effectiveness and acceptability of sertraline and citalopram in major depressive disorder: pragmatic randomized open-label comparison.", "Randomized trial of sertraline versus venlafaxine XR in major depression: efficacy and discontinuation symptoms.", "Double-blind placebo-controlled pilot study of sertraline in military veterans with posttraumatic stress disorder.", "Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder.", "A double-blind multicenter trial comparing sertraline and fluoxetine in outpatients with major depression.", "A randomized trial of sertraline as a cessation aid for smokers with a history of major depression.", "A double-blind multicenter trial comparing sertraline and citalopram in patients with major depression treated in general practice.", "Preventing depression after stroke: Results from a randomized placebo-controlled trial.", "Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression.", "A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients.", "A double-blind, placebo-controlled trial of sertraline for depressive symptoms in patients with stable, chronic schizophrenia.", "Sertraline is more effective than imipramine in the treatment of non-melancholic depression: results from a multicentre, randomized study.", "Double-blind comparison of sertraline and placebo in stroke patients with minor depression and less severe major depression.", "Probing the safety of medications in the frail elderly: evidence from a randomized clinical trial of sertraline and venlafaxine in depressed nursing home residents.", "A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline.", "Randomized, double-blind, placebo-controlled, crossover study of sertraline (Zoloft) for the treatment of hot flashes in women with early stage breast cancer taking tamoxifen.", "Efficacy and response time to sertraline versus fluoxetine in the treatment of unipolar major depressive disorder.", "Placebo-controlled trial of sertraline in the treatment of children with generalized anxiety disorder.", "Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial.", "The Norwegian naturalistic treatment study of depression in general practice (NORDEP)-I: randomised double blind study.", "Randomized, double-blind comparison of venlafaxine and sertraline in outpatients with major depressive disorder. Venlafaxine 631 Study Group.", "Sertraline treatment of major depression in patients with acute MI or unstable angina.", "Comparison of sertraline and nortriptyline in the treatment of major depressive disorder in late life.", "Antidepressant efficacy and safety of low-dose sertraline and standard-dose imipramine for the treatment of depression in older adults: results from a double-blind, randomized, controlled clinical trial.", "[Efficacy and acceptability of tianeptine and sertraline in the acute treatment phase of depression].", "Double-blind, multicenter comparison of sertraline and amitriptyline in elderly depressed patients.", "A double-blind, placebo-controlled study of sertraline in the prevention of depression in stroke patients.", "Sertraline versus paroxetine in major depression: clinical outcome after six months of continuous therapy.", "Escitalopram Versus Citalopram and Sertraline: A Double-Blind Controlled, Multi-centric Trial in Indian Patients with Unipolar Major Depression.", "A placebo-controlled, randomized clinical trial comparing sertraline and imipramine for the treatment of dysthymia.", "Older community residents with depression: long-term treatment with sertraline. Randomised, double-blind, placebo-controlled study.", "Comparative efficacy of sertraline vs. fluoxetine in patients age 70 or over with major depression.", "Escitalopram versus sertraline in the treatment of major depressive disorder: a randomized clinical trial." ]	[ "Sertraline is a selective serotonin reuptake inhibitor (SSRI) for which marketing approval has been obtained recently in Germany. The results of several double-blind, placebo-controlled studies have demonstrated that sertraline has a clear antidepressive effect. However these studies have been conducted in outpatient populations. In the context of this multicenter study, a total of 160 inpatients were treated with sertraline 50-150 mg or amitriptyline 75-225 mg over a period of 6 weeks in a double-blind fashion. Sixty-two patients in the sertraline and 59 patients in the amitriptyline group were evaluated for efficacy in the according-to-protocol (ATP) population; 80 sertraline and 75 amitriptyline patients were evaluated for safety in the Intention-to-treat population (ITT). No statistically significant differences were detected between the two groups in the efficacy analysis performed on the basis of the Hamilton Depression Scale (HAM-D) total score and Clinical Global Impression (CGI). Due to its sedating properties, amitriptyline was found to be significantly more effective with regard to the HAM-D factor \"sleep disturbance\". The safety analysis, which was based on the CGI, the global assessment at the end of study and a score for somatic adverse events (FSUCL) revealed statistically significant advantages of sertraline over amitriptyline. Amitriptyline was associated with more autonomic and circulatory side effects, while epigastric complaints occurred more often with sertraline. The incidence of nausea - a typical SSRI side effect - was the same in both groups.", "Several previous studies, including a meta-analysis, reported no significant differences between various selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder. However, because of the different chemical structure of SSRIs and the difference in the frequency of serotonin transporter polymorphisms between ethnic groups, a head-to-head comparative study between SSRIs in different populations may be enlightening. We compared the efficacy and adverse effect profiles of citalopram and sertraline in a double-blinded randomized clinical trial in a Chinese population of drug-naïve patients with first-episode major depressive disorder. Fifty-one patients were randomly assigned to citalopram or sertraline treatment. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary outcome. Efficacy and adverse effects were analyzed in an intent-to-treat population. Efficacy was analyzed using a last-observation-carried-forward method for early terminators. There were no significant differences in demographic characteristics at baseline. No significant differences were found in MADRS scores between citalopram and sertraline at baseline (36.6 ± 5.5 vs 38.2 ± 4.9; P = 0.322) or at the end of treatment (week 6; 10.8 ± 10.0 vs 16.7 ± 11.3; P = 0.082). However, MADRS scores in the citalopram group were significantly lower at week 1 (25.2 ± 8.5 vs 30.4 ± 6.1; P = 0.029) and week 3 (15.9 ± 10.0 vs 22.1 ± 8.7; P = 0.037). Overall, treatment-emergent adverse effects were reported by 14.3% and 28.6% of patients in the citalopram and sertraline groups, respectively. In conclusion, citalopram and sertraline were both efficacious and well tolerated. However, citalopram exhibited a significantly faster onset than sertraline during the early weeks of treatment and tended to have a better efficacy in overall treatment, although the statistic was not significant.", "This study was designed to compare the efficacy, safety, tolerability profiles, and effects on quality of life of the serotonin selective reuptake inhibitor antidepressant sertraline versus the nonselective tricyclic antidepressant amitriptyline and placebo in patients with major depression.\n Outpatients with DSM-III-R major depression were randomly assigned to double-blind treatment for 8 weeks with sertraline (50-200 mg daily), amitriptyline (50-150 mg daily), or matching placebo. Assessments included the Hamilton Rating Scale for Depression, Montgomery-Asberg Depression Rating Scale, Clinical Global Impressions-Severity of Illness scale, Clinical Global Impressions-Improvement scale, Global Assessment Scale, Profile of Mood States, Beck Depression Inventory, Quality of Life Enjoyment and Satisfaction Questionnaire, and Health-Related Quality of Life battery.\n All treatment groups demonstrated statistically significant improvement from baseline in depression ratings by Week 1 and thereafter. The antidepressant effects of amitriptyline and sertraline were significantly (p < .05) greater than placebo and did not differ significantly from each other. Sertraline was associated with significantly (p < .05) greater subjective (i.e., patient-rated) improvement in mood than amitriptyline or placebo. Both active drugs were associated with greater improvements than placebo on most quality of life measurements. On several items, sertraline, but not amitriptyline, was superior to placebo. There was a discernible effect of sertraline earlier than amitriptyline on most quality of life scales. Amitriptyline therapy was associated with significantly more treatment-related adverse events, and discontinuations due to treatment-related adverse events, in comparison to both sertraline and placebo therapy.\n Sertraline and amitriptyline each were effective treatments for major depression as assessed by both physician- and patient-rated scales. These results show that sertraline therapy is better tolerated than amitriptyline therapy. Quality of life was also improved by effective antidepressant treatment, with sertraline showing a tendency to produce greater improvements on quality of life measures.", "Brain serotonin is known to possess sympathoinhibitory properties. The aim of this clinical physiologic study was to determine whether sertraline, a selective serotonin reuptake inhibitor, facilitates the rate of recovery of cardiac autonomic function after an acute myocardial infarction (MI) in patients with depression.\n Thirty-eight post-MI depressed patients were randomized to receive either sertraline 50 mg per day or placebo for 6 months. Depression was defined as a score >15 on the standardized Inventory to Diagnose Depression questionnaire taken at prehospital discharge and again within 2 weeks of the acute infarct. Eleven stable post-MI nondepressed patients served as a nonrandomized reference group during follow-up. Twenty-seven patients completed the randomization. All 3 groups were followed up closely in a multidisciplinary post-MI clinic where they underwent serial testing for both time and frequency domain heart rate variability (HRV) indices at baseline (1-2 weeks after MI) and at 6, 10, 14, 18, and 22 weeks. The rate of recovery of HRV was determined by use of a growth curve model based on repeated-measures analysis of variance. There was a linear rate of increase in the SD of 24-hour N-N intervals (SDNN) in the sertraline-treated group that paralleled that of the nondepressed reference group. This contrasted with a modest but significant decline in SDNN in the placebo group from 2 to 22 weeks (t = 2.10, P <.05). However, the short-term power spectral indices, while trending toward a more rapid rate of recovery in the treated group, did not reach statistical significance compared with the placebo group.\n In depressed patients who have survived the acute phase of an MI sertraline facilitates the rate of recovery of SDNN, a recognized predictor of clinical outcome.", "To compare the efficacy and safety of sertraline and amitriptyline in a German outpatient population.\n Patients with Major Depression (DSM-III-R) and HAM-D (21 items) > or = 21 in 19 German centers received double-blind treatment with sertraline (initial dose 50 mg, titration up to 100 mg) or amitriptyline (75 mg, up to 150 mg) over 6 weeks. HAM-D (21 items), HAM-D Bech, CGI, DSI and SDS were evaluated for the efficacy analysis. FSUCL (Fischer Somatic and Undesired Effects Check List) and spontaneously reported adverse events were used for safety analysis.\n Of the 240 patients enrolled in the study, 205 (100 sertraline; 105 amitriptyline) were evaluable for efficacy. No statistically significant differences were detected between the two groups in the ITT and ATP efficacy analyses. Response, defined as score 1 (very much improved) or 2 (much improved) of the CGI improvement score, was 76% in the sertraline and 81% in the amitriptyline group (efficacy evaluable patients = ATP population). In the structured FSUCL, the side-effect burden (FSUCL score >2 for drug related symptoms) was significantly higher in the amitriptyline group at all follow up visits (p<0.05).\n Both sertraline and amitriptyline are suitable for the treatment of Major Depression; sertraline is comparable to amitriptyline with regard to efficacy, and offers the additional benefit of a more favorable safety profile.", "Sertraline may produce dual neurotransmitter effects similar to the serotonin-norepinephrine reuptake inhibitors (SNRIs); however, it has been tested against an SNRI in only 1 previous study, and never at an optimal dose. The objective of the current multisite study was to compare relatively higher doses of sertraline (i.e., 150 mg/day) and venlafaxine extended release (XR) (225 mg/day) in outpatients with major depressive disorder.\n Subjects with DSM-IV major depressive disorder were randomly assigned to 8 weeks of double-blind treatment with sertraline (N = 82) or venlafaxine XR (N = 78). The study ran from January 2002 through January 2003. The primary outcome measure was the Quality of Life Enjoyment and Satisfaction Questionnaire; secondary outcome variables included the 17-item Hamilton Rating Scale for Depression.\n Both treatments led to significant improvement in depressive symptoms and quality-of-life measures. No significant differences were noted between treatment groups for final scores on the primary or secondary measures. The treatment groups did not differ significantly in the percentage of responders (sertraline = 55%, venlafaxine XR = 65%; intent-to-treat [ITT] sample) or remitters (sertra-line = 38%, venlafaxine XR = 49%; ITT sample), although the proportions are similar to those found in earlier selective serotonin reuptake inhibitor (SSRI) vs. venlafaxine meta-analyses. In patients who achieved the maximum dose of drug and maintained it for 3 weeks, response rates were similar to those found at lower doses (sertraline = 59%, venlafaxine XR = 70%); however, remission rates for this sample were comparable for both drug groups (sertraline = 48%, venlafaxine XR = 50%).\n The efficacies of sertraline and venlafaxine XR were comparable. Although response and remission rates did not differ statistically, the rates were analogous to those reported in previous meta-analyses. However, at clinically relevant higher doses, the remission rates were very similar.\n ClinicalTrials.gov identifier NCT00179283.", "Previous comparative studies of the selective serotonin reuptake inhibitors (SSRIs) have rarely included a placebo control group and have rarely demonstrated significant between-group differences. The study reported on here was a placebo-controlled comparison of the antidepressant effects of two SSRIs, citalopram and sertraline.\n Three hundred twenty-three patients with DSM-IV-defined major depressive disorder were randomized to 24 weeks of double-blind treatment with citalopram (20-60 mg/day), sertraline (50-150 mg/day), or a placebo. The primary efficacy measure was the Hamilton Depression Rating Scale (HAMD) and the primary statistical analysis was an analysis of variance comparing the change from baseline to the last observation carried forward in each treatment group.\n Both citalopram and sertraline produced significantly greater improvement than placebo on the HAMD, the Montgomery-Asberg Depression Rating Scale, and the Clinical Global Impression Scale. Significant improvement was observed at earlier timepoints in the citalopram group than the sertraline group; however, sertraline treatment was associated with increased gastrointestinal side effects and a tendency toward early discontinuation, and analyses that excluded early dropouts revealed similar acute efficacy for the two active treatments. The Hamilton Anxiety Scale demonstrated a significant anxiolytic effect of citalopram, but not sertraline, relative to placebo.\n This study confirms the antidepressant efficacy of two SSRIs, citalopram and sertraline. It is hypothesized that the more consistent evidence of antidepressant activity that was observed early in treatment in the citalopram group was related to more pronounced antianxiety effects and better tolerability upon initiation of therapy.", "Major depression is a common psychiatric disorder in the elderly population. The efficacy of tricyclic antidepressants is well established, and selective serotonin reuptake inhibitors appear to have a similar effectiveness along with advantages in terms of tolerability and safety. Given the lack of literature data regarding fluvoxamine in the treatment of depressed elderly patients, the aim of the present study was to compare its efficacy and tolerability with those of sertraline in a sample of elderly patients.\n Under double-blind conditions, 93 hospitalized patients older than 59 years, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a major depressive episode, were randomly assigned to receive sertraline (150 mg daily) or fluvoxamine (200 mg daily) for 7 weeks. The clinical response was defined as a reduction on the Hamilton Rating Scale for Depression score to 8 or below.\n At study completion, the response rates were 55.6% (25/45) and 71.8% (28/39) for sertraline and fluvoxamine, respectively. No significant difference in final response rates was found between the 2 treatment groups (P = 0.12). A repeated-measures analysis of variance on Hamilton Rating Scale for Depression scores revealed a significantly different decrease of depressive symptoms between the 2 treatment groups, favoring fluvoxamine (P = 0.007). The overall safety profile of sertraline and fluvoxamine was favorable with no differences between the 2 drugs.\n The results of this double-blind trial show that sertraline and fluvoxamine may be effective compounds in the treatment of elderly depression with the latter showing some advantage in terms of speed of response. These findings warrant further replication in placebo-controlled studies.", "An eight-week double-blind, multicentre study was performed to evaluate the efficacy and safety of sertraline vs. fluoxetine in the treatment of major depression (DSM-III-R). There were 108 out-patients, from nine Italian centres, entered into the study, of whom 88 were evaluable (48 sertraline, 40 fluoxetine). The final mean daily dose of sertraline was 72 mg and for fluoxetine it was 28 mg. Both treatment groups showed a statistically significant improvement from baseline at one week, and this was maintained until the end of treatment for all of the following measures: Hamilton Rating Scales for Depression and Anxiety, the Montgomery Asberg Depression Rating Scale, Clinical Global Impressions Scale, Zung Self-Rating Scale for Anxiety and the Leeds Sleep Evaluation Questionnaire. Although there was a numerical advantage for sertraline on several efficacy measures, there was no statistically significant difference found between the treatment groups. The incidence of adverse events was similar for both treatments; 40.4% for sertraline and 39.3% for fluoxetine. However, adverse events were generally rated by patients as of lower severity in the sertraline group. In addition, for the fluoxetine group, there was a higher incidence of agitation, anxiety and insomnia than for sertraline. Sertraline was considered to be better tolerated than fluoxetine overall, since only 9.6% of sertraline-treated patients discontinued treatment due to therapy failure whereas in the fluoxetine-treated group this figure was 19.6%. By contrast, 13.5% of sertraline-treated patients discontinued prematurely because of clinical improvement, compared with 10.7% of fluoxetine-treated patients.", "There has been a paucity of well-designed studies comparing selective serotonin reuptake inhibitor (SSRI) medications in the treatment of depression in the elderly. This multicenter study was designed to examine the efficacy and safety of sertraline and fluoxetine in depressed elderly outpatients. A secondary objective was to examine the effects of SSRI treatment on quality of life and cognitive function.\n Two hundred thirty-six outpatients 60 years of age and older who met DSM-III-R criteria for major depressive disorder received 1 week of single-blind placebo before being randomly assigned to 12 weeks of double-blind, parallel-group treatment with flexible daily doses of either sertraline (range, 50-100 mg) or fluoxetine (range, 20-40 mg). Primary efficacy measures consisted of the 24-item Hamilton Rating Scale for Depression and Clinical Global Impressions scale ratings. Secondary outcome assessments included clinician- and patient-rated measures of depression symptoms and factors, cognitive functioning, and quality of life, as well as plasma drug concentrations, which were correlated with clinical response.\n Both drugs produced a similarly positive response on the primary efficacy measures, with 12-week responder rates of 73% for sertraline and 71% for fluoxetine. Sertraline-treated patients showed statistically greater cognitive improvement on several measures. Both drugs were safe and well tolerated.\n Data indicate that both drugs are effective antidepressants for the treatment of depressed elderly outpatients. Differences in cognitive performance effects deserve further investigation.", "Citalopram and sertraline are widely prescribed selective serotonin reuptake inhibitors (SSRIs). There is no conclusive evidence to show superiority of citalopram or sertraline in terms of efficacy or tolerability. Hence this study was designed to compare short term efficacy and safety of citalopram and sertraline in major depressive disorder (MDD) in Indian patients.\n In an open, randomized study, 100 patients were divided into two groups. In Group A (n = 50) patients received citalopram (20-60 mg/day) for 6 weeks. In Group B (n = 50) patients received sertraline (50-150 mg/day) for 6 weeks. Patients were evaluated at baseline and then at 1, 2, 3, 4, 5, and 6 weeks.\n There was significant improvement in Hamilton depression rating scale (HDRS), Montgomery and Asberg depression rating scale (MADRS) and Amritsar depressive inventory (ADI) scores (p < 0.05) with both the drugs. However, the decrease in score was more with citalopram (p < 0.05). Onset of action of citalopram was earlier as compared to sertraline (p < 0.05). The number of responders and remitters was also more with citalopram (p < 0.05). No serious adverse event was reported in either of the groups.\n Citalopram had shown better efficacy, earlier onset of action and more number of responders and remitters as compared to sertraline in MDD in Indian patients.\n Copyright 2007 John Wiley & Sons, Ltd.", "The comparative efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) was recently debated. Meta-analyses, based mainly on fluoxetine comparator data, suggest that the SNRI venlafaxine has superior efficacy to SSRIs in treatment of major depression.\n To compare quality of life (QOL), efficacy, safety, and tolerability associated with sertraline and venlafaxine extended release (XR) for treatment of DSM-IV major depression.\n This was an 8-week, double-blind, randomized study of sertraline (50-150 mg/day) versus venlafaxine XR (75-225 mg/day), followed by a 2-week taper period. Subjects were recruited from 7 sites in Turkey and 6 sites in Australia between October 2002 and July 2003. The primary outcome measure was the Quality of Life Enjoyment and Satisfaction Questionnaire. Secondary outcome measures included measures of depression (including response and remission), anxiety, pain, safety (e.g., blood pressure), and tolerability (e.g., discontinuation symptoms).\n A total of 163 subjects received study treatment (women, 69%; mean age, 37.0 [SD = 12.9] years). No significant differences in QOL or efficacy were noted between treatments on the primary or secondary endpoints for the total study population or the anxious depression and severe depression subgroups. A priori analyses of symptoms associated with treatment discontinuation demonstrated no difference between treatment groups. However, in post hoc analyses, sertraline was associated with less burden of moderate to severe discontinuation symptoms. Venlafaxine XR was associated with a relative increase in mean blood pressure (supine diastolic blood pressure, -4.4 mm Hg difference at week 8/last observation carried forward).\n Sertraline and venlafaxine XR demonstrated comparable effects on QOL and efficacy in treatment of major depression, although sertraline may be associated with a lower symptom burden during treatment discontinuation and a reduced risk of blood pressure increase.", "The efficacy of sertraline in the treatment of civilian posttraumatic stress disorder (PTSD) has been established by two large placebo-controlled trials. The purpose of the current pilot study was to obtain preliminary evidence of the efficacy of sertraline in military veterans suffering from PTSD. Outpatient Israeli military veterans with a DSM-III-R diagnosis of PTSD were randomized to 10 weeks of double-blind treatment with sertraline (50-200 mg/day; N = 23, 83% male, mean age = 41 years) or placebo (N = 19, 95% male, mean age = 38 years). Efficacy was evaluated by the Clinician-Administered PTSD Scale (CAPS-2) and by Clinical Global Impression Scale-Severity (CGI-S) and -Improvement (CGI-I) ratings. Consensus responder criteria consisted of a 30% or greater reduction in the CAPS-2 total severity score and a CGI-I rating of \"much\" or \"very much\" improved. The baseline CAPS-2 total severity score was 94.3 +/- 12.9 for sertraline patients, which is notably higher than that reported for most studies of civilian PTSD. On an intent-to-treat endpoint analysis, sertraline showed a numeric but not statistically significant advantage compared with placebo on the CAPS-2 total severity and symptom cluster scores. In the study completer analysis, the mean CGI-I score was 2.4 +/- 0.3 for sertraline and 3.4 +/- 0.3 for placebo (t = 2.55, df = 30, p = 0.016), CGI-I responder rates were 53% for sertraline and 20% for placebo (chi2 = 3.62, df = 1, p = 0.057), and combined CGI-I and CAPS-2 responder rates (>or=30% reduction in baseline CAPS-2 score) were 41% for sertraline and 20% for placebo (chi2 = 1.39, df = 1, p = 0.238). Sertraline treatment was well tolerated, with a 13% discontinuation rate as a result of adverse events. This pilot study suggests that sertraline may be an effective treatment in patients with predominantly combat-induced PTSD, although the effect size seems to be somewhat smaller than what has been reported in civilian PTSD studies. Adequately powered studies are needed to confirm these results and to assess whether continued treatment maintains or further improves response.", "Posttraumatic stress disorder (PTSD) is a common illness associated with significant disability. Few large, placebo-controlled trials have been reported.\n Outpatients with a DSM-III-R diagnosis of moderate-to-severe PTSD were randomized to 12 weeks of double-blind treatment with either sertraline (N = 100) in flexible daily doses in the range of 50 to 200 mg or placebo (N = 108). Primary outcome measures consisted of the Clinician-Administered PTSD Scale (CAPS-2) total severity score, the patient-rated Impact of Event Scale (IES), and the Clinical Global Impression-Severity (CGI-S) and -Improvement (CGI-I) ratings.\n Mixed-effects analyses found significantly steeper improvement slopes for sertraline compared with placebo on the CAPS-2 (t = 2.96, P =.003), the IES (t = 2.26, P =.02), the CGI-I score (t = 3.62, P<.001), and the CGI-S score (t = 4.40, P<.001). An intent-to-treat end-point analysis found a 60% responder rate for sertraline and a 38% responder rate for placebo (chi(2)(1) = 8.48, P =.004). Sertraline treatment was well tolerated, with a 9% discontinuation rate because of adverse events, compared with 5% for placebo. Adverse events that were significantly more common in subjects given sertraline compared with placebo consisted of insomnia (35% vs 22%), diarrhea (28% vs 11%), nausea (23% vs 11%), fatigue (13% vs 5%), and decreased appetite (12% vs 1%).\n The results of the current study suggest that sertraline is a safe, well-tolerated, and significantly effective treatment for PTSD.", "Sertraline and fluoxetine have pharmacokinetic and pharmacologic differences, which may be of clinical relevance.\n A randomized, double-blind, parallel-group study of 6 weeks' duration comparing the efficacy and safety of sertraline (50-100 mg/day) with those of fluoxetine (20-40 mg/day) was conducted in 286 psychiatric outpatients with DSM-III-R major depression or bipolar disorder (depressed). Primary efficacy measurements consisted of the 17-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions (CGI) scale. Secondary measurements included the Hamilton Rating Scale for Anxiety (HAM-A), the Raskin Depression Scale, the Covi Anxiety Scale, and the Leeds Sleep Questionnaire. Additionally, scores for two items and five factors from the HAM-D were analyzed.\n Efficacy was based on 124 evaluable patients in each treatment group. As measured by HAM-D and CGI-Severity scores, there was a significant (p < .001) improvement from baseline to each follow-up visit in both treatment groups with no statistically significant difference between groups. There was also no significant difference in the proportion of responders in each group. CGI-Improvement responder rates were 69% for sertraline and 67% for fluoxetine. Results of secondary efficacy measurements followed the same trend, although from the second week of treatment there was a numerical advantage (not statistically significant) for sertraline over fluoxetine in improving anxiety symptoms as measured by the total HAM-A score. Headache and nausea were the most frequently reported events for both drugs. The incidence of early patient withdrawals due to treatment-emergent adverse events was 14% for sertraline and 13% for fluoxetine. The starting dosage (sertraline 50 mg/day, fluoxetine 20 mg/day) was the final dosage in 76% of patients in both treatment groups.\n Sertraline and fluoxetine were equally effective and well tolerated in patients with major depression and associated anxiety.", "Evidence that major depression can be a significant hindrance to smoking cessation prompted this examination of the usefulness of sertraline as a cessation aid for smokers with a history of major depression. Specifically, sertraline's efficacy for smoking abstinence and its effects on withdrawal symptoms were evaluated.\n The study design included a 1-week placebo washout, a 9-week double-blind, placebo-controlled treatment phase followed by a 9-day taper period, and a 6-month drug-free follow-up. One hundred thirty-four smokers with a history of major depression were randomly assigned to receive sertraline (N=68) or matching placebo (N=66); all received intensive individual cessation counseling during nine clinic visits.\n Sertraline treatment produced a lower total withdrawal symptom score and less irritability, anxiety, craving, and restlessness than placebo. However, the abstinence rates did not significantly differ between treatment groups: 28.8% (19 of 66) for placebo and 33.8% (23 of 68) for sertraline at the end of treatment and 16.7% (11 of 66) for placebo and 11.8% (eight of 68) for sertraline at the 6-month follow-up. No moderating effects of single or recurrent major depression, depressed mood at baseline, nicotine dependence level, or gender were observed.\n Sertraline did not add to the efficacy of an intensive individual counseling program in a double-blind, placebo-controlled study. However, given that the end-of-treatment abstinence rate for the placebo group was much higher than expected, it is unclear whether a ceiling effect of the high level of psychological intervention received by all subjects prevented an adequate test of sertraline.", "The purpose of this double-blind, multicenter trial was to compare the efficacy and safety of sertraline (50-150 mg/day) with those of citalopram (20-60 mg/day) in patients with major depression in general practice during 24 weeks of treatment. The patients were assessed using the Montgomery-Asberg Depression Rating Scale and the Clinical Global Impressions of severity and improvement scales. Observed and spontaneously reported adverse events were recorded and side-effects were assessed by means of the UKU Side-Effect Scale. Altogether 400 patients were randomized into the study. A total of 308 patients completed the 24-week study in accordance with the protocol. A significant reduction in the total Montgomery-Asberg Depression Rating Scale scores was observed in both treatment groups as early as 2 weeks, with no statistically significant differences between the drugs. In the intention to treat-last observation carried forward analysis 76% responded to treatment in the sertraline and 81% in the citalopram group. The final mean doses were 82 mg/day (64% higher than baseline) in the sertraline group and 34 mg/day (70% higher than baseline) in the citalopram group. The response rate in completers in accordance with protocol was 90% in the sertraline group and 93% in the citalopram group. The side-effects were those usually seen, and both sertraline and citalopram were considered to be well tolerated. It was concluded that patients with major depression in general practice respond well to 24 weeks of treatment with sertraline or citalopram. With regard to efficacy, no statistically significant differences were found between the drugs.", "We designed this study to determine whether the daily treatment of nondepressed acute stroke patients with sertraline reduced the incidence of depression at follow-up.\n 111 patients with recent stroke (< 2 weeks; International Classification of Diseases, Tenth Revision criteria) were randomly assigned to treatment with placebo (N = 56) and sertraline (N = 55, 50 mg once daily) in this double-blind, placebo-controlled 24-week clinical trial. Subjects were recruited from the 2 largest teaching hospitals of Western Australia between June 2002 and June 2004. The primary endpoint of interest was development of clinically significant depressive symptoms as assessed by a Hospital Anxiety and Depression Scale-depression subscale score of 8 or above, or as diagnosed by the treating physician during 24 weeks.\n There was no significant difference in the incidence of depressive symptoms during 24 weeks of treatment (16.7% [8/48] sertraline vs. 21.6% [11/51] placebo, rate ratio = 0.8, 95% CI = 0.3 to 2.1, p = .590). The trial medication was discontinued by 51.8% (29/56) of patients assigned placebo and 47.3% (26/55) assigned sertraline (p = .634), most often because of perceived side effects or because the treating physician introduced an antidepressant medication.\n Twenty-four-week treatment with 50 mg of sertraline once daily initiated within 2 weeks of onset of acute stroke is not a significantly more effective strategy to prevent 6-month depression than usual care plus placebo among nondepressed stroke patients. New pharmacologic and nonpharmacologic strategies need to be developed to reduce the health and financial burden associated with depression after stroke.", "A double-blind, placebo- and amitriptyline-controlled comparison study was performed to evaluate the antidepressant efficacy of sertraline, a specific serotonin uptake inhibitor. Patients with DSM-III-defined major depression randomly received either sertraline (N = 149), amitriptyline (N = 149), or placebo (N = 150) once daily for the 8-week study period. The mean final daily medication dose for the all-patients group was 145 mg and 104 mg for the sertraline- and amitriptyline-treatment groups, respectively. As measured by the Hamilton Rating Scale for Depression and the Clinical Global Impressions Scale, both the sertraline and amitriptyline treatment groups showed a significantly greater improvement from baseline (p less than or equal to .001) than the placebo group. The sertraline group had a higher proportion of gastrointestinal complaints and male sexual dysfunction than either the amitriptyline or the placebo group. The amitriptyline group showed a higher proportion of anticholinergic and sedative side effects and dizziness compared with patients who received either sertraline or placebo.", "Depression is associated with considerable morbidity and mortality. As depressive disorders carry a high risk of relapse, treatment strategies include the use of a 6-month continuation period after resolution of the acute episode. Tolerability is of major importance when determining compliance and outcome during long-term therapy. Due to the superior tolerability profile of the selective serotonin reuptake inhibitors (SSRIs) over the older tricyclic antidepressants (TCAs), the former may be more suitable for extended therapy. Comparative studies have not shown differences between the SSRIs in terms of efficacy, but side-effect profiles may vary. A multicenter, double-blind, comparative study of sertraline and fluoxetine was carried out in outpatients fulfilling DSM-III-R criteria for major depressive disorder. Patients were randomised to receive sertraline (50-150 mg, n = 118) or fluoxetine (20-60 mg, n = 120) for 24 weeks. Assessments for depression (HAM-D, HAD, CGI-I, CGI-S), anxiety (Covi), sleep (Leeds Sleep Evaluation scale) and quality of life (SIP) were made at study entry and at weeks 2, 4, 8, 12, 18 and 24. All adverse events were recorded to allow evaluation of tolerability. In total, 88 patients in the sertraline group completed the study compared with 79 in the fluoxetine group. Side effects were responsible for the premature treatment withdrawal of seven (6%) sertraline patients and 12 (10%) fluoxetine patients. Two-hundred and thirty-four patients were included in an ITT analysis up to last visit (116 sertraline, 118 fluoxetine). At study endpoint, both treatments produced a significant improvement over baseline on all efficacy variables (P < 0.001). Although the magnitude of global changes in depression, anxiety, and quality of life was larger with sertraline than fluoxetine, none of the between-group differences reached statistical significance. However, significant differences in favour of sertraline were observed for individual HAM-D items including item 4 (insomnia onset) (P = 0.04), item 9 (agitation) (P = 0.02), and item 13 (general somatic symptoms) (P = 0.008). In addition, sertraline was associated with significantly superior performance on the Leeds Sleep Evaluation scale and on SIP items relating to sleep and rest, emotional behaviour and ambulation. Both sertraline and fluoxetine were well tolerated with no significant differences between treatments.", "There have been no studies specifically examining the efficacy of selective serotonin reuptake inhibitor antidepressants for the symptoms of depression in schizophrenia. This study aimed to determine the efficacy and safety of sertraline as a treatment for depressive symptoms in patients with stable, chronic schizophrenia. The Beck Depression Inventory (BDI) was used as the principal outcome measure and other measures of depressive symptoms as secondary outcome measures. Twenty-six patients were entered into a double-blind, placebo-controlled, 8-week trial of sertraline and were included in the intent-to-treat (ITT) analysis (13 in each group). Eight patients in the sertraline group and 12 in the placebo group completed at least four weeks in the study and were considered to have had adequate treatment. On the ITT analysis, the mean score on the BDI fell 14.5% for the sertraline group and 5.6% for the placebo group (p > 0.05); the mean score on the Hamilton Depression Rating Scale (HDRS) fell 16.99% for the sertraline group and 8.3% for the placebo group (p > 0.05). When the analysis was repeated for those who had received adequate treatment, the mean BDI score fell by 28% for the sertraline group and 6% for the placebo group (p = 0.1); the mean HDRS score fell 31% for the sertraline group and 8.6% for the placebo group (p = 0.02). On the Clinical Global Impression-Improvement Scale, 10 of the 13 patients on sertraline improved against four of the 13 in the placebo group (p = 0.05). Sertraline-treated patients showed a significant improvement on the anxiety/ depression subscale of the BPRS on ITT analysis (F = 10.1, p = 0.004). There was no significant effect on negative or positive symptoms. Sertraline was well tolerated. The results suggest that sertraline is useful as a treatment for depressive symptoms in schizophrenia.", "The acute treatment efficacy, tolerability, and effects on health-related quality of life of sertraline (50-200 mg/day) versus imipramine (75-225 mg/day) were compared in outpatients with non-melancholic depression. The study employed an open-label, parallel-group design. One hundred and sixteen patients were randomized to receive sertraline and 123 to receive imipramine for 8 weeks. In the intent-to-treat (ITT), last-observation-carried-forward (LOCF) analysis, sertraline produced statistically significantly greater improvements in depressive (21-item Hamilton Depression Rating Scale [HAM-D(21)] scores of 24.9 and 24.4 were reduced to 10.3 and 13.1 at endpoint, P<.005) and anxiety symptoms (Hamilton Anxiety Rating Scale [HAM-A] scores of 21.8 and 21.9 were reduced to 9.5 and 13.9, P<.01), as well as in response (69.0% versus 53.7% at endpoint, P=.016) and remission rates (51.3% versus 38.0% at endpoint, P=.041) from week 4 onwards compared with imipramine. The proportion of patients who were 'very much improved' or 'much improved' (Clinical Global Impressions Scale of Improvement [CGI-I] score of 1 or 2) was significantly higher at endpoint in the sertraline group (76.1%) than in the imipramine group (62.8%) (P=.028). At week 8, patients in both treatment groups showed clear improvements in quality of life, although nonstatistically significant differences were evident in the quality of life of sertraline- versus imipramine-treated patients. Sertraline was significantly superior in tolerability with less discontinuations due to adverse events (10.3%) compared with the imipramine group (24.4%) (P=.004). It was concluded that sertraline is more effective than imipramine in the acute treatment of depressive and anxiety symptoms in patients with non-melancholic depression.", "Poststroke depression is a frequent condition and important to treat. The aim of this trial was to study the efficacy and tolerability of sertraline.\n In 4 Swedish stroke centers, 123 patients (aged 70.7 +/- 9.9 years) were enrolled during the period September 1998 to January 2001 in a randomized, double-blind, placebo-controlled 26-week trial, at a mean of 128 +/- 97 days (range, 3-375 days) after stroke, if they fulfilled DSM-IV criteria of major depressive episode (N = 76) or minor depressive disorder (N = 47). The primary efficacy variable was a change in depression assessed by the Montgomery-Asberg Depression Rating Scale. The Emotional Distress Scale (EDS) was administered and the occurrence of emotionalism and quality of life (QoL) were assessed, as well as neurologic recovery. Efficacy analyses were intention-to-treat, short-term (week 6) and long-term (week 26).\n Of the 123 patients, 62 were treated with sertraline (50-100 mg/day) and 61 with placebo. Both groups improved substantially, with no differences between the treatments, either for major depressive episode or minor depressive disorder, or for short- or long-term antidepressant effect and neurologic outcome. EDS revealed a better outcome with sertraline at week 6 (p < .05). At week 26, the improvement in QoL was better in sertraline patients (p < .05) and there was a trend for emotionalism (p = .07). No serious side effects were seen.\n Poststroke depression as measured by a conventional depression rating scale improved over time irrespective of treatment. Positive effects specific to sertraline were identified in emotional distress, emotionalism, and QoL. The study indicates that poststroke emotional reactions comprise depression and other domains susceptible to pharmacologic therapy.", "In nursing home residents and other frail elderly patients, old age and potential drug-drug and drug-disease interactions may affect the relative safety and efficacy of medications. The purpose of this study was to examine the efficacy and tolerability of venlafaxine and sertraline for the treatment of depression among nursing home residents.\n The study was a 10-week randomized, double-blind, controlled trial of venlafaxine (doses up to 150 mg/day) versus sertraline (doses up to 100 mg/day) among 52 elderly nursing home residents with a DSM-IV depressive disorder and, at most, moderate dementia. The primary measure of outcome was the Hamilton Rating Scale for Depression (HAM-D). Adverse events were monitored and recorded systematically during the trial.\n Twelve subjects were discontinued due to serious adverse events (SAE), 5 were discontinued due to other significant side effects, and 2 withdrew consent. Tolerability estimated by the time to termination was lower for venlafaxine than sertraline for serious adverse events (log rank statistic = 5.28, p =.022), for serious adverse events or side effects (log rank statistic = 8.08, p =.005), or for serious adverse events, side effects, or withdrawal of consent (log rank statistic = 10.04, p =.002). Mean (SD) HAM-D scores at baseline were 20.2 (3.4) for sertraline and 20.3 (3.7) for venlafaxine; intent-to-treat endpoint HAM-D scores were 12.2 (5.1) and 15.7 (6.2) (F = 3.45; p =.069). There were no differences in categorical responses for the intent-to-treat sample or completers.\n In this frail elderly population, venlafaxine was less well tolerated and, possibly, less safe than sertraline without evidence for an increase in efficacy. This unexpected finding demonstrates the need for systematic research on the safety of drugs in the frail elderly.", "Sexual dysfunction, a frequently reported side effect of many antidepressants, may result in patient dissatisfaction and noncompliance with treatment regimens. This paper describes the results of the first placebo-controlled comparison of the efficacy, safety, and effects on sexual functioning of sustained-release bupropion (bupropion SR) and the selective serotonin reuptake inhibitor sertraline. This randomized, double-masked, double-dummy, parallel-group, multicenter trial enrolled 360 patients with moderate-to-severe recurrent major depression. Patients were treated with bupropion SR 150 to 400 mg/d, sertraline 50 to 200 mg/d, or placebo for up to 8 weeks. Patients' depression and sexual functioning were assessed at weekly or biweekly clinic visits; safety was assessed by regular monitoring of adverse events, vital signs, and body weight. Treatment groups were similar at baseline in terms of age, sex, and race, and most patients had a diagnosis of moderate uncomplicated depression. Patients treated with bupropion SR or sertraline showed similar improvements on all efficacy measures; both active treatments were superior to placebo in improving scores on all rating scales for depression at various time points. Significantly more patients treated with sertraline experienced orgasmic dysfunction throughout the study than did patients treated with bupropion SR or placebo (P < 0.001). Headache was the most frequently reported adverse event in all 3 treatment groups and occurred with similar frequency in each group (30% to 40%). Nausea (31%), diarrhea (26%), insomnia (18%), and somnolence (17%) occurred in significantly more patients in the sertraline group than in the bupropion SR group (18%, 7%, 13%, and 3%, respectively) and the placebo group (10%, 11%, 4%, and 6%, respectively). Dry mouth occurred more frequently with bupropion SR (19%) than with sertraline (14%) or placebo (12%), although the differences were not significant. Changes in vital signs were similar in all groups. Similar (small, but not statistically significant) decreases in mean body weight were seen in both the bupropion SR (-1.06 kg) and sertraline (-0.79 kg) groups, whereas the placebo group experienced a minor increase (0.21 kg). Although bupropion SR and sertraline were similarly well tolerated and effective in the treatment of depression, sertraline treatment was more often associated with sexual dysfunction and certain other adverse events compared with bupropion SR and placebo. Therefore, bupropion SR may be an appropriate choice as an antidepressant for the treatment of sexually active patients.", "We observed the relief of hot flashes in breast cancer survivors taking tamoxifen and treated with sertraline for depression. Our objective was to assess the effect of sertraline on the frequency and severity of hot flashes, mood status, and health-related quality of life. We used a randomized, double-blind, placebo-controlled, crossover study using 6 weeks of sertraline (50 mg each morning) versus placebo. Study participants were 62 breast cancer survivors from an oncology clinic in a tertiary care center on adjuvant tamoxifen reporting bothersome hot flashes. Patients were asked to keep a daily hot flash diary to record hot flash frequency and severity, from which hot flash scores (frequency x severity) were calculated. The Center for Epidemiologic Studies depression scale and Functional Assessment of Cancer Therapy--Breast (FACT-B) (at baseline, 6 weeks, and 12 weeks) were used to assess mood and quality of life. Sixty-two women were accrued. Forty-seven women (median age 53.9 years, range 36.6-77.1 years; 89% postmenopausal; 85.5% Caucasian) completed the first 6 weeks and 39 completed 12 weeks. The baseline daily hot flash frequency and score were 5.8 (standard deviation 4.1) and 11.5 (14.0), respectively. At the end of the first 6 weeks, hot flash frequency decreased by 50% in 36% of those taking sertraline compared to 27% taking placebo. In the crossover analysis, sertraline was significantly more effective than placebo: women crossing from placebo to sertraline had a decrease (-0.9 and -1.7) in hot flash frequency and score, whereas those crossing from sertraline to placebo had an increase (1.5 and 3.4) in hot flash frequency and score (p = 0.03 and 0.03). Forty-eight percent preferred the sertraline period, 11% preferred the placebo period, and 41% had no preference (p = 0.006). Measures of depression and quality of life were within normal range and did not change significantly within treatment groups. Sertraline decreases hot flashes in breast cancer survivors taking tamoxifen and women prefer sertraline to placebo. Further study of sertraline for the management of hot flashes is warranted.", "Few studies have compared the treatment efficacy of the 2 selective serotonin reuptake inhibitors sertraline and fluoxetine.\n A randomized, single-blind, parallel-group study of 10 weeks' duration comparing the efficacy of sertraline, 50 mg/day; sertraline, 100 mg/day; and fluoxetine, 20 mg/day, was conducted in 44 psychiatric outpatients with DSM-IV unipolar major depressive disorder. Antidepressant dosages were doubled at 6 weeks for subjects who had not achieved remission. Primary outcome measurements included the 21-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions-Improvement scale (CGI-I), with scores of < or = 7 on the HAM-D and < or = 2 on the CGI-I representing a positive treatment response, i.e., remission.\n At 4 weeks, significant differences in rate of positive treatment response were noted, with 0% for sertraline, 50 mg; 46% for sertraline, 100 mg; and 31% for fluoxetine, 20 mg (p = .023). At 6 weeks, positive treatment response rates were 21%, 43%, and 31% for subjects taking 50 mg of sertraline, those taking 100 mg of sertraline, and those taking 20 mg of fluoxetine, respectively, with treatment groups no longer differing significantly from each other. In subjects for whom antidepressant dose was doubled at week 6, response rates at week 10 (4 weeks on increased dose) were 40% for sertraline, 100 mg; 43% for sertraline, 200 mg; and 55% for fluoxetine, 40 mg.\n Subjects taking sertraline, 100 mg, and fluoxetine, 20 mg, demonstrated an earlier treatment response compared with subjects taking sertraline, 50 mg. For patients without a positive response at 6 weeks, an increased antidepressant dose resulted in remission for a substantial proportion of patients when assessed 4 weeks later.", "The study compared the safety and efficacy of sertraline, a selective serotonin reuptake inhibitor, and placebo in the treatment of generalized anxiety disorder in children and adolescents.\n The study subjects were 22 children and adolescents age 5-17 years who met the DSM-IV criteria for generalized anxiety disorder according to the Anxiety Disorders Interview Schedule for Children-Revised and who had a Hamilton Anxiety Rating Scale score > or = 16. The patients underwent a 2-3-week prestudy evaluation period, followed by a 9-week double-blind treatment phase in which they were randomly assigned in blocks of four to receive either sertraline or pill placebo. The maximum dose of sertraline was 50 mg/day. Primary outcome measures were the Hamilton anxiety scale and the Clinical Global Impression scale.\n The Hamilton anxiety scale total score, psychic factor, and somatic factor and the Clinical Global Impression severity and improvement scales showed significant differences with treatment in favor of sertraline over placebo beginning at week 4. Self-report measures reflected these results at the end of treatment.\n The results of this double-blind, placebo-controlled trial suggest that sertraline at the daily dose of 50 mg is safe and efficacious for the treatment of generalized anxiety disorder in children and adolescents.", "Despite the high prevalence, chronicity, and associated comorbidity of posttraumatic stress disorder (PTSD) in the community, few placebo-controlled studies have evaluated the efficacy of pharmacotherapy for this disorder.\n To determine if treatment with sertraline hydrochloride effectively diminishes symptoms of PTSD of moderate to marked severity.\n Twelve-week, double-blind, placebo-controlled trial preceded by a 2-week, single-blind placebo lead-in period, conducted between May 1996 and June 1997.\n Outpatient psychiatric clinics in 8 academic medical centers and 6 clinical research centers.\n A total of 187 outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition diagnosis of PTSD and a Clinician Administered PTSD Scale Part 2 (CAPS-2) minimum total severity score of at least 50 at baseline (mean age, 40 years; mean duration of illness, 12 years; 73% were women; and 61.5% experienced physical or sexual assault).\n Patients were randomized to acute treatment with sertraline hydrochloride in flexible daily dosages of 50 to 200 mg/d, following 1 week at 25 mg/d (n=94); or placebo (n=93).\n Baseline-to-end-point changes in CAPS-2 total severity score, Impact of Event Scale total score (IES), and Clinical Global Impression-Severity (CGI-S), and CGI-Improvement (CGI-I) ratings, compared by treatment vs placebo groups. Results Sertraline treatment yielded significantly greater improvement than placebo on 3 of the 4 primary outcome measures (mean change from baseline to end point for CAPS-2 total score, -33.0 vs -23.2 [P =.02], and for CGI-S, -1.2 vs -0.8 [P=.01]; mean CGI-I score at end point, 2.5 vs 3.0 [P=.02]), with the fourth measure, the IES total score, showing a trend toward significance (mean change from baseline to end point, -16.2 vs -12.1; P=.07). Using a conservative last-observation-carried-forward analysis, treatment with sertraline resulted in a responder rate of 53% at study end point compared with 32% for placebo (P=.008, with responder defined as >30% reduction from baseline in CAPS-2 total severity score and a CGI-I score of 1 [very much improved], or 2 [much improved]). Significant (P<.05) efficacy was evident for sertraline from week 2 on the CAPS-2 total severity score. Sertraline had significant efficacy vs placebo on the CAPS-2 PTSD symptom clusters of avoidance/numbing (P=.02) and increased arousal (P=.03) but not on reexperiencing/intrusion (P=.14). Sertraline was well tolerated, with insomnia the only adverse effect reported significantly more often than placebo (16.0% vs 4.3%; P=.01).\n Our data suggest that sertraline is a safe, well-tolerated, and effective treatment for PTSD.", "To evaluate the efficacy of emotional support and counselling combined with placebo or antidepressants with single or dual mechanism of action in the treatment of depression in primary care.\n Randomised double blind study.\n Several locations in Norway.\n 372 patients with depression.\n Improvement (clinical remission) reported both by the patient (Montgomery Asberg depression rating scale) and the physician (clinical global improvement and impression scales).\n Intention to treat analyses showed 47% remission in patients randomised to placebo compared with 61% remission in patients randomised to sertraline (odds ratio 0.56, 95% confidence interval 0.33 to 0.96) and 54% in patients randomised to mianserin (0.75, 0.44 to 1.27). Women responded better than men (1.86, 1.17 to 2.96). Subgroup analyses showed that subjects with recurrent depression (n=273) responded more frequently to sertraline than to placebo (0.43, 0.23 to 0.82) than those having their first episode of depression (1.18, 0.39 to 3.61). Statistically significant interactions between type of drug treatment and history of depression were not shown by logistic regression.\n The combination of active drug and simple psychological treatment (counselling, emotional support, and close follow up over a 24 week period) was more effective than simple psychological treatment alone, in particular for those with recurrent depression. Overall, women may benefit more than men. If confirmed in future studies, the findings should lead to more differentiated treatment guidelines for depression in primary care.", "This 8-week, double-blind, randomized trial compared the efficacy and tolerability of venlafaxine and sertraline in patients with major depression.\n Outpatients (N = 147) with DSM-IV major depressive disorder and a baseline 21-item Hamilton Rating Scale for Depression (HAM-D) score of at least 18 were randomly assigned to venlafaxine, 37.5 mg b.i.d., or sertraline, 50 mg once daily. From day 15, the doses could be increased to venlafaxine, 75 mg b.i.d., or sertraline, 50 mg b.i.d. Efficacy was assessed with the 21-item HAM-D, the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impressions scale (CGI) using a modified intent-to-treat analysis.\n No significant differences were noted between treatments for mean HAM-D, MADRS, or CGI scores. At week 8, the HAM-D response rate was 83% with venlafaxine (N = 75) and 68% with sertraline (N = 72) (p = .05). A HAM-D score less than 10 was recorded in 68% of venlafaxine-treated and 45% of sertraline-treated patients at week 8 (p = .008). Among patients who increased their dose, the remission rate (HAM-D score < 10) was 67% with venlafaxine and 36% with sertraline at week 8 (p < .05). The overall discontinuation rate was 21% with venlafaxine and 17% with sertraline. The most common adverse events with venlafaxine were nausea, headache, and sweating and with sertraline were nausea, headache, and diarrhea.\n Among patients who increased their dose, approximately twice as many experienced a remission with venlafaxine, which is a more clinically relevant endpoint than response and represents the proportion of patients who have recovered or are well.", "Major depressive disorder (MDD) occurs in 15% to 23% of patients with acute coronary syndromes and constitutes an independent risk factor for morbidity and mortality. However, no published evidence exists that antidepressant drugs are safe or efficacious in patients with unstable ischemic heart disease.\n To evaluate the safety and efficacy of sertraline treatment of MDD in patients hospitalized for acute myocardial infarction (MI) or unstable angina and free of other life-threatening medical conditions.\n Randomized, double-blind, placebo-controlled trial conducted in 40 outpatient cardiology centers and psychiatry clinics in the United States, Europe, Canada, and Australia. Enrollment began in April 1997 and follow-up ended in April 2001.\n A total of 369 patients with MDD (64% male; mean age, 57.1 years; mean 17-item Hamilton Depression [HAM-D] score, 19.6; MI, 74%; unstable angina, 26%).\n After a 2-week single-blind placebo run-in, patients were randomly assigned to receive sertraline in flexible dosages of 50 to 200 mg/d (n = 186) or placebo (n = 183) for 24 weeks.\n The primary (safety) outcome measure was change from baseline in left ventricular ejection fraction (LVEF); secondary measures included surrogate cardiac measures and cardiovascular adverse events, as well as scores on the HAM-D scale and Clinical Global Impression Improvement scale (CGI-I) in the total randomized sample, in a group with any prior history of MDD, and in a more severe MDD subgroup defined a priori by a HAM-D score of at least 18 and history of 2 or more prior episodes of MDD.\n Sertraline had no significant effect on mean (SD) LVEF (sertraline: baseline, 54% [10%]; week 16, 54% [11%]; placebo: baseline, 52% [13%]; week 16, 53% [13%]), treatment-emergent increase in ventricular premature complex (VPC) runs (sertraline: 13.1%; placebo: 12.9%), QTc interval greater than 450 milliseconds at end point (sertraline: 12%; placebo: 13%), or other cardiac measures. All comparisons were statistically nonsignificant (P> or = .05). The incidence of severe cardiovascular adverse events was 14.5% with sertraline and 22.4% with placebo. In the total randomized sample, the CGI-I (P =.049), but not the HAM-D (P =.14), favored sertraline. The CGI-I responder rates for sertraline were significantly higher than for placebo in the total sample (67% vs 53%; P =.01), in the group with at least 1 prior episode of depression (72% vs 51%; P =.003), and in the more severe MDD group (78% vs 45%; P =.001). In the latter 2 groups, both CGI-I and HAM-D measures were significantly better in those assigned to sertraline.\n Our results suggest that sertraline is a safe and effective treatment for recurrent depression in patients with recent MI or unstable angina and without other life-threatening medical conditions.", "This study was designed to evaluate the comparative efficacy and safety of sertraline and nortriptyline for the treatment of major depressive disorder in older adults.\n A double-blind, parallel group design was used to compare 210 outpatients, 60 years of age and older, who met DSM-III-R criteria for major depressive episode and had a minimum Hamilton Depression Rating Scale score of 18. The patients were randomly assigned to 12 weeks of treatment with either sertraline (50-150 mg/day) or nortriptyline (25-100 mg/day).\n The safety profiles of the two treatments were similar except that nortriptyline treatment was associated with a significant increase in pulse rate, whereas sertraline was associated with a nonsignificant decrease. Efficacy of both drugs was similar for both treatments at all time points, with 71.6% (N=53 of 74) of the sertraline-treated patients and 61.4% (N=43 of 70) of the nortriptyline-treated patients achieving responder status by week 12. Time to response was also similar, with more than 75% of the improvement in scores on the Hamilton depression scale having occurred by week 6. Secondary efficacy measures (posttreatment measures of cognitive function, memory, and quality of life) revealed a significant advantage for sertraline treatment.\n Primary efficacy measures showed sertraline and nortriptyline to be similarly effective. With secondary outcome measures there was consistent evidence of an advantage for the sertraline-treated group. The clinical impact of these measures on the long-term well-being of elderly depressed patients should be examined in a study of maintenance treatment.", "This study compared the efficacy and tolerability of 150 mg/day imipramine and 50 mg/day sertraline for the treatment of a major depressive episode (DSM-IV) in older adults (N = 55) in an 8-week, randomized, double-blind, controlled clinical trial. Intention-to-treat analysis (last observation carried forwards) showed a reduction of 50% or more on the baseline scores of the Montgomery-Asberg Rating Scale (MADRS) in 60.7% and 55.6% of patients receiving imipramine and sertraline, respectively (p = .698). Full remission of symptoms (MADRS < 9) was observed in 50.0% and 51.8% of patients, respectively (p = .891). Side effects were more frequent among patients treated with imipramine (86.7%) than among patients treated with sertraline (42.1%) (p = .008). Dropout rates were high in both groups (46.4% and 29.6% respectively, p =.200). These results indicate that imipramine and sertraline are equally effective for the treatment of major depression in later life, although adverse reactions are more frequent among subjects treated with imipramine than with sertraline.", "Efficacy and acceptability of tianeptine were investigated in a multicenter, randomized, double blind, and sertraline-controlled study. As a total, 212 in- or outpatients with DSM IV major depression single episode, recurrent and bipolar depression, were treated for 42 days either with tianeptine (37.5 mg) or with sertraline (50 mg). At inclusion, sociodemographic, physical and psychological parameters showed no significant intergroup differences. MADRS responders (50% reduction of baseline score) were 66% and 67% with tianeptine and sertraline, respectively. No statistical interdrug differences were observed either in the number of withdrawals or in the efficacy and acceptability parameters.", "Two hundred forty-one elderly depressed patients entered the 8-week, double-blind phase of this parallel-group, multicenter study; 161 patients were randomized to receive sertraline (50-200 mg/day) and 80 were randomized to receive amitriptyline (50-150 mg/day). Among evaluable patients, there were no statistically significant differences between treatments in any of the primary efficacy variables: change in total Hamilton Rating Scale for Depression (HAM-D) score (17 items), percentage change in HAM-D score, change in HAM-D Item 1, change in Clinical Global Impressions (CGI) Severity score, change in the Depression Factor of the 56-item Hopkins Symptom Checklist, and the CGI Improvement score at the last visit. Similar results were obtained using data from all patients (intention-to-treat analysis), except that amitriptyline was superior in HAM-D Total score (p = .044). The two drugs produced a similar degree of response: on the basis of the HAM-D criterion, 69.4% of sertraline patients and 62.5% of amitriptyline patients responded, and, on the basis of CGI criterion, 79.5% of sertraline and 73.4% of amitriptyline patients responded. Twenty-eight percent of the sertraline patients withdrew from the study because of a treatment-related side effect and 2.5% (4) because of a laboratory abnormality. In comparison, 35% of the amitriptyline patients withdrew because of treatment-related side effects. Sertraline was associated with a statistically lower frequency of somnolence, dry mouth, constipation, ataxia, and pain and a higher frequency of nausea, anorexia, diarrhea/loose stools, and insomnia; thus, anticholinergic effects were less common and gastrointestinal effects were more common with sertraline than with amitriptyline.(ABSTRACT TRUNCATED AT 250 WORDS)", "The authors tested the effect of sertraline in the prevention of poststroke depression. After experiencing an acute ischemic stroke, nondepressed patients (N=137) were randomly assigned to 12 months of double-blind treatment with either sertraline (N=70) or placebo (N=67). Kaplan-Meier analysis showed sertraline to have significantly superior prophylactic efficacy compared with placebo. Two definitions of clinical depression were used: total score >18 on the HAM-D(17) and score >or=9 on the HAM-D(6). Approximately 10% of the sertraline-treated group developed depression according to either definition, whereas 30% developed depression in the placebo group. On the HAM-D(6) the superiority of sertraline to placebo was demonstrated already after 6 weeks of therapy. Treatment was well tolerated; patients treated with sertraline experienced significantly fewer adverse events.", "reuptake inhibitors (SSRIs) during continuation therapy. This investigation reports the differential effect of 6 months of treatment with sertraline versus paroxetine for symptoms of depression, quality of life, and personality outcomes. Outpatients with unipolar major depression (DSM-III-R) were randomly assigned to receive 24 weeks of double-blind treatment with flexible doses of paroxetine (20-40 mg) or sertraline (50-150 mg). Assessments included the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression Scale, the Battelle Quality of Life Questionnaire, and the Structured Clinical Interview for DSM-III-R Personality Disorders screen questionnaire. One hundred seventy-six patients (mean age, 43 years; 64% female; baseline MADRS, 30.3) were treated with sertraline and 177 patients (mean age, 42 years; 71% female; MADRS, 30.7) with paroxetine. Antidepressant efficacy during continuation therapy was sustained, with only 2% of patients receiving sertraline and 9% of patients receiving paroxetine suffering a relapse. Continuation therapy resulted in a substantial conversion of responders during short-term treatment to full remission: remitter rates increased from 52% to 80% for sertraline and from 57% to 74% for paroxetine. The improvements in quality of life were related to a reduced depression score. SSRI treatment had significant beneficial effects on both categorical and dimensional measures of personality. A logistic regression analysis identified early response (25% reduction in MADRS scores at week 2) as the most important predictor of treatment response, whereas high severity, chronicity, and poor baseline quality of life had no effect. Both treatments were well-tolerated, with sertraline having a somewhat lower side effect profile. Sertraline and paroxetine demonstrated comparable efficacy during short-term and continuation therapy. Treatment was associated with significant improvement in quality of life and with reductions in axis II personality psychopathology.", "The present randomized, double blind, parallel group, controlled, multi-centric trial was designed to evaluate the efficacy and tolerability of escitalopram in comparison with citalopram and sertraline in the treatment of major depressive disorder. Outpatients (N=214) with an ongoing/newly diagnosed ICD-10 major depressive episode and a Hamilton Rating Scale for Depression (HAM-D) score of > 18 were randomly assigned to citalopram, 20-40 mg/day (74 patients), escitalopram, 10-20 mg/day (69 patients) and sertraline, 50-150 mg/day (71 patients), for a 4-week double-blind treatment period, with dosage adjustment (after 2 weeks of treatment) according to the response to treatment. Clinical response was evaluated by the 17 items HAM-D and the Clinical Global Impression (CGI) scales, which were recorded at baseline and at weekly intervals. Tolerability was evaluated by observed/spontaneously reported adverse changes in laboratory parameters (baseline and after 4 weeks). Response rate was defined as a decrease in HAM-D score by 50% from baseline and remission rate was defined as a HAM-D score of < 8. Response rate at the end of two week were 58% for escitalopram (10mg/day), 49% for citalopram (20mg/day) and 52% for sertraline (50-100mg/day). Response rate at the end of four week were 90% for escitalopram (10-20mg/day), 86% for citalopram (20-40mg/day) and 97% for sertraline (100-150mg/day). The Remission rates at the end of four weeks were 74% for escitalopram, 65% for citalopram and 77% for sertraline. Adverse experiences were reported by 45% of patients in escitalopram group, 58% patients in citalopram and 56% patients in the sertraline group. Additionally, there were lesser dropouts and lesser requirement for dose escalation in escitalopram than in citalopram and sertraline group. In conclusion Escitalopram, the Senantiomer of the citalopram is a safe and effective antidepressant in the Indian population. It has potentially superior efficacy than citalopram and a comparable efficacy to sertraline with fewer side effects than both citalopram and sertraline.", "Despite the high prevalence of dysthymia and its associated morbidity, few controlled trials have evaluated the efficacy of antidepressant medication for this disorder. A 12-week, double-blind, placebo-controlled, randomized, multicenter trial was performed to evaluate the safety and efficacy of sertraline hydrochloride and imipramine hydrochloride in treating dysthymia.\n A total of 416 outpatients (271 women and 145 men) aged 25 to 65 years with DSM-III-R-defined, early-onset, primary dysthymia without concurrent major depression were randomized to 12 weeks of treatment with sertraline, imipramine, or placebo.\n Both active treatments resulted in significantly reduced scores on the 17-item Hamilton Rating Scale for Depression (P = .04 and P = .01 for sertraline and imipramine vs placebo, respectively), the Montgomery-Asberg Depression Rating Scale (P = .01 and P = .003 vs placebo, respectively), Hopkins Symptom Checklist (P < .05), and the self-rated version of the Inventory of Depressive Symptoms (P < .05). With the use of a Clinical Global impressions improvement score of 1 or 2 (very much or much improved) to define response, response rates were 59% for sertraline, 64% for imipramine, and 44% for placebo (P = .02 for sertraline vs placebo and P < .001 for imipramine vs placebo). A significantly greater proportion of patients receiving imipramine than those receiving sertraline or placebo discontinued treatment because of adverse events (P = .001 and P < .001, respectively).\n Pharmacotherapy provides considerable relief from the symptoms of dysthymia in patients suffering from this chronic affective disorder, with both sertraline and imipramine being more effective than placebo. The greater tolerability of sertraline is an important consideration because of the chronicity of dysthymia, which may require prolonged treatment with antidepressant medication.", "Despite a growing use of selective serotonin reuptake inhibitors in older people, only one trial has examined their prophylactic efficacy in people aged 65 years and over.\n To examine the efficacy of sertraline in preventing the recurrence of depression in older people living in the community.\n Participants were openly treated with sertraline and then randomised into a double-blind, placebo-controlled continuation/maintenance study of about 2 years duration. Drug dosage was maintained at levels that achieved remission.\n No significant difference between the sertraline and placebo groups was found in the proportion of recurrences (-7.9%; 95% CI -28.06 to 12.23). Increased age and minor residual symptoms during the continuation phase were associated with recurrence.\n Sertraline at therapeutic dosage does not provide significant protection against recurrence.", "Using data from a larger 12-week clinical trial, the authors evaluated the comparative efficacy and safety of sertraline (n=42) and fluoxetine (n=33) in patients over age 70 with a diagnosis of major depressive disorder. Similar improvement on measures of depression, including remission of depressive symptoms, was evident, although significantly more sertraline-treated patients achieved a criterion clinical response. Significantly greater improvement for the sertraline group was apparent on the Digit Symbol Substitution Test, but not on two other measures of cognitive functioning. Although there was no difference in the rate of adverse events experienced, fluoxetine-treated patients lost significantly more body weight over the 12-week trial than did sertraline-treated patients, whereas the latter group exhibited significantly more \"shaking. \"", "This trial was conducted to compare the efficacy and tolerability of a fixed dose of escitalopram 10 mg/day with sertraline optimally dosed within its recommended dose range (50-200 mg/day) for the treatment of major depressive disorder.\n In this multicenter trial, depressed patients (DSM-IV defined; baseline Montgomery-Asberg Depression Rating Scale [MADRS] 22) aged 18-80 years were randomly assigned to 8 weeks of double-blind treatment with escitalopram (10 mg/day) or sertraline (50-200 mg/day) following a 1-week single-blind placebo lead-in period. There was no placebo comparison arm. Sertraline was initiated at 50 mg/day, and could be increased by 50 mg/day at weekly intervals based on clinical need and tolerability at the lower dose level. The blind was maintained with matching double-blind placebo capsules for the escitalopram group. Change from baseline to endpoint in MADRS total score (last observation carried forward) was the primary efficacy measure.\n A total of 212 patients received double-blind medication. At week 8, the mean sertraline dosage was 144 mg/day (median = 150 mg/day). Mean changes from baseline to endpoint in MADRS scores were -19.1 and -18.4 for the escitalopram and sertraline groups, respectively. At endpoint, 75% and 70% of escitalopram- and sertraline-treated patients, respectively, were responders (> or =50% improvement from baseline in mean MADRS scores). Both treatments were generally well tolerated; only 2% and 4% of patients prematurely discontinued escitalopram and sertraline treatment, respectively, due to adverse events.\n No differences in efficacy were observed for fixed-dose escitalopram 10 mg/day and sertraline flexibly dosed from 50-200 mg/day. At these doses, both escitalopram and sertraline were generally well tolerated." ]	This systematic review and meta-analysis highlighted a trend in favour of sertraline over other antidepressive agents both in terms of efficacy and acceptability, using 95% confidence intervals and a conservative approach, with a random effects analysis. However, the included studies did not report on all the outcomes that were pre-specified in the protocol of this review. Outcomes of clear relevance to patients and clinicians were not reported in any of the included studies.
CD000222	[ "7815243", "8675168" ]	[ "Effect of a medium dose of ursodeoxycholic acid with or without taurine supplementation on the nutritional status of patients with cystic fibrosis: a randomized, placebo-controlled, crossover trial.", "Ursodeoxycholic acid for liver disease associated with cystic fibrosis: a double-blind multicenter trial. The Italian Group for the Study of Ursodeoxycholic Acid in Cystic Fibrosis." ]	[ "Ursodeoxycholic acid administration has been reported to improve cholestasis and inflammatory activity in primary biliary cirrhosis and, in an uncontrolled study, also in young adults with cystic fibrosis (CF) and chronic cholestasis. As an improvement in nutritional status was also observed in these young adult patients, we investigated whether the administration of a medium dose of ursodeoxycholic acid ameliorates the nutritional status of malnourished young adult CF patients with chronic liver disease. The study included 51 patients (27 male patients and 24 female patients; age range, 8-32 years; median, 14) with body mass percentiles < 90%. Patients were randomly assigned to receive either ursodeoxycholic acid (10-12 mg/kg/day) alone or with taurine (18-22 mg/kg/day). Patients were followed in a crossover fashion within each group; 6 months of treatment was randomly alternated with 6 months of placebo. Nine patients dropped out before concluding the study. Liver function tests, nutritional status, and coefficients of fat absorption were determined at entry and after each 6 months of placebo or treatment. Nutritional status and fat absorption were not significantly modified by either treatment. Liver function tests improved after ursodeoxycholic acid administration only in patients with concomitant chronic liver disease. Our findings indicate that 6 months of therapy with a medium dose of ursodeoxycholic acid, either alone or with taurine, does not improve the nutritional status of young malnourished CF patients. Higher doses given for longer periods might be worth investigating.", "Liver disease is increasingly recognized as a major cause of morbidity in cystic fibrosis (CF). Preliminary data suggest that ursodeoxycholic acid (UDCA) may be beneficial for treatment of this manifestation. We performed a double-blind, multicenter trial in these patients to establish efficacy and safety of UDCA in terms of the improvement of clinical and nutritional indicators besides standard liver function tests. We also intended to establish whether taurine supplementation has a beneficial effect in patients receiving UDCA. From June to December 1990, we enrolled in 12 centers 55 CF patients with liver disease (39 male subjects; median age, 13.8 years). They were randomly assigned to receive for 1 year one of the following treatments: UDCA (15 mg/kg body weight daily) plus taurine (30 mg/kg body weight daily), UDCA plus placebo, placebo plus taurine, or double placebo. Clinical and laboratory evaluations were performed every 3 months. After 1 year, deterioration of overall clinical conditions, as indicated by the Shwachman-Kulczycki score (SKS), occurred in patients who received placebo but not in those who received UDCA (P = .025). Patients treated with UDCA also showed an improvement in gamma-glutamyl transpeptidase (GGT) (P = .004) and 5'-nucleotidase (P = .006) levels. Treatment with taurine was followed by a significant increase in serum prealbumin levels (P = .053), a trend toward a reduction in fat malabsorption, and no effect on the biochemical profile. No severe side effects occurred with any treatment. Thus, we concluded that UDCA administration improves clinical and biochemical parameters in CF patients with liver disease. Taurine supplementation may be indicated in patients with severe pancreatic insufficiency and poor nutritional status." ]	There are few trials assessing the effectiveness of ursodeoxycholic acid. There is insufficient evidence to justify its routine use in cystic fibrosis.
CD004085	[ "16137357", "8951252", "10051081", "8120720", "9255192", "11098980" ]	[ "High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669].", "The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome.", "A prospective randomized comparison of conventional mechanical ventilation and very early high frequency oscillatory ventilation in extremely premature newborns with respiratory distress syndrome.", "Prospective, randomized comparison of high-frequency oscillation and conventional ventilation in candidates for extracorporeal membrane oxygenation.", "Randomized, multicenter trial of inhaled nitric oxide and high-frequency oscillatory ventilation in severe, persistent pulmonary hypertension of the newborn.", "Inhaled nitric oxide reduces the need for extracorporeal membrane oxygenation in infants with persistent pulmonary hypertension of the newborn." ]	[ "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.", "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.", "To compare the effectiveness and safety of very early high-frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CMV) in treatment of the respiratory distress syndrome (RDS) and to evaluate their impact on the incidence of chronic pulmonary disease and early and late morbidity of very low-birthweight neonates.\n A prospective randomized clinical trial.\n Tertiary neonatal intensive care unit in the Perinatology Center in Prague.\n 43 premature newborns, delivered in the Department of Obstetrics in the Perinatology Center, were randomly divided into two groups (HFOV and CMV) immediately after delivery; 2 patients in each group died, 2 fulfilled crossover criteria from CMV to HFOV, and 2 were excluded because of congenital malformations. Nineteen patients treated with HFOV were therefore compared with 18 infants in the CMV group.\n The two contrasting modes of ventilation were introduced immediately after intubation. Maintenance of optimal lung volume in HFOV to optimize oxygenation and the therapeutic administration of surfactant after fulfilling defined criteria are important points of the strategy and design of the study.\n Except for a higher proportion of males in the HFOV group (p<0.02), the basic clinical characteristics (gestational age, birthweight, Apgar score at 5 min, umbilical arterial pH), the two groups were similar. In the acute stage of RDS, infants treated with HFOV had higher proximal airway distending pressure with HFOV for 6 h after delivery (p<0.05). For a period of 12 h after delivery lower values for the alveolar-arterial oxygen difference (p<0.03) were noted. The number of patients who did not require surfactant treatment was higher in the HFOV group (11 vs. 1, p<0.001). In the HFOV group the authors found a lower roentgenographic score at 30 days of age (p<0.03) and a lower clinical score in the 36th postconceptional week (p<0.05), using these two scoring systems for assessing chronic lung disease according to Toce scale. The incidence of pneumothorax, pulmonary interstitial emphysema, intraventricular hemorrhage and retinopathy of prematurity in both groups was the same.\n HFOV, when applied early and when the clinical strategy of maintenance of optimal lung volume is used, improves oxygenation in the acute stage of RDS, reduces the need of surfactant administration, and can decrease the injury to lung tissue even in extremely immature newborns to whom surfactant is administered therapeutically.", "To compare the safety and efficacy of high-frequency oscillation (HFO) with conventional ventilation in the treatment of neonates with respiratory failure.\n We conducted a multicenter, prospective, randomized trial. Patients were stratified according to pulmonary diagnosis and then were randomly selected for conventional ventilation or HFO. A balanced crossover design offered patients who met criteria of treatment failure a trial of the alternative mode of ventilation.\n Four tertiary, level 3 neonatal intensive care units accepting regional referrals for extracorporeal membrane oxygenation.\n Neonates were eligible for enrollment if their gestational age was > 34 weeks, their birth weight was > or = 2 kg, they were < 14 days of age, they required fractional inspired oxygen > 0.50 and a mean airway pressure > 0.98 kPa (10 cm H2O) to support adequate oxygenation, and they required a peak inspiratory pressure > 2.9 kPa (30 cm H2O) and a rate > 40 breaths per minute to support adequate ventilation. Exclusion criteria were lethal congenital anomalies, profound shock, need for cardiopulmonary resuscitation, and failure to obtain consent.\n Of 79 patients studied, 40 were assigned to conventional ventilation and 39 to HFO. Neonates randomly assigned to HFO required higher peak pressure (3.8 +/- 0.5 vs 3.3 +/- 0.8 kPa, 39 +/- 5 vs 34 +/- 8 cm H2O; p = 0.004) and more often met extracorporeal membrane oxygenation criteria (67% vs 40%; p = 0.03) at study entry than did those given conventional ventilation. Twenty-four patients (60%) assigned to conventional ventilation met treatment failure criteria compared with 17 (44%) of those assigned to HFO (not significant). Of the 24 patients in whom conventional ventilation failed, 15 (63%) responded to HFO; 4 (23%) of the 17 in whom HFO failed responded to conventional ventilation (p = 0.03). There were no differences between the two groups with respect to outcome, need for extracorporeal membrane oxygenation, or complications.\n We conclude that HFO is a safe and effective rescue technique in the treatment of neonates with respiratory failure in whom conventional ventilation fails.", "Although inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves oxygenation in newborn infants with persistent pulmonary hypertension, its effects are variable. We hypothesized (1) that the response to iNO therapy is dependent on the primary disease associated with persistent pulmonary hypertension of the newborn (PPHN) and (2) that the combination of high-frequency oscillatory ventilation (HFOV) with iNO would be efficacious in patients for whom either therapy alone had failed.\n To determine the relative roles of iNO and HFOV in the treatment of severe PPHN, we enrolled 205 neonates in a randomized, multicenter clinical trial. Patients were stratified by predominant disease category: respiratory distress syndrome (n = 70), meconium aspiration syndrome (n = 58), idiopathic PPHN or pulmonary hypoplasia (excluding congenital diaphragmatic hernia) (\"other\": n = 43), and congenital diaphragmatic hernia (n = 34); they were then randomly assigned to treatment with iNO and conventional ventilation or to HFOV without iNO. Treatment failure (partial pressure of arterial oxygen [PaO2] < 60 mm Hg) resulted in crossover to the alternative treatment; treatment failure after crossover led to combination treatment with HFOV plus iNO. Treatment response with the assigned therapy was defined as sustained PaO2 of 60 mm Hg or greater.\n Baseline oxygenation index and PaO2 were 48 +/- 2 and 41 +/- 1 mm Hg, respectively, during treatment with conventional ventilation. Ninety-eight patients were randomly assigned to initial treatment with HFOV, and 107 patients to iNO. Fifty-three patients (26%) recovered with the initially assigned therapy without crossover (30 with iNO [28%] and 23 with HFOV [23%]; p = 0.33). Within this group, survival was 100% and there were no differences in days of mechanical ventilation, air leak, or supplemental oxygen requirement at 28 days. Of patients whose initial treatment failed, crossover treatment with the alternate therapy was successful in 21% and 14% for iNO and HFOV, respectively (p = not significant). Of 125 patients in whom both treatment strategies failed, 32% responded to combination treatment with HFOV plus iNO. Overall, 123 patients (60%) responded to either treatment alone or combination therapy. By disease category, response rates for HFOV plus iNO in the group with respiratory syndrome and the group with meconium aspiration syndrome were better than for HFOV alone or iNO with conventional ventilation (p < 0.05). Marked differences in outcomes were noted among centers (percent death or treatment with extracorporeal membrane oxygenation = 29% to 75%).\n We conclude that treatment with HFOV plus iNO is often more successful than treatment with HFOV or iNO alone in severe PPHN. Differences in responses are partly related to the specific disease associated with PPHN.", "We previously reported improved oxygenation, but no change, in rates of extracorporeal membrane oxygenation (ECMO) use or death among infants with persistent pulmonary hypertension of the newborn who received inhaled nitric oxide (NO) with conventional ventilation, irrespective of lung disease. The goal of our study was to determine whether treatment with inhaled NO improves oxygenation and clinical outcomes in infants with persistent pulmonary hypertension of the newborn and associated lung disease who are ventilated with high-frequency oscillatory ventilation (HFOV).\n Single-center, prospective, randomized, controlled trial.\n Newborn intensive care unit of a tertiary care teaching hospital.\n We studied infants with a gestational age of > or =34 wks who were receiving mechanical ventilatory support and had echocardiographic and clinical evidence of pulmonary hypertension and hypoxemia (PaO2 < or =100 mm Hg on FIO2 = 1.0), despite optimal medical management Infants with congenital heart disease, diaphragmatic hernia, or other major anomalies were excluded.\n The treatment group received inhaled NO, whereas the control group did not. Adjunct therapies and ECMO criteria were the same in the two groups of patients. Investigators and clinicians were not masked as to treatment assignment, and no crossover of patients was permitted.\n Primary outcome variables were mortality and use of ECMO. Secondary outcomes included change in oxygenation and duration of mechanical ventilatory support and supplemental oxygen therapy. Forty-two patients were enrolled. Baseline oxygenation and clinical characteristics were similar in the two groups of patients. Infants in the inhaled NO group (n = 21) had improved measures of oxygenation at 15 mins and 1 hr after enrollment compared with infants in the control group (n = 20). Fewer infants in the inhaled NO group compared with the control group were treated with ECMO (14% vs. 55%, respectively; p = .007). Mortality did not differ with treatment assignment.\n Among infants ventilated by HFOV, those receiving inhaled NO had a reduced need for ECMO. We speculate that HFOV enhances the effectiveness of inhaled NO treatment in infants with persistent pulmonary hypertension of the newborn and associated lung disease." ]	The findings of this systematic review suggest that HFO was a promising treatment for ALI and ARDS prior to the uptake of current lung protective ventilation strategies. These findings may not be applicable with current conventional care, pending the results of large multi-centre trials currently underway.
CD003611	[ "17768579", "19144672", "18392378", "6610435", "3306163", "12595838", "10807441", "15077078", "10807440", "6982689", "14690727", "11094581", "16129870", "19261602", "16943938", "12579104", "14978593", "10993856", "17501880", "11500582", "17000910", "10385778", "16760210", "9168080", "17694684", "10463708", "12140498", "10440141", "18157419", "10440143", "10525926", "6148617", "15999046", "16214831", "11603446", "10921700", "17302724", "6965579", "10757152", "12466506", "17383335", "8817135", "9083869", "1898142", "12407614", "12238830", "15302102", "18242535", "21358799", "17599879", "9052343", "11590456", "8103611", "19996947", "10684499", "11117910", "10353130", "11265951", "10362203", "16948756", "17426275", "16380589", "15928285", "16733171", "18775050", "3871883", "12830063", "17298190", "3535474", "6979982", "18263874", "15763533", "9400034", "10942743", "11320383", "10881805", "14736444", "9237602", "19245970", "2903581", "7560608", "12866763", "15520310", "7642012", "316976", "11312480", "18657672", "10800794", "14992881", "10898425", "16326295", "16274096", "16644334", "12615792", "1860198", "12204730", "9768925", "2736988", "11786452", "9582043" ]	[ "Prevention of atrial fibrillation with moderate doses of amiodarone in the postoperative period of cardiac surgery is safe and effective in patients with high risk for developing this arrhythmia.", "Prevention of atrial fibrillation after coronary artery bypass grafting via atrial electromechanical interval and use of amiodarone prophylaxis.", "Influence of external temporary biatrial pacing on the prevention of atrial fibrillation after coronary artery bypass without extracorporeal circulation.", "Arrhythmias after coronary bypass surgery.", "Predictors, prevention, and long-term prognosis of atrial fibrillation after coronary artery bypass graft operations.", "Double-blind, placebo-controlled, randomized trial of prophylactic metoprolol for reduction of hospital length of stay after heart surgery: the beta-Blocker Length Of Stay (BLOS) study.", "Atrial pacing for the prevention of atrial fibrillation after cardiovascular surgery.", "A comparison between oral antiarrhythmic drugs in the prevention of atrial fibrillation after cardiac surgery: the pilot study of prevention of postoperative atrial fibrillation (SPPAF), a randomized, placebo-controlled trial.", "Effective prevention of atrial fibrillation by continuous atrial overdrive pacing after coronary artery bypass surgery.", "Arrhythmia prophylaxis using propranolol after coronary artery surgery.", "Prevention of atrial fibrillation after cardiac valvular surgery by epicardial, biatrial synchronous pacing.", "Intravenous amiodarone or magnesium sulphate is not cost-beneficial prophylaxis for atrial fibrillation after coronary artery bypass surgery.", "Impact of a patient decision aid on care among patients with nonvalvular atrial fibrillation: a cluster randomized trial.", "Prophylactic cavotricuspid isthmus block during atrial fibrillation ablation in patients without atrial flutter: a randomised controlled trial.", "Role of biatrial pacing in prevention of atrial fibrillation after coronary artery bypass surgery.", "Intravenous magnesium sulfate prophylaxis for atrial fibrillation after coronary artery bypass surgery.", "Effectiveness of metoprolol in preventing atrial fibrillation and flutter in the postoperative period of coronary artery bypass graft surgery.", "Randomized controlled study investigating the effect of biatrial pacing in prevention of atrial fibrillation after coronary artery bypass grafting.", "Preoperative beta-blocker use reduces atrial fibrillation in off-pump coronary bypass surgery.", "Effectiveness of bi-atrial pacing for reducing atrial fibrillation after coronary artery bypass graft surgery.", "Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery: results of the ARMYDA-3 (Atorvastatin for Reduction of MYocardial Dysrhythmia After cardiac surgery) study.", "Prophylactic oral amiodarone compared with placebo for prevention of atrial fibrillation after coronary artery bypass surgery.", "Amiodarone prophylaxis for atrial fibrillation of high-risk patients after coronary bypass grafting: a prospective, double-blinded, placebo-controlled, randomized study.", "Beta blockade to prevent atrial dysrhythmias following coronary bypass surgery.", "Magnesium infusion and postoperative atrial fibrillation: a randomized clinical trial.", "A patient decision aid regarding antithrombotic therapy for stroke prevention in atrial fibrillation: a randomized controlled trial.", "A prospective, randomized, controlled trial of an emergency department-based atrial fibrillation treatment strategy with low-molecular-weight heparin.", "Oral d,l sotalol reduces the incidence of postoperative atrial fibrillation in coronary artery bypass surgery patients: a randomized, double-blind, placebo-controlled study.", "Effect of temporary right atrial pacing in prevention of atrial fibrillation after coronary artery bypass graft surgery.", "Intravenous amiodarone for the prevention of atrial fibrillation after open heart surgery: the Amiodarone Reduction in Coronary Heart (ARCH) trial.", "[Efficacy of metoprolol in prevention of supraventricular arrhythmias after coronary artery bypass grafting].", "Prevention of ventricular fibrillation during acute myocardial infarction by intravenous propranolol.", "The effects of steroids on the occurrence of postoperative atrial fibrillation after coronary artery bypass grafting surgery: a prospective randomized trial.", "Catheter ablation treatment in patients with drug-refractory atrial fibrillation: a prospective, multi-centre, randomized, controlled study (Catheter Ablation For The Cure Of Atrial Fibrillation Study).", "Magnesium infusion dramatically decreases the incidence of atrial fibrillation after coronary artery bypass grafting.", "Prophylaxis of supraventricular and ventricular arrhythmias after coronary artery bypass grafting with low-dose sotalol.", "Temporary atrial pacing in the prevention of postoperative atrial fibrillation.", "Propranolol for prevention of postoperative cardiac arrhythmias: a randomized study.", "Arrhythmia prophylaxis after coronary artery bypass grafting: regimens of magnesium sulfate administration.", "A comparison of rate control and rhythm control in patients with atrial fibrillation.", "Practical regimen for amiodarone use in preventing postoperative atrial fibrillation.", "Efficacy and safety of low-dose propranolol versus diltiazem in the prophylaxis of supraventricular tachyarrhythmia after coronary artery bypass grafting.", "Atrial fibrillation after coronary artery bypass surgery: predictors and the role of MgSO4 replacement.", "Prophylaxis of atrial fibrillation with magnesium sulfate after coronary artery bypass grafting.", "Postoperative oral amiodarone as prophylaxis against atrial fibrillation after coronary artery surgery.", "Combination of sotalol and magnesium prevents atrial fibrillation after coronary artery bypass grafting.", "Prevention of atrial fibrillation after cardioversion: results of the PAFAC trial.", "Single procedure efficacy of isolating all versus arrhythmogenic pulmonary veins on long-term control of atrial fibrillation: a prospective randomized study.", "Evaluation of bachmann bundle pacing versus right atrial pacing in prevention of atrial fibrillation after coronary artery bypass surgery.", "Intravenous and oral amiodarone for the prevention of postoperative atrial fibrillation in patients undergoing off-pump coronary artery bypass surgery.", "Propafenone for conversion and prophylaxis of atrial fibrillation. Propafenone Atrial Fibrillation Trial Investigators.", "Effect of amiodarone on atrial fibrillation after coronary artery bypass surgery.", "Oral sotalol reduces the incidence of atrial fibrillation after coronary artery bypass surgery.", "Perioperative intravenous amiodarone does not reduce the burden of atrial fibrillation in patients undergoing cardiac valvular surgery.", "Significance of Supraventricular Tachyarrhythmias After Coronary Artery Bypass Graft Surgery and Their Prevention by Low-Dose Sotalol: A Prospective Double-Blind Randomized Placebo-Controlled Study.", "Rhythm or rate control in atrial fibrillation--Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial.", "Epicardial, biatrial synchronous pacing for prevention of atrial fibrillation after cardiac surgery.", "Oral amiodarone for prevention of atrial fibrillation after open heart surgery, the Atrial Fibrillation Suppression Trial (AFIST): a randomised placebo-controlled trial.", "Evaluation of right atrial and biatrial temporary pacing for the prevention of atrial fibrillation after coronary artery bypass surgery.", "Effect of low-dose amiodarone and magnesium combination on atrial fibrillation after coronary artery surgery.", "Corticosteroids for the prevention of atrial fibrillation after cardiac surgery: a randomized controlled trial.", "Prophylactic Oral Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularization, Valve Replacement, or Repair: PAPABEAR: a randomized controlled trial.", "Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial.", "Relationship between atrial histopathology and atrial fibrillation after coronary bypass surgery.", "Catheter ablation of atrial fibrillation in patients with diabetes mellitus type 2: results from a randomized study comparing pulmonary vein isolation versus antiarrhythmic drug therapy.", "Arrhythmia prophylaxis after aorta-coronary bypass. The effect of minidose propranolol.", "Amiodarone reduces the incidence of atrial fibrillation after coronary artery bypass grafting.", "Randomized clinical trial of a postdischarge pharmaceutical care program vs regular follow-up in patients with heart failure.", "Prevention of atrial fibrillation or flutter by acebutolol after coronary bypass grafting.", "Efficacy of low-dose propranolol in preventing postoperative supraventricular tachyarrhythmias: a prospective, randomized study.", "N-acetylcysteine for the prevention of postoperative atrial fibrillation: a prospective, randomized, placebo-controlled pilot study.", "Right atrial overdrive pacing does not prevent atrial fibrillation after coronary artery bypass surgery.", "Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery.", "Effects of biatrial pacing in prevention of postoperative atrial fibrillation after coronary artery bypass surgery.", "Single-day loading dose of oral amiodarone for the prevention of new-onset atrial fibrillation after coronary artery bypass surgery.", "Intraoperative amiodarone as prophylaxis against atrial fibrillation after coronary operations.", "Effect of rate or rhythm control on quality of life in persistent atrial fibrillation. Results from the Rate Control Versus Electrical Cardioversion (RACE) Study.", "Beta-blocker effects on postoperative atrial fibrillation.", "A randomized assessment of the incremental role of ablation of complex fractionated atrial electrograms after antral pulmonary vein isolation for long-lasting persistent atrial fibrillation.", "Supraventricular tachyarrhythmias after coronary bypass surgery--a double blind randomized trial of prophylactic low dose propranolol.", "Efficacy and proarrhythmic hazards of pharmacologic cardioversion of atrial fibrillation: prospective comparison of sotalol versus quinidine.", "A randomized clinical trial of the efficacy of radiofrequency catheter ablation and amiodarone in the treatment of symptomatic atrial fibrillation.", "Prevention of iatrogenic atrial tachycardia after ablation of atrial fibrillation: a prospective randomized study comparing circumferential pulmonary vein ablation with a modified approach.", "[A comparison between flecainide and sotalol in the prevention of recurrences of paroxysmal atrial fibrillation].", "beta-Blockade therapy for supraventricular tachyarrhythmias after coronary surgery: a propranolol withdrawal syndrome?", "A beta-blocker, not magnesium, is effective prophylaxis for atrial tachyarrhythmias after coronary artery bypass graft surgery.", "The effects of atorvastatin on the occurrence of postoperative atrial fibrillation after off-pump coronary artery bypass grafting surgery.", "Ineffectiveness and potential proarrhythmia of atrial pacing for atrial fibrillation prevention after coronary artery bypass grafting.", "The efficacy of supplemental magnesium in reducing atrial fibrillation after coronary artery bypass grafting.", "Use of metoprolol CR/XL to maintain sinus rhythm after conversion from persistent atrial fibrillation: a randomized, double-blind, placebo-controlled study.", "Perioperative magnesium supplementation to prevent atrial fibrillation after off-pump coronary artery surgery: a randomized controlled study.", "Effectiveness of triple-site triggered atrial pacing for prevention of atrial fibrillation after coronary artery bypass graft surgery.", "Antiarrhythmic efficacy of azimilide in patients with atrial fibrillation. Maintenance of sinus rhythm after conversion to sinus rhythm.", "Asymptomatic or \"silent\" atrial fibrillation: frequency in untreated patients and patients receiving azimilide.", "Stroke Prevention in Atrial Fibrillation Study. Final results.", "The effect of preoperative digitalis and atenolol combination on postoperative atrial fibrillation incidence.", "Modifying risk for extracorporeal circulation: trial of four antiinflammatory strategies.", "Prophylactic treatment of postperfusion bleeding using EACA.", "Brief intervention during hospital admission to help patients to give up smoking after myocardial infarction and bypass surgery: randomised controlled trial.", "Effect of local medical opinion leaders on quality of care for acute myocardial infarction: a randomized controlled trial." ]	[ "To assess if prophylaxis with moderate doses of amiodarone in the postoperative period of cardiac surgery (coronary artery bypass grafting and/or valve surgery), reduces the incidence of atrial fibrillation in patients with high risk for developing this arrhythmia.\n A randomized and prospective clinical study involving 68 patients who underwent elective cardiac surgery. Mean age was 64 years and 59% of participants were males. Patients with three or more risk factors for atrial fibrillation, according to the literature, were randomized into two groups to receive or not prophylaxis with amiodarone in the first postoperative day. The dose administered ranged from 600 mg/day to 900 mg/day, intravenously, on the first postoperative day, followed by 400 mg/day orally until hospital discharge or until completing seven days. The other patients, who presented two or fewer risk factors, were followed up until hospital discharge. All patients were evaluated by means of cardiac and/or electrocardiographic monitoring.\n In the group treated with amiodarone, 7% of patients presented atrial fibrillation, whereas in the control group 70% of patients developed arrhythmia. Among the non-randomized individuals (with two or fewer risk factors), only 24% presented atrial fibrillation.\n The prophylactic use of amiodarone was effective in the prevention of atrial fibrillation in patients with three or more risk factors for this arrhythmia. This treatment can be useful to reduce stay at the Intensive Care Unit and, consequently, the complications originating from longer hospitalization.", "In our previous study, we defined a cut-off point of 120 ms for atrial electromechanical interval (AEMi) to determine the risk of atrial fibrillation (AF) occurrence. Accordingly, the present study sought to investigate whether or not a prophylactic perioperative administration of amiodarone could reduce the incidence of AF in a high-risk group (AEMi >120 ms) undergoing coronary artery bypass grafting (CABG). In this prospective, randomized study, 100 patients with AEMi >120 ms received either amiodarone (n=50) or placebo (n=50). The endpoints were AF occurrence after CABG and hospital and intensive care unit (ICU) lengths of stay after CABG. The incidence of postoperative AF was significantly higher in the placebo group than that of the amiodarone group (88% of patients in control group vs. 16% of patients in amiodarone group, P<0.0001). The prophylactic therapy with amiodarone significantly reduced the ICU length of stay (2.28+/-1.00 vs. 3.60+/-0.90 days, P<0.0001) and hospital length of stay (5.64+/-2.35 vs. 7.78+/-1.46 days, P<0.0001). The incidence of postoperative AF among patients with high AEMi was significantly reduced by a prophylactic amiodarone treatment, resulting in shorter ICU and hospital stays.", "Atrial fibrillation is the most common complication after myocardial revascularization, and it increases morbidity/mortality.\n The purpose of this prospective randomized study was to test the hypothesis that temporary biatrial pacing is effective in reducing the incidence of postoperative atrial fibrillation after myocardial revascularization.\n Ninety-eight non-consecutive patients who had undergone off-pump myocardial revascularization received two temporary electrodes attached to the right and left atria, which were connected to either pair of atrial pacemaker electrodes, in addition to the leads implanted in the right ventricle. Two groups of patients were randomized (control: 49 patients with no biatrial pacing; therapeutic: 49 patients with biatrial pacing). The variables of interest were atrial fibrillation (present or absent) and length of hospital stay.\n The incidence of atrial fibrillation was 36.73% in the control group and 14.29% in the therapeutic group (p=0.0194). Length of hospital stay was 7.00 +/- 2.82 days for patients with no atrial fibrillation (n=73) and 9.20 +/- 2.87 days for patients with atrial fibrillation (n=25) (p=0.0001). Age was an important predictor of arrhythmia and ranged between 62.34 +/- 9.00 years in the group with no atrial fibrillation and 67.20 +/- 7.42 years in the group with atrial fibrillation (p=0.0170).\n Compared to controls, prophylactic temporary biatrial pacing is effective in preventing atrial fibrillation. Hospital stay was longer for patients who developed postoperative atrial fibrillation, and age was an important predictor for the development of arrhythmia.", "Ninety patients undergoing coronary bypass surgery were studied prospectively by bedside and subsequent ambulatory electrocardiographic monitoring to investigate the incidence, possible causes, and prevention of atrial fibrillation. Patients with good left ventricular function were divided randomly into a control group or groups treated with digoxin or propranolol. In the control group the incidence of atrial fibrillation was 27% and of significant ventricular extrasystoles 3%. Propranolol reduced the incidence of atrial fibrillation (14.8%), whereas digoxin had no effect and increased the incidence of ventricular extrasystoles. Age, sex, severity of symptoms, cardiomegaly, heart failure, previous myocardial infarction, and number of grafts did not affect the result. The operative myocardial ischaemic time was related to the occurrence of atrial fibrillation. There was also a significant relation between atrial fibrillation and bundle branch block. Atrial fibrillation is common after coronary artery grafting; it may be due to diffuse myocardial ischaemia or hypothermic injury. The incidence may be reduced by beta blockade.", "Multiple trials have suggested the use of digoxin, digoxin and propranolol, or timolol to prevent atrial fibrillation after coronary artery bypass grafting. No trial has evaluated the efficacy of digoxin verus propranolol. Furthermore, the predictors of postoperative atrial fibrillation and the long-term consequence of atrial fibrillation that reverts to sinus rhythm have not been established. One hundred fifty patients were randomized to receive no drug, propranolol (20 mg every 6 hours), or digoxin (0.5 mg followed by 0.25 mg daily). Twenty-seven patients were excluded from data analysis. In the remaining 123 patients, no preoperative parameter (age, sex, diabetes, hypertension, smoking, electrocardiographic p wave morphology, or preoperative digoxin or propranolol therapy), intraoperative parameter (bypass time, aortic cross-clamp time, or number of vessels bypassed), or postoperative parameter (peak creatinine kinase, congestive heart failure, or pericarditis) by univariate or multivariate analysis predicted patients at risk for atrial fibrillation. Sustained atrial fibrillation developed in 37.5% of control and 32.6% of digoxin-treated patients. Only 16.2% of propranolol-treated patients had sustained atrial fibrillation (p less than 0.03). There were no in-hospital complications in those patients with atrial fibrillation. After 26 +/- 7 months follow-up, those patients with postoperative atrial fibrillation had no increased incidence of angina, cerebral vascular accident, myocardial infarction, or sudden death. Therefore, in this select population, propranolol prophylaxis is effective but discretionary.", "Atrial fibrillation (AF) is a common complication of heart surgery. Previous studies have shown that there is an association between postoperative AF and prolongation of hospital length of stay. No previous trials have been primarily directed at demonstrating that the use of drugs that prevent AF would shorten length of stay and reduce the costs of postoperative care.\n A randomized, double-blind, placebo-controlled trial of metoprolol was performed in patients immediately after nonemergent heart surgery. Metoprolol was given orally at a dose of 100 mg per day after the patient's arrival in the intensive care unit until hospital discharge or 14 days, whichever was sooner. This dose was increased to 150 mg per day after the enrollment of 411 patients. The primary outcome measure of the study was hospital length of stay from admission to intensive care unit until hospital discharge. There were 1000 patients enrolled, evenly distributed to the metoprolol and placebo groups.\n There was a 20% reduction in the risk of AF developing with metoprolol, from 39% of patients to 31% of patients (P =.01). There was no effect of treatment on hospital length of stay, which was 152 +/- 61 hours for placebo and 155 +/- 90 hours for metoprolol (P = 0.79). The cost of postoperative care in the 2 treatment groups was similar.\n Prophylactic metoprolol reduces the risk of AF after heart surgery. It does not reduce hospital length of stay. Although it is cost effective for the reduction of AF, it did not reduce the overall cost of care.", "The purpose of this study was to determine the efficacy of atrial pacing in the prevention of atrial fibrillation following cardiovascular surgery.\n Although pharmacologic therapy has been used to help prevent postoperative atrial fibrillation, it suffers from limited efficacy and adverse effects. In the nonoperative setting, novel pacing strategies have been shown to reduce recurrences of atrial fibrillation and prolong arrhythmia-free periods in patients with paroxysmal atrial arrhythmias.\n A total of 154 patients (115 men; mean age, 65 +/- 10 years; ejection fraction, 53 +/- 10%) undergoing cardiac surgery (coronary artery bypass surgery, 88.3%; aortic valve replacement, 4.5%; coronary bypass + aortic valve replacement, 7.1%) had right and left atrial epicardial pacing electrodes placed at the time of surgery. Patients were randomized to either no pacing, right atrial (RAP), left atrial (LAP) or biatrial pacing (BAP) for 72 h after surgery. Beta-adrenergic blocking agents were administered concurrently to all patients following surgery.\n There was a reduction in the incidence of postoperative atrial fibrillation from 37.5% in patients receiving no postoperative pacing to 17% (p < 0.005) in patients assigned to one of the three pacing strategies. The length of hospital stay was reduced by 22% from 7.8 +/- 3.7 days to 6.1 +/- 2.3 days (p = 0.003) in patients assigned to postoperative atrial pacing. The incidence of atrial fibrillation was lower in each of the paced groups (RAP, 8%; LAP, 20%; BAP, 26%) compared with patients who did not receive postoperative pacing (37.5%).\n Postoperative atrial pacing, in conjunction with beta-blockade, significantly reduced both the incidence of atrial fibrillation and the length of hospital stay following cardiovascular surgery. Additional studies are needed to determine the most effective anatomic pacing site.", "Atrial fibrillation (AF) frequently occurs after cardiac surgical procedures, and beta-blockers, sotalol, and amiodarone may reduce the frequency of AF after open heart surgery. This pilot trial was designed to test whether each of the active oral drug regimens is superior to placebo for prevention of postoperative AF and whether there are differences in favor of 1 of the preventive strategies.\n We conducted a randomized, double-blinded, placebo-controlled trial in which patients undergoing cardiac surgery in the absence of heart failure and without significant left ventricular dysfunction (n = 253; average age, 65 +/- 11 years) received oral amiodarone plus metoprolol (n = 63), metoprolol alone (n = 62), sotalol (n = 63), or placebo (n = 65). Patients receiving combination therapy (amiodarone plus metoprolol) and those receiving sotalol had a significantly lower frequency of AF (30.2% and 31.7%; absolute difference, 23.6% and 22.1%; odds ratios [OR], 0.37 [95% CI, 0.18 to 0.77, P <.01 vs placebo] and 0.40 [0.19 to 0.82, P =.01 vs placebo]) compared with patients receiving placebo (53.8%). Treatment with metoprolol was associated with a 13.5% absolute reduction of AF (P =.16; OR, 0.58 [0.29 to 1.17]. Treatment effects did not differ significantly between active drug groups. Adverse events including cerebrovascular accident, postoperative ventricular tachycardia, nausea, and dyspepsia, in hospital death, postoperative infections, and hypotension, were similar among the groups. Bradycardia necessitating dose reduction or drug withdrawal occurred in 3.1% (placebo), 3.2% (combined amiodarone and metoprolol; P =.65 vs placebo), 12.7% (sotalol; P <.05 vs placebo), and 16.1% (metoprolol; P <.05 vs placebo). Patients in the placebo group had a nonsignificantly longer length of hospital stay as compared with the active treatment groups (13.1 +/- 8.9 days vs 11.3 +/- 7; P =.10), with no significant difference between the active treatment groups.\n Oral active prophylaxis with either sotalol or amiodarone plus metoprolol may reduce the rate of AF after cardiac surgery in a population at high risk for postoperative AF. Treatment with metoprolol alone resulted in a trend to a lower risk for postoperative AF.", "The present study was aimed to evaluate the efficacy of a specific algorithm with continuous atrial dynamic overdrive pacing to prevent atrial fibrillation (AF) after coronary artery bypass graft (CABG) surgery.\n Atrial fibrillation occurs in 30% to 40% of patients after cardiac surgery with a peak incidence on the second day. It still represents a challenge for postoperative prevention and treatment and may have medical and cost implications.\n Ninety-six consecutive patients undergoing CABG for severe coronary artery disease and in sinus rhythm without antiarrhythmic therapy on the second postoperative day were randomized to have or not 24 h of atrial pacing through temporary epicardial wires using a permanent dynamic overdrive algorithm. Holter ECGs recorded the same day in both groups were analyzed to detect AF occurrence.\n No difference was observed in baseline data between the two study groups, particularly for age, male gender, history of AF, ventricular function, severity of coronary artery disease, preoperative beta-adrenergic blocking agent therapy or P-wave duration. The incidence of AF was significantly lower (p = 0.036) in the paced group (10%) compared with control subjects (27%). Multivariate analysis showed AF incidence to increase with age (p = 0.051) but not in patients with pacing (p = 0.078). It decreased with a better left ventricular ejection fraction only in conjunction with atrial pacing (p = 0.018).\n We conclude that continuous atrial pacing with an algorithm for dynamic overdrive reduces significantly incidence of AF the second day after CABG surgery, particularly in patients with preserved left ventricular function.", "Sixty patients undergoing coronary artery bypass grafting operations with cold potassium cardioplegia as the method of myocardial preservation either received low-dose oral propranolol (10 mg every 6 hours; 28 patients) or served as controls (32 patients). The study period began after extubation and ended at the time of hospital discharge. On the fourth postoperative day, 24-hour Holter monitoring was performed to assess additional subtle differences in arrhythmias. The overall incidence of symptomatic postoperative arrhythmias was 31% in the control group: 6 patients (19%) had atrial fibrillation or flutter and 4 patients (12%), ventricular arrhythmias. By contrast, 1 patient (4%) in the propranolol group had atrial fibrillation, and no patient had ventricular arrhythmias. The difference in overall arrhythmia rates between the two groups is significant (p less than 0.025). Twenty-four-hour Holter monitoring demonstrated no additional differences in the frequency of simple or complex atrial or ventricular ectopy between the two groups. We conclude that the incidence of postoperative arrhythmias following coronary artery bypass operation is diminished by the oral administration of prophylactic low-dose propranolol. When compared with our previous study [1], in which the method of myocardial preservation was intermittent aortic cross-clamping and moderate hypothermia, there is no difference in the overall incidence of postoperative arrhythmias.", "Postoperative atrial fibrillation (AF) after cardiac surgery is a frequent complication after valvular surgery (30-60%). The purpose of this prospective, randomized study was to determine if biatrial synchronous pacing reduces postoperative AF after cardiac valvular surgery as compared to conventional therapy.\n Eighty patients subjected to valvular surgery (52 men, age 66 +/- 10 years) were randomized to one of two groups: one group was treated with biatrial, synchronous pacing (BAP) for 72 h postoperatively (n=40) the other group received no atrial pacing (controls; n=40). All patients had one pair of epicardial wires attached to the right atrium. An additional electrode was placed to the left atrium in the BAP group. These patients were continuously paced at a rate of 10 beats per minute higher than the intrinsic rate starting immediately after surgery. All patients were monitored with full disclosure telemetry or Holter monitors to identify onset of AF.\n Eighteen of the 40 patients in the control group (45%) developed AF within the first 3 days postoperatively as compared to eight patients (20%) in the BAP group (P=0.02). No complications occurred associated with the placement, maintenance and removal of the atrial pacing electrodes.\n Temporary, biatrial synchronous pacing during the first 3 postoperative days is safe and has a significant rhythm-stabilizing effect in patients undergoing valvular cardiac surgery.", "Our aims were to examine whether the administration of amiodarone or magnesium sulphate after coronary artery bypass graft surgery (CABG) could reduce the occurrence of atrial fibrillation, and to identify the risk factors associated with atrial fibrillation after CABG. Patients scheduled for elective CABG (n = 155) were allocated randomly, in a controlled double-blind study, to receive immediately after surgery a 72-h infusion of amiodarone (900 mg per 24 h), magnesium (4 g per 24 h) or placebo (0.9% NaCl; 50 ml per 24 h) intravenously. A 72-h Holter ECG was recorded concomitantly. The primary end-point was the prevention of atrial fibrillation; its onset was considered as prophylactic failure. An interim safety analysis was performed in 147 patients. The cumulative occurrence of atrial fibrillation was 27% in the placebo group, 14% in the amiodarone group (P = 0.14) and 23% in the magnesium group (P = 0.82). Although amiodarone delayed the onset of the first tachyarrhythmic episode (P = 0.02), it was associated with the need for longer periods of vasoactive drug infusion and invasive monitoring and a longer stay in the intensive care unit. Variables associated with the onset of atrial fibrillation were older age (odds ratio 1.9) and a plasma magnesium concentration at 24 h of less than 0.95 mmol litre-1 (odds ratio 6.7). Postoperative administration of amiodarone reduced the occurrence of atrial fibrillation after elective CABG surgery, but was associated with a longer duration of cardiovascular instability and longer need for intensive care; magnesium prophylaxis had no effect. Advanced age and a low plasma magnesium concentration are risk factors for postoperative atrial fibrillation.", "Too few patients with nonvalvular atrial fibrillation (NVAF) receive appropriate antithrombotic therapy. We tested the short-term (primary outcome) and long-term (secondary outcome) effect of a patient decision aid on the appropriateness of antithrombotic therapy among patients with NVAF.\n We conducted a cluster randomized trial with blinded outcome assessment involving 434 NVAF patients from 102 community-based primary care practices. Patients in the intervention group received a self-administered booklet and audiotape decision aid tailored to their personal stroke risk profile. Patients in the control group received usual care. The primary outcome measure was change in antithrombotic therapy at 3 months. Appropriateness of therapy was defined using the American College of Chest Physicians (ACCP) recommendations.\n The mean patient age was 72 years, and the median duration of NVAF was 5 years. In the control group, there was a 3% decrease over 3 months in the number of patients receiving therapy appropriate to their risk of stroke (40% [85/215] at baseline v. 37% [79/215] at 3 months). In the intervention group, the number of patients receiving therapy appropriate to their stroke risk increased by 9% (32% [69/219] at baseline v. 41% [89/219] at 3 months). Although the proportion of patients whose therapy met the ACCP treatment recommendations did not differ between study arms at baseline (p = 0.11) or 3 months (p = 0.44), there was a 12% absolute improvement in the number of patients receiving appropriate care in the intervention group compared with the control group at 3 months (p = 0.03). The beneficial effect of the decision aid did not persist (p = 0.44 for differences between study arms after 12 months).\n There was short-term improvement in the appropriateness of antithrombotic care among patients with NVAF who were exposed to a decision aid, but the improvement did not persist.", "This randomised trial evaluated if patients with atrial fibrillation (AF) and no history of atrial flutter (AFL) had any benefit of prophylactic cavotricuspid isthmus block (CTIB) in addition to circumferential pulmonary vein ablation (CPVA).\n 149 patients with AF (54% paroxysmal) were randomised to CPVA and CTIB (group CTIB+, n = 73) or CPVA alone (group CTIB-, n = 76). Patients were followed for 12 months with repetitive 7-day Holter monitoring after 3, 6 and 12 months.\n Six patients (4%) had cardiac tamponade, and one patient had a stroke. No difference was found in the cumulative AFL-free rate between the two treatment groups (CTIB+: 88% vs CTIB-: 84%, hazard ratio (HR) 0.80, 95% CI (0.34 to 1.90), p = 0.61). There was no difference in the cumulative AF-free rate between the groups (CTIB+: 34% vs CTIB-: 32%, HR 0.93, 95% CI (0.63 to 1.38), p = 0.71). Overall, 33% of the patients were free of AF after a single procedure. Including reprocedures, a complete or partial beneficial effect was noted in 62% of the patients at 12 months. At 12-month follow-up, 24 (50%) patients with documented AF or AFL in the Holter recordings were asymptomatic.\n It was not possible to demonstrate any beneficial effect of CTIB in addition to CPVA with regard to AFL or AF recurrences during follow-up. Repetitive long-term Holter monitoring demonstrated a 33% rate of freedom from AF during a 1-year follow-up. Including additional CPVA procedures, a clinical effect was noted in 62% of the patients at 12 months. Patients with AF or AFL recurrences were often asymptomatic.", "Atrial fibrillation (AF) after coronary artery bypass graft surgery (CABG) constitutes the most common sustained arrhythmia and results in prolonged hospitalization. The purpose of this study was to assess simultaneous right and left atrial pacing as prophylaxis for postoperative atrial fibrillation.\n From July 2003 to May 2004, 120 patients without structural heart disease and who underwent CABG were randomly classified into one of the following 3 groups: biatrial pacing (BAP), left atrial pacing (LAP), and no pacing (control). Atrial pacing was performed for 4 days. Post-CABG AF was significantly reduced in BAP group compared to single-site and control group (BAP, 17.5%; LAP, 30%; control, 45%; p=0.02). The mean length of hospital stay was significantly reduced in BAP group. Hospital charges were not significantly different between three groups. The mean length of hospital stay was most significantly reduced in BAP group (6.1+/-1.2 versus 9.0+/-4.1 days in the control groups; p=0.002, and 8.7+/-1.3 days in LAP groups; p=0.01). The mean length of stay in the intensive care unit was also significantly reduced in the BAP group (2.8+/-0.7 versus 4.6+/-4.5 days in control group; p=0.04, and 4.2+/-3.2 days in LAP group; p=0.01).\n Simultaneous right and left atrial pacing is well tolerated and is more effective in preventing post-CABG AF than single-site pacing, and, results in a shortened hospital stay. Identifying patients at risk for developing postoperative AF and using this prophylactic method may be the optimal effective strategy.", "Atrial fibrillation is a rhythm disorder commonly seen early after coronary artery bypass grafting, and it increases morbidity.\n To investigate the effectiveness of magnesium sulfate in the prophylaxis of atrial fibrillation, we conducted a prospective, randomized, placebo-controlled clinical study on 200 consecutive patients in whom we performed elective and initial coronary artery bypass grafting operations. In each group 50% of patients underwent beating-heart operations. In the treatment group 100 patients (76 men and 24 women; mean age, 57.63 +/- 9.68 years) received 24.34 mEq (3 g) of magnesium sulfate in 100 mL of saline solution that was administered over 2 hours (50 mL/h) preoperatively, perioperatively, and at postoperative days 0, 1, 2, and 3. In the control group 100 patients (74 men and 26 women; mean age, 59.96 +/- 9.29 years) received only 100 mL of saline solution according to the same administration schedule as the treatment group.\n Atrial fibrillation developed in 15 patients from the treatment group and in 16 patients from the control group. The arrhythmia developed after 37.87 +/- 12.76 and 45.26 +/- 15.27 hours in the treatment and control groups, respectively. Although a significant relationship was found between low magnesium sulfate levels and increased incidence of atrial fibrillation (P <.05), when the incidence of postoperative atrial fibrillation is concerned, no significant difference was found between the 2 groups (P >.05). Also, no significant difference was found between operations with cardiopulmonary bypass and beating-heart operations in terms of atrial fibrillation incidence (P >.05). However, atrial fibrillation extended the duration of hospital stay in both groups (P <.05).\n Our findings indicate that magnesium sulfate infusion alone is not sufficient for the prophylaxis of atrial fibrillation.", "To assess the effectiveness of metoprolol in preventing clinically detectable atrial fibrillation (AF) and flutter after coronary artery bypass graft (CABG) surgery.\n An open, randomized study was carried out to treat 200 patients who had undergone isolated CABG surgery with extracorporeal circulation. The patients were randomized to either receive metoprolol orally or not to receive the medication in the postoperative period. The outcomes were the detection of sustained atrial AF and flutter, which were symptomatic or required treatment. The patients with the following characteristics were excluded from the study: baseline left ventricular ejection fraction < 35%; previous AF; history of bronchospasm; second- and third-degree atrioventricular blocks, low cardiac output, and heart failure.\n Arrhythmias occurred in 11 out of 100 patients in the metoprolol group and in 24 out of 100 patients in the control group (P=0.02). The relative risk (RR) was 0.46 (95% CI = 0.24-0.88), and the number necessary to treat (NNT) and avoid the outcome was 8 patients. AF was the arrhythmia most frequently observed (30/35). In 38 patients aged 70 years or more, the arrhythmias occurred in 2 out of 19 patients in the metoprolol group and in 10 out of 19 patients in the control group (c2 Yates: P=0.01). The relative risk was 0.20 (95% CI = 0.05-0.79) and the number necessary to treat was 2 patients.\n Metoprolol is effective in preventing AF and flutter in the postoperative period of CABG surgery, and this effect was more evident in the group of elderly patients.", "Atrial fibrillation (AF) is a common problem after CABG. Prevention with prophylactic drug therapy has had limited success, therefore alternative approaches are required. This study investigated the role of biatrial pacing compared with no pacing on AF incidence after isolated first-time CABG.\n During surgery, temporary pacing leads were placed in the lateral wall of the right atrium and at the roof of the left atrium in Bachmann's bundle to allow bipolar pacing and sensing at each site. After surgery, all patients were connected to an external pacemaker (Chorum ELA) that also acted as a Holter monitor. Patients were consecutively randomized to either 4 days of biatrial pacing at a base rate of 80 bpm or to no pacing (control group, base rate 30 bpm). End points included an episode of AF lasting >1 hour on pacemaker Holter, clinically detected AF, intensive care unit (ICU) and hospital stay, and postoperative complications. One hundred thirty patients were randomized. Biatrial pacing significantly reduced both monitored (13.8% versus 38.5%, P:=0.001) and clinical (10.8% versus 33.8%, P:=0.002) episodes of AF. Median ICU (19 versus 24 hours, P:=NS) and mean hospital stay (7.7+/-6.9 versus 9.7+/-10, P:=NS) did not significantly change. The number of postoperative complications was lower in the biatrial group (13 versus 35, P:=0. 001).\n Biatrial pacing after CABG significantly decreases the incidence of AF. This is associated with reduced postoperative complications and a trend toward reduced ICU and hospital stay.", "Atrial fibrillation (AF) after coronary artery bypass graft surgery constitutes the most common sustained arrhythmia and results in many complications. The purpose of this study was to assess the effects of prophylactic use of beta-blockers against atrial fibrillation in off-pump surgery patients in the early postoperative period.\n From 2002 to 2005, 78 patients were enrolled and 41 patients received 50 mg metoprolol succinate daily, which was initiated minimum four days before surgery. Preoperative beta-blocking therapy was continued until the morning of surgery. Thirty-seven patients were free of beta-blocker therapy. Esmolol was used within same range of doses in both groups during operations. Both groups received metoprolol succinate following operations. The frequency of AF occurrence was analysed from the operation time to the sixth postoperative day. Results: Sixteen patients developed AF with an overall incidence of 22.5%. Four patients from the study group and three patients from the control group were excluded from the study because of transfer to on-pump surgery. There was no difference with regard to the number of grafts carried out, duration of operations and ventilation, intensive care unit stay and inotropic need among groups. Length of hospital stay did not differ among groups either. There was a higher incidence of postoperative AF in patients without beta-blocker prophylaxis (11.7-32.4% P=0.049).\n Low-dose postoperative beta-adrenergic blockade is valuable for patients who receive these medications before off-pump coronary artery bypass grafting procedures and may be beneficial against AF in all patients.", "Atrial fibrillation (AF) is common after cardiac surgery and adds significant cost and morbidity. The use of prophylactic pacing strategies to prevent post-operative AF has been controversial. We previously performed a pilot study which suggested that the combination of beta-blockers and bi-atrial pacing (BAP) may reduce AF after cardiac surgery. We prospectively randomized 118 patients to continuous BAP for up to 96 hours post-operatively versus standard therapy. All patients were treated with beta-blockers as tolerated. Patients were paced in the AAI mode at a rate of 100 pulses per minute. The primary endpoint of the study was the occurrence of sustained AF (>10 minutes). There was a significant reduction in the incidence of AF in the BAP group among patients undergoing coronary artery bypass graft surgery with or without aortic valve replacement (35 % vs. 19 % AF; OR=0.38, 95 % CI 0.15, 0.93; p <0.05). Including patients undergoing isolated aortic valve surgery (n=7), there remained a strong trend toward a reduction of AF with pacing (no atrial pacing [NAP] vs. BAP; 35 % vs. 21 % AF; OR=0.48, 95 % CI 0.21, 1.11; p=0.08). Patients age 70 or greater benefited most from pacing (NAP vs. BAP; 55 vs. 25 % AF; p<0.05), while those less than 70 years of age did not (17 vs. 18 % p=NS). There was a significant reduction in the amount of time spent in the intensive care unit among patients receiving BAP (50+/-40 vs. 37+/-25 h; p<0.05).BAP together with beta-blockade after coronary artery bypass graft surgery reduces the incidence of post-operative atrial AF. Elderly patients (age 70 or greater) appear to benefit most, and may be a group to whom this therapy should be targeted.", "Atrial fibrillation (AF) after cardiac surgery is associated with increased risk of complications, length of stay, and cost of care. Observational evidence suggests that patients who have undergone previous statin therapy have a lower incidence of postoperative AF. We tested this observation in a randomized, controlled trial.\n Two hundred patients undergoing elective cardiac surgery with cardiopulmonary bypass, without previous statin treatment or history of AF, were enrolled. Patients were randomized to atorvastatin (40 mg/d, n=101) or placebo (n=99) starting 7 days before operation. The primary end point was incidence of postoperative AF; secondary end points were length of stay, 30-day major adverse cardiac and cerebrovascular events, and postoperative C-reactive protein (CRP) variations. Atorvastatin significantly reduced the incidence of AF versus placebo (35% versus 57%, P=0.003). Accordingly, length of stay was longer in the placebo versus atorvastatin arm (6.9+/-1.4 versus 6.3+/-1.2 days, P=0.001). Peak CRP levels were lower in patients without AF (P=0.01), irrespective of randomization assignment. Multivariable analysis showed that atorvastatin treatment conferred a 61% reduction in risk of AF (odds ratio 0.39, 95% confidence interval 0.18 to 0.85, P=0.017), whereas high postoperative CRP levels were associated with increased risk (odds ratio 2.0, 95% confidence interval 1.2 to 7.0, P=0.01). The incidence of major adverse cardiac and cerebrovascular events at 30 days was similar in the 2 arms.\n Treatment with atorvastatin 40 mg/d, initiated 7 days before surgery, significantly reduces the incidence of postoperative AF after elective cardiac surgery with cardiopulmonary bypass and shortens hospital stay. These results may influence practice patterns with regard to adjuvant pharmacological therapy before cardiac surgery.", "Postoperative atrial fibrillation occurs in 20% to 40% of patients undergoing coronary artery bypass grafting (CABG) and contributes to delayed recovery, increased length of stay, and increased hospital cost. Measures at preventing postoperative atrial fibrillation have had mixed results. We report a double-blind trial comparing oral amiodarone with placebo for the prevention of atrial fibrillation after CABG.\n All patients undergoing CABG were considered eligible. Exclusion criteria included bradycardia (<50 beats/min), prior Atrial fibrillation, concurrent therapy with antiarrhythmic drugs, or concomitant valve surgery. Patients were given 2 g of amiodarone (73 patients) or placebo (70 patients) in divided doses 1 to 4 days before surgery and 400 mg daily for 7 days postoperatively. Atrial fibrillation occurred in 24.7% (18 of 43) of patients receiving amiodarone and 32. 8% (23 of 70) of patients receiving placebo (P =.30). Heart rate at onset of atrial fibrillation was 133.4 +/- 26.6 beats/min for amiodarone compared with 152.9 +/- 31.6 beats/min for placebo (P =. 04). Duration of atrial fibrillation was 10.2 +/- 8.1 hours for amiodarone compared with 16.2 +/- 27.5 hours for placebo (P =.67). Patients receiving both beta-blockade and amiodarone had a 16.7% incidence of atrial fibrillation compared with 31.9% in the remaining patients (P =.10). Atrial fibrillation was associated with an increased cost of $7011 compared with those who remained in sinus rhythm ($23,869 +/- $20,894 vs $16,857 +/- $5401 in sinus rhythm). Hospital cost of those taking amiodarone was $18,895 +/- $13,267 compared with $18,839 +/- $11,537.18 for placebo (P =.42).\n Postoperative CABG atrial fibrillation is associated with prolonged hospital stay and increased cost. Prophylactic oral amiodarone did not statistically alter the incidence or duration of atrial fibrillation after CABG, although favorable trends were noted. Hospital cost was not affected by therapy with amiodarone.", "Atrial fibrillation (AF) occurs often in patients after coronary artery bypass grafting (CABG) and can result in increased morbidity and mortality. Previous studies using P-wave signal-averaged electrocardiogram (P-SAECG) have shown that patients with a longer filtered P-wave duration (FPD) have a high risk of AF after CABG. We have shown that patients with an FPD > or = 124 ms and a root-mean-square voltage of the last 20 ms of the P-wave 20 < or = 3.7 microV have an increased risk of AF after surgery. Accordingly, the aim of this study was to investigate whether or not prophylactic peri-operative administration of amiodarone could reduce the incidence of AF in this high-risk group undergoing CABG identified by P-SAECG.\n In this prospective, double-blinded, placebo-controlled, randomized study, 110 patients received either amiodarone (n = 55) or placebo (n = 55). During CABG, two patients of both groups died. Amiodarone was given as 600 mg oral single dose one day before and from days 2 through 7 after surgery. In addition, amiodarone was also administered intravenously during surgery in a 300-mg bolus for 1 h and as a total maintenance dose of 20 mg/kg weight over 24 h on the first day following surgery. The primary endpoint was the occurrence of AF after CABG. The secondary endpoint was the hospitalization length of stay after CABG. The baseline characteristics were similar in both treatment groups. The incidence of post-operative AF was significantly higher in the placebo group compared with the amiodarone group (85 vs. 34% of patients, P < 0.0001). The prophylactic therapy with amiodarone significantly reduced the intensive care (1.8 +/- 1.7 vs. 2.4 +/- 1.5 days, P = 0.001) and hospitalization length of stay (11.3 +/- 3.4 vs. 13.0 +/- 4.3 days, P = 0.03). In the amiodarone group, concentrations of amiodarone and desethylamiodarone differed significantly between patients with AF and sinus rhythm (amiodarone: 0.96 +/- 0.5 vs. 0.62 +/- 0.4 microg/mL, P = 0.02; desethylamiodarone: 0.65 +/- 0.2 vs. 0.48 +/- 0.1 microg/mL, P = 0.04).\n The incidence of post-operative AF among high-risk patients was significantly reduced by a prophylactic amiodarone treatment resulting in a shorter time of intensive care unit and hospital stay. Our data supports the prophylactic use of amiodarone in peri-operative period in patients at high risk for AF after CABG.", "Atrial fibrillation and atrial flutter (AF) frequently complicate coronary artery bypass surgery (CABG) and increase hospital stay as well as morbidity. Studies of drug prophylaxis to prevent AF with beta-adrenergic blocking agents administered in fixed doses have had conflicting results.\n One hundred patients were randomized to receive metoprolol or placebo following CABG. A dosing algorithm was used to achieve clinically significant beta-adrenergic blockade.\n There was no significant difference between the incidence of AF in the metoprolol (24%) and placebo (26%) groups. However, the incidence of AF in all patients having CABG at this institution declined over the period of the study from 31% to 23% (P < .025), in association with the adoption of a continuous technique of cardioplegia delivery.\n Metoprolol is not efficacious for the prevention of post-CABG AF even when dosage is titrated to achieve clinical evidence of beta blockade. It is likely that the adoption of a continuous cardioplegia technique caused a reduction in our incidence of post-CABG AF.", "Postoperative arrhythmias are among the most common complications of cardiac surgery. Total serum magnesium concentration will change after coronary bypass surgery but compensatory prophylactic administration of magnesium has remained a controversial issue. We studied whether prophylactic administration of magnesium could prevent post-coronary artery bypass grafting (CABG) arrhythmias and evaluated the effects of diabetes mellitus on prophylactic magnesium administration.\n In a clinical trial, 345 consecutive CABG candidates were randomly assigned to study (n = 166, 48.1%) and control groups. Patients in study group received supplemental magnesium infusion as following: 2 g [corrected] after induction of anesthesia until cardio-pulmonary bypass and then 8 g upon arrival in Intensive Care Unit (ICU) until 24 hr. Total serum magnesium concentration was measured at four designated time points: onset of induction, and 0, 24 and 48 hr after ICU admission. Cardiac arrhythmias were sought with a 12-lead electrocardiogram (ECG) from the end of surgery up till discharge.\n Atrial Fibrillation (Af) occurred in 34 patients (9.9%). Total serum magnesium concentration was significantly higher in patients who received supplemental magnesium (P < 0.001) and significantly lower in Af patients (P= 0.02). Among non-diabetics, Af incidence was significantly lower in study group compared with control group.\n The occurrence of atrial fibrillation correlates with serum magnesium level. Diabetes mellitus probably hampers prophylactic effect of supplemental magnesium in preventing the occurrence of Af.", "Decision aids are tools designed to help patients participate in the clinical decision-making process.\n To determine whether use of an audiobooklet (AB) decision aid explaining the results of a clinical trial affected the decision-making process of study participants.\n Randomized controlled trial conducted from May 1997 to April 1998.\n Fourteen centers that participated in the Stroke Prevention in Atrial Fibrillation (SPAF) III trial.\n A total of 287 patients from the SPAF III aspirin cohort study, in which patients with atrial fibrillation and a relatively low risk of stroke received 325 mg/d of aspirin and were followed up for a mean of 2 years.\n At the end of SPAF III, participants were randomized to be informed of the study results with usual care plus use of an AB (AB group) vs usual care alone (control group). The AB included pertinent information to help patients decide whether to continue taking aspirin or switch to warfarin.\n Patients' ability to make choices regarding antithrombotic therapy, and 6-month adherence to these decisions. Their knowledge, expectations, decisional conflict (the amount of uncertainty about the course of action to take), and satisfaction with the decision-making process were also measured.\n More patients in the AB group made a choice about antithrombotic therapy than in the control group (99% vs 94%; P = .02). Patients in the AB group were more knowledgeable and had more realistic expectations about the risk of stroke and hemorrhage (in the AB group, 53%-80% correctly estimated different risks; in the control group, 16%-28% gave correct estimates). Decisional conflict and satisfaction were similar for the 2 groups. After 6 months, a similar percentage of patients were still taking their initial choice of antithrombotic therapy (95% vs 93%; P = .44).\n For patients with atrial fibrillation who had participated in a major clinical trial, the use of an AB decision aid improved their understanding of the benefits and risks associated with different treatment options and helped them make definitive choices about which therapy to take. Further studies are necessary to evaluate the acceptability and impact of decision aids in other clinical settings.", "We assess an alternative accelerated clinical pathway approach to the management of patients with newly diagnosed or new-onset atrial fibrillation (AF).\n A prospective, randomized pilot study of 2 AF disease-management strategies was conducted at a single university hospital. A traditional approach of hospital admission versus an accelerated emergency department-based strategy with low-molecular-weight heparin and early cardioversion to sinus rhythm was assessed in a cohort of patients with uncomplicated AF. The primary end points were length of stay and total actual direct costs.\n Eighteen patients were randomized over a 15-month period. The accelerated treatment strategy in the ED resulted in a substantial decrease in length of stay (2.1+/-2.3 versus <1 day) and a favorable trend toward mean cost reduction ($1,706+/-$1,512 versus $879+/-$394; P =.15). The clinical outcomes (rate of sinus rhythm at discharge and follow-up and complications caused by AF) related to AF were similar in the 2 groups.\n A disease-management strategy for new, uncomplicated AF that uses an ED-outpatient treatment pathway results in a shorter length of stay at potentially lower cost. The results of this pilot study warrant further investigation.", "The purpose of this prospective, randomized, double-blind, placebo-controlled study was to assess the efficacy of preoperatively and postoperatively administered oral d,l sotalol in preventing the occurrence of postoperative atrial fibrillation (AF).\n Atrial fibrillation is the most common arrhythmia following coronary artery bypass surgery (CABG). Its etiology, prevention and treatment remain highly controversial. Furthermore, its associated morbidity results in a prolongation of the length of hospital stay post-CABG.\n A total of 85 patients, of which 73 were to undergo CABG and 12 CABG plus valvular surgery (ejection fraction > or = 28% and absence of clinical heart failure), were randomized to receive either sotalol (40 patients; mean dose = 190 +/- 43 mg/day) started 24 to 48 h before open heart surgery and continued for four days postoperatively, or placebo (45 patients, mean dose = 176 +/- 32 mg/day).\n Atrial fibrillation occurred in a total of 22/85 (26%) patients. The incidence of postoperative AF was significantly (p = 0.008) lower in patients on sotalol (12.5%) as compared with placebo (38%). Significant bradycardia/hypotension, necessitating drug withdrawal, occurred in 2 of 40 (5%) patients on sotalol and none in the placebo group (p = 0.2). None of the patients on sotalol developed Torsade de pointes or sustained ventricular arrhythmias. Postoperative mortality was not significantly different in sotalol versus placebo (0% vs. 2%, p = 1.0). Patients in the sotalol group had a nonsignificantly shorter length of hospital stay as compared with placebo (7 +/- 2 days vs. 8 +/- 4 days; p = 0.24).\n The administration of sotalol, in dosages ranging from 80 to 120 mg, was associated with a significant decrease (67%) in postoperative AF in patients undergoing CABG without appreciable side effects. Sotalol should be considered for the prevention of postoperative AF in patients undergoing CABG in the absence of heart failure and significant left ventricular dysfunction.", "To evaluated the effects of temporary atrial pacing to prevent the atrial fibrillation following coronary artery bypass graft surgery and the risk factors to the occurrence of this arrhytmia.\n We have studied 160 patients who, at the end of coronary artery bypass graft surgery, were submitted to epicardial electrode implantation in the right atrium lateral wall. They were randomized into two groups: non-pacing (NP) group and right atrial (RA) pacing group. The cardiac rhythm was monitorized over 72 hours following to the end of surgery and the variables studied were as follow: incidence of atrial fibrillation; the risk factors pre-, intra-, and postoperative for its occurrence, and postoperative events.\n There were 21 (13.1%) episodes of atrial fibrillation, 20 in the NP group and one in the RA group. The relative risk (RR) for the development of atrial fibrillation was 0.18 (95% CI; 0.05-0.60) for the RA group when compared to the NP group. The logistic regression identified that the study variables, such as younger age; use of beta-blockers in the preoperative, and the presence of right atrial pacing had been associated to a lower Odds ratios (ORs) for the occurrence of atrial fibrillation in the postoperative.\n The temporary atrial pacing reduced the incidence of atrial fibrillation after the CABG surgery. Older age and a non-atrial pacing were the independent predictive factors of the occurrence of this arrhythmia.", "This study was designed to test whether intravenous (i.v.) amiodarone would prevent atrial fibrillation and decrease hospital stay after open heart surgery.\n Atrial fibrillation commonly occurs after open heart procedures and is thought to be a significant determinant for prolongation of hospitalization. Oral amiodarone given preoperatively appears to reduce the incidence of atrial fibrillation. This study was designed to test whether the more rapid-acting i.v. formulation of amiodarone given postoperatively would reduce the incidence of atrial fibrillation.\n Three hundred patients undergoing standard open heart surgery were randomized in a double-blind fashion to i.v. amiodarone (1 g/day for 2 days) versus placebo immediately after open heart surgery. The primary end points of the trial were incidence of atrial fibrillation and length of hospital stay. Baseline clinical variables and mortality and morbidity data were collected.\n Atrial fibrillation occurred in 67/142 (47%) patients on placebo versus 56/158 (35%) on amiodarone (p = 0.01). Length of hospital stay for the placebo group was 8.2 +/- 6.2 days, and 7.6 +/- 5.9 days for the amiodarone group (p = 0.34). No differences were noted in baseline variables, morbidity or mortality.\n Low-dose i.v. amiodarone was safe and effective in reducing the incidence of atrial fibrillation after heart surgery, but did not significantly alter length of hospital stay.", "Atrial fibrillation is in 20-50% the most frequent dysrhythmia after coronary artery bypass grafting (CABG) and a possible cause for hemodynamical complications and prolongation off the medical treatment in patients. Therefore, the effect of beta-blocking with metoprolol for prevention of supraventricular arrhythmias (SVA) was investigated in a prospective and randomized trial. 200 patients after CABG were randomized in a drug and control group (average age 63.2 years, 154 male, 46 female). Patients of the drug group (n=100) were treated with metoprolol (1mg/kg/BW) beginning on day one after operation, whereas patients of the control group (n=100) received therapy only in case of occurrence of atrial fibrillation. ECG, blood pressure, and electrolyte concentrations were measured regularly until the tenth day after surgery. Reasons for exclusion were an ejection fraction (< 30%, SA- and AV-block or simultaneous application of epinephrine and metoprolol. There were no significant differences between the patients of drug and control group with respect to age, sex ejection fraction, previous medication, number and type of bypass grafts, cardiopulmonary bypass time, and perioperative ischemic events. However, a statistically significant difference was seen in the occurrence of supraventricular arrhythmias in both groups, 4 patients of the therapy group (4%) in contrast to 37 patients of the control (37%) developed supraventricular arrhythmias during the postoperative observation period (p<0.0001). Both groups differed in total time of hospital stay by 1.5 days (control group: 9.83+/-2.88 days; drug group: 8.42+/-2.81 days), which was statistically significant (p<0.05). All patients of the drug group could be discharged with a stable sinus rhythm, whereas 7 patients of the control group were discharged with persistent atrial fibrillation. The difference was statistically significant as well (p<0.01). Neither typical side effects of metoprolol, nor AV-blocks, bradycardia (f<60/min) or symptoms of low blood pressure could be observed. The conclusion of this trial is a recommendation for a preventive application of 50mg metoprolol/day after coronary artery bypass surgery, which can reduce the incidence of SVA as well as the hospital stay statistically significant.", "A trial of intravenous followed by oral propranolol, started within 4 h of onset of suspected myocardial infarction and continued over 27 h, was carried out in 735 patients; 364 received propranolol, 371 were controls. Ventricular fibrillation during the first 48 h after entry to the trial occurred in 2 treated patients and in 14 controls (p = 0.006). Rates of hospital mortality, complications other than ventricular fibrillation, and progression from threatened to completed infarction did not differ between treated and control patients. Ventricular fibrillation was not apparently prevented by prior beta-blocker treatment, which was not a reason for exclusion from the trial. This intravenous/oral propranolol regimen seems to prevent ventricular fibrillation due to evolving myocardial infarction.", "Atrial fibrillation remains one of the most common postoperative complications of coronary artery bypass grafting. Despite many clinical studies, there is still no consensus regarding the best prevention strategy for atrial arrhythmia. A randomized, double-blind, placebo-controlled trial was conducted to determine the effect of steroids on the occurrence of atrial fibrillation after elective coronary artery bypass grafting.\n Eighty-eight consecutive patients were prospectively entered in this study. No patient had documented or suspected arrhythmias before surgery. Forty-three patients received 1 g of methylprednisolone before surgery and 4 mg of dexamethasone every 6 hours for 1 day after surgery, and 43 patients received only placebo. The primary end point was the overall occurrence of postoperative atrial fibrillation.\n Postoperative atrial fibrillation occurred in 9 (21%) of the 43 patients in the steroid group, as compared with 22 (51%) of the 43 patients in the placebo group ( P = .003). Minor postoperative complications occurred in 15 steroid patients (35%) and in 6 patients (14%) receiving placebo ( P = .01). Major complications occurred in 4 patients who received steroids (9%) and in 2 patients (5%) who received placebo ( P = .68; for all complications, P = .05).\n Prophylactic short-term steroid administration in patients undergoing coronary artery bypass grafting significantly reduced postoperative atrial fibrillation. In this study, there was no significant difference between the steroid group and the placebo group with regard to the length of hospital stay; however, the steroid group had more complications, which may contribute to prolonged hospitalization.", "We conducted a multi-centre, prospective, controlled, randomized trial to investigate the adjunctive role of ablation therapy to antiarrhythmic drug therapy in preventing atrial fibrillation (AF) relapses in patients with paroxysmal or persistent AF in whom antiarrhythmic drug therapy had already failed.\n One hundred and thirty seven patients were randomized to ablation and antiarrhythmic drug therapy (ablation group) or antiarrhythmic drug therapy alone (control group). In the ablation group, patients underwent cavo-tricuspid and left inferior pulmonary vein (PV)-mitral isthmus ablation plus circumferential PV ablation. The primary end-point of the study was the absence of any recurrence of atrial arrhythmia lasting >30 s in the 1-year follow-up period, after 1-month blanking period. Three (4.4%) major complications were related to ablation: one patient had a stroke during left atrium ablation, another suffered transient phrenic paralysis, and the third had a pericardial effusion which required pericardiocentesis. After 12 months of follow-up, 63/69 (91.3%) control group patients had at least one AF recurrence, whereas 30/68 (44.1%) (P<0.001) ablation group patients had atrial arrhythmia recurrence (four patients had atrial flutter, 26 patients AF).\n Ablation therapy combined with antiarrhythmic drug therapy is superior to antiarrhythmic drug therapy alone in preventing atrial arrhythmia recurrences in patients with paroxysmal or persistent AF in whom antiarrhythmic drug therapy has already failed.", "Atrial fibrillation (AF) is one of the most common complications of cardiac surgery. Magnesium, like several other pharmacologic agents, has been used in the prophylaxis of postoperative AF with varying degrees of success. However, the dose and the timing of magnesium prophylaxis need to be clarified. The purpose of this study was to assess the effect of intermittent magnesium infusion on postoperative AF.\n A total of 200 consecutive patients who had elective, isolated, first-time coronary artery bypass grafting were prospectively randomized to two groups. Patients in the magnesium group (n = 100) received 6 mmol MgSO4 infusion in 100 mL 0.9% NaCl solution (25 mL/h) the day before surgery, just after cardiopulmonary bypass, and once daily for 4 days after surgery. Patients in the control group (n = 100) received only 100 mL 0.9% NaCl solution (25 mL/h) at the same time points.\n Postoperative AF occurred in 2 (2%) patients in the magnesium group and in 21 (21%) patients in the control group (p < 0.001). Atrial fibrillation started, on average, 49.4 +/- 16.8 hours postoperatively. The postoperative length of hospital stay was not significantly different in patients with AF (7.4 +/- 8.0 days) compared with patients without AF (5.4 +/- 1.1 days; p = 0.236).\n The use of magnesium in the preoperative and early postoperative periods is highly effective in reducing the incidence of AF after coronary artery bypass grafting.", "Supraventricular tachyarrhythmia (SVT) commonly occurs shortly after coronary artery bypass grafting (CABG), but ventricular arrhythmias are less documented.\n On the 1st postoperative day, 206 consecutive eligible patients were prospectively randomized to a sotalol group (80 mg b.i.d.; n = 103) or a control group without beta-blockade or antiarrhythmic drugs (n = 103).\n The SVT incidence (predominantly atrial fibrillation) accounted for 16% in the sotalol group versus 48% (p < 0.00001). Multivariate analysis showed that sotalol reduced the SVT incidence (p < 0.00001, odds ratio, 0.20; 95% confidence interval, 0.09 to 0.42), whereas a lower preoperative left ventricular ejection fraction (p = 0.019) and older age (p = 0.031) were independent risk factors of SVT occurrence. The Holter electrocardiographic analysis (24 hours) demonstrated that sotalol (32 versus 92; p = 0.031) decreased the median number of ventricular events, mostly isolated premature ventricular beats. Neither ventricular proarrhythmia effect nor \"torsades de pointes\" were detected. Despite strict hemodynamic-based selection, sotalol had to be discontinued in 8 patients (7.8%), for reasons related to asthma in 3 or cardiac reasons in 5.\n Oral low-dose sotalol provided considerable and reliable protection in selected nondepressed cardiac function patients, reducing the occurrence of both supraventricular and ventricular arrhythmias after CABG.", "Atrial fibrillation (AF) is a common complication after coronary artery bypass grafting (CABG). Since its prevention with prophylactic drug therapy has limited success, alternative approaches are desirable. This study examined the efficacy of atrial or biatrial pacing, compared with no pacing, on the incidence of AF after isolated CABG.\n From August 2002 to September 2004, 240 patients underwent CABG. After surgery, right and left atrial epicardial pacing wires were implanted for 72 hours of temporary pacing. Patients were randomly assigned to one of three groups: no pacing (control group), right atrial (RA), and biatrial (BiA) pacing. Cardiac rhythm was monitored continuously during intensive care, or daily on the ward. The primary endpoints of this study were an episode of AF occurring up to 72 hours after CABG and the risk factors correlated with this event.\n Atrial and BiA pacing significantly lowered the incidence (1.25% vs 25%, P = 0.001) of AF episodes, and were both correlated (odd ratio 0.038; 95% confidence interval 0.005-0.29) with a decrease in rates of postoperative AF. Multivariable analysis identified older age (odd ratio 1.074; 95% confidence interval 1.024-1.12) and no pacing as independent risk factors of postoperative AF.\n Temporary right atrial or biatrial pacing after CABG significantly decreased the postoperative incidence of AF. Multivariable analysis identified older age and no pacing as predictors of AF occurrence.", "Two hundred twenty-three patients were randomly selected to receive propranolol, 10 mg orally every 6 hours, or to serve as controls after coronary artery bypass grafting. The study began at the time of discharge from the intensive care unit. Patients were ineligible if they had cardiac arrhythmias while in the intensive care unit, low cardiac output requiring catecholamine support, or bradycardia requiring a pacemaker. In the control group, cardiac arrhythmias for which treatment was necessary developed in 31 of 136 patients (23%), atrial fibrillation or flutter in 24 patients (18%), and ventricular arrhythmias in 7 (5%). In the group receiving propranolol, cardiac arrhythmias requiring treatment developed in 9 of 87 patients (10%), atrial fibrillation or flutter in 7 (8%), and ventricular arrhythmias in 2 (2%). The difference in frequency with which cardiac arrhythmias occurred between the two groups is significantly different (p less than 0.05). We conclude that propranolol is effective in the prevention of cardiac arrhythmias following coronary artery bypass grafting.", "Arrhythmias are common after open heart surgery and may be related to hypomagnesaemia due to cardiopulmonary bypass. Although perioperative prophylactic Mg2+ administration may prevent arrhythmias after coronary artery bypass grafting (CABG), clear indications as well as the timing of Mg2+ substitution and dose regimen need to be clarified. Aim of this study was to evaluate the antiarrhythmic effects of Mg2+ infusion in patients who underwent elective CABG.\n Ninety-seven patients who underwent elective CABG were divided in four Groups. In Group A 1 g of magnesium sulfate was added to the pump prime, Group B received 1 g in the pump prime plus 5 mmol/L in the cardioplegic solution, Group C received 5 mmol/L in the cardioplegic solution, and Group D was a placebo control Group. Groups A, B, and C also received 24 h continuous infusion of magnesium sulfate at 10 mmol/L. Three-channel electrocardiogram (II-V5-V6) continuous monitoring was performed 12 hours preoperatively and 48 hours postoperatively. Blood samples were taken for subsequent Serum magnesium measurements, at five different time points before, during and after CBP.\n In all Groups serum Mg2+ levels were reduced during CPB (Time 2) and statistically significant differences from pre-anaesthesia levels (Time 1) were noted (p <0.05). In Groups A, B, and C Serum Mg2+ levels increased progressively from Time 3 to Time 5; in Group D serum Mg2+ levels were still much lower at Time 5. Significant differences (p<0.05) were noted for Groups B and C vs Groups A and D in atrial ectopics, atrial fibrillation, and ventricular arrhythmic events.\n Our results demonstrate that Mg2+ sulfate administration regimens used in Group B and C reduce postoperative arrhythmic events in patients undergoing CABG.", "There are two approaches to the treatment of atrial fibrillation: one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm, and the other is the use of rate-controlling drugs, allowing atrial fibrillation to persist. In both approaches, the use of anticoagulant drugs is recommended.\n We conducted a randomized, multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death. The primary end point was overall mortality.\n A total of 4060 patients (mean [+/-SD] age, 69.7+/-9.0 years) were enrolled in the study; 70.8 percent had a history of hypertension, and 38.2 percent had coronary artery disease. Of the 3311 patients with echocardiograms, the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent. There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy (mortality at five years, 23.8 percent and 21.3 percent, respectively; hazard ratio, 1.15 [95 percent confidence interval, 0.99 to 1.34]; P=0.08). More patients in the rhythm-control group than in the rate-control group were hospitalized, and there were more adverse drug effects in the rhythm-control group as well. In both groups, the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic.\n Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy, and there are potential advantages, such as a lower risk of adverse drug effects, with the rate-control strategy. Anticoagulation should be continued in this group of high-risk patients.\n Copyright 2002 Massachusetts Medical Society", "Postoperative atrial fibrillation occurs in 5% to 65% of patients undergoing cardiac surgery. Although postoperative atrial fibrillation is often regarded as a temporary, benign, operation-related problem, it is associated with a twofold to threefold increase in risk of adverse events, including permanent or transient stroke, acute myocardial infarction, and death.\n This randomized, controlled, double-blinded trial included 250 eligible consecutively enrolled patients undergoing coronary artery bypass grafting (CABG). They received 300 mg of amiodarone/placebo administered intravenously over 20 minutes on the first postoperative day and an oral dose of 600 mg of amiodarone or placebo twice daily for the first 5 postoperative days.\n The patients in amiodarone prophylaxis experienced a reduction in risk of atrial fibrillation of 14% (95% confidence interval [CI], 5.0% to 24%), with the number needed to treat at 6.9 (95% CI, 4.2 to 20), and the results for symptomatic atrial fibrillation showed a risk reduction of 18% (95% CI, 9.4% to 26), with the number needed to treat at 5.7 (95% CI, 3.9 to 11). Of the patients who developed atrial fibrillation in the placebo group, 84% experienced a symptomatic attack versus only 43% in the amiodarone group.\n Postoperative prophylaxis with a high dose of oral amiodarone after an intravenous bolus infusion is a safe, practical, feasible, and effective regimen for CABG patients. It significantly diminishes the occurrence of postoperative atrial fibrillation.", "Supraventricular tachyarrhythmias (SVT) complicate postoperative management after coronary bypass surgery in about 30% of all patients. Though a prophylactic treatment both with beta-adrenergic blocking agents and the calcium antagonist diltiazem has been used for the prevention of post-operative SVT, no study yet has performed a prospective comparison of the efficacy of these therapies.\n To investigate the prophylactic effect of either a calcium antagonist (diltiazem, 0.1 mg/kg per h i.v.) or a beta-adrenergic blocking agent (propranolol, 10 mg every 6 h postoperatively), we randomized prospectively 103 consecutive patients into three groups, the third one serving as a control group. Anti-arrhythmic medication was started with the procedure and was continued until the 3rd postoperative day.\n Preoperative conditions were the same for the three groups concerning age, extent of coronary heart disease, ventricular function and heart-related medication. There were no differences in intraoperative parameters or postoperative enzyme patterns. Diltiazem was ineffective in preventing SVT, the incidence being exactly the same as in the control group (35%). Propranolol reduced the occurrence of SVT significantly (7%, P < 0.05). Furthermore, patients treated with diltiazem needed positive inotropic support more often in the first hours after surgery than patients of the control group (30% vs 5%, P < 0.01).\n The perioperative administration of low-dose propranolol is considered a safe and effective drug prophylaxis to avoid the occurrence of SVT after bypass surgery.", "Supraventricular arrhythmias continue to complicate the postoperative course of patients undergoing myocardial revascularization. The aim of the study was to identify factors associated with atrial fibrillation (AF) and to determine the efficacy of postoperative magnesium sulphate (MgSO4) replacement on the incidence of AF after coronary artery bypass grafting (CABG) operation.\n Fifty patients undergoing CABG were studied prospectively. Consenting patients with good left ventricular function and without any documented arrhythmias were randomly divided into two groups of 25 patients each in a double-blind fashion. The clinical characteristics of both groups were similar. In the study group, 200 mEq MgSO4 was given for the first 5 postoperative days, in the control group, placebo was given instead of MgSO4.\n Five (20%) patients in the control group and one (4%) patient in the MgSO4 group experienced AF. There was no significant relationship between the development of AF and the following variables: age; sex; diabetes mellitus; hypertension; previous myocardial infarction; smoking; extension of coronary artery disease; aortic cross-clamp time; number of grafts; cardiopulmonary bypass time; postoperative pericarditis; and anemia.\n The use of MgSO4 in early postoperative period is effective in reducing the incidence of AF after CABG in patients with good ventricular function.", "Ninety-nine consecutive consenting patients were prospectively entered into a randomized, double-blind, placebo-controlled trial to determine the efficacy of postoperative magnesium therapy on the incidence of cardiac arrhythmias after elective coronary artery bypass grafting. No patient had documented or suspected arrhythmias preoperatively. Forty-nine patients received 178 mEq of magnesium given over the first 4 postoperative days, and 50 patients received only placebo. The clinical characteristics of both groups were similar. The preoperative mean serum magnesium concentration was similar in both study (1.90 mEq/L) and placebo (1.90 mEq/L) groups. The mean postoperative serum magnesium concentration in study patients was significantly elevated over postoperative days 1 through 4 when compared with preoperative levels (p less than 0.001). The postoperative mean serum magnesium concentration in control patients declined and remained significantly depressed through postoperative day 3 (p less than 0.001), but increased to preoperative levels by postoperative day 4. The mean serum magnesium concentration was significantly greater in the study patients as compared with the control patients over postoperative days 1 through 4 (p less than 0.001). Although there was no significant difference between groups with respect to episodes of ventricular arrhythmias, there was a significant decrease in the number of episodes of atrial fibrillation in the group receiving magnesium therapy (p less than 0.02). There were no recognized adverse effects of magnesium therapy. Prophylactic magnesium administration seems to lessen the incidence and severity of atrial fibrillation after coronary artery bypass grafting.", "To assess the prophylactic effect of postoperative oral amiodarone on the incidence and severity of atrial fibrillation (AF) after coronary artery surgery.\n Prospective, randomized, blinded, controlled study.\n University hospital.\n Patients who had coronary artery surgery (n = 200).\n Patients in group 1 (n = 100) received oral amiodarone, 15 mg/kg, 4 hours after arrival in the intensive care unit, followed by 7 mg/kg/d until hospital discharge. Patients in group 2 (n = 100) received placebo.\n Incidence, duration, and recurrence of new episodes of AF and maximal ventricular rate response were recorded from day 0 until hospital discharge. Side effects related to amiodarone and complications induced by new-onset AF were noted. The incidence of new-onset AF (12% v 25%) and maximal ventricular rate response (120 +/- 21 beats/min v 135 +/- 24 beats/min) were significantly lower in the amiodarone group. There were no side effects related to the administration of amiodarone. The incidence of complications induced by AF was comparable between the 2 groups.\n Postoperative prophylactic oral amiodarone after coronary artery surgery is safe and effective in reducing the incidence of new-onset AF and maximal ventricular rate response.\n Copyright 2002, Elsevier Science (USA). All rights reserved.", "Atrial fibrillation (AF) is a common complication reported in 20% to 40% of patients after coronary operations. Sotalol alone and magnesium alone have been shown to partially decrease the incidence of AF. The goal of this study was to evaluate the efficacy of these two pharmacological agents, used alone or in combination, to reduce postoperative AF.\n Two hundred seven consecutive coronary artery bypass patients (mean age 62 +/- 11 years) were randomized to receive sotalol alone (80 mg twice daily for 5 days starting from the morning of the first postoperative day) (group S), magnesium alone (1.5 g daily for 6 days starting in the operating room just before cardiopulmonary bypass) (group M), both pharmacologic agents at the same dosages (group S+M), or no antiarrhythmic agents (group CTR). All patients with an ejection fraction less than 0.40 were excluded.\n The incidence of postoperative AF was 11.8% (6/51) in the S group, 14.8% (8/54) in the M group, 1.9% (1/52) in the S+M group, and 38% (19/50) in the CTR group. The following differences were significant: group CTR versus groups S, M, and S+M with values of p = 0.002, p = 0.007 and p < 0.0001, respectively; and group S+M versus groups S and M with p = 0.04 and p = 0.01, respectively.\n Incidence of AF after coronary operation was significantly reduced by the administration of sotalol alone and magnesium alone; more importantly, the incidence was further reduced by combining these agents.", "In patients with persistent atrial fibrillation (AF), the efficacy and safety of two anti-arrhythmic drugs in preventing the recurrence of AF after successful direct current (DC) cardioversion was prospectively assessed in a multi-centre double-blind, placebo-controlled, randomised trial using daily trans-telephonic monitoring.\n 1182 patients with persistent AF were prospectively enrolled, 848 patients were successfully cardioverted and then randomised to either sotalol (383 patients), quinidine plus verapamil (377 patients) or placebo (88 patients). The primary outcome parameter was AF recurrence or death. All patients received an event recorder (Tele-ECG) and had to record and transmit via telephone at least one ECG per day during follow-up. The mean follow-up period was 266 days. A total of 191,103 Tele-ECGs were recorded and transmitted. The primary outcome parameter (AF recurrence of any kind or death) was observed in 572 patients (67%) in whom at least one episode of AF recurrence was documented during follow-up, in 348 patients (41%) AF recurrence was persistent. The recurrence rates after one year for any AF were 83% for placebo, 67% for sotalol and 65% for quinidine plus verapamil, the latter being statistically superior to placebo but not different from sotalol. The recurrence rates for the secondary outcome parameter persistent AF were 77%, 49% and 38%, respectively. Quinidine plus verapamil was significantly superior to placebo and to sotalol. About 95% of all AF recurrences were initially detected in the daily Tele-ECG, about 70% of all AF recurrences occurred completely asymptomatic. Adverse events on sotalol and quinidine plus verapamil were comparable with the exception that all torsade de pointes tachycardias occurred on sotalol.\n Anti-arrhythmic treatment after DC cardioversion of persistent AF significantly decreases the recurrence rates of persistent AF compared to placebo with superiority of quinidine plus verapamil compared to sotalol. Symptoms were not reliable as clinical surrogates to detect episodes of AF.", "Current atrial fibrillation (AF) ablation involves isolation of all pulmonary veins (PVs) with or without additional linear lesions. However, whether such extensive ablation is necessary is unclear.\n The purpose of this study was to assess the efficacy of different ablation strategies on long-term AF control.\n We prospectively randomized patients to undergo isolation of all versus arrhythmogenic PVs (identified by standardized stimulation protocol). PV isolation was guided by circular mapping catheter. The endpoint was entry/exit block persisting for > or = 20 minutes. Patients were evaluated at three clinic visits (at 6 weeks, 6 months, and 1 year) and multiple transtelephonic monitoring periods. Antiarrhythmic drugs were discontinued at 6 weeks. Primary study endpoint was long-term AF control (freedom or >90% reduction in AF burden off or on previously ineffective antiarrhythmic drugs at 1 year after a single ablation procedure).\n Over a 20-month period, 105 patients (76 men and 29 women, age 57 +/- 9 years; paroxysmal AF = 77) were randomized, and 103 patients completed 1-year follow-up (51 patients in all-PV arm, 52 patients in arrhythmogenic PV arm). The primary endpoint was achieved in 75 (73%) patients and was similar in patients randomized to all-PV arm versus arrhythmogenic PV arm [38 (75%) patients vs 37 (71%) patients, respectively; odds ratio 1.18, 95% confidence interval 0.50, 2.83, P = .70]. Secondary study endpoints, including freedom from AF off antiarrhythmic drugs, total procedure/fluoroscopy times, and occurrence of serious adverse events, were not different between the two groups.\n In a randomized comparison, isolation of arrhythmogenic veins was as efficacious as empiric isolation of all veins in achieving long-term AF control.", "In patients undergoing coronary artery bypass surgery (CABGS), occurrence of atrial fibrillation (AF) is common in the postoperative period and is associated with increased morbidity with longer intensive unit care (ICU) and hospital stay. Prevention with antiarrhythmic drugs is of limited success and associated with significant side effects. Therefore alternative approaches, such as Bachmann Bundle pacing, are required.\n 154 consecutive patients, mean age 58±8.8 years, including 134 males and 20 females, were randomized to three groups; Group I : No pacing n= 54, Group II : RA pacing n= 52, Group III : Bachmann Bundle pacing n= 48. All the groups were well matched with regard to age, left atrial size, ejection fraction and use of beta blockers. Patients in Groups II and III were continually paced at a rate of 100 beats per minute (bpm) or at 10 bpm more than patients' intrinsic heart rate. All the patients were monitored for 72 hours by telemetry and occurrence of AF was noted. Incidence of AF was 0% (none of 48 patients) in Group III as compared to 16.6% in Group I (9 of 54 patients) (p 0.003) and 12.5% in Group II (5 of 52 patients) (p 0.03). There was a trend towards shorter ICU stay in Group III (3.9 days) as compared to Group II (4.5 days) and Group I (4.1 days). Among the three groups, the reduction in mean P wave duration also was greater in Bachmann bundle paced group.\n In patients undergoing CABGS, Bachmann bundle pacing is superior to right atrial / no pacing in the post operative period for preventing occurrence of AF and reducing ICU stay, commensurate with a reduction in mean P wave duration on surface ECG.", "Atrial fibrillation is still a frequent complication that increases morbidity after coronary artery bypass grafting. This prospective randomized study is designed to define efficacy of postoperative amiodarone prophylaxis in preventing atrial fibrillation after off-pump coronary artery bypass grafting.\n One hundred forty-four patients who underwent elective off-pump coronary artery bypass grafting were enrolled for the study. Seventy-six patients (amiodarone group) received 5 mg/kg loading amiodarone infusion in the first postoperative hour, followed by 10 mg/kg for the first 24 hours. After 24 hours, patients received 600 mg/day amiodarone orally for 7 days and 200 mg/day until the end of the postoperative first month. Sixty-eight patients received placebo (control group).\n Preoperative characteristics and operative variables of the patients were similar in both groups. Incidence of new-onset atrial fibrillation and maximal ventricular rate response were recorded. The incidence of new-onset atrial fibrillation (11.8% versus 26.5%) (P = .025) and maximal ventricular rate response (109 +/- 13.8 beats/min versus 124.5 +/- 13.9 beats/min) (P = .011) were significantly lower in the amiodarone group. Duration of atrial fibrillation was 17.5 +/- 8.1 hours for the amiodarone group compared with 32.7 +/- 12 hours for the control group (P = .002).\n Postoperative intravenous amiodarone prophylaxis followed by oral amiodarone significantly reduces the incidence of atrial fibrillation after off-pump coronary artery bypass grafting and the ventricular rate during atrial fibrillation.", "Pharmacologic therapy is widely used for restoration of sinus rhythm and prevention of recurrences of atrial fibrillation. Because concerns have been raised about their potential proarrhythmic effects, therapeutic regimens should be evaluated by placebo-controlled studies to determine their efficacy and safety. One hundred thirty-six patients with persistent atrial fibrillation were randomized to receive propafenone 2 mg/kg over 30 minutes, followed by oral propafenone 150 mg 3 times daily or matching placebo. Nonresponders to intravenous therapy underwent direct-current cardioversion. Both responders to intravenous therapy and converters to sinus rhythm after direct-current cardioversion were followed for 6 months in a double-blind oral treatment period of propafenone 150 mg 3 times daily or matching placebo. Pharmacologic conversion to sinus rhythm was achieved in 29% of the patients taking propafenone and in 17% of patients taking placebo (p > or = 0.10). Subsequent direct-current cardioversion in nonresponders was equally successful (70%) in both groups (p > or = 0.10). The proportion of patients free from recurrent symptomatic arrhythmia at 6 months was 67% for the propafenone and 35% for the placebo group (p < 0.01). Time to atrial fibrillation relapse was more favorable with propafenone than with placebo (p < 0.001). The incidence of drug-related side effects was 10% in the propafenone group and 14% in the placebo group. Thus, \"slow\" infusion of propafenone seems to be of limited value for terminating atrial fibrillation. Oral propafenone at a low dosage 150 mg 3 times daily is well tolerated and effective in maintaining sinus rhythm for 6 months after pharmacologic or electrical restoration of sinus rhythm.", "Atrial fibrillation occurs in 10% 40% of patients undergoing coronary artery bypass grafting. This study investigates whether prophylactic Amiodarone use reduces the rate of atrial fibrillation post myocardial revascularisation.\n In a prospective study conducted at the Cardiothoracic Center over a 6 month period, 192 patients were randomized to either Amiodarone or placebo. The Amiodarone group received Amiodarone infusion followed by oral Amiodarone on a decreasing dose for a total period of 6 weeks. The placebo group were started on an infusion of dextrose 5% solution and then maintained on a matched regimen of placebo tablets for a corresponding period of time.\n Of the 100 patients recruited for the Amiodarone arm of the study, 12 were excluded for a variety of reasons detailed in the discussion with atrial fibrillation occurring in 28 (a rate of 32%). Of the 92 controls, 32 developed atrial fibrillation (a rate of 35%). There were no significant differences between the groups. The maximum ventricular rate during atrial fibrillation however, was significantly slower in the Amiodarone group (108+/-18) compared to (136+/-22) P<0.05. Moreover, there were no significant differences in the mortality rates between the 2 groups; a rate of 3% (3 of 88) in the Amiodarone group as opposed to 3% (3 of 92) in the controls.\n In this study prophylactic Amiodarone did not reduce the rate of atrial fibrillation post coronary artery bypass surgery. However, it reduced the maximum ventricular rate. Amiodarone had no effect on mortality post coronary artery bypass.", "Episodes of atrial fibrillation or flutter frequently complicate the postoperative course after coronary bypass surgery. A hundred and one patients undergoing coronary artery bypass surgery were randomized to oral pre- and postoperative treatment with sotalol, a non-selective beta-blocking agent with class-III antiarrhythmic properties (50 patients), or to half the preoperative beta-blocking dose according to the routine of the department (51 patients). Thus, there was no equipotency regarding beta blockade in the two groups. The incidence of atrial fibrillation was 10% in the sotalol group and 29% in the comparison group, p = 0.028. In 10% of the sotalol patients the dose had to be reduced or stopped compared to in none the group given routine treatment. The patients who developed atrial fibrillation were older, but otherwise there was no statistically significant difference between the two groups. Sotalol was effective in reducing the incidence of atrial fibrillation. However, careful titration of the optimal dose should be performed in order to avoid side effects of the beta blockade.", "Atrial fibrillation is a common complication after cardiac surgery. Postoperative atrial fibrillation is associated with increased risks of morbidity and mortality, and, therefore, preventive strategies using oral amiodarone have been developed but are often unpractical. Intravenous amiodarone administered after the induction of anesthesia and continued postoperatively for 48 h could represent an effective strategy to prevent postoperative atrial fibrillation in patients undergoing cardiac valvular surgery.\n Single-center, double-blinded, double-dummy, randomized controlled trial in patients undergoing valvular surgery. Patients received either an intravenous loading dose of 300 mg of amiodarone or placebo in the operating room, followed by a perfusion of 15 mg . kg(-1) . 24 h(-1) for 2 days. The primary endpoint was the development of atrial fibrillation occurring at any time within the postoperative period.\n One hundred twenty patients were randomly assigned (mean age was 65 +/- 11 yr). Overall atrial fibrillation occurred more frequently in the perioperative intravenous amiodarone group compared with the placebo group (59.3 vs. 40.0%; P = 0.035). Four preoperative factors were found to be independently associated with a higher risk of developing postoperative atrial fibrillation: older age (P = 0.0003), recent myocardial infarction (<6 months; P = 0.026), preoperative angina (P = 0.0326), and use of a calcium channel blocker preoperatively (P = 0.0078) when controlling for groups.\n In patients undergoing cardiac valvular surgery, a strategy using intravenous amiodarone for 48 h is not efficacious in reducing the risk of atrial fibrillation during cardiac valvular surgery.", "BACKGROUND: The single most frequent complication after coronary artery bypass graft surgery is the occurrence of supraventricular tachyarrhythmias leading to a prolonged hospital stay. Although several drugs have been used to treat these arrhythmias, effective prevention was only possible with beta-blocking drugs in selected patients. It was, therefore, the aim of the present study to evaluate the significance of supraventricular tachyarrhythmias in presence of today's cardioprotective management in a broad spectrum of patients and to assess the possible preventive effect and safety of low-dose sotalol after coronary artery bypass graft surgery. METHODS AND RESULTS: In a prospective randomized double-blind placebo-controlled trial, 220 consecutive patients referred for elective coronary artery bypass graft surgery were randomized to 80 mg sotalol twice daily (n = 110) or matching placebo (n = 110) for 3 months with the first dose given 2 hours before surgery. There were no significant differences in baseline characteristics between the two groups. Low-dose sotalol reduced the rate of supraventricular arrhythmias from 43% (placebo) to 25% (sotalol, P <.01), which was atrial fibrillation in 83%, flutter in 7%, and other supraventricular arrhythmias in 10%. Only 7% of all arrhythmias were observed after day 9. Hospital stay was 11 +/- 4 days in patients with supraventricular arrhythmias versus 9 +/- 2 days (P <.001) in patients without. On the fourth postoperative day, heart rate was lower in the sotalol group (75 +/- 12 versus 86 +/- 14 beats per min; P <.0001), but QTc was not significantly prolonged (sotalol, 0.44 +/- 0.03; placebo, 0.43 +/- 0.03; P, ns). Study medication had to be discontinued due to side effects in 6.4% of sotalol and 3.6% of placebo patients (P, ns), but relevant side effects occurred only in two sotalol patients late after surgery. CONCLUSIONS: These data show that without antiarrhythmic therapy the incidence of supraventricular arrhythmias after coronary artery bypass graft surgery is high (43%) and that supraventricular arrhythmias were associated with a prolonged hospital stay (+/-2 days). Prophylactic treatment with low-dose sotalol reduced the incidence of supraventricular arrhythmias significantly (by 40%), thereby reducing overall hospital stay in treated patients. Because more than 90% of all supraventricular arrhythmic episodes occurred within 10 days after surgery and considering the small proarrhythmic effect of sotalol late after surgery, prophylactic treatment with sotalol may be recommended for the first 10 postoperative days to safely reduce supraventricular tachyarrhythmias.", "Atrial fibrillation is the most commonly encountered sustained cardiac arrhythmia. Restoration and maintenance of sinus rhythm is believed by many physicians to be superior to rate control only. However, there are no prospective data that compare both therapeutic strategies.\n The Pharmacological Intervention in Atrial Fibrillation (PIAF) trial was a randomised trial in 252 patients with atrial fibrillation of between 7 days and 360 days duration, which compared rate (group A, 125 patients) with rhythm control (group B, 127 patients). In group A, diltiazem was used as first-line therapy and amiodarone was used in group B. The primary study endpoint was improvement in symptoms related to atrial fibrillation.\n Over the entire observation period of 1 year, a similar proportion of patients reported improvement in symptoms in both groups (76 responders at 12 months in group A vs 70 responders in group B, p=0.317). Amiodarone administration resulted in pharmacological restoration of sinus rhythm in 23% of patients. Walking distance in a 6 min walk test was better in group B compared with group A, but assessment of quality of life showed no differences between groups. The incidence of hospital admission was higher in group B (87 [69%] out of 127 vs 30 [24%] out of 125 in group A, p=0.001). Adverse drug effects more frequently led to a change in therapy in group B (31 [25%] patients compared with 17 [14%] in group A, p=0.036).\n With respect to symptomatic improvement in patients with atrial fibrillation, the therapeutic strategies of rate versus rhythm control yielded similar clinical results overall. However, exercise tolerance is better with rhythm control, although hospital admission is more frequent. These data may serve as a basis to select therapy in individual patients.", "About 30% of patients develop AF after open heart surgery. Biatrial synchronous pacing (BSP) has been shown to promote sinus rhythm in patients with paroxysmal AF refractory to drug therapy. We conducted a prospective, randomized study to test the effect of BSP via epicardial electrodes on the incidence of AF after heart surgery, as compared to conventional therapy. To apply BSP, we attached two epicardial electrodes to the right and one to the left atrium. Immediately following surgery, BSP was initiated in the AAI-Mode at a rate of 10 beats/min above the underlying rhythm (maximum 110 beats/min) and continued for 3 days, during which the rhythm was continually monitored. After 21 (age 63 +/- 9 years) of the planned 200 patients, the study was prematurely aborted because of the proarrhythmic effect of BSP: 6 of the 12 patients treated with BSP developed sensing failure (P amplitude < 1 mV), which provoked AF in 5 of these 6 patients. BSP was discontinued due to diaphragmal stimulation in two patients and due to ventricular stimulation by a dislocated left atrial electrode in one patient. Two patients in the control group (n = 9) developed AF. Using the available standard technology, BSP via epicardial electrodes is not suitable to suppress AF after heart surgery, primarily due to postoperative deterioration of atrial sensing and its profibrillatory effect. In patients requiring atrial pacing after heart surgery, sensing thresholds must be closely monitored to prevent induction of AF.", "Beta-blockers and amiodarone reduce the frequency of atrial fibrillation after open-heart surgery but the effectiveness of oral amiodarone in older patients already receiving beta-blockers is unknown. We have assessed the efficacy of oral amiodarone in preventing atrial fibrillation in patients aged 60 years or older undergoing open-heart surgery.\n We did a randomised, double-blind placebo-controlled trial in which patients undergoing open-heart surgery (n=220, average age 73 years) received amiodarone (n=120) or placebo (n=100). Patients enrolled less than 5 days before surgery received 6 g of amiodarone or placebo over 6 days beginning on preoperative day 1. Patients enrolled at least 5 days before surgery received 7 g over 10 days beginning on preoperative day 5.\n Patients on amiodarone had a lower frequency of any atrial fibrillation (22.5% vs 38.0%; p=0.01; absolute difference 15.5% [95% CI 3.4-27.6%]), and there were significant differences in favour of the active drug for symptomatic atrial fibrillation (4.2% vs 18.0%, p=0.001), cerebrovascular accident (1.7% vs 7.0%, p=0.04), and postoperative ventricular tachycardia (1.7% vs 7.0%, p=0.04). Beta-blocker use (87.5% amiodarone vs 91.0% placebo), nausea (26.7% vs 16.0%), 30-day mortality (3.3% vs 4.0%), symptomatic bradycardia (7.5% vs 7.0%), and hypotension (14.2% vs 10.0%) were similar.\n Oral amiodarone prophylaxis in combination with beta-blockers prevents atrial fibrillation and symptomatic fibrillation and reduces the risk of cerebrovascular accidents and ventricular tachycardia.", "The purpose of this study was to determine if atrial pacing is effective in reducing postoperative atrial fibrillation (AF).\n Atrial fibrillation after coronary artery bypass grafting (CABG) is a common problem for which medical management has been disappointing. Atrial-based pacing has become an attractive nonpharmacologic therapy for the prevention of AF.\n Sixty-one post-CABG patients (mean age = 65 years) were randomized to one of three groups: no atrial pacing (NAP), right atrial pacing (RAP) or biatrial pacing (BAP). Each patient had one set of atrial wires attached to both the right and left atria, respectively, at the conclusion of surgery. Patients in the RAP and BAP groups were continuously paced at a rate of 100 pulses per minute for 96 h or until the onset of sustained AF (>10 min). All patients were monitored with Holter monitors or full disclosure telemetry to identify the onset of AF. The primary end point of the study was the first onset of sustained AF.\n There was no significant difference in the proportion of patients developing AF in the three groups (NAP = 33%; RAP = 29%; BAP = 37%; p > 0.7). However, for the subset of patients on beta-adrenergic blocking agents after CABG, there was a trend toward less AF in the paced groups. There were no serious complications related to pacing, although in three patients the pacemaker appeared to induce AF by pacing during atrial repolarization.\n Continuous right or biatrial pacing in the postoperative setting is safe and well tolerated. We did not find that post-CABG pacing prevented AF in this pilot study; however, the role of combined pacing and beta-blockade merits further study.", "To evaluate whether postoperative administration of intravenous low-dose amiodarone and magnesium sulfate (MgSO(4)) combination would reduce the incidence of atrial fibrillation following coronary artery bypass grafting (CABG) in normomagnesemic high-risk patients for postoperative atrial fibrillation (POAF).\n A total of 136 patients undergoing elective CABG and had > or =3 risk factors for POAF were prospectively randomized to one of three groups, to receive a single dose of amiodarone (5 mg/kg) and MgSO(4) (1.5 g) (combination group, n = 44), or an equal dose of amiodarone (amiodarone group, n = 44) or equal volumes of saline (control group, n = 48) at early postoperative period. Continuous electrocardiographic (ECG) monitoring was performed for the first 48 hours and an ECG was recorded every 8 hours later. POAF longer than 30 minutes or for any length requiring treatment, and the drug-related side effects were recorded.\n The study population showed a homogeneous distribution regarding risk factors for POAF and there was no significant difference in patient characteristics, echocardiographic variables, or operative variables among three groups. POAF developed in 4 patients in combination group, in 16 patients in amiodarone group and in 16 patients in control group, representing a 24% relative risk reduction between the combination group and control group (p = 0.023). No statistically significant difference regarding incidence of POAF was observed between amiodarone and control groups.\n Combined prophylactic therapy with amiodarone and MgSO(4) at the early postoperative period without a maintenance phase is an effective, simple, well-tolerated, and possibly cost-effective regimen to prevent POAF in normomagnesemic, high-risk patients.", "Atrial fibrillation (AF) is the most common arrhythmia to occur after cardiac surgery. An exaggerated inflammatory response has been proposed to be one etiological factor.\n To test whether intravenous corticosteroid administration after cardiac surgery prevents AF after cardiac surgery.\n A double-blind, randomized multicenter trial (study enrollment August 2005-June 2006) in 3 university hospitals in Finland of 241 consecutive patients without prior AF or flutter and scheduled to undergo first on-pump coronary artery bypass graft (CABG) surgery, aortic valve replacement, or combined CABG surgery and aortic valve replacement.\n Patients were randomized to receive either 100-mg hydrocortisone or matching placebo as follows: the first dose in the evening of the operative day, then 1 dose every 8 hours during the next 3 days. In addition, all patients received oral metoprolol (50-150 mg/d) titrated to heart rate.\n Occurrence of AF during the first 84 hours after cardiac surgery.\n The incidence of postoperative AF was significantly lower in the hydrocortisone group (36/120 [30%]) than in the placebo group (58/121 [48%]; adjusted hazard ratio, 0.54; 95% confidence interval, 0.35-0.83; P = .004; number needed to treat, 5.6). Compared with placebo, patients receiving hydrocortisone did not have higher rates of superficial or deep wound infections, or other major complications.\n Intravenous hydrocortisone reduced the incidence of AF after cardiac surgery.\n clinicaltrials.gov Identifier: NCT00442494.", "Atrial tachyarrhythmias after cardiac surgery are associated with adverse outcomes and increased costs. Previous trials of amiodarone prophylaxis, while promising, were relatively small and yielded conflicting results.\n To determine whether a brief perioperative course of oral amiodarone is an effective and safe prophylaxis for atrial tachyarrhythmias after cardiac surgery overall and in important subgroups.\n Double-blind randomized controlled trial of 601 patients listed for nonemergent coronary artery bypass graft (CABG) surgery and/or valve replacement/repair surgery between February 1, 1999, and September 26, 2003, at a tertiary care hospital. The patients were followed up for 1 year.\n Oral amiodarone (10 mg/kg daily) or placebo administered 6 days prior to surgery through 6 days after surgery (13 days). Randomization was stratified for subgroups defined by age, type of surgery, and use of preoperative beta-blockers.\n Incidence of atrial tachyarrhythmias lasting 5 minutes or longer that prompted therapy by the sixth postoperative day.\n Atrial tachyarrhythmias occurred in fewer amiodarone patients (48/299; 16.1%) than in placebo patients (89/302; 29.5%) overall (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.34-0.69; P<.001); in patients younger than 65 years (19 [11.2%] vs 36 [21.1%]; HR, 0.51 [95% CI, 0.28-0.94]; P = .02); in patients aged 65 years or older (28 [21.7%] vs 54 [41.2%]; HR, 0.45 [95% CI, 0.27-0.75]; P<.001); in patients who had CABG surgery only (22 [11.3%] vs 46 [23.6%]; HR, 0.45 [95% CI, 0.26-0.79]; P = .002); in patients who had valve replacement/repair surgery with or without CABG surgery (25 [23.8%] vs 44 [44.1%]; HR, 0.51 [95% CI, 0.31-0.84; P = .008); in patients who received preoperative beta-blocker therapy (27 [15.3%] vs 42 [25.0%]; HR, 0.58 [95% CI, 0.34-0.99]; P = .03); and in patients who did not receive preoperative beta-blocker therapy (20 [16.3%] vs 48 [35.8%]; HR, 0.40 [95% CI, 0.22-0.71]; P<.001), respectively. Postoperative sustained ventricular tachyarrhythmias occurred less frequently in amiodarone patients (1/299; 0.3%) than in placebo patients (8/302; 2.6%) (P = .04). Dosage reductions of blinded therapy were more common in amiodarone patients (34/299; 11.4%) than in placebo patients (16/302; 5.3%) (P = .008). There were no differences in serious postoperative complications, in-hospital mortality, or readmission to the hospital within 6 months of discharge or in 1-year mortality.\n Oral amiodarone prophylaxis of atrial tachyarrhythmias after cardiac surgery is effective and may be safe overall and in important patient subgroups. Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00251706.", "Treatment with antiarrhythmic drugs and anticoagulation is considered first-line therapy in patients with symptomatic atrial fibrillation (AF). Pulmonary vein isolation (PVI) with radiofrequency ablation may cure AF, obviating the need for antiarrhythmic drugs and anticoagulation.\n To determine whether PVI is feasible as first-line therapy for treating patients with symptomatic AF.\n A multicenter prospective randomized study conducted from December 31, 2001, to July 1, 2002, of 70 patients aged 18 to 75 years who experienced monthly symptomatic AF episodes for at least 3 months and had not been treated with antiarrhythmic drugs.\n Patients were randomized to receive either PVI using radiofrequency ablation (n=33) or antiarrhythmic drug treatment (n=37), with a 1-year follow-up.\n Recurrence of AF, hospitalization, and quality of life assessment.\n Two patients in the antiarrhythmic drug treatment group and 1 patient in the PVI group were lost to follow-up. At the end of 1-year follow-up, 22 (63%) of 35 patients who received antiarrhythmic drugs had at least 1 recurrence of symptomatic AF compared with 4 (13%) of 32 patients who received PVI (P<.001). Hospitalization during 1-year follow-up occurred in 19 (54%) of 35 patients in the antiarrhythmic drug group compared with 3 (9%) of 32 in the PVI group (P<.001). In the antiarrhythmic drug group, the mean (SD) number of AF episodes decreased from 12 (7) to 6 (4), after initiating therapy (P = .01). At 6-month follow-up, the improvement in quality of life of patients in the PVI group was significantly better than the improvement in the antiarrhythmic drug group in 5 subclasses of the Short-Form 36 health survey. There were no thromboembolic events in either group. Asymptomatic mild or moderate pulmonary vein stenosis was documented in 2 (6%) of 32 patients in the PVI group.\n Pulmonary vein isolation appears to be a feasible first-line approach for treating patients with symptomatic AF. Larger studies are needed to confirm its safety and efficacy.", "Postoperative atrial fibrillation is common after coronary surgery. The cellular condition of atrial myocytes might play a part in the postoperative development of atrial fibrillation. Our study aimed to investigate whether patients in whom postoperative atrial fibrillation develops show pre-existent alterations in histopathology of the right atrium and how such changes are expressed in relation to the use of cardiopulmonary bypass.\n Seventy patients undergoing elective coronary revascularization were prospectively randomized to on-pump conventional surgery (conventional coronary artery bypass grafting, n = 35) or off-pump surgery on the beating heart (off-pump coronary artery bypass grafting, n = 35). Samples from the right atrial appendage were immediately collected after opening the pericardium. In the on-pump group samples were also taken after weaning from cardiopulmonary bypass. Focusing on degenerative alterations, histology was studied by means of light microscopy and for confirmation of particular findings by means of electronic microscopy.\n Twenty-two (31%) patients had postoperative atrial fibrillation, with the rate not being different between the off-pump coronary artery bypass grafting and conventional coronary artery bypass grafting groups (P = .797). Left atrial enlargement and inotropic requirement were related to atrial fibrillation. Interstitial fibrosis, vacuolization, and nuclear derangement of myocytes were the histologic abnormalities associated with the development of postoperative atrial fibrillation. However, in multivariate analysis fibrosis was confounded by myocyte vacuolization (P = .002) and nuclear derangement (P = .016), representing independent atrial fibrillation predictors. As expected, the conventional coronary artery bypass grafting and off-pump coronary artery bypass grafting groups showed similar histology, but more importantly, no atrial changes were detected in relation to cardiopulmonary bypass exposure in the conventional coronary artery bypass grafting group. Atrial histology showed degenerative changes that correlated with advanced age and left atrial enlargement.\n Our study supports the contention that atrial fibrillation after coronary surgery is associated with pre-existing histopathologic changes of the right atrium. Patients randomly allocated to off-pump coronary artery bypass grafting procedures showed a similar rate of atrial fibrillation and a similar relationship to atrial histology as did those exposed to cardiopulmonary bypass. Cardiopulmonary bypass did not cause additional changes in tested histology variables.", "Atrial fibrillation (AF) and diabetes mellitus type 2 (DM2) often coexist; however, a small number of patients with DM2 undergoing catheter ablation (CA) of AF have been included in previous studies. The aim of this study was to evaluate safety and efficacy of ablation therapy in DM2 patients with drug refractory AF.\n From January 2005 to September 2006, 70 patients with a diagnosis of DM2 and paroxysmal (n = 29) or persistent (n = 41) AF were randomized to receive either pulmonary vein isolation or a new antiarrhythmic drug treatment (ADT) with a 1-year follow-up. The primary endpoint was the time to first AF recurrence. By Kaplan-Meier analysis, at the end of follow-up, 42.9% of patients in the ADT group and 80% of patients who received a single ablation procedure and were without medications were free of AF (P = 0.001). In the ablation group, a significant improvement in quality-of-life (QoL) scores as compared with ADT group was observed. Six patients in the ADT group (17.1%) developed significant adverse drug effects. Hospitalization rate during follow-up was higher in the ADT group (P = 0.01). The only complication attributable to ablation was one significant access-site hematoma.\n In patients with DM2, CA of AF provides significant clinical benefits over the ADT and appears to be a reasonable approach regarding feasibility, effectiveness, and low procedural risk.", "After aorta-coronary bypass grafting, 164 consecutive patients were randomized to receive propranolol 5 mg every 6 hours orally (n = 82) or to serve as control subjects (n = 82). All patients were receiving beta blockers preoperatively. There were no significant differences between the two groups. The incidence of sustained supraventricular (nonsinus) tachyarrhythmias was 23% in the control group and 9.8% in the treated group (p = 0.02). The incidence of ventricular arrhythmias was 15% in the control group and 2.4% in the treated group (p = 0.005). The overall difference in clinically important arrhythmias was 38% in the control group and 12.2% in the treated group (p = 0.0002). We conclude that low-dose oral propranolol in patients who were receiving beta blockers preoperatively is effective in reducing the incidence of clinically important arrhythmias occurring after aorta-coronary bypass grafting.", "The purpose of this study was to evaluate the safety and efficacy of postoperative administration of prophylactic amiodarone in the prevention of new-onset postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting.\n In this prospective study 157 patients were randomly divided into two groups: 77 patients (amiodarone group) received intravenous amiodarone in a dose of 10 mg/kg/d for postoperative 48 hours. On postoperative day 2 oral amiodarone was started with a dose of 600 mg/d for 5 days, 400 mg/d for the following 5 days, and 200 mg/d for 20 days, and 80 patients received placebo (control group).\n Preoperative patient characteristics and operative variables were similar in the two groups. Postoperative atrial fibrillation occurred in 8 patients (10.4%) receiving amiodarone and in 20 (25.0%) patients receiving placebo (P =.017). Duration of atrial fibrillation was 12.8 +/- 4.8 hours for the amiodarone group compared with 34.7 +/- 28.7 hours for the control group (P =.003). The maximum ventricular rate during atrial fibrillation was slower in the amiodarone group than in the control group (105.9 +/- 19.1 beats per minute and 126.0 +/- 18.5 beats per minute, respectively, P =.016). The two groups had a similar incidence of complication other than rhythm disturbances (20.8% vs 20.0%, P =.904). Amiodarone group patients had shorter hospital stays than that of control group patients (6.8 +/- 1.7 days vs 7.8 +/- 2.9 days, P =.014). The in-hospital mortality was not different between two groups (1.3% vs 3.8, P =.620).\n Postoperative intravenous amiodarone, followed by oral amiodarone, appears to be effective in the prevention of new-onset postoperative atrial fibrillation. It also reduces ventricular rate and duration of atrial fibrillation after coronary artery bypass grafting. It is well tolerated and decreases the length of hospital stay.", "To assess the efficacy of a multifactorial educational intervention carried out by a pharmacist in patients with heart failure (HF).\n A randomized, prospective, open clinical trial in patients admitted for HF. The patients assigned to the intervention group received information about the disease, drug therapy, diet education, and active telephone follow-up. Visits were completed at 2, 6, and 12 months. Hospital re-admissions, days of hospital stay, treatment compliance, satisfaction with the care received, and quality of life (EuroQol) were evaluated; a financial study was conducted in order to assess the possible impact of the program. The intervention was performed by the pharmacy department in coordination with the cardiology unit.\n 134 patients were included, with a mean age of 75 years and a low educational level. The patients of the intervention group had a higher level of treatment compliance than the patients in the control group. At 12 months of follow-up, 32.9% fewer patients in the intervention group were admitted again vs. the control group. The mean days of hospital stay per patient in the control group were 9.6 (SD=18.5) vs. 5.9 (SD=14.1) in the intervention group. No differences were recorded in quality of life, but the intervention group had a higher score in the satisfaction scale at two months [9.0 (SD=1.3) versus 8.2 (SD=1.8) p=0.026]. Upon adjusting a Cox survival model with the ejection fraction, the patients in the intervention group had a lower risk of re-admission (Hazard ratio 0.56; 95% CI: 0.32-0.97). The financial analysis evidenced savings in hospital costs of euro 578 per patient that were favorable to the intervention group.\n Postdischarge pharmaceutical care allows for reducing the number of new admissions in patients with heart failure, the total days of hospital stay, and improves treatment compliance without increasing the costs of care.", "Supraventricular tachyarrhythmias are common after coronary artery bypass graft surgery (CABG) and may have deleterious hemodynamic consequences. To determine if acebutolol, a cardioselective beta-blocking drug, prevents such tachyarrhythmias after CABG, 100 consecutive patients, aged 30 to 77 years (mean +/- standard deviation 53 +/- 9), were entered into a randomized, controlled study. Exclusion criteria were: contraindications to beta-blocking drugs, left ventricular aneurysm, major renal failure, history of cardiac arrhythmia and cardiac arrhythmia during the immediate postoperative period. From 36 hours after surgery until discharge (usually on the seventh day), 50 patients were given 200 mg of acebutolol (or 400 mg if weight was more than 80 kg) orally twice a day (dosage than modified to maintain a heart rate at rest between 60 and 90 beats/min). The 50 patients in the control group did not receive beta-blocking drugs after CABG. The 2 groups were comparable in angina functional class, ejection fraction, number of diseased vessels, antianginal therapy before CABG, number of bypassed vessels and duration of cardiopulmonary bypass All patients were clinically evaluated twice daily and had continuous electrocardiographic monitoring and daily electrocardiograms. A 24-hour continuous electrocardiogram was recorded in the last 20 patients.(ABSTRACT TRUNCATED AT 250 WORDS)", "A prospective, randomized study was performed in 100 consecutive patients undergoing coronary artery bypass surgery to assess the efficacy of the early reinstitution of propranolol in reducing the incidence of postoperative supraventricular tachyarrhythmias (SVT). Patients were randomized to receive propranolol 10 mg every 6 hours enterally starting the morning after surgery (Group I, 50 patients) or to serve as controls (Group II, 50 patients). No patient was excluded because of poor ventricular function, need for urgent revascularization, or transient necessity for ionotropic support. Both groups had a comparable incidence of risk factors, previous infarction, unstable angina, and abnormal ventricular function. The extent of coronary disease, preoperative propranolol dose, and number of grafts performed were also similar. SVT occurred in 3/50 (6%) patients in Group I compared with 14/50 (28%) in Group II (p less than 0.01). There were no preoperative or intraoperative discriminators to predict the occurrence of SVT. In addition, perioperative infarction and the need for mechanical or pharmacologic circulatory support did not predispose to SVT. The data indicate that early administration of propranolol should be given to all patients after myocardial revascularization to decrease the incidence of these postoperative rhythm disturbances.", "Oxidative stress has recently been implicated in the pathophysiology of atrial fibrillation (AF). The aim of the present study was to evaluate the effects of antioxidant agent N-acetylcysteine (NAC) on postoperative AF.\n The population of this prospective, randomized, double-blind, placebo-controlled study consisted of 115 patients undergoing coronary artery bypass and/or valve surgery. All the patients were treated with standard medical therapy and were randomized to NAC group (n = 58) or placebo (saline, n = 57). An AF episode >5 min during hospitalization was accepted as endpoint. During follow-up period, 15 patients (15/115, 13%) had AF. The rate of AF was lower in NAC group compared with placebo group (three patients in NAC group [5.2%] and 12 patients in placebo group [21.1%] had postoperative AF; odds ratio [OR] 0.20; 95% confidence interval [CI] 0.05 to 0.77; P = 0.019). In the multivariable logistic regression analysis, independent predictors of postoperative AF were left atrial diameter (OR, 1.18; 95% CI, 1.06-1.31; P = 0.002) and the use of NAC (OR, 0.20; 95% CI, 0.04-0.91; P = 0.038).\n The result of this study indicates that NAC treatment decreases the incidence of postoperative AF.", "The purpose of this prospective randomized study was to investigate the efficacy of atrial overdrive pacing (AOP) and bradycardia prevention pacing (BPP) in the prophylaxis of atrial fibrillation (AF) after coronary artery bypass surgery (CABG).\n One hundred and twenty-four on-pump CABG patients were randomized into three groups: AOP, BPP, and NP (no pacing). AOP patients were paced via epicardial wires using an atrial preference pacing algorithm, and BPP patients were paced in the AAI mode with a base rate of 60/min. Patients were paced for 48 h starting on the first postoperative day. The endpoint of the study was the first onset of AF lasting longer than 5 min.\n Preoperative risk factors and surgical data of patients did not differ between the AOP, BPP and NP groups. Pacing was technically successful in 80.5% of patients in the AOP and in 92.7% in the BPP groups. The incidence of AF in the AOP (26.8%), BPP (19.5%) and NP (28.6%) groups did not differ significantly. In the AOP group, AF in three patients was probably induced by inappropriate pacing due to sensing failure.\n Atrial overdrive pacing and bradycardia prevention pacing were not effective in the prevention of AF after CABG.", "Atrial fibrillation occurs commonly after open-heart surgery and may delay hospital discharge. The purpose of this study was to assess the use of preoperative amiodarone as prophylaxis against atrial fibrillation after cardiac surgery.\n In this double-blind, randomized study, 124 patients were given either oral amiodarone (64 patients) or placebo (60 patients) for a minimum of seven days before elective cardiac surgery. Therapy consisted of 600 mg of amiodarone per day for seven days, then 200 mg per day until the day of discharge from the hospital. The mean (+/-SD) preoperative total dose of amiodarone was 4.8+/-0.96 g over a period of 13+/-7 days.\n Postoperative atrial fibrillation occurred in 16 of the 64 patients in the amiodarone group (25 percent) and 32 of the 60 patients in the placebo group (53 percent) (P=0.003). Patients in the amiodarone group were hospitalized for significantly fewer days than were patients in the placebo group (6.5+/-2.6 vs. 7.9+/-4.3 days, P=0.04). Nonfatal postoperative complications occurred in eight amiodarone-treated patients (12 percent) and in six patients receiving placebo (10 percent, P=0.78). Fatal postoperative complications occurred in three patients who received amiodarone (5 percent) and in two who received placebo (3 percent, P= 1.00). Total hospitalization costs were significantly less for the amiodarone group than for the placebo group ($18,375+/-$13,863 vs. $26,491+/-$23,837, P=0.03).\n Preoperative oral amiodarone in patients undergoing complex cardiac surgery is well tolerated and significantly reduces the incidence of postoperative atrial fibrillation and the duration and cost of hospitalization.", "Atrial fibrillation (AF) is common after coronary artery bypass surgery (CABG) and results in prolonged hospitalization. The purpose of this study was to evaluate the efficacy of biatrial pacing in preventing post-CABG AF compared with single-site atrial pacing.\n A total of 132 patients who had no history of AF and who underwent CABG were randomized to 1 of the following 4 groups: biatrial pacing (BiA), left atrial pacing (LA), right atrial pacing (RA), or no pacing (control) in postoperative period. Overdrive atrial pacing was performed for 5 days. The incidence of AF was significantly reduced in the BiA group (12.5%) compared with the other 3 groups (LA, 36.4%; RA, 33.3%; control, 41. 9%; P<0.05). The mean length of hospital stay was significantly reduced in the BiA group. At baseline, the mean P-wave duration (P(dur)) and dispersion (P(dis)) were not prolonged. BiA pacing resulted in the most significant percentage of reduction in P(dis) when compared with the LA or RA groups (BiA, 42+/-8%; LA, 13+/-6%; RA, 10+/-9%; P<0.05 for BiA versus LA or RA). No significant differences existed in mean P(dur) and P(dis) between patients who developed AF and those who remained in sinus rhythm at baseline. However, only those patients who remained in sinus rhythm had a significant reduction in mean P(dur) and P(dis) after pacing therapy.\n Biatrial overdrive pacing is more effective in preventing post-CABG AF than single-site atrial pacing; this therapy also results in a shortened hospital stay. The overall reduction in atrial activation time with BiA pacing was reflected in the reduction in P(dis).", "Various regimens have been proposed for the prevention of postoperative atrial fibrillation, including the use of intravenous and oral amiodarone. The purpose of this study was to determine the effectiveness of a single-day loading dose of oral amiodarone in prophylaxis of atrial fibrillation during the 7 days after coronary artery bypass surgery.\n We conducted a double-blind, randomized, placebo-controlled study encompassing 315 consecutive patients who underwent coronary artery bypass surgery. They received either amiodarone (159 patients) or placebo (156 patients). Therapy consisted of a single oral loading dose of 1200 mg of amiodarone 1 day before surgery, followed by the maintenance dose of 200 mg daily during the next 7 days. Only episodes of atrial fibrillation lasting more than 1 hour or associated with hemodynamic compromise were taken into consideration.\n Overall, the incidence of atrial fibrillation was similar in patients who received amiodarone (31/159, 19.5%) and placebo (33/156, 21.2%) (P = .78). However, amiodarone reduced the incidence of atrial fibrillation in elderly patients (age > or = 60 years): it occurred in 20 of 75 (26.7%) patients on amiodarone and in 28 of 65 (43.1%) patients in the placebo group (P = .05). There were no differences between the study groups regarding the postoperative intrahospital morbidity and mortality and the duration of hospital stay.\n A single-day loading dose of oral amiodarone (1200 mg) does not prevent postoperative atrial fibrillation in a general population of patients undergoing coronary artery bypass surgery. However, it appears that this regimen reduces the occurrence of postoperative atrial fibrillation in elderly patients.", "New onset of atrial fibrillation is a frequent complication after coronary artery bypass grafting and is a major cause of postoperative morbidity. Preoperative oral treatment with amiodarone hydrochloride has been shown to be efficacious as prophylaxis. The present study investigated whether intraoperative use of intravenous amiodarone has a preventive effect on the incidence of atrial fibrillation after coronary revascularization.\n In a prospective study, 150 consecutive patients (mean age, 63 +/- 8 years; 132 men and 18 women) undergoing coronary artery bypass grafting were randomly assigned to one of three groups. Two groups received different doses of intravenous amiodarone (group I, 300-mg bolus and 20 mg x kg(-1) x day(-1) for 3 days; group II, 150-mg bolus and 10 mg x kg(-1) x day(-1) for 3 days) after aortic cross-clamping and one group, placebo (group III). Continuous electrocardiographic online monitoring was performed for 10 days. Arrhythmias were analyzed with respect to type, frequency, duration, and clinical relevance.\n New onset of atrial fibrillation occurred in 24% of patients in group I, 28% in group II, and 34% in group III (p = not significant). Atrial fibrillation with a rapid ventricular response (>120 beats per minute) was significantly more frequent in the control group (group I, 14%; group II, 24%; group III, 32%; p < 0.05, group I versus group III) and appeared significantly earlier (group I, day 4.3 +/- 2.5; group II, day 4.8 +/- 2.9; group III, day 2.6 +/- 1.3; p < 0.05, group III versus groups I and II). Temporary atrial pacing because of bradycardia (<60 beats per minute) was necessary significantly more often in group I (group I, 48%; group II, 40%; group III, 28%; p < 0.05, group I versus group III). Early mortality rate (group I, 4%; group II, 2%; group III, 4%), rate of perioperative complications (group I, 14%; group II, 20%; group III, 14%), and duration of hospital stay (group I, 14.0 days; group II, 14.4 days; group III, 14.7 days) were not different between groups.\n Intraoperative prophylactic use of amiodarone does not prevent new onset of atrial fibrillation in patients undergoing coronary artery bypass grafting and had no effect on outcome. Therefore, intraoperative prophylactic treatment with amiodarone at the tested doses does not appear to be justified.", "We studied the influence of rate control or rhythm control in patients with persistent atrial fibrillation (AF) on quality of life (QoL).\n Atrial fibrillation may cause symptoms like fatigue and dyspnea. This can impair QoL. Treatment of AF with either rate or rhythm control may influence QoL.\n Quality of life was assessed in patients included in the Rate Control Versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study (rate vs. rhythm control in persistent AF). Rate control patients (n = 175) were given negative chronotropic drugs and oral anticoagulation. Rhythm control patients (n = 177) received serial electrocardioversion, antiarrhythmic drugs, and oral anticoagulation, as needed. Quality of life was studied using the Short Form (SF)-36 health survey questionnaire at baseline, one year, and the end of the study (after 2 to 3 years of follow-up). At baseline, QoL was compared with that of healthy control subjects. Patient characteristics related to QoL changes were determined.\n Mean follow-up was 2.3 years. At baseline, QoL was lower in patients than in age-matched healthy controls. At study end, under rate control, three subscales of the SF-36 improved. Under rhythm control, no significant changes occurred compared with baseline. At study end, QoL was comparable between both groups. The presence of complaints of AF at baseline, a short duration of AF, and the presence of sinus rhythm (SR) at the end of follow-up, rather than the assigned strategy, were associated with QoL improvement.\n Quality of life is impaired in patients with AF compared with healthy controls. Treatment strategy does not affect QoL. Patients with complaints related to AF, however, may benefit from rhythm control if SR can be maintained.", "To determine whether restarting of Beta Blocker following cardiac surgery would reduce the incidence and the severity of post-operative atrial fibrillation (AF).\n 210 patients who underwent elective coronary artery bypass grafting were randomized to control (C) (n = 105) and Beta Blockers (BB) (n = 105) groups. Preoperatively all patients were on one type or another of betablockers. Postoperatively only the (BB) group received the medication. Both groups were well matched and had the same cardioplegic technique.\n It was found that; (1) post op (AF) developed in 40 patients of group (C) and in 18 patients of group (BB) P value < 0.02. (2) 73% of (AF) patients in group (C) and 81% in group (BB) were older than 70 years of age. (3) 76% of the (AF) in (BB) group versus 43% in (C) group were converted to sinus rhythm or to a stable controlled rhythm within 24 h or less. P value < 0.01.\n The results indicate that restarting the Beta Blockers in the post-operative period after coronary bypass grafts significantly control the incidence and the severity of atrial fibrillation. Also it confirms the strong relation between the older age and (AF) occurrence.", "This study sought to determine whether ablation of complex fractionated atrial electrograms (CFAEs) after antral pulmonary vein isolation (APVI) further improves the clinical outcome of APVI in patients with long-lasting persistent atrial fibrillation (AF).\n Ablation of CFAEs has been reported to eliminate persistent AF. However, residual pulmonary vein arrhythmogenicity is a common mechanism of recurrence.\n In this randomized study, 119 consecutive patients (mean age 60 +/- 9 years) with long-lasting persistent AF underwent APVI with an irrigated-tip radiofrequency ablation catheter. Antral pulmonary vein isolation resulted in termination of AF in 19 of 119 patients (Group A, 16%). The remaining 100 patients who still were in AF were randomized to no further ablation and underwent cardioversion (Group B, n = 50) or to ablation of CFAEs in the left atrium or coronary sinus for up to 2 additional hours of procedure duration (Group C, n = 50).\n Atrial fibrillation terminated during ablation of CFAEs in 9 of 50 patients (18%) in Group C. At 10 +/- 3 months after a single ablation procedure, 18 of 50 (36%) in Group B and 17 of 50 (34%) in Group C were in sinus rhythm without antiarrhythmic drugs (p = 0.84). In Group A, 15 of 19 patients (79%) were in sinus rhythm. A repeat ablation procedure was performed in 34 of 100 randomized patients (for AF in 30 and atrial flutter in 4). At 9 +/- 4 months after the final procedure, 34 of 50 (68%) in Group B and 30 of 50 (60%) in Group C were in sinus rhythm without antiarrhythmic drugs (p = 0.40).\n Up to 2 h of additional ablation of CFAEs after APVI does not appear to improve clinical outcomes in patients with long-lasting persistent AF.", "In the present study 75 patients were double blind randomized either to receive 10 mg propranolol orally 4 times a day (35 patients) or a placebo (40 patients). Episodes of clinically important supraventricular tachyarrhythmias were recorded in the first 4 postoperative days. They appeared in 5 of 35 patients receiving propranolol and in 5 of 40 patients receiving placebo (no statistically significant difference). In conclusion this study indicates the need for further evaluation to clarify if low-dose propranolol or any other drug is effective in reducing the frequency of SVT in the early postoperative period after coronary artery bypass surgery.", "This study compared the efficacy and safety of sotalol and quinidine for conversion and prevention of recurrent atrial fibrillation.\n Atrial fibrillation is the most common arrhythmia. Pharmacologic therapy has been advocated for both immediate restoration of sinus rhythm and prevention of recurrent atrial fibrillation. Quinidine is the therapeutic mainstay for both purposes, but its safety has recently been questioned. Although sotalol has been used successfully to maintain sinus rhythm after direct current cardioversion, its efficacy in pharmacologically reverting atrial fibrillation has not been examined.\n Fifty consecutive patients with persistent atrial fibrillation were randomized to receive quinidine or sotalol for up to 7 days to restore sinus rhythm. Patients were followed up for 6 months.\n Quinidine was more effective than sotalol in terminating atrial fibrillation (60% vs. 20%, p = 0.009). When nonresponders to drug therapy underwent subsequent direct current cardioversion, total conversion rates in the quinidine and sotalol groups were comparable (88% vs. 68%, p = 0.17), as was the efficacy of the two drugs in preventing recurrent atrial fibrillation. Side effects necessitating drug discontinuation were more often observed with quinidine. No patient receiving sotalol but four patients receiving quinidine had drug-associated arrhythmia (torsade de pointes in three patients, sustained ventricular tachycardia in one patient). Precordial QT dispersion determined on the surface electrocardiogram (ECG) increased with quinidine (mean +/- SD 34 +/- 9 vs. 44 +/- 16 ms, p = 0.02), indicating enhanced inhomogeneity in ventricular repolarization. There was no change in QT dispersion in patients receiving sotalol (36 +/- 18 vs. 40 +/- 17 ms, p = 0.44).\n Quinidine is more effective than sotalol in terminating atrial fibrillation but is associated with more side effects. The proarrhythmic risk may be related to quinidine's propensity to increase disparity in ventricular repolarization. This risk warrants careful ECG monitoring during the 1st 4 to 7 days of therapy. Because most proarrhythmic effects occurred shortly after restoration of sinus rhythm, observation should continue > or = 2 to 3 days after sinus rhythm is reestablished.", "The limited efficacy and proarrhythmic risks of antiarrhythmia agents have resulted in alternative therapeutic approaches. Radiofrequency ablation has been reported to be an effective treatment of patients with atrial fibrillation. However, there is no randomized clinical trial comparing drug and radiofrequency ablation. The authors randomized 30 patients with chronic atrial fibrillation refractory to medication into amiodarone and radiofrequency ablation. The primary objective of this study was to compare the efficacy of amiodarone and radiofrequency ablation in the maintenance of sinus rhythm at 1 year after randomization. Pulmonary vein isolation and linear ablation of right atrium was the technique used for radiofrequency ablation. There were no significant differences in baseline patient characteristics between the 2 groups. The results of this study showed that the probability of free from atrial fibrillation was better in the radiofrequency ablation group compared to amiodarone (78.6% in the ablation group and 40% in the amiodarone group, p = 0.018). Radiofrequency ablation results in a significant reduction in symptoms relating to atrial fibrillation and a significant improvement in quality of life, whereas amiodarone had no significant effect on symptoms and quality of life. There was an ischemic stroke as a major complication related to radiofrequency ablation. Amiodarone was associated with adverse effects in 46.7 per cent of patients and needed discontinuation in 1 patient. In conclusion, radiofrequency ablation is an effective alternative treatment in patients with atrial fibrillation refractory to medication.", "Circumferential pulmonary vein ablation (CPVA) is effective in curing atrial fibrillation (AF), but new-onset left atrial tachycardia (AT) is a potential complication. We evaluated whether a modified CPVA approach including additional ablation lines on posterior wall and the mitral isthmus would reduce the incidence of AT after PV ablation.\n A total of 560 patients (291 men, 52%; age, 56.5+/-7.3 years) entered the study; 280 were randomized to CPVA alone (group 1) and 280 to modified CPVA (group 2). The primary end point was freedom from AT after the procedure. In group 1, 28 patients (10%) experienced new-onset AT, and 41 (14.3%) experienced recurrent AF. In group 2, 11 patients (3.9%) experienced AT, and 36 (12.9%) had recurrent AF. Group 1 was more likely to experience AT than group 2 (P=0.005). Freedom from AF after ablation was similar in both groups (P=0.57). Among those in group 1, gap-related macroreentrant AT was documented in 23 of the 28 patients (82%), and focal AT was found in 5 (18%). In group 2, gap-related macroreentrant AT was found in 8 of the 11 patients (73%), and focal AT was seen in 3 (27%). Two patients in group 1 and 1 patient in group 2 had both AT and AF. The strongest predictor of AT was the presence of gaps (P<0.001).\n Modified CPVA is as effective as CPVA in preventing AF but is associated with a lower risk of developing incessant AT.", "Aim of the present study was to assess the efficacy and safety of flecainide (F) and sotalol (S) for the prevention of recurrences of paroxysmal atrial fibrillation (PAF).\n Sixty-six patients with PAF (> or = 3 episodes of atrial fibrillation in the last year) in sinus rhythm, were randomized to pharmacological oral treatment with F (20 patients-Group A), with S (20 patients-Group B) and placebo (P) (26 patients-Group C). During the follow-up (one year duration) were evaluated on I, III, VI and XII months the number and tolerance of the atrial fibrillation recurrences, cardiac and/or noncardiac side effects. The patients with more than two recurrences in the same follow-up interval withdrew from the study. In each patient 14 clinical and laboratory variables were evaluated.\n After 12 months were arrhythmia-free respectively 70% of Group A patients, 60% of Group B patients, 27% of Group C patients. Univariate analysis showed that treatment with F was related to decrease of atrial fibrillation recurrences (one recurrence 67%, two recurrences 81%, three recurrences 81%), treatment with S was related to decrease of recurrences (two recurrences 59%); the variable most significantly related to the risk of arrhythmia recurrence is the higher value of basal cardiac rate (one recurrence t = 2.15, two t = 2.22, three t = 2.96, four t = 2.06). There was not statistically significant difference in maintenance of sinus rhythm at the end of the follow-up between the groups of patients on F and S (p = 0.163); treatment efficacy was significantly higher than P (p = 0.002). Multivariate analysis showed that treatment with F and S decreases the risk of arrhythmia recurrence respectively of 85% and 76% versus placebo at the end of the follow-up. The incidence of cardiac and/or noncardiac side effects was not clinically significant.\n F and S are both effective and safe for prevention of PAF, with 70% and 60% respectively of patients arrhythmia-free after 12 months of treatment. Side effects were common, but clinically significant adverse events were uncommon. A higher value of basal cardiac rate was predictive of atrial fibrillation recurrences in the patients during treatment.", "A high incidence of cardiac arrhythmias and hypertension has been noted after coronary artery bypass surgery in patients previously treated with oral propranolol. Forty-two patients undergoing coronary bypass surgery had propranolol withdrawal 10 hours before surgery and were randomized into a group treated with propranolol immediately postoperatively, and a nontreatment group. Patients treated with prophylactic propranolol had a significantly lower incidence of postoperative supraventricular arrhythmias compared to patints who received no prophylaxis. All the arrhythmias responded rapidly to 1 mg of intravenous propranolol therapy, whether it was used as a primary treatment or as a supplement to prophylactic propranolol. The findings suggest that (1) there is a high incidence of supraventricular arrhythmias and sinus tachycardia after coronary artery bypass which might reflect an abrupt propranolol withdrawal, and (2) that perioperative prophylactic or supplementary propranolol therapy will successfully prevent or treat most of these arrhythmias.", "To evaluate magnesium as a sole or adjuvant agent with currently used prophylactic drugs in suppressing postoperative atrial tachyarrhythmias (POAT) after coronary artery bypass graft (CABG) surgery.\n Single-center prospective, randomized clinical trial.\n University hospital.\n Patients (n = 400) undergoing CABG surgery.\n Patients were randomized among 6 prophylaxis regimens: (1) control (no antiarrhythmics), (2) magnesium only, (3) digoxin only, (4) magnesium and digoxin, (5) propranolol only, and (6) magnesium and propranolol. Patients randomized to a regimen including magnesium received 12 g given during 96 hours postoperatively. Patients in a digoxin regimen received 1 mg after cardiopulmonary bypass and 0.25 mg daily. Patients in a propranolol regimen received 1 mg intravenously every 6 hours until able to take 10 mg orally 4 times a day. Prophylaxis regimens were discontinued after 4 days postoperatively.\n The primary outcome was a sustained POAT or discharge from the hospital. Control patients had an incidence of POAT (38%) not significantly different from patients in magnesium-only (38%), digoxin-only (31%), and magnesium with digoxin (37%) regimens. Patients treated with propranolol had a significant reduction in POAT. Nearly identical POAT rates in the propranolol-only (18%) and propranolol with magnesium (19%) groups support the lack of efficacy of magnesium in this trial. Study design allowed analysis of and showed a beta-blocker withdrawal effect in addition to suppressive benefit of postoperative beta-blockers.\n beta-Blocker prophylaxis is indicated to reduce the incidence of POAT in CABG surgery patients and to prevent a beta-blocker withdrawal effect in patients receiving these medications preoperatively. Digoxin and magnesium as sole or adjuvant agents do not offer suppressive or ventricular rate reduction benefits in POAT.\n Copyright 2001 by W.B. Saunders Company", "Atrial fibrillation (AF) after coronary artery bypass graft (CABG) surgery is still the most common arrhythmic complication. This study evaluated whether pretreatment with atorvastatin protects against AF after off-pump CABG.\n One hundred twenty-four patients without a history of AF or previous statin use, who were scheduled to undergo elective off-pump CABG, were enrolled. Patients were randomized to control group (n = 62) or to atorvastatin group (n = 62) who were administered atorvastatin 20 mg/d for 3 days before the surgery. Primary outcome was the incidence of postoperative AF. Secondary outcomes were major adverse cardiac and cerebrovascular events, persistent AF at 1 month, and identification of the markers to predict inhospital postoperative AF.\n The incidence of AF was significantly lower in the atorvastatin group than in the control group (13% vs 27%, P = .04). The incidence of major adverse cardiac and cerebrovascular events and persistent AF at 1 month was similar in comparisons between the groups. Postoperative peak N-terminal pro-brain natriuretic peptide levels were significantly higher in the patients with AF (P = .03). Multivariate analysis identified pretreatment with atorvastatin as an independent factor associated with a significant reduction in postoperative AF (odds ratio 0.34, P = .04). Higher postoperative peak N-terminus pro-B-type natriuretic peptide levels were associated with the development of postoperative AF (odds ratio 1.02 per 100 pg/mL, P = .03).\n Pretreatment with atorvastatin significantly reduced the occurrence of postoperative AF after off-pump CABG.", "Atrial pacing is often used empirically to suppress atrial ectopy and prevent atrial fibrillation after coronary artery bypass grafting.\n To determine whether atrial overdrive pacing reduces atrial fibrillation and atrial ectopy after coronary artery bypass grafting, 100 patients were randomized to no atrial pacing (Control) versus AAI pacing at 10 beats/min or more above the resting heart rate (Paced), started by postoperative day 1 and continued through day 4. Major end points were new atrial fibrillation and frequency of atrial ectopy during the first 4 days after coronary artery bypass grafting.\n Atrial fibrillation occurred by day 4 in 13 of 51 (25.5%) Paced and in 14 of 49 (28.6%) Control patients, p = 0.90. Control patients who developed atrial fibrillation had significantly more atrial ectopy than those who did not. Atrial ectopy was paradoxically more frequent in the Paced group (2,106+/-428 versus 866+/-385 per 24 hours, p = 0.0001). Loss of capture, sensing, and consistent atrial pacing occurred frequently during atrial pacing.\n Contrary to prevailing opinion and practice, postoperative atrial overdrive pacing significantly increases atrial ectopy and does not reduce the likelihood of atrial fibrillation.", "Atrial fibrillation after coronary artery bypass is reported from 17% to 53%. Hypomagnesemia after this surgery is considered a contributing factor.\n Two hundred-two coronary bypass patients were randomized to magnesium (n = 105) or placebo (n = 97). The experimental group received 80-mg magnesium sulfate per kilogram ideal weight in 100 mL dextrose 5% water 30 minutes preoperatively. Postoperatively, patients received 8-mg magnesium sulfate per kilogram ideal weight intravenous per hour more than 48 hours. The control group received dextrose 5% water at these intervals.\n After the first bolus serum magnesium was experimental 4.75 mg/dL versus control 1.91 mg/dL, p less than 0.001, and remained different until postoperative day 4 (experimental 2.33 mg/dL vs control 2.26 mg/dL, p = 0.24). Atrial appendage and strap muscle were analyzed after the first bolus and after revascularization. There were no differences between groups in tissue magnesium or calcium. Urinary magnesium was elevated in the experimental (experimental 324.5 mg/24 hours, vs control 45.1 mg/24 hours, p = 0.01). Calcium excretion was higher (experimental 370 mg/24 hours vs control 186 mg/24 hours, p < 0.001) and was associated with lower serum calcium. Serum calcium was higher in the control through the fourth postoperative day. The incidence of atrial fibrillation was experimental 32 of 105 (30.5%) versus control 41 of 97 (42.3%) p = 0.08. Atrial fibrillation was different on the first postoperative day (experimental 3/105, 2.9% vs control 9/97, 9.3%), p = 0.05.\n Overall prophylactic magnesium supplementation does not significantly reduce atrial and ventricular arrhythmias. The only significant benefit of magnesium supplementation was on the first postoperative day.", "The primary objective of the present study was to assess the efficacy of metoprolol CR/XL to reduce the risk of relapse after cardioversion of persistent atrial fibrillation to sinus rhythm.\n Indirect data from studies with d,l sotalol provide evidence that the beta-blocking effects of the compound are important in maintaining sinus rhythm after cardioversion of atrial fibrillation.\n After successful conversion to sinus rhythm, 394 patients with a history of persistent atrial fibrillation were randomly assigned to treatment with metoprolol CR/XL or placebo. The two treatment groups were similar with respect to all pretreatment characteristics. Patients were seen on an outpatient basis for recording of resting electrocardiogram (ECG) after one week, one, three and six months of follow-up or whenever they felt that they had a relapse into atrial fibrillation or experienced an adverse event.\n In the metoprolol CR/XL group, 96 patients (48.7%) had a relapse into atrial fibrillation compared with 118 patients (59.9%) in the placebo group (p = 0.005). Heart rate in patients after a relapse into atrial fibrillation was significantly lower in the metoprolol group (98 +/- 23 beats/min) than in the placebo group (107 +/- 27 beats/min). The rate of adverse events reported was similar in both groups when the difference in follow-up time was taken into account.\n The results of this double-blind, placebo-controlled study in patients after cardioversion of persistent atrial fibrillation showed that metoprolol CR/XL was effective in preventing relapse into atrial fibrillation or flutter.", "Atrial fibrillation is a common complication after cardiac surgery. Magnesium is an effective and safe antiarrhythmic agent for arrhythmias that develop after cardiac surgery. The authors performed a study to evaluate the role of perioperative magnesium for prophylaxis of atrial fibrillation after off-pump coronary artery surgery.\n Randomized controlled study.\n University teaching hospital.\n One hundred sixty consecutive patients undergoing elective, isolated, off-pump coronary artery bypass grafting were prospectively randomized into 2 groups.\n Patients in the magnesium group (n = 80) received a 2.5-g (20 mEq) magnesium sulphate infusion intraoperatively over 30 minutes, and the placebo group (n = 80) received normal saline solution.\n Postoperative atrial fibrillation occurred in 16 of 80 patients (20%) in the magnesium group and in 18 of 80 (22.5%) in the placebo group (p = 0.9).\n The use of 2.5 g of intraoperative magnesium showed no effect in preventing atrial fibrillation after off-pump coronary artery bypass.", "Recently, several temporary multisite pacing methods have been developed for prevention of postoperative atrial fibrillation (AF).\n In this study, we evaluated the effect of triple-site temporary triggered pacing in the AAT mode on the development of AF in patients undergoing coronary artery bypass graft (CABG) at high risk for developing postoperative AF.\n A total of 70 patients undergoing CABG were randomly assigned either to pacing group (study group, n = 35 patients) or to no pacing group (control group, n = 35 patients). The external pacemaker was programmed to pace at the atrial triggered mode at a lower rate of 40 beats/min for 4 days.\n Atrial fibrillation, defined as lasting > 30 s, occurred in 4 patients (11.4%) in the study group and in 16 patients (45.7%) in the control group (p = 0.003). Sustained AF, defined as AF lasting > 10 min, also was observed less frequently in the study group than in the control group (11.6 vs. 37.1%, p = 0.024). Triple-site triggered atrial pacing was observed to reduce the incidence of AF by 75% and the incidence of sustained AF by 69%.\n We believe that multiple-site temporary pacing in the triggered mode is an effective way of preventing postoperative AF. This technique may be used especially in patients at high risk of developing AF.", "Azimilide dihydrochloride (azimilide) is an investigational antiarrhythmic drug that has been tested in patients with a variety of arrhythmias. In patients with atrial fibrillation, it has shown excellent efficacy in some previous trials and minimal efficacy in others.\n Patients who had symptomatic atrial fibrillation for > 48 hours but < 6 months were eligible for this multicenter, randomized, placebo-controlled clinical trial. Patients were admitted to a hospital and randomly assigned to receive either azimilide 125 mg or a matched placebo twice daily for 3 days and then once daily. Patients who were in sinus rhythm spontaneously or had sinus rhythm restored by electric cardioversion on day 4 were discharged from the hospital. Recurrence of atrial fibrillation was documented by electrocardiogram. In the primary efficacy analysis, time to recurrence in the 2 treatment groups was compared with the log-rank test in the subgroup of patients with structural heart disease. Safety was assessed as deaths, adverse events, and serious adverse events.\n A total of 446 patients were randomized in the study; 314 were in the subgroup with structural heart disease. The median time to arrhythmia recurrence in both treatment groups with structural heart disease was 13 days, and the difference between treatments was not significant (P = .4596, n = 314). The relative risk for recurrence (placebo:azimilide) was 1.104 (95% CI 0.849-1.436). There was 1 death in the placebo group and 3 in the azimilide group.\n Azimilide did not demonstrate clinically important or statistically significant efficacy in reducing the risk for arrhythmia recurrence in patients with structural heart disease who were in atrial fibrillation and converted to sinus rhythm.", "Asymptomatic, or \"silent\" atrial fibrillation could increase the risk of stroke. Little is known about the frequency of asymptomatic atrial fibrillation in patients who also have symptomatic atrial fibrillation; similarly, little is known about the effect of antiarrhythmic drug therapy on asymptomatic atrial fibrillation.\n Patients in sinus rhythm with a history of symptomatic atrial fibrillation or atrial flutter received placebo or azimilide (35 to 125 mg) once daily for 6 or 9 months in 4 similar double-blind trials. The end point was the first recurrence of a symptomatic ECG-documented supraventricular arrhythmia. Routine transtelephonic electrocardiograms, in the absence of symptoms, were recorded for 30 seconds every 2 weeks until patients completed follow-up or documented a symptomatic supraventricular arrhythmia. Of the 1380 patients, 489 received placebo. Among these patients receiving placebo, 303 transmitted at least one routine ECG while asymptomatic. Asymptomatic atrial fibrillation was recorded in 50 (17%) within 6 months and before recurrence of symptomatic supraventricular arrhythmia. In the 3 trials evaluating azimilide in therapeutic doses (100 and 125 mg), asymptomatic atrial fibrillation occurred in 49 of 382 (13%) receiving azimilide and 43 of 233 (18%) receiving placebo. Although drug effect on time to first asymptomatic event was not statistically significant (hazard ratio, 0.70; P=0.09), there was a 40% reduction in asymptomatic atrial fibrillation on azimilide compared with placebo (P=0.03) when repeated observations were considered.\n Asymptomatic atrial fibrillation is common in untreated patients with a history of symptomatic atrial fibrillation (and is likely underestimated by this analysis). Azimilide may reduce the occurrence of this silent arrhythmia.", "Atrial fibrillation in the absence of rheumatic valvular disease is associated with a fivefold to sevenfold increased risk of ischemic stroke.\n The Stroke Prevention in Atrial Fibrillation Study, a multicenter, randomized trial, compared 325 mg/day aspirin (double-blind) or warfarin with placebo for prevention of ischemic stroke and systemic embolism (primary events), and included 1,330 inpatients and outpatients with constant or intermittent atrial fibrillation. During a mean follow-up of 1.3 years, the rate of primary events in patients assigned to placebo was 6.3% per year and was reduced by 42% in those assigned to aspirin (3.6% per year; p = 0.02; 95% confidence interval, 9-63%). In the subgroup of warfarin-eligible patients (most less than 76 years old), warfarin dose-adjusted to prolong prothrombin time to 1.3-fold to 1.8-fold that of control reduced the risk of primary events by 67% (warfarin versus placebo, 2.3% versus 7.4% per year; p = 0.01; 95% confidence interval, 27-85%). Primary events or death were reduced 58% (p = 0.01) by warfarin and 32% (p = 0.02) by aspirin. The risk of significant bleeding was 1.5%, 1.4%, and 1.6% per year in patients assigned to warfarin, aspirin, and placebo, respectively.\n Aspirin and warfarin are both effective in reducing ischemic stroke and systemic embolism in patients with atrial fibrillation. Because warfarin-eligible patients composed a subset of all aspirin-eligible patients, the magnitude of reduction in events by warfarin versus aspirin cannot be compared. Too few events occurred in warfarin-eligible patients to directly assess the relative benefit of aspirin compared with warfarin, and the trial is continuing to address this issue. Patients with nonrheumatic atrial fibrillation who can safely take either aspirin or warfarin should receive prophylactic antithrombotic therapy to reduce the risk of stroke.", "The most frequent arrhythmia after coronary artery bypass surgery is atrial fibrillation (AF). The prevention and treatment of this type of arrhythmia is subobtimal. Digitalis, beta-blockers, diltiazem and amiodarone are the preferred drugs for the treatment. This study was designed to compare the effects of preoperatively started digitalis and atenolol in combination and separately, on the incidence of AF that occurs within 7 days following the operation.\n One-hundred and sixty patients who had similar demographic properties were randomly grouped as group I, that preoperatively received combined drug therapy (n=40), group II preoperatively used digitalis (n=40), group III atenolol (n=40), and group IV was the control group (n=40).\n Postoperative AF incidence was 25, 15,4, and 17,9% in groups IV, III, and II, respectively, whereas it was 5% in group I which was lower than all other groups, but the difference was only significant between groups I and IV (P=0.012).\n The combined use of atenolol and digitalis preoperatively was considered as an efficient treatment for lowering the incidence of AF following coronary artery bypass surgery.", "Despite recent rediscovery of beating heart cardiac surgical techniques, extracorporeal circulation remains appropriate for most heart operations. To minimize deleterious effects of cardiopulmonary bypass, antiinflammatory strategies have evolved.\n Four state-of-the-art strategies were studied in a prospective, randomized, preoperatively risk stratified, 400-patient study comprising primary (n = 358), reoperative (n = 42), coronary (n = 307), valve (n = 27), ascending aortic (n = 9), and combined operations (n = 23). Groups were as follows: standard, roller pump, membrane oxygenator, methylprednisolone (n = 112); aprotinin, standard plus aprotinin (n = 109); leukocyte depletion, standard plus a leukocyte filtration strategy (n = 112); and heparin-bonded circuitry, centrifugal pumping with surface modification (n = 67).\n Analysis of variance, linear and logistic regression, and Pearson correlation were applied. Actual mortality (2.3%) was less than half the risk stratification predicted mortality (5.7%). The treatment strategies effectively attenuated markers of the inflammatory response to extracorporeal circulation. Compared with the other groups the heparin-bonded circuit had highly significantly decreased complement activation (p = 0.00001), leukocyte filtration blunted postpump leukocytosis (p = 0.043), and the aprotinin group had less fibrinolysis (p = 0.011). Primary end points, length of stay, and hospital charges, were positively correlated with operation type, age, pump time, body surface area, stroke, pulmonary sequelae, predicted risk for stroke, predicted risk for mortality, and risk strata/treatment group interaction (p = 0.0001). In low-risk patients, leukocyte filtration reduced length of stay by 1 day (p = 0.02) and mean charges by $2,000 to $6,000 (p = 0.05). For high-risk patients, aprotinin reduced mean length of stay up to 10 fewer days (p = 0.02) and mean charges by $6,000 to $48,000 (p = 0.0007).\n These pharmacologic and mechanical strategies significantly attenuated the inflammatory response to extracorporeal circulation. This translated variably into improved patient outcomes. The increased cost of treatment was offset for selected strategies through the added value of significantly reduced risk.", "To determine the effects of prophylactic treatment with EACA for blood loss after cardipulmonary bypass surgery, 350 consecutive patients undergoing open-heart surgery were studied. One hundred seventy patients received an initial dose of 5 g of EACA prior to skin incision, followed by intravenous administration of 1 g/h for the next 6 to 8 h. The control group received saline solution in the same fashion. The EACA-treated group had decreased chest tube blood loss 24 h postoperatively. In addition, EACA-treated patients had fewer myocardial infarctions, cerebrovascular accidents or reoperations for bleeding. Treated patients needed fewer units of blood transfusions than the nontreated group. There was no incidence of hyperthrombotic state or other side effects in the EACA-treated group. We concluded that prophylactic treatment with EACA for open-heart surgery requiring extracorporeal circulation may reduce the total blood loss and the number of blood transfusions in a safe and tolerable manner.", "To evaluate a smoking cessation intervention that can be routinely delivered to smokers admitted with cardiac problems.\n Randomised controlled trial of usual care compared with intervention delivered on hospital wards by cardiac rehabilitation nurses.\n Inpatient wards in 17 hospitals in England.\n 540 smokers admitted to hospital after myocardial infarction or for cardiac bypass surgery who expressed interest in stopping smoking.\n Brief verbal advice and standard booklet (usual care). Intervention lasting 20-30 minutes including carbon monoxide reading, special booklet, quiz, contact with other people giving up, declaration of commitment to give up, sticker in patient's notes (intervention group).\n Continuous abstinence at six weeks and 12 months determined by self report and by biochemical validation at these end points. Feasibility of the intervention and delivery of its components.\n After six weeks 151 (59%) and 159 (60%) patients remained abstinent in the control and intervention group, respectively (P=0.84). After 12 months the figures were 102 (41%) and 94 (37%) (P=0.40). Recruitment was slow, and delivery of the intervention was inconsistent, raising concerns about the feasibility of the intervention within routine care. Patients who received the declaration of commitment component were almost twice as likely to remain abstinent than those who did not receive it (P<0.01). Low dependence on tobacco and high motivation to give up were the main independent predictors of positive outcome. Patients who had had bypass surgery were over twice as likely to return to smoking as patients who had had a myocardial infarction.\n Single session interventions delivered within routine care may have insufficient power to influence highly dependent smokers.", "The effectiveness of recruiting local medical opinion leaders to improve quality of care is poorly understood.\n To evaluate a guideline-implementation intervention of clinician education by local opinion leaders and performance feedback to (1) increase use of lifesaving drugs (aspirin and thrombolytics in eligible elderly patients, beta-blockers in all eligible patients) for acute myocardial infarction (AMI), and (2) decrease use of a potentially harmful therapy (prophylactic lidocaine).\n Randomized controlled trial with hospital as the unit of randomization, intervention, and analysis.\n Thirty-seven community hospitals in Minnesota.\n All patients with AMI admitted to study hospitals over 10 months before (1992-1993, N=2409) or after (1995-1996, N=2938) the intervention.\n Using a validated survey, we identified opinion leaders at 20 experimental hospitals who influenced peers through small and large group discussions, informal consultations, and revisions of protocols and clinical pathways. They focused on (1) evidence (drug efficacy), (2) comparative performance, and (3) barriers to change. Control hospitals received mailed performance feedback.\n Hospital-specific changes before and after the intervention in the proportion of eligible patients receiving each study drug.\n Among experimental hospitals, the median change in the proportion of eligible elderly patients receiving aspirin was +0.13 (17% increase from 0.77 at baseline), compared with a change of -0.03 at control hospitals (P=.04). For beta-blockers, the respective changes were +0.31 (63% increase from 0.49 at baseline) vs +0.18 (30% increase from baseline) for controls (P=.02). Lidocaine use declined by about 50% in both groups. The intervention did not increase thrombolysis in the elderly (from 0.73 at baseline), but nearly two thirds of eligible nonrecipients were older than 85 years, had severe comorbidities, or presented after at least 6 hours.\n Working with opinion leaders and providing performance feedback can accelerate adoption of some beneficial AMI therapies (eg, aspirin, beta-blockers). Secular changes in knowledge and hospital protocols may extinguish outdated practices (eg, prophylactic lidocaine). However, it is more difficult to increase use of effective but riskier treatments (eg, thrombolysis) for frail elderly patients." ]	Prophylaxis to prevent atrial fibrillation after cardiac surgery with any of the studied pharmacological or non-pharmacological interventions may be favored because of its reduction in the rate of atrial fibrillation, decrease in the length of stay and cost of hospital treatment and a possible decrease in the rate of stroke. However, this review is limited by the quality of the available data and heterogeneity between the included studies. Selection of appropriate interventions may depend on the individual patient situation and should take into consideration adverse effects and the cost associated with each approach.
CD006774	[ "17260365", "20049950", "19491859", "19891665", "15133864" ]	[ "Randomized, placebo-controlled trial of low molecular weight heparin in active ulcerative colitis.", "Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: a double-blind, randomized study.", "Safety and efficacy of a new 3.3 g b.i.d. tablet formulation in patients with mild-to-moderately-active ulcerative colitis: a multicenter, randomized, double-blind, placebo-controlled study.", "Clinical trial: oral colon-release parnaparin sodium tablets (CB-01-05 MMX) for active left-sided ulcerative colitis.", "Different therapy for different types of ulcerative colitis in China." ]	[ "In several open and 1 controlled trial, unfractionated heparin was effective in the treatment of active ulcerative colitis (UC). Low molecular weight heparin (LMWH) had a similar effect in several open studies.\n We studied the efficacy, safety, and tolerability of LMWH in mild to moderately active UC in a randomized, double-blind, placebo-controlled trial. In all, 29 patients with a mild or moderate recurrence of UC during salicylate treatment were randomized to receive either reviparin 3,436 IU (n = 15) subcutaneously twice daily or placebo (n = 14). The study period was 8 weeks. Treatment was discontinued if there was no improvement at 4 weeks or at any disease progression. Primary outcome measure was clinical improvement at 8 weeks measured by the Colitis Activity Index (CAI) and the Clinical Symptoms Grading (CSG, based on the CAI). Endoscopic and histologic grading and quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) were secondary outcome measures. Patients were closely monitored for adverse events.\n Twenty of 29 patients finished the 8-week treatment period (reviparin versus placebo: 11 versus 9; P = 0.70). There was no difference in CSG, CAI, endoscopic and histologic grading, or IBDQ. Treatment was well tolerated and no serious adverse events occurred.\n In this study, treatment with LMWH showed no significant clinical advantage compared to placebo in mild to moderately active UC.", "Mesalamine is the first-line drug for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two mesalamine formulations for the induction of remission in patients with UC.\n In a multicenter, double-blind, randomized study, 229 patients with mild-to-moderate active UC were assigned to 4 groups: 66 and 65 received a pH-dependent release formulation of 2.4 g/day (pH-2.4 g) or 3.6 g/day (pH-3.6 g), respectively; 65 received a time-dependent release formulation of 2.25 g/day (Time-2.25 g), and 33 received placebo (Placebo). The drugs were administered three times daily for eight weeks. The primary endpoint was a decrease in the UC disease activity index (UC-DAI).\n In the full analysis set (n = 225) the decrease in UC-DAI in each group was 1.5 in pH-2.4 g, 2.9 in pH-3.6 g, 1.3 in Time-2.25 g and 0.3 in Placebo, respectively. These results demonstrate the superiority of pH-3.6 g over Time-2.25 g (P = 0.003) and the noninferiority of pH-2.4 g to Time-2.25 g. Among the patients with proctitis-type UC, a significant decrease in UC-DAI was observed in pH-2.4 g and pH-3.6 g as compared to Placebo, but not in Time-2.25 g. No differences were observed in the safety profiles.\n Higher dose of the pH-dependent release formulation was more effective for induction of remission in patients with mild-to-moderate active UC. Additionally, the pH-dependent release formulation was preferable to the time-dependent release formulation for patients with proctitis-type UC (UMIN Clinical Trials Registry, no. C000000288).", "To evaluate the safety and efficacy of a new twice-daily balsalazide disodium 1.1 g tablet dosing regimen (6.6 g/day, three tablets twice daily) for the treatment of mild-to-moderately-active ulcerative colitis (UC).\n In a double-blind, multicenter study patients with symptoms of acute UC and a baseline Modified Mayo Disease Activity Index (MMDAI) score between 6 and 10, inclusive, with a subscale rating of > or =2 for both rectal bleeding and mucosal appearance were randomized to receive 3.3 g of balsalazide or placebo tablets twice daily for 8 weeks. The primary end point was the proportion of patients achieving clinical improvement (> or =3 point improvement in MMDAI) and improvement in rectal bleeding (> or =1 point improvement) at 8 weeks. Safety assessments were conducted from baseline through 2-weeks post-treatment.\n A total of 249 patients (166 balsalazide, 83 placebo) received at least 1 dose of study medication. The mean MMDAI score at baseline was 7.9; 62% of patients had a score > or =8.0 (moderate disease). A significantly larger proportion of patients achieved clinical improvement and improvement in rectal bleeding in the balsalazide group vs. the placebo group (55 vs. 40%, P=0.02). The most common adverse events reported were worsening of UC and headache; both were reported more often in the placebo group.\n Balsalazide disodium 1.1 g tablets administered as 3.3 g twice daily are effective, well tolerated and significantly better than placebo for improving signs and symptoms of mild-to-moderately-active UC. This new formulation with a reduced pill and dosing burden offers the potential to improve convenience and compliance in patients with active UC.", "The administration of parnaparin sodium as oral colon-release tablets (CB-01-05 MMX) has been proposed as a novel approach for the treatment of ulcerative colitis (UC).\n To assess the efficacy and the tolerability of 8 weeks' oral daily administration of 210 mg of parnaparin sodium compared with placebo in subjects treated with stable-doses of oral aminosalicylates.\n This multicenter, randomized, double-blind proof of concept trial compared the efficacy of CB-01-05 MMX 210 mg tablets to placebo in 141 subjects with mild to moderately active left-sided UC treated with stable-doses of aminosalicylates. The efficacy was assessed by clinical activity index (CAI), endoscopic index (EI) and histological score (HS).\n A total of 121 subjects (61 in test group and 60 in control group) formed the per protocol (PP) population. After 8 weeks of treatment, clinical remission was achieved in 83.6% of the CB-01-05 MMX group, and in 63.3% in the comparator group (P = 0.011). This effect was also significantly evident in the test group at week 4 (P = 0.028). A significant difference was also detected in rectal bleeding, (disappeared respectively in 75.4% and 55.0%; P = 0.018), and in mucosal friability (recovered respectively in 80.3% and in 56.7%; P = 0.005).\n CB-01-05 MMX was safe and significantly effective in treating subjects with mild-to-moderate left-sided UC treated with stable-doses of aminosalicylates.", "To study the different therapy for different types of ulcerative colitis (UC) in China.\n Among 102 UC patients, 42 chronic relapse type UC patients were randomly divided into olsalazine sodium treatment group (n=21) and SASP group (n=21). Clinical effects and safety were observed in the 2 groups. Forty-two first episode type UC patients were randomly divided into Heartleaf houttuynia herb treatment group (n=21) and SASP group (n=21). Clinical effects were observed in the 2 groups while ultrastructure of colonic mucosa, ICAM-1 and the pressure of distant colon were studied in Heartleaf houttuynia herb group. Eighteen patients (8 males, 10 females) with refractory UC and unresponsive to high-dose prednisolone and sulfasalazine therapy more than one month were treated with Kangshuanling (7200 U/d). Prednisolone was gradually stopped and sulfasalazine was maintained. Stool frequency, rectal bleeding, colonoscopy, general well-being, histology were observed and CD62p, CD63, CD54, Pgp-170 (flow cytometry), TXA2 (RIA), blood platelet aggregation rate and thrombosis length in vitro were assessed.\n In the 42 chronic relapse type UC patients, the overall clinical effects of olsalazine sodium group (complete remission in 16, improvement in 4, inefficiency in 1) were better than those of SASP group (complete remission in 10, improvement in 4, inefficiency in 7, P<0.05). Symptomatic remission of olsalazine sodium group (complete remission in 15, partial remission in 5, inefficiency in 1) was better than that of SASP group (complete remission in 10, partial remission in 5, inefficiency in 6, P<0.05). The colonoscopic remission of olsalazine sodium group(complete remission in 11, partial remission in 9, inefficiency in 1) was better than that of SASP group (complete remission in 7, partial remission in 8, inefficiency in 6, P<0.05). The histologic remission of olsalazine sodium group (complete remission in 13, partial remission in 7, inefficiency in in 1) was better than that of SASP group (complete remission in 6, partial remission in 10, inefficiency in 5, P<0.05). The side effects of gastrointestinal tract in olsalazine sodium group were less than those of SASP group except for frequency of watery diarrhea. No other side effects were observed in olsalazine sodium group while ALT increase, WBC decrease and skin eruption were observed in SASP group. Two patients relapsed in olsalazine sodium group while 8 cases relapsed in SASP group during the flow-up period (from six months to one year). In the 42 first episode type UC patients, the clinical effect of Heartleaf houttuynia herb group (complete remission in 20, 95.2%; improvement in 1, 4.8%) was better than that of SASP group (complete remission in 15, 72.4%, improvement in 5, 23.8%; inefficiency in 1, 3.8%, P<0.01). The time of stool frequency recovering to normal (5.6+/-3.3 d), and blood stool disappearance (6.7+/-3.8 d) and abdominal pain disappearance (6.1+/-3.5 d) in Heartleaf houttuynia herb group was all shorter than that in SASP group (9.5+/-4.9 d, 11.7+/-6.1 d, 10.6+/-5.3 d, P<0.01). Heartleaf houttuynia herb could inhibit the epithelial cell apoptosis of colonic mucous membrane and the expression of ICAM-1 (45.8+/-5.7% vs 30.7+/-4.1%, P<0.05). Compared with normal persons, the mean promotive speed of contraction wave stepped up (4.6+/-1.6 cm/min vs 3.2+/-1.8 cm/min, P<0.05) and the mean amplitude of the wave decreased (14.2+/-9.3 kPa vs 18.4+/-8.0 kPa, P<0.05) in active UC patients. After treatment with Heartleaf houttuynia herb, these 2 indexes improved significantly (17.3+/-8.3 kPa, 3.7+/-1.7 cm/min, P<0.05). In normal persons, the postprandial pressure of sigmoid (2.9 +/-0.9 kPa) was higher than that of descending colon (2.0+/-0.7 kPa) and splenic flexure (1.7+/-0.6 kPa), while the colonic pressure (1.5+/-0.5 kPa, 1.4+/-0.6 kPa, 1.3+/-0.6 kPa) decreased significantly (P<0.05) in active UC patients. After treatment with Heartleaf houttuynia herb, the colonic pressure (2.6+/-0.8 kPa, 1.8+/-0.6 kPa, 1.6+/-0.5 kPa) recovered to normal. The pain threshold Heartleaf houttuynia herb, the colonic pressure (2.6+/-0.8 kPa, 1.8+/-0.6 kPa, 1.6+/-0.5 kPa) recovered to normal. The pain threshold of distant colon (67.3+/-18.9 mL) in active UC patients decreased significantly compared with that of normal persons (216.2+/-40.8 mL, P<0.05) and recovered to normal after treatment with Heartleaf houttuynia herb(187.4+/-27.2 mL, P<0.05). In the 18 refractory UC patients with platelet activation, after more than 4 wk of combined Kangshuanling and sulfasalazine therapy, 16 patients achieved clinical remission, with a highly significant statistical difference (P<0.01) between pre-and post-treatment mean scores for all disease parameters: stool frequency (8.2/d vs 1.6/d), rectal bleeding (score 2.7 vs 0.3), colonoscopy (score 2.6 vs 1.1), histology (score 12.0 vs 5.0), general well being (score 4.0 vs 0.6) and CD62p (8.0+/-3.1% vs 4.1+/-1.8%), CD63 (6.3+/-2.1% vs 3.2+/-1.6%), TXA2 (548+/-85 ng/L vs 390+/-67 ng/L), platelet aggregation rate (43.2+/-10.7% vs 34.8+/-8.1%), thrombosis length in vitro (2.3+/-0.6 cm vs 1.8+/-0.3 cm), CD54 in blood (26.9+/-6.9% vs 14.4+/-5.1%), CD54 in tissues (51.1+/-6.2% vs 23.1+/-4.1%), Pgp-170 in blood (18.9+/-3.9% vs 10.4+/-2.7%), Pgp-170 in tissues (16.5+/-3.2% vs 10.2+/-2.3%, P<0.01 or 0.05).\n Based on the characteristics of UC cases in China, different therapy should be given to different types of UC with expected satisfactory results." ]	There is evidence to suggest that LMWH may be effective for the treatment of active UC. When administered by extended colon-release tablets, LMWH was more effective than placebo for treating outpatients with mild to moderate disease. This benefit needs to be confirmed by further randomized controlled studies. The same benefits were not seen when LMWH was administered subcutaneously at lower doses. There is no evidence to support the use of UFH for the treatment of active UC. A further trial of UFH in patients with mild disease may also be justified. Any benefit found would need to be weighed against a possible increased risk of rectal bleeding in patients with active UC.
CD000547	[ "8473466", "9853762", "8203435", "7672654", "8018618", "15656211", "16253978", "11679528", "2115379", "7936386", "15705369", "15790607", "12383322", "7618457", "19423098", "10374092", "12456626" ]	[ "Pre-operative gonadotrophin-releasing hormone agonist treatment in surgery for uterine leiomyomata.", "Treatment with a gonadotrophin releasing hormone agonist before hysterectomy for leiomyomas: results of a multicentre, randomised controlled trial.", "Gonadotropin-releasing hormone agonist use before hysterectomy.", "[Preoperative management of uterine leiomyomatosis using pituitary gonadotropin-releasing hormone analogues].", "Treatment with the gonadotrophin releasing hormone-agonist goserelin before hysterectomy for uterine fibroids.", "Short-term postoperative GnRH analogue or danazol treatment after conservative surgery for stage III or IV endometriosis before ovarian stimulation: a prospective, randomized study.", "A comparative randomized trial to assess the impact of oral contraceptive pretreatment on follicular growth and hormone profiles in GnRH antagonist-treated patients.", "Post-operative GnRH analogue treatment after conservative surgery for symptomatic endometriosis stage III-IV: a randomized controlled trial.", "Treatment with GnRH agonists before myomectomy and the risk of short-term myoma recurrence.", "[Short-term treatment with leuprolide acetate depot before surgical intervention for uterine leiomyomatosis].", "A randomized prospective trial comparing gonadotropin-releasing hormone (GnRH) antagonist/recombinant follicle-stimulating hormone (rFSH) versus GnRH-agonist/rFSH in women pretreated with oral contraceptives before in vitro fertilization.", "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.", "Comparison of ovarian cyst formation in women using the levonorgestrel-releasing intrauterine system vs. hysterectomy.", "Trial of routine gonadotropin releasing hormone agonist treatment before abdominal hysterectomy for leiomyoma.", "Reducing blood loss at myomectomy with use of a gelatin-thrombin matrix hemostatic sealant.", "Laparoscopic myomectomy in premenopausal women with and without preoperative treatment using gonadotrophin-releasing hormone analogues.", "Effectiveness of combined GnRH analogue plus raloxifene administration in the treatment of uterine leiomyomas: a prospective, randomized, single-blind, placebo-controlled clinical trial." ]	[ "To determine whether pre-operative treatment with gonadotrophin-releasing hormone (GnRH) analogue may have a beneficial effect on surgery outcome, 53 patients with symptomatic fibroid uteri awaiting myomectomy or transabdominal hysterectomy (TAH), were randomly divided into a study group (n = 29) and a control group (n = 24). The study group of patients were treated by an i.m. injection of D-Trp6 LHRH microcapsules at 2 months and 1 month prior to surgery. The control group had no pre-operative treatment. Haemoglobin concentration and oestradiol, follicle-stimulating hormone and luteinizing hormone concentrations were measured at 2 months and 1 month prior to surgery, and at surgery. The duration of surgery was shorter in the study group (49 versus 70 min in the hysterectomy group) and intra-operative blood loss was less (208 versus 309 ml in the hysterectomies and 320 versus 476 ml in the myomectomies). Pre-operative treatment with GnRH-agonists which induces shrinkage of the uterus and fibroids is therefore efficient in shortening the duration of surgery, and diminishing the intra-operative blood loss in surgery for fibroid uteri. Such pre-operative treatment is therefore a useful addition to surgery in cases with symptomatic fibroid uteri.", "To ascertain whether uterine shrinkage induced by a gonadotrophin releasing hormone agonist before hysterectomy for fibroids increases the possibility of a vaginal procedure.\n A multicentre, prospective, randomised, controlled study.\n One hundred and twenty-seven premenopausal women with a uterine volume of 12 to 16 gestational weeks.\n Twelve weeks of triptorelin depot treatment before hysterectomy or immediate surgery.\n Number of vaginal and abdominal hysterectomies, operating time, blood loss, degree of difficulty of the procedure, perioperative serum haemoglobin and haematocrit levels, hospital stay, and patients' overall satisfaction with treatment.\n After randomisation, four women withdrew from the study, leaving 60 women in the triptorelin arm and 63 in the immediate surgery arm. At baseline evaluation a vaginal hysterectomy was indicated in seven women allocated to pre-operative medical therapy (12%), and in 10 of those allocated to immediate surgery (16%). Clinical assessment after the 12-week GnRH agonist course showed that abdominal hysterectomy was no longer indicated in 25/53 women (47%) as a vaginal procedure appeared appropriate. Thus the overall rate of indication for a vaginal procedure in the pre-operative medical treatment arm was 32/60 cases (53%), with a between-group difference of 37% (95% CI, 26% to 51%; chi2(1) = 19.18, P < 0.0001; OR 6.06; 95% CI, 2.60 to 14.10). Pre- and post-operative serum haemoglobin and haematocrit levels were significantly higher in the GnRH agonist than in the immediate surgery arm. No appreciable difference was observed between the groups in the other intra- and post-operative variables, including patients' satisfaction.\n Pre-operative GnRH agonist therapy increased the rate of vaginal hysterectomy in selected women with fibroids and uterine volume of 12 to 16 gestational weeks.", "Our purpose was to compare the effects of leuprolide acetate in patients with symptomatic uterine leiomyoma before hysterectomy.\n Group I (n = 90) included patients with a pretreatment uterine size of 14 to 18 gestational weeks and group II (n = 60) included patients with uteri > 18 weeks' gestational size. Patients in both groups were randomized to either immediate hysterectomy or 2 months of preoperative gonadotropin-releasing hormone agonist.\n All patients in the two groups with a pretreatment hemoglobin < 11.0 gm/dl randomized to agonist had a significant (p < 0.05) increase (> or = 1.5 gm/dl) in hemoglobin level. Patients in group I who received preoperative agonist were more likely to undergo vaginal hysterectomy (80% vs 13%, p < 0.05) than were patients who did not receive preoperative agonist. Patients undergoing vaginal hysterectomy had a shorter hospital stay, decreased operative blood loss, and a shorter convalescence period than did those undergoing abdominal hysterectomy. In group II, in spite of a mean uterine volume reduction of 51.3%, intraoperative morbidity, operative blood loss, hospital stay, and postoperative convalescence period did not differ between treatment arms.\n The preoperative administration of gonadotropin-releasing hormone agonist in patients with a uterus of 14 to 18 weeks' size increases the use of vaginal hysterectomy, decreases intraoperative blood loss, and shortens hospital stay and convalescence. Preoperative gonadotropin-releasing hormone agonist for patients with a preoperative hemoglobin < 11.0 gm/dl reduces the risk of preoperative transfusion. Preoperative gonadotropin-releasing hormone use in the nonanemic patient with a uterine size > or = 18 weeks' gestational size doses not appear to lower operative morbidity.", "Uterine leiomyomatosis shows a frequency from 25 to 30% in reproductive age women. Traditional treatment is hysterectomy or myomectomy independently from fertility wishes of the woman. Its growth has been associated to estrogenic activity. Because of this, several substances have been used to diminish tumour size, pre-operatively. The use of analogues of liberating hormone of hypophysiary gonadotropins (GnRH), given to favor surgical technique, to diminish trans-operative bleeding and to avoid blood transfusions. Clinical efficiency of the use of nafarelin acetate in women with uterine leyomiomatosis, pre-operatively during three months, was studied in this paper. The study was prospective, comparative, blind and with longitudinal measurements. Twenty eight women were included. Group I (n = 13) and Group II (n = 15) control without treatment. Observation units included FSH, LH, E2, BHC, HCT, USG basal, 30, 60, 90 days. Results showed a diminution of more than 80% of the initial uterine volume, and of 30% of the myomas independently measured. Side effects, tolerance and efficacy of the used compound, are mentioned.", "To investigate the effect of the gonadotrophin releasing hormone (GnRH)-agonist goserelin, given by monthly subcutaneous injection for three months prior to total abdominal hysterectomy for uterine leiomyomata, on the pre-operative symptoms, difficulty of operation and operative blood loss.\n Randomised placebo-controlled study.\n Patients were recruited from the gynaecological outpatient departments from hospitals in Edinburgh, Glasgow and Newcastle.\n Seventy-one premenopausal women with uterine leiomyomata who were on the waiting list for hysterectomy.\n After the presence of leiomyomata was confirmed using ultrasonography, the women were randomised to receive either the GnRH-agonist goserelin by monthly subcutaneous injection or a sham injection for three months prior to operation. At the monthly visits, patients were asked about treatment related symptoms, fibroid related symptoms, and their bleeding patterns. Blood was taken for haematological assessment.\n Haemoglobin concentrations at recruitment, at operation and post-operatively, pre-operative symptoms, operative difficulty and blood loss and post-operative complications.\n Treatment with goserelin induced amenorrhoea in over 80% of the women, and this was associated with a significant rise in haemoglobin level. At the time of operation, fibroid related symptoms were less in the goserelin group than in the placebo group. The hysterectomy was technically easier and the median (range) operative blood loss was significantly lower in the goserelin group compared with the placebo group (187 (60-600) ml vs 308 (118-1000) ml respectively; P < 0.05, Wilcoxon signed rank test). There was no difference between the two groups in the duration of hospital stay or the frequency of post-operative complications. The fibroids were smaller at the time of operation in the goserelin group, and more women treated with goserelin were able to have their operations through a transverse incision.\n This study demonstrates the benefits of goserelin in women having total abdominal hysterectomy for uterine leiomyomata.", "To assess the effect of short-term use of a gonadotropin releasing hormone (GnRH) analogue for 3 months before ovarian stimulation in patients with stage III and IV endometriosis after conservative surgery.\n Eleven patients were randomly selected to receive intramuscular injections of GnRH analogue, leuprolide acetate (3.75 mg), every 28 days, or 400 mg danazol orally 2 times per day for 3 months before ovarian stimulation after conservative laparoscopic or laparotomy surgeryfor stage III and IV symptomatic endometriosis (group 1), as compared with 30 patients who had received no postoperative treatment with GnRH analogue or danazol but underwent ovarian stimulation immediately after thefirst menses within 3 months postoperatively (group 2).\n Although the number of oocytes retrieved and number of embryos per cycle were significantly higher in group 1, the pregnancy rate per cycle in group 1 was not significantly different from that in group 2 (18% vs. 20%). The cumulative pregnancy rate at 12 months was 54.5% and 56.7% in group 1 and group 2, respectively. With regard to recurrence of disease after 24 months of follow-up, group 2 had a statistically significantly higher recurrence rate (13.3%) than did group 1 (0%).\n Short-term use of GnRH analogue before ovarian stimulation in women with stage III or IV endometriosis confers no definite benefits on pregnancy rates per cycle when compared with patients who received ovarian stimulation within 3 months after conservative surgery.", "This randomized controlled trial was designed to assess the impact of oral contraceptive (OC) scheduling with a GnRH antagonist (ganirelix) regimen on the ovarian response of women undergoing recombinant FSH (rFSH) stimulation for IVF, compared with a non-scheduled ganirelix regimen and a long GnRH agonist (nafarelin) protocol.\n A total of 110 women was treated with an OC and ganirelix, 111 with ganirelix alone and 111 with nafarelin. The OC (containing 30 microg ethinylestradiol/150 microg desogestrel) was taken for 14-28 days and stopped 2 days prior to the start of rFSH treatment. Primary efficiency parameters were the number of cumulus-oocyte complexes (per attempt) and the number of grade 1 or 2 embryos (per attempt).\n In terms of follicular growth and hormone profiles, the OC-scheduled antagonist regimen mimicked the agonist regimen rather than the (non-scheduled) GnRH antagonist regimen. In the OC-scheduled GnRH antagonist group and the nafarelin group (versus the non-scheduled antagonist group), pituitary suppression was more profound at the start of stimulation (P < or = 0.001), there was a slower start of follicular growth (P < or = 0.001), longer stimulation was required (11.7 and 10.3 days respectively versus 9.4; P < or = 0.001), and more rFSH was used (2667 and 2222 IU versus 1966 IU; P < or = 0.001). In the three groups, the number of oocytes was similar (13.1, 12.9 and 11.5 respectively; not significant) as well as the number of good quality embryos (5.1, 5.7 and 5.0 respectively; not significant).\n OC treatment prior to the rFSH/ganirelix regimen can be successfully applied to schedule patients, although more days of stimulation and more rFSH are required than with a non-scheduled GnRH antagonist regimen.", "In order to decrease endometriosis recurrence after surgical therapy, it has been proposed to use a post-surgical oestrogen-lowering medical treatment. Results from previous trials on this topic are contradictory.\n A total of 89 women were randomized, by computer-generated list, after laparoscopic conservative surgery for symptomatic endometriosis stage III-IV to receive monthly i.m. injections of gonadotrophin-releasing hormone (GnRH) analogue, leuprolide acetate depot (3.75 mg) for 3 months (n = 44) or to an expectant management (n = 45). All patients were followed up every 6 months for evaluation of pain symptoms, fertility and objective disease recurrence.\n During the follow-up, which ranged from 6-36 months, five (33%) of the 15 women who wanted children and who were allocated the GnRH analogue and six (40%) of the 15 given no treatment became pregnant (not significant). Moderate/severe pelvic pain recurred during the follow-up in 10 (23%) of the women allocated the GnRH analogue and 11 (24%) of those allocated no treatment; the cumulative pain recurrence rates at 18 months were 23 and 29% respectively (not significant). Four women (9%) treated with GnRH analogue and four women (9%) who received no treatment had objective disease recurrence as demonstrated by gynaecological examination and/or pelvic ultrasonography.\n This study does not support the routine post-operative use of a 3 month course of GnRH analogue in women with symptomatic endometriosis stage III-IV.", "Twenty-four women with symptomatic multiple uterine myomas were allocated randomly to treatment with buserelin, 1200 micrograms/day intranasally, for 3 months followed by myomectomy (n = 8) or to immediate myomectomy (n = 16). Pre-operative treatment with buserelin reduced the mean uterine volume from 432 (SD 165) to 242 (SD 82) ml (P less than 0.01) but intra-operative blood loss and postoperative morbidity were not significantly less in this group. Six months after operation, pelvic examination was normal in all the patients. However, ultrasonography with transvaginal probe demonstrated the presence of myomas of less than 1.5 cm in five women (63%) treated pre-operatively with the analogue and in two women (13%) who underwent immediate surgery (P less than 0.05). Induction of a period of hypo-oestrogenism before myomectomy seems to favour short-term recurrence of uterine myomas, limiting the efficacy of surgery.", "It has been amply demonstrated that uterine leiomyoma possess estrogen receptors. On the basis of this presupposition, it is considered logical to use GnRH-agonists which, by reducing the level of estrogen, also reduce the volume of the leiomyoma, although to a varying extent. The maximum reduction which can be obtained occurs, according to published data, between 3 and 6 months of treatment, attaining mean values of approximately 50%. In the author's experience the treatment period was shortened even further by administering only 2 vials of leuprolide depot each month to women who subsequently underwent hysterectomy. The sample group comprised 30 women with uterine leiomyomatosis, of whom 15 were treated with a GnRH analogue and 15 with placebo. The reduction of uterine volume was evaluated by echography and was found to be 40% in the treated group, whereas non change was detected in the \"placebo-group\".", "To compare the effects of oral contraceptive (OC) pill pretreatment in recombinant FSH/GnRH-antagonist versus recombinant FSH/GnRH-agonist stimulation in in vitro fertilization (IVF) patients, and to evaluate optimization of retrieval day.\n Prospective, randomized, multicenter study.\n Private practice and university centers.\n Eighty patients undergoing IVF who met the appropriate inclusion criteria.\n Four study centers recruited 80 patients. The OC regimen began on cycle days 2 to 4 and was discontinued on a Sunday after 14 to 28 days. The recombinant FSH regimen was begun on the following Friday. The GnRH-agonist group was treated with a long protocol; the GnRH-antagonist was initiated when the lead follicle reached 12 to 14 mm. When two follicles had reached 16 to 18 mm, hCG was administered.\n The primary outcome measures were the number of cumulus-oocyte complexes, day of the week for oocyte retrieval, and total dose and days of stimulation of recombinant FSH. Secondary efficacy variables included pregnancy and implantation rate; serum E(2) levels on stimulation day 1; serum E(2), P, and LH levels on the day of hCG administration; follicle size on day 6 and day of hCG administration; the total days of GnRH-analogue treatment; total days on OC; total days from end of OC to oocyte retrieval; and the cycle cancellation rate.\n Patient outcomes were similar for the days of stimulation, total dose of gonadotropin used, two-pronuclei embryos, pregnancy (44.4% GnRH-antagonist vs. 45.0% GnRH-agonist, P=.86) and implantation rates (22.2% GnRH-antagonist vs. 26.4% GnRH-agonist, P=.71). Oral contraceptive cycle scheduling resulted in 78% and 90% of retrievals performed Monday through Friday for GnRH-antagonist and GnRH-agonist. A one day delay in OC discontinuation and recombinant FSH start would result in over 90% of oocyte retrievals occurring Monday through Friday in both groups.\n The OC pretreatment in recombinant FSH/GnRH-antagonist protocols provides a patient-friendly regimen and can be optimized for weekday retrievals. No difference was seen in number of 2PN embryos, cryopreserved embryos, embryos transferred, implantation and pregnancy rates between the two stimulation protocols.", "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 analyze the effect of the levonorgestrel-releasing intrauterine system (LNG-IUS) on ovarian cyst formation, endometrial thickness and the size of uterus and uterine fibroids by ultrasonography.\n This was a prospective, randomized trial comparing the LNG-IUS and hysterectomy in 236 women (age range 35-49 years) referred for menorrhagia. Transvaginal ultrasound examination was used to study the presence of ovarian cysts, uterine size, endometrial thickness, and the size of the uterus and uterine fibroids during a 12-month follow-up period.\n At baseline examination, 12 ovarian cysts were detected, eight in the LNG-IUS group and four in the hysterectomy group. During the follow-up period, 14 new cysts had emerged at 6 months and 14 new cysts had emerged at 12 months in the LNG-IUS group, whereas the corresponding figures in the hysterectomy group were three and eight, respectively. All but one of the 14 new cysts (94.1%) detected at 6 months in the LNG-IUS group resolved spontaneously, whereas two out of the eight cysts detected at the baseline examination persisted for 12 months. Three cysts were removed at operation. The relative risk of the occurrence of ovarian cysts was significantly higher in women with LNG-IUS, compared with women who underwent hysterectomy. LNG-IUS did not affect the size of the uterus or uterine fibroids, but it was associated with a decrease in endometrial thickness. The occurrence of cysts did not correlate with age or follicle stimulating hormone levels, but a weak positive correlation between the occurrence of cysts and the presence of irregular bleeding was observed.\n LNG-IUS use in the treatment of menorrhagia was associated with the development of ovarian cysts, but these were symptomless and showed a high rate of spontaneous resolution. LNG-IUS did not affect the size of the uterus or the size of uterine fibroids, but decreased the thickness of the endometrium.", "To investigate the usefulness of a routine short term treatment with gonadotropin releasing hormone agonist (D-Trp-6-LHRH depot) before abdominal hysterectomy for leiomyoma.\n Prospective, comparative, randomized study.\n A teaching hospital of Barcelona University.\n Fifty premenopausal women requiring hysterectomy as treatment for symptomatic leiomyomas. Twenty-three patients were randomized to receive gonadotropin releasing hormone agonist treatment before hysterectomy (cases), and 27 patients were randomized to immediate hysterectomy (controls).\n Type of abdominal incision, operating time, operative hemoglobin and hematocrit decrease, postoperative morbidity, and days in hospital.\n In the agonist treated group mean uterine volume decreased and mean hemoglobin and hematocrit significantly rose after 8 weeks of treatment. Operative time was similar in both groups of patients but the number of women having Pfannenstiel incision was significantly higher in the cases. Mean operative hemoglobin and hematocrit decrease and postoperative morbidity were lower in the cases. There was a trend for shorter postoperative hospital stays in the agonist treated group.\n Our results favor the routine use of a short term gonadotropin releasing hormone agonist treatment before abdominal hysterectomy for leiomyoma in order to decrease operative blood loss and postoperative morbidity.", "To evaluate the hemostatic efficacy and handling of gelatin-thrombin matrix in abdominal myomectomy.\n Prospective and randomized trial.\n University teaching hospital.\n Women (n = 50) with uterine fibroids with a uterine size equivalent to > or =16 weeks gestation.\n Gelatin-thrombin matrix (FloSeal Matrix; Baxter Healthcare Corp., Fremont, CA) was delivered to the site of the uterine bleeding during myomectomy.\n Patient age, parity, number of myomas, operative time, blood loss, transfusion, intraoperative and postoperative complications, and length of hospitalization were evaluated.\n The average blood loss during surgery was 80 +/- 25.5 mL for the FloSeal group and 625 +/- 120.5 mL for the control group. Intraoperative blood transfusion was necessary in five patients from the control group. Postoperative blood loss was 25 +/- 5 mL for the FloSeal group and 250 +/- 75 mL for the control group. Length of the postoperative hospital stay was 2.5 +/- 1.2 days for FloSeal group and 4.5 +/- 1.3 for the control group. No major immediate or delayed complications were observed in either group.\n Reductions in hemorrhage in FloSeal-treated women undergoing a myomectomy are encouraging, and provide evidence for the ability of gelatin-thrombin matrix to reduce blood loss when applied immediately and directly to bleeding uterine tissue.", "The present study was undertaken in order to evaluate the usefulness or otherwise of preoperative gonadotrophin-releasing hormone (GnRH) analogue treatment prior to laparoscopic myomectomy. From June 1993 through December 1996, 60 premenopausal women aged between 25 and 42 years and with a sonographic diagnosis of intramural or subserous myomas were selected for laparoscopic myomectomy at the Department of Obstetrics and Gynaecology of the Catholic University of The Sacred Heart, Rome. According to a computer-generated sequence, 30 patients were submitted to three cycles of GnRH analogue treatment prior to surgery, whereas no preoperative treatment was prescribed to the other 30 patients. Laparoscopic myomectomy was successfully performed in all patients for a total of 174 myomas excised laparoscopically. The patients' mean age, the number of myomas per patient, the mean diameter of the myomas, parity and estimated blood loss were similar in both groups. The operative time was significantly longer in the group of patients submitted to GnRH analogue treatment than that of the group of patients not submitted to any preoperative medical therapy (157.5 +/- 74.71 versus 112.33 +/- 54.71 min; P = 0.01). No intra-operative complications occurred. In no case was blood transfusion necessary. Two patients developed post-operative fever (temperature > 38 degrees C.). The mean length of hospital stay was 2.39 days and was similar in both groups. Thirteen spontaneous pregnancies occurred among 24 infertile patients (54.1%). The pregnancy rate for these patients was similar in both groups. The viable term delivery rate was 45.8%. The authors conclude that laparoscopic myomectomy is a feasible and safe procedure. The post-operative pregnancy rate for infertile patients is similar to that following laparotomic myomectomy. The present study suggests that preoperative GnRH analogue treatment does not offer any significant advantages for laparoscopic myomectomy.", "Raloxifene hydrochloride is a synthetic non-steroidal drug used for the prevention and treatment of post-menopausal osteoporosis. Pre-clinical and clinical data have shown that raloxifene may have a beneficial effect on leiomyomas. The aim of this prospective single-blind, randomized, placebo-controlled clinical trial was to evaluate the effectiveness of the addition of raloxifene to GnRH analogues on uterine, leiomyoma, and non-leiomyoma sizes, and on the occurrence of leiomyoma-related symptoms.\n After randomization using a computer-generated list, 100 pre-menopausal women with symptomatic uterine leiomyomas received either leuprolide acetate depot plus raloxifene 60 mg daily (group A) or leuprolide plus placebo tablet (group B) for six cycles of 28 days. At baseline and after treatment, uterine, leiomyoma and non-leiomyoma sizes, and leiomyoma-related symptoms were evaluated for each woman. Analysis was by intention-to-treat method.\n After six cycles of treatment, a significant decrease in uterine, leiomyoma, and non-leiomyoma sizes was detected in both groups in comparison with baseline. At the same time, no significant difference in uterine and non-leiomyoma sizes was observed between the groups. Leiomyoma sizes were significantly (P < 0.05) lower in group A than in group B. No difference was observed in leiomyoma-related symptoms between groups throughout the study period.\n In women treated with GnRH analogue, the raloxifene administration induces a higher reduction of leiomyoma sizes." ]	The use of GnRH analogues for 3 to 4 months prior to fibroid surgery reduce both uterine volume and fibroid size. They are beneficial in the correction of pre-operative iron deficiency anaemia, if present, and reduce intra-operative blood loss. If uterine size is such that a mid-line incision is planned, this can be avoided in many women with the use of GnRH analogues. For patients undergoing hysterectomy, a vaginal procedure is more likely following the use of these agents.
CD006142	[ "8455969", "19853518", "2140432", "15082950", "9252001", "15109505", "2363027", "6601789", "19920718", "17057564", "2946016", "16323384" ]	[ "TENS for children's procedural pain.", "Feasibility study of Transcutaneous Electrical Nerve Stimulation (TENS) for cancer bone pain.", "A controlled trial of transcutaneous electrical nerve stimulation (TENS) and exercise for chronic low back pain.", "Evaluation of TENS during screening flexible sigmoidoscopy.", "Transcutaneous nerve stimulation (TENS) during the first stage of labour: a randomized clinical trial.", "Pain reducing effect of three types of transcutaneous electrical nerve stimulation in patients with chronic pain: a randomized crossover trial.", "Comparison of TENS treatments in hemiplegic shoulder pain.", "Transcutaneous electrical nerve stimulation (TENS) as compared to placebo TENS for the relief of acute oro-facial pain.", "Transcranial DC stimulation coupled with TENS for the treatment of chronic pain: a preliminary study.", "Efficacy of transcutaneous electrical nerve stimulation (tens) for chronic low-back pain in a multiple sclerosis population: a randomized, placebo-controlled clinical trial.", "Efficacy of electroacupuncture and TENS in the rehabilitation of chronic low back pain patients.", "A randomized clinical trial of TENS and exercise for patients with chronic neck pain." ]	[ "A 3 x 6 factorial design with a double blind and placebo control was employed to investigate the effect of TENS treatment on pain produced by venipuncture. The three treatment groups consisted of TENS, placebo-TENS and control. Subjects were blocked into six 2-year age groups (ages: 5-17 years). During the period of the study, 896 children attending the outpatient laboratory of a general hospital were screened and 514 children completed the study. The data which were collected before venipuncture included expected pain and state anxiety. Following venipuncture, pain intensity was measured with a vertical visual analogue scale (VAS) and pain affect was assessed with McGrath's faces scale. Significant main effects for treatment and age groups were obtained. Pain intensity and affect were lowest for the TENS group and highest for the control group. The pain scores were greatest for lower age groups and lowest for higher age groups. The results of this study support the use of TENS for children's pain and the need for interventions for children's procedural pain.", "This multicenter study assessed the feasibility of conducting a phase III trial of transcutaneous electrical nerve stimulation (TENS) in patients with cancer bone pain recruited from palliative care services. Eligible patients received active and placebo TENS for 1 hour at site of pain in a randomized crossover design; median interval between applications 3 days. Responses assessed at 30 and 60 minutes included numerical and verbal ratings of pain at rest and on movement, and pain relief. Recruitment, tolerability, adverse events, and effectiveness of blinding were also evaluated. Twenty-four patients were randomised and 19 completed both applications. The intervention was well tolerated. Five patients withdrew: 3 due to deteriorating performance status, and 2 due to increased pain (1 each following active and placebo TENS). Confidence interval estimation around the differences in outcomes between active and placebo TENS suggests that TENS has the potential to decrease pain on movement more than pain on rest. Nine patients did not consider that a placebo was used; the remaining 10 correctly identified placebo TENS. Feasibility studies are important in palliative care prior to undertaking clinical trials. Our findings suggest that further work is required on recruitment strategies and refining the control arm before evaluating TENS in cancer bone pain.\n Cancer bone pain is common and severe, and partly mediated by hyperexcitability. Animal studies suggest that Transcutaneous Electrical Nerve Stimulation can reduce hyperalgesia. This study examined the feasibility of evaluating TENS in patients with cancer bone pain in order to optimize methods before a phase III trial.\n Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.", "A number of treatments are widely prescribed for chronic back pain, but few have been rigorously evaluated. We examined the effectiveness of transcutaneous electrical nerve stimulation (TENS), a program of stretching exercises, or a combination of both for low back pain. Patients with chronic low back pain (median duration, 4.1 years) were randomly assigned to receive daily treatment with TENS (n = 36), sham TENS (n = 36), TENS plus a program of exercises (n = 37), or sham TENS plus exercises (n = 36). After one month no clinically or statistically significant treatment effect of TENS was found on any of 11 indicators of outcome measuring pain, function, and back flexion; there was no interactive effect of TENS with exercise. Overall improvement in pain indicators was 47 percent with TENS and 42 percent with sham TENS (P not significant). The 95 percent confidence intervals for group differences excluded a major clinical benefit of TENS for most outcomes. By contrast, after one month patients in the exercise groups had significant improvement in self-rated pain scores, reduction in the frequency of pain, and greater levels of activity as compared with patients in the groups that did not exercise. The mean reported improvement in pain scores was 52 percent in the exercise groups and 37 percent in the nonexercise groups (P = 0.02). Two months after the active intervention, however, most patients had discontinued the exercises, and the initial improvements were gone. We conclude that for patients with chronic low back pain, treatment with TENS is no more effective than treatment with a placebo, and TENS adds no apparent benefit to that of exercise alone.", "The expectation of pain is a statistically significant factor negatively affecting patient compliance with current screening flexible sigmoidoscopy recommendations. Numerous pain reduction modalities have been studied with limited success. Transcutaneous electrical nerve stimulation (TENS) has been used to treat pain of various origins. The purpose of this pilot study was to determine the efficacy of TENS in reducing discomfort experienced during screening flexible sigmoidoscopy.A double-blind study was conducted in which 90 subjects were randomized to receive TENS, sham TENS, or control (standard care). The same pulse frequency and intensity were used for all subjects in the TENS group. Subjects completed preprocedural and postprocedural questionnaires, and the endoscopist completed a postprocedural questionnaire. A slight, but statistically insignificant (p =.526) reduction in the mean pain score reported by the TENS group was noted when compared with the sham TENS and control groups (2.00, 2.27, and 2.23 respectively). In light of the fact that only one pulse frequency and intensity of the TENS intervention were used in this study, further study with this safe and cost-effective modality is warranted.", "Our objective was to study the efficacy of transcutaneous electrical nerve stimulation (TENS) in reducing pain during the first stage of labour. Using a prospective randomized placebo-controlled, double blind clinical trial, a patient-controlled analgesia system was used to measure differences in outcome. Trials took place in a labour unit at the St. Antonius Hospital, Nieuwegein, The Netherlands, during a period of 18 months. Forty-six patients, during the first stage of labour, were treated with TENS, and 48 with a placebo apparatus. Main outcome measures were pain relief, amount of administered analgesics, obstetrical and neonatal outcome, and side effects. No significant differences occurred between groups in the number of requests for pethidine/promethazine. The foetal outcome in both groups was the same. TENS and placebo were considered equally effective by both patients and staff. In conclusion, TENS was not more effective than a placebo apparatus in relieving pain during the first stage of labour. No adverse side-effects occurred.", "Transcutaneous electrical nerve stimulation (TENS) is a frequently applied therapy in chronic pain although evidence for effectiveness is inconclusive. Several types of TENS, based on different combinations of frequency, pulse duration and intensity, exist. The precise mechanism of action and the relevance of combinations of stimulus parameters are still unclear. To compare the effectiveness of three types of TENS we conducted a randomized, single blinded crossover trial. Patients received two times a 2-week period of daily TENS treatment, separated by a washout period of 2 weeks. In total, 180 chronic pain patients were randomized into three groups. In group 1, high frequency, low intensity TENS (HFT) was compared with high frequency, high intensity TENS (HIT). In groups 2 and 3, HFT and HIT were compared with a control TENS (COT). The order of applying the different modalities of TENS in each group was also randomized. Primary outcome was the patient's overall assessment of effectiveness and pain reduction (VAS). No differences were found in patient's assessment or pain reducing effect between the three groups, indicating no superiority of one type of TENS. In total, 56% continued TENS after the 2-week treatment period. At 6 months, 42% of all patients still used TENS. We concluded that there were no differences in effectiveness for the three types of TENS used in this study. Because no placebo group was included, no definite conclusions on effectiveness of TENS in general in the treatment of chronic pain could be made.", "The aim of this paper is to evaluate the effectiveness of high-intensity versus low-intensity transcutaneous electrical nerve stimulation (TENS) and versus placebo for treatment of hemiplegic shoulder pain. Three groups of 20 patients each (A, B, C) were studied. In group A high-intensity TENS was delivered at 3 times the sensory threshold with frequency of 100 Hz; in group B low-intensity TENS was delivered at the sensory threshold with frequency of 100 Hz. Group C received placebo stimulation. The treatment protocol consisted of 12 sessions (4 weeks). Before treatment, at the end of it and one month after, passive range of motion (PROM) for flexion, extension, abduction and external rotation were evaluated. Statistically significant improvements of PROMs were recorded for group A, but not for groups B or C.", "The present paper describes the effect of high frequency, low frequency and placebo TENS on acute oro-facial pain in 62 patients, attending to an emergency clinic for dental surgery; they had all suffered pain for 1-4 days. The patients were randomly assigned to one of three groups receiving either high frequency (100 Hz), low frequency (2 Hz) or placebo TENS. In the two groups receiving TENS (42 patients) 16 patients reported a reduction in pain intensity exceeding 50%; out of these 16 patients, 4 patients reported complete relief of pain. In the placebo group (20 patients) 2 patients reported a pain reduction of more than 50%; out of these 2 patients, none reported a complete pain relief. Mechanical vibratory stimulation augmented the pain reduction obtained by TENS in 5 out of 10 patients.", "Based on evidence showing that electrical stimulation of the nervous system is an effective method to decrease chronic neurogenic pain, we aimed to investigate whether the combination of 2 methods of electrical stimulation-a method of peripheral stimulation [transcutaneous electrical nerve stimulation (TENS)] and a method of noninvasive brain stimulation [transcranial direct current stimulation (tDCS)]-induces greater pain reduction as compared with tDCS alone and sham stimulation.\n We performed a preliminary, randomized, sham-controlled, crossover, clinical study in which 8 patients were randomized to receive active tDCS/active TENS (\"tDCS/TENS\" group), active tDCS/sham TENS (\"tDCS\" group), and sham tDCS/sham TENS (\"sham\" group) stimulation. Assessments were performed immediately before and after each condition by a blinded rater.\n The results showed that there was a significant difference in pain reduction across the conditions of stimulation (P=0.006). Post hoc tests showed significant pain reduction as compared with baseline after the tDCS/TENS condition [reduction by 36.5% (+/-10.7), P=0.004] and the tDCS condition [reduction by 15.5% (+/-4.9), P=0.014], but not after sham stimulation (P=0.35). In addition, tDCS/TENS induced greater pain reduction than tDCS (P=0.02).\n The results of this pilot study suggest that the combination of TENS with tDCS has a superior effect compared with tDCS alone.", "This study was designed to investigate the hypoalgesic effects of self-applied transcutaneous electrical nerve stimulation (TENS) on chronic low-back pain (LBP) in a multiple sclerosis (MS) population.\n Ninety participants with probable or definite MS (aged 21 to 78 y) presenting with chronic LBP were recruited and randomized into 3 groups (n=30 per group): (1) low-frequency TENS group (4 Hz, 200 micros); (2) high-frequency TENS group (110 Hz, 200 micros); and (3) placebo TENS. Participants self-applied TENS for 45 minutes, a minimum of twice daily, for 6 weeks. Outcome measures were recorded at weeks 1, 6, 10, and 32. Primary outcome measures included: Visual Analog Scale for average LBP and the McGill Pain Questionnaire. Secondary outcome measures included: Visual Analog Scale for worst and weekly LBP, back and leg spasm; Roland Morris Disability Questionnaire; Barthel Index; Rivermead Mobility Index; Multiple Sclerosis Quality of Life-54 Instrument, and a daily logbook. Data were analyzed blind using parametric and nonparametric tests, as appropriate.\n Results indicated a statistically significant interactive effect between groups for average LBP (P=0.008); 1-way analysis of covariance did not show any significant effects at any time point once a Bonferonni correction was applied (P>0.05). However, clinically important differences were observed in some of the outcome measures in both active treatment groups during the treatment and follow-up periods.\n Although not statistically significant, the observed effects may have implications for the clinical prescription and the use of TENS within this population.", "Fifty-four patients treated in a 3-week inpatient rehabilitation program were randomly assigned to and accepted treatment with electroacupuncture (n = 17), TENS (low intensity transcutaneous nerve stimulation, n = 18), and TENS dead-battery (placebo, n = 18). Outcome measures included estimates of pain (on a Visual Analogue Scale) and disability by both physician and patient, physical measures of trunk strength and spine range of motion, as well as the patient's perceptions of the relative contribution of the education, exercise training, and the electrical stimulation. Analyses of variance were utilized to determine effects of treatment (electroacupuncture, TENS, placebo) across time (admission, discharge, and return) for the outcome measures. There were no significant differences between treatment groups with respect to their overall rehabilitation. All 3 treatment groups ranked the contribution of the education as being greater than the electrical stimulation. However, the electroacupuncture group consistently demonstrated greater improvement on the outcome measures than the other treatment groups. For the visual analogue scale measure of average pain, there was a statistical trend at the return visit suggesting that the acupuncture group was experiencing less pain.", "To investigate the effect of transcutaneous electrical nerve stimulation (TENS) on acupuncture points and neck exercise in chronic neck pain patients.\n A randomized clinical trial.\n Hospital-based practice.\n Two hundred and eighteen patients with chronic neck pain.\n Subjects were randomized into three groups, receiving either (1) TENS over the acupuncture points plus infrared irradiation (TENS group); (2) exercise training plus infrared irradiation (exercise group); or (3) infrared irradiation alone (control); twice a week for six weeks.\n The values of verbal numeric pain scale, Northwick Park Neck Pain Questionnaire, and isometric neck muscle strength were assessed before, at the end of the six-week treatment, and at the six-month follow-up.\n Results demonstrated that after the six-week treatment, significant improvement in the verbal numerical pain scale was found only in the TENS group (0.60+/-2.54, p = 0.027) and the exercise group (1.57+/-2.67, p < 0.001). Though significant reduction in Northwick Park Neck Pain Questionnaire score was found in all three groups, post-hoc tests showed that both the TENS and the exercise group produced better improvement (0.38+/-0.60% and 0.39+/-0.62% respectively) than the control group (0.23+/-0.63%). Significant improvement (p = < 0.001 to 0.03) in neck muscle strength was observed in all three groups, however, the improvement in the control group was not clinically significant and it could not be maintained at the six-month follow-up.\n After the six-week treatment, patients in the TENS and exercise group had a better and clinically relevant improvement in disability, isometric neck muscle strength, and pain. All the improvements in the intervention groups were maintained at the six-month follow-up." ]	There are no changes to the conclusions since the original version of the review was published in issue 2, 2009. Due to insufficient extractable data in the studies included in this review, we are unable to make any definitive conclusions about the effectiveness of TENS as an isolated treatment for acute pain in adults.
CD002922	[ "20833738", "20169461", "20605876", "12209517", "19369404", "16221103", "16820790", "12840090", "15082482", "6398121", "3511372", "16306519", "19478041", "11036121", "782464", "16372814", "12488405", "15015070", "10470708", "3890307", "309095", "21177013", "8815753", "11863119", "2649221", "8159300", "21573588", "6546359", "7194733", "12839376", "1106277", "367574" ]	[ "Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial.", "Is mycophenolate mofetil superior to pulse intravenous cyclophosphamide for induction therapy of proliferative lupus nephritis in Egyptian patients?", "Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study.", "Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide.", "Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis.", "Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis.", "Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial.", "A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies.", "EULAR randomised controlled trial of pulse cyclophosphamide and methylprednisolone versus continuous cyclophosphamide and prednisolone followed by azathioprine and prednisolone in lupus nephritis.", "A new six-drug antiblastic regimen (R 14) at low doses (micropolychemotherapy) compared to CMF in the treatment of metastatic breast cancer: phase III study.", "Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs.", "Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis.", "Is combination rituximab with cyclophosphamide better than rituximab alone in the treatment of lupus nephritis?", "Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group.", "Prednisone and azathioprine compared to prednisone plus low-dose azathioprine and cyclophosphamide in the treatment of diffuse lupus nephritis.", "Intravenous dexamethasone-cyclophosphamide pulse therapy in comparison with oral methylprednisolone-azathioprine therapy in patients with pemphigus: results of a multicenter prospectively randomized study.", "Randomized adjuvant trial of tamoxifen and goserelin versus cyclophosphamide, methotrexate, and fluorouracil: evidence for the superiority of treatment with endocrine blockade in premenopausal patients with hormone-responsive breast cancer--Austrian Breast and Colorectal Cancer Study Group Trial 5.", "Pulse cyclophosphamide therapy in steroid-dependent nephrotic syndrome.", "Intravenous immunoglobulin compared with cyclophosphamide for proliferative lupus nephritis.", "Cyclophosphamide, adriamycin and platinum (CAP) combination chemotherapy, a new effective approach in the treatment of disseminated breast cancer. Preliminary report.", "Treatment of diffuse proliferative lupus nephritis with prednisone and combined prednisone and cyclophosphamide.", "Short-term outcomes of induction therapy with tacrolimus versus cyclophosphamide for active lupus nephritis: A multicenter randomized clinical trial.", "Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial.", "Comparative effects of plasmapheresis and intravenous cyclophosphamide on urinary podocyte excretion in patients with proliferative Lupus nephritis.", "Randomized clinical trial of CFP versus CMFP in women with metastatic breast cancer.", "Cyclosporin versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized controlled trial.", "Combination chemotherapy with cmf (cyclophosphamide, methotrexate, 5-Fluorouracil) versus cnf (mitoxantrone, 5-Fluorouracil, cyclophosphamide) in advanced breast-cancer - a multicenter randomized study.", "Comparison of melphalan with cyclophosphamide, methotrexate, and 5-fluorouracil in patients with ovarian cancer.", "Cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil in advanced prostatic cancer: a randomized trial.", "Azathioprine versus sulfasalazine in maintenance of remission in severe ulcerative colitis.", "Azathioprine plus prednisone compared with prednisone alone in the treatment of systemic lupus erythematosus. Report of a prospective controlled trial in 24 patients.", "Low dose chemotherapy of metastatic breast cancer with cyclophosphamide, adriamycin, methotrexate, 5-fluorouracil (CAMF) versus sequential cyclophosphamide, methotrexate, 5-fluorouracil (CMF) and adriamycin." ]	[ "Long-term immunosuppressive treatment does not efficiently prevent relapses of lupus nephritis (LN). This investigator-initiated randomised trial tested whether mycophenolate mofetil (MMF) was superior to azathioprine (AZA) as maintenance treatment.\n A total of 105 patients with lupus with proliferative LN were included. All received three daily intravenous pulses of 750 mg methylprednisolone, followed by oral glucocorticoids and six fortnightly cyclophosphamide intravenous pulses of 500 mg. Based on randomisation performed at baseline, AZA (target dose: 2 mg/kg/day) or MMF (target dose: 2 g/day) was given at week 12. Analyses were by intent to treat. Time to renal flare was the primary end point. Mean (SD) follow-up of the intent-to-treat population was 48 (14) months.\n The baseline clinical, biological and pathological characteristics of patients allocated to AZA or MMF did not differ. Renal flares were observed in 13 (25%) AZA-treated and 10 (19%) MMF-treated patients. Time to renal flare, to severe systemic flare, to benign flare and to renal remission did not statistically differ. Over a 3-year period, 24 h proteinuria, serum creatinine, serum albumin, serum C3, haemoglobin and global disease activity scores improved similarly in both groups. Doubling of serum creatinine occurred in four AZA-treated and three MMF-treated patients. Adverse events did not differ between the groups except for haematological cytopenias, which were statistically more frequent in the AZA group (p=0.03) but led only one patient to drop out.\n Fewer renal flares were observed in patients receiving MMF but the difference did not reach statistical significance.", "Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis. The aim of this study was to evaluate the efficacy of MMF compared with IVC in the induction therapy of proliferative lupus nephritis.\n We randomly assigned 47 patients with newly diagnosed active proliferative lupus nephritis class III or IV to open-label oral MMF 2 g/day for 6 months or intravenous cyclophosphamide 0.5-1 g/m(2) monthly for 6 months in addition to corticosteroids.\n In the intention-to-treat analysis, 14 of the 24 patients (58.33%) receiving MMF and 12 of the 23 patients receiving cyclophosphamide (52.17%) had remission (P = 0.48); complete remission occurred in 6 of the 24 patients (25%) and 5 of the 23 patients (21.74%), respectively (P = 0.53). Improvements in packed cell volume, the erythrocyte sedimentation rate, anti-double-stranded DNA antibodies titer (anti-dsDNA), serum complement, proteinuria, urinary activity, renal function, serum soluble interleukin-2 receptor alpha concentration and the systemic lupus activity measure score were similar in both groups. Two patients assigned to MMF and another patient assigned to IVC developed end-stage renal failure with commencement of dialysis. Adverse events were similar. Major infections occurred in two patients in each group. There was no difference in gastrointestinal side effects, but more diarrhea occurred in those receiving MMF.\n In this 24-week trial, MMF or IVC combined with corticosteroids demonstrated equal efficacy in inducing remission of proliferative lupus nephritis.", "Intravenous cyclophosphamide is considered to be the standard of care for the treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide. Forty patients with clinically active proliferative lupus nephritis were randomly assigned to one of two sequential induction and maintenance treatment regimens based either on cyclophosphamide or Cyclosporine A. The primary outcomes were remission (defined as normal urinary sediment, proteinuria <0.3 g/24 h, and stable s-creatinine) and response to therapy (defined as stable s-creatinine, 50% reduction in proteinuria, and either normalization of urinary sediment or significant improvement in C3) at the end of induction and maintenance phase. Secondary outcomes were incidence of adverse events, and relapse-free survival. At the end of the induction phase, 24% of the 21 patients treated by cyclophosphamide achieved remission, and 52% achieved response, as compared with 26% and 43%, respectively of the 19 patients treated by the Cyclosporine A. At the end of the maintenance phase, 14% of patients in cyclophosphamide group, and 37% in Cyclosporine A group had remission, and 38% and 58% respectively response. Treatment with Cyclosporine A was associated with transient increase in blood pressure and reversible decrease in glomerular filtration rate. There was no significant difference in median relapse-free survival. In conclusion, Cyclosporine A was as effective as cyclophosphamide in the trial of sequential induction and maintenance treatment in patients with proliferative lupus nephritis and preserved renal function.(ClinicalTrials.gov identifier: NCT00976300)", "Glomerulonephritis is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low-dose IV CYC prescribed as a remission-inducing treatment, followed by azathioprine (AZA) as a remission-maintaining treatment.\n In this multicenter, prospective clinical trial (the Euro-Lupus Nephritis Trial [ELNT]), we randomly assigned 90 SLE patients with proliferative glomerulonephritis to a high-dose IV CYC regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by AZA. Intent-to-treat analyses were performed.\n Followup continued for a median of 41.3 months in the low-dose group and 41 months in the high-dose group. Sixteen percent of those in the low-dose group and 20% of those in the high-dose group experienced treatment failure (not statistically significant by Kaplan-Meier analysis). Levels of serum creatinine, albumin, C3, 24-hour urinary protein, and the disease activity scores significantly improved in both groups during the first year of followup. Renal remission was achieved in 71% of the low-dose group and 54% of the high-dose group (not statistically significant). Renal flares were noted in 27% of the low-dose group and 29% of the high-dose group. Although episodes of severe infection were more than twice as frequent in the high-dose group, the difference was not statistically significant.\n The data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis, a remission-inducing regimen of low-dose IV CYC (cumulative dose 3 gm) followed by AZA achieves clinical results comparable to those obtained with a high-dose regimen.", "Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m(2) in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.", "The aim of the present study was to evaluate the efficacy of mycophenolate mofetil in the induction therapy of proliferative lupus nephritis.\n Forty-four patients from eight centres with newly diagnosed lupus nephritis World Health Organization class III or IV were randomly assigned to either mycophenolate mofetil (MMF) 2 g/day for 6 months or intravenous cyclophosphamide (IVC) 0.75-1 g/m(2) monthly for 6 months in addition to corticosteroids.\n Remission occurred in 13 out of 25 patients (52%) in the IVC group and 11 out of 19 patients (58%) in the MMF group (P = 0.70). There were 12% in the IVC group and 26% in the MMF group that achieved complete remission (P = 0.22). Improvements in haemoglobin, the erythrocyte sedimentation rate, serum albumin, serum complement, proteinuria, urinary activity, renal function and the Systemic Lupus Erythematosus Disease Activity Index score were similar in both groups. Twenty-four follow-up renal biopsies at the end of therapy showed a significant reduction in the activity score in both groups. The chronicity index increased in both groups but was only significant in the IVC group. Adverse events were similar. Major infections occurred in three patients in each group. There was no difference in gastrointestinal side-effects.\n MMF in combination with corticosteroids is an effective induction therapy for moderately severe proliferative lupus nephritis.", "Until recently, intravenous cyclophosphamide pulses with oral corticosteroids were regarded standard therapy for proliferative lupus nephritis (LN). Azathioprine, a less toxic alternative, was never proven to be inferior. In the first Dutch lupus nephritis study (enrollment between 1995 and 2001), we randomized 87 proliferative LN patients to either cyclophosphamide pulses (750 mg/m(2), 13 pulses in 2 years) combined with oral prednisone (CY) or to azathioprine (2 mg/kg/day in 2 years) combined with intravenous pulses of methylprednisolone (3 x 3 pulses of 1000 mg) and oral prednisone (AZA). After a median follow-up of 5.7 years (interquartile range 4.1-7.2 years), doubling of serum creatinine was more frequent in the AZA group, although not statistically significant (relative risk (RR): 4.1, with 95% confidence interval (95% CI): 0.8-20.4). Relapses occurred more often in the AZA group (RR: 8.8, 95% CI: 1.5-31.8). Creatinine and proteinuria at last visit did not differ between the two treatment arms. Moreover, 88.4% of the patients in the AZA arm were still free of cyclophosphamide treatment. During the first 2 years, the frequency of remission was not different, but infections, especially herpes zoster virus infections (HZV) were more frequent in the AZA group. Parameters for ovarian function did not differ between the two groups. In conclusion, in this open-label randomized controlled trial, cyclophosphamide was superior to azathioprine with regard to renal relapses and HZV. At last follow-up, there were no differences in serum creatinine or proteinuria between the two groups. However, since our study lacked sufficient power, longer follow-up is needed to reveal putative differences.", "The primary systemic vasculitides usually associated with autoantibodies to neutrophil cytoplasmic antigens include Wegener's granulomatosis and microscopic polyangiitis. We investigated whether exposure to cyclophosphamide in patients with generalized vasculitis could be reduced by substitution of azathioprine at remission.\n We studied patients with a new diagnosis of generalized vasculitis and a serum creatinine concentration of 5.7 mg per deciliter (500 micromol per liter) or less. All patients received at least three months of therapy with oral cyclophosphamide and prednisolone. After remission, patients were randomly assigned to continued cyclophosphamide therapy (1.5 mg per kilogram of body weight per day) or a substitute regimen of azathioprine (2 mg per kilogram per day). Both groups continued to receive prednisolone and were followed for 18 months from study entry. Relapse was the primary end point.\n Of 155 patients studied, 144 (93 percent) entered remission and were randomly assigned to azathioprine (71 patients) or continued cyclophosphamide (73 patients). There were eight deaths (5 percent), seven of them during the first three months. Eleven relapses occurred in the azathioprine group (15.5 percent), and 10 occurred in the cyclophosphamide group (13.7 percent, P=0.65). Severe adverse events occurred in 15 patients during the induction phase (10 percent), in 8 patients in the azathioprine group during the remission phase (11 percent), and in 7 patients in the cyclophosphamide group during the remission phase (10 percent, P=0.94 for the comparison between groups during the remission phase). The relapse rate was lower among the patients with microscopic polyangiitis than among those with Wegener's granulomatosis (P=0.03).\n In patients with generalized vasculitis, the withdrawal of cyclophosphamide and the substitution of azathioprine after remission did not increase the rate of relapse. Thus, the duration of exposure to cyclophosphamide may be safely reduced.\n Copyright 2003 Massachusetts Medical Society", "To compare the efficacy and side effects of intermittent pulse cyclophosphamide plus methylprednisolone with continuous oral cyclophosphamide plus prednisolone, followed by azathioprine, in patients with proliferative glomerulonephritis caused by systemic lupus erythematosus (SLE).\n A multicentre randomised controlled trial was conducted between June 1992 and May 1996 involving eight European centres. All patients satisfied the American College of Rheumatology criteria for SLE and had biopsy proven proliferative lupus nephritis. All received corticosteroids in addition to cytotoxic drugs, as defined in the protocol, for two years. The trial was terminated after four years as recruitment was disappointing.\n 32 SLE patients with lupus nephritis were recruited: 16 were randomised to intermittent pulse cyclophosphamide and 16 to continuous cyclophosphamide plus azathioprine. Mean duration of follow up was 3.7 years in the continuous group (range 0 to 5.6) and 3.3 years in the pulse group (range 0.25 to 6). Three patients were excluded from the pulse therapy group as they were later found to have pure mesangial glomerulonephritis. Two patients in the continuous therapy group developed end stage renal failure requiring dialysis, but none in the intermittent pulse therapy (p = 0.488; NS). There were similar numbers of side effects and withdrawals from treatment in both groups. There were three deaths: two in the intermittent pulse therapy group and one in the continuous therapy group.\n There was no statistically significant difference in efficacy and side effects between the two regimens. Infectious complications occurred commonly, so careful monitoring is required during treatment.", "Two groups of 23 patients each, having advanced breast cancer, entered this prospective and randomized study. One group was treated with the conventional schedule of CMF (cyclophosphamide 100 mg/m2/po from the first to the 14th day, methotrexate 40 mg/m2/iv the first and the 8th day, 5-fluorouracil 600 mg/m2/iv the first and the 8th day), and the other was treated with a new six-drug regimen, administered at low doses (R 14: cyclophosphamide 2 mg/kg/iv, vincristine 0.01 mg/kg/iv, vinblastine 0.1 mg/kg/iv, the first day and 5-fluorouracil 5 mg/kg/iv, methotrexate 0.7 mg/kg/iv, adriamycin 0.5 mg/kg/iv the 2nd day every 21 days). The remission rate was 35% (8/23) and 39% (9/23) for CMF and R 14 respectively. The median duration of objective remission was 6 months for CMF and 5 months for R 14 regimen. The median survival time of responding patients was 18 months for CMF and 14 months for R 14. This study shows that the new six-drug regimen at low doses is effective (regarding subjective, objective response and survival rate), and its toxicity is no higher than that of CMF (the incidence of leukopenia was significantly lower during the first course). Therefore, R 14 should be considered an alternative regimen to CMF in the treatment of advanced and, possibly, early breast cancer. The advantages for using R 14 are: 1) it is less toxic (a single dose is a very small amount of medicine compared to what is usually administered), 2) an iv administration always follows a therapeutic program (while in a CMF schedule cyclophosphamide is self-administered by the patient).", "We evaluated renal function in 107 patients with active lupus nephritis who participated in long-term randomized therapeutic trials (median follow-up, seven years). For patients taking oral prednisone alone, the probability of renal failure began to increase substantially after five years of observation. Renal function was better preserved in patients who received various cytotoxic-drug therapies, but the difference was statistically significant only for intravenous cyclophosphamide plus low-dose prednisone as compared with high-dose prednisone alone (P = 0.027). The advantage of treatment with intravenous cyclophosphamide over oral prednisone alone was particularly apparent in the high-risk subgroup of patients who had chronic histologic changes on renal biopsy at study entry. Patients treated with intravenous cyclophosphamide have not experienced hemorrhagic cystitis, cancer, or a disproportionate number of major infections. We conclude that, as compared with high-dose oral prednisone alone, treatment of lupus glomerulonephritis with intravenous cyclophosphamide reduces the risk of end-stage renal failure with few serious complications.", "Since anecdotal series and small, prospective, controlled trials suggest that mycophenolate mofetil may be effective for treating lupus nephritis, larger trials are desirable.\n We conducted a 24-week randomized, open-label, noninferiority trial comparing oral mycophenolate mofetil (initial dose, 1000 mg per day, increased to 3000 mg per day) with monthly intravenous cyclophosphamide (0.5 g per square meter of body-surface area, increased to 1.0 g per square meter) as induction therapy for active lupus nephritis. A change to the alternative regimen was allowed at 12 weeks in patients who did not have an early response. The study protocol specified adjunctive care and the use and tapering of corticosteroids. The primary end point was complete remission at 24 weeks (normalization of abnormal renal measurements and maintenance of baseline normal measurements). A secondary end point was partial remission at 24 weeks.\n Of 140 patients recruited, 71 were randomly assigned to receive mycophenolate mofetil and 69 were randomly assigned to receive cyclophosphamide. At 12 weeks, 56 patients receiving mycophenolate mofetil and 42 receiving cyclophosphamide had satisfactory early responses. In the intention-to-treat analysis, 16 of the 71 patients (22.5 percent) receiving mycophenolate mofetil and 4 of the 69 patients receiving cyclophosphamide (5.8 percent) had complete remission, for an absolute difference of 16.7 percentage points (95 percent confidence interval, 5.6 to 27.9 percentage points; P=0.005), meeting the prespecified criteria for noninferiority and demonstrating the superiority of mycophenolate mofetil to cyclophosphamide. Partial remission occurred in 21 of the 71 patients (29.6 percent) and 17 of the 69 patients (24.6 percent), respectively (P=0.51). Three patients assigned to cyclophosphamide died, two during protocol therapy. Fewer severe infections and hospitalizations but more diarrhea occurred among those receiving mycophenolate.\n In this 24-week trial, mycophenolate mofetil was more effective than intravenous cyclophosphamide in inducing remission of lupus nephritis and had a more favorable safety profile.\n Copyright 2005 Massachusetts Medical Society.", "To assess if combination rituximab and cyclophosphamide is more effective than rituximab monotherapy as an induction therapy for proliferative lupus nephritis.\n A randomized open-label pilot study in which 9 patients received rituximab alone and 10 patients received two doses rituximab + intravenous cyclophosphamide. The clinical, laboratory and renal histological changes were assessed after 48 weeks of treatment.\n At week 48, four patients had a complete response, 11 patients achieved partial response, 2 patients remained the same or stable and 2 worsened. There were no statistical differences in the proportion of patients with complete or partial response between the two groups. None of the variables was an independent predictor of response at week 48. Nine patients had significant improvement in activity indices in renal biopsies, but there were no significant differences between the two groups. Overall, 18 out of 19 patients were found to have effective B-cell depletion. The median duration of complete B-cell depletion in all patients was 22 weeks. There were no statistically significant differences in the proportion of patients with complete depletion at weeks 4, 8, 24 and 48 between the two groups except at week 2.\n Rituximab monotherapy appears to be effective as induction therapy in lupus nephritis. The addition of cyclophosphamide offers no additional improvement in clinical, laboratory and renal histological assessment or the duration of B-cell depletion at 48 weeks. Large-scale studies with longer duration are needed to confirm these findings.", "The combination of cyclophosphamide and prednisolone is effective for the treatment of severe lupus nephritis but has serious adverse effects. Whether mycophenolate mofetil can be substituted for cyclophosphamide is not known.\n In 42 patients with diffuse proliferative lupus nephritis we compared the efficacy and side effects of a regimen of prednisolone and mycophenolate mofetil given for 12 months with those of a regimen of prednisolone and cyclophosphamide given for 6 months, followed by prednisolone and azathioprine for 6 months. Complete remission was defined as a value for urinary protein excretion that was less than 0.3 g per 24 hours, with normal urinary sediment, a normal serum albumin concentration, and values for serum creatinine and creatinine clearance that were no more than 15 percent above the base-line values. Partial remission was defined as a value for urinary protein excretion that was between 0.3 and 2.9 g per 24 hours, with a serum albumin concentration of at least 30 g per liter.\n Eighty-one percent of the 21 patients treated with mycophenolate mofetil and prednisolone (group 1) had a complete remission, and 14 percent had a partial remission, as compared with 76 percent and 14 percent, respectively, of the 21 patients treated with cyclophosphamide and prednisolone followed by azathioprine and prednisolone (group 2). The improvements in the degree of proteinuria and the serum albumin and creatinine concentrations were similar in the two groups. One patient in each group discontinued treatment because of side effects. Infections were noted in 19 percent of the patients in group 1 and in 33 percent of those in group 2 (P = 0.29). Other adverse effects occurred only in group 2; they included amenorrhea (in 23 percent of the patients), hair loss (19 percent), leukopenia (10 percent), and death (10 percent). The rates of relapse were 15 percent and 11 percent, respectively.\n For the treatment of diffuse proliferative lupus nephritis, the combination of mycophenolate mofetil and prednisolone is as effective as a regimen of cyclophosphamide and prednisolone followed by azathioprine and prednisolone but is less toxic.", "A 1-year double-blind crossover study comparing prednisone and azathioprine to prednisone plus low-dose azathioprine and cyclophosphamide was carried out in 14 patients with diffuse lupus nephritis. Low-dose triple therapy had no apparent therapeutic advantage over prednisone plus azathioprine. Cyclophosphamide-induced ovarian failure and hematuria were not avoided by its use in low dose.", "Pemphigus is a potentially life-threatening autoimmune blistering skin disease usually treated with high-dose corticosteroids in combination with immunosuppressive drugs. In a multicenter, prospectively randomized study we compared efficacy and side effects of a dexamethasone-cyclophosphamide (D/C) pulse therapy with a methylprednisolone-azathioprine (M/A) therapy in 22 patients with newly diagnosed pemphigus vulgaris and pemphigus foliaceus.\n The 11 patients of the M/A group were treated with daily doses of methylprednisolone (initially 2 mg/kg body weight) and azathioprine (2-2,5 mg/kg body weight) which were subsequently tapered. D/C pulse therapy in 11 patients consisted of intravenous administration of 100 mg dexamethasone/d on 3 consecutive days along with cyclophosphamide (500 mg) on day one. Pulses were initially repeated every 2-4 weeks and then at increasing intervals. In between the pulses, oral cyclophosphamide (50 mg) was given daily for 6 months.\n Within 24 months after treatment initiation, 5/11 patients of the D/C group had a remission (complete remissions after discontinuation of therapy in 3 patients) and 6/11 patients had a progression. In the M/A group, there were remissions in 9/11 patients (complete remissions after discontinuation of therapy in 3 patients) and progression in 1/11 patients. There were more relapses in M/A therapy after remission than in D/C therapy. Side effects were more common in the M/A group. These differences were not significant (p > 0,05).\n Because of the high number of progressions in patients treated with D/C therapy, we can not confirm the encouraging results of earlier reports about pulse D/C therapy. Nevertheless D/C therapy seemed to be better tolerated and, in case of primary efficacy, was associated with fewer recurrences than M/A therapy.", "Effective adjuvant treatment modalities in premenopausal breast cancer patients today include chemotherapy, ovariectomy, and tamoxifen administration. The purpose of Austrian Breast and Colorectal Cancer Study Group Trial 5 was to compare the efficacy of a combination endocrine treatment with standard chemotherapy.\n Assessable trial subjects (N = 1,034) presenting with hormone-responsive disease were randomized to receive either 3 years of goserelin plus 5 years of tamoxifen or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Stratification criteria included tumor stage and grade, number of involved nodes, type of surgery, and steroid hormone receptor content. Relapse-free survival (RFS) was defined as time from randomization to first relapse, local recurrence, or contralateral incidence, and overall survival (OS) as time to date of death.\n With a 60-month median follow-up, 17.2% of patients in the endocrine group and 20.8% undergoing chemotherapy developed relapses. Local recurrences emerged in 4.7% and 8.0%, respectively. RFS and local recurrence-free survival differed significantly in favor of endocrine therapy (P =.037 and P =.015), with a similar trend observed in OS (P =.195).\n Overall, our data suggest that the goserelin-tamoxifen combination is significantly more effective than CMF in the adjuvant treatment of premenopausal patients with stage I and II breast cancer.", "Intravenous cyclophosphamide (IVCP) has been shown to be effective in lupus nephritis. This is a randomized controlled trial to compare the effectiveness of IVCP with oral cyclophosphamide (OCP) in patients with steroid-dependent (SD) idiopathic nephrotic syndrome (INS). Forty-seven consecutive children who were SD were randomized to receive either OCP (2 mg/kg per dayx12 weeks) or IVCP (500 mg/m(2) per month IVx6 months) after achieving a steroid-induced remission. The response was evaluated in terms of remission, change in steroid response status, duration of remission (i.e., proteinuria-free days), side effects, and compliance. Of the 47, IVCP was given to 26 children and OCP to 21 children. The demographic data, histopathology, biochemical profile, and duration of follow-up in the two groups were similar. On Kaplan-Meier survival analysis, the median proteinura-free time was 360+/-88 days compared with 96+/-88 days in the OCP group (values median+/-SE, log rank P=0.05). The actuarial cumulative sustained remission in our study was 73% in IVCP compared with 38.1% in OCP at 6 months after therapy, but was almost identical (18.6% in IVCP vs. 19%in OCP) after 2 years. Thus in our study the overall improvement in steroid response category from SD to sustained remission, infrequent relapser, and frequent relapser (88% in IVCP vs. 57% in OCP) was significantly better in the IVCP group, although the number of children with persistent remission tended to be similar at 2 years. Furthermore, the response was observed with a 40% lower cumulative dose than OCP. Hence, we conclude that IVCP is a safe and effective therapeutic modality in children with INS who are SD.", "Among 14 randomised patients with proliferative lupus nephritis, monthly intravenous immunoglobulin maintained remission over 18 months, similar to standard intravenous cyclophosphamide treatment. Pulsed immunoglobulin may be a useful alternative therapy in lupus nephritis.", "The prospective controlled Phase III clinical trial tested the therapeutic value of the cis-platinum-adriamycin-cyclophosphamide combination (CAP), compared with the combination including cyclophosphamide, methotrexate, 5-fluorouracil, vincristine and prednisolone (CMFVP), in untreated metastatic breast cancer. One hundred and twenty-three patients (greater than 2 cycles) were evaluated: 61 on the CAP, and 62 on the CMFVP schedule. An objective response (CR + PR) to CAP combination chemotherapy was achieved in 72% of patients (43/61), with a high rate (36%) of complete remissions. In terms of metastatic site, the response rate appeared to be particularly high in soft tissue and visceral organ (lung, liver) metastases. In the CMFVP group, an objective response was noted in 26 of 62 patients (42%), with 16% complete remissions. The difference in overall therapeutic response - and in the complete remission rate as well - was statistically significant to the advantage of the CAP regimen (P less than 0.01). The duration of remissions was 6-28 + months (means = 14) for the CAP, and 4-15 + months (mean = 9) for the CMFVP schedule. Toxic side effects were more pronounced in the CAP group, particularly myelosuppression, with anemia prevailing. Side effects of CMFVP treatment were moderate. In 39 CMFVP previously treated cases, CAP was administered as second-line treatment, and an objective response was observed in 51% of cases (20/39). Results of this controlled trial showed the advantage of the CAP combination chemotherapy in the treatment of metastatic breast cancer.", "To evaluate the effectiveness of cyclophosphamide in the treatment of lupus nephritis, we designed a prospective study of patients with diffuse proliferative lupus nephritis. Twenty-six patients received prednisone (average dose, 40 mg per day) and 24 combined prednisone (average dose, 29 mg per day) and cyclophosphamide (average dose, 107 mg per day) for six months. Thereafter, all patients received maintenance doses of prednisone. Most of the patients improved (84 per cent) after six months of initial treatment with either program. Early progression of disease, ending mainly in end-stage renal disease, was equally frequent in the two treatment groups in patients with already advanced disease. In a four-year follow-up study there was a higher incidence (P approximately 0.04) and average rate (P approximately 0.02) of clinical recurrence of nephritis in the group initially given only steroid than in the group initially given both drugs. However, the proportion of patients alive after four years with stable or improved renal function was similar in the two treatment groups.", "Intravenous cyclophosphamide with prednisone is an effective treatment for lupus nephritis, but with significant toxicities. We compared the efficacy and safety of tacrolimus versus intravenous cyclophosphamide as induction therapy.\n Multicenter noninferiority randomized controlled trial.\n 81 patients with biopsy-proven lupus nephritis from 9 nephrology centers in China from 2006-2008.\n Prednisone and either tacrolimus (n = 42) or intravenous cyclophosphamide (n = 39) for 6 months. Tacrolimus was started at 0.05 mg/kg/d and titrated to achieve a trough blood concentration of 5-10 ng/mL. Intravenous cyclophosphamide was initiated at 750 mg/m² of body surface area, then adjusted to 500-1,000 mg/m² every 4 weeks for a total of 6 pulse treatments.\n The primary outcome was complete remission (proteinuria with protein excretion <0.3 g/24 h, serum albumin ≥3.5 g/dL, normal urinary sediment, and normal or stable serum creatinine level) at 6 months. Response (complete or partial remission), clinical parameters, and adverse effects were secondary end points.\n After the 6-month induction therapy, the tacrolimus group achieved higher cumulative probabilities of complete remission and response (52.4% vs 38.5% and 90.5% vs 82.1%, respectively) than the intravenous cyclophosphamide group, but differences were not statistically significant (log-rank test, P = 0.2 and P = 0.7, respectively). Proteinuria [corrected] was significantly decreased in tacrolimus- versus intravenous cyclophosphamide-treated patients after the first month of treatment, even with adjustment for baseline proteinuria (protein excretion, 1.76 vs 2.40 g/d; P = 0.02 for the log-transformed analysis). [corrected] After treatment, serum creatinine levels and estimated glomerular filtration rates were not significantly different between treatment groups. Adverse effects, such as leukopenia and gastrointestinal symptoms, were less frequent in the tacrolimus group.\n Nonblinded, small sample size, and short duration of follow-up.\n In conjunction with prednisone, induction therapy with tacrolimus is at least as efficacious as intravenous cyclophosphamide and prednisone in producing complete remission of lupus nephritis and has a more favorable safety profile.\n Copyright Â© 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.", "Uncertainty exists about the efficacy and toxicity of bolus therapy with methylprednisolone or of the combination of methylprednisolone and cyclophosphamide in the treatment of lupus nephritis.\n To determine 1) whether intensive bolus therapy with methylprednisolone is an adequate substitute for bolus therapy with cyclophosphamide and 2) whether the combination of methylprednisolone and cyclophosphamide is superior to bolus therapy with methylprednisolone or cyclophosphamide alone.\n Randomized, controlled trial with at least 5 years of follow-up.\n Government referral-based research hospital.\n 82 patients with lupus nephritis who had 10 or more erythrocytes per high-power field, cellular casts, proteinuria (> 1 g of protein per day), and a renal biopsy specimen that showed proliferative nephritis.\n Bolus therapy with methylprednisolone (1 g/m2 body surface area), given monthly for at least 1 year; bolus therapy with cyclophosphamide (0.5 to 1.0 g/m2 body surface area), given monthly for 6 months and then quarterly; or bolus therapy with both methylprednisolone and cyclophosphamide.\n 1) Renal remission (defined as < 10 dysmorphic erythrocytes per high-power field, the absence of cellular casts, and excretion of < 1 g of protein per day without doubling of the serum creatinine level), 2) prevention of doubling of the serum creatinine level, and 3) prevention of renal failure requiring dialysis.\n Renal remission occurred in 17 of 20 patients in the combination therapy group (85%), 13 of 21 patients in the cyclophosphamide group (62%), and 7 of 24 patients in the methylprednisolone group (29%) (P < 0.001). Twenty-eight patients (43%) did not achieve renal remission. By life-table analysis, the likelihood of remission during the study period was greater in the combination therapy group than in the methylprednisolone group (P = 0.028). Combination therapy and cyclophosphamide therapy were not statistically different. Adverse events were amenorrhea (seen in 41% of the cyclophosphamide group, 43% of the combination therapy group, and 7.4% of the methylprednisolone group), cervical dysplasia (seen in 11% of the cyclophosphamide group. 7.1% of the combination therapy group, and 0% of the methylprednisolone group), avascular necrosis (seen in 11% of the cyclophosphamide group, 18% of the combination therapy group, and 22% of the methylprednisolone group), herpes zoster (seen in 15% of the cyclophosphamide group, 21% of the combination therapy group, and 3.7% of the methylprednisolone group) and at least one infection (seen in 26% of the cyclophosphamide group. 32% of the combination therapy group, and 7.4% of the methylprednisolone group).\n Monthly bolus therapy with methylprednisolone was less effective than monthly bolus therapy with cyclophosphamide. A trend toward greater efficacy with combination therapy was seen.", "Intravenous cyclophosphamide (IVC) in combination with steroids is standard therapy for Lupus nephritis. Reduction of autoantibodies and circulating immune complexes can be used in the treatment of autoimmune diseases. The aim of the present study was to compare the effects of IVC pulse therapy and double-filtration plasmapheresis (DFPP) on proteinuria and urinary excretion of podocytes in adult patients with diffuse proliferative Lupus nephritis (DPLN). Twenty patients were randomly assigned to two groups. Group A (n = 10) was treated with IVC (0.75 - 1.0 g/m2 body surface area) pulse therapy, given as boluses once a month for 6 consecutive months, combined with oral corticosteroid (up to 1 mg/kg/day) administration. Group B (n = 10) was treated with a combination of DFPP (performed 1-2 times weekly) and corticosteroid (up to I mg/kg/ day). The total average number of treatments was 8.4 and the therapeutic efficacies were evaluated after 6 months. Twenty healthy individuals participated as a control group. Urinary podocytes were examined by immunofluorescence with monoclonal antibodies against podocalyxin. Both Group A and Group B reduced proteinuria (p < 0.001) as well as the number of urinary podocytes (p < 0.001). Differences between the 2 treatment outcomes were not statistically significant. Cyclophosphamide pulse therapy and DFPP may be similarly effective in the treatment of podocyte injury in patients with DPLN.", "A randomized trial was performed to determine relative efficacy and toxicity of two first-line combination chemotherapy regimens in women with metastatic breast cancer: CFP (cyclophosphamide, 5-fluorouracil, prednisone) and CMFP (cyclophosphamide, 5-fluorouracil, methotrexate, prednisone). Both regimens have reported efficacy in this setting but differ in dosages and scheduling of the agents they have in common. Three hundred thirty-six women with no prior chemotherapy for metastatic disease were eligible and evaluable, and 309 had either measurable or evaluable disease and were assessable for objective response. Responses were seen in 65 of 153 (42%) on CFP and 83 of 156 (53%) on CMFP (two-sided P = 0.06). Median durations of response were 7.1 months for CFP and 8.5 months for CMFP (log-rank, two-sided P = 0.67). Considering all 336 patients, the median times to disease progression were 4.7 months for CFP and 6.2 months for CMFP (log-rank P = 0.31) and median survivals were 15.2 and 14.9 months, respectively (log-rank P = 0.88). Covariate analysis did not alter these findings. Median leukocyte nadirs were 1800 for CFP and 1500 for CMFP, with 22% and 21%, respectively, having nadirs less than 1000/microliters. Emesis was more frequent on CFP (49%) than on CMFP (26%) but was severe in only 7% and 5%, respectively. It is concluded that despite a higher response rate on CMFP and some differences in toxicities including a higher reported incidence of emesis on CFP, there was no substantial difference in efficacy or tolerability between the two regimens.", "To compare the efficacy (maintenance of remission), safety and tolerability of cyclosporin (CsA) with those of cyclophosphamide in patients with steroid-dependent or frequently relapsing nephrotic syndrome (NS).\n Open, prospective, randomized, multicentre, controlled study for parallel groups, stratified for adults and children. The setting was in nephrological departments in Italy.\n Seventy-three patients with steroid-sensitive idiopathic NS admitted to the study were randomly assigned to cyclophosphamide (2.5 mg/kg/day) for 8 weeks or CsA (5 mg/kg/day in adults, 6 mg/kg/day in children) for 9 months, tapered off by 25% every month until complete discontinuation at month 12. Seven patients lost to follow up were not considered in the analysis. The remaining 66 patients were followed up for 3-24 months after randomization.\n Relapse-free survival; number of N.S. relapses/patient/year; cumulative dose of prednisone/patient; laboratory investigations (kidney and liver functions, haematological parameters); incidence of adverse events.\n At month 9, 26 of 35 CsA-treated patients were still in complete remission and a further five patients were in partial remission; 18 of 28 cyclophosphamide-treated patients were in complete remission, and one in partial remission (P = NS). No difference between adults and children was seen with either treatment. The risk of relapse was similar between frequent relapsers (19 of 22) and steroid-dependent patients (8 of 14) given CsA, and those given cyclophosphamide (5 of 15 and 6 of 15). The mean number of relapses per year and the mean dose of prednisone per year were significantly less (P < 0.001) in both groups for the experimental year than for the year before randomization. At 2 years, 25% of the patients given CsA (50% adults and 20% children) and 63% of those given cyclophosphamide (40% adults and 68% children) had not had any relapse of NS. Tolerance to the two drugs was generally good. The CsA-related side-effects were mild and disappeared after drug discontinuation.\n This study shows that both treatments are effective and well tolerated; more patients given cyclophosphamide had stable remissions.", "A multicentric randomized study was conducted to compare the CNF regimen (cyclophosphamide at 600 mg/m2/iv, mitoxantrone at 10 mg/m2/iv, 5-fluorouracil at 600 mg/m2/iv) with the CMF regimen (methotrexate at 40 mg/m2/iv instead of mitoxantrone) administered every 3 weeks to previously untreated locally advanced or metastatic breast cancer patients. In 119 patients evaluable for therapeutic response, complete plus partial response rate was 44% for CNF and 29% for CMF (p>0.05; 95% C.I.: CNF=32%-56%, CMF=18%-40%). No statistically significant difference regarding time to progression, over survival or response to second-line chemotherapy with Epidoxorubicin was observed between the two regimens. Both regimens were well tolerated, but the percent of alopecia and leucopenia was significantly higher in the CNF patient group (31% versus 5% and 18% versus 0%, respectively; p<0.01). In conclusion, CNF was demonstrated to be slightly more toxic but more effective as compared to CMF (global response: 44% versus 29%, respectively). These findings should be taken into consideration when planning future studies of adjuvant chemotherapy.", "Melphalan (L-PAM) was compared to (C) cyclophosphamide, (M) methotrexate, and (F) 5-fluorouracil (CMF) in 413 patients with advanced ovarian carcinoma. L-PAM was given 3.5 mg/m2 twice daily for 5 days every 5 weeks. CMF doses were: C, 400 mg/m2; M, 15 mg/m2; and F, 400 mg/m2 IV on days 1 and 8 every 28 days. Three hundred seventy-five patients have been analyzed (L-PAM, 190; CMF, 185). One hundred fifty-three patients (41%) had measurable disease, 109 (29%) had evaluable disease, and 113 (30%) had nonmeasurable, nonevaluable disease. Response rates for patients with measurable and evaluable disease combined were similar: L-PAM, 32/130 (24%) (15% complete response); CMF, 47/132 (35%) (18% complete response). Patients with Stage IV measurable disease had a greater response rate to CMF, 22/52 (42%) versus L-PAM, 6/39 (15%). Survival and time to treatment failure were similar for both treatment regimens. Survival was improved in responders. Medians are: complete response, 28.1 months; partial response, 12.3 months; and no response, 6.7 months. Disease stage, performance status and age were identified as important prognostic variables for both survival and time to treatment failure.", "Thirty-two evaluable patients with metastatic carcinoma of the prostate were entered into a prospective randomized trial comparing cyclophosphamide (CYC) with a combination of cyclophosphamide, methotrexate, and fluorouracil (CMF). Progressive disease after endocrine manipulation was noted in 97% (31/32) of patients before entry. Stable disease (S) was observed in 9 of 17 patients treated with CYC. One partial response (PR) and seven stable responses occurred in the 15 CMF patients. Median duration of stable response was 4.5 months for CYC and 4.5 months on CMF. Median survival of patients with PR and S receiving CYC was 10.1 and for CMF 8.8 months. Patients with progressive disease survived a median 1.7 and 2.6 months with CYC and CMF, respectively. Toxicity was moderate, and no deaths were attributable to sepsis or bleeding. Almost all patients in this study had bone lesions as the dominant site of disease; this made objective assessment of response difficult. There was no significant improvement in response conferred by the combination regimen. Although patients with metastatic prostatic cancer may benefit from chemotherapy, impressive clinical responses are uncommon.", "Azathioprine is useful as a steroid-sparing drug in patients with ulcerative colitis. Its role as monotherapy in the maintenance of disease remission has not been evaluated.\n In this prospective, randomized, open-label study, 25 patients with severe ulcerative colitis received either azathioprine (2.5 mg/Kg/day; Group A, n = 12) or sulfasalazine (6 g/day; Group B, n = 13). All patients received oral corticosteroids in a tapering dosage schedule initially. Treatment failure was defined as either disease relapse or drug withdrawal because of adverse effects.\n Five of 12 patients in Group A and 8 of 13 patients in Group B had sustained remission during the stipulated study period of 18 months (p = ns). Two patients in Group A had to stop azathioprine because of adverse effects (bone marrow suppression and acute pancreatitis). In Group A, all patients who had treatment failure developed it in the first half of the study while in Group B treatment failure occurred in both halves.\n The relapse rate of ulcerative colitis on maintenance therapy with azathioprine or sulfasalazine is comparable; there was a trend towards earlier treatment failure with azathioprine.", "A prospective, randomized drug trial compared prednisone (60 mg per day initially) to azathioprine (3 to 4 mg/kg of body weight - day initially) plus prednisone in 24 patients with life-threatening systemic lupus erythematosus. Each group contained patients matched for age, sex, disease duration, previous therapy, and clinical and laboratory features of lupus erythematosus. During a mean follow-up period of 18 to 24 months, there were no significant differences between the two groups in number of deaths, renal or extrarenal manifestations of disease, serum complement levels, DNA antibodies, antinuclear antibody titers, lupus erythematosus cells, or Coombs' antibodies. There was no convincing evidence of a steroid-sparing effect of azathioprine. Side effects attributable to steroids were equally common in both groups; infections were not increased in the combination therapy group. Azathioprine was hepatotoxic in doses of 200 mg daily or more. Azathioprine was not a useful adjunct to corticosterolds in short-term therapy of a small number of patients with severe systemic lupus.", "Seventy-eight advanced breast cancer patients with hormone-resistant disease or visceral metastases were randomized to receive either of two low dose regimens consisting of cyclophosphamide (C), methotrexate (M), 5-fluorouracil (F), and Adriamycin (A) as their initial chemotherapy. One group was treated with CAMF, and the other with CMF until progression, followed by A (CMF leads to A). C was given at 50 mg/m2, po, days 1-14; M at 20 mg/m2, F at 300 mg/m2, and A at 20 mg/m2, iv, days 1 and 8 of each 28-day cycle. The response rates for CAMF vs. CMF did not differ significantly (complete and partial responses-62% vs. 49%; stabilizations-23% vs. 31%). Responses by site of metasis, median times to progression and median survivals were similar for both groups. Poor and good risk partial responders had similar survivals. Twelve percent of CMF patients treated with Adriamycin at the time of progression had partial responses with an associated improved survival. Since CMF is as effective as CAMF, but has less toxicity, low dose therapy with CMF is more acceptable than CAMF as an initial chemotherapy regimen for metastatic breast cancer. Adriamycin may be reserved for subsequent regression induction." ]	MMF is as effective as cyclophosphamide in inducing remission in lupus nephritis, but is safer with a lower risk of ovarian failure. MMF is more effective than azathioprine in maintenance therapy for preventing relapse with no increase in clinically important side effects. Adequately powered trials with long term follow-up are required to more accurately define the risks and eventual harms of specific treatment regimens.
CD005411	[ "16243954", "12755982", "8737434", "16737346", "15066200", "12356708", "15659884", "12817353", "15188323", "11176553", "11298072", "11294376", "19707060", "3528240", "12358871", "18807252", "19926502", "16159043", "19588640", "17272285", "16389536", "16737349", "7853047" ]	[ "A multifaceted intervention according to the Audit Project Odense method improved secondary prevention of ischemic heart disease: a randomised controlled trial.", "Recurrent aphthous stomatitis unresponsive to topical corticosteroids: a study of the comparative therapeutic effects of systemic prednisone and systemic sulodexide.", "Small group intervention vs formal seminar for improving appropriate drug use.", "Rational prescribing in primary care (RaPP): a cluster randomized trial of a tailored intervention.", "An outreach intervention to implement evidence based practice in residential care: a randomized controlled trial [ISRCTN67855475].", "Educational strategies to promote evidence-based community pharmacy practice: a cluster randomized controlled trial (RCT).", "Multidisciplinary HIV adherence intervention: a randomized study.", "Modifying dyspepsia management in primary care: a cluster randomised controlled trial of educational outreach compared with passive guideline dissemination.", "Multifaceted intervention to improve rheumatologists' management of glucocorticoid-induced osteoporosis: a randomized controlled trial.", "One-to-one versus group sessions to improve prescription in primary care: a pragmatic randomized controlled trial.", "Outcomes of a randomized controlled trial of a clinical pharmacy intervention in 52 nursing homes.", "Feedback on prescribing rate combined with problem-oriented pharmacotherapy education as a model to improve prescribing behaviour among general practitioners.", "The tools of an evidence-based culture: implementing clinical-practice guidelines in an Israeli HMO.", "Systemic administration of antibiotics in the management of venous ulcers. A randomized clinical trial.", "Multifaceted support to improve clinical decision making in diabetes care: a randomized controlled trial in general practice.", "Combined intervention programme reduces inappropriate prescribing in elderly patients exposed to polypharmacy in primary care.", "Pilot study on recurrent aphthous stomatitis (RAS): a randomized placebo-controlled trial for the comparative therapeutic effects of systemic prednisone and systemic montelukast in subjects unresponsive to topical therapy.", "A group randomized trial to improve safe use of nonsteroidal anti-inflammatory drugs.", "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.", "The MEDMAN study: a randomized controlled trial of community pharmacy-led medicines management for patients with coronary heart disease.", "Changing antibiotics prescribing practices in health centers of Khartoum State, Sudan.", "Rational prescribing in primary care (RaPP): economic evaluation of an intervention to improve professional practice.", "Cumulative meta-analysis of clinical trials builds evidence for exemplary medical care." ]	[ "No single quality improvement instrument has proved consistently effective, but multifaceted interventions are believed to have the greatest impact. However, only little is known regarding what combinations are likely to be successful.\n To evaluate the impact of a multifaceted intervention strategy combining GP registrations, outreach visits and feedback, targeting secondary prevention of ischemic heart disease in general practice.\n A randomised controlled trial including 28 GPs in Ringkjøbing County, Denmark. Half of the GPs received outreach visits and feedback on their prescribing of heart disease drugs. Evaluation was based on registration of consultations with patients suffering from ischemic heart disease.\n The intervention had a statistically significant impact on prescribing of lipid lowering drugs [odds ratio 1.59; 95% confidence interval (CI) 1.00 to 2.53] and acetylsalicylic acid (odds ratio 2.54; 95% CI 1.21 to 5.31).\n An intervention strategy combining outreach visits, feedback and GP registrations is a promising way of improving the quality of preventive treatment in general practice.", "Recurrent aphthous stomatitis (RAS) is a common oral condition, the etiology of which remains largely unclear. Numerous therapeutic protocols have been tried. Apart from immunomodulators, no therapy is unequivocally effective, and many systemic therapies have potential adverse effects.\n To compare, in patients with frequent RAS unresponsive to conventional therapies, the therapeutic effectiveness of systemic prednisone with that of systemic sulodexide, a low-molecular-weight heparin with immunosuppressive activity but few adverse effects.\n The study involved a group of 30 patients suffering from frequent minor RAS over >or= 4 months unresponsive to topical corticosteroids. Patients were randomly assigned to one of three study groups: blind therapy with systemic sulodexide or systemic prednisone and control (no treatment). The outcomes were assessed blind on the basis of the days to recovery from pain and days to recovery from ulceration (epithelialization) during the first month of therapy; the number of aphthae appearing during the second month of therapy; and the number of aphthae appearing in the 2 months after the end of the 2-month treatment cycle.\n The effectiveness of systemic sulodexide was almost comparable with that of systemic prednisone in patients with frequent RAS, without significant adverse effects.", "In an attempt to evaluate the efficacy of different methods of interventions to improve the appropriate use of drugs for acute diarrhoea, a controlled study has been carried out in 6 districts in Yogyakarta and Central Java provinces, Indonesia. This study was designed to investigate the impacts of two different methods of educational intervention, i.e. a small group face-to-face intervention and a formal seminar for prescribers, on prescribing practice in acute diarrhoea. The districts were randomly assigned into 3 groups and 15 health centers were selected from each district. Prescribers in Group 1 underwent a small group face-to-face intervention conducted in the respective health center. Those in Group 2 attended a formal seminar conducted at the district level. Prescribers in Group 3 served as the control group. Both interventions were given on a single occasion without follow-up supervision or monitoring. Written information materials on the appropriate management of acute diarrhoea were developed and were provided to all prescribers in the intervention groups. Focus group discussions (FGDs) involving prescribers and consumers in the 6 districts were carried out to identify various underlying motivations of drug use in acute diarrhoea. The findings of the FGDs were used as part of the intervention materials. To evaluate the impacts of these interventions on prescribing practice, a prescribing survey for patients under five years old with acute diarrhoea was carried out in health centers covering 3-month periods before and after the intervention. The results showed that both interventions were equally effective in improving the levels of knowledge of prescribers about the appropriate management of acute diarrhoea. They were also partially effective in improving the appropriate use of drugs, reducing the use of non-rehydration medications. There was a highly significant reduction of antimicrobial usage either after small-group face-to-face intervention (77.4 +/- 2.7% to 60.4 +/- 2.9%; P < 0.001) or formal seminar (82.3 +/- 3.0% to 72.3 +/- 3.6%; P < 0.001), and the former caused significantly (P < 0.001) greater reduction than the latter. There was also a significant (P < 0.01) reduction in the usage of antidiarrhoeals after both interventions, i.e. from 20.3 +/- 3.7% to 12.5 +/- 3.3% (P < 0.01) after face-to-face intervention and from 48.5 +/- 4.1% to 27.0 +/- 4.3% (P < 0.01) after seminar. However, the formal seminar had a significantly (P < 0.01) greater impact than the small group face-to-face intervention. There was also a trend toward increased oral rehydration solution (ORS) usage after both interventions, but this did not achieve the level of statistical significance (P > 0.05). No changes were observed in the control group. Although the small group face-to-face intervention did not appear to offer greater impacts over large seminars in improving the appropriate use of drugs in acute diarrhoea, since the unit cost of training is far less costly than the seminar, it might be feasibly implemented in the existing supervisory structure of the health system.", "A gap exists between evidence and practice regarding the management of cardiovascular risk factors. This gap could be narrowed if systematically developed clinical practice guidelines were effectively implemented in clinical practice. We evaluated the effects of a tailored intervention to support the implementation of systematically developed guidelines for the use of antihypertensive and cholesterol-lowering drugs for the primary prevention of cardiovascular disease.\n We conducted a cluster-randomized trial comparing a tailored intervention to passive dissemination of guidelines in 146 general practices in two geographical areas in Norway. Each practice was randomized to either the tailored intervention (70 practices; 257 physicians) or control group (69 practices; 244 physicians). Patients started on medication for hypertension or hypercholesterolemia during the study period and all patients already on treatment that consulted their physician during the trial were included. A multifaceted intervention was tailored to address identified barriers to change. Key components were an educational outreach visit with audit and feedback, and computerized reminders linked to the medical record system. Pharmacists conducted the visits. Outcomes were measured for all eligible patients seen in the participating practices during 1 y before and after the intervention. The main outcomes were the proportions of (1) first-time prescriptions for hypertension where thiazides were prescribed, (2) patients assessed for cardiovascular risk before prescribing antihypertensive or cholesterol-lowering drugs, and (3) patients treated for hypertension or hypercholesterolemia for 3 mo or more who had achieved recommended treatment goals. The intervention led to an increase in adherence to guideline recommendations on choice of antihypertensive drug. Thiazides were prescribed to 17% of patients in the intervention group versus 11% in the control group (relative risk 1.94; 95% confidence interval 1.49-2.49, adjusted for baseline differences and clustering effect). Little or no differences were found for risk assessment prior to prescribing and for achievement of treatment goals.\n Our tailored intervention had a significant impact on prescribing of antihypertensive drugs, but was ineffective in improving the quality of other aspects of managing hypertension and hypercholesterolemia in primary care.", "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.", "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.", "Maintaining greater than 95% adherence to antiretroviral medication is necessary in order to have the greatest therapeutic impact on HIV infection. Furthermore, evidence suggests that adherence rates of between 70% and 89% are significantly associated with viral rebound and the development of drug resistance. Adherence rates at and above the 95% level are difficult for patients to achieve and maintain. Our aim was to determine if an adherence intervention could improve adherence among patients attending an ambulatory care clinic at a large public hospital. The intervention was delivered by a multidisciplinary team of health care professionals and consisted of education coupled with the provision of devices designed to assist patient memory and adherence. A crucial component of the intervention consisted of the identification of patient specific barriers to adherence and the development of strategies to circumvent these problems. Adherence was assessed using patient self-report over the past 4, 7, and 28 days and by calculation of the Morisky score. The study was conducted as a randomised controlled trial using the stepped wedge design with a total of 68 subjects randomised to receive the intervention over a 20-week period. Adherence before and after the intervention formed the analysis. There was a significant decrease in the number of missed doses over the past 4 (1.9 to 1.0, p < 0.001), 7 (3.0 to 1.8, p < 0.001) and 28 (7.4 to 4.2, p < 0.001) days and a decrease in the Morisky score, indicating an improvement in medication taking behaviour (1.3 to 0.5 p < 0.001).", "Quality improvement initiatives in health services rely upon the effective introduction of clinical practice guidelines. However, even well constructed guidelines have little effect unless supported by dissemination and implementation strategies.\n To test the effectiveness of 'educational outreach' as a strategy for facilitating the uptake of dyspepsia management guidelines in primary care.\n A pragmatic, cluster-randomised controlled trial of guideline introduction, comparing educational outreach with postal guideline dissemination alone.\n One-hundred and fourteen general practices (233 general practitioners) in the Salford and Trafford Health authority catchment area in the northwest of England.\n All practices received guidelines by post in July 1997. The intervention group practices began to receive educational outreach three months later. This consisted of practice-based seminars with hospital specialists at which guideline recommendations were appraised, and implementation plans formulated. Seminars were followed up with 'reinforcement' visits after a further 12 weeks. Outcome measures were: (a) the appropriateness of referral for; and (b) findings at, open access upper gastrointestinal endoscopy; (c) costs of GP prescriptions for acid-suppressing drugs, and (d) the use of laboratory-based serological tests for Helicobacter pylori. Data were collected for seven months before and/or after the intervention and analysed by intention-to-treat.\n (a) The proportion of appropriate referrals was higher in the intervention group in the six-month post-intervention period (practice medians: control = 50.0%, intervention = 63.9%, P < 0.05); (b) the proportion of major findings at endoscopy did not alter significantly; (c) there was a greater rise in overall expenditure on acid-suppressing drugs in the intervention as compared with the control group (+8% versus +2%, P = 0.005); and (d) the median testing rate per practice for H pylori in the post-intervention period was significantly greater in the intervention group (four versus O, P < 0.001).\n This study suggests that educational outreach may be more effective than passive guideline dissemination in changing clinical behaviour. It also demonstrates that unpredictable and unanticipated outcomes may emerge.", "To assess the effectiveness of a multifaceted intervention to improve the management of glucocorticoid-induced osteoporosis (GIOP).\n Of 21 rheumatologists, 11 were randomly assigned to a 3-part intervention consisting of a lecture and discussion regarding optimal management of GIOP, a confidential doctor-specific audit regarding management of GIOP, and a reminder mailing including concise pharmacologic recommendations. The remaining 10 rheumatologists received no special education. Patients with rheumatoid arthritis (RA) taking oral glucocorticoids seen in the 2 months after the intervention were followed for 6 months. Medical records were assessed to determine the proportion undergoing bone mineral density testing or receiving pharmacologic interventions for GIOP during the 6 months before and 6 months after the intervention.\n There were 373 patients with RA taking oral glucocorticoids whose records were assessed. Patients in both arms of the trial were similar with respect to age, sex, menopausal status, glucocorticoid dosage and duration, duration of RA, disease-modifying antirheumatic drug use, and the proportion with comorbid conditions. At baseline, there was no significant difference between the patients with respect to osteoporosis medication use (intervention 32% versus control 34%) or bone densitometry use (intervention 9% versus control 5%). After the intervention and a 6-month followup period, there were no differences in treatment (intervention 33% versus control 38%) or bone densitometry use (intervention 8% versus control 8%). Adjusting for patient and physician characteristics did not significantly change these results.\n A multifaceted intervention for GIOP, including doctor education, practice audit, and treatment suggestions, had no significant benefit on testing or treatment by rheumatologists over a 6-month followup period. Other intervention approaches need to be tested.", "The objective of the study was to evaluate the effectiveness of 2 educational strategies aimed at improving prescribing standards in primary care.\n A pragmatic controlled trial was designed; the study population included general and family practitioners in Galicia (northwestern Spain) divided into 3 study groups: a one-to-one education group (n = 98), a by-group education group (n = 92), and a control group (n = 405). The educational intervention included explicit recommendations for selecting nonsteroidal anti-inflammatory drugs (NSAIDs) for inflammation signs. Some of the subjects were given reminders. Mixed-effect linear models were applied to data analysis. Analyses were done by intention-to-treat. The dependent variable is a rate with a numerator that is the number of prescribed units of the NSAIDs recommended during intervention; the denominator is the total number of prescribed units of the NSAID total.\n One-to-one education obtained an average prescribing behavior improvement of 6.5% (P < 0.001) in the 9 months after intervention. In the education group, the average improvement was 2.4% (P < 0.05) for the same period. Statistically significant differences were observed between the group intervention and one-to-one groups. The reminder increased significantly the effectiveness of the one-to-one intervention.\n A single, short educational session to primary care doctors can improve their prescribing standards during long periods of > or = 9 months. Of the 2 strategies followed in the trial, one-to-one education has shown to be the most effective. Results also show that the effectiveness of these interventions increases when presented together with written material.", "To evaluate whether a year long clinical pharmacy program involving development of professional relationships, nurse education on medication issues, and individualized medication reviews could change drug use, mortality and morbidity in nursing home residents.\n A cluster randomised controlled trial, where an intervention home was matched to three control homes, was used to examine the effect of the clinical pharmacy intervention on resident outcomes. The study involved 905 residents in 13 intervention nursing homes and 2325 residents in 39 control nursing homes in south-east Queensland and north-east New South Wales, Australia. The outcome measures were: continuous drug use data from government prescription subsidy claims, cross-sectional drug use data on prescribed and administered medications, deaths and morbidity indices (hospitalization rates, adverse events and disability indices).\n This intervention resulted in a reduction in drug use with no change in morbidity indices or survival. Differences in nursing home characteristics, as defined by cluster analysis with SUDAAN, negated intervention-related apparent significant improvements in survival. The use of benzodiazepines, nonsteroidal anti-inflammatory drugs, laxatives, histamine H2-receptor antagonists and antacids was significantly reduced in the intervention group, whereas the use of digoxin and diuretics remained similar to controls. Overall, drug use in the intervention group was reduced by 14.8% relative to the controls, equivalent to an annual prescription saving of A64 dollars per resident (approximately 25 pound sterling).\n This intervention improved nursing home resident outcomes related to changes in drug use and drug-related expenditure. The continuing divergence in both drug use and survival at the end of the study suggests that the difference would have been more significant in a larger and longer study, and even more so using additional instruments specific for measuring outcomes related to changes in drug use.", "To develop a working model with which prescribing behaviour among general practitioners might be influenced.\n Intervention based on feedback on prescribing rates and problem-oriented educational outreach visits, using educational material and local opinion leaders. Randomised study with three parallel intervention groups of general practitioners, which also served as controls for each other. The pharmacotherapeutic fields chosen were hypertension, peptic ulcer/dyspepsia and depression. Prescription data were retrieved from the electronic patient records for periods of 1 year before and after the intervention.\n Six health care centres and three continuing medical education groups in Stockholm.\n Forty general practitioners.\n Drug prescribing rates and patterns before and after the intervention.\n In the hypertension field, desired trends in fractional prescribing (favouring diuretics and beta blocking agents) were recorded, with a significant (P < 0.05) effect on prescriptions for agents acting on the renin-angiotensin system, despite a pre-existing prescribing behaviour already much in line with the goals. In the peptic ulcer/dyspepsia field, desired trends were recorded for both types of therapies addressed. The fractional prescribing rates for proton-pump inhibitors decreased from 61.0% to 52.6% in the intervention arm and increased from 68.1% to 76.0% in the control arm (not significant due to low power). The depression group focused on better general attention to the disease and only minor changes were registered.\n Feedback of individual prescribing rates, combined with problem-oriented educational outreach visits, is a promising model for the improvement of prescribing behaviour. Data from the electronic patient record were feasible for feedback on prescribing rates.", "Although clinical-practice guidelines (CPGs) are implemented on the assumption that they will improve the quality, efficiency, and consistency of health care, they generally have limited effect in changing physicians' behavior. The purpose of this study was to design and implement an effective program for formulating, promulgating, and implementing CPGs to foster the development of an evidence-based culture in an Israeli HMO.\n The authors implemented a four-stage program of stepwise collaborative efforts with academic institutions composed of developing quantitative tools to evaluate prescribing patterns, updating CPGs, collecting MDs' input via focus groups and quantitative surveys, and conducting a randomized controlled trial of a two-stage, multipronged intervention. The test case for this study was the development, dissemination, and implementation of CPG for the treatment of acute uncomplicated cystitis in adult women. Interventions in the form of a lecture at a conference and a letter with personalized feedback were implemented, both individually and combined, to improve physicians' rates of prescribing the first-line drug, nitrofurantoin, and, in the absence of nitrofurantoin, adhering to the recommended duration of three days of treatment with ofloxacin.\n The tools and data-generating capabilities designed and constructed in Stage I of the project were integral components of all subsequent stages of the program. Personalized feedback alone was sufficient to improve the rate of adherence to the guidelines by 19.4% (95% CI = 16.7, 22.1).\n This study provides a template for introducing the component of experimentation essential for cultivating an evidence-based culture. This process, composed of collaborative efforts between academic institutions and a managed care organization, may be beneficial to other health care systems.", "Forty-seven patients with chronic venous leg ulcers were included in a randomized clinical trial to evaluate the efficacy of systemically administered antibiotics in healing with condition. One group was treated by means of elastic support bandages only, whereas the other one received the same local treatment plus systemic antibiotics. No statistically relevant difference was noted between the two groups in healing rates of ulcers or in changes of the microbiologic flora. The results of our study do not support the routine administration of systemic antibiotics in the management of chronic venous leg ulcers.", "To evaluate the effectiveness of a multifaceted intervention to improve the clinical decision making of general practitioners (GPs) for patients with diabetes. To identify practice characteristics which predict success.\n Cluster randomized controlled trial with 124 practices and 185 GPs in The Netherlands. The intervention group received feedback reports and support from a facilitator; the control group received no special attention. Outcome measures were the compliance rates with evidence-based recommendations pertaining to discussion of body weight control, discussion of problems with medication, blood pressure measurement, foot examination, eye examination, initiating anti-diabetic medication or increasing the dosage in cases of uncontrolled blood glucose, and scheduling a follow-up appointment.\n The GPs reported on their clinical decision making in 1410 consultations with Type 2 diabetic patients at baseline and 1449 consultations after the intervention period. The intervention resulted in statistically significant improvement for two of the seven outcome measures: foot examination (odds ratio 1.68; 95% confidence interval 1.19-2.39) and eye examination (1.52; 1.07-2.16). Discussion of problems with medication showed a near significant trend towards increased benefit for the intervention group (1.52; 0.99-2.32). Practice characteristics were not found to be related to the success of the intervention.\n Feedback reports with support from facilitators appear to increase rates of foot examination and eye examination in general practice. Alternative interventions should be explored to improve the pursuit of metabolic control by GPs.", "To evaluate the effect of a combined or a single educational intervention on the prescribing behaviour of general practitioners (GPs). The primary endpoint was effect on inappropriate prescribing according to the Medication Appropriateness Index (MAI).\n General practitioners were randomised to either (1) a combined intervention consisting of an interactive educational meeting plus feedback on participating patients' medication, (2) a single intervention with an interactive educational meeting or (3) a control group (no intervention). Elderly (>65 years) patients exposed to polypharmacy (>or=5 medications) were identified and approached for inclusion. Data on medications prescribed over a 3-month period were collected, and the GPs provided detailed information on their patients before and after the intervention. A pre- and post-MAI were scored for all medications.\n Of the 277 GPs invited to participate; 41 (14.8%) volunteered. Data were obtained from 166 patients before and after the intervention. Medication appropriateness improved in the combined intervention group but not in the single intervention group. The mean change in MAI and number of medications was -5 [95% confidence interval (CI) -7.3 to -2.6] and -1.03 (95% CI -1.7 to -0.30) in the combined intervention group compared with the group with the educational meeting only and the no intervention group.\n A combined intervention consisting of an interactive educational meeting plus recommendations given by clinical pharmacologists/pharmacists concerning specific patients can improve the appropriateness of prescribing among elderly patients exposed to polypharmacy. This study adds to the limited number of well-controlled, randomised studies on overall medication appropriateness among elderly patients in primary care. Important limitations to the study include variability in data provided by participating GPs and a low number of GPs volunteering for the study.", "Recurrent aphthous stomatitis (RAS) is characterized by recurrent painful oral ulcers whose etiology remains largely unknown. Numerous therapeutic protocols have been tried so far, but effectiveness remains an issue.\n To test a new drug for patients with recurrent oral aphthae nonresponsive to local corticosteroid therapy, we compared the therapeutic effectiveness and adverse effects of systemic prednisone and systemic montelukast in a placebo-controlled trial.\n Sixty patients suffering from minor RAS for > or =6 months were studied and randomly assigned to 3 groups of 20 each in a double-blind study. Patients of group A took 25 mg prednisone orally daily for 15 days, 12.5 mg daily for 15 days, 6.25 mg daily for 15 days, then 6.25 mg on alternate days for 15 days. Patients of group B took 10 mg montelukast orally every evening and then on alternate days for the second month. Patients of group C took 100 mg cellulose (placebo) by mouth daily for the first month and on alternate days for the second month. Outcomes assessed were days til pain cessation, days to ulcer healing, and number of aphthae occurring during the follow-up period.\n Both prednisone and montelukast were effective in reducing the number of lesions and improving pain relief and ulcer healing when compared with placebo. Prednisone was more effective than montelukast in pain cessation (P < .0001) and in accelerating ulcer healing (P < .0001). However, adverse drug reactions recorded during the entire trial were more common in the prednisone group compared with montelukast (10%) and placebo (10%).\n These data suggest that the effectiveness of systemic montelukast is similar to that of systemic prednisone in patients with RAS. The lack of serious side effects makes montelukast a candidate drug to use in cases of RAS where pharmacologic therapy for long periods is needed.\n Copyright 2010 Mosby, Inc. All rights reserved.", "To determine whether audit/feedback and educational materials improve adherence to recommendations for laboratory monitoring and cytoprotective agents to detect and prevent adverse events caused by nonsteroidal anti-inflammatory agents (NSAIDs).\n Controlled, cluster-randomized trial.\n Physicians commonly prescribing NSAIDs were identified within a large managed care organization and randomized to a control or an intervention group (audit/feedback with peer-derived benchmarks and continuing medical education). Medical records were examined 10 months before and after the intervention for clinical data and receipt of complete blood count (CBC), creatinine testing, and cytoprotective agents (process measures). Primary analysis compared intervention versus control physicians among those who initially performed below a peer-derived benchmark. General estimating equations accounted for patient clustering.\n Of 101 physicians initially randomized, 85 remained eligible (38 internists, 36 family physicians, 11 rheumatologists) postintervention. Mean percent change in performance between intervention and control physicians for CBC monitoring was 16% versus 10%; for creatinine monitoring, 0% versus 17%; and use of cytoprotective agents, -3% versus -1%. None of these changes were significant. Rheumatology specialty, number of NSAID prescriptions and physician visits, and patient risk factors for NSAID-related toxicity were more strongly associated with improved safety practices than the intervention.\n Audit/feedback and educational materials had no observed effect on improving NSAID-related safety practices. Potentially contributing factors include high baseline performance (ceiling effect), dilution of the intervention effect by case mix and provider factors, nonreceipt of intervention materials, and diverse indications for lab tests.", "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.", "There have been recent moves to extend the role of the community pharmacist to include medicine management.\n A randomized controlled trial was conducted in nine sites in England. Patients with coronary heart disease were identified from general practice computer systems, recruited and randomized (2:1) to intervention or control. The 12-month intervention comprised an initial consultation with a community pharmacist to review appropriateness of therapy, compliance, lifestyle, social and support issues. Control patients received standard care. The primary outcome measures were appropriate treatment [derived from the National Service Framework (NSF)], health status (SF-36, EQ-5D) and an economic evaluation. Secondary outcome measures were patient risk of cardiovascular death and satisfaction.\n The study involved 1493 patients (980 intervention and 513 control), 62 pharmacists and 164 GPs. No statistically significant differences between intervention and control groups were shown at follow-up for any of the primary outcome measures such as numbers on aspirin or lifestyle measures. There were few differences in quality of life (SF-36) between the intervention and control groups at baseline or follow-up or with overall EQ-5D score over time. The total National Health Service cost increased between baseline and at 12 months in both groups but to a greater extent in the intervention group. Significant improvements were found in the satisfaction score for patients' most recent pharmacy visit for prescription medicines among the intervention group, compared with control group. Self-reported compliance was good for both groups at baseline and no significant differences were shown at follow-up.\n There was no change in the proportion of patients receiving appropriate medication as defined by the NSF. The pharmacist-led service was more expensive than standard care.", "A major problem with inappropriate use of antibiotics is the emergence of resistance. Thus, cost-effective interventional strategies are required to improve their use. This study aimed to evaluate the effect of multifaceted interventions on prescribing practices of antibiotics in health centers of Khartoum State, Sudan.\n Twenty health centers were randomly assigned to receive: (1) no intervention; (2) audit and feedback; (3) audit and feedback + seminar; or (4) audit and feedback + academic detailing. A total of 1,800 patient encounters, 30 from each health center, were randomly collected. The total number of encounters with antibiotics prescribed were determined in each health center and they were evaluated with regard to antibiotic choice, dose and duration of therapy before the study and at 1 and 3 months post-intervention.\n In comparison to the control group, the prescriber targeted interventions involving audit and feedback, together with academic detailing (4), reduced the mean number of encounters with an antibiotic prescribed by 6.3 and 7.7 (p<0.001) at 1 and 3 months post-intervention, respectively. In addition, the mean number of encounters with an inappropriate antibiotic with respect to diagnosis, doses and/ or duration of therapy was reduced by 5.3 and 5.9 (p<0.001) at 1 and 3 months post-intervention, respectively. For audit and feedback together with seminars (3) and for audit and feedback alone (2), the corresponding reductions were 5.3, 7.1, 4.4 and 5.1 (p<0.001) and 1.4, 2.8, 1.8 and 1.9 (p>0.05), respectively.\n Inappropriate prescribing patterns of antibiotics in health centers of Khartoum State, Sudan, are alarmingly high. Multifaceted interventions involving audit and feedback combined with either academic detailing or seminars appear more effective in changing prescribing practices of antibiotics than audit and feedback alone.", "Interventions designed to narrow the gap between research findings and clinical practice may be effective, but also costly. Economic evaluations are necessary to judge whether such interventions are worth the effort. We have evaluated the economic effects of a tailored intervention to support the implementation of guidelines for the use of antihypertensive and cholesterol-lowering drugs. The tailored intervention was evaluated in a randomized trial, and was shown to significantly increase the use of thiazides for patients started on antihypertensive medication, but had little or no impact on other outcomes. The increased use of thiazides was not expected to have an impact on health outcomes.\n We performed cost-minimization and cost-effectiveness analyses on data from a randomized trial involving 146 general practices from two geographical areas in Norway. Each practice was randomized to either the tailored intervention (70 practices; 257 physicians) or control group (69 practices; 244 physicians). Only patients that were being started on antihypertensive medication were included in the analyses. A multifaceted intervention was tailored to address identified barriers to change. Key components were an educational outreach visit with audit and feedback, and computerized reminders. Pharmacists conducted the visits. A cost-minimization framework was adopted, where the costs of intervention were set against the reduced treatment costs (principally due to increased use of thiazides rather than more expensive medication). The cost-effectiveness of the intervention was estimated as the cost per additional patient being started on thiazides. The net annual cost (cost minimization) in our study population was 53,395 US dollars, corresponding to 763 US dollars per practice. The cost per additional patient started on thiazides (cost-effectiveness) was 454 US dollars. The net annual savings in a national program was modeled to be 761,998 US dollars, or 540 US dollars per practice after 2 y. In this scenario the savings exceeded the costs in all but two of the sensitivity analyses we conducted, and the cost-effectiveness was estimated to be 183 US dollars.\n We found a significant shift in prescribing of antihypertensive drugs towards the use of thiazides in our trial. A major reason to promote the use of thiazides is their lower price compared to other drugs. The cost of the intervention was more than twice the savings within the time frame of our study. However, we predict modest savings over a 2-y period.", "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." ]	No single treatment was found to be effective and therefore the results remain inconclusive in regard to the best systemic intervention for RAS. This is likely to reflect the poor methodological rigour of trials, and lack of studies for certain drugs, rather than the true effect of the intervention. It is also recognised that in clinical practice, individual drugs appear to work for individual patients and so the interventions are likely to be complex in nature. In addition, it is acknowledged that systemic interventions are often reserved for those patients who have been unresponsive to topical treatments, and therefore may represent a select group of patients.
CD004974	[ "10929921", "11399700", "21255253", "8414777", "21464382", "19434268", "17687129", "12475845", "18179756", "12578443", "11980553", "10195971", "17207457", "22054336", "3805711", "15930204", "12677565", "19549342", "1549149", "15604156", "11843924", "16176400", "15801580", "12612363", "15684116", "18831749", "20181120", "19108951", "19099594", "14498765", "11593439", "15482502", "18580613", "8436464", "20008423", "16923370", "7489431", "11930093", "11157606", "12499347", "11470387", "20491709" ]	[ "Primary prevention of acute respiratory tract infections in children using a bacterial immunostimulant: a double-masked, placebo-controlled clinical trial.", "Safety and efficacy of two courses of OM-85 BV in the prevention of respiratory tract infections in children during 12 months.", "A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study).", "Stimulation of nonspecific immunity to reduce the risk of recurrent infections in children attending day-care centers. The Epicrèche Research Group.", "A randomized controlled trial of home injury hazard reduction: the HOME injury study.", "Management for the children with otitis media with effusion in the tertiary hospital.", "Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia.", "Immunostimulation with OM-85 in children with recurrent infections of the upper respiratory tract: a double-blind, placebo-controlled multicenter study.", "Intranasal flunisolide treatment in children with adenoidal hypertrophy.", "Prevention of otitis media by adenoidectomy in children younger than 2 years.", "Abstracts of randomized controlled trials presented at the society for pediatric research meeting: an example of publication bias.", "Preventing injuries in children: cluster randomised controlled trial in primary care.", "Evaluation of exposure with response-prevention for obsessive compulsive disorder in childhood and adolescence.", "Enhancing ventilation in homes of children with asthma: pragmatic randomised controlled trial.", "Bacterial lysate (I.R.S. 19) applied intranasally in the prevention of acute respiratory diseases in children: a randomized double-blind study.", "Nonsevere acute otitis media: a clinical trial comparing outcomes of watchful waiting versus immediate antibiotic treatment.", "Randomized controlled trials in pediatric surgery: could we do better?", "Medication diaries do not improve outcomes with highly active antiretroviral therapy in Kenyan children: a randomized clinical trial.", "Methotrexate in resistant juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and The Cooperative Children's Study Group.", "Providing child safety equipment to prevent injuries: randomised controlled trial.", "A prospective, single-blind, randomized controlled trial of antiseptic cream for recurrent epistaxis in childhood.", "Three-year follow-up of clinical and inflammation parameters in children monosensitized to mites undergoing sub-lingual immunotherapy.", "Behavioral counseling for reducing children's ETS exposure: implementation in community clinics.", "Can parents who smoke socialise their children against smoking? Results from the Smoke-free Kids intervention trial.", "A randomized, double-blind, placebo-controlled noninferiority trial of amoxicillin for clinically diagnosed acute otitis media in children 6 months to 5 years of age.", "Echinacea purpurea and osteopathic manipulative treatment in children with recurrent otitis media: a randomized controlled trial.", "Effectiveness of a single-session early psychological intervention for children after road traffic accidents: a randomised controlled trial.", "Evaluating the effectiveness of exposure and acceptance strategies to improve functioning and quality of life in longstanding pediatric pain--a randomized controlled trial.", "A randomized trial on effectiveness of artemether-lumefantrine versus artesunate plus amodiaquine for unsupervised treatment of uncomplicated Plasmodium falciparum malaria in Ghanaian children.", "Ribosomal immunostimulation: assessment of studies evaluating its clinical relevance in the prevention of upper and lower respiratory tract infections in children and adults.", "Evaluation of an inter-organizational prevention program against injuries among the elderly in a WHO Safe Community.", "A new social communication intervention for children with autism: pilot randomised controlled treatment study suggesting effectiveness.", "Early virological suppression with three-class antiretroviral therapy in HIV-infected African infants.", "Prophylaxis for recurrent acute otitis media: a Brazilian study.", "Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: a noninferiority trial.", "[Interventions to prevent accidental injuries in children between 7 and 13 years of age].", "Anticholinergic prophylaxis does not prevent emesis following strabismus surgery in children.", "Treatment of childhood encopresis: a randomized trial comparing three treatment protocols.", "4A randomized trial of prolonged prone positioning in children with acute respiratory failure.", "Iron supplementation improves iron status and reduces morbidity in children with or without upper respiratory tract infections: a randomized controlled study in Colombo, Sri Lanka.", "Generalizability of trial results based on randomized versus nonrandomized allocation of OME infants to ventilation tubes or watchful waiting.", "EPA supplementation improves teacher-rated behaviour and oppositional symptoms in children with ADHD." ]	[ "Acute respiratory tract infections (ARTIs) are among the main causes of morbidity and mortality in children. The bacterial extract OM-85 BV has shown some protective effect for ARTIs in preschool children and a reduction in exacerbations of chronic bronchitis in adults.\n This trial reports results of a double-masked, placebo-controlled, parallel-group clinical study that assessed the efficacy and tolerability of OM-85 BV in the prevention of ARTIs in school girls living in an orphanage.\n Two hundred girls (age range, 6 to 13 years) living in an orphanage entered the trial. Participants were randomly allocated to receive either OM-85 BV or placebo for 10 consecutive days a month for 3 consecutive months. Patients were followed up for 6 months, including the administration period. The trial began in September 1996 and finished in March 1997. Primary end points were the type and number of infections. Secondary end points included when an infection occurred, time to clinical cure, severity of infection, absenteeism from school due to an ARTI, number of antibiotics or other drugs prescribed, and duration of concomitant drug treatment.\n During the trial, patients in the OM-85 BV group experienced 143 ARTIs (135 upper ARTIs and 8 otitis episodes) and patients in the placebo group experienced 299 ARTIs (273 upper ARTIs, 1 lower ARTI, and 25 otitis episodes). The median number of ARTIs was 1.0 (0.0, 3.0; 5th percentile, 95th percentile) in the OM-85 BV group compared with 3.0 (2.0, 4.0; 5th percentile, 95th percentile) in the placebo group. This difference was statistically significant (P < 0.001). Participants who received OM-85 BV also showed significantly better results (P < 0.001) than participants who received placebo in terms of median duration of illness, median number of missed school days due to an ARTI, median number of antibiotic and drug courses, and median duration of concomitant treatment. There were significant differences (P < 0.05) in severity of ARTIs during month 4 of the trial, with patients receiving OM-85 BV showing less severe ARTIs than patients receiving placebo and shorter mean time to clinical cure from the second month to the fourth month. No adverse events related to the trial medications were reported. Conclusions: OM-85 BV had a preventive effect on ARTIs in the school girls, with a reduction in the antibiotic requirements and the duration of ARTIs. Future studies are needed to further explore the role of OM-85 BV in the prevention of ARTIs.", "Acute respiratory tract infections (ARTIs) are among the main causes of morbidity and mortality in children. The bacterial extract OM-85 BV (bronchovaxom) has shown protective effect for ARTIs on children. We report a double-blind, placebo-controlled, parallel, prospective clinical trial to assess the safety and efficacy of two courses of OM-85 BV in the prevention of ARTIs in susceptible children during 12 months.\n Fifty-four susceptible children from 1 to 12 years of age living in the metropolitan area of Chihuahua City were selected. They were randomized to receive either OM-85 BV or placebo (one capsule a day for 10 days a month for 3 consecutive months) at the beginning of the trial and 6 months later with the same schedule. Patients were followed up for 12 months, including the administration period. The trial began in July 1997 and ended in April 1999.\n The number (mean +/- SD) of ARTIs was 5.04 +/- 1.99 (median, 5.0) in the OM-85 BV group vs 8.0 +/- 2.55 (median, 8.0) in the placebo group, with a mean difference of - 2.96 (95% confidence interval [CI], - 4.22 to - 1.7). The number of antibiotic courses was 2.46 +/- 2.08 (median, 1.5) in the treatment group vs 4.46 +/- 2.08 (median, 4.0) in the control group, a difference of - 2.0 (95% CI, - 3.14 to - 0.86). The total duration of ARTIs was 35.23 +/- 17.64 days (median, 30.5 days) in the OM-85 BV group vs 60.75 +/- 25.44 days (median, 55.0 days) in the placebo group, ie, a difference of - 25.52 days (95% CI, - 37.56 to - 13.47 days), p < 0.001 by Student's t test and Mann-Whitney U test for all the items. Four patients in the OM-85 BV group had five adverse events. Only one episode of skin rash was related to the medication intake. Six patients in the control group had six adverse events.\n OM-85 BV had a preventive effect on ARTI in the susceptible children for 12 months with an important reduction on the antibiotic requirements and the number of days of suffering ARTIs.", "Prevention of arthropathy is a major goal of hemophilia treatment. While studies in adults have demonstrated an impact of prophylaxis on the incidence of joint bleeds and patients' well-being in terms of improved quality of life (QoL), it is unclear whether or not prophylaxis influences the outcome and perception of well- of children with hemophilia.\n This randomized controlled study compared the efficacy of prophylaxis with episodic therapy in preventing hemarthroses and image-proven joint damage in children with severe hemophilia A (factor VIII <1%) over a 10-year time period.\n Forty-five children with severe hemophilia A, aged 1-7 years (median 4), with negative clinical-radiologic joint score at entry and at least one bleed during the previous 6 months, were consecutively randomized to prophylaxis with recombinant factor VIII (25 IU kg(-1) 3 × week) or episodic therapy with ≥25 IU kg(-1) every 12-24 h until complete clinical bleeding resolution. Safety, feasibility, direct costs and QoL were also evaluated.\n Twenty-one children were assigned to prophylaxis, 19 to episodic treatment. Children on prophylaxis had fewer hemarthroses than children on episodic therapy: 0.20 vs. 0.52 events per patient per month (P < 0.02). Plain-film radiology showed signs of arthropathy in six patients on prophylaxis (29%) vs. 14 on episodic treatment (74%) (P < 0.05). Prophylaxis was more effective when started early (≤36 months), with patients having fewer joint bleeds (0.12 joint bleeds per patient per month) and no radiologic signs of arthropathy.\n This randomized trial confirms the efficacy of prophylaxis in preventing bleeds and arthropathy in children with hemophilia, particularly when it is initiated early in life.\n © 2011 International Society on Thrombosis and Haemostasis.", "A randomized, double blind, placebo-controlled clinical trial was performed in 423 children attending day-care centers to assess whether stimulating nonspecific immunity would reduce the incidence of recurrent infections. The drug used for the trial (Imocur) is an extract obtained from eight different species of bacteria. At the end of the total follow-up period (3 months with treatment and 4.5 months without), the risk for > or = 4 episodes of upper respiratory infections was not significantly lower in the treated group than in the placebo group (26.7% vs. 33.8%, relative risk, 0.79; 95% confidence interval, 0.59 to 1.06). In an exploratory analysis limited to the 3-month treatment period, however, we observed a 48% reduction in the risk of presenting > or = 3 episodes of upper respiratory infections: 9.5% vs. 18.3%, respectively, in the treatment group and the placebo group (relative risk, 0.52; 95% confidence interval, 0.31 to 0.86). Similar results were found for the risk of > or = 1 episode of gastroenteritis. We also observed a strong correlation between the drug efficacy and age; this observation is coherent with the underlying pathophysiologic model in which the immune system matures with age.", "To test the efficacy of installing safety devices in the homes of young children on total injury rates and on injuries deemed a priori modifiable by the installation of these devices.\n A nested, prospective, randomized controlled trial.\n Indoor environment of housing units.\n Mothers and their children from birth to 3 years old participating in the Home Observation and Measures of the Environment study. Among 8878 prenatal patients, 1263 (14.2%) were eligible, 413 (32.7%) agreed to participate, and 355 were randomly assigned to the intervention (n = 181) or control (n = 174) groups.\n Installation of multiple passive measures (eg, stair gates, cabinet locks, and smoke detectors) to reduce exposure to injury hazards. Injury hazards were assessed at home visits by teams of trained research assistants using a validated survey.\n Modifiable and medically attended injury (ie, telephone calls, office visits, and emergency visits for injury).\n The mean age of children at intervention was 6.3 months. Injury hazards were reduced in the intervention homes but not in the control homes at 1 and 2 years (P < .004). There was no difference in the rate for all medically attended injuries in intervention children compared with controls: 14.3 injuries (95% confidence interval [CI], 9.7-21.1 injuries) vs 20.8 injuries (95% CI, 14.4-29.9 injuries) per 100 child-years (P = .17); but there was a significant reduction in the rate of modifiable medically attended injuries in intervention children compared with controls: 2.3 injuries (95% CI, 1.0-5.5 injuries) vs 7.7 injuries (95% CI, 4.2-14.2 injuries) per 100 child-years (P = .03).\n An intervention to reduce exposure to hazards in homes led to a 70% reduction in the rate of modifiable medically attended injury.\n clinicaltrials.gov Identifier: NCT00129324.", "Recently, new evidence-based recommendations have been introduced for diagnosing and managing otitis media with effusion (OME) in children. However, there are some difficulties to follow the general guidelines in the tertiary hospitals. The purpose is to evaluate the efficiency of antibiotics or antihistamines for treatment of children with OME in the tertiary hospital with a randomized prospective clinical study.\n Eighty-four children with OME who had been diagnosed in the tertiary hospital were randomized to receive 5 different medications for 2 weeks. We prescribed antibiotics (amoxicillin-clavulanate syrup) in Group I (n=16), antibiotics/steroids (prednisolone) in Group II (n=18), antibiotics/antihistamines (ebastine) in Group III (n=15), antibiotics/steroids/antihistamines in Group IV (n=17), and mucolytics (ivy leaf extract) in Group V (n=17) for control. We followed-up children every 2 weeks and evaluated the state of OME at 3 months.\n Thirty six (42.9%) of 84 children were resolved within average 6.9 weeks after the treatments. Thirty-six (42.9%) were treated with ventilation tube insertion and 12 patients (14.3%) were observed. There was no difference in the resolution rates of OME among the five different protocols (P>0.05). There was no difference in the resolution rates among groups who used steroids, antihistamines, steroids and antihistamines, or other medications to manage 42 children with allergies (P>0.05).\n In the tertiary hospital, the cure rate of children with OME was not as high as well-known, and antibiotics or anti-allergic medications were not more effective than control. We may, therefore, need any other guidelines which are different from the previous evidence-based recommendations, including early operation in the tertiary hospitals.", "Effective ways to prevent arthropathy in severe hemophilia are unknown.\n We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to an enhanced episodic infusion schedule of at least three doses totaling a minimum of 80 IU of factor VIII per kilogram of body weight at the time of a joint hemorrhage. The primary outcome was the incidence of bone or cartilage damage as detected in index joints (ankles, knees, and elbows) by radiography or magnetic resonance imaging (MRI).\n Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P=0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups.\n Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597 [ClinicalTrials.gov].).\n Copyright 2007 Massachusetts Medical Society.", "Recurrent upper respiratory tract infections (URTIs) are common illnesses in young children. As the immunoactive bacterial extract OM-85 has been shown to prevent these infections in both adults and children, the aim of the present trial was to investigate further its efficacy and safety in infection-prone children.\n This is a randomized, double-blind, placebo-controlled, multicenter study with OM-85 in 232 patients aged 36 to 96 months with recurrent URTIs. Treatment was one capsule daily during month 1 and during 10 days in months 3 to 5. URTI was defined by the presence of at least two of the following: rhinitis, pharyngitis, cough, hoarseness, temperature > or = 38.5 degrees C, or URTI-related prescription of an antibiotic.\n OM-85-treated patients had a lower rate of URTIs (p < 0.05). The cumulated difference in URTIs between the two groups reached - 0.40 URTIs per patient in 6 months, corresponding to a 16% reduction in the active-treatment group with respect to placebo. The largest difference was observed in the patients having had three or more URTIs during the study period; odds ratios for three or more URTIs were 0.51 (95% confidence interval, 0.29 to 0.91) and 0.65 (95% confidence interval, 0.37 to 1.11) after 5 months and 6 months, respectively. The difference between OM-85 and placebo was independent of age but was more important in patients reporting a larger number of URTIs in the previous year. Patients' global assessment showed improvement in comparison to the previous season in the majority of the cases (OM-85, 78.4% of cases; placebo, 75.5%); however, there were more cases reporting worsening with placebo (6.4% vs 0.9%; p = 0.05).\n OM-85 treatment significantly reduced the rate of URTIs, particularly in children with a history of frequent URTIs. Safety and tolerance of test medication were good, comparable to placebo.", "Adenoidal hypertrophy (AH) represents one of the most frequent indications for surgery in children and it has been proposed that treatment with intranasal corticosteroids can decrease the size of AH. Therefore, the aim of the study is to evaluate the effect of the use of intranasal flunisolide among children affected by AH. 178 children with AH were evaluated in this randomised and controlled study. Inclusion criteria for the study required that each patient had to have a III or IV degree of AH on the initial endoscopic examination. Children were treated with intranasal flunisolide or isotonic saline solution for 8 weeks. After treatment, endoscopy was performed to re-evaluate AH degree. Flunisolide treatment was associated with significant (p less than 0.04) reduction of AH degree. There was moreover a consistent reduction of children (46 out of 58) proposed to adenoidectomy. No clinically important adverse events were reported. In conclusion, this preliminary study demonstrates that an 8-week treatment with intranasal flunisolide is significantly associated with reduction of AH, thus preventing the recurrence to adenoidectomy, and is safe.", "To test the effect of adenoidectomy in connection with tympanostomy compared with tympanostomy only in preventing otitis media in children younger than 2 years.\n Prospective trial with randomized and nonrandomized arms.\n Primary care study clinics.\n The study participants were selected from 2497 children who had been enrolled in the Finnish Otitis Media Vaccine Trial at the age of 2 months. A total of 306 children, aged 1 to 2 years, who had experienced recurrent episodes of otitis media were randomized into 2 treatment groups: tympanostomy with or without adenoidectomy. Of the 306 children, 137 were operated on according to random basis (randomized trial). The 169 children whose parents declined participation in the randomized trial were operated on according to the parents' preferences (nonrandomized trial). All children were followed up until 2 years of age. The mean follow-up time was 7 months.\n The rate of acute otitis media episodes.\n The average reduction in the rate of all acute otitis media episodes in the adenoidectomy group was 19% (95% confidence interval [CI], -14% to 43%) among children enrolled in the randomized trial and 25% (95% CI, -13% to 50%) in the nonrandomized trial. The reduction in the randomized trial was mainly due to reduction in the rate of pneumococcal otitis media (58%, 95% CI, 16%-79%).\n In children younger than 2 years, concurrent adenoidectomy during the insertion of tympanostomy tubes does not seem to have a major advantage over the insertion of tympanostomy tubes alone in preventing otitis media.", "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.", "To assess the effectiveness of safety advice at child health surveillance consultations, provision of low cost safety equipment to families receiving means tested state benefits, home safety checks, and first aid training on frequency and severity of unintentional injuries in children at home.\n Cluster randomised controlled trial.\n 36 general practices in Nottingham.\n All children aged 3-12 months registered with participating practices.\n A package of safety advice at child health surveillance consultations at 6-9, 12-15, and 18-24 months; provision of low cost safety equipment to families on means tested state benefits; and home safety checks and first aid training by health visitors.\n Primary outcomes measures were frequency and severity of medically attended injuries. Secondary outcome measures were self reported safety practices, possession and use of safety equipment, knowledge and confidence in dealing with first aid, and perceptions of risk of injury and risk of hazards assessed by postal questionnaire at baseline and follow up at 25 months.\n At baseline, both groups had similar risk factors for injury, sociodemographic characteristics, safety practices, possession and use of safety equipment, knowledge and confidence in dealing with first aid, and perceptions of risk. No significant difference was found in frequency of at least one medically attended injury (odds ratio 0.97, 95% confidence interval 0.72 to 1.30), at least one attendance at an accident and emergency department for injury (1.02, 0.76 to 1.37), at least one primary care attendance for injury (0.75, 0.48 to 1.17), or at least one hospital admission for injury (0.69, 0.42 to 1.12). No significant difference in the secondary outcome measures was found between the intervention and control groups.\n The intervention package was not effective in reducing the frequency of minor unintentional injuries in children at home, and larger trials are required to assess the effect on more severe injuries.", "The present study was undertaken to estimate the effect of exposure plus response-prevention (E/RP), delivered alone intensively over 5-weeks and without concomitant pharmacotherapy, for children and adolescents with OCD. Twenty children and adolescents with OCD, not receiving medication for this condition, were randomized to E/RP or a wait-list condition. Statistically and clinically significant symptomatic improvement was found in the E/RP group compared with controls, with improvement maintained at follow-up an average of 14 weeks later. Effect size in the main intention-to-treat analysis was 1.23 and in the secondary per protocol analysis was 1.64. This study lends further support to the view that E/RP is an effective treatment for childhood OCD.", "Few robust studies have tested whether enhancing housing also improves health.\n To evaluate the effectiveness of installing ventilation systems, and central heating where necessary, in the homes of children with moderate or severe asthma.\n Pragmatic randomised controlled trial (RCT) in homes within Wrexham County Borough, Wales, UK.\n A pragmatic RCT was carried out, of a tailored package of housing improvements providing adequate ventilation and temperature, following inspection by a housing officer. One hundred and ninety-two children with asthma aged 5 to 14 years, identified from general practice registers, were randomised to receive this package, either immediately or a year after recruitment. At baseline, and after 4 and 12 months, parents reported their child's asthma-specific and generic quality of life, and days off school.\n The package improved parent-reported asthma-specific quality of life significantly at both 4 and 12 months. At 12 months, this showed an adjusted mean difference between groups of 7.1 points (95% confidence interval [CI] = 2.8 to 11.4, P= 0.001): a moderate standardised effect size of 0.42. The generic quality-of-life scale showed reported physical problems were significantly reduced at 4 months, but not quite at 12 months, when the mean difference was 4.5 (95% CI = -0.2 to 9.1, P= 0.061). The improvement in psychosocial quality of life at 12 months was not significant, with a mean difference of 2.2 (95% CI = -1.9 to 6.4, P= 0.292). Parent-reported school attendance improved, but not significantly.\n This novel and pragmatic trial, with integrated economic evaluation, found that tailored improvement of the housing of children with moderate to severe asthma significantly increases parent-reported asthma-related quality of life and reduces physical problems. Collaborative housing initiatives have potential to improve health.", "A controlled trial was undertaken to test I.R.S. 19 (a commercial intranasal spray) versus placebo in the prevention of acute respiratory diseases (ARD) in 825 maternity-school children in three cities; another control group of 327 children received neither I.R.S. 19 nor placebo. The spraying was done twice a day for a total of 20 spraying days in each child; sprayings were interrupted on weekends and during absence, the mean spraying period being 34 calendar days. During the 6-month study (1 November to 30 April) the children were monitored for ARD morbidity causing absence from school. A total of 1,585 such ARD cases occurred; their etiology was not investigated. The indices evaluated were: total duration of ARD-associated absence, ARD incidence, and mean duration of one illness. With the administration schedule used, I.R.S. 19 did not, in an overall evaluation, surpass placebo in any of these indices in either normal children or a subgroup of children with presumed enhanced ARD susceptibility.", "The widespread use of antibiotics for treatment of acute otitis media (AOM) has resulted in the emergence of multidrug-resistant pathogens that are difficult to treat. However, it has been shown that most children with nonsevere AOM recover without ABX. The objective of this study was to evaluate the safety, efficacy, acceptability, and costs of a non-ABX intervention for children with nonsevere AOM.\n Children 6 months to 12 years old with AOM were screened by using a novel AOM-severity screening index. Parents of children with nonsevere AOM received an educational intervention, and their children were randomized to receive either immediate antibiotics (ABX; amoxicillin plus symptom medication) or watchful waiting (WW; symptom medication only). The investigators, but not the parents, were blinded to enrollment status. Primary outcomes included parent satisfaction with AOM care, resolution of symptoms, AOM failure/recurrence, and nasopharyngeal carriage of Streptococcus pneumoniae strains resistant to ABX. Secondary outcomes included medication-related adverse events, serious adverse events, unanticipated AOM-related office and emergency department visits and telephone calls, the child's absence from day care or school resulting from AOM, the parent's absence from school or work because of their child's AOM, and costs of treatment. Subjects were defined as failing (days 0-12) or recurring (days 13-30) if they experienced a higher AOM-severity score on reexamination.\n A total of 223 subjects were recruited: 73% were nonwhite, 57% were <2 years old, 47% attended day care, 82% had experienced prior AOM, and 83% had not been fully immunized with heptavalent pneumococcal vaccine. One hundred twelve were randomized to ABX, and 111 were randomized to WW. Ninety-four percent of the subjects were followed to the 30-day end point. Parent satisfaction with AOM care was not different between the 2 treatment groups at either day 12 or 30. Compared with WW, symptom scores on days 1 to 10 resolved faster in subjects treated with immediate ABX. At day 12, among the immediate-ABX group, 69% of tympanic membranes and 25% of tympanograms were normal, compared with 51% of normal tympanic membranes and 10% of normal tympanograms in the WW group. Parents of children in the ABX group gave their children fewer doses of pain medication than did parents of children in the WW group. Subjects in the ABX group experienced 16% fewer failures than subjects in the WW group. Of the children in the WW group, 66% completed the study without needing ABX. Immediate ABX resulted in eradication of S pneumoniae carriage in the majority of children, but S pneumoniae strains cultured from children in the ABX group at day 12 were more likely to be multidrug-resistant than strains from children in the WW group. More ABX-related adverse events were noted in the ABX group, compared with the WW group. No serious AOM-related adverse events were observed in either group. Office and emergency department visits, phone calls, and days of work/school missed were not different between groups. Prescriptions for ABX were reduced by 73% in the WW group compared with the ABX group. Costs of ABX averaged $47.41 per subject in the ABX group and $11.43 in the WW group.\n Sixty-six percent of subjects in the WW group completed the study without ABX. Parent satisfaction was the same between groups regardless of treatment. Compared with WW, immediate ABX treatment was associated with decreased numbers of treatment failures and improved symptom control but increased ABX-related adverse events and a higher percent carriage of multidrug-resistant S pneumoniae strains in the nasopharynx at the day-12 visit. Key factors in implementing a WW strategy were (a) a method to classify AOM severity; (b) parent education; (c) management of AOM symptoms; (d) access to follow-up care; and (e) use of an effective ABX regimen, when needed. When these caveats are observed, WW may be an acceptable alternative to immediate ABX for some children with nonsevere AOM.", "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.", "As highly active antiretroviral therapy (HAART) becomes increasingly available to African children, it is important to evaluate simple and feasible methods of improving adherence in order to maximize benefits of therapy.\n HIV-1-infected children initiating World Health Organization non-nucleoside reverse transcriptase-inhibitor-containing first-line HAART regimens were randomized to use medication diaries plus counselling, or counselling only (the control arm of the study). The diaries were completed daily by caregivers of children randomized to the diary and counselling arm for nine months. HIV-1 RNA, CD4+ T cell count, and z-scores for weight-for-age, height-for-age and weight-for-height were measured at a baseline and every three to six months. Self-reported adherence was assessed by questionnaires for nine months.\n Ninety HIV-1-infected children initiated HAART, and were followed for a median of 15 months (interquartile range: 2-21). Mean CD4 percentage was 17.2% in the diary arm versus 16.3% in the control arm at six months (p = 0.92), and 17.6% versus 18.9% at 15 months (p = 0.36). Virologic response with HIV-1 RNA of <100 copies/ml at nine months was similar between the two arms (50% for the diary arm and 36% for the control, p = 0.83). The weight-for-age, height-for-age and weight-for-height at three, nine and 15 months after HAART initiation were similar between arms. A trend towards lower self-reported adherence was observed in the diary versus the control arm (85% versus 92%, p = 0.08).\n Medication diaries did not improve clinical and virologic response to HAART over a 15-month period. Children had good adherence and clinical response without additional interventions. This suggests that paediatric HAART with conventional counselling can be a successful approach. Further studies on targeted approaches for non-adherent children will be important.", "The antimetabolite methotrexate has been shown in placebo-controlled trials to be effective in adults with rheumatoid arthritis. Methotrexate may also be effective in children with resistant juvenile rheumatoid arthritis, but the supporting data are from uncontrolled trials.\n Centers in the United States and the Soviet Union participated in this randomized, controlled, double-blind trial designed to evaluate the effectiveness and safety of orally administered methotrexate. Patients received one of the following treatments each week for six months: 10 mg of methotrexate per square meter of body-surface area (low dose), 5 mg of methotrexate per square meter (very low dose), or placebo. The use of prednisone (less than or equal to 10 mg per day) and two nonsteroidal antiinflammatory drugs was also allowed.\n The 127 children (mean age, 10.1 years) had a mean duration of disease of 5.1 years; 114 qualified for the analysis of efficacy. According to a composite index of several response variables, 63 percent of the children who received low-dose methotrexate improved, as compared with 32 percent of those in the very-low-dose group and 36 percent of those in the placebo group (P = 0.013). As compared with the placebo group, the low-dose group also had significantly larger mean reductions from base line in the number of joints with pain on motion (-11.0 vs. -7.1), the pain-severity score (-19 vs. -11.5), the number of joints with limited motion (-5.4 vs. -0.7), and the erythrocyte sedimentation rate (-19.0 vs. -6 mm per hour). In the methotrexate groups only three children had the drug discontinued because of mild-to-moderate side effects; none had severe toxicity.\n Methotrexate given weekly in low doses is an effective treatment for children with resistant juvenile rheumatoid arthritis, and at least in the short term this regimen is safe.", "To assess the effectiveness of safety advice and safety equipment in reducing unintentional injuries for families with children aged under 5 years and living in deprived areas.\n Randomised controlled trial.\n 47 general practices in Nottingham.\n 3428 families with children under 5.\n A standardised safety consultation and provision of free and fitted stair gates, fire guards, smoke alarms, cupboard locks, and window locks.\n Primary outcome measures were whether a child in the family had at least one injury that required medical attendance and rates of attendance in primary and secondary care and of hospital admission for injury over a two year period. Secondary outcome measures included possession of safety equipment and safety practices.\n No significant difference was found in the proportion of families in which a child had a medically attended injury (odds ratio 1.14, 95% confidence interval 0.98 to 1.50) or in the rates of attendance in secondary care (incidence rate ratio 1.02, 0.90 to 1.13) or admission to hospital (1.02, 0.70 to 1.48). However, children in the intervention arm had a significantly higher attendance rate for injuries in primary care (1.37, 1.11 to 1.70, P = 0.003). At both one and two years' follow up, families in the intervention arm were significantly more likely to have a range of safety practices, but absolute differences in the percentages were relatively small.\n The intervention resulted in significant improvements in safety practices for up to two years but did not reduce injuries that necessitated medical attendance. Although equipment was provided and fitted free of charge, the observed changes in safety practices may not have been large enough to affect injury rates.", "Epistaxis is common in children. Trials show antiseptic cream is as effective as cautery, but it is not known whether either is better than no treatment. We wished to know the efficacy of cream in children with recurrent epistaxis. The design was a single-blind, prospective, randomized controlled trial set in the Otolaryngology clinic in a children's hospital. The participants were 103 children referred by their general practitioner for recurrent epistaxis. Excluded were those with suspected tumours, bleeding disorders or allergies to constituents of the cream. Referral letters were randomized to treatment and no treatment groups. Treatment was antiseptic cream to the nose twice daily for 4 weeks, which was prescribed by the general practitioner before clinic attendance. All children were given an appointment for 8 weeks after randomization. The main outcome measures were the proportion of children in each group with no epistaxis in the 4 weeks preceding clinic review. Complete data were available for 88 (85%) of the children. Of the treatment group, 26/47 (55%) had no epistaxis in the 4 weeks before the clinic appointment. Of the controls, 12/41 (29%) had no epistaxis over the 4 weeks. This is a relative risk reduction of 47% for persistent bleeding (95% CI 9-69%) and an absolute risk reduction of 26% (95% CI 12-40%), giving a number needed to treat of 3.8 (95% CI 2.5-8.5). We conclude that antiseptic cream is an effective treatment for recurrent epistaxis in children.", "Parallel follow-up of clinical and inflammatory markers during sub-lingual immunotherapy (SLIT) is highly beneficial. Twenty-four children (age 4-16) monosensitized to house dust mite were randomized to receive either active or placebo SLIT for 1 yr in a double-blind placebo controlled design (Marcucci et al., Allergy 2003: 58: 657-62). Thereafter, for 2 yr they all received active treatment. Symptom scores for rhinitis, asthma, and drug usage were daily recorded. Eosinophil cationic protein (ECP) and tryptase in sputum and nasal secretions, serum and nasal mite-specific immunoglobulin E (IgE) were recorded before treatment and at 10-12 months intervals. Nasal ECP and nasal tryptase after specific nasal provocation tests were significantly reduced as compared to baseline values (p = 0.0043 and 0.0195, respectively) in the third year of active treatment. None of the other inflammatory parameters was increased. In placebo treated patients all these parameters tended to decrease only after switching to active treatment. Clinical scores did not improve in treated vs. placebo patients in the double-blind placebo-controlled phase of the study. In both cohorts a clinical benefit was observed as intra-group score reduction as compared to baseline. A significant difference was reached in patients treated for 2 yr for rhinitis and asthma (p = 0.0009 and 0.0019, respectively) but not for drug usage and in patients treated for 3 yr for rhinitis, asthma, and drug usage (p = 0.0105, 0.0048, and 0.02, respectively). SLIT in children monosensitized to mites reverted the spontaneous increase in nasal IgE and in local parameters of allergic inflammation. These outcomes were followed by a consolidated clinical improvement in the second and third year of treatment.", "The present randomized controlled trial tested the effectiveness of a behavioral counseling program for reducing children's exposure to environmental tobacco smoke (ETS). Counseling was delivered by clinic staff as part of well-child health care services in a community clinic setting. A total of 150 mothers with children aged 4 years or younger were recruited. Parent-reported and children's urinary cotinine measures of ETS exposure were obtained at baseline, 3 months, 6 months (post-test), and 12 months (follow-up). Saliva samples were obtained from mothers who reported quitting smoking, for objective verification by thiocyanate analysis. After baseline, mothers were randomly assigned to a measures-only control condition or an intervention consisting of seven behavioral counseling sessions over 6 months. Counseling included behavioral contracting, self-monitoring, problem solving, and positive reinforcement. Results indicated acceptable test-retest reliability and validity of measures. Parent-reported measures indicated that, in both groups, children's exposure to their mothers' tobacco smoke in the home and to all tobacco smoke declined steeply from baseline to 6 months post-test, and remained essentially level during follow-up. Mothers' smoking rates followed the same pattern. Children's urinary cotinine concentrations did not show significant change over time in either group. Findings on the fidelity of treatment implementation suggest that the structure and funding of the community clinic health care system and associated staff turnover and training issues resulted in participants receiving a less efficacious intervention than in our past efficacy trials. Implications for future effectiveness trials are discussed.", "To evaluate Smoke-free Kids, a new home based programme to assist parents who smoke in socializing their children against smoking.\n Two year randomised controlled trial.\n At baseline, 887 adult smokers who had an abstinent child in the third grade (ages 7-8 years); 671 adults and children were retained through the 24 month follow up.\n Programme modules, newsletters, incentives, support calls.\n Anti-smoking socialisation; susceptibility to smoking.\n Of 327 parents randomised to treatment, 210 obtained adequate treatment by using at least three of five core modules. Programme efficacy analyses, which compared these parents with controls (n = 344), showed that exposure to adequate treatment predicted significantly higher levels in nearly all categories of anti-smoking socialisation three months post-intervention. Two years post-baseline, children of parents who reported adequate treatment scored significantly higher than controls on attributes that reduce susceptibility to smoking, and they scored significantly lower than controls on attributes that raise susceptibility to smoking. Programme effectiveness analyses compared all parents randomised to treatment (n = 327) with controls (n = 344). Treatment effects were evident for several socialisation outcomes; however, these effects were smaller and less consistent than those from the efficacy analyses. Similarly, although treated children scored higher than controls on attributes that reduce susceptibility and lower than controls on attributes that raise susceptibility, several of these between-group differences were not significant.\n Given adequate exposure to the Smoke-free Kids programme, significant beneficial effects were observed on anti-smoking socialisation in households where parents smoke cigarettes, and significant beneficial effects were observed on children's susceptibility to smoking after two years. Improving programme acceptance and utilisation is necessary before programme effectiveness can be demonstrated.", "Debate continues with respect to a \"watch and wait\" approach versus immediate antibiotic treatment for the initial treatment of acute otitis media. In this double-blind noninferiority trial, we compared clinical improvement rates at 14 days for children (6 months to 5 years of age) with acute otitis media who were randomly assigned to receive amoxicillin or placebo.\n We enrolled healthy children who presented to clinics or the emergency department with a new episode of acute otitis media during the fall and winter months in Ottawa (from December 1999 to the end of March 2002). The children were randomly assigned to receive amoxicillin (60 mg/kg daily) or placebo for 10 days. Telephone follow-up was performed on each of days 1, 2 and 3 and once between day 10 and day 14. The primary outcome was clinical resolution of symptoms, defined as absence of receipt of an antimicrobial (other than the amoxicillin in the treatment group) at any time during the 14-day period. Secondary outcomes were the presence of pain and fever and the activity level in the first 3 days, recurrence rates, and the presence of middle ear effusion at 1 and 3 months.\n According to clinical scoring, 415 of the 512 children who could be evaluated had moderate disease. At 14 days 84.2% of the children receiving placebo and 92.8% of those receiving amoxicillin had clinical resolution of symptoms (absolute difference -8.6%, 95% confidence interval -14.4% to -3.0%). Children who received placebo had more pain and fever in the first 2 days. There were no statistical differences in adverse events between the 2 groups, nor were there any significant differences in recurrence rates or middle ear effusion at 1 and 3 months.\n Our results did not support the hypothesis that placebo was noninferior to amoxicillin (i.e., that the 14-day cure rates among children with clinically diagnosed acute otitis media would not be substantially worse in the placebo group than the treatment group). Nevertheless, delaying treatment was associated with resolution of clinical signs and symptoms in most of the children.", "Recurrent otitis media is a common problem in young children. Echinacea and osteopathic manipulative treatment have been proposed as preventive measures, but have been inadequately studied. This study was designed to assess the efficacy of Echinacea purpurea and/or osteopathic manipulative treatment (OMT) for prevention of acute otitis media in otitis-prone children.\n A randomized, placebo-controlled, two-by-two factorial trial with 6-month follow-up, conducted 1999 - 2002 in Tucson, Arizona. Patients were aged 12-60 months with recurrent otitis media, defined as three or more separate episodes of acute otitis media within six months, or at least four episodes in one year. Ninety children (44% white non-Hispanic, 39% Hispanic, 57% male) were enrolled, of which 84 had follow-up for at least 3 months. Children were randomly assigned to one of four protocol groups: double placebo, echinacea plus sham OMT, true OMT (including cranial manipulation) plus placebo echinacea, or true echinacea plus OMT. An alcohol extract of Echinacea purpurea roots and seeds (or placebo) was administered for 10 days at the first sign of each common cold. Five OMT visits (or sham treatments) were offered over 3 months.\n No interaction was found between echinacea and OMT. Echinacea was associated with a borderline increased risk of having at least one episode of acute otitis media during 6-month follow-up compared to placebo (65% versus 41%; relative risk, 1.59, 95% CI 1.04, 2.42). OMT did not significantly affect risk compared to sham (44% versus 61%; relative risk, 0.72, 95% CI 0.48, 1.10).\n In otitis-prone young children, treating colds with this form of echinacea does not decrease the risk of acute otitis media, and may in fact increase risk. A regimen of up to five osteopathic manipulative treatments does not significantly decrease the risk of acute otitis media.\n ClinicalTrials.gov Identifier: NCT00010465.", "Road traffic accidents (RTAs) are the leading health threat to children in Europe, resulting in 355,000 injuries annually. Because children can suffer significant and long-term mental health problems following RTAs, there is considerable interest in the development of early psychological interventions. To date, the research in this field is scarce, and currently no evidence-based recommendations can be made.\n To evaluate the effectiveness of a single-session early psychological intervention, 99 children age 7-16 were randomly assigned to an intervention or control group. The manualised intervention was provided to the child and at least one parent around 10 days after the child's involvement in an RTA. It included reconstruction of the accident using drawings and accident-related toys, and psychoeducation. All of the children were interviewed at 10 days, 2 months and 6 months after the accident. Parents filled in questionnaires. Standardised instruments were used to assess acute stress disorder (ASD), posttraumatic stress disorder (PTSD), depressive symptoms and behavioural problems.\n The children of the two study groups showed no significant differences concerning posttraumatic symptoms and other outcome variables at 2 or at 6 months. Interestingly, analyses showed a significant intervention x age-group effect, indicating that for preadolescent children the intervention was effective in decreasing depressive symptoms and behavioural problems.\n This study is the first to show a beneficial effect of a single-session early psychological intervention after RTA in preadolescent children. Therefore, an age-specific approach in an early stage after RTAs may be a promising way for further research. Younger children can benefit from the intervention evaluated here. However, these results have to be interpreted with caution, because of small subgroup sizes. Future studies are needed to examine specific approaches for children and adolescents. Also, the intervention evaluated here needs to be studied in other groups of traumatised children.\n Clinical Trial Registry: ClinicalTrials.gov: NCT00296842.", "Although several studies have illustrated the effectiveness of cognitive behavior therapy (CBT) on adult pain patients, there are few randomized controlled trials on children and adolescents. There is particularly a need for studies on pediatric patients who are severely disabled by longstanding pain syndromes. Acceptance and Commitment Therapy, as an extension of traditional CBT, focuses on improving functioning and quality of life by increasing the patient's ability to act effectively in concordance with personal values also in the presence of pain and distress. Following a pilot study, we sought to evaluate the effectiveness of an ACT-oriented intervention based on exposure and acceptance strategies and to compare this with a multidisciplinary treatment approach including amitriptyline (n=32). The ACT condition underwent a relatively brief treatment protocol of approximately 10 weekly sessions. Assessments were made before and immediately after treatment, as well as at 3.5 and 6.5 months follow-up. Prolonged treatment in the MDT group complicated comparisons between groups at follow-up assessments. Results showed substantial and sustained improvements for the ACT group. When follow-up assessments were included, ACT performed significantly better than MDT on perceived functional ability in relation to pain, pain intensity and to pain-related discomfort (intent-to-treat analyses). At post-treatment, significant differences in favor of the ACT condition were also seen in fear of re/injury or kinesiophobia, pain interference and in quality of life. Thus, results from the present study support previous findings and suggest the effectiveness of this ACT-oriented intervention for pediatric longstanding pain syndromes.", "Numerous trials have demonstrated high efficacy and safety of artemisinin-based combination therapy (ACT) under supervised treatment. In contrast, effectiveness studies comparing different types of ACT applied unsupervised are scarce. The aim of this study was to compare effectiveness, tolerability and acceptance of artesunate plus amodiaquine (ASAQ) against that of artemether-lumefantrine (AL) in Ghanaian children with uncomplicated Plasmodium falciparum malaria.\n A randomized open-label trial was conducted at two district hospitals in the Ashanti region, Ghana, an area of intense malaria transmission. A total of 246 children under five years of age were randomly assigned to either ASAQ (Arsucam) or AL (Coartem). Study participants received their first weight-adjusted dose under supervision. After the parent/guardian was advised of times and mode of administration the respective three-day treatment course was completed unobserved at home. Follow-up visits were performed on days 3, 7, 14 and 28 to evaluate clinical and parasitological outcomes, adverse events, and haematological recovery. Length polymorphisms of variable regions of msp1 and msp2 were determined to differentiate recrudescences from reinfections. Acceptance levels of both treatment regimens were assessed by means of standardized interviews.\n Adequate clinical and parasitological responses after AL and ASAQ treatment were similar (88.3% and 91.7%, respectively). Interestingly, more late clinical failures until day 28 occurred in AL-treated children than in those who received ASAQ (17.5% and 7.3%, respectively; Hazard Ratio 2.41, 95% CI 1.00-5.79, p < 0.05).Haematological recovery and drug tolerability were not found to be significantly different in both study arms. The acceptance of treatment with ASAQ was higher than that with AL (rank-scores 10.6 and 10.3, respectively; p < 0.05).\n Unobserved AL and ASAQ treatment showed high adequate clinical and parasitological responses, though AL was inferior in preventing late clinical failures.", "To review the efficacy of the ribosomal immunostimulant Ribomunyl in preventing upper and lower respiratory tract infections.\n Review of studies of 3 and 6 months' duration comprising part of the international registration file.\n Data from 2117 patients (1215 children and 902 adults); ribosomal immunostimulant n = 1062, placebo n = 1055.\n Nineteen randomised, double-blind, placebo-controlled clinical trials were performed between 1983 and 1994 in Europe. In children with ear-nose-throat (ENT) infections, 3 months' ribosomal immunostimulant treatment significantly decreased the mean number of recurrences (27-68% reduction), and reduced the duration of infection (28-66% reduction) and antibacterial requirement (29-60% reduction). Ribosomal immunostimulant was similarly effective in children with ENT and bronchopulmonary infections, reducing the mean number of recurrences by 32-61% compared with placebo. In children with otitis media, ribosomal immunostimulant reduced recurrences by 10-53% and also reduced the duration of infection, antibacterial use and local surgery requirement. Results obtained from studies of 6 months' duration confirmed or extended these results. In adult patients with ENT or mixed respiratory infections, ribosomal immunostimulant produced similar reductions to those seen in children for recurrent infections (54-78% reduction), duration of infection (42-79% reduction) and antibacterial use (38% reduction).\n These results clearly demonstrate that ribosomal immunostimulant is effective in preventing and in reducing upper and lower respiratory tract infections in children and adults.", "The aim of the study was to evaluate the outcome of a participatory community-based prevention program against injuries among the elderly. A population-based quasi-experimental design was used with pre- and post-implementation measurements in an intervention and a control area. The program was based on cross-sectoral participation in detecting and taking action against injuries among the elderly. Change in the relative risk of injury was estimated by the odds ratio. Morbidity in moderately (AIS 2) severe injury in the study area was reduced from 46 per 1000 population years to 25 per 1000 population years (odds ratio 0.55; 95% confidence interval 0.46-0.65), while the minor (AIS 1) injuries increased (odds ratio 1.55; 95% confidence interval 1.21-1.91). The risk of severe or fatal (AIS 3-6) injuries remained constant. In the study area, only a slight decrease in the total morbidity rate was observed (odds ratio 0.87; 95% confidence interval 0.77-0.99). In the control area, there was no evident change in the total morbidity rates. Falls decreased or showed a tendency to decrease in the age groups 65 to 79-y-old in the study area, while they increased in the older age group. The results indicate that no sharp boundaries should be drawn between safety education, physical conditioning, environmental adjustments and secondary prevention measures when planning safety promotion among the elderly. Future studies should address these issues along with the methodological complexity associated with assessment of participatory community-based safety promotion programs.", "Psychosocial treatments are the mainstay of management of autism in the UK but there is a notable lack of a systematic evidence base for their effectiveness. Randomised controlled trial (RCT) studies in this area have been rare but are essential because of the developmental heterogeneity of the disorder. We aimed to test a new theoretically based social communication intervention targeting parental communication in a randomised design against routine care alone.\n The intervention was given in addition to existing care and involved regular monthly therapist contact for 6 months with a further 6 months of 2-monthly consolidation sessions. It aimed to educate parents and train them in adapted communication tailored to their child's individual competencies. Twenty-eight children with autism were randomised between this treatment and routine care alone, stratified for age and baseline severity. Outcome was measured at 12 months from commencement of intervention, using standardised instruments.\n All cases studied met full Autism Diagnostic Interview (ADI) criteria for classical autism. Treatment and controls had similar routine care during the study period and there were no study dropouts after treatment had started. The active treatment group showed significant improvement compared with controls on the primary outcome measure--Autism Diagnostic Observation Schedule (ADOS) total score, particularly in reciprocal social interaction--and on secondary measures of expressive language, communicative initiation and parent-child interaction. Suggestive but non-significant results were found in Vineland Adaptive Behaviour Scales (Communication Sub-domain) and ADOS stereotyped and restricted behaviour domain.\n A Randomised Treatment Trial design of this kind in classical autism is feasible and acceptable to patients. This pilot study suggests significant additional treatment benefits following a targeted (but relatively non-intensive) dyadic social communication treatment, when compared with routine care. The study needs replication on larger and independent samples. It should encourage further RCT designs in this area.", "Infants infected with HIV-1 perinatally despite single-dose nevirapine progress rapidly. Data on treatment outcome in sub-Saharan African infants exposed to single-dose nevirapine are urgently required. This feasibility study addresses efficacy of infant antiretroviral therapy in this setting.\n HIV-infected infants in Durban, South Africa, received randomized immediate or deferred (when CD4 cell count reached <20%) four-drug antiretroviral therapy (zidovudine/lamivudine/nelfinavir/nevirapine). Genotyping for non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was undertaken pre-antiretroviral therapy. Monthly follow-up to 1-year post-antiretroviral therapy included viral load, CD4 cell count and verbal/measured adherence monitoring.\n All 63 infants were exposed to single-dose nevirapine. Twenty-one out of 51 (39%) infants with baseline genotyping results had NNRTI resistance (most frequently Y181C; 20%). Forty-three infants were randomized to immediate antiretroviral therapy (ART): three withdrew pre-antiretroviral therapy; 36 out of 40 completed 1-year of ART. Twenty infants received deferred ART: 17 reached CD4 cell counts less than 20% (median d99) and 13 out of 17 started antiretroviral therapy in year 1. Verbal and measured adherence was 99% and 95%, respectively. One-year post-ART, 49 out of 49 (100%) infants had a viral load less than 400 copies/ml; 46 out of 49 (94%) had viral load less than 50 copies/ml. Ten infants (20%) required second-line ART due to virological failure or tuberculosis treatment, therefore 39 out of 49 (80%) achieved viral load less than 400 copies/ml by intention-to-treat. Time to viral load less than 50 copies/ml correlated with maternal CD4 cell count (r = -0.42; P = 0.005) and infant pre-ART viral load (r = 0.64; P < 0.001). NNRTI mutations had no significant effect on virological suppression. Infants starting immediate compared with deferred ART had fewer illness episodes (P = 0.003), but no significant difference in virological suppression.\n Excellent adherence and virological suppression are achievable in infants, despite high-frequency NNRTI mutations and rapid disease progression. Infants remain relatively neglected in roll-out programmes and ART provision must be expanded.", "We enrolled 60 children with recurrent acute otitis media (AOM) in a study of the effectiveness of antimicrobial prophylaxis. All children were entered into the study following an acute episode of infection treated with amoxicillin (AMX) for 10 days. Following therapy, the children were re-examined, and then randomly assigned to receive either trimethoprim-sulfamethoxazole (TMP-SMX), amoxicillin (AMX) or a placebo (PLA). Twenty children were included in each group. Each drug was administered once a day at bedtime, at 1/3 the therapeutic dose, for 3 months. Children were re-evaluated with pneumootoscopy during episodes of acute illness and with pneumootoscopy and impedance tympanometry (TYMP) at monthly intervals. We observed a significantly increased rate of recurrent AOM in children receiving placebo compared with those who received antibiotics (50% vs. 17% P < 0.005). Both prophylactic antibiotics were equally effective in preventing recurrent AOM (recurrence rate 20% TMP-SMX, 15% AMX). We also observed that recurrences in children receiving placebo occurred earlier in the study period than in those receiving antibiotics. These results suggest that antimicrobial prophylaxis in children with recurrent acute otitis media is effective in reducing subsequent disease. The similar efficacy of both antibiotics tested suggests that the less expensive agent should be used.", "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.", "Accidents are an important cause of childhood injury. It is hypothesized that safety education programs can reduce accidents in primary school-aged children. This study aimed to determine whether child and parent safety education programs can decrease the incidence of accidental injury in children when compared with controls.\n The study population (aged 7-13 years) were recruited from four local primary schools, and randomly assigned into an Intervention or a Control group. The Intervention group received child and parent safety education and was taught injury prevention strategies. The Control group received no injury prevention education or intervention. The incidence of accidental injury was compared between the two groups.\n In the first year after intervention the incidence of accidental injury was 262 cases in the Intervention group (8.26%) and 234 cases (8.67%) in the Control group (P > 0.05). In the second year after intervention, however, the incidence of accidental injury was significantly less in the Intervention group (211 cases, 6.54%) compared with the Control group (229 cases, 8.63%) (P < 0.01).\n Injury prevention strategies and child and parent safety education can reduce risks of accidental injury in children.", "One hundred and twenty-one children were studied in this prospective, randomized double-blind, placebo-controlled comparison of the effectiveness of anticholinergic prophylaxis for the prevention of emetic symptoms following strabismus surgery. The children were allocated to three groups, to receive placebo (n = 40), glycopyrrolate (n = 40) or atropine (n = 41). The incidence of intraoperative oculocardiac reflex (OCR) and of postoperative emetic symptoms for 24 h was recorded. The incidence of OCR was 55% in the placebo group compared with 5% and 2% in the glycopyrrolate and atropine groups respectively (P < 0.05). Thirty percent (12/40) of patients in the placebo group, 25% (10/40) in the glycopyrrolate group, and 22% (9/41) in the atropine group experienced nausea and/or vomiting (difference not significant). It is concluded that prophylactic administration of anticholinergic agents during strabismus surgery in children despite being effective against the occurrence of the oculocardiac reflex, does not reduce the incidence of emetic symptoms.", "To compare short- and long-term effectiveness of three additive treatment protocols in children experiencing chronic encopresis.\n Children, 6 to 15 years of age, who experienced at least weekly fecal soiling for 6 months or longer were eligible for the study. Children were randomly assigned to a group that received intensive medical therapy (IMT), a group that received intensive medical therapy plus a behavior management program called enhanced toilet training (ETT), or a group that received intensive medical therapy with enhanced toilet training and external anal sphincter electromyographic biofeedback (BF). Data concerning toileting habits were collected for 14 consecutive days before an initial visit, and at 3, 6, and 12 months after initiation of therapy. All data were collected using a computerized voice-mail system that telephoned the families each day. At 12 months, children were classified as significantly improved (reduction in soiling, P < 0.001) or cured (<one fecal accident in 2 weeks).\n Eighty-seven children participated in the study, 72 boys and 15 girls. Mean age at enrollment was 8.6 +/- 2.0 years, and mean duration of symptoms was 58.2 +/- 38.5 months. At 12 months, the cure rates for the IMM, ETT, and BF groups were 36, 48, and 39, respectively (not significant). The improvement rates for these three groups were 45, 78, and 54, respectively (P < 0.05). These results were very stable over time (r > 0.90, P < 0.001 in each case). Response to treatment during the first 2 weeks of therapy was highly predictive of outcome at 3, 6, and 12 months (P < 0.0001). Children in the ETT group used less laxative medication (P < 0.04) and required fewer treatment contacts (P = 0.08) than children in the IMM group. All three treatments resulted in significant increases in daily bowel movements passed in the toilet and self-initiated toileting, and resulted in decreases in average daily soiling at 3, 6, and 12 months (P < 0.05).\n Enhanced toilet training is somewhat more effective in treating childhood encopresis than either intensive medical therapy or anal sphincter biofeedback therapy. Although similar total cure rates at 1 year can be expected with these three forms of therapy, enhanced toilet training results in statistically significant decreases in the daily frequency of soiling for the greatest number of children.", "To compare the effect of the prone position (PP) vs supine position (SP) on oxygenation in children with acute respiratory failure (ARF).\n Prospective, randomized controlled trial.\n A 36-bed pediatric critical-care unit in a tertiary-care, university-based children's hospital.\n Ten children (mean [SD] age, 5 +/- 3.6 years) with ARF with a baseline oxygenation index (OI) of 22 +/- 8.5.\n Following a period of stabilization in the SP, baseline data were collected and patients were randomized to one of two groups in a two-crossover study design: group 1, supine/prone sequence; group 2, prone/supine sequence. Each position was maintained for 12 h. Lung mechanics and acute response to inhaled nitric oxide were examined in each position.\n OI was significantly better in the PP compared to the SP over the 12-h period (analysis of variance, p = 0.0016). When patients were prone, a significant improvement in OI was detected (7.9 +/- 5.3; p = 0.002); this improvement occurred early (within 2 h in 9 of 10 patients) and was sustained over the 12-h study period. Static respiratory system compliance and resistance were not significantly affected by the position change. Inhaled nitric oxide had no effect on oxygenation in either position. Urine output increased while prone, resulting in a significantly improved fluid balance (+ 6.6 +/- 15.2 mL/kg/12 h in PP vs + 18.9 +/- 13.6 mL/kg/12 h in SP; p = 0.041). No serious adverse effects were detected in the PP.\n In children with ARF, oxygenation is significantly superior in the PP than in the SP. This improvement occurs early, remains sustained for a 12-h period, and is independent of changes in lung mechanics.", "Iron deficiency anemia and recurrent infections are common among children of low socioeconomic status.\n The objective was to evaluate the effects of iron supplementation on iron status and morbidity in children with or without infection.\n Children aged 5-10 y were recruited for a randomized, controlled, double-blind study from outpatients attending the Children's Hospital, Colombo, Sri Lanka. Clinical, inflammatory, nutritional, and iron statuses were determined at baseline and after the intervention. Children with a history of recurrent upper respiratory tract infections (URTIs) and with laboratory and clinical evidence of a current URTI constituted the infection group (n = 179), and children without infection constituted the control group (n = 184). Subjects in both groups were supplemented with ferrous sulfate (60 mg Fe) or placebo once daily for 8 wk. Morbidity from URTIs, the number of gastrointestinal infections, and compliance were recorded every 2 wk.\n The overall prevalence of anemia was 52.6%. Iron supplementation significantly improved iron status by increasing hemoglobin (P < 0.001) and serum ferritin (P < 0.001) concentrations from baseline values in the children with or without infection. There was no significant improvement in iron status in the children who received placebo. In both the infection group and the control group, the mean number of URTI episodes and the total number of days sick with an URTI during the period of intervention were significantly lower (P < 0.005 and P < 0.001, respectively) in the children who received iron supplements than in those who received placebo.\n Iron supplementation significantly improves iron status and reduces morbidity from URTIs in children with or without infection.", "The objective was to study the generalizability of trial results by comparing randomized patients to eligible but nonrandomized patients who received the same management. Implementation of trial results is only justifiable when the results can be generalized to the total domain population. The design was a multicentre randomized controlled trial on the effect of early screening and treatment with ventilation tubes on infants with otitis media with effusion. Randomized (n = 187) and nonrandomized eligible patients (n = 133) were followed up. The study population comprised children who were detected by auditory screening at the age of 9-12 months and who were subsequently diagnosed with persistent bilateral otitis media with effusion for 4-6 months. A significant difference was found in the distribution of some prognostic factors: more randomized children had older siblings, did not attend day care and had mothers with a lower educational level than the nonrandomized children. These factors, however, did not modify the outcome. No differences were found in mean hearing levels between the randomized and nonrandomized children: in both the randomized and nonrandomized children ventilation tubes improved the hearing level, especially after 6 months. However, in the long term (12 months), the hearing levels were equal again. The results of the randomized and nonrandomized patients were comparable. The results of this trial appear to be generalizable to the total domain population. The procedure of following up both randomized and nonrandomized patients is recommended when there is concern about selective participation and reduced generalizability.", "Measure efficacy of eicosapentaenoic acid (EPA) in children with attention deficit hyperactivity disorder (ADHD).\n Randomized controlled trial (RCT) of 0.5 g EPA or placebo (15 weeks) in 92 children (7-12 years) with ADHD. Efficacy measure was Conners' Parent/Teacher Rating Scales (CPRS/CTRS). Fatty acids were analysed in serum phospholipids and red blood cell membranes (RBC) at baseline and endpoint with gas chromatography.\n EPA improved CTRS inattention/cognitive subscale (p = 0.04), but not Conners' total score. In oppositional children (n = 48), CTRS total score improved ≥25% in 48% of the children receiving EPA vs. 9% for placebo [effect size (ES) 0.63, p = 0.01]. In less hyperactive/impulsive children (n = 44), ≥25% improvement was seen in 36% vs. 18% (ES 0.41, n.s.), and with both these types of symptoms 8/13 with EPA vs. 1/9 for placebo improved ≥25% (p = 0.03). Children responding to treatment had lower EPA concentrations (p = 0.02), higher AA/EPA (p = 0.005) and higher AA/DHA ratios (p = 0.03) in serum at baseline. Similarly, AA/EPA (p = 0.01), AA/DHA (p = 0.038) and total omega-6/omega-3 ratios (p = 0.028) were higher in RBC, probably because of higher AA (p = 0.011).\n Two ADHD subgroups (oppositional and less hyperactive/impulsive children) improved after 15-week EPA treatment. Increasing EPA and decreasing omega-6 fatty acid concentrations in phospholipids were related to clinical improvement.\n © 2010 The Author(s)/Journal Compilation © 2010 Foundation Acta Paediatrica." ]	This review shows that IS reduce the incidence of ARTIs by 40% on average in susceptible children. Studies in healthy children are not available. Although the safety profile in the studies was good, some IS may be unsafe. ARTI-susceptible children may benefit from IS treatment. Further high-quality trials are needed and we encourage national health authorities to conduct large, multicentre, double-blind, placebo-controlled RCTs on the role of IS in preventing ARTIs in children.
CD009513	[ "15294086", "16770291", "17891043", "15751766" ]	[ "Adherence to antiretroviral therapy in HIV-infected pediatric patients improves with home-based intensive nursing intervention.", "Home visits to improve adherence to highly active antiretroviral therapy: a randomized controlled trial.", "Telephone support to improve antiretroviral medication adherence: a multisite, randomized controlled trial.", "A randomized controlled trial to enhance antiretroviral therapy adherence in patients with a history of alcohol problems." ]	[ "Adherence to combination antiretroviral therapy (ART) has been shown to be a determining factor in controlling viral replication, maintaining immunologic function and long-term survival in HIV-positive individuals. Little information is available on strategies to improve adherence in pediatric HIV-infected patients. We conducted a randomized, nonblinded, pilot study to determine if a home-based nursing intervention would improve medication adherence. The study was offered to all eligible HIV-positive patients receiving care at Connecticut Children's Medical Center's (CCMC) Pediatric and Youth HIV Program. Sixty-seven percent (37/55) of the patients and their caretakers participated. We randomized participants to either standard of care or the intervention trial. The intervention was designed to improve knowledge and understanding of HIV infection and HIV medications and to resolve or modify barriers to adherence. Both groups completed pre- and post-intervention questionnaires, assessing their knowledge and understanding of HIV, ART, and adherence. Adherence was estimated objectively from medication refill history and subjectively from a self-report score. We also inferred adherence from pre- to post-test plasma viral load and CD4+ T-cell percentages. The knowledge score (p = 0.02) and medication refill history (p = 0.002) improved significantly in the intervention group. The adherence self-report score improved, although not significantly (p = 0.07). We did not observe statistical differences in CD4+ T-cell counts or viral load between groups. We conclude that our home-based nursing intervention helped HIV-positive children and their families in better adhering to prescribed medication regimens.", "Few rigorously designed studies have documented the efficacy of interventions to improve medication adherence among patients prescribed highly active antiretroviral. Data are needed to justify the use of limited resources for these programs.\n A 2-arm, randomized, controlled trial evaluated the efficacy of a community-based, home-visit intervention to improve medication adherence. Participants were 171 HIV-infected adults prescribed a minimum of 3 antiretroviral agents. The majority had a past or current history of substance abuse. Subjects were randomly assigned to receive home visits for 1 year or usual care. Medication adherence was assessed with Medication Event Monitoring stem caps at 3-month intervals from randomization through 3 months after the conclusion of the intervention.\n A larger proportion of subjects in the intervention group demonstrated adherence greater than 90% compared with the control group at each time point after baseline. The difference over time was statistically significant (Extended Mantel-Haenszel test: 5.80, P = 0.02). A statistically significant intervention effect on HIV-RNA level or CD4 cell count was not seen, but there was a statistically significant association between greater than 90% adherence and an undetectable HIV-RNA over time (P < 0.03).\n Home visits from a nurse and a community worker were associated with medication adherence greater than 90% among a cohort of socially vulnerable people living with HIV/AIDS in northeastern United States.", "To determine whether proactive telephone support improves adherence to antiretroviral therapy (ART) and clinical outcomes when compared to standard care.\n A multisite, randomized controlled trial (RCT) was conducted with 109 ART-naive subjects coenrolled in AIDS Clinical Trials Group (ACTG) 384. Subjects received standard clinic-based patient education (SC) or SC plus structured proactive telephone calls. The customized calls were conducted from a central site over 16 weeks by trained registered nurses. Outcome measures (collected over 64 weeks) included an ACTG adherence questionnaire and 384 study endpoints.\n For the primary endpoint, self-reported adherence, a significantly better overall treatment effect was observed in the telephone group (P = 0.023). In a post hoc analysis, composite adherence scores, taken as the first 2 factor scores from a principal components analysis, also found significant intervention benefit (P = 0.023 and 0.019 respectively). For the 384 primary study endpoint, time to regimen failure, the Kaplan-Meier survival curve for the telephone group remained above the SC group at weeks 20 to 64; a Cox proportional hazard model that controlled for baseline RNA stratification, CD4, gender, age, race/ethnicity, and randomized ART treatment arm suggested the telephone group tended to have a lower risk for failure (hazard ratio = 0.68; 95% confidence interval: 0.38 to 1.23).\n Findings indicate that customized, proactive telephone calls have good potential to improve long-term adherence behavior and clinical outcomes.", "To assess the effectiveness of an individualized multicomponent intervention to promote adherence to antiretroviral therapy (ART) in a cohort of HIV-infected individuals with a history of alcohol problems.\n We conducted a randomized controlled trial to compare the usual medical follow-up with an adherence intervention.\n The principal enrolment site was Boston Medical Center, a private, not-for-profit, academic medical institution.\n HIV-infected patients with a history of alcohol problems on ART. A total of 151 were enrolled and 141 (93%) were assessed at follow-up. Intervention: A nurse, trained in motivational interviewing, completed the following over 3 months in four encounters: addressed alcohol problems; provided a watch with a programmable timer to facilitate pill taking; enhanced perception of treatment efficacy; and delivered individually tailored assistance to facilitate medication use.\n Prior 30-day adherence > or =95%, prior 3-day adherence of 100%, CD4 cell count, HIV RNA and alcohol consumption, each at both short- and long-term follow-up.\n At follow-up, no significant differences in medication adherence, CD4 cell count, HIV RNA or alcohol consumption were found (all P values >0.25).\n A multicomponent intervention to enhance adherence among HIV-infected individuals with a history of alcohol problems was not associated with changes in medication adherence, alcohol consumption or markers of HIV disease progression. The failure to change adherence in a group at high risk for poor adherence, despite utilizing an intensive individual-focused patient intervention, supports the idea of addressing medication adherence with supervised medication delivery or markedly simplified dosing regimens." ]	A home-based nursing intervention has the potential to improve ART adherence, but more evidence is needed. Medication diaries do not appear to have an effect on adherence or disease outcomes. Two interventions, an LPV/r-containing regimen and peer support therapy for adolescents, did not demonstrate improvements in adherence, yet demonstrated greater viral load suppression compared to control groups, suggesting a different mechanism for improved health outcomes. Well-designed evaluations of interventions to improve paediatric adherence to ART are needed.
CD001800	[ "11832254", "17196274", "17880478", "314119", "10069785", "17767899", "10092561", "2271343", "15718182", "16924183", "12707240", "10493846", "12370553", "12031725", "15605326", "18513526", "11401128", "8978226", "19675115", "17239677", "1588521", "17981851", "14512778", "8360063", "12520156", "2024598", "20435864", "15923147", "11207837", "11823086", "10929164", "2011669", "20854564", "16026656", "18212034", "17967593", "10867086", "18088263", "1874262", "9032501", "11163735", "10767227", "7050369" ]	[ "Guideline-based early rehabilitation after myocardial infarction. A pragmatic randomised controlled trial.", "Home-based versus hospital-based rehabilitation after myocardial infarction: A randomized trial with preference arms--Cornwall Heart Attack Rehabilitation Management Study (CHARMS).", "A nurse-led cardiac rehabilitation programme improves health behaviours and cardiac physiological risk parameters: evidence from Chengdu, China.", "Brief group therapy in myocardial infarction rehabilitation: three- to four-year follow-up of a controlled trial.", "Randomized, controlled trial of long-term moderate exercise training in chronic heart failure: effects on functional capacity, quality of life, and clinical outcome.", "The Birmingham Rehabilitation Uptake Maximisation Study (BRUM). Home-based compared with hospital-based cardiac rehabilitation in a multi-ethnic population: cost-effectiveness and patient adherence.", "Changes in cardiorespiratory fitness, psychological wellbeing, quality of life, and vocational status following a 12 month cardiac exercise rehabilitation programme.", "A controlled trial of community based coronary rehabilitation.", "Randomised controlled trial of cardiac rehabilitation in elderly patients with heart failure.", "Cardiac rehabilitation vs. home exercise after coronary artery bypass graft surgery: a comparison of heart rate recovery.", "Improved exercise tolerance and quality of life with cardiac rehabilitation of older patients after myocardial infarction: results of a randomized, controlled trial.", "Improved physical fitness and quality of life following training of elderly patients after acute coronary events. A 1 year follow-up randomized controlled study.", "A controlled trial of hospital versus home-based exercise in cardiac patients.", "Effectiveness of three models for comprehensive cardiovascular disease risk reduction.", "A short course of cardiac rehabilitation program is highly cost effective in improving long-term quality of life in patients with recent myocardial infarction or percutaneous coronary intervention.", "Hospital-based comprehensive cardiac rehabilitation versus usual care among patients with congestive heart failure, ischemic heart disease, or high risk of ischemic heart disease: 12-month results of a randomized clinical trial.", "Exercise training intervention after coronary angioplasty: the ETICA trial.", "Psychological rehabilitation after myocardial infarction: multicentre randomised controlled trial.", "Effectiveness of a video-based exercise programme to reduce falls and improve health-related quality of life among older adults discharged from hospital: a pilot randomized controlled trial.", "Heart failure and a controlled trial investigating outcomes of exercise training (HF-ACTION): design and rationale.", "Benefits and weaknesses of a cardiac rehabilitation programme.", "Exercise capacity, physical activity patterns and outcomes six years after cardiac rehabilitation in patients with heart failure.", "Clinical trial of an Internet-based case management system for secondary prevention of heart disease.", "Alternatives for cardiac rehabilitation patients unable to return to a hospital-based program.", "Effects of phase III cardiac rehabilitation programs on health-related quality of life in elderly patients with coronary artery disease: Juntendo Cardiac Rehabilitation Program (J-CARP).", "Effects on quality of life with comprehensive rehabilitation after acute myocardial infarction.", "Outpatient pulmonary rehabilitation following acute exacerbations of COPD.", "Effects of a problem-based learning rehabilitation programme on quality of life in patients with coronary artery disease.", "Exercise training for rehabilitation and secondary prevention of falls in geriatric patients with a history of injurious falls.", "A randomized trial of the efficacy of multidisciplinary care in heart failure outpatients at high risk of hospital readmission.", "Effect of a preoperative intervention on preoperative and postoperative outcomes in low-risk patients awaiting elective coronary artery bypass graft surgery. A randomized, controlled trial.", "Recovery after myocardial infarction. Effects of a caring rehabilitation programme.", "LiFE Pilot Study: A randomised trial of balance and strength training embedded in daily life activity to reduce falls in older adults.", "Psychological effects of a short behavior modification program in patients with acute myocardial infarction or coronary artery bypass grafting. A randomized controlled trial.", "A pilot randomized controlled trial to evaluate the benefit of the cardiac rehabilitation paradigm for the non-acute ischaemic stroke population.", "Effects of a home-based exercise program on clinical outcomes in heart failure.", "Program participation, exercise adherence, cardiovascular outcomes, and program cost of traditional versus modified cardiac rehabilitation.", "A randomized controlled trial of a community nurse-supported hospital discharge programme in older patients with chronic heart failure.", "Comparison of a rehabilitation programme, a counselling programme and usual care after an acute myocardial infarction: results of a long-term randomized trial. P.RE.COR. Group.", "The effects of a community-based pulmonary rehabilitation programme on exercise tolerance and quality of life: a randomized controlled trial.", "Comprehensive local muscle training increases aerobic working capacity and quality of life and decreases neurohormonal activation in patients with chronic heart failure.", "Long-term effects of outpatient rehabilitation of COPD: A randomized trial.", "Exercise after myocardial infarction: a controlled trial." ]	[ "To determine the effectiveness of individualised educational behavioural treatment delivered by cardiac nurses in hospital compared to usual care for patients following acute myocardial infarction.\n One hundred and fourteen consecutive patients were randomised to receive the intervention or usual care. Outcome assessment was by self-report questionnaire (the Hospital Anxiety and Depression Scale and Dartmouth COOP Health Status), interview at 1 month, and self-report at 3 and 12 months. The primary outcome was improvement in the Dartmouth COOP total score from baseline to 3 months.\n Four patients needed to be treated to give an additional patient with improvement in health status at 3 months (number needed to treat [NNT] 4, 95% confidence intervals [CIs] 3 to 12). The intervention group were more confident about returning to activities 1 month after discharge from hospital. Treated patients had fewer further treatment needs.\n An individualised educational behavioural treatment delivered by cardiac nurses in hospital may have substantial benefits. A large-scale pragmatic RCT is needed.", "Participation in cardiac rehabilitation after acute myocardial infarction is sub-optimal. Offering home-based rehabilitation may improve uptake. We report the first randomized study of cardiac rehabilitation to include patient preference.\n To compare the clinical effectiveness of a home-based rehabilitation with hospital-based rehabilitation after myocardial infarction and to determine whether patient choice affects clinical outcomes.\n Pragmatic randomized controlled trial with patient preference arms.\n Rural South West England.\n Patients admitted with uncomplicated myocardial infarction were offered hospital-based rehabilitation classes over 8-10 weeks or a self-help package of six weeks' duration (the Heart Manual) supported by a nurse. Primary outcomes at 9 months were mean depression and anxiety scores on the Hospital Anxiety Depression scale, quality of life after myocardial infarction (MacNew) score and serum total cholesterol.\n Of the 230 patients who agreed to participate, 104 (45%) consented to randomization and 126 (55%) chose their rehabilitation programme. Nine month follow-up data were available for 84/104 (81%) randomized and 100/126 (79%) preference patients. At follow-up no difference was seen in the change in mean depression scores between the randomized home and hospital-based groups (mean difference: 0; 95% confidence interval, -1.12 to 1.12) nor mean anxiety score (-0.07; -1.42 to 1.28), mean global MacNew score (0.14; -0.35 to 0.62) and mean total cholesterol levels (-0.18; -0.62 to 0.27). Neither were there any significant differences in outcomes between the preference groups.\n Home-based cardiac rehabilitation with the Heart Manual was as effective as hospital-based rehabilitation for patients after myocardial infarction. Choosing a rehabilitation programme did not significantly affect clinical outcomes.", "The aim of this study was to examine the effect of a cardiac rehabilitation programme on health behaviours and physiological risk parameters in patients with coronary heart disease in Chengdu, China.\n Epidemiological studies indicate a dose-, level- and duration-dependent relationship exists between cardiac behavioural and physiological risks and coronary heart disease incidence as well as subsequent cardiac morbidity and mortality. Cardiac risk factor modification has become the very primary goal of modern cardiac rehabilitation programmes.\n A randomized controlled trial was conducted. Coronary heart disease patients (n = 167) who met the sampling criteria in two tertiary medical centres in Chengdu, south-west China, were randomly assigned to either an intervention group (the cardiac rehabilitation programme) or control group (the routine care). The change of health behaviours (walking performance, step II diet adherence, medication adherence, smoking cessation) and physiological risk parameters (serum lipids, blood pressure, body weight) were assessed to evaluate the programme effect.\n Patients in the intervention group demonstrated a significantly better performance in walking, step II diet adherence, medication adherence; a significantly greater reduction in serum lipids including triglyceride, total cholesterol, low-density lipoprotein; and significantly better control of systolic and diastolic blood pressure at three months. The majority of these positive impacts were maintained at six months. The effect of the programme on smoking cessation, body weight, serum high-density lipoprotein, was not confirmed.\n A cardiac rehabilitation programme led by a nurse can significantly improve the health behaviours and cardiac physiological risk parameters in coronary heart disease patients. Nurses can fill significant treatment gaps in the risk factor management of patients with coronary heart disease.\n This study raises attention regarding the important roles nurses can play in cardiac rehabilitation and the unique way for nurses to meet the rehabilitative care needs of coronary heart disease patients. Furthermore, the hospital-home bridging nature of the programme also created a model for interfacing the acute care and community rehabilitative care.", "A trial of brief group therapy as part of a rehabilitation program for postmyocardial infarction (MI) patients was carried out. Forty-four patients surviving their first MI were randomly allocated to either group therapy or control group status and were followed over 4 years. An additional group of 17 patients were referred for post-MI group therapy sessions after the termination of the controlled experiment and were followed for 3 years. Patients who received group therapy had significantly less follow-up coronary morbidity and mortality, and returned to work at significant higher percentages than control patients. Although neither group therapy nor control group patients meaningfully altered conventional coronary risk factors, group therapy patients (in the controlled trial) successfully altered selected coronary-prone behaviors. Educational information regarding the physiological and psychological aspects of coronary heart disease, presented in the group therapy sessions, was forgotten over follow-up. It is concluded that the supportive aspects of the group therapy experience played the most important role in determining the rehabilitation advantages seen for treatment patients.", "It is still a matter of debate whether exercise training (ET) is a beneficial treatment in chronic heart failure (CHF).\n To determine whether long-term moderate ET improves functional capacity and quality of life in patients with CHF and whether these effects translate into a favorable outcome, 110 patients with stable CHF were initially recruited, and 99 (59+/-14 years of age; 88 men and 11 women) were randomized into 2 groups. One group (group T, n=50) underwent ET at 60% of peak &f1;O2, initially 3 times a week for 8 weeks, then twice a week for 1 year. Another group (group NT, n=49) did not exercise. At baseline and at months 2 and 14, all patients underwent a cardiopulmonary exercise test, while 74 patients (37 in group T and 37 in group NT) with ischemic heart disease underwent myocardial scintigraphy. Quality of life was assessed by questionnaire. Ninety-four patients completed the protocol (48 in group T and 46 in group NT). Changes were observed only in patients in group T. Both peak &f1;O2 and thallium activity score improved at 2 months (18% and 24%, respectively; P<0. 001 for both) and did not change further after 1 year. Quality of life also improved and paralleled peak VO2. Exercise training was associated both with lower mortality (n=9 versus n=20 for those with training versus those without; relative risk (RR)=0.37; 95% CI, 0.17 to 0.84; P=0.01) and hospital readmission for heart failure (5 versus 14; RR=0.29; 95% CI, 0.11 to 0.88; P=0.02). Independent predictors of events were ventilatory threshold at baseline (beta-coefficient=0.378) and posttraining thallium activity score (beta-coefficient -0.165).\n Long-term moderate ET determines a sustained improvement in functional capacity and quality of life in patients with CHF. This benefit seems to translate into a favorable outcome.", "To evaluate the relative effectiveness and cost-effectiveness of a home-based programme of cardiac rehabilitation using the Heart Manual, with centre-based programmes. It also sought to explore the reasons for non-adherence to cardiac rehabilitation programmes.\n An individually randomised trial, with minimisation for age, gender, ethnicity, initial diagnosis and hospital of recruitment. Participants were followed up after 6, 12 and 24 months by questionnaire and clinical assessment. Individual semistructured interviews were undertaken in the homes of a purposive sample of patients who did not adhere to their allocated programme, and focus groups were undertaken with groups of patients who adhered to the programmes.\n Four hospitals in predominantly inner-city, multi-ethnic, socio-economically deprived areas of the West Midlands in England, for 2 years from 1 February 2002.\n A total of 525 patients who had experienced a myocardial infarction (MI) or coronary revascularisation within the previous 12 weeks.\n All the rehabilitation programmes included exercise, relaxation, education and lifestyle counselling. All patients were seen by a cardiac rehabilitation nurse prior to hospital discharge and provided with information about their condition and counselling about risk factor modification. The four centre-based programmes varied in length from nine sessions at weekly intervals of education, relaxation and circuit training to 24 individualised sessions over 12 weeks of mainly walking, fixed cycling and rowing with group-based education. The home-based programme consisted of an appropriate version of the Heart Manual, home visits and telephone contact. The Heart Manual was introduced to patients on an individual basis, either in hospital or on a home visit. Home visits by a nurse took place at approximately 1, 6 and 12 weeks after recruitment, with a telephone call at 3 weeks. At the final visit, patients were encouraged to maintain their lifestyle changes and to continue with their exercise programme. Where needed, follow-up was made by a rehabilitation nurse who spoke Punjabi. An audiotape of an abridged version of the Heart Manual in Punjabi accompanied the manual for patients with a limited command of English.\n Primary outcomes were smoking cessation, blood pressure, total and high-density lipoprotein cholesterol, exercise capacity measured by the incremental shuttle walking test and psychological status measured by the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes included self-reported diet, physical activity, cardiac symptoms and quality of life. Health service resource use and costs of rehabilitation programmes from health service and societal perspectives were also measured. Adherence to the physical activity element of the rehabilitation programmes was measured by questionnaire 6, 9 and 12 weeks.\n No clinically or statistically significant differences were found in any of the primary or secondary outcome measures between the home- and centre-based groups. Significant improvements in total cholesterol, smoking prevalence, the HADS anxiety score, self-reported physical activity and diet were seen in both arms between baseline and the 6-month follow-up. Five or more contacts with a cardiac rehabilitation nurse were received by 96% of home-based participants, whereas only 56% of centre-based participants attended this many rehabilitation classes. The direct rehabilitation costs to the health service were significantly higher for the home-based programme (mean cost 198 pounds versus 157 pounds for the centre-based programme), but when patient costs were included the mean cost of the centre-based arm rose to 182 pounds. Patients' reasons for not taking up or adhering to cardiac rehabilitation were multifactorial and very individual. Other health problems limited some patients' ability to exercise. Most non-adherers found some aspects of their cardiac rehabilitation programme helpful. Many had adapted advice on rehabilitation and were continuing to exercise in other ways and had made lifestyle changes, particularly to their diet. The home-based patients' lack of motivation to exercise on their own at home was a major factor in non-adherence. The focus groups revealed little diversity of views among patients from each programme. Patients in the hospital programme enjoyed the camaraderie of group exercise and the home-based patients valued the wealth of information and advice in the Heart Manual.\n A home-based cardiac rehabilitation programme for low- to moderate-risk patients does not produce inferior outcomes compared with the traditional centre-based programmes. With the level of home visiting in this trial, the home-based programme was more costly to the health service, but with the difference in costs borne by patients attending centre-based programmes. Different reasons were given by home and hospital cardiac rehabilitation patients for not taking up or adhering to cardiac rehabilitation, with home-based patients often citing a lack of motivation to exercise at home. Social characteristics, individual patient needs and the location of cardiac rehabilitation programmes need to be taken into account in programme design to maximise participation. Research is recommended into cardiac rehabilitation in patients from ethnic minority groups; measurement tools to assess physical activity and dietary change; evaluating the Heart Manual in patients who decline centre-based cardiac rehabilitation; the implementation of home-based programmes in the UK; and strategies that sustain physical activity in the long term.", "To examine and evaluate improvements in cardiorespiratory fitness, psychological wellbeing, quality of life, and vocational status in postmyocardial infarction patients during and after a comprehensive 12 month exercise rehabilitation programme.\n The sample population comprised 124 patients with a clinical diagnosis of myocardial infarction (122 men and two women).\n 62 patients were randomly allocated to a regular weekly aerobic training programme, three times a week for 12 months, and compared with 62 matched controls who did not receive any formal exercise training. A five year follow up questionnaire/interview was subsequently conducted on this population to determine selected vocational/lifestyle changes.\n Significant improvements in cardiorespiratory fitness (p < 0.01-0.001), psychological profiles (p < 0.05-0.001), and quality of life scores (p < 0.001) were recorded in the treatment population when compared with their matched controls. Although there were no significant differences in mortality, a larger percentage of the regular exercisers resumed full time employment and they returned to work earlier than the controls. Controls took lighter jobs, lost more time from work, and suffered more non-fatal reinfarctions (p < 0.05-0.01).\n Regularly supervised and prolonged aerobic exercise training improves cardiorespiratory fitness, psychological status, and quality of life. The trained population also had a reduction in morbidity following myocardial infarction, and significant improvement in vocational status over a five year follow up period.", "Two hundred patients who had suffered an acute myocardial infarction 4-6 weeks before entered a randomised controlled trial of exercise treatment at a community sports centre supervised by a general practitioner. Eighty one per cent of the treatment group continued to exercise until they returned to work and 73% completed three months' exercise. There were no serious complications of the exercise course. The prevalence of angina pectoris fell by 10% in the treatment group but rose by 60% in the control group. The perceived energy level rose by significantly more in the treatment group than in the controls. The rise in predicted maximum oxygen uptake was significantly greater in the treatment group than in the control group as was the reduction in the double product (a reflection of myocardial workload) at peak exercise. Coronary rehabilitation in the community can be both safe and effective.", "Heart failure, a condition predominantly affecting the elderly, represents an ever-increasing clinical and financial burden for the NHS. Cardiac rehabilitation, a service that incorporates patient education, exercise training and lifestyle modification, requires further evaluation in heart failure management.\n The aim of this study was to determine whether a cardiac rehabilitation programme improved on the outcomes of an outpatient heart failure clinic (standard care) for patients, over 60 years of age, with chronic heart failure.\n Two hundred patients (60-89 years, 66% male) with New York Heart Association (NYHA) II or III heart failure confirmed by echocardiography were randomised. Both standard care and experimental groups attended clinic with a cardiologist and specialist nurse every 8 weeks. Interventions included exercise prescription, education, dietetics, occupational therapy and psychosocial counselling. The main outcome measures were functional status (NYHA, 6-min walk), health-related quality of life (MLHF and EuroQol) and hospital admissions.\n There were significant improvements in MLHF and EuroQol scores, NYHA classification and 6-min walking distance (meters) at 24 weeks between the groups (p<0.001). The experimental group had fewer admissions (11 vs. 33, p<0.01) and spent fewer days in hospital (41 vs. 187, p<0.001).\n Cardiac rehabilitation, already widely established in the UK, offers an effective model of care for older patients with heart failure.", "The autonomic dysfunction is known to adversely affect clinical outcome in patients with cardiovascular disease, and exercise training has been shown to modify the sympathovagal control of heart rate. The purposes of this study were to investigate the effect of cardiac rehabilitation on heart rate recovery in patients who received coronary artery bypass grafting (CABG) and compare the effect with that of a home-based exercise program.\n Fifty-four male patients having undergone CABG were randomly assigned to a cardiac rehabilitation exercise program (n = 18), a home-based exercise program (n = 18), and a control group (n = 18) for 12 wks to evaluate the differences in heart rate recovery among groups.\n Patients in the cardiac rehabilitation group had significant increases in heart rate recovery (19.1 +/- 6.2 vs. 14.0 +/- 5.4 beats/min, P = 0.022) compared with those in the control group. There were no significant differences in heart rate recovery between cardiac rehabilitation and home-based exercise groups (16.2 +/- 4.8 beats/min) or between home-based exercise and control groups. All three groups had significantly improved heart rate recovery compared with their baseline data (P < 0.001, < 0.001, and 0.007).\n Our results point out that a cardiac rehabilitation exercise program has a positive effect on heart rate recovery in patients having undergone CABG and is consistent with the autonomic improvement. Although the home-based exercise group did not reveal statistical significances over those in the control group, it had comparable efficacy to that demonstrated in the cardiac rehabilitation group.", "Whether cardiac rehabilitation (CR) is effective in patients older than 75 years, who have been excluded from most trials, remains unclear. We enrolled patients 46 to 86 years old in a randomized trial and assessed the effects of 2 months of post-myocardial infarction (MI) CR on total work capacity (TWC, in kilograms per meter) and health-related quality of life (HRQL).\n Of 773 screened patients, 270 without cardiac failure, dementia, disability, or contraindications to exercise were randomized to outpatient, hospital-based CR (Hosp-CR), home-based CR (Home-CR), or no CR within 3 predefined age groups (middle-aged, 45 to 65 years; old, 66 to 75 years; and very old, >75 years) of 90 patients each. TWC and HRQL were determined with cycle ergometry and Sickness Impact Profile at baseline, after CR, and 6 and 12 months later. Within each age group, TWC improved with Hosp-CR and Home-CR and was unchanged with no CR. The improvement was similar in middle-aged and old persons but smaller, although still significant, in very old patients. TWC reverted toward baseline by 12 months with Hosp-CR but not with Home-CR. HRQL improved in middle-aged and old CR and control patients but only with CR in very old patients. Complications were similar across treatment and age groups. Costs were lower for Home-CR than for Hosp-CR.\n Post-MI Hosp-CR and Home-CR are similarly effective in the short term and improve TWC and HRQL in each age group. However, with lower costs and more prolonged positive effects, Home-CR may be the treatment of choice in low-risk older patients.", "Cardiac rehabilitation including exercise training is of proven value in ischaemic heart disease. However, elderly patients frequently are not encouraged to participate in such programmes. This study evaluates the physiological effects and self-reported quality of life after an aerobic outpatient group-training programme in subjects above the age of 65 years.\n A consecutive series of 101 patients (males 80%) aged 65-84 (mean 71) years recovering from an acute coronary event were randomized to either a supervised out patient group-training programme (n=50) or to a control group (n=51). The two groups were well balanced as regards clinical characteristics. The compliance in the training group was 87%. Exercise tolerance increased in the trained group from 104 to 122 and 111 W after 3 and 12 months respectively. The corresponding values were 102, 105 and 105 W among controls. Parameters, such as quality of life, self-estimated level of physical activity, fitness and well-being were graded higher by the trained patients than those who served as controls on the two occasions of follow-up.\n Aerobic group-training of elderly patients recovering from an acute coronary event beneficially influences physical fitness and several parameters expressing quality of life. Great care has to be taken to preserve the initial effects by continued training.\n Copyright 1999 The European Society of Cardiology.", "Large numbers of patients who stand to benefit from the exercise training component of cardiac rehabilitation are not being served due to access issues. Home-based exercise training may be a potentially useful alternative to training in institutional environments.\n The purpose of this study was to examine the benefit of 6 months of hospital-based exercise training versus 6 months of monitored, home-based exercise training with respect to physical, quality of life, and social support outcomes in patients after coronary artery bypass graft (CABG) surgery.\n Randomized controlled trial of \"direct-to-home\" (Home; = 120) versus \"direct-to-hospital\" (Hosp; = 122) exercise training, 35-49 d post CABG surgery. The primary outcome was peak exercise capacity, measured by peak oxygen consumption (VO(2)) on a symptom-limited cycle ergometer exercise test. Secondary outcomes were health-related quality of life (measured by the SF-36) and social support (measured by the ISEL). Measurements were taken at baseline and after 3 and 6 months of exercise training.\n The study groups had similar demographic and health profiles at baseline. Peak VO(2) improved significantly in both groups after 6 months of exercise training; 36% in the Hosp group (1,222.1 +/- 269.0 mL x min(-1) to 1,497.2 +/- 594.3 mL x min(-1); < 0.0001) and 31% in the Home group (1,260.3 +/- 306.5 mL x min(-1) to 1,433.4 +/- 589.7 mL x min(-1); < 0.05). The Home group reported greater total social support than the Hosp group at 3 (36.2 +/- 4.5 vs 34.0 +/- 6.7; < 0.0001) and 6 months (36.0 +/- 4.9 vs 34.6 +/- 6.4; = 0.05). The Home group demonstrated a greater improvement in health-related quality of life (physical) by 6 months in comparison to the Hosp patients (51.2 +/- 6.4 vs 48.6 +/- 7.1; = 0.004).\n This study suggests that low-risk CABG surgery patients may be served as well or better with a monitored, home-based exercise program than with an institution-based program.", "Cost and accessibility contribute to low participation rates in phase 2 cardiac rehabilitation programs in the United States. In this study, we compared the clinical effectiveness of 2 less costly and potentially more accessible approaches to cardiovascular risk reduction with that of a contemporary phase 2 cardiac rehabilitation program. Low- or moderate-risk patients (n = 155) with coronary artery disease (CAD) were randomly assigned to 12 weeks of participation in a contemporary phase 2 cardiac rehabilitation program (n = 52), a physician supervised, nurse-case-managed cardiovascular risk reduction program (n = 54), or a community-based cardiovascular risk reduction program administered by exercise physiologists guided by a computerized participant management system based on national clinical guidelines (n = 49). In all, 142 patients (91.6%) completed testing at baseline and after 12 weeks of intervention. For patients with abnormal (i.e., not at the goal level) baseline values, statistically significant (p < or =0.05) improvements were observed with all 3 interventions for multiple CAD risk factors. No statistically significant risk factor differences were observed among the 3 programs. For patients with a baseline maximal oxygen uptake < 7 metabolic equivalents, cardiorespiratory fitness increased to a greater degree in patients in the cardiac rehabilitation program and the community-based program versus the physician-supervised, nurse- case-managed program. These data have important implications for cost containment and increasing accessibility to clinically effective comprehensive cardiovascular risk reduction services in low- or moderate-risk patients with CAD.", "To evaluate the long-term effect of a cardiac rehabilitation and prevention program (CRPP) on quality of life (QOL) and its cost effectiveness.\n Prospective, randomized controlled trial.\n University-affiliated outpatient cardiac rehabilitation and prevention center.\n A total of 269 patients (76% men; mean age, 64+/-11 y) with recent acute myocardial infarction (AMI; n=193) or after elective percutaneous coronary intervention (PCI; n=76) were randomized in a ratio of 2 to 1.\n Patients received either CRPP (an 8-wk exercise and education class in phase 2) or conventional therapy without exercise program (control group). They were followed until they had completed all 4 phases of the program (ie, 2 y).\n QOL assessments, by using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and Symptoms Questionnaire, were performed at the end of each phase. Direct health care cost was calculated, whereas cost utility was estimated as money spent (in US dollars) per quality-adjusted life-year (QALY) gained.\n In the CRPP group, 6 of the 8 SF-36 dimensions improved significantly by phase 2 and were maintained throughout the study period. Patients were less anxious and depressed, and felt more relaxed and contented. In the control group, none of the SF-36 dimensions were improved by phase 2, and bodily pain was increased. In phase 4, only 4 dimensions were improved. Symptoms were unchanged except for increased hostility score. There was a significant gain in net time trade-off in the CRPP group after phase 2. The direct health care expenses in the CRPP and control groups were 15,292 dollars and 15,707 dollars per patient, respectively. Therefore, the cost utility calculated was 640 dollars saved per QALY gained. Savings attributable to CRPP were primarily explained by the lower rate (13% vs 26% of patients, chi2 test=3.9, P <.05) and cost of subsequent PCI (P =.01).\n In an era of managing patients with coronary heart disease, a short-course CRPP was highly cost effective in providing better QOL to patients with recent AMI or after elective PCI. In addition, the improvement of QOL was quick and sustained for at least 2 years after CRPP.", "Current guidelines broadly recommend comprehensive cardiac rehabilitation (CCR), although evidence for this is still limited. We investigated the 12-month effect of hospital-based CCR versus usual care (UC) for a broadly defined group of cardiac patients within the modern therapeutic era of cardiology.\n We conducted a centrally randomized single-center clinical trial with blinded assessment of the primary outcome: registry-based composite of total mortality, myocardial infarction, or acute first-time readmission due to heart disease. Other outcomes were hospitalization, risk profile, and quality of life. The trial included 770 participants (20-94 years) with congestive heart failure (12%), ischemic heart disease (58%), or high risk of ischemic heart disease (30%). Comprehensive cardiac rehabilitation is composed of 6 weeks of intensive intervention and systematic follow-up for 10.5 months.\n We randomized 380 patients to CCR versus 390 to UC. Randomization was well balanced. The primary outcome occurred in 31% of both groups (relative risk 0.96, 95% confidence interval 0.78-1.26). Compared with the UC group, CCR significantly reduced length of stay by 15% (95% confidence interval 1.1%-27.1%, P = .04), mean number of cardiac risk factors above target (4.5 vs 4.1, P = .01), patients with systolic blood pressure below target (P = .003), physically inactivity (P = .01), and unhealthy dietary habits (P = .0003). Short-Form-36 and Hospital Anxiety and Depression Scale did not differ significantly.\n At 12 months, the CCR and UC groups did not differ regarding the primary composite outcome. Comprehensive cardiac rehabilitation significantly reduced length of hospital stay and improved cardiac risk factors.", "The goal of this study was to determine the effects of exercise training (ET) on functional capacity and quality of life (QOL) in patients who received percutaneous transluminal coronary angioplasty (PTCA) or coronary stenting (CS), the effects on the restenosis rate and the outcome.\n It is unknown whether ET induces beneficial effects after coronary angioplasty.\n We studied 118 consecutive patients with coronary artery disease (mean age 57+/-10 years) who underwent PTCA or CS on one (69%) or two (31%) native epicardial coronary arteries. Patients were randomized into two matched groups. Group T (n = 59) was exercised three times a week for six months at 60% of peak VO2. Group C (n = 59) was the control group.\n Only trained patients had significant improvements in peak VO2 (26%, p < 0.001) and quality of life (26.8%, p = 0.001 vs. C). The angiographic restenosis rate was unaffected by ET (T: 29%; C: 33%, P = NS) and was not significantly different after PTCA or CS. However, residual diameter stenosis was lower in trained patients (-29.7%, p = 0.045). In patients with angiographic restenosis, thallium uptake improved only in group T (19%; p < 0.001). During the follow-up (33+/-7 months) trained patients had a significantly lower event rate than controls (11.9 vs. 32.2%, RR: 0.71, 95% confidence interval [CI]: 0.60 to 0.91, p = 0.008) and a lower rate of hospital readmission (18.6 vs. 46%, RR: 0.69, 95% CI: 0.55 to 0.93, p < 0.001).\n Moderate ET improves functional capacity and QOL after PTCA or CS. During the follow-up, trained patients had fewer events and a lower hospital readmission rate than controls, despite an unchanged restenosis rate.", "To evaluate rehabilitation after myocardial infarction.\n Randomised controlled trial of rehabilitation in unselected myocardial infarction patients in six centres, baseline data being collected on admission and by structured interview (of patients and spouses) shortly after discharge and outcome being assessed by structured interview at six months and clinical examination at 12 months.\n Six district general hospitals.\n All 2328 eligible patients admitted over two years with confirmed myocardial infarction and discharged home within 28 days.\n Rehabilitation programmes comprising psychological therapy, counselling, relaxation training, and stress management training over seven weekly group outpatient sessions for patients and spouses.\n Anxiety, depression, quality of life, morbidity, use of medication, and mortality.\n At six months there were no significant differences between rehabilitation patients and controls in reported anxiety (prevalence 33%) or depression (19%). Rehabilitation patients reported a lower frequency of angina (median three versus four episodes a week), medication, and physical activity. At 12 months there were no differences in clinical complications, clinical sequelae, or mortality.\n Rehabilitation programmes based on psychological therapy, counselling, relaxation training, and stress management seem to offer little objective benefit to patients who have experienced myocardial infarction compared with previous reports of smaller trials.", "Falls, loss of health-related quality of life and physical capacity, reduced participation in activities of daily living, and increased fear of falling are all potential outcomes for older adults discharged from hospital. A low-cost video based exercise programme may address this.\n This study was a randomized controlled trial with blinded outcomes assessment and a six-month follow-up.\n Participants were older adults (>65 years) using a mobility aid discharged from a tertiary hospital in Brisbane, Australia, without referral for community-based rehabilitation services.\n A digital video disk-based programme encompassing six exercise types each with six levels of difficulty. A home visit from a project physiotherapist was conducted to ensure patient safety. Control group patients received usual care.\n Falls, health-related quality of life, participation in activities of daily living, physical capacity and fear of falling.\n Study participants (n = 53, 19 intervention, 34 control) experienced decreasing health-related quality of life, several falls (72), and lower levels of participation in activities of daily living over the six-month follow-up. The intervention group did not differ significantly from the control group in terms of the outcomes examined, though a non-significant reduction in the rate of falls was observed. Intervention group participants complied with the exercise programme well during the first two weeks following discharge from hospital but then reduced their compliance levels thereafter.\n The intervention may be beneficial for reducing the rate of falls in this patient population though further research with a larger sample size is indicated.", "Although there are limited clinical data to support the use of exercise training as a means to reduce mortality and morbidity in patients with heart failure, current guidelines state that exercise is beneficial.\n The objective of this trial is to determine whether exercise training reduces all-cause mortality or all-cause hospitalization for patients with left ventricular systolic dysfunction and heart failure symptoms. After undergoing baseline assessments to determine whether they can safely exercise, patients are randomized to either usual care or exercise training. Patients in the exercise training arm attend 36 supervised facility-based exercise training sessions. Exercise modalities are cycling or walking. After completing 18 sessions, patients initiate home-based exercise and then transition to solely home-based exercise after completing all 36 sessions. Patients return for facility-based training every 3 months to reinforce their exercise training program. Patients are followed for up to 4 years. Physiologic, quality-of-life, and economic end points that characterize the effect of exercise training in this patient population will be measured at baseline and at intervals throughout the trial. Blood samples will be collected to examine biomarkers such as brain natriuretic peptide, tumor necrosis factor, and C-reactive protein.\n Because of its relatively low cost, high availability, and ease of use, exercise training is an intervention that could be accessible to most patients with heart failure. The HF-ACTION trial is designed to definitively assess the effect of exercise training on the clinically relevant end points of mortality, hospitalization, and quality of life in patients with heart failure.", "The British Heart Foundation and the Chest, Heart and Stroke Association have allocated funds to develop cardiac rehabilitation programmes. We have recently completed and now evaluate an exercise-based rehabilitation course reinforced with advice about return to normal activity for 110 patients who had suffered acute myocardial infarction. Patients admitted to the Plymouth cardiac care unit were randomised into groups: a control group to receive standard hospital care, and a rehabilitation group who, in addition, received an exercise programme reinforced with advice. Patients were assessed at entry to the study and at intervals thereafter. Assessment was by questionnaire and objective tests consisting of a 12-minute walking test and weekly outpatient pedometry. In the rehabilitation group patients were able to walk further and faster, return to work earlier, undertake more housework, and resume normal sexual activity; they were less short of breath and did not experience more angina. However, the rehabilitation course brought little benefit to the patients' perception of well-being and their anxiety about health or their outlook on life. Exercise and advice are important components of a rehabilitation programme, but more attention needs to be given to the psychological aspects of recovery from a heart attack.", "To determine the short- and long-term effects of an intensive, concentrated rehabilitation programme in patients with chronic heart failure.\n Randomized controlled trial, with one-month and six-year evaluations.\n Residential rehabilitation centre in Switzerland.\n Fifty patients with chronic heart failure, randomized to exercise or control groups.\n A rehabilitation programme lasting one month, including educational sessions, a low-fat diet, and 2 hours of individually prescribed exercise daily.\n Exercise test responses, health outcomes and physical activity patterns.\n Peak Vo(2) increased 21.4% in the exercise group during the rehabilitation programme (P<0.05), whereas peak Vo(2) did not change among controls. After the six-year follow-up period, peak Vo(2) was only slightly higher than that at baseline in the trained group (7%, NS), while peak Vo(2) among controls was unchanged. During long-term follow-up, 9 and 12 patients died in the exercise and control groups, respectively (P = 0.63). At six years, physical activity patterns tended to be higher in the exercise group; the mean energy expenditure values over the last year were 2,704 +/- 1,970 and 2,085 +/- 1,522 kcal/week during recreational activities for the exercise and control groups, respectively. However, both groups were more active compared to energy expenditure prior to their cardiac event (P<0.001).\n Six years after participation in a residential rehabilitation programme, patients with chronic heart failure had slightly better outcomes than control subjects, maintained exercise capacity and engaged in activities that exceed the minimal amount recommended by guidelines for cardiovascular health.", "Despite demonstrated benefits of cardiac rehabilitation and risk factor reduction, only 11% to 38% of eligible patients with cardiovascular disease (CVD) participate in cardiac rehabilitation programs. Women and older adults are particularly less likely to participate in cardiac rehabilitation. In an effort to broaden access to cardiac rehabilitation, the authors developed an alternative Internet-based program that allows nurse case managers to provide risk factor management training, risk factor education, and monitoring services to patients with CVD.\n The evaluation consisted of a randomized, clinical trial involving 104 patients with CVD, 53 of whom used the program as a special intervention (SI) for 6 months and 51 of whom received usual care (UC).\n The results indicate that fewer cardiovascular events occurred among the SI subjects (15.7%) than among the UC subjects (4.1%) (P =.053), resulting in a gross cost savings of $1418 US dollars per patient. With a projected program cost of $453 USD per patient, the return on investment is estimated at 213%. More weight loss occurred in the SI group (-3.68 pounds) than in the UC group (+.47 pounds) (P =.003). The differences between the two groups in terms of blood pressure, lipid levels, depression scores, minutes of exercise, and dietary habits were not statistically significant.\n An Internet-based case management system could be used as a cost-effective intervention for patients with CVD, either independently or in conjunction with traditional cardiac rehabilitation.", "To determine the effectiveness of a home exercise program using transtelephonic exercise monitoring (TEM).\n Prospective, two-group experimental, random assignment.\n Urban centered hospital and surrounding community.\n Twenty cardiac rehabilitation patients entering a Phase II cardiac rehabilitation program.\n Maximal oxygen consumption, blood pressure, pressure-rate product, workload.\n Twenty male cardiac patients were randomly enrolled in either a 12-week home- or hospital-based exercise program. Maximal exercise tolerance tests were conducted, before and after exercise intervention, on a computer-driven bicycle ergometer. Subjects trained 3 days per week for 12 weeks on a bicycle ergometer for a maximum of 35 minutes at 75% of maximum heart rate reserve or functional capacity.\n Posttraining results showed significant improvement in cardiac function for both groups. Two patients in the TEM group developed new arrhythmias while exercising that required medication changes; however, no medical emergencies arose in either exercise group. Independent Student t test showed no significant difference between groups before or after training.\n We conclude that TEM is an effective alternative for the rehabilitation of patients who are unable to return to a hospital-based program.", "The purpose of this prospective randomized controlled trial was to assess the impact of phase III comprehensive cardiac rehabilitation (CR) on health-related quality of life (HRQOL) in elderly patients with coronary artery disease (CAD). Thirty-eight elderly males (mean age, 70 years) with CAD were stratified as the intervention group (n=20) and the control group (n=18). In the intervention group, patients participated in CR for 6 months, whereas in the control group, they received standard care. Validated questionnaires were obtained to evaluate HRQOL using the Medical Outcome Study Short-Form 36 Health Status Survey (SF-36), State-trait anxiety inventory questionnaire (STAI) and Self-rating Depression Scale (SDS) at baseline and after 6 months. At baseline, scores of SF-36 except for general health, STAI and SDS were not different in either group. After 6 months, in the intervention group, scores of bodily pain, general health, vitality and mental health of SF-36 improved significantly compared with baseline. State anxiety scores also improved significantly (p<0.01), but SDS depression scores were not improved. In the control group, none of the parameters significantly changed. These results indicate that elderly patients with CAD should be vigorously encouraged to pursue CR even in chronic phase III.", "This investigation was designed to determine the impact of a brief period of cardiac rehabilitation, initiated within 6 weeks of acute myocardial infarction (AMI), on both disease-specific and generic health-related quality of life, exercise tolerance and return to work after AMI. With a stratified, parallel group design, 201 low-risk patients with evidence of depression or anxiety, or both, after AMI, were randomized to either an 8-week program of exercise conditioning and behavioral counseling or to conventional care. Although the differences were small, significantly greater improvement was seen in rehabilitation group patients at 8 weeks in the emotions dimension of a new disease-specific, health-related Quality of Life Questionnaire, in their state of anxiety and in exercise tolerance. All measures of health-related quality of life in both groups improved significantly over the 12-month follow-up period. However, the 95% confidence intervals around differences between groups at the 12-month follow-up effectively excluded sustained, clinically important benefits of rehabilitation in disease-specific (limitations, -2.70, 1.40; emotions, -4.86, 1.10, where negative values favor conventional care and positive values favor rehabilitation) and generic health-related quality of life (time trade-off, -0.062, 0.052; quality of well-being, -0.042, 0.035) or in exercise tolerance (-38.5, 52.1 kpm/min); also, return to work was similar in the 2 groups (relative risk, 0.93; confidence interval, 0.71, 1.64).(ABSTRACT TRUNCATED AT 250 WORDS)", "BACKGROUND Exacerbations of chronic obstructive pulmonary disease (COPD) are characterised by increased dyspnoea, reduced quality of life and muscle weakness. Re-exacerbation and hospital admission are common. Pulmonary rehabilitation (PR) administered after hospital admission for an exacerbation can improve quality of life and exercise capacity. OBJECTIVE To determine whether outpatient post-exacerbation PR (PEPR) could reduce subsequent hospital admission episodes. METHODS Patients admitted to hospital for an exacerbation of COPD were randomised to receive either usual follow-up care (UC) or PEPR after discharge. Hospital admission and emergency department attendances for COPD exacerbations were recorded over a 3-month period and analysed on an intention-to-treat basis. Secondary outcomes included exercise capacity and quadriceps strength. RESULTS 60 patients underwent concealed randomisation at the time of their hospital discharge (UC: n=30, mean (SD) age 65 (10) years, forced expiratory volume in 1 s (FEV(1)) 52 (22)% predicted; PEPR: n=30, 67(10) years, 52 (20)% predicted). The proportion of patients re-admitted to hospital with an exacerbation was 33% in the UC group compared with 7% in those receiving PEPR (OR 0.15, 95% CI 0.03 to 0.72, p=0.02). The proportion of patients that experienced an exacerbation resulting in an unplanned hospital attendance (either admission or review and discharge from the emergency department) was 57% in the UC group and 27% in those receiving PEPR (OR 0.28, 95% CI 0.10 to 0.82, p=0.02). CONCLUSIONS Post-exacerbation rehabilitation in COPD can reduce re-exacerbation events that require admission or hospital attendance over a 3-month period. Clinical Trials Registration Number NCT00557115.", "The aim of cardiac rehabilitation (CR) is not only physical improvement but also increased quality of life (QoL). A CR programme based upon problem based learning (PBL) philosophy was developed, to achieve and apply new knowledge related to coronary artery disease (CAD). The aim of this paper was to evaluate the impact of the PBL programme on QoL.\n 207 consecutive patients <70 years of age with a recent event of CAD were randomised to a PBL group (n=104) or a control group (n=103). In addition to standard treatment, the PBL patients participated in 13 group sessions during 1 year, where individual learning needs and behavioural changes were focused upon. QoL was measured by the Ladder of Life, Self-Rated Health (SRH), SF 36, and Cardiac Health Profile (CHP).\n Significant differences between the groups, favouring the PBL patients, were found by global instruments: more optimistic expectations of the future QoL and a better general condition. No differences were found by SRH, SF 36 or subscales of CHP, but QoL increased in both groups during the year.\n The main outcome was that QoL improved in both groups with some effects favouring the PBL programme.", "To determine the safety and efficacy of an exercise protocol designed to improve strength, mobility, and balance and to reduce subsequent falls in geriatric patients with a history of injurious falls.\n A randomized controlled 3-month intervention trial, with an additional 3-month follow-up.\n Out-patient geriatric rehabilitation unit.\n Fifty-seven female geriatric patients (mean age 82 +/- 4.8 years; range 75-90) admitted to acute care or inpatient rehabilitation with a history of recurrent or injurious falls including patients with acute fall-related fracture.\n Ambulatory training of strength, functional performance, and balance 3 times per week for 3 months. Patients of the control group attended a placebo group 3 times a week for 3 months. Both groups received an identical physiotherapeutic treatment 2 times a week, in which strengthening and balance training were excluded.\n Strength, functional ability, motor function, psychological parameters, and fall rates were assessed by standardized protocols at the beginning (T1) and the end (T2) of intervention. Patients were followed up for 3 months after the intervention (T3).\n No training-related medical problems occurred in the study group. Forty-five patients (79%) completed all assessments after the intervention and follow-up period. Adherence was excellent in both groups (intervention 85.4 +/- 27.8% vs control 84.2 +/- 29.3%). The patients in the intervention group increased strength, functional motor performance, and balance significantly. Fall-related behavioral and emotional restrictions were reduced significantly. Improvements persisted during the 3-month follow-up with only moderate losses. For patients of the control group, no change in strength, functional performance, or emotional status could be documented during intervention and follow-up. Fall incidence was reduced nonsignificantly by 25% in the intervention group compared with the control group (RR:0.753 CI:0.455-1.245).\n Progressive resistance training and progressive functional training are safe and effective methods of increasing strength and functional performance and reducing fall-related behavioral and emotional restrictions during ambulant rehabilitation in frail, high-risk geriatric patients with a history of injurious falls.", "We sought to determine whether a multidisciplinary outpatient management program decreases chronic heart failure (CHF) hospital readmissions and mortality over a six-month period.\n Hospital admission for CHF is an important problem amenable to improved outpatient management.\n Two hundred patients hospitalized with CHF at increased risk of hospital readmission were randomized to a multidisciplinary program or usual care. A study cardiologist and a CHF nurse evaluated each patient and made recommendations to the patient's primary physician before randomization. The intervention team consisted of a cardiologist, a CHF nurse, a telephone nurse coordinator and the patient's primary physician. Contact with the patient was on a prespecified schedule. The CHF nurse followed an algorithm to adjust medications. Patients in the nonintervention group were followed as usual. The primary outcome was the composite of the number of CHF hospital admissions and deaths over six months, compared by using a log transformation t test by intention-to-treat analysis.\n The median age of the study patients was 63.5 years, and 39.5% were women. There were 43 CHF hospital admissions and 7 deaths in the intervention group, as compared with 59 CHF hospital admissions and 13 deaths in the nonintervention group (p = 0.09). The quality-of-life score, percentage of patients on target vasodilator therapy and percentage of patients compliant with diet recommendations were significantly better in the intervention group. Cost per patient, in 1998 U.S. dollars, was similar in both groups.\n This study demonstrates that a six-month, multidisciplinary approach to CHF management can improve important clinical outcomes at a similar cost in recently hospitalized high-risk patients with CHF.", "In publicly funded health care systems, a waiting period for such services as coronary artery bypass graft surgery (CABG) is common. The possibility of using the waiting period to improve patient outcomes should be investigated.\n To examine the effect of a multidimensional preoperative intervention on presurgery and postsurgery outcomes in low-risk patients awaiting elective CABG.\n Randomized, controlled trial.\n A regional cardiovascular surgery center in a tertiary care hospital, southwestern Ontario, Canada.\n 249 patients on a waiting list for elective CABG whose surgeries were scheduled for a minimum of 10 weeks from the time of study recruitment.\n During the waiting period, the treatment group received exercise training twice per week, education and reinforcement, and monthly nurse-initiated telephone calls. After surgery, participation in a cardiac rehabilitation program was offered to all patients.\n Postoperative length of stay was the primary outcome. Secondary outcomes were exercise performance, general health-related quality of life, social support, anxiety, and utilization of health care services.\n Length of stay differed significantly between groups. Patients who received the preoperative intervention spent 1 less day [95% CI, 0.0 to 1.0 day] in the hospital overall (P = 0.002) and less time in the intensive care unit (median, 2.1 hours [CI, -1.2 to 16 hours]; P = 0.001). During the waiting period, patients in the intervention group had a better quality of life than controls. Improved quality of life continued up to 6 months after surgery. Mortality rates did not differ.\n The waiting period for elective procedures, such as CABG, may be used to enhance in-hospital and early-phase recovery, improving patients' functional abilities and quality of life while reducing their hospital stay.", "The aim of the study was to evaluate a multifactorial rehabilitation programme based on interdisciplinary caring efforts for myocardial infarction (MI) patients. Randomly chosen MI-patients participated, either in a six-month rehabilitation programme (intervention group = 53) or in routine cardiac follow-ups (control group = 63). Subjective and objective instruments were used for measuring their health recovery. Biophysical improvements were showed as an increased physical capacity (p less than 0.001) using a submaximal exercise test six months after MI, and less reinfarctions (p less than 0.024) twelve months after MI, to the intervention patients' advantage. Psychological improvements were demonstrated in a higher life satisfaction (p less than 0.001) six months and (0.1 greater than p greater than 0.05) twelve months after MI to the intervention patients' advantage. Social improvements were indicated as a better leisure situation (p less than 0.004) six months after MI, and as a better partner situation (p less than 0.010), including a less influenced sex life (p less than 0.017), twelve months after MI to the intervention patients' advantage. As to the overall view, the caring rehabilitation programme appeared to be required for the MI-patients' health recovery. In order to be able to reach an optimal state of human health, an even more individualised programme seems to be necessary.", "Exercise as a falls prevention strategy is more complex with people at risk than with the general population. The Lifestyle approach to reducing Falls through Exercise (LiFE) involves embedding balance and lower limb strength training in habitual daily routines.\n A total of 34 community-residing people aged ≥70 years were randomised either into the LiFE programme or into a no-intervention control group and followed up for six months. Inclusion criteria were two or more falls or an injurious fall in the past year.\n There were 12 falls in the intervention group and 35 in the control group. Therelative risk (RR) analysis demonstrated a significant reduction in falls (RR = 0.23; 0.07-0.83). There were indications that dynamic balance (P = 0.04 at three months) and efficacy beliefs (P = 0.04 at six months) improved for the LiFE programme participants. In general, secondary physical and health status outcomes, which were hypothesised as potential mediators of fall risk, improved minimally and inconsistently.\n LiFE was effective in reducing recurrent falls in this at-risk sample. However, there were minimal changes in secondary measures. The study was feasible in terms of recruitment, randomisation, blinding and data collection. A larger randomised trial is needed to investigate long-term efficacy, mechanisms of benefit and clinical significance of this new intervention.", "The effects of a short intervention on behavioral risk factor modification in patients with coronary artery disease (CAD) on Type A behavior, vital exhaustion, and depression were studied in a randomized controlled trial.\n Acute myocardial infarction patients or patients who underwent coronary artery bypass grafting (CABG) were randomly assigned to an 8-week multiple risk modification group program (n = 94) or to a control group (n = 90) that received usual care with standard physical exercise training. Patients were assessed before intervention, directly after intervention, and at 9-month follow-up.\n The intervention was effective in reducing hostility and total Type A behavior at postintervention (P = .01) and at 9-month follow-up (P = .03). The intervention had no overall impact on vital exhaustion and depression, measured by the Beck Depression Inventory (BDI), whereas we unexpectedly found that the percentage of patients with major depression was reduced in the control group but not in the intervention group.\n The results indicate that a short behavioral intervention for coronary patients can result in relatively large and persistent reductions in cognitive aspects of Type A behavior and hostility, in particular. In view of the unwanted findings on the diagnosis of depression, however, we do not unequivocally advise the intervention to the general population of AMI and CABG patients.", "To evaluate risk factor reduction and health-related quality of life following a 10-week cardiac rehabilitation programme in non-acute ischaemic stroke subjects.\n Single-blinded randomized control trial.\n Outpatient rehabilitation.\n Forty-eight community-dwelling ischaemic stroke patients (38 independently mobile, 9 requiring assistance, 1 non-ambulatory) were randomly assigned to intervention or control groups by concealed allocation.\n The trial consisted of a 10-week schedule with measures taken at weeks 1 and 10. Both groups continued usual care (excluding aerobic exercise); intervention subjects attended 16 cycle ergometry sessions of aerobic-training intensity and two stress-management classes.\n Cardiac risk score (CRS); VO(2) (mL O(2)/kg per minute) and Borg Rate of Perceived Exertion (RPE) assessed during a standardized ergometry test; Hospital Anxiety and Depression Scale (HADS); Frenchay Activity Index; Fasting Lipid Profiles and Resting Blood Pressure.\n Group comparison with independent t-tests showed significantly greater improvement at follow-up by intervention subjects than controls in VO(2) (intervention 10.6 +/-1.6 to 12.0 +/- 2.2, control 11.1 +/-1.8 to 11.1 +/-1.9 t=4.734, P<0.001) and CRS (intervention 13.4 +/-10.1 to 12.4 +/-10.5, control 9.4 +/-6.7 to 15.0 +/-6.1 t=-2.537, P<0.05). RPE rating decreased in intervention subjects (13.4 +/-12.2 to 12.4 +/-2.0) and increased in controls (13.8 +/-1.8 to 14.4 +/-1.6); Mann-Whitney U (U = 173.5, P<0.05). Within-group comparison showed significant decrease in the HADS depression subscale in the intervention group alone (5.1 +/-3.4 to 3.0 +/-2.8) (Wilcoxon signed ranks test Z=-3.278, P<0.001).\n Preliminary findings suggest non-acute ischaemic stroke patients can improve their cardiovascular fitness and reduce their CRS with a cardiac rehabilitation programme. The intervention was associated with improvement in self-reported depression.", "The aim of this study was to determine the effects of a home-based exercise program on clinical outcomes. Exercise training improves exercise capacity in patients with heart failure (HF) but the long-term effects on clinical outcomes remain unknown.\n We randomized 173 patients with systolic HF to control (n = 87) or home-based exercise (n = 86). The primary end point was a composite of all-cause hospitalizations, emergency department admissions, urgent transplantation, and death at 12 months. Functional performance (as assessed by cardiopulmonary exercise testing and the 6-minute walk test), quality of life, and psychological states were measured at baseline, 3 months, and 6 months.\n There was no significant difference between experimental and control groups in the combined clinical end point at 12 months and in functional status, quality of life, or psychological states over 6 months. Patients in the exercise group had a lower incidence of multiple (2 or more) hospitalizations compared with the control group: 12.8% versus 26.6%, respectively (P = .018).\n A home-based walking program that incorporated aerobic and resistance exercise did not result in improved clinical outcomes at 1-year follow-up in this cohort of patients with systolic HF. However, the exercise program resulted in reduced rehospitalization rates.", "Common concerns with the traditional protocol (TP) for cardiac rehabilitation include suboptimal program participation, poor facilitation of independent exercise, the use of costly continuous electrocardiographic (ECG) monitoring, and lack of insurance reimbursement. To address these concerns, a reduced cost-modified protocol (MP) was developed to promote independent exercise. Eighty low- to moderate-risk cardiac patients were randomized to a TP (n = 42) or a MP (n = 38) and were compared over 6 months on program participation, exercise adherence, cardiovascular outcomes, and program costs. During month 1, patients followed identical regimens, including 3 ECG-monitored exercise sessions/week, with encouragement to achieve >/=5 thirty-minute sessions/week. In week 5, the TP continued with a facility-based regimen including 3 exercise sessions/week for 6 months and used ECG monitoring the initial 3 months. The MP discontinued ECG monitoring in week 5 and were gradually weaned to an off-site exercise regimen that was complemented with educational support meetings and telephone follow-up. Compared with TP patients, MP patients had higher rates of off-site exercise over 6 months (p = 0.05), and total exercise (on site + off site) during the final 3 months (p = 0.03). Also, MP patients were less likely to drop out (p = 0.05). Both protocols promoted comparable improvements in maximal oxygen uptake (p <0.05), blood lipids (p <0.001), and hemodynamic measurements (p <0.002). The MP cost $738 less/patient than the TP and required 30% less staff (full-time equivalents). These results suggest that a reduced cost MP was as effective as an established TP in improving physiologic outcomes while demonstrating higher rates of exercise adherence and program participation. Thus, the MP or a similar protocol has applicability to hospitals with large capitated or managed care populations to provide cost-effective cardiovascular risk reduction to patients.", "To evaluate the effectiveness and cost-effectiveness of a community nurse-supported hospital discharge programme in preventing hospital re-admissions, improving functional status and handicap of older patients with chronic heart failure.\n Randomized controlled trial; 105 hospitalized patients aged 60 years or over with chronic heart failure and history of hospital admission(s) in previous year were randomly assigned into intervention group (n = 49) and control group (n = 56) for six months. Intervention group subjects received community nurse visits before discharge, within seven days of discharge, weekly for four weeks, then monthly. Community nurse liaised closely with a designated specialist in hospital and were accessible to subjects during normal working hours. Control and intervention group subjects were followed up in the same specialist medical clinics. Primary outcome was the rate of unplanned re-admission at six months. Secondary outcomes were number of unplanned re-admissions, six-minute walking distance, London Handicap Scale and public health care and personal care costs.\n At sixth months, the re-admission rates were not significantly different (46 vs. 57% in control subjects, p = 0.233, Chi-square test). But the median number of re-admissions tended to lower in the intervention group (0 vs. 1 in control group, p = 0.057, Mann Whitney test). Intervention group subjects had less handicap in independence (median change 0 vs. 0.5 in control subjects, p = 0.002, Mann Whitney test), but there was no difference in six-minute walking distance. There was no significant group difference in median total public health care and personal care costs.\n Community nurse-supported post-discharge programme was effective in preserving independence and was probably effective in reducing the number of unplanned re-admissions. The cost benefits to public health care were not significant.\n Older chronic heart failure patients are likely to benefit from post-discharge community nurse intervention programmes. More comprehensive health economic evaluation needs to be undertaken.", "One hundred and eighty-two male post myocardial infarction patients under 65 years old were randomized 30 to 60 days after the acute event into a 6-week rehabilitation programme (RP), a counselling programme without exercise training training (CP) and usual care (UC). Follow-up visits and exercise tests on a bicycle ergometer were performed 2, 12 and 24 months after randomization. Baseline characteristics were identical in the three groups. The percentage of patients reaching the maximal heart rate at exercise test was higher in the RP group even after 2 years (UC = 24%, CP = 13%, RP = 50%, P = 0.001). The number of deaths at 2 years was respectively 4, 5 and 0 in the UC, CP and RP groups (P = 0.08). If UC and CP groups are combined and tested against RP the difference is statistically significant (P = 0.03). Reinfarction rates were similar in the three groups (UC = 10%, CP = 7%, RP = 7%). This study confirms that a rehabilitation programme seems worth recommending in young patients with uncomplicated myocardial infarction.", "The present multicentre study evaluates the differences in efficacy between a 3 month rehabilitation programme including drug treatment, and a 3 month control period of drug treatment only, for asthmatic patients and patients with chronic obstructive pulmonary disease (COPD). The programme was run by physiotherapists in eight local practices, and included exercise training, patient education, breathing retraining, evacuation of mucus, relaxation techniques, and recreational activities. In a randomized controlled trial with a cross-over design, the effects of rehabilitation were evaluated 3 and 6 months after baseline measurements in terms of exercise tolerance and quality of life (QOL). Exercise tolerance was assessed using submaximal cycle ergometer tests and 6 min walking tests. QOL was evaluated by means of the Chronic Respiratory Disease Questionnaire (CRDQ). After 3 months, the patients who started with rehabilitation showed significant improvements in endurance time (421 s) and cardiac frequency (6 beats.min-1) during cycling, walking distance (39 m), and total CRDQ score (17 points) compared to the control group. These improvements were still significant after 6 months. Additional analysis indicated that the asthmatic patients and the patients with COPD responded to rehabilitation in a similar way, with the exception that there was a greater improvement in walking distance for asthmatics. Improvements in exercise tolerance were not significantly correlated with improvements in QOL. Rehabilitation of patients with asthma or chronic obstructive pulmonary disease in local physiotherapy practices improves exercise tolerance and quality of life.", "Beneficial training outcomes have been reported in patients with chronic heart failure (CHF) following leg exercise training. However, data from more comprehensive training programs are limited. The aim of this study was to test the hypothesis that exercise training applying the concept of comprehensive local muscle training can improve aerobic and functional working capacity as well as quality of life in patients with CHF.\n Twenty-four men and women [age 63+/-9 years (mean+/-S.D.)] with stable, moderate chronic heart failure (left ventricular ejection fraction 30+/-10%), were investigated in a randomized controlled study with a training group of 16 patients and a control group of 8 patients. The training was performed as an aerobic resistance training by activating all the main muscle groups, one at a time. The patients exercised for 1 h, three times per week for 8 weeks.\n Patient groups did not differ at baseline. Peak oxygen uptake (8%, P<0.03), the distance walked in a 6-min walking test (11%, P<0.002), the health-related quality of life (P<0.001) and plasma norepinephrine levels at rest (32%, P<0.003) and at submaximal intensities (P<0.03) improved after training. No changes were found in the control group, except for decreased peak oxygen uptake (P<0.02) and quality of life scores (P<0.03).\n Since comprehensive physical training activating a minor muscle mass at a time markedly improves exercise capacity and quality of life and reduces catecholamine levels, it can be recommended for the rehabilitation of patients with CHF under supervision of a physical therapist.", "To examine the short- and long-term effects of an outpatient pulmonary rehabilitation program for COPD patients on dyspnea, exercise, health-related quality of life, and hospitalization rate.\n Secondary-care respiratory clinic in Barcelona.\n We conducted a randomized controlled trial with blinding of outcome assessment and follow-up at 3, 6, 9, 12, 18, and 24 months. Sixty patients with moderate to severe COPD (age 65 +/- 7 years; FEV(1) 35 +/- 14%) were recruited. Thirty patients randomized to rehabilitation received 3 months of outpatient breathing retraining and chest physiotherapy, 3 months of daily supervised exercise, and 6 months of weekly supervised breathing exercises. Thirty patients randomized to the control group received standard care.\n We found significant differences between groups in perception of dyspnea (p < 0.0001), in 6-min walking test distance (p < 0.0001), and in day-to-day dyspnea, fatigue, and emotional function measured by the Chronic Respiratory Questionnaire (p < 0. 01). The improvements were evident at the third month and continued with somewhat diminished magnitude in the second year of follow-up. The PR group experienced a significant (p < 0.0001) reduction in exacerbations, but not the number of hospitalizations. The number of patients needed to treat to achieve significant benefit in health-related quality of life for a 2-year period was approximately three.\n Outpatient rehabilitation programs can achieve worthwhile benefits that persist for a period of 2 years.", "Six weeks after acute myocardial infarction, 303 men were randomly divided into exercise and control groups. The exercise group attended the hospital gymnasium twice weekly for a three-month supervised exercise course. Both groups were exercise tested before and after the course and at subsequent follow-up. The exercise group increased their physical fitness greatly compared with the control group. Eight per cent of the exercise group died during the period of follow-up, compared with 14 per cent of the control group; this difference is not significant. There was an apparent improvement in mortality in those with inferior MI who completed the exercise course, which was not seen in those with MI in other sites. For many patients after MI progressive exercise is safe, improves physical fitness and may reduce mortality for those after inferior MI." ]	Exercise-based cardiac rehabilitation is effective in reducing total and cardiovascular mortality (in medium to longer term studies) and hospital admissions (in shorter term studies) but not total MI or revascularisation (CABG or PTCA). Despite inclusion of more recent trials, the population studied in this review is still predominantly male, middle aged and low risk. Therefore, well-designed, and adequately reported RCTs in groups of CHD patients more representative of usual clinical practice are still needed. These trials should include validated health-related quality of life outcome measures, need to explicitly report clinical events including hospital admission, and assess costs and cost-effectiveness.
CD006210	[ "19915206" ]	[ "Effects of a multifaceted minimal-lift environment for nursing staff: pilot results." ]	[ "Nursing staff are at risk for musculoskeletal injuries because of the physical nature of patient handling. The purpose of this study is to examine the effectiveness of a multifaceted minimal-lift environment on reported equipment use, musculoskeletal injury rates, and workers' compensation costs for patient-handling injuries. The pilot study consists of a mixed measures design, with both descriptive and quasi-experimental design elements. The intervention consists of engineering (minimal-lift equipment), administrative (nursing policy), and behavioral (peer coach program) controls. The comparison nursing unit has received engineering controls only. The convenience sample includes nursing staff employed on two medical-surgical nursing units, who provide direct patient care at least 50% of the time. Nursing staff employed in a multifaceted lift environment report greater lift equipment use and experience less injury, with reduced worker's compensation costs." ]	One study was included in this review. This review therefore indicates that, at present, there is insufficient evidence to support or refute the impact of the physical healthcare environment on work-related outcomes of healthcare staff. Methodological shortcomings, particularly confounding with other variables and the lack of adequate control conditions, partially account for this lack of evidence. Given these methodological issues, the field is in need of well-conducted controlled trials.
CD006272	[ "19135415", "8589019", "8082100", "9391542", "10595816", "15202162", "8265095", "10388135", "8695248", "9552067", "16766588", "7738628", "10532104", "7749764", "12075944" ]	[ "Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial.", "Ondansetron versus granisetron, both combined with dexamethasone, in the prevention of cisplatin-induced emesis. Italian Group of Antiemetic Research.", "Ondansetron versus granisetron in the prevention of chemotherapy-induced nausea and vomiting. Results of a prospective randomized trial.", "A comparative study of intravenous granisetron versus intravenous and oral ondansetron in the prevention of nausea and vomiting associated with moderately emetogenic chemotherapy.", "A prospective randomized trial of the anti-emetic efficacy of ondansetron and granisetron during bone marrow transplantation.", "Single-dose oral granisetron versus multidose intravenous ondansetron for moderately emetogenic cyclophosphamide-based chemotherapy in pediatric outpatients with acute lymphoblastic leukemia.", "Ondansetron compared with granisetron in the prophylaxis of cisplatin-induced acute emesis: a multicentre double-blind, randomised, parallel-group study. The Ondansetron and Granisetron Emesis Study Group.", "A Comparison of Oral Ondansetron and Intravenous Granisetron for the Prevention of Nausea and Emesis Associated with Cisplatin-Based Chemotherapy.", "An open randomised cross-over study on granisetron versus ondansetron in the prevention of acute emesis induced by moderate dose cisplatin-containing regimens.", "Single-dose oral granisetron has equivalent antiemetic efficacy to intravenous ondansetron for highly emetogenic cisplatin-based chemotherapy.", "A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy.", "Comparative clinical trial of granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. The Granisetron Study Group.", "[Evaluation of the anti-emetic effectiveness of two drug formulations of Ondansetron in combined chemotherapy for children with malignant tumors].", "Randomized double-blind crossover ondansetron-dexamethasone versus ondansetron-placebo study for the treatment of chemotherapy-induced nausea and vomiting in pediatric patients with malignancies.", "Comparison of granisetron and ramosetron for the prevention of nausea and vomiting after thyroidectomy." ]	[ "Palonosetron is a second-generation 5-hydroxytryptamine 3 (5-HT(3))-receptor antagonist that has shown better efficacy than ondansetron and dolasetron in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy, and similar efficacy to ondansetron in preventing CINV in patients receiving highly emetogenic chemotherapy. In this phase III, multicentre, randomised, double-blind, double-dummy, stratified, parallel-group, active-comparator trial, we assessed the efficacy and safety of palonosetron versus granisetron for chemotherapy-induced nausea and vomiting, both of which were administered with dexamethasone in patients receiving highly emetogenic chemotherapy.\n Between July 5, 2006, and May 31, 2007, 1143 patients with cancer who were receiving highly emetogenic chemotherapy (ie, cisplatin, or an anthracycline and cyclophosphamide combination [AC/EC]) were recruited from 75 institutions in Japan, and randomly assigned to either single-dose palonosetron (0.75 mg), or granisetron (40 microg/kg) 30 min before chemotherapy on day 1, both with dexamethasone (16 mg intravenously) on day 1 followed by additional doses (8 mg intravenously for patients receiving cisplatin or 4 mg orally for patients receiving AC/EC) on days 2 and 3. A non-deterministic minimisation method with a stochastic-biased coin was applied to the randomisation of patients. Covariates known to effect emetic risk, such as sex, age, and type of highly emetogenic chemotherapy, were used as stratification factors of minimisation to ensure balance between the treatment groups. Primary endpoints were the proportion of patients with a complete response (defined as no emetic episodes and no rescue medication) during the acute phase (0-24 h postchemotherapy; non-inferiority comparison with granisetron) and the proportion of patients with a complete response during the delayed phase (24-120 h postchemotherapy; superiority comparison with granisetron). The non-inferiority margin was predefined in the study protocol as a 10% difference between groups in the proportion of patients with complete response. The palonosetron dose of 0.75 mg was chosen on the basis of two dose-determining trials in Japanese patients. All patients who received study treatment and highly emetogenic chemotherapy were included in the efficacy analyses (modified intention to treat). This trial is registered with ClinicalTrials.gov, number NCT00359567.\n 1114 patients were included in the efficacy analyses: 555 patients in the palonosetron group and 559 patients in the granisetron group. 418 of 555 patients (75.3%) in the palonosetron group had complete response during the acute phase compared with 410 of 559 patients (73.3%) in the granisetron group (mean difference 2.9% [95% CI -2.70 to 7.27]). During the delayed phase, 315 of 555 patients (56.8%) had complete response in the palonosetron group compared with 249 of 559 patients (44.5%) in the granisetron group (p<0.0001). The main treatment-related adverse events were constipation (97 of 557 patients [17.4%] in the palonosetron group vs 88 of 562 [15.7%] in the granisetron group) and raised concentrations of serum aminotransferases (aspartate aminotransferase: 24 of 557 [4.3%] vs 34 of 562 [6.0%]; alanine aminotransferase: 16 of 557 [2.9%] vs 33 of 562 [5.9%]); no grade 4 main treatment-related adverse events were reported.\n When administered with dexamethasone before highly emetogenic chemotherapy, palonosetron exerts efficacy against chemotherapy-induced nausea and vomiting which is non-inferior to that of granisetron in the acute phase and better than that of granisetron in the delayed phase, with a comparable safety profile for the two treatments.\n Taiho Pharmaceutical (Tokyo, Japan).", "Differences in pharmacodynamic and pharmacokinetic characteristics among serotonin-receptor antagonists have been reported in preclinical studies. This prompted us to carry out a study to determine whether such differences are important in terms of clinical efficacy or tolerability.\n 973 consecutive cancer patients scheduled to receive cisplatin for the first time (at doses > or = 50 mg2), entered a double-blind multicenter randomized study comparing intravenous ondansetron 8 mg versus granisetron 3 mg. Dexamethasone 20 mg was added to both serotonin antagonists. On days 2 to 4 after chemotherapy all patients received oral metoclopramide plus intramuscular dexamethasone as antiemetic prophylaxis for delayed emesis. Nausea and vomiting were assessed daily until day 6 after chemotherapy.\n We evaluated 966 patients (483 receiving ondansetron and 483 granisetron). Complete protection from acute vomiting/nausea was obtained in 79.3%/72.0% of patients receiving ondansetron and in 79.9%/71.8% of those receiving granisetron. Complete protection from delayed vomiting/nausea as obtained in 69.7%/52.9% and 70.0%/49.6% of patients receiving the ondansetron or granisetron regimens, respectively. Adverse effects were mild and not significantly different between the two antiemetic regimens.\n Ondansetron 8mg and granisetron 3 mg, both combined with dexamethasone, showed similar efficacy and tolerability in the prevention of cisplatin-induced emesis. The choice between the two regimens can be dictated by their respective purchase prices.", "A single-institution, prospective, randomized open trial was performed to compare ondansetron and granisetron in the prevention of chemotherapy-related nausea and vomiting. The effect of antemetic drugs was analyzed indipendently for patients treated with highly emetogenic chemotherapy (Study 1), and those treated with moderately emetogenic regimens (Study 2).\n In Study 1, 182 patients treated with chemotherapeutic regimens containing high dose cisplatin (more than 70 mg/m2) were randomized to receive 24 mg of ondasentron intravenously (i.v.) or 3 mg of granisetron i.v. for the control of acute emesis. Patients treated with fractionated chemotherapy and those followed-up for delayed emesis also received 8 mg of ondansetron orally twice a day or 3 mg of granisetron i.v. on the days after Day 1. In Study 2, 164 patients were randomized to receive either 16 mg of ondansetron i.v. or 3 mg of granisetron i.v. to prevent emesis in the first 24 hours.\n In the ondansetron group in Study 1, a complete response (CR) (i.e., no vomiting, nausea possible) from acute emesis was achieved in 52% of cases, a major response (MR) in 29%, and a minor response (MiR) in 14%. In the granisetron group in Study 1, a CR was seen in 49% of patients, an MR in 24%, and an MiR in 12%. Failure was recorded in 5% and 15% of cases in the ondansetron and granisetron groups, respectively. No statistically significant difference in any response category was seen between the two groups. In the ondansetron group, a complete protection from delayed emesis was recorded in 39% of cases, an MR in 32%, an MiR in 21%, and failure in 16%. In the granisetron arm, 36% of the patients had a CR, 22% had an MR, 14% had an MiR, and 14% experienced treatment failure. Again, these differences did not reach statistical significance. In Study 2, no statistical significant difference was observed between the ondansetron arm and the granisetron arm, both for acute and delayed emesis. Both ondansetron and granisetron were tolerated very well by most patients, with no severe side effects. In the group of patients treated with ondansetron, however, the incidence of headache (9%) was higher than in the group treated with granisetron (4%).\n These data suggest that although both ondansetron and granisetron are very effective drugs for the control of acute emesis, their efficacy against delayed emesis is still not entirely satisfactory.", "We conducted a prospective, randomized, open, single-center, parallel group study comparing the anti-emetic efficacy and toxicity of granisetron with that of ondansetron in patients receiving moderately emetogenic chemotherapy. From December 1994 to May 1995, patients who were to receive moderately emetogenic chemotherapy for the first time or who had not received chemotherapy (80 to 100 mg/m2 of cisplatin or 40 mg/m2 of doxorubicin) within 4 weeks previously were enrolled in this study. The following anti-emetic regimens were used: 3 mg of granisetron were given intravenously before chemotherapy for a single dose; 8 mg of ondansetron were given intravenously before chemotherapy and then every 8 hours for a total of 3 doses, plus 8 mg of an oral maintenance dose every 12 hours for 5 consecutive days. We evaluated 97 patients (48 received granisetron and 49 received ondansetron). In the first 24 hours after chemotherapy, complete and major responses were achieved in 76.6% of the patients receiving granisetron and in 72.9% of patients receiving ondansetron (p = 0.9033). Additionally, there was no difference in the control of delayed nausea and vomiting between the two groups (51.1% versus 54.2%, p = 0.9200), and there were no significant adverse effects or toxicities. We have concluded that a single dose of granisetron is as effective in prophylaxis of emesis induced by moderately emetogenic chemotherapy as a triple dose of ondansetron plus oral maintenance.", "To determine the comparative anti-emetic efficacy of ondansetron and granisetron in patients undergoing bone marrow transplantation, we performed a double-blind, randomized trial in pediatric and adult patients receiving transplants at the University of Minnesota. The results in 187 patients stratified by age (<18 years, n = 51; > or =18 years, n = 136) were analyzed. The average number of emetic episodes in the entire group from day -7 to 2 was 0.86/day for patients receiving ondansetron and 0.73/day for those receiving granisetron (p = 0.32). No differences were noted between the two drugs in total days of complete or major control of emesis or in the number of requests for additional drugs to alleviate symptoms of nausea. The use of total-body irradiation-containing conditioning regimens was associated with a decreased number of emetic episodes compared with regimens of chemotherapy alone. Perceived nausea was evaluated using a nausea scoring system, and no differences were apparent between the granisetron and ondansetron groups; however, reported nausea was significantly higher in females (p<0.01) and in the adult population (p = 0.05). We conclude that both ondansetron and granisetron provide good control of nausea and vomiting experienced with conditioning regimens for bone marrow transplantation. The relative cost of the drugs within an institution must be considered in developing standard anti-emetic regimens for bone marrow transplantation.", "This prospective study was designed to compare the efficacy of ondansetron with granisetron in terms of complete emesis control and time spent in an ambulatory care setting in children with acute lymphoblastic leukemia (ALL) undergoing moderately emetogenic cyclophosphamide-based chemotherapy. The costs for both treatments are also examined. A total of 33 children (mean age: 7.8 +/- 4.9 year) were studied during 66 chemotherapy cycles. Analysis was based on 33 courses of a single oral dose of granisetron and 33 courses of ondansetron incorporating 2 intravenous doses of ondansetron 0.15 mg/kg followed by 1 dose of the same dosage orally. There was no significant difference between the 2 treatments in terms of overall efficacy (McNemar's chi-square test). Twenty of 33 patients (60.6%) receiving granisetron and 15 of 33 patients (45.5%) receiving ondansetron experienced no emesis 24 h after chemotherapy (p = .227). Boys experienced greater rates of vomiting than did girls despite antiemetic treatment; however, no apparent reason for the gender discrepancy was noted. Both antiemetic regimens have similar antiemetic efficacy for treating the moderately emetogenic effects associated with cyclophosphamide-based chemotherapy. It is possible that the granisetron regimen may be preferable because it is simpler to administer and more cost-effective.", "This is the first international, multi-centre, double-blind, randomised, parallel group study to directly compare the efficacy and safety profile of a single intravenous dose of ondansetron (8 or 32 mg) with granisetron (3 mg) in the control of cisplatin-induced acute emesis. A total of 496 patients were randomised to receive one of three anti-emetic treatments prior to cisplatin chemotherapy (> or = 50 mg/m2). Of these, 165 and 162 patients received 8 and 32 mg of ondansetron, respectively, and 169 patients received 3 mg of granisetron. Complete control of emesis (0 emetic episodes) over 24 h was reported in 59% of patients in the 8-mg ondansetron group, 51% of patients in the 32-mg ondansetron group and 56% of patients in the granisetron group. Complete or major control (< or = 2 emetic episodes) was achieved in 76 and 74% of patients in the 8- and 32-mg ondansetron group, respectively, compared with 78% of patients in the granisetron group. Nausea graded none or mild 24 h after the start of cisplatin infusion was reported in 71 and 69% of patients in the 8- and 32-mg ondansetron groups, respectively, and in 73% of patients in the granisetron group. There were no significant differences between the treatment groups when global satisfaction scores were compared. Logistic regression models were fitted to assess any interaction between treatments and prognostic factors (age, gender, alcohol use, cisplatin dose or concomitant chemotherapy) on complete or major response, but there was no evidence of interaction for any factor. All three anti-emetic treatments were well tolerated and no severe or unexpected drug-related adverse events were observed with ondansetron or granisetron. Headache, the most reported drug-related adverse event for all three treatment groups, occurred in 9% of all patients. In summary, no significant difference was observed between any of the treatment groups with respect to emesis, nausea or drug-related adverse events.", "PURPOSE: To compare the efficacy and safety of oral ondansetron with i.v. granisetron each given as a single dose prior to administration of highly emetogenic cisplatin chemotherapy. PATIENTS AND METHODS: Chemotherapy-naive patients with histologically confirmed malignancies were randomized to receive a single 24 mg ondansetron hydrochloride tablet plus a 50 ml i.v. infusion of normal saline, or a single 10 µg/kg (50 ml) i.v. infusion of granisetron plus a placebo tablet in this multicenter, double-blind, parallel-group trial. Study drug was administered 30 min prior to a single i.v. infusion of cisplatin (50-75 mg/m²), given over a period of </= 3 h. Concurrent administration of corticosteroids was not allowed. Efficacy measurements included the number of emetic episodes, need for rescue medication, and patient assessments of nausea and appetite. Complete response (CR) was defined as no emetic episodes, rescue, or withdrawal; major response was defined as one or two episodes. Safety was evaluated by monitoring adverse events and changes in laboratory parameters. RESULTS: A total of 371 patients entered the study and received study drug, of whom 184 received ondansetron and 187 received granisetron. For all parameters tested, a single 24 mg oral ondansetron tablet was at least as effective as i.v. granisetron. CR was achieved in 58% of ondansetron-treated patients and 51% of granisetron-treated patients (95% confidence interval on the difference: -4% to 17%). Subjective assessments revealed no difference with regard to complete control of nausea, appetite, or satisfaction with antiemetic therapy. Both drugs were well tolerated; the most common adverse event was headache. CONCLUSION: A single 24 mg oral dose of ondansetron is at least as safe and effective as a single i.v. infusion of 10 µg/kg of granisetron in preventing nausea and vomiting induced by highly emetogenic cisplatin chemotherapy.", "The aim of the study was to compare granisetron (GRA) with ondansetron (OND) in the prevention of acute emesis in consecutive chemotherapy-naive patients admitted to our department to receive a cytotoxic treatment containing cisplatinum (CP) at a dose > or = 50 mg/m2. Eligible patients were randomised at their first cycle to receive either OND or GRA with cross-over of the anti-emetic treatment on the second cycle. The cytotoxic treatments included five different multidrug regimens containing CP (median dose 60 mg/m2, range 50-70 mg/m2) administered on day 1 and repeated every 21-28 days. OND was administered at the dose of 8 mg x 3 i.v. on day 1 and 8 mg x 2 orally on day 2. GRA was always administered at the dose of 3 mg i.v. on day 1. 124 patients entered the study. 58 patients received OND at their first cycle and 66 received GRA. Complete protection of acute emesis with OND and GRA was observed, with the first and second cycles combined as follows: nausea 53 and 60%, vomiting 68 and 71%, respectively (no statistically significant difference). The cross-over analysis comprising 101 patients confirmed no difference between the two anti-emetic treatments. 21 patients (19%) on OND and 14 patients (12%) on GRA suffered headaches (P = 0.15). 25 (25%) patients preferred OND, 45 (45%) preferred GRA, while 31 (30%) expressed no preference (P = 0.003). However, these differences also depended on the sequence of anti-emetics in the cross-over. In conclusion, in this study, a single dose of GRA is demonstrated to be as effective as multiple doses of OND in the prevention of acute emesis.", "To compare the antiemetic efficacy of a single dose of an oral antiemetic (granisetron 2 mg) with a single dose of an intravenous (i.v.) antiemetic (ondansetron 32 mg) given before cisplatin-based chemotherapy.\n This was a multicenter, randomized, double-blind, parallel-group study. Patients (N = 1,054) scheduled to receive cisplatin (> or = 60 mg/m2)-based chemotherapy were randomized to receive either 2 mg of oral granisetron tablets 1 hour before chemotherapy (n = 534) or i.v. ondansetron (32 mg) 30 minutes before chemotherapy (n = 520). The primary efficacy end point was total control (no emesis, no nausea, and no use of antiemetic rescue medication) over the initial 24 hours after the start of chemotherapy. Dexamethasone or methylprednisolone were permitted, but not required, as concomitant prophylactic antiemetics.\n Total control was equivalent 24 hours after cisplatin chemotherapy for single-dose oral granisetron (54.7%) and i.v. ondansetron (58.3%) (95% confidence interval [CI], -9.6 to 2.4). Similar proportions of patients remained nausea-free in the granisetron group (55.4%) and the ondansetron group (59%) (95% CI, -9.6 to 2.4). The rate of complete control of emesis was 61.2% in the granisetron group and 67.1% in the ondansetron group (95% CI, -11.7 to -0.1). Both treatment regimens were well tolerated, with similar patterns of adverse reactions, generally of a mild degree. The most common side effects included constipation (14%), headache (15%), and diarrhea (10%).\n Oral granisetron, administered as a single 2-mg dose, provided equivalent total antiemetic control when compared with i.v. ondansetron (32 mg) in patients who received highly emetogenic, cisplatin-based chemotherapy.", "This pivotal phase III trial evaluated the efficacy and safety of palonosetron in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC).\n Patients were randomized to a single intravenous dose of palonosetron 0.25 mg or 0.75 mg, or ondansetron 32 mg prior to HEC. Dexamethasone pre-treatment (with stratification) was used at investigator discretion. The primary efficacy endpoint was the proportion of patients with complete response (CR) during the first 24 h post-chemotherapy (acute phase).\n In the intent-to-treat analysis (n = 667), palonosetron 0.25 mg and 0.75 mg were at least as effective as ondansetron in preventing acute CINV (59.2%, 65.5%, and 57.0% CR rates, respectively); CR rates were slightly higher with palonosetron than ondansetron during the delayed (24-120 h) and overall (0-120 h) phases. Two thirds of patients (n = 447) received concomitant dexamethasone. Patients pre-treated with palonosetron 0.25 mg plus dexamethasone had significantly higher CR rates than those receiving ondansetron plus dexamethasone during the delayed (42.0% versus 28.6%) and overall (40.7% versus 25.2%) phases. Palonosetron and ondansetron were well tolerated.\n Single-dose palonosetron was as effective as ondansetron in preventing acute CINV following HEC, and with dexamethasone pre-treatment, its effectiveness was significantly increased over ondansetron throughout the 5-day post-chemotherapy period.", "To compare the efficacy and safety of granisetron and ondansetron, serotonin (5-HT3) receptor antagonists shown to be effective in the prevention of chemotherapy-induced emesis.\n In a double-blind, randomized, stratified, parallel-group study, the efficacy and safety of granisetron and ondansetron were compared in 987 chemotherapy-naive patients who received cisplatin in doses > or = 60 mg/m2. Granisetron was administered as a single dose of 10 or 40 micrograms/kg before the start of chemotherapy. Ondansetron was administered in doses of 0.15 mg/kg before and 4 and 8 hours after the start of chemotherapy. The three treatment groups were well-matched with respect to demographic characteristics and the dose of cisplatin administered.\n For all evaluations, single doses of granisetron 10 or 40 micrograms/kg were as effective as three 0.15-mg/kg doses of ondansetron. Total control (no vomiting, no retching, no nausea, and no use of rescue) was attained by 38%, 41%, and 39% of all patients who received granisetron 10 microgram/kg, granisetron 40 micrograms/kg, and ondansetron, respectively. No vomiting or retching and no use of rescue antiemetics were reported in 47%, 48%, and 51% of patients who received granisetron 10 micrograms/kg, granisetron 40 micrograms/kg, and ondansetron, respectively; no nausea and no use of rescue antiemetics were reported in 39%, 42%, and 40% of patients, respectively.\n All three treatment regimens were well-tolerated. The results of this study indicate that a single dose of granisetron 10 or 40 micrograms/kg is as effective as three doses of ondansetron 0.15 mg/kg in the prevention of nausea and vomiting induced by cisplatin chemotherapy.", "A double-blind randomized comparison (protocol S3AB4003, Glaxo Wellcome, Great Britain) carried out in a group of 52 children showed that the 5-HT3-receptor antagonist ondansetron (in syrup) effectively prevented vomiting, nausea and loss of appetite caused in combination chemotherapy with highly- or moderately emetogenic cytostatic drugs in 92.3; 69.3 and 81.0%, respectively. Treatment was given to patients who were on dexamethasone. With intravenous injection of ondansetron plus dexamethasone, per os, said indices were 88.5; 73.2%; 73.2%, respectively, thus showing no significant differences. No side-effects were observed with either regimen.", "To determine whether the addition of dexamethasone to ondansetron (OND + DEX) is a more effective antiemetic regimen than ondansetron (OND) alone in children receiving chemotherapy.\n Children who had solid tumors and who were receiving highly emetogenic chemotherapy, including cisplatin, carboplatin, cyclophosphamide, and ifosfamide, were randomized (1:1) in a double-blind fashion to receive either OND 0.15 mg/kg intravenously (i.v.) 30 min before and 4 and 8 h after chemotherapy and placebo, or OND + DEX (same OND doses plus DEX 8 mg/m2 i.v. 30 min before chemotherapy, followed by 16 mg/m2 in divided doses) as antiemetics. The patients were crossed over to the other antiemetic regimen when receiving an identical course of chemotherapy. Patients were monitored for emetic episodes, nausea, appetite, sense of well-being, and antiemetic adverse events.\n A total of 33 patients were evaluated. Sixty-one percent of the patients receiving OND + DEX regimens had a complete response for emetic episodes as compared with 23% with OND alone. Combined complete and major responses (two or less emetic episodes) were 86% for OND + DEX and 67% for OND. Failure for emetic episodes (more than five vomitings/day) were seen only in 7-10% of the total population. Minimal or no nausea was experienced in 74% of OND + DEX courses and in 52% of the OND courses. Appetite was better in OND + DEX courses (p = 0.006). Both antiemetic arms had similar adverse events. Mild to moderate sedation occurred in about half of the courses, followed by restlessness (29%), headache (17%), diarrhea (17%), and hiccups (2%).\n The combination of ondansetron and dexamethasone is superior to ondansetron alone to control emetic episodes in children receiving highly emetogenic chemotherapy (p = 0.04).", "Postoperative nausea and vomiting (PONV) are common after thyroidectomy. Granisetron, a selective 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, is more effective than the traditional antiemetics droperidol and metoclopramide for the prevention of PONV after thyroidectomy. Ramosetron, another new selective antagonist of 5-HT3 receptor, has been shown to have more potent and longer-acting properties than granisetron against cisplatin-induced emesis in ferrets.\n This study was undertaken to compare the efficacy and tolerability of granisetron and ramosetron for the prevention of PONV after thyroidectomy.\n In this randomized, double-blind study, patients received granisetron 3 mg or ramosetron 0.3 mg intravenously at the end of surgery. A standard general anesthetic technique and postoperative analgesia were used. Emetic episodes and safety were assessed during the first 24 hours and the second 24 hours after anesthesia.\n Eighty patients (15 men, 65 women) aged 33 to 58 years were included in the study. Each study group consisted of 40 patients. There were no differences between groups with regard to patient demographics. The percentage of patients who were emesis free (no nausea, no retching, no vomiting) 0 to 24 hours after anesthesia was 83% (33 of 40) with granisetron and 88% (35 of 40) with ramosetron; the corresponding rates 24 to 48 hours after anesthesia were 63% (25 of 40) and 90% (36 of 40), respectively (P = 0.004). The safety profile of the two 5-HT3 receptor antagonists was comparable, as no clinically serious adverse effects caused by the study drug were observed in either of the groups.\n Prophylactic antiemetic therapy with ramosetron was comparable to therapy with granisetron for the prevention of PONV 0 to 24 hours after anesthesia in patients who underwent thyroidectomy; 24 to 48 hours after anesthesia, ramosetron was more ef- fective than granisetron for prophylaxis against PONV in this population." ]	Ondansetron and granisetron appear to be equivalent drugs for the prevention of acute and delayed emesis following the use of highly emetogenic chemotherapy. According to one single trial the combination of palonosetron and dexamethasone was superior to granisetron and dexamethasone in controlling delayed emesis. However, more evidence is needed before palonosetron could become the candidate 5-HT3 RA for the control of delayed emesis induced by highly emetogenic chemotherapy.
CD004827	[ "20145608", "17690340", "17803667", "18410562", "18813028", "18701826", "12150178", "12150179", "22472744", "20400916", "16393304", "15815206", "14518142", "7872284" ]	[ "Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients.", "Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations.", "Efficacy of Lactobacillus rhamnosus GG in acute watery diarrhoea of Indian children: a randomised controlled trial.", "Clinical trial: effectiveness of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) in the prevention of antibiotic-associated diarrhoea in children.", "Efficacy of high-dose Lactobacillus rhamnosus GG in controlling acute watery diarrhea in Indian children: a randomized controlled trial.", "Bifidobacterium longum PL03, Lactobacillus rhamnosus KL53A, and Lactobacillus plantarum PL02 in the prevention of antibiotic-associated diarrhea in children: a randomized controlled pilot trial.", "Effect of probiotic Lactobacillus strains in young children hospitalized with acute diarrhea.", "Effect of probiotic Lactobacillus strains on acute diarrhea in a cohort of nonhospitalized children attending day-care centers.", "Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized, double-blind, placebo-controlled trial.", "Efficacy of Lactobacillus GG in aboriginal children with acute diarrhoeal disease: a randomised clinical trial.", "Treatment of acute infectious diarrhoea in infants and children with a mixture of three Lactobacillus rhamnosus strains--a randomized, double-blind, placebo-controlled trial.", "A randomized formula controlled trial of Bifidobacterium lactis and Streptococcus thermophilus for prevention of antibiotic-associated diarrhea in infants.", "Effect of Lactobacillus strains and Saccharomyces boulardii on persistent diarrhea in children.", "Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo." ]	[ "Standard therapies for antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) have limited efficacy. Probiotic prophylaxis is a promising alternative for reduction of AAD and CDAD incidence.\n In this single-center, randomized, double-blind, placebo-controlled dose-ranging study, we randomized 255 adult inpatients to one of three groups: two probiotic capsules per day (Pro-2, n=86), one probiotic capsule and one placebo capsule per day (Pro-1, n=85), or two placebo capsules per day (n=84). Each probiotic capsule contained 50 billion c.f.u. of live organisms (Lactobacillus acidophilus CL1285 +Lactobacillus casei LBC80R Bio-K+ CL1285). Probiotic prophylaxis began within 36 h of initial antibiotic administration, continued for 5 days after the last antibiotic dose, and patients were followed for an additional 21 days.\n Pro-2 (15.5%) had a lower AAD incidence vs. Pro-1 (28.2%). Each probiotic group had a lower AAD incidence vs. placebo (44.1%). In patients who acquired AAD, Pro-2 (2.8 days) and Pro-1 (4.1 days) had shorter symptom duration vs. placebo (6.4 days). Similarly, Pro-2 (1.2%) had a lower CDAD incidence vs. Pro-1 (9.4%). Each treatment group had a lower CDAD incidence vs. placebo (23.8%). Gastrointestinal symptoms were less common in the treatment groups vs. placebo and in Pro-2 vs. Pro-1.\n The proprietary probiotic blend used in this study was well tolerated and effective for reducing risk of AAD and, in particular, CDAD in hospitalized patients on antibiotics. A dose-ranging effect was shown with 100 billion c.f.u., yielding superior outcomes and fewer gastrointestinal events compared to 50 billion c.f.u. (ClinicalTrials.gov number NCT00958308).", "To compare the efficacy of five probiotic preparations recommended to parents in the treatment of acute diarrhoea in children. Design Randomised controlled clinical trial in collaboration with family paediatricians over 12 months.\n Primary care.\n Children aged 3-36 months visiting a family paediatrician for acute diarrhoea.\n Children's parents were randomly assigned to receive written instructions to purchase a specific probiotic product: oral rehydration solution (control group); Lactobacillus rhamnosus strain GG; Saccharomyces boulardii; Bacillus clausii; mix of L delbrueckii var bulgaricus, Streptococcus thermophilus, L acidophilus, and Bifidobacterium bifidum; or Enterococcus faecium SF68.\n Primary outcomes were duration of diarrhoea and daily number and consistency of stools. Secondary outcomes were duration of vomiting and fever and rate of admission to hospital. Safety and tolerance were also recorded.\n 571 children were allocated to intervention. Median duration of diarrhoea was significantly shorter (P<0.001) in children who received L rhamnosus strain GG (78.5 hours) and the mix of four bacterial strains (70.0 hours) than in children who received oral rehydration solution alone (115.0 hours). One day after the first probiotic administration, the daily number of stools was significantly lower (P<0.001) in children who received L rhamnosus strain GG and in those who received the probiotic mix than in the other groups. The remaining preparations did not affect primary outcomes. Secondary outcomes were similar in all groups.\n Not all commercially available probiotic preparations are effective in children with acute diarrhoea. Paediatricians should choose bacterial preparations based on effectiveness data.\n Current Controlled Trials ISRCTN56067537 [controlled-trials.com].", "To evaluate the role of Lactobacillus rhamnosus GG (LGG) as probiotic in acute watery diarrhoea (AWD).\n Hospital-based study.\n Randomised, controlled, blinded trial.\n All patients of AWD (n = 684) admitted over 1-year period were invited to participate in the study as per predefined inclusion and exclusion criteria and were randomised to intervention and control groups. After adequate rehydration the intervention group (n = 330) received ORS with probiotic powder containing 60 million cells of LGG, while the control group (n = 332) received ORS alone twice daily for a minimum period of 7 days or till diarrhoea ceased. During the study period all patients received ORS and/or IV fluids for ongoing losses, and nutritional supplementation. None of them received any antibiotic or antidiarrhoeal medication. After exclusion of 16 patients, 646 (323 in each arm) patients completed the study. The daily frequency and total duration of diarrhoea and vomiting and the length of hospital stay were studied. Data were analysed by SPSS-10 software. Statistical significance was calculated by Student's t-test and chi2-test.\n Rotavirus was isolated in 75.85%. There was no significant difference between treatment groups in the daily frequency or duration of diarrhoea or vomiting or in the length of hospital stay. No complication was observed from the use of LGG.\n LGG supplementation does not decrease the frequency and duration of diarrhoea and vomiting in children with AWD, and does not reduce hospital stay in these patients.", "Convincing evidence that probiotic administration can lower the risk of antibiotic-associated diarrhoea is limited to certain micro-organisms.\n To determine the efficacy of administration of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) for the prevention of antibiotic-associated diarrhoea in children.\n Children (aged 3 months to 14 years) with common infections were enrolled in a double-blind, randomized, placebo-controlled trial in which they received standard antibiotic treatment plus 2 x 10(10) colony forming units of a probiotic (n = 120) or a placebo (n = 120), administered orally twice daily throughout antibiotic treatment. Analyses were by intention to treat.\n Any diarrhoea (>or=3 loose or watery stools/day for >or=48 h occurring during or up to 2 weeks after the antibiotic therapy) occurred in nine (7.5%) patients in the probiotic group and in 20 (17%) patients in the placebo group (relative risk, RR 0.45, 95% confidence interval, CI 0.2-0.9). Three (2.5%) children in the probiotic group developed AAD (diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea) compared to nine (7.5%) in the placebo group (RR 0.33, 95% CI 0.1-1.06). No adverse events were observed.\n Administration of L. rhamnosus (strains E/N, Oxy and Pen) to children receiving antibiotics reduced the risk of any diarrhoea, as defined in this study.", "To evaluate the effective dose of Lactobacillus rhamnosus GG (LGG) as probiotic in acute watery diarrhea (AWD) in Indian children.\n Hospital-based study.\n Randomized, controlled, blinded trial.\n All patients of AWD admitted over 1 year were included in the study. They were randomized into 3 groups to receive either only oral rehydration solution (ORS) (group A/control), ORS+LGG powder containing 10(10) colony forming units (CFU) (group B), or ORS+LGG powder containing 10(12) CFU (group C) twice daily for a minimum period of 7 days or until diarrhea stopped along with correction of dehydration. None of them received any other drug such as antibiotic or antidiarrheal medication. The duration and frequency of diarrhea and vomiting were studied. Data were analyzed by SPSS-10 software.\n The study comprised of 559 patients, group A/controls (n=185), group B (n=188), and group C (n=186). All the groups were similar with respect to age, number of breastfed infants, presentation with dehydration, degree of protein energy malnutrition, and rotavirus infection. The frequency and duration of diarrhea, requirement for intravenous therapy, and hospital stay were significantly lower in both the intervention groups compared with the controls. There was no significant difference between the 2 intervention groups. No complication was observed from the doses of LGG used.\n Both the doses of LGG (10(10) and 10(12) CFU) were equally effective to decrease the frequency and duration of diarrhea and reduction in hospital stay in patients of AWD.", "To determine the efficacy of a combination of Bifidobacterium longum PL03, Lactobacillus rhamnosus KL53A and Lactobacillus plantarum PL02 for the prevention of antibiotic-associated diarrhea in children.\n Seventy-eight children (age: 5 months to 16 years) with otitis media, and/or respiratory tract infections, and/or urinary tract infections were enrolled in a double-blind randomized control trial in which they received standard antibiotic treatment plus a food supplement containing 10(8) colony-forming units of B. longum, L. rhamnosus and L. plantarum (n = 40) or a placebo (n = 38) orally twice daily for the duration of antibiotic treatment.\n Patients receiving probiotics had a similar rate of diarrhea (> or =3 loose or watery stools/day for > or =48 h occurring during or up to 2 weeks after the antibiotic therapy) as those receiving placebo (relative risk 0.5, 95% CI 0.06-3.5). The mean number of stools per day was significantly lower in the experimental group (mean difference -0.3 stool/day, 95% CI -0.5 to -0.07). No adverse events were reported.\n The administration of the 3 probiotics did not significantly alter the rate of diarrhea, although it reduced the frequency of stools per day. As the overall frequency of diarrhea was surprisingly low, these results should be interpreted with caution.\n 2008 S. Karger AG, Basel.", "Oral bacteriotherapy promotes recovery from acute childhood diarrhea, but few strains have been shown to have therapeutic potentials. We examined the effect of two newly identified probiotic Lactobacillus strains in acute childhood diarrhea.\n Sixty-nine children were randomized during hospitalization for acute diarrhea to receive a mixture of Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 12246, 10(10) colony-forming units of each strain or placebo twice daily for 5 days. Before selection of these stains their potential probiotic characteristics were demonstrated in vitro and in healthy volunteers.\n In patients receiving probiotics, the diarrheal phase was reduced by 20%. The duration of diarrhea was 82 h in the treatment group vs. 101 h in the control group (not significant, P = 0.07). However, 3 of 30 patients from the treatment group vs. 13 of 39 from the control group still had loose stools at the end of the study period (P = 0.03). In patients with diarrhea for <60 h before start of treatment (early intervention), a clear effect of the probiotics was demonstrated (80 h in the treatment group vs. 130 h in the control group, P = 0.003). After early intervention, the length of hospitalization was reduced by 48% (3.5 vs. 1.7 days, P = 0.03). At the end of the intervention, rotavirus antigen was found in 12% of patients from the treatment group vs. 46% from the control group (P = 0.02).\n The two probiotics, L. rhamnosus 19070-2 and L. reuteri DSM 12246, ameliorated acute diarrhea in hospitalized children and reduced the period of rotavirus excretion. Oral bacteriotherapy was associated with a reduced length of hospital stay. The beneficial effects were most prominent in children treated early in the diarrheal phase.", "Certain strains of lactobacilli have been shown to promote recovery from rotavirus enteritis in hospitalized children. Few studies have examined the effect of probiotics in nonhospitalized children with mild diarrhea.\n We studied in a randomized placebo-controlled trial the effect of lyophilized Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 12246, 10(10) colony-forming units of each strain twice daily for 5 days, on acute diarrhea in children in a cohort of children recruited from local day-care centers. The duration of diarrhea and assessment of stool consistency were recorded by the parents.\n In patients treated with the selected Lactobacillus strains, the mean duration of diarrhea after intervention was reduced (76 h in patients treated with probiotics vs. 116 h in the placebo group; P = 0.05). In patients with diarrhea for <60 h before start of treatment (early intervention), a more pronounced effect of probiotics was found. The time to recovery after early treatment was 79 h vs. 139 h in the placebo group (P = 0.02); 1 of 17 patients treated early vs. 6 of 13 in the control group still had loose stools 120 h after start of treatment (P = 0.03).\n In children from day-care centers with mild gastroenteritis, the combination of L. rhamnosus 19070-2 and L. reuteri DSM 12246 was effective in reducing the duration of diarrhea.", "Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Probiotics were effective in preventing AAD and CDAD in several randomized controlled trials. This study was aimed at testing the effect of Saccharomyces boulardii on the occurrence of AAD and CDAD in hospitalized patients.\n A single-center, randomized, double-blind, placebo-controlled, parallel-group trial was performed. Patients being prescribed antibiotics or on antibiotic therapy for <48 h were eligible. Exclusion criteria were ongoing diarrhea, recent assumption of probiotics, lack of informed consent, inability to ingest capsules, and severe pancreatitis. Patients received a capsule containing S. boulardii or an indistinguishable placebo twice daily within 48 h of beginning antibiotic therapy, continued treatment for 7 days after antibiotic withdrawal, and were followed for 12 weeks after ending antibiotic treatment.\n Of 562 consecutive eligible patients, 275 patients aged 79.2 ± 9.8 years (134 on placebo) were randomized and 204 aged 78.4 ± 10.0 years (98 on placebo) completed the follow-up. AAD developed in 13.3% (13/98) of the patients receiving placebo and in 15.1% (16/106) of those receiving S. boulardii (odds ratio for S. boulardii vs. placebo, 1.16; 95% confidence interval (CI), 0.53-2.56). Five cases of CDAD occurred, 2 in the placebo group (2.0%) and 3 in the probiotic group (2.8%; odds ratio for S. boulardii vs. placebo, 1.40; 95% CI, 0.23-8.55). There was no difference in mortality rates (12.7% vs. 15.6%, P=0.60).\n In elderly hospitalized patients, S. boulardii was not effective in preventing the development of AAD.", "The effectiveness of probiotic therapy for acute rotavirus infectious diarrhoea in an indigenous setting with bacterial/parasitic diarrhoea is unclear. In the present study, we assessed the efficacy of probiotics in Australian Aboriginal children in the Northern Territory admitted to hospital with diarrhoeal disease.\n A randomised double-blind placebo-controlled study was conducted in Aboriginal children (ages 4 months-2 years), admitted to hospital with acute diarrhoeal disease (>3 loose stools per day). Children received either oral Lactobacillus GG (5 x 10(9) colony-forming units 3 times per day for 3 days; n = 33) or placebo (n = 31). Small intestinal functional capacity was assessed by the noninvasive 13C-sucrose breath test on days 1 and 4.\n Both groups showed mean improvement in the sucrose breath test after 4 days; however, there was no difference (mean, 95% confidence interval) between probiotic (2.9 [cumulative percentage of dose recovered at 90 minutes]; 1.7-4.2) and placebo (3.7; 2.3-5.2) groups. Probiotics did not change the duration of diarrhoea, total diarrhoea stools, or diarrhoea score compared with placebo. There was a significant (P < 0.05) difference in diarrhoea frequency on day 2 between probiotics (3.3 [loose stools]; 2.5-4.3) and placebo (4.7; 3.8-5.7) groups.\n Lactobacillus GG did not appear to enhance short-term recovery following acute diarrhoeal illness in this setting.", "Multiple studies document that probiotics are effective in treating infectious diarrhoea in children. Lactobacillus rhamnosus GG is the most extensively studied but effectiveness of other strains has been poorly examined.\n To determine whether L. rhamnosus strains (573L/1; 573L/2; 573L/3) (Lakcid L, Biomed, Lublin, Poland) would be effective in shortening infectious diarrhoea.\n In a randomized, double-blind, placebo-controlled trial, 87 children (age range: 2 months to 6 years) with infectious diarrhoea were administered Lakcid L at a dose 1.2 x 10(10) CFU or placebo, twice daily, for 5 days. Primary outcome measure was the duration of diarrhoea. Secondary measures were duration of parenteral rehydration, adverse events, and gastrointestinal tract colonization by administered strains.\n In an intention to treat analysis of 87 children, the mean duration of diarrhoea in the treated group: 84 +/- 56 h; placebo: 96 +/- 72 h (P = 0.36). In rotavirus infection: 76 +/- 35 h vs. 115 +/- 67 h (P = 0.03), respectively. Duration of parenteral rehydration: 15 +/- 14 h vs. 38 +/- 33 h (P = 0.006). Gut colonization by administered strains was 80% and 41% at five and 14 days, respectively. No adverse events were noted.\n Administration of L. rhamnosus strains shortens the duration of rotaviral diarrhoea in children but not of diarrhoea of any aetiology. Intervention shortens the time of intravenous rehydration.", "This clinical trial was carried out to determine whether oral treatment with a commercial probiotic formula containing Bifidobacterium lactis and Streptococcus thermophilus would reduce the frequency of antibiotic-associated diarrhea (AAD) in infants.\n In this double-bind formula controlled study, 80 infants, 6 to 36 months of age, were randomly assigned to receive a commercial formula containing 10 viable cells of B. lactis and 10 viable cells of S. thermophilus at the initiation of antibiotics for a duration of 15 days. The infants were assessed daily for formula intake, stool frequency, and stool consistency for a total duration of 30 days. Seventy-seven infants received nonsupplemented formula for the entire duration.\n There was a significant difference in the incidence of AAD in the children receiving probiotic-supplemented formula (16%) than nonsupplemented formula (31%).\n The present study shows that prevention against AAD in infants was obtained by oral treatment with daily dose of B. lactis and S. thermophilus.", "The efficacy of probiotics on persistent diarrhea remains uncertain. The purpose of this study was to evaluate the effect of Lactobacillus sp and Saccharomyces boulardii on persistent diarrhea in children. In a double-blind trial eighty-nine children, aged 6-24 months were randomly distributed to receive pasteurized cow milk containing 2 viable lyophilized strains Lactobacillus casei and Lactobacillus acidophillus strains CERELA, (10(10)-10(12) colony-forming units per g) (n = 30), or lyophilized S. boulardii, (10(10)-10(12) colony forming units per g) (n = 30) or pasteurized cow milk as placebo (n = 29); on each diet 175 g was given twice a day for a 5 day period. Number of depositions, duration of illness and frequency of vomiting were considered. Enteric pathogens were isolated from stools in 40% of the patients, 27% had rotavirus. Lactobacillus and S. boulardii significantly reduced the number of depositions (p < 0.001) and diarrheal duration (p < 0.005). Similarly both significantly (p < 0.002) reduced vomiting as compared with placebo. There was no difference between treatments depending on rotavirus status. In conclusion, L. casei and L. acidophillus strains CERELA and S. boulardii are useful in the management of persistent diarrhea in children.", "To determine the safety and efficacy of a new preventive agent for antibiotic-associated diarrhea (AAD) in patients receiving at least one beta-lactam antibiotic.\n A double-blinded, placebo-controlled, parallel group study was performed in a high-risk group of hospitalized patients receiving a new prescription for a beta-lactam antibiotic and having no acute diarrhea on enrollment. Lyophilized Saccharomyces boulardii or placebo (1 g/day) was given within 72 h of the start of the antibiotic(s) and continued until 3 days after the antibiotic was discontinued, after which the patients were followed for 7 wk.\n Of the 193 eligible patients, significantly fewer, 7/97 (7.2%), patients receiving S. boulardii developed AAD compared with 14/96 (14.6%) on placebo (p = 0.02). The efficacy of S. boulardii for the prevention of AAD was 51%. Using a multivariate model to adjust for two independent risk factors for AAD (age and days of cephalosporin use), the adjusted relative risk was significantly protective for S. boulardii (RR = 0.29, 95% CI = 0.08, 0.98).\n The prophylactic use of S. boulardii given with a beta-lactam antibiotic resulted in a significant reduction of AAD with no serious adverse reactions." ]	Despite heterogeneity in probiotic strain, dose, and duration, as well as in study quality, the overall evidence suggests a protective effect of probiotics in preventing AAD. Using 11 criteria to evaluate the credibility of the subgroup analysis on probiotic dose, the results indicate that the subgroup effect based on dose (≥5 billion CFU/day) was credible. Based on high-dose probiotics, the number needed to treat (NNT) to prevent one case of diarrhea is seven (NNT 7; 95% CI 6 to 10). However, a GRADE analysis indicated that the overall quality of the evidence for the primary endpoint (incidence of diarrhea) was low due to issues with risk of bias (due to high loss to follow-up) and imprecision (sparse data, 225 events). The benefit for high dose probiotics (Lactobacillus rhamnosus or Saccharomyces boulardii) needs to be confirmed by a large well-designed randomized trial. More refined trials are also needed that test strain specific probiotics and evaluate the efficacy (e.g. incidence and duration of diarrhea) and safety of probiotics with limited losses to follow-up. It is premature to draw conclusions about the efficacy and safety of other probiotic agents for pediatric AAD. Future trials would benefit from a standard and valid outcomes to measure AAD.
CD005497	[ "15632336", "16202939", "12850599", "15050984", "15333602", "18307077", "17077230", "16022849", "20399951", "18398664" ]	[ "Direct access to emergency contraception through pharmacies and effect on unintended pregnancy and STIs: a randomized controlled trial.", "Advance supply of emergency contraception: a randomized trial in adolescent mothers.", "Advance supply of emergency contraception. effect on use and usual contraception--a randomized trial.", "The effects of advance provision of emergency contraception on adolescent women's sexual and contraceptive behaviors.", "Effect of advanced provision of emergency contraception on women's contraceptive behaviour: a randomized controlled trial.", "Advance provision of emergency contraceptive pills reduces treatment delay: a randomised controlled trial among Swedish teenage girls.", "Impact of increased access to emergency contraceptive pills: a randomized controlled trial.", "Advanced provision of emergency contraception to postnatal women in China makes no difference in abortion rates: a randomized controlled trial.", "A randomized controlled trial of the effect of advanced supply of emergency contraception in postpartum teens: a feasibility study.", "Computer-assisted provision of emergency contraception a randomized controlled trial." ]	[ "It is estimated that half of unintended pregnancies could be averted if emergency contraception (EC) were easily accessible and used.\n To evaluate the effect of direct access to EC through pharmacies and advance provision on reproductive health outcomes.\n A randomized, single-blind, controlled trial (July 2001-June 2003) of 2117 women, ages 15 to 24 years, attending 4 California clinics providing family planning services, who were not desiring pregnancy, using long-term hormonal contraception or requesting EC.\n Participants were assigned to 1 of the following groups: (1) pharmacy access to EC; (2) advance provision of 3 packs of levonorgestrel EC; or (3) clinic access (control).\n Primary outcomes were use of EC, pregnancies, and sexually transmitted infections (STIs) assessed at 6 months; secondary outcomes were changes in contraceptive and condom use and sexual behavior.\n Women in the pharmacy access group were no more likely to use EC (24.2%) than controls (21.0%) (P = .25). Women in the advance provision group (37.4%) were almost twice as likely to use EC than controls (21.0%) (P<.001) even though the frequency of unprotected intercourse was similar (39.8% vs 41.0%, respectively, P = .46). Only half (46.7%) of study participants who had unprotected intercourse used EC over the study period. Eight percent of participants became pregnant and 12% acquired an STI; compared with controls, women in the pharmacy access and advance provision groups did not experience a significant reduction in pregnancy rate (pharmacy access group: adjusted odds ratio [OR], 0.98; 95% confidence interval [CI], 0.58-1.64; P = .93; advance provision group: OR, 1.10; 95% CI, 0.66-1.84, P = .71) or increase in STIs (pharmacy access group: adjusted OR, 1.08, 95% CI, 0.71-1.63, P = .73; advance provision group: OR, 0.94, 95% CI, 0.62-1.44, P = .79). There were no differences in patterns of contraceptive or condom use or sexual behaviors by study group.\n While removing the requirement to go through pharmacists or clinics to obtain EC increases use, the public health impact may be negligible because of high rates of unprotected intercourse and relative underutilization of the method. Given that there is clear evidence that neither pharmacy access nor advance provision compromises contraceptive or sexual behavior, it seems unreasonable to restrict access to EC to clinics.", "To examine whether the advanced provision of emergency contraception (AEC) to parenting youth would increase emergency contraception (EC) utilization, and whether AEC would impact the rates of unprotected sex and contraception use.\n Subjects were randomized to receive either information about EC or information and an actual supply of AEC. Subjects were interviewed at baseline, 6 and 12-month follow-up.\n Urban non-medical case management office.\n 160 adolescent mothers (ages 13 to 20) who were receiving case management services.\n Advance supply of emergency contraception.\n Emergency contraception use, sexual activity, unprotected intercourse, contraceptive methods and use.\n Parenting teens who received AEC were much more likely to have used it than the control group at the 6-month interview (83% vs. 11%) and the 12-month interview (64% vs. 17%). Teens in the AEC treatment group were more likely to have unprotected sex at the 12-month follow-up interview (69% vs. 45%). There was no difference in condom use between the groups at either the 6-month, or the 12-month follow-up interviews.\n Advance provision of emergency contraception in parenting teens increases the likelihood of its use, and does not affect the use of condoms, or hormonal methods of birth control. Parenting teens who receive AEC may be more likely to have unprotected sex.", "To evaluate whether advance provision of emergency contraception increases its use and/or adversely affects usual contraceptive practices.\n We performed a randomized controlled trial comparing advance provision of emergency contraception with usual care in 370 postpartum women from an inner-city public hospital. Participants were followed for 1 year; 85% were available for at least one follow-up session. All participants received routine contraceptive education. The intervention group received a supply of emergency contraception (eight oral contraceptive pills containing 0.15 mg of levonorgestrel and 30 microg of ethinyl estradiol) and a 5-minute educational session. We compared use of emergency contraception and changes in contraceptive behaviors between groups.\n Women provided with pills were four times as likely to have used emergency contraception as women in the control group over the course of the year (17% versus 4%; relative risk [RR] 4.0; 95% confidence interval [CI] 1.8, 9.0). Women were no more likely to have changed to a less effective method of birth control (30% versus 33%; RR 0.92; 95% CI 0.63, 1.3), or to be using contraception less consistently (18% versus 25%; RR 0.74; 95% CI 0.45, 1.2). About half of each group reported at least one episode of unprotected intercourse during follow-up, but women who received emergency contraception were six times as likely to have used it (25% versus 4%; RR 5.8; 95% CI 2.1, 16.4).\n Advance provision of emergency contraception significantly increased use without adversely affecting use of routine contraception. It is safe and appropriate to provide emergency contraception to all postpartum women before discharge from the hospital.", "Advance provision of emergency contraception (EC) may increase timely access and improve effectiveness, but the impact on adolescent sexual and contraceptive behaviors is not known.\n To determine whether adolescents given advance EC have higher sexual and contraceptive risk-taking behaviors compared to those obtaining it on an as-needed basis.\n Randomized trial conducted at urban, hospital-based adolescent clinic in Pittsburgh, PA, from June 1997 to June 2002.\n 301 predominantly minority, low-income, sexually active adolescent women, age 15-20 years, not using long-acting contraception.\n Advance EC vs instruction on how to get emergency contraception.\n Self-reported unprotected intercourse and use of condoms, EC, and hormonal contraception ascertained by monthly 10-minute telephone interviews for 6 months post-enrollment. Reported timing of EC use after unprotected intercourse.\n At both 1- and 6-month followup interviews, there were no differences between advance EC and control groups in reported unprotected intercourse within the past month or at last intercourse. At 6 months, more advance EC participants reported condom use in the past month compared to control group participants (77% vs 62%, P=0.02), but not at last intercourse (advance EC 83% vs control 78%, P=0.34). There were no significant differences by group in hormonal contraception use reported by advance EC or control groups in the past month (44% vs 53%, P=0.19) or at last intercourse (48% vs 58%, P=0.20). At the first followup, the advance group reported nearly twice as much EC use as the control group (15% vs 8%, P=0.05) but not at the final followup (8% vs 6%, P=0.54). Advance EC group participants began their EC significantly sooner (11.4 hours vs 21.8 hours, P=0.005).\n Providing advance EC to adolescents is not associated with more unprotected intercourse or less condom or hormonal contraception use. In the first month after enrollment, adolescents provided with advance EC were nearly twice as likely to use it and began EC sooner, when it is known to be more effective.", "Emergency contraception (EC) can prevent pregnancy but is under-used. Advanced provision increases use but the effect on contraceptive behaviour varies.\n Women aged 18-45 years, using less effective contraceptives, were randomized to either advanced provision of three courses of EC (intervention) or to obtaining each course from clinic (control). EC use and contraceptive behaviour were monitored for 1 year.\n In all, 1030 women were recruited in 6 months. The mean+/-SD number of courses of EC used in intervention versus control group was 0.56+/-1.2 versus 0.20+/-0.6 (P<0.001). In the intervention group, 47% women aged <26 years used at least one course of EC compared with 23% of older women (P<0.001). The majority of women used condoms before (intervention 89%, control 91%) and during the study (89% for both groups). Consistency of contraceptive use was higher during the study (65 versus 60% of women in both groups) (P<0.001). There were 17 unplanned pregnancies, eight in the intervention group, six of whom did not use EC in the conception cycle.\n Advanced provision increases EC use especially among young women in Hong Kong. Contraceptive choice and consistency of use remains the same even among young women.", "To evaluate an intervention involving advance provision of emergency contraceptive pills (ECP) to Swedish teenage girls.\n Some 420 girls aged 15-19, requesting ECP at a local youth clinic were randomly assigned to intervention group (IG) (n=214) or control group (CG) (n=206). Both groups received ECP on request. The IG received one extra dose of ECP, condoms and an information leaflet regarding ECP and condom use. Main outcome measures were differences between IG and CG regarding ECP use, time span between unprotected intercourse and ECP intake, contraceptive use, and sexual risk taking. Questionnaires were completed at the initial visit, and the girls were followed up by structured telephone interviews 3 and 6 months later.\n At the 3-month follow-up, girls in the IG were almost twice as likely to have used ECP compared to girls in the CG (IG: 24.0%, CG: 13%, p=0.02), and they used it sooner after unprotected intercourse (mean time IG: 13.61 h, CG: 25.47 h, p=0.007). Significant differences persisted 6 months after the intervention (ECP use IG: 31%, CG: 19%, p=0.01; and mean time IG: 15.59 h, CG: 26.38 h, p=0.006). No significant differences were found in the use of regular hormonal contraceptives or condoms at either follow-up. About 40% of the girls in both groups had risked pregnancy during the follow-up period, but only half of these had used ECP.\n This intervention shortened the time interval from unprotected intercourse to pill intake without jeopardising contraceptive use and without increasing sexual risk taking.", "To assess how a strategy to maximize access to emergency contraceptive pills would affect rates of pregnancy and sexually transmitted infections.\n Sexually active women, 14-24 years old, were randomly assigned to two methods of access to emergency contraceptive pills: increased access (two packages of pills dispensed in advance with unlimited resupply at no charge) or standard access (pills dispensed when needed at usual charges). Participants were followed for 1 year to assess incidence of pregnancy, gonorrhea, chlamydia, and trichomonas.\n The numbers of women enrolled in the increased and standard access groups were 746 and 744, respectively. More than 93% of participants completed a full year of follow-up. The incidence of pregnancy was similar in both groups (increased access group: 9.9/100 woman years, 95% confidence interval [CI] 7.7-12.6; standard access group: 10.5/100 woman years, 95% CI 8.2-13.2). Aggregate rates of gonorrhea, chlamydia, and trichomonas were also similar in the two groups (increased access group: 6.9/100 woman years, 95% CI 5.1-9.1; standard access group: 7.6/100 woman years, 95% CI 5.7-9.9). The increased access group used emergency contraceptive pills substantially more often and sooner after coitus than the standard access group. No other differences were noted between groups in self-reported measures of sexual behavior and contraceptive use.\n This intensive strategy to enhance access to emergency contraceptive pills substantially increased use of the method and had no adverse impact on risk of sexually transmitted infections. However, it did not show benefit in decreasing pregnancy rates.\n II-1.", "Emergency contraception (EC) prevents pregnancy, and it has been suggested that widespread use could reduce abortion rates; however, the use is limited. Providing EC in advance of need increases use, but there is no direct evidence that it reduces unintended pregnancy. In a randomized controlled trial of 2000 women after childbirth in Shanghai, all women not wishing to use hormonal contraception or an intrauterine device (IUD) were given a supply of condoms. Those in the intervention group also received three courses of mifepristone 10 mg with instructions for use as EC. Follow-up was by telephone at 16, 32 and 52 weeks. Over 88% of women in both groups completed 1 year of follow-up. Women with a supply of EC were more than twice as likely to use it, and to use it more than once (p<.001 for both) than women without a supply. There was no difference in pregnancy rates at 1 year (38/832 vs. 32/817). EC was not used in 89% of conception cycles, as women did not recognize the need for it. Increased use of EC may not reduce abortion rates.", "The study was conducted to test the feasibility of conducting a randomized controlled contraceptive trial in postpartum teens and to assess whether postpartum advanced supply of emergency contraception (EC) to teenaged mothers helps to prevent repeat pregnancies of close proximity.\n We performed a randomized controlled trial of 50 postpartum teens at an urban academic medical center. Participants in the intervention arm received routine postpartum contraceptive care and advanced supply of one pack of EC pills with unlimited supply thereafter upon request. The routine care arm (RCA) received routine postpartum contraceptive care. We asked open-ended questions about how we might maximize study retention and implemented the participants' requests in both arms.\n Our retention rate was 78%. There were three (13%) pregnancies out of 23 participants in the intervention arm and eight (30%) pregnancies out of 27 participants in the RCA. The risk of pregnancy occurring in the intervention arm was 0.57 times that of the RCA (95% CI 0.20-1.60; p=.23).\n A randomized controlled trial of postpartum teens to receive and not to receive advanced supply of EC is both feasible and necessary. Our study provides preliminary data to suggest that advanced supply of EC may help decrease repeat teen pregnancies.", "Emergency contraception (EC) can prevent unintended pregnancy. However, many women continue to lack information needed to use EC effectively and clinician time to counsel women about EC is limited.\n To evaluate whether computer-assisted provision of EC can increase knowledge and use of EC among women able to access EC without a prescription.\n We conducted a randomized controlled trial in which the intervention group received a 15-minute computerized educational session and 1 pack of EC. The control group received education about periconception folate supplementation, but no information about EC. Participants were contacted 7 months after enrollment.\n Four hundred forty-six women recruited from 2 urgent care clinics in San Francisco in 2005.\n Knowledge of EC, use of EC, and self-reported pregnancy.\n At follow-up, women in the intervention group answered an average of 2 more questions about EC correctly than they had at baseline, whereas women in the control group answered only 1 more item correctly (2.0 vs 1.2, p < .001). There was a trend toward more use of EC during the study period in the intervention group (10% vs 4% of women followed, p = .06; 6% vs 3%, p = .09 of women enrolled). Fewer women in the intervention group were pregnant at the time of follow-up (0.8% vs 6.5%, p = .01 of women followed; 0.5% vs 4.0%, p = .01 of women enrolled).\n Computer-assisted provision of EC in urgent care waiting areas increased knowledge of EC in a state where EC had been available without a prescription for 3 years." ]	Advance provision of emergency contraception did not reduce pregnancy rates when compared to conventional provision. Results from primary analyses suggest that advance provision does not negatively impact sexual and reproductive health behaviors and outcomes. Women should have easy access to emergency contraception, because it can decrease the chance of pregnancy. However, the interventions tested thus far have not reduced overall pregnancy rates in the populations studied.
CD004302	[ "8628460", "8967757" ]	[ "A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. ALS CNTF Treatment Study Group.", "A placebo-controlled trial of recombinant human ciliary neurotrophic (rhCNTF) factor in amyotrophic lateral sclerosis. rhCNTF ALS Study Group." ]	[ "Ciliary neurotrophic factor (CNTF) is a neuroactive cytokine found in Schwann cells, which appears to be released in response to nerve injury. The ALS CNTF Treatment Study (ACTS) clinical trial was a phase II-III randomized, placebo-controlled, double-blind study designed to evaluate the safety, tolerability, and efficacy of subcutaneous administration of recombinantly produced human CNTF (rHCNTF) in slowing disease progression in 730 patients with amyotrophic lateral sclerosis (ALS). Patients were randomized to receive 30 micrograms/kg or 15 micrograms/kg rHCNTF or placebo subcutaneously three times a week for 9 months. The primary endpoint of the study, the slope of decline of isometric muscle strength in treated versus placebo patients, showed no statistically significant difference between rHCNTF and placebo-treated patients, and was complicated by an initial statistically significant decrease in strength early in rHCNTF-treated patients. Mortality was similar in all three study arms. There were no statistically significant treatment effects among the secondary measures. Side effects of rHCNTF included anorexia, weight loss, and cough and were sufficient to limit dosing in many patients.", "Preclinical investigations indicated that recombinant human ciliary neurotrophic factor (rhCNTF) may have potential as therapy for amyotrophic lateral sclerosis (ALS). We evaluated the safety and efficacy of rhCNTF in a prospective, double-blind, placebo-controlled trial in 570 patients with ALS. Patients were randomized to receive 0.5, 2, or 5 micrograms/kg/day rhCNTF, or placebo, for 6 months. The primary efficacy end point was the change from baseline to the last on-treatment value of a combination megascore for limb strength (maximum voluntary isometric contraction) and pulmonary function. Secondary end points included individual arm and leg megascores, pulmonary function tests, an activities-of-daily-living outcome measure, and survival. The four treatment groups were similar at baseline with respect to age, sex, disease duration, and muscle strength values. At all doses tested, rhCNTF had no beneficial effect on the primary or secondary end points. Certain adverse events, as follows, appeared to be dose related: injection site reactions, cough, asthenia, nausea, anorexia, weight loss, and increased salivation. There was an increased number of deaths at the highest dose level. rhCNTF had no beneficial effect on any measure of ALS progression. There were increased adverse events in the 5 micrograms/kg group and increased deaths." ]	Ciliary neurotrophic factor treatment had no significant effect on amyotrophic lateral sclerosis progression. At high concentrations, several side effects were observed. A combination of ciliary neurotrophic factor with other neurotrophic factors (as suggested by results on animal models) and more efficient delivery methods should be tested.
CD007006	[ "12182264", "9605896", "12704016", "21783053", "8882672", "11265827", "16919803", "11236404", "19996048", "7751483", "11889277", "8634730", "15625713", "18645518", "15838199", "1990853", "17940861", "15166533", "16774462", "17721102", "8924256", "8018438", "15249566" ]	[ "Reducing STD and HIV risk behavior of substance-dependent adolescents: a randomized controlled trial.", "Abstinence and safer sex HIV risk-reduction interventions for African American adolescents: a randomized controlled trial.", "Reducing the sexual risk behaviors of HIV+ individuals: outcome of a randomized controlled trial.", "A clinic-based motivational intervention improves condom use among subgroups of youth living with HIV.", "Evaluation of an HIV risk reduction intervention among African-American homosexual and bisexual men.", "Schoolwide effects of a multicomponent HIV, STD, and pregnancy prevention program for high school students.", "A brief individualized computer-delivered sexual risk reduction intervention increases HIV/AIDS preventive behavior.", "Efficacy of a preventive intervention for youths living with HIV.", "Efficacy of sexually transmitted disease/human immunodeficiency virus sexual risk-reduction intervention for african american adolescent females seeking sexual health services: a randomized controlled trial.", "Cognitive-behavioral intervention to reduce African American adolescents' risk for HIV infection.", "Safer choices: reducing teen pregnancy, HIV, and STDs.", "A randomized, controlled effectiveness trial of an AIDS prevention program for low-income African-American youths.", "Group-based HIV risk reduction intervention for adolescent girls: evidence of feasibility and efficacy.", "Clinic-based intervention reduces unprotected sexual behavior among HIV-infected patients in KwaZulu-Natal, South Africa: results of a pilot study.", "Effects of a peer-led behavioral intervention to reduce HIV transmission and promote serostatus disclosure among HIV-seropositive gay and bisexual men.", "HIV risk behavior reduction following intervention with key opinion leaders of population: an experimental analysis.", "The impact of an integrated treatment on HIV risk behavior among homeless youth: a randomized controlled trial.", "Effect of brief safer-sex counseling by medical providers to HIV-1 seropositive patients: a multi-clinic assessment.", "All4You! A randomized trial of an HIV, other STDs, and pregnancy prevention intervention for alternative school students.", "Biological and behavioural impact of an adolescent sexual health intervention in Tanzania: a community-randomized trial.", "The efficacy of brief group counseling in HIV risk reduction among homosexual Asian and Pacific Islander men.", "Outcome of psychoeducation for HIV risk reduction.", "Efficacy of an HIV prevention intervention for African American adolescent girls: a randomized controlled trial." ]	[ "A randomized controlled trial assessed 3 interventions designed to increase safer sex behaviors of substance-dependent adolescents. Participants (N = 161) received 12 sessions of either a health information intervention (I only), information plus skills-based safer sex training (I + B), or the same experimental condition plus a risk-sensitization manipulation (I + M + B). The I + B and I + M + B conditions, as compared with the I only condition, (a) produced more favorable attitudes toward condoms; (b) reduced the frequency of unprotected vaginal sex; and (c) increased behavioral skill performance, frequency of condom-protected sex, percentage of intercourse occasions that were condom protected, and number of adolescents who abstained from sex. The intervention that included the risk-sensitization procedure was more resistant to decay. An unexpected finding was that the I + B and I + M + B conditions produced substantial increases in sexual abstinence.", "African American adolescents are at high risk of contracting sexually transmitted infection with human immunodeficiency virus (HIV), but which behavioral interventions to reduce risk are most effective and who should conduct them is not known.\n To evaluate the effects of abstinence and safer-sex HIV risk-reduction interventions on young inner-city African American adolescents' HIV sexual risk behaviors when implemented by adult facilitators as compared with peer cofacilitators.\n Randomized controlled trial with 3-, 6-, and 12-month follow-up.\n Three middle schools serving low-income African American communities in Philadelphia, Pa.\n A total of 659 African American adolescents recruited for a Saturday program.\n Based on cognitive-behavioral theories and elicitation research, interventions involved 8 1-hour modules implemented by adult facilitators or peer cofacilitators. Abstinence intervention stressed delaying sexual intercourse or reducing its frequency; safer-sex intervention stressed condom use; control intervention concerned health issues unrelated to sexual behavior.\n Self-reported sexual intercourse, condom use, and unprotected sexual intercourse.\n Mean age of the enrollees was 11.8 years; 53% were female and 92.6% were still enrolled at 12 months. Abstinence intervention participants were less likely to report having sexual intercourse in the 3 months after intervention than were control group participants (12.5% vs 21.5%, P=.02), but not at 6- or 12-month follow-up (17.2% vs 22.7%, P=.14; 20.0% vs 23.1%, P=.42, respectively). Safer-sex intervention participants reported significantly more consistent condom use than did control group participants at 3 months (odds ratio [OR]=3.38; 95% confidence interval [CI], 1.25-9.16) and higher frequency of condom use at all follow-ups. Among adolescents who reported sexual experience at baseline, the safer-sex intervention group reported less sexual intercourse in the previous 3 months at 6- and 12-month follow-up than did control and abstinence intervention (adjusted mean days over prior 3 months, 1.34 vs 3.77 and 3.03, respectively; P< or =.01 at 12- month follow-up) and less unprotected intercourse at all follow-ups than did control group (adjusted mean days, 0.04 vs 1.85, respectively, P<.001, at 12-month follow-up). There were no differences in intervention effects with adult facilitators as compared with peer cofacilitators.\n Both abstinence and safer-sex interventions can reduce HIV sexual risk behaviors, but safer-sex interventions may be especially effective with sexually experienced adolescents and may have longer-lasting effects.", "Testing behavioral interventions to increase safer sex practices of HIV+ individuals has the potential to significantly reduce the number of new infections. This study evaluated a behavioral intervention designed to reduce the sexual risk behaviors of HIV+individuals. HIV+individuals (N = 387) who reported engaging in unprotected sex with HIV- or partners of unknown serostatus were randomly assigned to (a) a single counseling session targeting problem areas identified by the participant in 3 possible intervention domains (i.e., condom use, negotiation, disclosure); (b) a single-session comprehensive intervention that covered all 3 intervention domains; (c) the same comprehensive intervention, plus 2 monthly booster sessions; or (d) a 3-session diet and exercise attention-control condition. The median number of unprotected sex acts decreased from 14 at baseline to 6, 6, and 4 at 4-, 8-, and 12-month follow-ups, respectively. A repeated measures analysis of variance revealed a significant decrease in unprotected sex acts across all groups across time. A significant Group x Time interaction revealed that the comprehensive-with-boosters group had the most unprotected sex at 8-month follow-up as compared to the other 3 groups. These findings suggest that a brief intervention can result in large reductions in HIV transmission risks among HIV+individuals, but the relative benefit of one intervention approach over another remains unclear.", "More than 50% of youth living with HIV (YLH) have unprotected sex. In previous studies, we reported effects of a motivational interviewing-based multirisk reduction intervention, \"Healthy Choices\" in improving motivation, depression, and viral load in YLH. In this study, we report the effect of the intervention on increasing condom use.\n Six waves of longitudinal data (n = 142) across a period from baseline through 15 months postintervention were analyzed. The developmental trajectory modeling method was used for program effect evaluation.\n The three groups detected with distinct sexual risks were: Persistent low sexual risk (PLSR), delayed high sexual risk, and high and growing sexual risk with regard to levels and time trajectories of condom use throughout the trial. Receiving Healthy Choices increased the likelihood to be in the PLSR group (63% vs. 32%, p < .01) and reduced the likelihood to be in the delayed high sexual risk group (16% vs. 50%, p < .05). Receiving the intervention was also associated with progressive reductions in no-condom sex for PLSR youth (adjusted β = -.325, p < .01) and high and growing sexual risk youth (adjusted β = -.364, p < .01).\n The motivational interviewing-based program Healthy Choices, when delivered in clinic settings, can prevent unprotected sex in subgroups of YLH, although more intensive interventions may be needed to change risk trajectories among those at highest risk of transmitting the AIDS virus. Developmental trajectory analysis provides an alternative approach to evaluate program effects for study samples that contain distinct subgroups.\n Copyright © 2011 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.", "To provide the first data which evaluates an HIV risk reduction intervention designed to reduce HIV high-risk sexual behavior in African-American homosexual and bisexual men.\n Participants (n = 318) were recruited from bars, bathhouses, and erotic bookstores, and through homosexual African-American organizations, street out-reach, media advertisements, and personal referrals of individuals aware of the study.\n Participants were randomized into a single or triple session experimental group or a wait-list control group. Both experimental interventions included AIDS risk education, cognitive-behavioral self-management training, assertion training, and attempts to develop self-identity and social support. Data collection involved assessments of self-reported changes in sexual behavior at 12- and 18-month follow-up.\n Participants in the triple session intervention greatly reduced their frequency of unprotected anal intercourse (from 46 to 20%) at the 12-month follow-up evaluation and (from 45% to 20%) at the 18-month follow-up evaluation. However, levels of risky behavior for the control group remained constant (from 26 to 23% and from 24 to 18%) at 12- and 18-month follow-up evaluations, respectively. In addition, levels of risky behavior for the single session intervention decreased only slightly (from 47 to 38% and from 50 to 38%) at the 12- and 18-month follow-up evaluations, respectively.\n Results were interpreted to demonstrate the superiority of a triple session over a single session intervention in reducing risky sexual behavior in this cohort.", "Few studies have tested schoolwide interventions to reduce sexual risk behavior, and none have demonstrated significant schoolwide effects. This study evaluates the schoolwide effects of Safer Choices, a multicomponent, behavioral theory-based HIV, STD, and pregnancy prevention program, on risk behavior, school climate, and psychosocial variables. Twenty urban high schools were randomized, and cross-sectional samples of classes were surveyed at baseline, the end of intervention (19 months after baseline), and 31 months afterbaseline. At 19 months, the program had a positive effect on the frequency of sex without a condom. At 31 months, students in Safer Choices schools reported having sexual intercourse without a condom with fewer partners. The program positively affected psychosocial variables and school climate for HIV/STD and pregnancy prevention. The program did not influence the prevalence of recent sexual intercourse. Schoolwide changes in condomuse demonstrated that aschool-based program can reduce the sexual risk behavior of adolescents.", "One objective of translational science is to identify elements of human immunodeficiency virus (HIV) risk-reduction interventions that have been shown to be effective and find new ways of delivering these interventions to the community to ensure that they reach the widest possible audience of at-risk individuals. The current study reports the development and evaluation of a computer-delivered, theory-based, individually tailored HIV risk-reduction intervention.\n This study evaluated the effectiveness of a custom computerized HIV/AIDS risk reduction intervention at increasing HIV/AIDS preventive behaviors in a randomized trial with 157 college students. The intervention content and delivery were based on the Information-Motivation-Behavioral Skills Model of Health Behavior Change and used Motivational Interviewing techniques. Participants completed a baseline assessment of HIV prevention information, motivation, behavioral skills and behavior, attended two brief computer-delivered intervention sessions, and completed a follow-up assessment.\n As compared to the control group (a nutrition education tutorial), participants who interacted with the computer-delivered HIV/AIDS risk reduction intervention exhibited a significant increase in risk reduction behavior. Specifically, participants reported a greater frequency of keeping condoms available and displayed greater condom-related knowledge at a four-week follow-up session; among sexually active participants, there was a significant increase in self-reported condom use.\n Delivery of brief individually tailored HIV/AIDS risk reduction interventions via computer may be an effective HIV/AIDS prevention approach for adolescents. More research is needed to further support the effectiveness of this type of intervention and determine the generalizability of these findings to economically and educationally disadvantaged adolescents.", "HIV transmission behaviors and health practices of HIV-infected youths were examined over a period of 15 months after they received a preventive intervention.\n HIV-infected youths aged 13 to 24 years (n = 310; 27% African American, 37% Latino) were assigned by small cohort to (1) a 2-module (\"Stay Healthy\" and \"Act Safe\") intervention totaling 23 sessions or (2) a control condition. Among those in the intervention condition, 73% attended at least 1 session.\n Subsequent to the \"Stay Healthy\" module, number of positive lifestyle changes and active coping styles increased more often among females who attended the intervention condition than among those in the control condition. Social support coping also increased significantly among males and females attending the intervention condition compared with those attending the control condition. Following the \"Act Safe\" module, youths who attended the intervention condition reported 82% fewer unprotected sexual acts, 45% fewer sexual partners, 50% fewer HIV-negative sexual partners, and 31% less substance use, on a weighted index, than those in the control condition.\n Prevention programs can effectively reduce risk acts among HIV-infected youths. Alternative formats need to be identified for delivering interventions (e.g., telephone groups, individual sessions).", "To evaluate the efficacy of an intervention to reduce incident sexually transmitted disease (STD) and enhance STD/human immunodeficiency virus (HIV)-preventive behaviors and psychosocial mediators.\n A randomized controlled trial of an HIV prevention program.\n Clinic-based sample in Atlanta, Georgia.\n African American adolescent females (N = 715), aged 15 to 21 years, seeking sexual health services. Participants completed an audio computer-assisted self-interview and provided self-collected vaginal specimens for STD testing. Intervention Intervention participants received two 4-hour group sessions and 4 telephone contacts over a 12-month period, targeting personal, relational, sociocultural, and structural factors associated with adolescents' STD/HIV risk, and were given vouchers facilitating male partners' STD testing/treatment. Main Outcome Measure Incident chlamydial infections.\n Over the 12-month follow-up, fewer adolescents in the intervention had a chlamydial infection (42 vs 67; risk ratio [RR], 0.65; 95% confidence interval [CI], 0.42 to 0.98; P = .04) or recurrent chlamydial infection (4 vs 14; RR, 0.25; 95% CI, 0.08 to 0.83; P = .02). Adolescents in the intervention also reported a higher proportion of condom-protected sex acts in the 60 days preceding follow-up assessments (mean difference, 10.84; 95% CI, 5.27 to 16.42; P < .001) and less frequent douching (mean difference, -0.76; 95% CI, -1.15 to -0.37; P = .001). Adolescents in the intervention were also more likely to report consistent condom use in the 60 days preceding follow-up assessments (RR, 1. 41; 95% CI, 1.09 to 1.80; P = .01) and condom use at last intercourse (RR, 1.30; 95% CI, 1.09 to 1.54; P = .005). Intervention effects were observed for psychosocial mediators of STD/HIV-preventive behaviors.\n Interventions for African American adolescent females can reduce chlamydial infections and enhance STD/HIV-preventive behaviors and psychosocial mediators of STD/HIV-preventive behaviors. Trial Registration clinicaltrials.gov Identifier: NCT00633906.", "Two hundred forty-six African American adolescents were randomly assigned to an educational program or an 8-week intervention that combined education with behavior skills training including correct condom use, sexual assertion, refusal, information provision, self-management, problem solving, and risk recognition. Skill-trained participants (a) reduced unprotected intercourse, (b) increased condom-protected intercourse, and (c) displayed increased behavioral skills to a greater extent than participants who received information alone. The patterns of change differed by gender. Risk reduction was maintained 1 year later for skill-trained youths. It was found that 31.1% of youths in the education program who were abstinent at baseline had initiated sexual activity 1 year later, whereas only 11.5% of skills training participants were sexually active. The results indicate that youths who were equipped with information and specific skills lowered their risk to a greater degree, maintained risk reduction changes better, and deferred the onset of sexual activity to a greater extent than youths who received information alone.", "This study evaluated the long-term effectiveness of Safer Choices, a theory-based, multi-component educational program designed to reduce sexual risk behaviors and increase protective behaviors in preventing HIV, other STDs, and pregnancy among high school students.\n The study used a randomized controlled trial involving 20 high schools in California and Texas. A cohort of 3869 ninth-grade students was tracked for 31 months from fall semester 1993 (baseline) to spring semester 1996 (31-month follow-up). Data were collected using self-report surveys administered by trained data collectors. Response rate at 31-month follow-up was 79%.\n Safer Choices had its greatest effect on measures involving condom use. The program reduced the frequency of intercourse without a condom during the three months prior to the survey, reduced the number of sexual partners with whom students had intercourse without a condom, and increased use of condoms and other protection against pregnancy at last intercourse. Safer Choices also improved 7 of 13 psychosocial variables, many related to condom use, but did not have a significant effect upon rates of sexual initiation.\n The Safer Choices program was effective in reducing important risk behaviors for HIV, other STDs, and pregnancy and in enhancing most psychosocial determinants of such behavior.", "Some interventions to reduce the risk of the acquired immunodeficiency syndrome (AIDS) that target youths have resulted in short-term increases in self-reported condom use. However, long-term intervention effects have not been assessed.\n Can a theoretically and culturally based, AIDS-risk reduction intervention delivered to naturally formed peer groups increase self-reported condom use among African-American early adolescents at 6 and 12 months of follow-up?\n A randomized, controlled trial of a community-based intervention delivered in eight weekly sessions involved 76 naturally formed peer groups consisting of 383 (206 intervention and 177 control) African-American youths 9 to 15 years of age. A theory-based, culturally and developmentally tailored instrument that assessed perceptions, intentions, and self-reported sexual behaviors was administered to all subjects at baseline (preintervention) and 6 and 12 months later.\n At baseline, 36% of youths were sexually experienced, and by 12 months of follow-up, 49% were sexually experienced. Self-reported condom use rates were significantly higher among intervention than control youths (85% vs 61%; P<.05) at the 6-month follow-up. However, by 12 months, rates were no longer significantly higher among intervention youths. The intervention impact at 6 months was especially strong among boys (85% vs 57%; P<.05) and among early teens (13 to 15 years old) (95% vs 60%; P<.01). Self-reported condom use intention was also increased among intervention youths at 6 months but not at 12 months. Some perceptions were positively affected at 6 months, but the change did not persist at 12 months.\n High rates of sexual intercourse underscore the urgent need for effective AIDS-risk reduction interventions that target low-income urban, African-American preteens and early teens. A developmentally and culturally tailored intervention based on social-cognitive theory and delivered to naturally formed peer groups recruited from community settings can increase self-reported condom use. The strong short-term improvements in behaviors and intentions followed by some relapse over longer periods argue for a strengthened program and research focus on sustainability.", "The purposes of this pilot study were (a) to assess the feasibility of a community-based, small group HIV risk reduction intervention with adolescent girls, and (b) to obtain preliminary evidence of the efficacy of this theoretically-guided intervention using a controlled design. The feasibility of the intervention was demonstrated by successfully implementing it with 33 sexually-active, single girls. Preliminary evidence of the efficacy of the intervention was obtained using a randomized trial with 62 sexually-active, single girls. Data obtained at a 3-month follow-up assessment showed that girls who received the HIV-related intervention improved their HIV-related knowledge and enhanced their motivation for risk reduction compared to girls who received a control (health promotion) intervention. Effect sizes suggest that the HIV intervention also reduced several risk behaviors (e.g., vaginal sex without a condom, giving oral sex, and alcohol and drug use before sex). Challenges to implementation and suggestions for intervention enhancement are discussed.\n (c) 2004 Wiley Periodicals, Inc.", "To evaluate the feasibility, fidelity, and effectiveness of a human immunodeficiency virus (HIV) prevention intervention delivered to HIV-infected patients by counselors during routine clinical care in KwaZulu-Natal, South Africa.\n A total of 152 HIV-infected patients, aged 18 years and older, receiving clinical care at an urban hospital in South Africa, were randomly assigned to intervention or standard-of-care control counselors. Intervention counselors implemented a brief risk reduction intervention at each clinical encounter to help patients reduce their unprotected sexual behavior. Self-report questionnaires were administered at baseline and 6 months to assess number of unprotected sex events in previous 3 months.\n Intervention was delivered in 99% of routine patient visits and included a modal 8 of 8 intervention steps. Although HIV-infected patients in both conditions reported more vaginal and anal sex events at 6-month follow-up than at baseline, patients who received the counselor-delivered intervention reported a significant decrease over time in number of unprotected sexual events. There was a marginally significant increase in these events among patients in the standard-of-care control condition.\n A counselor-delivered HIV prevention intervention targeting HIV-infected patients seems to be feasible to implement with fidelity in the South African clinical care setting and effective at reducing unprotected sexual behavior.", "To evaluate the effects of an enhanced peer-led intervention on transmission risk behavior and serostatus disclosure of HIV-seropositive gay and bisexual men.\n A randomized intervention trial.\n HIV-seropositive gay and bisexual men were recruited from New York City and San Francisco and were randomly assigned to either a standard or an enhanced intervention. The standard intervention consisted of one session that provided safer sex information. The enhanced intervention consisted of six sessions and included safer sex information, interactive learning activities, and discussion groups that were facilitated by HIV-seropositive peers. Participants completed audio computer-assisted self interview (A-CASI) assessments at baseline and 3 and 6-month follow-ups. Optional testing for sexually transmitted infections was offered at baseline and the 6-month follow-up.\n A total of 811 participants met the inclusion criteria for outcome analyses. Of these, 85 and 90% were retained for the 3 and 6-month follow-ups, respectively. Compared with the standard intervention, fewer men assigned to the enhanced intervention reported unprotected receptive anal intercourse with a negative or unknown-serostatus partner at 3 months (21 versus 26%, P < 0.05). However, there were no other significant differences in transmission risk or serostatus disclosure at 3 or 6 months.\n The enhanced intervention was associated with only a limited reduction in transmission risk at 3 months relative to the standard intervention. The characteristics of the intervention that may have reduced its efficacy are identified and directions for future research are suggested.", "Peer norms influence the adoption of behavior changes to reduce risk for HIV (human immunodeficiency virus) infection. By experimentally intervening at a community level to modify risk behavior norms, it may be possible to promote generalized reductions in HIV risk practices within a population.\n We trained persons reliably identified as popular opinion leaders among gay men in a small city to serve as behavior change endorsers to their peers. The opinion leaders acquired social skills for making these endorsements and complied in talking frequently with friends and acquaintances. Before and after intervention, we conducted surveys of men patronizing gay clubs in the intervention city and in two matched comparison cities.\n In the intervention city, the proportion of men who engaged in any unprotected anal intercourse in a two-month period decreased from 36.9 percent to 27.5 percent (-25 percent from baseline), with a reduction from 27.1 percent to 19.0 percent (-30 percent from baseline) for unprotected receptive anal intercourse. Relative to baseline levels, there was a 16 percent increase in condom use during anal intercourse and an 18 percent decrease in the proportion of men with more than one sexual partner. Little or no change was observed among men in the comparison cities over the same period of time.\n Interventions that employ peer leaders to endorse change may produce or accelerate population behavior changes to lessen risk for HIV infection.", "While many studies provide useful information on the risk behaviors in which homeless youth engage, few prior studies evaluate Human Immunodeficiency Virus (HIV) risk related reduction strategies. In this study, homeless youth (n = 180) were recruited from a drop-in center and randomly assigned to one of two conditions, either an integrated individual cognitive-behavioral treatment and HIV prevention intervention that focused on skills building and education or to treatment as usual. All youth were assessed at entry into the program and at 3 and 6 month follow-up points. Findings showed an interaction between treatment condition, age and time. In the interaction, youth assigned to the integrated treatment reported greater condom usage than youth assigned to treatment as usual, with younger youth assigned to treatment as usual showing no change in condom use. The number of sexual partners reported by youth in both treatment conditions was also reduced over time. However, youth in both conditions continued to engage in other high-risk behaviors. The integrated treatment findings are promising and suggest that interventions which target both HIV risk behavior in addition to other life areas (substance use, mental health and housing) among homeless youth may be necessary in order to significantly impact high-risk behaviors among this unique group.", "To test the efficacy of brief, safer-sex counseling by medical providers of HIV-positive patients during medical visits.\n Six HIV clinics in California.\n Clinics were randomized to intervention arms evaluated with cohorts of randomly selected patients measured before and after the intervention.\n Five-hundred and eighty-five HIV-positive persons, sexually active prior to enrollment.\n Prevention counseling from medical providers supplemented with written information. Two clinics used a gain-framed approach (positive consequences of safer-sex), two used a loss-frame approach (negative consequences of unsafe sex), and two were attention-control clinics (medication adherence). Interventions were given to all patients who attended the clinics.\n Self-reported unprotected anal or vaginal intercourse (UAV).\n Among participants who had two or more sex partners at baseline, UAV was reduced 38% (P < 0.001) among those who received the loss-frame intervention. UAV at follow-up was significantly lower in the loss-frame arm [odds ratio (OR), 0.42; 95% confidence interval (CI), 0.19-0.91; P = 0.03] compared with the control arm. Using generalized estimating equations (GEE) to adjust for clustering did not change the conclusions (OR, 0.34; 95% CI, 0.24-0.49; P = 0.0001). Similar results were obtained in participants with casual partners at baseline. No effects were seen in participants with only one partner or only a main partner at baseline. No significant changes were seen in the gain-frame arm.\n Brief provider counseling emphasizing the negative consequences of unsafe sex can reduce HIV transmission behaviors in HIV-positive patients presenting with risky behavioral profiles.", "This study evaluated All4You!, a theoretically based curriculum designed to reduce sexual risk behaviors associated with HIV, other STDs, and unintended pregnancy among students in alternative schools. The study featured a randomized controlled trial involving 24 community day schools in northern California. A cohort of 988 students was assessed four times during an 18-month period using a self report questionnaire. At the 6-month follow-up, the intervention reduced the frequency of intercourse without a condom during the previous 3 months, the frequency of intercourse without a condom with steady partners, and the number of times students reported having intercourse in the previous 3 months. It also increased condom use at last intercourse. These behavioral effects were no longer statistically significant at the 12- and 18-month follow-ups. The All4You! intervention was effective in reducing selected sexual risk behaviors among students in alternative school settings; however, the effects were modest and short term.", "The impact of a multicomponent intervention programme on the sexual health of adolescents was assessed in rural Tanzania.\n A community-randomized trial.\n Twenty communities were randomly allocated to receive either a specially designed programme of interventions (intervention group) or standard activities (comparison group). The intervention had four components: community activities; teacher-led, peer-assisted sexual health education in years 5-7 of primary school; training and supervision of health workers to provide 'youth-friendly' sexual health services; and peer condom social marketing. Impacts on HIV incidence, herpes simplex virus 2 (HSV2) and other sexual health outcomes were evaluated over approximately 3 years in 9645 adolescents recruited in late 1998 before entering years 5, 6 or 7 of primary school.\n The intervention had a significant impact on knowledge and reported attitudes, reported sexually transmitted infection symptoms, and several behavioural outcomes. Only five HIV seroconversions occurred in boys, whereas in girls the adjusted rate ratio (intervention versus comparison) was 0.75 [95% confidence interval (CI) 0.34, 1.66]. Overall HSV2 prevalences at follow-up were 11.9% in male and 21.1% in female participants, with adjusted prevalence ratios of 0.92 (CI 0.69, 1.22) and 1.05 (CI 0.83, 1.32), respectively. There was no consistent beneficial or adverse impact on other biological outcomes. The beneficial impact on knowledge and reported attitudes was confirmed by results of a school examination in a separate group of students in mid-2002.\n The intervention substantially improved knowledge, reported attitudes and some reported sexual behaviours, especially in boys, but had no consistent impact on biological outcomes within the 3-year trial period.", "The incidence of AIDS is increasing at a higher rate among homosexual Asian and Pacific Islanders (API) than white homosexual men in the United States. The number of homosexual API men engaging in unsafe sex is increasing at an alarming rate. HIV risk reduction is urgently needed in this population.\n We developed and evaluated culturally appropriate brief group counseling with 329 self-identified homosexual API recruited in San Francisco between 1992 and 1994. Participants were randomized into a single, 3-h skills training group or a wait-list control group. The intervention consisted of four components: (1) development of positive self-identity and social support, (2) safer sex education, (3) eroticizing safer sex, and (4) negotiating safer sex. Data were collected at baseline and 3 months after the intervention.\n Significant reductions in number of sexual partners were observed among all treatment subjects, regardless of ethnicity (P = 0.003). Treatment decreased the number of partners reported at 3-month follow-up by 46% [95% confidence interval (CI), 28-77]. Chinese and Filipino men further benefited from the intervention: treatment subjects from these two ethnic groups reduced unprotected anal intercourse at follow-up by more than half when compared to their counterparts (odds ratio = 0.41; 95% CI, 0.19-0.89; P = 0.024).\n We demonstrated the efficacy of brief group counseling in reducing HIV risk among homosexual API. Cities with significant API populations should adopt culturally tailored skills training as part of HIV prevention strategies for this group of homosexual men.", "Our objectives were to assess the effects of a psychoeducational (PE) program designed to reduce HIV risk behaviors in recovering drug abusers and to evaluate mediating variables associated with risk reduction as described by the AIDS Risk Reduction Model (ARRM). Consecutive admissions to a Department of Veterans Affairs drug dependence inpatient treatment program (n = 152) were randomly assigned to PE or a standard information (INFO) condition. PE involved a 6-hour small group intervention designed to enhance knowledge and attitudes regarding HIV prevention, improve skills in condom use and needle sterilization, and modify high-risk sex- and drug-related behaviors. The INFO condition involved presentation of audiovisual and printed HIV prevention material with similar content. Following intervention, PE subjects showed significantly enhanced self-efficacy, condom use skills, and sexual communication skills relative to the INFO group. At 3-month follow-up, the PE group showed significantly greater reductions on some measures of sexual HIV risk behaviors relative to the INFO group. Hypotheses derived from the ARRM regarding presumed relationships between positive changes in mediating variables (e.g., self-efficacy and sexual communication) and ultimate outcome variables (e.g., condom use) were supported.", "African American adolescent girls are at high risk for human immunodeficiency virus (HIV) infection, but interventions specifically designed for this population have not reduced HIV risk behaviors.\n To evaluate the efficacy of an intervention to reduce sexual risk behaviors, sexually transmitted diseases (STDs), and pregnancy and enhance mediators of HIV-preventive behaviors.\n Randomized controlled trial of 522 sexually experienced African American girls aged 14 to 18 years screened from December 1996 through April 1999 at 4 community health agencies. Participants completed a self-administered questionnaire and an interview, demonstrated condom application skills, and provided specimens for STD testing. Outcome assessments were made at 6- and 12-month follow-up.\n All participants received four 4-hour group sessions. The intervention emphasized ethnic and gender pride, HIV knowledge, communication, condom use skills, and healthy relationships. The comparison condition emphasized exercise and nutrition.\n The primary outcome measure was consistent condom use, defined as condom use during every episode of vaginal intercourse; other outcome measures were sexual behaviors, observed condom application skills, incident STD infection, self-reported pregnancy, and mediators of HIV-preventive behaviors.\n Relative to the comparison condition, participants in the intervention reported using condoms more consistently in the 30 days preceding the 6-month assessment (unadjusted analysis, intervention, 75.3% vs comparison, 58.2%) and the 12-month assessment (unadjusted analysis, intervention, 73.3% vs comparison, 56.5%) and over the entire 12-month period (adjusted odds ratio, 2.01; 95% confidence interval [CI], 1.28-3.17; P =.003). Participants in the intervention reported using condoms more consistently in the 6 months preceding the 6-month assessment (unadjusted analysis, intervention, 61.3% vs comparison, 42.6%), at the 12-month assessment (unadjusted analysis, intervention, 58.1% vs comparison, 45.3%), and over the entire 12-month period (adjusted odds ratio, 2.30; 95% CI, 1.51-3.50; P<.001). Using generalized estimating equation analyses over the 12-month follow-up, adolescents in the intervention were more likely to use a condom at last intercourse, less likely to have a new vaginal sex partner in the past 30 days, and more likely to apply condoms to sex partners and had better condom application skills, a higher percentage of condom-protected sex acts, fewer unprotected vaginal sex acts, and higher scores on measures of mediators. Promising effects were also observed for chlamydia infections and self-reported pregnancy.\n Interventions for African American adolescent girls that are gender-tailored and culturally congruent can enhance HIV-preventive behaviors, skills, and mediators and may reduce pregnancy and chlamydia infection." ]	Many abstinence-plus programs appear to reduce short-term and long-term HIV risk behavior among youth in high-income countries. Evidence for program effects on biological measures is limited. Evaluations consistently show no adverse program effects for any outcomes, including the incidence and frequency of sexual activity. Trials comparing abstinence-only, abstinence-plus, and safer-sex interventions are needed.
CD001730	[ "6437487", "7660408", "17335327", "1998929", "9407576", "8357287", "8185149", "10404919", "11509308" ]	[ "Day hospital rehabilitation--effectiveness and cost in the elderly: a randomised controlled trial.", "Outcomes of elderly stroke patients. Day hospital versus conventional medical management.", "Are day hospitals effective for acutely ill psychiatric patients? A European multicenter randomized controlled trial.", "Effectiveness of a geriatric day hospital.", "A randomized trial of geriatric liaison intervention in elderly medical inpatients.", "A negative trial of inpatient geriatric consultation. Lessons learned and recommendations for future research.", "Comprehensive discharge planning for the hospitalized elderly. A randomized clinical trial.", "Chronic care clinics: a randomized controlled trial of a new model of primary care for frail older adults.", "Stroke rehabilitation after hospital discharge: a randomized trial comparing domiciliary and day-hospital care." ]	[ "The effectiveness and cost of day hospital care in rehabilitation were studied in a randomised controlled trial in 120 elderly patients who were assessed at referral and six weeks and five months later in activities of daily living skills and mood. Day hospital patients were compared with a control group, who were managed as they would have been before the availability of day hospital care. Day hospital patients showed a significant improvement in performance of activities of daily living at six weeks but not at five months; however, they had a sustained improvement in mood. The cost of day hospital rehabilitation was one third greater than that of rehabilitation by alternative means. In its current form the geriatric day hospital is not a cheap alternative to other means of rehabilitation. Expensive components of the day hospital should be critically re-examined and renewed emphasis placed on sufficient inpatient beds, domiciliary services, and day care centres.", "Much controversy exists over the value of geriatric day hospitals in the rehabilitation of elderly patients, and cerebrovascular accident is a particularly common diagnosis among patients referred to these day hospitals. We carried out a prospective, randomized study to compare the outcomes of elderly stroke patients managed by a geriatric team using a day hospital facility versus conventional medical management.\n One hundred twenty elderly patients with acute stroke were randomized to inpatient care on a stroke ward under the care of either a neurologist or a geriatric team. Those under the care of neurologists were hospitalized until the attending physician felt that the patients had reached full rehabilitation potential. Patients under the care of the geriatric team were discharged home as soon as the team felt they were able to cope and given follow-up rehabilitation at the day hospital. Family or community support was arranged when necessary for both treatment groups. On recruitment, patient demographics, medical history, clinical features related to stroke, and functional ability as measured by the Barthel Index were noted. Subjects were reviewed at 3 and 6 months to assess functional level, hospital and outpatient services received, general well-being, mood, and level of satisfaction. Costs of treatment of the two groups were also compared.\n Functional improvement (Barthel Index score) was greater in the group managed by the geriatricians with a day hospital facility compared with the conventional group at 3 months (P = .03). There were also fewer outpatient visits among the day hospital patients at 6 months (P = .03). No significant difference was found in costs between the two treatment groups.\n Compared with conventional medical management, care in the geriatric day hospital hastened functional recovery and reduced outpatient visits in elderly stroke patients without additional cost.", "Acute psychiatric day care has been proposed as an alternative to conventional inpatient care, yet the evidence of its effectiveness is inconsistent and based only on single-site studies in 3 countries. The aim of this multicenter randomized controlled trial was to establish the effectiveness of acute day hospital care in a large sample across a range of mental health care systems.\n The trial was conducted from December 2000 to September 2003 in 5 European countries, with a sample of 1117 voluntarily admitted patients. Immediately before or very shortly after admission to the participating psychiatric facilities, patients were randomly allocated to treatment in a day hospital or an inpatient ward. Psychopathology, treatment satisfaction, subjective quality of life, and social disabilities were assessed at admission, at discharge, and 3 and 12 months after discharge. An intention-to-treat analysis was conducted using fixed-effects linear models with structured error covariance matrices and covariates.\n Day hospital care was as effective as conventional inpatient care with respect to psychopathologic symptoms, treatment satisfaction, and quality of life. It was more effective on social functioning at discharge and at the 3- and 12-month follow-up assessments.\n This study, which has more than doubled the existing evidence base, has shown that day hospital care is as effective on clinical outcomes as conventional inpatient care and more effective on social outcomes.\n ClinicalTrials.gov identifier NCT00153959.", "To determine whether there is a difference in the quality of life between elderly patients managed in a day hospital and those receiving conventional care.\n Randomized controlled trial; assessment upon entry to study and at 3, 6 and 12 months afterward.\n Geriatrician referral-based secondary care.\n A total of 113 consecutively referred elderly patients with deteriorating functional status believed to have rehabilitation potential; 55 were assessed and treated by an interdisciplinary team in a day hospital (treatment group), and 58 were assessed in an inpatient unit or an outpatient clinic or were discharged early with appropriate community services (control group).\n Barthel Index, Rand Questionnaire, Global Health Question and Geriatric Quality of Life Questionnaire (GQLQ).\n Eight study subjects and four control subjects died; the difference was insignificant. Functional status deteriorated over time in the two groups; although the difference was not significant there was less deterioration in the control group. The GQLQ scores indicated no significant difference between the two groups in the ability to perform daily living activities and in the alleviation of symptoms over time but did show a trend favouring the control group. The GQLQ scores did indicate a significant difference in favour of the control group in the effect of treatment on emotions (p = 0.009).\n The care received at the day hospital did not improve functional status or quality of life of elderly patients as compared with the otherwise excellent geriatric outpatient care.", "The aim of this study was to examine the effect of psychogeriatric intervention in a group of elderly medical inpatients over 75 years of age. In addition to usual care, intervention consisted of multidisciplinary joint treatment by a psychogeriatric team. The main purpose of intervention was to obtain the optimal level of physical functioning.\n In a prospective randomized trial the effect of the intervention (N = 140) compared with usual care (N = 97) was estimated for physical functioning, length of stay, and nursing home placement within 12 months of discharge.\n Substantially more patients assigned to the intervention group improved in their physical functioning, and fewer became worse. The mean length of stay was 5 days shorter for the intervention group. There were more readmissions to hospital in the usual care group (29.9%) compared with the intervention group (17.4%). Of the patients assigned to the intervention treatment, 18% were admitted to a nursing home. In the usual care group this was 27%. The effects of intervention remained statistically significant for all the outcome variables after controlling for possible confounding baseline characteristics.\n The intervention we studied had clinically relevant effects on important outcome variables. Psychiatric co-morbidity was an important risk factor for the outcome of the patients in our study. By combining elements from a psychiatric and geriatric consultation service with elements from a unit-driven service, we were able to improve health care for the elderly in our hospital in a feasible and cost-effective way.", "To determine the effectiveness of inpatient interdisciplinary geriatric consultation provided during hospitalization to frail, elderly subjects. SUBJECTS AND SITE: Admission cohort of 197 men admitted from 1985 through 1989, aged 65 years or more, meeting proxy criteria for frailty, living within follow-up area, without terminal illness, and without prolonged nursing home residence.\n Randomized controlled trial of inpatient geriatric consultation at a tertiary care Veterans Affairs hospital. Differences were determined between groups in the Physical Self-Maintenance Scale, Instrumental Activities of Daily Living, Mini-Mental State Examination, Morale Scale, and nursing home and health care utilization.\n No differences were seen between groups in any measure after the intervention or during 1 year of follow-up. Intervention implementation may have been incomplete due to compliance and resource availability.\n This trial is not definitive in determining whether geriatric consultation is effective or ineffective. Lessons learned from this research indicate that future studies should target frail subjects, include intervention-specific measures, and be conducted with direct control of comprehensive resources.", "To study the effects of a comprehensive discharge planning protocol, designed specifically for the elderly and implemented by nurse specialists, on patient and caregiver outcomes and cost of care.\n Randomized clinical trial.\n Hospital of the University of Pennsylvania.\n 276 patients and 125 caregivers. Patients were 70 years and older and were placed in selected medical and surgical cardiac diagnostic-related groups.\n Group differences in patient outcomes (length of initial hospital stay, length of time between initial hospital discharge and readmission, and rehospitalization rates) and charges for care (charges for initial hospitalization, rehospitalizations, health services after discharge, and nurse specialist services) were measured 2, 6, and 12 weeks after discharge.\n From the initial hospital discharge to 6 weeks after discharge, patients in the medical intervention group had fewer readmissions, fewer total days rehospitalized, lower readmission charges, and lower charges for health care services after discharge. No differences in these outcomes were found between the surgical intervention and control groups during this period.\n Study findings support the need for comprehensive discharge planning designed for the elderly and implemented by nurse specialists to improve their outcomes after hospital discharge and to achieve cost savings. The findings also suggest that this intervention had its greatest effect in delaying or preventing rehospitalization of patients in the medical intervention group during the first 6 weeks after discharge.", "To determine whether a new model of primary care, Chronic Care Clinics, can improve outcomes of common geriatric syndromes (urinary incontinence, falls, depressive symptoms, high risk medications, functional impairment) in frail older adults.\n Randomized controlled trial with 24 months of follow-up. Physician practices were randomized either to the Chronic Care Clinics intervention or to usual care.\n Nine primary care physician practices that comprise an ambulatory clinic in a large staff-model HMO in western Washington State.\n Those patients aged 65 and older in each practice with the highest risk for being hospitalized or experiencing functional decline.\n Intervention practices (5 physicians, 96 patients) held half-day Chronic Care Clinics every 3 to 4 months. These clinics included an extended visit with the physician and nurse dedicated to planning chronic disease management; a pharmacist visit that emphasized reduction of polypharmacy and high-risk medications; and a patient self-management/support group. Control practices (4 physicians, 73 patients) received usual care.\n Changes in self-reported urinary incontinence, frequency of falls, depressive symptoms, physical function, and satisfaction were analyzed using an intention-to-treat analysis adjusted for baseline differences, covariates, and practice-level variation. Prescriptions for high-risk medications and cost/utilization data obtained from administrative data were similarly analyzed.\n After 24 months, no significant improvements in frequency of incontinence, proportion with falls, depression scores, physical function scores, or prescriptions for high risk medications were demonstrated. Costs of medical care including frequency of hospitalization, hospital days, emergency and ambulatory visits, and total costs of care were not significantly different between intervention and control groups. A higher proportion of intervention patients rated the overall quality of their medical care as excellent compared with control patients (40.0% vs 25.3%, P = .10).\n Although intervention patients expressed high levels of satisfaction with Chronic Care Clinics, improved outcomes for selected geriatric syndromes were not demonstrated. These findings suggest the need for developing greater system-wide support for managing geriatric syndromes in primary care and illustrate the challenges of conducting practice improvement research in a rapidly changing delivery system.", "To compare the effectiveness and costs of a new domiciliary rehabilitation service for elderly stroke patients with geriatric day-hospital care.\n Randomized controlled trial.\n Stroke patients aged 55+ who required further rehabilitation after hospital discharge or after referral to geriatricians from the community.\n Poole area, East Dorset, a mixed urban/rural area on the south coast of England.\n Primary-changes between hospital discharge and 6-month follow-up in physical function as measured by Barthel index. Secondary-changes over this period in Rivermead Mobility Index and mental state (Philadelphia Geriatric Centre Morale Scale) and differences in social activity (Frenchay Activities Index) and generic health status (SF-36). Health service and social service cost per patient were compared for the two groups.\n 180 patients were eligible and 140 (78%) were randomized. The groups were well balanced for age, sex, social class and initial Barthel index. We achieved follow-up in 88% of subjects who were alive at 6 months. We detected no significant differences in patient outcomes, although there was a non-significant improvement in measures of physical function and social activity in the domiciliary group. Domiciliary patients had more physiotherapy time per session and more district nurse time, and made greater use of social service day centres and home helps. Total cost per patient did not differ significantly between the two groups, with reduced health service costs in the domiciliary arm offset by higher social service costs.\n No significant differences were detected in the effectiveness of the two services. Neither service influenced patients' mental state, and their social activity remained low. Total costs were similar. A mixed model of day-hospital and domiciliary care may be most cost-effective for community stroke rehabilitation, but this requires further evaluation." ]	Medical day hospital care for the elderly appears to be more effective than no intervention but may have no clear advantage over other forms of comprehensive elderly medical services.
CD003293	[ "12835516", "8410110", "17308269", "16325695", "3881176", "3909798", "3047339" ]	[ "Phase III study of combined chemohormonal therapy in metastatic prostate cancer (ECOG 3882): an Eastern Cooperative Oncology Group study.", "Multiple-drug weekly chemotherapy versus standard combination regimen in small-cell lung cancer: a phase III randomized study conducted by the European Lung Cancer Working Party.", "Sequenced compared with simultaneous anthracycline and cyclophosphamide in high-risk stage I and II breast cancer: final analysis from INT-0137 (S9313).", "Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial.", "Randomized trial of combination chemotherapy in hormone-resistant metastatic prostate carcinoma.", "Randomized clinical trial of doxorubicin alone or combined with mitolactol in women with advanced breast cancer and prior chemotherapy exposure.", "Adjuvant chemotherapy for patients with high-grade soft-tissue sarcomas of the extremity." ]	[ "This study, a phase III multicenter randomized trial opened by ECOG in April 1983 and closed in June 1986 was designed to evaluate whether a combination of doxorubicin and an intravenous formulation of diethylstilbestrol diphosphate (DES) was superior to doxorubicin alone in men with hormone refractory prostate cancer. All patients received doxorubicin at a dose of 50 mg/m2 iv every 3 wk either alone or with 1 g DES iv daily for 5 d followed by 1 g iv twice weekly for four cycles (12 wk). The 51 evaluable patients with visceral metastases displayed a significantly increased response rate (27% vs 63%) on the combined therapy arm (p = 0.04). However, the 111 evaluable patients with osseous disease exhibited no difference in response rate between either arm with a p-value of >0.99. Similarly, clinical response rates revealed no difference between the two arms. Cases of cardiac toxicity graded as severe, life threatening, or lethal in the combined therapy arm were 10 times more frequent in the combined-therapy arm than in the doxorubicin-alone group (6.75% compared to 0.7%). This difference was statistically significant (p = 0.0041). All of the cases of superficial and deep venous thrombosis occurred on the combined-therapy arm. There were no other significant differences in the numbers of grade 3 or 4 toxic events. The most common toxicity was hematologic. Failure-free survival duration did reach statistical significance in the combined-therapy group (p = 0.012), although the actual durations were short (2.6-3.2 mo). There was no difference in overall survival between the two groups.", "A randomized trial was conducted in patients with small-cell lung cancer (SCLC) to determine if survival can be improved by a weekly chemotherapy regimen combining various drugs.\n Two hundred twenty-three patients were randomized to receive either six courses of a multiple-drug combination (MDC) regimen (Adriamycin [ADR; doxorubicin; Farmitalia Carlo Erba, Milan, Italy] 25 mg/m2 intravenously [i.v.] on day 1; etoposide [VP16] 120 mg/m2 i.v. on day 1; cyclophosphamide [CPA] 500 mg/m2 i.v. on day 1; cisplatin 60 mg/m2 i.v. on day 8; vindesine [VDS] 3 mg/m2 i.v. on day 8; vincristine [VCR] 2 mg i.v. on day 15; methotrexate [MTX] 100 mg/m2 i.v. on day 15), or a standard chemotherapy (SC) regimen (ADR 50 mg/m2 i.v. on day 1; CPA 1 g/m2 i.v. on day 1; VP16 80 mg/m2 i.v. on days 1 to 3).\n In 98 MDC-treated and 101 SC-treated assessable patients, we observed 69% and 62% objective responses rates, respectively. There was no significant difference in survival, with median durations and 2-year overall survival rates of 49 and 43 weeks and 8.5% and 7.9%, respectively. There was a significant increase in response rate in favor of MDC patients with limited disease (84% v 62%). Toxicity was tolerable, although SC was more hematotoxic, with 76% (v 59%) experiencing leukopenia and 17% (v 7%) experiencing thrombocytopenia (grades III and IV). If the cumulative doses received were nearly equal to the scheduled cumulative doses in both arms, the total relative dose-intensity (RDI) was significantly higher in the SC arm. The difference was due to increased treatment delays in the MDC arm.\n Weekly MDC failed to improve survival rates in patients with SCLC.", "We conducted a phase III randomized study of two adjuvant treatment schedules of doxorubicin (A) and cyclophosphamide (C) in early-stage breast cancer to determine if administration of sequential single agents (A --> C) results in superior disease-free survival (DFS) and overall survival (OS) versus the same total dose given in combination (AC).\n High-risk node-negative or low-risk node-positive breast cancer patients received AC given: (arm I) concurrently (AC) doxorubicin 54 mg/m2 and cyclophosphamide 1.2 g/m2 intravenously (IV) every 3 weeks for six cycles; or (arm II) in sequence (A C) doxorubicin 40.5 mg/m2 IV days 1 and 2 every 3 weeks for four cycles followed by cyclophosphamide 2.4 gm/m2 IV every 2 weeks for three cycles. Total dose and duration were identical, but the intensity of each drug was increased on A C. Both arms included granulocyte colony-stimulating factor support and prophylactic antibiotics. All but premenopausal women with receptor negative tumors received tamoxifen after chemotherapy.\n Between 1994 and 1997, 3,176 patients were randomly assigned. Arms were well balanced; 48% of eligible patients were node-negative and 48% were estrogen receptor-positive. No significant differences in OS or DFS were observed; 5-year estimates of OS (95% CI) were 88% (87% to 90%) on AC and 89% (87% to 91%) on A --> C. Grade 4 hematologic toxicity was greater on A --> C, but nonhematological grade 4 was similar.\n The overall result does not support superiority of dose-intense sequenced single agents. The greater toxicity of higher doses of single agents does not support their sequential use.", "Breast cancer with extensive axillary-lymph-node involvement has a poor prognosis after conventional treatment. In trials with historical controls, high-dose chemotherapy produced improved outcomes. We compared an intensive double-cycle high-dose chemotherapy regimen with an accelerated conventionally dosed regimen in high-risk breast cancer in a multicentre trial.\n Patients with at least nine positive nodes were randomly assigned either two courses of accelerated (2-week intervals, with filgrastim support), conventionally dosed epirubicin and cyclophosphamide followed by two courses of high-dose chemotherapy (epirubicin, cyclophosphamide, and thiotepa supported by peripheral-blood progenitors) or four identical cycles of epirubicin and cyclophosphamide followed by three cycles of accelerated cyclophosphamide, methotrexate, and fluorouracil. The primary endpoint was event-free survival. Analyses were done both by intention to treat and per protocol.\n 403 patients were enrolled; 201 were assigned high-dose chemotherapy and 202 conventional treatment. The mean number of positive nodes was 17.6, and median follow-up was 48.6 months. 4-year event-free survival (intention-to-treat analysis) was 60% (95% CI 53-67) in the high-dose chemotherapy group and 44% (37-52) in the control group (p=0.00069). The corresponding overall survival was 75% (69-82) versus 70% (64-77; p=0.02). There were no treatment-related deaths.\n Our finding of significant improvements in both event-free and overall survival for high-dose chemotherapy compared with a dose-dense conventional regimen contrasts with the results of other studies. The discrepancy might be due partly to design differences (tandem, brief induction) between our regimen and those studied in other trials. This approach merits further study.", "A prospective randomized study was conducted in 51 patients with stage D hormone-resistant prostatic carcinoma, comparing a combination of doxorubicin and lomustine (DC) with cyclophosphamide and 5-FU (CF). Patients were assessed objectively (employing National Prostate Cancer Project criteria) and subjectively (using a numerical scoring scheme). Each regimen was well tolerated with acceptable levels of myelosuppression. The objective partial response rate was 57% for DC and 8% for CF. Objective stabilization occurred, respectively, in 14% and 44% of the patients. Similarly, DC demonstrated a significantly superior subjective response rate (partial plus complete) of 82%, compared to 48% for CF. Patients with poor initial performance status or liver involvement had significantly lower response rates and reduced survival. Overall, there was no significant difference in survival between the two arms, reflecting the similarity between DC and CF in total objective response rate (partial response plus stable disease). DC provided superior palliation and was well tolerated by an essentially geriatric population.", "One hundred fifty-one women with advanced breast cancer who had failed prior chemotherapy were randomized to monthly courses of doxorubicin (60 mg/m2 I.V. day 1, observation after 500 mg/m2) or doxorubicin (40 mg/m2 I.V. day 1; maximum 500 mg/m2) and mitolactol (135 mg/m2 orally, days 1-10; 180 mg/m2 after maximum doxorubicin). Median survival times were 232 days for doxorubicin and 225 days for doxorubicin + mitolactol, and median times to progression were 112 days and 97 days, respectively. Results are inconsistent with a 25% improvement in survival or time to progression for doxorubicin + mitolactol (p = 0.04 and 0.02, respectively, adjusted for stratification factors but not multiple testing). Regression rates for all patients, both measurable and evaluable, were 30% for doxorubicin alone and 26% for doxorubicin + mitolactol. Regression rates were significantly higher in patients with measurable indicator lesions. Cardiac toxicity was seen in four patients, all of whom were receiving doxorubicin alone. It appears that the combination of doxorubicin + mitolactol is not substantially more effective than doxorubicin alone in women with advanced breast cancer and prior chemotherapy exposure.", "We have previously reported the results of a randomized trial that demonstrated the survival benefit of adjuvant chemotherapy in the treatment of patients with high-grade extremity sarcomas compared with no chemotherapy. This regimen included doxorubicin, cyclophosphamide, and methotrexate. This report updates and extends our experience. The median follow-up of this trial is now 7.1 years and reveals a 5-year disease-free survival of 75% and 54% for chemotherapy and no chemotherapy groups, respectively (two-sided P [P2] = .037). The 5-year overall survival for patients in this trial was 83% and 60% for the chemotherapy and no chemotherapy groups, respectively, with a trend towards improved survival in the chemotherapy arm (P2 = .124). Because of doxorubicin-induced cardiomyopathy we performed a subsequent randomized trial comparing this high-dose regimen to reduced cumulative doses of doxorubicin and cyclophosphamide without methotrexate. Eighty-eight patients were entered into this trial which has a median follow-up of 4.4 years. The 5-year disease-free and overall survival for patients treated with the reduced doses of chemotherapy was 72% and 75%, respectively, and was not significantly different from the high-dose regimen. No patients developed congestive heart failure on this study. We conclude that adjuvant chemotherapy improves disease-free survival in patients with extremity soft-tissue sarcomas. The overall survival advantage in patients receiving adjuvant chemotherapy in our initial randomized high-dose chemotherapy trial has diminished though it continues to favor the chemotherapy group. A reduced-dose chemotherapy regimen was found to be comparable to the high-dose regimen." ]	Compared to single-agent doxorubicin, the combination chemotherapy regimens evaluated, given in conventional doses, produced only marginal increases in response rates, at the expense of increased toxic effects and with no improvements in overall survival.
CD006006	[ "7843707", "8780576", "7762065", "8605558", "10693639", "11477342", "11389707", "12297843" ]	[ "A double-blind, randomized, placebo-controlled trial of prostaglandin E1 in liver transplantation.", "Prostaglandin E1 administration following orthotopic liver transplantation: a randomized prospective multicenter trial.", "Enisoprost in liver transplantation.", "Postoperative intravenous infusion of alprostadil (PGE1) does not improve renal function in hepatic transplant recipients.", "Administration of prostacyclin after liver transplantation: a placebo controlled randomized trial.", "The effects of lipid-lowering agents on acute renal allograft rejection.", "Effect of lovastatin, an HMG CoA reductase inhibitor, on acute renal allograft rejection.", "Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study." ]	[ "A double-blind placebo-controlled trial of intravenous prostaglandin PGE1 (40 micrograms/h) was conducted in adult orthotopic liver transplant recipients. Infusion was started intraoperatively and continued for up to 21 days. Patients were followed up for 180 days postoperatively. Among 172 patients eligible for treatment in the study, 160 could be evaluated (78 PGE1; 82 placebo). Patient and graft survival were similar (PGE1: 16 deaths, 9 retransplantations [7 survivors]; controls: 15 deaths, 6 retransplantations [3 survivors]). In patients with surviving grafts, however, PGE1 administration resulted in a 23% shorter mean duration of hospitalization following transplantation (PGE1: 24.4 days; controls: 31.8 days; P = .02) and a 40% shorter length of time postoperatively in the intensive care unit (PGE1: 8.2 days; controls 13.7 days; P = .05). Reduced needs for renal support (P = .03) or surgical intervention other than retransplantation (P = .02) were also noted with PGE1 use. Further, PGE1 administration resulted in a trend toward improved survival rates in patients with mild renal impairment (preoperative serum creatinine 1.5 mg percent or greater; P = .08). Neither the incidence of acute cellular rejection nor of primary nonfunction was significantly different in the two groups. Phlebitis was the only complication that was more common during PGE1 administration, (PGE1: 9; controls: 4). These results suggest that PGE1 use in hepatic allograft recipients reduces morbidity and may result in sizable cost reductions.", "Prostaglandin E1 (PGE1) has been used after orthotopic liver transplantation (OLT) based on limited clinical data suggesting PGE1 infusion improves immediate hepatic allograft function. The aim of this study was to conduct a randomized double-blinded multicenter trial to evaluate the effect of PGE1 on early hepatic and renal function in patients undergoing OLT.\n One hundred eighteen patients were randomized to receive either PGE1 or crystalloid placebo intravenously after allograft revascularization. Primary end points were incidence of primary allograft nonfunction (PNF) or severe renal dysfunction.\n The incidence of PNF was 6.7% (4 of 60) and 6.9% (4 of 58) in the control and PGE1 groups, respectively. PGE1 infusion was, however, associated with improved early renal function (mean peak creatinine level of 1.4 +/- 1.0 and 2.0 +/- 1.0 in patients treated with PGE1 and placebo, respectively; P < 0.001). Severe renal dysfunction occurred more frequently in the placebo group (26.7%) than in the PGE1 group (13.8%; P = 0.65). Additionally, dialysis treatments were more frequent in the placebo group (0.7 +/- 2.0 per patient) than in the PGE1 group (0.2 +/- 1.0 per patient; P = 0.10). Initial intensive care unit stay was shorter in patients treated with PGE1 (4.0 +/- 3.6 days) compared with controls (10.5 +/- 17.1 days) (P < 0.01).\n PGE1 administration after OLT resulted in improved renal function and decreased initial postoperative intensive care unit stay but did not affect the incidence of PNF.", "Previous human studies in renal transplant recipients have shown a lower incidence of acute rejection and cyclosporine-associated acute nephrotoxicity when prostaglandins are administered in conjunction with standard immunosuppressants. This study evaluates the effects of enisoprost (EP), a synthetic PGE methyl ester analog, in a single-center, prospective, randomized, double-blind, placebo-controlled, parallel group trial in 81 consecutive adult patients undergoing orthotopic liver transplantation (OLT). The subjects received EP 100 mg p.o. t.i.d. (n = 40) or placebo (n = 41) for the first 12 weeks after OLT. Immunosuppression was based on cyclosporine, azathioprine, and corticosteroids. Effective renal plasma flow and glomerular filtration rate were determined at 4 and 12 weeks after OLT. Eighty-one patients entered the study; sixty-six patients completed the 16-week study period. There were no statistically significant differences between EP- and placebo-treated groups at 12 weeks for creatinine clearance, glomerular filtration rate, and effective renal plasma flow. At least 1 episode of cyclosporine nephrotoxicity occurred in 7/40 patients (17.5%) in the EP group compared with 9/41 patients (20.0%) in the placebo group (P = 0.781). There was no significant difference in the incidence of graft rejection episodes in the 2 groups. Enisoprost, as used in this study, does not have any beneficial effect on renal function or incidence of rejection in OLT recipients.", "Acute renal failure is a frequent complication following orthotopic hepatic transplantation. A reduction in the synthesis of intrarenal vasodilator prostaglandins has been proposed as having an important role in the pathogenesis of renal insufficiency associated with hepatic dysfunction, as well as in the nephrotoxicity associated with cyclosporine and FK506 immunosuppressive therapy. Therefore, administration of vasodilator prostaglandins may improve renal function following hepatic transplantation. This study was designed to determine the effect of continuous intravenous alprostadil (prostaglandin E1) on postoperative renal function in hepatic transplant patients.\n In a randomized, double-blind, placebo-controlled trial, 21 patients who had undergone orthotopic hepatic transplantation and had a measured postoperative glomerular filtration rate (GFR) of less that 50 mL/minute received intravenous alprostadil at 0.6 microgram/kg/hour or placebo for five days. Glomerular filtration rate and effective renal plasma flow (ERPF) were measured by a single-injection clearance method using a radionuclide agent in 53 patients within 12 hours after admission to our surgical intensive care unit. Usual postoperative care was not modified. Radionuclide GFR and ERPF measurements were repeated on postoperative day 3. Serum creatinine was measured preoperatively and postoperatively on day 3 and on day 5. A 24-hour serum creatinine clearance was measured on days 1, 5, and 14. Urine output was recorded hourly during the infusion period.\n Ten patients received alprostadil, and 11 patients received placebo. There was a significant increase in GFR and ERPF in both groups on post-operative day 3 as compared with baseline values. There was no difference in GFR and ERPF between the two groups on day 3 (48 +/- 18 and 246 +/- 68 mL/minute in the alprostadil group compared with 53 +/- 17 and 270 +/- 131 mL/minute in the placebo group). Serum creatinine levels increased on day 3 in both groups but returned to baseline by day 5.\n These results indicate that a reversible decrease in GFR is common on hepatic transplant patients during the postoperative period. Administration of a continuous intravenous infusion of alprostadil in the immediate postoperative period had no effect on renal function when compared with placebo.", "The shortage of suitable organs for liver grafts is responsible for the use of marginal donors for liver transplantation (OLT). If these liver grafts function poorly initially after OLT, a supportive therapy is necessary. The purpose of this study was to evaluate the effects of prostacyclin (PGI2) on postoperative liver graft function after OLT. A total of 30 adult recipients of primary OLT were randomized to either receive PGI2 (4 ng/kg per min body weight, n = 15) or a placebo for 6 d. To evaluate regional splanchnic oxygenation a fiberoptic pulmonary-artery catheter was inserted into a hepatic vein and the difference between mixed venous oxygen content and hepatic venous oxygen content was determined (deltaO2). Measurements were performed directly after transplantation and at 6, 12, 24 and 48 h postoperatively. A significant correlation between deltaO2 and the level of transaminases (ALT/AST) was observed 24 and 48 h after transplantation (p < 0.05). PGI2 treatment induced a significant decrease in deltaO2 after 24 and 48 h after reperfusion (p < 0.05). Peak AST levels tended to be lower in the PGI2 treatment group (418 +/- 99 vs. 638 +/- 156 U/L, p < 0.1). These results suggest that administration of PGI2 after OLT improves hepatic-splanchnic oxygenation and may thereby reduce reperfusion injury after OLT.", "Preliminary results from clinical trials suggest that 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors may help prevent acute renal allograft rejection. However, the mechanism for this putative effect of 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors, and whether it is independent of lipid-lowering per SE are unknown.\n Immediately after renal transplantation we randomly allocated (proportioned 2:1:2) patients to: 1) simvastatin (10 mg/day, n=53), 2) simvastatin placebo plus gemfibrozil (dose adjusted for renal function, n=36), and 3) simvastatin placebo (n=52).\n Simvastatin, but not gemfibrozil, reduced total and low density lipoprotein cholesterol during the first 90 days posttransplant. There were no major adverse effects of therapy. However, there were no effects of treatment on acute rejection. Indeed, survival free of acute rejection at 90 days was 72% in the simvastatin group, 72% in the gemfibrozil group, and 77% in the placebo control group (P=0.771). A post hoc power analysis suggested that there was only a 7.5% chance that a true effect of simvastatin on acute rejection (versus placebo) was not detected, and a 2.5% chance that an effect of gemfibrozil on acute rejection (versus placebo) was not detected in this study.\n Lipid-lowering agents may not reduce the incidence of acute renal allograft rejection. However, additional studies are needed to confirm this observation. In the mean time, many if not most renal transplant recipients should be treated with HMG-CoA reductase inhibitors starting early posttransplant to prevent cardiovascular disease complications. The results of this study suggest that starting lipid-lowering therapy immediately after renal transplantation is both safe and effective in lowering total and low density lipoprotein cholesterol.", "3-Hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitors are established anti-lipidemic agents. They also exert immunomodulatory effects. Two recent reports suggest that pravastatin may be useful in decreasing the incidence and severity of acute rejections (ARs) in heart and kidney transplant recipients. We undertook this prospective, randomized, placebo-controlled, double blind trial to investigate the effect of lovastatin on acute renal allograft rejection. Sixty-five consecutive, one-haplotype-matched, living related first renal transplant recipients were randomized to receive either lovastatin 20 mg/d or placebo for 3 months, in addition to cyclosporine, azathioprine, and steroids. Lipid levels, AR episodes, and liver and muscle enzymes were followed for 3 months post-transplant. At the end of the study period, lovastatin had successfully controlled lipid levels. However, there was no effect on AR episodes (15.15% in the treatment group vs. 18.75% in the placebo group).", "Patients with liver cirrhosis and a superimposed acute injury with progressive hyperbilirubinemia have a high mortality. A prospective, controlled study was performed to test whether hyperbilirubinemia, 30-day survival, and encephalopathy would be improved by extracorporeal albumin dialysis (ECAD). Twenty-four patients were studied; 23 patients had cirrhosis; 1 had a prolonged cholestatic drug reaction and was excluded from per protocol (PP) analysis. Patients had a plasma bilirubin greater than 20 mg/dL and had not responded to prior standard medical therapy (SMT). Patients were randomized to receive SMT with ECAD or without (control). ECAD was performed with an extracorporeal device that dialyzes blood in a hollow fiber dialyzer (MW cutoff < 60 kd) against 15% albumin. Albumin-bound molecules transfer to dialysate albumin that is regenerated continuously by passage through a charcoal and anion exchange column and a conventional dialyzer. ECAD was associated with improved 30-day survival (PP, 11 of 12 ECAD, 6 of 11 controls; log rank P <.05). Plasma bile acids and bilirubin decreased on average by 43% and 29%, respectively, in the ECAD group after 1 week of treatment, but not in the control group. Renal dysfunction and hepatic encephalopathy improved in the ECAD group, but worsened significantly in the control group. ECAD was safe, with adverse events being rare and identical in both groups. In conclusion, ECAD appears to be effective and safe for the short-term treatment of patients with cirrhosis and superimposed acute injury associated with progressive hyperbilirubinemia and may be useful for increasing survival in such patients awaiting liver transplantation." ]	We found no evidence that the administration of prostaglandins to liver transplanted patients reduces the risk of death, primary non-function of the allograft, or liver re-transplantation. Prostaglandins might reduce the risk of acute kidney failure requiring dialysis, but the quality of the evidence is considered only moderate due to high risk of bias in most of the included trials. Moreover, there are risks of outcome measure reporting bias and random errors. Therefore, further randomised, placebo-controlled trials are deemed necessary.
CD008246	[ "8014707", "9462190" ]	[ "Flow-synchronized ventilation of preterm infants with respiratory distress syndrome.", "Randomised trial of volume controlled versus time cycled, pressure limited ventilation in preterm infants with respiratory distress syndrome." ]	[ "Asynchrony of delivered and spontaneous breaths in mechanically ventilated infants may impair gas exchange and prolong the need for assisted ventilation. We conducted a randomized, controlled trial of a patient-triggered, flow-synchronized ventilator on 30 preterm infants with respiratory distress syndrome who weighed between 1100 and 1500 gm at birth. Entry criteria included radiographic evidence of respiratory distress syndrome and the need for mechanical ventilation and surfactant replacement therapy. Patients were assigned to either conventional time-cycled, pressure-limited ventilation or patient-triggered, flow-synchronized ventilation in an assist/control mode. Otherwise clinical management was identical. Time to extubation was the primary outcome measure. Patients treated with flow-synchronized ventilation were weaned more rapidly and had a significantly shorter mean time to extubation than those treated with time-cycled, pressure-limited ventilation, 119 versus 271 hours, p = 0.0152. In addition, there was no difference in the rate of complications between the two groups. There were, however, considerable reductions in patient charges of $4344 per patient in the flow-synchronized ventilation group.", "Fifty preterm infants weighing 1200 g or more with clinical and radiographic evidence of respiratory distress syndrome, requiring both mechanical ventilation and exogenous surfactant replacement, were randomly allocated to receive either volume controlled ventilation or time cycled, pressure limited ventilation. Tidal volume delivery in each group was deliberately controlled at 5-8 ml/kg so that the only difference between the two groups was the ventilatory modality, the manner in which tidal volume was delivered. The rest of the ventilatory management and clinical care was done according to protocol. The two modes of ventilation were compared by determining the time required to achieve pre-determined success criteria, based on either the alveolar-arterial oxygen gradient or the mean airway pressure as a standard against which the speed of weaning could be objectively assessed. Infants randomised to volume controlled ventilation met success criteria sooner and had a shorter duration of mechanical ventilation. These babies also had a significantly lower incidence of intraventricular haemorrhages and abnormal periventricular echodensities on ultrasound scans. Volume controlled ventilation seems to be both safe and effective in this group of patients." ]	There is insufficient evidence to determine the safety and efficacy of flow-cycled compared to time-cycled synchronized ventilation in neonates. Large randomized clinical trials using a parallel-group design and reporting on clinically important outcomes are warranted.
CD008534	[ "16962532", "18271883" ]	[ "A randomized comparison of suturing techniques for episiotomy and laceration repair after spontaneous vaginal birth.", "Postpartum perineal repair performed by midwives: a randomised trial comparing two suture techniques leaving the skin unsutured." ]	[ "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.", "To compare a continuous suture technique with interrupted stitches using inverted knots for postpartum perineal repair of second-degree lacerations and episiotomies.\n A double-blind randomised controlled trial.\n A Danish university hospital with more than 4800 deliveries annually.\n A total of 400 healthy primiparous women with a vaginal delivery at term. METHOD Randomisation was computer-controlled. Structured interviews and systematic assessment of perineal healing were performed by research midwives blinded to treatment allocation at 24-48 hours, 10 days and 6 months postpartum. Pain was evaluated using a visual analogue scale and the McGill Pain Questionnaire. Wound healing was evaluated using the REEDA scale and by assessment of gaping wounds >0.5 cm. Analysis complied with the intention-to-treat principle.\n The primary outcome was perineal pain 10 days after delivery. Secondary outcomes were wound healing, patient satisfaction, dyspareunia, need for resuturing, time elapsed during repair and amount of suture material used.\n A total of 400 women were randomised; 5 women withdrew their consent, leaving 395 for follow up. The follow-up rate was 98% for all assessments after delivery. No difference was seen in perineal pain 10 days after delivery. No difference was seen in wound healing, patient satisfaction, dyspareunia or need for resuturing. The continuous suture technique was significantly faster (15 versus 17 minutes, P = 0.03) and less suture material was used (one versus two packets, P < 0.01).\n Interrupted, inverted stitches for perineal repair leaving the skin unsutured appear to be equivalent to the continuous suture technique in relation to perineal pain, wound healing, patient satisfaction, dyspareunia and need for resuturing. The continuous technique, however, is faster and requires less suture material, thus leaving it the more cost-effective of the two techniques evaluated." ]	There is limited evidence available from RCTs to guide the choice between surgical or non-surgical repair of first- or second-degree perineal tears sustained during childbirth. Two studies find no difference between the two types of management with regard to clinical outcomes up to eight weeks postpartum. Therefore, at present there is insufficient evidence to suggest that one method is superior to the other with regard to healing and recovery in the early or late postnatal periods. Until further evidence becomes available, clinicians' decisions whether to suture or not can be based on their clinical judgement and the women's preference after informing them about the lack of long-term outcomes and the possible chance of a slower wound healing process, but possible better overall feeling of well being if left un-sutured.
CD002270	[ "10207925", "9708751" ]	[ "Acetazolamide and furosemide for posthemorrhagic hydrocephalus of the newborn.", "International randomised controlled trial of acetazolamide and furosemide in posthaemorrhagic ventricular dilatation in infancy. International PHVD Drug Trial Group." ]	[ "The authors evaluated the efficacy of acetazolamide (ACZ) and furosemide (FUR) in avoiding ventricular shunting procedures in preterm infants with posthemorrhagic hydrocephalus (PHH) and increased intracranial pressure (ICP). Preterm infants were screened for PHH (defined as ventriculomegaly [VM] and increased ICP measured with the Ladd fiberoptic monitor). PHH infants were randomized to ACZ and FUR treatment or serial lumbar puncture (LP) and monitored until not receiving medications or having undergone shunting. Of 69 infants with IVH screened for the study, 39 never developed VM, 14 developed VM, without increased ICP, and 16 developed PHH. Ten PHH infants were randomized to ACZ and FUR treatment and six to serial LP. Nine (90%) of the 10 infants assigned to the ACZ and FUR group avoided shunting. Nephrocalcinosis developed in a significant proportion of treated infants. Three (50%) of the six LP group infants did not require shunting procedures (P = 0.118). The authors conclude that ACZ and FUR therapy is useful in the treatment of preterm infants with PHH. Because a significant number of infants treated with both ACZ and FUR developed nephrocalcinosis, close monitoring for increased calcium excretion in the urine, or use of ACZ without FUR, is advised.", "Furosemide and acetazolamide are widely used in the treatment of posthaemorrhagic ventricular dilatation (PHVD) in the hope of avoiding the need for surgical management, but this approach has not been evaluated in a controlled trial. This multicentre randomised controlled trial tested the hypothesis that these drugs would reduce the rate of shunt placement and increase disability-free survival at 1 year of age.\n Between 1992 and 1996, 177 infants aged less than 3 months past term, and with ventricular width more than 4 mm above 97th centile after intraventricular haemorrhage, were randomly assigned standard therapy alone or standard therapy plus treatment with acetazolamide (100 mg/kg daily) and furosemide (1 mg/kg daily). A minimisation algorithm ensured balance between groups with respect to both referral centre and the presence of a cerebral parenchymal lesion on cerebral ultrasonography at enrolment. The trial was stopped in September, 1996, because the data showed a clear advantage with standard therapy.\n We report outcomes for 151 infants whose expected date of delivery was before the end of 1995, with complete information at 1 year for 129 infants. The median gestational age was 28 weeks, mean birthweight 1299 g, and mean postnatal age at enrolment 25 days. 44% had a parenchymal lesion at randomisation. Death or shunt placement occurred in 49 of 75 infants allocated drugs plus standard therapy, compared with 35 of 76 allocated to standard therapy alone. The relative risk was 1.42 (95% CI 1.06-1.90; p=0.026), which is equivalent to one extra death or shunt placement for every five infants allocated drug therapy. 84% (52/62) of infants assigned drug therapy had died or were disabled or impaired at 1 year, compared with 60% (40/67) of those assigned standard therapy (relative risk 1.40 [1.12-1.76]; p=0.012).\n These preliminary results suggest that the use of acetazolamide and furosemide in preterm infants with PHVD is associated with a higher rate of shunt placement and increased neurological morbidity, and so cannot be recommended." ]	Acetazolamide and furosemide therapy is neither effective nor safe in treating post-hemorrhagic ventricular dilatation. Acetazolamide and furosemide cannot be recommended as therapy for post hemorrhagic hydrocephalus.
CD002243	[ "6384785", "12186604", "12133187", "9559600", "3306374", "18184957", "786190", "16625008", "20103758", "2888017", "10321661", "17992396", "6712466", "17710485", "15474134", "19177141", "18184958", "16276166", "11087152" ]	[ "The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study.", "Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.", "Physiological-dose steroid therapy in sepsis [ISRCTN36253388].", "Reversal of late septic shock with supraphysiologic doses of hydrocortisone.", "A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock.", "Hydrocortisone therapy for patients with septic shock.", "Steroids in the treatment of clinical septic shock.", "Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.", "Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial.", "Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. The Veterans Administration Systemic Sepsis Cooperative Study Group.", "Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study.", "Early dexamethasone treatment for septic shock patients: a prospective randomized clinical trial.", "The cardiopulmonary response to massive doses of steroids in patients with septic shock.", "Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization.", "Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial.", "A comparison of two regimens of topical corticosteroids in the treatment of patients with bullous pemphigoid: a multicenter randomized study.", "Intensive insulin therapy and pentastarch resuscitation in severe sepsis.", "Low-dose hydrocortisone improves shock reversal and reduces cytokine levels in early hyperdynamic septic shock.", "Double-blind comparison of two corticosteroid regimens plus mycophenolate mofetil and cyclosporine for prevention of acute renal allograft rejection." ]	[ "To determine whether corticosteroids are efficacious in severe septic shock, we conducted a prospective study of 59 patients randomly assigned to a methylprednisolone, dexamethasone, or control group. Patients were treated 17.5 +/- 5.4 hours (mean +/- S.E.M.) after the onset of shock, and 55 patients required vasopressor agents. Early in the hospital course, reversal of shock was more likely in patients who received corticosteroids than in those who did not. Four (19 per cent) of 21 methylprednisolone-treated, 7 (32 per cent) of 22 dexamethasone-treated, and none of 16 control patients had reversal of shock 24 hours after drug administration (corticosteroid groups vs. control group, P less than 0.05). Patients treated with corticosteroids within four hours after the onset of shock had a higher incidence of shock reversal (P less than 0.05). At 133 hours after drug administration, 17 (40 per cent) of 43 corticosteroid-treated patients had died, and 11 (69 per cent) of 16 control patients had died (P less than 0.05). However, these differences in reversal of shock and survival disappeared later in the course. Overall, 16 (76 per cent) of 21 patients receiving methylprednisolone, 17 (77 per cent) of 22 patients receiving dexamethasone, and 11 (69 per cent) of 16 controls in the hospital died. We conclude that corticosteroids do not improve the overall survival of patients with severe, late septic shock but may be helpful early in the course and in certain subgroups of patients.", "Septic shock may be associated with relative adrenal insufficiency. Thus, a replacement therapy of low doses of corticosteroids has been proposed to treat septic shock.\n To assess whether low doses of corticosteroids improve 28-day survival in patients with septic shock and relative adrenal insufficiency.\n Placebo-controlled, randomized, double-blind, parallel-group trial performed in 19 intensive care units in France from October 9, 1995, to February 23, 1999.\n Three hundred adult patients who fulfilled usual criteria for septic shock were enrolled after undergoing a short corticotropin test.\n Patients were randomly assigned to receive either hydrocortisone (50-mg intravenous bolus every 6 hours) and fludrocortisone (50- micro g tablet once daily) (n = 151) or matching placebos (n = 149) for 7 days.\n Twenty-eight-day survival distribution in patients with relative adrenal insufficiency (nonresponders to the corticotropin test).\n One patient from the corticosteroid group was excluded from analyses because of consent withdrawal. There were 229 nonresponders to the corticotropin test (placebo, 115; corticosteroids, 114) and 70 responders to the corticotropin test (placebo, 34; corticosteroids, 36). In nonresponders, there were 73 deaths (63%) in the placebo group and 60 deaths (53%) in the corticosteroid group (hazard ratio, 0.67; 95% confidence interval, 0.47-0.95; P =.02). Vasopressor therapy was withdrawn within 28 days in 46 patients (40%) in the placebo group and in 65 patients (57%) in the corticosteroid group (hazard ratio, 1.91; 95% confidence interval, 1.29-2.84; P =.001). There was no significant difference between groups in responders. Adverse events rates were similar in the 2 groups.\n In our trial, a 7-day treatment with low doses of hydrocortisone and fludrocortisone significantly reduced the risk of death in patients with septic shock and relative adrenal insufficiency without increasing adverse events.", "The aim of the study was to assess the prognostic importance of basal cortisol concentrations and cortisol response to corticotropin, and to determine the effects of physiological dose steroid therapy on mortality in patients with sepsis.\n Basal cortisol level and corticotropin stimulation test were performed within 24 hours in all patients. One group (20 patients) received standard therapy for sepsis and physiological-dose steroid therapy for 10 days; the other group (20 patients) received only standard therapy for sepsis. Basal cortisol level was measured on the 14th day in patients who recovered. The outcome of sepsis was compared.\n Only Sequential Organ Failure Assessment (SOFA) score was found related to mortality, independent from other factors in multivariate analysis. No significant difference was found between the changes in the percentage of SOFA scores of the steroid therapy group and the standard therapy group in survivors, nor between the groups in basal and peak cortisol levels, cortisol response to corticotropin test and mortality. The mortality rates among patients with occult adrenal insufficiencies were 40% in the steroid therapy group and 55.6% in the standard therapy group.\n There was a trend towards a decrease in the mortality rates of the patients with sepsis who received physiological-dose steroid therapy. In the advancing process from sepsis to septic shock, adrenal insufficiency was not frequent as supposed. There was a trend (that did not reach significance) towards a decrease in the mortality rates of the patients with sepsis who received physiological-dose steroid therapy.", "Preliminary studies have suggested that low doses of corticosteroids might rapidly improve hemodynamics in late septic shock treated with catecholamines. We examined the effect of hydrocortisone on shock reversal, hemodynamics, and survival in this particular setting.\n Prospective, randomized, double-blind, placebo-controlled study.\n Two intensive care units of a University hospital.\n Forty-one patients with septic shock requiring catecholamine for >48 hrs.\n Patients were randomly assigned either hydrocortisone (100 mg i.v. three times daily for 5 days) or matching placebo.\n Reversal of shock was defined by a stable systolic arterial pressure (>90 mm Hg) for > or =24 hrs without catecholamine or fluid infusion. Of the 22 hydrocortisone-treated patients and 19 placebo-treated patients, 15 (68%) and 4 (21%) achieved 7-day shock reversal, respectively, a difference of 47% (95% confidence interval 17% to 77%; p = .007). Serial invasive hemodynamic measurements for 5 days did not show significant differences between both groups. At 28-day follow-up, reversal of shock was higher in the hydrocortisone group (p = .005). Crude 28-day mortality was 7 (32%) of 22 treated patients and 12 (63%) of 19 placebo patients, a difference of 31% (95% confidence interval 1% to 61%; p = .091). Shock reversal within 7 days after the onset of corticosteroid therapy was a very strong predictor of survival. There were no significant differences in outcome in responders and nonresponders to a short corticotropin test. The respective rates of gastrointestinal bleeding and secondary infections did not differ between both groups.\n Administration of modest doses of hydrocortisone in the setting of pressor-dependent septic shock for a mean of >96 hrs resulted in a significant improvement in hemodynamics and a beneficial effect on survival. These beneficial effects do not appear related to adrenocortical insufficiency.", "The use of high-dose corticosteroids in the treatment of severe sepsis and septic shock remains controversial. Our study was designed as a prospective, randomized, double-blind, placebo-controlled trial of high-dose methylprednisolone sodium succinate for severe sepsis and septic shock. Diagnosis was based on the clinical suspicion of infection plus the presence of fever or hypothermia (rectal temperature greater than 38.3 degrees C [101 degrees F] or less than 35.6 degrees C [96 degrees F]), tachypnea (greater than 20 breaths per minute), tachycardia (greater than 90 beats per minute), and the presence of one of the following indications of organ dysfunction: a change in mental status, hypoxemia, elevated lactate levels, or oliguria. Three hundred eighty-two patients were enrolled. Treatment--either methylprednisolone sodium succinate (30 mg per kilogram of body weight) or placebo--was given in four infusions, starting within two hours of diagnosis. No significant differences were found in the prevention of shock, the reversal of shock, or overall mortality. In the subgroup of patients with elevated serum creatinine levels (greater than 2 mg per deciliter) at enrollment, mortality at 14 days was significantly increased among those receiving methylprednisolone (46 of 78 [59 percent] vs. 17 of 58 [29 percent] among those receiving placebo; P less than 0.01). Among patients treated with methylprednisolone, significantly more deaths were related to secondary infection. We conclude that the use of high-dose corticosteroids provides no benefit in the treatment of severe sepsis and septic shock.", "Hydrocortisone is widely used in patients with septic shock even though a survival benefit has been reported only in patients who remained hypotensive after fluid and vasopressor resuscitation and whose plasma cortisol levels did not rise appropriately after the administration of corticotropin.\n In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned 251 patients to receive 50 mg of intravenous hydrocortisone and 248 patients to receive placebo every 6 hours for 5 days; the dose was then tapered during a 6-day period. At 28 days, the primary outcome was death among patients who did not have a response to a corticotropin test.\n Of the 499 patients in the study, 233 (46.7%) did not have a response to corticotropin (125 in the hydrocortisone group and 108 in the placebo group). At 28 days, there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin (39.2% in the hydrocortisone group and 36.1% in the placebo group, P=0.69) or between those who had a response to corticotropin (28.8% in the hydrocortisone group and 28.7% in the placebo group, P=1.00). At 28 days, 86 of 251 patients in the hydrocortisone group (34.3%) and 78 of 248 patients in the placebo group (31.5%) had died (P=0.51). In the hydrocortisone group, shock was reversed more quickly than in the placebo group. However, there were more episodes of superinfection, including new sepsis and septic shock.\n Hydrocortisone did not improve survival or reversal of shock in patients with septic shock, either overall or in patients who did not have a response to corticotropin, although hydrocortisone hastened reversal of shock in patients in whom shock was reversed. (ClinicalTrials.gov number, NCT00147004.)\n 2008 Massachusetts Medical Society", "A prospective (Part I) and a retrospective (Part II) study were used to determine the safety and efficacy of corticosteroids in the treatment of septic shock. In Part I, 172 consecutive patients in septic shock admitted over an 8-year period were treated with either steroid or saline: 43 received dexamethasone (DMP), 43 received methylprednisolone (MPS), and 86 received saline. The study was double-blind and randomized, and the three groups were compared for age, severity of shock, presence of underlying disease, and year of study. In the 86 saline-treated patients, the mortality rate was 38.4% (33/86); in the steroid-treated patients, it was 10.4% (9/86). With MPS the mortality rate was 11.6% (5/43), and with DMP it was 9.3% (4/43). Thus, overall mortality was significantly less in the steroid-treated group than in the control group. Further, there was no significant difference in mortality rate between the DMP- and the MPS-treated patients. In Part II, 328 patients were studied retrospectively. One-hundred sixty were treated without steroid, and 168 were treated with either DMP or MPS. Again, the two groups of patients were compared for severity of shock, underlying disease, age, and year of study. Mortality among patients treated without steroid was 42.5% (68/160) and among patients treated with steroid was 14% (24/168); there was no significant difference in mortality rate between DMP- and MPS-treated patients. In Parts I and II combined, complications occurred in 6% of steroid-treated patients with no significant difference between DMP- and MPS-treated groups.", "Persistent acute respiratory distress syndrome (ARDS) is characterized by excessive fibroproliferation, ongoing inflammation, prolonged mechanical ventilation, and a substantial risk of death. Because previous reports suggested that corticosteroids may improve survival, we performed a multicenter, randomized controlled trial of corticosteroids in patients with persistent ARDS.\n We randomly assigned 180 patients with ARDS of at least seven days' duration to receive either methylprednisolone or placebo in a double-blind fashion. The primary end point was mortality at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days, biochemical markers of inflammation and fibroproliferation, and infectious complications.\n At 60 days, the hospital mortality rate was 28.6 percent in the placebo group (95 percent confidence interval, 20.3 to 38.6 percent) and 29.2 percent in the methylprednisolone group (95 percent confidence interval, 20.8 to 39.4 percent; P=1.0); at 180 days, the rates were 31.9 percent (95 percent confidence interval, 23.2 to 42.0 percent) and 31.5 percent (95 percent confidence interval, 22.8 to 41.7 percent; P=1.0), respectively. Methylprednisolone was associated with significantly increased 60- and 180-day mortality rates among patients enrolled at least 14 days after the onset of ARDS. Methylprednisolone increased the number of ventilator-free and shock-free days during the first 28 days in association with an improvement in oxygenation, respiratory-system compliance, and blood pressure with fewer days of vasopressor therapy. As compared with placebo, methylprednisolone did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness.\n These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death. (ClinicalTrials.gov number, NCT00295269.).\n Copyright 2006 Massachusetts Medical Society.", "Corticosteroid therapy induces potentially detrimental hyperglycemia in septic shock. In addition, the benefit of adding fludrocortisone in this setting is unclear.\n To test the efficacy of intensive insulin therapy in patients whose septic shock was treated with hydrocortisone and to assess, as a secondary objective, the benefit of fludrocortisone.\n A multicenter, 2 x 2 factorial, randomized trial, involving 509 adults with septic shock who presented with multiple organ dysfunction, as defined by a Sequential Organ Failure Assessment score of 8 or more, and who had received hydrocortisone treatment was conducted from January 2006 to January 2009 in 11 intensive care units in France.\n Patients were randomly assigned to 1 of 4 groups: continuous intravenous insulin infusion with hydrocortisone alone, continuous intravenous insulin infusion with hydrocortisone plus fludrocortisone, conventional insulin therapy with hydrocortisone alone, or conventional insulin therapy with intravenous hydrocortisone plus fludrocortisone. Hydrocortisone was administered in a 50-mg bolus every 6 hours, and fludrocortisone was administered orally in 50-microg tablets once a day, each for 7 days.\n In-hospital mortality.\n Of the 255 patients treated with intensive insulin, 117 (45.9%), and 109 of 254 (42.9%) treated with conventional insulin therapy died (relative risk [RR], 1.07; 95% confidence interval [CI], 0.88-1.30; P = .50). Patients treated with intensive insulin experienced significantly more episodes of severe hypoglycemia (<40 mg/dL) than those in the conventional-treatment group, with a difference in mean number of episodes per patient of 0.15 (95% CI, 0.02-0.28; P = .003). At hospital discharge, 105 of 245 patients treated with fludrocortisone (42.9%) died and 121 of 264 (45.8%) in the control group died (RR, 0.94; 95% CI, 0.77-1.14; P = .50).\n Compared with conventional insulin therapy, intensive insulin therapy did not improve in-hospital mortality among patients who were treated with hydrocortisone for septic shock. The addition of oral fludrocortisone did not result in a statistically significant improvement in in-hospital mortality.\n clinicaltrials.gov Identifier: NCT00320099.", "We conducted a multicenter randomized, double-blind, placebo-controlled trial of early short-term, high-dose methylprednisolone sodium succinate in 223 patients with clinical signs of systemic sepsis and a normal sensorium (112 received glucocorticoid and 111 placebo). Patients also received antibiotics and intravenous fluids. Glucocorticoid or placebo was administered intravenously by a bolus (30 mg per kilogram of body weight over 15 minutes) followed by infusion of 5 mg per kilogram per hour for nine hours. The average time between the diagnosis of sepsis and infusion was 2.8 hours. The principal end point was 14-day mortality, which was similar in the placebo (22 percent) and glucocorticoid (21 percent) groups (P = 0.97). Mortality was also not significantly different between those receiving placebo and those receiving glucocorticoid in subgroups with evidence of sepsis (21 vs. 19 percent), gram-negative bacteremia (27 vs. 7 percent), gram-positive bacteremia (18 vs. 26 percent), or all gram-negative infections (25 vs. 17 percent). Resolution of secondary infection within 14 days was significantly higher in patients receiving placebo (12 of 23) than in those receiving glucocorticoid (3 of 16) (P = 0.03), but mortality rates were similar in both treatment groups for those with unresolved infection (36 vs. 31 percent). We conclude that early high-dose glucocorticoid therapy does not reduce mortality significantly in patients with systemic sepsis who have a normal sensorium, and therefore should not be used as adjunctive therapy.", "To investigate the effects of stress doses of hydrocortisone on the duration of vasopressor therapy in human septic shock.\n Prospective, randomized, double-blind, single-center study.\n Twenty-bed multidisciplinary intensive care unit in a 1400-bed university hospital.\n Forty consecutive patients who met the ACCP/SCCM criteria for septic shock. An additional criterion for inclusion in the study was vasopressor support and high-output circulatory failure with a cardiac index of >4 L/min/m2 after fluid resuscitation (pulmonary capillary wedge pressure: 12-15 mm Hg) and without the use of positive inotropes such as dobutamine or dopexamine. The primary study end point was the time to cessation of vasopressor support (norepinephrine or epinephrine in any dose, dopamine > or = 6 microg/kg/min). Secondary study end points were the evolution of hemodynamics and the multiple organ dysfunction syndrome (MODS). The severity of illness at recruitment was graded using the Acute Physiology and Chronic Health Evaluation II and the Simplified Acute Physiology Score II scoring systems. MODS was described by the Sepsis-related Organ Failure Assessment score.\n All eligible patients were prospectively randomized to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was started with a loading dose of 100 mg given within 30 mins and followed by a continuous infusion of 0.18 mg/ kg/hr. When septic shock had been reversed, the dose of hydrocortisone was reduced to 0.08 mg/kg/hr. This dose was kept constant for 6 days. As soon as the underlying infection had been treated successfully or sodium serum concentrations had increased to >155 mmol/L, the hydrocortisone infusion was tapered in steps of 24 mg/day. Physiologic saline solution was the placebo.\n Hemodynamic and oxygen-derived variables were measured at previously defined time points over a study period of 5 days. Relevant clinical and laboratory measurements were registered for a study period of 14 days to assess the evolution of organ dysfunction. Baseline data at recruitment did not differ between the two groups. Shock reversal was achieved in 18 of the 20 patients treated with hydrocortisone vs. 16 of the 20 patients treated with placebo. Hydrocortisone significantly reduced the time to cessation of vasopressor support. The median time of vasopressor support was 2 days (1st and 3rd Quartiles, 1 and 6 days) in the hydrocortisone-treated group and 7 days (1st and 3rd Quartiles, 3 and 19 days) in the placebo group (p = .005 Breslow test). There was a trend to earlier resolution of the organ dysfunction syndrome in the hydrocortisone group.\n Infusion of stress doses of hydrocortisone reduced the time to cessation of vasopressor therapy in human septic shock. This was associated with a trend to earlier resolution of sepsis-induced organ dysfunctions. Overall shock reversal and mortality were not significantly different between the groups in this low-sized single-center study.", "Sepsis and septic shock are very common conditions among critically ill patients that lead to multiple organ dysfunction syndrome (MODS) and death. Our purpose was to investigate the efficacy of early administration of dexamethasone for patients with septic shock, with the aim of halting the progression towards MODS and death.\n Prospective, randomized, double-blind, single-center study, developed in a surgical intensive care unit at Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo.\n The study involved 29 patients with septic shock. All eligible patients were prospectively randomized to receive either a dose of 0.2 mg/kg of dexamethasone (group D) or placebo (group P), given three times at intervals of 36 hours. The patients were monitored over a seven-day period by means of the sequential organ failure assessment score.\n Patients treated with dexamethasone did not require vasopressor therapy for as much time over the seven-day period as did the placebo group (p = 0.043). Seven-day mortality was 67% in group P (10 out of 15) and 21% in group D (3 out of 14) (relative risk = 0.31, 95% confidence interval 0.11 to 0.88). Dexamethasone enhanced the effects of vasopressor drugs.\n Early treatment with dexamethasone reduced the seven-day mortality among septic shock patients and showed a trend towards reduction of 28-day mortality.", "The effects of massive doses of steroids on septic shock were tested in 48 patients being treated for extensive cellulitis, wet gangrene, or severe peritonitis. From diagnosis until maximum weight gain (average, 47 hours), they received an average of 17.7 L of crystalloid solution and 1.0 L of blood and voided 3.1 L of urine. Of the 48 patients, 23 were selected in random fashion to receive dexamethasone sodium phosphate (6 mg/kg) over 48 hours. The average age (55 years), duration of shock (36 minutes), and insult were similar for both groups. Each group received similar volumes of fluid and blood. Steroid therapy was associated with a statistically significant rise in diastolic pressure (88 v 78 mm Hg), mean arterial pressure (105 v 95 mm Hg), and central venous pressure (16 v 10 cm H2O). Concomitant blood volume was lower in patients treated with steroids (5.2 v 6.1 L). All differences between the two groups disappeared after 48 hours when steroid therapy was discontinued. No differences were noted in morbidity and five patients in each group died.", "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.", "Corticosteroids have been used to treat head injuries for more than 30 years. In 1997, findings of a systematic review suggested that these drugs reduce risk of death by 1-2%. The CRASH trial--a multicentre international collaboration--aimed to confirm or refute such an effect by recruiting 20000 patients. In May, 2004, the data monitoring committee disclosed the unmasked results to the steering committee, which stopped recruitment.\n 10008 adults with head injury and a Glasgow coma score (GCS) of 14 or less within 8 h of injury were randomly allocated 48 h infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury and death or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation. Analysis was by intention to treat. Effects on outcomes within 2 weeks of randomisation are presented in this report. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN74459797.\n Compared with placebo, the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids (1052 [21.1%] vs 893 [17.9%] deaths; relative risk 1.18 [95% CI 1.09-1.27]; p=0.0001). The relative increase in deaths due to corticosteroids did not differ by injury severity (p=0.22) or time since injury (p=0.05).\n Our results show there is no reduction in mortality with methylprednisolone in the 2 weeks after head injury. The cause of the rise in risk of death within 2 weeks is unclear.", "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.", "The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids.\n In a multicenter, two-by-two factorial trial, we randomly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES 200/0.5), or modified Ringer's lactate for fluid resuscitation. The rate of death at 28 days and the mean score for organ failure were coprimary end points.\n The trial was stopped early for safety reasons. Among 537 patients who could be evaluated, the mean morning blood glucose level was lower in the intensive-therapy group (112 mg per deciliter [6.2 mmol per liter]) than in the conventional-therapy group (151 mg per deciliter [8.4 mmol per liter], P<0.001). However, at 28 days, there was no significant difference between the two groups in the rate of death or the mean score for organ failure. The rate of severe hypoglycemia (glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was higher in the intensive-therapy group than in the conventional-therapy group (17.0% vs. 4.1%, P<0.001), as was the rate of serious adverse events (10.9% vs. 5.2%, P=0.01). HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer's lactate.\n The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses. (ClinicalTrials.gov number, NCT00135473.)\n 2008 Massachusetts Medical Society", "To investigate the effect of low-dose hydrocortisone on time to shock reversal, the cytokine profile, and its relation to adrenal function in patients with early septic shock.\n Prospective, randomized, double-blind, single-center study.\n Medical intensive care unit of a university hospital.\n Forty-one consecutive patients with early hyperdynamic septic shock.\n After inclusion and a short adrenocorticotropic hormone test, all patients were randomized to receive either low-dose hydrocortisone (50-mg bolus followed by a continuous infusion of 0.18 mg/kg body of weight/hr) or matching placebo. After shock reversal, the dose was reduced to 0.06 mg/kg/hr and afterward slowly tapered. Severity of illness was estimated using Acute Physiology and Chronic Health Evaluation II score and Sequential Organ Failure Assessment score.\n Time to cessation of vasopressor support (primary end point) was significantly shorter in hydrocortisone-treated patients compared with placebo (53 hrs vs. 120 hrs, p < .02). This effect was more profound in patients with impaired adrenal reserve. Irrespective of endogenous steroid production, cytokine production was reduced in the treatment group with lower plasma levels of interleukin-6 and a diminished ex vivo lipopolysaccharide-stimulated interleukin-1 and interleukin-6 production. Interleukin-10 levels were unaltered. Adverse events were not more frequent in the treatment group.\n Treatment with low-dose hydrocortisone accelerates shock reversal in early hyperdynamic septic shock. This was accompanied by reduced production of proinflammatory cytokines, suggesting both hemodynamic and immunomodulatory effects of steroid treatment. Hemodynamic improvement seemed to be related to endogenous cortisol levels, whereas immune effects appeared to be independent of adrenal reserve.", "Renal transplant recipients experience adverse events attributed to corticosteroid therapy.\n This was a multicenter, randomized, double-blind, 6-month, controlled steroid dose-reduction study in renal transplant recipients with an unblinded 6-month follow-up. In the low/stop arm, corticoste. roids were given at half the dosage of control for 3 months from the date of transplantation, and then withdrawn. Both arms received mycophenolate mofetil and cyclosporine. The primary endpoint was the incidence of biopsy-proven acute rejection at 6 months posttransplantation.\n There were 248 patients in the control group and 252 in the low/stop group. At 6 months the low/stop group had more biopsy-proven acute rejection episodes than the control (23% vs. 14%; P=0.008). At 12 months this increased to 25% vs. 15%. Most rejections were Banff grade I. Twelve-month graft loss was 5% in the low/stop group vs. 4% in the control. At 6 and 12 months serum cholesterol (P<0.01, P<0.01), triglycer. ides (P<0.01, P<0.01), and systolic blood pressure (P<0.001, P<0.001) were lower in the low/stop group. Diastolic pressure was lower (P<0.01) and lumbar spine bone density was greater (P<0.01) in the low/ stop group at 12 months.\n In renal transplant recipients treated with mycophenolate mofetil and cyclosporine, reduction and early withdrawal of the prophylactic corticosteroid dose is feasible without an unacceptable increase in serious rejection episodes. This is accompanied by a significant reduction of steroid-related adverse events." ]	Overall, corticosteroids did not change mortality in severe sepsis and septic shock. A long course of low dose corticosteroids reduced 28-day mortality without inducing major complications; metabolic disorders were increased.
CD005958	[ "11493843", "15770171", "14521638", "10828925", "14965404", "8066514", "18408345", "15507794", "21303529", "9854760", "11607869", "2556518", "9431627", "17621203", "15613603" ]	[ "A randomized controlled trial to prevent patient lift and transfer injuries of health care workers.", "Implementation of the Dutch low back pain guideline for general practitioners: a cluster randomized controlled trial.", "Randomized controlled trial of education and feedback for implementation of guidelines for acute low back pain.", "A controlled trial of an educational pamphlet to prevent disability after occupational low back injury.", "Implementation of RCGP guidelines for acute low back pain: a cluster randomised controlled trial.", "Intensive physical and psychosocial training program for patients with chronic low back pain. A controlled clinical trial.", "Effect of nursing assistance tools on preventing musculoskeletal pain among staff in schools for disabled children.", "Early intervention for the management of acute low back pain: a single-blind randomized controlled trial of biopsychosocial education, manual therapy, and exercise.", "A randomised controlled trial of preventive spinal manipulation with and without a home exercise program for patients with chronic neck pain.", "A randomized trial of a lay person-led self-management group intervention for back pain patients in primary care.", "[Coordinative treatment and quality of life - a randomised trial of nurses with back pain].", "Randomized controlled trial of an educational booklet for patients presenting with back pain in general practice.", "A population-based, randomized clinical trial on back pain management.", "Active exercise, education, and cognitive behavioral therapy for persistent disabling low back pain: a randomized controlled trial.", "Intensive education combined with low tech ergonomic intervention does not prevent low back pain in nurses." ]	[ "Randomized controlled trial (RCT).\n To compare the effectiveness of training and equipment to reduce musculoskeletal injuries, increase comfort, and reduce physical demands on staff performing patient lifts and transfers at a large acute care hospital.\n Back injury to nursing staff during patient handling tasks is a major issue in health care. The value of mechanical assistive devices in reducing injuries to these workers is unclear.\n This three-armed RCT consisted of a \"control arm,\" a \"safe lifting\" arm, and a \"no strenuous lifting\" arm. A medical, surgical, and rehabilitation ward were each randomly assigned to each arm. Both intervention arms received intensive training in back care, patient assessment, and handling techniques. Hence, the \"safe lifting\" arm used improved patient handling techniques using manual equipment, whereas the \"no strenuous lifting\" arm aimed to eliminate manual patient handling through use of additional mechanical and other assistive equipment.\n Frequency of manual patient handling tasks was significantly decreased on the \"no strenuous lifting\" arm. Self-perceived work fatigue, back and shoulder pain, safety, and frequency and intensity of physical discomfort associated with patient handling tasks were improved on both intervention arms, but staff on the mechanical equipment arm showed greater improvements. Musculoskeletal injury rates were not significantly altered.\n The \"no strenuous lifting\" program, which combined training with assured availability of mechanical and other assistive patient handling equipment, most effectively improved comfort with patient handling, decreased staff fatigue, and decreased physical demands. The fact that injury rates were not statistically significantly reduced may reflect the less sensitive nature of this indicator compared with the subjective indicators.", "Cluster randomized controlled trial for a multifaceted implementation strategy.\n To assess the effectiveness of tailored interventions (multifaceted implementation strategy) to implement the Dutch low back pain guideline for general practitioners with regard to adherence to guideline recommendations.\n Guidelines for the management of low back pain in primary care have been developed in various countries, but little is known about the optimal implementation strategy. A multifaceted implementation strategy was developed to overcome identified barriers to the implementation of the Dutch low back pain guideline for general practitioners.\n General practitioners were randomized to an intervention or a control group. The general practitioners in the intervention group (n = 21) received tailored interventions consisting of the Dutch low back pain guideline for general practitioners, a 2-hour educational and clinical practice workshop; two scientific articles on low back pain management; the guideline for occupational physicians; a tool for patient education; and a tool for reaching agreement on low back care with physical, exercise, and manual therapists. The control group (n = 20) received no intervention. The participating general practitioners were asked to recruit consecutive patients with a new episode of low back pain as the main reason for consultation. General practitioners completed registration forms of each individual consultation with regard to the main outcome measures: advice and information, referral to other health-care providers, and prescription of medication.\n Forty-one of the 67 randomized general practitioners reported on a total of 616 consultations for 531 patients with nonspecific low back pain. The advice and explanation provided by the general practitioners, the prescription of paracetamol or nonsteroidal anti-inflammatory drugs, and prescription of pain medication on atime contingent or a pain contingent basis showed no statistically significant differences between the intervention and control groups. There were also no differences in overall referral rate. However, in follow-up consultations fewer patients were referred to a physical or exercise therapist by the general practitioners in the intervention group than in the control group.\n The multifaceted intervention strategy modestly improved implementation (for parts of the recommendations in) the Dutch low back pain guideline by general practitioners and produced small concomitant changes in patient management. The implementation strategy produced fewer referrals to therapists during follow-up consultations.", "The effect of clinical guidelines on resource utilization for complex conditions with substantial barriers to clinician behavior change has not been well studied. We report the impact of a multifaceted guideline implementation intervention on primary care clinician utilization of radiologic and specialty services for the care of acute low back pain.\n Physician groups were randomized to receive guideline education and individual feedback, supporting patient education materials, both, or neither. The impact on guideline adherence and resource utilization was evaluated during the 12-month period before and after implementation.\n Fourteen physician groups with 120 primary care physician and associate practitioners from 2 group model HMO practices.\n Guideline implementation utilized an education/audit/feedback model with local peer opinion leaders. The patient education component included written and videotaped materials on the care of low back pain.\n The clinician intervention was associated with an absolute increase in guideline-consistent behavior of 5.4% in the intervention group versus a decline of 2.7% in the control group (P =.04). The patient education intervention produced no significant change in guideline-consistent behavior, but was poorly adopted. Patient characteristics including duration of pain, prior history of low back pain, and number of visits during the illness episode were strong predictors of service utilization and guideline-consistent behavior.\n Implementation of an education and feedback-supported acute low back pain care guideline for primary care clinicians was associated with an increase in guideline-consistent behavior. Patient education materials did not enhance guideline effectiveness. Implementation barriers could limit the utility of this approach in usual care settings.", "Randomized controlled trial.\n To test the ability of an educational pamphlet to improve recovery in terms of pain, work status, and health care utilization after occupational low back injury.\n Low back pain and disability persist as occupational health problems of epidemic proportions. Because interventions based on biomechanical models have had limited impact, recent educational approaches to preventing back problems have stressed psychosocial recovery issues.\n A pamphlet was developed by compiling activity resumption, self-care, and attitudinal advice from recent publications. The pamphlet was sent at random to half of all consenting workers reporting back pain within 11 days of occupational injury between 7/96 and 6/97. Three and 6 months later, back pain, work status, health care use, and pamphlet impact outcomes were assessed through structured telephone interviews.\n Of the 726 eligible workers, 486 consented to participate. Consenters and nonconsenters and intervention and control groups were similar in initial demographic variables. The pamphlet had no statistically significant impact at the 0.05 significance level on pain severity or reduction, health care visits, or work absence. Of the 229 pamphlet recipients, 129 thought it had provided useful information, but only 25 thought it had helped them return to work more quickly.\n In this trial, a pamphlet stressing psychosocial recovery issues did not prevent or reduce postinjury pain, health care use, or work absence.", "The Royal College of General Practitioners (RCGP) has produced guidelines for the management of acute low back pain in primary care.\n To investigate the impact on patient management of an educational strategy to promote these guidelines among general practitioners (GPs).\n Group randomised controlled trial, using the health centre as the unit of randomisation.\n Primary care teams in north-west England.\n Twenty-four health centres were randomly allocated to an intervention or control arm. Practices in the intervention arm were offered outreach visits to promote national guidelines on acute low back pain, as well as access to fast-track physiotherapy and to a triage service for patients with persistent symptoms.\n Twenty-four centres were randomised. Two thousand, one hundred and eighty-seven eligible patients presented with acute low back pain during the study period: 1049 in the intervention group and 1138 in the control group. There were no significant differences between study groups in the proportion of patients who were referred for X-ray, issued with a sickness certificate, prescribed opioids or muscle relaxants, or who were referred to secondary care, but significantly more patients in the intervention group were referred to physiotherapy or the back pain unit (difference in proportion = 12.2%, 95% confidence interval [CI] = 2.8% to 21.6%).\n The management of patients presenting with low back pain to primary care was mostly unchanged by an outreach educational strategy to promote greater adherence to RCGP guidelines among GPs. An increase in referral to physiotherapy or educational programmes followed the provision of a triage service.", "The authors conducted a controlled clinical trial with 1-year follow-up to define the effectiveness of an intensive physical and psychosocial training program on patients with low back pain.\n The intervention group included 152 patients (mean age 40.5 yr, Million index 45.1/100), and the reference group included 141 patients (mean age 40.4 yr, Million-index 44.5/100).\n The progressive intervention program consisted of intensive physical training and psychosocial activation. The outcomes were physical and psychosocial measures, the pain and disability index (Million), sick leaves, and occupational handicap.\n The intervention was more efficient with respect to physical measures and pain and disability index. There were only mild or no differences in changes between the study groups in psychologic variables, sick leaves, or retirement.\n The intervention program could improve physical disability, but to improve occupational handicap, activities of the whole society (social legislation, labor market policy) are needed.", "Objective is to clarify whether nursing assistance tools (a mat with attached handles, a pair of trousers with knee pads and a waist holding belt) prevent musculoskeletal pain, such as low back pain and upper arm pain, and depression, and improve the burden on the lower back and upper arm among staff in schools for disabled children. This study design was a non-randomized intervention trial. The subjects were 41 staff in two schools for disabled children in Japan. Nursing assistance tools were used with the intervention group to help with their nursing activities. We investigated the one-month prevalence of low back pain and the degree of burden on the lower back using a questionnaire at the baseline and at the end point 4 to 6 months later. The prevalence of low back pain did not change significantly in either group. In the intervention group, the prevalence of upper arm pain decreased from 47.6% at the baseline to 23.8% at the end point (p=0.063). The percentage of participants with a high level of burden on the lower back from excretory nursing activity decreased from 57.1% at the baseline to 33.3% at the end point (p=0.063) in the intervention group. These results suggest that nursing assistance tools may prevent upper arm pain and improve the burden on the lower back among staff in schools for disabled children; however, these tools did not significantly prevent low back pain and depression.", "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.", "Evidence indicates that supervised home exercises, combined or not with manual therapy, can be beneficial for patients with non-specific chronic neck pain (NCNP). The objective of the study is to investigate the efficacy of preventive spinal manipulative therapy (SMT) compared to a no treatment group in NCNP patients. Another objective is to assess the efficacy of SMT with and without a home exercise program.\n Ninety-eight patients underwent a short symptomatic phase of treatment before being randomly allocated to either an attention-group (n = 29), a SMT group (n = 36) or a SMT + exercise group (n = 33). The preventive phase of treatment, which lasted for 10 months, consisted of meeting with a chiropractor every two months to evaluate and discuss symptoms (attention-control group), 1 monthly SMT session (SMT group) or 1 monthly SMT session combined with a home exercise program (SMT + exercise group). The primary and secondary outcome measures were represented by scores on a 10-cm visual analog scale (VAS), active cervical ranges of motion (cROM), the neck disability index (NDI) and the Bournemouth questionnaire (BQ). Exploratory outcome measures were scored on the Fear-avoidance Behaviour Questionnaire (FABQ) and the SF-12 Questionnaire.\n Our results show that, in the preventive phase of the trial, all 3 groups showed primary and secondary outcomes scores similar to those obtain following the non-randomised, symptomatic phase. No group difference was observed for the primary, secondary and exploratory variables. Significant improvements in FABQ scores were noted in all groups during the preventive phase of the trial. However, no significant change in health related quality of life (HRQL) was associated with the preventive phase.\n This study hypothesised that participants in the combined intervention group would have less pain and disability and better function than participants from the 2 other groups during the preventive phase of the trial. This hypothesis was not supported by the study results. Lack of a treatment specific effect is discussed in relation to the placebo and patient provider interactions in manual therapies. Further research is needed to delineate the specific and non-specific effects of treatment modalities to prevent unnecessary disability and to minimise morbidity related to NCNP. Additional investigation is also required to identify the best strategies for secondary and tertiary prevention of NCNP.\n ClinicalTrials.gov: NCT00566930.", "Randomized, controlled trial.\n To evaluate a four-session self-management group intervention for patients with pain in primary care, led by trained lay persons with back pain. The intervention was designed to reduce patient worries, encourage self-care, and reduce activity limitations.\n Randomized trials of educational interventions suggest that activating interventions may improve back pain outcomes. Expert opinion increasingly regards effective self-management of back pain as important in achieving good outcomes. In this study, an educational intervention designed to activate patients and support effective self-management was evaluated.\n Six to 8 weeks after a primary care visit for back pain, patients were invited to participate in an educational program to improve back pain self-management. Those showing interest by returning a brief questionnaire became eligible for the study. Participants (n = 255) randomly were assigned to either a self-management group intervention or to a usual care control group. The effect of the intervention, relative to usual care, was assessed 3, 6, and 12 months after randomization, controlling for baseline values. The intervention consisted of a four-session group applying problem-solving techniques to back pain self-management, supplemented by educational materials (book and videos) supporting active management of back pain. The groups were led by lay persons trained to implement a fully structured group protocol. The control group received usual care, supplemented by a book on back pain care.\n Participants randomly assigned to the self-management groups reported significantly less worry about back pain and expressed more confidence in self-care. Roland Disability Questionnaire Scores were significantly lower among participants in the self-management groups relative to the usual care controls at 6 months (P = 0.007), and this difference was sustained at 12 months at borderline significance levels (P = 0.09). Among self-management group participants, 48% showed a 50% or greater reduction in Roland Disability Questionnaire Score at 6 months, compared with 33% among the usual care controls.\n Self-management groups led by trained lay persons following a structured protocol were more effective than usual care in reducing worries, producing positive attitudes toward self-care, and reducing activity limitations among patients with back pain in primary care.", "The influence of strength training on back conditions has been demonstrated quite well, whereas coordinative training being a major component of physical therapy regarding preventive and rehabilitative treatment of back pain is used only occasionally and has been evaluated even more rarely. One has to consider this fact regarding the still growing number of musculo-skeletal diseases.\n The influence of several preventive therapies (coordination training in spacecurl, kinaesthetics/back protective patient transfer) has been investigated with regard to coordination, back pain and quality of life in a randomised controlled study.\n We used an assessment-set consisting of a specially devised questionnaire regarding job demands, sports activity and back pain and the WHOQOL-BREF for control of quality of life. These methods were combined with body surface electromyography and posturography. Those methods enabled us to determine parameters such as coordination, back pain and quality of life at 3 different stages (untrained individuals) and 4 points (trained individuals) respectively.\n Trained individuals showed a significant reduction of back pain frequency (p = 0.016) before and after training. In comparison there was no difference in untrained individuals. Furthermore trained individuals showed an increase in quality of life of 5.4 % (p = 0.028), whereas again there was no difference in untrained individuals. Somatic diagnostics (body surface electromyography, posturography) showed significant changes only in the trained group.\n The used coordination training program is enhancing coordination and reducing back pain whilst having a positive effect upon the quality of life of an individual.", "A randomized controlled trial was used to evaluate an educational booklet on back pain for patients presenting to five group practices during one calendar year. The booklet had no immediate effect on consultations for back pain, but in the period from two weeks to one year after presentation significantly fewer patients in the group receiving the booklet consulted with back pain (35.6%) than in the control group (42.2%) (P less than 0.05). There were no significant differences between the booklet and control groups in certified absence from work owing to back pain. Referral to hospital, referral to physiotherapy, admissions to hospital and laminectomies were all less common in the booklet group. The reduction in the combined referral rate to physiotherapy and hospital, and the reduction in laminectomy rate almost reached statistical significance at the 5% level. In replying to a questionnaire sent one year after entry to the study 94.1% of respondents in the booklet group said that they had read the book, 84.0% said that they found it useful, and 68.0% said that they still had a copy. Scores on a 15-item test of knowledge about back pain were significantly higher in the group of patients who had received the booklet than in the control group. The results suggest that the booklet had some effect in altering both the knowledge and behaviour of patients with back pain. The provision of an educational booklet was a method of giving information which was appreciated by both patients and doctors.", "Population-based randomized clinical trial.\n To develop and test a model of management of subacute back pain, to prevent prolonged disability.\n The present management of back pain seems inadequate, and development of innovative models has been urged.\n A model for the treatment of subacute work-related back pain has been developed and evaluated in a population-based randomized clinical trial. Workers (n = 130) from eligible workplaces in the Sherbrooke area (N = 31), who had been absent from work for more than 4 weeks for back pain, were randomized, based on their workplace, in one of four treatment groups: usual care, clinical intervention, occupational intervention, and full intervention (a combination of the last two). The duration of absence from regular work and from any work was evaluated using survival analysis. Functional status and pain were compared at study entry and after 1 year of follow-up.\n The full intervention group returned to regular work 2.41 times faster than the usual care intervention group (95% confidence interval 1.19-4.89; P < 0.01). The specific effect of the occupational intervention accounted for the most important part of this result, with a rate ratio of return to regular work of 1.91 (95% confidence interval = 1.18-3.10; P < 0.01). Pain and disability scales demonstrated either a statistically significant reduction or a trend toward reduction in the three intervention groups, compared with the trend in the usual care intervention group.\n Close association of occupational intervention with clinical care is of primary importance in impeding progression toward chronicity of low back pain.", "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.", "To evaluate the effectiveness of an intensive educational and low-tech ergonomic intervention programme aimed at reducing low back pain (LBP) among home care nurses and nurses' aids.\n In 1999, 345 home care nurses and nurses' aids in four Danish municipalities were studied. Participants in two municipalities constituted the intervention group and participants in the other two served as the control group. In the intervention group, participants were divided into small groups, each of which was assigned one specially trained instructor. During weekly meetings participants were educated in body mechanics, patient transfer, and lifting techniques, and use of low-tech ergonomic aids. In the control group, participants attended a one time only three hour instructional meeting. Information on LBP was collected using the Standardised Nordic Questionnaire supplemented with information on number of episodes of LBP and care seeking due to LBP during the past year.\n A total of 309 nurses and nurses' aids returned the questionnaire at baseline and 255 at follow up in August 2001. At follow up, no significant differences were found between the two groups for any of the LBP variables, and both groups thought that education in patient transfer techniques had been helpful. Within group changes in LBP status was not related to the intervention or to satisfaction with participating in the project.\n Intensive weekly education in body mechanics, patient transfer techniques, and use of low-tech ergonomic equipment was not superior to a one time only three hour instructional meeting for home care nurses and nurses' aids." ]	There is moderate quality evidence that MMH advice and training with or without assistive devices does not prevent back pain or back pain-related disability when compared to no intervention or alternative interventions. There is no evidence available from RCTs for the effectiveness of MMH advice and training or MMH assistive devices for treating back pain. More high quality studies could further reduce the remaining uncertainty.
CD001435	[ "9843104" ]	[ "Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis." ]	[ "Toxic epidermal necrolysis (TEN) is associated with a 30% death rate. Tumour necrosis factor alpha (TNF-alpha) has been implicated in the pathogenesis of TEN. Thalidomide is a potent inhibitor of TNF-alpha action. We did a double-blind, randomised, placebo-controlled study of thalidomide in TEN.\n The patients received a 5-day course of thalidomide 400 mg daily or placebo. The main endpoint was the progression of skin detachment after day 7. Secondary endpoints were the severity of the disease, evaluated with the simplified acute physiology score (SAPS), and the mortality. TNF-alpha and interleukin 6 were measured.\n The study was stopped because there was excess mortality in the thalidomide group--ten of 12 patients died compared with three of ten in the placebo group (Fisher's exact test with Katz's approximation, relative risk=2.78, p=0.03). After adjustment for SAPS, mortality remained significantly higher in the thalidomide group than in the placebo group (exact logistic regression mid-p=0.007; 95% CI for odds ratio 2.7 to infinity). Plasma TNF-alpha concentration was higher in the thalidomide group than the placebo group on day 2, though the difference was not significant (Wilcoxon rank-sum test p=0.07).\n Even though few patients were included, our data suggest that thalidomide is detrimental in TEN, possibly because of a paradoxical enhancement of TNF-alpha production." ]	Treatment with thalidomide was not shown to be effective and was associated with significantly higher mortality than placebo. There is no reliable evidence on which to base treatment for toxic epidermal necrolysis, a disease commonly associated with mortality rates of around 30%. More research is required to understand the mechanisms of toxic epidermal necrolysis. International multi-centre studies are needed in the form of randomised controlled trials, to evaluate treatments for toxic epidermal necrolysis, especially those using high doses of steroid and intravenous immunoglobulins.
CD006625	[ "12610718", "10870870", "20724402", "16585434", "16585435", "18794652", "17526456", "15933483", "15323587", "20428302", "12920411", "9270900" ]	[ "Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study.", "A comparison of the effects of quetiapine ('seroquel') and haloperidol in schizophrenic patients with a history of and a demonstrated, partial response to conventional antipsychotic treatment. PRIZE Study Group.", "Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial.", "Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment.", "Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic.", "Quetiapine addition to serotonin reuptake inhibitors in patients with severe obsessive-compulsive disorder: a double-blind, randomized, placebo-controlled study.", "Comparison of clozapine-amisulpride and clozapine-quetiapine combinations for patients with schizophrenia who are partially responsive to clozapine: a single-blind randomized study.", "Adding quetiapine to SRI in treatment-resistant obsessive-compulsive disorder: a randomized controlled treatment study.", "A double-blind, randomized, placebo-controlled trial of quetiapine addition in patients with obsessive-compulsive disorder refractory to serotonin reuptake inhibitors.", "Prevention of schizophrenia relapse with extended release quetiapine fumarate dosed once daily: a randomized, placebo-controlled trial in clinically stable patients.", "Mirtazapine orally disintegrating tablet versus sertraline: a prospective onset of action study.", "Multiple fixed doses of \"Seroquel\" (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. The Seroquel Trial 13 Study Group." ]	[ "Switching patients from one antipsychotic to another can lead to tolerability problems or transient symptom exacerbations. It is important to compare switching strategies to determine which methods produce the best possible patient outcomes.\n To investigate the efficacy, safety and tolerability of three dosing strategies for switching chronic, stable patients with schizophrenia from current oral antipsychotic monotherapy to once-daily oral aripiprazole monotherapy.\n Patients in this 8-week, open-label, outpatient study were randomized to: 1). immediate initiation of 30 mg/day aripiprazole with simultaneous immediate discontinuation of current antipsychotic; 2). immediate initiation of 30 mg/day aripiprazole while tapering off current antipsychotic over 2 weeks; or 3). up-titrating aripiprazole to 30 mg/day over 2 weeks, while simultaneously tapering off current antipsychotic. Efficacy assessments included PANSS, CGI-S, and CGI-I scores. Safety assessments included: adverse events (AEs) recording, evaluation of extrapyramidal symptoms (EPS), vital signs, ECG, and clinical laboratory tests.\n Efficacy with aripiprazole was maintained during the study with numerical improvements compared with baseline in all three groups. The overall incidence of AEs was broadly comparable across all groups, and AEs were generally mild to moderate in severity and time-limited. Discontinuations due to AEs were comparable across the groups. No deterioration in EPS occurred in any group. The reduction in body weight and plasma prolactin levels following switch to aripiprazole were comparable across the three groups.\n Any of the three strategies evaluated can be used safely for switching patients to aripiprazole from antipsychotic monotherapy. Furthermore, patients' symptoms may continue to improve after switching to aripiprazole.", "Quetiapine ('Seroquel') is a well-tolerated, novel, atypical antipsychotic with consistent efficacy in the treatment of schizophrenia. To date, no clinical studies have evaluated the effect of quetiapine in patients who only partially respond to conventional antipsychotics, yet this type of patient is most frequently seen by psychiatrists. Therefore, this international, multicentre, double-blind study was conducted to compare the efficacy and tolerability of 8 weeks' treatment of quetiapine 600 mg/day with haloperidol 20 mg/day in 288 patients who had a history of partial response to conventional antipsychotics and displayed a partial or no response to 1 month of fluphenazine (20 mg/day) treatment. Patients on quetiapine tended to have greater improvement than those on haloperidol in the primary efficacy measure, mean Positive and Negative Symptom Scale (PANSS) score, after 4 weeks' treatment (-9.05, -5.82, respectively, P = 0.061) and at study end (-11.50, -8.87, respectively, P = 0.234). Similarly, there was a trend towards patients on quetiapine demonstrating greater improvements in the secondary efficacy measures (Clinical Global Impression, PANSS subscale and Brief Psychiatric Rating Scale scores) [week 4 (baseline) to week 12 (end)], but the difference between treatments did not reach significance. Significantly more patients on quetiapine than on haloperidol showed a clinical response-patient response rates, defined as > 20% reduction in PANSS total score between weeks 4 and 12, were 52.2% for quetiapine and 38.0% for haloperidol (P = 0.043). Patients receiving quetiapine required less anticholinergic medication (P < 0.011), had greater reduction in extrapyramidal symptoms (EPS) (P = 0.005) and fewer treatment-emergent EPS-related adverse events compared to those on haloperidol (P < 0.001). Serum prolactin concentrations were elevated at the end of fluphenazine treatment in 73% of patients. Between weeks 4 and 12, elevated serum prolactin concentrations significantly decreased in quetiapine-treated patients compared to those receiving haloperidol (P < 0.001). At the end of quetiapine treatment, 83% of patients had normal prolactin levels while only 21% of patients receiving haloperidol were within the normal range. These results suggest that quetiapine may make a valuable contribution to the management of patients with a history of partial response to conventional antipsychotics.", "To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment.\n 12 month randomised, double blind, placebo controlled trial.\n Early psychosis outpatient clinics in Hong Kong.\n 178 patients with first episode psychosis who had received at least one year of antipsychotic drug treatment between September 2003 and July 2006 and had no positive symptoms of psychosis.\n Patients received either maintenance treatment with quetiapine (400 mg/day) or placebo and were followed up for the next 12 months or until a relapse occurred.\n Relapse assessed monthly and defined as re-emergence of psychotic symptoms (delusions, conceptual disorganisation, hallucinations, suspiciousness, and unusual thought content) according to predefined thresholds.\n 178 patients were randomised (89 to quetiapine and 89 to placebo). The Kaplan-Meier estimate of the risk of relapse at 12 months was 41% (95% confidence interval 29% to 53%) for the quetiapine group and 79% (68% to 90%) for the placebo group (P<0.001). Although quetiapine was generally well tolerated, the rate of discontinuation due to adverse or serious adverse events was greater in the quetiapine group (18%; 16/89) than in the placebo group (8%; 7/89) (relative risk 2.29, 95% confidence interval 0.99 to 5.28; chi(2)=3.20, df=1; P=0.07).\n In a group of asymptomatic patients with first episode psychosis and at least one year of previous antipsychotic drug treatment, maintenance treatment with quetiapine compared with placebo resulted in a substantially lower rate of relapse during the following year. Trial registration Clinical trials NCT00334035.", "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.", "In the treatment of schizophrenia, changing antipsychotics is common when one treatment is suboptimally effective, but the relative effectiveness of drugs used in this strategy is unknown. This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic.\n Subjects with schizophrenia (N=444) who had discontinued the atypical antipsychotic randomly assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) investigation were randomly reassigned to double-blind treatment with a different antipsychotic (olanzapine, 7.5-30 mg/day [N=66]; quetiapine, 200-800 mg/day [N=63]; risperidone, 1.5-6.0 mg/day [N=69]; or ziprasidone, 40-160 mg/day [N=135]). The primary aim was to determine if there were differences between these four treatments in effectiveness measured by time until discontinuation for any reason.\n The time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months). Among patients who discontinued their previous antipsychotic because of inefficacy (N=184), olanzapine was more effective than quetiapine and ziprasidone, and risperidone was more effective than quetiapine. There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability (N=168).\n Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic, risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason.", "Although many patients with obsessive-compulsive disorder (OCD) benefit from treatment with serotonin reuptake inhibitors (SRIs), it is estimated that 40% to 60% of them do not respond. The objective of the present study was to evaluate the efficacy of quetiapine added to baseline treatment with SRIs for the treatment of OCD in severely ill adult subjects.\n Forty patients (21 men, 19 women) with primary OCD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria participated in a 12-week, double-blind, placebo-controlled trial. They were randomly assigned to dosages of quetiapine titrated up to 400 mg/d (n = 20) or to placebo (n = 20) in addition to their SRI treatment. During the continuation phase (weeks 6-12), subjects received different dosages between 400 and 600 mg/d depending on clinical response. At entry, all patients were unresponsive to at least 1 course of at least 12 weeks of treatment with SRIs at defined doses. The total Yale-Brown Obsessive-Compulsive Scale score was the primary efficacy parameter.\n Intention-to-treat, last-observation-carried-forward analysis demonstrated a mean +/- SD decrease in Yale-Brown Obsessive-Compulsive Scale score of 5.2 +/- 5.4 in the quetiapine group and 3.9 +/- 4.9 in the placebo group. The analysis of treatment effects between the 2 groups showed no significant difference. There were no significant group differences in any of the other self-rating scales or clinician-administered rating scales.\n In this study, augmentation of SRI treatment with quetiapine in severe OCD had no additional effect.", "Schizophrenia is a devastating psychiatric disorder. Clozapine has long been the gold standard for treatment of patients with treatment-resistant schizophrenia; however, some patients are only partially responsive to clozapine treatment. Augmentation of clozapine treatment might enhance its effectiveness in partial responders, but only a few studies have investigated possible augmentation strategies. This study compared the effectiveness and tolerability of the combination of amisulpride and clozapine with the combination of quetiapine and clozapine in patients who were only partially responsive to clozapine monotherapy. Fifty-six treatment-resistant patients who were partially responsive to clozapine were randomly assigned to receive amisulpride or quetiapine along with an ongoing stable dose of clozapine. Fifty patients completed the study. Patients were evaluated at baseline and at the first, third, sixth, and eighth weeks. Efficacy measures consisted of the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS), and the Clinical Global Impression (CGI) scale. Tolerability and adverse effects were assessed with the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and the Simpson Angus Scale (SAS). A substantial improvement occurred in both groups by the end of the eighth week; however, the improvement associated with amisulpride was significantly greater than that seen with quetiapine. This difference was noted as early as the third week of follow-up in terms of CGI scores, and by the sixth week with regard to BPRS, SANS, and SAPS scores. Both drugs were well tolerated, as measured by UKU and SAS. Improvement favoring clozapine+amisulpride could be attributed to the selective D2/D3 binding property of amisulpride, which had an additional effect in improving symptoms of schizophrenia. The authors concluded that amisulpride seems to be effective and well tolerated for augmentation purposes in clozapine-resistant patients.", "This study aimed to determine the efficacy and tolerability of adding quetiapine to a serotonin reuptake inhibitor in treatment-resistant obsessive-compulsive disorder (OCD). Twenty-one adult treatment-resistant OCD patients were randomized to 16 weeks of augmentation with either quetiapine (n = 11) or placebo (n = 10). Patients with significant comorbidities, including tic-spectrum disorders, were not included. The treatment was well tolerated, with only one premature dropout in each treatment-group. The primary analysis showed that individuals in the quetiapine-treated group showed a 14% mean improvement in baseline Yale-Brown Obsessive-Compulsive Scale scores at study endpoint compared with a 6% improvement in those treated with placebo, but this difference did not reach statistical significance (F<1). Three patients treated with quetiapine met criteria for clinical response, compared to one patient who was treated with placebo. Larger studies are needed to explore the efficacy of second generation antipsychotics, such as quetiapine, when used as adjunct treatment in resistant OCD.", "Although serotonin reuptake inhibitors (SRIs) are the most effective pharmacologic treatment currently available for patients with obsessive-compulsive disorder (OCD), 40% to 60% of patients do not respond to this treatment. This study was conducted to evaluate the efficacy and tolerability of quetiapine in addition to an SRI for treatment-refractory patients with OCD.\n Forty patients (10 men/30 women, mean +/- SD age = 35.2 +/- 12.1 years; range, 18-60 years) with primary OCD according to DSM-IV criteria who were recruited between February 2001 and December 2002 were randomly assigned in an 8-week, double-blind, placebo-controlled trial to receive dosages titrated upward to 300 mg/day of quetiapine (N = 20) or placebo (N = 20) in addition to their SRI treatment. At entry, all patients were unresponsive to courses of treatment with at least 2 different SRIs at a maximum tolerated dose for 8 weeks. During the study, primary efficacy was assessed according to change from baseline on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). A responder was defined as having a final Clinical Global Impressions-Improvement scale rating of \"very much improved\" or \"much improved\" and a decrease of > or = 35% in Y-BOCS score.\n An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean +/- SD decrease in Y-BOCS score of 9.0 +/- 7.0 (31%) in the quetiapine group and 1.8 +/- 3.4 (7%) in the placebo group (F=16.99, df=1,38; p <.001). Eight (40%) of 20 patients in the quetiapine group and 2 (10%) of 20 patients in the placebo group were responders (chi2=4.8, df=1, p=.028). The most common side effects in the quetiapine group were somnolence, dry mouth, weight gain, and dizziness.\n The results of this study show that quetiapine in addition to an SRI is beneficial for patients with OCD who do not respond to SRI treatment alone.", "Introduction: This long-term, randomized, double-blind, placebo-controlled study examined the efficacy of extended release quetiapine fumarate (quetiapine XR) in preventing psychotic relapse in schizophrenia.Methods: Three hundred twenty-seven clinically stable patients with schizophrenia were switched to open-label quetiapine XR (300mg on Day 1, 600mg on Day 2, followed by flexible dosing [400-800mg/day]) for a 16-week stabilization phase. Thereafter, patients who were clinically stable for four months were randomized to flexible doses of quetiapine XR (400-800mg/day) or placebo. Primary endpoint was time to first schizophrenia relapse after randomization. Secondary endpoints included risk of relapse at six months. Interim analyses were planned after 45 and 60 relapses and final analysis after 90 relapses. Maximal treatment time was one year.Results: The study was terminated after the first interim analysis showed a significant difference between randomized treatment groups. Time to relapse was significantly longer in quetiapine XR-treated patients versus placebo (hazard ratio 0.16 [95% confidence interval 0.08, 0.34]; p=0.001). Fewer quetiapine XR-treated patients relapsed versus those receiving placebo (10.7% vs. 41.4%, respectively). Estimated risk of relapse at six months was significantly lower with quetiapine XR (14.3%) compared with placebo (68.2%; p=0.0001). The incidence of treatment-related adverse events (AEs) was similar between quetiapine XR and placebo groups (18% and 21% of patients, respectively) and only one percent of patients in each group withdrew because of AEs.Conclusion: Once-daily quetiapine XR (400-800mg/day) was effective in preventing relapse in patients with clinically stable schizophrenia. Quetiapine XR was well tolerated during longer-term use.", "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.", "Five fixed doses of the atypical antipsychotic \"Seroquel\" (quetiapine) were evaluated to delineate a dose-response relationship, as measured by changes from baseline in Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), and Modified Scale for the Assessment of Negative Symptoms (SANS) summary scores, and to compare efficacy and tolerability opposite placebo and haloperidol. Three hundred sixty-one patients from 26 North American centers entered this double-blind, placebo-controlled trial with acute exacerbation of chronic schizophrenia (DSM-III-R). Patients who completed a single-blind, placebo washout phase were randomized to double-blind treatment with quetiapine (75, 150, 300, 600, or 750 mg daily), haloperidol (12 mg daily), or placebo and evaluated weekly for 6 weeks. At end point, significant differences (p < 0.05, analysis of covariance) in adjusted mean changes from baseline were identified between the four highest doses of quetiapine and placebo for BPRS total, BPRS positive-symptom cluster, and CGI Severity of Illness item scores and between quetiapine 300 mg and placebo for SANS summary score. Differences between quetiapine and haloperidol were not significant. Dose-response modeling showed significant linear and quadratic functions of quetiapine dose for all primary efficacy variables. Notably, no significant safety concerns were identified as dose increased. Quetiapine was no different from placebo across the dose range studied regarding incidence of extrapyramidal symptoms or change in prolactin concentrations. Quetiapine is well tolerated and clinically effective in the treatment of schizophrenia. It is both superior to placebo and comparable to haloperidol in reducing positive symptoms at doses ranging from 150 to 750 mg/day and in reducing negative symptoms at a dose of 300 mg/day." ]	Best available evidence from trials suggests that most people who start quetiapine stop taking it within a few weeks. Comparisons with amisulpride, aripiprazole, sertindole and zotepine do not exist. Most data that has been reported within existing comparisons are of very limited value because of assumptions and biases within them. There is much scope for further research into the effects of this widely used drug.
CD007260	[ "9596436", "671684", "8850394", "16772625" ]	[ "Effectiveness of mechanical versus manual chest compressions in out-of-hospital cardiac arrest resuscitation: a pilot study.", "External cardiac compression. A randomized comparison of mechanical and manual techniques.", "Active compression-decompression cardiopulmonary resuscitation does not improve survival in patients with prehospital cardiac arrest in a physician-manned emergency medical system.", "Manual chest compression vs use of an automated chest compression device during resuscitation following out-of-hospital cardiac arrest: a randomized trial." ]	[ "A prospective, randomized effectiveness trial was undertaken to compare mechanical versus manual chest compressions as measured by end-tidal CO2 (ETCO2) in out-of-hospital cardiac arrest patients receiving advanced cardiac life support (ACLS) resuscitation from a municipal third-service, emergency medical services (EMS) agency. The EMS agency responds to approximately 6,700 emergencies annually, 79 of which were cardiac arrests in 1994, the study year. Following endotracheal intubation, all cardiac arrest patients were placed on 100% oxygen via the ventilator circuit of the mechanical cardiopulmonary resuscitation (CPR) device. Patients were randomized to receive mechanical CPR (TCPR) or human/manual CPR (HCPR) based on an odd/even day basis, with TCPR being performed on odd days. ETCO2 readings were obtained 5 minutes after the initiation of either TCPR or HCPR and again at the initiation of patient transport to the hospital. All patients received standard ACLS pharmacotherapy during the monitoring interval with the exception of sodium bicarbonate. CPR was continued until the patient was delivered to the hospital emergency department. Age, call response interval, initial electrocardiogram (ECG) rhythm, scene time, ETCO2 measurements, and arrest outcome were identified for all patients. Twenty patients were entered into the study, with 10 in each treatment group. Three patients in the TCPR group were excluded. Measurements in the HCPR group revealed a decreasing ETCO2 during the resuscitation in 8 of 10 patients (80%) and an increasing ETCO2 in the remaining 2 patients. No decrease in ETCO2 was noted in the TCPR group, with 4 of 7 patients (57%) actually showing an increased reading and 3 of 7 patients (43%) showing a constant ETCO2 reading. The differences in the ETCO2 measurements between TCPR and HCPR groups were statistically significant. Both groups were similar with regards to call response intervals, patient ages, scene times, and initial ECG rhythms. One patient in the TCPR group was admitted to the hospital but later died, leaving no survivors in the study. TCPR appears to be superior to standard HCPR as measured by ETCO2 in maintaining cardiac output during ACLS resuscitation of out-of-hospital cardiac arrest patients.", "To compare the effectiveness of manual and mechanical chest compression during cardiopulmonary resuscitation, 50 patients who suffered cardiac arrest were randomly allocated to receive manual or mechanical chest compression. Randomization was performed after failure of initial resuscitative measures but within ten minutes after the onset of cardiac arrest (mean, 6.4 +/- 1.2 min). Ten patients from each group survived longer than one hour following resuscitation. Three from the mechanical group and two from the manual group were eventually able to leave the hospital. Thus mechanical compression appears comparable with manual compression when manual compression is performed under ideal conditions. Mechanical chest compression may be employed when trained personnel are not readily available or where manual compression is technically difficult to perform.", "To examine the efficacy of a new method of cardiac resuscitation, active compression-decompression cardiopulmonary resuscitation (ACD CPR), in prehospital cardiac arrest.\n Prospective, randomized, controlled trial.\n Physician-manned Mobile Intensive Care Unit (MICU) of a university hospital, serving a population of 200,000.\n Adult patients with prehospital nontraumatic cardiac arrest treated by the MICU.\n Patients were randomized to standard chest compression according to American Heart Association (AHA) recommendations (group 1, 30 patients) or to the new technique (group 2, 26 patients). ACD was performed by use of a hand-held suction device. In both groups, advanced life support was performed as recommended by the AHA.\n Rate of patients regaining a spontaneous circulation (ROSC), hospital discharge rate, and mean carbon dioxide content during resuscitation were recorded. ROSC rates in groups 1 and 2 were 40% and 38.5%, respectively. Four patients (13.3%) in group 1 and three patients (11.5%) in group 2 were discharged (group 1 v group 2: n.s.). Anatomic conditions precluded the application of ACD CPR in 5 patients. The new technique was found to impose greater physical efforts than STD CPR. Capnography was performed in 23 patients (mean value: STD CPR: 11.9 +/- 4.7 mmHg, ACD CPR: 13.7 +/- 4.9 mmHg [n.s.]).\n ACD CPR did not improve, outcome and practical performance was complicated. Therefore, this technique should not be performed routinely, or without strict supervision in prehospital cardiac arrest.", "High-quality cardiopulmonary resuscitation (CPR) may improve both cardiac and brain resuscitation following cardiac arrest. Compared with manual chest compression, an automated load-distributing band (LDB) chest compression device produces greater blood flow to vital organs and may improve resuscitation outcomes.\n To compare resuscitation outcomes following out-of-hospital cardiac arrest when an automated LDB-CPR device was added to standard emergency medical services (EMS) care with manual CPR.\n Multicenter, randomized trial of patients experiencing out-of-hospital cardiac arrest in the United States and Canada. The a priori primary population was patients with cardiac arrest that was presumed to be of cardiac origin and that had occurred prior to the arrival of EMS personnel. Initial study enrollment varied by site, ranging from late July to mid November 2004; all sites halted study enrollment on March 31, 2005.\n Standard EMS care for cardiac arrest with an LDB-CPR device (n = 554) or manual CPR (n = 517).\n The primary end point was survival to 4 hours after the 911 call. Secondary end points were survival to hospital discharge and neurological status among survivors.\n Following the first planned interim monitoring conducted by an independent data and safety monitoring board, study enrollment was terminated. No difference existed in the primary end point of survival to 4 hours between the manual CPR group and the LDB-CPR group overall (N = 1071; 29.5% vs 28.5%; P = .74) or among the primary study population (n = 767; 24.7% vs 26.4%, respectively; P = .62). However, among the primary population, survival to hospital discharge was 9.9% in the manual CPR group and 5.8% in the LDB-CPR group (P = .06, adjusted for covariates and clustering). A cerebral performance category of 1 or 2 at hospital discharge was recorded in 7.5% of patients in the manual CPR group and in 3.1% of the LDB-CPR group (P = .006).\n Use of an automated LDB-CPR device as implemented in this study was associated with worse neurological outcomes and a trend toward worse survival than manual CPR. Device design or implementation strategies require further evaluation.\n clinicaltrials.gov Identifier: NCT00120965." ]	There is insufficient evidence from human RCTs to conclude that mechanical chest compressions during cardiopulmonary resuscitation for cardiac arrest is associated with benefit or harm. Widespread use of mechanical devices for chest compressions during cardiac is not supported by this review. More RCTs that measure and account for CPR process in both arms are needed to clarify the potential benefit from this intervention.
CD003617	[ "10535880", "12072596", "8391042", "15489585", "19052125" ]	[ "A randomized, controlled trial of maintenance interferon therapy for patients with chronic hepatitis C virus and persistent viremia.", "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.", "Randomised trial of lymphoblastoid alpha-interferon in chronic hepatitis C. Effects on inflammation, fibrogenesis and viremia.", "Histological response in patients treated by interferon plus ribavirin for hepatitis C virus-related severe fibrosis.", "Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon." ]	[ ": At least half of patients with chronic hepatitis C virus (HCV) fail to respond to interferon or interferon/ribavirin therapy. Histological improvement is observed in some nonresponders. We conducted a randomized, controlled trial to determine if maintenance interferon therapy could prevent histological progression in this subset of nonresponders.\n Fifty-three patients with chronic HCV were enrolled. All were HCV-RNA positive after 6 months of treatment with interferon alfa-2b but had a histological response. Twenty-seven of the patients were randomly assigned to continue interferon (3 MU 3 times weekly) for 24 months; 26 patients discontinued treatment and were observed prospectively. Alanine aminotransferase (ALT) level and HCV-RNA titer were monitored, and liver biopsy was repeated every 12 months.\n Before interferon therapy, the 2 groups were well matched for all demographic factors, serum ALT (94.0 +/- 15.6), log HCV-RNA titer (5. 85 +/- 0.15 copies/mL), histology score (9.5 +/- 0.2), and percentage with cirrhosis (25%). After 6 months of treatment, significant reductions (P < 0.05) in serum ALT level (62.6 +/- 9.6), log HCV-RNA titer (4.79 +/- 0.13 copies/mL), and hepatic inflammation (4.0 +/- 0.2) were observed. These improvements were maintained in the patients randomized to continue interferon. Stopping treatment was associated with an increase in serum ALT, log HCV-RNA, and hepatic inflammation back to baseline. After 30 months of treatment, mean fibrosis score declined from 2.5 to 1.7 and 80% of patients had histological improvement (P < 0.03). Discontinuation of interferon was associated with an increase in mean fibrosis score from 2.2 to 2.4 and worsening of hepatic histology in 30% of patients (P < 0.01).\n These data support the hypothesis that maintenance interferon may prevent histological progression of chronic HCV in patients who remain viremic.", "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.", "Seventy-two patients with chronic hepatitis C were included in a randomised trial of lymphoblastoid interferon versus no treatment. Thirty-six patients entered each group. Interferon was given in a step-down schedule for 12 months. Aminotransferase activities became normal during treatment in 30 of 36 (83.3%) treated patients, but in only 1 out of 36 (2.7%) non-treated cases (p < 0.001). However, a reactivation of the disease during the interferon course was observed in 12 patients after a mean of 5.58 +/- 1.55 months of therapy, and a post-treatment relapse was observed in 5 additional cases. The remaining 13 patients (36%) had sustained normalization of the aminotransferase levels for 15.27 +/- 10.34 months (range 3-30) after discontinuation of interferon, thus representing a long-term sustained remission of the disease. Knodell's histological activity index decreased in all treatment patients, except for 3 non-responders (91.5%), but in only 9 of 36 non-treated cases (25%) (p < 0.001). Procollagen type III peptide levels normalized in most cases (83%) with a sustained response. A significant decrease in the detection of hepatitis C virus RNA was observed in patients with a sustained response (p < 0.05). Anti-interferon antibodies were only detected in one non-responder. Thus, interferon diminishes inflammatory and fibrogenic activity in the majority of patients with chronic hepatitis C and abolishes viremia in most of the patients with a sustained response.", "Studies of viral hepatitis C have suggested that fibrosis can regress, at least in patients with sustained virological response. A recent study suggested that cirrhosis was reversible in sustained and non-virological responders.\n To study fibrosis progression rate and cirrhosis reversion in patients treated for severe fibrosis with interferon or interferon + ribavirin.\n Ninety-nine patients were treated with interferon + ribavirin and 64 with interferon. The Metavir fibrosis score and the semiquantitative fibrosis score (SFS) were used to assess fibrosis.\n In sustained responders, fibrosis progression rate decreased from 0.26 Metavir unit (interquartile range: 0.19-0.34) to -0.67 (-0.67 to 0) (P < 0.0001) and from 0.81 SFS unit (0.48-1.13) to -1.33 (-3.67 to 0) (P < 0.0001). In non-responders, fibrosis progression rate decreased from 0.25 Metavir unit (0.17-0.33) before treatment to 0 (0-0) during treatment (P = 0.002) and from 0.63 SFS unit (0.49-1.12) to 0 (-2.67-1.33) (P = 0.18). Six out of 18 (33%) sustained virological responders and four of 43 (9%) non-responders regressed from cirrhosis (F4) to severe fibrosis (F3) (P = 0.058). No patient with cirrhosis had a decrease of Metavir fibrosis score of 2 points.\n Interferon can slow fibrosis progression in sustained virological responders with severe fibrosis. In patients with a non-virological response and treated for 12 months the fibrosis progression rate was nil, meaning that only fibrosis stabilization could be obtained in these patients. Then, longer treatment duration (3-4 years) could be evaluated in non-virological responders.", "In patients with chronic hepatitis C who do not have a response to antiviral treatment, the disease may progress to cirrhosis, liver failure, hepatocellular carcinoma, and death. Whether long-term antiviral therapy can prevent progressive liver disease in such patients remains uncertain.\n We conducted a randomized, controlled trial of peginterferon alfa-2a at a dosage of 90 microg per week for 3.5 years, as compared with no treatment, in 1050 patients with chronic hepatitis C and advanced fibrosis who had not had a response to previous therapy with peginterferon and ribavirin. The patients, who were stratified according to stage of fibrosis (622 with noncirrhotic fibrosis and 428 with cirrhosis), were seen at 3-month intervals and underwent liver biopsy at 1.5 and 3.5 years after randomization. The primary end point was progression of liver disease, as indicated by death, hepatocellular carcinoma, hepatic decompensation, or, for those with bridging fibrosis at baseline, an increase in the Ishak fibrosis score of 2 or more points.\n We randomly assigned the patients to receive peginterferon (517 patients) or no therapy (533 patients) for 3.5 years. The level of serum aminotransferases, the level of serum hepatitis C virus RNA, and histologic necroinflammatory scores all decreased significantly (P<0.001) with treatment, but there was no significant difference between the groups in the rate of any primary outcome (34.1% in the treatment group and 33.8% in the control group; hazard ratio, 1.01; 95% confidence interval, 0.81 to 1.27; P=0.90). The percentage of patients with at least one serious adverse event was 38.6% in the treatment group and 31.8% in the control group (P=0.07).\n Long-term therapy with peginterferon did not reduce the rate of disease progression in patients with chronic hepatitis C and advanced fibrosis, with or without cirrhosis, who had not had a response to initial treatment with peginterferon and ribavirin. (ClinicalTrials.gov number, NCT00006164.)\n 2008 Massachusetts Medical Society" ]	The clinical data were limited to patients with histologic evidence of severe fibrosis who were retreated with pegylated interferon. In this scenario, retreatment with interferon did not appear to provide significant clinical benefit and, when only the trials at low risk of bias were considered, retreatment for several years may even have increased all-cause mortality. Such treatment also produced adverse events. On the other hand, the treatment did result in improvement in some surrogate outcomes, namely sustained viral responses and histologic evidence of inflammation. Interferon monotherapy retreatment cannot be recommended for these patients. No clinical data are available for patients with less severe fibrosis. The sustained viral response cannot be used as a surrogate marker for hepatitis C treatment in this clinical setting with low sustained viral response rates and needs to be validated in others in which higher sustained viral response rates are reported.
CD006714	[ "6996483" ]	[ "Midtrimester abortion by dilatation and evacuation versus intra-amniotic instillation of prostaglandin F2 alpha: a randomized clinical trial." ]	[ "To compare the safety and feasibility of midtrimester abortion by outpatient dilatation and evacuation (D-E) versus inpatient intra-amniotic instillation of prostaglandin F2 alpha (PGF2 alpha), we performed a randomized clinical trial with 100 subjects estimated to be 13 to 18 menstrual weeks pregnant. Subjects undergoing D-E abortion had significantly better compliance with the assigned treatment (100% vs. 88%, < 0.05) and less delay prior to abortion (mean 3.7 vs. 10.1 days, p < 0.001). Subjects receiving PGF2 alpha had a relative risk of sustaining a complication 5.7 times that of subjects undergoing D-E (95% confidence interval 2.1-15.3, p < 0.001). Subjects receiving PGF 2 alpha also had significantly higher rates of vomiting and diarrhea (p < 0.01). Midtrimester abortion by outpatient D-E appears to be more acceptable to women, faster, and safer than by instillation of PGF2 alpha." ]	Dilation and evacuation is superior to instillation of prostaglandin F2 α. The current evidence also appears to favour D&E over mifepristone and misoprostol, however larger randomised trials are needed.
CD008262	[ "19401897", "18547863", "17261562", "17654228", "17978833", "10362390", "19308790", "12627305", "16558514", "19074671", "10730995", "19211945", "12792207", "11380379" ]	[ "A single 10-min bout of cold-water immersion therapy after strenuous plyometric exercise has no beneficial effect on recovery from the symptoms of exercise-induced muscle damage.", "Effect of water immersion methods on post-exercise recovery from simulated team sport exercise.", "Ice-water immersion and delayed-onset muscle soreness: a randomised controlled trial.", "Influence of cold-water immersion on indices of muscle damage following prolonged intermittent shuttle running.", "Effect of hydrotherapy on the signs and symptoms of delayed onset muscle soreness.", "Effects of cold water immersion on the symptoms of exercise-induced muscle damage.", "Effects of cold-water immersion on physical performance between successive matches in high-performance junior male soccer players.", "The use of magnetic resonance imaging to evaluate the effects of cooling on skeletal muscle after strenuous exercise.", "Effect of whirlpool therapy on the signs and symptoms of delayed-onset muscle soreness.", "Effect of cold water immersion on postexercise parasympathetic reactivation.", "Hyperbaric oxygen therapy does not affect recovery from delayed onset muscle soreness.", "Physiological responses to cold water immersion following cycling in the heat.", "Effects of intermittent exposure to hyperbaric oxygen for the treatment of an acute soft tissue injury.", "Immersion in water in the first stage of labor: a randomized controlled trial." ]	[ "The purpose of this study was to examine the effectiveness of a single bout of cold-water immersion on recovery from exercise-induced muscle damage. Eighteen physically active female volunteers (age 19.9 (+/-0.97 years), height 1.66 (+/-0.05 m), mass 63.7 (+/-10 kg), completed 10 sets of 10 counter-movement jumps to induce muscle damage and were randomly allocated to a control or treatment group. The treatment group was given a single 10-min bout of lower limb cold-water immersion therapy at 10 degrees C immediately following damage-inducing exercise. Indicators of muscle damage (plasma creatine kinase activity, perceived soreness and maximal voluntary contraction of the quadriceps) were assessed immediately prior to counter-movement jumps, and at 1, 24, 48, 72 and 96 h, following the damaging exercise. Significant (p = 0.05) time effects were recorded on all indicators of muscle damage, but there were no significant group or group x time interaction effects found on any of the measured variables. The results indicate that a single bout of cold-water immersion after a damaging bout of exercise has no beneficial effects on the recovery from exercise-induced muscle damage.", "This study aimed to compare the efficacy of hot/cold contrast water immersion (CWI), cold-water immersion (COLD) and no recovery treatment (control) as post-exercise recovery methods following exhaustive simulated team sports exercise. Repeated sprint ability, strength, muscle soreness and inflammatory markers were measured across the 48-h post-exercise period. Eleven male team-sport athletes completed three 3-day testing trials, each separated by 2 weeks. On day 1, baseline measures of performance (10 m x 20 m sprints and isometric strength of quadriceps, hamstrings and hip flexors) were recorded. Participants then performed 80 min of simulated team sports exercise followed by a 20-m shuttle run test to exhaustion. Upon completion of the exercise, and 24h later, participants performed one of the post-exercise recovery procedures for 15 min. At 48 h post-exercise, the performance tests were repeated. Blood samples and muscle soreness ratings were taken before and immediately after post-exercise, and at 24h and 48 h post-exercise. In comparison to the control and CWI treatments, COLD resulted in significantly lower (p<0.05) muscle soreness ratings, as well as in reduced decrements to isometric leg extension and flexion strength in the 48-h post-exercise period. COLD also facilitated a more rapid return to baseline repeated sprint performances. The only benefit of CWI over control was a significant reduction in muscle soreness 24h post-exercise. This study demonstrated that COLD following exhaustive simulated team sports exercise offers greater recovery benefits than CWI or control treatments.", "To determine if ice-water immersion after eccentric quadriceps exercise minimises the symptoms of delayed-onset muscle soreness (DOMS).\n A prospective randomised double-blind controlled trial was undertaken. 40 untrained volunteers performed an eccentric loading protocol with their non-dominant leg.\n Participants were randomised to three 1-min immersions in either ice water (5+/-1 degrees C) or tepid water (24 degrees C).\n Pain and tenderness (visual analogue scale), swelling (thigh circumference), function (one-legged hop for distance), maximal isometric strength and serum creatine kinase (CK) recorded at baseline, 24, 48 and 72 h after exercise. Changes in outcome measures over time were compared to determine the effect of group allocation using independent t tests or Mann-Whitney U tests.\n No significant differences were observed between groups with regard to changes in most pain parameters, tenderness, isometric strength, swelling, hop-for-distance or serum CK over time. There was a significant difference in pain on sit-to-stand at 24 h, with the intervention group demonstrating a greater increase in pain than the control group (median change 8.0 vs 2.0 mm, respectively, p = 0.009).\n The protocol of ice-water immersion used in this study was ineffectual in minimising markers of DOMS in untrained individuals. This study challenges the wide use of this intervention as a recovery strategy by athletes.", "The aim of this study was to assess the effects of cold-water immersion (cryotherapy) on indices of muscle damage following a bout of prolonged intermittent exercise. Twenty males (mean age 22.3 years, s = 3.3; height 1.80 m, s = 0.05; body mass 83.7 kg, s = 11.9) completed a 90-min intermittent shuttle run previously shown to result in marked muscle damage and soreness. After exercise, participants were randomly assigned to either 10 min cold-water immersion (mean 10 degrees C, s = 0.5) or a non-immersion control group. Ratings of perceived soreness, changes in muscular function and efflux of intracellular proteins were monitored before exercise, during treatment, and at regular intervals up to 7 days post-exercise. Exercise resulted in severe muscle soreness, temporary muscular dysfunction, and elevated serum markers of muscle damage, all peaking within 48 h after exercise. Cryotherapy administered immediately after exercise reduced muscle soreness at 1, 24, and 48 h (P < 0.05). Decrements in isometric maximal voluntary contraction of the knee flexors were reduced after cryotherapy treatment at 24 (mean 12%, s(x) = 4) and 48 h (mean 3%, s(x) = 3) compared with the control group (mean 21%, s(x) = 5 and mean 14%, s(x) = 5 respectively; P < 0.05). Exercise-induced increases in serum myoglobin concentration and creatine kinase activity peaked at 1 and 24 h, respectively (P < 0.05). Cryotherapy had no effect on the creatine kinase response, but reduced myoglobin 1 h after exercise (P < 0.05). The results suggest that cold-water immersion immediately after prolonged intermittent shuttle running reduces some indices of exercise-induced muscle damage.", "This study independently examined the effects of three hydrotherapy interventions on the physiological and functional symptoms of delayed onset muscle soreness (DOMS). Strength trained males (n = 38) completed two experimental trials separated by 8 months in a randomised crossover design; one trial involved passive recovery (PAS, control), the other a specific hydrotherapy protocol for 72 h post-exercise; either: (1) cold water immersion (CWI: n = 12), (2) hot water immersion (HWI: n = 11) or (3) contrast water therapy (CWT: n = 15). For each trial, subjects performed a DOMS-inducing leg press protocol followed by PAS or one of the hydrotherapy interventions for 14 min. Weighted squat jump, isometric squat, perceived pain, thigh girths and blood variables were measured prior to, immediately after, and at 24, 48 and 72 h post-exercise. Squat jump performance and isometric force recovery were significantly enhanced (P < 0.05) at 24, 48 and 72 h post-exercise following CWT and at 48 and 72 h post-exercise following CWI when compared to PAS. Isometric force recovery was also greater (P < 0.05) at 24, 48, and 72 h post-exercise following HWI when compared to PAS. Perceived pain improved (P < 0.01) following CWT at 24, 48 and 72 h post-exercise. Overall, CWI and CWT were found to be effective in reducing the physiological and functional deficits associated with DOMS, including improved recovery of isometric force and dynamic power and a reduction in localised oedema. While HWI was effective in the recovery of isometric force, it was ineffective for recovery of all other markers compared to PAS.", "Cryotherapy is an effective treatment for acute sports injury to soft tissue, although the effect of cryotherapy on exercise-induced muscle damage is unclear. The aim of this study was to assess the effects of cold water immersion on the symptoms of exercise-induced muscle damage following strenuous eccentric exercise. After performing a bout of damage-inducing eccentric exercise (eight sets of five maximal reciprocal contractions at 0.58 rad x s(-1)) of the elbow flexors on an isokinetic dynamometer, 15 females aged 22.0+/-2.0 years (mean +/- s) were allocated to a control group (no treatment, n = 7) or a cryotherapy group (n = 8). Subjects in the cryotherapy group immersed their exercised arm in cold water (15 degrees C) for 15 min immediately after eccentric exercise and then every 12 h for 15 min for a total of seven sessions. Muscle tenderness, plasma creatine kinase activity, relaxed elbow angle, isometric strength and swelling (upper arm circumference) were measured immediately before and for 3 days after eccentric exercise. Analysis of variance revealed significant (P < 0.05) main effects for time for all variables, with increases in muscle tenderness, creatine kinase activity and upper arm circumference, and decreases in isometric strength and relaxed elbow angle. There were significant interactions (P<0.05) of group x time for relaxed elbow angle and creatine kinase activity. Relaxed elbow angle was greater and creatine kinase activity lower for the cryotherapy group than the controls on days 2 and 3 following the eccentric exercise. We conclude that although cold water immersion may reduce muscle stiffness and the amount of post-exercise damage after strenuous eccentric activity, there appears to be no effect on the perception of tenderness and strength loss, which is characteristic after this form of activity.", "In this study, we investigated the effect of water immersion on physical test performance and perception of fatigue/recovery during a 4-day simulated soccer tournament. Twenty high-performance junior male soccer players (age 15.9 +/- 0.6 years) played four matches in 4 days and undertook either cold-water immersion (10 +/- 0.5 degrees C) or thermoneutral water immersion (34 +/- 0.5 degrees C) after each match. Physical performance tests (countermovement jump height, heart rate, and rating of perceived exertion after a standard 5-min run and 12 x 20-m repeated sprint test), intracellular proteins, and inflammatory markers were recorded approximately 90 min before each match and 22 h after the final match. Perceptual measures of recovery (physical, mental, leg soreness, and general fatigue) were recorded 22 h after each match. There were non-significant reductions in countermovement jump height (1.7-7.3%, P = 0.74, eta(2) = 0.34) and repeated sprint ability (1.0-2.1%, P = 0.41, eta(2) = 0.07) over the 4-day tournament with no differences between groups. Post-shuttle run rating of perceived exertion increased over the tournament in both groups (P < 0.001, eta(2) = 0.48), whereas the perceptions of leg soreness (P = 0.004, eta(2) = 0.30) and general fatigue (P = 0.007, eta(2) = 0.12) were lower in the cold-water immersion group than the thermoneutral immersion group over the tournament. Creatine kinase (P = 0.004, eta(2) = 0.26) and lactate dehydrogenase (P < 0.001, eta(2) = 0.40) concentrations increased in both groups but there were no changes over time for any inflammatory markers. These results suggest that immediate post-match cold-water immersion does not affect physical test performance or indices of muscle damage and inflammation but does reduce the perception of general fatigue and leg soreness between matches in tournaments.", "The purpose of this study was to investigate the separate effects of cooling during the acute (within 60 min post-exercise) or subacute (24-168 h post-exercise) phase on skeletal muscle after exercise. Twenty-eight male subjects [mean (SD) 23.8 (1.8) years] were randomly assigned to the control (COTG, n=10), cold-water immersion (CWIG, n=9), and double-cold-water immersion groups (DCWIG, n=9). The cold-water immersion (15 min) was administered to the subjects' legs after calf-raise exercise (CWIG: after recording initial post-exercise measures, DCWIG: after recording initial and 24 h post-exercise measures). Magnetic resonance T2-weighted images were obtained to calculate the T2 relaxation time (T2) of the triceps surae muscle before, immediately after, and at the following times post-exercise: 20, 40, and 60 min, and 24, 48, 96 and 168 h. In addition, the ankle joint range of motion, serum creatine kinase and lactate dehydrogenase, and muscle soreness level were investigated before and after exercise. In all groups, significant T2 elevations in the gastrocnemius muscle appeared from immediately after to 60 min after exercise (P<0.05). Thereafter, COTG showed significantly re-elevated T2 levels in the gastrocnemius at 96-168 h post-exercise (P<0.05), while CWIG and DCWIG showed significantly smaller T2 values than the COTG at 96 h post-exercise (P<0.05). In addition, COTG showed larger increases in serum enzymes at 96 h post-exercise (not significant) and significantly greater muscle soreness levels at 48 h post-exercise (P<0.05) than the cooling groups. The results of this study may suggest that cooling has no dramatic effect, but some minor effects on reducing exercise-induced muscle edema in the subacute phase and relieving the extent of the damaged muscle cells.", "To determine the efficacy of warm whirlpool, cold whirlpool, and contrast therapy in the treatment of delayed-onset muscle soreness.\n Subjects performed eccentric contractions of the elbow flexors and received 4 treatments: immediately postexercise and 24, 48, and 72 hours postexercise. Treatments consisted of 24-minute treatments with warm whirlpool, cold whirlpool, contrast therapy, or no treatment.\n Fifty-six sex-matched volunteers from the University of Pittsburgh.\n Measurements were taken at 5 assessment times: pre-exercise (0 hours); prior to treatment at 24, 48, and 72 hours postexercise; and at 96 hours postexercise. Dependent variables were degrees of resting elbow flexion, active elbow flexion, and extension; perceived soreness values on a Graphic Pain Rating Scale; and maximal voluntary isometric contraction. A repeated-measures analysis of variance (group by time) and Tukey post hoc analysis were used to determine which treatment groups differed significantly in returning subjects to pre-exercise values.\n Cold whirlpool and contrast therapy were found to return subjects to baseline values of resting elbow flexion and perceived soreness significantly more than warm whirlpool or no treatment (P < .01). Additionally, warm whirlpool was found to be more effective than no treatment in the return of resting elbow flexion (P < .01).\n These results suggest that cold whirlpool and contrast therapy are more effective than warm whirlpool or no treatment in alleviating delayed-onset muscle soreness in the elbow flexors.", "The aim of the present study was to assess the effect of cold water immersion (CWI) on postexercise parasympathetic reactivation. Ten male cyclists (age, 29 +/- 6 yr) performed two repeated supramaximal cycling exercises (SE(1) and SE(2)) interspersed with a 20-min passive recovery period, during which they were randomly assigned to either 5 min of CWI in 14 degrees C or a control (N) condition where they sat in an environmental chamber (35.0 +/- 0.3 degrees C and 40.0 +/- 3.0% relative humidity). Rectal temperature (T(re)) and beat-to-beat heart rate (HR) were recorded continuously. The time constant of HR recovery (HRRtau) and a time (30-s) varying vagal-related HR variability (HRV) index (rMSSD(30s)) were assessed during the 6-min period immediately following exercise. Resting vagal-related HRV indexes were calculated during 3-min periods 2 min before and 3 min after SE(1) and SE(2). Results showed no effect of CWI on T(re) (P = 0.29), SE performance (P = 0.76), and HRRtau (P = 0.61). In contrast, all vagal-related HRV indexes were decreased after SE(1) (P < 0.001) and tended to decrease even further after SE(2) under N condition but not with CWI. When compared with the N condition, CWI increased HRV indexes before (P < 0.05) and rMSSD(30s) after (P < 0.05) SE(2). Our study shows that CWI can significantly restore the impaired vagal-related HRV indexes observed after supramaximal exercise. CWI may serve as a simple and effective means to accelerate parasympathetic reactivation during the immediate period following supramaximal exercise.", "This study investigated whether hyperbaric oxygen therapy (HBOT) improves recovery after exercise-induced muscle injury.\n Healthy male subjects (N = 24) were randomly assigned to either a placebo group or a HBOT group. Subjects were tested for maximal isometric strength (preexercise) of their right elbow flexors. Each subject then completed a high-force eccentric workout of the elbow flexor muscle group to induce delayed onset muscle soreness (DOMS). On the seven successive days after this workout, the subjects were exposed to a hyperbaric environment of 2.5 ATA for 60 min, inspiring either a normoxic mixture (P(I)O2 = 0.2 ATA; placebo group) or a hyperoxic gas mixture (P(I)O2 = 2.5 ATA; HBOT group). Before the eccentric workout and daily for the next 10 d, measurements were obtained regarding: maximal isometric muscle strength of the elbow flexor muscles, right upper arm circumferences, and rating of the perceived muscle soreness.\n Isometric strength decreased significantly from preexercise levels of 25.1 +/- 3.8 kp to postexercise levels of 12.0 +/- 4.6 kp, for the HBOT group, and from 24.6 +/- 3.4 kp to 12.5 +/- 3.7 kp, respectively, for the placebo group. Over the 10-d recovery period, there was no difference in the rate of recovery of muscle strength between the two groups. Perceived soreness peaked at about 48 h after exercise with no difference between groups. Also, the exercise-induced increases in arm circumference were similar in the two groups.\n These results indicate that HBOT is not an effective therapy for the treatment of DOMS.", "Cold water immersion (CWI) has become a popular means of enhancing recovery from various forms of exercise. However, there is minimal scientific information on the physiological effects of CWI following cycling in the heat.\n To examine the safety and acute thermoregulatory, cardiovascular, metabolic, endocrine, and inflammatory responses to CWI following cycling in the heat.\n Eleven male endurance trained cyclists completed two simulated approximately 40-min time trials at 34.3 +/- 1.1 degrees C. All subjects completed both a CWI trial (11.5 degrees C for 60 s repeated three times) and a control condition (CONT; passive recovery in 24.2 +/- 1.8 degrees C) in a randomized cross-over design. Capillary blood samples were assayed for lactate, glucose, pH, and blood gases. Venous blood samples were assayed for catecholamines, cortisol, testosterone, creatine kinase, C-reactive protein, IL-6, and IGF-1 on 7 of the 11 subjects. Heart rate (HR), rectal (Tre), and skin temperatures (Tsk) were measured throughout recovery.\n CWI elicited a significantly lower HR (CWI: Delta 116 +/- 9 bpm vs. CONT: Delta 106 +/- 4 bpm; P = .02), Tre (CWI: Delta 1.99 +/- 0.50 degrees C vs. CONT: Delta 1.49 +/- 0.50 degrees C; P = .01) and Tsk. However, all other measures were not significantly different between conditions. All participants subjectively reported enhanced sensations of recovery following CWI.\n CWI did not result in hypothermia and can be considered safe following high intensity cycling in the heat, using the above protocol. CWI significantly reduced heart rate and core temperature; however, all other metabolic and endocrine markers were not affected by CWI.", "To assess the hypothesis that subjects exposed to intermittent hyperbaric oxygen treatments would recover from signs and symptoms indicative of delayed-onset muscle soreness faster than subjects exposed to normoxic air.\n Randomized, double-blinded study with a 4-day treatment protocol.\n University-based sports medicine clinic.\n Sixteen sedentary female university students.\n All subjects performed 300 maximal voluntary eccentric contractions (30 sets of 10 repetitions per minute) of their nondominant leg (110 to 35 degrees of knee flexion) at a slow speed (30 degrees per second) on a dynamometer to elicit muscle damage and injury. Hyperbaric oxygen treatments consisted of 100% oxygen for 60 minutes at 2.0 atmospheres absolute (ATA), while the control group received 21% oxygen at 1.2 ATA for the same amount of time. Both groups received treatment immediately after the induction of delayed-onset muscle soreness and each day thereafter for a period of 4 days (day 1 postexercise through day 4 postexercise).\n Dependent variables (perceived muscle soreness, isokinetic strength, quadriceps circumference, creatine kinase, and malondialdehyde) were assessed at baseline (preexercise, day 0), 4 hours postexercise (day 1), 24 hours postexercise (day 2), 48 hours postexercise (day 3), and 72 hours postexercise (day 4). Magnetic resonance images (T2 relaxation time/short tip inversion recovery) were assessed at baseline (day 0), 24 hours postexercise (day 3), and 72 hours postexercise (day 5).\n Repeated-measures analysis of variance was performed on all of the dependent variables to assess differences between treatment and control groups. Analyses revealed no significant differences between groups for treatment effects for any of the dependent variables (pain, strength, quadriceps circumference, creatine kinase, malondialdehyde, or magnetic resonance images).\n The findings of this study suggest that hyperbaric oxygen therapy is not effective in the treatment of exercise-induced muscle injury as indicated by the markers evaluated.", "Current forms of analgesia often have significant side effects for women in labor. Bathing in warm water during labor has been reported to increase a woman's comfort level and cause a reduction in painful contractions. The objective of this trial was to compare immersion in warm water during labor with traditional pain management for a range of clinical and psychological outcomes.\n A prospective randomized controlled trial of 274 pregnant women, who were free from medical and obstetric complications and expecting a singleton pregnancy at term, was conducted at the Women's and Children's Hospital, a maternity tertiary referral center in Adelaide, South Australia. Women in labor were randomized to an experimental group who received immersion in a bath or to a nonbath group who received routine care. Pharmacological pain relief was the primary outcome that was measured, and secondary outcomes included maternal and neonatal clinical outcomes, factors relating to maternal and neonatal infectious morbidity, psychological outcomes, and satisfaction with care.\n The use of pharmacological analgesia was similar for both the experimental and control groups; 85 and 77 percent, respectively, used major analgesia. No statistical differences were observed in the proportion of women requiring induction and augmentation of labor or in rates of perineal trauma, length of labor, mode of delivery, or frequency of cardiotocographic trace abnormalities. Neonatal outcomes (birthweight, Apgar score, nursery care, meconium-stained liquor, cord pH estimations) revealed no statistically significant differences. Infants of bath group women required significantly more resuscitation than routine group women. Routine group women rated their overall experience of childbirth more positively than bath group women. Psychological outcomes, such as satisfaction with care or postnatal distress, were the same for both groups.\n Bathing in labor confers no clear benefits for the laboring woman but may contribute to adverse effects in the neonate." ]	There was some evidence that cold-water immersion reduces delayed onset muscle soreness after exercise compared with passive interventions involving rest or no intervention. There was insufficient evidence to conclude on other outcomes or for other comparisons. The majority of trials did not undertake active surveillance of pre-defined adverse events. High quality, well reported research in this area is required.
CD008844	[ "17182126", "17521544", "16531621", "16820564", "20947859", "10573067", "16877299" ]	[ "Feasibility and safety of granulocyte colony-stimulating factor treatment in patients with acute myocardial infarction.", "[Regenerative therapy in patients with a revascularized acute anterior myocardial infarction and depressed ventricular function].", "Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial.", "Differential effect of intracoronary infusion of mobilized peripheral blood stem cells by granulocyte colony-stimulating factor on left ventricular function and remodeling in patients with acute myocardial infarction versus old myocardial infarction: the MAGIC Cell-3-DES randomized, controlled trial.", "AXIS: a trial of intravenous granulocyte colony-stimulating factor in acute ischemic stroke.", "Randomized, placebo-controlled, double-blind, multicenter trial of efficacy and safety of granulocyte colony-stimulating factor in liver transplant recipients.", "Cerebrospinal and peripheral human immunodeficiency virus type 1 load in a multisite, randomized, double-blind, placebo-controlled trial of D-Ala1-peptide T-amide for HIV-1-associated cognitive-motor impairment." ]	[ "This study examined feasibility and safety of granulocyte colony-stimulating factor (G-CSF) treatment for patients with acute myocardial infarction (AMI).\n Forty patients with AMI related with the left anterior descending coronary artery, who underwent successful percutaneous coronary intervention (PCI), were randomized into G-CSF group (n=18) or Control group (n=22). G-CSF treatment was started within 24 h after PCI. 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) was performed at 4 days and 6 months after AMI. SPECT data was analyzed for LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF) and myocardial perfusion.\n LVEF at 6 months was significantly better than that at 4 days in G-CSF group (p=0.013), but not changed in Control group (p=0.245). Although no significant difference was observed for LVEDV between the two groups, LVESV tended to be decreased only in G-CSF group. In G-CSF group, defect score (DS) was significantly decreased from 4 days to 6 months after AMI. Restenosis rate at 6 months after AMI was not significantly different between the two groups.\n G-CSF treatment for patients with AMI was effective and did not have any clinical and angiographic adverse effects.", "It is difficult to distinguish the effects early revascularization and regenerative therapy have on left ventricular function in patients with acute myocardial infarction (AMI). This study was an investigation into three groups of patients who had a revascularized anterior wall AMI and depressed left ventricular function (i.e., ejection fraction < 45%). The aim was to compare changes in left ventricular function between patients who received regenerative therapy and those who did not.\n Patients were randomly assigned to receive either an intracoronary infusion of autologous mononuclear bone marrow cells (Group I; n=10) or systemic administration of granulocyte colony-stimulating factor (G-CSF) (Group II; n=10), or to a control group (Group III; n=10). In Group I, intracoronary infusion was carried out 7(2) days after AMI. Group-II patients received a 10-day course of subcutaneous G-CSF injections, 10 .g/kg per day starting 5 days after AMI. Ventricular function was assessed at baseline and 3-month follow-up.\n A 20% increase in mean ejection fraction was observed in Group I, compared with increases of 4% (P<.01) and 6% (P<.05) in Groups II and III, respectively.\n Intracoronary infusion of mononuclear bone marrow cells in patients with AMI and poor ventricular function was associated with better short-term functional recovery than previously reported. However, mobilization of stem cells by G-CSF did not have a significant influence on functional recovery.", "Phase 1 clinical trials of granulocyte-colony stimulating factor (G-CSF) treatment after myocardial infarction have indicated that G-CSF treatment is safe and may improve left ventricular function. This randomized, double-blind, placebo-controlled trial aimed to assess the efficacy of subcutaneous G-CSF injections on left ventricular function in patients with ST-elevation myocardial infarction.\n Seventy-eight patients (62 men; average age, 56 years) with ST-elevation myocardial infarction were included after successful primary percutaneous coronary stent intervention <12 hours after symptom onset. Patients were randomized to double-blind treatment with G-CSF (10 microg/kg of body weight) or placebo for 6 days. The primary end point was change in systolic wall thickening from baseline to 6 months determined by cardiac magnetic resonance imaging (MRI). An independent core laboratory analyzed all MRI examinations. Systolic wall thickening improved 17% in the infarct area in the G-CSF group and 17% in the placebo group (P=1.0). Comparable results were found in infarct border and noninfarcted myocardium. Left ventricular ejection fraction improved similarly in the 2 groups measured by both MRI (8.5 versus 8.0; P=0.9) and echocardiography (5.7 versus 3.7; P=0.7). The risk of severe clinical adverse events was not increased by G-CSF. In addition, in-stent late lumen loss and target vessel revascularization rate in the follow-up period were similar in the 2 groups.\n Bone marrow stem cell mobilization with subcutaneous G-CSF is safe but did not lead to further improvement in ventricular function after acute myocardial infarction compared with the recovery observed in the placebo group.", "The efficacy of intracoronary infusion of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSCs) has not been compared between patients with acute (AMI) versus old myocardial infarction (OMI). In addition, the potential risk of restenosis associated with G-CSF-based stem cell therapy has not been evaluated in the setting of drug eluting stent (DES) implantation.\n We randomly allocated 96 patients with myocardial infarction who underwent coronary revascularization with DES for the culprit lesion into 4 groups. Eighty-two patients completed 6-month follow-up; AMI cell infusion (n=25), AMI control (n=25), OMI cell infusion (n=16), and OMI control group (n=16). In cell infusion groups, PBSCs were mobilized by G-CSF for 3 days and delivered to infarcted myocardium via intracoronary infusion. The AMI cell infusion group showed a significant additive improvement in left ventricular ejection fraction (LVEF) and remodeling compared with controls (change of LVEF: +5.1+/-9.1% versus -0.2+/-8.6%, P<0.05; change of end-systolic volume: -5.4+/-17.0 mL versus 6.5+/-21.9 mL, P<0.05). In OMI patients, however, there was no significant change of LVEF and ventricular remodeling in spite of significant improvement of coronary flow reserve after cell infusion. G-CSF-based cell therapy did not aggravate neointimal growth with DES implantation.\n Intracoronary infusion of mobilized PBSCs with G-CSF improves LVEF and remodeling in patients with AMI but is less definite in patients with OMI. G-CSF-based stem cell therapy with DES implantation is both feasible and safe, eliminating any potential for restenosis.", "Granulocyte colony-stimulating factor (G-CSF) is a promising stroke drug candidate. The present phase IIa study assessed safety and tolerability over a broad dose range of G-CSF doses in acute ischemic stroke patients and explored outcome data.\n Four intravenous dose regimens (total cumulative doses of 30-180 μg/kg over the course of 3 days) of G-CSF were tested in 44 patients in a national, multicenter, randomized, placebo-controlled dose escalation study (NCT00132470; www.clinicaltrial.gov). Main inclusion criteria were a 12-hour time window after stroke onset, infarct localization to the middle cerebral artery territory, a baseline National Institutes of Health Stroke Scale range of 4 to 22, and presence of diffusion-weighted imaging/perfusion-weighted imaging mismatch.\n Concerning the primary safety end points, we observed no increase of thromboembolic events in the active treatment groups, and no increase in related serious adverse events. G-CSF led to expected increases in neutrophils and monocytes that resolved rapidly after end of treatment. We observed a clinically insignificant drug-related decrease of platelets. As expected from the low number of patients, we did not observe significant differences in clinical outcome in treatment vs. placebo. In exploratory analyses, we observed an interesting dose-dependent beneficial effect of treatment in patients with DWI lesions > 14-17 cm³.\n We conclude that G-CSF was well-tolerated even at high dosages in patients with acute ischemic stroke, and that a substantial increase in leukocytes appears not problematic in stroke patients. In addition, exploratory analyses suggest treatment effects in patients with larger baseline diffusion-weighted imaging lesions. The obtained data provide the basis for a second trial aimed to demonstrate safety and efficacy of G-CSF on clinical end points.", "Infection and rejection are two common complications after liver transplants. In a preliminary study, administration of granulocyte colony-stimulating factor (G-CSF) to liver transplant recipients was associated with a decrease in sepsis episodes, sepsis-related deaths, and rejection compared with a historical control group of patients. The purpose of this study was to evaluate further the efficacy of G-CSF in liver transplant patients in a randomized, placebo-controlled, double-blind, multicenter trial.\n Adult patients with a United Network Organ Sharing classification of 1 or 2 were randomized to receive a placebo, 100 microg/day of G-CSF or 300 microg/day of G-CSF. The study drug was started preoperatively and then continued after the transplant for a maximum of 21 days. Patients were evaluated for microbiologically-documented infection, biopsy-proven rejection, number of treatments for rejection, length of stay in the intensive care unit and hospital, graft survival, death, and adverse events.\n During the first 30 days after the transplant, the median peak white blood cell count was 16.5x10(9)/L, 34.6x10(9)L, and 54.8x10(9)/L for the placebo, low-dose G-CSF, and high-dose G-CSF patients, respectively. The incidence of infection was 30% in G-CSF patients (34 of 114 patients) and 34% in placebo patients (20 of 58 patients). Except for more nosocomial pneumonias in the G-CSF patients (7 in 114 patients vs. 0 in 58 patients, P=0.056), the types of infections and causative organisms were also similar in both treatment groups. Although the number of treatments for clinically suspected or proven rejection was similar in the G-CSF and placebo patients, biopsy-proven rejection occurred more often in G-CSF patients (34 of 114 patients or 30%) than placebo patients (11 of 58 patients or 19%) (P=0.093). There were no cases of graft loss caused by rejection. G-CSF had no effect on length of stay in the intensive-care unit or hospital. There were 22 G-CSF patients (18%) and 10 placebo patients (15%) who died within 120 days after the transplant. No serious adverse events were attributed to G-CSF.\n Despite producing substantial increases in the white blood cell count after the transplant, G-CSF had no beneficial effects on infection, rejection, or survival in this study. Biopsy-proven rejection and nosocomial pneumonias were more common in patients treated with G-CSF compared with those taking the placebo. No serious adverse events were attributed to G-CSF.", "D-Ala1-peptide T-amide (DAPTA) has shown neuroprotection in vitro against gp120-induced loss of dendritic arborization and is promulgated as a CCR5 antagonist. A multisite, randomized, double-blind clinical trial of DAPTA versus placebo prior to combination antiretroviral therapy conducted with human immunodeficiency virus (HIV)-1 seropositive participants having cognitive impairment showed no overall cognitive effect, though subgroups with greater impairment and CD4 cell counts of 201 to 500 cells/mm3 at baseline showed significant improvement. The objective of this study was to examine whether intranasal administration of DAPTA at a dose of 2 mg three times per day (tid) was associated with a reduction of cerebrospinal fluid (CSF) and peripheral (plasma and serum) viral load among a subgroup of participants completing 6 months of treatment. Baseline and 6-month CSF (n = 92) and peripheral (plasma n = 33; serum n = 24) viral load were measured by the Roche Ultrasensitive assay, version 1.5, with reflexive use of the AMPLICOR assay and preservation of the blind. A DAPTA treatment indicator variable was tested using generalized linear models on change in viral load. Peripheral load (combined plasma and serum) was significantly reduced in the DAPTA-treated group. No group differences in CSF viral load were found. This retrospective study on a limited subgroup of the original trial sample indicated that DAPTA treatment may reduce peripheral viral load without concomitant CSF effects. Future studies should be undertaken to confirm the existence of this result and the CSF-periphery dissociation observed with respect to HIV-1-associated cognitive-motor impairment." ]	Limited evidence from small trials suggested a lack of benefit of G-CSF therapy in patients with AMI. Since data of the risk of bias regarding blinding of personnel were not conclusive, larger RCTs with appropriate power calculations and longer follow up durations are required in order to address current uncertainties regarding the clinical efficacy and therapy-related adverse events of G-CSF treatment.
CD008348	[ "12971850", "17915147", "3535601" ]	[ "[Early intravenous thrombolysis with recombinant tissue plasminogen activator for acute cerebral infarction].", "[Randomized controlled clinical trial of a home care unit intervention to reduce readmission and death rates in patients discharged from hospital following admission for heart failure].", "Intravenous heparin for the prevention of stroke progression in acute partial stable stroke." ]	[ "To evaluate the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) and to explore the most suitable dosage of rt-PA in the early treatment of the Chinese patients with acute cerebral infarction (ACI).\n The patients who suited for the standard were divided into three groups. Group A received rt-PA at 0.9 mg/kg, group B received rt-PA at 0.7 mg/kg, and group C did not receive any thrombolytic therapy. In thrombolytic groups, rt-PA at 8 mg was injected intravenously in a bolus at first and then the rest was given over 60 minutes. The maximal dosage was 90 mg. The Chinese stroke scale (CSS) and Barthel Index (BI) were used to evaluate the recovery of neurological functions after rt-PA treatment for 24 hours and 90 days. The hemorrhagic rate and 30 days mortality rate were also analysed.\n In group A the CSS significant effective rate was 41.18 percent at 24 hours and 76.47 percent at 90 days after thrombolysis. At 90 days BI significant effective rate was 58.82 percent. At 30 days hemorrhagic rate was 8.82 percent and mortality rate was 5.88 percent. In group B, the CSS significant effective rate was 39.39 percent at 24 hours and 69.70 percent at 90 days. At 90 days, BI significant effective rate was 54.55 percent, and at 30 days, hemorrhagic rate was 9.09 percent and mortality rate was 9.09 percent. In group C, the CSS significant effective rate was 21.21 percent, at 24 hours and 30.30 percent at 90 days (P>0.05). At 90 days, BI was 21.21 percent the mortality rate was 9.09 percent. At 30 days the mortality rate was no significant difference within three groups At 90 days, significant effective rate was 73.13 percent vs. 30.30 percent in thrombolytic and control groups (P=0.001 7). The significant disability rate was 13.43 percent vs. 24.24 percent.\n For Chinese individuals, with ACI, rt-PA thrombolysis was effective and safe. The dosage of 0.9 mg/kg for foreign people also fitted for Chinese individuals.", "To determine the effectiveness of a primarily educational intervention in heart failure (HF) patients implemented in a home care unit.\n This randomized controlled clinical trial involved 279 HF patients who were discharged from a tertiary-care hospital between February 2001 and June 2002. Patients with dementia, terminal non-cardiac disease, or chronic obstructive pulmonary disease were excluded. Data collected included the cause of cardiac decompensation. A primarily educational intervention was implemented in the patient's home for up to 15 days after hospital discharge. Treatment was adjusted during the first week if necessary. The primary outcome measure was the 1-year cumulative incidence of readmission or death. Secondary measures were the incidence of readmission, mortality, and emergency department admission. Telephone interviews were carried out 3, 6 and 12 months after discharge, and clinical records were updated when necessary. Emergency department admission in the first 6 months was monitored.\n At 1-year follow-up, 62 of the 137 patients (45.3%) in the intervention group had been readmitted or died, compared with 75 of the 142 (52.8%) in the control group, (relative risk=0.86, P=.232). Among patients who suffered decompensation because failure to adhere to treatment, 16 of the 45 (35.6%) in the intervention group were readmitted or died, compared with 34 of the 56 (60.7%) control group patients (relative risk=0.59, P=.016).\n This intervention is feasible but, when applied indiscriminately to every discharged heart failure patient, the best that can be expected is only a modest reduction in readmission and death rates, which, in this study in particular, did not achieve statistical significance.", "In a double-blind, placebo-controlled trial, 225 patients with acute partial stable thrombotic stroke were randomly assigned to receive continuous intravenous heparin therapy or placebo for 7 days for the prevention of stroke progression or death. No statistically significant difference between the two groups was found in degree of neurologic change; incidence of stroke progression after 7 days; or functional activity level of survivors at 7 days, 3 months and at 1 year after treatment. Compared with controls, a statistically significant greater number of patients in the group receiving heparin died in the year after the stroke. These deaths occurred 3 to 12 months after the initial stroke and probably were not related to treatment. Results of this study do not support the use of intravenous heparin to treat patients who have had acute partial stroke." ]	Sonothrombolysis appears to reduce death or dependency at three months (although CIs are quite wide), and increases recanalisation without clear hazard. A larger clinical trial is warranted.
CD006624	[ "15465981", "12464464", "12442883", "16199834", "12684609", "15076013", "18562423", "15641867" ]	[ "Randomized, controlled, double-blind multicenter comparison of the efficacy and tolerability of ziprasidone and olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder.", "Amisulpride vs. risperidone in chronic schizophrenia: results of a 6-month double-blind study.", "A double-blind, randomised comparative trial of amisulpride versus olanzapine in the treatment of schizophrenia: short-term results at two months.", "Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia.", "Amisulpride versus risperidone in the treatment of schizophrenic patients: a double-blind pilot study in Taiwan.", "A double-blind, randomized comparative trial of amisulpride versus olanzapine for 6 months in the treatment of schizophrenia.", "Efficacy and tolerability of ziprasidone versus risperidone as augmentation in patients partially responsive to clozapine: a randomised controlled clinical trial.", "Efficacy and tolerability of ziprasidone versus risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder: an 8-week, double-blind, multicenter trial." ]	[ "Limited randomized, controlled trial data exist on possible differences between atypical antipsychotics in efficacy, overall tolerability, and important indices of health status. The authors compared the efficacy and tolerability of ziprasidone and olanzapine in the treatment of acutely ill inpatients with schizophrenia or schizoaffective disorder.\n In this 6-week, multicenter, double-blind, parallel-design, flexible-dose trial, patients were randomly assigned to receive ziprasidone (N=136) or olanzapine (N=133). Primary efficacy measures were improvement in Brief Psychiatric Rating Scale and Clinical Global Impression (CGI) severity scale scores; secondary measures were scores on the CGI improvement scale, Positive and Negative Syndrome Scale, and Calgary Depression Scale for Schizophrenia. Tolerability assessments included fasting lipid profiles, fasting glucose and insulin measurements, electrocardiography, and monitoring of vital signs and body weight.\n The overall mean daily doses were 129.9 mg (SD=27.3) for ziprasidone and 11.3 mg (SD=2.8) for olanzapine. Both antipsychotics were efficacious in improving symptoms and global illness severity. The two treatment groups did not differ significantly in primary or secondary efficacy measures at endpoint or in by-visit analysis. Both agents were well tolerated. Body weight, total cholesterol, triglycerides, and low-density lipoprotein cholesterol significantly increased with olanzapine but not with ziprasidone; all between-group comparisons of these variables were significant and favored ziprasidone. Olanzapine, but not ziprasidone, was associated with significant increases in fasting insulin level. No patient in either group exhibited a corrected QT interval >/=500 msec.\n During 6 weeks' treatment, ziprasidone and olanzapine demonstrated comparable antipsychotic efficacy. Differences favoring ziprasidone were observed in metabolic parameters.", "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.", "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.", "The efficacy and safety of olanzapine were compared with those of ziprasidone.\n This was a multicenter randomized, double-blind, parallel-group, 28-week study of patients with schizophrenia. Patients were randomly assigned to treatment with 10-20 mg/day of olanzapine or 80-160 mg/day of ziprasidone. The primary efficacy measure was the Positive and Negative Syndrome Scale total score. Secondary efficacy and safety measures included Positive and Negative Syndrome Scale subscales as well as mood, quality of life, and extrapyramidal symptom scales. Safety was evaluated by recording treatment-emergent adverse events and measuring vital signs and weight.\n The study was completed by significantly more olanzapine-treated patients (165 of 277, 59.6%) than ziprasidone-treated patients (115 of 271, 42.4%). At 28 weeks, the olanzapine-treated patients showed significantly more improvement than the ziprasidone-treated patients on the Positive and Negative Syndrome Scale overall scale and all subscales and on the Clinical Global Impression ratings of severity of illness and improvement. The responder rate was higher for olanzapine than for ziprasidone. Extrapyramidal symptoms were not significantly different between groups in change-to-endpoint analyses, but results favored olanzapine on baseline-to-maximum changes. Weight change was significantly greater with olanzapine (mean=3.06 kg, SD=6.87) than with ziprasidone (mean=-1.12 kg, SD=4.70). Fasting lipid profiles were significantly superior in the ziprasidone group; there was no significant difference in fasting glucose level.\n Olanzapine treatment resulted in significantly greater psychopathology improvement and higher response and completion rates than ziprasidone treatment, while ziprasidone was superior for weight change and lipid profile.", "The atypical antipsychotics, amisulpride and risperidone, have different receptor affinity characteristics. Although the relative efficacy of both drugs compared to conventional antipsychotics is well established, it remains unclear how the efficacy of amisulpride compares with risperidone. There have been no controlled studies comparing amisulpride to risperidone in Asian patients. The purpose of this study was to compare the efficacy and safety of amisulpride with that of risperidone in Taiwanese schizophrenic patients.\n Patients with productive positive symptoms (n = 48) were enrolled into this double-blind, randomized pilot study for 6 weeks. Patients received either amisulpride (400-800 mg/day) or risperidone (4-8 mg/day). Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI), Social and Occupational Functioning Assessment Scale (SOFAS), and patients' subjective responses to treatment were assessed during the trial period. Adverse events were recorded at each follow-up visit.\n At the end of the trial, the mean dosage was 630 +/- 134 mg/day and 6.88 +/- 1.54 mg/day for amisulpride and risperidone, respectively. There was no significant difference in the reduction of the PANSS total score (amisulpride -24.1 versus risperidone -28.4, p = 0.999), the PANSS positive subscale score (amisulpride -6.8 versus risperidone -8.3, p = 0.467), the PANSS negative subscale score (amisulpride -5.6 versus risperidone -6.4, p = 0.999), or the CGI score between the two groups. The extrapyramidal symptom ratings, the improvement in the SOFAS (amisulpride 11.1 versus risperidone 10.0) and the subjective response (amisulpride 82% versus risperidone 83%) were comparable. No serious adverse events were recorded in either treatment group. There was a statistically significant body weight gain in the risperidone group. In contrast, there was a statistically, though not clinically, significant reduction of blood pressure and heart rate in the amisulpride group.\n This study suggests that amisulpride is as effective as risperidone in the treatment of patients with schizophrenia. Both drugs were well tolerated, but had different side effect profiles.", "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.", "Patients suffering from schizophrenic psychoses sometimes insufficiently respond to antipsychotic monotherapy and then combination approaches are preferred. We aimed in validating the add-on of ziprasidone and risperidone to clozapine, and we performed a randomised head-to-head trial. Patients with partial response to clozapine were randomly attributed to augmentation with ziprasidone (n = 12) or risperidone (n = 12). Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), the Hamilton Depression Scale (HAMD), the Clinical Global Impression (CGI) and the Global Assessment of Functioning (GAF). Furthermore, several safety and tolerability measures were obtained. After six weeks, both groups showed significant reductions of positive and negative symptoms. In addition, affective state, psychosocial functioning and clozapine side effects improved without significant differences between the groups. Both approaches were well tolerated. However, the ziprasidone group experienced a small elongation of the QTc interval and a reduction of extrapyramidal symptoms. Patients under clozapine-risperidone therapy developed a rise of serum prolactin levels. The clozapine augmentation with ziprasidone or risperidone resulted in significant psychopathological improvements. The side effects differed between the treatment groups. Further head-to-head comparisons of atypical antipsychotics as add-on to clozapine are necessary.", "More head-to-head comparisons of antipsychotics are needed to discern the relative efficacy and safety profiles of these compounds. Thus, we compared ziprasidone and risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder.\n Patients with DSM-III-R acute exacerbation of schizophrenia or schizoaffective disorder were randomly assigned to double-blind ziprasidone 40 to 80 mg b.i.d. (N = 149) or risperidone 3 to 5 mg b.i.d (N = 147) for 8 weeks. Primary efficacy measures included Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions-Severity of Illness scale (CGI-S) score; secondary measures included scores on the PANSS negative sub-scale, CGI-Improvement scale (CGI-I), and PANSS-derived Brief Psychiatric Rating Scale (BPRSd) total and core items. Safety assessments included movement disorder evaluations, laboratory tests, electrocardiography, vital signs, and body weight. Efficacy analyses employed a prospectively defined Evaluable Patients cohort. Treatment equivalence was conferred if the lower limit of the 95% confidence interval of the ziprasidone/risperidone ratio of least-squares mean change from baseline was > 0.60. Data were gathered from August 1995 to January 1997.\n Equivalence was demonstrated in PANSS total scores, CGI-S scores, PANSS negative subscale scores, BPRSd total and core item scores, and PANSS total and CGI-I responder rates. Both agents were well tolerated. Risperidone exhibited a significantly higher Movement Disorder Burden (MDB) score (p < .05) and higher incidences of prolactin elevation and clinically relevant weight gain. However, compared with current recommendations, study dosing may have been high for some risperidone-treated patients (mean dose = 7.4 mg/day) and low for some ziprasidone-treated patients (mean dose = 114.2 mg/day).\n Both agents equally improved psychotic symptoms, and both were generally well tolerated, with ziprasidone demonstrating a lower MDB score and less effect on prolactin and weight than risperidone." ]	There is little randomised evidence comparing amisulpride with other second generation antipsychotic drugs. We could only find trials comparing amisulpride with olanzapine, risperidone and ziprasidone. We found amisulpride may be somewhat more effective than ziprasidone, and more tolerable in terms of weight gain and other associated problems than olanzapine and risperidone. These data, however, are based on only ten short to medium term studies and therefore too limited to allow for firm conclusions. Note: the 47 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.
CD008058	[ "15993304", "10323611", "10748957", "2381003" ]	[ "Treatment of second degree facial burns with allografts--preliminary results.", "Management of partial thickness facial burns (comparison of topical antibiotics and bio-engineered skin substitutes).", "The role of alternative therapy in the management of partial thickness burns of the face--experience with the use of moist exposed burn ointment (MEBO) compared with silver sulphadiazine.", "Comparison of a hydrocolloid dressing and silver sulfadiazine cream in the outpatient management of second-degree burns." ]	[ "Facial burns are very common and have significant clinical impact. However, the treatment regimen for superficial to deep facial burns is not well defined. The purpose of this study was to investigate the effects of cadaver skin grafting in deep partial thickness facial burns in comparison to standard care. In a prospective open study design severely injured patients with superficial and deep partial thickness burns were randomized into the group receiving open treatment with silversulfadiazine (standard n=5) or into the group receiving early superficial debridement followed by coverage with glycerolized cadaver skin (n=5). The outcome measures were time and quality of wound healing, and incidence of hypertrophic scarring at 3 and 6 months post burn. There were no significant differences in demographics between groups. In the group treated with the allogenic material time to reepithelialization was 10.5 days, while it was 12.4 days in the silversulfadiazine group (p<0.05). Scar quality was found to be significantly improved in the allogenic treatment group. Three and 6 months postburn there were no patients with significant hypertrophic scarring in the allogenic group while there were two patients who developed hypertrophic scars in the silversulfadiazine group (p<0.05). In this study, we demonstrated that glyzerolized cadaver allograft skin represents a superior biological dressing for shallow and deep partial thickness facial burns. This is in concordance with other reports on scalds. It would be worthwhile to perform more clinical studies with a larger number of patients to further evaluate the effect and function of allogenic skin for facial burns.", "This study compared the effect of standard topical antibiotic management versus a biological skin substitute wound closure for mid-partial thickness burns of the face. Adult patients with mid-dermal facial burns produced by flash flames or flame exposure were studied using a randomized prospective study design. Total daily burn care time, pain (0-10 scale) and healing time were monitored. Immediately after partial thickness debridement, the entire face burn, including ears, was closed with a bioengineered skin substitute coated with fibronectin (TransCyte) or treated by the open technique using bacitracin ointment applied 2-3 times daily. 21 patients were studied, with 10 patients in the skin substitute group. We found a significant decrease in wound care time 0.35 +/- 0.1 versus 1.9 +/- 0.5 h, decrease in pain of 2 +/- 1 versus 4 +/- 2 and re-epithelialization time 7 +/- 2 versus 13 +/- 4 days in the skin substitute group compared to topical antibiotics. We can conclude that a bioengineered skin substitute significantly improves the management and healing rate of partial thickness facial burns, compared to the standard open topical ointment technique.", "Conventional management of partial thickness facial burn wounds includes the use of silver sulphadiazine dressings. Silver sulphadiazine forms an overlying slough that makes wound healing assessment difficult. Moist exposed burn ointment (MEBO) has been proposed as the ideal burn wound dressing both for burns of the face and other sites. Proponents of MEBO claim that it accelerates wound healing and results in scarless wound healing and at the same time reduce bacterial colonisation and the need for analgesics. We present here our experience with MEBO in the management of partial thickness burns of the face.\n One hundred and fifteen patients with partial thickness burns were randomly assigned to conventional treatment or MEBO. Out of this, 112 were analysed. Thirty-nine patients sustained facial burns; 17 received MEBO and 22 received silver sulphadiazine. Patients were followed up daily until the burn wounds were reduced by 75% of original body surface area (BSA).\n In patients with facial burns, MEBO was similar to silver sulphadiazine therapy with respect to rate of wound healing. Minimal slough was present over the wounds in MEBO-treated wounds resulting in clearer assessment of healing progression.\n Advantages of MEBO as compared to silver sulphadiazine in the management of partial thickness burns of the face include convenient change of dressing and easier assessment of healing progression. This suggests that MEBO is a useful alternative therapy for partial thickness burns of the face.", "The purpose of this prospective randomized study was to evaluate the use of an occlusive hydrocolloid dressing (Duoderm hydroactive, Squibb) and silver sulfadiazine (Silvadene, Marion) cream in the outpatient management of second-degree burns. The inclusion criteria consisted of burns less than 15% total body surface area that were evaluated within 24 hours of injury and did not require hospital admission. Fifty patients were randomly assigned after having been screened through a list of seven exclusion criteria. On initial evaluation the burns were photographed and screened for causative agent, location, size, depth, tetanus status, and presence of associated burns and injuries. Patients were seen in followup at least biweekly and evaluated for wound bed healing, wound margin healing, pain, number of dressing changes between visits, and ease of dressing application and removal. On final evaluation the burns were photographed and inspected for appearance of the healed burn, repigmentation, wound contraction, approximate time for dressing change, patient compliance, limitation of activity, overall impression of the treatment, and number of days for complete healing. Results were compared using a two-tailed t-test with p less than 0.01. Both groups were statistically similar in age, sex, and size. Duoderm-treated burns had statistically significantly better wound healing, repigmentation, less pain, fewer dressing changes, less time for dressing changes, and less cost. Duoderm-treated patients had statistically significantly less limitation of activity, better patient compliance, greater patient comfort, better overall acceptance, and felt the treatment was more aesthetically pleasing. The results reveal that the Duoderm Hydroactive dressings are superior to Silvadene cream in the outpatient management of second-degree burns." ]	There is insufficient high quality research and evidence to enable conclusions to be drawn about the effects of topical interventions on wound healing in people with facial burns.
CD005158	[ "11519503", "16531616" ]	[ "Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation.", "Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events." ]	[ "Despite current treatments, patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events. We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients.\n We randomly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel (300 mg immediately, followed by 75 mg once daily) (6259 patients) or placebo (6303 patients) in addition to aspirin for 3 to 12 months.\n The first primary outcome--a composite of death from cardiovascular causes, nonfatal myocardial infarction, or stroke--occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group (relative risk with clopidogrel as compared with placebo, 0.80; 95 percent confidence interval, 0.72 to 0.90; P<0.001). The second primary outcome--the first primary outcome or refractory ischemia--occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group (relative risk, 0.86; 95 percent confidence interval, 0.79 to 0.94; P<0.001). The percentages of patients with in-hospital refractory or severe ischemia, heart failure, and revascularization procedures were also significantly lower with clopidogrel. There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group (3.7 percent vs. 2.7 percent; relative risk, 1.38; P=0.001), but there were not significantly more patients with episodes of life-threatening bleeding (2.2 percent [corrected] vs. 1.8 percent; P=0.13) or hemorrhagic strokes (0.1 percent vs. 0.1 percent).\n The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation. However, the risk of major bleeding is increased among patients treated with clopidogrel.", "Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events.\n We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes.\n The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin (relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P=0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P=0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent (relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P=0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P=0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel (3.9 percent vs. 2.2 percent, P=0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo (relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P=0.046).\n In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes. (ClinicalTrials.gov number, NCT00050817.).\n Copyright 2006 Massachusetts Medical Society." ]	The available evidence demonstrates that the use of clopidogrel plus aspirin is associated with a reduction in the risk of cardiovascular events and an increased risk of bleeding compared with aspirin alone. Only in patients with acute non-ST coronary syndrome benefits outweigh harms.
CD003118	[ "7951964", "9046143", "11601430" ]	[ "Effect of pronation and supination orthosis on Morton's neuroma and lower extremity function.", "Surgery of Morton's neuroma: dorsal or plantar approach?", "Interventional neurophysiology for pain control: duration of pain relief following repetitive transcranial magnetic stimulation of the motor cortex." ]	[ "Twenty-three adult patients with Morton's neuroma of one foot were randomized to receive in-shoe orthoses made from a hard, compressed, felt material that would either pronate or supinate both feet. The response of the neuroma pain was measured using subjective visual analogue scales, an objective examination, and the MACTAR patient-specific measure of maximal function. The development of any other lower limb symptoms was also recorded. The pain associated with Morton's neuroma was not significantly altered by changing the position of the foot with the compressed felt orthosis. Forcibly pronating the foot did not produce a significant incidence of lower limb symptoms in the short term.", "In this prospective study, 52 patients with 55 neuromas were studied in two groups. 26 patients underwent excision of the neuroma through a plantar approach and 26 through a dorsal approach. Average follow-up was 3.1 years after excision. Histology confirmed a neuroma in 51 cases. Results show that in the dorsal group weight-bearing and return to work was faster, and the duration of hospital stay was shorter, than in the plantar group. There were five painful scars in the plantar group and two in the dorsal group.", "The chronic electrical stimulation of a motor cortical area corresponding to a painful region of the body, by means of surgically-implanted epidural electrodes is a validated therapeutical strategy to control medication-resistant neurogenic pain. Repetitive transcranial magnetic stimulation (rTMS) permits to stimulate non-invasively and precisely the motor cortex. We applied a 20-min session of rTMS of the motor cortex at 10 Hz using a 'real' or a 'sham' coil in a series of 14 patients with intractable pain due to thalamic stroke or trigeminal neuropathy. We studied the effects of rTMS on pain level assessed on a 0-10 visual analogue scale from day 1 to day 12 following the rTMS session. A significant pain decrease was observed up to 8 days after the 'real' rTMS session. This study shows that a transient pain relief can be induced in patients suffering from chronic neurogenic pain during about the week that follows a 20-min session of 10 Hz-rTMS applied over the motor cortex." ]	There is insufficient evidence with which to assess the effectiveness of surgical and non-surgical interventions for Morton's neuroma. Well designed trials are needed to begin to establish an evidence base for the treatment of Morton's neuroma pain.
CD004786	[ "3114506", "10432161" ]	[ "Prospective study of replacing administration sets for intravenous therapy at 48- vs 72-hour intervals. 72 hours is safe and cost-effective.", "A randomized trial of 72- versus 24-hour intravenous tubing set changes in newborns receiving lipid therapy." ]	[ "We prospectively studied the safety of replacing intravenous delivery systems, including those used in total parenteral nutrition, at 72- compared with 48-hour intervals in 487 patients. Although the prevalence of contamination of intravenous fluid was higher in administration sets replaced at 72-hour intervals (10/664, 1.5%) than in sets replaced every 48 hours (6/710, 0.8%), the difference is not statistically significant. Contamination in both groups was almost exclusively with small numbers of coagulase-negative staphylococci (range, 1 to 27 colony-forming units/mL); no contaminated infusion was associated with clinical signs of sepsis or concordant bacteremia. Contaminants were recovered less frequently from peripheral venous infusions (0.6%) than from infusions used for central venous access or hemodynamic monitoring (1.5%) or total parenteral nutrition (3.6%); infusions in an intensive care unit were more frequently contaminated (2.5%) than infusions on medical and surgical wards (0.9%). These data indicate that extrinsic contamination of intravenous fluid is a rare cause of endemic nosocomial septicemia, and for most infusions it is unnecessary to routinely replace delivery systems more frequently than every 72 hours.", "To compare the microbial contamination rate of infusate in the intravenous tubing of newborns receiving lipid therapy, replacing the intravenous delivery system at 72-hour versus 24-hour intervals.\n Infants requiring intravenous lipid therapy were randomly assigned to have intravenous sets changed on a 72- or a 24-hour schedule, in a 3:1 ratio, in order to compare the infusate contamination rates in an equivalent number of tubing sets.\n A 35-bed, teaching, referral, neonatal intensive-care unit (NICU).\n All neonates admitted to the NICU for whom intravenous lipid was ordered.\n Patients were randomized in pharmacy, on receipt of the order for intravenous lipid therapy, to either 72- or 24-hour administration set changes, and followed until 1 week after discontinuation of lipids or discharge from the NICU. Microbial contamination of the infusate was assessed in both groups at the time of administration set changes. Contamination rates were analyzed separately for the lipid and amino acid-glucose tubing sets. Patient charts were reviewed for clinical and epidemiological data, including birth weight, gestational age, gender, age at start of lipid therapy, duration of parenteral nutrition, and type of intravenous access.\n During the study period, 1,101 and 1,112 sets were sampled in the 72- and 24-hour groups, respectively. Microbial contamination rates were higher in the 72-hour group than the 24-hour group for lipid infusions (39/1,101 [3.54%] vs 15/1,112 [1.35%]; P=.001) and for amino acid infusions (12/1,093 [1.10%] vs 4/1,103 [0.36%]; P=.076). Logistic regression analysis controlling for birth weight, gestational age, and type of venous access showed that only the tubing change interval was significantly associated with lipid set contaminations (odds ratio, 2.69; P=.0013). The rate of blood cultures ordered was higher in the 72- versus the 24-hour group (6.11 vs 4.99 per 100 patient days of total parenteral nutrition; P=.017), and a higher proportion of infants randomized to the 72-hour group died (8% vs 4%; P=.05), although the excess deaths could not clearly be attributed to bacteremia.\n Microbial contamination of infusion sets is significantly more frequent with 72- than with 24-hour set changes in neonates receiving lipid solutions. This may be associated with an increased mortality rate." ]	Some evidence supports maintaining intravenous fluids rather than restricting them in the first 48 hours in settings with high mortality rates and where patients present late. However, where children present early and mortality rates are lower, there is insufficient evidence to guide practice.
CD002773	[ "8285749", "6109989", "1468386", "9389261" ]	[ "Randomised trial of routine versus selective paralysis during ventilation for neonatal respiratory distress syndrome.", "Pancuronium during mechanical ventilation speeds recovery of lungs of infants with hyaline membrane disease.", "Effect of morphine and pancuronium on the stress response in ventilated preterm infants.", "Comparison of suxamethonium and different combinations of rocuronium and mivacurium for rapid tracheal intubation in children." ]	[ "The strategy of non-selective neuromuscular paralysis was compared with that of synchronised (fast rate) ventilation and selective paralysis in infants receiving mechanical ventilation for respiratory distress syndrome with chronic lung disease as the primary outcome measure. One hundred and ninety three infants weighing under 2000 g were randomly allocated to receive either pancuronium during mechanical ventilation in the acute phase of respiratory distress syndrome (non-selective group) or synchronised ventilation (initial ventilatory rate at or above that of the infant's) (selective group). Infants in the selective group received pancuronium if they were consistently expiring during the inspiratory phase of the ventilator cycle. There was no significant difference between the groups with respect to birth weight, gestation, and sex distribution. There was no significant difference between the group with respect to death (selective 19%, non-selective 16%), pneumothorax (selective 14%, non-selective 14%), chronic lung disease (selective 49%), non-selective 47%), and oxygen dependency at 36 weeks' postmenstrual age (selective 32%, non-selective 39%). Routine paralysis of ventilated infants has potential complications that may be avoided by using synchronised ventilation. As the latter is not associated with an increased incidence of long term respiratory complications, it is concluded that it is the optimum strategy of the two for ventilating infants with respiratory distress syndrome.", "Spontaneous breathing during mechanical ventilation in newborn infants may damage the lung. To find out whether the prevalence of lesions which might be due to trauma was reduced by muscle relaxation, fifty infants who required mechanical ventilation of hyaline membrane disease were randomly assigned to treated and control groups. The treated infants were kept muscle relaxed with pancuronium bromide until they needed a FiO2 of 0.40 or less during ventilation. The mean birthweight, gestational age, age at entry to the trial, duration of intubation and ventilation, FiO2 during the acute phase of the illness, and ventilator pressures were closely comparable in the two groups. Two of twenty-six treated infants and one of twenty-four controls died. Four treated and five control infants acquired pneumothoraces and/or interstitial emphysema. The length of time that the treated infants required added oxygen was significantly less than in the control infants. All treated infants were breathing room air spontaneously by one month of age whereas seven control infants were still dependent on added oxygen, needing an average FiO2 of 0.35 to achieve a mean PaO2 of 6.5 kPa (49 mm Hg). These seven infants required added oxygen until they were 5-18 (mean 10) weeks old. Muscle relaxation during mechanical ventilation for hyaline membrane disease speeds recovery of the lungs, probably owing to a reduction in traumatic damage.", "Ninety-five premature newborns who had hyaline membrane disease and were struggling against the ventilator were randomised to one of three treatment groups: morphine (group M), pancuronium (group P) or morphine with pancuronium (group M+P). The dose of morphine was 50 micrograms/kg per h but was increased to 100 micrograms/kg per h in group M infants if they continued to struggle. The dosage of pancuronium was 100 micrograms/kg given as required to inhibit spontaneous respiration. Plasma catecholamine levels were measured on entry and at 24 h. Blood pressure and ventilatory requirements were determined on entry and at 6 h. The clinical outcome of the infants was documented. Group M infants (n = 29) showed a significant reduction in noradrenaline levels (median change -2.2 nmols/l (range -47.2 to +7.2 nmols/l), although seven were withdrawn from this group because of failure to settle. Group P (n = 28) and group M+P (n = 38) showed no significant change in noradrenaline levels. Comparison between the groups showed that group M infants had a significant reduction in noradrenaline levels compared with group P. The immediate effects of treatment on blood pressure and ventilatory requirements were similar in the three groups. The clinical outcome did not differ for any of the measured parameters. When adequate sedation is achieved, morphine may reduce the stress of newborn intensive care.", "The use of suxamethonium in children is associated with undesirable side effects. The synergistic effect of a rocuronium-mivacurium combination can be considered as an acceptable alternative to suxamethonium in clinical practice. The calculated ED50 of the rocuronium-mivacurium mixture was only 62% of the predicted value assuming a purely additive interaction. The use of this combination has not been evaluated in children. In this two-part study, we assessed the intubating conditions and pharmacodynamics of suxamethonium, rocuronium, mivacurium or a rocuronium-mivacurium combinations in children. We studied 120 ASA I children of both sexes, aged 3-10 yr. Children were premedicated with trimeprazine 2 mg kg-1 orally, and received fentanyl 2 micrograms kg-1 and propofol 2 mg kg-1 for induction of anaesthesia. They were allocated randomly to receive one of the following drugs or drug combinations: suxamethonium 1.0 mg kg-1, mivacurium 0.2 mg kg-1, rocuronium 0.6 or 0.9 mg kg-1, mivacurium 0.1 mg kg-1 with rocuronium 0.3 mg kg-1 or mivacurium 0.15 mg kg-1 with rocuronium 0.45 mg kg-1. In part 1, 60 s after administration of the neuromuscular blocking drug or drug combination, tracheal intubation was performed in 60 children by mimicking rapid sequence induction, and intubating conditions were evaluated by a blinded investigator according to a standard score. In part 2, neuromuscular monitoring was established before administration of neuromuscular blocking agent(s) and the time from injection of drug or drug combination until complete ablation of T1 (onset) and recovery of T1 to 25% (duration) were recorded in another 60 children. The frequency of distribution of excellent or good intubating conditions in the higher dose of rocuronium and the combination groups were similar to those in the suxamethonium group, but significantly different (P < 0.05) from those in the mivacurium group. Mean onset time was faster in the suxamethonium (55.1 (SD 11.4) s), rocuronium 0.9 mg kg-1 (70.5 (37.7) s), mivacurium 0.1 mg kg-1 with rocuronium 0.3 mg kg-1 (67 (35.9) s) and mivacurium 0.15 mg kg-1 with rocuronium 0.45 mg kg-1 (55 (26.7) s) groups compared with the mivacurium 0.2 mg kg-1 (116 (26.8) s) and rocuronium 0.6 mg kg-1 (97.9 (29) s) groups. This study demonstrated that the combination of rocuronium 0.45 mg kg-1 and mivacurium 0.15 mg kg-1 could possibly be considered as an acceptable alternative to suxamethonium when rapid sequence induction of anaesthesia is indicated in children because it provides uniform excellent intubating conditions and complete neuromuscular block in < 60 s." ]	For ventilated preterm infants with evidence of asynchronous respiratory effort, neuromuscular paralysis with pancuronium seems to have a favourable effect on intraventricular haemorrhage and possibly on pneumothorax. However, uncertainty remains regarding the long-term pulmonary and neurologic effects and the safety of prolonged use of pancuronium in ventilated newborn infants. There is no evidence from randomised trials on the effects of neuromuscular blocking agents other than pancuronium. The routine use of pancuronium or any other neuromuscular blocking agent in ventilated newborn infants cannot be recommended based on current evidence.
CD007046	[ "11205200", "10885603", "9440756", "1354275" ]	[ "Optimum duration of oral adjuvant chemotherapy of HCFU for colorectal cancer; review of 5-year follow-up.", "The Scottish and Manchester randomised trial of neo-adjuvant chemotherapy for advanced cervical cancer.", "Prospectively randomized trial of postoperative adjuvant chemotherapy in patients with high-risk colon cancer.", "Randomised controlled trial of adjuvant chemotherapy by portal-vein perfusion after curative resection for colorectal adenocarcinoma." ]	[ "To investigate the optimal duration of oral HCFU administration for minimization of side effects induced by long-term administration.\n In total, 155 patients allocated to two groups of different duration of the therapy were reviewed: twice or three times per day doses of oral HCFU (8 mg/Kg body weight/day) for 3 months vs. 12 months.\n Though statistically significant difference was not found in cumulative survival and disease-free rates between the groups due to so many violations of duration of therapy, when reanalyzing the variables in order of real duration of therapy, those rates were significantly higher in patients treated for 300 and more days than less than 300 days (g-Wilcoxon test: p < 0.04). No significant difference was observed in the background factors between the groups.\n At least 300 days is suggested to be necessary to obtain the optimal effectiveness of adjuvant chemotherapy for curatively resected colorectal cancer.", "204 eligible patients were entered into a multicentre randomised trial of neo-adjuvant chemotherapy prior to radical radiotherapy. The aim of this study was to assess whether there was any survival advantage in patients undergoing chemotherapy and radiotherapy compared with those given radiotherapy alone. Patients were aged up to 70 years, performance status 0-1/2, with bulky stage IIb, stage III or stage IVa squamous or adenosquamous carcinoma. Three cycles of methotrexate 100 mg/m2 and cisplatin 50 mg/m2 were given at 2-weekly intervals before radical radiotherapy. 104 eligible patients received the combination treatment and 100 radiotherapy only. The two arms of the study were well balanced for tumour and patient characteristics. The response rate to chemotherapy was 49%, 33% of patients in the radiotherapy (XRT) alone arm and 45% of the combination arm were clinically free of tumour at the end of treatment. The median follow-up for surviving patients is 5.4 years (range: 11 months-8 years) and 84% have been followed-up for more than 4 years. 134 patients have died (68 XRT only, 66 combined arm). The median survival RT alone was 111 weeks (95% confidence interval (CI) 72-151 weeks), combination arm 125 weeks (95% CI 79-170 weeks). The estimated death ratio is 0.79 (P = 0.19, 95% CI 0.56-1.12). The estimated 3-year survival is 40% (95% CI 30-50%) RT only compared with 47% (95% CI 37-57%) in the combination arm. Acute and late toxicity of radiotherapy was not increased by the addition of chemotherapy.", "This study had two major goals: (1) to assess the effectiveness of a regimen of fluorouracil (5-FU) plus levamisole plus leucovorin as postoperative surgical adjuvant therapy for patients with high-risk colon cancer, and (2) to evaluate 6 months versus 12 months of chemotherapy.\n Patients with poor-prognosis stage II or III colon cancer were randomly assigned to receive adjuvant chemotherapy with either intensive-course 5-FU and leucovorin combined with levamisole, or a standard regimen of 5-FU plus levamisole. Patients were also randomly assigned to receive either 12 months or 6 months of chemotherapy, which resulted in four treatment groups.\n Eight hundred ninety-one of 915 patients entered (97.4%) were eligible. The median follow-up duration is 5.1 years for patients still alive. There was a difference among the four treatment groups with respect to patient survival, and a significant duration-by-regimen interaction was observed. Specifically, standard 5-FU plus levamisole was inferior to 5-FU plus leucovorin plus levamisole when treatment was given for 6 months (5-year survival rate, 60% v 70%; P < .01).\n There was no significant improvement in patient survival when chemotherapy was given for 12 months compared with 6 months. When chemotherapy was given for 6 months, standard 5-FU plus levamisole was associated with inferior patient survival compared with intensive-course 5-FU plus leucovorin plus levamisole. These data suggest that 5-FU plus levamisole for 6 months should not be used in clinical practice, whereas 6 months of treatment with 5-FU plus leucovorin plus levamisole is effective.", "About half the patients treated with curative resection for colorectal cancer do not survive long-term. Adjuvant chemotherapy given during and after surgery may prevent hepatic metastases and improve patient survival. In patients with colorectal cancer, we have done a multicentre, randomised controlled trial comparing five-year survival after intraportal infusion of fluorouracil (1 g per day) plus heparin (10,000 U per day) (130 patients) or heparin alone (123) during curative resection and for 7 days thereafter, or after resection alone (145). There was no reduction in liver metastasis or increased overall survival advantage in either active-treatment arm of the study. However, patients who had stage III, Dukes' C (lymph-node-positive) tumours resected and were treated with fluorouracil plus heparin had a significant (p less than 0.03) survival advantage of about 16% compared with surgery-only controls. Further study of intraportal infusion of chemotherapeutic agent as adjuvant treatment to surgery in patients with colorectal cancer appears worthwhile." ]	The present meta-analysis confirmed that adjuvant chemotherapy of CRC should not last for more than 6 months. Prolonged duration would result in lower benefit to risk ratio. However, the results do not make it possible to favour either 3 or 6 month durations. They should help design a future RCT comparing different durations of continuous treatment.
CD005188	[ "15485728", "1913409", "15904750", "11812810", "8050255", "9243440", "10408998", "16461871", "15006907", "16085200", "10432913", "15068574", "1861939", "8859184", "16916871", "11897462", "1907834", "15515991", "17149995", "2677271", "9441569", "16263978", "8341774", "20157016", "15802479", "12950483", "18337049", "12763714", "21252632", "9635532", "15336581", "9481466", "20219315", "8139302", "8563365", "12632705", "10723618", "6208312", "10901494" ]	[ "Telephone reminders are effective in recruiting nonresponding patients to randomized controlled trials.", "Use of reminders for preventive procedures in family medicine.", "Can just-in-time, evidence-based \"reminders\" improve pain management among home health care nurses and their patients?", "Telephone reminders are a cost effective way to improve responses in postal health surveys.", "Patient-specific reminder letters and pediatric well-child-care show rates.", "A randomized trial of the impact of telephone and recorded delivery reminders on the response rate to research questionnaires.", "Effect of mailed reminders on the response rate in surveys among patients in general practice.", "Effect of telephone reminder/recall on adolescent immunization and preventive visits: results from a randomized clinical trial.", "A large population-based randomized controlled trial to increase attendance at screening for cervical cancer.", "Initial nonresponders had an increased response rate after repeated questionnaire mailings.", "Public health in managed care: a randomized controlled trial of the effectiveness of postcard reminders.", "Synchronizing clinician engagement and client motivation in telephone counseling.", "Increasing patient knowledge, satisfaction, and involvement: randomized trial of a communication intervention.", "The effect of patient and physician reminders on use of screening mammography in a health maintenance organization. Results of a randomized controlled trial.", "The use of text messaging to improve attendance in primary care: a randomized controlled trial.", "Effectiveness of telephone support in increasing physical activity levels in primary care patients.", "Evaluation of a follow-up system in a county health department's immunization clinic.", "Crossing the digital divide: evaluating online communication between patients and their providers.", "Use and impact of an automated telephone outreach system for asthma in a managed care setting.", "A controlled trial to improve delivery of preventive care: physician or patient reminders?", "Effectiveness of computer-generated reminders for increasing discussions about advance directives and completion of advance directive forms. A randomized, controlled trial.", "Using the internet to provide information prescriptions.", "Evaluation of telephoned computer-generated reminders to improve immunization coverage at inner-city clinics.", "Effects of a mail and telephone intervention on breast health behaviors.", "A randomized trial of electronic clinical reminders to improve quality of care for diabetes and coronary artery disease.", "Effect of a triage-based E-mail system on clinic resource use and patient and physician satisfaction in primary care: a randomized controlled trial.", "Nurse and patient communication profiles in a home-based telehealth intervention for heart failure management.", "Population-based randomized controlled trial of a stage-targeted physical activity intervention.", "Mobile phone technologies improve adherence to antiretroviral treatment in a resource-limited setting: a randomized controlled trial of text message reminders.", "How reminders given to patients and physicians affected pap smear use in a health maintenance organization: results of a randomized controlled trial.", "Improving completion of advance directives in the primary care setting: a randomized controlled trial.", "Randomized controlled study of customized preventive medicine reminder letters in a community practice.", "A randomized controlled trial of communication training with primary care providers to improve patient-centeredness and health risk communication.", "Automated telephone reminders in tuberculosis care.", "A computer-generated reminder system improves physician compliance with diabetes preventive care guidelines.", "Effectiveness of report cards based on chart audits of residents' adherence to practice guidelines on practice performance: a randomized controlled trial.", "Empowering older patients to communicate more effectively in the medical encounter.", "The efficacy of personalized audiovisual patient-education materials.", "Effectiveness of physician-based assessment and counseling for exercise in a staff model HMO." ]	[ "Studies investigating means of recruiting participants to randomized controlled trials (RCTs) are sparse. We investigated the effects of telephone reminders as a recruitment strategy.\n Sick-listed employees received a written invitation to participate in a study comparing standard treatments with a solution-focused follow-up and were randomly allocated to an intervention or control group (n=703). Those who did not respond within 2 weeks received either 'no reminder' (n=242) or 'attempted telephone reminder' (n=256). Outcome was enrollment to the RCT.\n An intention to recruit analysis revealed no significant differences between the groups (P=.229). An intention to phone analysis among nonresponders revealed significant differences between 'no reminder' (recruited 4.5%) and 'attempted telephone reminder' (recruited 12.1%) (P=.003, odds ratio 2.89, 95% confidence interval [CI] 1.42-5.90). An analysis of numbers needed to phone showed that to recruit one more person in this group of nonresponders, we needed to phone 13 persons (95% CI=8-33).\n Systematic use of telephone calls can increase the recruitment rate among nonresponders in RCTs.", "To compare the effectiveness of three computerized reminder systems in the delivery of five preventive procedures in family practice.\n Prospective, randomized, controlled study.\n Ottawa Civic Hospital Family Medicine Centre.\n Of 8502 patients 15 years of age or more who were not in a hospital or institution 5883 were randomly assigned, by family, to a control group, a physician reminder group (passive) or a telephone or letter reminder group (active). The remaining 2619 patients were not included in the randomized portion of the study but were monitored.\n During 1 year the patients in the active reminder groups received a telephone call or letter reminding them of any overdue preventive procedures; for those in the passive reminder group the physician was reminded at an office visit to provide any overdue service.\n Rates of completion of the preventive procedures required.\n All three reminder systems significantly improved the delivery of preventive services (p less than 0.001). The procedure completion rates were 42.0% in the letter reminder group, 42.0% in the telephone reminder group, 33.7% in the physician reminder group and 14.1% in the randomized control group. The use of a letter was more cost-effective than the telephone system, but the physician reminder system was the most cost-effective.\n Computerized reminder systems do improve the delivery of preventive services in family practice.", "The purpose of this randomized, controlled, home care intervention was to test the effectiveness of two nurse-targeted, e-mail-based interventions to increase home care nurses' adherence to pain assessment and management guidelines, and to improve patient outcomes. Nurses from a large urban non-profit home care organization were assigned to usual care or one of two interventions upon identification of an eligible cancer patient with pain. The basic intervention consisted of a patient-specific, one-time e-mail reminder highlighting six pain-specific clinical recommendations. The augmented intervention supplemented the initial e-mail reminder with provider prompts, patient education material, and clinical nurse specialist outreach. Over 300 nurses were randomized and outcomes of 673 of their patients were reviewed. Data collection involved clinical record abstraction of nurse care practices and patient interviews completed approximately 45 days after start of care. The intervention had limited effect on nurse-documented care practices but patient outcomes were positively influenced. Patients in the augmented group improved significantly over the control group in ratings of pain intensity at its worst, whereas patients in the basic group had better ratings of pain intensity on average. Other outcomes measures were also positively influenced but did not reach statistical significance. Our findings suggest that although reminders have some role in improving cancer pain management, a more intensive approach is needed for a generalized nursing workforce with limited recent exposure to state-of-the-art pain management practices.", "To assess the effectiveness of a telephone reminder in increasing responses to postal surveys and to calculate the differential costs per completed questionnaire.\n Randomised controlled trial.\n Australian university and rehabilitation medicine practice.\n The trial was conducted in 1999 among the 143 non-respondents to a questionnaire about work related neck and upper body disorders. The questionnaire was sent to two Australian female samples: 200 office workers (Sample A) and 92 former rehabilitation medicine patients (Sample B). A reminder letter, another copy of the questionnaire and a final letter were sent at two week intervals. Half of the non-respondents within each sample were randomly selected to receive a telephone reminder just after the second mailout of the questionnaire. All direct costs were calculated.\n Responses were significantly higher among those who received the telephone reminder intervention (relative risk 2.54, 95% confidence intervals 1.43 to 4.52). Analysed by intention to phone, 47% of non-respondents in Sample A and 38% in Sample B returned a complete questionnaire after the intervention, compared with 21% and 10%, respectively, in the control groups. For the 112 women (combined samples) who returned completed questionnaires before randomisation, the average cost per respondent was AUD14. There was a higher total cost for the intervention groups (AUD851 versus AUD386 for controls), but the significantly higher number of additional completed responses (31 versus 12) resulted in a 15% lower marginal cost per completed questionnaire in those groups.\n Telephone reminders are cost effective in improving responses to postal surveys.", "The objective of this study was to determine whether patient-specific letters, which describe the content of an upcoming well-child appointment, improve the show rate of well-child appointments better than postcard reminders. In this prospective clinical trial conducted at a pediatric continuity clinic in a teaching hospital, 288 newborns were randomized to a letter, postcard, or control group. For every well-child appointment, families were sent either a letter pertaining to the particular well-child appointment or a postcard; the control group received no reminders. There were no differences in demographics among the groups. The show rates between the letter and postcard groups were not different, but were significantly higher than the show rate for the control group (75.0%, 73.7%, and 67.5%, respectively; P < .05). A cost comparison between the use of postcards versus not using postcards revealed a benefit in the former. We concluded postcard reminders are effective in improving show rates for well-child-care visits, and that patient-specific letters have no additional benefit above that of postcard reminders.", "A range of factors have been shown to affect the response rate to mailed questionnaires, but particular strategies to improve patients' response in trials conducted in general practice require further study.\n Non-responders in a larger trial were randomized to receive a telephone or recorded delivery reminder on the third contact. The cost of administration of each method was estimated.\n Significantly more patients returned completed questionnaires when sent questionnaires by recorded delivery, although the cost per patient contacted was nearly three times more than for contact by telephone.\n Our study indicates that sending reminders by recorded delivery, although more expensive, is more effective than telephone reminders for recruiting patients to a study in general practice using research questionnaires.", "Randomized trials were performed in Denmark and The Netherlands to determine the effect of mailed reminders on the response rate in surveys among patients in general practice. In both countries, general practitioners handed out questionnaires to 200 adult patients who came to visit them. An intervention group of 100 patients received reminders at 3 weeks after the visit, whereas a control group of the remaining 100 patients did not receive reminders. The response rate was significantly higher in the intervention groups than in the control group in The Netherlands (86% versus 55%, respectively) but not in Denmark (87% versus 81%, respectively). Mailed reminders can improve the response rate in surveys related to a general practice, but they are not effective in all situations.", "To measure the effect of telephone-based reminder/recall on immunization and well-child care (WCC) visit rates among adolescents in urban practices.\n Randomized clinical trial of telephone-based reminder/recall over 18 months.\n Four urban primary care practices.\n Adolescents aged 11 to 14 years.Intervention Adolescents within practices were randomized to study (n = 1496) or control groups (n = 1510). The study group was sent audiotaped telephone reminders about a scheduled or needed immunization or WCC visit. Households were called weekly if there was no response; telephone numbers were updated weekly. Controls received standard care.\n Baseline demographics and immunization and WCC visit rates were similar for study and control groups. The intervention was largely ineffective in improving immunization or WCC visit rates. Although at the end of the study, the study group had slightly higher hepatitis B coverage (3 vaccinations) (62% vs 57.8%; P = .02), WCC visits were the same (53% and 54%), and impact on other vaccinations was minimal. The effect of reminder/recall was equivalent across demographic subgroups (e.g., age, race/ethnicity, insurance). The major factor limiting intervention effectiveness was inaccurate telephone numbers. Seventy-one percent of study subjects with single telephone numbers throughout the study had a WCC visit vs 25% of study subjects with multiple/changed telephone numbers and 54% of controls (P<.001).\n An intensive telephone reminder and recall system was only minimally successful in improving immunization and WCC visit rates among urban adolescents. Lack of success was largely owing to changed or inaccurate telephone numbers.", "Although cervical cancer is one of the potentially most preventable malignancies, it is still fairly common. In settings with established screening programs, increased compliance is important for future reduction in cervical cancer incidence, but it is presently unclear how this can be effectively achieved.\n We conducted a randomized controlled trial including all 12,240 women invited to organized screening in Sweden. To increase compliance, three successive interventions were tested: (a) modified invitation versus the standard invitation letter, (b) reminder letter to nonattenders after the first intervention versus no reminder letter, and (c) phone reminder to nonattenders after the reminder letter versus no phone reminder. We analyzed the proportion of women attending screening after each intervention and the cumulative proportion after the interventions as well as the cumulative proportions of cytologic abnormalities.\n The modified invitation did not increase attendance compared with the standard invitation letter [difference 1.3% 95% confidence interval (CI) -0.3 to 2.9]. In contrast, a reminder letter increased the proportion of women attending with 9.2% (95% CI 7.9-10.5) compared with women who did not receive a reminder letter, and a phone reminder increased the proportion of women attending with 31.4% (95% CI 26.9-35.9). Combinations of modified invitation, written reminder, and phone reminder almost doubled attendance within 12 months, and the number of detected cytologic abnormalities was more than tripled.\n Simple reminders by mail and phone can drastically increase women's participation in Papanicolaou smear screening and increase the number of detected precursor lesions and thereby save lives.", "There is a growing evidence base on methods to improve response rates in surveys among patients. This study aimed to determine the additional effect of two intensive follow-up procedures compared to a simple follow-up procedure.\n Randomized controlled trial that compared repeated mailing of the questionnaire and a request to explain nonparticipation with a simple reminder card. The study population comprised 955 elderly adults registered with 26 general practitioners in The Netherlands.\n A total of 530 adults (56%) returned the questionnaire within 3 weeks and a total of 640 (67%) after follow-up. Repeated mailing of the questionnaire had additional effect compared to the simple reminder card in the group of initial nonresponders (relative risk=1.60, 95% confidence interval: 1.11-2.31), but not regarding the overall response rate. A request to explain nonparticipation did not have additional effect.\n Repeated mailing of the questionnaire increased the effectiveness of follow-up among initial nonresponders.", "This study evaluated the effectiveness of an annual public health intervention in a managed care setting.\n Managed care organization members 65 years and older who received influenza immunization in 1996 were randomized to an intervention group (mailed a postcard reminder to receive an influenza vaccination in 1997) or a control group (no postcard). Vaccination rates for both groups were assessed monthly.\n Members receiving the intervention were no more likely to be immunized (78.6%) than members of the control group (77.2%, P = .222). Members were vaccinated at the same pace regardless of vaccination history and postcard intervention status.\n Postcard reminders were not an effective intervention among seniors who had been vaccinated the previous year.", "Health care increasingly incorporates telephone counseling, but the interactions supporting its delivery are not well understood. The authors' clinical trial of a tailored, nurse-administered smoking cessation intervention for surgical patients included a telephone counseling component and provided an opportunity to describe the interaction dynamics of proactive telephone counseling over the course of 4 months. Tape-recorded telephone counseling calls for 56 consecutively enrolled individuals randomized to the intervention group resulted in a data set of 368 calls, which were transcribed and analyzed using constant comparative methods. The findings revealed varying interaction dynamics depending on the nurse's level of engagement with participants and participants' motivation to stop smoking. The authors identified four interaction dynamics: affirming/working, chasing/skirting, controlling/withdrawing, and avoiding commitment. Shifts in interaction dynamics were common and influenced the provision of support both positively and negatively. The findings challenge many assumptions underlying telephone counseling and suggest strategies to improve its delivery.", "A brief educational intervention to promote effective communication between physicians, children, and parents during pediatric office visits was designed and tested. A randomized clinical trial involving 141 children (5- to 15-year-olds) tested the effectiveness of the intervention to improve the process and outcome of medical care. The intervention was contained in three brief videotapes (one each for parents, physicians, and patients) and in accompanying written materials. Materials were designed to build skills and motivation for increased child competence and participation during pediatric medical visits. Control subjects saw health education videotapes and received materials comparable in length with those of experimental subjects. Postintervention medical visit process was analyzed using videotapes of visits. Visit outcomes, assessed with standardized instruments and interviews, included children's rapport with physicians, children's anxiety, children's preference for an active health role, children's recall of information, parents' satisfaction with the medical visit, and physician satisfaction. Results indicated that physicians in the intervention group, compared with their counterparts in the control group, more often included children in discussions of medical recommendations (50% vs 29%, t = 2.39, P less than .05); that children in the intervention group, compared with control children, recalled more medication recommendations (77% vs 47%, P less than .01) and reported greater satisfaction and preference for an active health role; and that the intervention and control groups did not differ in parent satisfaction, physician satisfaction, or child anxiety. The results suggest that a brief educational intervention administered during waiting room time can positively impact physician-child rapport and children's preference for an active role in health and their acquisition of medical information.", "Despite its demonstrated efficacy in reducing breast carcinoma mortality, screening mammography remains underutilized and its promotion in the primary care setting provides an important opportunity for intervention.\n A randomized controlled trial was conducted in two sites of a health maintenance organization (HMO) serving an urban, minority population to evaluate the impact of patient and physician reminders on site visitation and mammography use. Eligible women (n = 2368) were randomly assigned to 1 of 4 intervention combinations (patient and physician reminders individually, together, or neither). The patient reminder letter invited mammography-due women to visit. The physician reminder was a notice placed in the medical record of mammography-due women. Logistic analysis and survival analysis were used to investigate the relationship of intervention status to visitation, time to a visit, and mammography use.\n The patient reminder intervention had no effect upon rates of study year visitation or mammography at either site. However, among HMO Site 2 enrollees with entitlement insurance, the median time to the next visit was reduced from 12 to 9 weeks in association with assignment to patient reminder intervention. The physician reminder intervention was also effective in increasing the rate of completed mammography at Site 2 among all assignees (36% vs. 22% for those with vs. those without physician reminders) and among assignees who visited (59% vs. 43%).\n Patient reminder letters had limited impact on visitation in this setting. Physician reminders are more effective but sites vary in their responsiveness. Further improvement in mammography utilization will require a better understanding of the determinants of patient and physician behavior.", "Non-attendance is common in primary care and previous studies have reported that reminders were useful in reducing broken appointments.\n To determine the effectiveness of a text messaging reminder in improving attendance in primary care.\n Multicentre three-arm randomized controlled trial.\n Seven primary care clinics in Malaysia. Participants. Patients (or their caregivers) who required follow-up at the clinics between 48 hours and 3 months from the recruitment date. Interventions. Two intervention arms consisted of text messaging and mobile phone reminders 24-48 hours prior to scheduled appointments. Control group did not receive any intervention. Outcome measures. Attendance rates and costs of interventions.\n A total of 993 participants were eligible for analysis. Attendance rates of control, text messaging and mobile phone reminder groups were 48.1, 59.0 and 59.6%, respectively. The attendance rate of the text messaging reminder group was significantly higher compared with that of the control group (odds ratio 1.59, 95% confidence interval 1.17 to 2.17, P = 0.005). There was no statistically significant difference in attendance rates between text messaging and mobile phone reminder groups. The cost of text messaging reminder (RM 0.45 per attendance) was lower than mobile phone reminder (RM 0.82 per attendance).\n Text messaging reminder system was effective in improving attendance rate in primary care. It was more cost-effective compared with the mobile phone reminder.", "Physician counseling of patients to increase physical activity has had limited success in changing behavior. Providing organizational support to primary care providers and their patients may increase effectiveness.\n This study evaluates the effectiveness of a telephone-based intervention to increase physical activity among patients who exercised <15 minutes daily and wanted to increase their physical activity over a 6-month period.\n This was a randomized controlled trial, conducted from 1997 to 1998, of 316 patients aged 18 to 65 who were recruited from a mailed health risk assessment. Baseline and 6-month post-intervention telephone assessments were conducted by telephone.\n One family physician's patients in a suburban community.\n Three sessions of telephone-delivered motivational counseling.\n Physical activity score (11-item Physician-Based Assessment and Counseling for Exercise [PACE]) 6 months after the intervention.\n After adjusting for baseline exercise, there was a significantly higher level of self-reported exercise among individuals randomized to the intervention at the 6-month follow-up. The mean level of activity at follow-up for the intervention group was a PACE score of 5.37, compared to 4.98 in the control group (p<0.05). In the secondary analysis, which was limited to individuals who received the intervention, the effect was stronger (PACE score of 5.58 compared to 4.94, p<0.013).\n Patients can be recruited using a health-screening questionnaire to receive a telephone-delivered behavioral intervention to successfully increase their physical activity levels.", "We designed a pilot follow-up system using two mailed reminders and evaluated it for use in the immunization clinic of a relatively large county health department in Washington State. Compliance with the recommended interval for DTP immunizations increased by 33.9% in the group of children receiving two postcard reminders compared to the control group. Over half of the respondents (52%) in the control group and 28% in the intervention group reported that transportation barriers and clinic problems prevented their return.", "To address provider, payer, and patient concerns about the use of online communication in healthcare settings by performing a randomized controlled trial of a Web-based patient-provider communication tool in primary care.\n Forty-one staff physicians and 91 residents in 4 primary care centers were randomized to a Web-based online communication system. Patients of intervention physicians were encouraged to communicate via the system about health issues, scheduling, prescription renewals, referrals, and billing. Data collected included patient Web use, e-mail use, telephone calls, visit distribution, and physician and patient attitudes toward and satisfaction with communication.\n One thousand thirty-eight patients sent 2238 messages during the 40-week study. Half of the messages were directly related to a patient's health; half were administrative. Patient Web use peaked at 8.5 weekly messages per 100 scheduled visits. Patient e-mail and telephone volume remained similar across groups. Intervention physicians reported more positive attitudes toward Web-based communication than control physicians (mean Web benefits scale score, 4.0 vs 1.1; P = .008), but there were no between-group differences in attitudes toward communication in general. Patients and physicians reported differential preferences for the use of online communication based on problem complexity and sensitivity.\n Web-based messaging was lower than expected because of patient-related factors and limitations of the technology. Patients, physicians, and staff had positive attitudes toward online communication. There was no detectable difference in communication volume between study groups, but more sensitive measures of work burden need to be developed and evaluated.", "To test the ability of an automated telephone outreach intervention to reduce acute healthcare utilization and improve quality of life among adult asthma patients in a large managed care organization.\n Randomized clinical trial.\n Patients with persistent asthma were randomly assigned to telephone outreach (automated = 3389, live caller = 192) or usual care (n = 3367). Intervention participants received 3 outreach calls over a 10-month period. The intervention provided brief, supportive information and flagged individuals with poor asthma control for follow-up by a provider. A survey was mailed to 792 intervention participants and 236 providers after the intervention. Additional feedback was obtained as part of the final intervention contact.\n The intent-to-treat analysis found no significant differences between the intervention and usual-care groups for medication use, healthcare utilization, asthma control, or quality of life. Post hoc analyses found that, compared with the control group, individuals who actually participated in the intervention were significantly more likely to use inhaled steroids and to have had a routine medical visit for asthma during the follow-up period and less likely to use short-acting beta-agonists. They also reported higher satisfaction with their asthma care and better asthma-specific quality of life. Of surveyed providers, 59% stated the program helped them to clinically manage their asthma patients and 70% thought the program should be continued.\n This study did not find improved health outcomes in the primary analyses. The intervention was well accepted by providers, however, and the individuals who participated in the calls appeared to have benefited from them. These findings suggest that further studies of automated telephone outreach interventions seem warranted.", "To improve the delivery of preventive care in a medical clinic, a controlled trial was conducted of two interventions that were expected to influence delivery of preventive services differently, depending on level of initiative required of the physician or patient to complete a service.\n A prospective, controlled trial of five-months' duration.\n A university hospital-based, general medical clinic.\n Thirty-nine junior and senior medical residents who saw patients in stable clinic teams throughout the study.\n A computerized reminder system for physicians and a patient questionnaire and educational hand-out on preventive care.\n Delivery of five of six audited preventive services improved significantly after the interventions were introduced. The computerized reminder alone increased completion rates of services that relied primarily on physician initiative; the questionnaire alone increased completion rate of the service that depended more on patient compliance as well as on some physician-dependent services. Both interventions used together were slightly less effective in improving performance of physician-dependent services than the computerized reminder used alone.\n These interventions can improve the delivery of preventive care but they differ in their impacts on physician and patient behaviors. Overall, the computer reminder was the more effective intervention.", "Physicians can increase the rate of completion of advance directive forms by discussing directives with their patients, but the means by which physicians can be induced to initiate these discussions are unclear. Computer-generated reminders have been shown to increase physician compliance with practice guidelines.\n To determine the effects of computer-generated reminders to physicians on the frequency of advance directive discussions between patients and their primary caregivers and the frequency of consequent establishment of advance directives.\n Randomized, controlled trial with a 2 x 2 factorial design.\n An outpatient general medicine practice associated with an urban public hospital.\n Participants were 1) 1009 patients who were at least 75 years of age or were at least 50 years of age with serious underlying disease and 2) 147 primary care physicians (108 housestaff and 39 faculty).\n Computer-generated reminders that recommended discussion of one or both of two types of advance directives compared with no reminders.\n Discussions about advance directives, determined by patient interviews after all scheduled patient-physician outpatient encounters, and completed advance directive forms. The study period was approximately 1 year.\n Physicians who did not receive reminders (controls) discussed advance directives with 4% of the study patients compared with 24% for physicians who received both types of reminders (adjusted odds ratio, 7.7 [95% CI, 3.4 to 18]; P < 0.001). Physicians who did not receive reminders completed advance directive forms with only 4% of their study patients compared with 15% for physicians who received both types of reminders (adjusted odds ratio, 7.0 [CI, 2.9 to 17]; P < 0.001). Overall, 45% of patients with whom advance directives were discussed completed at least one type of advance directive.\n Simple computer-generated reminders aimed at primary caregivers can increase the rates of discussion of advance directives and completion of advance directive forms among elderly outpatients with serious illnesses.", "An information prescription is the provision of specific information to a patient on how to help manage a health problem. The Internet is being used increasingly as a source for information prescriptions, with clinicians directing patients to specific Web sites. As with any health care intervention, patients' lack of compliance is a barrier to the effectiveness of Web-based information prescriptions (WebIPs). WebIPs cannot be helpful if patients do not review the information prescribed for them.\n The main objective of this study was to quantify the percentage of families who visit a Web site that was specifically prescribed by their physician. In addition, the use of an e-mail reminder was used to determine if it increases the likelihood that families will visit the prescribed Web site. Finally, barriers to accessing the prescribed Web site were identified.\n Children were eligible if they presented to the pediatric gastroenterology clinic with chronic constipation and/or encopresis and their family had an active e-mail account and access to the Internet in their home. During their clinic visit, physicians instructed families to visit a Web site that provided educational information pertinent to their child's problem. Families were given a form with the Web-site address and a log-in identification number. Two days after their clinic visit, half of the families received an e-mail reminding them to visit the Web site. Families were contacted 1 week after their clinic visit to identify barriers to accessing the Web site.\n Eighty-three families participated in the study. Of the 83 families, 54 (65%) visited the prescribed Web site within 1 week of their clinic visit. Families who received e-mail reminders were significantly more likely to visit the Web site than families who did not receive an e-mail reminder (77% vs 53%). This difference could not be explained by the type or speed of Internet connection or how frequently they accessed the Internet or e-mail. The most common reasons that families cited for not accessing the Web site were \"I forgot\" and \"I didn't have time.\" Few families cited technical reasons for not accessing the Web site.\n Almost two thirds of the families given a WebIP logged on to the prescribed Web site. The probability that families would access the site was increased by 45% with an e-mail reminder. Clearly, e-mail prompts improve compliance to WebIPs. As content and treatment programs continue to proliferate on the Web, it is important to identify barriers and solutions to them to improve overall compliance.", "The authors evaluated the effectiveness of computer-generated telephoned reminders used to raise the rates of on-time immunization among preschool-age children in two public clinics in Atlanta, GA. The overall effect of the intervention on immunization levels appeared to be minimal (crude relative risk = 1.07, 95 percent confidence interval = 0.78, 1.46), in part because only about 80 percent of children in both the randomly selected intervention group and in the control group were members of a household with a telephone number listed in clinic records. However, logistic regression analysis indicated that 36 of 68 children (52.9 percent) in the intervention group whose households were reached were vaccinated within 30 days of their due dates, compared to 31 of 75 children (41.3 percent) in the control group whose household telephone numbers were recorded but not called (adjusted odds ratio = 2.12, 95 percent confidence interval = 1.01, 4.46). This analysis indicates that telephoned reminders demonstrated a level of effectiveness in improving immunization levels at inner-city clinics that recommends further trial and study.", "This study evaluated a mail and telephone intervention to improve breast health behaviors while maintaining quality of life. Women recruited from the general public were randomized to a stepped-intensity intervention consisting of mailings, telephone calls, and counseling (if requested or appropriate given a woman's genetic risk for breast cancer) or to a delayed treatment control group. Outcomes (mammography screening and quality of life) were measured at baseline in a telephone survey and again at a 12-month follow-up period. Women in the intervention group significantly increased screening mammography uptake by 12% and quality of life by 5.3 scale points compared to control participants. Changes in knowledge of breast cancer, genetic testing, and cancer worry all significantly predicted intervention changes. This successful intervention can help women make better breast health choices without causing increased worry.", "The aim of this study was to evaluate the impact of an integrated patient-specific electronic clinical reminder system on diabetes and coronary artery disease (CAD) care and to assess physician attitudes toward this reminder system.\n We enrolled 194 primary care physicians caring for 4549 patients with diabetes and 2199 patients with CAD at 20 ambulatory clinics. Clinics were randomized so that physicians received either evidence-based electronic reminders within their patients' electronic medical record or usual care. There were five reminders for diabetes care and four reminders for CAD care.\n The primary outcome was receipt of recommended care for diabetes and CAD. We created a summary outcome to assess the odds of increased compliance with overall diabetes care (based on five measures) and overall CAD care (based on four measures). We surveyed physicians to assess attitudes toward the reminder system.\n Baseline adherence rates to all quality measures were low. While electronic reminders increased the odds of recommended diabetes care (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.01-1.67) and CAD (OR 1.25, 95% CI 1.01-1.55), the impact of individual reminders was variable. A total of three of nine reminders effectively increased rates of recommended care for diabetes or CAD. The majority of physicians (76%) thought that reminders improved quality of care.\n An integrated electronic reminder system resulted in variable improvement in care for diabetes and CAD. These improvements were often limited and quality gaps persist.", "E-mail communication between patients and their providers has diffused slowly in clinical practice. To address concerns about the use of this technology, we performed a randomized controlled trial of a triage-based e-mail system in primary care. DESIGN AND PATIENTS/PARTICIPANTS: Physicians in 2 university-affiliated primary care centers were randomized to a triage-based e-mail system promoted to their patients. E-mails from patients of intervention physicians were routed to a central account and parsed to the appropriate staff for response. Control group physicians and their patients did not have access to the system. We collected information on patient e-mail use, phone calls, and visit distribution by physician over the 10 months and performed physician and patient surveys to examine attitudes about communication.\n E-mail volume was greater for intervention versus control physicians (46 weekly e-mails per 100 scheduled visits vs 9 in the control group at the study midpoint; P <.01) but there were no between-group differences in phone volume (67 weekly phone calls per 100 scheduled visits vs 55 in the control group; P =.45) or rates of patient no-shows (5% in both groups; P =.77). Intervention physicians reported more favorable attitudes toward electronic communication than did control physicians but there were no differences in attitudes toward patient or staff communication in general. There were few between-group differences in patient attitudes toward electronic communication or communication in general.\n E-mail generated through a triage-based system did not appear to substitute for phone communication or to reduce visit no-shows in a primary care setting. Physicians' attitudes toward electronic communication were improved, but physicians' and patients' attitudes toward general communication did not change. Growth of e-mail communication in primary care settings may not improve the efficiency of clinical care.", "This study compared differences in nurse and patient communication profiles between two telehealth modes: telephone and videophone, and evaluated longitudinal changes in communication, nurse perceptions, and patient satisfaction.\n Subjects were enrolled in a randomized controlled clinical trial evaluating a 90-day home-based intervention for heart failure. Telephone (n=14) and videophone (n=14) interactions were audio taped and analyzed using the Roter Interaction Analysis System.\n Nurses were more likely to use open-ended questions, back-channel responses, friendly jokes, and checks for understanding on the telephone compared to videophone. Compliments given and partnership were more common on the videophone. Patients were more likely to give lifestyle information and approval comments on the telephone, and used more closed-ended questions on the videophone. Nurses perceptions of the interactions were not different between the telephone and videophone, nor did their perceptions change significantly over the course of the intervention. There were no significant differences in patient satisfaction between the telephone and videophone.\n The results of this study did not support use of a videophone over the telephone.\n It is critical to match technologies to patient needs and use the least complex technology possible. When considering use a videophone, health care providers should critically examine the trade-offs between additional complexities with the added value of the visual interaction.", "Intervention trials with self-selected participants have shown that mailed stage-targeted print materials can increase participation in physical activity in the short term. We examined the effects of a mailed stage-targeted print intervention designed to promote physical activity, in a random sample of adults living in a regional city.\n Participants (n = 462, 40-60 years of age) were randomly allocated to an intervention (n = 227) or control group (n = 235). Measures included validated 2-week physical activity recall and stage of motivational readiness for physical activity. The intervention consisted of a single mailing of a letter and full-color stage-targeted booklets (specific to precontemplation, contemplation, preparation, and action/maintenance) 1 week postbaseline. Follow-up interviews were conducted at 2 and 6 months postbaseline.\n After 2 months, participants in the intervention group were significantly more likely to meet the current American College of Sports Medicine/Centers for Disease Control and Prevention recommendation for sufficient physical activity than those in the control group (adjusted odds ratio [OR] = 2.40; 95% confidence interval [CI] = 1.44-3.99). After 6 months, intervention participants who reported receiving and reading the intervention materials were significantly more likely to be meeting the sufficient physical activity criterion compared with the control group (adjusted OR = 2.03; 95% CI = 1.16-3.56).\n The stage-targeted print intervention was effective in promoting short-term increases in physical activity and was most effective for participants who recognized and used the materials. This low-cost, generalizable intervention has demonstrated potential as a practical population-based physical activity promotion strategy. Further research is required before widespread dissemination would be justified, as additional strategies may be required to ensure sustained change.", "There is limited evidence on whether growing mobile phone availability in sub-Saharan Africa can be used to promote high adherence to antiretroviral therapy (ART). This study tested the efficacy of short message service (SMS) reminders on adherence to ART among patients attending a rural clinic in Kenya.\n A randomized controlled trial of four SMS reminder interventions with 48 weeks of follow-up.\n Four hundred and thirty-one adult patients who had initiated ART within 3 months were enrolled and randomly assigned to a control group or one of the four intervention groups. Participants in the intervention groups received SMS reminders that were either short or long and sent at a daily or weekly frequency. Adherence was measured using the medication event monitoring system. The primary outcome was whether adherence exceeded 90% during each 12-week period of analysis and the 48-week study period. The secondary outcome was whether there were treatment interruptions lasting at least 48 h.\n In intention-to-treat analysis, 53% of participants receiving weekly SMS reminders achieved adherence of at least 90% during the 48 weeks of the study, compared with 40% of participants in the control group (P = 0.03). Participants in groups receiving weekly reminders were also significantly less likely to experience treatment interruptions exceeding 48 h during the 48-week follow-up period than participants in the control group (81 vs. 90%, P = 0.03).\n These results suggest that SMS reminders may be an important tool to achieve optimal treatment response in resource-limited settings.", "Despite its effectiveness as a method of controlling cervical carcinoma, the use of Pap smear testing remains incomplete, and its promotion in the primary care setting provides an important opportunity for intervention.\n The authors conducted a randomized controlled trial that involved three sites of a health maintenance organization (HMO) serving an urban minority population. Their aim was to evaluate the impact of reminders given to patients and physicians on site visitation by patients and Pap smear use. Eligible women (n=5801) were randomly assigned to 1 of 4 intervention combinations (in which reminders were given to either the patient or the physician, to both, or to neither). If they were ineligible for patient reminder intervention, patients were randomized only to physician reminder intervention (the presence or absence of it). The letter of reminder mailed to the patient invited women due for Pap smears to visit the HMO site, and the reminder for physicians was a medical record notice that a Pap smear was due. Logistic and survival analyses were used to investigate the correlation of intervention status with visitation, interval of time to a visit, and Pap smear use.\n In the primary intent-to-treat analysis, there was no significant effect of either patient or physician reminder interventions on rates of visitation or Pap smear completion. The secondary efficacy analyses demonstrated no overall effect of either patient or physician reminders, but effects among subgroups of women at individual HMO sites were noted. At Site 3, there was an apparent increase in time to the next visit among the subgroup of women with a chronic illness (16 weeks with intervention vs. 9 weeks without). With the physician reminder, the odds that a Pap smear would be given during the study year were increased among women without a previous Pap smear at Site 1 (adjusted odds ratio=1.39) and those with a chronic illness at Site 2 (adjusted odds ratio=3.38).\n Reminders given to patients and physicians had a limited impact on visitation by patients to the HMO sites or Pap smear completion. Although some subgroups of women may benefit, the authors also observed a possibly unfavorable impact among other subgroups. These results emphasize the importance of identifying more effective interventions, targeting them to women most likely to benefit, and not overlooking the possibility that preventive intervention will have an unanticipated adverse effect.", "Since 1991, hospitals have asked patients whether they have advance directives, but few patients complete these documents. We assessed two simple interventions to improve completion of advance directives among elderly or chronically ill outpatients.\n We conducted a cluster randomized controlled trial involving 1079 patients from five general medicine clinics that were affiliated with an academic medical center. Patients were either > or =70 years of age or > or =50 years old with a chronic illness. The study comprised three arms: physician reminders recommending documentation of advance directives, physician reminders plus mailing advance directives to patients together with educational literature, or neither intervention (control). The main outcome measure was completion of an advance directive.\n After 28 weeks, 1.5% (5/332) of patients in the physician reminder group, 14% (38/277) in the physician reminder plus patient mailing group, and 1.8% (5/286) in the control group had completed advance directives. In multivariate analyses, patients in the physician reminder plus patient mailing group were much more likely than controls to have completed advance directives (odds ratio [OR] = 5.9; 95% confidence interval [CI]: 1.5 to 22), whereas patients in the physician reminder-only group were no more likely than controls to have completed advance directives (OR = 0.88; 95% CI: 0.21 to 3.7).\n Mailing health care proxy and living will forms and literature to patients before an appointment at which their physicians received a reminder about advance directives yielded a small but significant improvement in completion of these documents. A physician reminder alone did not have an effect.", "To test the effectiveness of customized, family-oriented reminder letters in activating patients to seek appropriate preventive services.\n Randomized clinical trial. One group received computer-generated, customized letters explaining recommended preventive procedures for each family member. A second group received a form letter listing recommendations for all preventive procedures for all age and sex groups. A third group (control group) received no letters.\n A private medical centre, without university affiliation, in rural Quebec.\n From 8770 patients who met study criteria, 719 families were randomly selected. Data were available for 1971 of 1998 patients in these families.\n The Family Received Index is the proportion of all procedures for which a family was overdue that they received. The Family End-of-study Up-to-date Index is the proportion of procedures for which the family was eligible and for which they were up-to-date at the end of the study.\n The Family Received Index for families mailed customized letters was more than double the index for patients not mailed letters (Kruskal-Wallis P = .0139). Comparison of the Family End-of-study Up-to-date indices also demonstrated that families of patients sent customized letters were more likely to be up-to-date than families not sent letters (Kruskal-Wallis P = .0054). No statistically significant difference appeared between the number of preventive measures received by the control group and the form-letter group.\n This study demonstrates a clinically small but statistically significant value to customizing reminder letters.", "to determine the efficacy and effectiveness of training to improve primary care providers' patient-centered communication skills and proficiency in discussing their patients' health risks.\n twenty-eight primary care providers participated in a baseline simulated patient interaction and were subsequently randomized into intervention and control groups. Intervention providers participated in training focused on patient-centered communication about behavioral risk factors. Immediate efficacy of training was evaluated by comparing the two groups. Over the next 3 years, all providers participated in two more sets of interactions with patients. Longer term effectiveness was assessed using the interaction data collected at 6 and 18 months post-training.\n The intervention providers significantly improved in patient-centered communication and communication proficiencies immediately post-training and at both follow-up time points.\n this study suggests that the brief training produced significant and large differences in the intervention group providers which persisted 2 years after the training.\n the results of this study suggest that primary care providers can be trained to achieve and maintain gains in patient-centered communication, communication skills and discussion of adverse childhood events as root causes of chronic disease.\n 2010 Elsevier Ireland Ltd. All rights reserved.", "This study assessed the impact of automated telephone reminders in a population of 2,008 patients scheduled for appointments in a public health tuberculosis clinic. Overall, remainders increased appointment attendance from 52% to 62%. Reminders were more effective for some applications than others, but the effectiveness of reminders did not differ significantly across patient age, sex, or ethnicity. Counter to theoretical predictions, neither attribution of the reminder message to an authority nor a statement stressing the importance of the appointment significantly increased the effectiveness of the reminder above the level obtained without these enhancements.", "Computerized reminder systems have been shown to be effective in improving physician compliance with preventive services guidelines. Very little has been published about the use of computerized reminders for preventive care in diabetes. We implemented a computer-generated reminder system for diabetes care guidelines in a randomized controlled study in the outpatient clinics of 35 internal medicine residents at the University of Utah and Salt Lake Veterans Affairs Hospitals. After a six month study period, compliance with the recommended care significantly improved in both the intervention group that received patient-specific reminders about the guidelines (38.0% at baseline, 54.9% at follow-up) and the control group that received a nonspecific report (34.6% at baseline, 51.0% at follow-up). There was no significant difference between the two groups. Both clinic sites showed similar improvement over baseline levels of compliance. Residents who completed encounter forms used by the system showed a significantly greater improvement in compliance than those who did not complete encounter forms (19.7% vs. 7.6%, p = 0.006). The improvements in guideline compliance were seen in all areas of diabetes preventive care studied, and significant improvements were seen with recommended items from the medical history, physical exam, laboratory testing, referrals, and patient education. The use of encounter forms by the providers significantly improved documented compliance with the guidelines in almost all categories of preventive care. These results suggest that computerized reminder systems improve compliance with recommended care more by facilitating the documentation of clinical findings and the ordering of recommended procedures than by providing the clinician with patient-specific information about guideline compliance status. Further study is needed to understand the implications of these findings to the development of future computerized reminder systems for chronic diseases such as diabetes.", "Medical record audits have been used to provide physicians with feedback about their compliance with preventive health and disease management recommendations.\n To determine if report cards summarizing medicine residents' preventive health and disease management practices can be used as a feedback tool to improve practice performance.\n Randomized, blinded, controlled study of 44 internal medicine residents using an individualized 78-item report card based on outpatient record audits.\n Four hundred ninety-seven charts were retrospectively audited at baseline and 284 charts in follow-up. There were no significant differences in baseline performance between the residents in the intervention and control group. There were no differences in performance scores between residents receiving report cards and those who had not in immunizations, counseling, total preventive health, diabetes, hypertension, and total disease management.\n Intensive data-based feedback using report cards may not be a successful way to improve ambulatory performance of medical house officers.", "Active involvement of patients in medical encounters has been associated with several desirable outcomes, including greater satisfaction, increased adherence to treatment, and positive treatment outcomes. Older patients, particularly the very old and less well educated, are more likely to place physicians in a dominant role and themselves in a submissive role. Intervention trials to increase patient involvement have shown positive results. Activation interventions with older patients to increase a sense of control and self-efficacy are promising. Most of the attention to improving doctor-patient interaction has been directed toward physicians. The results of these few intervention trials support increased attention to patient behaviors.", "Patient education is considered an important component of primary care medicine. The traditional methods of patient education have been physician-patient dialogue and printed handouts. This study compares the relative efficacy of pamphlets, one-to-one dialogue, and audiovisual presentations. The results indicate that the slide and sound presentation was most effective in conveying patient information.", "Few primary care physicians routinely counsel for exercise, despite the benefits of physical activity and the high prevalence of inactivity. The objective of this study is to assess the effectiveness of Physician-Based Assessment and Counseling for Exercise (PACE), a brief, behavior-based tool for primary care providers counseling healthy adults.\n This study is a randomized controlled trial of 812 patients age 30 years or older registered for well visits at 32 primary care physician offices at a staff model health maintenance organization. Intervention physicians were trained to deliver PACE exercise counseling protocols at the index visit, and one reminder telephone call occurred at 1 month. An enhanced intervention group received additional activity reminders.\n At the 6-month follow-up, the control group did not differ significantly from the intervention group for energy expended (2,048 kcal/week versus 2,108 kcal/ week, P = 0.77), time spent in walking or other moderate to vigorous activities (202 min/week versus 187 min/ week, P = 0.99), mental health, physical function, or behaviors previously shown to predict activity change. Among the intervention patients, the stages-of-change score for Contemplators increased significantly compared with controls (P = 0.03), but without a significant change in energy expended. Baseline levels of physical activity counseling were high (50%), as were baseline patient physical activity levels (61% exercised at least three times a week).\n These results suggest that a one-time PACE counseling session with minimal reinforcement, in a setting with high baseline levels of activity, does not further increase activity. The finding that Contemplators advanced in stage of behavior change suggests that further studies are needed to examine long-term, repeated counseling interventions." ]	Personalized postcards or phone calls are effective, and home visits, and facilitators, may be effective. Reminders to physicians are not. There is insufficient good evidence for other interventions.
CD009622	[ "16340187", "6127747", "6149738", "8625628" ]	[ "Diazepam to improve acute stroke outcome: results of the early GABA-Ergic activation study in stroke trial. a randomized double-blind placebo-controlled trial.", "Prophylactic effect of neuroleptics in symptom-free schizophrenics.", "Ketazolam treatment for spasticity: double-blind study of a new drug.", "Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial." ]	[ "We tested whether diazepam, a GABA-ergic drug that also inhibits brain nitric monoxide formation, improves acute stroke prognosis.\n 880 patients, randomized within 12 h of acute stroke, received diazepam 10 mg or placebo by rectiole, as soon as possible, followed by 10-mg tablets twice daily for 3 days. Primary outcome was independence (Rankin score <3) at 3 months; secondary outcome was complete recovery (Barthel index >or=95 or Rankin score <or=1).\n Intention-to-treat analyses on all 849 patients with full follow-up (50.4% on diazepam): odds ratio (OR) 1.14, 95% CI 0.87-1.49 for primary endpoint, and an OR of 1.26 (0.90-1.76) for complete recovery, both favoring diazepam. Adjusted analyses for all stroke patients (843): OR 1.20 (0.87-1.65), and 1.25 (0.89-1.74), respectively, and for all infarct patients (748): OR 1.31 (0.93-1.85), and 1.46 (1.02-2.09; p=0.037), respectively. Analyses restricted to cardioembolic infarct patients (200) showed treatment benefit for the primary outcome: OR 2.26, 95% CI 1.07-4.76, p=0.032, and complete recovery: OR 2.65, 95% CI 1.06-6.59, p=0.037. About one third of ischemic stroke patients had 'any adverse event', without any difference between treatment groups. In 95 intracerebral hemorrhage patients, frequency of pneumonia and death were higher in the diazepam group than in the placebo group: 35 and 10%, 22 and 12%, respectively.\n Although point estimates favored diazepam treatment in various analyses, our data did not confirm our primary hypothesis. Diazepam treatment seems beneficial in cardioembolic infarct patients, is safe in acute ischemic stroke, but may better be avoided in intracerebral hemorrhage.\n Copyright (c) 2006 S. Karger AG, Basel.", "Prophylactic effects of psychotropic drugs on 55 schizophrenics in remission were evaluated for 3 years in a double-blind controlled study employing a cross-over design. Patients were randomly assigned to the following drugs orally administered twice a day: placebo; diazepam 15 mg; imipramine 50 mg; chlorpromazine 75 mg; and haloperidol 3 mg. The number of days of remission for each patient was recorded. Since only two patients received all five drug treatments, the data were analyzed using the number of days allocated to the \"first assigned drugs\" only and the cross-over aspect of the experimental design was disregarded. All patients treated with either the placebo, diazepam or imipramine relapsed within a year. On the other hand, four patients treated with chlorpromazine, or with haloperidol, were in remission for more than 1 year. Fifty percent of the patients relapsed within 16 days with placebo; 88 days with diazepam; 30 days with imipramine; 165 days with chlorpromazine; and 74 days with haloperidol. Within a year, only chlorpromazine significantly prolonged the remission state as compared to placebo and imipramine. At the end of the 3-year trial, both chlorpromazine and haloperidol significantly prolonged the remission state as compared to the other three drugs. These data suggest that neuroleptic treatment for a longer period is vitally important to prevent relapse even in schizophrenics in remission and that such a trial seems an efficient method for investigating the prophylactic effects of neuroleptics.", "A minor tranquilizer, ketazolam, was tested in a double-blind, randomized, crossover study of 50 patients for its effects in neurologic spasticity. The drug was compared with diazepam (widely accepted as an effective antispasticity agent) and a placebo. The patients with spasticity were almost all cases of multiple sclerosis (24) or stroke (24). Thirty-nine patients completed the study. There was not statistically significant superiority of either diazepam or ketazolam, but both relieved symptoms significantly better than the placebo, as measured clinically and by electromyographic recording of deep tendon reflexes. Ketazolam is a relatively safe and clinically effective antispasticity agent (especially for patients with multiple sclerosis). The well-known \"big 3\"--dantrolene sodium, baclofen, and diazepam--produce large and small problems in many individual cases; hence, ketazolam now offers a safe and clinically useful alternative.", "To assess the effect of three different alcohol withdrawal therapy regimens in traumatized chronic alcoholic patients with respect to the duration of mechanical ventilation and the frequency of pneumonia and cardiac disorders during their intensive care unit (ICU) stay.\n A prospective, randomized, blinded, controlled clinical trial.\n A university hospital ICU.\n Multiple-injured alcohol-dependent patients (n=180) transferred to the ICU after admission to the emergency room and operative management. A total of 180 patients were included in the study; however, 21 patients were excluded from the study after assignment.\n Patients who developed actual alcohol withdrawal syndrome were randomized to one of the following treatment regimens: flunitrazepam/clonidine (n=54); chlormethiazole/haloperidol (n=50); or flunitrazepam/haloperidol (n=55). The need for administration of medication was determined, using a validated measure of the severity of alcohol withdrawal (Revised Clinical Institute Withdrawal Assessment for Alcohol Scale).\n The duration of mechanical ventilation and major intercurrent complications, such as pneumonia, sepsis, cardiac disorders, bleeding disorders, and death, were documented. Patients did not differ significantly between groups regarding age, Revised Trauma and Injury Severity Score and Acute Physiology and Chronic Health Evaluation II score on admission. In all except four patients in the flunitrazepam/clonidine group, who continued to hallucinate, the Revised Clinical Institute Withdrawal Assessment for Alcohol Scale decreased to <20 after initiation of therapy. ICU stay did not significantly differ between groups (p=.1669). However, mechanical ventilation was significantly prolonged in the chlormethiazole/haloperidol group (p=.0315) due to an increased frequency of pneumonia (p=.0414). Cardiac complications were significantly (p=.0047) increased in the flunitrazepam/clonidine group.\n There was some advantage in the flunitrazepam/clonidine regimen with respect to pneumonia and the necessity for mechanical ventilation. However, four (7%) patients had to be excluded from the study due to ongoing hallucinations during therapy. Also, cardiac complications were increased in this group. Thus, flunitrazepam/haloperidol should be preferred in patients with cardiac or pulmonary risk. Further studies are required to determine which therapy should be considered." ]	This review does not provide the evidence to support the use of GABA receptor agonists (chlormethiazole or diazepam) for the treatment of patients with acute ischemic or hemorrhagic stroke. Chlormethiazole appeared to be beneficial in improving functional independence in patients with TACS according to the subgroup analysis, but this result must be interpreted with great caution. More well-designed RCTs with large samples of TACS would be required for further confirmation. However, somnolence and rhinitis are frequent adverse events related to chlormethiazole.
CD006061	[ "10983198", "12197996", "12600852", "15531671", "11976158", "17100860", "20851308", "14633807", "20087379", "9648703", "10889804" ]	[ "A prospective study of whole-grain intake and risk of type 2 diabetes mellitus in US women.", "Whole-grain intake and the risk of type 2 diabetes: a prospective study in men.", "Whole-grain and fiber intake and the incidence of type 2 diabetes.", "Changes in whole-grain, bran, and cereal fiber consumption in relation to 8-y weight gain among men.", "Effect of whole grains on insulin sensitivity in overweight hyperinsulinemic adults.", "An educational programme for peer review groups to improve treatment of chronic heart failure and diabetes mellitus type 2 in general practice.", "Randomized, controlled trial promotes physical activity and reduces consumption of sweets and sodium among overweight and obese adults.", "The Finnish Diabetes Prevention Study (DPS): Lifestyle intervention and 3-year results on diet and physical activity.", "Effects of controlled school-based multi-component model of nutrition and lifestyle interventions on behavior modification, anthropometry and metabolic risk profile of urban Asian Indian adolescents in North India.", "The effects of monosodium glutamate in adults with asthma who perceive themselves to be monosodium glutamate-intolerant.", "The Finnish Diabetes Prevention Study." ]	[ "This study examined the association between intake of whole vs refined grain and the risk of type 2 diabetes mellitus.\n We used a food frequency questionnaire for repeated dietary assessments to prospectively evaluate the relation between whole-grain intake and the risk of diabetes mellitus in a cohort of 75,521 women aged 38 to 63 years without a previous diagnosis of diabetes or cardiovascular disease in 1984.\n During the 10-year follow-up, we confirmed 1879 incident cases of diabetes mellitus. When the highest and the lowest quintiles of intake were compared, the age and energy-adjusted relative risks were 0.62 (95% confidence interval [CI] = 0.53, 0.71, P trend < .0001) for whole grain, 1.31 (95% CI = 1.12, 1.53, P trend = .0003) for refined grain, and 1.57 (95% CI = 1.36, 1.82, P trend < .0001) for the ratio of refined- to whole-grain intake. These findings remained significant in multivariate analyses. The findings were most evident for women with a body mass index greater than 25 and were not entirely explained by dietary fiber, magnesium, and vitamin E.\n These findings suggest that substituting whole- for refined-grain products may decrease the risk of diabetes mellitus.", "Certain dietary components may play a role in the prevention of type 2 diabetes.\n We examined prospectively the associations between whole- and refined-grain intake and the risk of type 2 diabetes in a large cohort of men.\n Men from the Health Professionals Follow-up Study without a history of diabetes or cardiovascular disease in 1986 (n = 42898) were followed for </=12 y. Intakes of whole and refined grains, measured every 4 y by use of food-frequency questionnaires, were used to predict subsequent type 2 diabetes risk through multivariate analysis.\n We ascertained 1197 cases of incident type 2 diabetes. After adjustment for age; physical activity; cigarette smoking; alcohol consumption; family history of diabetes; and fruit, vegetable, and energy intakes, the relative risk of type 2 diabetes was 0.58 (95% CI: 0.47, 0.70; P for trend < 0.0001) comparing the highest with the lowest quintile of whole-grain intake. The association was moderately attenuated when additionally adjusted for body mass index (relative risk: 0.70; 95% CI: 0.57, 0.85; P for trend = 0.0006). Intake of refined grains was not significantly associated with risk of type 2 diabetes. After further adjustment for magnesium intake, cereal fiber intake, and glycemic load, the association between whole grains and type 2 diabetes was attenuated and the trend no longer significant.\n In men, a diet high in whole grains is associated with a reduced risk of type 2 diabetes in men that may be mediated by cereal fiber. Efforts should be made to replace refined-grain with whole-grain foods.", "Epidemiologic evidence of a preventive effect of whole grain against type 2 diabetes is mainly based on data from women. Information specific to men and women is needed.\n The objective was to study the relation between the intake of whole grain and fiber and the subsequent incidence of type 2 diabetes.\n The design was a cohort study of 2286 men and 2030 women aged 40-69 y and initially free of diabetes. Food consumption data were collected from 1966 through 1972 with the use of a dietary history interview covering the habitual diet during the previous year. During a 10-y follow-up, incident type 2 diabetes cases were identified in 54 men and 102 women from a nationwide register.\n Whole-grain consumption was associated with a reduced risk of type 2 diabetes. The relative risk (adjusted for age, sex, geographic area, smoking status, body mass index, energy intake, and intakes of vegetables, fruit, and berries) between the highest and lowest quartiles of whole-grain consumption was 0.65 (95% CI: 0.36, 1.18; P for trend = 0.02). Cereal fiber intake was also associated with a reduced risk of type 2 diabetes. The relative risk between the extreme quartiles of cereal fiber intake was 0.39 (95% CI: 0.20, 0.77; P = 0.01).\n An inverse association between whole-grain intake and the risk of type 2 diabetes was found. The similar result for cereal fiber intake suggests that the whole-grain association is due to cereal fiber or another factor related to cereal fiber intake.", "Epidemiologic studies that directly examine changes in whole-grain consumption in relation to weight gain are sparse, and characterization of this association has been obscured by methodologic inconsistencies in the assessment of whole grains.\n We aimed to ascertain the associations between changes in new quantitative estimates of whole-grain intake and 8-y weight gain among US men.\n The study was conducted in a prospective cohort of 27 082 men aged 40-75 y at baseline in 1986. Data on lifestyle factors were obtained periodically by using self-reported questionnaires, and participants measured and reported their body weight in 1986 and 1994.\n In multivariate analyses, an increase in whole-grain intake was inversely associated with long-term weight gain (P for trend < 0.0001). A dose-response relation was observed, and for every 40-g/d increment in whole-grain intake from all foods, weight gain was reduced by 0.49 kg. Bran that was added to the diet or obtained from fortified-grain foods further reduced the risk of weight gain (P for trend = 0.01), and, for every 20 g/d increase in intake, weight gain was reduced by 0.36 kg. Changes in cereal and fruit fiber were inversely related to weight gain. No associations were observed between changes in refined-grain or added germ consumption and body weight.\n The increased consumption of whole grains was inversely related to weight gain, and the associations persisted after changes in added bran or fiber intakes were accounted for. This suggests that additional components in whole grains may contribute to favorable metabolic alterations that may reduce long-term weight gain.", "Epidemiologic studies have found whole-grain intake to be inversely associated with the risk of type 2 diabetes and heart disease.\n We tested the hypothesis that whole-grain consumption improves insulin sensitivity in overweight and obese adults.\n This controlled experiment compared insulin sensitivity between diets (55% carbohydrate, 30% fat) including 6-10 servings/d of breakfast cereal, bread, rice, pasta, muffins, cookies, and snacks of either whole or refined grains. Total energy needs were estimated to maintain body weight. Eleven overweight or obese [body mass index (in kg/m(2)): 27-36] hyperinsulinemic adults aged 25-56 y participated in a randomized crossover design. At the end of each 6-wk diet period, the subjects consumed 355 mL (12 oz) of a liquid mixed meal, and blood samples were taken over 2 h. The next day a euglycemic hyperinsulinemic clamp test was administered.\n Fasting insulin was 10% lower during consumption of the whole-grain than during consumption of the refined-grain diet (mean difference: -15 +/- 5.5 pmol/L; P = 0.03). After the whole-grain diet, the area under the 2-h insulin curve tended to be lower (-8832 pmol.min/L; 95% CI: -18720, 1062) than after the refined-grain diet. The rate of glucose infusion during the final 30 min of the clamp test was higher after the whole-grain diet (0.07 x 10(-4) mmol.kg(-1).min(-1) per pmol/L; 95% CI: 0.003 x 10(-4), 0.144 x 10(-4)).\n Insulin sensitivity may be an important mechanism whereby whole-grain foods reduce the risk of type 2 diabetes and heart disease.", "Peer review groups are considered helpful for quality improvement in primary care. An interactive educational programme for small peer groups was developed, focusing on the implementation of newly developed treatment guidelines. The aim is to evaluate the effect of the programme on adherence to treatment guidelines in general practice.\n A cluster randomized trial using a balanced incomplete block design was used; one arm received a programme on treatment of chronic heart failure (CHF), the other on hypertension treatment in diabetes mellitus type 2 (T2DM). A random sample of 10 CHF and 10 T2DM patients per GP was drawn, for whom data were extracted from electronic patient records 1 years before and 6 months after the intervention. The outcomes were prescribing of ACE inhibitors, and antihypertensive treatment in T2DM. The effect was analysed separately for both programmes using multilevel regression models.\n All 27 peer review groups in one region in the Netherlands were randomized, of which 16 participated. No significant effects were observed in the CHF group or in the T2DM group. The opportunity for change was limited, as only 53% of the CHF patients and 60% of the T2DM patients had a contact with their GP between the intervention and follow-up measurement.\n The peer review programme was not successful for changing the treatment of chronic patients, although the programme focused on dealing with barriers perceived by the participants. Not all problems perceived can be solved in a peer group discussion.", "The present study sought to assess the impact of an intervention to reduce weight and control risk factors of noncommunicable chronic diseases in overweight or obese adults who are users of primary and secondary healthcare units of the public health system of Pelotas, Brazil. We hypothesized that individuals who received an educational intervention regarding how to lose weight and prevent other noncommunicable chronic disease risk factors through nutrition would lose weight and acquire active habits during leisure time more frequently than individuals under regular care. Two hundred forty-one participants from the Nutrition Outpatient Clinic of the Medical Teaching Hospital of the Federal University of Pelotas, Brazil, aged 20 years or older and classified as overweight or obese were randomly allocated to either the intervention group (IG; n = 120) or control group (CG; n = 121). The IG received individualized nutritional care for 6 months, and the CG received individualized usual care of the health services. Intention-to-treat analyses showed that at 6 months, mean fasting glycemia and daily consumption of sweet foods and sodium were reduced, and the time spent on physical leisure activity was increased in IG. Analysis of adherence to the protocol of the study revealed that individuals from IG had lost more in body weight, waist circumference, and fasting glucose compared to the CG. Leisure time physical activity increased in IG. Individuals adhered equally to the dietetic recommendations, irrespective of the nutrition approach that was used.\n Copyright © 2010 Elsevier Inc. All rights reserved.", "To describe the 1) lifestyle intervention used in the Finnish Diabetes Prevention Study, 2) short- and long-term changes in diet and exercise behavior, and 3) effect of the intervention on glucose and lipid metabolism.\n There were 522 middle-aged, overweight subjects with impaired glucose tolerance who were randomized to either a usual care control group or an intensive lifestyle intervention group. The control group received general dietary and exercise advice at baseline and had an annual physician's examination. The subjects in the intervention group received additional individualized dietary counseling from a nutritionist. They were also offered circuit-type resistance training sessions and advised to increase overall physical activity. The intervention was the most intensive during the first year, followed by a maintenance period. The intervention goals were to reduce body weight, reduce dietary and saturated fat, and increase physical activity and dietary fiber.\n The intervention group showed significantly greater improvement in each intervention goal. After 1 and 3 years, weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control group, respectively. Measures of glycemia and lipemia improved more in the intervention group.\n The intensive lifestyle intervention produced long-term beneficial changes in diet, physical activity, and clinical and biochemical parameters and reduced diabetes risk. This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system.", "To study the effectiveness of a multi-component intervention model of nutrition and lifestyle education on behavior modification, anthropometry and metabolic risk profile of urban Asian-Indian adolescents in North India.\n Two schools matched for student strength and middle socioeconomic strata were randomly allocated to intervention and control group. Changes in nutrition-related knowledge, attitude, lifestyle practices, food frequency and body image of eleventh-grade students (15-17 years) in both schools were tested using a validated questionnaire. Anthropometric and biochemical measurements were made using standard methods. Segmental body composition analysis was carried out using an 8-electrode multifrequency bioelectrical impedance method of body fat estimation.\n At 6 months follow-up, significant improvement in several domains of knowledge was observed in intervention children (n=99; males=60; females=39) as compared with control school children (n=102; males=61; females=41). In the intervention group, significantly lower proportion of children consumed aerated drinks (15.1%; P<0.001) and energy-dense unhealthy foods (8.9%; P=0.03), whereas significantly higher proportion brought tiffin (packed lunch) to school (14.9%; P=0.004) and brought a fruit in their tiffin (30.7%; P<0.001) as compared with the control group. Significant decrease in mean waist circumference (P=0.02, 95% confidence interval (CI)=-2.43,-0.17), sagittal abdominal diameter (P<0.001, 95% CI=-0.82,-0.09), waist-to-hip ratio (P=0.02, 95% CI=-0.03,-0.004) and fasting blood glucose (P=0.05, 95% CI=-0.09, 5.00) was seen in intervention as compared with control school children.\n Multi-component model of nutrition and lifestyle education was successful in improving the nutrition-related knowledge, eating habits and lifestyle practices, and resulted in beneficial changes in anthropometric and biochemical profiles of the Asian Indian adolescents. This model should be applied on countrywide basis to prevent obesity and diabetes.", "Many previous clinical studies of food-induced asthma suffer from inadequate baseline or control data. A statistically valid, randomized, double-blind, placebo-controlled, monosodium glutamate (MSG)-challenge protocol was developed for identifying early and late asthmatic reactions in an individual.\n We sought to determine whether MSG would induce bronchoconstriction in a group of adults with asthma who perceived that they were MSG sensitive.\n Twelve subjects (seven women, mean age 35.3 years) with clinically documented asthma and a perception of MSG-induced asthma were recruited. FEV1 and peak expiratory flow data were obtained for 3 whole control days, as well as time-matched data for 3 separate challenge days (1 gm MSG, 5 gm MSG, and 5 gm lactose [placebo]). Opaque capsule challenges were given as a single dose in the morning after an overnight fast. Subjects complied with an elimination diet throughout the study. Nonspecific bronchial hyperresponsiveness was measured at baseline, after the control days, and at the conclusion of the challenges. Venous blood samples were taken at baseline and on each challenge day to determine soluble inflammatory marker (eosinophil cationic protein and tryptase) activity.\n No immediate or definite late asthmatic reactions occurred. One subject's FEV1 declined more than 15% on MSG challenge, but 95% confidence limits for the control-day spirometry showed that this decline was within her daily variation, hence the challenge was deemed to be negative. No significant changes in bronchial hyperresponsiveness or soluble inflammatory markers were found.\n MSG-induced asthma was not demonstrated in this study. This study highlighted the importance of adequate baseline and control data and indicated that such a rigorous protocol for individual assessment is feasible.", "The aim of the Finnish Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying type 2 diabetes in individuals with impaired glucose tolerance (IGT) and to evaluate the effect of the programme on the risk factors of atherosclerotic vascular diseases and the incidence of cardiovascular events. In this ongoing study, a total of 523 overweight subjects with IGT based on two oral glucose tolerance tests were randomized to either an intervention group or a control group. The main measure in the intervention group is individual dietary advice aimed at reducing weight and intake of saturated fat and increasing intake of dietary fibre. The intervention subjects are individually guided to increase their level of physical activity. The control group receives general information about the benefits of weight reduction, physical activity and healthy diet in the prevention of diabetes. A pilot study began in 1993, and recruitment ended in 1998. By the end of April 1999 there were 65 new cases of diabetes, 34 drop-outs and one death. The weight reduction was greater (-4.6 kg) at 1 year in the intervention group (n = 152) than in the control group (n = 143, -0.9 kg, P < 0.0001), and this difference was sustained in the second year of follow-up. At 1 year 43.4% and at 2 years 41.8% of the intervention subjects had achieved a weight reduction of at least 5 kg, while the corresponding figures for the control subjects were 14.0 and 12.0% (P < 0.001 between the groups). At 1 year the intervention group showed significantly greater reductions in 2 h glucose, fasting and 2 h insulin, systolic and diastolic blood pressure, and serum triglycerides. Most of the beneficial changes in cardiovascular risk factors were sustained for 2 years. These interim results of the ongoing Finnish Diabetes Prevention Study demonstrate the efficacy and feasibility of the lifestyle intervention programme." ]	The evidence from only prospective cohort trials is considered to be too weak to be able to draw a definite conclusion about the preventive effect of whole grain foods on the development of T2DM. Properly designed long-term randomised controlled trials are needed. To facilitate this, further mechanistic research should focus on finding a set of relevant intermediate endpoints for T2DM and on identifying genetic subgroups of the population at risk that are most susceptible to dietary intervention.
CD004347	[ "9754744" ]	[ "Survival of three types of veneer restorations in a clinical trial: a 2.5-year interim evaluation." ]	[ "In this clinical trial, 180 veneer restorations (VRs) were evaluated. The purpose of the study was to collect survival data and to find possible relations between survival and (1) 'type of VR', (2) 'preparation design', (3) 'operator' and (4) the patient-related variables 'tooth-type' and 'vitality of the tooth'.\n The restorations were provided by seven dentists in 1 12 patients on central and lateral maxillary incisors. Experimental variables were: 'type of VR' (either direct resin composite (DC), indirect resin composite (IC) or porcelain (P)), 'preparation design' (with and without incisal overlap) and 'operator'. Failures were recorded at two levels: absolute failure (need for new restoration) and relative failure (need for repair). Survival was defined at three levels: (1) survival of original restoration (Sr, endpoints: 'absolute' failures), (2) functional survival (Sf, endpoints: 'relative' failures) and (3) overall survival (SO, endpoints: both 'absolute-' and 'relative failures').\n The variable 'type of VR' showed significant influence on Sf and So but not on Sr. Sf and So rates of P, IC and DC were, respectively: Sf-P, 94%; So-P, 94%; Sf-IC, 94%; So-IC, 90%; Sf-DC, 80%; So-DC, 74%. VRs on vital teeth showed a significantly better survival than VRs on non-vital teeth at all survival levels.\n Preparation of the incisal edge for incisal coverage is considered to be unnecessary to assure or improve the strength of VRs. Veneers on non-vital teeth showed higher risk to fail than veneers placed on vital teeth. Porcelain veneers showed the best overall survival." ]	There is no reliable evidence to show a benefit of one type of veneer restoration (direct or indirect) over the other with regard to the longevity of the restoration.
CD002765	[ "11149033", "9972405", "11913801", "12607659", "2571469", "9489309", "11132739", "11803323", "17130328", "1616156", "11575284", "7753141", "8988832", "16159043", "15839218", "11190708", "9609409", "12000983", "7588670", "7514506", "17678776", "2404429" ]	[ "Perioperative renal protection in patients with obstructive jaundice using drug combinations.", "Tenoxicam does not alter renal function during anaesthesia in normal individuals.", "The effects of fenoldopam on renal function in patients undergoing elective aortic surgery.", "Pain treatment with a COX-2 inhibitor after coronary artery bypass operation: a randomized trial.", "The use of anxiolytic and parasympathomimetic agents in the treatment of postoperative urinary retention following anorectal surgery. A prospective, randomized, double-blind study.", "[Does the preoperative administration of ketorolac improve postoperative analgesia].", "Non-steroidal anti-inflammatory drugs in treatment of postoperative pain after cardiac surgery.", "Renal dose dopamine in open heart surgery. Does it protect renal tubular function?", "Minor infection encouraged by steroid administration during cardiac surgery.", "Mechanisms of renal hemodynamic impairment during infrarenal aortic cross-clamping.", "Selective postoperative inhibition of gastrointestinal opioid receptors.", "Effect of a prior-authorization requirement on the use of nonsteroidal antiinflammatory drugs by Medicaid patients.", "Dose-response of flurbiprofen on postoperative pain and emesis after paediatric strabismus surgery.", "A group randomized trial to improve safe use of nonsteroidal anti-inflammatory drugs.", "[Effect of nonsteroidal anti-inflammatory drugs and paracetamol on hemodynamic changes during postoperative analgesia in children].", "Effect of pre-emptive hydromorphone administration on postoperative pain relief--a randomized controlled trial.", "Ibuprofen does not impair renal function in patients undergoing infrarenal aortic surgery with epidural anaesthesia.", "Role of dopamine in renal dysfunction during laparoscopic surgery.", "Peri-operative administration of rectal diclofenac sodium. The effect on renal function in patients undergoing minor orthopaedic surgery.", "Hydromorphone patient-controlled analgesia (PCA) after coronary artery bypass surgery.", "Comparison of the modulatory effects of four different fast-track anesthetic techniques on the inflammatory response to cardiac surgery with cardiopulmonary bypass.", "Effect of angiotensin converting enzyme inhibition on blood pressure and renal function during open heart surgery." ]	[ "The effectiveness of dopamine alone or in combination with mannitol or furosemide in preventing postoperative renal dysfunction in patients with obstructive jaundice was assessed in this study.\n Forty patients having obstructive jaundice were randomly allocated into 4 equal groups. Preoperative hydration was performed by infusing all patients 1L of 5% dextrose the night before surgery and another 1L in the morning before surgery. Intra- and postoperative maintenance of adequate intravascular volume was assured by fluid and blood replacement guided by the monitoring of central venous pressure urine output and blood pressure. The 1st group was kept as a control. The other 3 groups received dopamine 2.5 micrograms/kg/min for 2 postoperative days starting before surgery. The 2nd group was maintained on dopamine alone, while mannitol (0.25 g/kg), every 12 hours for 2 postoperative days, was added to the 3rd group. Similarly furosemide (1 mg/kg) every 12 hours for 2 postoperative days, was infused to the patients of the 4th group. Postoperative renal functions were assessed by 24-hour urine output, serum creatinine, creatinine clearance and urine to plasma osmolality ratio.\n All these tests did not show significant changes in the 1st, 2nd and 7th postoperative days. Only transient decreased creatinine clearance and elevated serum creatinine were observed in the patients of the 4th group in the 1st and 2nd postoperative days. This may be attributed to fluid imbalance induced by furosemide in these patients who were older than the other groups.\n The study showed that careful attention to perioperative hydration is the cornerstone in preserving adequate renal function following surgery in patients with obstructive jaundice. Administration of dopamine alone or in combination with mannitol or furosemide did not confer more renal protection.", "Anaesthesia and surgery alter renal function. Inhibition of prostaglandin synthesis by non-steroidal anti-inflammatory drugs (NSAIDs) administered with anaesthesia may further compromise renal function.\n To study the effects of tenoxicam (NSAID) administered immediately prior to anaesthesia on renal function in normal individuals undergoing routine surgery.\n A randomised single blind placebo controlled study comparing tenoxicam (40 mg intravenously) with placebo was carried out in 20 healthy (ASA I) patients undergoing lower spinal surgery. Glomerular filtration rate (GFR) was determined by creatinine clearance and renal tubular function measured as osmolar and free water clearance.\n GFR fell by 60% at the end of surgery but returned to pre-operative values by six hours post-operatively. There was no difference between placebo or tenoxicam with regard to changes in GFR. Tubular function was not altered by tenoxicam.\n Current clinical practice of using NSAIDs for post-operative analgesia in low risk individuals appears to have no adverse effects on renal function.", "Postoperative renal impairment is a recognized complication of infrarenal aortic cross-clamping. Our hypothesis was that the renal vasodilating and natriuretic effects of fenoldopam mesylate, a selective dopamine (DA1) agonist, would preserve renal function in patients undergoing elective infrarenal aortic cross-clamping.\n A prospective, randomized, double blind controlled clinical trial was performed. Twenty-eight ASA II-III patients undergoing elective aortic surgery requiring infrarenal aortic cross-clamping were studied. According to random allocation, patients received either fenoldopam (0.1 microg kg(-1) min(-1)) or placebo intravenously prior to surgical skin incision until release of the aortic clamp. Plasma creatinine, creatinine clearance, urinary output, fractional excretion of sodium, and free water clearance were measured: (a) prior to admission to hospital; (b) during the period from insertion of the urinary catheter until application of the aortic cross-clamp; (c) during the period of aortic cross-clamping; (d) 0-4 h, and (e) 4-8 h after release of the clamp and on days 1, 2, 3, and 5 postoperatively.\n Fenoldopam (0.1 microg kg(-1)min(-1)) administration was not associated with haemodynamic instability. On application of the aortic cross-clamp creatinine clearance decreased significantly in the placebo (83 +/- 20 to 42 +/- 29 mL min(-1) (mean +/- SD)) (P < 0.01) but not in the fenoldopam group, and this decrease persisted for at least 8 h after release of the cross-clamp (83 +/- 20 to 54 +/- 33 mL min(-1) (mean +/- SD)) (P < 0.05). Plasma creatinine concentration increased significantly from baseline on the first postoperative day in the placebo group (87 +/- 12 to 103 +/- 28 micromolL(-1) (mean +/- SD)) (P < 0.01) but not in the fenoldopam group.\n These findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect during and after infrarenal aortic cross-clamping.", "Adequate analgesic medication is mandatory after cardiac operations. Cyclooxygenase-2 inhibitors represent a new therapeutic option, acting primarily on the response to inflammation.\n We compared a cyclooxygenase-2 inhibitor (etodolac) with two traditional drugs: a nonselective cyclooxygenase inhibitor (diclofenac) and a weak opioid (tramadol) on postoperative pain and renal function in patients undergoing coronary artery bypass operations. Sixty consecutive patients were randomized into three groups: (1) group A patients who received tramadol; (2) group B patients who received diclofenac; and (3) group C patients who received etodolac. For measurement of analgesic effect, the visual analogue scale was assessed up to postoperative day 4. Creatinine-clearance was determined before and at the end of study medication, and serum creatinine and urea were monitored daily for renal effects. Study medication was given on postoperative days 2 and 3. Side effects and additional pain medication were recorded.\n The visual analogue scale was lower in group C (p < 0.05) from postoperative days 2 to 4 and in group B (p < 0.05) from postoperative days 3 to 4 compared with group A. Amount of additional pain medication and incidence of side effects were significantly less in group C compared with group A. We observed a short-lasting elevation of serum creatinine and urea in groups B and C compared with group A (p < 0.05).\n At the doses analyzed, etodolac and diclofenac produced better postoperative pain relief with less side-effects than tramadol. A short-lasting impairment of renal function was found in patients treated with etodolac and diclofenac.", "Approximately 30 percent of patients undergoing anorectal surgery will develop acute urinary retention. The cause of this complication is poorly understood. Anxiety, anal distention, bladder distention as a result of vigorous hydration during surgery, and reflex inhibition of the urinary bladder detrusor muscle secondary to pain have been postulated as contributing factors. A four-armed prospective, double-blind, randomized trial was carried out to determine whether an anxiolytic agent (midazolam, 5 mg intramuscularly) and/or a parasympathomimetic agent (bethanechol, 10 mg subcutaneously) reduce the incidence of postoperative urinary retention following anorectal surgery. One hundred thirty-two patients (ages, 18 to 50 years), in acute urinary retention 6 to 12 hours following anorectal surgery, were enrolled. Sixty-nine percent of patients responded to bethanechol. Side effects were minimal. Midazolam alone had no effect on retention. Bethanechol and midazolam in combination resulted in less retention than midazolam and a placebo (P less than 0.05). Bethanechol alone was better than a placebo (P less than 0.002). Mean intraoperative intravenous fluid volume for the entire study group was 900 cc. Initial postoperative urinary volumes of patients who failed the treatment protocol were significantly higher than in those responding to bethanechol (mean of 527 cc vs. 241 cc, P less than 0.001). The use of an anxiolytic agent was not effective in the treatment of postoperative urinary retention. Bladder distention may increase the incidence of urinary retention. Bethanechol, in a dose of 10 mg subcutaneously, significantly lowered the incidence of postoperative urinary catheterization and should be considered as initial treatment of postoperative urinary retention following anorectal surgery.", "1) To verify the usefulness of ketorolac administration (30 mg i.v.) before a surgical operation in terms of postoperative analgesia improvement; 2) To evaluate the impact of preoperative ketorolac administration on perioperative renal function and on intraoperative water balance; 3) to evaluate the presence of adverse effect due to preoperative NSAID use.\n Prospective randomized trial.\n University surgical department.\n Forty adult patients undergoing major abdominal surgery, randomized in 2 groups: in group 1 ketorolac (30 mg i.v.) was administered immediately after the induction and, for postoperative analgesia, ketorolac (30 mg i.v.) was administered beginning at the time of skin closure; in group 2 no ketorolac was administered before the operation and postoperative treatment was the same. Buprenorphine (0.3 mg i.m.) was administered in case of unsatisfactory analgesia. Fluids infused and diuresis were measured intraoperatively. One, 6 and 24 hours after the end of operation pain was evaluated using pain intensity score and VAS. The day after the operation serum creatinine and urea were measured.\n No statistically significant differences were found between groups regarding fluids infused, intraoperative diuresis, postoperative pain, adverse effects and number of bleeding episodes. More than 50% of patients, in either groups, required opioids administration.\n Ketorolac (30 mg i.v.) administration before a major abdominal operation does not improve postoperative analgesia nor determines significant alterations in renal function or increase in the frequency of abnormal bleedings. Opiate administration is necessary in more than 50% of the patients to achieve adequate analgesia.", "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.", "This prospective, randomized study assessed the effect of dopamine on renal tubular function in patients who had coronary artery bypass grafting.\n Two groups of patients with normal preoperative renal function were randomly divided into a dopamine group (n=11), who received dopamine in a dose of 2 mg/kg x min, and a control group (n=11), who received no treatment. Dopamine infusion was initiated 24 hours before the operation and was continued for 48 hours postoperatively. Measurements of renal function obtained 2 days before the operation were considered preoperative and were repeated on the 1st, 3rd, and 7th postoperative days. Urinary excretion of b2-Microglobulin (b2-M), considered a sensitive means for diagnosing proximal tubular damage, was measured during the early (day 3) and late (day 7) postoperative period.\n There were no significant differences respect to the clearances of creatinine, osmotic, and free-water in the dopamine group compared with the control group (p>0.05). Urine microalbumin levels significantly increased on postoperative day 3 in both groups. During the early postoperative period, excretion of urine b2-M was significantly greater in the dopamine group than in the control group (p<0.05).\n Consequently, in patients with normal preoperative renal and cardiac function scheduled for elective coronary artery bypass grafting, renal dose dopamine infusion alone may not provide sufficient protection on tubular function and increases renal tubular injury during the early postoperative period.", "The aim of this study was to investigate whether steroid administration would increase the risk of postoperative infection. Sixty adults who underwent elective cardiac surgery under cardiopulmonary bypass were prospectively randomized into two groups. Thirty-one patients received hydrocortisone (50 mg x kg(-1)) before and after cardiopulmonary bypass, the other 29 served as controls. Various hemodynamic and pulmonary measurements were obtained perioperatively, and the white blood cell counts and levels of C-reactive protein were checked up to the 14(th) postoperative day. Steroid administration did not have any favorable effects during the perioperative period. Re-administration of antibiotics was needed in 7 patients (22.6%) after the 7(th) postoperative day in the steroid group, and in 3 (10.3%) in the control group. The peak white cell counts and C-reactive protein levels after the 7(th) postoperative day were significantly higher in the steroid group. Steroid administration offered no clinical benefit to patients undergoing cardiac surgery with cardiopulmonary bypass, and it may encourage minor infections in the late postoperative period.", "Infrarenal aortic cross-clamping is associated with impairment of renal hemodynamics due to vasoconstriction, the mechanism of which remains under debate. To assess the renal effect of two potent renal vasodilators (enalapril, a converting enzyme inhibitor, and nicardipine, a calcium antagonist), 24 patients scheduled for reconstructive aortic surgery were randomly allocated to one of three treatment groups (n = 8 each) and received either a placebo, nicardipine, or enalapril. Anesthesia consisted of flunitrazepam, fentanyl, pancuronium, and, occasionally, droperidol. Although aortic cross-clamping was associated with no change in mean arterial blood pressure, decreased cardiac output and increased systemic vascular resistance occurred in control patients (33% and 43%, respectively, both P less than 0.05 versus baseline) and nicardipine-treated patients (51.7% and 67.7%, respectively, both P less than 0.05 versus baseline); however, changes in cardiac output and systemic vascular resistance failed to reach significance in enalapril-treated patients. Glomerular filtration rate (technetium 99-diethylenetriaminepentacetic acid clearance) and effective renal plasma flow (iodo-Hippuran 131 clearance) decreased for the duration of aortic cross-clamping in control patients (42.9% and 18.5%, respectively, both P less than 0.05 versus baseline) and enalapril-treated patients (34.0% and 38.1%, respectively, both P less than 0.05 versus baseline), but no change was observed in nicardipine-treated patients. These results suggest that the reninangiotensin system is not an important determinant of the renal vasoconstriction associated with aortic cross-clamping. In contrast, renal dysfunction may be alleviated by the dihydropyridine derivative nicardipine, which probably acts at the level of the preglomerular resistance vessels.", "Postoperative recovery of gastrointestinal function and resumption of oral intake are critical determinants of the length of hospital stay. Although opioids are effective treatments for postoperative pain, they contribute to the delayed recovery of gastrointestinal function.\n We studied the effects of ADL 8-2698, an investigational opioid antagonist with limited oral absorption that does not readily cross the blood-brain barrier, on postoperative gastrointestinal function and the length of hospitalization. We randomly assigned 79 patients--including 1 whose surgery was canceled--to receive one capsule containing 1 mg or 6 mg of ADL 8-2698 or an identical-appearing placebo capsule two hours before major abdominal surgery and then twice daily until the first bowel movement or until discharge from the hospital. Data were analyzed for 26 patients in each of the three groups; all received opioids for postoperative pain relief. Observers who were unaware of the group assignments evaluated the outcomes.\n Fifteen patients underwent partial colectomy and 63 underwent total abdominal hysterectomy. Patients given 6 mg of ADL 8-2698 had significantly faster recovery of gastrointestinal function than those given placebo. The median time to the first passage of flatus decreased from 70 to 49 hours (P=0.03), the median time to the first bowel movement decreased from 111 to 70 hours (P=0.01), and the median time until patients were ready for discharge decreased from 91 to 68 hours (P=0.03). Effects in the group that received 1 mg of ADL 8-2698 were less pronounced.\n Selective inhibition of gastrointestinal opioid receptors by an antagonist with limited oral absorption that does not readily cross the blood-brain barrier speeds recovery of bowel function and shortens the duration of hospitalization.", "Prior authorization--mandatory advance approval for the use of expensive medications--is now the primary method by which Medicaid programs control expenditures for drugs. However, whether this policy reduces expenditures for specific drugs without causing the unwanted substitution of other drugs or medical services has been largely unstudied. We evaluated the effects of a prior-authorization policy involving nongeneric nonsteroidal antiinflammatory drugs (NSAIDs) in the Medicaid program in Tennessee.\n We compared monthly Medicaid expenditures that were potentially affected by the policy change during the year before and the two years after its implementation. We studied prescriptions for NSAIDs, other analgesic or antiinflammatory drugs, and psychotropic drugs, as well as outpatient services and inpatient admissions for the management of pain or inflammation.\n At the midpoint of the base-line year, 495,821 people were enrolled in Medicaid. During that year, mean annualized Medicaid expenditures for NSAID prescriptions amounted to $22.41. Expenditures decreased by 53 percent (95 percent confidence interval, 48 to 57 percent) during the next two years, for an estimated savings of $12.8 million. The reduction in expenditures resulted from the increased use of generic NSAIDs, as well as from a 19 percent decrease in overall NSAID use (95 percent confidence interval, 13 to 25 percent). There was no concomitant increase in Medicaid expenditures for other medical care. Regular users of nongeneric NSAIDs, those most affected by the policy change, had similar reductions in NSAID expenditures and use, with no increase in expenditures for other medical care.\n Prior-authorization requirements may be highly cost effective with regard to expenditures for NSAIDs, drugs that have very similar efficacy and safety but substantial variation in cost.", "Intravenous flurbiprofen, a non-steroidal antiinflammatory drug (NSAID), has been used recently for postoperative pain relief in adults. The drug is also likely to have antiemetic property. The present study was undertaken to investigate the effect of flurbiprofen on postoperative pain and emesis in children undergoing strabismus surgery, which is well known to produce postoperative nausea and vomiting.\n In a prospective, randomised, controlled clinical trial, 90 children aged 2-11 yr received saline (control), flurbiprofen 0.5 mg.kg-1, or flurbiprofen 1 mg.kg-1. Saline and flurbiprofen were administered i.v. immediately after induction of anaesthesia. Anaesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded observer using an objective pain scale (OPS). No opioids or antiemetics were administered throughout the study. The incidence and frequency of vomiting were compared among groups.\n Flurbiprofen 1 mg.kg-1 provided lower OPS (highest) scores during the eight hours after surgery and a reduced requirement for postoperative supplementary analgesic (diclofenac suppository) compared with the other two regimens. The two doses of flurbiprofen failed to decrease the incidence and frequency of vomiting.\n These data suggest that preoperative flurbiprofen 1 mg.kg-1 iv is a simple and effective approach to postoperative pain relief but not to the prevention of emesis following paediatric strabismus surgery.", "To determine whether audit/feedback and educational materials improve adherence to recommendations for laboratory monitoring and cytoprotective agents to detect and prevent adverse events caused by nonsteroidal anti-inflammatory agents (NSAIDs).\n Controlled, cluster-randomized trial.\n Physicians commonly prescribing NSAIDs were identified within a large managed care organization and randomized to a control or an intervention group (audit/feedback with peer-derived benchmarks and continuing medical education). Medical records were examined 10 months before and after the intervention for clinical data and receipt of complete blood count (CBC), creatinine testing, and cytoprotective agents (process measures). Primary analysis compared intervention versus control physicians among those who initially performed below a peer-derived benchmark. General estimating equations accounted for patient clustering.\n Of 101 physicians initially randomized, 85 remained eligible (38 internists, 36 family physicians, 11 rheumatologists) postintervention. Mean percent change in performance between intervention and control physicians for CBC monitoring was 16% versus 10%; for creatinine monitoring, 0% versus 17%; and use of cytoprotective agents, -3% versus -1%. None of these changes were significant. Rheumatology specialty, number of NSAID prescriptions and physician visits, and patient risk factors for NSAID-related toxicity were more strongly associated with improved safety practices than the intervention.\n Audit/feedback and educational materials had no observed effect on improving NSAID-related safety practices. Potentially contributing factors include high baseline performance (ceiling effect), dilution of the intervention effect by case mix and provider factors, nonreceipt of intervention materials, and diverse indications for lab tests.", "The purpose of the present study was to comparatively assess the adequacy of postoperative analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol in children undergone \"minor\" surgical interventions. For postoperative analgesia in children, the authors used paracetamol in a single dose of 25-30 mg/kg, diclofenac in a dose of 1.5-2.0 mg/kg, which were rectally administered as suppositories, as well as diclofenac in the same dose as intramuscular injections (Group 1). A comparison was made with postoperative analgesia using analgin and promedole (Group 2 (control)). Group 1 comprised 63 patients and Group 2 included 26 patients with identical diseases (inguinal hernias, varicocele, phimosis). Functional parameters were recorded in patients in the lying position before, 30 min, 1, 2, and 3 hours after surgery. The efficiency of postoperative analgesia was evaluated, by using central hemodynamic parameters that many investigators consider to be one of the major criteria for the adequacy of anesthesia. Comparison of postoperative data has revealed a difference between the groups, which suggests that the use of NSAIDs and paracetamol for preventive and postoperative analgesia in children substantially improves the postoperative period and promotes a rapid rehabilitation in patients. Comparative analysis of the efficiency of postoperative analgesia of the above agents has indicated that diclofenac and paracetamol have a sufficient analgesic activity and at the same time do not show the adverse reactions unique to narcotic analgesics.", "Pre-emptive analgesia represents a treatment strategy which tries to prevent the development of pain by inhibiting central reactions to peripheral sensory stimuli. In a prospective randomized double-blind placebo-controlled study, the effect of oral premedication with 4 mg of a slow-release hydromorphone preparation on postoperative piritramide consumption and subjective pain perception is being evaluated.\n 96 women undergoing hysterectomy were randomly assigned to four study groups. Patients from groups 1 and 2 received hydromorphone and placebo respectively two hours before surgery, while those from groups 3 and 4 were given the same substances one hour after the end of the operation. Postoperative pain relief was provided by a patient-controlled infusion pump with piritramide. The intensity of postoperative pain as perceived by the patients was quantified on a visual analogue scale. Piritramide consumption and pain scores were recorded at 1 and 24 hours after surgery. Approval of the local Ethics Committee had been obtained beforehand as well as written informed consent from the patients.\n No significant differences in piritramide consumption were observed in between the four study groups. Visual analogue scale (VAS) ratings at 1 and 24 hours after surgery did not show any significant differences either--irrespective of whether the patients had received hydromorphone or placebo preoperatively or postoperatively.\n In our study, oral administration of 4 mg of slow-release hydromorphone did not show any greater pre-emptive analgesic effect than placebo.", "To investigate the effect of preoperative ibuprofen administration on renal function during and after infrarenal aortic surgery under thoracolumbar epidural anaesthesia (EPA).\n A prospective randomised, double-blinded clinical study.\n Operation room and intensive care unit in a university hospital.\n Twenty-six consecutive patients scheduled for elective infrarenal aortic surgery.\n The patients were prospectively randomised to receive 400 mg ibuprofen intravenously (i.v.) or a placebo aliquot before surgery.\n We assessed renal function by calculating creatinine clearance, and fractional sodium excretion before surgery (baseline), 1 h after cross-clamping (intraoperative), 6 h after cross-clamping (postoperative) and 24 h after cross-clamping (on the 1 st postoperative day). At each point in time, we additionally registered haemodynamics and determined the plasma concentration of 6-keto-PGF1alpha (stable metabolite of prostacyclin, PGI2), bicyclic PGE2 (stable metabolite of PGE1 E2), active renin, aldosterone and vasopressin by radioimmunoassays. Throughout the observation period the renal function parameters mostly remained within the normal range without a significant difference between ibuprofen- and placebo-treated patients (creatinine clearance: baseline 41 +/- 3 vs 38 +/- 6, intraoperative 57 +/- 8 vs 64 +/- 11, postoperative 64 +/- 9 vs 56 +/- 9, first postoperative day 43 +/- 5 vs 47 +/- 6 ml x min x m(-2), means +/- SEM). The plasma levels of 6-keto-PGF1alpha (68 +/- 8 vs 380 +/- 71* ng x l(-1)), bicyclic PGE2 (57 +/- 5 vs 88 +/- 9* ng x l(-1)) and vasopressin (14 +/- 7 vs 45 +/- 10* ng x l(-1), p < 0.0125), however, were significantly higher during the intraoperative period in the placebo-treated patients.\n The inhibition of endogenous prostaglandin release by ibuprofen does not substantially impair renal function during infrarenal aortic surgery under EPA.", "Sympathetic vascular insult and hemodynamic changes represent the most reliable explanation of renal impairment resulting from acute intraabdominal pressure. We evaluated the effects of low-dose dopamine administration during a long-lasting surgical laparoscopic procedure.\n For this study 40, patients submitted to a colorectal laparoscopic procedure with 15 mmHg of intraabdominal pressure were randomly allocated to two groups: 20 receiving 2 mg/kg/min of dopamine and 20 receiving the same perfusion of saline. Hemodynamic parameters, renal function, urinary output, and creatinine clearance, were studied.\n The hemodynamic parameters were similar in both groups. The urinary output decreased during the intraoperative period only the saline group (p = 0.4). Then 2 h postoperatively, it increased in both groups, and no statistically significant differences were found between the groups. The creatinine clearance decreased in both groups during the intraoperative time, but it was worse in the saline group (-28 +/- 120 vs -194 +/- 106; p = 0.022). During the postoperative period, both groups showed improvement, but in control group the values remained lower than at baseline (p = 0.04), and significantly lower than in the dopamine group (230 +/- 337 vs 100 +/- 192; p = 0.012).\n An intrabdominal pressure of 15 mmHg induces a time-limited renal dysfunction, and low doses of dopamine could prevent this undesirable effect.", "In a randomized, double-blind study, we administered placebo and diclofenac sodium 100 mg suppositories 1 h pre-operatively and on the first post-operative morning to 22 adult patients undergoing minor orthopaedic surgery. A standardized post-operative intravenous fluid regimen was instituted until oral fluids were tolerated. Renal function was assessed pre-operatively, and on the first and second post-operative days by the measurement of urine output, creatinine, urea, sodium, potassium and NAG (N-acetyl-b-D-glucosaminidase) levels and serum creatinine, urea, sodium and potassium concentrations. On the first post-operative day, the diclofenac group demonstrated a reduced urinary sodium excretion. On the second post-operative day, a reduced urinary NAG/creatinine ratio was observed in the diclofenac group when compared to placebo. We conclude that peri-operative administration of diclofenac causes changes in renal function consistent with prostaglandin inhibition on the first post-operative day but had no lasting adverse effects in this group of patients. Our results reinforce the need for caution when administering this drug in the context of pre-existing renal impairment.", "We conducted a study to compare the effectiveness of patient-controlled analgesia (PCA) technique to conventional analgesic therapy (CAT) after coronary artery bypass graft (CABG). The PCA group received hydromorphone 0.1 mg.hr-1 basal infusion and bolus doses of 0.2 mg Q 5 min (maximum 1.2 mg.hr-1) while the CAT group received morphine 2.5 mg iv Q 30 min prn until extubation followed by prn meperidine 1 mg.kg-1 im Q 4 hr or acetaminophen 325 mg with codeine 30 mg po (1 or 2 tablets) when oral intake was possible. The degree of pain was assessed using a Visual Analogue Scale (VAS) starting after extubation and every 6-8 hr for the next 60 hr. Holter monitoring was initiated one hour after patient arrival in the Intensive Care Unit (ICU) and continued for 72 hr. Other measured variables were pulmonary function, sedation, side effects and total opioid requirements. Results show that the day-to-day VAS pain score decreased in the PCA group (P < 0.001) while it remained unchanged in CAT patients. The PCA patients had lower VAS pain scores at extubation (P < 0.05). During the third postoperative day, the PCA group had a lower VAS pain score, a lower incidence of severe pain defined as a score > 5 on the VAS scale, and a reduced incidence of myocardial ischaemia (P < 0.01). However, there was no difference in the duration, severity, area under the curve (AUC), or heart rate during ischaemic events. Postoperative pulmonary function was abnormal in both groups (NS) with minimal recovery by the fourth day.(ABSTRACT TRUNCATED AT 250 WORDS)", "To test the hypothesis that the choice of anesthesia technique for coronary artery surgery influences the degree and magnitude of the subsequent inflammatory response and its consequences.\n Prospective, randomized, comparative study.\n Major university teaching hospital.\n Sixty patients undergoing elective surgery.\n Patients were randomized into an alfentanil group, a high-dose remifentanil group, a low-dose remifentanil group, or a thoracic epidural group, in combination with a propofol target-controlled infusion. The study was blinded for the opioid, except in the epidural group. Tight control of perioperative hemodynamic parameters was maintained, and the postoperative management was strictly standardized. Bactericidal permeability-increasing protein as an indicator of the polymorphonuclear neutrophil response, interleukin-6 as an inducer of the acute-phase response, and lipopolysaccharide-binding protein and C-reactive protein as parameters of the acute phase response were determined at regular intervals. Ventilator dependency and analgesia were evaluated as clinical outcome measures.\n Interleukin-6 levels increased in all groups. Plasma levels in the epidural group were significantly higher at all time points than in the other groups. The increase in the plasma levels of bactericidal permeability-increasing protein, lipopolysaccharide-binding protein, and C-reactive protein showed the same pattern in all groups, and no significant differences among the 4 groups were observed.\n Supplementation of a fast-track anesthetic technique with epidural analgesia preserves hemodynamic stability and is associated with faster extubation times (p = 0.003) and less postoperative pain (p = 0.045). Thoracic epidural analgesia was associated with significantly higher levels of IL-6 throughout the study period as compared with the total intravenous anesthesia groups. The exact clinical relevance of this finding remains unclear.", "Activation of the renin-angiotensin system during open heart surgery may have consequences both beneficial in sustaining blood pressure and deleterious in compromising renal hemodynamics. The influence of short-term pretreatment with captopril on blood pressure and renal function was assessed double-blind versus placebo in 18 patients without pre-existing cardiac or renal failure, and undergoing coronary artery bypass. No difference in blood pressure and fluid requirement during the surgical period was observed between groups receiving captopril or placebo. Effective renal plasma flow and glomerular filtration rate decreased in the placebo group whereas they remained unaltered in the captopril group; during cardiopulmonary bypass, urinary excretion of sodium was greater in patients receiving captopril than those receiving placebo. These results suggest that captopril pretreatment does not compromise the control of blood pressure and renal function during open heart surgery; additional studies on the protective value of angiotensin-converting enzyme inhibitors are warranted in patients at higher risk for developing renal failure." ]	NSAIDs caused a clinically unimportant transient reduction in renal function in the early postoperative period in patients with normal preoperative renal function. NSAIDs should not be withheld from adults with normal preoperative renal function because of concerns about postoperative renal impairment.
CD004263	[ "8782340", "12744870", "14575762", "11734734", "1557929", "2975452", "9323616" ]	[ "The quest for trials on the efficacy of human vaccines. Results of the handsearch of Vaccine.", "Safety and immunogenicity of an oral, inactivated enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Bangladeshi children 18-36 months of age.", "Non-clinical and phase I clinical trials of a Vero cell-derived inactivated Japanese encephalitis vaccine.", "Prospective, randomized, placebo-controlled evaluation of the safety and immunogenicity of three lots of intranasal trivalent influenza vaccine among young children.", "A randomized phase II study of a new tick-borne encephalitis vaccine using three different doses and two immunization regimens.", "[Characteristics of the clinical and immunologic safety of inactivated influenza vaccines in children undergoing multiple immunizations].", "Phase 1 trial of a candidate rotavirus vaccine (RV3) derived from a human neonate." ]	[ "We report the results of the handsearch of all the issues of Vaccine from 1983 to 1994 to identify randomized and controlled clinical trials (RCTs and CCTs) with the aim of setting up a Cochrane data base of vaccine trials. We read 1119 original papers and located 231 trials of which 117 (50.6%) were RCTs and 114 (49.4%) were CCTs. This compared with a MEDLINE search yield of only 60 trials (25.9% of reports identified by handsearching). Hepatitis B vaccine was the most popular topic (25.5% of trial reports), followed by influenza (13.4% of trial reports) and Hepatitis A (10.4% of trial reports). Seventy per cent of trials had been carried out in Europe or North America and mean overall trial size was 1136 patients (median 110). Overall only 20 trial reports mentioned placebo explicitly, while 22 reports contained data on both overall and arm size which could not be reconciled. Reviewers of vaccine trials should not base searches exclusively on MEDLINE as they are likely to miss up to 75% of trial reports. Vaccine should adopt a standardized format of reporting of trials and contributors should conform to these rules.", "A phase II safety and immunogenicity study of an oral-formalin inactivated enterotoxigenic Escherichia coli (ETEC) vaccine containing six colonization factors (CFA/I, CS1, CS2, CS3, CS4, CS5) and 1mg of recombinant cholera toxin B subunit (the CF-BS-ETEC vaccine) was carried out in an urban slum of Dhaka city in Bangladesh. The study was carried out in a double blinded, placebo controlled design in 158 children, 18-36 months of age. Children were given two doses of the CF-BS-ETEC vaccine or the placebo which consisted of E. coli K12. The vaccine was well tolerated. The immune response was studied in 60 children (30 each in the placebo and vaccine group). Significant vaccine specific IgA antibody-secreting cell (ASC) responses were seen 7 days after ingestion of the first and second dose of the vaccine. The responses to CFA/I (P<or=0.001), CS2 (P=0.021), CS4 (P=0.009) and rCTB (P<or=0.001) were elevated in the vaccines in comparison to the pre-immune values and in comparison to those seen in the placebo recipients (P=0.018 to <0.001). Vaccines but not placebo recipients also showed significantly increased IgM ASC responses to all three CF antigens that were tested (P=0.012 to <0.001) and IgG-ASCs to rCTB (P<0.001). Peak ASC levels were reached after one dose of the vaccine with no further increase or decrease after the second dose. The vaccine recipients also responded with IgA plasma antibodies to CFA/I, CS1, CS2, CS4 and rCTB after one or two doses of the vaccine (P=0.01 to <0.001). Subjects in the placebo group failed to mount responses to any of the antigens. The vaccine also induced responses in mucosal IgA antibodies in feces to CFA/I, CS2 and rCTB (61, 88 and 69% responder frequency, respectively) and the magnitude of the response was elevated in comparison to the pre-immune levels (P=0.031 to <0.001) and to the levels of the control group (P=0.003 to <0.001). This study thus shows that the CF-BS-ETEC vaccine is well tolerated in children, 18-36 months of age and gives rise to significant systemic and mucosal IgA antibody responses.", "The safety and effectiveness of a Vero cell-derived inactivated Japanese encephalitis (JE) vaccine were compared with those of a current JE vaccine in non-clinical studies and a phase I clinical trial. The single-dose toxicity study showed no toxicity of either the current JE vaccine or the investigational Vero cell-derived JE vaccine. In a local irritation study, the degree of irritation caused by both vaccines was determined to be the same as that induced by normal saline. To investigate genotoxicity, a chromosomal aberration test was conducted and the results were negative. Both JE vaccines were administered to a group of 30 subjects who were seronegative (neutralizing antibody titer <10(1)) for JEV virus (Beijing-1 Strain). Each subject was subcutaneously inoculated twice at an interval of 1-4 weeks, followed by an additional booster inoculation 4-8 weeks later, and clinical reactions and serological responses were subsequently investigated. Adverse drug reactions of local reaction, headache and malaise were mild, occurring at a rate of 6.7 and 20.0% after administration of the Vero cell-derived JE vaccine and the current JE vaccine, respectively. The seroconversion rate after three doses of both JE vaccines was 100%, while the geometric mean titer for the Vero cell-derived and current JE vaccines was 10(2.35) and 10(2.03), respectively. These results suggest that the safety and effectiveness of the Vero cell-derived inactivated JE vaccine are equal to those of the currently available conventional vaccine in humans, and that the Vero cell-derived vaccine could be a useful second-generation JE vaccine.", "Trivalent formulations of an experimental, cold-adapted, intranasal influenza (CAIV) vaccine have been shown to be safe, immunogenic and efficacious in young children.\n We evaluated the safety and immunogenicity of three consistency lots of CAIV in children 12 to 36 months of age randomized to one of five groups: Groups 1, 2 and 3 received separate lots containing A/Shenzhen/227/95 (H1N1), A/Wuhan/359/95(H3N2) and B/Harbin/7/94-like viral strains. Group 4 received an earlier efficacy trial lot which included a different H1N1 strain (A/Texas/36/91-like); and Group 5 received placebo. We performed strain-specific serum hemagglutination inhibition antibody levels against type A (H3N2 or H1N1) or type B as appropriate.\n Overall 474 children received 2 doses, 2 months apart. Each lot was well-tolerated, and there were no significant group differences between consistency lots in the proportion of children with fever and local or systemic reactions after vaccination. The 3 consistency lots were not statistically different with regard to immunogenicity as measured by seroconversion or absolute geometric mean titer. Immune responses were more robust among initially seronegative children and for H3N2 and B strains than for H1N1 strains. After 2 doses of vaccine 97, 84 and 62% had hemagglutination inhibition titers > or = 1/32 against A/H3N2, B and H1N1 strains, respectively. For A/H3N2 only, immune responses after 1 dose of vaccine are similar to those seen after 2 doses.\n Each consistency lot of CAIV is as or more immunogenic than a lot used in a large efficacy trial.", "A new, highly purified inactivated tick-borne encephalitis (TBE) vaccine (FSME-Vaccine Behring, BI 71.061) was recently registered in Germany. A multinational phase II study was performed in seven centres located in areas endemic for TBE. A total of 379 healthy adults were randomly allocated into three dosage groups (1.0, 1.5 and 2.0 micrograms antigen per dose, respectively) and into two immunization schedules [vaccination with one dose of 0.5 ml intramuscularly on days 0, 7 and 21 (abbreviated schedule), or on days 0, 28 and 300 (conventional schedule)]. Antibody response to vaccination was assayed by enzyme-linked immunosorbent assay (ELISA), haemagglutination inhibition test (HIT) and neutralization test (NT). Seroconversion rates in the different groups 28 days after one single dose were 75.3-83.5% in ELISA, 35.8-50.6% in HIT, and 100% in NT. All vaccinees showed seroconversion in all tests on day 42 in the conventional schedule and on day 35 in the abbreviated schedule, with the exception of one subject, who remained seronegative in HIT only. Geometric mean titres (GMT) of about 3000 in ELISA were achieved by two vaccinations in the conventional schedule and showed a booster increase to 5500-8000 GMT after revaccination on day 300. Overall frequency of adverse events (related and unrelated) was 37% (conventional schedule) and 46% (abbreviated schedule) after the first, 9% and 21% after the second, and 5% and 15% after the third vaccination, respectively. Generally, side effects were mild and transient, including mainly headache, fever, malaise and local irritation. Serious, vaccine-related side effects did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)", "In a strictly controlled epidemiological trial on 12,643 school children aged 11-14 years the reactogenic properties and safety of killed influenza chromatographic vaccine under the conditions of multiple immunization were studied. A single immunization dose of the vaccine (0.2 ml) contained the hemagglutinins of influenza viruses A/Philippines/82 (H3N3) and A/Kiev/59/79 (H1N1), 3.5 micrograms each. The preparation was introduced by means of a jet injector. The vaccine was shown to be clinically and immunologically safe under the conditions of the regular multiple immunization of children over the period of 4 years.", "To conduct a phase 1 safety and tolerability trial of an oral rotavirus vaccine candidate RV3 in healthy volunteers.\n Double blind placebo controlled trial of a single 1 mL oral dose (6.5 x 10(5) fluorescing focus units [FFU]/mL) in 10 healthy young men, 10 3-4 year old children and 10 3 month old infants with a 4 week surveillance period. The study was undertaken at a children's hospital and nearby community in Melbourne, Australia.\n All subjects successfully completed the trial. There were no significant side-effects attributable to the vaccine preparation in any age group. No shedding of vaccine virus was detected by enzyme immunoassay. There was evidence of an immune response in serum and/or gut secretions in two of five vaccinees in each age group.\n RV3 rotavirus vaccine appears to be safe and well tolerated. Evidence of immunogenicity in some subjects after a single dose encourages further trials to determine immunogenicity after three doses, after reduction of viral dose, and without prior administration of buffer." ]	Only one of the three currently used vaccines has been assessed for efficacy in a RCT. Other RCTs have assessed their safety, however, and they appear to cause only occasional mild or moderate adverse events. Further trials of effectiveness and safety are needed for the currently used vaccines, especially concerning dose levels and schedules. Trials investigating several new vaccines are planned or in progress.
CD004260	[ "1537158", "18608367", "1512910", "20142693", "1471839", "2743665", "9007770", "18442423", "3430154", "3335558", "8615108", "3188866", "16445331" ]	[ "The influence of continuous passive motion on the results of total knee arthroplasty.", "Continuous passive motion as an adjunct to active exercises in early rehabilitation following total knee arthroplasty - a randomized controlled trial.", "A controlled evaluation of continuous passive motion in patients undergoing total knee arthroplasty.", "Use of inpatient continuous passive motion versus no CPM in computer-assisted total knee arthroplasty.", "Beneficial effects of continuous passive motion after total condylar knee arthroplasty.", "Continuous passive motion versus physical therapy in total knee arthroplasty.", "The effect of continuous passive motion duration and increment on range of motion in total knee arthroplasty patients.", "Effectiveness of prolonged use of continuous passive motion (CPM), as an adjunct to physiotherapy, after total knee arthroplasty.", "Continuous passive motion after total knee arthroplasty.", "Deep-vein thrombosis and continuous passive motion after total knee arthroplasty.", "Continuous passive motion compared to active physical therapy after knee arthroplasty: similar hospitalization times in a randomized study of 68 patients.", "No effect of continuous passive motion after arthroplasty of the knee.", "Effectiveness of continuous passive motion and conventional physical therapy after total knee arthroplasty: a randomized clinical trial." ]	[ "Twenty-two primary total knee arthroplasties were prospectively randomized into one of two treatment protocols. Ten of these patients were managed in the hospital after surgery by means of a postoperative splint. The remaining 12 patients were placed immediately postoperatively in the recovery room into the continuous passive motion (CPM) device. The study compares the range of motion, analgesic use, hospital stay, and the volume of hemovac output in the two groups. These cases demonstrated two statistically significant findings with the use of CPM: (1) decreased use of narcotic analgesics and (2) decreased length of hospital stay.", "Continuous passive motion is frequently used post-operatively to increase knee range of motion after total knee arthroplasty in spite of little conclusive evidence. The aim of this study was to examine whether continuous passive motion (CPM) as an adjunct to active exercises had any short time effects (after one week and three months) on pain, range of motion, timed walking and stair climbing.\n A randomized controlled trial was conducted. A total of 63 patients undergoing primary TKA were randomly assigned into an experimental group receiving CPM and active exercises and a control group receiving active exercises only. Outcomes were assessed by goniometer, visual analogue scale (VAS), timed 'Up and Go' test (TUG), timed 40 m walking distance and timed stair climbing.\n There were no statistical differences between the treatment groups for any outcome measures either at one week or after three months. For the whole group, a significant and 50% reduction in pain score was found after three months (p < 0.01). Compared with before surgery, a significantly impaired knee flexion range of motion (p < 0.01) and a significantly decreased number of patients able to climb stairs were found after three months (p < 0.01).\n CPM was not found to have an additional short-time effect compared with active physiotherapy. After three months considerable pain relief was obtained for the whole group, the patients preoperative ROM was not restored and the number of patients able to climb stairs had decreased.", "To evaluate the efficacy of continuous passive motion (CPM) in the postoperative management of patients undergoing total knee arthroplasty.\n A randomized controlled single-blind trial of CPM plus standardized rehabilitation vs standard rehabilitation alone.\n A referral hospital for arthritis and musculoskeletal care.\n Consecutive patients with end-stage osteoarthritis or rheumatoid arthritis undergoing primary total knee arthroplasty who had at least 90 degrees of passive knee flexion. One hundred fifty-four patients were eligible and 102 patients agreed to participate and were randomized. Ninety-three patients completed the study protocol.\n Continuous passive motion machines programmed for rate and specified arc of motion within 24 hours of surgery with range increased daily as tolerated with standardized rehabilitation program compared with standardized rehabilitation program alone.\n Primary outcomes were pain, active and passive knee range of motion, swelling (or circumference), quadriceps strength at postoperative day 7, as well as complications, length of stay, and active and passive range of motion and function at 6 weeks.\n Use of CPM increased active flexion and decreased swelling and the need for manipulations but did not significantly affect pain, active and passive extension, quadriceps strength, or length of hospital stay. At 6 weeks there were no differences between the two groups in either range of motion or function. In this series, use of CPM resulted in a net savings of $6764 over conventional rehabilitation in achieving these results.\n For the average patient undergoing total knee arthroplasty, CPM is more effective in improving range of motion, decreasing swelling, and reducing the need for manipulation than is conventional therapy and lowers cost.", "Continuous passive motion (CPM) has shown positive effects on tissue healing, edema, hemarthrosis, and joint function (L. Brosseau et al., 2004). CPM has also been shown to increase short-term early flexion and decrease length of stay (LOS) ( L. Brosseau et al., 2004; C. M. Chiarello, C. M. S. Gundersen, & T. O'Halloran, 2004). The benefits of CPM for the population of patients undergoing computer-assisted total knee arthroplasty (TKA) have not been examined.\n The primary objective of this study was to determine whether the use of CPM following computer-assisted TKA resulted in differences in range of motion, edema/drainage, functional ability, and pain.\n This was an experimental, prospective, randomized study of patients undergoing unilateral, computer-assisted TKA. The experimental group received CPM thrice daily and physical therapy (PT) twice daily during their hospitalization. The control group received PT twice daily and no CPM during the hospital stay. Both groups received PT after discharge. Measurement included Knee Society scores, Western Ontario McMaster Osteoarthritis Index values, range of motion, knee circumference, and HemoVac drainage. Data were collected at various intervals from preoperatively through 3 months.\n Although the control group was found to be higher functioning preoperatively, there was no statistically significant difference in flexion, edema or drainage, function, or pain between groups through the 3-month study period.", "A randomised, controlled study of the use of postoperative continuous passive motion (CPM) and immobilisation regimen after total condylar knee arthroplasty was performed. CPM resulted in a significant increase in both the early and late range of knee flexion. This increase occurred in both rheumatoid and osteoarthritic patients. The improvement of 10 degrees at 12 months allowed additional important function to be attained. CPM resulted in significantly earlier discharge from hospital. It did not increase the clinical incidence of wound healing problems, nor did it significantly increase the postoperative fixed flexion deformity or the extension lag. CPM can be recommended as a safe and effective modality to achieve more rapid and more successful postoperative rehabilitation after knee arthroplasty.", "To determine the justification of a continuous passive motion machine in the treatment of postoperative total knee arthroplasties, a comparative study of 50 consecutive patients with simultaneous bilateral total knee arthroplasties was undertaken. The patients served as their own controls because one randomly selected knee was placed in the machine while the remaining knee was treated with physical therapy only. There was no significant difference in the range of motion during the eight days of hospitalization or the follow-up visits at two weeks, two months, six months, and one year. There was a significant decrease in the swelling about the knee. The continuous passive motion treated knees appeared to be generally weaker as revealed by more extensor lags and flexor tightness at discharge from the hospital. Also, increased costs incurred from the need for additional equipment and increased staff time made the machine neither cost-effective nor beneficial.", "There is insufficient information on continuous passive motion (CPM) parameters in total knee arthroplasty patients for optimal patient outcomes. We compared CPM duration and increments on active and passive range of motion (ROM) in patients who underwent a unilateral total knee arthroplasty due to degenerative joint disease. Forty-five total knee arthroplasty patients were randomly assigned to either a control group, a short CPM duration (3-5 hours per day) group with CPM ROM increased 5 degrees twice daily, a short CPM duration group with CPM ROM increased daily to patient tolerance, a long CPM duration (10-12 hours per day) group with CPM ROM increased 5 degrees twice daily, or a long CPM duration group with CPM ROM increased daily to patient tolerance. Active and passive flexion and extension were measured goniometrically on each postoperative day that the patient was treated by physical therapy. No statistically significant differences between groups were found for baseline and final postoperative ROM. The CPM groups did not maintain the parameters assigned and were combined, revealing an enhanced rate of change of flexion. Most patients opted for a CPM duration of between 4 and 8 hours per day and the patient-preferred CPM incremental increase in ROM was 6-7 degrees/day.", "Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty. Although research suggests that Continuous Passive Motion (CPM) should be implemented in the first rehabilitation phase after surgery, there is substantial debate about the duration of each session and the total period of CPM application. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered.\n In a randomised controlled trial we investigated the effectiveness of prolonged CPM use in the home situation as an adjunct to standardised PT. Efficacy was assessed in terms of faster improvements in range of motion (RoM) and functional recovery, measured at the end of the active treatment period, 17 days after surgery. Sixty patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment were randomised over two treatment groups. The experimental group received CPM + PT for 17 consecutive days after surgery, whereas the usual care group received the same treatment during the in-hospital phase (i.e. about four days), followed by PT alone (usual care) in the first two weeks after hospital discharge. From 18 days to three months after surgery, both groups received standardised PT. The primary focus of rehabilitation was functional recovery (e.g. ambulation) and regaining RoM in the knee.\n Prolonged use of CPM slightly improved short-term RoM in patients with limited RoM at the time of discharge after total knee arthroplasty when added to a semi-standard PT programme. Assessment at 6 weeks and three months after surgery found no long-term effects of this intervention Neither did we detect functional benefits of the improved RoM at any of the outcome assessments.\n Although results indicate that prolonged CPM use might have a small short-term effect on RoM, routine use of prolonged CPM in patients with limited RoM at hospital discharge should be reconsidered, since neither long-term effects nor transfer to better functional performance was detected.\n ISRCTN85759656.", "Sixty-two patients undergoing primary total knee arthroplasty were studied prospectively. There were 42 patients in whom continuous passive motion (CPM) was used after surgery and 20 controls. The two groups were comparable with respect to age, diagnosis, sex, weight, and preoperative deformity and motion. The mean length of time required for CPM patients to achieve 90 degrees of flexion (9.1 days) was shorter than that for the control group (13.8 days). At the time of discharge from the hospital, however, there was no significant difference between the groups in amount of either flexion or extension. All patients had venograms performed after arthroplasty; the incidence of positive studies indicating thrombophlebitis was 45% in CPM patients and 75% in controls. These data demonstrate that CPM after knee arthroplasty enables patients to recover motion more quickly and affords some protection against deep vein thrombosis.", "Seventy-five of 150 consecutive patients who underwent total knee arthroplasty had routine physiotherapy and seventy-five had continuous passive motion of the lower limb that had been operated on as well as routine physiotherapy. A pulmonary embolus did not develop in any patient, but about 40 per cent had thrombosis in the veins of the calf, whether passive motion had been administered or not. Radiographically, the deep-vein thrombosis was seen to extend into or proximal to the popliteal vessel in 5 per cent of the patients in each group. Sex, age, obesity, or a history of hypertension or diabetes did not influence the incidence of venous thrombosis, but there was a higher incidence in patients in whom cement was used for fixation of the total knee components, irrespective of the use of continuous passive motion of the limb.", "68 consecutive patients who had primary knee arthroplasties because of arthrosis were randomized to postoperative continuous passive motion (CPM) or active physical therapy (APT). Rehabilitation in both groups was initiated on the first postoperative day. The CPM group sustained less postoperative knee swelling with more rapid initial improvement in knee flexion than did the APT group, but there were no differences between the groups in knee flexion at discharge. Postoperative pain rating and hospitalization times were similar in the two groups.", "We randomly allocated 54 patients to active physical therapy only or this combined with 2 hours of passive knee motion twice daily from 2-12 days after total knee arthroplasty. The range of knee motion was measured on the 14th postoperative day. We found no difference between the groups. We concluded that 4 hours' passive motion daily in addition to early, active physical therapy does not improve the range of knee motion or promote mobilization after arthroplasty.", "This randomized clinical trial was conducted to compare the effectiveness of 3 in-hospital rehabilitation programs with and without continuous passive motion (CPM) for range of motion (ROM) in knee flexion and knee extension, functional ability, and length of stay after primary total knee arthroplasty (TKA).\n Eighty-one subjects who underwent TKA for a diagnosis of osteoarthritis were recruited.\n All subjects were randomly assigned to 1 of 3 groups immediately after TKA: a control group, which received conventional physical therapy intervention only; experimental group 1, which received conventional physical therapy and 35 minutes of CPM applications daily; and experimental group 2, which received conventional physical therapy and 2 hours of CPM applications daily. All subjects were evaluated once before TKA and at discharge. The primary outcome measure was active ROM in knee flexion at discharge. Active ROM in knee extension, Timed \"Up & Go\" Test results, Western Ontario and McMaster Universities Osteoarthritis Index questionnaire scores, and length of stay were the secondary outcome measures.\n The characteristics of and outcome measurements for the subjects in the 3 groups were similar at baseline. No significant difference among the 3 groups was demonstrated in primary or secondary outcomes at discharge.\n The results of this study do not support the addition of CPM applications to conventional physical therapy in rehabilitation programs after primary TKA, as applied in this clinical trial, because they did not further reduce knee impairments or disability or reduce the length of the hospital stay." ]	The effects of continuous passive motion on knee range of motion are too small to justify its use. There is weak evidence that continuous passive motion reduces the subsequent need for manipulation under anaesthesia.
CD000022	[ "1889273", "12379544", "3063043", "3033040", "6998390", "11500337", "2194417", "3324594", "10021717", "1734249", "10645510", "3046651", "12067168", "10351117", "15843938", "8238160", "9069004", "11533321", "2658918", "8051377", "17236918", "10768245", "6710299", "10934078", "1626207", "2810183" ]	[ "Antibiotic prophylaxis of respiratory tract infection in mechanically ventilated patients. A prospective, blinded, randomized trial of the effect of a novel regimen.", "Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections, organ dysfunctions, and mortality in critically ill surgical patients: a prospective, stratified, randomized, double-blind, placebo-controlled clinical trial.", "Failure of topically applied antibiotics, added to systemic prophylaxis, to reduce perineal wound infection in abdominoperineal excision of the rectum.", "Prevention of colonization and respiratory infections in long-term ventilated patients by local antimicrobial prophylaxis.", "Prophylactic antibiotics in vascular surgery. Topical, systemic, or both?", "Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study.", "Antibiotics in elective colon surgery. A randomized trial of oral, systemic, and oral/systemic antibiotics for prophylaxis.", "Single-dose v. short-term antibiotic therapy for prevention of wound infection in general surgery. A prospective, randomized double-blind trial.", "Use of surfactant for prophylaxis versus rescue treatment of respiratory distress syndrome: experience from an Italian-Bulgarian trial.", "A controlled trial in intensive care units of selective decontamination of the digestive tract with nonabsorbable antibiotics. The French Study Group on Selective Decontamination of the Digestive Tract.", "An evaluation of statewide strategies to reduce antibiotic overuse.", "A double-blind randomized controlled trial on the use of prophylactic antibiotics in patients undergoing elective caesarean section.", "Oral versus systemic antibiotic prophylaxis in elective colon surgery: a randomized study and meta-analysis send a message from the 1990s.", "Use of a polyvalent bacterial lysate in patients with recurrent respiratory tract infections: results of a prospective, placebo-controlled, randomized, double-blind study.", "Prospective, randomised study on antibiotic prophylaxis in colorectal surgery. Is it really necessary to use oral antibiotics?", "Randomized trial of prophylactic antibiotic therapy after preterm amnion rupture.", "Decrease in nosocomial pneumonia in ventilated patients by selective oropharyngeal decontamination (SOD).", "A community intervention trial to promote judicious antibiotic use and reduce penicillin-resistant Streptococcus pneumoniae carriage in children.", "Oral prophylaxis with neomycin and erythromycin in colorectal surgery. More proof for efficacy than failure.", "[Antibiotic prophylaxis in a priori cesarean sections without a high risk of infection. Experiences of a Tunisian maternity department].", "Does prophylactic administration of systemic antibiotics prevent postoperative inflammatory complications after third molar surgery?", "Antibiotic prophylaxis in percutaneous endoscopic gastrostomy (PEG)--results from a prospective randomized multicenter trial.", "Oral is superior to systemic antibiotic prophylaxis in operations upon the colon and rectum.", "Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription.", "Prophylactic antibiotics in the insertion of Tenckhoff catheters.", "Comparison of two prophylactic single-dose intravenous antibiotic regimes in the treatment of patients undergoing elective colorectal surgery in a district general hospital." ]	[ "The objective of this study was to assess the effect of a novel regimen of antibiotic prophylaxis on the incidence of lower respiratory tract infection in patients requiring prolonged (at least five days) mechanical ventilation. The design was a controlled, prospective, randomized trial, with blinded comparison of the groups regarding the incidence of respiratory tract infection in an intensive care unit of a university hospital. After determination of the APACHE II score for severity of disease, 88 patients were randomly divided in three groups. Twenty-four of these patients did not complete five days of mechanical ventilation, and eight were withdrawn for other reasons. Fifty-six patients (18 in group 1, 21 in group 2, 17 in group 3) completed the study. Patients in both control groups 1 and 2 did not receive antibiotic prophylaxis, but the two groups differed in the antibiotic policy in case of infection. Patients in group 3 received antibiotic prophylaxis consisting of norfloxacin, polymyxin E, and amphotericin B, applied topically in oropharynx and stomach from time of ICU admission until extubation, and intravenous cefotaxime 500 mg three times a day during the first five days of admission. In both control groups, about 90 percent of the patients acquired microbial colonization of oropharynx or stomach. In group 3, only 12 percent and 24 percent of the patients acquired colonization of oropharynx and stomach, respectively (p less than 0.001). This resulted in a reduction of the incidence of lower respiratory tract infection (78 percent in group 1, 62 percent in group 2, 6 percent in group 3 [p = 0.0001]). The regimen of antibiotic prophylaxis studied prevented respiratory tract infection in mechanically ventilated patients. Antibiotic prophylaxis should be considered in all patients expected to require prolonged mechanical ventilation.", "We prospectively studied the impact of an antibiotic prophylaxis regimen on the incidence of infections, organ dysfunctions, and mortality in a predominantly surgical and trauma intensive care unit (ICU) population. A total of 546 patients were enrolled and stratified according to Acute Physiology and Chronic Health Evaluation (APACHE)-II scores. They were then randomized to receive either 2 x 400 mg of intravenous ciprofloxacin for 4 days, together with a mixture of topical gentamicin and polymyxin applied to the nostrils, mouth, and stomach throughout their ICU stay or to receive intravenous and topical placebo. When receiving prophylaxis, significantly fewer patients acquired infections (p = 0.001, risk ratio [RR], 0.477; 95% confidence interval [CI], 0.367-0.620), especially pneumonias (6 versus 29, p = 0.007), other lower respiratory tract infections (39 versus 70, p = 0.007), bloodstream infections (14 versus 36, p = 0.007), or urinary tract infections (36 versus 60, p = 0.042). Also, significantly fewer patients acquired severe organ dysfunctions (63 versus 96 patients, p = 0.0051; RR, 0.636; 95% CI, 0.463-0.874), especially renal dysfunctions (17 versus 38; p = 0.018). Within 5 days after admission, 24 patients died in each group, whereas 28 patients receiving prophylaxis and 51 receiving placebo died in the ICU thereafter (p = 0.0589; RR, 0.640; 95% CI, 0.402-1.017). The overall ICU mortality was not statistically different (52 versus 75 fatalities), but the mortality was significantly reduced for 237 patients of the midrange stratum with APACHE-II scores of 20-29 on admission (20 versus 38 fatalities, p = 0.0147; RR, 0.508; 95% CI, 0.295-0.875); there was still a favorable trend after 1 year (51 versus 60 fatalities; p = 0.0844; RR, 0.720; 95% CI, 0.496-1.046). Surveillance cultures from tracheobronchial, oropharyngeal, and gastric secretions and from rectal swabs did not show any evidence for the selection of resistant microorganisms in the patients receiving prophylaxis.", "In a prospective, randomized trial, prophylactic use of topical antibiotics in addition to systemic prophylaxis was studied in patients undergoing abdominoperineal amputation of the rectum. All patients received gentamicin 80 mg and metronidazole 500 mg intravenously at induction of anesthesia, followed by the same dose 8 hourly for 48 hours. In accordance with the randomization, half of the patients were additionally given gentamicin 160 mg + metronidazole 400 mg topically into the perineal wound at closure. Perineal wound infection appeared in 19 of the 41 patients who received both systemic and topical prophylaxis, and in 18 of the 38 with only systemic antibiotics. Cell-mediated immunity was preoperatively assessed with a skin test (Multitest) in all but three patients. Impairment of cell-mediated immunity was associated with significantly heightened rate of wound infection, and these patients did not benefit from topical antibiotics.", "In a randomized clinical trial the prophylactic effects of locally administered antimicrobials on quantitative colonization and respiratory infections were studied in intubated patients with an expected period of mechanical ventilation of greater than 6 days. Nineteen patients received 50 mg of polymyxin B and 80 mg of gentamicin distributed among nose, oropharynx and stomach at 6-h intervals, as well as 300 mg of amphotericin B in the oropharynx. Twenty untreated patients served as controls. In the control group colonization by respiratory pathogens was more common (oropharynx 19 vs 6 patients (p less than 0.001); trachea 19 vs 11 (p less than 0.01)), and the number as well as the count of the colonizing species was usually higher. Fourteen patients of the control group developed respiratory infections, including nine cases of pneumonia, as compared to four patients with prophylaxis, including one case of pneumonia (p less than 0.01). Pneumonia-associated deaths were prevented with prophylaxis; however, the overall mortality remained unchanged. Respiratory infections in the prophylaxis group were associated with organisms resistant to the agents used, but the overall occurrence of resistance was not increased, as compared to the control group. We conclude that unrestrained upper airway colonization by respiratory pathogens and respiratory tract infection were causally related. Local antimicrobial prophylaxis proved to be a highly effective strategy for the prevention of potentially life-threatening pneumonias in critically ill patients, but in the present study the host setting appeared to be the major determinant of outcome.", "A prospective, randomized, blinded study was performed to determine whether prophylactic antibiotics would reduce the incidence of infection in peripheral vascular surgery and whether the route of antibiotic administration was important. Patients undergoing a vascular procedure with a groin incision were allocated to one of four groups with respect to prophylactic antibiotics. Group I received no antibiotic. Group II had topical cephradine instilled in their incisions prior to closure. Group III received a 24-hour perioperative course of intravenous cephradine, and Group IV received both topical and intravenous cephradine. Groin and abdominal incisional infections were significantly reduced (p < 0.01) among patients who received prophylactic antibiotics by either the topical, systemic, or combined routes of administration. No significant differences were noted among the three antibiotic groups. Profundoplasty, femoral embolectomy, and femoral aneurysm repair were each associated with an increased incidence of infection (p < 0.01). Other risk factors were only important in patients not receiving antibiotics. Either intraoperative topical antibiotics or perioperative systemic antibiotics prevent infection in peripheral vascular surgery, but antibiotic administration by both routes is unnecessary.", "Colonization of the intestinal tract has been assumed to be important in the pathogenesis of ventilator-associated pneumonia (VAP), but relative impacts of oropharyngeal, gastric, or intestinal colonization have not been elucidated. Our aim was to prevent VAP by modulation of oropharyngeal colonization, without influencing gastric and intestinal colonization and without systemic prophylaxis. In a prospective, randomized, placebo-controlled, double-blind study, 87 patients received topical antimicrobial prophylaxis (gentamicin/ colistin/vancomycin 2% in Orabase, every 6 h) in the oropharynx and 139 patients, divided over two control groups, received placebo (78 patients were studied in the presence of patients receiving topical prophylaxis [control group A] and 61 patients were studied in an intensive care unit where no topical prophylaxis was used [control group B]). Baseline characteristics were comparable in all three groups. Topical prophylaxis eradicated colonization present on admission in oropharynx (75% in study group versus 0% in control group A [p < 0.00001] and 9% in control group B patients [p < 0.00001]) and in trachea (52% versus 22% in A [p = 0.03] and 7% in B [p = 0.004]). Moreover, topical prophylaxis prevented acquired oropharyngeal colonization (10% versus 59% in A [p < 0.00001] and 63% in B [p < 0.00001]). Colonization rates in stomach and intestine were not affected. Incidences of VAP were 10% in study patients, 31% in Group A, and 23% in Group B patients (p = 0.001 and p = 0.04, respectively). This was not associated with shorter durations of ventilation or ICU stay or better survival. Oropharyngeal colonization is of paramount importance in the pathogenesis of VAP, and a targeted approach to prevent colonization at this site is a very effective method of infection prevention. Keywords: cross infection, prevention and control; respiration, artificial, adverse effects; antibiotics, administration and dosage infection control methods; pneumonia, etiology, prevention and control; intubation, intratracheal, adverse effects", "A prospective, randomized double-blind study was undertaken to compare the efficacy of three prophylactic regimens (oral neomycin and erythromycin, intravenous cefoxitin, and a combination of both oral and intravenous antibiotics) in patients undergoing elective colorectal surgery. One hundred sixty-nine patients were randomized and 146 patients were evaluable. Septic complications occurred in 11.4 per cent of patients receiving oral antibiotics only, in 11.7 per cent of patients receiving intravenous cefoxitin alone, and in 7.8 per cent of patients receiving both oral and intravenous antibiotics. These differences were not statistically different. The greatest number of septic complications occurred in those patients with anastomotic disruptions. Two patients died (1.3%), both of whom had major anastomotic failures. There was no advantage between any of the groups in the incidence of wound infection (3.9-6.8%). Thus, no advantage could be identified in this study in the combination of oral and intravenous antibiotics in elective colorectal surgery.", "To investigate the effectiveness of a single-dose antibiotic regimen for preventing postoperative wound infection, a prospective, randomized double-blind trial was carried out in patients undergoing \"clean-contaminated\", \"contaminated\" or \"clean\" (vascular) surgery. Both elective and emergency operations were included. Single-dose (preoperative) prophylaxis was compared with short-term prophylaxis (1 dose preoperatively and 2 doses postoperatively). The antibiotics were penicillin, tobramycin and metronidazole in various combinations, and comparisons between single-dose and short-term prophylaxis were made with all the regimens. The incidence of wound infection was 5/277 (1.8%) in the short-term group and 9/287 (3.1%) in the single-dose group. The difference was not statistically significant. Nor was statistically significant difference found when the type of operation and the degree of contamination were considered. Single-dose antibiotic prophylaxis thus gave a low incidence of postoperative wound infection, even in \"clean-contaminated\" or \"contaminated\" cases.", "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.", "Selective decontamination of the digestive tract with topical nonabsorbable antibiotics has been reported to prevent nosocomial infections in patients receiving mechanical ventilation, and the procedure is used widely in Europe. However, it is unclear whether selective decontamination improves survival.\n We conducted a randomized, double-blind multicenter study in which 445 patients receiving mechanical ventilation in 15 intensive care units were given either prophylactic nonabsorbable antibiotics (n = 220) or a placebo (n = 225). Topical antibiotics (tobramycin, colistin sulfate, and amphotericin B) or a placebo was administered through a nasogastric tube and applied to the oropharynx throughout the period of ventilation. The main end points were the mortality rate in the intensive care unit and within 60 days of randomization.\n A total of 142 patients died in the intensive care unit; 75 (34 percent) in the treatment group and 67 (30 percent) in the placebo group (P = 0.37). Mortality within 60 days of randomization was similar in the two groups (P = 0.40), even after adjustment for factors that were either unbalanced or individually predictive of survival in the two groups (P = 0.70). Pneumonia developed in 59 patients (13 percent) in the intensive care unit within 30 days of enrollment in the study (33 in the placebo group and 26 in the treatment group, P = 0.42). Pneumonia acquired in the intensive care unit and due to gram-negative bacilli was less frequent (P = 0.01) in the treatment group than in the placebo group. The total charges for antibiotics were 2.2 times higher in the treatment group.\n Selective decontamination of the digestive tract does not improve survival among patients receiving mechanical ventilation in the intensive care unit, although it substantially increases the cost of their care.", "The rapid increase of antibiotic resistance poses a significant threat to human health. Overuse of antibiotics has been linked to rates of antibiotic resistance. This study assessed the utility of two common interventions--1) practice profiling and feedback and 2) patient education materials--implemented to decrease antibiotic prescribing for pediatric upper respiratory infections (URIs).\n Based on Medicaid regions in Kentucky, primary care physicians managing pediatric respiratory infections in Medicaid were randomized into four groups. Groups received either 1) performance feedback only, 2) patient education materials only, 3) both feedback and education materials, or 4) no intervention. Participating physicians had their antibiotic prescribing assessed for the period of July 1, 1996, to November 30, 1997, with an intervention in June 1997. The study included 216 physicians and 124,092 episodes of care.\n All groups increased in proportion of episodes with antibiotics between the pre-intervention and post-intervention periods. Prescribing in the patient education group and the patient education and feedback group increased at a significantly lower rate than in the control group. Physicians did not change their coding of illness to justify antibiotics after the intervention, and there was no significant generalization of effect of the pediatric intervention on prescribing for adult URIs.\n These interventions demonstrate little if any impact on promoting appropriate antibiotic prescribing. Antibiotic prescribing for viral respiratory infections continues to increase, suggesting concomitant increases in antibiotic resistance.", "In a double-blind randomized controlled study 232 patients undergoing elective lower segment caesarean section were randomly allocated to receive a pre-operative prophylactic dose of a combination of crystalline penicillin and chloramphenicol or a placebo. The two groups were comparable in terms of patient characteristics and operation variables. The group receiving antibiotics had significantly fewer febrile and infectious morbid events and thus spent fewer days in hospital than the group receiving the placebo.", "To compare the efficacy of combined oral and systemic antibiotics (combined) versus systemic antibiotics (systemic) alone in preventing surgical site infection in elective surgery of the colon, and to perform a meta-analysis of randomized studies comparing combined versus systemic antibiotics in elective colon surgery.\n A double-blind, placebo-controlled, randomized clinical trial.\n The Queen Elizabeth Hospital, Montreal, a university-affiliated community hospital.\n Two hundred and fifteen patients scheduled to undergo elective surgery of the colon.\n Patients were randomized to receive neomycin and metronidazole orally (109 patients) or identical placebos (106 patients) on the final preoperative day. All were given amikacin and metronidazole intravenously just before operation. Thirteen randomized series comparing combined and systemic antibiotic prophylaxis in elective colon surgery were identified for meta-analysis.\n Rates of postoperative surgical site infections: risk differences, risk ratios (RRs) and 95% confidence intervals (CIs); organisms found in the colon and wound fat at surgery, and in infected wounds.\n Three patients in the systemic group, and 5 in the combined group were excluded. Wound infections occurred in 5 patients in the combined group but in 17 in the systemic group (p < 0.01, RR = 0.29, 95% CI 0.11-0.75). Bacteria isolated from wound infections and wound fat were similar to those found in the colon. They were more frequent in the colon in the systemic group (p < 0.001) and occurred in wound fat in the systemic group twice as often as in the combined group (p < 0.001). By stepwise logistic regression, the presence of bacteria in wound fat at surgery was the strongest predictor of postoperative wound infection (p < 0.002). In the meta-analysis, the summary weighted risk difference in surgical site infections between groups (d(w)) and the summary RR both favoured combined prophylaxis (d(w) = 0.56, 95% CI 0.26-0.86; RR = 0.51, 95% CI 0.24-0.78; p < 0.001).\n In elective surgery of the colon combined oral and systemic antibiotics are superior to systemic antibiotics in preventing surgical site infections. Orally administered antibiotics add value by reducing bacterial loading of the colon and wound fat contamination, both associated with postoperative wound infection. Meta-analysis of randomized clinical trials reported from 1975 to 1995 supports these conclusions.", "Respiratory tract infections (RTIs) are the most common infections in humans, and it is difficult to effectively treat patients with increased susceptibility to these ailments. LW 50020 (Luivac; Paspat oral), an oral immunomodulator consisting of the antigens of seven bacteria commonly involved in RTIs, has been developed for the induction of specific and nonspecific immune responses of the mucosa-associated lymphoid tissue. In this placebo-controlled study, the efficacy and safety of the tablet formulation of LW 50020 were evaluated in children and adults with recurrent RTIs. Tablets were taken once daily during two periods of 4 weeks each, interrupted by a treatment-free interval of 4 weeks. The main endpoint of the study, a clinical severity score that evaluated treatment benefits, was significantly lower in the second study period in patients treated with the bacterial lysate compared to patients given placebo. A comparison of the infection rates in the first and second study periods of patients treated with LW 50020 revealed a placebo-corrected reduction of 39% in children and a placebo-corrected reduction of 44% in adolescents and adults. The placebo-corrected duration of infections was shortened by 47% in children and by 55% in older patients. No serious drug-related side effects occurred. This study demonstrated that the oral bacterial immunomodulator LW 50020 is efficacious in treating patients with recurrent RTIs.", "The use of prophylactic antibiotics in addition to mechanical cleansing is the current standard of care prior to colonic surgery. The question of whether the antibiotics should be administered intravenously or orally, or by both routes, remains controversial. Our aim was to compare three methods of prophylactic antibiotic administration in elective colorectal surgery.\n Three hundred consecutive elective colorectal resections were studied. All patients had preoperative mechanical colon cleansing with oral sodium phosphate and intravenous antibiotic prophylaxis with cefoxitin (one dose before skin incision and two postoperative doses). Patients were randomised to one of the following three groups: group A: three doses of oral antibiotic (neomycin and metronidazole) at the time of mechanical colon cleansing; group B: one dose of oral antibiotic; group C: no oral antibiotics. All patients were followed during their hospital stay and at 7, 14 and 30 days post-surgery.\n Vomiting occurred in 31%, 11% and 9% of the studied patients (groups A, B and C, respectively) (p<0.001). Nausea was present in 44%, 18% and 13% of patients (p<0.001). Abdominal pain was recorded in 13%, 10% and 4% of patients (p: 0.077). Wound infection was present in 7%, 8% and 6% and suture dehiscence occurred in 2%, 2% and 3% of the patients in the three groups (no differences among them). Neither were differences found among the three groups in terms of urinary infections, pneumonia, postoperative ileus or intra-abdominal abscess.\n The addition of three doses of oral antibiotics to intravenous antibiotic prophylaxis is associated with lower patient tolerance in terms of increased nausea, vomiting and abdominal pain, and has shown no advantages in the prevention of postoperative septic complications. Therefore, we recommend that oral antibiotics should not be used prior to colorectal surgery.", "Our purpose was to determine whether maternal administration of prophylactic ampicillin or erythromycin after preterm amnion rupture is associated with maternal or neonatal benefits.\n Women with singleton pregnancies between 24 and 33 weeks 6 days of gestation were eligible if they had no immediate indication for delivery. After giving informed consent, patients were randomized either to receive ampicillin (erythromycin if penicillin allergic) until delivery or to enter a control group. Women whose cervical cultures were positive for either group B streptococci or Neisseria gonorrhoeae received treatment. Tocolytics and corticosteroids were not used.\n From January 1990 to February 1992 117 patients (antibiotics 59, control 58) were recruited and analyzed. Prophylactic antibiotics were associated with a longer latent phase (mean 12 vs 7.0 days, p = 0.004) and fewer maternal infectious complications (29% vs 60%, p = 0.001). A higher incidence of neonatal necrotizing enterocolitis was observed in the treatment group (14% vs 3.5%, p = 0.05). Other neonatal complications, including death, were lower in the treatment group, but none attained statistical significance (p = 0.09 to 0.33).\n The use of prophylactic antibiotics in selected patients after preterm amnion rupture appears to have a demonstrable maternal benefit. Large, multicenter trials may demonstrate a significant neonatal benefit or confirm any adverse outcomes.", "To determine the influence of selective oropharyngeal decontamination (SOD) on the rate of colonization and infection of the respiratory tract in intensive care patients requiring mechanical ventilation for more than 4 days. A financial assessment was also performed.\n Randomized, prospective, controlled study using amphotericin B, colistin sulfate (polymyxin E), and tobramycin applied to the oropharynx and systemic cefotaxime prophylaxis.\n Anesthesiology intensive care unit (ICU) of a 1500-bed hospital.\n A total of 88 patients admitted as emergencies and intubated within less than 24 h were enrolled. Fifty-eight patients received SOD and 30 patients served as controls. Randomization was in the proportion of 2 : 1 study patients to controls.\n Microbiological samples from the oropharynx and other infected sites were taken at the time of admission, then twice a week and after extubation.\n With the use of SOD, colonization was significantly reduced. Furthermore, the infection rate decreased from 77% in the controls to 22% in the study patients. Staphylococcus aureus was the main potential pathogen causing colonization and pneumonia. Number of days in the ICU, duration of ventilation, and mortality were not significantly decreased. The total cost of antibiotics was reduced. Development of resistance was not observed.\n The use of SOD significantly reduced the colonization and pneumonia and the total charge for antibiotics. The length of stay in the ICU, duration of ventilation, and mortality were similar. No resistance was observed. Staphylococcus aureus was selected by SOD in some patients and the clinical relevance needs further observation.", "Inappropriate use of antibiotics is common in primary care, and effective interventions are needed to promote judicious antibiotic use and reduce antibiotic resistance. The objective of this study was to assess the impact of parent and clinician education on pediatric antibiotic prescribing and carriage of penicillin-nonsusceptible Streptococcus pneumoniae in child care facilities.\n A nonrandomized, controlled, community intervention trial was conducted in northern Wisconsin Clinicians. Clinic staff received educational materials and small-group presentations; materials were distributed to parents through clinics, child care facilities, and community organizations. Prescribing data were analyzed for 151 clinicians who provided primary pediatric care; nasopharyngeal carriage of penicillin-nonsusceptible S pneumoniae was assessed for 664 children in the baseline period (January-June 1997) and for 472 children in the postintervention period (January-June 1998).\n The median number of solid antibiotic prescriptions per clinician declined 19% in the intervention region and 8% in the control region. The median number of liquid antibiotic prescriptions per clinician declined 11% in the intervention region, compared with an increase of 12% in the control region. Retail antibiotic sales declined in the intervention region but not in the control region. Among participating children in child care facilities, there were no significant differences in antibiotic use or penicillin-nonsusceptible S pneumoniae colonization between the intervention and control regions.\n A multifaceted educational program for clinicians and parents led to community-wide reductions in antibiotic prescribing, but in child care facilities, there was no apparent impact on judicious antibiotic use or colonization with drug-resistant S pneumoniae. Longer follow-up time or greater reductions in antibiotic use may be required to identify changes in the pneumococcal susceptibility.", "In an open, prospective, and randomized investigation on the prophylactic efficacy of peroral neomycin sulfate-erythromycin base vs intravenous ceftriaxone-metronidazole preparation in colorectal surgery, no significantly diverging results between regimens were recorded (1/27 [3.7%] and 2/27 [7.4%] wound infections, respectively). Commentary is made about the diverging results from earlier studies on antimicrobial prophylaxis and on the multifactorial causality of surgical infection. We believe that variables such as physical condition of the patients, virulence and local resistance patterns of bacteria, and technical skill of the surgeons are far more important in regard to the postoperative outcome concerning septic complications than is the choice of proper antibiotics. Thus, to determine the efficacy of antimicrobial prophylaxis, we call for larger investigations in the future, preferably double-blind, where it is possible to better control and diminish the influence of determinants other than the antibiotics being compared.", "This study was conducted to evaluate the effect of antibiotic prophylaxy on decreasing the frequency of postoperative infections after cesarean sections performed in cases with no prior indication of a high risk of infection.\n A prospective randomized study included 269 cesarean sections without a high risk of infection performed in the Maternity and Neonatology Ward of the Sousse Hospital from February 1991 to July 1991. The patients were randomly divided into two groups. One group received an antibiotic prophylactic treatment including cephapirine, gentamicin and metronidazole) and the second group was given no treatment.\n Antibiotic prophylactic therapy led to a reduction of infectious morbidity after cesarean section in patients without high risk o infection from 33% to 11%. A 66% rate of efficacy was observed. In addition, antibiotics given in this context led to substantial cost reduction both by reducing the cost of antibiotics prescribed in the postoperative period and by reducing the number of days of hospitalization, and thus total cost.\n This study demonstrated the effectiveness of antibiotic prophylaxy for cesarean sections in patients without a high risk of infection. Nevertheless, a reevaluation of the antibiotic protocols and a rigorous operative procedure are essential.", "To estimate and compare the frequencies of inflammatory complications after third molar (M3) surgery in subjects receiving intravenous prophylactic antibiotics or saline placebo.\n Using a placebo-controlled, double-blind, randomized clinical trial, the investigators enrolled a sample composed of subjects who required extraction of at least 1 impacted M3 and requested intravenous sedation or general anesthesia. The predictor variable was treatment group classified as active treatment (penicillin or clindamycin for penicillin-allergic subjects) or placebo (0.9% saline). Study medications were randomly assigned. Both surgeon and subject were blinded to treatment assignment. The medication was administered intravenously prior to any incision. The outcome variable was postoperative inflammatory complication classified as present or absent and included alveolar osteitis (AO) or surgical site infection (SSI). Other variables were demographic, anatomic, or operative. Descriptive and bivariate statistics were computed. Statistical significance was set at P < or = .05, single-tailed test of hypothesis.\n The sample was composed of 118 subjects (n = 59 per study group). In the active treatment group, there were no postoperative inflammatory complications. In the placebo group, 5 subjects (8.5%) were diagnosed with SSI, (P = .03). No subject met the case definition for AO. All SSIs were associated with the removal of partial bony or full bony impacted mandibular M3s.\n In the setting of third molar removal, these results suggest that the use of intravenous antibiotics administered prophylactically decrease the frequency of SSIs. The authors cannot comment on the efficacy of intravenous antibiotics in comparison to other antibacterial treatment regimens, eg chlorhexidine mouthrinse or intrasocket antibiotics.", "To determine the efficacy of antibiotic prophylaxis in percutaneous endoscopic gastrostomy (PEG) as a part of a standardized regimen.\n An open prospective randomised multicenter study in 216 patients. 106 received ceftriaxone 1 g i.v. 30 min preinterventionally and 110 no study medication. A standardized protocol was followed for PEG preparation, insertion, and aftercare; all patients received a 15 French gastrostomy tube. Follow-up of local and systemic infection and clinical course was continued to postintervention day 10. An aggregate erythema and exudation score > 3 or the presence of pus was taken as indicative of peristomal infection. The pharmacoeconomics of antibiotic use were also examined.\n In no-prophylaxis patients, wound infection rates were 23.6% on day 4 and 24.5% on day 10 vs. 7.6% (p < 0.05) and 11.4% (p < 0.05), respectively, in prophylaxis patients. Results were disproportionally better in tumor patients in comparison with neurological patients. Patients systemic infection rates were 11.8% vs. 1.9% in noprophylaxis vs. prophylaxis (p < 0.05), and overall infection rates 36.3% vs. 13.3%, respectively (p < 0.05). Pneumonia was more frequent in patients with underlying neurological disease and reduced in the prophylaxis group. Antibiotic and application costs were similar in both groups (p = 0.400).\n Single-dose ceftriaxone 1 g is a effective prophylaxis against local and systemic infection after PEG and should be a part of a standard regimen.", "The prophylactic effect of a short preoperative loading dose of oral neomycin and erythromycin upon infectious complications following elective operations upon the colon and rectum was compared with the prophylactic effect of systemic administration of metronidazole and gentamicin preoperatively and postoperatively. In this randomized prospective clinical study, 45 patients received neomycin-erythromycin while 48 received metronidazole-gentamicin; all patients were prepared mechanically using whole gut irrigation with a mannitol solution. Both groups were comparable in sex, age, clinical diagnosis and type of operation performed. In the neomycin-erythromycin group, 41 of 45 patients had an uncomplicated postoperative course versus 35 of 48 patients in the other group (p less than 0.001) and fewer wound infections (p less than 0.05). We conclude that the better results observed with the neomycin-erythromycin combination is probably an addition of two effects--the decrease in colon flora and the adequate serum levels of antibiotics during the operation.", "Inappropriate antibiotic use for pulmonary infiltrates is common in the intensive care unit (ICU). We sought to devise an approach that would minimize unnecessary antibiotic use, recognizing that a gold standard for the diagnosis of nosocomial pneumonia does not exist. In a randomized trial, clinical pulmonary infection score (CPIS) (Pugin, J., R. Auckenthaler, N. Mili, J. P. Janssens, R. D. Lew, and P. M. Suter. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic \"blind\" bronchoalveolar lavage fluid. Am. Rev. Respir. Dis. 1991;143: 1121-1129) was used as operational criteria for decision-making regarding antibiotic therapy. Patients with CPIS </= 6 (implying low likelihood of pneumonia) were randomized to receive either standard therapy (choice and duration of antibiotics at the discretion of physicians) or ciprofloxacin monotherapy with reevaluation at 3 d; ciprofloxacin was discontinued if CPIS remained </= 6 at 3 d. Antibiotics were continued beyond 3 d in 90% (38 of 42) of the patients in the standard as therapy compared with 28% (11 of 39) in the experimental therapy group (p = 0.0001). In patients in whom CPIS remained </= 6 at the 3 d evaluation point, antibiotics were still continued in 96% (24 of 25) in the standard therapy group but in 0% (0 of 25) of the patients in the experimental therapy group (p = 0.0001). Mortality and length of ICU stay did not differ despite a shorter duration (p = 0.0001) and lower cost (p = 0.003) of antimicrobial therapy in the experimental as compared with the standard therapy arm. Antimicrobial resistance, or superinfections, or both, developed in 15% (5 of 37) of the patients in the experimental versus 35% (14 of 37) of the patients in the standard therapy group (p = 0.017). Thus, overtreatment with antibiotics is widely prevalent, but unnecessary in most patients with pulmonary infiltrates in the ICU. The operational criteria used, regardless of the precise definition of pneumonia, accurately identified patients with pulmonary infiltrates for whom monotherapy with a short course of antibiotics was appropriate. Such an approach led to significantly lower antimicrobial therapy costs, antimicrobial resistance, and superinfections without adversely affecting the length of stay or mortality.", "We assessed the efficacy of preoperative antibiotic prophylaxis in a prospective trial for patients undergoing insertion of Tenckhoff catheters for continuous ambulatory peritoneal dialysis (CAPD). The prophylactic regimen was a single dose of cefazolin (500 mg) and gentamicin (80 mg) given intravenously half an hour before surgery. There was no significant difference in the number of exit site infections (8 in the antibiotic group vs. 8 in the controls) and the number of episodes of peritonitis (5 in the antibiotic group vs. 2 in the controls). Our study showed that prophylactic preoperative antibiotics did not reduce the number of exit site infections and peritonitis after the insertion of Tenckhoff catheters.", "Two hundred and twenty-nine patients were entered into a study to compare the effectiveness and safety of two single-shot antibiotic regimes in patients undergoing elective colorectal surgery in two district general hospitals. A single shot of intravenous (IV) latamoxef disodium was as effective as an IV combination of cefuroxime and metronidazole in control of wound infection following elective large bowel surgery when given as a bolus at the time of anaesthetic induction. The incidence of major wound infection was 6% and was evenly distributed in the two treatment groups. Half the major wound infections were associated with faecal fistulae. A single shot of IV antibiotic at the time of anaesthetic induction was safe, simple and an effective prophylaxis against major wound infection. There was a low incidence (1.3%) of serious postoperative bleeding and no serious adverse reactions were noted. The overall mortality was 9%. Death was significantly related to elderly patients, a poor performance status, operative contamination and wound infections." ]	A combination of topical and systemic prophylactic antibiotics reduces RTIs and overall mortality in adult patients receiving intensive care. Treatment based on the use of topical prophylaxis alone reduces respiratory infections but not mortality. The risk of resistance occurring as a negative consequence of antibiotic use was appropriately explored only in one trial which did not show any such effect.
CD007472	[ "11806295", "7954233", "12515103", "19092335", "16710858", "11896097", "18424367", "12143204", "11286304", "2200559", "16427543", "773198", "15798459", "12734081" ]	[ "[Trimetazidine prevents ischemia-reperfusion injury in hepatic surgery under vascular clamping].", "Treatment of liver metastases from colorectal cancer with hepatic artery occlusion, intraportal 5-fluorouracil infusion, and oral allopurinol. A randomized clinical trial.", "[Coronary artery disease observed in general hospitals: ETTIC study. Comparison between trimetazidine and mononitrate isosorbide for patients receiving betablockers].", "A randomized controlled trial on pharmacological preconditioning in liver surgery using a volatile anesthetic.", "Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: a prospective randomized study.", "Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy--an intergroup study.", "Ischemic preconditioning improves postoperative outcome after liver resections: a randomized controlled study.", "The role of allopurinol in human liver ischemia/reperfusion injury: a prospective randomized clinical trial.", "Anti-ischaemic efficacy and tolerability of trimetazidine administered to patients with angina pectoris: results of three studies.", "Prospective randomized controlled trial of hepatic arterial embolization or infusion chemotherapy with 5-fluorouracil and degradable starch microspheres for colorectal liver metastases.", "Ischemic preconditioning for major liver resection under vascular exclusion of the liver preserving the caval flow: a randomized prospective study.", "Effect of methylprednisolone on myocardial preservation during coronary artery surgery.", "Complete versus selective portal triad clamping for minor liver resections: a prospective randomized trial.", "Feasibility of adjuvant hepatic arterial infusion of chemotherapy after radiofrequency ablation with or without resection in patients with hepatic metastases from colorectal cancer." ]	[ "Clamping the hepatic pedicle (or Pringle's manoeuvre) is frequently used to reduce blood loss during liver surgery. This induces a normothermic ischaemia of the overall liver. In this study we have investigated the anti-ischaemic effect of trimetazidine during surgery on hydatid cysts of the liver requiring vascular clamping of the hepatic pedicle. Seventy-six hepatic pericystectomies were performed under a 40 min normothermic ischaemia. Two randomized groups including 38 patients each received daily either trimetazidine (80 mg/kg, group 1) or placebo (group 2) for 5 days before surgery. The effect of trimetazidine was evaluated on different parameters, the macroscopic appearance of the tissue, the ATP content in liver biopsies obtained before and after 15, 30 and 60 min reperfusion, the activity of the aminotransferase in the plasma and the plasma concentrations of reduced and oxidized gluthatione. No mortality was observed. The duration of hospital stay was reduced for patients treated with trimetazidine (8 +/- 1 days compared with 11 +/- 1.5 days for patients in group 2; p < 0.05). Morbidity rate was lower in group 1 (11 per cent) than in group 2 (18.5 per cent) but the decrease was not significant. Trimetazidine treatment reduced cytolysis (p < 0.05 on day 1, day 3, day 5), increased liver ATP content and limited the increase of reduced and oxidized gluthatione in the plasma during reperfusion. These results suggest that trimetazidine alleviates ischaemia-reperfusion injury during liver surgery and may allow extension of the ischaemic period without damage to the liver.", "Regional therapy for colorectal liver metastases aimed at prolonging survival has not been tested fully in a randomized trial with untreated control subjects. This study explored the efficacy of temporary hepatic artery occlusion followed by intraportal infusion of 5-fluorouracil (5-FU) and oral allopurinol as biochemical modulators in prolonging the survival of patients with nonresectable liver metastases and no extrahepatic cancer.\n Eighty-four patients were considered for randomization, of whom 24 were excluded at laparotomy because of extrahepatic cancer (n = 17) or resectable lesions (n = 5). In two patients, no cancer was identified in the liver. Thirty-two patients were allocated to receive treatment, and 28 were allocated to receive no regional or systemic treatment. Six patients were excluded after randomization because of major protocol violations.\n The median survival time for patients was 17 months (range, 0-66), and for control subjects, the median was 8 months (range, 0-31). Log rank analysis demonstrated a significant survival benefit for treatment versus no treatment (P = 0.0039). (In two patients, early death was due to toxicity from the wrong dose of 5-FU and the wrong route of administration, respectively; the mean and median survival were reduced by 1 month).\n This study identified a treatment modality that prolongs survival in patients with nonresectable liver metastases and no extrahepatic metastases from colorectal cancer, suggesting that control subjects receiving no therapy may not be necessary in future randomized trials.", "The extended use of interventional surgery of revascularisation has modified the prognosis and the evolution of ischaemic heart diseases. However, both coronary artery bypass graft and percutaneous transluminal coronary angioplasty failed to make the symptomatic or subclinical ischaemic manifestations of chronic coronary insufficiency disappear. The interest of using betablockers as a first-line therapy was widely demonstrated. However, their combination with another efficient molecule is often necessary. The aim of this trial has been to appreciate the efficiency of the association of a betablocker with either trimetazidine or with isosorbide monoitrate. Hundred and eighty five patients retaining a positive effort test despite 100 mg of atenolol, received in addition, either 60 mg of trimetazidine (93 cases) of 60 mg of isosorbide mononitrate (92 cases) for a two-month period and are then re-evaluated at the end of this period. The ischaemic threshold is delayed in a significant way in both groups (p < 0.0001; trimetazidine +7%, isosorbide mononitrate +10.7%). Twenty-three percent of the exercise tests under trimetzidine and 19% under isosorbide mononitrate become negative after two months of the therapeutic combination. The clinical improvement is even clearer with the disappearance of the angina crisis during the week before the second exercise test in 63% of the cases under trimetazidine and 54% of the cases under isosorbide mononitrate, among the patients who had kept it under atenolol at the inclusion. In conclusion, the combination of a second efficient molecule, trimetazidine or isosorbide mononitrate, brings a functional and objective improvement to patients with insufficient chronic coronary disease not totally controlled using a betablocker, even with high dosage. One should notice two important advantages in favour of the trimetazidine: one is practical due to a better tolerance (lack of cephalalgia), the other is conceptual (use of the complementary metabolic approach of cellular oxygenation rather than the haemodynamic approach of nitrate compounds which are already in concurrency with all other anti-ischaemic molecules).", "To evaluate the effects of pharmacological preconditioning with a volatile anesthetic in patients undergoing liver resection with inflow occlusion.\n In liver surgery, ischemic preconditioning and intermittent clamping are the only established protective strategies to reduce tissue damage due to ischemia during inflow occlusion. Preconditioning with volatile anesthetics has provided protection against cardiac and renal ischemic injury in several animal models through NO and HO-1 pathways. But pharmacological preconditioning has never been tested in patients undergoing liver surgery in a randomized trial.\n Sixty-four patients undergoing liver surgery with inflow occlusion were randomized intraoperatively for preconditioning with sevoflurane or not (ClinicalTrials.gov NCT00516711). Anesthesia was performed intravenously with propofol. Thirty minutes before inflow occlusion propofol was replaced by sevoflurane in the preconditioning group. Primary endpoint was postoperative liver injury assessed by peak values of liver transaminases. Postoperative complications were recorded according to an established scoring system.\n Sevoflurane preconditioning significantly limited the postoperative increase of serum transaminase levels by 261 U/L (95% CI, 65 to 458; P = 0.01) for the ALT and by 239 (95% CI, -2 to 480; P = 0.05) for the AST corresponding to decreases of baseline levels of 35% and 31%, respectively. Patients with steatosis had an even better benefit than patients without steatosis. The rates of any complication (risk ratio 0.46; 95% CI, 0.25 to 0.85; P = 0.006) and of severe complications requiring invasive procedures (risk ratio 0.25; 95% CI, 0.06 to 1.08; P = 0.05) were also lowered by preconditioning.\n This first randomized trial of pharmacological preconditioning in liver surgery in humans showed a protective effect of preconditioning with volatile anesthetics. This strategy may provide a new and easily applicable therapeutic option to protect the liver and to lower complication rates.", "Hepatic injury secondary to warm ischemia-reperfusion (I/R) injury and alterations in haemostatic parameters are often unavoidable events after major hepatic resection. The release of inflammatory mediator is believed to play a significant role in the genesis of these events. It has been suggested that preoperative steroid administration may reduce I/R injury and improve several aspects of the surgical stress response. The aim of this prospective randomized study was to investigate the clinical benefits on I/R injury and systemic responses of preoperatively administered corticosteroids. Seventy-six patients undergoing liver resection were randomized either to a steroid group or to a control group. Patients in the steroid group received preoperatively 500 mg of methylprednisolone. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, coagulation parameters, and inflammatory mediators, interleukin 6 and tumor necrosis factor alpha were compared between the 2 groups. Length of stay, and type and number of complications were recorded as well. Postoperative serum levels of ALT, AST, total bilirubin, and inflammatory cytokines were significantly lower in the steroid than in the control group at postoperative days 1 and 2. Changes in hemostatic parameters were also significantly attenuated in the steroid group. In conclusion, the incidence of postoperative complications in the steroid group tended to be significantly lower than the control group. It is of clinical interest that preoperative steroids administration before major surgery may reduce I/R injury, maintain coagulant/anticoagulant homeostasis, and reduce postoperative complications by modulating the inflammatory response.", "Despite technical improvements that have minimized the morbidity and mortality of hepatic surgery, the long-term outcome of resection of hepatic metastases of colorectal cancer remains poor, with the majority of patients experiencing treatment failure in the liver. Because arterial chemotherapy regimens targeted to the liver have demonstrated high response rates, an intergroup trial of adjuvant therapy for patients undergoing hepatic resection of liver metastases from colorectal cancer was initiated.\n Patients with one to three potentially resectable metastases were randomized preoperatively to receive no further therapy (control arm, 56 patients) or postoperative hepatic arterial floxuridine combined with intravenous continuous-infusion fluorouracil (chemotherapy arm, 53 patients). After exclusion of patients identified as ineligible for the planned treatment at the time of surgery, there were 45 control patients and 30 on the chemotherapy arm. The study was powered to evaluate improvement in time to recurrence and hepatic disease-free survival, not overall survival.\n The 4-year recurrence-free rate was 25% for the control arm and 46% for the chemotherapy group (P =.04). The 4-year liver recurrence-free rate was 43% in the control group and 67% in the chemotherapy group (P =.03). The median survival of the 75 assessable patients was 49 months for the control arm and 63.7 months for the chemotherapy arm (P =.60). The median survival of all 109 patients was 47 months for the control arm compared with 34 months for the chemotherapy arm (P =.19)\n These data demonstrate that adjuvant intra-arterial and intravenous chemotherapy was beneficial in prolonging time to recurrence and pre-venting hepatic recurrence after hepatic resection of colorectal cancer.", "Clamping of the portal triad (Pringle maneuver) prevents blood loss during liver resection, but leads to liver injury upon reperfusion. Ischemic preconditioning (IP) has been shown to protect the liver against prolonged ischemic injury in animal models. However, the clinical value of this procedure has not yet been established.\n 61 Patients undergoing hepatic resection under inflow occlusion were randomized to either to receive (Group-A n = 30) or not to receive (Group-B n = 31) an IP (10 minutes of ischemia followed 10 minutes of reperfusion).\n Mean (+/- SD)/ Group-A vs. Group-B. Pringle time of 34 +/- 14 and 33 +/- 12 minutes and the extent of resected liver tissue (2.7 +/- 1.3 vs. 2.7 +/- 1.1 segments) were comparable in both groups. Complications, including death, severe liver dysfunction and biliary leakage occurred in 6 patients of Group-A vs. 14 patients of Group-B (p<0.05). Intraoperative blood loss was significantly lower in Group-A (1.28 +/- 0.91 l vs. 1.94 +/- 0.76 l; p<0.001) with 5 vs. 15 patients requiring transfusions (p<0.01). In a multivariate analysis the duration of the Pringle maneuver (p<0.05) and the absence of preconditioning (p<0.05) were independent predictors for the occurrence of postoperative complications.\n IP protects against reperfusion injury, reduces the incidence of complications after hepatic resection under inflow occlusion and is simple to use in clinical practice.", "To investigate the effect of pretreatment with allopurinol on oxidative stress during reperfusion and the role in liver tissue protection in partial liver resections for colorectal cancer metastases confined to the liver.\n Prospective, randomized, clinical trial, single center, Leiden University Medical Center, The Netherlands.\n Curative partial liver resection of colorectal metastases in 16 patients with or without allopurinol pretreatment, between June 1992 and February 1994.\n Partial liver resections with Pringle maneuver, intravenous allopurinol versus no allopurinol.\n The effect of allopurinol on liver cell damage caused by ischemia/reperfusion studied by measuring malondialdehyde, glutathione, glutathione disulfide, vitamin C, liver enzymes and blood clotting factors in blood samples. Morbidity and mortality were also evaluated.\n Pretreatment with allopurinol had no significant effect on any of our study parameters.\n Because ischemia/reperfusion damage is little in our study, pretreatment with allopurinol is of no value.", "Several clinical studies have compared the anti-ischaemic properties of trimetazidine used as monotherapy with those of standard anti-anginal therapy. In the treatment of uncontrolled angina pectoris, the addition of a metabolic agent such as trimetazidine to existing therapy with a haemodynamic agent would appear to confer advantages over the addition of a second haemodynamic agent. Here we report the results of three studies conducted in Poland, the Czech Republic and Hungary that provide additional evidence for the beneficial effects of combining trimetazidine with a conventional haemodynamic agent such as beta-blockers, long-acting nitrate or calcium channel blockers. This combination provided significant benefits in terms of improved exercise capacity and decreased number of angina attacks along with a good tolerability profile.", "Survival benefit from hepatic artery embolization (HAE) or hepatic arterial infusion chemotherapy (HAI) in patients with unresectable colorectal liver metastases has not previously been assessed in a randomized controlled trial. Sixty-one patients were randomized, 20 to receive no treatment, 22 to receive HAE, and 19 to receive HAI with 5-fluorouracil and degradable starch microspheres. Both treatments were acceptable to the patients in terms of low treatment morbidity rate. Median survival from diagnosis of metastases was 9.6 months for controls, 8.7 months for the HAE group and 13.0 months in the HAI group. There was no apparent survival benefit for the HAE group. The increased survival in the HAI group was observed in all the subgroups analysed but failed to reach statistical significance. The greatest observed benefit was achieved in the subgroup with less than 50 per cent hepatic replacement with tumour at presentation (median survival from diagnosis 10.0 months for controls, 10.2 months for HAE and 23.6 months for HAI); 36 per cent of patients developed extrahepatic disease recurrence. No significant benefit has been shown from either HAE or HAI, but a more carefully selected group of patients with only low volume hepatic disease may benefit from HAI therapy.", "Two randomized prospective studies suggested that ischemic preconditioning (IP) protects the human liver against ischemia-reperfusion injury after hepatectomy performed under continuous clamping of the portal triad. The primary goal of this study was to determine whether IP protects the human liver against ischemia-reperfusion injury after hepatectomy under continuous vascular exclusion with preservation of the caval flow.\n Sixty patients were randomly divided into two groups: with (n=30; preconditioning group) and without (n=30; control group) IP (10 minutes of portal triad clamping and 10 minutes of reperfusion) before major hepatectomy under vascular exclusion of the liver preserving the caval flow. Serum concentrations of aspartate transferase, alanine transferase, glutathione-S-transferase, and bilirubin and prothrombin time were regularly determined until discharge and at 1 month. Morbidity and mortality were determined in both groups.\n Peak postoperative concentrations of aspartate transferase were similar in the groups with and without IP (851 +/- 1,733 IU/L and 427 +/- 166 IU/L respectively, p=0.2). A similar trend toward a higher peak concentration of alanine transferase and glutathione-S-transferase was indeed observed in the preconditioning group compared with the control group. Morbidity and mortality rates and lengths of ICU and hospitalization stays were similar in both groups.\n IP does not improve liver tolerance to ischemia-reperfusion after hepatectomy under vascular exclusion of the liver with preservation of the caval flow. This maneuver does not improve postoperative liver function and does not affect morbidity or mortality rates. The clinical use of IP through 10 minutes of warm ischemia in this technique of hepatectomy is not currently recommended.", "It has been proposed that a single preoperative dose of a corticosteroid may protect the myocardium from ischemic injury during open heart surgery. To test this hypothesis, a prospective, randomized, double blind study was carried out in ninety-five patients undergoing coronary bypass surgery using intermittent ischemic arrest with systemic and local hypothermia. Half the patients received 2 gm (approximately 30 mg/kg) of methylprednisolone 2 hours prior to the initiation of cardiopulmonary bypass and the other half received a placebo. Postoperative electrocardiograms and blood levels of serum creatine phosphokinase (CPK), lactic dehydrogenase (LDH), and serum glutamic oxalacetic transaminase (SGOT) were compared in the two groups. No apparent difference was noted in the number of patients with significantly elevated levels of CPK, LDH, or SGOT or in the number with positive isoenzyme patterns of CPK and LDH. Moreover, there was no significant difference in the mean values of CPK, LDH, or SGOT between the two groups. The number of patients with electrocardiographic evidence of myocardial injury (10 per cent) was the same in both groups and no difference was noted in (1) the ease with which patients could be weaned from cardiopulmonary bypass, (2) postoperative arrhythmias, (3) postoperative bleeding, (4) postoperative respiratory insufficiency, and (5) length of hospital stay. It is concluded that a single preoperative dose of 2 gm of methylprednisolone offers no demonstrable protection to the myocardium from the effects of ischemia during coronary artery bypass surgery.", "To evaluate the feasibility, safety, efficacy, amount of hemorrhage, postoperative complications, and ischemic injury of selective clamping in patients undergoing minor liver resections.\n Inflow occlusion can reduce blood loss during hepatectomy. However, Pringle maneuver produces ischemic injury to the remaining liver. Selective hemihepatic vascular occlusion technique can reduce the severity of visceral congestion and total liver ischemia.\n Eighty patients undergoing minor hepatic resection were randomly assigned to complete clamping (CC) or selective clamping (SC). Hemodynamic parameters, including portal pressure and the hepatic venous pressure gradient (HVPG), were evaluated. The amount of blood loss, measurements of liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and postoperative evolution were also recorded.\n No differences were observed in the amount of hemorrhage (671 +/- 533 mL versus 735 +/- 397 mL; P = 0.54) or the patients that required transfusion (10% versus 15%; P = 0.55). There were no differences on postoperative morbidity between groups (38% versus 29%; P = 0.38). Cirrhotic patients with CC had significantly higher ALT (7.7 +/- 4.6 versus 4.5 +/- 2.7 mukat/L, P = 0.01) and AST (10.2 +/- 8.7 versus 4.9 +/- 2.1 mukat/L; P = 0.03) values on the first postoperative day than SC. The multivariate analysis demonstrated that high central venous pressure, HVPG >10 mm Hg, and intraoperative blood loss were independent factors related to morbidity.\n Both techniques of clamping are equally effective and feasible for patients with normal liver and undergoing minor hepatectomies. However, in cirrhotic patients selective clamping induces less ischemic injury and should be recommended. Finally, even for minor hepatic resections, central venous pressure, HVPG, and intraoperative blood loss are factors related to morbidity and should be considered.", "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." ]	Trimetazidine, methylprednisolone, and dextrose may protect against ischaemia reperfusion injury in elective liver resections performed under vascular occlusion, but this is shown in trials with small sample sizes and high risk of bias. The use of these drugs should be restricted to well-designed randomised clinical trials before implementing them in clinical practice.
CD001288	[ "8625660", "11243949", "19863361", "9713447", "10343624", "15363007" ]	[ "Effects of long-term treatment with corticosteroids in COPD.", "Systemic glucocorticoids in severe exacerbations of COPD.", "Effect of fluticasone propionate/salmeterol (250/50) on COPD exacerbations and impact on patient outcomes.", "Randomised controlled trial of inhaled corticosteroids in patients with chronic obstructive pulmonary disease.", "Long term effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis.", "Does addition of inhaled steroid to combined bronchodilator therapy affect health status in patients with COPD?" ]	[ "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.", "This study aimed to compare the efficacies of 3-day and 10-day courses of methylprednisolone (MP) treatment in severe COPD exacerbations necessitating hospitalization for respiratory failure.\n Prospective, randomized, single-blind study.\n Tertiary-care center.\n Thirty-six patients were included in the study and randomized into two groups: group 1 received MP, 0.5 mg/kg q6h for 3 days, and group 2 was administered the same dosage of MP for the first 3 days, after which it was tapered and terminated on the tenth day. There was no difference between the groups for age, baseline FEV(1), PaO(2), PaCO(2), and pH levels. One patient in group 1 who developed pneumothorax and one patient in group 2 who had steroid-related psychosis could not complete the study.\n Both groups showed significant improvements in PaO(2) and FEV(1) levels, but these were more marked in group 2 (p = 0.012 and p = 0.019, respectively). There was a significant increase in FVC levels in group 2 only (p = 0.003). Group 2 also had a more marked improvement in dyspnea on exertion. There was no difference between the two groups with regards to other parameters, including pH, PaCO(2) levels, and other symptom scores. Six patients in group 1 and five patients in group 2 developed new exacerbations within the following 6 months. Hyperglycemia occurred in two patients in each group.\n In severe COPD exacerbations, a 10-day course of steroid treatment is more effective than a 3-day course in improving the outcome, but has no benefit in reducing exacerbation rates.", "Prevention and treatment of COPD exacerbations are recognized as key goals in disease management. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/salmeterol 250 mcg/50 mcg (FSC 250/50) and salmeterol 50 mcg (SAL) twice-daily on moderate/severe exacerbations. Subjects received treatment with FSC 250/50 during a one month run-in, followed by randomization to FSC 250/50 or SAL for 52 weeks. Moderate/severe exacerbations were defined as worsening symptoms of COPD requiring antibiotics, oral corticosteroids and/or hospitalization. In 797 subjects with COPD (mean FEV(1) = 0.98L, 34% predicted normal), treatment with FSC 250/50 significantly reduced the annual rate of moderate/severe exacerbations by 30.4% compared with SAL (1.10 and 1.59 per subject per year, respectively, p < 0.001), the annual rate of exacerbations requiring oral corticosteroids by 34% (p < 0.001) and the annual rate of moderate/severe exacerbations requiring hospitalization by 36% (p = 0.043). Clinical improvements observed during run-in treatment with FSC 250/50 were better maintained over 52 weeks with FSC 250/50 compared to SAL. Statistically significant reductions in albuterol use, dyspnea scores, and nighttime awakenings and numerical benefits on quality of life were seen with FSC 250/50 compared with SAL. The incidence of adverse events was similar across groups. Pneumonia was reported more frequently with FSC 250/50 compared with SAL (7% vs. 2%). FSC 250/50 is more effective than SAL at reducing the rate of moderate/severe exacerbations. These data confirm the beneficial effect of FSC on the management of COPD exacerbations and support the use of FSC in patients with COPD.", "Inhaled corticosteroids are known to be beneficial for patients with asthma, but their role in treating patients with stable chronic obstructive pulmonary disease (COPD) remains controversial. A study was undertaken to determine whether inhaled corticosteroids are of functional benefit in patients who did not show improvement with a trial of oral corticosteroids.\n In phase I patients with stable COPD were given a two week course of oral placebo followed by two weeks of prednisone 40 mg per day in a single blind manner to distinguish between responders and non-responders to oral corticosteroids. In phase II a double blind, randomised, parallel group trial of inhaled budesonide 1600 micrograms per day versus placebo was carried out in 79 nonresponders to oral corticosteroids. The primary outcome measure was forced expiratory volume in one second (FEV1), and secondary outcome measures were exercise capacity, dyspnoea with exertion, quality of life, peak expiration flow rate, and respiratory symptoms.\n Randomisation allocated 39 subjects to inhaled corticosteroids and 40 to placebo. There was no difference in the change in FEV1 from baseline between the treatment and placebo groups; mean difference -12 ml (95% CI -88 to 63) at three months and -4 ml (95% CI -95 to 87) at six months. The proportion of patients with a 15% or greater improvement was no higher among those receiving inhaled corticosteroids than in the placebo group at any of the follow up visits. Changes in secondary outcomes were also no different.\n Inhaled corticosteroids, even at high doses, were of no physiological or functional benefit in these patients with advanced COPD.", "The role of inhaled corticosteroids in the long term management of chronic obstructive pulmonary disease (COPD) is still unclear. A meta-analysis of the original data sets of the randomised controlled trials published thus far was therefore performed. The main question was: \"Are inhaled corticosteroids able to slow down the decline in lung function (FEV1) in COPD?\"\n A Medline search of papers published between 1983 and 1996 was performed and three studies were selected, two of which were published in full and one in abstract form. Patients with \"asthmatic features\" were excluded from the original data. Ninety five of the original 140 patients treated with inhaled corticosteroids (81 with 1500 micrograms beclomethasone daily, six with 1600 micrograms budesonide daily, and eight with 800 micrograms beclomethasone daily) and 88 patients treated with placebo (of the initial 144 patients) were included in the analysis. The effect on FEV1 was assessed by a multiple repeated measurement technique in which points of time in the study and treatment effects (inhaled corticosteroids compared with placebo) were investigated.\n No baseline differences were observed (mean age 61 years, mean FEV1 45% predicted). The estimated two year difference in prebronchodilator FEV1 was +0.034 l/year (95% confidence interval (CI) 0.005 to 0.063) in the inhaled corticosteroid group compared with placebo. The postbronchodilator FEV1 showed a difference of +0.039 l/year (95% CI -0.006 to 0.084). No beneficial effect was observed on the exacerbation rate. Worsening of the disease was the reason for drop out in four patients in the treatment group compared with nine in the placebo group. In the treatment group six of the 95 subjects dropped out because of an adverse effect which may have been related to the treatment compared with two of the 88 patients in the placebo group.\n This meta-analysis in patients with clearly defined moderately severe COPD showed a beneficial course of FEV1 during two years of treatment with relatively high daily dosages of inhaled corticosteroids.", "Withdrawal of corticosteroid is associated with a deterioration of health status in COPD. In this study the aim was to determine whether high dose inhaled corticosteroid improves quality of life in patients with COPD.\n In total, 38 male patients with moderate COPD were included in the study. Baseline quality of life scores were determined using a Turkish version of the St George's Respiratory Questionnaire (SGRQ). Patients were randomly divided into two groups. Group 1 consisted of 20 patients who received existing bronchodilator therapy plus inhaled corticosteroid (800 micro g budesonide) for 12 weeks, while 18 patients in group 2 received bronchodilator and placebo. The SGRQ was repeated after the treatment period.\n All patients were male and mean age was 67 +/- 8.2 years. Symptom, activity, impact, and total scores were assessed and a difference of four units with treatment was considered to be clinically significant. Total score and activity score were decreased by six units and eight units, respectively, in the placebo group while symptom and impact scores did not change significantly. Total scores and the three component scores improved significantly in the corticosteroid group compared to the placebo group (Deltatotal score: -22 in corticosteroid group, -6 in placebo group, P < 0.01).\n Inhaled corticosteroid improved quality of life scores in patients with COPD, without significant improvement in airflow obstruction parameters. Since improvement of health status is one of the important aims in COPD treatment, use of inhaled corticosteroids should be considered from this perspective." ]	Treatment of an exacerbation of COPD with oral or parenteral corticosteroids significantly reduces treatment failure and the need for additional medical treatment and shortens hospital stay. It increases the rate of improvement in lung function and dyspnoea and the improvement continues during treatment, but there is a significantly increase in the risk of an adverse drug event occurring. The optimal dose and length of treatment regime needs to be better defined.
CD007906	[ "9534826", "11157431", "10353452", "11989986", "12027240", "9545998", "7953039", "17335327", "16675365", "16153354", "16816304", "15240438", "15113492", "475542", "19833787", "17592908", "9366661", "15271109", "7953031", "16267182", "7561818", "15240088", "12456522", "8353699", "7487784", "21159375", "2836295", "6578788", "18088263" ]	[ "Intensive case management for the severely mentally ill. Controlled trial.", "Intellectual functioning and outcome of patients with severe psychotic illness randomised to intensive case management. Report from the UK700 trial.", "Intensive case management in Australia: a randomized controlled trial.", "Heavy users of acute psychiatric beds: randomized controlled trial of enhanced community management in an outer London borough.", "Outcome of case management based on the strengths model compared to standard care. A randomised controlled trial.", "Randomized trial of general hospital and residential alternative care for patients with severe and persistent mental illness.", "Family-based intervention for schizophrenic patients in China. A randomised controlled trial.", "Are day hospitals effective for acutely ill psychiatric patients? A European multicenter randomized controlled trial.", "Effectiveness of an intervention to reduce sickness absence in patients with emotional distress or minor mental disorders: a randomized controlled effectiveness trial.", "A trial of problem-solving by community mental health nurses for anxiety, depression and life difficulties among general practice patients. The CPN-GP study.", "Outcomes of an effectiveness trial of cognitive-behavioural intervention by mental health nurses in schizophrenia.", "Effect of joint crisis plans on use of compulsory treatment in psychiatry: single blind randomised controlled trial.", "Exploratory cluster randomised controlled trial of shared care development for long-term mental illness.", "A comparative trial of home and hospital psychiatric care. One-year follow-up.", "Randomized controlled trial of outpatient mentalization-based treatment versus structured clinical management for borderline personality disorder.", "Psychoeducation in schizophrenia: 7-year follow-up concerning rehospitalization and days in hospital in the Munich Psychosis Information Project Study.", "A randomized trial of assertive community treatment for homeless persons with severe mental illness.", "A randomized, controlled trial of an intensive community nurse-supported discharge program in preventing hospital readmissions of older patients with chronic lung disease.", "Home-based versus hospital-based care for people with serious mental illness.", "A whole system study of intermediate care services for older people.", "Comparative effectiveness of three approaches to serving people with severe mental illness and substance abuse disorders.", "A randomized controlled trial of a mutual support group for family caregivers of patients with schizophrenia.", "Advance directives for patients compulsorily admitted to hospital with serious mental illness. Randomised controlled trial.", "A controlled trial of home-based acute psychiatric services. I: Clinical and social outcome.", "The effect on hospital admissions of psychiatric case management involving general practitioners: preliminary results.", "Effectiveness of an intervention led by lay health counsellors for depressive and anxiety disorders in primary care in Goa, India (MANAS): a cluster randomised controlled trial.", "Assertive case management in three CMHCs: a controlled study.", "Psychiatric hospital versus community treatment: the results of a randomised trial.", "A randomized controlled trial of a community nurse-supported hospital discharge programme in older patients with chronic heart failure." ]	[ "The aim was to compare the efficacy of intensive clinical case management (ICM) with standard community care in the management of 'hard to treat' patients with a severe mental illness.\n A randomised controlled trial was carried out in East Lambeth, a deprived area of inner London. Seventy people with psychosis designated as 'hard to treat' by referring teams were included; 35 were randomised to ICM (case load eight patients per worker), and 35 to standard care, which offered follow-up by a community psychiatric nursing service (30 patients per worker). Outcome measures were admissions and hospital bed utilisation; contact with services; symptomatology; social behaviour; social functioning; quality of life; patients' satisfaction with care at 9 and 18 months.\n There were no differences in patients' symptoms, social behaviour or social functioning. Quality of life was significantly improved in patients receiving ICM at 9 months. Satisfaction with care was significantly greater among case-managed patients. All ICM patients remained in contact with services throughout the study, while six control patients were refusing all contact with services at 18 months.\n ICM failed to improve the clinical outcome of 'hard to treat' patients. The service was successful in maintaining contact with patients, was greatly appreciated and had a positive effect on their perceived quality of life.", "Little research has been carried out on the benefits of intensive case management (ICM) for people with borderline IQ and severe mental illness.\n To compare outcome and costs of care of patients with severe psychotic illness with borderline IQ to patients of normal IQ and to assess whether ICM is more beneficial for the former than for the latter.\n The study utilises data from the UK700 multi-centre randomised controlled trial of case management. The main outcome measure was the number of days spent in hospital for psychiatric reasons. Secondary outcomes were costs of care and clinical outcome.\n ICM was significantly more beneficial for borderline-IQ patients than those of normal IQ in terms of reductions in days spent in hospital, hospital admissions, total costs and needs and increased satisfaction.\n ICM appears to be a cost-effective strategy for a subgroup of patients with severe psychosis with cognitive deficits.", "This study compared intensive case management (ICM) with standard clinical case management in a well-resourced community mental health service in Australia. A total of 73 severely disabled clients of an existing clinical service were randomly allocated to either ICM (caseload 10 clients per clinician) or standard case management (caseload up to 30 clients per clinician) and followed up for 12 months. A greater proportion of clients receiving ICM showed improved social functioning, these clients had fewer psychiatric hospital admissions involving police, and were more likely to engage and remain in treatment compared to those who received standard case management. Clients receiving ICM did not show a reduction in hospitalization duration or total number of episodes. It is suggested that future studies of ICM should focus on which aspects of treatment produce positive outcomes, how they can be applied to routine clinical settings, and over what period of time outcomes are sustained.", "Heavy users of psychiatric services, often defined as the population that uses the most beds, consume a large part of the resources used by the whole service, despite being relatively small in number. Any intervention that reduces heavy use is therefore likely to lead to significant savings, and enhancement of standard care using a form of intensive case management akin to assertive community treatment was thought to be a pragmatic strategy for testing in this group.\n The effectiveness of enhanced community management (ECM) was compared with standard care alone in heavy users, who represented the 10% of patients with the highest number of hospital admissions and occupied bed days over the previous 6.5 years in an outer London borough. One hundred and ninety-three patients were randomly assigned to ECM or standard care and their use of services was determined after 1 and 2 years, with assessments of costs, clinical symptoms, needs, and social function made before entry into the study and after 1 and 2 years.\n Despite a 24 fold increase in community contacts in the study group, there were no significant differences between the two groups in any of the main outcome measures. Small savings on in-patient and day-hospital service costs were counterbalanced by the increased costs of outpatient and community care for the subjects assigned to ECM. Clinical outcome data derived from interviews in two-thirds of the subjects were similar in both groups.\n Providing additional intensive community focused care to a group of heavy users of psychiatric in-patient services in an outer London borough does not lead to any important clinical gains or reduced costs of psychiatric care.", "The outcome of less intensive case management services, such as the strengths model, is still inconclusive, which suggests a need for more controlled studies. The aim of the present study was to investigate the outcome of a strengths model of case management service (SCM) compared to standard care.\n Seventy-seven clients with a mental illness and a serious impairment in functioning in social contacts, housing or work situation were randomly allocated to SCM or standard care. Outcome was assessed with regard to use of psychiatric services, changes in symptomatology, psychosocial functioning, social network, needs for care, quality of life and client satisfaction with care. The follow-up period was 36 months.\n The results showed a greater reduction in needs for care in clients receiving SCM. No differences in clinical or social outcome were shown. Clients receiving SCM also used significantly less days in psychiatric inpatient services and were generally more satisfied with the psychiatric services offered.\n SCM failed to improve clinical and social outcome compared to standard care, but was more successful in reducing days spent in hospital, and the clients were also more satisfied with the service compared to standard care.", "Severe and persistent mental illnesses are often lifelong and characterized by intermittent exacerbations requiring hospitalization. Providing needed care within budgetary constraints to this largely publicly subsidized population requires technologies that reduce costly inpatient episodes. The authors report a prospective randomized trial to test the clinical effectiveness of a model of acute residential alternative treatment for patients with persistent mental illness requiring hospital-level care.\n Patients enrolled in the Montgomery County, Md., public mental health system who experienced an illness exacerbation and were willing to accept voluntary treatment were randomly assigned to the acute psychiatric ward of a general hospital or a community residential alternative. There were no psychopathology-based exclusion criteria. Treatment episode symptom improvement, satisfaction, discharge status, and 6-month pre- and postepisode acute care utilization, psychosocial functioning, and patient satisfaction were assessed.\n Of 185 patients, 119 (64%) were successfully placed at their assigned treatment site. Case mix data indicated that patients treated in the hospital (N = 50) and the alternative (N = 69) were comparably ill. Treatment episode symptom reduction and patient satisfaction were comparable for the two settings. Nine (13%) of 69 patients randomly assigned to the alternative required transfer to a hospital unit; two (4%) of 50 patients randomly assigned to the hospital could not be stabilized and required transfer to another facility. Psychosocial functioning, satisfaction, and acute care use in the 6 months following admission were comparable for patients treated in the two settings and did not differ significantly from functioning before the acute episode.\n Hospitalization is a frequent and high-cost consequence of severe mental illness. For patients who do not require intensive general medical intervention and are willing to accept voluntary treatment, the alternative program model studied provides outcomes comparable to those of hospital care.", "We developed and evaluated a comprehensive, ongoing intervention for families of schizophrenic patients appropriate for China's complex family relationships and unique social environment.\n Sixty-three DSM-III-R schizophrenic patients living with family members were enrolled when admitted to hospital and randomly assigned to receive standard care or a family-based intervention that included monthly 45-minute counselling sessions focused on the management of social and occupational problems, medication management, family education, family group meetings, and crisis intervention.\n At 6, 12, and 18-month follow-ups by blind evaluators, the proportion of subjects rehospitalised was lower, the duration of rehospitalisation was shorter, and the duration of employment was longer in the experimental group than in the control group; these differences were statistically significant at the 12 and 18-month follow-ups and were not explained by differences in drug compliance. Family intervention was associated with significantly lower levels of family burden.\n This intervention is less costly than standard treatment, is suitable for urban families of schizophrenic patients in China and feasible given the constraints of the Chinese mental health system.", "Acute psychiatric day care has been proposed as an alternative to conventional inpatient care, yet the evidence of its effectiveness is inconsistent and based only on single-site studies in 3 countries. The aim of this multicenter randomized controlled trial was to establish the effectiveness of acute day hospital care in a large sample across a range of mental health care systems.\n The trial was conducted from December 2000 to September 2003 in 5 European countries, with a sample of 1117 voluntarily admitted patients. Immediately before or very shortly after admission to the participating psychiatric facilities, patients were randomly allocated to treatment in a day hospital or an inpatient ward. Psychopathology, treatment satisfaction, subjective quality of life, and social disabilities were assessed at admission, at discharge, and 3 and 12 months after discharge. An intention-to-treat analysis was conducted using fixed-effects linear models with structured error covariance matrices and covariates.\n Day hospital care was as effective as conventional inpatient care with respect to psychopathologic symptoms, treatment satisfaction, and quality of life. It was more effective on social functioning at discharge and at the 3- and 12-month follow-up assessments.\n This study, which has more than doubled the existing evidence base, has shown that day hospital care is as effective on clinical outcomes as conventional inpatient care and more effective on social outcomes.\n ClinicalTrials.gov identifier NCT00153959.", "The purpose of this study was to evaluate the effectiveness of an activating intervention designed to reduce sick leave duration in patients with emotional distress or minor mental disorders.\n In a 1.5-year randomized controlled trial, 194 patients with minor mental disorders received either an experimental intervention by social workers or general practitioners' usual care. The intervention focused on understanding causes, developing and implementing problem-solving strategies and promoting early work resumption. Outcome measures were sick leave duration, mental health and physical health (questionnaires included the Hospital Anxiety and Depression Scale, the Four-Dimensional Symptom Questionnaire and SF-36), all measured at baseline at and 3, 6 and 18 months later. Multilevel analyses were used to evaluate differences between groups.\n The groups did not differ significantly on any of the outcome measures, except that the experimental group reported higher satisfaction with treatment.\n Although the intervention has benefits, it was not successful at its primary goal (i.e., to reduce sick leave duration in patients with emotional distress or minor mental disorders). Programs aimed at the reduction of sick leave duration may yield better results if targeted at patients with more severe emotional problems than at those with exclusively emotional distress or minor mental disorders, or if delivered by caregivers who are closer to the work environment than are social workers, such as occupational physicians.", "To compare the effectiveness of community mental health nurse (CMHN) problem-solving and generic CMHN care, against usual general practitioner (GP) care in reducing symptoms, alleviating problems, and improving social functioning and quality of life for people living in the community with common mental disorders; and to undertake a cost comparison of each CMHN treatment compared with usual GP care.\n A pragmatic, randomised controlled trial with three arms: CMHN problem-solving, generic CMHN care and usual GP care.\n General practices in two southern English counties were included in the study. CMHNs were employed by local NHS trusts providing community mental health services.\n Participants were GP patients aged 18--65 years with a new episode of anxiety, depression or reaction to life difficulties and had to score at least 3 points on the General Health Questionnaire-12 screening tool. Symptoms had to be present for a minimum of 4 weeks but no longer than 6 months.\n Patients were randomised to one of three groups: (1) CMHN problem-solving treatment, (2) generic CMHN treatment, or (3) usual GP care. All three groups of patients remained free to consult their GPs throughout the course of the study, and could be prescribed psychotropic drug treatments.\n Patients were assessed at baseline, and 8 weeks and 26 weeks after randomisation. The primary outcome measure was psychological symptoms measured on the Clinical Interview Schedule -- Revised. Other measures included social functioning, health-related quality of life, problem severity and satisfaction. The economic outcomes were evaluated with a cost--utility analysis.\n Twenty-four CMHNs were trained to provide problem-solving under supervision, and another 29 were referred patients for generic support. In total, 247 patients were randomised to the three arms of the study, referred by 98 GPs in 62 practices. All three groups of patients were greatly improved by the 8-week follow-up. No significant differences were found between the groups at 8 weeks or 26 weeks in symptoms, social functioning or quality of life. Greater satisfaction with treatment was found in the CMHN groups. CMHN care represented a significant additional health service cost and there were no savings in sickness absence.\n The study found that specialist mental health nurse support is no better than support from GPs for patients with anxiety, depression and reactions to life difficulties. The results suggest that healthcare providers could consider adopting policies of restricting referrals of unselected patients with common mental disorders to specialist CMHNs, although there may be other roles in primary care that CMHNs could play effectively. Further research should address the predictors of chronicity in common mental disorders and target extra treatment. More research is also needed into the effectiveness and cost-effectiveness of problem-solving treatment for other disorders, of facilitated self-help treatments for common mental disorders and of CMHN care for people with severe and enduring mental illnesses, as well as the prevention of mental disorders.", "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.", "To investigate whether a form of advance agreement for people with severe mental illness can reduce the use of inpatient services and compulsory admission or treatment.\n Single blind randomised controlled trial, with randomisation of individual patients. The investigator was blind to allocation.\n Eight community mental health teams in southern England.\n 160 people with an operational diagnosis of psychotic illness or non-psychotic bipolar disorder who had experienced a hospital admission within the previous two years.\n The joint crisis plan was formulated by the patient, care coordinator, psychiatrist, and project worker and contained contact information, details of mental and physical illnesses, treatments, indicators for relapse, and advance statements of preferences for care in the event of future relapse.\n Admission to hospital, bed days, and use of the Mental Health Act over 15 month follow up.\n Use of the Mental Health Act was significantly reduced for the intervention group, 13% (10/80) of whom experienced compulsory admission or treatment compared with 27% (21/80) of the control group (risk ratio 0.48, 95% confidence interval 0.24 to 0.95, P = 0.028). As a consequence, the mean number of days of detention (days spent as an inpatient while under a section of the Mental Health Act) for the whole intervention group was 14 compared with 31 for the control group (difference 16, 0 to 36, P = 0.04). For those admitted under a section of the Mental Health Act, the number of days of detention was similar in the two groups (means 114 and 117, difference 3, -61 to 67, P = 0.98). The intervention group had fewer admissions (risk ratio 0.69, 0.45 to 1.04, P = 0.07). There was no evidence for differences in bed days (total number of days spent as an inpatient) (means 32 and 36, difference 4, -18 to 26, P = 0.15 for the whole sample; means 107 and 83, difference -24, -72 to 24, P = 0.39 for those admitted).\n Use of joint crisis plans reduced compulsory admissions and treatment in patients with severe mental illness. The reduction in overall admission was less. This is the first structured clinical intervention that seems to reduce compulsory admission and treatment in mental health services.", "Primary care clinicians have a considerable amount of contact with patients suffering from long-term mental illness. The United Kingdom's National Health Service now requires general practices to contribute more systematically to care for this group of patients.\n To determine the effects of Mental Health Link, a facilitation-based quality improvement programme designed to improve communication between the teams and systems of care within general practice. Design of study: Exploratory cluster randomised controlled trial.\n Twenty-three urban general practices and associated community mental health teams.\n Practices were randomised to service development as usual or to the Mental Health Link programme. Questionnaires and an audit of notes assessed 335 patients' satisfaction, unmet need, mental health status, processes of mental and physical care, and general practitioners' satisfaction with services and beliefs about service development. Service use and intervention costs were also measured.\n There were no significant differences in patients' perception of their unmet need, satisfaction or general health. Intervention patients had fewer psychiatric relapses than control patients (mean = 0.39 versus 0.71, respectively, P = 0.02) but there were no differences in documented processes of care. Intervention practitioners were more satisfied and services improved significantly for intervention practices. There was an additional mean direct cost of pound 63 per patient with long-term mental illness for the intervention compared with the control.\n Significant differences were seen in relapse rates and practitioner satisfaction. Improvements in service development did not translate into documented improvements in care. This could be explained by the intervention working via the improvements in informal shared care developed through better link working. This type of facilitated intervention tailored to context has the potential to improve care and interface working.", "The effectiveness of community-based treatment stressing home care was compared with hospital-based psychiatric care. One hundred and fifty-five patients destined for inpatient psychiatric care were randomly assigned to Home Care (76 patients) and to Hospital Care (79 patients). Symptoms, role functioning, and psychosocial burden on the family were similar at admission, one month, three months, six months, and one year. The mean in-hospital stay of Hospital Care patients was 41.7 days compared with a mean stay of 14.5 days for Home Care patients. The difference in the amount of ambulatory care received by patients in the two groups was not significant. The evidence is consistent: community-based psychiatric care is an effective alternative to hospital-based care for many but not all severely disabled patients. The active ingredients of successful community treatment are known, yet the lag in implementing these programs persists.", "This randomized controlled trial tested the effectiveness of an 18-month mentalization-based treatment (MBT) approach in an outpatient context against a structured clinical management (SCM) outpatient approach for treatment of borderline personality disorder.\n Patients (N=134) consecutively referred to a specialist personality disorder treatment center and meeting selection criteria were randomly allocated to MBT or SCM. Eleven mental health professionals equal in years of experience and training served as therapists. Independent evaluators blind to treatment allocation conducted assessments every 6 months. The primary outcome was the occurrence of crisis events, a composite of suicidal and severe self-injurious behaviors and hospitalization. Secondary outcomes included social and interpersonal functioning and self-reported symptoms. Outcome measures, assessed at 6-month intervals, were analyzed using mixed effects logistic regressions for binary data, Poisson regression models for count data, and mixed effects linear growth curve models for self-report variables.\n Substantial improvements were observed in both conditions across all outcome variables. Patients randomly assigned to MBT showed a steeper decline of both self-reported and clinically significant problems, including suicide attempts and hospitalization.\n Structured treatments improve outcomes for individuals with borderline personality disorder. A focus on specific psychological processes brings additional benefits to structured clinical support. Mentalization-based treatment is relatively undemanding in terms of training so it may be useful for implementation into general mental health services. Further evaluations by independent research groups are now required.", "According to most of the relevant guidelines, psychoeducation is considered a basic part of routine therapy for patients with schizophrenia; scientific proofs of its efficacy are based mainly on the results of 1- and 2-year follow-ups. Therefore, the long-term effects of psychoeducation over a period of 7 years were investigated in regard to rehospitalization rates and hospital days.\n Of 101 patients with DSM-III-R or ICD-9 schizophrenia randomly allocated to either an intervention group or a control group between 1990 and 1994, 48 patients were available for follow-up after 7 years. During their index stay, the 24 patients of the intervention group and their key relatives each received a separate psychoeducational group therapy. The 24 patients of the control group received the usual treatment. After index discharge, all 48 patients received a comparable outpatient treatment. Main outcome measures were rehospitalization rate, number of intervening hospital days, compliance, and mean number of consumed chlorpromazine (CPZ) units.\n Seven years after index discharge, the rate of rehospitalization was 54% in the intervention group and 88% in the control group. The rate of rehospitalization per patient was 1.5 in the intervention group and 2.9 in the control group (p < .05). In the intervening period, the mean number of hospital days spent in a psychiatric hospital was 75 in the intervention group and 225 days in the control group. (p < .05). The mean number of consumed CPZ units after 7 years was 354 in the intervention and 267 in the control group.\n Seven years after psychoeducational group therapy, significant effects on the long-term course of the illness can be found. Therefore, the integration of psychoeducation into standard therapy for schizophrenia should become obligatory.", "This experiment evaluated the effectiveness of an innovative program of assertive community treatment (ACT) for homeless persons with severe and persistent mental illnesses.\n One hundred fifty-two homeless persons with severe and persistent mental illness were randomized to either the experimental ACT program or to usual community services. Baseline assessments included the Structured Clinical Interview for DSM-III-R, Quality-of-Life Interview, Colorado Symptom Index, and the Medical Outcomes Study 36-Item Short Form Health Survey. All assessments (except the Structured Clinical Interview) were repeated at the 2-, 6-, and 12-month follow-up evaluations.\n Subjects in the ACT program used significantly fewer psychiatric inpatient days, fewer emergency department visits, and more psychiatric outpatient visits than the comparison subjects. The ACT subjects also spent significantly more days in stable community housing, and they experienced significantly greater improvements in symptoms, life satisfaction, and perceived health status.\n Relative to usual community care, the ACT program for homeless persons with severe and persistent mental illness shifts the locus of care from crisis-oriented services to ongoing outpatient care and produces better housing, clinical, and life satisfaction outcomes.", "To evaluate the effectiveness of an intensive community nurse (CN)-supported discharge program in preventing hospital readmissions of older patients with chronic lung disease (CLD).\n Randomized, controlled trial.\n Two acute hospitals in the same health region in Hong Kong.\n One hundred fifty-seven hospitalized patients aged 60 and older with a primary diagnosis of CLD and at least one hospital admission in the previous 6 months.\n CNs made home visits within 7 days of discharge, then weekly for 4 weeks and monthly until 6 months. CNs coordinated closely with a geriatric or respiratory specialist in hospital. Subjects had telephone access to CNs during normal working hours from Monday to Saturday.\n The primary outcome was the rate of unplanned readmission within 6 months. The secondary outcomes were the rate of unplanned readmission within 28 days, number of unplanned readmissions, hospital bed days, accident and emergency room attendance, functional and psychosocial status, and caregiver burden.\n One hundred forty hospitalized patients completed the trial. Intervention group subjects had a higher rate of unplanned readmission within 6 months than control group subjects (76% vs 62%, P=.080, chi2 test). There was no significant group difference in any of the secondary outcomes except that intervention group subjects did better on social handicap scores.\n There was no evidence that an intensive CN-supported discharge program can prevent hospital readmissions in older patients with CLD.", "A controlled study tested whether the superior outcome of community care for serious mental illness (SMI) in Madison and in Sydney would also be found in inner London.\n Patients from an inner London catchment area who faced emergency admission for SMI (many were violent or suicidal) were randomised to 20 months or more of either home-based care (Daily Living Programme, DLP; n = 92), or standard in-patient and later out-patient care (controls, n = 97). Most DLP patients had brief in-patient stays at some time. Measures included number and duration of in-patient admissions, independent ratings of clinical and social function, and patients' and relatives' satisfaction.\n Outcome was superior with home-based care. Until month 20, DLP care improved symptoms and social adjustment slightly more, and enhanced patients' and relatives' satisfaction. From 3 to 18 months DLP care greatly reduced the number of in-patient bed days as long as the DLP team was responsible for any in-patient phase its patients had. Cost was less. DLP care did not reduce the number of admissions, nor of deaths from self-harm (3 DLP, 2 control). One DLP patient killed a child. Even at 20 months many DLP and control patients still had severe symptoms, poor social adjustment, no job, and need for assertive follow-up and heavy staff input. (Beyond 20 months most gains were lost apart from satisfaction.)\n It is unclear how much the gain until 20 months from home-based care was due to its site of care, its being problem-centred, its teaching of daily living skills, its assertive follow-up, the home care team's keeping responsibility for any in-patient phase, its coordination of total care (case management), or to other care components. Home-based care is hard to organise and vulnerable to many factors, and needs careful training and clinical audit if gains are to be sustained.", "Intermediate care (IC) services have been widely introduced in England and have the strategic objectives of reducing hospital and long-term care use. There is uncertainty about the clinical outcomes of these services and whether their strategic aims will be realised.\n A metropolitan city in northern England.\n A quasi-experimental study comparing a group of older people before and after the introduction of an IC service. A quota sampling method was used to match the groups.\n Patients presenting as emergency admissions to two elderly care departments with falls, confusion, incontinence or immobility. Intervention: a city-wide service in which a joint care management team (multi-agency, multi-disciplinary) assessed patient need and purchased support and rehabilitation from sector-based IC teams.\n Nottingham Extended Activities of Daily Living score, Barthel Index, Hospital Anxiety and Depression score, mortality, readmission to hospital, and new institutional care placement at 3, 6 and 12 months post-recruitment.\n There were 800 and 848 patients, respectively, in the control and intervention groups. Clinical outcomes, hospital and long-term care use were similar between the groups. Uptake of IC was lower than anticipated at 29%. An embedded case-control study comparing the 246 patients who received IC with a matched sample from the control group demonstrated similar clinical outcomes but increased hospital bed days used over 12 months (mean +8 days; 95% CI 3.1-13.0).\n This city-wide IC service was associated with similar clinical outcomes but did not achieve its strategic objectives of reducing long-term care and hospital use.", "This study examines the rationale for and relative effectiveness of three intervention models for treating people with severe mental illness and substance abuse disorders: Twelve Step recovery, behavioral skills training, and intensive case management. Using clinical trial methods, 132 dually diagnosed clients were assigned to three service approaches. Changes in client psychosocial outcomes, and psychiatric and substance abuse symptomatology were tracked over a 24-month period. Differential effectiveness was evident, with clients in the behavioral skills group demonstrating the most positive and significant differences in psychosocial functioning and symptomatology, compared with the Twelve Step recovery approach. However, the case management intervention also resulted in several positive and important differences compared with the Twelve Step recovery approach. We also found significant changes over time, not only at 6 months but increasingly positive changes in psychosocial functioning at 12 and 18 months as well. These results underscore the need for clinical trials to further examine the relative cost effectiveness of treatment approaches for dually disordered clients and to incorporate means of assessing subgroup differences so that the interventions being tested can be further refined and targeted to a broad set of needs among the dually diagnosed.", "This randomized controlled trial examined the effectiveness of a 12-session mutual support group conducted over 3-months for Chinese family caregivers of a relative with schizophrenia compared with routine family support services in Hong Kong. Forty-eight family caregivers from two psychiatric outpatient clinics were allocated randomly to an experimental (mutual support and usual outpatient care) group (n = 24) or a control (usual outpatient care only) group (n = 24). Data were collected prior to, 1 week and 3 months after the intervention. Families allocated to the mutual support group experienced decreased levels of family burden and increased family functioning and these changes were significantly greater than those of the controls at both post-intervention time points. The experimental group also showed a significant decrease in the duration of patient re-hospitalization (the total number of days of psychiatric hospitalization) at 3 months compared with the control group. This suggests that the mutual support group provided a more responsive service for patients than standard care. However, there was no significant difference in family service utilization between the two groups. The findings indicate that a mutual support group can provide benefits for family caregivers of people with schizophrenia that go beyond those provided by routine family support.\n Copyright 2004 Elsevier Ltd.", "An advance directive is a statement of a person's preferences for treatment, should he or she lose capacity to make treatment decisions in the future.\n To evaluate whether use of advance directives by patients with mental illness leads to lower rates of compulsory readmission to hospital.\n In a randomised controlled trial in two psychiatric services in inner London, 156 in-patients about to be discharged from compulsory treatment under the Mental Health Act were recruited. The trial compared usual psychiatric care with usual care plus the completion of an advance directive. The primary outcome was the rate of compulsory readmission.\n Fifteen patients (19%) in the intervention group and 16 (21%) in the control group were readmitted compulsorily within 1 year of discharge. There was no difference in the numbers of compulsory readmissions, numbers of patients readmitted voluntarily, days spent in hospital or satisfaction with psychiatric services.\n Users' advance instruction directives had little observable impact on the outcome of care at 12 months.", "While research has shown community-based psychiatric care to be as good as, or better than, hospital-based care, generalisation to clinical practice has been difficult. This prospective, randomised controlled study examined a community-based approach feasible within NHS conditions. Ninety-four patients were randomly allocated to experimental and 78 to control treatments and followed for one year. The groups were well matched apart from an excess of psychotic control patients. No differences in clinical or social functioning outcome were found. Both groups improved substantially on clinical measures in the first six weeks, with some slow consolidation thereafter. There were three suicides in the control group and one in the experimental group. Access to care was better in the experimental group (93% attended assessment) than in the control group (75% attended assessment).", "A two year follow-up of two matched groups of subjects with chronic severe mental illness was performed in order to evaluate a new psychiatric case management system. One group (n = 59) received care through psychiatric case management, using an assertive community treatment model that directly involved general practitioners. The other group, matched for age, sex, diagnostic group and number of hospital admissions, received standard outpatient care. Comparing the two years before and after case management, the experimental group showed a dramatic fall in inpatient admission days while the control group admission days remained the same (median difference in admission days across matched subject pairs = 64.5, 95% C.I. from 134.5 to 16). The experimental group remained out of hospital longer before first readmission (Kaplan-Meier survival analysis, P = 0.002). This type of case management programme can shorten or prevent admissions to psychiatric hospitals of patients with chronic mental illness, and increase their time before readmission.", "Depression and anxiety disorders are common mental disorders worldwide. The MANAS trial aimed to test the effectiveness of an intervention led by lay health counsellors in primary care settings to improve outcomes of people with these disorders.\n In this cluster randomised trial, primary care facilities in Goa, India, were assigned (1:1) by computer-generated randomised sequence to intervention or control (enhanced usual care) groups. All adults who screened positive for common mental disorders were eligible. The collaborative stepped-care intervention offered case management and psychosocial interventions, provided by a trained lay health counsellor, supplemented by antidepressant drugs by the primary care physician and supervision by a mental health specialist. The research assessor was masked. The primary outcome was recovery from common mental disorders as defined by the International Statistical Classification of Diseases and Related Health Problems-10th revision (ICD-10) at 6 months. This study is registered with ClinicalTrials.gov, number NCT00446407.\n 24 study clusters, with an equal proportion of public and private facilities, were randomised equally between groups. 1160 of 1360 (85%) patients in the intervention group and 1269 of 1436 (88%) in the control group completed the outcome assessment. Patients with ICD-10-confirmed common mental disorders in the intervention group were more likely to have recovered at 6 months than were those in the control group (n=620 [65·0%] vs 553 [52·9%]; risk ratio 1·22, 95% CI 1·00-1·47; risk difference=12·1%, 95% CI 1·6%-22·5%). The intervention had strong evidence of an effect in public facility attenders (369 [65·9%] vs 267 [42·5%], risk ratio 1·55, 95% CI 1·02-2·35) but no evidence for an effect in private facility attenders (251 [64·1%] vs 286 [65·9%], risk ratio 0·95, 0·74-1·22). There were three deaths and four suicide attempts in the collaborative stepped-care group and six deaths and six suicide attempts in the enhanced usual care group. None of the deaths were from suicide.\n A trained lay counsellor-led collaborative care intervention can lead to an improvement in recovery from CMD among patients attending public primary care facilities.\n The Wellcome Trust.\n Copyright © 2010 Elsevier Ltd. All rights reserved.", "At three community mental health centers (CMHCs) in Indiana, 167 clients at risk for rehospitalization were randomly assigned to experimental groups receiving assertive case management (ACM) or to control groups eligible to receive all other aftercare services at the centers. During a six-month follow-up period, experimental clients received an average of one visit a week from the ACM team, usually in the client's home or in community settings. Overall, ACM clients were rehospitalized an average of 9.2 days, significantly less than the 30.8 days for controls. In two of the three centers, significant rehospitalization differences were also found between ACM and control groups. No differences were found between groups in quality of life, medication compliance, involvement in CMHC programs, or contacts with the legal system in any of the centers. The most cost-effective center had savings of about +5,500 for each ACM client.", "One hundred and twenty patients presenting for admission were randomly allocated into two groups. Controls received standard hospital care and after-care. Projects were not admitted if this could be avoided; instead they and their relatives were provided with comprehensive community treatment and a 24-hour crisis service. Patients with a primary diagnosis of alcohol or drug dependence, organic brain disorder or mental retardation were excluded. During the 12 months study period, 96% of controls were admitted, 51% more than once. Of the projects, 60% were not admitted at all and only 8% were admitted more than once. Controls spent an average of 53.5 days in psychiatric hospitals; projects spent an average of 8.4 days. Community treatment did not increase the burden upon the community, was considered to be significantly more satisfactory and helpful by patients and their relatives, achieved a clinically superior outcome, and cost less than standard care and after-care.", "To evaluate the effectiveness and cost-effectiveness of a community nurse-supported hospital discharge programme in preventing hospital re-admissions, improving functional status and handicap of older patients with chronic heart failure.\n Randomized controlled trial; 105 hospitalized patients aged 60 years or over with chronic heart failure and history of hospital admission(s) in previous year were randomly assigned into intervention group (n = 49) and control group (n = 56) for six months. Intervention group subjects received community nurse visits before discharge, within seven days of discharge, weekly for four weeks, then monthly. Community nurse liaised closely with a designated specialist in hospital and were accessible to subjects during normal working hours. Control and intervention group subjects were followed up in the same specialist medical clinics. Primary outcome was the rate of unplanned re-admission at six months. Secondary outcomes were number of unplanned re-admissions, six-minute walking distance, London Handicap Scale and public health care and personal care costs.\n At sixth months, the re-admission rates were not significantly different (46 vs. 57% in control subjects, p = 0.233, Chi-square test). But the median number of re-admissions tended to lower in the intervention group (0 vs. 1 in control group, p = 0.057, Mann Whitney test). Intervention group subjects had less handicap in independence (median change 0 vs. 0.5 in control subjects, p = 0.002, Mann Whitney test), but there was no difference in six-minute walking distance. There was no significant group difference in median total public health care and personal care costs.\n Community nurse-supported post-discharge programme was effective in preserving independence and was probably effective in reducing the number of unplanned re-admissions. The cost benefits to public health care were not significant.\n Older chronic heart failure patients are likely to benefit from post-discharge community nurse intervention programmes. More comprehensive health economic evaluation needs to be undertaken." ]	ICM was found effective in ameliorating many outcomes relevant to people with severe mental illnesses. Compared to standard care ICM was shown to reduce hospitalisation and increase retention in care. It also globally improved social functioning, although ICM's effect on mental state and quality of life remains unclear. ICM is of value at least to people with severe mental illnesses who are in the sub-group of those with a high level of hospitalisation (about 4 days/month in past 2 years) and the intervention should be performed close to the original model. It is not clear, however, what gain ICM provides on top of a less formal non-ICM approach. We do not think that more trials comparing current ICM with standard care or non-ICM are justified, but currently we know of no review comparing non-ICM with standard care and this should be undertaken.
CD008500	[ "20598077", "19121589", "11288011", "1962900", "10436448", "15457363", "17208082", "10717252" ]	[ "PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma.", "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.", "Prevention of venous thromboembolism after knee arthroscopy with low-molecular weight heparin (reviparin): Results of a randomized controlled trial.", "Thromboprophylactic effect of low molecular weight heparin started in the evening before elective general abdominal surgery: a comparison with low-dose heparin.", "Venographic comparison of subcutaneous low-molecular weight heparin with oral anticoagulant therapy in the long-term treatment of deep venous thrombosis.", "Venous thromboembolism prophylaxis after head and spinal trauma: intermittent pneumatic compression devices versus low molecular weight heparin.", "Self-managed long-term low-molecular-weight heparin therapy: the balance of benefits and harms.", "Effect of low molecular weight heparin (Certoparin) versus unfractionated heparin on cancer survival following breast and pelvic cancer surgery: A prospective randomized double-blind trial." ]	[ "Venous thromboembolism (VTE) occurs in 20-30% of patients with malignant glioma per year of survival. We tested the efficacy of long-term dalteparin low-molecular-weight heparin (LMWH) for prevention of VTE in these patients.\n Adults with newly diagnosed malignant glioma were randomized to receive dalteparin 5000 anti-Xa units or placebo, both subcutaneously once daily for 6 months starting within 4 weeks of surgery. Treatment continued for up to 12 months. The primary outcome was the cumulative risk of VTE over 6 months. The target sample size was 512 patients. Events were adjudicated by a committee unaware of treatment.\n The trial began in 2002 and closed in May 2006 because of expiration of study medication. Ninety-nine patients were randomized to LMWH and 87 to placebo. Twenty-two patients developed VTE in the first 6 months: nine in the LMWH group and 13 in the placebo group [hazard ratio (HR) = 0.51, 95% confidence interval (CI): 0.19-1.4, P = 0.29]. At 6 months, there were three major bleeds on LMWH and none on placebo; at 12 months, 5 (5.1%) major bleeds on LMWH and 1 (1.2%) on placebo occurred (HR = 4.2, 95% CI: 0.48-36, P = 0.22). All major bleeds were intracranial and occurred while on study medication. The 12-month mortality rates were 47.8% for LMWH and 45.4% for placebo (HR = 1.2, 95% CI: 0.73-2.0, P = 0.48).\n Trends suggesting reduced VTE and increased intracranial bleeding were seen in the LMWH thromboprophylaxis group. The role of long-term anticoagulant thromboprophylaxis in patients with brain tumors remains uncertain.\n © 2010 International Society on Thrombosis and Haemostasis.", "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.", "Deep venous thrombosis (DVT) is a common, important complication of major orthopaedic surgery, particularly knee arthroplasty. Knee arthroscopy is increasingly performed on an outpatient basis. Few reports have elucidated the incidence of venous thromboembolism (VTE) in patients undergoing arthroscopic surgery receiving no prophylaxis. The objective of the present trial was to evaluate the risk of VTE in those patients and to determine efficacy and safety of a low-molecular weight heparin (LMWH) in preventing VTE.\n This is the first controlled randomized trial using objective diagnostic methods with blinded outcome assessment to reveal the incidence of VTE in outpatient arthroscopy and determine efficacy and safety of a LMWH (reviparin sodium) in preventing VTE in these patients.\n There were 262 patients undergoing elective knee arthroscopy prospectively randomized to receive either no treatment or reviparin once daily subcutaneously for 7 to 10 days. The blindly assessed primary outcome measure was the incidence of DVT detected by compression color-coded sonography. Both groups were comparable with regard to demographics and baseline characteristics.\n 239 patients were evaluable (122 no treatment, 117 receiving LMWH). 6 DVT were detected - 5 in the control group (5/117 - 4.1%) and only one in the active treatment group (1/116 - 0.85%). This particular patient had a low level of protein C and a subnormal level of protein S. The odds ratio of 4.95 approximates a relative risk reduction of about 80%. Treatment with reviparin was safe and well tolerated. There was no major bleeding, four patients with minor bleedings. One patient had a transitory fall in platelet count below 100 giga-particles/L without any clinical symptoms.\n Patients undergoing knee arthroscopy have a moderate risk of VTE and effective prophylaxis can be achieved with LMWH (reviparin).", "A prospective randomized double-blind trial was performed comparing conventional low-dose heparin with a LMWH fragment (Kabi 2165, Fragmin) for thromboprophylaxis in elective general abdominal surgical patients. The first dose of the fragment was given in the evening before surgery, and thereafter every evening. There were 1002 analyzable patients, 826 having received correct prophylaxis. Sixty three percent of the patients were operated on for malignant diseases. The frequency of DVT was significantly reduced among patients with correct prophylaxis with the heparin fragment (9.2 to 5.0%, p = 0.02). In patients with malignancies the reduction was from 11.2 to 6.4% (p = 0.06). The frequency of bleeding was 6.7% among the heparin fragment patients and 2.7% among the patients given conventional heparin (p = 0.01). The corresponding frequencies for patients with malignancies were 3.2 and 2.8%, respectively (p = 0.28). All bleedings were minor and of no clinical significance. Local pain at the injection site was reported significantly less often among patients with the fragment. Twenty patients died, 13 with malignant disease, mortality being the same in the two groups. It is concluded that heparin fragment administered in the evening before surgery and then every evening is a practically acceptable alternative to prevent postoperative DVT in patients undergoing elective abdominal surgery, also when the histology shows malignancy. Thus, the advantages of using LMWH compared with conventional low-dose heparin are simplified administration routines, better thromboprophylactic effect, and less local pain at injection sites. A disadvantage is the slight increase in hemorrhagic side effects, all of minor clinical importance and not seen in patients undergoing surgery for malignancy.", "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.", "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.", "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.", "Recent studies suggest that low molecular weight heparin (LMW heparin) therapy in malignancy may improve cancer survival following surgical resection. We studied prospectively whether cancer mortality during follow-up in women with previously untreated breast, and pelvic cancer is reduced in those who randomly received LMW heparin (Certoparin) compared to patients given unfractionated heparin (UF heparin) for thrombosis prophylaxis during primary surgery. In a prospective, randomized, double-blind clinical trial, 160 patients received Certoparin and 164 UF heparin until post-operatively day 7. Survival estimations are based on the outcome data from a subset of 140 LMW heparin - and 147 UF heparin recipients. Long-term survival in the Certoparin group compared to the UF heparin group was significantly improved after 650 days (P=0. 0066) but not thereafter when analysis was performed on all cancer cell types combined. In the probability estimates survival benefit within this time was restricted to patients with pelvic cancer but was not observed in breast cancer. However, in breast cancer patients who received LMW heparin the impact of classical tumor prognostic markers was statistically significant after 1,050 days but not after 650 days. Thus, breast cancer patients with unfavorable prognosis seem to benefit in terms of survival advantage from LMW heparin within the 650 days after surgery. These results suggest that improvement in cancer survival can be achieved after even a short course of treatment with LMWH (compared to UFH) given for DVT prophylaxis in the post-operative period. An effect of UFH on disease outcome is not excluded. Further definitive trials of LMWH vs. placebo for cancer outcome (rather then DVT) using doses and schedules that may be more optimal are indicated." ]	Primary thromboprophylaxis with LMWH significantly reduced the incidence of symptomatic VTE in ambulatory cancer patients treated with chemotherapy. However, the lack of power hampers definite conclusions on the effects on major safety outcomes, which mandates additional studies to determine the risk to benefit ratio of LMWH in this setting.
CD006095	[ "15179608", "20145608", "22472744", "2494098", "17604300", "16572062", "7939431", "15740542", "18469732", "17690340", "12403254", "18955525", "22371721", "9570649", "18410562", "16292090", "18701826", "19138244", "7872284", "17287932", "15815206", "12953945", "20400916", "18402597", "12150179", "9421320", "12500005" ]	[ "Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of C. difficile diarrhoea.", "Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients.", "Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized, double-blind, placebo-controlled trial.", "Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: a prospective study.", "Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial.", "Prophylactic Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea: a prospective study.", "Treatment of Clostridium difficile associated diarrhea and colitis with an oral preparation of teicoplanin; a dose finding study. The Swedish CDAD Study Group.", "Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a randomized double-blind placebo-controlled trial.", "Probiotic Escherichia coli Nissle 1917 versus placebo for treating diarrhea of greater than 4 days duration in infants and toddlers.", "Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations.", "Prevention of antibiotic-associated diarrhea in infants by probiotics.", "Clinical outcomes, safety, and pharmacokinetics of OPT-80 in a phase 2 trial with patients with Clostridium difficile infection.", "Efficacy of BIO K+ CL1285 in the reduction of antibiotic-associated diarrhea - a placebo controlled double-blind randomized, multi-center study.", "The lack of therapeutic effect of Saccharomyces boulardii in the prevention of antibiotic-related diarrhoea in elderly patients.", "Clinical trial: effectiveness of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) in the prevention of antibiotic-associated diarrhoea in children.", "Efficacy and safety of Saccharomyces boulardii in prevention of antibiotic-associated diarrhoea due to Helicobacterpylori eradication.", "Bifidobacterium longum PL03, Lactobacillus rhamnosus KL53A, and Lactobacillus plantarum PL02 in the prevention of antibiotic-associated diarrhea in children: a randomized controlled pilot trial.", "Feasibility and tolerability of probiotics for prevention of antibiotic-associated diarrhoea in hospitalized US military veterans.", "Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo.", "The probiotic Escherichia coli strain Nissle 1917 (EcN) stops acute diarrhoea in infants and toddlers.", "A randomized formula controlled trial of Bifidobacterium lactis and Streptococcus thermophilus for prevention of antibiotic-associated diarrhea in infants.", "Lactobacillus plantarum 299v for the treatment of recurrent Clostridium difficile-associated diarrhoea: a double-blind, placebo-controlled trial.", "Efficacy of Lactobacillus GG in aboriginal children with acute diarrhoeal disease: a randomised clinical trial.", "Efficacy of Clostridium butyricum preparation concomitantly with Helicobacter pylori eradication therapy in relation to changes in the intestinal microbiota.", "Effect of probiotic Lactobacillus strains on acute diarrhea in a cohort of nonhospitalized children attending day-care centers.", "Successful control of Clostridium difficile infection in an elderly care unit through use of a restrictive antibiotic policy.", "Limitations of probiotic therapy in acute, severe dehydrating diarrhea." ]	[ "Colonic infection with Clostridium difficile, leading to pseudomembranous colitis, is a common complication of antibiotic therapy, especially in elderly patients. It has been suggested that non-pathogenic probiotic bacteria might prevent the development and recurrence of C. difficile infection. This double-blind, placebo-controlled study examines the role of probiotic administration in the prevention of C. difficile-associated diarrhoea (CDAD) in elderly patients receiving antibiotic therapy. Consecutive patients (150) receiving antibiotic therapy were randomised to receive either a probiotic containing both Lactobacillus and Bifidobacterium or placebo for 20 days. Upon admission to hospital, bowel habit was recorded and a faecal sample taken. Trial probiotic or placebo was taken within 72 h of prescription of antibiotics, and a second stool sample was taken in the event of development of diarrhoea during hospitalisation or after discharge. Of the randomised patients, 138 completed the study, 69 with probiotics in conjunction with antibiotics and 69 with antibiotics alone. On the basis of development of diarrhoea, the incidence of samples positive for C. difficile-associated toxins was 2.9% in the probiotic group compared with 7.25% in the placebo-control group. When samples from all patients were tested (rather than just those developing diarrhoea) 46% of probiotic patients were toxin-positive compared with 78% of the placebo group.", "Standard therapies for antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) have limited efficacy. Probiotic prophylaxis is a promising alternative for reduction of AAD and CDAD incidence.\n In this single-center, randomized, double-blind, placebo-controlled dose-ranging study, we randomized 255 adult inpatients to one of three groups: two probiotic capsules per day (Pro-2, n=86), one probiotic capsule and one placebo capsule per day (Pro-1, n=85), or two placebo capsules per day (n=84). Each probiotic capsule contained 50 billion c.f.u. of live organisms (Lactobacillus acidophilus CL1285 +Lactobacillus casei LBC80R Bio-K+ CL1285). Probiotic prophylaxis began within 36 h of initial antibiotic administration, continued for 5 days after the last antibiotic dose, and patients were followed for an additional 21 days.\n Pro-2 (15.5%) had a lower AAD incidence vs. Pro-1 (28.2%). Each probiotic group had a lower AAD incidence vs. placebo (44.1%). In patients who acquired AAD, Pro-2 (2.8 days) and Pro-1 (4.1 days) had shorter symptom duration vs. placebo (6.4 days). Similarly, Pro-2 (1.2%) had a lower CDAD incidence vs. Pro-1 (9.4%). Each treatment group had a lower CDAD incidence vs. placebo (23.8%). Gastrointestinal symptoms were less common in the treatment groups vs. placebo and in Pro-2 vs. Pro-1.\n The proprietary probiotic blend used in this study was well tolerated and effective for reducing risk of AAD and, in particular, CDAD in hospitalized patients on antibiotics. A dose-ranging effect was shown with 100 billion c.f.u., yielding superior outcomes and fewer gastrointestinal events compared to 50 billion c.f.u. (ClinicalTrials.gov number NCT00958308).", "Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Probiotics were effective in preventing AAD and CDAD in several randomized controlled trials. This study was aimed at testing the effect of Saccharomyces boulardii on the occurrence of AAD and CDAD in hospitalized patients.\n A single-center, randomized, double-blind, placebo-controlled, parallel-group trial was performed. Patients being prescribed antibiotics or on antibiotic therapy for <48 h were eligible. Exclusion criteria were ongoing diarrhea, recent assumption of probiotics, lack of informed consent, inability to ingest capsules, and severe pancreatitis. Patients received a capsule containing S. boulardii or an indistinguishable placebo twice daily within 48 h of beginning antibiotic therapy, continued treatment for 7 days after antibiotic withdrawal, and were followed for 12 weeks after ending antibiotic treatment.\n Of 562 consecutive eligible patients, 275 patients aged 79.2 ± 9.8 years (134 on placebo) were randomized and 204 aged 78.4 ± 10.0 years (98 on placebo) completed the follow-up. AAD developed in 13.3% (13/98) of the patients receiving placebo and in 15.1% (16/106) of those receiving S. boulardii (odds ratio for S. boulardii vs. placebo, 1.16; 95% confidence interval (CI), 0.53-2.56). Five cases of CDAD occurred, 2 in the placebo group (2.0%) and 3 in the probiotic group (2.8%; odds ratio for S. boulardii vs. placebo, 1.40; 95% CI, 0.23-8.55). There was no difference in mortality rates (12.7% vs. 15.6%, P=0.60).\n In elderly hospitalized patients, S. boulardii was not effective in preventing the development of AAD.", "Saccharomyces boulardii, a nonpathogenic yeast, has been widely used in Europe to prevent antibiotic-associated diarrhea (AAD). We performed a prospective double-blind controlled study to investigate AAD in hospitalized patients and to evaluate the effect of S. boulardii, a living yeast, given in capsule form concurrently with antibiotics. Over 23 mo, 180 patients completed the study. Of the patients receiving placebo, 22% experienced diarrhea compared with 9.5% of patients receiving S. boulardii (p = 0.038). Risk factors found to be associated with AAD were multiple antibiotic combinations (containing clindamycin, cephalosporins, or trimethoprim-sulfamethoxazole) and tube feeding. Clostridium difficile, an anaerobe found in the stools of most patients with pseudomembranous colitis, was variably associated with AAD. We evaluated the role of C. difficile in AAD in the study population and found no significant association between the presence of C. difficile or cytotoxin with AAD. Approximately 33% of the patients without diarrhea harbored at least one C. difficile-positive stool and nearly 50% of these patients had detectable cytotoxin. Similar values were obtained in patients with diarrhea. Of C. difficile-positive patients, 31% (5/16) on placebo developed diarrhea compared with 9.4% (3/32) on S. boulardii; this difference was not statistically significant (p = 0.07). There were no discernable adverse effects of yeast administration. We conclude that S. boulardii reduces the incidence of antibiotic-associated diarrhea in hospitalized patients.", "To determine the efficacy of a probiotic drink containing Lactobacillus for the prevention of any diarrhoea associated with antibiotic use and that caused by Clostridium difficile.\n Randomised double blind placebo controlled study.\n 135 hospital patients (mean age 74) taking antibiotics. Exclusions included diarrhoea on admission, bowel pathology that could result in diarrhoea, antibiotic use in the previous four weeks, severe illness, immunosuppression, bowel surgery, artificial heart valves, and history of rheumatic heart disease or infective endocarditis.\n Consumption of a 100 g (97 ml) drink containing Lactobacillus casei, L bulgaricus, and Streptococcus thermophilus twice a day during a course of antibiotics and for one week after the course finished. The placebo group received a longlife sterile milkshake.\n Primary outcome: occurrence of antibiotic associated diarrhoea. Secondary outcome: presence of C difficile toxin and diarrhoea.\n 7/57 (12%) of the probiotic group developed diarrhoea associated with antibiotic use compared with 19/56 (34%) in the placebo group (P=0.007). Logistic regression to control for other factors gave an odds ratio 0.25 (95% confidence interval 0.07 to 0.85) for use of the probiotic, with low albumin and sodium also increasing the risk of diarrhoea. The absolute risk reduction was 21.6% (6.6% to 36.6%), and the number needed to treat was 5 (3 to 15). No one in the probiotic group and 9/53 (17%) in the placebo group had diarrhoea caused by C difficile (P=0.001). The absolute risk reduction was 17% (7% to 27%), and the number needed to treat was 6 (4 to 14).\n Consumption of a probiotic drink containing L casei, L bulgaricus, and S thermophilus can reduce the incidence of antibiotic associated diarrhoea and C difficile associated diarrhoea. This has the potential to decrease morbidity, healthcare costs, and mortality if used routinely in patients aged over 50.\n National Research Register N0016106821.", "Interest to probiotics for the prevention and treatment of antibiotic-associated diarrhea is increasing gradually. The most promising seems to be Saccharomyces boulardii . Using a double-blind controlled study, we investigated the preventive effect of S. boulardii on the development of antibiotic-associated diarrhea in patients under antibiotherapy but not requiring intensive care therapy.\n All the patients were hospitalized at the Gulhane Military Medical Academy, Department of Infectious Diseases and Clinical Microbiology. S. boulardii was given twice daily during the course of antibiotic therapy and application was initiated in all patients as late as after 48 hours of antibiotic therapy. A total of 151 patients completed the study.\n The antibiotic-associated diarrhea development ratio in placebo group was 9% (7/78) and in the study group 1.4% (1/73) (p < 0.05). Stool samples from the patients with antibiotic-associated diarrhea were stored at -70 degrees C and Clostiridium difficile toxin A assay was performed using Enzyme Immune Assay as late as in seven days. C. difficile toxin A assay yielded positive results in two (2/7) stool samples from the patients with antibiotic-associated diarrhea in the placebo group and a negative result in the only patient who developed antibiotic-associated diarrhea in the study group.\n The results implied that prophylactic use of Saccharomyces boulardii resulted in reduced, with no serious side effects, antibiotic-associated diarrhea in hospitalized patients.", "92 patients with antibiotic-associated diarrhea were randomized to receive oral teicoplanin 100 mg twice daily for 7 days (BID group); or 50 mg 4 times daily for 3 days, followed by 100 mg twice daily for 4 days (QID group) in a randomized, double-blind, multicentre study. Clostridium difficile was demonstrated by culture and/or cytotoxin test in 49 (53%) patients, of whom 47 (23 male, 24 females, mean age 65 years; 23 in the BID group, 24 in the QID group) were evaluable for clinical efficacy. Prior treatment with cephalosporins was registered in 49%, isoxazolyl-penicillins in 33% and clindamycin in 20% of the C. difficile positive patients. On the last day of treatment, 96% (23 of 24 patients) in the QID group were found cured, compared with 70% (16 of 23 patients) in the BID group (p = 0.02). On days 2 and 3 of treatment, QID group patients had significantly fewer loose stools per day (p < 0.05) than those of the BID group. Clinical recurrence, within 4 weeks post-treatment, occurred in 35% and 33% of the patients in the BID and QID groups, respectively. The bacteriological elimination rate 4 weeks post-treatment was 55% in the BID group and 59% in the QID group. The study was terminated prematurely due to the unexpectedly high clinical failure and recurrence rate in C. difficile positive patients treated with the BID dosage regimen.", "Co-treatment with Saccharomyces boulardii appears to lower the risk of antibiotic-associated diarrhoea in adults receiving broad-spectrum antibiotics.\n To determine whether S. boulardii prevents antibiotic-associated diarrhoea in children.\n A total of 269 children (aged 6 months to 14 years) with otitis media and/or respiratory tract infections were enrolled in a double-blind, randomized placebo-controlled trial in which they received standard antibiotic treatment plus 250 mg of S. boulardii (experimental group, n = 132) or a placebo (control group, n = 137) orally twice daily for the duration of antibiotic treatment. Analyses were based on allocated treatment and included data from 246 children.\n Patients receiving S. boulardii had a lower prevalence of diarrhoea (> or =3 loose or watery stools/day for > or =48 h occurring during or up to 2 weeks after the antibiotic therapy) than those receiving placebo [nine of 119 (8%) vs. 29 of 127 (23%), relative risk: 0.3, 95% confidence interval: 0.2-0.7]. S. boulardii also reduced the risk of antibiotic-associated diarrhoea (diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea) compared with placebo [four of 119 (3.4%) vs. 22 of 127 (17.3%), relative risk: 0.2; 95% confidence interval: 0.07-0.5]. No adverse events were observed.\n This is the first randomized-controlled trial evidence that S. boulardii effectively reduces the risk of antibiotic-associated diarrhoea in children.", "Administering probiotics can prevent or cure some forms of diarrhea. The efficacy of probiotic Escherichia coli Nissle 1917 (EcN) in infants and toddlers with diarrhea >4 days was tested by a double-blind trial.\n One hundred fifty-one children aged 1-47 months with nonspecific diarrhea were randomized to receive either EcN suspension (N = 75) or placebo (N = 76). Diarrhea had to meet the following definition: >3 watery or loose nonbloody stools in 24 hours of a diarrheal episode persisting for >4 consecutive days but < or =14 days. All children were well nourished or only moderately malnourished, mildly dehydrated, and received oral rehydration at study commencement. They were treated orally with 1-3 mL EcN suspension (1 mL contains 10 viable cells) or placebo daily for 21 days. Primary objective was to confirm a better response rate (reduction of daily stool frequency to < or =3 watery or loose stools over > or =4 days) with EcN.\n The 7-day response was higher for the EcN group than placebo (EcN 78.7%, placebo 59.2%). Significant differences were observed on days 14 (EcN 93.3%, placebo 65.8%, P = 0.0017) and 21 (EcN 98.7%, placebo 71.1%, P < 0.001). Kaplan-Meier survival analysis resulted in a significant difference of 3.3 days between the groups (P < 0.0001); median time to response for EcN was 2.4 and 5.7 for placebo. EcN was safe and well tolerated.\n In the conditions of this trial EcN was a suitable remedy for diarrhea >4 days in young children.", "To compare the efficacy of five probiotic preparations recommended to parents in the treatment of acute diarrhoea in children. Design Randomised controlled clinical trial in collaboration with family paediatricians over 12 months.\n Primary care.\n Children aged 3-36 months visiting a family paediatrician for acute diarrhoea.\n Children's parents were randomly assigned to receive written instructions to purchase a specific probiotic product: oral rehydration solution (control group); Lactobacillus rhamnosus strain GG; Saccharomyces boulardii; Bacillus clausii; mix of L delbrueckii var bulgaricus, Streptococcus thermophilus, L acidophilus, and Bifidobacterium bifidum; or Enterococcus faecium SF68.\n Primary outcomes were duration of diarrhoea and daily number and consistency of stools. Secondary outcomes were duration of vomiting and fever and rate of admission to hospital. Safety and tolerance were also recorded.\n 571 children were allocated to intervention. Median duration of diarrhoea was significantly shorter (P<0.001) in children who received L rhamnosus strain GG (78.5 hours) and the mix of four bacterial strains (70.0 hours) than in children who received oral rehydration solution alone (115.0 hours). One day after the first probiotic administration, the daily number of stools was significantly lower (P<0.001) in children who received L rhamnosus strain GG and in those who received the probiotic mix than in the other groups. The remaining preparations did not affect primary outcomes. Secondary outcomes were similar in all groups.\n Not all commercially available probiotic preparations are effective in children with acute diarrhoea. Paediatricians should choose bacterial preparations based on effectiveness data.\n Current Controlled Trials ISRCTN56067537 [controlled-trials.com].", "Probiotics administration has been claimed to prevent antibiotic-associated diarrhea. The investigators thus conducted a double blind, placebo controlled study of providing probiotics to infants and children with severe bacterial infections and receiving broad spechum antibiotics. The results of the study showed that the group receiving probiotics had fewer diarrheal episodes (37.5%) than the control group (80%), although the numbers were too small for statistical analysis. In conclusion, probiotics administration to patients receiving high doses of broad spectrum antibiotics may prevent the occurrence of antibiotic-associated diarrhea. A further study with a larger number is required.", "OPT-80, a novel, minimally absorbed macrocycle, is a candidate treatment option for Clostridium difficile infection (CDI) based on cure without recurrence of CDI in the hamster challenge model, good in vitro activity against C. difficile, and relative sparing of commensal gram-negative anaerobes. In this open-label, dose-ranging clinical trial, 48 evaluable subjects were randomized to receive either 50, 100, or 200 mg of OPT-80 orally every 12 h for 10 days as treatment for mild to moderately severe CDI. OPT-80 was well tolerated by all subjects. Plasma concentrations were below the lower limit of quantitation in almost one-half of patients and typically <or=20 ng/ml across the dose range; the mean fecal concentrations exceeded the MIC at which 90% of the isolates tested are inhibited by 2,000- to 10,000-fold with increasing dosages. Resolution of diarrhea within 10 days was achieved in 10/14 patients (71%), 12/15 patients (80%), and 15/16 patients (94%), and the median time to resolution of diarrhea was reduced from 5.5 to 3.0 days with increasing dosages. Across all groups, the clinical cure rate, which was defined as resolution of diarrheal disease without the need for further treatment, was 41/45 patients (91%). Recurrence of CDI at approximately 1 month after treatment was observed in two (5%) patients, one each in the 100-mg and 400-mg groups. The apparent high clinical response, good tolerance, low recurrence rate, and more-complete and rapid symptom control with the highest dosage support the selection of the 200-mg twice-daily dose for further clinical development of OPT-80 for treatment of CDI.", "Antibiotic associated diarrhea (AAD) is a frequently encountered adverse event following antibiotic administration. Evidence suggests that probiotics may be beneficial in preventing and decreasing the severity of AAD.\n Adult patients who were prescribed antibiotics for 3-14 days were enrolled from eight Canadian centers. Study treatment was randomized at a 1 : 1 ratio of BIO-K+CL1285( (®) ) or placebo and was administered within 24 h of initiation to 5 days after termination of antibiotherapy. Patients were followed for 21 days after last dose of study treatment. The primary outcome was severity and incidence of AAD. Severity was measured by the total number of days with diarrhea and incidence was defined as the number of patients with at least one day with diarrhea over the total number of patients enrolled in the study.\n 216 patients were randomized to BIO-K+ and 221 to placebo. The mean (SD) number of days with diarrhea was 1.19. (3.20) days for the placebo and 0.67 (2.05) days for BIO-K+CL1285( (®) ) (p = 0.040). Adjusted multivariate linear regression results showed that the duration of diarrhea for BIO-K+CL1285 (®)vs. placebo was reduced by 51.5% (b[SE] = 0.515 [0.256], p = 0.045). The incidence of diarrhea was 21.8% for the BIO-K+ and 29.4% for the placebo group (OR = 0.667, p = 0.067). Multivariate logistic regression, showed that the adjusted odds ratio of AAD in patients receiving BIO-K+ vs. placebo was 0.627 (p = 0.037). Study treatment was well tolerated.\n BIO-K+ is effective for preventing and reducing the severity of AAD in patients receiving antibiotic therapy in a hospital setting.", "Diarrhoea is a common side effect of antibiotic therapy, especially in the elderly. Saccharomyces boulardii is a non-pathogenic yeast which has been demonstrated to reduce the frequency of diarrhoea in patients due to a variety of causes. We set out to assess its role in preventing antibiotic-related diarrhoea. Consecutive patients over the age of 65 admitted to medical wards, and who were being prescribed antibiotics, were randomized to receive either S. boulardii 113 g twice daily or placebo for as long as they received antibiotics. Bowel habit was monitored using a record of interdefaecatory intervals (IDI) and stool form graded 1-4 (hard to liquid). Stool samples were tested every fourth day for Clostridium difficile toxin. Of the 72 patients randomized, 69 completed the study. There was no difference in sex, age, duration of antibiotic use, length of hospital stay, IDI, stool form, the proportion of patients receiving laxatives, the number of patients experiencing watery stools (seven vs. five), or the presence of C. difficile toxin (five vs. three). No side effects were attributable to S. boulardii. There was no evidence that the concomitant use of S. boulardii with antibiotics alters patients' bowel habits or prevents the appearance of C. difficile toxin in the stool. Thus, S. boulardii cannot be recommended as a 'natural' way to prevent antibiotic-related diarrhoea. This highlights the need for proper evaluation of probiotics before their unrestricted use in medical practice.", "Convincing evidence that probiotic administration can lower the risk of antibiotic-associated diarrhoea is limited to certain micro-organisms.\n To determine the efficacy of administration of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) for the prevention of antibiotic-associated diarrhoea in children.\n Children (aged 3 months to 14 years) with common infections were enrolled in a double-blind, randomized, placebo-controlled trial in which they received standard antibiotic treatment plus 2 x 10(10) colony forming units of a probiotic (n = 120) or a placebo (n = 120), administered orally twice daily throughout antibiotic treatment. Analyses were by intention to treat.\n Any diarrhoea (>or=3 loose or watery stools/day for >or=48 h occurring during or up to 2 weeks after the antibiotic therapy) occurred in nine (7.5%) patients in the probiotic group and in 20 (17%) patients in the placebo group (relative risk, RR 0.45, 95% confidence interval, CI 0.2-0.9). Three (2.5%) children in the probiotic group developed AAD (diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea) compared to nine (7.5%) in the placebo group (RR 0.33, 95% CI 0.1-1.06). No adverse events were observed.\n Administration of L. rhamnosus (strains E/N, Oxy and Pen) to children receiving antibiotics reduced the risk of any diarrhoea, as defined in this study.", "Antibiotic-associated diarrhoea may develop during or following Helicobacter pylori eradication. We aimed to evaluate the efficacy and safety of Saccharomyces boulardii in preventing antibiotic-associated diarrhoea in patients receiving antibiotics for H. pylori eradication.\n In a multicentre prospective clinical trial, patients with peptic ulcer disease or non-ulcer dyspepsia were enrolled to receive clarithromycin, amoxicillin and omeprazole for H. pylori eradication for 14 days. These patients were then randomized to receive either S. boulardii 500 mg twice daily (treatment group) or no treatment (control group). The primary outcome measure was the development of diarrhoea during (treatment period) or within 4 weeks after treatment (follow-up period).\n Of the 389 patients that were enrolled, 376 completed the study. Within the treatment period, diarrhoea developed in 5.9% of patients in the treatment group and in 11.5% of patients in the control group (P = 0.049); and in the follow-up period, diarrhoea developed in 1.0% of patients in the treatment group and in 3.8% of patients in the control group (P = 0.09). Overall diarrhoea rates throughout the whole study period were 6.9% in the treatment group and 15.6% in the control group (P = 0.007). No significant difference was observed between the treatment and control groups in terms of adverse events.\n S. boulardii is an effective and safe treatment for prevention of antibiotic-associated diarrhoea when given concomitantly to patients receiving H. pylori eradication.", "To determine the efficacy of a combination of Bifidobacterium longum PL03, Lactobacillus rhamnosus KL53A and Lactobacillus plantarum PL02 for the prevention of antibiotic-associated diarrhea in children.\n Seventy-eight children (age: 5 months to 16 years) with otitis media, and/or respiratory tract infections, and/or urinary tract infections were enrolled in a double-blind randomized control trial in which they received standard antibiotic treatment plus a food supplement containing 10(8) colony-forming units of B. longum, L. rhamnosus and L. plantarum (n = 40) or a placebo (n = 38) orally twice daily for the duration of antibiotic treatment.\n Patients receiving probiotics had a similar rate of diarrhea (> or =3 loose or watery stools/day for > or =48 h occurring during or up to 2 weeks after the antibiotic therapy) as those receiving placebo (relative risk 0.5, 95% CI 0.06-3.5). The mean number of stools per day was significantly lower in the experimental group (mean difference -0.3 stool/day, 95% CI -0.5 to -0.07). No adverse events were reported.\n The administration of the 3 probiotics did not significantly alter the rate of diarrhea, although it reduced the frequency of stools per day. As the overall frequency of diarrhea was surprisingly low, these results should be interpreted with caution.\n 2008 S. Karger AG, Basel.", "Probiotics may be efficacious for the prevention of antibiotic-associated diarrhoea. The tolerability and acceptability of probiotics in an elderly US veteran population has not been assessed.\n To undertake a randomized trial to determine the tolerability and acceptability of a probiotic, Florajen in an elderly population with multiple comorbidities.\n Pilot randomized double-blind trial comparing a probiotic, Florajen to placebo for the prevention of antibiotic-associated diarrhoea in elderly hospitalized patients receiving antibiotics.\n Forty patients were enrolled and randomized. Antibiotic-associated diarrhoea occurred in 6/16 (37%) in the placebo group and 4/23 (17%) patients in the Florajen group, (RR 1.63, 95% CI 0.73-3.65, P = 0.15). Florajen was well tolerated in the study population with no major side effects that necessitated discontinuation.\n In this pilot study, Florajen was well tolerated in an elderly population, all of whom were taking several other medications. A larger study is needed to determine the effect of Florajen on antibiotic-associated diarrhoea and Clostridium difficile infection.", "To determine the safety and efficacy of a new preventive agent for antibiotic-associated diarrhea (AAD) in patients receiving at least one beta-lactam antibiotic.\n A double-blinded, placebo-controlled, parallel group study was performed in a high-risk group of hospitalized patients receiving a new prescription for a beta-lactam antibiotic and having no acute diarrhea on enrollment. Lyophilized Saccharomyces boulardii or placebo (1 g/day) was given within 72 h of the start of the antibiotic(s) and continued until 3 days after the antibiotic was discontinued, after which the patients were followed for 7 wk.\n Of the 193 eligible patients, significantly fewer, 7/97 (7.2%), patients receiving S. boulardii developed AAD compared with 14/96 (14.6%) on placebo (p = 0.02). The efficacy of S. boulardii for the prevention of AAD was 51%. Using a multivariate model to adjust for two independent risk factors for AAD (age and days of cephalosporin use), the adjusted relative risk was significantly protective for S. boulardii (RR = 0.29, 95% CI = 0.08, 0.98).\n The prophylactic use of S. boulardii given with a beta-lactam antibiotic resulted in a significant reduction of AAD with no serious adverse reactions.", "In most cases, acute diarrhoea will become self-limiting during the first few days after onset. For young children, however, health risks may develop when the disease lasts longer than 3 days. The purpose of the present trial was to determine whether the stool frequency of infants and toddlers suffering from acute diarrhoea could be normalised more quickly by administering the probiotic Escherichia coli Nissle 1917 (EcN) solution than by administering a placebo. The safety of EcN were also assessed. A total of 113 children (aged 2-47 months) with acute diarrhoea (> three watery or loose stools in 24 h) were randomised to either a group receiving the probiotic EcN suspension (n = 55) or a group receiving the placebo suspension (n = 58) in a confirmative, double-blind clinical trial. Depending on the age of patients, 1-3 ml per day of verum suspension (10(8) viable EcN cells per millilitre) or placebo were administered orally. The causes of the diarrhoea were viral rather than bacterial, but they were mainly unspecific infections. The median onset of treatment response (reduction of daily stool frequency to </= three watery or loose stools over at least 2 consecutive days) occurred more rapidly in the children receiving the EcN solution (2.5 days) than in those receiving the placebo (4.8 days), a significant difference (2.3 days; p = 0.0007). The number of patients showing a response was clearly higher (p < 0.0001) in the EcN group (52/55; 94.5%) than in the placebo group (39/58; 67.2%). EcN was found to be safe and well-tolerated, and it showed a significant superiority compared to the placebo in the treatment of acute diarrhoea in infants and toddlers.", "This clinical trial was carried out to determine whether oral treatment with a commercial probiotic formula containing Bifidobacterium lactis and Streptococcus thermophilus would reduce the frequency of antibiotic-associated diarrhea (AAD) in infants.\n In this double-bind formula controlled study, 80 infants, 6 to 36 months of age, were randomly assigned to receive a commercial formula containing 10 viable cells of B. lactis and 10 viable cells of S. thermophilus at the initiation of antibiotics for a duration of 15 days. The infants were assessed daily for formula intake, stool frequency, and stool consistency for a total duration of 30 days. Seventy-seven infants received nonsupplemented formula for the entire duration.\n There was a significant difference in the incidence of AAD in the children receiving probiotic-supplemented formula (16%) than nonsupplemented formula (31%).\n The present study shows that prevention against AAD in infants was obtained by oral treatment with daily dose of B. lactis and S. thermophilus.", "A double-blind, placebo-controlled trial was performed to analyse the ability of Lactobacillus plantarum 299v to prevent further recurrent episodes of Clostridium difficile-associated diarrhoea (RCDAD). Recurrence of clinical symptoms (main outcome) was seen in 4 of 11 patients who received metronidazole in combination with L. plantarum 299v and in 6 of 9 treated with metronidazole in combination with placebo. The lactobacilli treatment had no side-effects. Although the small sample size does not allow any conclusion to be drawn concerning the efficacy of L. plantarum in patients with RCDAD, these results may contribute to the ongoing discussion about the benefits of probiotics in patients with RCDAD and encourage the performance of larger multicentre studies.", "The effectiveness of probiotic therapy for acute rotavirus infectious diarrhoea in an indigenous setting with bacterial/parasitic diarrhoea is unclear. In the present study, we assessed the efficacy of probiotics in Australian Aboriginal children in the Northern Territory admitted to hospital with diarrhoeal disease.\n A randomised double-blind placebo-controlled study was conducted in Aboriginal children (ages 4 months-2 years), admitted to hospital with acute diarrhoeal disease (>3 loose stools per day). Children received either oral Lactobacillus GG (5 x 10(9) colony-forming units 3 times per day for 3 days; n = 33) or placebo (n = 31). Small intestinal functional capacity was assessed by the noninvasive 13C-sucrose breath test on days 1 and 4.\n Both groups showed mean improvement in the sucrose breath test after 4 days; however, there was no difference (mean, 95% confidence interval) between probiotic (2.9 [cumulative percentage of dose recovered at 90 minutes]; 1.7-4.2) and placebo (3.7; 2.3-5.2) groups. Probiotics did not change the duration of diarrhoea, total diarrhoea stools, or diarrhoea score compared with placebo. There was a significant (P < 0.05) difference in diarrhoea frequency on day 2 between probiotics (3.3 [loose stools]; 2.5-4.3) and placebo (4.7; 3.8-5.7) groups.\n Lactobacillus GG did not appear to enhance short-term recovery following acute diarrhoeal illness in this setting.", "Antibiotic associated diarrhea due to human intestinal microbiota abnormalities is a side effect of H. pylori eradication therapy. We examined intestinal microbiota changes during H. pylori eradication therapy and the preventive effect of CBM588 as a probiotic agent. Nineteen patients with gastro-duodenal ulcer were randomly divided into three groups: group A (without probiotics), group B (with regular doses of CBM588) and group C (with double doses of CBM588). The incidence of diarrhea and soft stools during H. pylori eradication therapy was 43% in group A and 14% in group B, while none of the patients in group C reported diarrhea or soft stools. Both bacterial counts and detection rates of bifidobacteria and/or obligate anaerobe were decreased by eradication therapy. However, bacterial counts of obligate anaerobes in group C were significantly higher than in group A (P < 0.05). Additionally, during eradication therapy C. difficile toxin A was detected in both group A and group B but not in group C. In conclusion, these results indicate that H. pylori eradication therapy induces antibiotic associated diarrhea due to abnormalities in intestinal microbiota and/or C. difficile. However, these side effects might be prevented by probiotics.", "Certain strains of lactobacilli have been shown to promote recovery from rotavirus enteritis in hospitalized children. Few studies have examined the effect of probiotics in nonhospitalized children with mild diarrhea.\n We studied in a randomized placebo-controlled trial the effect of lyophilized Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 12246, 10(10) colony-forming units of each strain twice daily for 5 days, on acute diarrhea in children in a cohort of children recruited from local day-care centers. The duration of diarrhea and assessment of stool consistency were recorded by the parents.\n In patients treated with the selected Lactobacillus strains, the mean duration of diarrhea after intervention was reduced (76 h in patients treated with probiotics vs. 116 h in the placebo group; P = 0.05). In patients with diarrhea for <60 h before start of treatment (early intervention), a more pronounced effect of probiotics was found. The time to recovery after early treatment was 79 h vs. 139 h in the placebo group (P = 0.02); 1 of 17 patients treated early vs. 6 of 13 in the control group still had loose stools 120 h after start of treatment (P = 0.03).\n In children from day-care centers with mild gastroenteritis, the combination of L. rhamnosus 19070-2 and L. reuteri DSM 12246 was effective in reducing the duration of diarrhea.", "Toxin-producing Clostridium difficile is the commonest bacterial cause of nosocomial diarrhoea and is a well recognized cause of hospital outbreaks in elderly care units. High C. difficile disease rates have been associated with the use of broad-spectrum antibiotics, especially cephalosporins. An outbreak of C. difficile infection in the elderly care unit at Gloucestershire Royal NHS Trust continued despite increased ward cleaning and strict implementation of infection control measures. A restrictive antibiotic policy that would maintain colonization resistance in the gastrointestinal tract was introduced throughout this unit. Patients admitted with suspected infection were prescribed intravenous (i.v.) benzylpenicillin 1.2-1.8 g every 6 h to cover streptococcal infections and i.v. trimethoprim 200 mg twice daily to cover urinary tract pathogens and Haemophilus influenzae. If the patient had septic shock a single iv dose of gentamicin was given (120-180 mg) to cover more resistant gram-negative bacilli. The following were monitored before and after the policy change. The number of cases of C. difficile toxin-positive diarrhoea; cefuroxime and total antibiotic use on the elderly care wards; patient mortality rates; and length of hospital stay: two hundred and fifty-two and 234 patients respectively with a discharge diagnosis of infection were admitted before and after the antibiotic policy change. Mortality rates and length of hospital stay were unchanged. Cefuroxime prescribing and total antibiotic prescribing costs fell by 5150 pounds sterling and 8622 pounds sterling respectively in the 7 month period after the change. Thirty-seven cases of C. difficile diarrhoea occurred in the period before and 16 in the period after the policy change. The incidence of C. difficile diarrhoea and of cefuroxime use has remained low since then. The use of narrow-spectrum antibiotics for hospital treatment of community-acquired infections in the elderly should be encouraged. Outbreaks of C. difficile diarrhoea should be managed with the combined approach of infection control and strict antibiotic policies.", "Recent studies have shown that probiotics, most commonly, may be useful in treating acute gastroenteritis. However, beneficial effects appear to be limited to a modest decrease in the duration of diarrhea. No studies have evaluated this therapy in moderate to severe dehydrating diarrhea in a metabolic facility.\n Male children less than 2 years of age were admitted to a metabolic unit of the Department of Pediatrics at the Federal University of Bahia, Brazil, with moderate dehydration and were randomized in a double-blind, placebo-controlled fashion. Oral rehydration solution (ORS) was administered per protocol and either placebo or was given in combination with the ORS. Output of urine, stool, and vomitus was recorded along with stool weight, nude body weight, and standard laboratory assessments for hydration.\n There was no significant reduction in diarrhea duration and stool output in the group. However, Kaplan-Meier survival analysis demonstrated that, even in moderate to severe diarrhea, resolution of the illness occurred so rapidly, that statistically significant benefits of probiotic therapy could not be demonstrated.\n Our data implies that colonization must occur before benefits of probiotics can be realized. Probiotics are, therefore, likely to be of limited benefit in treating diarrheal illnesses of short duration such as viral enteritis. The beneficial effects of probiotics may be limited to prophylactic usage in high-risk populations." ]	Based on this systematic review and meta-analysis of 23 randomized controlled trials including 4213 patients, moderate quality evidence suggests that probiotics are both safe and effective for preventing Clostridium difficile-associated diarrhea.
CD001751	[ "33086", "8330429", "16675091", "12380631", "3908675", "2866117", "6133791", "7028529", "2179780", "6387717", "2675496", "6996107", "380256", "2478336", "16784743", "1568520", "2951520", "364357", "322491", "3301905", "18373490", "15161117", "12151162", "75392", "9288368", "3540764", "3914177", "387065", "2919094", "8935744", "6351994", "345993", "17407641", "4871666", "3680556", "9065377", "2783493", "6448429", "12900528", "7050953", "7951404", "17378197", "7896157", "7577849", "2646753", "12586320", "10451565" ]	[ "Treating dysmenorrhea with anti-inflammatory agents: a double-blind trial with naproxen sodium.", "An attempt at real prophylaxis of primary dysmenorrhea: comparison between meclofenamate sodium and naproxen sodium.", "The efficacy and safety of aceclofenac versus placebo and naproxen in women with primary dysmenorrhoea.", "Comparison of the efficacy and safety of nonprescription doses of naproxen and naproxen sodium with ibuprofen, acetaminophen, and placebo in the treatment of primary dysmenorrhea: a pooled analysis of five studies.", "Efficacy of fenoprofen in the treatment of primary dysmenorrhea.", "Ibuprofen and naproxen-sodium in the treatment of primary dysmenorrhea: a double-blind cross-over study.", "Dysmenorrhea in women with intrauterine contraceptive device. Treatment with a prostaglandin synthetase inhibitor, naproxen.", "Treatment of primary dysmenorrhea with diclofenac sodium.", "Transcutaneous electrical nerve stimulation (TENS) for the treatment of primary dysmenorrhea: a randomized crossover comparison with placebo TENS and ibuprofen.", "Diflunisal compared with naproxen in the treatment of dysmenorrhea.", "[Magnesium--a new therapeutic alternative in primary dysmenorrhea].", "Analgesic efficacy of ibuprofen for treatment of primary dysmenorrhea.", "Clinical experience of naproxen in the treatment of primary dysmenorrhea.", "Comparison of ketoprofen and naproxen in the treatment of dysmenorrhoea, with special regard to the time of onset of pain relief.", "Randomized controlled trial assessing a traditional Chinese medicine remedy in the treatment of primary dysmenorrhea.", "A clinical trial of hydroxyethylrutosides in the treatment of haemorrhoids of pregnancy.", "Surgical treatment of primary dysmenorrhea with laparoscopic uterine nerve ablation.", "Naproxen sodium in dysmenorrhea. Its influence in allowing continuation of work/school activities.", "The treatment of dysmenorrhea with naproxen sodium: a report on two independent double-blind trials.", "Psychological treatments of dysmenorrhea: differential effectiveness for spasmodics and congestives.", "Efficacy and tolerability of lumiracoxib 200 mg once daily for treatment of primary dysmenorrhea: results from two randomized controlled trials.", "Efficacy and tolerability of lumiracoxib in the treatment of primary dysmenorrhoea.", "Valdecoxib, a cyclooxygenase-2-specific inhibitor, is effective in treating primary dysmenorrhea.", "Flufenamic acid in treatment of primary spasmodic dysmenorrhoea. A double-blind crossover study.", "Analgesic effect of a herbal medicine for treatment of primary dysmenorrhea--a double-blind study.", "Acupuncture for the management of primary dysmenorrhea.", "Piroxicam in primary dysmenorrhea.", "Indomethacin in the treatment of primary dysmenorrhoea.", "Dynamics and significance of placebo response in primary dysmenorrhea.", "Curative treatment of primary (spasmodic) dysmenorrhoea.", "Efficacy of ketoprofen in treating primary dysmenorrhea.", "Indomethacin in the treatment of primary dysmenorrhoea.", "Efficacy of a paracetamol and caffeine combination in the treatment of the key symptoms of primary dysmenorrhoea.", "Dysmenorrhoea unrelieved by an oral contraceptive.", "Alterations in intrauterine pressure, menstrual fluid prostaglandin F levels, and pain in dysmenorrheic women treated with nimesulide.", "A crossover comparison of bromfenac sodium, naproxen sodium, and placebo for relief of pain from primary dysmenorrhea.", "Transcutaneous electrical nerve stimulation in the relief of primary dysmenorrhea.", "Severe, primary dysmenorrhea treated with naproxen. A prospective, double-blind, crossover investigation.", "Analgesic efficacy of etoricoxib in primary dysmenorrhea: results of a randomized, controlled trial.", "Feldene in the symptomatic treatment of primary dysmenorrhoea.", "Pain of endometriosis: effects of nafarelin and danazol therapy.", "[Randomized controlled study on superficial needling for treatment of primary dysmenorrhea].", "[Treatment of primary dysmenorrhea. Comparative study of ibuprofen and mefenamic acid].", "Updating the clinical experience in endometriosis--the European perspective.", "[Piroxicam versus naproxen in primary dysmenorrhea].", "A study of co-treatment of nonsteroidal anti-inflammatory drugs (NSAIDs) with misoprostol for cervical priming before suction termination of first trimester pregnancy.", "[Menstrual prostaglandin and dysmenorrhea: modulation by non-steroidal antiinflammatory drugs]." ]	[ "Thirty-two dysmenorrheic patients participated in a double-blind trial of naproxen sodium for three consecutive menstrual cycles. The women were divided into two groups: 15 women were given naproxen sodium (the sodium salt of d-2-(6-methoxy-2-naphthyl) propionic acid) and 17 women received placebo tablets. The women were prescribed two tablets (550 mg) at the first sign of menstrual pain and one tablet (275 mg) thereafter every six hours, as required. There were no significant differences between the two groups in physical characteristics, obstetric and gynecologic histories, including the character of dysmenorrhea and pretreatment pain intensity scores (p = 0.7). Following intake of the drug or placebo, the participants rated the relief provided by the medication with a six-point scoring system. When the scores for pain relief were tallied for the three treatment cycles, the naproxen sodium group averaged 13.7 +/- 0.65 standard error, while the placebo group averaged 8.8 +/- 0.95 standard error out of a possible maximum relief score of 18. The difference between the two groups was statistically significant at p = 0.0004. Few patients reported side effects.", "Dysmenorrhea is a widespread phenomenon, affecting mainly young nulliparous women, often inducing difficulties in study or in work. Its pathogenesis involves a release of local vasoconstrictors like Prostaglandins and Leukotrienes. Modern therapy is based firstly on the administration of prostaglandin-Synthetase Inhibitors or Contraceptive Pills, with the aim of reducing the menstrual excess of pain inducing substances. In order to achieve more efficacy, on the basis of the already proven effectiveness of the Non Steroid Anti-Inflammatory Drugs (NSAID)s in this field, we recently set out to prevent dysmenorrhea in a double-blind randomized study with Meclofenamate Sorium and Naproxen Sodium. Through the observation of the drop in Basal Body Temperature which usually precedes menstrual flow, we were able to instruct our patients in the earlier recognition of impending menstrual onset, leading to earlier prevention of Prostaglandin and Leukotriene release. Meclofenamate Sodium in particular led to considerable pain reduction, with very good patient compliance and without significant complications, probably of its additional receptor effect.", "To determine the analgesic efficacy and safety of a single oral dose of aceclofenac 100 mg and compare that with placebo and naproxen 500 mg in women with primary dysmenorrhoea.\n In this double-blind, prospective, multicentre, randomised, three-way, crossover study, women were randomly assigned to receive one of six treatment sequences, comprising single oral doses of aceclofenac 100 mg, naproxen 500 mg or placebo, when menstrual pain reached a predetermined level of severity. A single dose of the assigned study medication was taken on three menstrual periods; a different medication was taken on each treatment day. Analgesic efficacy was determined by self-reported analgesia scoring and participants' and investigators' global evaluation of treatment effectiveness. Measurements also included physical examination and adverse events.\n Total pain relief scores were not statistically significantly different for aceclofenac and naproxen, and both were statistically significantly more effective than placebo (p = 0.019 and 0.002, respectively). This finding was supported by secondary endpoints including sum of pain intensity differences (SPID/8), peak analgesia (peak pain intensity and peak pain relief), and participants' and investigators' overall evaluation of effectiveness. Both aceclofenac and naproxen were well tolerated.\n Aceclofenac (100 mg) and naproxen (500 mg) effectively treated the pain associated with primary dysmenorrhoea, and both were more effective than placebo at easing menstrual pain assessed by various pain relief criteria.", "Dysmenorrhea is the most common menstrual complaint in young women, with a prevalence as high as 90%. It is responsible for substantial repeated short-term absenteeism from school and work in young women. Effective treatments are available, including nonsteroidal anti-inflammatory drugs (NSAIDs). In many countries, a variety of NSAIDs have become available as over-the-counter (OTC) drugs.\n The goal of this study was to compare the efficacy and safety of OTC doses of naproxen (400 mg) and naproxen/naproxen sodium (200/220 mg) with acetaminophen (1000 mg), ibuprofen (200 mg), and placebo in the treatment of primary dysmenorrhea.\n A pooled analysis of 5 trials was performed. Efficacy was assessed by pain relief, relief of other dysmenorrheic symptoms, time to backup medication or remedication, and treatment preference. Tolerability was assessed by recording adverse events (AEs).\n A total of 443 women were enrolled in the combined studies. Naproxen 400 mg provided greater pain relief than acetaminophen and placebo within 30 minutes of administration (P < 0.01 and P < 0.05, respectively). Furthermore, naproxen 400 mg and 200 mg provided greater pain relief than both acetaminophen (P < 0.01 and P < 0.05, respectively) and ibuprofen (P < 0.001 and P < 0.01, respectively) at 6 hours after administration. Both doses of naproxen had higher scores than placebo for symptom relief and drug preference (all P < 0.001). The AEs and their frequency were similar among the treatment groups. No serious AEs were reported.\n When administered at OTC doses, naproxen was effective in the relief of pain and other symptoms of primary dysmenorrhea and had a good safety profile in the population studied.", "We compared fenoprofen calcium, 200 mg; fenoprofen calcium, 400 mg; aspirin, 650 mg; and a placebo in 85 women for the relief of primary dysmenorrhea in a double-blind, clinical trial. The usefulness of these drugs was judged from data obtained over four consecutive menstrual periods on: restriction of daily activity, pain intensity scores, need for rescue analgesics, withdrawal due to lack of efficacy, and adverse events. Both fenoprofen, 200 mg, and fenoprofen, 400 mg, offered significant (P less than .01) pain relief when compared to placebo and aspirin. Analyses of data on 1, 2 and 3 indicated that aspirin was not significantly different from placebo. The aspirin-treated group reported the greatest number of adverse reactions, but the differences between the four groups were not statistically significant. Our study lends support to the concept of a \"plateau analgesic effect\" of nonsteroidal antiinflammatory drugs (NSAIDs): fenoprofen, 200 mg, appears to be as effective as fenoprofen, 400 mg. When this type of drug fails to provide relief for a woman suffering from primary dysmenorrhea, switching to another NSAID may be more appropriate than increasing the dosage and the probability of dosage-related side effects.", "The efficacy of ibuprofen and naproxen-sodium for the treatment of primary dysmenorrhea was evaluated in a double-blind cross-over study in 57 otherwise healthy women. The severity of pain reported by the patients was significantly (P less than 0.01) reduced during treatment with both ibuprofen and naproxen-sodium compared to the severity of pain before the first dose. The mean pain relief during treatment with ibuprofen was significantly (P less than 0.05) greater than during treatment with naproxen-sodium in the dosages indicated.", "Twenty-one women with intrauterine contraceptive devices (IUCD) and severe dysmenorrhea were studied. All the women who participated in the study had primary dysmenorrhea of varying intensities. The insertion of IUCD increased the intensity of dysmenorrheic pain. The effect of naproxen (Naprosyn) on pain alleviation was studied in a double-blind cross-over trial using naproxen and placebo. The effect of naproxen was significantly better than that of placebo (P less than 0.01). No severe side effects occurred during the treatment. There was no difference in the duration and amount of the menstrual blood flow during naproxen treatment compared to placebo according to the women's own judgement.", "The efficacy of diclofenac sodium was investigated in the painful symptoms of primary dysmenorrhea and in reducing menstrual bleeding. Thirty-five nulliparous women (17-28 yr of age) were included in a double-blind cross-over study for four menstrual periods, two periods with diclofenac sodium and two periods with placebo. The diclofenac sodium treatment (total of 58 periods) reduced the pain significantly in comparison with placebo (57 periods), as evaluated by subjective rating (P less than 0.001) and by a 6-point scale of pain intensity (P less than 0.05). Also the amount of menstrual bleeding was significantly reduced as measured by subjective rating (P less than 0.001) and by counting the number of sanitary pads used (P less than 0.05). The results indicate that diclofenac sodium in low dose (about 75 mg daily) is effective not only in reducing the pain at menstruation, but also the bleeding.", "In a randomized four-way crossover study, 32 women with primary dysmenorrhea were treated with transcutaneous electrical nerve stimulation (TENS) for two cycles, placebo (sham) TENS for one cycle, or ibuprofen 400 mg four times a day for one cycle. The TENS setting used was 100 pulses per second with 100-microsecond pulse widths. The subjects were allowed to adjust the amplitude to a comfortable level. The pain rescue medication was ibuprofen 400 mg as needed, up to 1600 mg/day. Significantly more subjects who had TENS treatment did not require rescue medication or required less backup ibuprofen at 0-4, 4-8, and 8-12 hours after the onset of dysmenorrhea and starting treatment, as well as during the first 24 hours and for the duration of the menstrual flow, when compared with placebo TENS or ibuprofen-treated cycles (Tukey multiple comparison, P less than .01). Transcutaneous electrical nerve stimulation significantly delayed the need for ibuprofen by an average of 5.9 hours, compared with 0.7 hours when using ibuprofen alone (P less than .05, paired t test). Transcutaneous electrical nerve stimulation alone provided good to excellent subjective pain relief in 42.4% of subjects, compared with 3.2% with placebo TENS, and significantly reduced diarrhea, menstrual flow, clot formation, and fatigue compared with placebo TENS. Transcutaneous electrical nerve stimulation plus less ibuprofen provided pain relief equivalent to that obtained with ibuprofen alone (71 and 75% of the subjects, respectively). We conclude that TENS is a safe, effective, non-medication method for managing primary dysmenorrhea and that TENS plus ibuprofen was the best overall treatment, as indicated by pain relief.", "A randomized double-blind cross-over study was carried out in 19 young female undergraduates with severe primary dysmenorrhea to compare the efficacy and tolerance of treatment with diflunisal and naproxen. All patients received both substances twice during four consecutive cycles. The first tablet was taken at the onset of dysmenorrheic symptoms and continued according to the individual need, maximally four tablets daily. The overall relieving effect was good or moderate in 73.7% of the diflunisal cycles and in 92.1% of the naproxen cycles. The difference was not statistically significant. One third of the women estimated decreased menstrual blood loss during treatment with both the drugs. Side effects were mild and did not cause discontinuation of the therapy. Diflunisal seems to be as equally effective in the treatment of primary dysmenorrhea as naproxen, which is a well-documented and widely used prostaglandin synthetase inhibitor.", "50 patients suffering from primary dysmenorrhoea were treated with Magnesium (Mg 5-longoral, Artesan GmbH) in a double-blind study. After a six-month period 21 out of 25 women showed a decline of symptoms, only 4 ones reported no therapeutical effect. For monitoring treatment results prostaglandin F2 alpha (PGF2 alpha) was measured every second month. On Mg-therapy conditions we achieved a reduction of PGF2 alpha in menstrual blood to 45% of value before treatment started. As against that 90% of basic concentration were estimated from women who received a placebo. Probably, the specific therapeutical effect of Mg based on inhibition of biosynthesis of PGF2 alpha but also on its direct muscle relaxant and vasodilatory effect. Beside the PG-synthesis and ovulation inhibitors the use of Magnesium is a potential, natural opportunity to treat primary dysmenorrhoea, which is widely free of side effects.", "Fifty-five women with primary dysmenorrhea were enrolled in a study which each took ibuprofen (400 mg), propoxyphene hydrochloride (64 mg), or a placebo alternately in consecutive menstrual cycles for relief of pain. Fifty-one completed the study during three successive cycles in this triple-blind, crossover, randomized investigation. Ibuprofen was clearly superior to propoxyphene and the placebo in patient preference, degree of relief, and need for supplementary analgesics. In addition, a significantly greater number of patients were able to pursue their normal daily functions during the ibuprofen cycle. Propoxyphene was superior to the placebo but not to the same extent as ibuprofen. Only three side effects were reported during the study, two relative to propoxyphene and one recorded during a placebo cycle. These data show that ibuprofen is an effective agent when used for treatment of dysmenorrhea without organic etiology.", "The effect of naproxen, Naprosyn, Syntex, in treatment of primary dysmenorrhea was studied in a double-blind, randomized, placebo controlled multicenter study. Nintyseven women, aged between 18--40 years, with severe dysmenorrhea, were treated with either naproxen, 48 women, or placebo, 49 women, for two consecutive menstrual cycles. No oral contraceptive was used. The patients were allowed to take supplementary analgesics 4--6 hours after the study drug was taken if adequate relief was not achieved. The recommended dose of naproxen was 1--2 tablets, 250 mg, as needed, with a maximum of 5 tablets daily. Medication was started at first sign of menstrual distress. Improvement was achieved in 70 per cent of the women in the naproxen group (good to excellent relief) but only in 30 per cent in the placebo group. This difference is statistically significant (p less than 0.001). There was much more supplementary medication used in the placebo group compared to the naproxen treated patients (p less than 0.001). Fewer patients had to stay in bed, or stay at home from work or school, in the naproxen group compared to the placebo group. Few side-effects were reported and most of them belonged to the dysmenorrhea symptomatology. No side-effects could be rement according to the patients' own judgement.", "In a double-blind, crossover study in 39 women with dysmenorrhoea, the effects of oral treatment with single doses of 100 mg ketoprofen and 500 mg naproxen were compared with regard to time for onset of pain relief and overall effect on symptoms. Assessments of pain severity using a visual analogue scale and an activity-related scale were made at 15-minute intervals for 2.5 hours. The results showed that ketoprofen was significantly more effective at 60 and 45 minutes, respectively, after intake of medicine and the differences remained significant until 120 and 105 minutes, respectively. Reduction in original pain by 50%, the patient's view on the overall effect after each treatment as well as a comparison of effects at the end of the study all differed significantly in favour of ketoprofen. No significant differences were found between treatments in the need for additional analgesic therapy after the 2-hour observation period or in the incidence of side-effects, which was low with both medications. It is suggested that ketoprofen could have a therapeutic advantage over naproxen, particularly in patients in whom menstrual pain develops rapidly.", "A proof-of-concept study to assess the safety and efficacy of a traditional Chinese medicine formula as treatment for primary dysmenorrhea showed no statistically significant benefit over placebo. However, some efficacy parameters suggested possible superiority of the active treatment and so a larger study needs to be performed to determine whether this remedy has a role in the treatment of dysmenorrhea.", "The safety and efficacy of 500 mg O-(beta-hydroxyethyl)rutosides given orally twice daily in the treatment of 97 patients with first-, second-, or third-degree haemorrhoids were investigated in a double-blind, randomized placebo-controlled trial. The rutosides produced a significant (P less than 0.001) improvement in patient-assessed subjective symptoms (pain, bleeding, exudation and pruritus) compared with placebo. There was also a significant (P less than 0.001) improvement in clinician-assessed subjective and objective signs (bleeding, inflammation and dilatation of the haemorrhoidal plexus) after 2 and 4 weeks' treatment compared with placebo. There were three mild, transient side-effects reported in the active treatment group and no drug-related problems in the pregnancy or delivery were observed. The results suggest that O-(beta-hydroxyethyl)rutosides provide a safe and effective treatment for women with haemorrhoids of pregnancy.", "With approximately 25% of dysmenorrheic patients reporting no improvement with nonsteroidal anti-inflammatory drugs, a study was devised to evaluate the effectiveness of a laparoscopic technique for the interruption of the uterosacral nerves. In a double-blind study of 21 patients with primary dysmenorrhea, 81% (9 of 11) reported significant relief from menstrual pain after the surgery. Performed as an outpatient procedure, laparoscopic uterine nerve ablation may alleviate dysmenorrheic complaints when other modalities have failed. Half the treated women reported continued relief of menstrual pain at 12 months. These results suggest that uterosacral nerve interruption may prove an effective alternative treatment for this menstrual disorder.", "Sixty-four women with primary dysmenorrhea participated in a double-blind, parallel trial of maproxen sodium versus placebo during three menstrual cycles. Comparative measures employed to assess the efficacy of the medications included changes in pain intensity during each dysmenorrheic episode, the degree of pain relief afforded, the necessity of using a supplementary analgesic, and the extent to which medication enabled the patients to continue their daily activities unimpeded. By these measures, naproxen sodium was significantly superior as compared to the placebo. Particularly striking was the fact that of 22 naproxen sodium treated women who historically had to stay at home from work and/or in bed, only 5 remained incapacitated compared with 21 of 26 patients of the placebo group. Only 1 patient experienced side effects (nausea and hypomenorrhea) from naproxen sodium.", "The efficacy of naproxen sodium (naproxen-Na) in dysmenorrhea has been established in two independent double-blind (placebo-controlled) studies. An initial dose of 550 mg. of naproxen-Na was followed by 275 mg. every six hours for a maximum of five days. Twenty patients were included in Study I (10 treated with naproxen-Na) and 23 patients in Study II (12 treated with naproxen-Na). Each patient received the medication during four dysmenorrheic episodes. Thus, a total of 172 treatment courses could be evaluated. A variety of efficacy criteria were measured: frequency of pill intake, changes in pain intensity, the degree of relief achieved by the medication, and need for additional analgesics. In both studies naproxen-Na was demonstrated to be superior to the placebo treatment with high statistical significance in each of these parameters.", "Two studies are reported, examining the effectiveness of psychological treatments for dysmenorrhea. In Experiment 1, 33 women with spasmodic dysmenorrhea were treated with relaxation alone, or relaxation plus imagery, or assigned to a waiting-list control condition; and 29 women with congestive dysmenorrhea were treated with relaxation alone, or assigned to a waiting-list control condition. In Experiment 2, 18 additional congestives were treated with a coping skills package, or this package plus relaxation; these two groups were compared with the two congestive groups from Experiment 1. The dependent measures were reports of symptom severity, general discomfort, resting time, and medication use. Consistent with the literature, the main findings of the present studies are: (a) relaxation training (alone or with imagery) effectively reduces resting time for spasmodics; and (b) none of the treatments was shown to be effective for congestive sufferers.", "Nonsteroidal anti-inflammatory drugs (NSAIDs) are established as treatment for managing pain associated with primary dysmenorrhea. However, the efficacy and tolerability of lumiracoxib 200 mg once daily (q.d.) has not previously been examined in primary dysmenorrhea.\n Two randomized, multicenter, double-blind, placebo-controlled, crossover studies of similar design have assessed the efficacy and tolerability of two regimens of lumiracoxib compared with placebo (Study 1) or naproxen and placebo (Study 2) in women (aged 18-45 years) with moderate to severe primary dysmenorrhea. In Study 1 (n = 132), patients received lumiracoxib 200 mg q.d., lumiracoxib 200 mg with a 200 mg redose (p.r.n.) on day 1, or placebo. In Study 2 (n = 144), patients received lumiracoxib 200 mg q.d., lumiracoxib 200 mg with a 200 mg redose p.r.n. on day 1, naproxen 500 mg twice daily (b.i.d.), or placebo. Patients recorded study medication use, efficacy assessments, and rescue medication use.\n The primary efficacy variable, summed (time-weighted) pain intensity difference (categorical scale) over the first 8 hours (SPID-8), was similar between all active treatments (e.g., p = 0.939 for naproxen 500 mg b.i.d. vs. lumiracoxib 200 mg q.d. in Study 2), and all active treatments were superior to placebo (p < 0.001). Median time-to-onset of analgesia was similar between lumiracoxib 200 mg q.d. and naproxen 500 mg b.i.d. Similar trends were observed for all other secondary efficacy variables. All treatments were well tolerated.\n Short-term administration of lumiracoxib 200 mg q.d. is effective and well tolerated and provides an alternative treatment option for the management of moderate to severe pain associated with primary dysmenorrhea.", "Two randomised, multicentre, double-blind, placebo- and active-controlled, 3-way crossover studies were performed to evaluate the efficacy and tolerability of the novel COX-2 selective inhibitor lumiracoxib in the treatment of primary dysmenorrhoea. Subjects with moderate-to-severe dysmenorrhoea received lumiracoxib 400 mg once daily (od), rofecoxib 50 mg od and placebo (Study 1; n = 84) or lumiracoxib 400 mg od, naproxen 500 mg twice daily and placebo (Study 2; n = 99). For the primary variable, summed pain intensity difference from 0 to 8 h on day 1 (SPID-8), all active treatments were superior to placebo in each study (p < 0.001); lumiracoxib was comparable to rofecoxib and naproxen. For PID (categorical scale), all active treatments were significantly better than placebo from 2 to 12 h; lumiracoxib was generally comparable to rofecoxib and naproxen. All treatments were well tolerated. Lumiracoxib 400 mg is effective and well tolerated in the treatment of primary dysmenorrhoea, with efficacy comparable to rofecoxib and naproxen.", "To compare the efficacy of the cyclooxygenase (COX)-2-specific inhibitor valdecoxib with naproxen sodium in treating menstrual pain associated with primary dysmenorrhea.\n This single-center, double-blind, placebo-controlled, randomized, crossover study compared the efficacy and safety of single oral doses of valdecoxib 20 mg and 40 mg with naproxen sodium 550 mg, or placebo, with an option of treatment for up to 3 days, twice daily. Efficacy was assessed by time-weighted sum of total pain relief, sum of pain intensity difference, time-specific pain relief, and pain intensity difference over 12 hours, time to rescue medication or first re-medication, the percentage of patients taking rescue medication, and patient's global evaluation of study medication.\n Mean time-weighted sum of total pain relief and sum of pain intensity difference were significantly superior to placebo for the first 8 and 12 hours after the initial dose of valdecoxib 20 mg (P <.01) and 40 mg (P <.001). Valdecoxib 20 mg and 40 mg were comparable to naproxen sodium 550 mg for all efficacy measures. Other differences in efficacy measures favoring the higher dose of valdecoxib did not achieve statistical significance, with the exception of sum of pain intensity difference-12. Both doses of valdecoxib were well tolerated.\n Both valdecoxib 20- and 40-mg doses were effective and well tolerated for the treatment of primary dysmenorrhea. Valdecoxib 20 mg and 40 mg demonstrate analgesic efficacy, based on onset, magnitude, and duration of analgesia that is similar to naproxen sodium, making it a potential choice for treating women with primary dysmenorrhea.", "A double-blind cross-over trial of flufenamic acid three times a day (200 mg) was carried out in forty-four patients with primary dysmenorrhoea. While on flufenamic for 3 months 82% of patients experienced significant pain relief. Associated gastrointestinal symptoms, i.e--vomiting and diarrhoea--were relieved in 66% and 52% patients respectively while on flufenamic acid. It is concluded that the fenamates are useful and safe drugs in the treatment of primary dysmenorrhoea.", "We evaluated the analgesic effect of Toki-shakuyaku-san (TSS) in women who had a combination of \"deficiency,\" of \"Yin,\" \"cold,\" and \"stagnated blood\" syndromes, and were suffering from dysmenorrhea. A diagnostic scoring system was used for determination of these conditions. We treated patients with either TSS or placebo during 2 menstrual cycles with a double-blind technique, and we followed them for 2 additional cycles. A significant alleviation of dysmenorrhea was observed in patients treated with TSS as compared to those treated with placebo. Our results suggest that TSS is effective for treatment of dysmenorrhea in patients with the above-mentioned conditions.", "The effectiveness of acupuncture in managing the pain of primary dysmenorrhea was investigated in a randomized and controlled prospective clinical study. Forty-three women were followed for one year in one of four groups: the Real Acupuncture group was given appropriate acupuncture and the Placebo Acupuncture group was given random point acupuncture on a weekly basis for three menstrual cycles; the Standard Control group was followed without medical or acupuncture intervention; the Visitation Control group had monthly nonacupuncture visits with the project physician for three cycles. In the Real Acupuncture group, 10 of 11 (90.9%) women showed improvement; in the Placebo Acupuncture group, 4 of 11 (36.4%); in the Standard Control group, 2 of 11 (18.2%); and in the Visitation Control group 1 of 10 (10%). There was a 41% reduction of analgesic medication used by the women in the Real Acupuncture group after their treatment series, and no change or increased use of medication seen in the other groups.", "Ninety-two patients with primary dysmenorrhea were included in a double-blind randomized crossover trial to study the efficacy of piroxicam on menstrual pain and associated symptoms, with placebo as control. Ninety patients completed the 4-month study period. Piroxicam afforded a highly significant relief from menstrual pain and reduced the need for the supplementary analgesic paracetamol. Piroxicam also had a significant effect on associated symptoms. The drug was well tolerated, with only a few side effects of a mild nature reported and with no difference between the piroxicam and placebo groups in this respect.", "Thirty-two patients were treated with placebo tablets or indomethacin (25 mg three times daily) in a six-month, double-blind, cross-over trial. During indomethacin therapy, 75 per cent of patients experienced significant pain relief while associated vomiting and diarrhoea were relieved in 44 per cent and 64 per cent of patients respectively. The efficacy of indomethacin was comparable to that of other prostaglandin synthetase inhibitors.", "A total of 55 patients with primary dysmenorrhea who had shown a favorable response to a preliminary treatment cycle with placebo were admitted to a double-blind study on placebo versus antiprostaglandin agents (naproxen and pirprofen). To evaluate the placebo effect and its duration, the treatment was given for 4 successive cycles. Whereas the antiprostaglandin agents were effective in most of the patients (in 80% of the pirprofen group and 85.7% of the naproxen group) and this efficacy was maintained throughout the study, a favorable response to placebo was observed in 84% in the first cycle, 29% in the second, 16% in the third and 10% in the fourth. The incidence of side effects was similar in the placebo and the active treatment groups (35.4% vs. 37.5%). It is postulated that a placebo effect in dysmenorrhea is due to a central analgesic mechanism mediated by endorphin release or possibly to psychological dynamics (mental or conditioning theories). However, this effect loses efficacy with time possibly due to a decreased susceptibility to the opioid action of the central nervous circuits responsible for menstrual pain perception or to deconditioning mechanisms.", "To prove the efficacy of oral vitamin B1 administration for the treatment of primary dysmenorrhoea, a randomised, double-blind, placebo-controlled study was carried out on 556 girls aged 12-21 yr, having moderate to very severe spasmodic dysmenorrhoea. Thiamine hydrochloride (vitamin B1) was given in a dose of 100 mg orally, daily for 90 days. The combined final results of both the 'active treatment first' group and the 'placebo first' group, after 90 days of vitamin B1 administration, were 87 per cent completely cured, 8 per cent relieved (pain almost nil to reduced) and 5 per cent showed no effect whatsoever. The results remained the same two months later as well when no drug was administered. Unlike all the current treatments which are suppression-oriented, this curative treatment directly treats the cause, is free from side effects, is inexpensive and easy to administer.", "A 6-month double-blind crossover trial compared ketoprofen with placebo in the treatment of primary dysmenorrhea in 27 women who satisfied explicit inclusion and exclusion criteria. The response to treatment was assessed with a pain scale and a disability scale and by noting amelioration of associated symptoms, such as nausea, vomiting, diarrhea, fatigue, dizziness and headache. Ketoprofen was significantly superior to placebo in relieving the pain (p less than 0.001), disability (p less than 0.001) and headache (p less than 0.01) associated with menstruation. No order effect of treatment was observed. Adverse effects were few and minimal.", "The efficacy of indomethacin, a prostaglandin synthetase inhibitor, in severe dysmenorrhoea was established in a double-blind crossover study using aspirin and placebo as the control drugs. Forty-seven female undergraduates were treated twice with each of the three substances during six consecutive menstrual cycles. Good or moderate relief was achieved in 71% of the cycles treated with indomethacin, in 40% of those treated with aspirin and in 21% of those treated with the placebo. Dizziness and drowsiness were cited by 14 patients (30%) as side-effects of indomethacin, none of these patients discontinued the therapy because all obtained good or moderate relief from dysmenorrhoea. Indomethacin proved to be a valuable agent, and significantly better than aspirin in the treatment of dysmenorrhoea. It allowed many dysmenorrhoeic women to carry out their normal activities and work during the menstrual period.", "Primary dysmenorrhoea is characterised by pain, cramping and backache at the time of menses. Despite the high prevalence of dysmenorrhoea, few sufficiently powered, placebo-controlled studies have examined the efficacy of over the counter analgesics in this condition. Furthermore, even fewer studies have directly examined the efficacy of analgesics on specific dysmenorrhoea symptoms. Research design and main outcome measures: This was a single-dose, placebo-controlled, double blind, crossover study carried out in 320 women with moderate-to-severe dysmenorrhoea pain. At 2 h following dosing, 1 g paracetamol plus 130 mg caffeine led to significantly greater pain relief compared to 1 g paracetamol alone (p < 0.05), 130 mg caffeine alone (p < 0.01) or placebo (p < 0.01). The combination was also significantly more effective in relieving abdominal cramping and backache compared to the other treatment arms. No major treatment related adverse events were reported during this study.\n When taken at recommended doses, both paracetamol and the combination of paracetamol and caffeine are safe and effective treatments for primary dysmenorrhoea. Consistent with results from other acute pain states, caffeine acts as an analgesic adjuvant and enhances the efficacy of paracetamol.", "nan", "A double-blind crossover study was carried out to evaluate the therapeutic efficacy of nimesulide and its effects on uterine activity, menstrual fluid prostaglandin F, and pain in women suffering from primary dysmenorrhea. Twenty-three women entered the clinical pharmacologic study. Intrauterine pressure was monitored with a microballoon-tipped catheter on the first day of menstruation. During the maximal pain period (based on monitoring in six patients), nimesulide significantly decreased intrauterine pressure; the measure of pain relief was consistent with decrease of uterine activity. In another six patients, the registration of intrauterine pressure during the submaximal pain period demonstrated that both in the nimesulide- and placebo-treated cycles, the uterine activity was at a lower mean level than that registered during maximal pain. Furthermore, when two 100-mg oral doses of nimesulide were administered to 11 dysmenorrheic women, in double-blind, crossover conditions with placebo as a blank reference, it brought about a reduction of menstrual fluid prostaglandin F2 levels from 382 to 94 ng/mL, (P less than .001). Fourteen women entered a four-cycle, double-blind, crossover therapeutic trial. Each patient was randomly assigned to one of two treatment sequences with nimesulide 200 mg/d PO or placebo. The therapy was judged very effective or good in 22 of 28 cycles treated with nimesulide compared with nine of 27 cycles treated with placebo (P less than .01). The amount of bleeding during the treated cycles did not change, and there were no complaints of untoward signs or symptoms related to the therapies.", "Single and multiple oral doses of bromfenac sodium (10 or 50 mg) were compared with naproxen sodium (550 mg loading/275 mg repeat doses) for the relief of pain from primary dysmenorrhea in 54 women using a crossover design. Pain intensity and pain relief were assessed over 6 h after the first dose, and global ratings were made at the end of day 1 and on day 2. A single dose of bromfenac 10 or 50 mg was as effective as the loading dose of naproxen sodium (550 mg) in relieving the pain from dysmenorrhea through a 6-h period. All three active treatments were statistically superior (p < 0.001) to placebo for the primary efficacy variables, 3-h and 6-h total pain relief and 3-h and 6-h summed pain intensity difference. All active treatments were statistically superior (p < 0.05) to placebo for the first dose and day 1 global assessments. One or more adverse study events were reported by 13 patients (25%) who received bromfenac 50 mg, 15 (29%) who received bromfenac 10 mg, 20 (38%) who received naproxen sodium, and 19 (37%) who received placebo. There were no clinically significant differences among the treatments in the types of adverse study events. No serious or unexpected adverse study events were reported, and no women withdrew from the study because of an adverse event. Bromfenac sodium (10 mg or 50 mg) is as effective as naproxen sodium (550 mg loading dose/275 mg repeat doses) for relief of pain from dysmenorrhea.", "The purpose of this study was to replicate a previous study to determine the effectiveness of acupuncture-like transcutaneous electrical nerve stimulation in treating primary dysmenorrhea. Twenty-one women with dysmenorrhea received a placebo pill or 30 minutes of acupuncture-like TENS. All subjects completed two pain questionnaires before treatment; immediately posttreatment; 30, 60, 120, and 180 minutes posttreatment; and the next morning upon awakening. Each woman also participated in a separate study measuring electrical resistance at four auricular acupuncture points before and immediately after treatment. The data were analyzed with a two-factor repeated-measures analysis of variance, which revealed statistical significance over time but not for group or interaction between group and time. Results revealed an average pain relief of at least 50% immediately posttreatment, indicating that acupuncture-like TENS may be useful for dysmenorrheic pain. This study also suggests that auriculotherapy via acupressure may relieve the pain of primary dysmenorrhea.", "26 women aged 15-45 with severe, primary dysmenorrhea were treated with naproxen (NAPROSYN, SYNTEX) and placebo during 2 x 2 consecutive menstrual cycles in a randomized, double-blind crossover study. The dosage of naproxen was 500 mg (2 tablets) initially, followed by 250 mg as needed, with a maximum of 1250 mg daily. In most cases medication started at the first sign of menstrual distress. 80 per cent of the women preferred naproxen to placebo. The number of tablets taken during each menstruation fell from a mean of 17.8 in the placebo period to 5.1 in the naproxen period. Likewise, additional analgesics fell from 7.1 to 1.6 and hours of bed rest from 16.4 to 1.2. Total number of days of sick leave per two menstruations decreased from 40 to 7. These differences are statistically significant (P < 0.001). The side effects were mild. CNS or gastrointestinal side effects were not seen. Naproxen changed the amount of bleeding in 12 and delayed bleeding in three. Two developed acne, which however gradually diminished during the next five bleeding periods treated with naproxen. The influence of prostaglandin synthetase inhibitors on the ovarian production of steroids is discussed.", "To determine the efficacy of etoricoxib in the treatment of primary dysmenorrhea.\n Seventy-three women were randomly assigned to receive single oral doses of etoricoxib 120 mg, placebo, or naproxen sodium 550 mg at the onset of moderate to severe pain associated with menses. During 3 consecutive menstrual cycles in this double-blind, 3-period, crossover study, pain intensity and pain relief were assessed over the 24-hour period following dosing, and global ratings of therapy were made at 8 and 24 h after dosing. Tolerability was assessed by spontaneous reports of adverse experiences.\n Etoricoxib 120 mg provided analgesic efficacy superior to placebo for the primary endpoint, total pain relief over 8 h (TOPAR8, p<0.001), and for all secondary endpoints (p<0.050). The analgesic effect of etoricoxib 120 mg over the first 8 h was similar to that of naproxen sodium 550 mg. All treatments were well tolerated.\n Etoricoxib 120 mg provided rapid and sustained analgesia that was superior to placebo and similar to that of naproxen sodium 550 mg.\n Copyright 2003 S. Karger AG, Basel", "nan", "To compare the efficacy of nafarelin acetate with danazol in the treatment of dysmenorrhea, dyspareunia, and pelvic pain associated with endometriosis.\n Prospective, randomized double-blind controlled study. PATIENTS, SETTING, TREATMENTS: Two hundred thirteen patients aged 18 to 48 with laparoscopically confirmed pelvic endometriosis and dysmenorrhea, dyspareunia or pelvic pain were randomly assigned to 6 months of treatment with either nafarelin acetate 800 micrograms per day or 400 micrograms per day, or danazol 800 micrograms per day.\n The percentage of patients with dysmenorrhea, dyspareunia or pelvic pain before treatment who still had these symptoms after 6 months of treatment and 6 months following completion of treatment. RESULTS [table: see text]\n Nafarelin acetate and danazol both provided significant relief of dysmenorrhea, dyspareunia, and pelvic pain during treatment and for 6 months following treatment in women with endometriosis.", "To observe clinical therapeutic effect of superficial needling at distal and proximal acupoints on primary dysmenorrhea (PD).\n One hundred and twenty cases of PD were randomly divided into a treatment group (n =60) and a control group (n = 60). The treatment group were treated with superficial needling at Sanyinjiao (SP 6) and the control group with oral administration of indometacin entric-coater tablets.\n Of the 120 cases, 116 cases completed the investigation. The total effective rate was 93. 3% in the treatment group and 75. 0% in the control group. The comprehensive therapeutic effect and the cured rate in the treatment group were significantly better than that in the control group (P<0. 001), with a more rapid effect and lasting a longer time than the control group.\n Clinical therapeutic effect of superficial needling at Sanyinjiao (SP 6) on primary dysmenorrhea is better than that of oral administration of indometacin entric-coater tablets.", "In double-blind studies, mefenamic acid (group A) was compared with ibuprofen (group B) in the treatment of primary dysmenorrhea in 60 patients, during two cycles. The initial pain intensity was 8.9 for group A and 8.5 for B. The medication were administered at cero time (when the colic begin) and each 8 hours during the menstrual period. The decrease of pain intensity was presented after the second pill administration in group A for 8.6 + 1.8 at 6.0 + 2.4 in the first cycle and 8.5 +/- 1.8 at 5.9 +/- 2.6 in the second cycle. The group B the decrease of pain was similar of 8.2 +/- 1.7 at 5.1 +/- 2.6 for the first cycle and the 8.2 +/- 1.7 at 4.7 +/- 2.6 in the second cycle of treatment. The number of tablets administered for both groups were for group A 5.5 and for B 4.4. The duration of pain were 22.1 hours for group A and 19.3 for B.", "In a large, double-blind, multicentre study, 269 patients with confirmed endometriosis were randomly allocated to receive either danazol (200 mg twice daily; n = 137) or gestrinone (2.5 mg twice weekly; n = 132) for 6 months. The two groups were comparable in terms of the staging of endometriosis by the American Fertility Society (1979) score. After the sixth month of treatment, repeat laparoscopy was performed. Clinical assessment, haematological and biochemical investigations were carried out during the 6 months of treatment and for a further 12 months' follow-up and are compared between the two groups. A total of 15 patients from the gestrinone group, including four patients with hirsutism, and 17 patients from the danazol group, including six patients with headache, withdrew because of adverse symptoms. An additional 22 patients, including 10 from the gestrinone group and 12 from the danazol group withdrew because of lack of efficacy, pregnancy, elevated hepatic function tests or for reasons unrelated to the trial. Total American Fertility Society scoring showed an improvement of 73.3% in 101 patients receiving gestrinone and 72.7% in 99 patients receiving danazol. The results showed a significant reduction in the severity of dysmenorrhoea by the third month in the danazol group and at 6 months in both groups. There was a significant (P < 0.001) increase in weight observed in both groups during treatment. Overall, the tolerability of danazol and gestrinone was good; however, significantly more patients with gestrinone complained of hirsutism while significantly more with danazol complained of leg cramps. During the 12 months of follow-up, mild, moderate or severe degrees of lower abdominal pain, dysmenorrhoea and deep dyspareunia all fluctuated, with no statistically significant increase in frequency in either group.", "In this study 198 patients with primary dysmenorrhea were entered into a double-blind, randomized crossover trial to study the efficiency of piroxicam compared to naproxen on menstrual pain and associated symptoms. The dosage for piroxicam was 40 mg on the first and second day of the menstrual cycle, and if necessary an additional 20 mg on the third day. The dosage for naproxen was 1,000 mg on the first and second day, and if necessary an additional 500 mg on the third day. Piroxicam and naproxen afforded high relief from menstrual pain and associated symptoms. The drugs were well tolerated with only a few side effects of a mild nature. There were no statistically significant differences between piroxicam and naproxen.", "This double-blind randomized control study was conducted to evaluate whether a nonsteroidal anti-inflammatory drug (NSAID) could act as an effective pain control method during first trimester suction abortion, and whether co-treatment of NSAID with misoprostol will decrease the efficacy of the cervical ripening effect of misoprostol. Subjects were randomized to receive misoprostol alone or misoprostol together with diclofenac sodium. Both groups of subjects suffered from similar incidence of preoperative side effects. Co-treatment of NSAID with misoprostol did not attenuate the cervical ripening efficacy of misoprostol. There was no significant pain reduction in the group treated with NSAID, except that a marginal benefit was found in the subgroup of multiparous women. About two thirds of the subjects in both treatment groups found that this was a satisfactory pain relief method during the procedure.", "The analgesic efficacy and tolerance of lysine clonixinate (LC) as well as LC-induced changes in menstrual prostaglandin levels were studied according to a prospective double-blind randomized crossover design, controlled with ibuprofen (I) and placebo (P). Treatment consisted in 4 consecutive phases: in the first phase, patients refrained from taking medication and during the remaining three phases, they received double-blind fixed doses of 1 tablet of lysine clonixinate 125 mg, I 400 mg or P, q.6 h. at random, three days before onset of menses and during 8 days thereafter. Controls were carried out at each menstrual cycle, assessing pain according to a scale from 0 to 4, onset of premenstrual and intramenstrual symptoms, relief of pain and occurrence of side-effects. During menstruation, patients recorded their assessments of pain in a diary and collected the whole menstrual bleeding during the first three days. The intensity of menstrual pain remained unchanged in controls upon admission (3.16) and during the phase with no treatment (3.04), but was significantly reduced with P (2.4), LC (1.79) and I (1.54). Significantly lower pain intensities compared with placebo were seen with active treatment phases. Forty-two percent of patients treated with P reported premenstrual pain which was significantly reduced to 17% with LC and to 12.5% with I. Active treatment phases revealed 21% of asymptomatic patients during premenstrual and menstrual periods and 71% (LC) and 75% (I) of cases with partial relief of pain. Patients' diaries showed significant pain reductions with LC and I, during the 1st and 2nd days compared with P; such differences were gradually reduced to nil by the 4th day. Levels of menstrual PGs changed according to pain intensity reductions from baseline (P: 29%, (NS); LC: 58% and I: 61%; both were statistically significant, p < 0.01)." ]	NSAIDs are an effective treatment for dysmenorrhoea, though women using them need to be aware of the significant risk of adverse effects. There is insufficient evidence to determine which (if any) individual NSAID is the safest and most effective for the treatment of dysmenorrhoea.
CD005943	[ "16225575", "20005647", "10453830", "2437967" ]	[ "First trimester threatened miscarriage treatment with human chorionic gonadotrophins: a randomised controlled trial.", "Dydrogesterone in threatened miscarriage: a Malaysian experience.", "Randomised trial comparing expectant with medical management for first trimester miscarriages.", "Double-blind controlled trial of progesterone substitution in threatened abortion." ]	[ "To determine whether administration of exogenous human chorionic gonadotrophin (hCG) treatment improve the pregnancy outcome in first trimester threatened miscarriages.\n A prospective, double blind, randomised, placebo-controlled trial.\n The Early Pregnancy Assessment Unit, Royal Bolton Hospital, Bolton, United Kingdom.\n One hundred and eighty-three women with vaginal bleeding and a viable fetus seen on ultrasound scan (USS) in the first 12 weeks of pregnancy.\n The patients were randomised to receive either hCG or placebo treatment until 14 weeks of gestation.\n The primary objective of the trial was to determine the miscarriage rate in the hCG arm compared from the placebo arm.\n Of the 183 cases, 87 were randomised to treatment with hCG while 96 were randomised to receive a placebo. Forty-seven (25%) did not comply with the study protocol. The mean [SD] gestational age at presentation was 7 [1.33] weeks. The mean [SD] age of women in study was 27 [5] years in the placebo and 28 [5] in the hCG group. The mean body mass index (kg/m(2)) was 25 [5] in the study. The number of patients actively bleeding per vaginum at presentation was 85 (93%) in placebo group and 79 (96%) in the hCG group. The median number of hCG or placebo injections for both groups was 7. Ten women (11%) in the placebo group proceeded to have a complete miscarriage, as did 10 women (12%) in the hCG group, relative risk (RR) [95% confidence interval (CI)] of 1.1 (0.63-1.6).\n Our study showed no evidence of a difference in the outcome of threatened miscarriages when treated with hCG in the first trimester, this may be because our study sample size was small and follow up was suboptimal. A large, randomised, multicentre trial is still needed to establish the usefulness of hCG treatment in cases of threatened miscarriage.", "Threatened miscarriage is a common problem during pregnancy.\n The aim of this prospective, open, randomised study was to determine whether dydrogesterone was more effective than conservative management alone in preventing miscarriage in women with vaginal bleeding up to week 16 of pregnancy. Women were excluded if they had a history of recurrent miscarriage. A total of 191 women were randomised to dydrogesterone (40 mg stat followed by 10mg twice daily) or conservative management (control group). The treatment was considered successful if the pregnancy continued beyond 20 weeks of gestation.\n The success rate in the dydrogesterone group was statistically significantly higher than that in the control group (87.5% vs. 71.6%; p<0.05). Miscarriage occurred in 12.5% of women in the dydrogesterone group compared with 28.4% in the control group (p<0.05). There were no differences between the groups with regard to the incidence of Caesarean section, placenta praevia, antepartum haemorrhage, preterm labour (weeks 28-36), pregnancy-induced hypertension or low birth weight (<2500 g) babies. There were no intrauterine deaths or congenital abnormalities in either group.\n Compared with conservative management, dydrogesterone had beneficial effects on maintaining pregnancy in women with threatened miscarriage.\n Copyright 2009 Elsevier Ireland Ltd. All rights reserved.", "To compare the efficacy of antiprogesterone (mifepristone) in combination with a synthetic prostaglandin E1 analogue (misoprostol) for outpatient treatment of miscarriages.\n One hundred and twenty-two women with first trimester miscarriages.\n The women were randomised to treatment with mifepristone 400 mg orally followed by a single oral dose of 400 microg misoprostol 48 hours later (n = 60) or expectant management (n = 62). Women were re-evaluated five days later. If retained intrauterine products of conception were found with an antero-posterior diameter above 15 mm on transvaginal ultrasound, surgical evacuation was performed.\n Eighty-two percent of the women randomised to pharmacological treatment and 76% of those randomised to expectant management had an empty uterine cavity after five days. Convalescence time was 1.8 days longer for women randomised to pharmacological treatment. Pain, bleeding, complications, and satisfaction with the treatment did not differ between the groups.\n Most cases of spontaneous incomplete miscarriage will become a complete miscarriage without intervention. This study shows that outpatient treatment with a combination of antiprogesterone and a prostaglandin E1 analogue did not increase the rate of complete miscarriage, compared with expectancy alone, by a clinical important degree.", "Between 1983 and 1984 a double-blind randomized study with progesterone substitution in threatened abortion was carried out. Fifty-six patients with vaginal bleeding during the first trimester of pregnancy, the internal cervical os being closed, were referred to the hospital. Twenty-five women (5th and 6th week of gestation) with positive serum concentrations of beta-hCG were admitted to the study without regard to sonogram results. In other 25 women (7th-10th week of pregnancy) and 6 women (greater than or equal to 11th week of pregnancy) fetal heart action and movement could be demonstrated by ultrasound. The patients were prescribed bed rest and vaginal suppositories twice daily, containing either 25 mg progesterone or only polyethylene glycol. The code was not broken until after completion of the study. Serial serum determinations of beta-hCG, estradiol-17 beta (E2), progesterone, and ultrasound were performed. Four patients had to be omitted from final analysis (two tubal pregnancies, one intrauterine infection, one sectio parva). Three of 26 patients progesterone (11%) and five of 26 patients with placebo (19%) had an abortion, which represented no significant difference. Frequency of abortion was increased in women more than 30 years old, in women with previous abortions and after ovulation induction. Progesterone treatment resulted in a significant elevation of serum progesterone concentrations (p less than 0.01), while beta-hCG and E2 were unchanged. The results of this study confirm that pregnancy outcome is favorable in women with bleeding and normal hormone concentrations without hormonal treatment and unfavorable in women with reduced beta-hCG and E2-concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)" ]	The data from this review suggest that the use of progestogens is effective in the treatment of threatened miscarriage with no evidence of increased rates of pregnancy-induced hypertension or antepartum haemorrhage as harmful effects to the mother, nor increased occurrence of congenital abnormalities on the newborn. However, the analysis was limited by the small number and the poor methodological quality of eligible studies (four studies) and the small number of the participants (421), which limit the power of the meta-analysis and hence of this conclusion.
CD007791	[ "12771264" ]	[ "Idebenone treatment in Friedreich patients: one-year-long randomized placebo-controlled trial." ]	[ "The authors carried out a 1-year, randomized, placebo-controlled trial of idebenone in 29 patients with Friedreich ataxia. They found significant reductions of interventricular septal thickness and left ventricular mass in the idebenone group vs the placebo group, with no improvement in other heart ultrasound measures or neurologic condition. The absolute cardiac changes were modest, but the findings suggest that larger trials should assess whether idebenone reduces ventricular hypertrophy in patients with Friedreich ataxia." ]	No RCT using idebenone or any other pharmacological treatment has shown significant benefit on neurological symptoms associated with Friedreich ataxia. Idebenone has shown a positive effect on left ventricular heart mass but the clinical relevance of this change was not assessed in the included study.
CD008817	[ "17919621", "22554673", "12698153" ]	[ "A randomized controlled trial of tacrolimus versus cyclosporine after lung transplantation.", "Tacrolimus and cyclosporine have differential effects on the risk of development of bronchiolitis obliterans syndrome: results of a prospective, randomized international trial in lung transplantation.", "Cyclosporine A versus tacrolimus in combination with mycophenolate mofetil and steroids as primary immunosuppression after lung transplantation: one-year results of a 2-center prospective randomized trial." ]	[ "The optimal maintenance immunosuppressive regimen after lung transplantation is uncertain.\n We conducted a randomized controlled trial of tacrolimus versus cyclosporine in combination with azathioprine and prednisone after lung transplantation. Ninety adults were randomized to tacrolimus (n = 44) or cyclosporine (n = 46). The primary end point was a composite of a cumulative acute rejection A score of 3 or higher, a cumulative lymphocytic bronchitis B score of 4 or higher, or the onset of bronchiolitis obliterans syndrome (BOS) stage 0-p.\n Recipients randomized to cyclosporine were significantly more likely to develop the primary end point than those randomized to tacrolimus. During the study period, the primary end point developed in 39 of 46 cyclosporine subjects compared with 24 of 44 tacrolimus subjects (p = 0.002); acute rejection or lymphocytic bronchitis end points developed in 29 of 46 cyclosporine subjects compared with 18 of 44 tacrolimus subjects (p = 0.036). Furthermore, BOS stage 0-p was more likely to develop in the cyclosporine group than in the tacrolimus group, but this was not statistically significant (log-rank p = 0.1). In addition, there was a trend to a higher incidence of diabetes among those in the tacrolimus group, but there was no significant difference in graft survival or the total number of infections, or in the incidence of hypertension, chronic kidney disease, or cancer between the 2 groups.\n Tacrolimus is associated with a lower burden of acute rejection and lymphocytic bronchitis and a trend to a greater freedom from BOS stage 0-p than cyclosporine after lung transplantation.", "Chronic lung allograft dysfunction, which manifests as bronchiolitis obliterans syndrome (BOS), is recognized as the primary cause of morbidity and mortality after lung transplantation. In this study we assessed the efficacy and safety of two de novo immunosuppression protocols to prevent BOS.\n Our study approach was a multicenter, prospective, randomized (1:1) open-label superiority investigation of de novo tacrolimus vs cyclosporine, with both study arms given mycophenolate mofetil and prednisolone after lung transplantation. Cytolytic induction therapy was not employed. Patients were stratified at entry for cystic fibrosis. Primary outcome was incidence of BOS 3 years after transplant (intention-to-treat analysis). Secondary outcomes were survival and incidence of acute rejection, infection and other adverse events.\n Group demographic data were well matched: 110 of 124 tacrolimus vs 74 of 125 cyclosporine patients were treated per protocol (p < 0.01 by chi-square test). Cumulative incidence of BOS Grade ≥1 at 3 years was 11.6% (tacrolimus) vs 21.3% (cyclosporine) (cumulative incidence curves, p = 0.037 by Gray's test, pooled over strata). Univariate proportional sub-distribution hazards regression confirmed cyclosporine as a risk for BOS (HR 1.97, 95% CI 1.04 to 3.77, p = 0.039). Three-year cumulative incidence of acute rejection was 67.4% (tacrolimus) vs 74.9% (cyclosporine) (p = 0.118 by Gray's test). One- and 3-year survival rates were 84.6% and 78.7% (tacrolimus) vs 88.6% and 82.8% (cyclosporine) (p = 0.382 by log-rank test). Cumulative infection rates were similar (p = 0.91), but there was a trend toward new-onset renal failure with tacrolimus (p = 0.09).\n Compared with cyclosporine, de novo tacrolimus use was found to be associated with a significantly reduced risk for BOS Grade ≥1 at 3 years despite a similar rate of acute rejection. However, no survival advantage was detected.\n Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.", "Cyclosporine (INN: ciclosporin) A or tacrolimus have been used mostly in combination with azathioprine as primary immunosuppression after lung transplantation. Benefit or risk deriving from the combination with mycophenolate mofetil are yet unknown.\n In a prospective, 2-center, open randomized trial, the combination of cyclosporine A, mycophenolate mofetil, and steroids was compared with tacrolimus, mycophenolate mofetil, and steroids as primary therapy after primary lung transplantation. All patients underwent induction therapy with rabbit antithymocyte globulin for 3 days. The 2 groups were compared with regard to patient survival, freedom from acute rejection, bronchiolitis obliterans, infectious episodes, and side effects.\n Between September 1997 and April 1999, 74 lung transplant recipients were randomized to receive either cyclosporine A (n = 37) or tacrolimus (n = 37). Groups were comparable with regard to age, sex, transplant procedure, and cytomegalovirus match. Mean follow-up was 507 +/- 258 and 508 +/- 248 days, respectively. Six- and 12-month survival was similar in both groups (89% vs 84% and 82% vs 71%, respectively; P =.748 at 12 months). Two patients from the cyclosporine A group were retransplanted. Freedom from acute rejection at 6 and 12 months was comparable between groups (46% vs 51% and 35% vs 46%, respectively; P =.774 at 12 months). The mean number of treated acute rejection episodes per 100 patient-days was higher in the cyclosporine A than in the tacrolimus group, but the difference was not statistically significant (0.32 +/- 0.42 vs 0.22 +/- 0.30, respectively; P =.097). Four patients from the cyclosporine A group had to be switched to tacrolimus to control ongoing rejection, whereas no patient from the tacrolimus group had to be switched to cyclosporine A. There was a trend toward more infections (0.7 +/- 0.36 vs 0.55 +/- 0.31, P =.059) in the cyclosporine A group. New-onset diabetes mellitus was observed in the tacrolimus group only (11% vs 0%, P =.151), whereas there was a higher incidence of hypertension (60% vs 11%, P =.03) in the cyclosporine A group.\n This 2-center, prospective randomized study showed high immunosuppressive potency of both cyclosporine A and tacrolimus in combination with mycophenolate mofetil. No significant difference in incidence of acute rejection was observed between the 2 groups. Moreover, survival and incidence of infection were similar. Incidence of drug-related adverse events were similar, yet their spectrum was different." ]	Tacrolimus may be superior to cyclosporin regarding bronchiolitis obliterans syndrome, lymphocytic bronchitis, treatment withdrawal, and arterial hypertension, but may be inferior regarding development of diabetes. No difference in mortality and acute rejection was observed between patients treated with tacrolimus and cyclosporin. There were few studies comparing tacrolimus and cyclosporin after lung transplantation, and the numbers of patients and events in the included studies were limited. Furthermore, the included studies were deemed to be at high risk of bias. Hence, more RCTs are needed to assess the results of the present review. Such studies ought to be conducted with low risks of systematic errors (bias) and of random errors (play of chance).
CD005056	[ "15121569", "11166751", "12635758", "16241013", "20027030", "11287024", "17628562", "10929961", "12678150", "7646610", "15502060", "1890479", "11864673", "15139942", "12193488" ]	[ "Paracervical block in incomplete abortion using manual vacuum aspiration: randomized clinical trial.", "Comparison of paracervical block techniques during first trimester pregnancy termination.", "Pain relief using paracervical block in patients undergoing manual vacuum aspiration of uterus.", "Randomized controlled trial of mefenamic acid vs paracervical block for relief of pain for outpatient uterine curettage.", "Paracervical block efficacy in office hysteroscopic sterilization: a randomized controlled trial.", "Paracervical block with and without conscious sedation: a comparison of the pain levels during egg collection and the postoperative side effects.", "A randomized comparison of different methods of analgesia in abortion using manual vacuum aspiration.", "Feasibility and pain control in outpatient hysteroscopy in postmenopausal women: a randomized trial.", "Double-blind randomized comparison of xylocaine and saline in paracervical block for diagnostic fractional curettage.", "Paracervical anesthesia for outpatient hysteroscopy.", "A multicenter randomized controlled trial comparing patient-controlled epidural with intravenous analgesia for pain relief in labor.", "Pain control after cesarean birth. Efficacy of patient-controlled analgesia vs traditional therapy (IM morphine).", "A randomized trial of intrapartum analgesia in women with severe preeclampsia.", "Patient-controlled analgesia versus conventional intramuscular injection: a cost effectiveness analysis.", "Iliohypogastric-ilioinguinal peripheral nerve block for post-Cesarean delivery analgesia decreases morphine use but not opioid-related side effects." ]	[ "To estimate the effectiveness of paracervical block in controlling pain among women treated with manual vacuum aspiration for an incomplete abortion\n A randomized clinical trial was conducted at Nuestra Señora de Altagracia, a maternal and perinatal referral hospital in the Dominican Republic. The sample size was based on a clinical difference of 1.5 points in the level of pain measured with the visual analog scale using 90% power and a sampling error of 0.04. Women who were at 12 weeks of gestation or less with an incomplete abortion were eligible to participate. They were randomly assigned to receive either the standard treatment of care (manual vacuum aspiration for uterine evacuation with psychological support but no paracervical block) or manual vacuum aspiration treatment with psychological support and paracervical block using 1.0% lidocaine. Patients with active infections, severe illnesses, psychiatric disorders, or allergies to lidocaine were excluded. Intraoperative pain as reported by the women and as documented by an external observer was measured.\n Although the paracervical block technique used showed a slight reduction in severe pain, there were no clinically or statistically significant differences in intraoperative pain between the 2 groups (relative risk 0.73; 95% confidence interval 0.43, 1.23) with 50% of all patients registering 7 or higher score on a visual analog pain scale of 0-10. However, statistically significant differences were found in each group when comparing the level of preoperative and intraoperative pain described by the patient (P <.001). The manual vacuum aspiration technique and the paracervical block were not accompanied by complications.\n The paracervical block technique used in this study along with psychological support was comparable with pain control using psychological support alone; neither pain management regimen provided sufficient pain control. It is recommended that randomized comparative studies be designed to determine the effectiveness of other paracervical block techniques and the efficacy of the use of analgesics in patients suffering from incomplete abortion treated with manual vacuum aspiration.", "To determine whether variations in chloroprocaine placement in paracervical blocks influence effectiveness, whether chloroprocaine is superior to saline, and what factors influence pain perception.\n Eighty-two women undergoing first trimester aspiration abortions were randomized to receive 1% chloroprocaine or saline at 3-5-7-9 or 4-8 o'clock positions. Using a 0--10 scale, women rated anxiety, dysmenorrhea, and pain associated with laminaria insertion, paracervical block, and aspiration.\n All four groups were similar in medical and demographic characteristics. Injection position did not influence pain ratings, but women who received chloroprocaine had less pain than those who received saline (6.3+/-2.3 vs. 7.8+/-2.0, P=0.002). Paracervical pain and dysmenorrhea were independently associated with aspiration pain scores (respective regression coefficients 0.49 and 0.26, P<0.008).\n There is no advantage to using a four-site paracervical block over a two-site technique, but chloroprocaine is superior to saline. Paracervical block may not provide adequate anesthesia during first trimester abortion, especially for women with significant dysmenorrhea.", "To evaluate pain relief using paracervical nerve block with 1% lignocaine injection in patients undergoing uterine evacuation by Manual Vacuum Aspiration (MVA) for the treatment of incomplete abortion.\n A randomized double blind clinical trial.\n Marie Stopes Health Centre, Nairobi.\n One hundred and forty two patients were recruited between September and October 1997. The intervention was random assignment to the study group (paracervical block with 1% lignocaine) or the placebo group (paracervical block with sterile water for injection). Intra and post operative assessment of pain was made using McGills and facial expression scales.\n The untreated group experienced significantly more pain than the treated group, especially lower abdominal pain and backache. The pain was especially marked intraoperatively, less so 30 minutes post-operatively.\n Based on the findings of this study, any patient going for manual vacuum aspiration for the treatment of incomplete abortion should be given Paracervical block as it is cost effective, easy to perform and with less side effects.", "To compare the efficacy of mefenamic acid vs paracervical block for pain relief during and after fractional curettage.\n Between January 1 and July 31, 2002, the authors enrolled 87 patients with abnormal uterine bleeding, who requested fractional curettage at the Outpatient Gynecologic Clinic, Srinagarind Hospital, Khon Kaen University. A simple randomization procedure was used to distribute the patients into a control group comprising 44 patients given a paracervical block and a treatment group comprising 43 patients given mefenamic acid (500 mg) 2 hours before starting the procedure.\n Pain was scored using a visual analogue scale (VAS range, 0 to 10).\n The median pain scores of the treatment types during endocervical, endometrial, immediately after, and 30 minutes after, fractional curettage were 2.5 vs 3.0 (p = 0.42), 6.5 vs 7.5 (p = 0.19), 4.0 vs 3.5 (p = 0.20) and 1.5 vs 1.0 (p = 0.17), respectively. The rate of complications was 6.8% (3 in 44) in the paracervical lignocaine injection group.\n The efficacy of pain relief for fractional curettage using oral mefenamic acid (500 mg) two hours before the procedure was not statistically different from the paracervical block, but there were fewer side effects. Mefenamic acid should be considered an alternate pain relief during fractional curettage.", "To estimate the efficacy of paracervical block compared with saline for pain relief during office hysteroscopic sterilization.\n This study was a randomized, placebo-controlled study of women desiring hysteroscopic sterilization. A paracervical block of 1% lidocaine or normal saline was administered before office hysteroscopic sterilization. Patients and investigators were blinded to assignments. A pre hoc power analysis determined that 40 women would be required per arm to detect a difference of 0.9 cm on a visual analog scale. Pain was recorded on a visual analog scale at multiple procedure time points. Individualized standardized pain scores were constructed by weighted reporting of objective and subjective sensation.\n A total of 103 consecutive women were eligible, and 80 women were randomized, with 40 per group. Thirty-seven (93%) in each group had successful placement. The lidocaine group showed significantly lower pain scores for tenaculum placement (mean+/-standard deviation: 0.97+/-1.28 compared with 3.00+/-2.41, P<.001) traversing the external cervical os (1.46+/-1.71 compared with 3.77+/-2.68, P<.001) and internal os (1.79+/-2.11 compared with 4.10+/-2.77, P<.001). There was no significant observed difference with device placement in tubal ostium (3.15+/-2.69 compared with 3.74+/-2.73, P=.33). Multivariable linear regression analysis demonstrated a relationship of pain to procedural time (P=.047) and to group assignment (P<.01).\n Paracervical block with 1% lidocaine provides effective pain relief for cervical manipulations during office hysteroscopic sterilization, but does not reduce the pain associated with upper uterine/tubal manipulation when placing the devices.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00811187.\n I.", "To compare the pain levels during egg collection and the subsequent postoperative side effects in patients receiving a paracervical block (PCB) with and without conscious sedation.\n A prospective, randomized, double-blind, and placebo-controlled study.\n A tertiary assisted reproduction unit.\n 150 patients undergoing egg collection.\n Randomized to receive PCB only (control group) and PCB in conjunction with conscious sedation (sedation group).\n Vaginal and abdominal pain levels; severity of postoperative side effects.\n The median pain levels during vaginal punctures were 12.0 (2.5th--97.5th centiles: 0--84.3) and 30.0 (2.5th--97.5th centiles: 0--100) in the sedation and placebo groups, respectively. The corresponding median abdominal pain levels were 16.5 (2.5th--97.5th centiles: 0--100) and 43.0 (2.5th--97.5th centiles: 0--100). The pain levels were significantly higher in the placebo group than the sedation group. There were no significant differences between the two groups in the severity of nausea, vomiting, dizziness, and drowsiness.\n Patients who received only a PCB during the egg collection experienced 2.5 times higher levels of vaginal and abdominal pain as compared to those who received both PCB and conscious sedation. The use of PCB along is not recommended for all patients but it may be considered with selected patients after they have been given extensive counseling.", "To estimate the effectiveness of different methods of analgesia among women treated with manual vacuum aspiration for spontaneous abortion.\n The 113 patients diagnosed with incomplete abortion and considered candidates for manual vacuum aspiration were randomly assigned to 3 groups of analgesic administration: diclofenac plus paracervical block; meperidine plus diclofenac; and meperidine alone. Pain levels were evaluated using the Wong Scale of Pain.\n The mean pain scores for the three groups were: diclofenac and paracervical block 5.4; meperidine plus diclofenac 5.0; meperidine 5.7 (P=0.57). Analysis of pain using the levels mild (0-3), moderate (4-6), and severe (7-10) showed no statistical significance among the 3 groups of analgesics. Adverse effects were more common in the groups using analgesia containing meperidine.\n There was no significant difference between the analgesics used among the 3 groups. Most of the patients, regardless of the analgesic used, reported moderate pain.", "Three methods of diagnostic hysteroscopy have been tested for both women's compliance and feasibility of procedures in postmenopause.\n Three hundred and sixty-two postmenopausal women were enrolled in a three-arm study: 5 mm diagnostic sheath (Group 1, 119 women), 5 mm sheath with paracervical block (Group 2, 121 women), and 3.5 mm sheath (Group 3, 121 women). CO2 was the distention medium. Both feasibility of hysteroscopy (procedures failed due to stenosis or incomplete distention of cavity) and discomfort of women have been recorded. Pain perception has been measured on a visual numerical rating scale. Statistical analysis was performed by t-test for unpaired samples and chi-square test.\n Paracervical block was per se painful in 18.2% and bleeding from injection site occurred in 38.8%. Hysteroscopy failure due to stenosis occurred in 9%, 10% and 0.4% of the three groups respectively (p<0.01). Intolerable pain was reported by 17% of women in Group 1, 6% in Group 2 (p<0.05) and in none of Group 3 (p<0.01). Pain score improved from Group 1 to Group 3 (p<0.01). Hysteroscopy was incomplete because of gas leakage in 1.7% of both Group 1 and 2 and in 13.2% of Group 3 (p<0.01).\n Pain perception in postmenopausal women was reduced when paracervical block was used, but discomfort was even less with the narrow sheath hysteroscope. The narrow sheath will expose to a high percentage of inconclusive procedures but it can be overcome by changing to the large sheath hysteroscope without affecting patient pain perception.", "Comparative study of the level of the reported pain between patients who received xylocaine and normal saline for paracervical block during fractional curettage was carried out in 70 patients in a double blind randomized controlled trial. One group of patients received xylocaine for paracervical block just before the procedure was performed while the other group received normal saline in the same manner. Self-reported pain intensity using visual analog scale was assessed at four time points including the first time point when Allis tissue forceps was applied on the cervix, the second and third time points when curettage was done on the endocervix and in the endometrial cavity respectively. The last time point was evaluated at 30 minutes after the procedure. The results of the study revealed pain occurring in patients in the normal saline group was more severe than those in the xylocaine group with statistically significant difference at the second time point (visual analog scale 4.80 +/- 2.7 in the normal saline group compared to 3.20 +/- 2.4 in the xylocaine group, p < 0.05) and third time point (visual analog scale 8.17 +/- 2.0 in the normal saline group compared to 4.94 +/- 3.1 in the xylocaine group, p < 0.05 ). On the contrary, pain occurring in patients in the normal saline group and xylocaine group was not statistically significantly different at the first time point (visual analog scale 3.62 +/- 2.7 in the normal saline group compared to 3.97 +/- 2.8 in the xylocaine group, p > 0.05) and the fourth time point (visual analog scale 1.34 +/- 2.0 in the normal saline group compared to 1.57 +/- 2.6 in the xylocaine group, p > 0.05). Before this study, there was an idea that normal saline solution could be considered for the paracervical injection solution. The explanation for this was the local anesthetic mechanism may be from distension of nerve capsules rather than blockage of specific autonomic nerves. However, this study showed that nerve capsule distension is not the only factor for pain control in paracervical block. An analgesic agent is still an important factor.", "One hundred seventy-seven women aged 41 +/- 8 (mean +/- SD) years, referred for evaluation of excessive uterine bleeding, were enrolled in an open-label randomized trial to evaluate the efficacy of local anesthesia before hysteroscopy in an outpatient population. The patients underwent hysteroscopy and endometrial biopsy with paracervical block by 10 mL of 1% mepivacaine hydrochloride solution (n = 87) or no local anesthesia (n = 90) and assessed lower abdominal and pelvic pain according to a 10-point linear analog scale. The mean +/- SD pain score was 4.5 +/- 2.0 at hysteroscopy and 5.2 +/- 2.1 at endometrial biopsy in the 87 subjects given a paracervical block versus 4.9 +/- 2.2 and 5.7 +/- 2.4 in the 90 women not given local anesthesia, without statistically significant differences. Paracervical anesthesia for routine outpatient hysteroscopy in premenopausal women may be superfluous.", "In this multicenter, randomized, controlled trial, we sought to determine whether patient-controlled epidural analgesia (PCEA) for labor affected the incidence of cesarean delivery when compared with patient-controlled IV opioid analgesia (PCIA). Healthy, term nulliparous patients in 4 Canadian institutions were randomly assigned to receive PCIA with fentanyl (n = 118) or PCEA with 0.08% bupivacaine and fentanyl 1.6 microg/mL (n = 124). There was no difference in the incidence of cesarean delivery-10.2% (12 of 118) versus 9.7% (12 of 124)-or instrumental vaginal delivery-21.2% (25 of 118) versus 29% (36 of 124)-between groups. The duration of the second stage of labor was increased in the PCEA group by a median of 23 min (P = 0.02). Fifty-one patients (43%) in the PCIA group received epidural analgesia: 39 (33%) because of inadequate pain relief and 12 (10%) to facilitate operative delivery. Patients in the PCIA group required more antiemetic therapy (17% versus 6.4%; P = 0.01) and had more sedation (39% versus 5%; P < 0.001). Maternal mean pain and satisfaction with analgesia scores were better in the PCEA group (P < 0.001 and P = 0.02, respectively). More neonates in the PCIA group required active resuscitation (52% versus 31%; P = 0.001) and naloxone (17% versus 3%; P < 0.001). These observations support the hypothesis that PCEA does not result in an increased incidence of obstetrical intervention compared with PCIA. PCEA provides superior analgesia and less maternal and neonatal sedation compared with PCIA.", "A clinical trial compared the efficacy of a mechanical device to deliver patient-controlled analgesia (PCA) (n = 25) with intramuscularly administered morphine (n = 17) for postcesarean pain management. Hypotheses were: (1) patient-controlled administration of narcotics will be superior (increased satisfaction, reduced pain, decreased sedation, increased ambulation, decreased length of stay), and (2) functional vital capacity will increase post-operatively with PCA. No differences in demographic variables were identified (P = less than or equal to .001). Differences in satisfaction (greater in PCA group, P = less than or equal to .05), ambulation (greater in PCA group, P = less than or equal to .001), amount of medication used (greater in PCA group, P = less than or equal to .001), and sedation level (less in PCA group, P = less than or equal to .05) were identified. No differences in vital capacity were identified. The hypothesis related to the superiority of PCA was accepted, while the association between PCA and increased vital capacity was not supported. The use of mechanical PCA devices provides an effective and safe means of managing postcesarean pain.", "To estimate whether the cesarean delivery rate differs between women with severe preeclampsia who receive intrapartum epidural analgesia versus patient-controlled intravenous opioid analgesia.\n Women with severe preeclampsia at at least 24 weeks' gestation were randomly assigned to receive either intrapartum epidural (n = 56) versus patient-controlled intravenous opioid analgesia (n = 60), and each was administered by a standardized protocol. The sample size was selected to have 80% power to detect at least a 50% difference in the predicted intergroup cesarean delivery rates. Data were analyzed by intent to treat.\n Selected maternal characteristics and neonatal outcomes were similar in the two groups. The cesarean delivery rates in the epidural group (18%) and the patient-controlled analgesia group (12%) were similar (P =.35). Women who received epidural analgesia were more likely to require ephedrine for the treatment of hypotension (9% versus 0%, P =.02), but their infants were less likely to require naloxone at delivery (9% versus 54%, P <.001). Epidural analgesia provided significantly better pain relief as determined by a visual analogue intrapartum pain score (P <.001) and a postpartum pain management survey (P =.002).\n Compared with patient-controlled intravenous opioid analgesia, intrapartum epidural analgesia did not significantly increase the cesarean delivery rate in women with severe preeclampsia at our level III center, and it provided superior pain relief.", "In previous studies comparing patient-controlled-analgesia and intramuscular pain management have been unable to provide conclusive evidence of the benefits of either method of postoperative pain control.\n The purpose of the study was to compare the efficacy and cost-effectiveness of intravenous patient-controlled-analgesia with intermittent intramuscular morphine for Chinese women in the first 24 hours following elective gynaecological surgery.\n A randomized control design was used. The main outcomes were level of pain and cost for the two types of pain management. Participants indicated their level of pain at rest and when deep breathing or coughing on a 100 mm Visual Analogue Scale, on seven occasions within 24 postoperative hours. Costs for the two types of pain management were based on the costs of equipment, drugs and nursing time.\n A total of 125 women participated in the study. Mean pain level over the 24 hours in the patient-controlled-analgesia group was significantly lower than in the intramuscular group (P < 0.001). Mean pain level over the seven occasions for the patient-controlled-analgesia group was 11.83 points (95% CI 7.14-16.52) lower when at rest and 11.73 points (95% CI 5.96-17.50) lower during motion than the intramuscular group. Cost per patient was $81.10 (Hong Kong) higher for patient-controlled-analgesia than for intramuscular pain management. Women in the patient-controlled-analgesia group had significantly greater satisfaction with pain management than those in the intramuscular group (P < 0.001), but reported significantly more episodes of nausea (P < 0.05).\n While patient-controlled-analgesia was more costly, it was also more effective than conventional on-demand intramuscular opioid injections after laparotomy for gynaecological surgery.", "To examine if ilioinguinal-iliohypogastric nerve block could reduce the need for post-Cesarean delivery morphine analgesia and thus reduce the incidence of opioid related adverse-effects.\n A multi-level technique for performing the nerve block with bupivacaine was developed and then utilized in this two-part study. Part one was a retrospective assessment of Cesarean delivery patients with and without ilioinguinal-iliohypogastric blocks to determine if the technique reduced patient controlled analgesia morphine use and thus would warrant further study. The second phase was a randomized double-blind placebo-controlled trial to compare post-Cesarean morphine use and the appearance of opioid-related side effects between the anesthetic and placebo-injected groups.\n Both phases demonstrated that our method of ilioinguinal-iliohypogastric nerve block significantly reduced the amount of iv morphine used by patients during the 24 hr following Cesarean delivery. In the retrospective assessment, morphine use was 49 +/- 30 mg in the block group vs 79 +/- 25 mg in the no block group (P = 0.0063). For the prospective trial, patients who received nerve blocks with bupivacaine had a similar result, self-administering 48 +/- 27 mg of morphine over 24 hr compared to 67 +/- 28 mg administered by patients who received infiltrations of saline. However, despite the significant decrease in morphine use, there was no reduction in opioid-related adverse effects: the incidences of nausea were 41% and 46% (P = 0.70) and for itching were 79% and 63% (P = 0.25) in the placebo and nerve block groups, respectively.\n A multi-level ilioinguinal-iliohypogastric nerve block technique can reduce the amount of systemic morphine required to control post-Cesarean delivery pain but this reduction was not associated with a reduction of opioid related adverse effects in our study group." ]	No technique provided reliable pain control in the 17 included studies. Some studies reported that women experienced severe pain (mean scores of 7 to 9 out of 10) during uterine intervention, irrespective of the analgesic technique used. We concluded that the available evidence fails to show whether paracervical block is inferior, equivalent or superior to alternative analgesic techniques, in terms of efficacy and safety, for women undergoing uterine interventions.
CD000359	[ "2082953", "6379022", "406875", "2651014", "15730352", "1418054", "18674411", "9447569" ]	[ "Lack of efficacy of hydergine in patients with Alzheimer's disease.", "Double-blind clinical and psychologic study of ergoloid mesylates (Hydergine) in subjects with senile mental deterioration.", "Pharmacotherapy for organic brain syndrome in late life. Evaluation of an ergot derivative vs placebo.", "Ergoloid mesylates ('Hydergine') in the treatment of mental deterioration in the elderly: a 6-month double-blind, placebo-controlled trial.", "Randomized controlled pilot trial of cabergoline, hydergine and levodopa/carbidopa: Los Angeles Cocaine Rapid Efficacy Screening Trial (CREST).", "Memantine in the treatment of mild to moderate dementia syndrome. A double-blind placebo-controlled study.", "Efficacy, safety and tolerability of rivastigmine capsules in patients with probable vascular dementia: the VantagE study.", "Clinical efficacy of Ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type." ]	[ "There is no effective pharmacologic treatment for Alzheimer's disease, the most common dementing illness in the United States. Hydergine, a combination of ergoloid mesylates, is the only approved medication for Alzheimer's disease, but despite widespread use its efficacy remains to be established. We conducted a clinical trial of Hydergine-LC, a newer preparation of ergoloid mesylates in the form of a liquid in a capsule (LC) that may have greater bioavailability, to determine its value in patients with Alzheimer's disease.\n Eighty older adults with probable Alzheimer's disease participated in this double-blind, placebo-controlled trial of Hydergine-LC for 24 weeks. The recommended dose of 1 mg orally three times daily was used. Cognition and behavior were evaluated before and after the trial, and the patients were monitored for adverse effects. The medication was safe and well tolerated. The Hydergine-LC group did not perform better after treatment than the placebo group on any test, and its performance was worse (P less than 0.01 and P less than 0.02, respectively) on one cognitive measure (Wechsler Adult Intelligence Scale Digit Symbol Substitution Task) and on one behavioral scale (the Geriatric Evaluation by Relatives Rating Instrument).\n Hydergine-LC appears to be ineffective as a treatment for Alzheimer's disease.", "A double-blind study of 24 weeks' duration was conducted to investigate the effects of ergoloid mesylates (Hydergine) on symptoms of senile mental deterioration. Fifty-eight residents of old people's homes were included in the trial. Thirty were treated with ergoloid mesylates and 28 with placebo, and the effects of treatment were determined by means of medical and psychological examinations. On the Sandoz Clinical Assessment Geriatric Scale, the group receiving ergoloid mesylates showed significant improvement in all items. The group receiving placebo showed slight deterioration. Psychological examination showed that no changes were observed for either group in quantitative psychometric test results, although qualitative aspects of performance such as attention and concentration did improve. There was a close correlation between improved cognitive function scores on the SCAG and improved evaluations of behavior during the psychological examinations. There were marked individual differences in the degrees of improvement.", "Evaluation of treatment modalities, including pharmacotherapy, for organic brain syndrome (OBS) has been difficult because of sampling and methodological problems, and comparisons of research studies are all but impossible. In this study, an ergot derivative, a combination of dihydroergocornine mesylate, dihydroergocristine mesylate, and dihydroergokryptine mesylate (Hydergine) was compared with placebo, using a double-blind technique in a sample of nursing home residents with evidence of OBS. An 18-category symptom rating scale was used for periodic assessment over a six-month interval. Comparisons of the two groups of subjects disclosed that the Hydergine-treated group showed statistically significantly more improvement in most of the variables measured, especially during the last three months of treatment. Furthermore, sophisticated analysis revealed that positive changes in cognitive function cannot be accounted for as a mere reflection, or \"halo\" effect, associated with improved mood and general sense of well-being.", "A double-blind, placebo-controlled trial was carried out in 97 elderly patients with age-related mental deterioration to assess the efficacy of ergoloid mesylates in improving their symptoms. Patients were allocated at random to receive either 4.5 mg ergoloid mesylates per day or a matching placebo tablet and were followed-up for 6 months after the start of treatment. Clinical examinations were performed by the doctor, using the EACG rating scale (a French version of the Sandoz Clinical Assessment Geriatric scale), and by the nurse, using the NOSIE scale, when patients entered the trial and repeated after 2, 4 and 6 months. Changes in the factors (symptom groups) covered by these scales were subjected to statistical analysis. After 6-months' treatment, a statistically significant difference in favour of the ergoloid mesylates group was observed for cognitive deficits (p less than 0.05), anxiety and mood depression (p less than 0.01), unsociability (p less than 0.01), retardation (p less than 0.05) and irritability (p less than 0.001). Treatment was very well tolerated. It was also observed that there was a progressive increase in efficacy throughout the trial; this indicates that treatment with ergoloid mesylates in patients with mental deterioration should be long-term.", "This study tested three dopaminergic medications against a common unmatched placebo condition: hydergine 1 mg three times daily (n = 15); levodopa/carbidopa 25/100 mg three times daily (n = 15); cabergoline 0.5 mg per week (n = 15); and placebo three times daily (n = 15) as potential pharmacotherapies for cocaine dependence.\n The four-parallel group, Cocaine Rapid Efficacy Screening Trial (CREST) design featured a 2-week baseline period followed by randomization to an 8-week medication condition that included 1 hour per week of cognitive behavioral drug counseling. A safety evaluation was conducted 4 weeks after termination.\n Outcomes included cocaine metabolites measured in urine, retention and self-reports for drug use, cocaine craving, clinical improvement, mood and HIV risk behaviors.\n Participants assigned to receive cabergoline provided more urine samples negative for cocaine metabolites (42.4%) than those assigned to receive placebo (25.0%), a statistically significant difference after controlling for baseline differences in self-reported cocaine use (F = 2.95, df = 3; P = 0.05). Cabergoline-treated participants demonstrated a significant improvement over placebo from baseline to week 8 when measured using the Addiction Severity Index (ASI) employment subscale (overall change = - 0.09, SD = 0.10, t = 2.36, P < 0.05). Safety and adverse event measures showed similar rates and types of complaints by treatment condition.\n These results, combined with the apparent safety of cabergoline when used with this population, provide empirical support for conducting a larger study of the medication.", "The efficacy and the tolerability of memantine (1-amino-3,5-dimethyladamantane hydrochloride, Akatinol Memantine, CAS 41100-52-1) were investigated in patients with mild to moderate dementia syndrome in a randomized two-centre placebo-controlled clinical study. The test substance was administered at a dose of 10 mg/d from day 1 to day 3 and then at a dose of 2 x 10 mg/d from day 4 to the end of treatment after 42 days. Altogether, 88 patients were recruited to the study; their average age was 71.5 years. The efficacy of memantine was judged on the basis of the baseline/6 week differences in the total sum scores of the Clinical Assessment Geriatric Scale (SCAG), the Gottfries-Bräne-Steen Scale (GBS), the SCAG and GBS subscales and the global assessment of the change in the patient's condition. The effects of memantine on performance were studied with the aid of psychomotor tests and a behaviour investigation relating to activities of daily living (ADL). The tolerability of memantine was assessed on the basis of the doctor's global assessment and of entries on structured documentation forms (DOTES/TWIS). Further safety parameters--in the form of clinicochemical tests and measurements of blood pressure and heart rate--were also monitored during the study. On both the psychopathological measurement level (SCAG, global assessment of the change in the patient's condition) and the behavioural level (GBS), confirmatory statistical analysis brought to light significant differences between memantine and placebo (p less than or equal to 0.05), these differences showing a superiority of memantine. The tolerability of memantine was good in the main. The observed adverse reactions were not serious and, except in 3 patients, were rated as causing little or no impairment. The present clinical study demonstrates the efficacy of memantine in patients suffering from mostly moderate dementia syndrome. Clinical and statistically relevant improvements in the dementia-induced disturbances were found on the both the psychopathological level (SCAG, CGI) and the behavioural level (GBS). On the performance level also, the ADL behaviour investigation detected a highly significant improvement in the quality of performance of instrumented activities of daily living under memantine. Also the time taken to carry out these tasks was significantly reduced in comparison with placebo.", "The aim was to evaluate the efficacy, safety and tolerability of rivastigmine capsules in patients diagnosed with probable vascular dementia (VaD).\n VantagE (Vascular Dementia trial studying Exelon) was a 24-week, multicentre, double-blind study. VaD patients aged 50-85 years were randomized to rivastigmine capsules (3-12 mg/day) or placebo. Efficacy assessments included global and cognitive performances, activities of daily living and neuropsychiatric symptoms. Adverse events were recorded. Additional exploratory analyses determined whether heterogeneity in pathologies and symptoms extended to differential treatment effects.\n NCT00099216.\n 710 patients were randomized. Rivastigmine demonstrated superiority over placebo on three measures of cognitive performance (Vascular Dementia Assessment Scale, Alzheimer's Disease Assessment Scale cognitive subscale, Mini-Mental State Examination; all p< or = 0.05, intent-to-treat population [ITT]), but not other outcomes. Predominant adverse events were nausea and vomiting. Exploratory analyses indicated that older patients (> or =75 years old), assumed more likely to also have Alzheimer's disease (AD) pathology, demonstrated significant cognitive responses to rivastigmine and a safety profile similar to that seen in AD patients. Younger patients, assumed less likely to have concomitant AD pathology, showed no efficacy response and were associated with slight elevations of blood pressure, cerebrovascular accidents and mortality. Rivastigmine-placebo differences in patients with, versus those without, medial temporal atrophy (also suggestive of concomitant AD) showed a numerical difference similar to that seen between the older versus younger patients, but did not attain statistical significance.\n Consistent with trials evaluating other cholinesterase inhibitors, rivastigmine did not provide consistent efficacy in probable VaD. The efficacy apparent on cognitive outcomes was derived from effects in older patients likely to have concomitant Alzheimer pathology. This is supportive of an existing argument that the putative cholinergic deficit in VaD reflects the presence of concomitant Alzheimer pathology.", "Among the psychiatric illnesses associated with old age primary degenerative dementia of the Alzheimer type (DAT) has gained increasing importance in recent years. Even though a curative treatment of the disease is currently impossible, various drugs can be used to slow down its progression. In the present study the influence of oral treatment with 240 mg/day of Ginkgo bilabo special extract EGb 761 (Tebonin forte, manufactured by Dr Willmar Schwabe, Karlsruhe) on the clinical course of DAT was investigated in a double-blind, randomized, placebo-controlled parallel-group design in 20 outpatients. The duration of treatment was 3 months. The primary outcome variable was the sum score in the SKT-test for the determination of attention and memory. Other psychometric tests (trailmaking test, ADAS, CGI) and electrophysiological investigations (EEG topography) were evaluated descriptively. Although the active-treatment group, with a mean sum score of 19.67 points in the, S.K.T., had a poorer baseline level than the placebo group (18.11 points), it experienced an improvement to 16.78 points under treatment with EGb 761 whereas the placebo group deteriorated to 18.89 points. The differences between the baseline and final values formed the basis for a statistical group comparison, which gave a result favourable to EGb 761, at a significance level of p < .013. In addition to this psychometric confirmation of efficacy, certain descriptive trends were found at the psychopathological (Clinical Global Impression) and dynamic functional (EEG findings) levels, which can be interpreted as evidence of effectiveness of Ginkgo biloba special extract EGb 761 in mild to moderate dementia and of local effects in the central nervous system. Inter-group differences in the ADAS cognitive and non-cognitive subscales did not reach statistical significance, probably because of the small sample size." ]	As in an earlier systematic review, we found hydergine to show significant treatment effects when assessed by either global ratings or comprehensive rating scales (based here on a smaller set of trials than in the earlier published systematic review because trials were required to have data that could conform with MetaView, the Cochrane Collaboration statistics software). The small number of trials available for analysis, however, limited the ability of subgroup analyses to identify statistically significant moderating effects. Unfortunately, most of the randomized, double-blind, and placebo-controlled trials of hydergine were conducted and published before the advent of consensus-based diagnostic standards of dementia in 1984; therefore diagnostic criteria were less specific. As a result, uncertainty remains regarding hydergine's efficacy in dementia.
CD007009	[ "19012818" ]	[ "Double-blind, placebo-controlled study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder." ]	[ "To evaluate the efficacy and safety of 30, 50, and 70 mg/day lisdexamfetamine dimesylate compared with placebo in adults with attention-deficit/hyperactivity disorder (ADHD).\n Following a 7- to 28-day washout, 420 adults aged 18 to 55 years with moderate to severe ADHD (DSM-IV-TR criteria) were treated with 30, 50, or 70 mg/day lisdexamfetamine or placebo, respectively, for 4 weeks (N = 119, 117, 122, and 62, respectively). The 50- and 70- mg/day groups underwent forced-dose titration. The primary efficacy measure was the clinician-determined ADHD Rating Scale (ADHD-RS) total score. The study was conducted from May 2006 to November 2006.\n Treatment groups were well matched at baseline, including in ADHD-RS scores. At endpoint, changes in ADHD-RS scores were significantly greater for each lisdexamfetamine dose than for placebo (placebo = -8.2, 30 mg/day lisdexamfetamine = -16.2, 50 mg/day lisdexamfetamine = -17.4, 70 mg/day lisdexamfetamine = -18.6; all p < .0001 vs. placebo), with no differences between doses. Significant differences relative to placebo were observed in each lisdexamfetamine group, beginning at week 1 and for each week throughout. The percentage of subjects who improved (Clinical Global Impressions-Improvement scale rating < or = 2) was significantly greater for each lisdexamfetamine dose than for placebo at each week and at endpoint (placebo = 29%, 30 mg/day lisdexamfetamine = 57%, 50 mg/day lisdexamfetamine = 62%, 70 mg/day lisdexamfetamine = 61%; all p < .01). Adverse events were generally mild and included dry mouth, decreased appetite, and insomnia.\n All 3 lisdexamfetamine doses were significantly more effective than placebo in the treatment of adults with ADHD, with improvements noted within 1 week. Lisdexamfetamine was generally well tolerated by these patients.\n Copyright 2008 Physicians Postgraduate Press, Inc." ]	There is very little evidence for the effectiveness of amfetamine for ADHD in people with ID . Prescribing in this population is based on extrapolation of research in people without ID. More research into effectiveness and tolerability is urgently needed.

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