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[ "14572560", "9351030", "8759659", "8284627", "11007222", "7698624", "9440631" ]

[ "Eradication of Helicobacter pylori improves the healing rate and reduces the relapse rate of nonbleeding ulcers in patients with bleeding peptic ulcer.", "Cure with omeprazole plus amoxicillin versus long-term ranitidine therapy in Helicobacter pylori-associated peptic ulcer bleeding.", "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.", "Treatment of Helicobacter pylori reduces the rate of rebleeding in peptic ulcer disease.", "Treatment of Helicobacter pylori in patients with duodenal ulcer hemorrhage--a long-term randomized, controlled study.", "Helicobacter pylori eradication reduces the rate of rebleeding in ulcer hemorrhage.", "One-week antibiotics versus maintenance acid suppression therapy for Helicobacter pylori-associated peptic ulcer bleeding." ]

[ "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.", "Long-term prophylaxis with ranitidine reduces the risk of recurrent bleeding in patients with a history of bleeding peptic ulcers. To date, no randomized study has been performed to compare cure of Helicobacter pylori infection versus H2 blocker prophylaxis in patients with bleeding peptic ulcer.\n In a prospective randomized study, 95 consecutive patients with H. pylori-associated peptic ulcer bleeding were randomized to either ranitidine prophylaxis (150 mg at night) for 2 years or to H. pylori-eradication with omeprazole 60 mg twice daily plus amoxicillin 750 mg three times daily for 10 days.\n (Intention-to-treat analysis). Forty-eight patients were enrolled in the ranitidine group; 47 in the omeprazole-plus-amoxicillin group. Mean follow-up was 576 days (77 to 730). Ulcer recurrence rate was 31.3% in the ranitidine group (group 1) versus 6.37% in the eradication group (group 2; p = 0.0018). More patients had recurrent bleeding in group 1 (8.3%) than in group 2 (4.2%) but we were not able to show a statistically significant difference with respect to recurrent bleeding between groups (p = 0.29). Definite cure of H. pylori infection was achieved in 89.3%.\n Cure of H. pylori infection reduces recurrence of peptic ulcer and therefore rebleeding more effectively than does long-term maintenance therapy with an H2 blocker.", "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.", "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.", "Eradication of Helicobacter pylori (H. pylori) in patients with uncomplicated duodenal ulcers prevents long-term recurrence of ulcers. We aimed to study whether treatment of H. pylori prevents the long-term recurrence of duodenal ulcer hemorrhage.\n Patients with duodenal ulcer bleeding and confirmed H. pylori infection were recruited. A total of 120 patients were randomly assigned to triple therapy (DeNoltab 120 mg, amoxycillin 500 mg, and metronidazole 300 mg four times daily) or DeNoltab 120 mg four times daily alone. No maintenance therapy was given during the follow-up period. The endpoints were the cumulative rates of symptomatic and bleeding duodenal ulcer recurrences.\n Of the patients receiving the triple regimen, 85.1% had H. pylori eradicated as compared to 2.0% of patients receiving DeNoltab (p < 0.05). More patients in the DeNoltab group than those in the Triple group had recurrence of ulcer bleeding, but this did not reach statistical significance (12/60 vs 6/60, p = 0.20). Logistic regression analysis on clinical, personal, and endoscopic characteristics identified persistent H. pylori infection as the only independent predictor of recurrence of duodenal ulcer bleeding.\n Treatment of H. pylori alone with the present bismuth-based triple therapy in patients with duodenal ulcer hemorrhage did not result in significant reduction in further bleeding episodes, although a trend was seen for the group that was given triple therapy. On the other hand, posttreatment H. pylori status was found to be an independent predictor of bleeding recurrence.", "To evaluate whether eradication with omeprazole and amoxicillin results in a reduction of ulcer recurrence and rebleeding in patients with Helicobacter pylori-associated duodenal ulcer hemorrhage, patients with upper gastrointestinal hemorrhage from duodenal ulcers with stigmata of recent hemorrhage, a drop in hemoglobin level of more than 2 g/dL, and documented H. pylori infection (by rapid urease test and histologic findings) were randomly assigned to receive omeprazole, 40 mg every day, and amoxicillin, 1 g twice a day, (Group A) or omeprazole alone, 40 mg every day, (Group B) for 2 weeks. No maintenance antiulcer therapy was given. Patients underwent a second endoscopy 4 weeks after completion of therapy and were followed for 1 year. Endoscopy was performed again at the end of 1 year. All patients showed ulcer healing 4 weeks after completion of therapy. H. pylori eradication rates were 83% (Group A) and 5% (Group B) (p < .001). Ulcer recurrences were significantly lower in Group A (3/29 or 10%) than in Group B (9/22 or 41%; p < .05). Comparison of Group A patients with eradication and Group B patients without eradication also revealed a significant difference in rates of ulcer relapse (1/24 or 4% versus 9/21 or 43%; p < .01). Rebleeding occurred significantly less often in the dual therapy group than in the omeprazole group (0/29 versus 6/22 or 27%; p < .01). Eradication of H. pylori significantly reduces the rates of ulcer recurrence and rebleeding in patients with duodenal ulcer bleeding. Dual therapy with omeprazole and amoxicillin should be considered in all H. pylori-positive patients with hemorrhage from duodenal ulcers.", "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." ]

[ "15492650", "7910792", "10094751", "9112891", "17277653", "12815798", "12582754", "12632130", "12960786", "16749570", "15711660", "12958684", "16206003", "16076335" ]

[ "Effect of intra-abdominal pressure level on gastric intramucosal pH during pneumoperitoneum.", "[Postlaparoscopic pain syndrome. Results of a prospective, randomized study].", "Hemodynamic consequences of high- and low-pressure capnoperitoneum during laparoscopic cholecystectomy.", "Randomized trial of different insufflation pressures for laparoscopic cholecystectomy.", "Prospective randomized trial on low-pressure versus standard-pressure pneumoperitoneum in outpatient laparoscopic cholecystectomy.", "Influence of different pressures of pneumoperitoneum on the autonomic system function during laparoscopy.", "A prospective randomized trial on comparison of low-pressure (LP) and standard-pressure (SP) pneumoperitoneum for laparoscopic cholecystectomy.", "Randomized trial of different intraabdominal pressures and acid-base balance alterations during laparoscopic cholecystectomy.", "Randomized comparison between different insufflation pressures for laparoscopic cholecystectomy.", "Lactate and acid base changes during laparoscopic cholecystectomy.", "Effects of low and high intra-abdominal pressure on immune response in laparoscopic cholecystectomy.", "The effect of different intraabdominal pressures on lipid peroxidation and protein oxidation status during laparoscopic cholecystectomy.", "Postoperative changes in liver function tests: randomized comparison of low- and high-pressure laparoscopic cholecystectomy.", "Randomized, prospective comparison of postoperative pain in low- versus high-pressure pneumoperitoneum." ]

[ "The present study was designed to examine the effect of intra-abdominal pressure level on gastric intramucosal pH using gastric tonometry during pneumoperitoneum. One hundred patients were prospectively randomized into 5 equal groups (N = 20 each). Intra-abdominal pressure levels were 8, 10, 12, 14, and 16 mm Hg in groups I, II, III, IV, and V, respectively. Intramucosal pH measurement was done 2 times: 30 minutes following insufflation and 1 hour after the ending of the surgery. In the first and second measurements, intramucosal pH values were found as 7.39 +/- 0.02 and 7.36 +/- 0.03 in group I; 7.41 +/- 0.03 and 7.38 +/- 0.03 in group II; 7.37 +/- 0.03 and 7.37 +/- 0.03 in group III; 7.36 +/- 0.03 and 7.37 +/- 0.03 in group IV; and 7.39 +/- 0.03, 7.36 +/- 0.03 in group V, respectively. Statistical significance was not found in the comparison of these values within the groups and between the groups (P > 0.005, for each). In conclusion, intra-abdominal pressure between 8 and 16 mm Hg did not cause significant difference in gastric intramucosal pH.", "The so-called post-laparoscopic algesia is a specific impairment of about 63% of the patients who undergo laparoscopic surgical operations. This impairment takes the form of mild to moderate shoulder pain. Eliminating the causes of pain has a clear advantage over symptomatic treatment using analgetics, a fact worth a good consideration especially with the post-operative sojourn at the hospital becoming shorter and shorter. In a prospective controlled study, involving 42 patients subdivided into four groups namely, higher or lower insufflation pressures, chemically inert insufflation gas and control groups; the use of analgetics, lung function, operation duration, amount of insufflated gas, intraperitoneal pH-values and post-operative complications in the various subgroups were compared to each other with regard to post-operative pain perception. The results did not show any significant differences among the groups regarding the main parameters like pH-value or different insufflation pressures etc. These results led to the termination of the study based on the raised criteria since we anticipated the actual cause of the shoulder pain to be due to an unknown factor. By the evaluation of the individual data, it became apparent that, the pains increase with increasing gas consumption, a fact which led to assumption that the pains are caused by a physical effect such as the cooling of the peritoneum.", "Peritoneal insufflation to 15 mmHg diminishes venous return and reduces cardiac output. Such changes may be dangerous in patients with a poor cardiac reserve. The aim of this study was to investigate the hemodynamic effects of high (15 mmHg) and low (7 mmHg) intraabdominal pressure during laparoscopic cholestectomy (LC) METHODS: Twenty patients were randomized to either high- or low-pressure capnoperitoneum. Anesthesia was standardized, and the end-tidal CO2 was maintained at 4.5 kPa. Arterial blood pressure was measured invasively. Heart rate, stroke volume, and cardiac output were measured by transesophageal doppler.\n There were 10 patients in each group. In the high-pressure group, heart rate (HR) and mean arterial blood pressure (MABP) increased during insufflation. Stroke volume (SV) and cardiac output were depressed by a maximum of 26% and 28% (SV 0.1 > p > 0.05, cardiac output p > 0. 1). In the low-pressure group, insufflation produced a rise in MABP and a peak rise in both stroke volume and cardiac output of 10% and 28%, respectively (p < 0.05).\n Low-pressure pneumoperitoneum is feasible for LC and minimizes the adverse hemodynamic effects of peritoneal insufflation.", "The factors affecting cardiorespiratory changes and postoperative pain after laparoscopic cholecystectomy are poorly understood. The aim of this study was to assess these changes in patients undergoing laparoscopic cholecystectomy at an insufflation pressure of 7.5 or 15 mmHg.\n Forty patients with similar preoperative characteristics were randomized, 20 to each group.\n There were no significant differences in intraoperative heart rate or cardiac index although the latter fell significantly soon after insufflation in both groups. The fall in cardiac index lasted longer (7 versus 2 min) and coincided with a slower rise in mean arterial pressure in those having 15 mmHg insufflation. Changes in peak airway pressure, end-tidal carbon dioxide and arterial blood gases were similar. After operation the low-pressure group had significantly less pain, better preservation of pulmonary function and were discharged home sooner (P = 0.015).\n Insufflation pressure significantly affects the haemodynamic changes and postoperative pain associated with laparoscopic cholecystectomy.", "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.", "The effects of different pressure values of pneumoperitoneum on the activity of the autonomic nervous system (ANS) have not been investigated in detail. In this prospective study, 20 patients qualified for laparoscopic cholecystectomy were randomised to either low-pressure (LP = 7 mmHg) or standard-pressure (SP = 12 mmHg) pneumoperitoneum groups, 10 patients each. The anesthesia was induced with fentanyl and thiopental and maintained with isoflurane. Ventilation was mechanically controlled (18 breaths per minute, end-tidal CO2 30-35 mmHg, instant capnometer monitoring). Intraabdominal pressure was maintained automatically by a CO2 insufflator. Patient were kept in a horizontal position. The ANS was evaluated by heart rate variability (HRV) analysis (POSTER ECG 2002 System) measured intraoperatively in three recordings of 5 minutes each: in awake patient, after induction of general anesthesia, and after creation of pneumoperitoneum. Power spectral analysis of HRV was applied, the low-frequency (LF = 0.05-0.15 Hz) and high frequency (HF = 0.15-0.45 Hz) spectral density of the HRV were analysed using the Fast Fourier Transform algorithm. The appropriate statistical analysis of data was performed. LF density decreased at the anesthetized stage and increased at the insufflated stage in both groups (p < 0.01). LP resulted in lower sympathetic activation than SP pneumoperitoneum (LF: 68.12 +/- 6.56 nu vs. 78.26 +/- 5.43 nu, p < 0.01; HF: 24 +/- 2.48 nu vs. 15.56 +/- 2.54 nu, p < 0.05). In conclusion: pneumoperitoneum leads to sympathetic activation of the ANS. LP in comparison to SP pneumoperitoneum with carbon dioxide results in significantly decreased sympathetic activation during laparoscopy.", "This study aimed to investigate the advantages and disadvantages of LP (7 mmHg) in comparison to SP (12 mm Hg) pneumoperitoneum in a prospective randomized clinical trial.\n 148 consecutive patients qualified for laparoscopic cholecystectomy (LC) due to uncomplicated symptomatic gallstones were randomized to either SPLC or LPLC. All the procedures were performed by the same experienced team of surgeons. The statistical analysis included sex, mean age, body mass index, ASA grade, operative time, complication rate, conversion rate, postoperative pain assessed by the Visual Analogue Scale of Pain (VAS) including the incidence of shoulder-tip pain, postoperative hospital stay, recovery time, and the quality of life (QOL) within 7 days following the operation. p <0.05 was considered as indicative of significance.\n Neither conversion to an open procedure nor major complications occurred in either group. The operative time was similar in both groups (LP 55.7 +/- 8.6 min vs SP 51.9 +/- 8.3 min). The mean postoperative pain score was 6.18 +/- 3.48 lower after LP than SPLC and the difference amounted to 22.2% (p <0.005). The incidence of shoulder-tip pain was 2.1 times lower after LP than SPLC (p <0.05). QOL within 7 days following the operation was remarkably better after LPLC than after SPLC (p <0.01).\n LP pneumoperitoneum is superior to SP pneumoperitoneum in terms of lower postoperative pain, a lower incidence of shoulder-tip pain, and a better QOL within 5 days following the operation. LP should be used for LC in cases of uncomplicated symptomatic gallstones as a recommended procedure as long as an adequate exposure is obtained with this technique.", "Experimental and clinical studies document risks of acid-base balance alterations toward acidosis and hypercapnia during intraperitoneal carbon dioxide insufflation. The aim of this study was to assess the influence of different insufflation pressures on arterial blood gas changes and acid-base alterations during laparoscopic cholecystectomy and immediately postoperatively.\n Thirty patients were randomized to receive either 10 or 15 mmHg insufflation pressure. Anesthesia was standardized for both groups. The following parameters of acid-base balance were recorded: pH, pCO2, pO2, base excess (BE), HCO3. Suitable data were analyzed by the Mann-Whitney U-test.\n Pneumoperitoneum with carbon dioxide caused a decrease in pH toward acidosis that was either respiratory or mixed in origin. There were no statistically significant differences in acid-base balance alterations between the two groups of patients.\n Carbon dioxide pneumoperitoneum causes alterations of the acid-base balance, mostly of respiratory or mixed type. Lowering of the insufflation pressure from 15 to 10 mmHg does not contribute to the elimination of acid-base balance alterations during laparoscopic cholecystectomy.", "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.", "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.", "Immunosuppression is directly related to the degree of trauma. The aim of this study is to compare the effects of low and high intra-abdominal pressure on immune response in moderate surgical trauma.\n Twenty-two patients, scheduled for laparoscopic cholecystectomy, were randomly allocated to one of 2 groups according to intra-abdominal pressure: low and high intra-abdominal pressure. This study was conducted in the Hacettepe University Faculty of Medicine, Operation Room, Ankara, Turkey. Serum interleukin (IL)-2 and IL-6 levels were measured.\n Serum IL-2 showed a significant decrease before the incision in high intra-abdominal pressure group. The increase in serum IL-6 at the end of surgery and postoperatively was lower in low intra-abdominal pressure group.\n These results, can be interpreted as the immune system, are less depressed when there is lower intra-abdominal pressure. This may have clinical implications in immunocompromised patients.", "This prospective, randomized, and controlled study was designed to investigate the effects of different intraabdominal pressures (IAPs) on lipid peroxidation and protein oxidation status during laparoscopic cholecystectomy (LC).\n Twenty-four patients (12 men, 12 women) who underwent LC at either 10 or 15 mmHg of IAP were randomized into two groups. Repeated blood samples were collected to measure thiobarbituric acid reactive substances (TBARS) levels to assess lipid peroxidation and protein carbonyl content and protein sulfhydryl groups to assess protein oxidation status.\n Serum protein carbonyls and TBARS levels were found to be increased immediately after desufflation in both study groups when compared to the preoperative levels. On the other hand, protein sulfhydryl levels were found to be decreased in both study groups. Although increases in protein carbonyls and TBARS levels were more prominent in patients who underwent LC at 15 mmHg of IAP, this difference was not statistically significant between both groups.\n The results suggest that both 15 and 10 mmHg of LAP could lead to an increased oxidative stress response during LC, but no difference was found between the groups.", "Pneumporeitoneum at 14 mmHg causes dangerous hemodynamic disturbances in some patients, leading to splanchnic ischemia. Laparoscopic cholecystectomy (LC) using low-pressure pneumoperitoneum (7 mmHg) minimizes adverse hemodynamic effects on hepatic portal blood flow and hepatic function. This study evaluated the changes in liver function tests after high-pressure LC (HPLC; 14 mmHg) and low-pressure LC (LPLC; 7 mmHg).\n For this study, 50 patients were randomly assigned to undergo either HPLC (n = 25) or LPLC (n = 25) Liver function tests including total bilirubin, gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were obtained preoperatively, then 24 and 48 h postoperatively. All patients had normal values on the preoperative liver function tests. The anesthesiologic protocol was uniform.\n The findings showed that ALT after 24 h (LPLC: 1473.72 +/- 654.85; HPLC: 2233.74 +/- 1247.33; p = 0.0096) and 48 h (LPLC: 1322.99 +/- 601.51; HPLC 2007.80 +/- 747.55; p = 0.0008) and AST after 24 h (LPLC: 1189.96 +/- 404.79 i.j.; HPLC: 1679.40 +/- 766.13; p = 0.0069) were increased in the patients who underwent HPLC. The AST levels after 48 h were statistically unchanged from baseline in both groups. Total bilirubin, ALP, and GGT levels remained unchanged from baseline in both groups, without a significant difference between the two groups.\n Because LPLC minimizes adverse hemodynamic effects on hepatic function, a low-pressure pneumoperitoneum should be considered for patients with compromised liver function, particularly those undergoing prolonged laparoscopic surgery.", "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." ]

[ "6842217", "21281410", "8747817", "20626310" ]

[ "Speech therapy for Parkinson's disease.", "Treating disordered speech and voice in Parkinson's disease online: a randomized controlled non-inferiority trial.", "Comparison of two forms of intensive speech treatment for Parkinson disease.", "The effectiveness of traditional methods and altered auditory feedback in improving speech rate and intelligibility in speakers with Parkinson's disease." ]

[ "Twenty-six patients with the speech disorder of Parkinson's disease received daily speech therapy (prosodic exercises) at home for 2 to 3 weeks. There were significant improvements in speech as assessed by scores for prosodic abnormality and intelligibility' and these were maintained in part for up to 3 months. The degree of improvement was clinically and psychologically important, and relatives commented on the social benefits. The use of a visual reinforcement device produced limited benefit over and above that from prosodic exercises alone, except to patients with severe speech disorder.", "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.", "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.", "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." ]

[ "22427772", "17318618", "18514907", "20973322", "17169543", "10911825" ]

[ "Mixture of Arnebia euchroma and Matricaria chamomilla (Marhame-Mafasel) for pain relief of osteoarthritis of the knee - a two-treatment, two-period crossover trial.", "Choosing between NSAID and arnica for topical treatment of hand osteoarthritis in a randomised, double-blind study.", "Nettle sting for chronic knee pain: a randomised controlled pilot study.", "Efficacy of symptomatic control of knee osteoarthritis with 0.0125% of capsaicin versus placebo.", "Efficacy of a comfrey root (Symphyti offic. radix) extract ointment in the treatment of patients with painful osteoarthritis of the knee: results of a double-blind, randomised, bicenter, placebo-controlled trial.", "Randomized controlled trial of nettle sting for treatment of base-of-thumb pain." ]

[ "Osteoarthritis is the most prevalent chronic non-infective joint arthritis. Because of its chronic disease nature, local drugs are preferred due to lower complications. In the present study, the new herbal pomade Marhame-Mafasel for knee osteoarthritis was used in a double-blind crossover trial. The aim of the study was to assess the efficacy and safety of Marhame-Mafasel pomade, which consists of several medical herbs including Arnebia euchroma and Matricaria chamomilla, in osteoarthritis of the knee.\n This study was a placebo-controlled double-blind crossover trial. Forty-two patients with pain associated with osteoarthritis of the knee (diagnosed by criteria of the European League against Rheumatism and physical examination) were drawn from patients attending the Clinic of Mostafa-Khomeini Hospital. In this study we assessed efficacy (analgesic effect and improved function) of herbal pomade Marhame-Mafasel, which was used locally in patients with primary osteoarthritis of the knee over three weeks. The instrument of the study was the Western Ontario and McMaster Universities (WOMAC) LK3.1 standard questionnaires.\n The participants in each group were 21 patients; 30 (71.4%) were women and 12 (28.6%) of them were men. The participants were between 40 and 76 years old. Six patients had mild arthritis, 15 had moderate arthritis and 21 had severe arthritis. The positive analgesic effect of the herbal pomade Marhame-Mafasel in primary knee osteoarthritis was proven. The herbal joint pomade Marhame-Mafasel had a significantly greater mean change in score compared to the placebo group for osteoarthritis severity (p < 0.05).\n Herbal pomade Marhame-Mafasel in comparison to placebo has more effect on reduction of pain of primary knee osteoarthritis.", "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.", "Non-pharmacological interventions for chronic knee pain are increasingly requested by patients and are recommended in current treatment guidelines. An intervention that has been used for many years for pain relief is nettle sting.\n To explore the feasibility of a definitive RCT of nettle sting for chronic knee pain, in particular the acceptability of the research to GPs and patients, and the optimal methods for recruitment and outcome measurement.\n Patient blinded pilot RCT, set in two inner city primary care practices in Plymouth, UK. Potential participants were identified from practice computerised databases using three different approaches: age and analgesic use, age and appropriate Read code, or age alone. Patients had to be aged between 55 and 80 years with knee pain and a presumptive clinical diagnosis of OA knee, with a baseline WOMAC pain subscale score of more than 4. They were randomised to receive either treatment with Urtica dioica, or placebo intervention with Urtica galeopsifolia daily for 1 week. The main outcome measure for the treatment effect was the WOMAC pain subscale; other outcomes included quantitative and qualitative data to inform the design of a future study.\n Out of 45 patients who were eligible, 42 were recruited. Invitations targeted at patients who were both currently receiving repeat prescriptions for non-steroidal or analgesic drugs and had relevant Read codes proved most efficient for recruitment. Mean baseline WOMAC pain subscale scores were 9.2 (S.D. 3.4) and 7.9 (2.3) in the two groups. The mean reduction in pain score at the end of treatment in the nettles group was 1.7 (95% confidence interval 0.6, 2.9) and in the controls 1.6 (CI 0.5, 2.7). All GP practices, and all patients approached, were willing to be involved in the research. Patients liked the treatment mostly because it was 'natural'. The sting was acceptable and viewed as a minor irritation.\n Research into nettle sting is acceptable to patients and GPs, and patients do not find the treatment more than a minor irritation. Larger rigorous studies are justified to determine the effectiveness of this ancient therapy.", "Knee osteoarthritis (OA) is prevalent and associated with both pain and functional disability. Current treatments aim to alleviate mild to moderate symptoms by various methods. Topical capsaicin (0.075% and 0.05%) has been evaluated for the treatment of the painful joints. A burning sensation was the most common side effect at these strengths. Therefore, the authors aimed to evaluate the efficacy of 0.0125% capsaicin gel (Capsika gel) compared to a placebo (the vehicle gel) in patients with symptomatic OA knee.\n This was a cross-over; double blinded, randomized, controlled trial of 100 patients with mild to moderate knee OA. All of the patients received either capsaicin gel or placebo gel applied to the affected knee, three times daily for 4 weeks with one week washout period after which the treatment switched to either capsaicin gel or placebo gel for the next 4 weeks. A blinded examiner used the visual analog scale (VAS) and WOMAC score to do weekly assessments.\n Subjects averaged 61 years of age (range, 44 to 82). During the enrollment phase, only female farmers presented. Mean body weight and height was 62.97 +/- 10.25 kg and 1.54 +/- 0.053 m, respectively The respective baseline VAS and WOMAC score was 6.40 +/- 1.64 and 51.65 +/- 13.3. The severity of OA, according to the KL criteria was: 83 patients with grade 2 and 16 with grade 3. The respective mean difference of VAS and total WOMAC score in the capsaicin group vs. the placebo group was statistically significant (p < 0.05). The mean difference of the WOMAC pain, stiffness and functional subscales in the capsaicin vs. the placebo group was also significant (p < 0.05). The only adverse event reported was a burning sensation. During the 4-week treatment with capsaicin, approximately 67% of patients had a burning sensation but none withdrew for this reason.\n 0.0125% capsaicin gel was an effective treatment in mildly to moderately painful OA knees. The burning sensation reported by patients in the capsaicin group was less disturbing than in previous studies and none of the present patients withdrew for this reason.", "This randomised, double-blind, bicenter, placebo-controlled clinical trial investigated the effect of a daily application of 6g Kytta-Salbe f (3 x 2 g) over a 3 week period with patients suffering from painful osteoarthritis of the knee. The two hundred and twenty patients examined consisted of 153 women and 67 men of an average age of 57.9 years. On average, the complaints relating to osteoarthritis of the knee had persisted for 6.5 years. Two hundred and twenty patients were included in the Full Analysis Set (FAS) and safety collective, 186 (84.5%) in the Valid Case Analysis Set (VCAS) collective. In the course of the trial, the visual analog scale (VAS) total score (primary target value) in the verum group dropped by 51.6 mm (54.7%) and in the placebo group by 10.1 mm (10.7%). The average difference between the groups of 41.5 mm (95% confidence interval=34.8 to 48.2 mm) or 44.0% is significant (p<0.001). The significance is confirmed through the evaluation of the diary, the VCAS evaluation and the separate assessment of the two centres. This also applies to the separate assessment of the VAS total score following pain at rest and on movement. The WOMAC (Western Ontario and McMaster Universities) total score (secondary target value) also improved similar to the VAS total score. At the end of the trial, a reduction by 60.4 mm (58.0%) was recorded for the verum group and a reduction of 14.7 mm (14.1%) for the placebo group. The average group difference of 45.7 mm (95% confidence interval=37.1 to 54.3 mm) or 43.9% is significant (p<0.001). The difference between the treatment groups increased systematically and significantly, in parallel with the duration of the treatment. Thus, the superiority of the treatment with Kytta-Salbe f over that with the placebo is proven, even by means of the multi-factorial multivariate analysis for repetitive measurements. In respect of the explorative secondary target values SF-36 (quality of life), angle measurement (mobility of the knee), CGI (clinical global impression) and global assessment of efficacy by the physician and the patient, a significant superiority (p<0.001 each) of the verum group over the placebo group was also proven. The results suggest that the comfrey root extract ointment is well suited for the treatment of osteoarthritis of the knee. Pain is reduced, mobility of the knee improved and quality of life increased.", "There are numerous published references to use of nettle sting for arthritis pain but no randomized controlled trials have been reported. We conducted a randomized controlled double-blind crossover study in 27 patients with osteoarthritic pain at the base of the thumb or index finger. Patients applied stinging nettle leaf (Urtica dioica) daily for one week to the painful area. The effect of this treatment was compared with that of placebo, white deadnettle leaf (Lamium album), for one week after a five-week washout period. Observations of pain and disability were recorded for the twelve weeks of the study. After one week's treatment with nettle sting, score reductions on both visual analogue scale (pain) and health assessment questionnaire (disability) were significantly greater than with placebo (P = 0.026 and P = 0.0027)." ]

[ "7767151", "3006228", "2997101", "2539180", "6326632", "6378236", "6359995", "2986508", "8149141", "15512809", "12243600", "8504271", "3554658", "7048914", "2669626", "6313595", "12523578" ]

[ "Acyclovir given as prophylaxis against oral ulcers in acute myeloid leukaemia: randomised, double blind, placebo controlled trial.", "Acyclovir prophylaxis in bone marrow transplant recipients.", "Once-daily intravenous acyclovir for prophylaxis of herpes simplex virus reactivation after marrow transplantation.", "The prophylactic role of intravenous and long-term oral acyclovir after allogeneic bone marrow transplantation.", "Oral acyclovir for prevention of herpes simplex virus reactivation after marrow transplantation.", "Oral acyclovir prophylaxis against herpes simplex virus in non-Hodgkin lymphoma and acute lymphoblastic leukaemia patients receiving remission induction chemotherapy. A randomised double blind, placebo controlled trial.", "Acyclovir prophylaxis against herpes simplex virus infection in patients with leukemia. A randomized, double-blind, placebo-controlled study.", "Oral acyclovir therapy for mucocutaneous herpes simplex virus infections in immunocompromised marrow transplant recipients.", "Oral acyclovir as prophylaxis for bacterial infections during induction therapy for acute leukaemia in adults. The Leukemia Group of Middle Sweden.", "Oral valacyclovir as prophylaxis against herpes simplex virus reactivation during high dose chemotherapy for leukemia.", "Valacyclovir versus acyclovir for HSV prophylaxisin neutropenic patients.", "Prostaglandin E2 for prophylaxis of oral mucositis following BMT.", "Sequential intravenous and twice-daily oral acyclovir for extended prophylaxis of herpes simplex virus infection in marrow transplant patients.", "Multicenter collaborative trial of intravenous acyclovir for treatment of mucocutaneous herpes simplex virus infection in the immunocompromised host.", "Effect of acyclovir on radiation- and chemotherapy-induced mouth lesions.", "Oral acyclovir prophylactic treatment of herpes simplex infection after bone marrow transplantation.", "Oral valacyclovir versus intravenous acyclovir in preventing herpes simplex virus infections in autologous stem cell transplant recipients." ]

[ "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.", "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.", "To determine the most convenient and least expensive regimen for prevention of recurrent herpes simplex virus (HSV) infection after marrow transplantation, we conducted a randomized, double-blind comparison of intravenous acyclovir 250 mg/m2 and placebo given once daily for four weeks. Six of 14 acyclovir and nine of 13 placebo recipients shed HSV during prophylaxis. All nine culture-positive placebo recipients developed associated lesions during prophylaxis compared to four of six acyclovir recipients. Median time to first culture-positive lesion was significantly delayed by acyclovir compared to placebo (33 days after transplant vs. 10; P = 0.05). Acyclovir-resistant HSV was recovered from one acyclovir recipient while receiving prophylactic acyclovir, and from two placebo recipients during subsequent administration of therapeutic acyclovir. Once-daily intravenous acyclovir can significantly delay time to appearance of culture-positive HSV lesions after marrow transplant, but virological and clinical breakthrough may occur and optimal prevention will require administration of intravenous acyclovir more than once daily.", "Eighty-two patients were randomly allocated to receive intravenous acyclovir 5 mg kg-1 t.d.s. for 23 days followed by oral acyclovir 800 mg 6-hourly for 6 months or matching placebos after allogeneic bone marrow transplantation. Herpes simplex and varicella zoster virus infections were significantly reduced during the period of administration of acyclovir. No reduction in cytomegalovirus infection was demonstrated. The drug was not toxic.", "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.", "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).", "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 randomized, double-blinded, placebo-controlled trial, we compared the therapeutic effect of oral acyclovir (400 mg five times daily for 10 days) with that of placebo in patients with marrow transplants and culture-proven recurrent mucocutaneous herpes simplex. Twelve patients received acyclovir and nine received placebo. Acyclovir treatment significantly shortened the median duration of viral shedding, new lesion formation, and time to first decrease in pain, resolution of pain, 50% healing, and total healing. These results compared favorably with those previously obtained with intravenous or topical acyclovir preparations. Oral acyclovir is highly effective for the treatment of recurrent mucocutaneous infections caused by herpes simplex virus in immunocompromised patients.", "We prospectively tested the hypothesis that prevention of herpes simplex virus infection with acyclovir might also reduce the incidence of bacterial infections in adult patients with acute leukaemia. During the first induction therapy a double-blind, randomized and placebo-controlled study was undertaken. Fifty-two patients were treated with 200 mg acyclovir orally four times daily throughout the induction period, whereas 55 patients received placebo. The groups were comparable with regard to age, cytotoxic chemotherapy and duration of neutropenia. Bacteraemias were significantly fewer in the acyclovir group (20 versus 41 episodes; P = 0.007). The number of isolated microorganisms causing bacterial or fungal infections was also lower during acyclovir prophylaxis (52 isolates, versus 93 isolates; P = 0.02). There was no significant difference between the groups with regard to the number of clinically documented infections or fevers of unknown origin. Herpes simplex virus isolations occurred only in the placebo group (P = 0.001). Thus, oral acyclovir prophylaxis was associated with reductions of all microbiologically documented infections suggesting that prevention of herpes simplex virus reactivation in acute leukaemia patients may reduce the occurrence of other infections.", "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.", "It is common practice to administer acyclovir as prophylaxis to patients with hematologic malignancies during neutropenia; however, effective therapy requires frequent dosing, which is difficult in this setting. Valacyclovir has greater oral bioavailability and requires less frequent dosing.\n To evaluate the efficacy and safety of valacyclovir compared with acyclovir.\n Patients who had been treated with chemotherapy or stem-cell transplantation were randomized to receive acyclovir 400 mg orally 3 times daily (n = 51), valacyclovir 500 mg orally twice daily (n = 48), or valacyclovir 250 mg orally twice daily (n = 52) during neutropenia.\n Clinical success, defined as the absence of an active herpes simplex virus (HSV) lesion or asymptomatic viral shedding, was similar between the 3 groups (acyclovir 96%, valacyclovir 500 mg 95%, valacyclovir 250 mg 100%). The overall rates of adverse events were similar in the 3 groups.\n Prophylactic treatment with valacyclovir is an effective and safe alternative to acyclovir for the prevention of HSV reactivation in patients with hematologic malignancies.", "Between October 1988 and December 1990, 60 patients with leukaemia (25 with AML, 19 ALL and 16 CML) undergoing BMT were randomised in a double-blind clinical trial to receive prostaglandin E2 (PGE) (Prostin E2, 0.5 mg per tablet) or placebo for prophylaxis of oral mucositis. Patients had to dissolve tablets in the mouth three times daily starting 7 days before BMT and continuing until 21 days after BMT. The incidence of severe oral mucositis was similar for both groups, 55% in patients receiving PGE and 52% in patients receiving placebo. The duration of severe mucositis did not differ between PGE and placebo groups (chi-square 0.95, p = NS). The incidence of HSV infection was significantly higher in patients receiving PGE. Patients with HSV infection receiving PGE also had a higher incidence of severe oral mucositis. The results presented indicate that PGE is not effective for prophylaxis of oral mucositis in BMT recipients.", "To define an effective and convenient means for providing extended prophylaxis of herpes simplex virus (HSV) infection to chronically immunocompromised patients, we studied a two-part regimen of intravenous, followed by oral, acyclovir after marrow transplantation. Seropositive patients were first given intravenous acyclovir until day 30 after transplant. Intravenous acyclovir (250 mgm/m2) given twice daily to 34 patients during this period was 90% virologically effective among those completing the prophylactic course. A randomized, double-blind comparison of twice-daily oral acyclovir (800 mg) and placebo was then conducted from day 31 to day 75 after transplant in 51 patients. Oral acyclovir significantly delayed the median time to first excretion of HSV when compared with placebo (greater than 100 vs. 70 days after transplant, P = 0.0006) and was completely effective in all patients for the duration of drug administration. Patients receiving extended prophylaxis appeared to have less-severe HSV infection when later recurrences did occur. Sequential intravenous and oral acyclovir given twice daily is an effective and convenient regimen for extended prophylaxis of HSV infection following marrow transplantation, and should be useful in other transplant patients or other chronically immunosuppressed patients as well.", "Intravenous acyclovir was evaluated in the treatment of 97 immunocompromised patients with mucocutaneous herpes simplex virus infection in a randomized, double-blind, placebo-controlled trial. Acyclovir recipients had significantly shorter periods of virus shedding (p less than 0.0002) and lesion pain (p less than 0.01), and more rapid lesion scabbing (p less than 0.004) and lesion healing (p less than 0.04). The most common adverse reaction was a low incidence of peripheral vein irritation; no serious toxicity could be definitely attributed to acyclovir treatment even in these seriously ill patients. Intravenous acyclovir offers both safe and effective treatment for mucocutaneous herpes simplex virus infection in the immunocompromised host.", "Several chemotherapeutic regimens and radiation therapy, if delivered to the oral mucosa, are associated with a high frequency of mouth lesions. The cause of this side effect is not known for certain, but in past studies it has sometimes been associated with the ability to culture herpes simplex virus type 1 from the mouth. In a double-blind prospective trial, patients with head and neck tumors treated with chemotherapy or radiation therapy were treated with either acyclovir or placebo. Although the frequency of culture-positive herpes simplex virus was low in the untreated group, it was significantly lower, zero, in the acyclovir-treated group. However, there were no differences in the frequency or type of mouth lesions experienced by patients receiving either radiation or chemotherapy who were taking acyclovir or placebo. These results suggest that herpes simplex virus is not a frequent cause or complication of oral lesions afflicting this patient population.", "In a double-blind controlled study, oral acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD); there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation.", "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." ]

[ "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." ]

[ "3514830", "1880663", "1444522", "2035325", "7780540", "1428134", "8827897", "13842162", "9141807", "8635828", "6071586", "2862419", "9875038" ]

[ "Use of oral vitamin K1 to prevent hemorrhagic disease of the newborn infant.", "Comparison of oral and parenteral vitamin K prophylaxis for prevention of late hemorrhagic disease of the newborn.", "Effects of oral and intramuscular vitamin K prophylaxis on vitamin K1, PIVKA-II, and clotting factors in breast fed infants.", "Vitamin K to neonates. Peroral versus intramuscular administration.", "[Efficacy of oral administration of a micellaar solution of vitamin K during the neonatal period].", "Comparative study of oral versus injectable vitamin K in neonates.", "Effects of oral and intramuscular vitamin K prophylaxis on PIVKA-II assay parameters in breastfed infants in Turkey.", "Observations on the prophylactic use of vitamin Kin the newborn infant.", "Prevention of subclinical vitamin K deficiency based on PIVKA-II levels: oral versus intramuscular route.", "Effect of oral water soluble vitamin K on PIVKA-II levels in newborns.", "Hemorrhagic disease of the newborn. Breast feeding as a necessary factor in the pathogenesis.", "Effect of vitamin K administration on acarboxy prothrombin (PIVKA-II) levels in newborns.", "A new mixed micellar preparation for oral vitamin K prophylaxis: randomised controlled comparison with an intramuscular formulation in breast fed infants." ]

[ "nan", "nan", "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.", "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.", "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.", "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.", "Protein induced by vitamin K absence (PIVKA-II) has been used for the evaluation of vitamin K deficiency in the newborn. Differing PIVKA-II detection rates in various studies on hemorrhagic disease of the newborn have not been explained satisfactorily. In this study we investigated the PIVKA-II values of 44 healthy breastfed infants, of whom 29 received vitamin K1 either orally (N = 13) or intramuscularly (n = 16), and the remaining 15 constituted the control group. PIVKA-II was detected in 15.3 percent (2/13) of the oral and 25 percent of the (4/16) intramuscular group on the third day of life. The detection rate was 93.3 percent (14/15) in the control group. However, at the one-month follow-up, there were no PIVKA-II positive infants. In conclusion, PIVKA-II positivity among breastfed Turkish infants on the third day of life was high compared to that in other studies, perhaps due to a delay in enzyme maturation related to racial, environmental and nutritional factors.", "nan", "nan", "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.", "nan", "PIVKA-II (protein induced by vitamin K absence or antagonist-II) was measured in two groups of newborns, one group being given 5 mg vitamin K at birth and the other untreated. The untreated group had a significantly higher proportion of PIVKA-II positive babies at 3 and 5 days of age than did the treated group. When vitamin K was administered to newborn babies whose normotest levels were less than 30%, it was found that the higher the pre-treatment PIVKA-II levels the greater the response to vitamin K, as monitored by the normotest. Thus PIVKA-II levels might be more useful than a coagulation test, since the low activity of vitamin K dependent coagulation factors sometimes reflects not vitamin K deficiency but impaired production of these factors because of immaturity. The findings support the view that vitamin K given prophylactically at birth will help to prevent neonatal bleeding.", "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." ]

[ "11376923", "1330470", "1319961", "17134849", "20545388", "8749726", "8556965", "1862788", "16040376", "8793307", "15730352", "15730346", "12062456", "16051446", "9097872", "10940543", "7762545", "16697124", "18164144" ]

[ "Methadone tapering plus amantadine to detoxify heroin-dependent inpatients with or without an active cocaine use disorder: two randomised controlled trials.", "Amantadine may facilitate detoxification of cocaine addicts.", "Treatment of cocaine dependence in methadone maintenance clients: a pilot study comparing the efficacy of desipramine and amantadine.", "Safety, tolerability and efficacy of levodopa-carbidopa treatment for cocaine dependence: two double-blind, randomized, clinical trials.", "Contingency management and levodopa-carbidopa for cocaine treatment: a comparison of three behavioral targets.", "Desipramine, amantadine, or fluoxetine in buprenorphine-maintained cocaine users.", "Amantadine does not reduce cocaine use or craving in cocaine-dependent methadone maintenance patients.", "Comparison of amantadine and desipramine combined with psychotherapy for treatment of cocaine dependence.", "Use of dopamine agonist pergolide in outpatient treatment of cocaine dependence.", "Amantadine in the early treatment of cocaine dependence: a double-blind, placebo-controlled trial.", "Randomized controlled pilot trial of cabergoline, hydergine and levodopa/carbidopa: Los Angeles Cocaine Rapid Efficacy Screening Trial (CREST).", "Efficacy screening trials of paroxetine, pentoxifylline, riluzole, pramipexole and venlafaxine in cocaine dependence.", "A screening trial of amantadine as a medication for cocaine dependence.", "Bromocriptine treatment for cocaine addiction: association with plasma prolactin levels.", "Bromocriptine for cocaine dependence. A controlled clinical trial.", "A double-blind, placebo-controlled outpatient trial of pergolide for cocaine dependence.", "Double-blind comparison of bromocriptine and placebo in cocaine withdrawal.", "A double-blind, placebo-controlled trial of amantadine, propranolol, and their combination for the treatment of cocaine dependence in patients with severe cocaine withdrawal symptoms.", "Levodopa pharmacotherapy for cocaine dependence: choosing the optimal behavioral therapy platform." ]

[ "The efficacy of methadone tapering plus amantadine to detoxify heroin-dependent patients with or without an active cocaine use disorder was studied in a closed unit with two successive double-blind, placebo-controlled, 14-day trials. In the first trial, 40 heroin-dependent inpatients with an active cocaine use disorder were treated using methadone tapering, as well as amantadine (200-300 mg per day) or placebo. In the second trial, 40 heroin-dependent inpatients without an active cocaine use disorder received the same treatment. In both the trials, amantadine did not have a statistically significant effect on treatment completion, nor did it contribute, in completers, to a more rapid reduction in craving and opiate withdrawal. In the first trial, women were six times more likely than men to be non-completers, and on the last day of treatment, the first trial's completers and non-completers presented a comparable clinical state.", "The effectiveness of amantadine hydrochloride was evaluated in a double-blind placebo controlled drug trial. The subjects were 42 cocaine dependent men enrolled in a day hospital program. Twenty-one patients were prescribed 100 mg/bid of amantadine to be taken over 10.5 days and 21 were prescribed an equivalent amount of placebo. The primary outcome measures were the Addiction Severity Index at 1 month after study entry and urines during the drug trial (end of weeks 1 and 2) and 1 month after study entry. Urines obtained at the end of the drug trial (2 weeks) indicated that the subjects receiving amantadine (93%) were more likely (P = 0.040) to be free of cocaine than the placebo (60%) subjects. Urine toxicology data at 1-month follow-up again indicated that more of the amantadine subjects (83%) were free of cocaine than the placebo (53%) subjects (p = 0.049); although no differences were found in self-reports of cocaine or other substance use in the past 30 days. The urine findings provided preliminary indication that amantadine may have some effectiveness in reducing cocaine use in cocaine dependent patients.", "We conducted a pilot study (N = 22) comparing the efficacy of desipramine and amantadine for treatment of cocaine dependence in methadone maintenance clients. The study which lasted 12 weeks, was double-blind, randomly assigned, and placebo-controlled. Subjects met DSM-III-R criteria for active cocaine dependence. All three groups' cocaine use, craving, and depressive symptoms declined significantly, but intergroup differences were not significant. Clients receiving desipramine were significantly more likely to remain in treatment and to be cocaine free at study completion. The results emphasize the importance of delivering comprehensive services to the cocaine user in methadone treatment. Further evaluations of these two medications as adjuncts in the treatment of cocaine dependence are needed.", "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.", "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.", "The clinical efficacy of promising cocaine anti-craving medications was examined in combination with buprenorphine. Twenty-one opioid-dependent cocaine abusers were enrolled in a double-blind, 12-week trial in which they received on a daily basis buprenorphine (8 mg, s.l.) plus either desipramine (150 mg, p.o.), amantadine (300 mg, p.o.), or fluoxetine (60 mg, p.o.). Urine samples and self-reported drug use were obtained 1-3 times/week. The order of greatest patient retention across the 12 weeks was desipramine (83.3%) > amantadine (66.7%) > fluoxetine (20.0%). The desipramine and amantadine groups appeared to have greater increases in opioid- and cocaine-free urines than the fluoxetine group. These results suggest that desipramine and amantadine may facilitate greater opioid and cocaine abstinence than fluoxetine.", "We tested the efficacy of amantadine to reduce cocaine use or craving in cocaine-dependent methadone maintained patients. Two doses of amantadine (200 mg p.o. daily, n = 16, and 200 mg p.o. bid, n = 21) were tested against placebo, n = 22, in a random assignment, double-blind clinical trial lasting nine weeks. Amantadine was well tolerated. However, neither dose of amantadine was more effective than placebo in reducing cocaine use and craving.", "We conducted a single-blind, random assignment, placebo-controlled, 12-week comparison of desipramine hydrochloride and amantadine hydrochloride as adjunctive treatments to counseling for cocaine dependence. Subjects were 54 outpatients who met DSM III-R criteria for active cocaine dependence and who completed a minimum of 2 weeks of treatment. Subjects treated with fixed doses of 200 mg/day desipramine (N = 17), 400 mg/day amantadine-placebo (N = 16), and placebo (N = 21) did not differ for lifetime cocaine use, lifetime histories of psychopathology, admission scores on psychometric assessments, and sociodemographics. All treatment groups demonstrated dramatic and persistent decreases in cocaine use, craving for cocaine, and psychiatric symptoms consequent to treatment. Although there was a trend for more dropouts by subjects taking desipramine, there were no significant differences among treatment groups regarding retention in treatment, craving for cocaine, and decreased cocaine use confirmed by urine toxicology. There was a trend for subjects treated with desipramine to maintain longer periods of cocaine abstinence. Mean plasma concentration of desipramine in a subsample of our subjects was less than that recommended for treatment of depression, thus the dosage of desipramine may have been subtherapeutic.", "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.", "A 4-week, double-blind, placebo-controlled trial of amantadine was conducted in 61 cocaine dependent outpatients. Subjects received 100 mg of amantadine 3 times daily. A follow-up visit was conducted at week 8. There were no significant differences between groups in treatment retention, or in the number of benzoylecgonine positive urine samples. Self-reported drug and alcohol use declined in both groups. At week 8 follow-up, self-reported drug use was significantly lower in the placebo group. Amantadine was not effective, and discontinuation of it may have been associated with an increase in cocaine use.", "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 two studies presented here were conducted to assess the efficacy of paroxetine, pentoxifylline, riluzole, venlafaxine and pramipexole as medications for the treatment of cocaine dependence.\n A multi-arm, modified blinded, placebo-controlled design was used.\n The studies were conducted at the Boston VA Healthcare System and the Boston University School of Medicine Medication Development Research Unit (MDRU).\n Participants met criteria for cocaine dependence during a 2-week screening period.\n Following random assignment to one of the treatment groups, subjects received active medication or placebo for 8 weeks in combination with cognitive behavioral counseling. In the first study the efficacy of the antidepressant paroxetine (20 mg daily), the phosphodiesterase inhibitor pentoxifylline (1200 mg daily) and the glutamate release inhibitor riluzole (100 mg daily) was assessed. The antidepressant venlafaxine (150 mg daily) and the dopamine agonist pramipexole (1.5 mg daily) were evaluated in the second study.\n Urine benzoylecgonine (BE) concentrations, self-report of cocaine use and global impression scores served as primary outcome measures. Secondary measures included assessments of cocaine craving and psychiatric functioning. Adverse events were monitored during the treatment period.\n None of the active medications produced greater reductions in urine BE concentrations over the treatment period than did placebo. There were trends for BE levels to become reduced in the pentoxifylline group during the first 4 weeks of treatment and for Addiction Severity Index (ASI) drug composite scores to be lower in the pentoxyfylline group at end-point compared to the placebo group. Significant within-group reductions in reported cocaine use and craving were found for all treatment groups, but none of the active medications were superior to placebo on these measures. The accuracy of self-reported cocaine use declined over the study period. Overall, the active medications were well tolerated.\n This study does not support the use of paroxetine, pentoxifylline, riluzole, venlafaxine or pramipexole for the treatment of cocaine dependence. However, these results need to be interpreted with caution because of the small size and lack of homogeneity of the experimental groups.", "This screening trial evaluated whether amantadine hydrochloride (100 mg bid) demonstrated sufficient clinical efficacy compared to placebo to recommend development as a pharmacotherapy for cocaine dependence. Participants were randomized to amantadine (n=34) or placebo (n=35) conditions in a 16-week, placebo-controlled, double blind trial with three times per week group counseling. Amantadine-treated participants were retained significantly longer than placebo. Based on results of a joint probability index for urine drug testing results (i.e. the proportion of cocaine-metabolite free urine samples divided by the number of participants assigned to the condition), participants assigned to amantadine were found to be significantly more likely to be cocaine abstinent on the last day of 8-weeks of treatment than participants assigned to placebo. Results at the end of 16 weeks of treatment were similar. Standard measures of urine drug testing consistently favored the amantadine condition over placebo, although not at levels of statistical significance. There was no statistical significance infrequency or severity of reported adverse events by treatment condition. Participants assigned to amantadine exhibited greater reductions in global staff ratings of cocaine dependence severity from baseline to termination compared with placebo. There were no significant differences in frequency or severity of reported adverse events by treatment condition. These results provide moderate support for further study of amantadine for the treatment of cocaine dependence.", "Bromocriptine is a dopamine receptor agonist used with mixed success in the treatment of cocaine addiction. Variations in dopamine receptor sensitivity may help account for these differences. We evaluated this question in a 24-week outpatient controlled clinical trial in 70 cocaine-abusing (DSM-III) men (86% African-American, mean age 34 years, mean 39 months of regular cocaine use [predominantly smoked]). Subjects received 4 weeks of inpatient treatment. During the last 2 weeks they were inducted onto bromocriptine (maximum dose 2.5mg po tid) (n=35) or placebo (n=35). Plasma prolactin concentrations were assayed before and after the first bromocriptine dose (1.25mg po) as a measure of dopamine receptor sensitivity. After discharge, subjects continued on medication with weekly group counseling. Bromocriptine significantly suppressed prolactin concentrations (4.4 ng/ml decrease), while placebo did not (0.1 ng/ml decrease). Both groups decreased their cocaine use, with no significant group differences in retention in treatment or proportion of cocaine-positive urine samples. There was no significant association between basal plasma prolactin concentrations or prolactin response to first bromocriptine dose and either outcome measure. These data do not support the efficacy of bromocriptine treatment nor a role for prolactin concentration in predicting treatment response.", "On the basis of the dopamine depletion theory, bromocriptine has been tested to treat cocaine withdrawal and dependence. The authors conducted a 6-week study with 1 week of pretreatment observation and 5 weeks of a randomized, double-blind, placebo-controlled clinical trial of bromocriptine for DSM-III-R-defined cocaine dependence in methadone-maintained male patients. The bromocriptine group (n = 24) did not differ from the placebo group (n = 26) in self-reported cocaine use, proportion of positive urine toxicology samples, craving for cocaine, resistance to cocaine use, or mood symptoms between the pretreatment baseline and the last week of the clinical trial. Both groups showed significant reduction in self-reported frequency of cocaine use, resistance to craving, and mood symptoms during participation in the protocol. The results of this study are consistent with recent clinical and laboratory findings in primary cocaine users. Despite initially promising pilot studies, recent evidence does not support the efficacy of bromocriptine to reduce cocaine use or craving.", "Results of preclinical studies suggest that pergolide, a mixed D(1)/D(2) dopamine receptor agonist, may be useful in treating cocaine dependence. To empirically investigate this possibility, we conducted a 5-year, double-blind, placebo-controlled clinical trial of two doses of pergolide (0.05 and 0.25 mg bid) in subjects with cocaine dependence and combined cocaine/alcohol dependence. Data analysis was performed on an intent to treat population (N=358) and a per protocol population (N=108) with urine drug screens (UDS) used as the main outcome measure. There were no significant effects on UDS at either pergolide dose. Pergolide had no significant effect on alcohol use in the comorbid alcohol/cocaine dependence group. Pergolide does not appear to have clinical value in the treatment of cocaine dependence or in decreasing alcohol use in cocaine-dependent individuals at the presently studied doses.", "Twenty-nine cocaine-dependent male veterans without other drug dependence completed a double-blind controlled, randomly-assigned study examining the efficacy of bromocriptine versus placebo in the management of cocaine abstinence symptomatology. Serum prolactin (PL) and growth hormone (GH) levels were obtained prior to and after the study was completed. Patients were seen daily and completed several self-report questionnaires, including the Symptom Checklist-90-Revised, the Beck Depression Inventory, and a Cocaine Craving Report. The patients were also asked to rate a variety of cocaine withdrawal symptoms. Overall, there did not appear to be any advantage to receiving bromocriptine versus placebo during the first 3 weeks following cocaine use cessation with the possible exception of changes in activity and appetite level. The placebo group showed a statistically significant increase in activity level during the first week in treatment and a significant increase in appetite throughout the study. Patients in both groups showed significant improvement in the other areas assessed, with improvement appearing to progress according to length of treatment. Hyperprolactinemia or abnormal GH levels were not found in this patient sample as a group. Thirty-four of the original 63 patients dropped out of the study. Seventeen received bromocriptine, and 17 received placebo. There was no significant difference between drug groups in incidence of retaining patients in treatment. The high dropout rate may reflect the difficulty incurred in retaining cocaine-dependent patients in treatment.", "This trial evaluated the efficacy of amantadine, propranolol and their combination in cocaine dependent patients with severe cocaine withdrawal symptoms.\n Cocaine withdrawal symptom severity was measured by the cocaine selective severity assessment (CSSA). One hundred and ninety-nine patients with high scores on the CSSA participated in a 10-week double-blind trial. Patients were randomly assigned to receive amantadine (300 mg/day), propranolol (100mg/day), a combination of amantadine (300 mg/day) and propranolol (100mg/day) or matching placebo capsules. The primary outcome measure was cocaine abstinence.\n In the intent-to-treat sample, there were no significant differences between the four medication groups in treatment retention. The odds of cocaine abstinence showed a marginally significant increase over time in the propranolol group (p=0.06) but not in the other three groups. In highly medication-adherent patients, treatment retention was significantly better in the propranolol group compared to the placebo group (p=0.01) and the odds of cocaine abstinence increased significantly over time in the propranolol group but not in the other three groups.\n In the intent-to-treat sample, none of the three active treatments (propranolol, amantadine or their combination) was significantly more effective than placebo in promoting abstinence from cocaine among patients who entered treatment with more severe cocaine withdrawal symptoms. Among patients highly adherent to study medication, propranolol treatment was associated with better treatment retention and higher rates of cocaine abstinence compared to placebo.", "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." ]

[ "9437624", "14563543", "9076653", "11258740", "12898500" ]

[ "Naltrexone pharmacotherapy for opioid dependent federal probationers.", "A randomised controlled trial of methadone maintenance treatment versus wait list control in an Australian prison system.", "Integrating the therapeutic community and work release for drug-involved offenders. The CREST Program.", "Multisystemic treatment of substance-abusing and dependent delinquents: outcomes, treatment fidelity, and transportability.", "Evaluation of a mental health treatment court with assertive community treatment." ]

[ "Federal probationers or parolees with a history of opioid addiction were referred by themselves or their probation/parole officer for a naltrexone treatment study. Participation was voluntary and subjects could drop out of the study at any time without adverse consequences. Following orientation and informed consent, 51 volunteers were randomly assigned in a 2:1 ratio to a 6-month program of probation plus naltrexone and brief drug counseling, or probation plus counseling alone. Naltrexone subjects received medication and counseling twice a week; controls received counseling at similar intervals. All therapy and medication were administered in an office located adjacent to the federal probation department. Fifty-two percent of subjects in the naltrexone group continued for 6 months and 33% remained in the control group. Opioid use was significantly lower in the naltrexone group. The overall mean percent of opioid positive urine tests among the naltrexone subjects was 8%, versus 30% for control subjects (p < .05). Fifty-six percent of the controls and 26% of the naltrexone group (p < .05) had their probation status revoked within the 6-month study period and returned to prison. Treatment with naltrexone and brief drug counseling can be integrated into the Federal Probation/Parole system with favorable results on both opioid use and re-arrest rates.", "The aim was to determine whether methadone maintenance treatment reduced heroin use, syringe sharing and HIV or hepatitis C incidence among prisoners.\n All eligible prisoners seeking drug treatment were randomised to methadone or a waitlist control group from 1997 to 1998 and followed up after 4 months. Heroin use was measured by hair analysis and self report; drugs used and injected and syringe sharing were measured by self report. Hepatitis C and HIV incidence was measured by serology.\n Of 593 eligible prisoners, 382 (64%) were randomised to MMT (n=191) or control (n=191). 129 treated and 124 control subjects were followed up at 5 months. Heroin use was significantly lower among treated than control subjects at follow up. Treated subjects reported lower levels of drug injection and syringe sharing at follow up. There was no difference in HIV or hepatitis C incidence.\n Consideration should be given to the introduction of prison methadone programs particular where community based programs exist.", "As the nation's first therapeutic community (TC) and work release center for drug involved offenders, CREST combines the basic elements of both modalities into an effective agent for behavioral change. This article explores the ways in which these elements are integrated and applied, and the outcome of such treatment as determined by subsequent substance abuse and criminal activity. Clients entering the program from prison progress through several phases of counseling, group interaction, confrontation, and education before they enter the work release phase, where they gain realistic experience and can implement what they learned in the TC concerning living drug free. Follow-up data collected at 6 and 18 months after entry into the program indicate that CREST clients have significantly lower relapse and recidivism rates than a comparable comparison group. CREST has similar effects on relapse and recidivism across sexes, racial/ethnic groups, and different age categories, although length of time in treatment and whether clients graduated do impact outcome variables.", "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.", "Without active engagement, many adults with serious mental illnesses remain untreated in the community and commit criminal offenses, resulting in their placement in the jails rather than mental health facilities. A mental health treatment court (MHTC) with an assertive community treatment (ACT) model of case management was developed through the cooperative efforts of the criminal justice and mental health systems. Participants were 235 adults with a serious mental illness who were booked into the county jail, and who volunteered for the study. An experimental design was used, with participants randomly assigned to MHTC or treatment as usual (TAU), consisting of adversarial criminal processing and less intensive mental health treatment. Results were reported for 6 and 12 month follow-up periods. Clients in both conditions improved in life satisfaction, distress, and independent living, while participants in the MHTC also showed reductions in substance abuse and new criminal activity. Outcomes are interpreted within the context of changes brought about in the community subsequent to implementation of the MHTC.\n Copyright 2003 John Wiley & Sons, Ltd." ]

[ "7675718", "14668503", "1527129", "18260482" ]

[ "Treatment of ulnar shaft fractures: a prospective, randomized study.", "A prospective, randomized trial comparing the limited contact dynamic compression plate with the point contact fixator for forearm fractures.", "Isolated ulnar shaft fractures. Comparison of treatment by a functional brace and long-arm cast.", "Conservative management of minimally displaced isolated fractures of the ulnar shaft." ]

[ "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.", "The most effective type of plate fixation for diaphyseal forearm fractures has not been defined. We performed a prospective, randomized trial in which the limited contact dynamic compression plate (LC-DCP) was compared with the Point Contact Fixator (PC-Fix) for the treatment of forearm fractures at one center.\n Ninety-two patients with 125 forearm fractures were recruited for the study and were randomly assigned to fracture fixation with one of the two devices. The average age of the patients was thirty-six years. The average duration of follow-up was twenty-two months. Patients were assessed periodically with use of radiographs and were assessed with regard to pain and function at time of the latest follow-up.\n Three patients (four fractures) in the PC-Fix group and five patients (five fractures) in the LC-DCP group had a delayed union, but no patient in either group had a nonunion. With the numbers available, there was no significant difference between the two groups with regard to operative time, time to union, callus formation, pain, or functional outcome. Deep infection occurred in one patient with a closed fracture in the PC-Fix group and in one patient with an open fracture in the LC-DCP group. In addition, one refracture occurred in each group. Both refractures occurred at the site of a screw track.\n Despite the differences in the concept of fracture fixation, these two implants appear to be equally effective for the treatment of diaphyseal forearm fractures.", "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.", "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." ]

[ "10448830", "8082624", "1907907", "8232945" ]

[ "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 (Neurontin) as add-on therapy in patients with partial seizures: a double-blind, placebo-controlled study. The International Gabapentin Study Group.", "Double-blind study of Gabapentin in the treatment of partial seizures.", "Gabapentin as add-on therapy in refractory partial epilepsy: a double-blind, placebo-controlled, parallel-group study. The US Gabapentin Study Group No. 5." ]

[ "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.", "A multicenter, double-blind, randomized, placebo-controlled study evaluated the efficacy and safety of gabapentin (Neurontin, GBP) as add-on therapy in 272 patients with refractory partial seizures who were receiving one to two standard antiepileptic drugs (AEDs). Efficacy assessments compared the frequency of partial seizures during the 12-week treatment phase (T) and the 12-week baseline period (B). The primary analysis compared data for patients receiving GBP 900 mg/day with placebo; the GBP 1,200-mg/day group provided dose-response data. Efficacy criteria were percentage of change in seizure frequency (PCH), responder rate (percentage of patients with > or = 50% reduction in seizure frequency), and response ratio, where RRatio = (T-B)/(T + B). Median PCH was -21.8% in the 900-mg/day group and -17.8% in the 1,200-mg/day group as compared with -0.3% in the placebo group. Responder rate was 22.9% in the 900-mg/day group and 10.1% in the placebo group (p = 0.020, Fisher's exact test). Adjusted mean RRatio was -0.136 in the 900-mg/day group and -0.025 in the placebo group (p = 0.0046, analysis of variance ANOVA). Results showed slightly greater improvement for the 1,200-mg/day than for the 900-mg/day group (RRatio = -0.157, responder rate 28.0%). Adverse events (AE) occurred in 69% of patients in the 900-mg/day group and in 64% in the 1,200-mg/day group as compared with 52% in patients receiving placebo as add-on therapy. The most frequent AE among patients treated with GBP were somnolence, dizziness, and fatigue. Clinical laboratory evaluations showed no clinically important trends and no evidence of hepatic or hematopoietic effects.(ABSTRACT TRUNCATED AT 250 WORDS)", "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.", "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." ]

[ "9113009" ]

[ "Randomised multicentre study of a low-protein diet on the progression of chronic renal failure in children. European Study Group of Nutritional Treatment of Chronic Renal Failure in Childhood." ]

[ "Some studies have suggested that a low-protein diet slows the deterioration of renal function in patients with chronic renal failure (CRF). The effects of a low-protein diet on renal function and growth, have not been assessed in a large, prospective randomised trial in children with CRF.\n A 2-year prospective, stratified, and randomised multicentre study recruited 191 patients aged 2-18 years. After a run-in period of at least 6 months, patients were stratified into either a progressive or non-progressive category based on the change in creatinine clearance in this period. The patients were also stratified into three renal-disease categories and then randomly assigned to a control or diet group. In the diet group, the protein intake was the lowest, safe WHO recommendation--i.e., 0.8-1.1 g/kg daily adjusted for age. All patients were advised to have a calorie intake of at least 70% of the WHO recommendations. Glomerular filtration rate (GFR) was measured every 2 months by creatinine clearance; dietary compliance was checked by urinary urea-nitrogen excretion and dietary diaries (weighing method). 112 patients completed an optional third year of the study.\n The low-protein diet did not affect growth. However, there was no effect of diet on the mean decline in creatinine clearance over 2 years (diet vs control: progressive group -9.7 [SD 8.0] vs -10.7 [11.8] mL/min per 1.73 m2; non-progressive group -2.5 [7.5] vs -4.3 [10.0] mL/min per 1.73 m2). Patients classified as having progressive disease were older and had a lower creatinine clearance and a higher blood pressure at randomisation, and had a greater decrease in creatinine clearance than non-progressive patients. On multivariate regression analysis proteinuria (partial R2 = 0.259) and systolic blood pressure (partial R2 = 0.087) were independent predictors of the change in GFR. Similar results were found after the study was extended for a third year.\n A low-protein diet for 3 years did not affect the decrease in renal function in children with CRF. Proteinuria and blood pressure explain a large part of the variability of, and may be causally related to the decline in the GFR." ]

[ "11228214", "2744182", "10575581", "12971145" ]

[ "A prospective, randomized study comparing day 2 and day 3 embryo transfer in human IVF.", "Early, late, and sequential embryo transfer in in vitro fertilization program: a preliminary report.", "Clinical outcome of day 2 versus day 3 embryo transfer using serum-free culture media: a prospective randomized study.", "Day 2 vs. day 3 embryo transfer after intracytoplasmic sperm injection. A prospective, randomized study." ]

[ "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.", "The timing of ET was evaluated by transferring four embryos at 44 to 48 hours, 68 to 72 hours, or equally dividing and sequentially transferring at 44 to 48 and 68 to 72 hours after insemination. Fifty-one patients were randomly allocated to one of the above protocols. The mean number of blastomeres of embryos transferred at 68 to 72 hours after insemination was significantly (P less than 0.0001) higher than those transferred at 44 to 48 hours. The number of embryos with good morphology was similar in all study groups. The pregnancy rate was similar in the three protocol groups, 53% at 44 to 48 hours, 59% at 64 to 72 hours, and 47% by sequential transfer. There probably is no advantage in delaying the transfer or dividing the embryos into two sequential transfers. It seems that sequential transfer is not associated with any harmful effect.", "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.", "To compare, in a prospective, randomized study, implantation and pregnancy rates between day 2 and day 3 embryo transfer intracytoplasmic sperm injection (ICSI).\n A total of 106 patients undergoing ICSI cycles who had at least 1 embryo suitable for cryopreservation were prospectively randomized into 2 groups: group I, embryo transfer performed on day 2; group II, embryo transfer performed on day 3.\n Patient ages did not differ (P = .58) between groups I (33.1 +/- 4.5) and II (32.7 +/- 4.4). The number of oocytes retrieved from group I (13.7 +/- 5.2) was similar (P = .82) to that retrieved from group II (13.7 +/- 5.4). In addition, there was no difference (P = .30) in the number of oocytes retrieved at metaphase II between groups I (10.6 +/- 4.4) and II (9.7 +/- 4.2). Fertilization and cleavage rates were also similar (P = .58 and P = .50, respectively) between groups I (78.2 +/- 14.0% and 98.7 +/- 4.3%) and II (76.2 +/- 14.8% and 99.8 +/- 1.24%, respectively). The total number of embryos and of embryos transferred were similar (P = .22 and P = .36; respectively) for groups I (8.0 +/- 3.0, 2.8 +/- 0.7) and II (7.16 +/- 3.2, 2.6 +/- 0.8). Pregnancy rates per transfer, implantation rates and abortion rates were also similar for groups I (43.4%, 20.8% and 8.7%, respectively) and II (41.5%, 24.1% and 23%, respectively) (P = 1.0, P = .57 and P = .24, respectively).\n The results suggest that extending the embryo culture period from 2 to 3 days for patients who had at least 1 embryo left for cryopreservation had no effect on implantation, pregnancy or abortion rates in an ICSI program." ]

[ "12855628", "11105182", "12836088", "12906958", "12126174", "10660922", "2883410", "10452208" ]

[ "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.", "Electroacupuncture for control of myeloablative chemotherapy-induced emesis: A randomized controlled trial.", "Randomized double-blind study of the Reliefband as an adjunct to standard antiemetics in patients receiving moderately-high to highly emetogenic chemotherapy.", "The efficacy of acupressure and acustimulation wrist bands for the relief of chemotherapy-induced nausea and vomiting. A University of Rochester Cancer Center Community Clinical Oncology Program multicenter study.", "Acustimulation wristbands for the relief of chemotherapy-induced nausea.", "Acupressure for nausea: results of a pilot study.", "Acupuncture to prevent cisplatin-associated vomiting.", "Transcutaneous electrical nerve stimulation as an adjunct for controlling chemotherapy-induced nausea and vomiting in gynecologic oncology patients." ]

[ "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.", "High-dose chemotherapy poses considerable challenges to emesis management. Although prior studies suggest that acupuncture may reduce nausea and emesis, it is unclear whether such benefit comes from the nonspecific effects of attention and clinician-patient interaction.\n To compare the effectiveness of electroacupuncture vs minimal needling and mock electrical stimulation or antiemetic medications alone in controlling emesis among patients undergoing a highly emetogenic chemotherapy regimen.\n Three-arm, parallel-group, randomized controlled trial conducted from March 1996 to December 1997, with a 5-day study period and a 9-day follow-up.\n Oncology center at a university medical center.\n One hundred four women (mean age, 46 years) with high-risk breast cancer.\n Patients were randomly assigned to receive low-frequency electroacupuncture at classic antiemetic acupuncture points once daily for 5 days (n = 37); minimal needling at control points with mock electrostimulation on the same schedule (n = 33); or no adjunct needling (n = 34). All patients received concurrent triple antiemetic pharmacotherapy and high-dose chemotherapy (cyclophosphamide, cisplatin, and carmustine).\n Total number of emesis episodes occurring during the 5-day study period and the proportion of emesis-free days, compared among the 3 groups.\n The number of emesis episodes occurring during the 5 days was lower for patients receiving electroacupuncture compared with those receiving minimal needling or pharmacotherapy alone (median number of episodes, 5, 10, and 15, respectively; P<.001). The electroacupuncture group had fewer episodes of emesis than the minimal needling group (P<.001), whereas the minimal needling group had fewer episodes of emesis than the antiemetic pharmacotherapy alone group (P =.01). The differences among groups were not significant during the 9-day follow-up period (P =.18).\n In this study of patients with breast cancer receiving high-dose chemotherapy, adjunct electroacupuncture was more effective in controlling emesis than minimal needling or antiemetic pharmacotherapy alone, although the observed effect had limited duration. JAMA. 2000;284:2755-2761.", "Our goal was to evaluate the efficacy and tolerability of the Reliefband as an adjunct to standard antiemetics in patients receiving moderately-high to highly emetogenic chemotherapy.\n Forty-nine adult cancer patients receiving moderately-high or highly emetogenic chemotherapy were randomized to receive either the active Reliefband ( n=26) or an inactive device ( n=23). Patients continued to receive all scheduled and as needed antiemetic agents as prescribed. The device was worn the day of chemotherapy administration for 5 days (days 1-5). Patients maintained a daily dairy of nausea severity, vomiting and retching episodes, and antiemetic medications taken. Each patient completed a Functional Living Index Emesis (FLIE) and a tolerability survey at the conclusion of the study. A Wilcoxon rank sum test was used to compare the number of vomiting episodes, severity of nausea and FLIE scores between the two groups.\n Patients wearing the active Relifband experienced less vomiting (Reliefband 1.9 versus inactive device 4.6 mean episodes; p=0.05), retching (1.4 versus 3.6 mean episodes; p=0.05), and nausea severity (0.91 versus 1.65 mean cm/day; p=0.01) over the 5-day period compared to patients wearing the inactive device. Vomiting was statistically significantly reduced during the delayed period (0.42 versus 1; p=0.032), whereas nausea was significantly reduced during the acute (0.71 versus 2.3; p=0.028) and delayed (1.8 versus 3.3; p=0.020) periods. FLIE scores did not differ between the two treatment groups (91 versus 80; p=0.088).\n This study suggests that patients receiving moderately-high to highly emetogenic chemotherapy who experience nausea and vomiting despite scheduled antiemetics may benefit from the use of the Reliefband as an adjunct to antiemetics. Limitations of this study include differences in risk factors for emesis, chemotherapy, and antiemetic regimens. A larger, better, controlled randomized study is needed to better define optimal use of this device.", "As an adjunct to standard antiemetics for the relief of chemotherapy-induced nausea and vomiting (NV), 739 patients were randomly assigned to either: 1) acupressure bands, 2) an acustimulation band, or 3) a no band control condition. Patients in the acupressure condition experienced less nausea on the day of treatment compared to controls (P<0.05). There were no significant differences in delayed nausea or vomiting among the three treatment conditions. Additional analyses revealed pronounced gender differences. Men in the acustimulation condition, but not the acupressure condition, had less NV compared to controls (P<0.05). No significant differences among the three treatment conditions were observed in women, although the reduction in nausea on the day of treatment in the acupressure, compared to the no band condition, closely approached statistical significance (P=0.052). Expected efficacy of the bands was related to outcomes for the acupressure but not the acustimulation conditions.", "Substantial evidence suggests that acupuncture-point stimulation may be effective in controlling side effects of chemotherapy.\n To examine the efficacy of an acustimulation wristband for the relief of chemotherapy-induced nausea.\n Randomized clinical trial using a 3-level crossover design.\n Three outpatient oncology clinics in the northeastern United States.\n Twenty-five women and 2 men who experienced moderate or more severe nausea following their first chemotherapy treatment.\n We compared active acustimulation of the Pericardium 6 (PC-6) point on the ventral surface of the wrist with sham acustimulation (a corresponding point on the posterior surface of the wrist). A control group received no acustimulation.\n Severity of nausea and quantity of antiemetic medication used.\n No statistically significant differences in average severity of nausea were observed between the 3 interventions. However, the data showed a difference close to statistical significance in the severity of delayed nausea reported during active acustimulation compared to no acustimulation (P <.06). In addition, patients took fewer antinausea pills during the active-acustimulation cycle of this experiment compared to the no-acustimulation phase (P < .05).\n Findings on the efficacy of an acustimulation band for the control of chemotherapy-induced nausea are positive but not conclusive. These findings provide ample justification for further study of acustimulation in clinical oncology.", "To compare differences in nausea experience and intensity in women undergoing chemotherapy for breast cancer between those receiving usual care plus acupressure training and treatment and those receiving only usual care.\n Single-cycle, randomized clinical trial.\n Outpatient oncology clinic in a major teaching medical center and a private outpatient oncology practice.\n Seventeen women participated in the study. The typical participant was 49.5 years old (SD = 6.0), Caucasian (59%), not married/partnered (76%), on disability (53%), born a U.S. citizen (76%), and heterosexual (88%); lived alone (59%); had at least graduated from high school (100%); and had an annual personal income of $50,000 or greater (65%).\n The intervention included finger acupressure bilaterally at P6 and ST36, acupressure points located on the forearm and by the knee. Baseline and poststudy questionnaires plus a daily log were used to collect data.\n Nausea experience measured by the Rhodes inventory of Nausea, Vomiting, and Retching and nausea intensity.\n Significant differences existed between the two groups in regard to nausea experience (p < 0.01) and nausea intensity (p < 0.04) during the first 10 days of the chemotherapy cycle, with the acupressure group reporting less intensity and experience of nausea.\n Finger acupressure may decrease nausea among women undergoing chemotherapy for breast cancer.\n This study must be replicated prior to advising patients about the efficacy of acupressure for the treatment of nausea.", "nan", "To evaluate the efficacy of a miniaturized portable transcutaneous electrical nerve stimulation (TENS) unit (ReliefBand) as an adjunct to standard antiemetic therapy for controlling nausea and vomiting induced by cisplatin-based chemotherapy in gynecologic oncology patients.\n Forty-two patients were enrolled in a randomized, double-blind, placebo-controlled parallel-subjects trial with a follow-up crossover trial. All patients received a standardized antiemetic protocol, then wore the ReliefBand continuously for 7 days.\n Thirty-two patients were evaluable for the parallel-subjects component, 16 in each group. The percentage of patients with absent or minimal nausea was 59% overall, which was similar to that for both the active (56%) and placebo (62%) groups. The incidence and severity of nausea and vomiting was similar for each group. Eighteen patients completed two consecutive cycles and were evaluable for the crossover component. The average age of the crossover patients and their dose intensity were comparable with those of the overall study population (56.3 versus 58.6 years and 22.7 versus 22.7 mg/m2/week, respectively). The percentage of cycles with absent or minimal nausea was 47% overall, which was similar to that of the active (50%) and placebo (44%) cycles. However, the severity of nausea was significantly lower in the active cycles during days 2 to 4. Patients averaged less than one episode of vomiting daily in each cycle.\n The ReliefBand is an effective adjunct to standard antiemetic agents for controlling nausea induced by cisplatin-based chemotherapy in gynecologic oncology patients." ]

[ "2390654", "2728417", "7903180" ]

[ "Coma arousal procedure: a therapeutic intervention in the treatment of head injury.", "Response of head-injured patients to sensory stimulation.", "Biochemical and physiological parameters of recovery in acute severe head injury: responses to multisensory stimulation." ]

[ "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.", "nan", "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." ]

[ "11837826", "17905960", "11837827", "10622478", "11372943", "9553537", "11380135", "15805203", "9524512", "8432572", "17012426", "2071200", "21593370", "11834991", "3733830" ]

[ "The Gotfried percutaneous compression plate compared with the conventional classic hip screw for the fixation of intertrochanteric fractures of the hip.", "A prospective, randomised study comparing the percutaneous compression plate and the compression hip screw for the treatment of intertrochanteric fractures of the hip.", "The external fixator compared with the sliding hip screw for pertrochanteric fractures of the femur.", "Extramedullary fixation of 107 subtrochanteric fractures: a randomized multicenter trial of the Medoff sliding plate versus 3 other screw-plate systems.", "Extramedullary fixation of 569 unstable intertrochanteric fractures: a randomized multicenter trial of the Medoff sliding plate versus three other screw-plate systems.", "Comparison of the compression hip screw with the Medoff sliding plate for intertrochanteric fractures.", "Femoral shortening in intertrochanteric fractures. A comparison between the Medoff sliding plate and the compression hip screw.", "Dynamic hip screw compared with external fixation for treatment of osteoporotic pertrochanteric fractures. A prospective, randomized study.", "RAB-plate vs Richards CHS plate for unstable trochanteric hip fractures. A randomized study of 233 patients with 1-year follow-up.", "Functional outcome after intertrochanteric fractures of the femur: does the implant matter? A prospective study of 100 consecutive cases.", "Comparison between external fixation and sliding hip screw in the management of trochanteric fracture of the femur in Nepal.", "Intertrochanteric fractures of the femur: a randomized prospective trial comparing the Pugh nail with the dynamic hip screw.", "Gotfried percutaneous compression plating compared with sliding hip screw fixation of intertrochanteric hip fractures: a prospective randomized study.", "The Gotfried PerCutaneous Compression Plate versus the Dynamic Hip Screw in the treatment of pertrochanteric hip fractures: minimal invasive treatment reduces operative time and postoperative pain.", "Trochanteric fractures of the femur. A randomised prospective trial comparing the Jewett nail-plate with the dynamic hip screw." ]

[ "We performed a randomised, prospective trial in 111 patients with intertrochanteric fractures of the hip comparing the use of the Gotfried percutaneous compression plate (PCCP) with that of the classic hip screw (CHS). Blood loss and transfusion requirement were less in the PCCP group but the operating time was significantly longer. The complication rate after operation was similar in both groups, and at a minimum follow-up of six months there was no difference in the rates of fracture healing or implant failure. The PCCP gives results which are similar to those obtained with a conventional device. Its suggested advantages seem to be theoretical rather than practical and, being a fixed-angle implant, it is not universally applicable.", "Limited access surgery is thought to reduce post-operative morbidity and provide faster recovery of function. The percutaneous compression plate (PCCP) is a recently introduced device for the fixation of intertrochanteric fractures with minimal exposure. It has several potential mechanical advantages over the conventional compression hip screw (CHS). Our aim in this prospective, randomised, controlled study was to compare the outcome of patients operated on using these two devices. We randomised 104 patients with intertrochanteric fractures (AO/OTA 31.A1-A2) to surgical treatment with either the PCCP or CHS and followed them for one year postoperatively. The mean operating blood loss was 161.0 ml (8 to 450) in the PCCP group and 374.0 ml (11 to 980) in the CHS group (Student's t-test, p < 0.0001). The pain score and ability to bear weight were significantly better in the PCCP group at six weeks post-operatively. Analysis of the radiographs in a proportion of the patients revealed a reduced amount of medial displacement in the PCCP group (two patients, 4%) compared with the CHS group (10 patients, 18.9%); Fisher's exact test, p < 0.02. The PCCP device was associated with reduced intra-operative blood loss, less postoperative pain and a reduced incidence of collapse of the fracture.", "In a prospective, randomised study we have compared the pertrochanteric external fixator (PF) with the sliding hip screw (SHS) in 100 consecutive patients who were allocated randomly to the two methods of treatment. Details of the patients and the patterns of fracture were similar in both groups. Follow-up was for six months. Use of the PF was associated with significantly less blood loss, a shorter operating time, reduced postoperative pain, shorter hospitalisation (p < 0.001), earlier mobilisation (p < 0.001) and a reduced rate of mechanical complications (p < 0.01). Superficial infection was significantly more common with the PF (p < 0.01), but without long-term adverse consequences. There were no differences in the healing of the fracture, mortality or final functional outcome. Our results indicate that the external fixator is an effective and safe device for treating pertrochanteric fractures and should be considered as a useful alternative to conventional fixation with the sliding hip screw.", "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.", "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.", "The Medoff sliding plate was designed to achieve compression along the femoral neck and the longitudinal axis of the femoral shaft theoretically to improve the treatment of intertrochanteric hip fractures. The Medoff sliding plate was compared with a standard compression hip screw in a randomized, prospective study for the fixation of 160 stable and unstable intertrochanteric fractures with an average followup of 9.5 months (range, 6-26 months). Overall, 91 fractures were treated using the compression hip screw and 69 were treated with the Medoff sliding plate. Stable fracture patterns (46) united without complication in both treatment groups. Unstable fractures (114) had an overall failure rate of 9.6%, 14% (nine patients) with the compression hip screw and 3% (two patients) with the Medoff plate; this difference was significantly different. The time to union for the 114 unstable fractures was not significantly different between the two devices. For all patients, no differences in lengths of hospitalization, return to ambulatory status before fracture, postoperative living status, or postoperative pain was observed between the two device groups. Use of the Medoff plate for all fracture types was associated with a significantly higher amount of blood loss and operating time.", "We compared 54 patients treated by a Medoff sliding plate (MSP) with 60 stabilised by a compression hip screw (CHS) in a prospective, randomised study of the management of intertrochanteric femoral fractures. Four months after the operation femoral shortening was determined from radiographs of both femora. In unstable fractures the mean femoral shortening was 15 mm with the MSP and 11 mm with the CHS (p = 0.03). A subgroup in which shortening was classified as large, comprising one-third of the patients in each group, had a similar extent of shortening, but more medialisation of the femoral shaft occurred in the CHS (26%) than in the MSP (12%) group (p = 0.03). Five postoperative failures of fixation occurred with the CHS and none with the MSP (p = 0.03). The marginally greater femoral shortening seen with the MSP compared with the CHS appeared to be justified by the improved control of impaction of the fracture. Biaxial dynamisation in unstable intertrochanteric fractures is a safe principle of treatment, which minimises the rate of postoperative failure of fixation.", "Although the use of a sliding hip screw is considered to be the preferred treatment for pertrochanteric femoral fractures, we theorized that external fixation could produce clinical outcomes equal to, if not better than, the outcomes obtained with conventional treatment. Furthermore, because external fixation is minimally invasive, we expected a lower rate of morbidity and a reduced need for blood transfusions. Therefore, we compared the two treatments in a clinical trial of elderly patients with pertrochanteric fracture.\n Forty consecutive elderly female patients who had a pertrochanteric fracture were randomized to be treated with either fixation with a 135 degrees four-hole sliding hip screw (Group A) or an external fixation device with hydroxyapatite-coated pins (Group B). The inclusion criteria were female gender, an age of at least sixty-five years, an AO/OTA type-A1 or A2 fracture, and a bone mineral density T-score of less than -2.5. There were no differences in patient age, fracture type, bone mineral density, comorbidities, length of hospital stay, or quality of reduction between the two groups.\n The average intraoperative time (and standard deviation) was 64 +/- 6 minutes in Group A and 34 +/- 5 minutes in Group B (p < 0.005). The average number of units of blood transfused postoperatively was 2.0 +/- 0.1 in Group A and none in Group B (p < 0.0001). Group B had less pain five days postoperatively (p < 0.05). Varus collapse of the fracture at six months averaged 6 degrees +/- 8 degrees in Group A and 2 degrees 1 degrees in Group B (p < 0.002). No pin-track infections occurred in Group B. The average Harris hip score at six months was 62 +/- 19 points in Group A and 63 +/- 17 points in Group B.\n This study showed that external fixation with hydroxyapatite-coated pins is an effective treatment for this fracture in this patient population. The operative time is brief, the blood loss is minimal, the fixation is adequate, and the reduction is maintained over time.", "We prospectively randomized 233 patients with unstable trochanteric hip fractures for treatment with a 120 degrees fixed angle blade-plate having a buttress rod (group A, n 111) or a 135 degrees compression hip screw (group B, n 122). The minimum follow-up time was 1 year. The ratio of technical failure was 9% in group A and 19% in group B (p = 0.06). 79 (87%) fractures in group A and 65 (68%) fractures in group B healed without any complication (p = 0.003). Malunion occurred in 2 cases in group A and in 15 cases in group B (p = 0.002).", "In a randomized study of 100 consecutive patients with an intertrochanteric fracture of the femur fixed internally either with a sliding hip screw or with a McLaughlin nail-plate, the functional outcome of the 6 months survivors has been analysed. There was no statistically significant difference between the two treatment groups with regard to the rehabilitation progress and recovery to the prefracture walking ability, pain and gait at 6 months. Of the 6 months survivors, 55 per cent whose fractures were unstable and 76 per cent whose fractures were stable regained 90 per cent or more of their individual prefracture walking ability. The incidence of failure by 'cutting-out', the reoperation rate and the mortality at 6 months were not statistically different in the two treatment groups.", "We conducted a randomised controlled trial to compare external fixation of trochanteric fractures of the femur with the more costly option of the sliding hip screw. Patients in both groups were matched for age (mean 67 years, 50 to 100) and gender. We excluded all pathological fractures, patients presenting at more than one week, fractures with subtrochanteric extension or reverse obliquity, multiple fractures or any bone and joint disease interfering with rehabilitation. The interval between injury and operation, the duration of surgery, the amount of blood loss, the length of hospital stay and the cost of treatment were all significantly higher in the sliding hip screw group (p < 0.05). The time to union, range of movement, mean Harris hip scores and Western Ontario and McMaster University knee scores were comparable at six months. The number of patients showing shortening or malrotation was too small to show a significant difference between the groups. Pin-track infection occurred in 18 patients (60%) treated with external fixation, whereas there was a single case of wound infection (3.3%) in the sliding hip screw group.", "Over a 14-month period, 100 consecutive cases of intertrochanteric fracture were randomly allocated to be treated by either Pugh nail-plate or Dynamic Hip Screw (DHS) fixation. Although there were 11 cases of malreduction and/or suboptimal positioning of the fixation device in the femoral head, only two of these gave long-term problems. Despite the difference in configuration of the devices and a considerable disparity in price, patient satisfaction and the incidence of untoward radiological features at an average of 6 months after surgery were similar in the two groups. A trifin-ended device would thus appear to be a reliable alternative to the more commonly used hip screw systems for intertrochanteric fracture.", "The use of a Gotfried percutaneous compression plate provides a minimally invasive technique for the fixation of intertrochanteric proximal femoral fractures. The purpose of this study was to determine if the percutaneous compression plate provided advantages compared with the sliding hip screw for treatment of A1 and A2 AO/OTA intertrochanteric proximal femoral fractures.\n An institutional review board-approved, prospective, randomized, single-blinded study was conducted at a level-I trauma center between July 2004 and September 2007. All patients who met the study criteria and provided informed consent were randomized to treatment with a sliding hip screw or percutaneous compression plate. Of the sixty-six patients who consented to participate, thirty-three were randomized to be treated with a sliding hip screw and thirty-three, with a percutaneous compression plate. Data evaluated included surgical time, incision length, blood loss, need for blood transfusion, and postoperative functional status. Follow-up included clinical findings, radiographs until healing was confirmed, functional and pain assessment scores, and the Short Form-36. The median follow-up period for surviving patients was thirty-six months.\n Sixty-six patients, forty-seven women and nineteen men, with a mean age of seventy-seven years were entered into the study. The treatment groups were similar with respect to study variables (p > 0.05). Operative times (forty-eight vs. seventy-eight minutes), incision length (56 vs. 82 mm), and blood loss (41 vs. 101 mL) significantly favored the percutaneous compression plate group (p < 0.001). The groups were similar immediately postoperatively; however, by discharge, fewer patients with a percutaneous compression plate required walking aids (40% vs. 59%). This trend continued throughout the study but was not significant. Pain with activity was lower throughout the study for the percutaneous compression plate group, but the difference was significant only at the three-month interval.\n Previously published reports showing shorter operative times and less blood loss with the percutaneous compression plate were reaffirmed. Compared with the sliding hip screw, the percutaneous compression plate resulted in a larger percentage of patients who were able to walk independently, consistently lower levels of pain with activity, and improved quality of life according to multiple scales of the Short Form-36, but the differences were not significant. Significant differences favoring the percutaneous compression plate were found with regard to operating times, incision length, and blood loss.", "The PerCutaneous Compression Plate (PCCP) was developed by Gotfried (Israel, Haifa) for minimal-approach osteosynthesis of pertrochanteric fractures.\n One hundred fifteen patients, aged 60 or more, with intertrochanteric fractures (AO type 31A1 or 31A2) were selected randomly for fixation with either the PCCP (53 patients) or the Dynamic Hip Screw (62 patients). All surviving patients were scheduled for a 1-year follow-up.\n Less invasive surgical stabilization of pertrochanteric fractures with the PCCP resulted in shorter theater and surgical time and reduced postoperative pain. The PCCP treatment showed a tendency toward a lower transfusion need and a reduction of fracture impaction; however, results were not statistically significant. There was a trend toward a higher mechanical complication rate with the PCCP: anatomic closed reduction without posterior sagging of the fracture and fluoroscopic control of the placement of the first neck screw in two directions are essential to avoid technical complications.\n Minimal invasive treatment of pertrochanteric fractures with the PCCP reduces operation time and postoperative pain.", "In a randomised prospective trial 98 elderly women with trochanteric fractures of the femur were treated with either a 135 degrees Jewett nail-plate or a 135 degrees Dynamic hip screw. The results at six weeks, three months and six months were statistically analysed. There were no significant differences in the two groups with regard to pain, length of hospital stay, morbidity or mortality. Although operative difficulties and open reduction were more common with the Dynamic hip screw, at the end of six months more patients in this group were mobile and there was significant radiological evidence of better compression without loss of fixation." ]

[ "15930204", "17846935", "1912887", "16968847", "21226577", "15684116", "4537206", "4190002", "1773154", "4384577", "11159657", "10657332", "6791864", "21226576" ]

[ "Nonsevere acute otitis media: a clinical trial comparing outcomes of watchful waiting versus immediate antibiotic treatment.", "Evaluation of phenoxymethylpenicillin treatment of acute otitis media in children aged 2-16.", "Acute red ear in children: controlled trial of non-antibiotic treatment in general practice.", "Wait-and-see prescription for the treatment of acute otitis media: a randomized controlled trial.", "A placebo-controlled trial of antimicrobial treatment 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.", "Efficacy of fixed combination antibiotics versus separate components in otitis media. Effectiveness of erythromycin estrolate, triple sulfonamide, ampicillin, erythromycin estolate- triple sulfonamide, and placebo in 280 patients with acute otitis media under two and one-half years of age.", "Treatment of acute otitis media: a controlled study of 142 children.", "Co-amoxiclav in recurrent acute otitis media: placebo controlled study.", "Otitis media. Clinical observations, microbiology, and evaluation of therapy.", "Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media.", "Primary care based randomised, double blind trial of amoxicillin versus placebo for acute otitis media in children aged under 2 years.", "Penicillin in acute otitis media: a double-blind placebo-controlled trial.", "Treatment of acute otitis media in children under 2 years of age." ]

[ "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 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.", "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.", "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.", "The efficacy of antimicrobial treatment in children with acute otitis media remains controversial.\n In this randomized, double-blind trial, children 6 to 35 months of age with acute otitis media, diagnosed with the use of strict criteria, received amoxicillin-clavulanate (161 children) or placebo (158 children) for 7 days. The primary outcome was the time to treatment failure from the first dose until the end-of-treatment visit on day 8. The definition of treatment failure was based on the overall condition of the child (including adverse events) and otoscopic signs of acute otitis media.\n Treatment failure occurred in 18.6% of the children who received amoxicillin-clavulanate, as compared with 44.9% of the children who received placebo (P<0.001). The difference between the groups was already apparent at the first scheduled visit (day 3), at which time 13.7% of the children who received amoxicillin-clavulanate, as compared with 25.3% of those who received placebo, had treatment failure. Overall, amoxicillin-clavulanate reduced the progression to treatment failure by 62% (hazard ratio, 0.38; 95% confidence interval [CI], 0.25 to 0.59; P<0.001) and the need for rescue treatment by 81% (6.8% vs. 33.5%; hazard ratio, 0.19; 95% CI, 0.10 to 0.36; P<0.001). Analgesic or antipyretic agents were given to 84.2% and 85.9% of the children in the amoxicillin-clavulanate and placebo groups, respectively. Adverse events were significantly more common in the amoxicillin-clavulanate group than in the placebo group. A total of 47.8% of the children in the amoxicillin-clavulanate group had diarrhea, as compared with 26.6% in the placebo group (P<0.001); 8.7% and 3.2% of the children in the respective groups had eczema (P=0.04).\n Children with acute otitis media benefit from antimicrobial treatment as compared with placebo, although they have more side effects. Future studies should identify patients who may derive the greatest benefit, in order to minimize unnecessary antimicrobial treatment and the development of bacterial resistance. (Funded by the Foundation for Paediatric Research and others; ClinicalTrials.gov number, NCT00299455.).", "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.", "nan", "Results of the use of ampicillin, penicillin G and symptomatic therapy in the treatment of acute otitis media in 142 children were compared. Antibiotic therapy conveyed significant benefit. No major differences were observed between penicillin and ampicillin, except in the age group under 3 years where ampicillin was associated with the best results. Ampicillin appears to be the drug of choice. Its superiority over symptomatic therapy was statistically significant. Long-term sequelae were not observed in any of the three treatment groups. The relative merits of erythromycin and ampicillin require further study.", "To determine the efficacy of coamoxiclav in children aged 6 months to 12 years with recurrent acute otitis media.\n A randomised double blind placebo controlled clinical trial.\n General practice in the Netherlands.\n 121 children with recurrent acute otitis media, defined by onset of otalgia and otoscopic signs of middle ear infection within four to 52 weeks after the previous attack. Confirmation of diagnosis and randomisation was done by otolaryngologists.\n Oral co-amoxiclav or placebo in weight related doses for seven days.\n An irregular clinical course defined as the presence of otalgia or a body temperature greater than or equal to 38 degrees C, or both, after three days.\n Eleven (16%; 95% confidence interval 9% to 28%) children had an irregular course in the co-amoxiclav group and 10 (19%; 9% to 31%) in the placebo group (difference not significant). Age, dichotomised at 2 years, was the only significant prognostic factor for irregular course of the disease (odds ratio 5.9; 1.8 to 19.1). Among children aged below 2 years, 28% (4/14) in the co-amoxiclav group and 58% (7/12) in the placebo group had irregular courses. For children 2 years and older these percentages were 13% (7/52) and 7% (3/41).\n Children with recurrent acute otitis media are at greater risk of an irregular clinical course of the disease than children with a first episode of acute otitis media. Co-amoxiclav has no significant benefit over placebo in treating children over 2 years with acute otitis media.", "nan", "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.", "To determine the effect of antibiotic treatment for acute otitis media in children between 6 months and 2 years of age.\n Practice based, double blind, randomised, placebo controlled trial.\n 53 general practices in the Netherlands.\n 240 children aged 6 months to 2 years with the diagnosis of acute otitis media.\n Amoxicillin 40 mg/kg/day in three doses.\n Persistent symptoms at day four and duration of fever and pain or crying, or both. Otoscopy at days four and 11, tympanometry at six weeks, and use of analgesic.\n Persistent symptoms at day four were less common in the amoxicillin group (risk difference 13%; 95% confidence interval 1% to 25%). The median duration of fever was two days in the amoxicillin group versus three in the placebo group (P=0.004). No significant difference was observed in duration of pain or crying, but analgesic consumption was higher in the placebo group during the first 10 days (4.1 v 2.3 doses, P=0.004). In addition, no otoscopic differences were observed at days four and 11, and tympanometric findings at six weeks were similar in both groups.\n Seven to eight children aged 6 to 24 months with acute otitis media needed to be treated with antibiotics to improve symptomatic outcome at day four in one child. This modest effect does not justify prescription of antibiotics at the first visit, provided close surveillance can be guaranteed.", "The effect of peroral penicillin-V (55 mg/kg/day in 7 days) on acute otitis media was studied in 149 children between the ages of 1 and 10 years in a double-blind, placebo-controlled investigation. The parameters of the disease employed were symptom scores for earache, fever and common cold, the use of analgetics, otoscopy, as well as tympanometry. The children were followed-up for 3 months. Penicillin had no effect on fever and common cold, but earache was significantly reduced on the 2nd day of treatment. The acute course of the disease was satisfactory in 69% of the children in the placebo group and in 86% in the penicillin group. In patients with pneumococci or haemolytic streptococci in the nasopharynx, the pain disappeared after 1-2 doses of penicillin, whereas the treatment had no effect in children with Haemophilus influenzae. There was no difference between the penicillin and the placebo groups with regard to the results of otoscopy and tympanometry after 1 week, 1 month and 3 months. No serious complications were observed. It is concluded that an attitude of \"masterly inactivity\" with regard to the treatment of acute otitis media is justifiable, provided sufficient analgesic treatment is given and also that the patient can be closely followed. As there are still many unanswered questions more controlled investigations are warranted.", "Recommendations vary regarding immediate antimicrobial treatment versus watchful waiting for children younger than 2 years of age with acute otitis media.\n We randomly assigned 291 children 6 to 23 months of age, with acute otitis media diagnosed with the use of stringent criteria, to receive amoxicillin-clavulanate or placebo for 10 days. We measured symptomatic response and rates of clinical failure.\n Among the children who received amoxicillin-clavulanate, 35% had initial resolution of symptoms by day 2, 61% by day 4, and 80% by day 7; among children who received placebo, 28% had initial resolution of symptoms by day 2, 54% by day 4, and 74% by day 7 (P=0.14 for the overall comparison). For sustained resolution of symptoms, the corresponding values were 20%, 41%, and 67% with amoxicillin-clavulanate, as compared with 14%, 36%, and 53% with placebo (P=0.04 for the overall comparison). Mean symptom scores over the first 7 days were lower for the children treated with amoxicillin-clavulanate than for those who received placebo (P=0.02). The rate of clinical failure--defined as the persistence of signs of acute infection on otoscopic examination--was also lower among the children treated with amoxicillin-clavulanate than among those who received placebo: 4% versus 23% at or before the visit on day 4 or 5 (P<0.001) and 16% versus 51% at or before the visit on day 10 to 12 (P<0.001). Mastoiditis developed in one child who received placebo. Diarrhea and diaper-area dermatitis were more common among children who received amoxicillin-clavulanate. There were no significant changes in either group in the rates of nasopharyngeal colonization with nonsusceptible Streptococcus pneumoniae.\n Among children 6 to 23 months of age with acute otitis media, treatment with amoxicillin-clavulanate for 10 days tended to reduce the time to resolution of symptoms and reduced the overall symptom burden and the rate of persistent signs of acute infection on otoscopic examination. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00377260.)." ]

[ "7741782", "3781700", "14140732" ]

[ "Clinical effectiveness of a combination of bromhexine and amoxicillin in lower respiratory tract infection. A randomized controlled trial.", "Possibility of interaction among antibiotics and mucolytics in children.", "CLINICAL TRIAL OF A NEW ANTI-TUSSIVE ('DIMYRIL')." ]

[ "A multicenter double-blind randomized trial was performed in 22 teaching hospitals to compare the clinical effectiveness of the combination of amoxicillin (CAS 26787-78-0) plus bromhexine (CAS 3572-43-8) versus amoxicillin alone given 4 times a day for 5 to 7 days in the treatment of clinically diagnosed community-acquired bacterial lower respiratory tract infections. 392 adult patients diagnosed clinically to have acute bronchitis or pneumonia of bacterial etiology were recruited for the study with 192 subjects given amoxicillin (250 mg) plus bromhexine (8 mg) (Drug AB) and 200 receiving amoxicillin (250 mg) (Drug AA) alone 4 times a day for 5 to 7 days. Clinical response, improvement in symptom scores using a visual analogue scale, and bacteriologic response were monitored at Days 3, 5 and 7 of treatment. Results showed that although 180/192 (94%) given Drug AB and 185/200 (93%) given Drug AA had favorable clinical response at the end of treatment, the infection was completely resolved for 89/192 (46%) among the Drug AB group and in 67/200 (34%) of patients on Drug AA (p = 0.022). Also, patients given Drug AB had significantly greater reduction of their symptom scores at Day 3 for symptoms of cough discomfort, cough frequency, ease of expectoration and sputum volume. Among the subset of patients with pneumonia, the cure rates for Drug AB and Drug AA were 24/50 (47%) and 11/50 (22%), respectively (p = 0.008). A respiratory pathogen was cultured in only 72/392 (18%) of subjects.(ABSTRACT TRUNCATED AT 250 WORDS)", "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.", "nan" ]

[ "12679312", "12373695", "1738570", "12911461", "18349204", "11964590", "12791434", "8895233", "16586190", "11166969", "14742379", "14970960", "19479153" ]

[ "Dextromethorphan mitigates phantom pain in cancer amputees.", "Gabapentin in postamputation phantom limb pain: a randomized, double-blind, placebo-controlled, cross-over study.", "Calcitonin in phantom limb pain: a double-blind study.", "NMDA-mediated mechanisms in cortical excitability changes after limb amputation.", "Chronic phantom limb pain: the effects of calcitonin, ketamine, and their combination on pain and sensory thresholds.", "Analgesic effects of intravenous lidocaine and morphine on postamputation pain: a randomized double-blind, active placebo-controlled, crossover trial.", "Efficacy of the NMDA-receptor antagonist memantine in patients with chronic phantom limb pain--results of a randomized double-blinded, placebo-controlled trial.", "The effect of ketamine on phantom pain: a central neuropathic disorder maintained by peripheral input.", "Efficacy of gabapentin in treating chronic phantom limb and residual limb pain.", "The effect of opioids on phantom limb pain and cortical reorganization.", "A placebo-controlled randomized crossover trial of the N-methyl-D-aspartic acid receptor antagonist, memantine, in patients with chronic phantom limb pain.", "Trial of amitriptyline for relief of pain in amputees: results of a randomized controlled study.", "Phantom limb pain relief by contralateral myofascial injection with local anaesthetic in a placebo-controlled study: preliminary results." ]

[ "Hyperexcitability of N-methyl-D-aspartate (NMDA) receptors may play a role in the persistence of phantom pain. Dextromethorphan (DM) blocks NMDA receptors.\n Eight cancer and two noncancer amputees with established, disabling phantom pain received oral DM 60 or 90 mg twice daily (BID) in a three-period double-blind crossover placebo-controlled trial. This followed an open-phase trial in which either dose was given three times daily if pain relief during the double-blind phase was <50% of pretreatment intensity. Patients then underwent a 3-month phase of treatment with the best regimen and a subsequent 1-month posttreatment follow-up.\n All patients reported a >50% decrease in pain intensity, better mood, and lower sedation in each treatment phase. Four individuals reported this level of pain relief with the 60-mg and one with the 90-mg BID regimen during the double-blind phase, whereas two amputees benefited from the 60-mg and three from the 90-mg thrice-daily regimen in the open-phase trial. One reported exacerbation of pain with the 90-mg BID regimen, and three reported pain rebound at the 1-month posttreatment follow-up phase. Three patients stopped all previous analgesic use during the study.\n Persistent phantom pain probably involves NMDA receptor hyperexcitability because DM 120 to 270 mg/day mitigated the pain satisfactorily.", "Severe phantom limb pain after surgical amputation affects 50% to 67% of patients and is difficult to treat. Gabapentin is effective in several syndromes of neuropathic pain. Therefore, we evaluated its analgesic efficacy in phantom limb pain.\n Patients attending a multidisciplinary pain clinic with phantom limb pain were enrolled into this randomized, double-blind, placebo-controlled, cross-over study. Other anticonvulsant therapy was discontinued. Each treatment was 6 weeks separated by a 1-week washout period. Codeine/paracetamol was allowed as rescue analgesia. The daily dose of gabapentin was titrated in increments of 300 mg to 2400 mg or the maximum tolerated dose. Patients were assessed at weekly intervals. The primary outcome measure was visual analog scale (VAS) pain intensity difference (PID) compared with baseline at the end of each treatment. Secondary measures were indices of sleep interference, depression (Hospital Anxiety and Depression [HAD] scale), and activities of daily living (Bartel Index).\n Nineteen eligible patients (mean age, 56 years; range, 24 to 68 years; 16 men) were randomized, of whom 14 completed both arms of the study. Both placebo and gabapentin treatments resulted in reduced VAS scores compared with baseline. PID was significantly greater than placebo for gabapentin therapy at the end of the treatment (3.2 +/- 2.1 v 1.6 +/- 0.7, P =.03). There were no significant differences between placebo and gabapentin therapy in terms of the number of tablets of rescue medication required, sleep interference, HAD scale, or Bartel Index. The medication was well tolerated with few reports of adverse effects.\n After 6 weeks, gabapentin monotherapy was better than placebo in relieving postamputation phantom limb pain. There were no significant differences in mood, sleep interference, or activities of daily living, but a type II error cannot be excluded for these variables.", "Salmon calcitonin (s-CT) has been shown to be a valuable analgesic in phantom limb pain (PLP) in several case reports. To evaluate these findings a double-blind crossover comparison of s-CT treatment versus placebo was initiated. Twenty-one out of 161 patients who had undergone major amputations and developed severe PLP 0-7 days after surgery were included in the study. For each patient a matched pair of infusions was prepared containing either 200 IU of s-CT or placebo. Group I (n = 11) was first given s-CT and group II (n = 10) placebo. When PLP reached a level of more than 3 on a numeric analogue scale (NAS) the first infusion was administered. The second infusion (crossover) or more infusions were given when the pain level again exceeded more than 3 on NAS. Using s-CT infusion, PLP was eased from a median of 7 to 4 on NAS in both groups (P less than 0.001), regardless of whether s-CT or placebo was given first. Placebo, however, did not change pain scores (median 7 on NAS, P greater than 0.1). In the s-CT group, but not in the placebo group, 4 individuals remained pain free without a second infusion. Any further treatment was performed with s-CT. One week after the first PLP treatment 19 patients (90%) had pain relief of more than 50%, 16 (76%) were completely pain free, and 15 (71%) never experienced PLP again. One year later 8 out of the 13 surviving patients (62%) still had more than 75% PLP relief. After 2 years PLP exceeded 3 on NAS in 5 individuals (42%), and the remaining 12 patients presented the same PLP as after 1 year. In conclusion, s-CT is a valuable treatment for PLP in the early postoperative period.", "The aim of our study was to determine the role of N-methyl-d-aspartate (NMDA)-mediated mechanisms in cortical excitability changes after limb amputation, and their possible relationship to phantom pain.\n Sixteen upper limb amputees who were suffering from chronic phantom pain received the NMDA-antagonist memantine or placebo for 3 weeks. Intracortical inhibition (ICI) and intracortical facilitation (ICF) were determined at baseline and on day 21 using transcranial magnetic stimulation. Simultaneously, phantom pain intensity was assessed.\n Memantine reduced ICF and enhanced ICI to roughly the same extent as seen in healthy subjects in a previous study. These changes were not correlated to the reduction of phantom pain.\n We therefore conclude that NMDA-mediated mechanisms influence changes of ICI and ICF occurring after limb amputation. However, our results suggest that these cortical excitability changes and phantom pain are independent of each other.", "Calcitonin was effective in a study of acute phantom limb pain, but it was not studied in the chronic phase. The overall literature on N-methyl-D-aspartate antagonists is equivocal. We tested the hypothesis that calcitonin, ketamine, and their combination are effective in treating chronic phantom limb pain. Our secondary aim was to improve our understanding of the mechanisms of action of the investigated drugs using quantitative sensory testing.\n Twenty patients received, in a randomized, double-blind, crossover manner, 4 i.v. infusions of: 200 IE calcitonin; ketamine 0.4 mg/kg (only 10 patients); 200 IE of calcitonin combined with ketamine 0.4 mg/kg; placebo, 0.9% saline. Intensity of phantom pain (visual analog scale) was recorded before, during, at the end, and the 48 h after each infusion. Pain thresholds after electrical, thermal, and pressure stimulation were recorded before and during each infusion.\n Ketamine, but not calcitonin, reduced phantom limb pain. The combination was not superior to ketamine alone. There was no difference in basal pain thresholds between the amputated and contralateral side except for pressure pain. Pain thresholds were unaffected by calcitonin. The analgesic effect of the combination of calcitonin and ketamine was associated with a significant increase in electrical thresholds, but with no change in pressure and heat thresholds.\n Our results question the usefulness of calcitonin in chronic phantom limb pain and stress the potential interest of N-methyl-D-aspartate antagonists. Sensory assessments indicated that peripheral mechanisms are unlikely important determinants of phantom limb pain. Ketamine, but not calcitonin, affects central sensitization processes that are probably involved in the pathophysiology of phantom limb pain.", "Phantom and stump pains, common sequelae of limb amputations, are significant impediments to rehabilitation of amputees. The pathophysiology and optimal treatment of postamputation pain states are unclear. While stump pain may result from neuromas in the stump, phantom pain is thought to be related to cortical reorganization. The authors hypothesized that morphine and lidocaine may have differential effectiveness on stump and phantom pains.\n The authors conducted a randomized double-blind, active-placebo-controlled, crossover trial to compare the analgesic effects of intravenous morphine and lidocaine on postamputation stump and phantom pains. An intravenous bolus followed by an intravenous infusion of morphine (0.05 mg/kg bolus + 0.2 mg/kg infusion over 40 min), lidocaine (1 mg/kg bolus + 4 mg/kg infusion) and the active placebo, diphenhydramine (10 mg bolus + 40 mg infusion), were performed on three consecutive days. Phantom and stump pain ratings and sedation scores were recorded at 5-min intervals using a 0-100 visual analog scale. Pain measures were initiated 30 min before drug infusion and continued until 30 min after the end of infusion. Subjects' self-reported pain relief and satisfaction were assessed at the end of each infusion.\n Thirty-one of 32 subjects enrolled completed the study. Eleven subjects had both stump and phantom pains, 11 and 9 subjects had stump and phantom pain alone, respectively. Baseline pain scores were similar in the three drug groups. Compared with placebo, morphine reduced both stump and phantom pains significantly (P < 0.01). In contrast, lidocaine decreased stump (P < 0.01), but not phantom pain. The changes in sedation scores for morphine and lidocaine were not significantly different from placebo. Compared with placebo, self-reported stump pain relief was significantly greater for lidocaine (P < 0.05) and morphine (P < 0.01), while phantom pain relief was greater only for morphine (P < 0.01). Satisfaction scores were significantly higher for lidocaine (mean +/- SD: 39.3 +/- 37.8, P < 0.01) and morphine (45.9 +/- 35.5, P < 0.01) when compared with placebo (9.6 +/- 21.0).\n Stump pain was diminished both by morphine and lidocaine, while phantom pain was diminished only by morphine, suggesting that the mechanisms and pharmacological sensitivity of stump and phantom pains are different.", "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.", "Hyperactivity of N-methyl D-aspartate (NMDA) receptors may be one of the factors in the maintenance of persistent stump and phantom limb pain. Ketamine (bolus at 0.1 mg/kg/5 min followed by an infusion of 7 micrograms/kg/min) was administered intravenously to 11 patients with established stump and phantom limb pain in a double-blind saline-controlled study. All 11 patients responded with a decrease in the rating of stump and phantom limb pain assessed by visual analogue scale (VAS) and McGill Pain Questionnaire (MPQ). Ketamine increased pressure-pain thresholds significantly. Wind-up like pain (pain evoked by repeatedly tapping the dysaesthetic skin area) was reduced significantly by ketamine. In contrast, no effect was seen on pain evoked by repeated thermal stimuli. Side effects were observed in nine patients. The results support the notion that stump and phantom pain are generated by activity in afferent fibres activated by mechanical but not by thermal stimuli and that the NMDA receptor is involved in the maintenance of postamputation pain states. NMDA receptor antagonists may have a potential in the treatment of stump and phantom limb pain.", "Twenty-four adults with phantom limb pain (PLP) and/or residual limb pain (RLP) participated in a double-blind crossover trial. Participants were randomly assigned to receive gabapentin or placebo and later crossed over to the other treatment, with a 5-week washout interval in which they did not receive medication. Gabapentin was titrated from 300 mg to the maximum dose of 3,600 mg. Measures of pain intensity, pain interference, depression, life satisfaction, and functioning were collected throughout the study. Analyses revealed no significant group differences in pre- to posttreatment change scores on any of the outcome measures. More than half of the participants reported a meaningful decrease in pain during the gabapentin phase compared with about one-fifth who reported a meaningful decrease in pain during the placebo phase. In this trial, gabapentin did not substantially affect pain. More research on the efficacy of gabapentin to treat chronic PLP and RLP is needed.", "The efficacy of oral retarded morphine sulphate (MST) was tested against placebo in a double-blind crossover design in 12 patients with phantom limb pain after unilateral leg or arm amputation. Two counterbalanced treatment phases of 4 weeks each were initiated with an intravenous test infusion of MST or Placebo. The titration phase was 2 weeks. The dose of MST was titrated to at least 70 mg/day and at highest 300 mg/day. Pain intensity was assessed hourly on visual analog scales during a 4-week treatment-free phase, both treatment phases and at two follow-ups (6 and 12 months). Reorganization of somatosensory cortex, electric perception and pain thresholds as well as selective attention were measured pre- and post-treatment. A significant pain reduction was found during MST but not during placebo. A clinically relevant response to MST (pain reduction of more than 50%) was evident in 42%, a partial response (pain reduction of 25-50%) in 8% of the patients. Neuromagnetic source imaging of three patients showed initial evidence for reduced cortical reorganization under MST concurrent with the reduction in pain intensity. Perception and pain thresholds were not significantly altered whereas attention was significantly lower under MST. Thus, opioids show efficacy in the treatment of phantom limb pain and may potentially influence also cortical reorganization. These data need to be replicated in larger patient samples.", "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.", "To evaluate whether amitriptyline is more effective than placebo in improving phantom limb pain or residual limb pain.\n Randomized controlled trial of amitriptyline for 6 weeks.\n University hospital.\n Thirty-nine persons with amputation-related pain lasting more than 6 months.\n Six-week trial of amitriptyline (titrated up to 125 mg/d) or an active placebo (benztropine mesylate).\n Analyses were conducted to examine whether there was a medication group effect on the primary outcomes (average pain intensity) and secondary outcome measures (disability, satisfaction with life, handicap).\n No significant differences were found between the treatment groups in outcome variables when controlling for initial pain scores.\n Our findings do not support the use of amitriptyline in the treatment of postamputation pain.", "To ascertain the existence of contralateral painful muscle areas mirroring phantom pain and to evaluate the short-term effects of anaesthetic vs saline, injected contra notlaterally to control phantom and phantom limb pain.\n Double-blinded cross-over study.\n Inpatients; rehabilitation institute.\n Eight lower limb amputees with phantom limb pain in the past 6 months.\n Either 1 ml of 0.25% bupivacaine or 0.9% saline injected alternately in each point with a 28-gauge needle, with 72 h between injections. Main outcome measurePhantom sensation modification and the intensity of phantom limb pain (visual analogue scale) before and after injections.\n Although present, painful muscle areas in the healthy limb do not mirror the topographical distribution of phantom limb pain. Sixty minutes after the injection, a statistically significant greater relief of phantom limb pain was observed after using local anaesthetic than when using saline injection (p = 0.003). Bupivacaine consistently reduced/abolished the phantom sensation in 6 out of 8 patients. These effects on phantom sensation were not observed after saline injections.\n Contralateral injections of 1 ml 0.25% bupivacaine in myofascial hyperalgesic areas attenuated phantom limb pain and affected phantom limb sensation. The clinical importance of this treatment method requires further investigation." ]

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[ "A randomized clinical trial comparing general exercise, McKenzie treatment and a control group in patients with neck pain.", "A randomized controlled trial of exercise and manipulative therapy for cervicogenic headache.", "Changes in cervicocephalic kinesthesia after a proprioceptive rehabilitation program in patients with neck pain: a randomized controlled study.", "Effect of two contrasting types of physical exercise on chronic neck muscle pain.", "A randomized clinical trial of TENS and exercise for patients with chronic neck pain.", "Two-year follow-up of a randomized clinical trial of spinal manipulation and two types of exercise for patients with chronic neck pain.", "Qigong versus exercise versus no therapy for patients with chronic neck pain: a randomized controlled trial.", "Cervical collar or physiotherapy versus wait and see policy for recent onset cervical radiculopathy: randomised trial.", "Effectiveness of dynamic muscle training, relaxation training, or ordinary activity for chronic neck pain: randomised controlled trial.", "Effectiveness of small daily amounts of progressive resistance training for frequent neck/shoulder pain: randomised controlled trial.", "Does group gymnastics at the workplace help in neck pain? A controlled study.", "Evaluation of the effects of different forms of physiotherapy in cervical pain.", "Effect of therapeutic exercise and sleeping neck support on patients with chronic neck pain: a randomized clinical trial.", "Efficacy of a C1-C2 self-sustained natural apophyseal glide (SNAG) in the management of cervicogenic headache.", "Randomized controlled trial of exercise for chronic whiplash-associated disorders.", "Qigong and exercise therapy for elderly patients with chronic neck pain (QIBANE): a randomized controlled study.", "A randomised controlled trial of preventive spinal manipulation with and without a home exercise program for patients with chronic neck pain.", "Neck/shoulder exercise for neck pain in air force helicopter pilots: a randomized controlled trial.", "Tension neck syndrome treated by acupuncture combined with physiotherapy: a comparative clinical trial (pilot study)." ]

[ "Seventy-seven patients with neck pain in the primary health care were included in a prospective, randomized clinical trial and randomly assigned to general exercise, McKenzie treatment, or a control group. Seventy patients completed the treatment; response rate 93% at 12-month follow-up. All three groups showed significant improvement regarding the main outcomes, pain intensity and Neck Disability Index, even at 12-month follow-up, but there was no significant difference between the groups. In all, 79% reported that they were better or completely restored after treatment, although 51% reported constant/daily pain. In the McKenzie group compared with the control group, a tendency toward greater improvement was noted for pain intensity at 3 weeks and at 6-month follow-up, and for post-treatment Neck Disability Index. Significant improvement in Distress and Risk Assessment Method scores was shown in the McKenzie group only. The three groups had similar recurrence rates, although after 12 months the McKenzie group showed a tendency toward fewer visits for additional health care. The study did not provide a definite evidence of treatment efficacy in patients with neck pain, however, there was a tendency toward a better outcome with the two active alternatives compared with the control group.", "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.", "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.", "The prevalence of neck muscle pain has steadily increased and especially pain from the descending part of the trapezius muscle has been associated with monotonous work tasks such as computer work. Physical exercise is generally recommended as treatment, but it is unclear which type of training is most effective. Our objective was to determine the effectiveness of specific strength training of the painful muscle versus general fitness training without direct involvement of the painful muscle (leg bicycling) on work-related neck muscle pain.\n We conducted a randomized controlled trial and recruited subjects from 7 workplaces characterized by monotonous jobs (e.g., computer-intensive work). Forty-eight employed women with chronic neck muscle pain (defined as a clinical diagnosis of trapezius myalgia) were randomly assigned to 10 weeks of specific strength training locally for the affected muscle, general fitness training performed as leg bicycling with relaxed shoulders, or a reference intervention without physical activity. The main outcome measure was an acute and prolonged change in intensity of neck muscle pain (100-mm visual analog scale [VAS]).\n A decrease of 35 mm (approximately 79%; P<0.001) in the worst VAS pain score over a 10-week period was seen with specific strength training, whereas an acute and transient decrease in pain (5 mm; P<0.05) was found with general fitness training.\n Specific strength training had high clinical relevance and led to marked prolonged relief in neck muscle pain. General fitness training showed only a small yet statistically significant acute pain reduction.", "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.", "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.", "Randomized controlled trial.\n To evaluate whether qigong is more effective than no treatment and not inferior to exercise therapy.\n Lifetime prevalence of chronic neck pain is close to 50%. Qigong is often used by patients, although, the evidence is still unclear.\n Patients (aged 20-60 years) with chronic neck pain (visual analog scale, VAS ≥ 40 mm) were randomized to 1) qigong or 2) exercise therapy (18 sessions over 6 months) or 3) waiting list (no treatment). At baseline and after 3 and 6 months, patients completed standardized questionnaires assessing neck pain (VAS), neck pain and disability, and quality of life (Short Form SF-36 questionnaire, SF-36). The primary endpoint was average pain in the last 7 days on VAS at 6-month follow-up. Statistical analysis included generalized estimation equation models adjusted for baseline values and patient expectation.\n A total of 123 patients (aged 46 ± 11 years, 88% women) suffering from chronic neck pain for 3.2 (SD ± 1.6) years were included. After 6 months, a significant difference was seen between the qigong and waiting list control groups (VAS mean difference: -14 mm [95%CI = -23.1 to -5.4], P = 0.002). Mean improvements in the exercise group were comparable to those in the qigong group (difference between groups -0.7 mm [CI = -9.1 to 7.7]) but failed to show statistical significance (P = 0.092). Neck pain and disability, and SF-36 results also yielded superiority of qigong over no treatment and similar results in the qigong and exercise therapy groups.\n Qigong was more effective than no treatment in patients with chronic neck pain. Further studies could be designed without waiting list control and should use a larger sample to clarify the value of qigong compared to exercise therapy.", "To evaluate the effectiveness of treatment with collar or physiotherapy compared with a wait and see policy in recent onset cervical radiculopathy.\n Randomised controlled trial.\n Neurology outpatient clinics in three Dutch hospitals.\n 205 patients with symptoms and signs of cervical radiculopathy of less than one month's duration\n Treatment with a semi-hard collar and taking rest for three to six weeks; 12 twice weekly sessions of physiotherapy and home exercises for six weeks; or continuation of daily activities as much as possible without specific treatment (control group).\n Time course of changes in pain scores for arm and neck pain on a 100 mm visual analogue scale and in the neck disability index during the first six weeks.\n In the wait and see group, arm pain diminished by 3 mm/week on the visual analogue scale (beta=-3.1 mm, 95% confidence interval -4.0 to -2.2 mm) and by 19 mm in total over six weeks. Patients who were treated with cervical collar or physiotherapy achieved additional pain reduction (collar: beta=-1.9 mm, -3.3 to -0.5 mm; physiotherapy: beta=-1.9, -3.3 to -0.8), resulting in an extra pain reduction compared with the control group of 12 mm after six weeks. In the wait and see group, neck pain did not decrease significantly in the first six weeks (beta=-0.9 mm, -2.0 to 0.3). Treatment with the collar resulted in a weekly reduction on the visual analogue scale of 2.8 mm (-4.2 to -1.3), amounting to 17 mm in six weeks, whereas physiotherapy gave a weekly reduction of 2.4 mm (-3.9 to -0.8) resulting in a decrease of 14 mm after six weeks. Compared with a wait and see policy, the neck disability index showed a significant change with the use of the collar and rest (beta=-0.9 mm, -1.6 to -0.1) and a non-significant effect with physiotherapy and home exercises.\n A semi-hard cervical collar and rest for three to six weeks or physiotherapy accompanied by home exercises for six weeks reduced neck and arm pain substantially compared with a wait and see policy in the early phase of cervical radiculopathy. Trial registration Clinical trials NCT00129714.", "To determine the effectiveness of dynamic muscle training and relaxation training for chronic neck pain.\n Randomised controlled trial.\n Five occupational healthcare centres, Tampere, Finland.\n 393 female office workers (mean age 45 years) with chronic non-specific neck pain randomly assigned to 12 weeks of dynamic muscle training (n = 135) or relaxation training (n = 128), plus one week of reinforcement training six months after baseline; or ordinary activity (control group; n = 130).\n Change in intensity of neck pain at three, six, and 12 months.\n No significant difference was found in neck pain between the groups at follow up. However, the range of motion for cervical rotation and lateral flexion increased more in the training groups than in the control group.\n Dynamic muscle training and relaxation training do not lead to better improvements in neck pain compared with ordinary activity.", "Regular physical exercise is a cornerstone in rehabilitation programs, but adherence to comprehensive exercise remains low. This study determined the effectiveness of small daily amounts of progressive resistance training for relieving neck/shoulder pain in healthy adults with frequent symptoms; 174 women and 24 men working at least 30 h per week and with frequent neck/shoulder pain were randomly assigned to resistance training with elastic tubing for 2 or 12 minutes per day 5 times per week, or weekly information on general health (control group). Primary outcomes were changes in intensity of neck/shoulder pain (scale 0 to 10), examiner-verified tenderness of the neck/shoulder muscles (total tenderness score of 0 to 32), and isometric muscle strength at 10 weeks. Compared with the control group, neck/shoulder pain and tenderness, respectively, decreased 1.4 points (95% confidence interval -2.0 to -0.7, p<0.0001) and 4.2 points (95% confidence interval -5.7 to -2.7, p<0.0001) in the 2-minute group and 1.9 points (95% confidence interval -2.5 to -1.2, p<0.0001) and 4.4 points (95% confidence interval -5.9 to -2.9, p<0.0001) in the 12-minute group. Compared with the control group, muscle strength increased 2.0 Nm (95% confidence interval 0.5 to 3.5Nm, p=0.01) in the 2-minute group and 1.7Nm (95% confidence interval 0.2 to 3.3 Nm, p=0.02) in the 12-minute group. In conclusion, as little as 2 minutes of daily progressive resistance training for 10 weeks results in clinically relevant reductions of pain and tenderness in healthy adults with frequent neck/shoulder symptoms. Trial registration: www.isrctn.org/ISRCTN60264809. In generally healthy adults with frequent neck/shoulder muscle pain, as little as 2 minutes of daily progressive resistance training reduces pain and tenderness.\n Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.", "The effects of group gymnastics on neck pain were studied among 44 women in a printing company. A randomized cross-over design was used with two groups matched according to the work task, frequency of symptoms, and age. The treatment consisted of gymnastics for 45 min once a week for 10 weeks. Neck pain was rated by visual analogue scale and pressure pain sensitivity of the neck muscles was measured with an algometer. The results showed no clear effects of the group gymnastics program. An equal and significant reduction in pain ratings was seen in both groups after the first intervention in the spring. Recurrence of symptoms was seen in both groups in September, and no significant reduction in pain occurred during the second intervention in the autumn. The results suggest a seasonal variation in neck symptoms which has to be considered when planning or evaluating intervention studies.", "nan", "To investigate the effects of therapeutic exercises and sleeping neck support contoured pillows on patients with chronic neck pain.\n Using a factorial design in a prospective clinical trial, participants were equally allocated at random to 4 treatment groups in the study: (1) placebo control, of hot or cold packs and massage; (2) sleeping neck support pillow and placebo; (3) active neck exercises and placebo; and (4) combined exercise and sleeping neck support pillow and placebo. Participants were treated by physical therapists over a 6 week period and assessed by masked independent assessors at 0, 3, 6, 12, 24 weeks, and 12 months, with the 12 week assessment being the primary decision time. The primary outcome measure was the Northwick Park Neck Pain Questionnaire (NPQ).\n For the 128/151 (85%) participants tested at 12 weeks, the NPQ descriptive statistics of count, mean (standard deviation) were: Initial: 128, 31.0 (11.3) at Week 12; All: 128, 18.5 (11.6); Control: 34, 18.6 (10.0); Pillow: 32, 21.5 (13.1); Active neck exercises: 29, 20.1 (11.6); and Combined: 33, 14.1 (10.6). Factorial analysis of variance showed that the main effects of Exercise (p = 0.146) and Pillow (p = 0.443) were not statistically significant; but the interaction of Exercise plus Pillow (p = 0.029) was statistically significant and clinically meaningful.\n Treatment by physiotherapists trained to teach both exercises and the use of a neck support pillow achieved the most favorable benefit for participants with chronic neck pain; either strategy alone was not more effective than a control regimen. Time was an important cofactor.", "Randomized, double-blind, placebo controlled trial.\n To determine the effect of a C1-C2 self-sustained natural apophyseal glide (SNAG) on cervicogenic headache.\n Cervicogenic headache is a common condition causing significant disability. Recent studies have shown a high incidence of C1-C2 dysfunction, evaluated by the flexion-rotation test (FRT), in subjects with cervicogenic headache. To manage this dysfunction, Mulligan has described a C1-C2 self-SNAG, though no studies have investigated the efficacy of this intervention approach.\n A sample of 32 subjects (mean _ SD age, 36 +/- 3 years) with cervicogenic headache and FRT limitation were randomized into a C1-C2 self-SNAG or placebo group. After an initial instruction and practice visit in the clinic, interventions consisted of exercises applied independently by the subject twice daily at home on a continual basis. FRT range was measured twice, before and immediately after the instruction and practice visit. Headache symptoms were determined by a headache index over time, assessed by questionnaire preintervention, at 4 weeks postintervention, and at 12 months postintervention.\n No differences were found in baseline measures between groups. Immediately after the initial instruction and practice visit performed with the supervision of the therapist, FRT range increased by 15 degrees (SD, 9) for the C1-C2 self-SNAG group (P < .001), which was significantly more than 5 degrees (SD, 5) for the placebo intervention (P < .001). There was also a significant interaction for the variable headache index between group and time (P < .001), indicating that group difference was dependent on time. There was no difference in headache index scores at baseline between groups. Headache index scores were substantially less in the C1-C2 self-SNAG group (mean +/- SD points at 4 weeks, 31 +/- 9; mean +/- SD points at 12 months, 24 +/- 9) compared to the placebo group (mean +/- SD points at 4 weeks, 51 +/- 15; mean +/- SD points at 12 months, 44 +/- 13) at 4 weeks (P < .001) and 12 months (P < .001), with an overall (+/-SD) reduction of 54% (+/-17%) for the individuals in the C1-C2 self-SNAG group.\n These results provide evidence for the efficacy of the C1-C2 self-SNAG technique in the management of individuals with cervicogenic headache.", "Whiplash-associated disorders are common and incur considerable expense in social and economic terms. There are no known effective treatments for those people whose pain and disability persist beyond 3 months. We conducted a randomized, assessor-blinded, controlled trial at two centres in Australia. All participants received 3 advice sessions. In addition the experimental group participated in 12 exercise sessions over 6 weeks. Primary outcomes were pain intensity, pain bothersomeness and function measured at 6 weeks and 12 months. Exercise and advice was more effective than advice alone at 6 weeks for all primary outcomes but not at 12 months. The effect of exercise on the 0-10 pain intensity scale was -1.1 (95%CI -1.8 to -0.3, p=0.005) at 6 weeks and -0.2 (0.6 to -1.0, p=0.59) at 12 months; on the bothersomeness scale the effect was -1.0 (-1.9 to -0.2, p=0.003) at 6 weeks and 0.3 (-0.6 to 1.3, p=0.48) at 12 months. The effect on function was 0.9 (0.3 to 1.6, p=0.006) at 6 weeks and 0.6 (-0.1 to 1.4, p=0.10) at 12 months. High levels of baseline pain intensity were associated with greater treatment effects at 6 weeks and high levels of baseline disability were associated with greater treatment effects at 12 months. In the short-term exercise and advice is slightly more effective than advice alone for people with persisting pain and disability following whiplash. Exercise is more effective for subjects with higher baseline pain and disability.", "The aim of this study was to evaluate the effectiveness of qigong compared with exercise therapy and no treatment. Elderly patients with chronic neck pain (>6 months) were randomly assigned to qigong or exercise therapy (each 24 sessions over a period of 3 months) or to a waiting list control. Patients completed standardized questionnaires at baseline and after 3 and 6 months. The main outcome measure was average neck pain on the visual analogue scale after 3 months. Secondary outcomes were neck pain and disability (NPAD) and quality of life (SF-36). One hundred seventeen patients (age, 76 +/- 8 years, 95% women) were included in the intention-to-treat analysis. The average duration of neck pain was 19.0 +/- 14.9 years. After 3 months, no significant differences were observed between the qigong group and the waiting list control group (visual analogue scale mean difference, -11 mm [CI, -24.0; 2.1], P = .099) or between the qigong group and the exercise therapy group (-2.5 mm [ - 15.4; 10.3], P = .699). Results for the NPAD were similar (qigong vs waiting list -6.7 (-15.4; 2.1), P = .135; qigong vs exercise therapy 2.3 (-6.2; 10.8); P = .600). We found no significant effect after 3 months of qigong or exercise therapy compared with no treatment. Further studies should include outcomes more suitable to elderly patients, longer treatment, and patients with less chronic pain.\n In a randomized controlled study, we evaluated whether a treatment of 24 qigong sessions over a period of 3 months is (1) superior to no treatment and (2) superior to the same amount of exercise therapy in elderly patients (age, 76 +/- 8 years, 95% women) with long-term chronic neck pain (19.0 +/- 14.9 years). After 3 and 6 months, we found no significant differences for pain, neck pain, disability, and quality of life among the 3 groups.", "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.", "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.", "To evaluate the effect of acupuncture combined with physiotherapy in comparison with acupuncture and physiotherapy performed alone in different parameters; pain intensity, muscle tension, functional disability and muscle strength in the treatment of tension neck syndrome (TNS).\n A prospective, comparative clinical trial.\n Acupuncture and Rehabilitation Department.\n TNS can occur in computer users. Acupuncture has been one alternative treatment in physiotherapeutic rehabilitation of musculoskeletal disorders.\n Forty-six patients with TNS. Interventions: Patients were allocated into three groups: Group-1 received physiotherapy (therapeutic exercises) combined with acupuncture; Group-2, acupuncture alone, and Group-3, physiotherapy alone; over a period of 10 weeks, with one or two sessions weekly.\n All patients had completed the protocols and were assessed using a visual analogue scale for pain intensity (VASpain) and muscle tension (VASmt), the Neck Disability Index: Brazilian Portuguese version for functional disability, and the cranio-cervical Flexion Test for isometric neck muscle strength (INMS); in the periods before treatment (baseline), after 10 weeks of treatment, and after 6 months of follow-up.\n All groups showed significant improvement (p < 0.001) in these parameters after 10 weeks of treatment and after 6 months of follow-up. Group-1 was superior to Group-3 in pain and functional disability improvements (p<0.05); and Group-1 was superior to both Group-2 (p < 0.01) and Group-3 (p < 0.05) in INMS. After 6 months of follow-up, the improvements of all groups were maintained (p < 0.05).\n The data suggested that acupuncture effect may facilitate and/or enhance physiotherapy performance in musculoskeletal rehabilitation for tension neck syndrome." ]

[ "12774949", "6339686", "2360466", "2711309", "8780077" ]

[ "Prophylactic anticonvulsants in patients with brain tumour.", "Phenytoin and postoperative epilepsy. A double-blind study.", "Influence of surgery and antiepileptic drugs on seizures symptomatic of cerebral tumours.", "Prophylactic anticonvulsants for prevention of immediate and early postcraniotomy seizures.", "A randomized, blinded, placebo-controlled trial of divalproex sodium prophylaxis in adults with newly diagnosed brain tumors." ]

[ "We conducted a clinical trial to determine if prophylactic anticonvulsants in brain tumour patients (without prior seizures) reduced seizure frequency. We stopped accrual at 100 patients on the basis of the interim analysis.\n One hundred newly diagnosed brain tumour patients received anticonvulsants (AC Group) or not (No AC Group) in this prospective randomized unblinded study. Sixty patients had metastatic, and 40 had primary brain tumours. Forty-six (46%) patients were randomized to the AC Group and 54 (54%) to the No AC Group. Median follow-up was 5.44 months (range 0.13-30.1 months).\n Seizures occurred in 26 (26%) patients, eleven in the AC Group and 15 in the No AC Group. Seizure-free survivals were not different; at three months 87% of the AC Group and 90% of the No AC Group were seizure-free (log rank test, p = 0.98). Seventy patients died (unrelated to seizures) and survival rates were equivalent in both groups (median survival = 6.8 months versus 5.6 months, respectively; log rank test, p = 0.50). We then terminated accrual at 100 patients because seizure and survival rates were much lower than expected; we would need > or = 900 patients to have a suitably powered study.\n These data should be used by individuals contemplating a clinical trial to determine if prophylactic anticonvulsants are effective in subsets of brain tumour patients (e.g. only anaplastic astrocytomas). When taken together with the results of a similar randomized trial, prophylactic anticonvulsants are unlikely to be effective or useful in brain tumour patients who have not had a seizure.", "A double-blind trial of phenytoin therapy following craniotomy was performed to test the hypothesis that phenytoin is effective in reducing postoperative epilepsy. A significant reduction in the frequency of epilepsy was observed in the group receiving the active drug up to the 10th postoperative week. Half of the seizures occurred in the first 2 weeks and two-thirds within 1 month of cranial surgery. High rates of epilepsy were observed after surgery in patients with meningioma, metastasis, aneurysm, and head injury. Routine prophylaxis with phenytoin (in a dosage of 5 to 6 mg/kg/day) would seem to be indicated, particularly in high-risk patients and, where possible, this treatment should be started 1 week preoperatively. Seizure control is best when therapeutic levels of phenytoin are maintained.", "One hundred and twenty-eight adult patients presenting with and operated on for supratentorial neoplasms were studied. Sixty-five had preoperative seizures and were treated with antiepileptic drugs (AEDs). Among the 63 patients without preoperative epileptic fits, 41 were given AEDs (either phenobarbital or phenytoin) as prophylactic treatment and 22 were not treated. The preoperative epilepsy course was considered with respect to tumour site and histological type. Early and late postoperative seizure occurrence was considered in the different groups of patients. The results suggest the usefulness of a short term preventive treatment with AEDs after surgery in patients without preoperative seizures. In patients with preoperative epilepsy, AEDs should be continued after surgery. However long-term AEDs treatment should not be recommended in patients without preoperative epilepsy. In fact, no significant difference in late seizure occurrence was found between preventively treated and untreated patients.", "Phenytoin (15 mg/kg) was administered intravenously to 189 patients shortly before their intracranial, supratentorial surgery was completed. Intravenous phenytoin of 5-6 mg/kg/day in three divided doses was administered daily for the first 3 postoperative days. Therapeutic serum levels (10-20 micrograms/mL) were achieved in 113 (59.8%) patients. An equally constituted, randomized control group of 185 patients received a placebo under identical conditions. The group receiving phenytoin had only one immediate and two early postoperative seizures. The 185 controls had four immediate and nine early postoperative seizures. None of the follow-up computed tomography scans of the patients with seizures showed postoperative hematoma. One patient had a significant tension pneumocranium, a possible cause of postoperative seizures. To avoid a decrease in the serum anticonvulsant level due to intraoperative blood loss, it is suggested that for patients who need an urgent or emergent craniotomy, prophylatic anticonvulsant medication should be given at least 20 minutes before completion of wound closure.", "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." ]

[ "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." ]

[ "15551366", "16118310", "4078214", "1388576" ]

[ "Effectiveness of community health workers for promoting use of safety eyewear by Latino farm workers.", "The effectiveness of a squash eyewear promotion strategy.", "Evaluation of the NSPB elementary school teaching units on eye health and safety.", "The effects of compliance cost and specific consequence information on the use of safety equipment." ]

[ "To evaluate The Community Health Worker \"promotor de salud\" (CHW) model is evaluated as a tool for reducing eye injuries in Latino farm workers.\n In 2001, 786 workers on 34 farms were divided into three intervention blocks: (A) CHWs provided protective eyewear and training to farm workers; (B) CHWs provided eyewear but no training to farm workers; (C) eyewear was distributed to farm workers with no CHW present and no training.\n Pre- and post-intervention questionnaires demonstrated greater self-reported use of eyewear in all blocks after the intervention (P < 0.0001), with Block A showing the greatest change compared to B (P < 0.0001) and C (P = 0.03); this was supported by field observations. Block A showed the greatest improvement in knowledge on questions related to training content.\n CHWs were an effective tool to train farm workers in eye health and safety, improving the use of personal protective equipment and knowledge.", "To evaluate the protective eyewear promotion (PEP) project, which was a comprehensive educational strategy to increase the use of appropriate protective eyewear by squash players.\n An ecological study design was used. Four squash venues in one playing association were randomly chosen to receive PEP and four in another association maintained usual practice and hence formed a control group. The primary evaluation measurements were surveys of cross sectional samples of players carried out before and after the intervention. The surveys investigated players' knowledge, behaviours, and attitudes associated with the use of protective eyewear. The survey carried out after the intervention also determined players' exposure to PEP. Univariate and multivariate analyses were undertaken to describe differences at PEP venues from pre- to post-intervention and to compare these with the control venues.\n The PEP players had 2.4 times the odds (95% confidence interval, 1.3 to 4.2) of wearing appropriate eyewear compared with control group players post-intervention, relative to the groups' pre-intervention baselines. Components of PEP, such as stickers and posters and the availability and prominent positioning of the project eyewear, were found to contribute to players adopting favourable eyewear behaviours.\n Components of the PEP intervention were shown to be effective. The true success will be the sustainability and dissemination of the project, favourable eyewear behaviours, and evidence of the prevention of eye injuries long into the future.", "The purpose of this study was to assess the effectiveness of elementary school teaching units on eye health and safety developed by the National Society to Prevent Blindness. Pretest and posttest scores on a questionnaire covering the units' information were compared for experimental and matched control groups from second, third, fifth and sixth grade classrooms in three states. The experimental groups showed significant increases in mean classroom scores. However, these increases were not as large as expected and suggest a need for additional development of the teaching units. Results of a teacher survey indicated that the teaching units produced positive changes in the students' knowledge, awareness and behavior related to eye health and safety. Parents reported no noticeable change in these areas as indicated by their responses to a survey. Recommendations for teachers, parents, care-givers, eye-care practitioners and their associated organizations to improve the eye health and safety of children are given.", "The effects of compliance cost and warning content on the use of protective eyewear by racquetball players were evaluated. Four-hundred-twenty subjects were observed for use of eye protection in a field setting. Results indicate that proximal placement of eyewear and the inclusion of specific consequence warning information increased safety equipment use. Implications of this research for augmenting warning effectiveness and safety are discussed." ]

[ "322847", "3666158", "12881382", "7931476" ]

[ "Review of local soft tissue recurrence of breast cancer irradiated with and without actinomycin-D.", "A trial of human alpha interferon as an adjuvant agent in breast cancer after loco-regional recurrence.", "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.", "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." ]

[ "Between 1962 and 1973, regionally recurrent breast cancer was treated in 156 patients by irradiation alone or irradiation with concurrent actinomycin-D. Thirty-two patients were entered into a randomized trial, and 124 patients were retrospectively reviewed. Local control with irradiation alone was achieved in 48 of 80 patients (60%) and in 60 of 76 patients (79%) treated with irradiation and actinomycin-D (p less than .05). Results were remarkably similar in the randomized and retrospective series.", "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.", "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.", "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." ]

[ "12216046", "9340238", "7212184", "12964289", "2599691", "10628247", "1356466", "10734596", "17456554", "12712026" ]

[ "Tap water for irrigation of lacerations.", "[Does a shower put postoperative wound healing at risk?].", "Effect of washing closed head and neck wounds on wound healing and infection.", "Is tap water a safe alternative to normal saline for wound irrigation in the community setting?", "Comparison of isotonic saline, distilled water and boiled water in irrigation of open fractures.", "Is routine procaine spirit application necessary in the care of episiotomy wound?", "Comparison between sterile saline and tap water for the cleaning of acute traumatic soft tissue wounds.", "[Modification of postoperative wound healing by showering].", "A multicenter comparison of tap water versus sterile saline for wound irrigation.", "Wound irrigation in children: saline solution or tap water?" ]

[ "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.", "A prospective randomized study was designed to determine the effect of postoperative water contact on tissue healing. A total of 121 patients undergoing open hernia repair was divided into two groups. The first group was permitted to shower postoperatively, allowing the wound to come into direct contact with the water, the second group was instructed to keep the incision dry. Water contact, wound healing and patient satisfaction were assessed. There was no difference in wound healing between the two groups and no manifest infection.", "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.", "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.", "A prospective randomised study was carried out on 86 patients with first, second and third degree open fractures in order to compare the effect of isotonic saline, distilled water and boiled water as irrigating fluids. The standard management consisted of emergency surgical toilet, use of broad spectrum antibiotics and fracture immobilization. The results show that the outcome was not affected by the type of irrigating fluid used.", "A randomised controlled trial to investigate the usefulness of local application of procaine spirit versus cleansing with water for care of episiotomy wound after normal vaginal delivery was conducted in 100 women.\n Fifty women entered the study arm and 50 entered the control arm of the study. Women in the two arms were similar in their demographic and obstetric characteristics.\n The pain scores on a verbal analogue scale was highest (score = 2.5) on Day 1 of the delivery. This was the same in women in both arms. The number of paracetamol tablets consumed was also low and was similar in both groups of women. By the fourteenth day of delivery, all the women were pain-free and the wound had healed well. It was noted that all the women maintained a high standard of perineal hygiene with a mean of 5 washes a day.\n It is concluded that in a woman with normal vaginal delivery, local application of procaine spirit is unnecessary in the care of a routine episiotomy wound.", "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.", "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 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.", "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." ]

[ "7615189", "9097988", "24891", "10648454", "2572495", "15362028", "7835575", "15362027" ]

[ "Prophylactic mesalamine treatment decreases postoperative recurrence of Crohn's disease.", "A randomized, placebo-controlled, double-blind trial of mesalamine in the maintenance of remission of Crohn's disease. The Canadian Mesalamine for Remission of Crohn's Disease Study Group.", "The long-term prophylactic effect of salazosulphapyridine (Salazopyrin) in primarily resected patients with Crohn's disease. A controlled double-blind trial.", "Prophylaxis of postoperative relapse in Crohn's disease with mesalamine: European Cooperative Crohn's Disease Study VI.", "Postoperative recurrence of Crohn's disease in relation to radicality of operation and sulfasalazine prophylaxis: a multicenter trial.", "Azathioprine and mesalamine for prevention of relapse after conservative surgery for Crohn's disease.", "Mesalamine in the prevention of endoscopic recurrence after intestinal resection for Crohn's disease. Italian Cooperative Study Group.", "Postoperative maintenance of Crohn's disease remission with 6-mercaptopurine, mesalamine, or placebo: a 2-year trial." ]

[ "Recurrence of Crohn's disease frequently occurs after surgery. A randomized controlled trial was performed to determine if mesalamine is effective in decreasing the risk of recurrent Crohn's disease after surgical resection is performed.\n One hundred sixty-three patients who underwent a surgical resection and had no evidence of residual disease were randomized to a treatment group (1.5 g mesalamine twice a day) or a placebo control group within 8 weeks of surgery. The follow-up period was a maximum of 72 months.\n The symptomatic recurrence rate (symptoms plus endoscopic and/or radiological confirmation of disease) in the treatment group was 31% (27 of 87) compared with 41% (31 of 76) in the control group (P = 0.031). The relative risk of developing recurrent disease was 0.628 (90% confidence interval, 0.40-0.97) for those in the treatment group (P = 0.039; one-tail test) using an intention-to-treat analysis and 0.532 (90% confidence interval, 0.32-0.87) using an efficacy analysis. The endoscopic and radiological rate of recurrence was also significantly decreased with relative risks of 0.654 (90% confidence interval, 0.47-0.91) in the effectiveness analysis and 0.635 (90% confidence interval, 0.44-0.91) in the efficacy analysis. There was only one serious side effect (pancreatitis) in subjects in the treatment group.\n Mesalamine (3.0 g/day) is effective in decreasing the risk of recurrence of Crohn's disease after surgical resection is performed.", "The efficacy of mesalamine for the maintenance of remission in patients with Crohn's disease is controversial. The aim of this study was to conduct a double-blind, placebo-controlled study of mesalamine (750 mg four times a day for 48 weeks) in maintaining remission in 293 patients with Crohn's disease. Patients were stratified according to the method of induction of remission (medical or surgical).\n Patients were assessed at weeks 4, 12, 24, 36, and 48. Relapse was defined as a Crohn's Disease Activity Index of >150 (+60 points over baseline).\n Of the 293 patients, 246 (84%) returned for at least 4 weeks of follow-up and were included in the final analysis. Thirty of the 118 (25%) who received mesalamine had a relapse compared with 47 of 128 (36%) receiving placebo (P = 0.056). Among those with relapse, the time to relapse was 119 days for the mesalamine-treated patients compared with 109 days for placebo-treated patients (P = NS). However, 25% of mesalamine-treated patients had relapsed by 249 days of follow-up compared with 154 days for placebo-treated patients. Subgroup analysis showed that patients with ileocecal-colonic disease or patients who were women had fewer relapses on mesalamine therapy than placebo-treated patients (21% vs. 41%, P = 0.018; and 19% vs. 41%, P = 0.003, respectively).\n Mesalamine treatment reduced relapse compared with placebo treatment, although conventional statistical significance was not achieved.", "nan", "This study investigated if long-term treatment with high-dose mesalamine reduces the risk of clinical relapse of Crohn's disease after surgical resection.\n In a prospective, randomized, double-blind, multicenter study, 4 g of mesalamine (Pentasa; Ferring A/S, Vanlose, Denmark) daily was compared with placebo in 318 patients. Treatment was started within 10 days after resective surgery and continued for 18 months. Primary outcome parameter was clinical relapse as defined by an increase in Crohn's Disease Activity Index, reoperation, septic complication, or newly developed fistula. Risk factors for recurrence were prospectively defined to be analyzed in a stepwise proportional hazards model.\n Cumulative relapse rates (+/-SE) after 18 months were 24.5% +/- 3.6% and 31.4% +/- 3.7% in the mesalamine (n = 152) and placebo (n = 166) groups, respectively (P = 0.10, log-rank test, 1-sided). Retrospective analysis showed a significantly reduced relapse rate with mesalamine only in a subgroup of patients with isolated small bowel disease (n = 124; 21.8% +/- 5.6% vs. 39.7% +/- 6.1%; P = 0.02, log-rank test). Probability of relapse was predominantly influenced by the duration of disease (P = 0.0006) and steroid intake before surgery (additional risk, P = 0.0003).\n Eighteen months of mesalamine, 4 g daily, did not significantly affect the postoperative course of Crohn's disease. Some relapse-preventing effect was found in patients with isolated small bowel disease.", "Recurrence rate is high after operation for Crohn's disease. A multicenter trial was performed to study the effect of radical or nonradical operation and of sulfasalazine prophylaxis versus placebo on postoperative recurrence rate in 232 patients with Crohn's disease. Sixteen medical and surgical centers participated in the study, 7 operating radically and 9 nonradically. The follow-up period lasted 3 years, the allocation to drug treatment was randomized and double blind. Recurrence was significantly less frequent and occurred later in patients who were operated nonradically. Patients on sulfasalazine prophylaxis had a better prognosis than on placebo. This effect was statistically significant in the first 2 years of treatment. Both strategies were additive: nonradical operation and sulfasalazine had the best prognosis, radical operation and placebo was worst. It is concluded that postoperative recurrence is best prevented by resecting nonradically and prescribing 3 g of sulfasalazine daily at least over 2 years.", "Because the reoperation rate for Crohn's disease is high after resective surgery, use of conservative surgery has increased. Mesalamine was investigated for the prevention of postoperative relapse, with disappointing results. The role of azathioprine in the postoperative setting is unknown. We aimed to compare the efficacy and safety of azathioprine and mesalamine in the prevention of clinical and surgical relapse in patients who have undergone conservative surgery for Crohn's disease.\n In a prospective, open-label, randomized study, 142 patients received azathioprine (2 mg. kg -1. day -1 ) or mesalamine (3 g/day) for 24 months. Clinical relapse was defined as the presence of symptoms with a Crohn's Disease Activity Index score >200 and surgical relapse as the presence of symptoms refractory to medical treatment or complications requiring surgery.\n After 24 months, the risk of clinical relapse was comparable in the azathioprine and mesalamine groups, both on intention-to-treat (odds ratio [OR], 2.04; 95% confidence interval [CI], 0.89-4.67) and per-protocol analyses (OR, 1.79; 95% CI, 0.80-3.97). No difference was observed with respect to surgical relapse at 24 months between the 2 groups. In a subgroup analysis, azathioprine was more effective than mesalamine in preventing clinical relapse in patients with previous intestinal resections (OR, 4.83; 95% CI, 1.47-15.8). More patients receiving azathioprine withdrew from treatment due to adverse events than those receiving mesalamine (22% vs. 8%; P = 0.04).\n While no difference was observed in the efficacy of azathioprine and mesalamine in preventing clinical and surgical relapses after conservative surgery, azathioprine is more effective in those patients who have undergone previous intestinal resection.", "Recurrence of lesions of Crohn's disease of the ileum within 1 year after so-called curative resection was well documented by endoscopy in 73%-93% of cases. This study investigated the efficacy of mesalamine in reduction of endoscopic recurrence after surgery.\n In a double-blind, multicenter clinical trial, 87 patients were treated with 3 g/day mesalamine (Pentasa) or with placebo within 1 month after surgery. After 12 months of treatment, severity of endoscopic lesions was recorded with a five-point score; when it was not possible to reach the anastomosis by endoscopy, a barium enema was performed.\n Seventeen clinical relapses (seven in the mesalamine group) were recorded. After 12 months, the endoscopic lesions were less frequent and less severe in the mesalamine group than were those in the placebo group (chi 2, 13.5; P < 0.008). The overall rate of severe recurrence (score of 3-4 on endoscopy or radiological documentation) was 24% in the mesalamine group and 56% in the placebo group (chi 2, 8.57; P < 0.004; difference 32%; 95% confidence interval, 22-52). The odds ratio for active treatment was 4.1.\n This study shows that mesalamine is useful in decreasing the rate and severity of endoscopic recurrences after curative surgery for ileal Crohn's disease.", "No therapy has been shown to reliably prevent the evolution of postoperative recurrence of Crohn's disease. The aim of the current trial was to compare 6-mercaptopurine (6-MP) and mesalamine with placebo for the prevention of clinical, endoscopic, and radiographic recurrence of Crohn's disease after resection and ileocolic anastomosis.\n Five centers randomized 131 patients to receive 6-MP (50 mg), mesalamine (3 g), or placebo daily in a double-blind, double-dummy trial. Patients had clinical assessments at 7 weeks and then every 3 months; colonoscopy at 6, 12, and 24 months; and small bowel series at 12 and 24 months. End points were clinical, endoscopic, and radiographic recurrence rates at 24 months.\n Clinical recurrence rates (intent to treat) by life-table analysis at 24 months were 50% (95% confidence interval [CI], 34%-68%), 58% (95% CI, 41%-75%), and 77% (95% CI, 61%-91%) in patients receiving 6-MP, mesalamine, and placebo, respectively. Endoscopic recurrence rates were 43% (95% CI, 28%-63%), 63% (95% CI, 47%-79%), and 64% (95% CI, 46%-81%), and radiographic recurrence rates were 33% (95% CI, 19%-54%), 46% (95% CI, 29%-66%), and 49% (95% CI, 30%-72%), respectively. 6-MP was more effective than placebo ( P < 0.05) at preventing clinical and endoscopic recurrence over 2 years. Patient withdrawals resulted in 69% of the study population evaluable for the clinical recurrence end point.\n 6-MP, 50 mg daily, was more effective than placebo at preventing postoperative recurrence of Crohn's disease and should be considered as a maintenance therapy after ileocolic resection." ]

[ "2852903", "2992839", "3027153", "1310834", "2847578", "8387933", "7560663", "7606516", "2847600", "3036020", "8087189", "2536255", "2167369", "7930301", "18475602", "8064072", "8412049", "2996580" ]

[ "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 pretreatment with nedocromil sodium and minocromil.", "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.", "Effect of nedocromil sodium on exercise-induced bronchoconstriction in children.", "Comparison of nedocromil sodium and sodium cromoglycate administered by pressurized aerosol, with and without a spacer device in exercise-induced asthma in children.", "Cromolyn versus nedocromil: duration of action in exercise-induced asthma in children.", "Effect of nedocromil sodium on exercise-induced bronchoconstriction exacerbated by inhalation of cold air.", "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 and exercise induced asthma.", "Inhibition of exercise-induced-asthma (EIA) by nedocromil sodium and sodium cromoglycate in children.", "Nedocromil sodium in exercise-induced bronchoconstriction in children.", "Attenuation of exercise induced asthma by nedocromil sodium and sodium cromoglycate.", "Comparison of the protective effects of cromolyn sodium and nedocromil sodium in the treatment of exercise-induced asthma in children.", "The Effect of Cromolyn Sodium and Nedocromil Sodium Administered by A pressurized Aerosol with A spacer Device on Exercise-Induced Asthma in Children.", "The preventive effect of nedocromil or furosemide alone or in combination on exercise-induced asthma in children.", "Nedocromil sodium in the prevention of exercise-induced bronchospasm in athletes with asthma.", "Nedocromil, a mucosal and connective tissue mast cell stabilizer, inhibits exercise-induced asthma." ]

[ "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.", "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.", "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.", "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.", "To compare the effectiveness of nedocromil sodium (NS) and sodium cromoglycate (SCG) administered by metered dose inhaler (MDI) in preventing exercise-induced asthma (EIA), 12 asthmatic children with EIA were studied in a randomized, double-blind, cross-over, placebo-controlled study. NS and SCG were given by MDI alone, and by MDI with a 700 ml spacer device (Fisonair, Fisons, UK), in order to assess the benefit of using such a device. Following a baseline exercise challenge, the protective effect of NS, SCG or placebo was evaluated in each subject. The percentage fall in forced expiratory volume in one second, and percentage protection were measured. NS and SCG provided a significant and comparable protection from EIA, and both were better than placebo. No further improvement was observed after drug administration via the spacer. Both NS and SCG are effective in preventing EIA in children, when administered at the recommended clinical dose, and the use of a spacer for administering the drug provides no advantage if the technique of inhalation is good.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "To compare the effectiveness of cromolyn sodium (CS) (10 mg) and nedocromil sodium (NS) (4 mg) administered by a metered dose inhaler (MDI) with a spacer device in preventing exercise-induced asthma (EIA), eight asthmatic children with EIA were studied in a randomized double-blind, cross-over, placebo-controlled study, CS and NS provided significant, comparable protection from EIA and both were better than placebo. We conclude that CS and NS administered by a pressurized aerosol with a spacer device provide equal protection against EIA in children.", "Recent evidence suggests that inhaled nedocromil and furosemide are effective in preventing asthma by ultrasonically nebulized distilled water, allergen, and exercise. There are, however, no studies that compare the effects of these two drugs. The aim of this study was to investigate the effect of inhaled furosemide (30 mg), nedocromil (4 mg), the combination of these two drugs, and placebo aerosol in preventing exercise-induced asthma.\n Twenty-four children with exercise-induced asthma, aged 6 to 16 years, performed a treadmill test before and 20 minutes after a single dose of drug(s) in a double-blind trial. Lung function measurements were taken before drug administration, before the exercise test (20 minutes after drug administration), and then 2, 4, 6, 8, 10, 15, 20, and 30 minutes after the exercise test.\n Both active drugs performed significantly better than placebo. In fact, the exercise challenge resulted in a mean maximum fall in forced expiratory volume in 1 second of 28.46% +/- 13.84% after administration of placebo, but of only 15.42% +/- 8.35% after administration of nedocromil (p < 0.001) and of 11.37% +/- 9.14% after administration of furosemide (p < 0.001). When the two drugs were given together, there was a statistically significant additive effect because the mean maximum fall in forced expiratory volume in 1 second was 5.75% +/- 3.57% (nedocromil vs nedocromil + fluorsemide: p < 0.001; furosemide vs nedocromil + furosemide: p < 0.01).\n This study suggests that nedocromil and furosemide provide a comparable effect in preventing exercise-induced asthma in children. The combined administration of the two drugs significantly increases the protective effects, suggesting a potential therapeutic use.", "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.", "Nedocromil, the disodium salt of a pyranoquinoline dicarboxylic acid, has a similar profile of activity to disodium cromoglycate (DSCG) but appears to be more active in stabilizing mucosal-type mast cells. In a double-blind placebo-controlled trial nedocromil (2 mg) was given by inhalation to eight asthmatic patients prior to a treadmill exercise task. There was a significant reduction in the fall in FEV1 (P less than 0.01) and FVC (P less than 0.05) after nedocromil when compared to placebo. This study indicates that nedocromil might be an effective anti-asthma agent and in addition may help define the role of the mucosal mast cell." ]

[ "9630000", "10722180", "9270900", "11768836", "10870870", "8690831", "11291531", "7585841", "9193196", "9350955" ]

[ "A comparison of bd and tid dose regimens of quetiapine (Seroquel) in the treatment of schizophrenia.", "A multicentre, double-blind, randomized comparison of quetiapine (ICI 204,636, 'Seroquel') and haloperidol in schizophrenia.", "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.", "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.", "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.", "ICI 204,636, an atypical antipsychotic: efficacy and safety in a multicenter, placebo-controlled trial in patients with schizophrenia. U.S. SEROQUEL Study Group.", "Neuropsychological change in patients with schizophrenia after treatment with quetiapine or haloperidol.", "ICI 204,636, a novel, atypical antipsychotic: early indication of safety and efficacy in patients with chronic and subchronic schizophrenia.", "Quetiapine in patients with schizophrenia. A high- and low-dose double-blind comparison with placebo. Seroquel Study Group.", "A comparison of quetiapine and chlorpromazine in the treatment of schizophrenia." ]

[ "Quetiapine (Seroquel, ICI 204,636) is an atypical antipsychotic that is effective in the treatment of both positive and negative symptoms of schizophrenia, and has a low propensity to cause extrapyramidal symptoms. The compound has a relatively short plasma elimination half-life (approximately 7 h). However, since dopamine D2 receptor occupancies correlate poorly with plasma concentrations of antipsychotics, plasma elimination half-life may not predict either duration of clinical effect or dosing frequency. Accordingly, the efficacy and tolerability of three dosing regimens (450 mg/day given in two or three divided doses daily, and 50 mg/day given twice daily) were compared in a 6-week, double-blind, randomized, multicentre, parallel-group study. The study recruited hospitalized men and women aged 18-65 years meeting DSM-IIIR criteria for acute exacerbation of chronic or subchronic schizophrenia. Six hundred and eighteen patients were randomly assigned to treatment with quetiapine 150 mg tid (n = 209), 225 mg bd (n = 200), or a comparator dose of 25 mg bd (n = 209). At day 42, the last day of randomized treatment and the primary timepoint for efficacy, quetiapine 450 mg/day was more effective than 50 mg/day: 225 mg bd was consistently superior to 25 mg bd in all measures of efficacy (total BPRS, P = 0.006; CGI severity, CGI improvement and SANS, P < 0.03), and 150 mg tid was statistically significantly superior to 25 mg bd with respect to BPRS total score (P = 0.05). The 225 mg bd and 150 mg tid groups were not significantly different from each other with respect to any efficacy measure. Quetiapine was generally well tolerated. Extrapyramidal symptom (EPS) adverse events were generally rare, and occurred with similar frequencies in the two 450 mg/day groups. Quetiapine was not associated with sustained increases in plasma prolactin at any dose. These data support the atypical profile developed from preclinical studies and show that quetiapine is an effective, well tolerated antipsychotic that can be given twice daily.", "Quetiapine (ICI 204,636, 'Seroquel') is a new atypical antipsychotic agent with a similar binding profile to the original atypical antipsychotic, clozapine. Its clinical efficacy has already been demonstrated at multiple fixed doses (150-750 mg/day) and has been suggested to be comparable with haloperidol (12 mg/day).\n This international, 6-week, multicentre, double-blind, randomized, parallel-group trial compared quetiapine with haloperidol (455 mg and 8 mg mean total daily doses, respectively) in 448 hospitalized patients with acute exacerbation of chronic or subchronic schizophrenia (DSM-III-R), in order to establish their equivalence in terms of efficacy, and the nature of their tolerability profiles, especially in terms of extrapyramidal symptoms (EPS) and serum prolactin levels.\n Both quetiapine and haloperidol produced a clear reduction in the Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression (CGI) Severity of Illness and Global Improvement scores. At day 42, the PANSS total score was reduced by -18.7+/-1.63 in the quetiapine group, and -22.1+/-1.63 in the haloperidol group (P = 0.13, between-treatment). Quetiapine was better tolerated than haloperidol in terms of EPS as demonstrated by the significant differences in the Simpson Scale and Abnormal Involuntary Movement Scale scores (P < 0.05). Although patients in both groups had elevated serum prolactin concentrations at baseline, mean serum prolactin concentration decreased (by 16.5 microg/l) in quetiapine-treated patients, yet increased (by 5.9 microg/l) in patients treated with haloperidol.\n Quetiapine is an effective and well tolerated antipsychotic of comparable efficacy to haloperidol and lacks the latter compound's effect on prolactin and EPS.", "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.", "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.", "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.", "ICI 204,636 is a new, potentially atypical antipsychotic. In early phase II trials, the antipsychotic was well tolerated and results suggested efficacy in the treatment of the positive and negative symptoms of schizophrenia. The efficacy and safety of ICI 204,636 were evaluated on a larger scale in a 6-week, multicenter, double-blind trial. Hospitalized patients who met DSM-III-R criteria for chronic or subchronic schizophrenia with acute exacerbation, as well as other criteria, were randomized to ICI 204,636 (75 to 750 mg daily) (N = 54) or placebo (N = 55). Patients were assessed weekly by use of the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), and Clinical Global Impression Scale (CGI) for efficacy and the Simpson Scale and Abnormal Involuntary Movement Scale for extrapyramidal side effects (EPS). Significant differences (p < or = 0.05) between treatment groups, which favored ICI 204,636, were identified throughout the trial. Endpoint differences were significant (by analysis of covariance) for BPRS factor IV (activation) and SANS scores and were marginally significant for total BPRS, BPRS factor III (thought disturbance), BPRS positive-symptom cluster, and CGI Severity of Illness item scores (p = 0.07, 0.09, 0.06, and 0.09, respectively). ICI 204,636 was well tolerated, although it was associated with mild transient increases in alanine aminotransferase and a higher incidence of somnolence and anticholinergic effects compared with placebo. In the dose range studied, treatment with ICI 204,636 did not induce EPS as determined by analysis of Simpson Scale total scores and lack of treatment-emergent acute dystonic reactions. Furthermore, ICI 204,636 did not produce sustained levels of prolactin; the mean change from baseline at endpoint (-7.2 micrograms/L) was comparable (p = 0.44) to that for placebo (-8.2 micrograms/L). These findings distinguish ICI 204,636 from standard antipsychotics and confirm preclinical predictions that ICI 204,636 is an atypical antipsychotic.", "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.", "We evaluated the effects of ICI 204,636 in 12 hospitalized patients with schizophrenia in a double-blind, placebo-controlled, parallel-group, rising-dose study. Patients met the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria for chronic or subchronic schizophrenia and had a total score > or = 30 on the 18-item Brief Psychiatric Rating Scale (BPRS) and a score > or = 3 on the Clinical Global Impression (CGI) Severity of Illness item. Patients received 21 days of double-blind treatment with increasing doses of ICI 204,636 (25 to 250 mg/d) or placebo. Efficacy was assessed using the BPRS and CGI. Response to treatment was defined as a > or = 30% decrease in the BPRS total score from baseline. Extrapyramidal symptoms and abnormal involuntary movements were assessed using the Simpson Scale and Abnormal Involuntary Movement Scale. Changes from baseline in the BPRS and CGI were significantly greater at end point for patients who received ICI 204,636 versus placebo (BPRS, -20.9 vs -4.8; CGI, -2.9 vs -1.0; P < 0.05, analysis of covariance; P < or = 0.06, Wilcoxon rank sum test). All patients in the ICI 204,636 group responded to treatment (P < 0.10) versus only two patients in the placebo group. Mild somnolence occurred in 50% of ICI 204,636-treated patients. No treatment-emergent extrapyramidal symptoms or dystonic reactions were observed. ICI 204,636 showed efficacy in the positive and negative symptoms of schizophrenia and was well tolerated.", "Quetiapine fumarate (Seroquel [ICI 204,636]) is an atypical dibenzothiazepine antipsychotic with a greater affinity for 5-hydroxytryptamine2 (5-HT2) receptors than for D2 dopamine receptors; its efficacy in patients with schizophrenia was shown in early phase 2 trials (maximum dose, 750 mg/d).\n In this multicenter, double-blind, placebo-controlled trial, 286 patients hospitalized with chronic or subchronic schizophrenia (DSM-III-R) were randomized to 6 weeks of treatment with high-dose quetiapine fumarate (< or = 750 mg/d), n = 96; low-dose quetiapine fumarate (< or = 250 mg/d), n = 94; or placebo, n = 96. The Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Severity of Illness item scores were the primary efficacy variables. Secondary efficacy variables included the BPRS positive-symptom cluster score, the Modified Scale for the Assessment of Negative Symptoms summary score (United States only), and the total score from the negative scale of the Positive and Negative Syndrome Scale (Europe only). Scores were analyzed using an analysis of covariance for change from baseline at end point with last observations carried forward. The model included baseline score (covariate), center, and treatment. Extrapyramidal symptoms were assessed using the Simpson-Angus Scale and the Barnes Akathisia Scale; abnormal involuntary movements were assessed using the Abnormal Involuntary Movement Scale. Frequency distributions of grouped change-from-baseline scores were analyzed using chi 2 tests.\n Of 280 patients in whom the efficacy of quetiapine was evaluated, 159 (42% of those receiving high-dose treatment; 57%, low-dose treatment; and 59%, placebo) withdrew before trial completion, primarily because of treatment failure. Significant (P < .001, BPRS; P = .003, Clinical Global Impression Severity of Illness item; and P = .003, BPRS positive-symptom cluster) differences were identified between patients receiving high-dose quetiapine and placebo for both primary efficacy variables, with end point differences in the BPRS positive-symptom cluster score showing quetiapine's consistency in reducing positive symptoms. The reduction of negative symptoms was less consistent; high-dose quetiapine was superior on the Modified Scale for the Assessment of Negative Symptoms but not on the negative scale of the Positive and Negative Syndrome Scale. Quetiapine was well tolerated and did not induce extrapyramidal symptoms, sustained elevations of prolactin, or clinically significant changes in hematologic parameters.\n Quetiapine is an effective antipsychotic with a favorable safety profile. The optimum dose is probably greater than 250 mg/d.", "A 6-week, double-blind, randomized, multicentre, parallel-group study was conducted to compare the efficacy of quetiapine ('Seroquel') (n=101) with that of chlorpromazine (n=100) in hospitalized patients with acute exacerbation of subchronic or chronic schizophrenia, or schizophreniform disorder. The tolerabilities of the two treatments were also compared. The mean daily doses of quetiapine and chlorpromazine at the end of the study were 407 mg and 384 mg, respectively. Both treatments were effective in the treatment of positive and negative symptoms, with a trend towards superior efficacy for quetiapine. The quetiapine group had a lower incidence of adverse events than the chlorpromazine group, and a low incidence of treatment-emergent extrapyramidal symptoms. Quetiapine was not associated with a sustained increase in serum prolactin. These clinical data support the preclinical profile of quetiapine as an atypical antipsychotic agent." ]

[ "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." ]

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[ "Trends in hormone therapy use before and after publication of the Women's Health Initiative trial: 10 years of follow-up.", "Changes in pattern of use, clinical characteristics and persistence rate of hormone replacement therapy among postmenopausal women after the WHI publication.", "Synergy between publication and promotion: comparing adoption of new evidence in Canada and the United States.", "Prescriptions for estrogen replacement therapy in Ontario before and after publication of the Women's Health Initiative Study.", "Impact of a multipronged education strategy on antibiotic prescribing in Quebec, Canada.", "Impact of the pravastatin or atorvastatin evaluation and infection therapy-thrombolysis in myocardial infarction 22/Reversal of Atherosclerosis with Aggressive Lipid Lowering trials on trends in intensive versus moderate statin therapy in Ontario, Canada.", "Changes in prescribing patterns following publication of the ALLHAT trial.", "The impact of the Women's Health Initiative study on incident clonidine use in Ontario, Canada.", "Effect of distributing an evidence-based guideline for prevention of osteoporosis on health education programs in municipal health centers: a randomized controlled trial.", "National use of postmenopausal hormone therapy: annual trends and response to recent evidence.", "Impact of a drug-use review program intervention on prescribing after publication of a randomized clinical trial.", "What impact have NICE guidelines had on the trends of hip arthroplasty since their publication? The results from the Trent Regional Arthroplasty Study between 1990 and 2005.", "Chest radiography guidelines for general practitioners: a practical approach.", "Changes in the use of postmenopausal hormone therapy after the publication of clinical trial results.", "Effect of an education program on decreasing catheter-related bloodstream infections in the surgical intensive care unit.", "Modified guidelines impact on antibiotic use and costs: duration of treatment for pneumonia in a neurosurgical ICU is reduced.", "Use of the statins in patients after acute myocardial infarction: does evidence change practice?", "The effect of the ACOG guideline on vaginal births after cesarean.", "Effect of periodic letters on evidence-based drug therapy on prescribing behaviour: a randomized trial.", "Impact of a drug bulletin on the knowledge, perception of drug utility, and prescribing behavior of physicians.", "Implementing a guideline for the treatment of type 2 diabetics: results of a cluster-randomized controlled trial (C-RCT).", "Primary care guidelines on consultation practices: the effectiveness of computerized versus paper-based versions. A cluster randomized controlled trial among newly qualified primary care physicians.", "Implementation of guidelines for sequential therapy with fluoroquinolones in a Belgian hospital.", "The impact of national guidelines for the prophylaxis of venous thromboembolism on the complications of arthroplasty of the lower limb.", "A randomized trial to increase smoking intervention by physicians. Doctors Helping Smokers, Round I.", "Drug treatment of stable angina pectoris and mass dissemination of therapeutic guidelines: a randomized controlled trial.", "Improving drug-therapy decisions through educational outreach. A randomized controlled trial of academically based \"detailing\".", "Change in clinical practice after publication of guidelines on breast cancer treatment.", "Lack of effect of guideline changes on LDL cholesterol reporting and control for diabetes visits in the U.S., 1995-2004.", "The impact of evidence-based guideline dissemination for the assessment and treatment of major depression in a managed behavioral health care organization.", "Impact of clinical trial results on national trends in alpha-blocker prescribing, 1996-2002.", "Promotion and prescribing of hormone therapy after report of harm by the Women's Health Initiative.", "Effects of mailed dissemination of the Royal College of Radiologists' guidelines on general practitioner referrals for radiography: a time series analysis.", "Trends in the use of lipid-lowering medications at discharge in patients with acute myocardial infarction: 1998 to 2006.", "New use of rosiglitazone decreased following publication of a meta-analysis suggesting harm.", "Reduction in the use of surgery for glue ear: did national guidelines have an impact?", "Results of a randomized controlled trial on statin use in dialysis patients had no influence on statin prescription.", "Primary care prescribing patterns in Ireland after the publication of large hypertension trials.", "Impact of effective health care bulletin on treatment of persistent glue ear in children: time series analysis.", "Randomized controlled trial of the effect of the Royal College of Radiologists' guidelines on general practitioners' referrals for radiographic examination.", "Guidelines and educational outreach visits from community pharmacists to improve prescribing in general practice: a randomised controlled trial.", "Predictors for prophylactic antithrombotic prescribing in ischaemic heart disease and the impact of national guidelines.", "Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study.", "Cluster randomized clinical trial (ISRCTN23732000) to evaluate the effectiveness of a diagnosis recognition and treatment guide for depressive disorders in primary care." ]

[ "The aim of this study was to assess the impact of the scientific evidence reported by Women's Health Initiative (WHI) trial on hormone therapy (HT) use in a 10-year follow-up retrospective cohort of women participating in a breast cancer screening program.\n Between 1998 and 2007, a retrospective cohort of participants in a population-based breast cancer screening program in the city of Barcelona (Catalonia, Spain) was assessed. The study population consisted of 50,918 women. Trends in current HT use and the annual rate of new users were analyzed by age group.\n From 1998, successive annual increases were found in the prevalence levels of HT use in all age groups. In 2002, the prevalence peaked at 11% in 50- to 54-year-olds and at 10.1% in 55- to 59-year-olds, followed by a sudden reversal and a progressive decrease. In 2007, 5 years after the publication of the WHI trial, the HT use decreased by 89.1% in 50- to 54-year-olds, 87.5% in 55- to 59-year-olds, 84.6% in 60- to 64-year-olds, and 66.0% in 65- to 69-year-olds. The percentage of new users also fell substantially after 2002.\n HT use decreased during the 5 years after the publication of the WHI. This reduction was especially marked in the first 2 years, when the decrease in new treatments exceeded the number of continuations. In the following 3 years, the decrease was approximately equal in both groups.", "The WHI was stopped prematurely because of an increased risk of breast cancer, stroke and cardiovascular diseases (CVD) in the hormone replacement therapy (HRT) arm of the trial. Changes in the use of HRT are expected.\n To assess the impact of the Women's Health Initiative (WHI) publication on the rate of HRT prescription, and the clinical characteristics and persistence rate of new users and its determinants.\n From the RAMQ databases, the total numbers of HRT prescriptions, and of new HRT's users were calculated between 2 January 1998 and 31 May 2003. To assess the clinical characteristics of women, two retrospective cohorts of new HRT's users were constructed before (pre-WHI) and after (post-WHI) the WHI study publication. The persistence rate after 1 year of follow-up was estimated using a Kaplan-Meier analysis. Cox regression models were used to estimate the rate ratio of HRT cessation.\n The total numbers of HRT users and of new users declined respectively by 28% and 50% in post-WHI. The standard dosage of HRT was significantly less used, while the proportion of women with risk factors of CVD or at very high risk of coronary artery disease (CAD) did not change. The rate of persistence in the pre-WHI cohort was 59% compared to 45% in the post-WHI (p < 0.0001), and women with risk factors of CVD or at very high risk of CAD were less likely to cease their HRT.\n One year after publication, significant changes had already occurred in the trends of use, women's characteristics and estrogen dosage. No change in the proportion of new users with CVD risk factors or at very high risk of CAD was seen.\n Copyright (c) 2006 John Wiley & Sons, Ltd.", "Few studies have examined the effect of new evidence from clinical trials on physician practice. We took advantage of differences in promotional activity in Canada and the United States for the Heart Outcomes Prevention and Evaluation (HOPE) study and the Randomized Aldactone Evaluation Study (RALES) to determine if publication of new evidence changes practice, and the extent to which promotion influences adoption of new evidence.\n We used longitudinal dispensing data, collected from 1998 to 2001, to examine changes in prescribing patterns for ramipril and other angiotensin-converting enzyme (ACE) inhibitors before and after the HOPE study. We also obtained estimates for promotional expenditures. We stratified analyses by country, to isolate the effect of promotion, and used interrupted time series methods to adjust for pre-existing prescribing trends. Similar analyses were conducted for spironolactone use before and after RALES.\n Publication of the HOPE study results was associated with rapid increases in the use of ramipril. After adjusting for pre-existing prescribing trends, ramipril prescribing increased by 12% per month (P = 0.001) in Canada versus 5% per month (P = 0.001) in the United States after the study results were presented and published. One year later, ramipril accounted for 30% of the ACE inhibitor market in Canada versus 6% in the United States. The year before publication of these results, expenditures for detailing increased by 20% in Canada (to 18 US dollars per physician) but decreased by 7% in the United States (to 13 US dollars per physician); the year after publication, spending increased to 27 US dollars per physician in Canada versus 23 US dollars per physician in the United States. In the absence of promotional activity for RALES in either country, publication of results was associated with more modest but similar increases of 2% per month (P = 0.001) in spironolactone use in both countries.\n Publication of new evidence is associated with modest changes in practice. Promotional activity appears to increase the adoption of evidence. Rather than relying on the publication of articles and creation of guidelines, those wishing to accelerate the adoption of new evidence may need to undertake more active promotion.", "nan", "Antibiotic overuse and resistance have become a major threat in the last 2 decades. Many programs tried to optimize antibiotic consumption in the inpatient setting, but the outpatient environment that represents the bulk of antibiotic use has been challenging. Following a significant rise of Clostridium difficile infections, all the health care stakeholders in the province of Quebec, Canada initiated a global education program targeting physicians and pharmacists.\n A bundle approach was used; 11 user-friendly guidelines were produced by a group of experts and sent to all physicians and pharmacists in Quebec in January 2005. Downloadable versions of guidelines were posted on a dedicated Web site. They were promoted by professional organizations, universities, and experts during educational events, and there was strong acceptance by the pharmaceutical industry with a willingness to follow the recommendations in their marketing. The Intercontinental Medical Statistics (IMS) database was used to analyze and compare Quebec's total outpatient prescriptions per 1000 inhabitants with those in the other Canadian provinces for 2 time periods: preintervention (January 2003 to December 2004), and postintervention (February 2005 to December 2007).\n In 2004, antibiotic consumption per capita was 23.3% higher in Canada generally than in Quebec. After the guidelines dissemination, the gap between Quebec and the other Canadian provinces increased by 4.1 prescriptions/1000 inhabitants (P = .0002), and the trend persisted 36 months later. Antibiotic costs fell $134.5/1000 inhabitants in Quebec compared with the rest of Canada (P = .054).\n The implementation of guidelines significantly reduced antibiotic prescriptions in Quebec compared with the rest of the country, and there was a strong trend toward significant cost reduction.", "In March 2004, the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial demonstrated that intensive lipid-lowering therapy (atorvastatin 80 mg/d) reduced progression of coronary atherosclerosis compared with moderate lipid-lowering therapy (pravastatin 40 mg/d). The following month, the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) study demonstrated the superiority of intensive (atorvastatin 80 mg/d) versus moderate (pravastatin 40 mg/d) lipid-lowering therapy for reducing death or cardiovascular events in patients suffering from an acute coronary syndrome. We sought to determine the impact of these 2 trials on trends in intensive versus moderate statin therapy in Ontario, Canada.\n This is a retrospective time-series analysis of statin prescribing between June 1997 and September 2004 in Ontario, Canada, for all residents age 65 years and older. The publication of the PROVE IT-TIMI 22 and REVERSAL trials was associated with a sustained and statistically significant increase in the number of prescriptions dispensed for atorvastatin 80 mg (range, 272 to 635 additional prescriptions per month), whereas the number of prescriptions filled for pravastatin 40 mg did not change. Similarly, it resulted in a temporal increase in the relative market share of atorvastatin at a dose of 80 mg versus that of atorvastatin at a dose of 40 mg. However, the proportion of simvastatin prescriptions for 80 mg relative to 40 mg did not change over time, implying a drug-specific effect rather than a class effect in prescribing practice.\n The publication of the PROVE IT-TIMI 22 and REVERSAL trials resulted in a significant sustained increase in the use of intensive compared with moderate statin therapy. This shift was evident primarily in an increased use of high-dose atorvastatin and did not appear to be generalizable to other statins.", "nan", "Following publication of the Women's Health Initiative (WHI) study, many women discontinued use of estrogen replacement therapy. There is some evidence that the antihypertensive agent clonidine can reduce the frequency of hot flashes associated with menopause.\n To determine the impact of the WHI study on incident use of clonidine in elderly women in Ontario, Canada.\n Retrospective, population-based administrative database design. Data on all residents of Ontario over the age of 65 years were included. Time series methods were used to analyze change in incident clonidine use following publication of the WHI study.\n Following publication of the WHI study, incident use of clonidine increased substantially among elderly women in Ontario, Canada. Similar trends were not observed for incident use of other antihypertensive medications.\n During a period of time in which a large proportion of women discontinued estrogen replacement therapy, incident use of clonidine increased. There is some evidence that a small number of women may have sought alternative relief from menopausal symptoms using other pharmacological therapies.", "Current health education programs for osteoporosis prevention are not strictly evidence-based. We assessed whether distribution of an evidence-based guideline improved such programs at municipal health centers.\n This randomized controlled trial evaluated 100 municipal health centers throughout Japan that were randomly selected from those that planned to revise osteoporosis prevention programs. The implementation status of educational items recommended by the guideline was assessed before and after the intervention by evaluators blinded to the allocation. After the pre-intervention assessment, centers were randomly allocated in a 1:1 ratio to intervention and control groups by a minimization method defining region and city/town as stratification factors. Centers in the intervention group were given copies of the guideline; centers in the control group were instructed to use any information except the guideline. Analyses were performed on an intention-to-treat basis.\n The guideline was used by 50% of the intervention group. Before the intervention, there was no significant difference in the evidence-based status of health education between the groups. The post-intervention assessment showed that the implementation rates of health education on dietary calcium intake for postmenopausal women and exercise for elderly persons were higher in the intervention group. Specific advice on intakes of calcium and vitamin D and exercise became more evidence-based in the intervention group.\n The findings suggest that the guideline helped healthcare professionals to improve health education programs by making them more evidence-based. However, the improvements seemed to be limited to items that the professionals felt prepared to improve.", "Postmenopausal hormone therapy use increased dramatically during the past 2 decades because of a prevailing belief in its health benefits. Recent evidence from randomized trials published in July 2002 demonstrated adverse cardiovascular disease events and other risks with hormone therapy in the form of oral estrogen combined with progestin.\n To describe patterns of hormone therapy use from 1995 until July 2003, including the impact of recent evidence.\n Two databases were used to describe national trends in hormone therapy use from January 1995 to July 2003. The National Prescription Audit database provided data on the number of hormone therapy prescriptions filled by retail pharmacies and the National Disease and Therapeutic Index database provided data on patient visits to office-based physicians during which hormone therapy was prescribed.\n Annual number of hormone therapy prescriptions and characteristics of visits to physicians during which hormone therapy was prescribed.\n Annual hormone therapy prescriptions increased from 58 million in 1995 to 90 million in 1999, representing approximately 15 million women per year, then remained stable through June 2002. Adoption of new oral estrogen/progestin combinations, primarily Prempro, accounted for most of this growth. Obstetrician/gynecologists provided more than 70% of hormone therapy prescriptions, and more than one third of patients were older than 60 years. Following the publication of trial results in July 2002, hormone therapy prescriptions declined in successive months. Relative to January-June 2002, prescriptions from January-June 2003 declined by 66% for Prempro and 33% for Premarin. Small increases were observed in vaginal formulations and in new prescriptions for low-dose Premarin. If prescription rates observed through July 2003 remain stable, a decline to 57 million prescriptions for 2003, similar to the rate in 1995, is projected.\n Clinical practice responded rapidly to recent evidence of harms associated with hormone therapy. Since July 2002, many patients have discontinued hormone therapy or are tapering to lower doses.", "The effect of a drug-use review (DUR) program intervention on physician prescribing after the results of a randomized clinical trial were published was studied. A Veterans Administration (VA) cooperative study published in June 1986 showed that congestive heart failure (CHF) patients who had hydralazine and isosorbide added to their drug therapy had less mortality than patients given digoxin and diuretics with or without prazosin. Physicians with at least one CHF patient who was receiving the less effective therapy were randomly assigned to intervention and control groups. In September 1986, intervention-group physicians (n = 288) were mailed a letter and questionnaire from the DUR program coordinator, the journal article, and a drug history profile of a CHF patient who might benefit from the information. Control physicians received no mailing. The questionnaire asked whether the physicians already knew about the VA study, intended to alter their prescribing, and could identify factors that would affect their decision. Two thirds of intervention-group physicians were already aware of the VA study. One third indicated that they intended to alter drug therapy based on the study results; factors significantly associated with the intent to adopt a change were physician training and experience, comments by peers, new drug availability, and the size of the reduction in mortality. During four months after the intervention, only 5 physicians in the two groups switched their patients to both hydralazine and isosorbide (full change); 23 switched them to at least one of the drugs or discontinued prazosin (partial change). There was no significant difference in the number of full or partial changes between groups.(ABSTRACT TRUNCATED AT 250 WORDS)", "The National Institute for Clinical Excellence (NICE) published the guidelines on the selection of prostheses for primary hip replacement in 2000. They supported the use of cemented hip prostheses to the exclusion of uncemented and hybrid implants. The information from the Trent (and Wales) Regional Arthroplasty Study has been examined to identify retrospectively the types of hip prostheses used between 1990 and 2005, and to assess the impact that the guidelines have had on orthopaedic practice. The results show that the publication of the NICE guidelines has had little impact on clinical practice, with the use of uncemented prostheses increasing from 6.7% (137) in 2001 to 19.2% (632) in 2005. The use of hybrid prostheses has more than doubled from 8.8% (181) to 22% (722) of all hips implanted in the same period. The recommendations made by NICE are not being followed, which calls into question their value.", "An intensive programme of guideline development and dissemination is not always practical. We designed general practitioner guidelines for chest radiography and disseminated them to a group of 33 practices selected randomly from the practices that refer more than five patients for chest radiography annually. The subsequent 2500 requests were analysed and demographic data, the referring practice and the relevant history noted. We documented a reduction in the proportion of referrals that were contrary to the guidelines by 30.5% (from 8.2% to 5.7%, P = 0.016), a reduction in referral rate with an inadequate history by 29.7% (from 15.5% to 10.9%, P = 0.0008) and an increase in the frequency that a presumptive diagnosis was stated by 14.5% (from 42.9% to 49.1%, P = 0.0025). There was no overall reduction in referral rate in the study group and the reasons for this are discussed. We conclude that guidelines for chest radiography are effective in reducing inappropriate requests and can also improve the clinical information provided.", "The recent publication of clinical trial results has led to a dramatic shift in the evidence about postmenopausal hormone therapy.\n To examine whether the publication of clinical trial results, specifically the Heart and Estrogen/progestin Replacement Study (HERS) in 1998 and the Women's Health Initiative (WHI) in 2002, has influenced the use of hormone therapy among postmenopausal women.\n Observational cohort (1997 to 2003).\n San Francisco Mammography Registry, San Francisco, California.\n Postmenopausal women between the ages of 50 and 74 years without a personal history of breast cancer who underwent mammography (151862 mammograms).\n Self-reported current use of hormone therapy.\n Among menopausal women who had mammography, it was estimated that 41% were currently using hormone therapy in 1997. Before the publication of HERS, the use of hormone therapy was increasing at a rate of 1% (95% CI, 0% to 2%) per quarter. After the publication of HERS, use decreased by 1% (CI, -3% to 0%) per quarter. In contrast, the publication of the WHI in 2002 was associated with a more substantial decline in the use of hormone therapy of 18% (CI, -21% to -16%) per quarter. Similar associations were observed for most subgroups of women, including women older than 65 years of age; women with a previous hysterectomy; and women who described their race or ethnicity as white, African American, Latina, Chinese, or Filipina.\n The release of the HERS data was temporally associated with a modest decline in the use of hormone therapy. In contrast, the release of the principal findings from the WHI was associated with a more substantial decline in use by postmenopausal women. The reason for the differences in decline may relate to the fact that the WHI results were widely publicized or were more applicable to most postmenopausal women because the WHI study was performed in healthy women.", "The purpose of the study was to determine whether an education initiative aimed at improving central venous catheter insertion and care could decrease the rate of primary bloodstream infections.\n Pre- and postintervention observational study.\n Eighteen-bed surgical/burn/trauma intensive care unit (ICU) in an urban teaching hospital.\n A total of 4,283 patients were admitted to the ICU between January 1, 1998, and December 31, 2000.\n A program primarily directed toward registered nurses was developed by a multidisciplinary task force to highlight correct practice for central venous catheter insertion and maintenance. The program consisted of a 10-page self-study module on risk factors and practice modifications involved in catheter-related infections as well as a verbal in-service at staff meetings. Each participant was required to take a pretest before taking the study module and an identical test after its completion. Fact sheets and posters reinforcing the information in the study module were also posted throughout the ICU.\n Seventy-four primary bloodstream infections occurred in 6874 catheter days (10.8 per 1000 catheter days) in the 18 months before the intervention. After the implementation of the education module, the number of primary bloodstream infections fell to 26 in 7044 catheter days (3.7 per 1000 catheter days), a decrease of 66% (p < .0001). The estimated cost savings secondary to the decreased infection rate for the 18 months after the intervention was between $185,000 and $2.808 million.\n A focused intervention primarily directed at the ICU nursing staff can lead to a dramatic decrease in the incidence of primary bloodstream infections. Educational programs may lead to a substantial decrease in cost, morbidity, and mortality attributable to central venous catheterization.", "To evaluate the impact of an intervention to reduce the duration of antibiotic treatment for pneumonia in a neurosurgical intensive care unit (ICU). The usage of antibiotics and the resultant costs were examined using interrupted time series analysis while resistance and device-associated infection rates are also described.\n In January 2004, revised guidelines for the use of antibiotics were implemented. As a consequence of this, the duration of antibiotic therapy for nosocomial pneumonia was reduced from 14 to 7 days, while for community-acquired pneumonia the period fell from 10 to 5 days. The effect on the antibiotic use density [AD; expressed as defined daily doses (DDD) per 1000 patient days (pd)] was calculated by segmented regression analysis of interrupted time series for the 24 months prior to (2002 and 2003) and after the intervention (2004 and 2005).\n The intervention was associated with a significant decrease in total AD from 949.8 to 626.7 DDD/1000 pd after the intervention. This was mainly due to reduced consumption of second-generation cephalosporins (-100.6 DDD/1000 pd), imidazoles (- 100.3 DDD/1000 pd), carbapenems (-33.3 DDD/1000 pd), penicillins with beta-lactamase inhibitor (-33.5 DDD/1000 pd) and glycopeptides (-30.2 DDD/1000 pd). Glycopeptide reduction might be associated with a significant decrease in the proportion of methicillin-resistant Staphylococcus aureus (8.4% before and 2.9% after the intervention). Similarly, total antibiotic costs/pd (Euro) showed a significant decrease from 13.16 Euro/pd before to 7.31 euro/pd after the intervention. This is a saving of 5.85 Euro/pd. The incidence of patients dying with pneumonia did not change significantly.\n The most conservative estimate of segmented regression analysis over a 48 month period showed that halving the duration of treatment for pneumonia results in a reduction of over 30% in antibiotic consumption and costs. Because respiratory infections are most common in ICU patients, interventions targeting a reduction in the duration of treatment of pneumonia might be extremely worthwhile.", "To compare the use of lipid-lowering agents in 42 628 elderly patients (aged > or =65 years) after acute myocardial infarction, before and after the publication of the Scandinavian Simvastatin Survival Study (4S), using the Ontario Myocardial Infarction Database.\n Multivariate regression models were created to estimate changes in the rate of statin use over time in monthly cohorts of elderly patients after acute myocardial infarction in Ontario from April 1, 1992, to March 31, 1997. Changes in the rate of statin use over time were estimated using patient and prescriber characteristics.\n We found a 3.6-fold significant increase in the monthly rate of statin use after the publication of 4S compared with before the publication of 4S (P<.001); specifically, the rate of increase in simvastatin and pravastatin sodium use was higher after the publication of 4S (P<.001 for each). Before the publication of 4S, the rate of increase in statin use in younger patients (aged 65-74 years) was 2.7 times higher than in older patients (aged > or =75 years) (P =.02), while after the publication of 4S, the rate of increase in statin use was only 1.8-fold higher in the younger group (P<.001). After the publication of 4S, there was a 1.6-fold higher rate of increase in statin use in male compared with female patients (P =.006). Also after the publication of 4S, specialists (cardiologists and internists) had a 2-fold higher rate of increased use of the statins than did generalists (P<.001).\n It is possible to shift practice if the evidence of benefit is strong, the intervention is easy to implement, and the intervention is marketed aggressively.", "nan", "The effect of regular and expected printed educational materials on physician prescribing behaviour has not been studied. We sought to measure the impact of a series of evidence-based drug therapy letters mailed to physicians in British Columbia on prescribing to newly treated patients.\n A paired, cluster randomized community design was used. The study population included 499 physicians from 24 local health areas in British Columbia. Local health areas were paired by number of physicians, and 1 of each pair was randomly selected and its physicians assigned to an intervention group or a control group. The intervention was 12 issues of an evidence-based series called Therapeutics Letter. Physicians in the control group (n = 241) received the letters 3-8 months after physicians in the intervention group (n = 258). The impact on prescribing to newly treated patients (defined as patients who had not previously made a claim for any medication from the class of drugs profiled in the letter) was analyzed using the drug claims database of BC Pharmacare, a publicly funded drug benefits program that covered all seniors and people receiving social assistance.\n The probability of prescribing a drug recommended in the Therapeutics Letter rather than another drug in the same class increased by 30% in the 3 months after the mailing of the letter relative to the preceding 3 months, adjusted for any before-after changes in the control group (relative risk 1.30; 95% confidence interval 1.13-1.52). No letter achieved statistical significance on its own. However, 11 of the 12 letters produced prescribing changes in the predicted direction such that the overall result was significant when their effect was combined.\n The combined effect of an ongoing series of printed letters distributed from a credible and trusted source can have a clinically significant effect on prescribing to newly treated patients.", "The impact of a drug bulletin was tested in a randomized controlled trial that included 186 family physicians. The length of the trial was six months. It was hypothesized that printed information, such as in drug bulletins, influences physician prescribing behavior by changing their knowledge of drug efficacy and adverse effects and their perceptions of drug utility. Therefore, the impact of a drug bulletin was evaluated on these domains of influence. Interview data were used to assess changes in knowledge, perceived drug utility, and stated prescribing. Health insurance funds' records were used to collect actual prescribing data. Information in the bulletin on the treatment of renal colic changed physicians' knowledge as well as perceived utility of drugs used for renal colic (p less than 0.05). Significant changes in stated prescribing were also found. On the other hand, advice in the same bulletin on the treatment of the irritable bowel syndrome (IBS) had no impact at all. It did not even improve the knowledge of the physicians about the drugs used for IBS. Apparently, the message about the treatment of IBS failed to gain the attention of the physicians. It is suggested that some messages are sufficiently transmitted through written information, and others that are seen as less relevant or too difficult to implement need more intensive strategies.", "In Italy many diabetics still lack adequate care in general practice. We assessed the effectiveness of different strategies for the implementation of an evidence-based guideline for the management of non-complicated type 2 diabetes among General Practitioners (GPs) of Lazio region.\n Three-arm cluster-randomised controlled trial with GPs as units of randomisation (clusters). 252 GPs were randomised either to an active strategy (training module with administration of the guideline), or to a passive dissemination (administration of the guideline only), or to usual care (control). Data on prescriptions of tests and drugs were collected by existing information systems, whereas patients' data came from GPs' databases. Process outcomes were measured at the cluster level one year after the intervention. Primary outcomes concerned the measurement of glycosilated haemoglobin and the commissioning of micro- and macrovascular complications assessment tests. In order to assess the physicians' drug prescribing behaviour secondary outcomes were also calculated.\n GPs identified 6395 uncomplicated type 2 patients with a high prevalence of cardiovascular risk factors. Data on GPs baseline performance show low proportions of glycosilated haemoglobin assessments. Results of the C-RCT analysis indicate that the active implementation strategy was ineffective relating to all primary outcomes (respectively, OR 1.06 [95% IC: 0.76-1.46]; OR 1.07 [95% IC: 0.80-1.43]; OR 1.4 [95% IC:0.91-2.16]. Similarly, passive dissemination of the guideline showed no effect.\n In our region compliance of GPs with guidelines was not enhanced by a structured learning programme. Implementation through organizational measures appears to be essential to induce behavioural changes.\n ISRCTN80116232.", "To compare the effects of computerized and paper-based versions of guidelines on recently qualified physicians' consultation practices.\n Two arm cluster randomized controlled trial. Physicians were randomized to receive computerized or textbook-based versions of the same guidelines for a 4-week study period. Physicians' compliance with guideline recommendations about laboratory, radiological, physical and other examinations, procedures, nonpharmacologic and pharmacologic treatments, physiotherapy, and referrals were measured by case note review.\n There were 139 recently qualified physicians working in 96 primary healthcare centers in Finland who participated in the study. Data on 4,633 patient encounters were abstracted, of which 3,484 were suitable for further analysis. Physicians' compliance with guidelines was high (over 80% for use of laboratory, radiology, physical examinations, and referrals). There were no significant differences in physicians' consultation practices in any of the measured outcomes between the computerized and textbook group.\n Guidelines are a useful source of information for recently qualified physicians working in primary care. However, the method of presentation of the guidelines (electronic or paper) does not have an effect on guideline use or their impact on decisions. Other factors should be considered when choosing the method of presentation of guidelines, such as information-seeking time, ease of use during the consultation, ability to update, production costs, and the physician's own preferences.", "This study measured the impact of three interventions for physicians, in order to implement guidelines for sequential therapy (intravenous to oral conversion) with fluoroquinolones.\n A Belgian university hospital with 1,065 beds. Method The first intervention consisted of the hospital-wide publication of guidelines in the local drug letter towards all prescribers. The consumption of fluoroquinolones was measured by means of an interrupted time-series (ITS) analysis 21 months before (period A) and 24 months after publication (period B). The second intervention was an educational interactive session, by infectious disease specialists, to the medical staff of orthopaedics and endocrinology. The third intervention comprised a proactive conversion programme on the abdominal surgery, gastro-enterology and plastic surgery wards, where pharmacists attached a pre-printed note with a suggestion to switch to an oral treatment every time a patient met the criteria for switching. The second and third intervention took place 6 months after the first intervention. Fluoroquinolone treatments were evaluated during a 2 month period before (group 1) and after the introduction of the second (group 2) and third (group 3) intervention.\n The monthly ratio of intravenous versus total fluoroquinolone consumption (daily defined doses per 1,000 bed days) was measured to assess the impact of the first intervention. The impact of the second and third intervention was measured in relation to the number of days that intravenous therapy continued beyond the day that the patient fulfilled the criteria for sequential therapy and the antibiotic cost.\n The ITS demonstrated a reduction of 3.3% in the ratio of intravenous versus total consumption after the publication of the guidelines (P = 0.011). In group 1, patients were treated intravenously for 4.1 days longer than necessary. This parameter decreased in group 2 to 3.5 days and in group 3 to 1.0 day (P = 0.006). The mean additional cost for longer intravenous treatment decreased from 188.0 euro in group 1, to 103.0 euro in group 2 and 44.0 euro in group 3 (P = 0.037).\n This study demonstrated that active implementation of guidelines is necessary. A proactive conversion programme by a pharmacist resulted in a reduction in the duration of the intravenous treatment, and the treatment cost.", "The National Institute for Clinical Excellence (NICE) produces recommendations on appropriate treatment within the National Health Service (NHS) in England and Wales. The NICE guidelines on prophylaxis for venous thromboembolism in orthopaedic surgery recommend that all patients be offered a low molecular weight heparin (LMWH). The linked hospital episode statistics of 219 602 patients were examined to determine the rates of complications following lower limb arthroplasty for the 12-month periods prior to and following the publication of these guidelines. These were compared with data from the National Joint Registry (England and Wales) regarding the use of LMWH during the same periods. There was a significant increase in the reported use of LMWH (59.5% to 67.6%, p < 0.001) following the publication of the guidelines. However, the 90-day venous thromboembolism events actually increased slightly following total hip replacement (THR, 1.69% to 1.84%, p = 0.06) and remained unchanged following total knee replacement (TKR, 1.99% to 2.04%). Return to theatre in the first 30 days for infection did not show significant changes. There was an increase in the number of patients diagnosed with thrombocytopenia, which was significant following THR (0.11% to 0.16%, p = 0.04). The recommendations from NICE are based on predicted reductions in venous thromboembolism events, reducing morbidity, mortality and costs to the NHS. The early results in orthopaedic patients do not support these predictions, but do show an increase in complications.", "Sixty-six physicians were randomized to three groups to conduct a 1-month campaign to help their patients stop smoking. The workshop group received free patient education materials and a 6-hour training workshop. The materials group received free patient education materials, and the no-assistance group received nothing. A telephone interview was completed with 89% of the 6767 eligible adult patients seen during the month of the campaign. The brief training program and patient education materials marginally increased the smoking intervention activities of volunteer physicians in private practice. Both workshop and materials physicians asked 54% of their smoking patients to stop; no-assistance physicians asked 40%. One year later, 36% of patients who had not even been asked by their doctors if they smoked reported that they had tried to stop smoking. If the physician had asked the patient if he or she smoked, the probability of a quit attempt was 47%. Patients who had been asked if they smoked were more likely to claim to have stopped (13%) than patients who had not been asked (9%). However, the proportion of patients claiming continued abstinence (range, 12% to 14%) was not related to the group of the physician.", "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.", "Improving precision and economy in the prescribing of drugs is a goal whose importance has increased with the proliferation of new and potent agents and with growing economic pressures to contain health-care costs. We implemented an office-based physician education program to reduce the excessive use of three drug groups: cerebral and peripheral vasodilators, an oral cephalosporin, and propoxyphene. A four-state sample of 435 prescribers of these drugs was identified through Medicaid records and randomly assigned to one of three groups. Physicians who were offered personal educational visits by clinical pharmacists along with a series of mailed \"unadvertisements\" reduced their prescribing of the target drugs by 14 per cent as compared with controls (P = 0.0001). A comparable reduction in the number of dollars reimbursed for these drugs was also seen between the two groups, resulting in substantial cost savings. No such change was seen in physicians who received mailed print materials only. The effect persisted for at least nine months after the start of the intervention, and no significant increase in the use of expensive substitute drugs was found. Academically based \"detailing\" may represent a useful and cost-effective way to improve the quality of drug-therapy decisions and reduce unnecessary expenditures.", "Several studies raise questions about whether clinical practice guidelines actually guide practice. We evaluated patterns of use of breast-conserving surgery (BCS) over time to examine the effect of guideline publication.\n Retrospective analysis of time-series data on breast cancer treatment. Multiple logistic regression analysis was performed, adjusting for covariates including the patient's age, comorbidity status and admission year, to assess whether the use of BCS was higher after publication of treatment guidelines.\n Five teaching hospitals participating in the Quality Improvement/Indicator Project (QIP) in Japan.\n Female breast cancer patients who received surgical treatment at five teaching hospitals from January 1996 through December 2007 (n = 2199).\n Rates of use of BCS.\n The proportion of BCS use increased from 26.4% before guideline publication to 59.9% after guideline publication in Japan. After controlling for other characteristics, the use of BCS has increased significantly over time, especially since 2001. Women aged 70 years and older (P=0.004) and those with any comorbidity (P < 0.001) were significantly less likely to receive BCS.\n This study demonstrated that the adjusted proportion of BCS has increased dramatically since 2001, 2 years after guideline publication in Japan and this is consistent with a relationship between guideline publication and a change in this clinical practice.", "nan", "This study tests whether a managed behavioral health care organization can influence adherence to practice guidelines for the treatment of major depression in a randomized trial of guideline dissemination. Guidelines were disseminated to mental health clinicians (N = 443) under one of three conditions: (1) a general mailing of guidelines to clinicians, (2) a mailing in which guidelines were targeted to a patient starting treatment with the clinician, and (3) no mailing of guidelines. The results showed no effects of guideline dissemination as measured by self-report of patients and clinicians and through episode characteristics derived from claims data, despite sentinel effects. Results also showed high rates of clinician-reported guideline adherence that were not detected in the claims data, indicating significant undertreatment of depression. Results suggest that mental health systems must look to other dissemination strategies to improve adherence to standards of care and raise the performance of independent practicing clinicians.", "Research on factors that influence prescribing patterns and the extent of change produced by clinical trial findings is limited.\n To examine the changes in prescribing of alpha-blockers for hypertension treatment before and after the April 2000 publication of the unfavorable Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) early termination involving the study's doxazosin mesylate arm. Changes in prescribing were considered in the context of other potential concurrent influences on medication use between 1996 and 2002, including changes in alpha-blocker drug prices, generic conversion, drug promotion, and competition.\n Using 2 national pharmaceutical market research reports published by IMS HEALTH, alpha-blocker prescription orders reported in the National Prescription Audit-a random computerized sample of about 20 000 of 29 000 retail, independent, and mail order pharmacies and mass merchandise and discount houses--and office-based physician alpha-blocker prescribing patterns reported in the National Disease and Therapeutic Index--a random stratified sample of about 3500 physician offices--were tracked.\n Trends in physician-reported use of alpha-blockers and alpha-blocker prescribing and dispensing by US pharmacies.\n There were steady increases in alpha-blocker new prescriptions, dispensed prescriptions, and physician drug use from 1996 through 1999. There was a moderate reversal in these trends following ALLHAT early termination and subsequent publications in early 2000. Between 1999 and 2002, new annual alpha-blocker prescription orders declined by 26% (from 5.15 million to 3.79 million), dispensed prescriptions by 22% (from 17.2 million to 13.4 million), and physician-reported drug use by 54% (from 2.26 million to 1.03 million). Other potential influences did not appear to have contributed significantly to this decline although cessation of alpha-blocker marketing may have hastened the decline.\n Modest yet statistically significant declines in the use of doxazosin and other alpha-blockers coincided with the early termination of the ALLHAT doxazosin arm. Although physicians responded to this new evidence, strategies to augment the impact of clinical trials on clinical practice are warranted.", "Little is known about how the pharmaceutical industry responds to evidence of harm associated with its products, such as the publication in July 2002 of the Women's Health Initiative Estrogen Plus Progestin Trial (WHI E+P) report demonstrating that standard-dose Prempro produced significant harm and lacked net benefits.\n To examine pharmaceutical industry response to the WHI E+P results by analyzing promotional expenditures for hormone therapy before and after July 2002.\n Nationally representative and prospectively collected longitudinal data (January 2001 through December 2003) on prescribing and promotion of hormone therapies were obtained from IMS Health and Consumer Media Reports.\n Trends in quarterly prescriptions for hormone therapy and expenditures on 5 modes of drug promotion: samples, office-based detailing, hospital-based promotion, journal advertisements, and direct-to-consumer advertising.\n Prior to the WHI E+P report, prescribing rates and promotional spending for hormone therapy were stable. In the quarter before the WHI E+P report (April-June 2002), 22.4 million prescriptions for hormone therapy were dispensed and 71 million dollars was spent on promotion (in annual terms, 350 dollars per year per US physician). Within 9 months of the report's publication (quarter 1 of 2003), there was a 32% decrease in hormone therapy prescriptions, and a nadir had been reached for promotional spending (37% decrease compared with pre-WHI E+P levels). Spending decreased for all promotional activities and most hormone therapies. Overall, the greatest declines were for samples (36% decrease as of quarter 1 of 2003) and direct-to-consumer advertising (100% decrease). The greatest declines in promotion occurred for standard-dose Prempro (61% decrease as of quarter 1 of 2003), the agent implicated by the WHI E+P report. More recently, promotional efforts have increased, particularly for lower-dose Prempro, a resurgence associated with modestly increased prescriptions for this newer agent.\n Concordant with its widespread use, hormone therapy was among the most heavily promoted medications prior to the WHI E+P report. Following reporting of the evidence of harm from this trial, there was a substantial decline in promotional spending for hormone therapy, particularly for the agents most directly implicated in the trial. Interrelated with the impact of the trial results themselves and the ensuing media coverage, reduced promotion may have contributed to a substantial decline in hormone therapy prescriptions.", "To evaluate the effect of postal dissemination of the third edition of the Royal College of Radiologists' (RCR) guidelines on general practitioner referrals for radiography.\n An interrupted time series using monthly data for 34 months before and 14 months after dissemination of the guidelines was employed. Data were abstracted for the period April 1994 to March 1998 from the computerized administrative systems of open access radiological services provided by two teaching hospitals in one region of Scotland. The time series results are contrasted with those obtained by using a simple before and after design.\n A total of 117 747 imaging requests from general practice were received in the two departments. There were no significant effects of disseminating the guidelines on the total number of requests, or on requests for individual examinations. If a simple before and after study had been used, then we would have erroneously concluded that significant changes had occurred in referral practice for 11 of the 18 procedures concerned.\n Mailing of copies of the RCR guidelines had a small effect on general practitioners' use of X-ray investigations of uncertain clinical significance. Additional dissemination and implementation strategies appear necessary to promote the use of guidelines.\n Copyright 2002 The Royal College of Radiologists.", "Compelling evidence demonstrates that certain lipid-lowering medications improve outcomes after acute myocardial infarction (AMI), but to what extent national utilization has increased in response to trials and guidelines has not been well studied. The objective of this study is to determine trends in the use of lipid-lowering medications at discharge for AMI.\n A time trend analysis was conducted on treatment rates with lipid-lowering medications from 1998 to 2006 in 996,364 patients with AMI hospitalized in 1,669 hospitals participating in the National Registry of Myocardial Infarction (NRMI) 3, 4, and 5.\n Between 1998 and 2006, use of lipid-lowering medications at discharge increased from 29.3% to 83.8%, (relative risk [RR] 2.86, 95% CI 2.84-2.89, P < .0001). Increased use was observed in men (RR 2.71) and women (RR 3.17); age younger than 65 years (RR 2.32) and 65 years or older (RR 3.46); teaching (RR 2.47) and nonteaching hospitals (RR 2.96); and in all regions of the country. After adjusting for multiple other independent predictors, the temporal increase in use of lipid-lowering medications remained highly significant (RR 2.70, 95% CI 2.68-2.73, P < .0001). A significant upward jump in the rate of lipid-lowering medication use was observed most notably in month 72, corresponding to the publication on the PROVE-IT trial (Pravastatin or Atorvastatin Evaluation and Infection Therapy trial).\n Use of lipid-lowering medications in patients hospitalized with AMI has increased substantially in the United States in the past 8 years. The increase in the lipid-lowering medication use was possibly accelerated by certain randomized clinical trial evidence demonstrating improved outcomes in this high-risk population.", "It is uncertain whether meta-analyses lead to changes in prescribing practices. We studied trends in the prescribing of glucose-lowering therapy before and after the publication of a meta-analysis suggesting harm from rosiglitazone.\n We examined the prescription records of all residents of Ontario, Canada, aged > or = 66 years. For each week between January and December 2007, we identified new users of five categories of glucose-lowering medications: rosiglitazone, pioglitazone, metformin, glibenclamide (glyburide) and insulin. The effect of the meta-analysis was assessed using interventional autoregressive integrated moving-average models.\n Following the release of the meta-analysis, there was a sudden decline in new users of rosiglitazone (P = 0.01), mirrored by a nearly identical but transient increase in new users of pioglitazone (P < 0.001). There was also a net decline in new users of thiazolidinediones as a class (P < 0.001). The number of new users of other glucose-lowering medications did not change.\n A highly-publicized meta-analysis regarding rosiglitazone's potential harms led to an abrupt decline in new users of the drug, as well as a transient surge in new use of pioglitazone.", "It is widely accepted that the passive dissemination of national clinical guidance has little or no impact on practice.\n To assess the impact in England of an Effective Health Care bulletin on childhood surgery for glue ear issued in 1992 and to understand the reasons for any change (or lack of change) in practice that ensued.\n Time series analysis of the rate of use of surgery by children under 10 years of age from 1975 to 1997/8 in 13 English health districts.\n Following a rise in the rate of surgery in public (National Health Service) hospitals from 1975 to 1985, the rate declined by 1.6% a year from 1986 to 1992/3. Following publication of the guidelines in November 1992, the rate of decline increased to 10.1% a year. Even after allowing for a slight increase in the use of independent (private) hospitals between 1992/3 and 1997/8, the overall rate of decline was at least 7.9%. It appears that the rate of referral of cases by primary care physicians (general practitioners) halved during this period. Several contextual factors are thought to have contributed to the effect of the guidelines, including pre-existing professional concern about the value of surgery, the introduction of an internal market into the NHS, and growing apprehension among parents fuelled by scepticism in the mass media. During this unprecedented period of rapid change in usage, staff delivering the service remained unaware of the alterations in their own practice.\n Passive dissemination of national guidelines can accelerate an existing trend in clinical practice if the context is hospitable. Policy makers should identify and target such situations.", "Randomized trials provide high-quality evidence for patient care. The Der Deutsche Diabetes Dialyse Studie (4D), a randomized study which demonstrated no benefit of statins among diabetic patients receiving hemodialysis, was published in July 2005. To determine effects of this study we conducted a retrospective, population-based, time series analysis with change-point regression to see if the rate of statin prescription to dialysis patients had been modified. We linked health administrative data for all diabetic hemodialysis patients living in Ontario, Canada, with similar characteristics to the 4D patient cohort. During the nearly 11-year period prior to study publication, the rate of statin use increased almost 14-fold, from 43 to 597 per 1000 patients. For 2.5 years after study publication, rather than diminish, statin use continued to rise to an absolute rate of 676 per 1000 patients. These temporal patterns in statin use closely mimicked trends in the diabetic population not receiving dialysis. The 4D trial had no impact on statin use when we restricted the analysis to incident statin prescriptions or expanded the characteristics of the dialysis patients considered for study. Thus, we found that publication of a large, expensive, randomized controlled trial in patients receiving hemodialysis had no immediate impact on clinical practice. The use of a common cardiovascular medication in this patient population appears to be influenced by other factors.", "This study assessed prescribing patterns of antihypertensive therapies (AHT) before and after the publication of the LIFE, ALLHAT and VALUE trials between 2000 and 2005.\n The Irish HSE-PCRS prescribing database was used to identify those initiated any AHT. Any change 12 months before and after the trial publications was examined using a segmented regression analysis.\n There was little or no effect of any of the trials on new AHT prescribing, except for ALLHAT where there was an increase in new prescriptions for ACE inhibitors, and VALUE with a slight increase in prescriptions for calcium channel blockers.\n Our findings show that there was little or no effect of any of the three clinical trials studied on new AHT prescribing patterns in Irish general practice. Future studies should assess any underlying barriers to implementing new evidence into clinical practice.", "nan", "The Royal College of Radiologists' guidelines aim to encourage more appropriate use of diagnostic radiology and so reduce the use of clinically unhelpful x-ray examinations.\n The object of this study was to conduct a randomized controlled trial of the introduction of the guidelines into general practice.\n A total of 62 practices (170 general practitioners) referring patients to St George's Hospital, London for diagnostic radiology were randomly allocated into two groups. Guidelines were sent to the 30 practices in the intervention group. Radiological referral patterns were compared in both groups before and after the introduction of guidelines.\n Practices which had received guidelines requested significantly fewer examinations of the spine, and made a significantly higher proportion of requests which conformed to the guidelines compared with practices which had not received the guidelines. There were no significant differences in the proportion of forms giving physical findings or in the proportion of positive findings at radiology.\n Introduction of guidelines can influence general practitioners' radiological referrals in the short term. Wider use of guidelines might help to reduce unnecessary irradiation of patients.", "To evaluate the effectiveness of guidelines with or without one-to-one educational outreach visits by community pharmacists in improving general practice prescribing for non-steroidal anti-inflammatory drugs (NSAIDs).\n Cluster randomised trial of 20 general practices within Avon, England. Practices were randomised to three groups: control; mailed guidelines; mailed guidelines plus educational outreach visits. General practitioners (GPs) in the latter group received two one-to-one outreach visits from community pharmacists. Changes in prescribing were measured using outcomes derived from prescribing analysis and cost (PACT) data. The primary outcome measure was change in the volume of prescribing for ibuprofen, diclofenac and naproxen as a percentage of total NSAID prescribing. Six secondary outcomes included other measures of prescribing quality and volume. A cost-benefit analysis was performed.\n No significant differences were observed for the primary outcome measure: practices receiving outreach visits prescribed only 2.1% [95% confidence interval (CI): -0.8 to 5.0] more of the three recommended NSAIDs than the control practices did and 1.6% (95% CI: -1.4 to 4.7) more than practices that received guidelines only. Following adjustment for multiple comparisons, only one secondary outcome showed a statistically significant difference between the groups: the proportion of prescribing of the five most frequently used drugs was 2.2% (95% CI: 0.9 to 3.6) higher in the educational outreach group compared with the control group. A net increase in costs was shown with both interventions.\n Although good prescribing at baseline in the participating practices limited the capacity for improvement, this trial provides no evidence that guidelines with or without educational outreach visits from community pharmacists lead to substantial improvements in prescribing behaviour.", "Assessment of predictors for initiating prophylactic antithrombotic prescribing for patients newly diagnosed with ischaemic heart disease (IHD) and the impact of the introduction of national guidelines.\n A retrospective case-control study was performed using pharmacy prescription data from 120,000 Dutch patients over a 5-year period. IHD patients were identified using as a marker multiple nitrate prescriptions [anatomical-chemical-therapeutic (ATC) code CO1D] indicating chronic use. Initiation of antithrombotic therapy was likewise identified using ATC codes B01AA and B01AC (oral anticoagulants and thrombocyte aggregation inhibitors), prescribed within 6 months following the first nitrate prescription. Statistically significant (P<0.05) predictors were assessed using multivariable analysis considering patient, prescriber and medication characteristics.\n Of the 2598 patients who met specified inclusion criteria for newly diagnosed IHD, approximately 35% was not prescribed any type of antithrombotic therapy. Male patients [odds ratio (OR) 2.4, 95% confidence interval (CI) 2.0-2.9], patients with cardiovascular (other than IHD) and diabetic co-morbidity (OR 6.4, 95% CI 4.8-7.9 and OR 1.6, 95% CI 1.1-2.1, respectively) and patients using isosorbide mononitrate rather than isosorbide dinitrate as anti-ischaemic main therapy (OR 2.1, 95% CI 1.3-2.5) were most likely to be prescribed antithrombotic therapy. Furthermore, initiating antithrombotic prescribing was more likely after the introduction of national guidelines (OR 1.4, 95% CI 1.1-1.7).\n Initiating antithrombotic prescribing in newly diagnosed IHD patients can be predicted by patient gender, certain co-morbidity and main type of nitrate therapy. The introduction of national guidelines has resulted in an increase of prophylactic antithrombotic prescribing in accordance with their contents.", "The Randomized Aldactone Evaluation Study (RALES) demonstrated that spironolactone significantly improves outcomes in patients with severe heart failure. Use of angiotensin-converting-enzyme (ACE) inhibitors is also indicated in these patients. However, life-threatening hyperkalemia can occur when these drugs are used together.\n We conducted a population-based time-series analysis to examine trends in the rate of spironolactone prescriptions and the rate of hospitalization for hyperkalemia in ambulatory patients before and after the publication of RALES. We linked prescription-claims data and hospital-admission records for more than 1.3 million adults 66 years of age or older in Ontario, Canada, for the period from 1994 through 2001.\n Among patients treated with ACE inhibitors who had recently been hospitalized for heart failure, the spironolactone-prescription rate was 34 per 1000 patients in 1994, and it increased immediately after the publication of RALES, to 149 per 1000 patients by late 2001 (P<0.001). The rate of hospitalization for hyperkalemia rose from 2.4 per 1000 patients in 1994 to 11.0 per 1000 patients in 2001 (P<0.001), and the associated mortality rose from 0.3 per 1000 to 2.0 per 1000 patients (P<0.001). As compared with expected numbers of events, there were 560 (95 percent confidence interval, 285 to 754) additional hyperkalemia-related hospitalizations and 73 (95 percent confidence interval, 27 to 120) additional hospital deaths during 2001 among older patients with heart failure who were treated with ACE inhibitors in Ontario. Publication of RALES was not associated with significant decreases in the rates of readmission for heart failure or death from all causes.\n The publication of RALES was associated with abrupt increases in the rate of prescriptions for spironolactone and in hyperkalemia-associated morbidity and mortality. Closer laboratory monitoring and more judicious use of spironolactone may reduce the occurrence of this complication.\n Copyright 2004 Massachusetts Medical Society", "nan" ]

[ "1531488", "18564952", "2143092", "16461169", "8423429", "9761803", "8976475", "16341712", "12394892", "15750369", "12045509" ]

[ "Functional outcomes of low back pain: comparison of four treatment groups in a randomized controlled trial.", "A comparison between chiropractic management and pain clinic management for chronic low-back pain in a national health service outpatient clinic.", "Low back pain of mechanical origin: randomised comparison of chiropractic and hospital outpatient treatment.", "Efficacy of treating low back pain and dysfunction secondary to osteoarthritis: chiropractic care compared with moist heat alone.", "The Hmax/Mmax ratio as an outcome measure for acute low back pain.", "A comparison of physical therapy, chiropractic manipulation, and provision of an educational booklet for the treatment of patients with low back pain.", "Trunk exercise combined with spinal manipulative or NSAID therapy for chronic low back pain: a randomized, observer-blinded clinical trial.", "A randomized clinical trial and subgroup analysis to compare flexion-distraction with active exercise for chronic low back pain.", "A randomized trial of medical care with and without physical therapy and chiropractic care with and without physical modalities for patients with low back pain: 6-month follow-up outcomes from the UCLA low back pain study.", "A randomized trial investigating a chiropractic manual placebo: a novel design using standardized forces in the delivery of active and control treatments.", "Effectiveness of four conservative treatments for subacute low back pain: a randomized clinical trial." ]

[ "The revised Oswestry Low Back Pain Questionnaire (ROLBPQ) and Roland-Morris Activity Scale (RMAS) were compared in a randomized controlled trial of chiropractic manipulation, stroking massage, corset and transcutaneous muscular stimulation (TMS). This trial employed specific inclusion and exclusion criteria, including nonspecific low back pain for a duration of 3 wk to 6 months and ages between 18 and 55. We had the opportunity to ask 85 patients to answer the questionnaires. Sixty-three patients, who completed the initial and final evaluations, were used for data analysis. Both ROLBPQ and RMAS showed good internal consistency with alpha coefficients ranging from .77 to .93. Both instruments showed a significant difference between the chiropractic manipulation and massage groups (p less than .05). RMAS was able to further show significant differences between the chiropractic manipulation and TMS groups, and between the corset and massage groups, but the ROLBPQ failed to do so. RMAS also showed that chiropractic manipulation had a better but nonsignificant result than corset, possibly due to insufficient sample size and/or duration of treatment. We conclude that both instruments are reliable for measuring low back pain disability, and chiropractic manipulation has a superior short-term benefit when compared to stroking massage and TMS in subacute low back pain patients. In addition, it appears that RMAS is preferable in a clinical trial situation for subacute low back pain because it is more sensitive than ROLBPQ to detect changes.", "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.", "To compare chiropractic and hospital outpatient treatment for managing low back pain of mechanical origin.\n Randomised controlled trial. Allocation to chiropractic or hospital management by minimisation to establish groups for analysis of results according to initial referral clinic, length of current episode, history, and severity of back pain. Patients were followed up for up two years.\n Chiropractic and hospital outpatient clinics in 11 centres.\n 741 Patients aged 18-65 who had no contraindications to manipulation and who had not been treated within the past month.\n Treatment at the discretion of the chiropractors, who used chiropractic manipulation in most patients, or of the hospital staff, who most commonly used Maitland mobilisation or manipulation, or both.\n Changes in the score on the Oswestry pain disability questionnaire and in the results of tests of straight leg raising and lumbar flexion.\n Chiropractic treatment was more effective than hospital outpatient management, mainly for patients with chronic or severe back pain. A benefit of about 7% points on the Oswestry scale was seen at two years. The benefit of chiropractic treatment became more evident throughout the follow up period. Secondary outcome measures also showed that chiropractic was more beneficial.\n For patients with low back pain in whom manipulation is not contraindicated chiropractic almost certainly confers worthwhile, long term benefit in comparison with hospital outpatient management. The benefit is seen mainly in those with chronic or severe pain. Introducing chiropractic into NHS practice should be considered.", "To evaluate the efficacy of chiropractic spinal manipulation, manual flexion/distraction, and hot pack application for the treatment of low back pain from osteoarthritis (OA) compared with moist heat alone.\n Two hundred fifty-two patients with low back pain secondary to OA were randomly assigned to either the treatment group (moist hot pack plus chiropractic care) or the moist heat group subjects, which attended 20 treatment sessions over several weeks. At sessions 1, 5, 10, 15, and 20, they rated pain using a visual analog pain scale, activities of daily living using the Oswestry Low Back Pain Questionnaire, and a range of motion (ROM) using the J-Tech Dual Digital Inclinometer (JTECH Medical Model no. AA036).\n Session I ratings indicated that the two groups were equivalent on all pain and flexion scores. The treatment group reported greater and more rapid pain reduction and greater and more rapid ROM improvement than the moist heat group. The treatment group also had greater improvements than the moist heat group in daily living activities in 4 of the 9 areas measured.\n Chiropractic care combined with heat is more effective than heat alone for treating OA-based lower back pain. Pain reduction occurs more rapidly and to a greater degree, and ROM increases more rapidly and to a greater degree.", "To evaluate the use of the Hmax/Mmax (H/M) ratio as an outcome measure for acute low back pain and to determine the change of this ratio in acute low back pain patients treated with spinal manipulation.\n Randomized clinical trial.\n Chiropractic college teaching clinic.\n Thirty-six patients with acute low back pain (pain of less than 2 wk duration) were referred by clinicians of the teaching clinic. Eligibility criteria for inclusion into the study consisted of the following: a score of eight or more on the Oswestry questionnaire, 33 mm or greater on a 100-mm visual analog scale, no involvement in litigation related to the low back pain complaint, patient not pregnant and no physical or electrodiagnostic signs of nerve root entrapment.\n The patients were randomly assigned to either a treatment or control group. The treatment group (n = 17) received treatment deemed appropriate by the clinician as long as it included a side-lying manipulation to the appropriate level. The control group (n = 19) received detuned ultrasound, application of a cold pack and 15-30 sec of very gentle soft tissue massage. Patients were treated three to five times over a period of 10 days and were subsequently reevaluated.\n The Hmax/Mmax ratio was calculated from the results of electrodiagnostic testing of the posterior tibial nerve. Extension/flexion ratio of the trunk musculature, Oswestry score and Visual Analog Scale score were also measured.\n The mean difference between H/M ratios pre- and postintervention for the group treated by chiropractic methods was -0.101 on the left and -0.117 on the right. The mean difference for the control group was 0.038 on the left and 0.036 on the right. Although not statistically significant, trends suggest that at the time of final assessment, the group receiving chiropractic care had improved more than the control group.\n The H/M ratio was found to be within normal limits in subjects with acute low back pain. The H/M ratio showed greater change in the group which received spinal manipulation, but the change was subtle. The results indicate that the H/M ratio may be of limited value in clinical practice.", "There are few data on the relative effectiveness and costs of treatments for low back pain. We randomly assigned 321 adults with low back pain that persisted for seven days after a primary care visit to the McKenzie method of physical therapy, chiropractic manipulation, or a minimal intervention (provision of an educational booklet). Patients with sciatica were excluded. Physical therapy or chiropractic manipulation was provided for one month (the number of visits was determined by the practitioner but was limited to a maximum of nine); patients were followed for a total of two years. The bothersomeness of symptoms was measured on an 11-point scale, and the level of dysfunction was measured on the 24-point Roland Disability Scale.\n After adjustment for base-line differences, the chiropractic group had less severe symptoms than the booklet group at four weeks (P=0.02), and there was a trend toward less severe symptoms in the physical therapy group (P=0.06). However, these differences were small and not significant after transformations of the data to adjust for their non-normal distribution. Differences in the extent of dysfunction among the groups were small and approached significance only at one year, with greater dysfunction in the booklet group than in the other two groups (P=0.05). For all outcomes, there were no significant differences between the physical-therapy and chiropractic groups and no significant differences among the groups in the numbers of days of reduced activity or missed work or in recurrences of back pain. About 75 percent of the subjects in the therapy groups rated their care as very good or excellent, as compared with about 30 percent of the subjects in the booklet group (P<0.001). Over a two-year period, the mean costs of care were $437 for the physical-therapy group, $429 for the chiropractic group, and $153 for the booklet group.\n For patients with low back pain, the McKenzie method of physical therapy and chiropractic manipulation had similar effects and costs, and patients receiving these treatments had only marginally better outcomes than those receiving the minimal intervention of an educational booklet. Whether the limited benefits of these treatments are worth the additional costs is open to question.", "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.", "Many clinical trials on chiropractic management of low back pain have neglected to include specific forms of care. This study compared two well-defined treatment protocols. The objective was to compare the outcome of flexion-distraction (FD) procedures performed by chiropractors with an active trunk exercise protocol (ATEP) performed by physical therapists. A randomized clinical trial study design was used. Subjects, 18 years of age and older, with a primary complaint of low back pain (>3 months) were recruited. A 100 mm visual analogue scale (VAS) for perceived pain, the Roland Morris (RM) Questionnaire for low back function, and the SF-36 for overall health status served as primary outcome measures. Subjects were randomly allocated to receive either FD or ATEP. The FD intervention consisted of the application of flexion and traction applied to specific regions in the low back, with the aid of a specially designed manipulation table. The ATEP intervention included stabilizing and flexibility exercises, the use of modalities, and cardiovascular training. A total of 235 subjects met the inclusion/exclusion criteria and signed the informed consent. Of these, 123 were randomly allocated to FD and 112 to the ATEP. Study patients perceived significantly less pain and better function after intervention, regardless of which group they were allocated to (P<0.01). Subjects randomly allocated to the flexion-distraction group had significantly greater relief from pain than those allocated to the exercise program (P=0.01). Subgroup analysis indicated that subjects categorized as chronic, with moderate to severe symptoms, improved most with the flexion-distraction protocol. Subjects categorized with recurrent pain and moderate to severe symptoms improved most with the exercise program. Patients with radiculopathy did significantly better with FD. There were no significant differences between groups on the Roland Morris and SF-36 outcome measures. Overall, flexion-distraction provided more pain relief than active exercise; however, these results varied based on stratification of patients with and without radiculopathy and with and without recurrent symptoms. The subgroup analysis provides a possible explanation for contrasting results among randomized clinical trials of chronic low back pain treatments and these results also provide guidance for future work in the treatment of chronic low back pain.", "A randomized clinical trial.\n To compare the effectiveness of medical and chiropractic care for low back pain patients in managed care; to assess the effectiveness of physical therapy among medical patients; and to assess the effectiveness of physical modalities among chiropractic patients.\n Despite the burden that low back pain places on patients, providers, and society, the relative effectiveness of common treatment strategies offered in managed care is unknown.\n Low back pain patients presenting to a large managed care facility from October 30, 1995, through November 9, 1998, were randomly assigned in a balanced design to medical care with and without physical therapy and to chiropractic care with and without physical modalities. The primary outcome variables are average and most severe low back pain intensity in the past week, assessed with 0 to 10 numerical rating scales, and low back-related disability, assessed with the 24-item Roland-Morris Disability Questionnaire.\n Of 1,469 eligible patients, 681 were enrolled; 95.7% were followed through 6 months. The mean changes in low back pain intensity and disability of participants in the medical and chiropractic care-only groups were similar at each follow-up assessment (adjusted mean differences at 6 months for most severe pain, 0.27, 95% confidence interval, -0.32-0.86; average pain, 0.22, -0.25-0.69; and disability, 0.75, -0.29-1.79). Physical therapy yielded somewhat better 6-month disability outcomes than did medical care alone (1.26, 0.20-2.32).\n After 6 months of follow-up, chiropractic care and medical care for low back pain were comparable in their effectiveness. Physical therapy may be marginally more effective than medical care alone for reducing disability in some patients, but the possible benefit is small.", "To evaluate the proposed manual placebo in terms of success in blinding patients to treatment group assignment and outcomes between the treatment groups.\n Randomized controlled trial.\n A chiropractic college research clinic in the midwestern United States.\n One hundred and eleven (111) individuals aged 18 years and over with subacute or chronic lowback pain.\n The active treatment consisted of flexion-distraction chiropractic manipulation and trigger point therapy and the control treatment of sham manipulation and effleurage; both groups received eight treatments over a 3-week period. The application of prescribed ranges of biomechanical forces for each treatment was standardized using specialized computerized equipment. \"Nontreatment\" aspects of the clinical encounter were to be standardized across groups. A primary clinician blinded to treatment assignment provided interpersonal interactions and treating clinicians delivered treatments with a minimum of interaction.\n The accuracy of the patient's perception of group assignment at visit 4 and the mean change in the Pain Disability Index (PDI) over the treatment period were the primary outcome variables.\n Patients in the control group were more likely to perceive their treatment assignment accurately than those in the active group (78% versus 54%, respectively). Patients in both treatment groups improved on the PDI and the Roland-Morris Questionnaire; there were no significant differences in improvement between the groups. Age, gender, prior chiropractic experience and expectation of treatment at baseline had no effect on outcomes.\n Patients in the control group were not successfully blinded; however, patients' perceptions of treatment group assignment did not significantly affect outcomes. The clinically significant improvement in both groups, independent of patient or clinician expectations, suggests the presence of therapeutic factors common to both groups, other than biomechanical force. Further studies examining other aspects of the clinical encounter, considered separately from biomechanical force, are warranted before arbitrarily designating any intervention as a \"placebo.\"", "A randomized, assessor-blinded clinical trial was conducted.\n To investigate the relative effectiveness of three manual treatments and back school for patients with subacute low back pain.\n Literature comparing the relative effectiveness of specific therapies for low back pain is limited.\n Among the 5925 inquiries, 206 patients met the specific admission criteria, and 200 patients randomly received one of four treatments for 3 weeks: back school, joint manipulation, myofascial therapy, and combined joint manipulation and myofascial therapy. These patients received assessments at baseline, after 3 weeks of therapy, and 6 months after the completion of therapy. The primary outcomes were evaluated using visual analog pain scales and Roland-Morris activity scales.\n All four groups showed significant improvement in pain and activity scores after 3 weeks of care, but did not show further significant improvement at the 6-month follow-up assessment. No statistically significant between-group differences were found either at the 3-week or 6-month reassessments.\n For subacute low back pain, combined joint manipulation and myofascial therapy was as effective as joint manipulation or myofascial therapy alone. Additionally, back school was as effective as three manual treatments." ]

[ "9252088", "16250039", "10419922", "15057894" ]

[ "The combination of ursodeoxycholic acid and methotrexate for primary biliary cirrhosis is not better than ursodeoxycholic acid alone.", "Methotrexate (MTX) plus ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis.", "Low-dose methotrexate is ineffective in primary biliary cirrhosis: long-term results of a placebo-controlled trial.", "A randomized controlled trial of colchicine plus ursodiol versus methotrexate plus ursodiol in primary biliary cirrhosis: ten-year results." ]

[ "Many therapies have been tried in primary biliary cirrhosis. It has been suggested that a combination of ursodeoxycholic acid and methotrexate may offer advantages. Because the benefit and safety of this combination is uncertain, we conducted this prospective, randomized, double-blind, controlled trial.\n Twenty-five patients with well-defined primary biliary cirrhosis were randomly assigned to receive either ursodeoxycholic acid (500 mg/day) plus methotrexate (10 mg/week) or ursodeoxycholic acid plus placebo for a period of 48 weeks. Clinical, biochemical and histologic evolution were assessed.\n In both groups the clinical response was similar and heterogeneous. In patients of ursodeoxycholic acid alone group, biochemical and histologic changes were comparable to those of patients of ursodeoxycholic acid plus methotrexate at 48 weeks. The addition of methotrexate was not associated with substantial adverse affects.\n The use of methotrexate in combination with ursodeoxycholic acid was not followed by an additive benefit over ursodeoxycholic acid alone, nor was substantial toxicity added. Unless larger and longer controlled trials with clinical, biochemical and histologic controls show it to be a safe and effective therapy for primary biliary cirrhosis, ursodeoxycholic acid+methotrexate should not be used as a proven and accepted treatment.", "This placebo-controlled, randomized, multicenter trial compared the effects of MTX plus UDCA to UDCA alone on the course of primary biliary cirrhosis (PBC). Two hundred and sixty five AMA positive patients without ascites, variceal bleeding, or encephalopathy; a serum bilirubin less than 3 mg/dL; serum albumin 3 g/dL or greater, who had taken UDCA 15 mg/kg daily for at least 6 months, were stratified by Ludwig's histological staging and then randomized to MTX 15 mg/m2 body surface area (maximum dose 20 mg) once a week while continuing on UDCA. The median time from randomization to closure of the study was 7.6 years (range: 4.6-8.8 years). Treatment failure was defined as death without liver transplantation; transplantation; variceal bleeding; development of ascites, encephalopathy, or varices; a doubling of serum bilirubin to 2.5 mg/dL or greater; a fall in serum albumin to 2.5 g/dL or less; histological progression by at least two stages or to cirrhosis. Patients were continued on treatment despite failure of treatment, unless transplantation ensued, drug toxicity necessitated withdrawal, or the patient developed a cancer. There were no significant differences in these parameters nor to the time of development of treatment failures observed for patients taking UDCA plus MTX, or UDCA plus placebo. The trial was conducted with a stopping rule, and was stopped early by the National Institutes of Health at the advice of our Data Safety Monitoring Board for reasons of futility. In conclusion, methotrexate when added to UDCA for a median period of 7.6 years had no effect on the course of PBC treated with UDCA alone.", "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.", "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." ]

[ "11403808" ]

[ "Endovascular versus surgical treatment in patients with carotid stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a randomised trial." ]

[ "Percutaneous transluminal angioplasty and stenting (endovascular treatment) can be used to treat carotid stenosis, but risks and benefits are uncertain. We therefore compared endovascular treatment with conventional carotid surgery.\n In a multicentre clinical trial, we randomly assigned 504 patients with carotid stenosis to endovascular treatment (n=251) or carotid endarterectomy (n=253). For endovascular patients treated successfully, we used stents in 55 (26%) and balloon angioplasty alone in 158 (74%). An independent neurologist followed up patients. Analysis was by intention to treat.\n The rates of major outcome events within 30 days of first treatment did not differ significantly between endovascular treatment and surgery (6.4% vs 5.9%, respectively, for disabling stroke or death; 10.0% vs 9.9% for any stroke lasting more than 7 days, or death). Cranial neuropathy was reported in 22 (8.7%) surgery patients, but not after endovascular treatment (p<0.0001). Major groin or neck haematoma occurred less often after endovascular treatment than after surgery (three [1.2%] vs 17 [6.7%], p<0.0015). At 1 year after treatment, severe (70-99%) ipsilateral carotid stenosis was more usual after endovascular treatment (25 [14%] vs seven [4%], p<0.001). However, no substantial difference in the rate of ipsilateral stroke was noted with survival analysis up to 3 years after randomisation (adjusted hazard ratio=1.04, 95% CI 0.63-1.70, p=0.9).\n Endovascular treatment had similar major risks and effectiveness at prevention of stroke during 3 years compared with carotid surgery, but with wide CIs. Endovascular treatment had the advantage of avoiding minor complications." ]

[ "8671131", "2303961", "1390143" ]

[ "A randomized controlled trial of electromagnetic therapy in the primary care management of venous leg ulceration.", "Effect of low frequency pulsing electromagnetic fields on skin ulcers of venous origin in humans: a double-blind study.", "A portable pulsed electromagnetic field (PEMF) device to enhance healing of recalcitrant venous ulcers: a double-blind, placebo-controlled clinical trial." ]

[ "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.", "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.", "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." ]

[ "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." ]

[ "1892197", "3382883", "2698515", "16765169", "7806870", "18292959", "11569654", "6626904" ]

[ "Effectiveness of antibiotic prophylaxis in preventing bacteriuria after multichannel urodynamic investigations: a blind, randomized study in 124 female patients.", "Is antibiotic prophylaxis necessary for routine urodynamic investigations? A controlled study in 100 patients.", "[Early antibiotic therapy following urodynamic examination. Results of a randomized, controlled study].", "Effectiveness of ciprofloxacin prophylaxis in preventing bacteriuria caused by urodynamic study: a blind, randomized study of 192 patients.", "Antibiotic prophylaxis for urodynamic testing in patients with spinal cord injury: a preliminary study.", "The usefulness of antibiotic prophylaxis in invasive urodynamics in postmenopausal female subjects.", "Antibiotic treatment to prevent urinary tract infections after urodynamic evaluation.", "Antibiotic prophylaxis after instrumentation for urodynamic testing." ]

[ "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.", "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.", "Forty-three young men from the Italian army underwent urodynamic tests following the diagnosis of enuresis. Of these, 37 were included in an assessment trial to define the rationale for early anti-bacterial therapy following the test. The subjects were subdivided into two groups: one group received 500 mg Cinoxacin b.i.d. for 5 days, and the other group was not treated. The comparison of results revealed a high incidence of irritative disorders in both groups (78.9% of treated subjects and 88.9% of untreated subjects) but the most significant complications were observed in the untreated group (feveret in 27.7% and one case of septic fever). Early anti-bacterial therapy following standard urodynamic tests therefore seems to be a ration tool in urological practice.", "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.", "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.", "This study aims to define the usefulness of antibiotic prophylaxis of urinary tract infection (UTI) in postmenopausal female undergoing invasive urodynamics (IU). Two hundred sixty-two postmenopausal females underwent IU. Before urodynamics, all females were double blindly randomized in two age stratified groups. Group 1 (130 patients) received oral antibiotic prophylaxis with a single 400-mg dose of norfloxacin. Group 2 (132 patients) received norfloxacin placebo. Statistical analysis was performed by a chi (2) test to evaluate differences between groups for UTI incidence rate. Fifty-four patients of 262 (20.6%) resulted affected by UTI [24 of 130 subjects who received antibiotic prophylaxis (18.4%) and 30 of 132 subjects who received placebo (22.7%)]. There was no statically significant difference (P = 0.242) regarding UTI incidence rate between patients who received and those who did not received antibiotic prophylaxis. UTI incidence rate in postmenopausal women undergoing urodynamics is not affected by administration of antibiotic prophylaxis at the desired level of efficacy.", "The aim of the study was to determine the efficacy of cotrimoxazole administration after urodynamic testing to prevent urinary tract infections. In a single-blind prospective randomized study 94 women who attended for urodynamic evaluation were included. After multichannel urodynamic testing, including two catheterizations, the women received a single dose of cotrimoxazole or placebo. A clean-catch urine specimen was tested for infection after 1 week. Seventy women returned a urine specimen after 1 week: 2/37 (5.4%) in the treatment and 2/33 (6.1%) in the placebo group had acquired a new urinary tract infection after urodynamics. One major and one minor adverse reaction to cotrimoxazole were reported. The power of the sample size was unfortunately too small to draw conclusions as to the efficacy of prophylaxis.", "This study of 96 women shows that there is doubtful value in routine antibiotic prophylaxis after urodynamic investigation. An unexpectedly high number of women harboured unsuspected infections at the time of evaluation despite prior screening, which suggests prophylaxis would be more useful if given before the tests." ]

[ "6371871", "4011672", "3549879", "3788652" ]

[ "A double-blind, controlled clinical trial of haloperidol decanoate and fluphenazine decanoate in the maintenance treatment of schizophrenia.", "Double-blind comparison of haloperidol decanoate and fluphenazine decanoate effectiveness, side-effects, dosage and serum levels during a six months' treatment for relapse prevention.", "Weight gain and prolactin levels in patients on long-term antipsychotic medication: a double-blind comparative trial of haloperidol decanoate and fluphenazine decanoate.", "Haloperidol decanoate and flupenthixol decanoate in schizophrenia. A long-term double-blind cross-over comparison." ]

[ "nan", "In this present study 31 schizophrenic patients were treated for six months for relapse prevention under double-blind conditions with either haloperidol decanoate (22) or fluphenazine decanoate (9). In respect of the prophylactic action, both depot neuroleptics proved to be equal during the comparatively short period of observation. In both groups a psychotic relapse occurred that could not be managed by increasing the depot dosage. No side-effects worth mentioning appeared in either group of patients; patients under haloperidol decanoate, however, only required half the quantity of anti-parkinson medication as compared with patients treated with fluphenazine decanoate, and also displayed extrapyramidal motor symptoms (EPMS) to a lesser degree. Patients received a mean monthly injection of 80 mg of Haloperidol, reaching steady-state serum levels of about 3 ng/ml in the third injection interval. Fluphenazine serum levels known so far for seven patients amount to 0.8 ng/ml after fluphenazine injections of 21 mg every 14 days.", "A one year double-blind trial of haloperidol decanoate and fluphenazine decanoate was conducted in nineteen out-patients who had previously received at least one year's treatment with fluphenazine decanoate and were already overweight, as judged by a Body Mass Index of 25+. Although the difference was not statistically significant, patients treated with haloperidol decanoate showed a trend to less weight gain than patients who continued on fluphenazine decanoate, even though the haloperidol to fluphenazine dose ratio was 4:1. No statistically significant changes in mental state were observed and the incidence of extrapyramidal side-effects in the two treatment groups was similar.", "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." ]

[ "3075503" ]

[ "Ticarcillin plus clavulanic acid (Timentin) compared with standard antibiotic regimes in the treatment of early and late neonatal infections." ]

[ "nan" ]

[ "11431240", "11927174", "11476123" ]

[ "Double-blind, placebo-controlled comparison of intramuscular olanzapine and intramuscular haloperidol in the treatment of acute agitation in schizophrenia.", "Comparison of rapidly acting intramuscular olanzapine, lorazepam, and placebo: a double-blind, randomized study in acutely agitated patients with dementia.", "A double-blind, randomized comparison of the efficacy and safety of intramuscular injections of olanzapine, lorazepam, or placebo in treating acutely agitated patients diagnosed with bipolar mania." ]

[ "The authors evaluated the comparative efficacy and safety of intramuscular olanzapine, intramuscular haloperidol, and intramuscular placebo for the treatment of acute agitation in schizophrenia.\n Hospitalized patients with schizophrenia received one to three injections of intramuscular olanzapine, 10 mg, intramuscular haloperidol, 7.5 mg, or intramuscular placebo over a 24-hour period. Agitation was measured with the excited component of the Positive and Negative Syndrome Scale and two additional scales.\n According to scores on the excited component of the Positive and Negative Syndrome Scale, both intramuscular olanzapine and intramuscular haloperidol reduced agitation significantly more than intramuscular placebo 2 and 24 hours following the first injection. Intramuscular olanzapine reduced agitation significantly more than intramuscular haloperidol 15, 30, and 45 minutes following the first injection. No patients treated with intramuscular olanzapine experienced acute dystonia, compared with 7% of those who were treated with intramuscular haloperidol. No significant QT(c) interval changes were observed in any patients.\n Intramuscular olanzapine represents a rapid, effective, and safe treatment for acute agitation in schizophrenia.", "This double-blind study investigated the efficacy and safety of rapid-acting intramuscular olanzapine in treating agitation associated with Alzheimer's disease and/or vascular dementia. At 2 h, olanzapine (5.0 mg, 2.5 mg) and lorazepam (1.0 mg) showed significant improvement over placebo on the PANSS Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES), and both 5.0 mg olanzapine and lorazepam showed superiority to placebo on the Cohen-Mansfield Agitation Inventory. At 24 h, both olanzapine groups maintained superiority over placebo on the PANSS-EC; lorazepam did not. Olanzapine (5.0 mg) and lorazepam improved ACES scores more than placebo. Simpson-Angus and Mini-Mental State Examination scores did not change significantly from baseline. Sedation (ACES > or =8), adverse events, and laboratory analytes were not significantly different from placebo for any treatment. No significant differences among treatment groups were seen in extrapyramidal symptoms or in corrected QT interval at either 2 h or 24 h, and no significant differences among treatment groups were seen in vital signs, including orthostasis. Intramuscular injection of olanzapine may therefore provide substantial benefit in rapidly treating inpatients with acute dementia-related agitation.", "There are no rapid-acting intramuscular formulations of atypical antipsychotics available for quickly calming an agitated patient with bipolar disorder. In this study, 201 agitated patients with bipolar mania were randomly assigned to receive one to three injections of the atypical antipsychotic olanzapine (10 mg, first two injections; 5 mg, third injection), the benzodiazepine lorazepam (2 mg, first two injections; 1 mg, third injection), or placebo (placebo, first two injections; olanzapine, 10 mg, third injection) within a 24-hour period. Agitation was measured at baseline, every 30 minutes for the first 2 hours, and at 24 hours after the first injection using the Positive and Negative Syndrome Scale-Excited Component subscale and two additional agitation scales. At 2 hours after the first injection, patients treated with olanzapine showed a significantly greater reduction in scores on all agitation scales compared with patients treated with either placebo or lorazepam. At 24 hours after the first injection, olanzapine remained statistically superior to placebo in reducing agitation in patients with acute mania, whereas patients treated with lorazepam were not significantly different from those treated with placebo or olanzapine. Furthermore, no significant differences among the three treatment groups were observed in safety measures, including treatment-emergent extrapyramidal symptoms, the incidence of acute dystonia, or QTc interval changes. These findings suggest that intramuscular olanzapine is a safe and effective treatment for reducing acute agitation in patients with bipolar mania." ]

[ "2258379", "16259546", "10993128", "8525856", "8263318", "16968574", "11206600", "11147927", "9547134", "17288677", "22298585", "11106136", "11352337", "11939866", "9413414", "8626364", "17196045", "9448656", "8942464", "16160624", "15042278", "7775364", "10667618", "10363731", "2258378", "11074227", "12927001", "10982198", "12053635", "12691786", "10823363", "10572324", "11910258", "10784465", "10837880", "12232543", "15744631", "8057000", "12920411", "10596735", "10184835", "16180148", "10732656" ]

[ "Double-blind, multicenter comparison of sertraline and amitriptyline in elderly depressed patients.", "Randomized trial of sertraline versus venlafaxine XR in major depression: efficacy and discontinuation symptoms.", "A double-blind study of the efficacy and safety of sertraline and clomipramine in outpatients with severe major depression.", "Moclobemide and sertraline in the treatment of depressive disorders: a comparative study.", "Double-blind study of the efficacy and safety of sertraline versus fluoxetine in major depression.", "A comparative, randomized, double-blind study of trazodone prolonged-release and sertraline in the treatment of major depressive disorder.", "Efficacy and response time to sertraline versus fluoxetine in the treatment of unipolar major depressive disorder.", "Double-blind, multicenter comparative study of sertraline versus amitriptyline in outpatients with major depression.", "A double-blind multicenter trial comparing sertraline and citalopram in patients with major depression treated in general practice.", "Escitalopram versus sertraline in the treatment of major depressive disorder: a randomized clinical trial.", "A double-blind comparison of sertraline and clomipramine in the treatment of major depressive disorder and associated anxiety in general practice.", "Sertraline versus paroxetine in major depression: clinical outcome after six months of continuous therapy.", "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.", "Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial.", "A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression.", "Nefazodone versus sertraline in outpatients with major depression: focus on efficacy, tolerability, and effects on sexual function and satisfaction.", "A randomized, double-blind, active-control study of sertraline versus venlafaxine XR in major depressive disorder.", "Double-blind comparison of bupropion sustained release and sertraline in depressed outpatients.", "Double-blind controlled trial of sertraline versus paroxetine in the treatment of delusional depression.", "Sertraline versus fluvoxamine in the treatment of elderly patients with major depression: a double-blind, randomized trial.", "Effects of serotonergic and noradrenergic antidepressants on auditory startle response in patients with major depression.", "A double-blind multicenter trial comparing sertraline and fluoxetine in outpatients with major depression.", "A 12-week study comparing moclobemide and sertraline in the treatment of outpatients with atypical depression.", "A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline.", "Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression.", "Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline.", "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 double-blind comparison of sertraline and fluoxetine in depressed elderly outpatients.", "St John's wort or sertraline? Randomized controlled trial in primary care.", "Sertraline is more effective than imipramine in the treatment of non-melancholic depression: results from a multicentre, randomized study.", "Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study.", "A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients.", "Acute efficacy of fluoxetine versus sertraline and paroxetine in major depressive disorder including effects of baseline insomnia.", "Comparison of sertraline and nortriptyline in the treatment of major depressive disorder in late life.", "Fluoxetine versus sertraline and paroxetine in major depression: tolerability and efficacy in anxious depression.", "[Efficacy and acceptability of tianeptine and sertraline in the acute treatment phase of depression].", "Efficacy and tolerability of hypericum extract STW3 in long-term treatment with a once-daily dosage in comparison with sertraline.", "A double-blind, placebo-controlled comparison of sertraline and dothiepin in the treatment of major depression in general practice.", "Mirtazapine orally disintegrating tablet versus sertraline: a prospective onset of action study.", "Sexual dysfunction associated with the treatment of depression: a placebo-controlled comparison of bupropion sustained release and sertraline treatment.", "Clinical and economic comparison of sertraline and fluoxetine in the treatment of depression. A 6-month double-blind study in a primary-care setting in France.", "[Comparison of reboxetine and sertraline in terms of efficacy and safety in major depressive disorder].", "Randomized, double-blind comparison of venlafaxine and sertraline in outpatients with major depressive disorder. Venlafaxine 631 Study Group." ]

[ "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 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.", "This study compared the efficacy and safety of the selective serotonin reuptake inhibitor sertraline with that of the tricyclic antidepressant clomipramine in patients with severe depression, as defined by a baseline 17-item Hamilton Depression Rating Scale (HAM-D) of at least 25. The study included 166 outpatients, randomized to double-blind treatment with sertraline (50-200 mg) or clomipramine (50-150 mg) for 8 weeks. The efficacy of both treatments was similar, 74% of patients in the sertraline group and 71% of clomipramine patients being classified as responders at the end-point, as defined by a Clinical Global Impression-Improvement (CGI-I) score of 1 or 2. Mean HAM-D scores fell from 29.8 at baseline to 12.3 at endpoint in the sertraline group, and from 29.6-12.7 in the clomipramine group. There were more withdrawals due to adverse events in the clomipramine group than in the sertraline group (17% versus 12%). Dry mouth, tremor, dizziness and constipation were all substantially more common in the clomipramine group, whereas diarrhoea/loose stools was more common in the sertraline group. Overall, sertraline was as effective as clomipramine in this group of severely depressed outpatients, and showed better tolerability.", "The efficacy and tolerability of moclobemide and sertraline were compared in a 13 week trial on 55 depressive patients. Patients were diagnosed according to DSM-III-R criteria using SCID (Structured Clinical Interview for DSM-III-R). The study group was composed of 48 patients with major depression and 7 with minor depression. Patients were randomized in two drug groups and raters were blind to the drugs patients used. HDRS and CGI were used to assess the change in depressive symptoms. Twenty seven patients received moclobemide and 28 patients received sertraline. The dose of moclobemide used was 300-600 mg/day and that of sertraline was 50-200 mg/day. At the end of 13 weeks mean drop in HDRS for the overall group was 14.78 and the response rate calculated as percentage of patients showing a 50% drop in HDRS score was 77.8. The response rate was 76.5% for moclobemide and 78.5% for sertraline. The difference was not significant. The side effects were assessed by using UKU Side Effects Rating Scale. The most three observed side effects were dry mouth, headache and insomnia.", "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.", "To evaluate the efficacy and safety of trazodone prolonged-release compared with sertraline in the treatment of patients with major depression.\n A total of 122 patients aged 19-64 years were enrolled in this multicenter, double-blind, double-dummy, randomized, comparator-controlled study. Patients received 7 days of single-blind placebo treatment followed by 6 weeks of double-blind treatment with trazodone prolonged-release 150-450 mg/day (n = 62) or sertraline 50-100 mg/day (n = 60).\n Efficacy was evaluated by mean changes from baseline in the Hamilton Depression Rating scale (HAM-D), Montgomery Asberg Depression Rating Scale, Hamilton Anxiety Rating scale, and the Clinical Global Impression-Global Improvement/Severity scores; and by the rates of patients responding to treatment and considered to be in remission. Time to onset of efficacy and safety were assessed.\n Trazodone and sertraline were equally effective in reducing depressive symptoms and promoting remission, and had similar onset times. In the Intent-to-Treat population, there were no significant differences in favor of trazodone at study endpoint in all efficacy measures, while a statistically significant difference was detected in the Per-Protocol population on HAM-D and in the percentage of responders. Analysis of HAM-D factors (anxiety/somatization, cognitive disturbance, retardation, and sleep disturbance) indicated that sleep disturbances were significantly less evident for patients taking trazodone at study endpoint. Adverse drug reactions, mostly of mild intensity, were reported in 42% of trazodone-treated patients (mainly of the nervous system) and 43% of sertraline-treated patients (mainly gastrointestinal). One event was considered to be serious: a patient treated with trazodone 450 mg/day showed moderate anxiety/tremor/insomnia and was hospitalized. Treatment was discontinued; the patient made a full recovery.\n This study showed that after 6 weeks, trazodone and sertraline were not different in reducing symptoms of depression and in producing disease remission. Tolerability profiles reflected the differing pharmacological properties of these antidepressants. Trazodone may be a therapeutic option in the treatment of patients with major depression showing prevalent sleep disturbances.", "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.", "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.", "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.", "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.", "In this double-blind study in primary care patients, the efficacy and safety of sertraline, an antidepressant which is a selective inhibitor of serotonin re-uptake, was compared with clomipramine. Patients with DSM-III-defined major depression and with significant anxiety randomly received 50-150 mg of either sertraline (N=51) or clomipramine (N=55) once daily for 6 weeks. The mean final daily dose was 63.5 mg sertraline and 60.6 mg clomipramine. Seventy five percent of sertraline-treated and 79% of clomipramine-treated patients were maintained on the lowest dose of 50 mg once daily. The mean scores of all the rating scales (HAM-D, HAM-A, HAD, CGI) showed similar efficacy between the treatments in reducing the symptoms of depression and anxiety. Clomipramine was less well tolerated than sertraline with a greater overall incidence of side effects, or significantly greater incidence of anticholinergic side effects and significantly more patient withdrawals due to side effects; 18% in the clomipramine group compared with 4% in the sertraline group. The results indicate that sertraline is an effective agent to use in primary care patients with depression and associated symptoms of anxiety and is better tolerated than the tricyclic comparator clomipramine.", "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.", "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.", "Extracts of Hypericum perforatum (St John's wort) are widely used for the treatment of depression of varying severity. Their efficacy in major depressive disorder, however, has not been conclusively demonstrated.\n To test the efficacy and safety of a well-characterized H perforatum extract (LI-160) in major depressive disorder.\n Double-blind, randomized, placebo-controlled trial conducted in 12 academic and community psychiatric research clinics in the United States.\n Adult outpatients (n = 340) recruited between December 1998 and June 2000 with major depression and a baseline total score on the Hamilton Depression Scale (HAM-D) of at least 20.\n Patients were randomly assigned to receive H perforatum, placebo, or sertraline (as an active comparator) for 8 weeks. Based on clinical response, the daily dose of H perforatum could range from 900 to 1500 mg and that of sertraline from 50 to 100 mg. Responders at week 8 could continue blinded treatment for another 18 weeks.\n Change in the HAM-D total score from baseline to 8 weeks; rates of full response, determined by the HAM-D and Clinical Global Impressions (CGI) scores.\n On the 2 primary outcome measures, neither sertraline nor H perforatum was significantly different from placebo. The random regression parameter estimate for mean (SE) change in HAM-D total score from baseline to week 8 (with a greater decline indicating more improvement) was -9.20 (0.67) (95% confidence interval [CI], -10.51 to -7.89) for placebo vs -8.68 (0.68) (95% CI, -10.01 to -7.35) for H perforatum (P =.59) and -10.53 (0.72) (95% CI, -11.94 to -9.12) for sertraline (P =.18). Full response occurred in 31.9% of the placebo-treated patients vs 23.9% of the H perforatum-treated patients (P =.21) and 24.8% of sertraline-treated patients (P =.26). Sertraline was better than placebo on the CGI improvement scale (P =.02), which was a secondary measure in this study. Adverse-effect profiles for H perforatum and sertraline differed relative to placebo.\n This study fails to support the efficacy of H perforatum in moderately severe major depression. The result may be due to low assay sensitivity of the trial, but the complete absence of trends suggestive of efficacy for H perforatum is noteworthy.", "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.", "The efficacy, tolerability, and effects on sexual function and satisfaction of nefazodone and sertraline were compared in a multicenter, randomized, double-blind, parallel-group study in outpatients with major depression.\n One hundred sixty patients, 18 years of age or older, who met DSM-III-R criteria for single or recurrent nonpsychotic major depressive episodes were randomly assigned to 6 weeks of treatment with either nefazodone (100-600 mg/day) or sertraline (50-200 mg/day). Symptoms were assessed before and during treatment using the 17-item Hamilton Rating Scale for Depression (HAM-D-17), Clinical Global Impressions (CGI) Improvement scale, the CGI Severity of Illness scale, and a sexual function questionnaire.\n Of 143 patients evaluable for efficacy, 72 received sertraline and 71 received nefazodone. The mean modal daily dose at endpoint was 148 mg for sertraline and 456 mg for nefazodone. Analysis of efficacy measures (HAM-D-17 and CGI) showed consistent and comparable improvement in symptoms of depression for both treatment groups. Sertraline had negative effects on sexual function and satisfaction in both men and women, and nefazodone had no adverse effect on sexual well-being. Safety assessments based on adverse events, vital sign measurements, electrocardiographs, physical examinations, and clinical laboratory tests revealed no serious adverse events or organ toxicity associated with nefazodone or sertraline administration.\n Nefazodone and sertraline are well tolerated, and there was no statistically significant difference in their antidepressant activity. Sertraline treatment has negative effects on sexual function and performance in both sexes, while nefazodone has none. These findings may have clinical implications when choosing antidepressant therapy.", "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.", "A sustained-release formulation of bupropion (bupropion SR), developed with an improved pharmacokinetic profile to permit less frequent dosing than the immediate-release form, has not been evaluated in active comparator trials. This randomized, double-blind, parallel-group trial was conducted to compare the efficacy and safety of bupropion SR and sertraline.\n Outpatients with moderate to severe major depressive disorder (DSM-IV) received bupropion SR (100-300 mg/day) or sertraline (50-200 mg/day) for 16 weeks. Psychiatric evaluations, including the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Clinical Global Impressions scale for Severity of Illness (CGI-S), and for Improvement (CGI-I) were completed, and adverse events were assessed in the clinic periodically throughout treatment. Patients' orgasm function was also assessed.\n Mean HAM-D, HAM-A, CGI-I, and CGI-S scores improved over the course of treatment in both the bupropion SR group and the sertraline group; no between-group differences were observed on any of the scales. Orgasm dysfunction was significantly (p < .001) more common in sertraline-treated patients compared with bupropion SR-treated patients. The adverse events of nausea, diarrhea, somnolence, and sweating were also experienced more frequently (p < .05) in sertraline-treated patients. No differences were noted between the two treatments for vital signs and weight.\n This double-blind comparison of bupropion SR and sertraline demonstrates that bupropion and sertraline are similarly effective for the treatment of depression. Both compounds were relatively well tolerated, and orgasm dysfunction, nausea, diarrhea, somnolence, and sweating were reported more frequently in sertraline-treated patients.", "In this study the authors evaluated the efficacy and the tolerability of sertraline and paroxetine in the treatment of delusional depression.\n Under double-blind conditions, 46 hospitalized patients who met the DSM-III-R criteria for major depression with psychotic features were treated with sertraline or paroxetine for 6 weeks.\n The response rates were 75% and 46% for sertraline and paroxetine, respectively. The dropout rate was substantial (41%) in the paroxetine group and was attributable to side effects.\n Selective serotonin reuptake inhibitors administered alone are useful in the treatment of delusional depression.", "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.", "Amplitude, habituation and prepulse inhibition (PPI) of the acoustic startle response (ASR) in rodents and humans are sensitive to psychotropic drugs. Studies with rodents suggest that an increase or decrease in serotonin level in the brain alters several modalities of the ASR. So far, little is known about serotonergic and noradrenergic startle modulation in humans.\n This study was designed to investigate the effects of the selective serotonin uptake inhibitor sertraline versus the selective noradrenalin uptake inhibitor reboxetine on magnitude, habituation and PPI of ASR in patients with major depression.\n We studied ASR in 23 patients with the diagnosis of major depression according to DSM-IV who were randomly treated either with sertraline or with reboxetine. Initially, ASR assessment was carried out when patients were drug-free for at least 2 weeks and again after 14 days of treatment.\n The habituation of ASR was strongly attenuated by sertraline and not significantly altered by reboxetine. None of the substances altered the startle reactivity. In addition, PPI was not altered by sertraline, but reboxetine tended to decrease PPI. The startle reactivity at baseline was correlated with improvement of depressive symptoms at the end of the study.\n These results provide the first evidence for different effects of noradrenergic and serotonergic antidepressants on the startle response in depressed patients.", "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.", "One hundred and ninety-seven outpatients with atypical depression [Atypical Depression Diagnostic Scale (ADDS) score=4] were randomized to 12 weeks of double-blind treatment with sertraline or moclobemide in a multicentre, parallel-group clinical trial. Patients were started on either 50 mg/day sertraline or 300 mg/day moclobemide. If the therapeutic response was not satisfactory after 4 weeks, the dose could be increased to either 100 mg/day sertraline or 450 mg/day moclobemide. Primary efficacy evaluations were the 29-item Hamilton Psychiatric Rating Scale for Depression (HAM-D) and the Clinical Global Impression of Improvement (CGI-I) response rate (much or very much improved) at study endpoint. Secondary efficacy evaluations included the ADDS, the Hamilton Anxiety Scale (HAMA), the Leeds Sleep Scale, and the Battelle Quality of Life Battery (BQOLB). In the analysis of the 172 patient efficacy-evaluable population, there was significant baseline to endpoint improvement in all primary and secondary efficacy assessments after treatment with either sertraline or moclobemide. At the endpoint, the proportion of responders on CGI-I, was 77.5% in the sertraline group and 67.5% in the moclobemide group (p=0.052). The baseline to endpoint mean 29-item HAM-D score decreased from 35.9 to 14.5 in the sertraline group and from 36.3 to 16.1 in the moclobemide group. Sertraline also resulted in a significantly (p < 0.05) greater degree of improvement at the endpoint, compared with moclobemide, in the proportion of remitters on the HAMA (total score < or = 7), ADDS Category IID (Rejection Sensitivity), Leeds Sleep Factor 4 (Integrity of Behaviour Following Awakening), and on three dimensions of the BQOLB (Energy/Vitality, Social Interaction and Life Satisfaction). There were no other significant differences between treatment groups. Overall, both medications were well tolerated. In this study, both sertraline and moclobemide improved the symptoms of atypical depression.", "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.", "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.", "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.", "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.", "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.", "To compare the change in severity of depressive symptoms and occurrence of side effects in primary care patients treated with St John's wort (SJW) and sertraline.\n Double-blind, randomized 12-week trial.\n Community-based offices of 12 family physicians practising in greater Montreal, Que.\n Eighty-seven men and women with major depression and an initial score of > or = 16 on the Hamilton Rating Scale for Depression (Ham-D).\n Patients were randomized to treatment with either sertraline (50 to 100 mg/d) or SJW (900 to 1800 mg/d) in a double-blind fashion. Assessment of depression was done at entry and at 2, 4, 8, and 12 weeks using the Ham-D, the Beck Depression Inventory (BDI), and a questionnaire asking about compliance and side effects.\n Changes from baseline in Ham-D and BDI scores and self-reported side effects.\n There were no important differences in changes in mean Ham-D and BDI scores (using intention-to-treat analysis), with and without adjustment for baseline demographic characteristics, between the two groups at 12 weeks. Significantly more side effects were reported in the sertraline group than in the SJW group at 2 and 4 weeks' follow up.\n The more benign side effects of SJW make it a good first choice for this patient population.", "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.", "Hypericum (St. John's wort) has been shown to be as efficacious and well tolerated as standard antidepressants in the treatment of depression but has not been compared with selective serotonin reuptake inhibitors (SSRIs).\n This study compared hypericum and the SSRI sertraline in the treatment of depression.\n In a double-blind, randomized study conducted in a community hospital, 30 male and female outpatients (19 women, 11 men; mean age, 45.5 years) with mild to moderate depression received 600 mg/d of a standardized extract of hypericum (LI 160) or 50 mg/d sertraline for I week, followed by hypericum 900 mg/d or sertraline 75 mg/d for 6 weeks.\n The severity of symptoms, as assessed by scores on the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impression scale, was significantly reduced in both treatment groups (P < 0.01). Clinical response (defined as a > or =50% reduction in HAM-D scores) was noted in 47% of patients receiving hypericum and 40% of those receiving sertraline. The difference was not statistically significant. Both agents were well tolerated. A post hoc power analysis indicated that failure to reach statistical significance between treatments resulted primarily from an absence of clinical differences rather than the small sample size.\n The hypericum extract was at least as effective as sertraline in the treatment of mild to moderate depression in a small group of outpatients.", "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.", "This study assessed whether fluoxetine, sertraline, and paroxetine differ in efficacy and tolerability in depressed patients and the impact of baseline insomnia on outcomes. Patients (N = 284) with DSM-IV major depressive disorder were randomly assigned in a double-blind fashion to fluoxetine, paroxetine, or sertraline for 10 to 16 weeks of treatment. Using the Hamilton Rating Scale for Depression (HAM-D) sleep disturbance factor score, patients were categorized into low (<4) or high (>or=4) baseline insomnia subgroups. Changes in depression and insomnia were assessed. Safety assessments included treatment-emergent adverse events (AEs), reasons for discontinuation, and AEs leading to discontinuation. In addition, AEs were evaluated within insomnia subgroups to determine emergence of activation or sedation. Depression improvement, assessed with the HAM-D-17 total score, was similar among treatments in all patients (p = 0.365) and the high (p = 0.853) and low insomnia (p = 0.415) subgroups. Insomnia improvement, assessed with the HAM-D sleep disturbance factor score, was similar among treatments in all patients (p = 0.868) and in the high (p = 0.852) and low insomnia (p = 0.982) subgroups. Analyses revealed no significant differences between treatments in the percentages of patients with substantial worsening, any worsening, worsening at endpoint, or improvement at endpoint in the HAM-D sleep disturbance factor in either insomnia subgroup. Treatments were well tolerated in most patients. No significant differences between treatments in the incidence of AEs suggestive of activation or sedation were seen in the insomnia subgroups. These data show no significant differences in acute treatment efficacy and tolerability across fluoxetine, sertraline, and paroxetine in major depressive disorder patients. Improvement in overall depression and in associated insomnia was achieved by most patients regardless of baseline insomnia.", "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.", "Major depression with high levels of anxiety (anxious depression) is a common subtype of depression associated with greater psychosocial impairment and poorer response to antidepressant treatment. It is unclear whether in this population there are differences in efficacy or tolerability across selective serotonin reuptake inhibitors. For this reason, using head-to-head acute treatment comparison, we compared efficacy and tolerability of fluoxetine, sertraline, and paroxetine among depressed patients with high levels of anxiety.\n Patients (N = 108) with DSM-IV major depression and high levels of anxiety (a HAM-D-Anxiety/Somatization Factor score > or =7) were randomized to fluoxetine, sertraline, or paroxetine treatment in a double-blind fashion. Changes in overall depression and anxiety were assessed.\n Patients demonstrated similar baseline-to-endpoint improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores. Patients also demonstrated similar change-over-time improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores, except at week one where fluoxetine- and sertraline-treated patients had statistically significantly greater improvement than paroxetine-treated patients in the HAM-D-Anxiety/Somatization Factor score. There were no significant differences across treatments in percentages of patients with substantial emergence, any worsening, or improvement at endpoint in individual HAM-D Items 9 (agitation), 10 (psychic anxiety), and 11 (somatic anxiety). Overall, all treatments were well tolerated.\n These data showed no significant differences in efficacy and tolerability of fluoxetine, sertraline, and paroxetine in patients with high levels of baseline anxiety symptoms during the acute treatment of major depression. Each treatment was similarly effective in improving depression in this subtype of patients with anxious depression.", "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.", "The objective of this double-blind, multi-center clinical study was to demonstrate the non-inferiority of hypericum extract versus sertraline in the treatment of moderate depression.\n A total of 241 patients with a diagnosis of moderate depressive disorder (according to ICD-10 criteria) were randomized with either 50 mg sertraline or 612 mg hypericum extract (hypericum group n = 123; sertraline group n = 118). According to the study protocol, 200 patients were treated for at least 12 weeks ( n = 102 hypericum extract; n = 98 sertraline); 81 patients in the hypericum group and 80 in the sertraline group were treated after week 12 for an additional 12 weeks. Thus, most patients were treated for a period of 6 months. The primary efficacy variable was the 17-item HAMD total score at the end of the first 12-week double-blind treatment period.\n After the first 12-week treatment period, the HAMD score decreased from almost identical initial values (22.0 +/- 1.1 for hypericum and 22.1 +/- 1.1 points for sertraline) to 8.3 +/- 5.5 points (hypericum) and 8.1 +/- 5.6 points (sertraline) (mean +/- SD) in the patients treated per-protocol (PP) population. The statistical test for non-inferiority (boundary delta = 3) revealed that hypericum extract is not inferior to sertraline ( P < 0.0001). The mean difference between the treatments was 0.1995 points, with a corresponding one-sided 97.5 % confidence interval (-infinity, 1.3772). In patients who continued treatment in the follow-up phase, the HAMD score at the end of the study was 5.7 +/- 4.8 points (hypericum group) and 7.1 +/- 6.3 points (sertraline group). Comparable improvement was also found for the von Zerssen's Adjective Mood Scale (BfS) and CGI during the first and second 12-week treatment period in both treatment groups. With 68.6 % of patients in the hypericum group and 70.4 % in the sertraline group, the percentage of patients rated as responders did not differ significantly between treatment groups (12 weeks). The adverse events of 12 patients in the hypericum group (9.8 %) and of 16 patients in the sertraline group (13.6 %) were possibly related to study medication. No basic differences in the treatment groups were observed and no interaction with concomitant medication was documented. In most cases , the investigators assessed the tolerability of hypericum extract and sertraline as \"good\" or \"very good.\"\n The results indicate that hypericum extract STW 3 is not inferior to sertraline and that it is a well-tolerated drug for the treatment of moderate depression. These favorable effects were achieved with a once-daily dose of 612 mg of hypericum extract given for up to 24 weeks.", "In a double-blind multi-centre study of general practice patients with DSM-III-R major depressive disorder, sertraline (50 or 100 mg/day) was compared with dothiepin (75 or 150 mg/day) and with placebo. There were 83, 96 and 90 patients evaluated in the respective treatment groups; treatment lasted 6 weeks. Patients were assessed on the MADRS, CGI, and Leeds Self-rating Scales. Statistically significant differences (p < 0.05) between sertraline and placebo were found on MADRS and CGI but not the Leeds Scales. In the mild subgroup analyses, there were no significant differences between sertraline and placebo. However, clear significant differences (p < 0.05) between sertraline and placebo were present in the severe subgroup. Dothiepin failed to achieve a statistically significant difference from placebo on any analyses. Seventy-six per cent of patients were treated with 50 mg sertraline and 81% of patients received 150 mg dothiepin. Both sertraline and dothiepin were generally well tolerated; the most frequent side effects with sertraline were nausea, dizziness and headache; with dothiepin the most frequent side effects were dry mouth, somnolence and headache.", "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.", "This study compared the sexual functioning effects as well as the safety and efficacy of bupropion sustained release (bupropion SR) and sertraline. Three hundred sixty-four patients with normal sexual functioning and recurrent major depression were treated with bupropion SR (150-400 mg/day), sertraline (50-200 mg/day), or placebo for 8 weeks in this randomized, double-blind, multicenter study. Patients' depression, sexual functioning, and overall safety were assessed at regular clinic visits. Significantly (P < 0.05) more patients treated with sertraline experienced orgasm dysfunction compared with patients treated with bupropion SR or placebo. Bupropion SR, but not sertraline, was statistically significantly superior to placebo in improving scores on all depression scales by the end of the study. Headache occurred with similar frequency in all groups. Gastrointestinal disturbances occurred more frequently with sertraline; insomnia and agitation occurred more frequently with bupropion SR. Small decreases in mean weight were seen with both active treatments; the placebo group experienced a minor increase in mean weight. Both bupropion SR and sertraline were generally well tolerated, although sertraline was more often associated with sexual dysfunction. Bupropion SR, but not sertraline, was statistically superior to placebo in relieving depression by the end of the study. Bupropion SR may offer advantages over sertraline in treating depressed patients concerned with sexual functioning.", "In a double-blind study in a primary-care setting in France, outpatients fulfilling DSM IV criteria for a major depressive episode were randomised to receive sertraline (50 to 150 mg/day; n = 122) or fluoxetine (20 to 60 mg/day; n = 120). Assessments, including clinical evaluation [Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions (CGI)] and quality of life [Functional Status Questionnaire (FSQ)], were made at study entry and after 4 and 6 months of treatment. Use of medical services, absences from work and productivity losses were recorded for calculation of direct and indirect costs from both the overall societal perspective and in terms of sickness insurance. In total, 231 patients (116 receiving sertraline, 115 receiving fluoxetine) were included in an intention-to-treat analysis assessed up to the last visit. Statistically significant clinical and quality-of-life improvements from baseline were observed in both treatment groups, with no between-group differences. Utilisation of medical resources was higher in fluoxetine-treated patients, with significantly more consultations with specialists. The 2 treatment groups were similar in terms of number of hospitalisations and duration of stay, whether related to depression or not. There were no significant differences between groups for work or productivity losses. Cost comparisons favoured sertraline treatment from both the societal (FF7780 vs FF8706) and sickness insurance (FF2936 vs FF3224) viewpoints, with cost differentials of FF926 and FF288, respectively. From the societal perspective, the total cost per patient over the 6-month course of the trial, irrespective of the study treatment given, was FF8241, and the corresponding sickness insurance cost was FF3079. At the time of the study, FF1 = $US0.1993.", "To compare the efficacy, safety and tolerability of reboxetine and sertraline in major depressive disorder (MDD).\n The study subjects consisted of 41 patients who met the DSM-IV MDD diagnostic criteria. Patients were randomly assigned to receive either reboxetine or sertraline. During the study the patients were assessed 6 times (baseline visit=day 0, visit 1=day 8, visit 2=day 22, visit 3=day 36, visit 4=day 57 and visit 5=day 78) over 11 weeks. Antidepressant response was measured by the Hamilton Depression Rating Scale (HDRS), Clinical Global Impressions-Severity of Illness (CGI-SI) and Global Impressions-Global Improvement (CGI-GI).\n Comparing the two groups in terms of response and remission (HAM-D< or =10) measures, the results were in favour of the reboxetine group at visits 2, 3 and 4. At visit 5, the scores were similar and no statistically significant difference was found between the two groups. However, when remission was evaluated as HAM-D< or =7, a significant statistical difference was found in favour of the reboxetine group. Evaluating the side effects, dry mouth, sweating, palpitation, headache, hot flushing and sedation were more frequent in the reboxetine group. Only one patient, in the reboxetine group, dropped out due to a side effect (constipation).\n Higher rates of full remission achievement, which is the main target of MDD treatment, in the reboxetine group compared with the sertraline group may be due to the suppression of anxiety symptoms by the noradrenergic feature of the drug. In order to understand the role of the noradrenergic system in treating MDD, larger patient samples are needed. Both reboxetine and sertraline were well tolerated and effective in treating MDD.", "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." ]

[ "8675168", "7815243" ]

[ "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.", "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." ]

[ "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.", "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." ]

[ "16215365", "12231488", "16572737", "17133185", "16137357", "7924362" ]

[ "Comparison of prone positioning and high-frequency oscillatory ventilation in patients with acute respiratory distress syndrome.", "High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized, controlled trial.", "Plasma soluble intercellular adhesion molecule-1 (sICAM-1) in pediatric ARDS during high frequency oscillatory ventilation: a predictor of mortality.", "High-frequency oscillatory ventilation following prone positioning prevents a further impairment in oxygenation.", "High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669].", "Prospective, randomized comparison of high-frequency oscillatory ventilation and conventional mechanical ventilation in pediatric respiratory failure." ]

[ "Both prone position and high-frequency oscillatory ventilation (HFOV) have the potential to facilitate lung recruitment, and their combined use could thus be synergetic on gas exchange. Keeping the lung open could also potentially be lung protective. The aim of this study was to compare physiologic and proinflammatory effects of HFOV, prone positioning, or their combination in severe acute respiratory distress syndrome (ARDS).\n : Prospective, comparative randomized study.\n A medical intensive care unit.\n Thirty-nine ARDS patients with a Pao2/Fio2 ratio <150 mm Hg at positive end-expiratory pressure > or =5 cm H2O.\n After 12 hrs on conventional lung-protective mechanical ventilation (tidal volume 6 mL/kg of ideal body weight, plateau pressure not exceeding the upper inflection point, and a maximum of 35 cm H2O; supine-CV), 39 patients were randomized to receive one of the following 12-hr periods: conventional lung-protective mechanical ventilation in prone position (prone-CV), HFOV in supine position (supine-HFOV), or HFOV in prone position (prone-HFOV).\n Prone-CV (from 138 +/- 58 mm Hg to 217 +/- 110 mm Hg, p < .0001) and prone-HFOV (from 126 +/- 40 mm Hg to 227 +/- 64 mm Hg, p < 0.0001) improved the Pao2/Fio2 ratio whereas supine-HFOV did not alter the Pao2/Fio2 ratio (from 134 +/- 57 mm Hg to 138 +/- 48 mm Hg). The oxygenation index ({mean airway pressure x Fio2 x 100}/Pao2) decreased in the prone-CV and prone-HFOV groups and was lower than in the supine-HFOV group. Interleukin-8 increased significantly in the bronchoalveolar lavage fluid (BALF) in supine-HFOV and prone-HFOV groups compared with prone-CV and supine-CV. Neutrophil counts were higher in the supine-HFOV group than in the prone-CV group.\n Although HFOV in the supine position does not improve oxygenation or lung inflammation, the prone position increases oxygenation and reduces lung inflammation in ARDS patients. Prone-HFOV produced similar improvement in oxygenation like prone-CV but was associated with higher BALF indexes of inflammation. In contrast, supine-HFOV did not improve gas exchange and was associated with enhanced lung inflammation.", "Observational studies of high-frequency oscillatory ventilation in adults with the acute respiratory distress syndrome have demonstrated improvements in oxygenation. We designed a multicenter, randomized, controlled trial comparing the safety and effectiveness of high-frequency oscillatory ventilation with conventional ventilation in adults with acute respiratory distress syndrome; 148 adults with acute respiratory distress syndrome (Pa(O2)/fraction of inspired oxygen <or= 200 mm Hg on 10 or more cm H2O positive end-expiratory pressure) were randomized to high-frequency oscillatory ventilation (n = 75) or conventional ventilation (n = 73). Applied mean airway pressure was significantly higher in the high-frequency oscillation group compared with the conventional ventilation group throughout the first 72 hours (p = 0.0001). The high-frequency oscillation group showed early (less than 16 hours) improvement in Pa(O2)/fraction of inspired oxygen compared with the conventional ventilation group (p = 0.008); however, this difference did not persist beyond 24 hours. Oxygenation index decreased similarly over the first 72 hours in both groups. Thirty-day mortality was 37% in the high-frequency oscillation group and was 52% in the conventional ventilation group (p = 0.102). The percentage of patients alive without mechanical ventilation at Day 30 was 36% and 31% in the high-frequency oscillation and conventional ventilation groups, respectively (p = 0.686). There were no significant differences in hemodynamic variables, oxygenation failure, ventilation failure, barotraumas, or mucus plugging between treatment groups. We conclude that high-frequency oscillation is a safe and effective mode of ventilation for the treatment of acute respiratory distress syndrome in adults.", "Soluble intercellular adhesion molecule-1 (sICAM-1), an important adhesion molecule that mediates leukocyte-endothelial interaction, has been identified as a marker for the outcome of acute respiratory tract infection. We postulate that plasma ICAM-1 may be a valuable marker for both biological and clinical severity of acute respiratory distress syndrome (ARDS). Sixteen pediatric patients (> 1 month and < 15 years of age) diagnosed with ARDS were recruited from the Pediatric Intensive Care Unit at King Chulalongkorn Memorial University Hospital, Bangkok. The patients were randomized to receive either high frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation. Plasma sICAM-1 was measured by enzyme linked immunosorbent assay (ELISA) on days 1, 3, 5 and 7 of ARDS. Plasma sICAM-1 levels in survivors and non-survivors of the HFOV and conventional treatment groups were compared. Nine and 7 patients constituted the control group receiving conventional treatment and HFOV group, respectively. Overall nine patients survived. The patients in the HFOV group had a better chance of survival compared to the controls (71% versus 31.5%), but it was not statistically significant (p = 0.2). The overall mortality was 45.7%. The mean plasma sICAM-1 levels (n = 13/16) were significantly elevated among non-survival patients as compared to survival patients at all time points, which indicates that an unfavorable outcome in ARDS is related to the degree of epithelial and endothelial alveolar cell injury. The elevation of plasma slCAM-1 on day 3 provided the best predictor of mortality (likelihood ratio 11.9, p < 0.001). It was concluded that HFOV facilitated a potentially better outcome compared to conventional treatment and it was associated with less lung injuries evidenced by lower plasma sICAM-1.", "The improvement in oxygenation with prone positioning is not persistent when patients with acute respiratory distress syndrome (ARDS) are turned supine. High-frequency oscillatory ventilation (HFOV) aims to maintain an open lung volume by the application of a constant mean airway pressure. The aim of this study was to show that HFOV is able to prevent the impairment in oxygenation when ARDS patients are turned back from the prone to the supine position.\n Prospective, comparative randomized study.\n A medical intensive care unit.\n Forty-three ARDS patients with a Pao2/Fio2 ratio <150 at positive end-expiratory pressure > or =5 cm H2O.\n After an optimization period, the patients were assigned to one of three groups: a) conventional lung-protective mechanical ventilation in the prone position (12 hrs) followed by a 12-hr period of conventional lung-protective mechanical ventilation in the supine position (CV(prone)-CV(supine)); b) conventional lung-protective mechanical ventilation in the supine position (12 hrs) followed by HFOV in the supine position (12 hrs) (CV(supine)-HFOV(supine)); or c) conventional lung-protective mechanical ventilation in the prone position (12 hrs) followed by HFOV in the supine position (CV(prone)-HFOV(supine) group).\n Pao2/Fio2 ratio was higher at the end of the study period in the CV(prone)-HFOV(supine) group than in the CV(prone)-CV(supine) group (p < .02). Venous admixture at the end of the study period was lower in the CV(prone)-HFOV(supine) group than in the two other groups.\n HFOV maintained the improvement in oxygenation related to prone positioning when ARDS patients were returned to the supine position.", "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 effectiveness of high-frequency oscillatory ventilation with conventional mechanical ventilation in pediatric patients with respiratory failure.\n Five tertiary care pediatric intensive care units.\n A prospective, randomized, clinical study with crossover.\n Seventy patients with either diffuse alveolar disease and/or airleak syndrome were randomized to receive high-frequency oscillatory ventilation or conventional mechanical ventilation.\n Patients randomized to receive high-frequency oscillatory ventilation were managed, using a strategy that consisted of aggressive increases in mean airway pressure to attain the \"ideal\" lung volume and to achieve an arterial oxygen saturation of > or = 90%, with an FIO2 of < or = 0.6. Patients who were randomized to receive conventional mechanical ventilation were treated with a strategy that utilized increases in end-expiratory pressure and inspiratory time to increase mean airway pressure and to limit increases in peak inspiratory pressure. Target blood gas values were the same for both groups. Crossover to the alternate ventilator was required if the patient met defined criteria for treatment failure.\n Physiologic data and ventilatory parameters were collected prospectively at predetermined intervals after randomization. Airleak Scores were derived daily, based on the chest radiograph and the patient's clinical condition. In the high-frequency oscillatory ventilation group, the PaO2/PAO2 ratio increased significantly and the oxygenation index (mean airway pressure x FIO2 x 100/PaO2) decreased significantly over time. There were no differences between the groups in duration of mechanical ventilation, frequency of airleak, Airleak Scores, or 30-day survival rates. Significantly fewer patients treated with high-frequency oscillatory ventilation required supplemental oxygenation at 30 days compared with patients managed with conventional ventilation. When ventilatory subgroups were compared, the patients managed with high-frequency oscillation only had significantly better ranked outcomes than patients managed with conventional ventilation only.\n Our results indicate that high-frequency oscillatory ventilation, utilizing an aggressive volume recruitment strategy, results in significant improvement in oxygenation compared with a conventional ventilatory strategy designed to limit increases in peak airway pressures. Furthermore, despite the use of higher mean airway pressures, the optimal lung volume strategy used in this study was associated with a lower frequency of barotrauma, as indicated by requirement for supplemental oxygen at 30 days, and improved outcome compared with conventional mechanical ventilation." ]

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[ "Intravenous magnesium sulfate prophylaxis for atrial fibrillation after coronary artery bypass surgery.", "Perioperative intravenous amiodarone does not reduce the burden of atrial fibrillation in patients undergoing cardiac valvular surgery.", "Effect of amiodarone on atrial fibrillation after coronary artery bypass surgery.", "Magnesium infusion and postoperative atrial fibrillation: a randomized clinical trial.", "Single-day loading dose of oral amiodarone for the prevention of new-onset atrial fibrillation after coronary artery bypass surgery.", "beta-Blockade therapy for supraventricular tachyarrhythmias after coronary surgery: a propranolol withdrawal syndrome?", "Supraventricular tachyarrhythmias after coronary bypass surgery--a double blind randomized trial of prophylactic low dose propranolol.", "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.", "Magnesium infusion dramatically decreases the incidence of atrial fibrillation after coronary artery bypass grafting.", "Effect of single dose magnesium on arrhythmias in patients undergoing coronary artery bypass surgery.", "Efficacy of low-dose propranolol in preventing postoperative supraventricular tachyarrhythmias: a prospective, randomized study.", "Hemodynamic effects and safety of sotalol in the prevention of supraventricular arrhythmias after coronary artery bypass surgery.", "Influence of external temporary biatrial pacing on the prevention of atrial fibrillation after coronary artery bypass without extracorporeal circulation.", "Long-term amiodarone therapy and the risk of complications after cardiac surgery: results from the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (CAMIAT).", "The efficacy of supplemental magnesium in reducing atrial fibrillation after coronary artery bypass grafting.", "Postoperative oral amiodarone as prophylaxis against atrial fibrillation after coronary artery surgery.", "Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery.", "Landiolol hydrochloride for prevention of atrial fibrillation after coronary artery bypass grafting: new evidence from the PASCAL trial.", "Predictors, prevention, and long-term prognosis of atrial fibrillation after coronary artery bypass graft operations.", "Oral sotalol reduces the incidence of atrial fibrillation after coronary artery bypass surgery.", "Efficacy and safety of low-dose propranolol versus diltiazem in the prophylaxis of supraventricular tachyarrhythmia after coronary artery bypass grafting.", "Practical regimen for amiodarone use in preventing postoperative atrial fibrillation.", "Effective prevention of atrial fibrillation by continuous atrial overdrive pacing after coronary artery bypass surgery.", "Posterior pericardiotomy reduces the incidence of supra-ventricular arrhythmias and pericardial effusion after coronary artery bypass grafting.", "Amiodarone versus digoxin and metoprolol combination for the prevention of postcoronary bypass atrial fibrillation.", "Magnesium sulfate prophylaxis after cardiac operations.", "Beta blockade to prevent atrial dysrhythmias following coronary bypass surgery.", "Arrhythmia prophylaxis after coronary artery bypass grafting: regimens of magnesium sulfate administration.", "Effects of posterior pericardiotomy on the incidence of pericardial effusion and atrial fibrillation after coronary revascularization.", "Effects of posterior pericardiotomy on the incidence of atrial fibrillation and chest drainage after coronary revascularization: a prospective randomized trial.", "Intravenous amiodarone for the prevention of atrial fibrillation after open heart surgery: the Amiodarone Reduction in Coronary Heart (ARCH) trial.", "Correction of ionized plasma magnesium during cardiopulmonary bypass reduces the risk of postoperative cardiac arrhythmia.", "Atrial pacing for the prevention of atrial fibrillation after cardiovascular surgery.", "Incidence and prevention of supraventricular tachyarrhythmias after coronary bypass surgery.", "Effectiveness of metoprolol in preventing atrial fibrillation and flutter in the postoperative period of coronary artery bypass graft surgery.", "Magnesium substitution and postoperative arrhythmias in patients undergoing coronary artery bypass grafting.", "Prevention and treatment of supraventricular tachycardia shortly after coronary artery bypass grafting: a randomized open trial.", "Combination of sotalol and magnesium prevents atrial fibrillation after coronary artery bypass grafting.", "Perioperative magnesium supplementation to prevent atrial fibrillation after off-pump coronary artery surgery: a randomized controlled study.", "The effect of preoperative digitalis and atenolol combination on postoperative atrial fibrillation incidence.", "Amiodarone reduces the incidence of atrial fibrillation after coronary artery bypass grafting.", "A beta-blocker, not magnesium, is effective prophylaxis for atrial tachyarrhythmias after coronary artery bypass graft surgery.", "Oral d,l sotalol reduces the incidence of postoperative atrial fibrillation in coronary artery bypass surgery patients: a randomized, double-blind, placebo-controlled study.", "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.", "Oral amiodarone for prevention of atrial fibrillation after open heart surgery, the Atrial Fibrillation Suppression Trial (AFIST): a randomised placebo-controlled trial.", "Electrocardiographic and antiarrhythmic effects of intravenous amiodarone: results of a prospective, placebo-controlled study.", "Effects of low dose propranolol after coronary bypass surgery.", "[Efficacy of metoprolol in prevention of supraventricular arrhythmias after coronary artery bypass grafting].", "Prevention of supraventricular tachyarrhythmias after open heart operation by low-dose sotalol: a prospective, double-blind, randomized, placebo-controlled study.", "Preoperative beta-blocker use reduces atrial fibrillation in off-pump coronary bypass surgery.", "Atenolol for the prevention of arrhythmias following coronary artery bypass grafting.", "Prevention of atrial fibrillation after cardiac valvular surgery by epicardial, biatrial synchronous pacing.", "The value of P dispersion on predicting atrial fibrillation after coronary artery bypass surgery: effect of magnesium on P dispersion.", "Arrhythmia prophylaxis after aorta-coronary bypass. The effect of minidose propranolol.", "Randomized controlled study investigating the effect of biatrial pacing in prevention of atrial fibrillation after coronary artery bypass grafting.", "Pacing of Bachmann's bundle after coronary artery bypass grafting.", "Prophylactic Oral Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularization, Valve Replacement, or Repair: PAPABEAR: a randomized controlled trial.", "Effects of amiodarone and thoracic epidural analgesia on atrial fibrillation after coronary artery bypass grafting.", "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.", "Effects of biatrial pacing in prevention of postoperative atrial fibrillation after coronary artery bypass surgery.", "Low-dose amiodarone for the prevention of atrial fibrillation after coronary artery bypass grafting in patients older than 70 years.", "Intraoperative amiodarone as prophylaxis against atrial fibrillation after coronary operations.", "Prophylaxis of atrial fibrillation with magnesium sulfate after coronary artery bypass grafting.", "Prophylaxis of supraventricular and ventricular arrhythmias after coronary artery bypass grafting with low-dose sotalol.", "Biatrial pacing vs. intravenous amiodarone in prevention of atrial fibrillation after coronary artery bypass surgery.", "Role of biatrial pacing in prevention of atrial fibrillation after coronary artery bypass surgery.", "The role of posterior pericardiotomy on the incidence of atrial fibrillation after coronary revascularization.", "Amiodarone prophylaxis for tachycardias after coronary artery surgery: a randomised, double blind, placebo controlled trial.", "The influence of intravenous magnesium sulphate on the occurrence of atrial fibrillation after coronary artery by-pass operation.", "Efficacy and safety of timolol for prevention of supraventricular tachyarrhythmias after coronary artery bypass surgery.", "Prophylactic oral amiodarone compared with placebo for prevention of atrial fibrillation after coronary artery bypass surgery.", "Effect of low-dose amiodarone and magnesium combination on atrial fibrillation after coronary artery surgery.", "Prevention of atrial fibrillation after coronary artery bypass grafting via atrial electromechanical interval and use of amiodarone prophylaxis.", "Temporary atrial pacing in the prevention of postoperative atrial fibrillation.", "Effectiveness of triple-site triggered atrial pacing for prevention of atrial fibrillation after coronary artery bypass graft surgery.", "Effectiveness of sotalol in preventing supraventricular tachyarrhythmias shortly after coronary artery bypass grafting.", "Prevention by acebutolol of rhythm disorders following coronary bypass surgery.", "Effect of temporary right atrial pacing in prevention of atrial fibrillation after coronary artery bypass graft surgery.", "Prophylactic magnesium sulphate vs. lidocaine during off-pump coronary artery bypass grafting.", "Effect of posterior pericardiotomy on postoperative supraventricular arrhythmias and late pericardial effusion (posterior pericardiotomy).", "Intravenous amiodarone for prevention of atrial fibrillation after coronary artery bypass grafting.", "Influence of propranolol on supraventricular tachycardia early after coronary artery revascularization. A randomized trial.", "Beta-blocker effects on postoperative atrial fibrillation.", "Amiodarone prophylaxis for atrial fibrillation of high-risk patients after coronary bypass grafting: a prospective, double-blinded, placebo-controlled, randomized study.", "Right atrial overdrive pacing does not prevent atrial fibrillation after coronary artery bypass surgery.", "A comparison of two individual amiodarone regimens to placebo in open heart surgery patients.", "Intravenous plus oral amiodarone, atrial septal pacing, or both strategies to prevent post-cardiothoracic surgery atrial fibrillation: the Atrial Fibrillation Suppression Trial II (AFIST II).", "Intravenous and oral amiodarone for the prevention of postoperative atrial fibrillation in patients undergoing off-pump coronary artery bypass surgery.", "Intravenous amiodarone or magnesium sulphate is not cost-beneficial prophylaxis for atrial fibrillation after coronary artery bypass surgery.", "Prevention of supraventricular tachyarrhythmia with low-dose propranolol after coronary bypass.", "Ineffectiveness and potential proarrhythmia of atrial pacing for atrial fibrillation prevention after coronary artery bypass grafting.", "Posterior pericardiotomy reduces the incidence of supra-ventricular arrhythmias following coronary artery bypass surgery.", "Effectiveness of bi-atrial pacing for reducing atrial fibrillation after coronary artery bypass graft surgery.", "Evaluation of right atrial and biatrial temporary pacing for the prevention of atrial fibrillation after coronary artery bypass surgery.", "Atrial fibrillation after coronary artery bypass surgery: predictors and the role of MgSO4 replacement.", "Effect of Sotalol in the prevention of atrial fibrillation following coronary artery bypass grafting.", "Continued propranolol administration following coronary bypass surgery. Antiarrhythmic effects.", "Magnesium-supplemented warm blood cardioplegia in patients undergoing coronary artery revascularization.", "Efficacy of nadolol in preventing supraventricular tachycardia after coronary artery bypass grafting.", "Epicardial, biatrial synchronous pacing for prevention of atrial fibrillation after cardiac surgery.", "Arrhythmia prophylaxis using propranolol after coronary artery 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.", "Evaluation of bachmann bundle pacing versus right atrial pacing in prevention of atrial fibrillation after coronary artery bypass surgery.", "Magnesium administration and dysrhythmias after cardiac surgery. A placebo-controlled, double-blind, randomized trial.", "Prevention of atrial fibrillation or flutter by acebutolol after coronary bypass grafting.", "Propranolol for prevention of postoperative cardiac arrhythmias: a randomized study.", "Magnesium and arrhythmias after coronary artery bypass surgery.", "The use of atenolol in the prevention of supraventricular arrhythmias following coronary artery surgery.", "Arrhythmias after coronary bypass surgery." ]

[ "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "To evaluate the safety and role of prophylactic administration of magnesium in preventing arrhythmias.\n This double blind randomized placebo controlled clinical trial was conducted at Aga Khan University Hospital on coronary artery bypass surgery patients. All patients were connected to holter monitor before induction of anaesthesia and this monitoring continued for 24 hours. Study drug containing either 2-grams of magnesium or normal saline was given after intubation. Levels of serum magnesium was checked preoperatively and then in ICU at 0, 6, 12, and 24 hours. Independent t-test and chi square test were used for analysis. Statistical significance was defined as p-value < 0.05.\n A total of 104 patients consented to participate in the study, 53 patients were randomly allocated in magnesium (Mg) group and 51 in placebo group. Two (3.77%) patients in magnesium group and five patients (9.8%) in placebo group developed atrial fibrillation. Incidence of ventricular and supraventricular tachycardia was also slightly higher in placebo. Mg level after arrival in CICU (Cardiac Intensive Care Unit) showed mean of 2.1 in magnesium group and 1.6 in placebo group (p = 0.6).\n Low magnesium levels were noticed in the placebo group after cardiopulmonary bypass and although prophylactic administration of magnesium sulphate was relatively safe but significant benefit on prevention of arrhythmias could not be attained.", "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.", "Sotalol is a beta-adrenergic blocking drug with the additional property of lengthening the cardiac action potential. These electrophysiologic properties render the drug attractive for use in the prevention of postoperative supraventricular arrhythmias (SVA), and previous studies have suggested that it was indeed effective. The hemodynamic response to sotalol and its safety early after coronary artery bypass graft (CABG) surgery were therefore studied. Forty-two patients undergoing CABG were randomly assigned either to receive sotalol to prevent postoperative SVA (25 patients) or to serve as controls (17 patients). Sotalol was started 6 hours after surgery if patients had a cardiac index > 2.8 L/min/m2 with a pulmonary capillary wedge pressure < 15 mmHg, and if they had no contraindications to the use of beta-blockers. The drug was given as a loading infusion of 1 mg/kg over 2 hours, followed by a maintenance infusion of 0.15 mg/kg/h for 24 hours. Three hours later, patients received the first oral dose of 80 mg to be repeated every 8 or 12 hours. Adverse effects necessitating discontinuation of the drug (bradycardia < 50 beats/min, systolic blood pressure < 90 mmHg, or cardiac index < 2.2 L/min/m2) occurred in six patients (24%) and were mainly related to the loading infusion. The hemodynamic data for patients who completed the study were characterized by a significant fall of the cardiac index caused by a lower heart rate without significant change of the stroke volume index. The incidence of supraventricular arrhythmias was not significantly different in the two groups (3/19 in the sotalol group, 5/17 in the control group).(ABSTRACT TRUNCATED AT 250 WORDS)", "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.", "This study was undertaken to determine the association between amiodarone therapy and risk of complications of cardiac surgery in patients in the randomized placebo-controlled, double-blind Canadian Amiodarone Myocardial Infarction Arrhythmia Trial.\n Prospectively collected data regarding postoperative complications in 82 patients who underwent cardiac surgery during Canadian Amiodarone Myocardial Infarction Arrhythmia Trial participation were analyzed; 36 patients were randomly assigned to receive amiodarone and 46 were assigned to receive placebo. Of the patients randomly assigned to receive amiodarone, 24 patients continued amiodarone treatment to within 7 days of the operation (active amiodarone group) and 12 patients had the amiodarone discontinued at least 7 days before the operation (discontinued amiodarone group).\n The baseline characteristics of the three groups were similar. The risks of ventricular fibrillation, atrial fibrillation, and respiratory complications were similar. The risk of requiring an intra-aortic balloon pump was significantly increased by amiodarone (34.8% vs 16.7% vs 8.7% for active amiodarone, discontinued amiodarone, and placebo groups, respectively, P =.024). There was no significant difference in the use of temporary pacing. Neither the mean duration of stay in the intensive care unit nor the 7- and 30-days mortalities were affected by amiodarone.\n Patients receiving long-term amiodarone treatment after myocardial infarction had a higher rate of intra-aortic balloon use after cardiac surgery. There was no increased risk of pulmonary complications, need for pacing, or death.", "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.", "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 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 occurs frequently after cardiac surgery and not only prolongs hospitalization but also influences the prognosis. We investigated whether landiolol hydrochloride, an ultrashort-acting beta-blocker, could reduce postoperative atrial fibrillation in a randomized controlled trial.\n The subjects were 140 patients undergoing coronary artery bypass grafting at the Nihon University School of Medicine. The primary end point was occurrence/non-occurrence of atrial fibrillation up to 1 week postoperatively. Logistic regression analysis was performed to investigate risk factors for atrial fibrillation among preoperative, perioperative, and postoperative variables.\n Atrial fibrillation occurred in 7 patients (10%) in the landiolol group versus 24 patients (34.3%) in the placebo group; the landiolol group had a significantly lower incidence (P = .0006). Postoperative heart rate was significantly lower in the landiolol group than in the placebo group. On returning to the intensive care unit, the landiolol group had significantly lower inflammatory and ischemic parameters. Medical costs were also significantly lower in the landiolol group. Multivariate analysis revealed that significant risk factors for atrial fibrillation were a European System for Cardiac Operative Risk Evaluation of 10 or more, preoperative non-use of angiotensin receptor blockers, and non-use of landiolol.\n Postoperative atrial fibrillation was reduced by treatment with landiolol hydrochloride. Amelioration of ischemia, an anti-inflammatory effect, and inhibition of sympathetic hypertonia by landiolol presumably reduced the occurrence of atrial fibrillation. Hypotension or bradycardia did not develop in any of the patients, indicating the safety of this beta-blocker. These findings suggest that landiolol hydrochloride could be useful in the perioperative management of patients undergoing cardiac surgery.\n Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.", "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.", "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.", "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.", "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.", "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.", "The aim of this prospective study was to demonstrate the effectiveness of posterior pericardiotomy in reducing the incidence pericardial effusions and consequently reducing the related supraventricular tachyarrhythmias and development of delayed posterior cardiac effusions.\n This prospective randomized study was carried out in 150 patients undergoing coronary artery bypass grafting in Bayindir Hospital Department of Cardiovascular Surgery between April 2000 and October 2001. One hundred and fifty patients were divided into two groups; each group included 75 patients. A 4-cm longitudinal incision was made parallel and posterior to the left phrenic nerve, extending from the left inferior pulmonary vein to the diaphragm in posterior pericardiotomy group (group I). Posterior pericardiotomy was not performed in conventional treatment group (group II).\n Atrial fibrillation was developed in seven patients (9.3%) in group I and in 24 patients (32%) in group II (P<0.001). Atrial flutter and other supraventricular tachyarrhythmia (SVT) prevalence was not statistically significant. Early pericardial effusion was developed 42.6% (32/75) and 10.6% (8/75), respectively, in group II and group I (P<0.0001), but no late pericardial effusion developed in group I despite seven (9.3%) late pericardial effusions developing in group II (P<0.013).\n Posterior pericardiotomy is a simple, safe and effective technique for reducing not only the prevalence of early pericardial effusion and related atrial fibrillation but also delayed posterior pericardial effusion and tamponade.", "This prospective randomized study aims at evaluation and comparison of the prophylactic effects of amiodarone versus digoxin and metoprolol combination in postcoronary bypass atrial fibrillation.\n A total of 241 consecutive patients undergoing elective coronary artery bypass grafting were randomly allocated into three groups. Patients in Group1 (n=77) received metoprolol 100 mg/24 h per oral (P.O.), preoperatively, 2x0.5 mg digoxin intravenously on the operating day and digoxin 0.25 mg P.O.+metoprolol 100 mg P.O. on the first postoperative day until discharge. Patients in Group 2 (n=72) received totally 1200 mg intravenous/24 h amiodarone which the 300 mg - bolus dose/1 h was given as soon as the operation had been finished. On the next day patients were administered 450 mg/24 h amiodarone i.v. and 600 mg/day in three doses P.O. were given until discharge. Group 3 (n=92) was the control group with no antiarrhythmic prophylaxis.\n Preoperative patient characteristics and operative parameters were similar in three groups. Atrial fibrillation occurred in 13 patients (16.8%) in Group 1, six patients (8.3%) in Group 2 and 31 patients (33.6%) in Group 3.\n Both study groups were effective in the prevention of postcoronary bypass atrial fibrillation with respect to control (P<0.01 in Group 1 and P<0.001 in Group 2).", "One hundred patients undergoing elective cardiac operations were randomized into placebo (n = 54) and magnesium (n = 46) groups. The magnesium group received six doses of 2.4 g (19.2 mEq) magnesium sulfate intravenously in the first 24 hours after the cardiac operation. The magnesium group had higher serum magnesium concentrations postoperatively (1.09 +/- 0.20 versus 0.75 +/- 0.13 mmol/L; p < 0.0001), postoperative day 1 (1.49 +/- 0.34 versus 0.70 +/- 0.12 mmol/L; p < 0.0001) and postoperative day 2 (0.96 +/- 0.19 versus 0.76 +/- 0.07 mmol/L; p < 0.0001). Patients in the magnesium group had a lower incidence of ventricular tachyarrythmias (VTs) (17.3% versus 51.9%; p = 0.0006), less need for treatment (6.5% versus 20.3%; p < 0.0001), fewer VT episodes/patient (0.3 +/- 0.8 versus 1.39 +/- 1.9; p < 0.0001), and a reduction in the severity of VTs as measured by the modified Lown grade (p = 0.0002). No differences were demonstrated with respect to supraventricular tachyarrythmias. The magnesium group had reduced absolute creatine kinase-MB levels (5.3 +/- 4.2 versus 28.4 +/- 28 IU/L; p = 0.001) as well as creatine kinase-MB fraction (0.01 +/- 0.02 versus 0.05 +/- 0.04; p = 0.001) on postoperative day 1. Serum magnesium concentrations were lower during VTs than during periods of sinus rhythm (0.75 +/- 0.75 versus 1.02 +/- 0.35 mmol/L; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)", "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.", "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.", "The aim of this prospective, randomized study was to assess the efficacy of posterior pericardiotomy in decreasing the prevalence of pericardial effusion and postoperative atrial fibrillation (AF).\n The study was performed in 100 patients who underwent elective coronary artery bypass grafting surgery (CABG) between October 2003 and July 2005. They were randomized to receive posterior pericardiotomy (Group A) or no posterior pericardiotomy (Group B). A 4-cm longitudinal incision was made parallel and posterior to the left phrenic nerve, extending from the left inferior pulmonary vein to the diaphragm in group A patients. Posterior pericardiotomy was not performed in group B patients.\n Early pericardial effusion developed in 6 patients (12%) of group A and 21 patients (42%) of group B; no late pericardial effusion developed in group A, but did in 3 patients (6%) of group B. The number of patients who developed postoperative AF was significantly lower in the fenestration group compared with the control group (10% vs. 30%, p < 0.010). The overall incidence of supraventricular tachycardia in patients with early pericardial effusion was significantly higher than in patients without early pericardial effusion (18 patients vs. 9 patients).\n These findings suggest that posterior pericardiotomy reduces the prevalence of early pericardial effusion and related AF by improving pericardial drainage in patients undergoing coronary artery bypass surgery.", "nan", "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.", "We conducted this randomized controlled trial to determine whether the intraoperative measurement and correction of ionized plasma magnesium can reduce the risk of cardiac arrhythmia after cardiopulmonary bypass. Eighty-five patients presenting for coronary artery bypass grafting were randomly assigned either to the magnesium-corrected group, which received magnesium sulfate on the basis of measured levels of ionized plasma magnesium (n = 43), or to the control group, in which magnesium levels were identified but not corrected (n = 42). Ionized magnesium was determined with an ion-selective electrode with minimal delay, and further samples were taken for laboratory analysis of total plasma magnesium. All patients had Holter electrocardiogram monitoring for 72 h after surgery. Total hypomagnesemia (45 patients; 53% of all patients) was more common than ionized hypomagnesemia (11 patients; 13%) before cardiopulmonary bypass. Both total and ionized magnesium levels declined further during the course of cardiopulmonary bypass in the control group. The incidence of ventricular tachycardia in the first 24 h was less frequent in the magnesium-corrected group (3 patients; 7%) than the control group (12 patients, 30%; P < 0.01). Patients in the magnesium-corrected group were more likely to display continuous sinus rhythm (Lown Grade 0) in the first 24 h (14 patients; 34%) than patients in the control group (2 patients, 5%; P < 0.001). Our results suggest that the intraoperative correction of ionized magnesium is associated with a reduction in postoperative ventricular arrhythmia in cardiac surgical patients.\n In this study the correction of ionized plasma magnesium during cardiopulmonary bypass was guided by measurements from an ion-selective electrode. This intervention resulted in a reduction in the incidence of postoperative ventricular tachycardia and an increased frequency of continuous sinus rhythm. Ion-selective electrodes constitute a convenient near-patient test, providing a basis for the targeted replacement of ionized plasma magnesium.", "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.", "Supraventricular tachyarrhythmias are a frequent complication encountered after coronary artery bypass grafting. A retrospective survey of 102 consecutive patients undergoing exclusive bypass grafting at St. Mary's Hospital supplemented by a review of 16 published reports over a period of 10 years revealed a mean incidence of post-operative tachyarrhythmia of 33.4% in 1344 patients (range 11.4-100%). One hundred and thirty two patients undergoing exclusive bypass surgery, were randomised prospectively in double blind fashion to receive either oral timolol or matched placebo approximately 24 hours after surgery. In the 66 patients receiving timolol, there was a significant reduction of post-operative arrhythmias compared to the 66 patients receiving placebo: from 19.7 to 7.5% (P less than 0.05). Of all arrhythmias, two thirds appeared under 48 hours after surgery. In the timolol group, 4 patients developed systemic hypotension. This was readily reversed by withdrawing the drug. No other side effects were noted. The use of oral timolol after coronary artery surgery significantly lowers the incidence of post-operative supraventricular arrhythmias.", "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.", "Sixty coronary artery bypass grafting patients were randomized to receive either magnesium sulphate or placebo for 4 days postoperatively. The magnesium substitution reduced the duration of atrial fibrillation or flutter (p < 0.05), but not the number of patients developing these arrhythmias. The number of ventricular ectopic beats was also reduced among patients receiving magnesium sulphate compared to placebo (p < 0.05). To evaluate whether the anti-arrhythmic effect of magnesium sulphate was explained by a faster resumption of cellular potassium postoperatively, skeletal muscle electrolyte concentrations were measured pre-operatively and on the third day postoperatively. No significant difference was found in skeletal muscle potassium or magnesium contents on the third day postoperatively when comparing the two groups. The serum magnesium level declined postoperatively in the placebo group, whereas an increase was found in patients receiving magnesium sulphate. We suggest magnesium substitution as a routine postoperatively, because this treatment seems to reduce the severity of postoperative arrhythmias.", "Supraventricular arrhythmias continue to complicate the postoperative course of patients following coronary artery bypass grafting. In a randomized, open, controlled trial we assessed the value of two different beta-blocking agents in the prevention and treatment of these arrhythmias. Of 151 consecutive patients undergoing coronary artery surgery, 39 were treated with metoprolol and 41 were treated with sotalol (a beta blocker with class III antiarrhythmic properties). Fifty patients served as a control group and received no prophylactic therapy. Twenty-one patients were eliminated from the study for various reasons, making a final total of 130 in the study group. In the metoprolol group 15.3% of patients developed supraventricular tachycardia SVT after coronary artery surgery, which was significantly less (p less than 0.05) than the incidence observed in the control group. However, in the group of patients receiving sotalol, 2.4% developed SVT (p less than 0.01 compared with the control group). Of 18 patients in the control group who developed SVT after randomization, 10 received sotalol and 4 metoprolol to terminate the arrhythmia. The mean time of termination of SVT after drug administration was 2.4 +/- 1.8 hours for treatment with sotalol and 13.6 +/- 9.8 hours for treatment with metoprolol. We conclude that sotalol significantly reduces the incidence of supraventricular tachycardia in the early period after coronary artery bypass surgery.", "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.", "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.", "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.", "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 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", "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.", "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.", "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 antiarrhythmic efficacy of intravenously administered amiodarone was examined in a prospective, randomized, placebo-controlled study that involved 77 patients after coronary artery bypass surgery. Amiodarone was given after surgery in a loading bolus of 300 mg for 2 hours followed by 1200 mg every 24 hours for 2 days and 900 mg every 24 hours for the next 2 days. Amiodarone suppressed both supraventricular and ventricular arrhythmias within 12 hours after the start of therapy. Particularly, the incidence of atrial fibrillation (5% vs 21% in the control group; p less than 0.05) and of nonsustained ventricular tachycardia (3% vs 16%; p less than 0.05) was reduced by amiodarone. Heart rate was slowed (p less than 0.001) and repolarization--as judged by JTc interval--was prolonged compared with the control group (p less than 0.01). In two patients, amiodarone infusion was stopped because of excessive QTc prolongation. No detrimental hemodynamic effects of the drug were observed. Thus the intravenous administration of amiodarone appears to be suitable for patients in whom rapid suppression of symptomatic supraventricular and ventricular arrhythmias is warranted in the presence of left ventricular dysfunction.", "This study was performed to record the occurrence of clinically important supraventricular tachyarrhythmias (SVA) during the first eight days following coronary bypass surgery after preoperative withdrawal of various betablockers and to investigate whether low dose propranolol medication postoperatively could reduce the occurrence of such arrhythmias. Forty patients with stable angina pectoris were postoperatively randomly assigned to either a group (B) receiving low doses of propranolol or to a group (A) not receiving this medication. The number of patients having episodes of clinically important SVA was recorded. Two out of sixteen patients in the propranolol group had such episodes compared with nine out of twenty without postoperative betablockade (p = 0.07). Thus among patients treated with various betablockers which were withdrawn prior to coronary surgery, the occurrence of postoperative clinically important SVA could not be significantly reduced by postoperative low dose propranolol administration.", "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.", "The aim of this prospective, double-blind, placebo-controlled trial was to assess the preventive effect and safety of low-dose sotalol after heart operation.\n Two hundred fifty-five consecutive patients referred for elective coronary artery bypass grafting (n = 220) or aortic valve operation (n = 35) were randomized to receive either 80 mg of sotalol twice daily (n = 126) or matching placebo (n = 129) for 3 months, with the first dose given 2 hours before operation.\n There were no significant baseline differences between the groups. Overall, supraventricular tachyarrhythmias occurred in 36% of patients (82% atrial fibrillation). Hospital stay was 11.6 +/- 5 days in patients with supraventricular arrhythmias, versus 9.5 +/- 2.4 days in patients without it (p < 0.0001). Low-dose sotalol reduced the rate of supraventricular arrhythmias from 46% (placebo) to 26% (sotalol; p = 0.0012), or by 43%. On the fourth postoperative day, heart rate was lower in the sotalol group (74 +/- 12 beats/min versus 85 +/- 15 beats/min; p < 0.0001) but the QT interval corrected for the heart rate was not prolonged (sotalol group, 0.44 +/- 0.03 second; placebo group, 0.43 +/- 0.03 second; p = not significant). Study medication had to be discontinued because of side effects in 5.6% of sotalol and 3.9% of placebo patients (p = not significant), with one possible proarrhythmic event occurring in a patient receiving sotalol.\n Because more than 90% of supraventricular arrhythmic episodes occurred within 9 days after operation and 70% of all possibly sotalol related side effects occurred after day 9, the findings in this study imply that prophylactic treatment with sotalol may be limited to the first 9 postoperative days.", "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.", "Seventy patients undergoing aortocoronary bypass grafting were randomized, double-blind, to receive either atenolol or placebo. There were 35 patients in each group. Patients received either atenolol 5 mg intravenously or matching placebo within 3 h of the completion of surgery. A second intravenous dose was administered 24 h following the first and then atenolol 50 mg orally or matching placebo was given for six days. Continuous Holter monitor recordings were obtained for the 24 h immediately preoperatively and continuously for eight days postoperatively. No patient received any antiarrhythmic drug preoperatively. Patients who required pharmacological intervention for the management of postoperative arrhythmias were withdrawn as treatment failures. Holter monitor analysis continued for 24 h following withdrawal of a treatment failure. All patients were analyzed according to the intention-to-treat principle. Both groups were comparable with respect to age, sex, severity of coronary artery disease, left ventricular ejection fraction, preoperative use of beta-blockers, bypass time, aortic cross-clamp time, number of grafts per patient and frequency of preoperative arrhythmias. Arrhythmia analysis was done manually. Supraventricular arrhythmias (atrial tachycardia, atrial fibrillation and atrial flutter) were classified as either mild (less than 0.5 mins, less than 140 beats/min), moderate (0.5 to 30 mins, 140 to 180 beats/min), or severe (longer than 30 mins, more than 180 beats/min). Ventricular arrhythmia analysis was performed with respect to isolated PVCs, couplets, triplets and episodes of nonsustained ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)", "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.", "AF is a frequent arrhythmia complicating CABG, and it is well known that dispersion and prolongation of P wave increases the risk of AF. The aim of this study was to investigate the effect of magnesium (Mg) treatment on P-wave duration and dispersion in patients undergoing CABG.\n The study included 148 consecutive patients (33 women, 115 men; mean age 62.1 +/- 7.0 years) undergoing CABG who were randomly allocated to two groups. Group A consisted of 93 patients to whom 1.5 g daily MgSO(4) infusion was applied the day before surgery, just after operation, and 4 days following surgery, and group B consisted of 55 control patients. From the preoperative and postoperative fourth day, 12-lead ECG recordings, duration of the P waves, and P-wave dispersions were calculated.\n There were no differences between the two groups with regard to age, sex, and blood Mg level. Comparison of the baseline and day 4 ECG measurements showed no difference as far as heart rates, duration of PQ, and QRS intervals were concerned. AF developed in 2 (2%) cases in group A and in 20 (36%) cases in group B (P < 0.001). There was no difference between the two groups when average basal P max, P min, P dispersion, and day 4 P min values were compared. In group A, fourth day P max (94.3 +/- 11.8 vs 101.0 +/- 13.2 ms; P = 0.0025) and P dispersion (38.2 +/- 9.2 vs 44.9 +/- 10.9 ms; P = 0.0002 ) were significantly lower as compared to group B. Comparing the patients who developed AF, and who did not, no difference was detected with regard to baseline P max, P min, P dispersion, and day 4 P min. Day 4 P max (95.1 +/- 11.8 vs 106.4 +/- 14.0 ms, P = 0.0015) and P dispersion (38.9 +/- 8.8 vs 50.7 +/- 13.0 ms, P = 0.001) of patients who developed AF were significantly higher. Baseline Mg levels were similar in patients who developed AF, and who did not, but the day 4 Mg level was significantly lower in AF group (2.0 +/- 0.23 vs 2.15 +/- 0.26 mg/dL, P < 0.001).\n Perioperative Mg treatment reduces P dispersion and the risk of developing AF in patients undergoing CABG.", "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.", "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.", "The purpose of this randomized, prospective trial was to determine if Bachmann's bundle pacing reduces the incidence of AF after CABG. The study included 161 patients with no history of AF who were randomized to three groups. Group 1 included 50 patients as controls. Group 2 included 60 patients who had an epicardial wire placed at the lateral wall of the right atrium. In the 51 patients of group 3, the wire was placed at the Bachmann's bundle. In groups 2 and 3, atrial pacing (AAI 96 beats/min) was initiated immediately after CABG and continued for 5 days. The study endpoint was AF lasting > or = 1 minute. Baseline clinical parameters were similar in all three groups. The incidence of AF was not reduced by pacing (group 1: 42%; group 2:48%; group 3:37%; P = NS). The paced P wave duration was increased in group 2 (129 +/- 14 ms vs group 3: 96 +/- 21 ms; P < 0.05). Paced P wave duration was a risk factor for postoperative AF (odds ratio 1.015; 95% CI 1.0021-1.028; P < 0.05). Analysis comparing the pacing groups revealed a reduction in AF during Bachmann's bundle pacing (50 vs 29%; P < 0.01). Pacing thresholds were significantly better at Bachmann's bundle compared to group 2. In conclusion, an anatomically guided pacing at the Bachmann's bundle does not reduce the overall incidence of postoperative AF compared to controls. However, the Bachmann's bundle offers favorable capabilities for postoperative a trial pacing, and thus it is a preferable site for electrode placement if postoperative atrial pacing is required.", "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.", "This study was designed to assess the effects of a perioperative dosing regimen of amiodarone administration, high thoracic epidural anesthesia (TEA), or a combination of the 2 regimens on atrial fibrillation (AF) after coronary artery bypass grafting (CABG).\n The study was prospective, controlled, and randomized and was performed in a tertiary health care center associated with a university.\n One hundred sixty-three patients scheduled for coronary artery bypass graft surgery.\n In this 2 x 2 factorial-designed study the patients were randomized to 1 of 4 regimens in which group E had perioperative TEA, group E+A had TEA and amiodarone, group A had amiodarone, and group C served as control. The epidural catheter was inserted at T1-3 the day before surgery. TEA groups received TEA for 96 hours. The amiodarone regimen consisted of a single loading dose of 1,800 mg of amiodarone orally. Intravenous infusion of amiodarone was started after induction of anesthesia and was administered at 900 mg over 24 hours for the subsequent 3 days.\n AF was documented using Holter monitoring. In group E 22 of 44 (50%), in group E+A 10 of 35 (28.6%), in group A 10 of 36 (27.8%), and in the control group 20 of 48 (41.7%) patients developed AF (odds ratio amiodarone/nonamiodarone 0.47 [0.24-0.90]; P = 0.02).\n The perioperative amiodarone regimen used in this study was effective in reducing the incidence of AF after CABG while TEA was not.", "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.", "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).", "Atrial fibrillation (AF) is one of the most common arrhythmia after coronary artery bypass grafting (CABG), which not only increases the suffering of the patients, but also prolongs hospital stay and enhances cost of care, especially for patients older than 70 years. This study was designed to evaluate the efficacy and safety of low-dose amiodarone in the prevention of AF after CABG, especially for the elderly.\n Two hundred and ten senile patients undergoing off-pump CABG were included in this prospective, randomized, double-blind and placebo controlled study. Patients were given 10 mg/kg of amiodarone (low-dose amiodarone group, n = 100) or placebo (control group, n = 110) daily for 7 days before surgery and followed by 200 mg of amiodarone or placebo daily for 10 days postoperatively.\n Postoperative AF occurred in 16 patients (16%) receiving amiodarone and in 36 (37.7%) patients receiving placebo (P = 0.006). AF occurred at (58.13 +/- 16.63) hours after CABG in the low-dose amiodarone group and at (45.03 +/- 17.40) hours in the control group (P = 0.018). The maximum ventricular rate during AF was significantly slower in the low-dose amiodarone group ((121.42 +/- 28.91) beats/min) than in the control group ((134.11 +/- 30.57) beats/min, P = 0.036). The duration of AF was (10.92 +/- 9.56) hours for the low-dose amiodarone group compared with (14.81 +/- 10.37) hours for the control group (P = 0.002). The postoperative left ventricular ejection fraction (LVEF) was significantly improved in the low-dose amiodarone group (from (59.9 +/- 10.3)% to (63.4 +/- 11.4)%, P = 0.001), and significantly higher compared with the control group ((58.5 +/- 10.7)%, P = 0.002). Both groups had a similar incidence of complication other than rhythm disturbances (12.0% vs 16.4%, P = 0.368). The low-dose amiodarone group patients had shorter hospital stays ((11.8 +/- 3.2) days vs (13.8 +/- 4.7) days, P = 0.001) and lower cost of care (RMB (79 115 +/- 16 673) Yuan vs RMB (84 997 +/- 21 587) Yuan, P = 0.031) than that of control group patients. The in-hospital mortality was not significantly different between the two groups (1.0% vs 0.9%, P = 0.946).\n Perioperative low-dose oral amiodarone appeared to be cost-effective in the prevention and delay of new-onset postoperative AF in aged patients. It significantly reduced ventricular rate and duration of AF after CABG, decreased hospital cost and stay, as well as promoted the amelioration of left ventricular systolic function. Furthermore, low-dose amiodarone was safe to use and well tolerated with low toxic and side effects, and did not increase the risk of complications and mortality. It is proved to be a first-line therapy and as routine prophylaxis for AF after CABG, especially for elderly patients complicated with left ventricular dysfunction.", "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.", "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.", "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.", "This study was aimed to compare the results of post operative biatrial pacing and i.v. amiodarone in prevention of AF. In a single blind randomized clinical trial, 210 patients scheduled for elective CABG surgery were randomized either to receive overdrive biatrial pacing, i.v. amiodarone or no intervention. Incidence of AF postoperatively evaluated. Pacing was successful in 83% of patients and 80% of patients in amiodarone group could receive their drug. Twenty and one patients developed AF. Incidence of AF in pace, amiodarone and control group was 10.7, 5.3 and 17.9%, respectively (p = 0.08). Comparing incidence of AF between pacing and control group, the difference was not significant (p = 0.2), but the difference between amiodarone and control groups was significant statistically (p = 0.03). Patients who developed AF were older but their left ventricular ejection fraction was not different with patients without AF. The ICU stay was higher in patients with AF. Use of i.v. amiodarone was more effective than biatrial pacing in prevention of post operative AF and we recommend use of this drug in high risk patients.", "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.", "Pericardial effusion and atrial fibrillation (AF) are two common complications in coronary revascularization surgery. The aim of this study was to evaluate the efficiency of posterior pericardiotomy in pericardial effusion and AF.\n This randomized prospective study includes 113 patients who underwent isolated CABG procedure between May 2000 and December 2000 in our hospital. Posterior pericardiotomy incision was done in Group I (n=54). Group II constituted the control group (n=59). Postoperative pericardial effusion was assessed by echocardiography and rhythm follow-up was done by the same cardiologist.\n There was no significant difference between study group and the control group considering the chest drainage (940.18+/-367.96 vs 894.92+/-360.65; p=0.507). The number of patients with remarkable intrapericardial effusion (>50 ml) was significantly lower in the posterior pericardiotomy group (25.93% vs 47.45%, p=0.020). The incidence of postoperative AF was no different between the posterior pericardiotomy group and the control group (12.96% vs 20.34%; p=0.32). In both groups, the incidence of AF was significantly higher in patients with mild or moderate pericardial effusion (29%), compared to patients with no or minimal pericardial effusion (10%), (p=0.017).\n Posterior pericardiotomy significantly reduces the pericardial effusion in coronary bypass procedure postoperatively. Patients with pericardial effusion were subjected to AF more frequently.", "Arrhythmias are a common cause of morbidity after cardiac surgery. This study assessed the efficacy of prophylactic amiodarone in reducing the incidence of atrial fibrillation or flutter and ventricular arrhythmias after coronary artery surgery.\n A double blind, randomised, placebo controlled trial. 60 patients received a 24 hour intravenous infusion of amiodarone (15 mg/kg started after removal of the aortic cross clamp) followed by 200 mg orally three times daily for 5 days, and 60 patients received placebo.\n 6 patients (10%) in the amiodarone group and 14 (23%) in the placebo group needed treatment for arrhythmias (95% confidence interval (95% CI) for the difference between groups was 0 to 26%, p = 0.05). The incidence of supraventricular tachycardia detected clinically and requiring treatment was lower in the amiodarone group (8% amiodarone v 20% placebo, 95% CI 0 to 24%, p = 0.07). The incidence detected by 24 hour Holter monitoring was similar (17% amiodarone v 20% placebo). Untreated arrhythmias in the amiodarone group were either clinically benign and undetected (n = 3) or the ventricular response rate was slow (n = 2). Age > 60 years was a positive risk factor for the development of supraventricular tachycardia in the amiodarone group but not in the placebo group. Fewer patients had episodes of ventricular tachycardia or fibrillation recorded on Holter monitoring in the amiodarone group (15% amiodarone v 33% placebo, 95% CI 3 to 33%, p = 0.02). Bradycardia (78% amiodarone v 48% placebo, 95% CI 14% to 46%, p < 0.005) and pauses (7% amiodarone v 0% placebo) occurred in more amiodarone treated patients. Bradycardia warranted discontinuation of treatment in one patient treated with amiodarone.\n The incidence of clinically significant tachycardia was reduced by amiodarone. The ventricular response rate was slowed in supraventricular tachycardia, but the induction of bradycardia may preclude the routine use of amiodarone for prophylaxis.", "To examine the influence of magnesium (Mg) on hypomagnesaemia and atrial fibrillation (AF) following coronary artery by-pass surgery, 140 consecutive patients were randomized to receive 70 mmol of magnesium sulphate intravenously (n = 69) or placebo (n = 71). Serum magnesium concentrations fell to 0.77 +/- 0.10 mmol.l-1 in the control group but rose to 1.09 +/- 0.17 mmol.l-1 in the Mg group (P < 0.001). The incidence of AF was 29% in the Mg group and 26% in the placebo group (NS). The AF patients were older, more of them had had prior AF episodes, their sinus rates (SR) were slower (78 +/- 10 vs 86 +/- 12 beats.min-1; P < 0.01) and serum Mg concentrations higher (0.89 +/- 0.21 vs 0.80 +/- 0.11 mmol.l-1; P < 0.05). The incidence of AF was 43% in the highest quartile of serum Mg and 23% among the rest (P = 0.056). In patients experiencing AF during the first three post-operative days, serum Mg concentrations were higher and SR slower on each day compared with non-AF patients. SR increased post-operatively less with high Mg levels (P = 0.044). In the Mg group, serum Mg and SR were the only independent predictors of AF. In conclusion, the incidence of post-operative AF is not decreased with magnesium. High Mg levels are likely to provoke AF probably by mechanisms that modify SR.", "Forty-one patients undergoing coronary artery bypass grafting were randomly assigned to receive prophylactic timolol or placebo, given in a double-blind fashion. beta-Adrenoceptor-blocking therapy was stopped at least one half-life before surgery. Three to 7 hr after surgery (304 +/- 56 min), 0.5 mg of timolol or placebo was given intravenously twice daily in a double-blind manner. When oral medications were resumed postoperatively, 10 mg of timolol twice daily or placebo was continued orally. Continuous electrocardiograms were recorded for 24 hr before and for 7 days after surgery with a standard cassette recorder. No patient received digoxin. Both groups were comparable for frequency of preoperative supraventricular arrhythmias, left ventricular ejection fraction, duration of cardiopulmonary bypass, aortic cross-clamp time, number of bypass grafts, and total duration of monitoring. Analysis of arrhythmias was done by hand counts, and supraventricular arrhythmias were divided into supraventricular tachycardia and atrial fibrillation and/or flutter. Timolol decreased the frequency of supraventricular tachycardia (581 episodes placebo vs 84 timolol; p less than .05) and of atrial fibrillation and/or flutter (291 episodes placebo vs five timolol; p less than .05). Timolol decreased the number of patients with severe (heart rate greater than 200 beats/min, duration greater than 50 beats) episodes of supraventricular tachycardia (four placebo vs 0 timolol; p less than .05) and also decreased the number of episodes of severe (heart rate greater than 200 beats/min, duration greater than 5 min) atrial fibrillation and/or flutter (16 placebo vs one timolol; p less than .005). There were differences in the durations of supraventricular arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)", "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.", "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.", "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 (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.", "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.", "To investigate the effectiveness and safety of low-dose sotalol (a class III antiarrhythmic beta-blocking agent) in the prevention of supraventricular tachyarrhythmias (SVTs) and to identify predictors for the occurrence of these arrhythmias shortly after coronary artery bypass grafting, 300 consecutive patients were randomized in a double-blind, placebo-controlled fashion. Patients with severely depressed left ventricular function or other contraindications for beta blockers were excluded. Beginning at 4 hours and up to the sixth day after surgery, 150 patients received 40 mg of sotalol every 6 hours. SVT was observed in 24 (16%) of 150 low-dose sotalol-and in 49 (33%) of 150 placebo-treated patients [p less than 0.005]. In patients receiving sotalol, atrial fibrillation was the only noted tachyarrhythmia, whereas in the placebo group, 42 (28%) patients had atrial fibrillation, 3 (2%) atrial flutter, 1 (0.7%) atrial tachycardia and 3 (2%) sinus tachycardia. Drug-related adverse effects necessitating discontinuation of the drug were noted in only 2 (1%) sotalol-treated patients and 4 (3%) placebo-treated patients (p = not significant). For both groups, univariate analysis indicated that older age, 1- or 2-vessel coronary artery disease, long bypass (greater than or equal to 150 minutes) and aorta cross-clamp time (greater than or equal to 120 minutes) were predictive variables for the occurrence of SVTs. Multivariate analysis showed that male sex (odds ratio 2.3), 1- or 2-vessel coronary artery disease (odds ratio 2.0) and older age (odds ratio 1.1) were independent risk factors for increased occurrence of postoperative SVT.(ABSTRACT TRUNCATED AT 250 WORDS)", "Seventy-one patients submitted routinely to coronary artery bypass surgery were randomized into 2 groups. Group A (32 patients) received 24 hr after initiation of surgery an intravenous perfusion of 100 mg of acebutolol given over 24 hr (22 cases) or 600 mg administered orally (10 cases). On subsequent days, they received 1200 mg of acebutolol/day orally. Group B (39 patients) was used as control. The groups were comparable in terms of age, sex, severity of coronary disease, preoperative therapy, duration of extracorporeal circulation, aortic clamping time, and immediate postoperative haemodynamic findings. No patient received digitalis. During hospital stay (10 days), 1 group A patient (3%) and 13 group B patients (33%; P less than 0.001) developed a sustained episode of atrial arrhythmia (fibrillation, flutter or atrial ectopic tachycardia). The majority of these rhythm disorders developed between days 2 and 4. On Holter monitoring on days 7-10, malignant ventricular extrasystoles (grades IV and V of Lown's classification) were more frequent in group B (65.2%) than in group A (19.3%; P less than 0.001). Haemodynamic measurements taken at rest performed in 27 patients on days 7-10 (16 patients of group A; 11 of group B). No difference was observed between the two groups. Acebutolol is a safe and efficacious drug for the prevention of arrhythmias following coronary surgery.", "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.", "nan", "The aim of this prospective study was to evaluate the effectiveness of posterior pericardiotomy from the point of pericardial effusion related with supraventricular tachycardia and development of delayed posterior cardiac effusions. Materials and methods: This prospective randomized study was carried out in 200 patients undergoing coronary artery bypass surgery in Gülhane Medical Academy Department of Cardiovascular Surgery between June 1996 and June 1997. Patients were divided into 2 groups; each group included 100 patients. Longitudinal incision was made parallel and posterior to the left phrenic nerve, extending from the left inferior pulmonary vein to the diaphragm in group I patients. Posterior pericardiotomy was not done in group II.\n Atrial fibrillation was developed in 6 patients (6%) in group I and in 34 patients (34%) in group II (P =.0000007). Atrial flutter and other supraventricular arrhythmia prevalence was not statistically significant. Early and late pericardial effusion were developed 54% and 21%, respectively, in group II, but neither early nor late pericardial effusion were developed in group I (P =.00001). Delayed pericardial tamponade was also significantly lower in group I (0% vs 10%; P =.001).\n Posterior pericardiotomy is technically easy to perform and a safe and effective technique that reduces not only the prevalence of early pericardial effusion and related atrial fibrillation but also delayed posterior pericardial effusion and tamponade.", "Atrial fibrillation occurs in 10% to 40% of patients who undergo coronary artery bypass grafting. This prospective study assesses the safety and efficacy of low-dose intravenous amiodarone in the prevention of atrial fibrillation after coronary artery bypass grafting.\n One hundred forty patients were randomly divided into two groups: an amiodarone group (n = 74) receiving intravenous amiadarone in a loading dose of 150 mg and maintenance dose of 0.4 mg x kg(-1) x h(-1) for 3 days before and 5 days after operation and a control group (n = 76) receiving matching infusions of 5% glucose solution.\n Atrial fibrillation occurred in 9 (12%) of the amiodarone group patients and in 26 (34%) of the control group patients during hospitalization (p < 0.01). The maximum ventricular rate during atrial fibrillation was significantly slower in the amiodarone group (107 +/- 21) than in the control group (138 +/- 24 beats per minute, p < 0.01). The duration of atrial fibrillation in the amiodarone group (1.1 +/- 1.2 hours) was significantly shorter than that in the control group (3.2 +/- 1.3 hours, p = 0.01). The two groups had no significant differences in incidence of major morbidity (8 of 74 versus 8 of 76 in amiodarone and control groups, respectively) or mortality (4 of 74 versus 5 of 76). However, the control group had significantly longer intensive care unit stays (132 +/- 24 versus 111 +/- 19 hours, p < 0.01).\n Perioperative low-dose intravenous amiodarone significantly reduces the incidence, ventricular rate, and duration of atrial fibrillation after coronary artery bypass grafting. Furthermore, low-dose intravenous amiodarone is well tolerated and does not increase the risk of intraoperative or postoperative complications.", "A total of 116 patients undergoing coronary revascularization were randomized preoperatively in a double-blind manner to receive 80 mg daily of propranolol or placebo in the postoperative period. Preoperatively, all patients had been receiving at least 80 mg of propranolol a day to the time of the operation. In addition, all patients had a left ventricular ejection fraction of 0.4 or more, no history of supraventricular tachyarrhythmia (SVT), and no need of digitalis preparations or other antiarrhythmic drugs. All patients were monitored for 5 days and propranolol or placebo was started 24 hours postoperatively. SVT was documented with biatrial electrograms in all cases. Study groups were similar in postoperative creatine kinase MB levels and postoperative weight gain, but the placebo group tended to be older and have more grafts per patient. Seven patients randomized were dropped from the study, two with perioperative infarction, four with persistent ventricular arrhythmias necessitating quinidine or procainamide, and one with persistent postoperative hypotension (placebo). There were no significant differences in the incidence of postoperative SVT in these two groups: 13.2% in the propranolol group and 16.1% in the placebo group. We conclude that 80 mg daily of propranolol given postoperatively to patients undergoing coronary revascularization does not effectively reduce the incidence of SVT.", "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.", "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.", "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.", "This study compares the ability of two oral amiodarone regimens to reduce the risk of atrial fibrillation (AF) as compared with the placebo among elderly open heart surgery (OHS) patients receiving beta blockade.\n This is a randomized, double-blinded, placebo-controlled trial of 220 patients undergoing OHS. Patients (average age, 73 years) received 7 g of oral amiodarone more than 10 days starting 5 days before OHS (slow load; n = 56), a 6 g oral amiodarone regimen more than 6 days starting 1 day before OHS (fast load; n = 64), or matching placebo in one of the two previously mentioned regimens (n = 100).\n Patients receiving the slow load amiodarone regimen had a significant reduction in the risk of AF (48.4%; p = 0.013), AF lasting more than 24 hours (76.5%; p = 0.003), symptomatic AF (90.0%; p = 0.002), and recurrent AF (64.5%; p = 0.025) as compared with the placebo. Patients receiving the fast load amiodarone regimen had significant reductions in the risk of AF lasting more than 24 hours (52.6%; p = 0.038) and symptomatic AF (65.0%; p = 0.024), but the incidence of any AF or any recurrence of AF only showed a trend toward significance (34.0% and 45.5%; p = 0.054 and 0.09, respectively).\n Oral amiodarone in a slow loading regimen provides significant suppression of all AF factors and can be used when a patient has started it at least 5 days before OHS. If a patient has less than 5 days before OHS, the fast loading regimen is an efficacious alternative as it provides significant benefits in preventing AF from lasting more than 24 hours and for preventing symptomatic AF. Both regimens were well tolerated and safe in elderly patients receiving beta blockade according to the hospital's standard protocol.", "The effect of a hybrid intravenous and oral prophylactic amiodarone regimen on postcardiothoracic surgery (CTS) atrial fibrillation (AF) is unknown. The impact of active atrial septal pacing on post-CTS AF has not been well characterized. In addition, the effect of using both amiodarone and atrial septal pacing together to prevent atrial fibrillation is unknown.\n Patients (n=160) were randomized to amiodarone or placebo and then to pacing or no pacing using a 2x2 factorial design. All therapies began within 6 hours post-CTS. Amiodarone was given by intravenous infusion for the first 24 hours (1050 mg total) followed by oral therapy for 4 postoperative days (4800 mg total). Atrial septal pacing was given for 96 hours. Amiodarone reduced the risk of AF by 43% and the risk of symptomatic AF by 68% (P=0.037 and P=0.019) versus placebo. Atrial septal pacing did not reduce AF or symptomatic AF incidence versus no pacing. The risk of post-CTS AF in the patients receiving amiodarone+pacing was lower than the placebo+no pacing and the placebo+pacing groups (57.9% and 60.5% reductions, P=0.047 and P=0.040, respectively).\n Amiodarone given as both an intravenous and oral regimen is effective at reducing post-CTS AF but atrial septal pacing is ineffective. Combining amiodarone and pacing is better than placebo with or without pacing but not amiodarone alone.", "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.", "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.", "Eighty-five patients receiving long-term propranolol therapy were randomized after aorta-coronary bypass grafting either to receive minidose propranolol (Group I) or to serve as controls (Group II). They were compared with 18 patients (Group III) who did not receive beta blocking agents prior to operation but were given propranolol postoperatively. Poor-risk patients (those having left ventricular aneurysms, low ejection fraction, or congestive heart failure) as well as patients who required catecholamines postoperatively were included in the study. All three groups were comparable with respect to all risk factors. Propranolol (5 to 10 mg/6 hr) was started through a nasogastric tube 6 hours after operation and continued orally in all patients in Groups I and III. Supraventricular tachyarrhythmia appeared in two of 37 patients in Group I (5%), 19 of 48 patients in Group II (40%), and five of 18 patients in Group III (27%). The incidence of supraventricular tachyarrhythmia was significantly lower in Group I than in Groups II and III (p less than 0.001, Group I versus Group II; p less than 0.01, Group I versus Group III). In conclusion, low-dose propranolol is very effective in preventing supraventricular tachyarrhythmia following aorta-coronary bypass in patients receiving beta blockers preoperatively. The increased tendency for postoperative supraventricular tachyarrhythmia to develop in these patients is attributed to hypersensitivity to adrenergic stimulation after propranolol withdrawal. The tachyarrhythmia can be prevented by early reinstitution of propranolol in low doses after the operation.", "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.", "A prospective study of 100 patients undergoing coronary artery bypass surgery was performed to demonstrate the effectiveness of a posterior pericardiotomy in reducing the incidence of pericardial effusions and, consequently, reducing the incidence of supraventricular arrhythmias in the post-operative period. Pericardial effusion occurred in 4 of 50 patients following a posterior pericardiotomy, whereas effusion occurred in 20 of 50 patients in whom a pericardiotomy was not created (P < 0.0005). Supra-ventricular arrhythmias occurred in 4 patients in the pericardiotomy group and 18 in the group treated without pericardiotomy (P < 0.005). No complications resulted from this procedure. We conclude that pericardiotomy is a simple, safe and effective method for reducing the incidence or pericardial effusion and thereby post-operative supra-ventricular arrhythmias.", "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.", "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.", "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.", "We assessed the efficacy of postoperatively administered oral Sotalol in preventing the occurrence of postoperative atrial fibrillation.\n Subjects were 80 consecutive patients undergoing coronary artery bypass grafting (CABG) randomized alternately into a Sotalol group (40 patients) administered 80 mg of oral Sotalol daily starting on the postoperative day 1 and continued for 14 days, and a control group (40 patients) matched for age and gender.\n The incidence of postoperative atrial fibrillation (21 patients) was significantly lower in the Sotalol group (6/40 patients; 15%) than in controls (15/40; 37.5%) (p < 0.05). Significant bradycardia or hypotension, necessitating drug withdrawal, occurred in 3 of 40 (7.5%) patients in the Sotalol group. None in the Sotalol group developed Torsardes de Pointes or sustained ventricular arrhythmias or other severe side effects. The sinus heart rate increased in both groups but less in the Sotalol group. QT, QRS, and QTc durations did not differ between groups. Postoperative hospital stay did not differ between groups.\n Oral Sotalol administration of 80 mg daily was associated with a significant decrease in postoperative atrial fibrillation in patients undergoing CABG without appreciable side effects. Sotalol should thus be considered in preventing postoperative atrial fibrillation in patients undergoing CABG in the absence of heart failure and significant left ventricular dysfunction.", "One hundred consecutive patients requiring propranolol hydrochloride before undergoing isolated aortocoronary bypass procedures were examined. In half the patients, propranolol therapy was discontinued, whereas the other half continued to receive intraoperative and postoperative propranolol regardless of clinical events. Although there were no preoperative differences in the apparent degree of coronary arterial disease or left ventricular function in the two groups, postoperative supraventricular arrhythmias were less frequent in the propranolol-treated group, most noticeably in those receiving less than 320 mg preoperatively. In patients who had received large preoperative doses (greater than or equal to 320 mg/day), there were no significant differences in postoperative supraventricular tachycardias. Continued propranolol therapy following isolated coronary bypass surgery appears to be a safe and efficacious method of decreasing the incidence of postoperative supraventricular tachycardias.", "Although there is growing evidence to suggest that the administration of magnesium (Mg2+) to patients undergoing coronary artery bypass grafting (CABG) and to patients after myocardial infarction is beneficial, the addition of Mg2+ to cardioplegic solutions remains controversial. The aim of this study was to compare the effects of intermittent warm blood cardioplegia with and without Mg2+ supplementation on the early postoperative clinical outcomes in patients undergoing both elective or urgent CABG.\n Four hundred patients undergoing CABG were prospectively randomized to receive either blood cardioplegia without Mg2+ (BC, n = 200) or supplemented with Mg2+ (BC-Mg2+, n = 200). Serial plasma Mg2+ concentrations were recorded at base line and postoperatively from days 1 to 4.\n Patient characteristics were similar and no significant differences were found in early mortality and morbidity in the two groups. Analysis of 178 patients undergoing urgent CABG for unstable symptoms (BC = 95, BC-Mg2+ = 83) demonstrated a significantly lower requirement for internal defibrillation and temporary epicardial pacing in the BC-Mg2+ group. Furthermore, there was a nearly twofold lower incidence of new postoperative atrial fibrillation in the BC-Mg2+ group compared with the BC group (19% versus 34%, p = 0.03). Postoperative plasma Mg2+ levels were consistently lower in those patients who developed new postoperative atrial fibrillation compared with those who did not (p = 0.05).\n The addition of Mg2+ to warm blood cardioplegia resulted in a lower incidence of intraoperative and postoperative arrhythmias in patients undergoing urgent CABG for unstable angina.", "To investigate the efficacy of nadolol in the prevention of supraventricular arrhythmias after coronary artery bypass graft (CABG) surgery, 148 patients undergoing elective CABG were randomized in double-blind, placebo-controlled fashion to receive either nadolol or placebo. The test medication was started on the first postoperative morning and maintained as a single daily dose for 6 weeks. Aside from routine daily clinical evaluation and postoperative electrocardiographic monitoring, patients underwent 24-hour Holter recording once preoperatively and 3 times postoperatively. Seven patients were excluded from the evaluation of efficacy analysis because of insufficient postoperative data. There were no significant differences between the patients receiving nadolol (n = 67) and those receiving placebo (n = 74) with respect to age, preoperative heart rate, previous medications (including beta blockers), incidence of previous myocardial infarction, frequency of preoperative ventricular and supraventricular arrhythmias, concomitant valvular heart disease, mean cardiopulmonary bypass time, mean aortic cross-clamp time, use of blood and crystalloid cardioplegia, mean number of bypass grafts placed, postoperative use of inotropic agents and catecholamines and incidence of perioperative myocardial infarction. Analysis of postoperative Holter recordings showed that the heart rate was consistently and significantly higher in the placebo group throughout the period of the study (p less than 0.001). The average number of premature atrial contractions was significantly smaller in the nadolol group (p less than 0.05), and nadolol patients had fewer ventricular premature complexes, couplets and non-sustained ventricular tachycardias during the first week postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)", "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.", "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.", "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.", "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.", "To determine whether magnesium administration is effective in reducing postoperative morbidity and mortality after cardiac surgery.\n Randomized, double-blind, placebo-controlled trial.\n A tertiary acute-care 500-bed university teaching hospital.\n Over a 6-month period, 100 patients electively scheduled for cardiac surgery involving cardiopulmonary bypass were studied.\n Fifty patients were randomized to receive an intravenous infusion of magnesium chloride, 2 g, and 50 patients received placebo intraoperatively after the termination of cardiopulmonary bypass.\n Magnesium-treated patients had a significantly decreased frequency (P < .04) of postoperative ventricular dysrhythmias (eight [16%] of 50) compared with placebo-treated patients (17 [34%] of 50). Patients who were normomagnesemic postoperatively had new supraventricular dysrhythmias less frequently (P < .03) than patients who were hypomagnesemic postoperatively (eight [17%] of 48 vs 19 [37%] of 52). Compared with placebo-treated patients, magnesium-treated patients had significantly higher (P < .02) postoperative cardiac indices in the intensive care unit (2.8 +/- 0.1 vs 2.5 +/- 0.1 L/min per m2). Patients with postoperative total and ultrafilterable hypomagnesemia had postoperative ventricular dysrhythmias (P < .04) and required prolonged mechanical ventilatory support (P < .01) more frequently than patients without postoperative hypomagnesemia.\n Total and ultrafilterable hypomagnesemia are prevalent findings in cardiac surgery patients, and postoperative hypomagnesemia is strongly associated with clinically important morbidity. Magnesium administration decreased the frequency of postoperative ventricular dysrhythmias and increased the stroke volume and thereby cardiac index in the early postoperative period.", "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)", "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 very common after cardiac surgery and are multifactorial. Magnesium is receiving increased consideration in the management of supraventricular and ventricular arrhythmias. This study was designed to evaluate the role of magnesium in preventing arrhythmias in hypokalemic (K < 3.5 mEq/L) and normokalemic (K > 3.5 mEq/L) patients with normal renal and ventricular function after coronary artery bypass grafting (CABG). One hundred forty patients ranging from 32 to 71 years of age who were scheduled for CABG were studied. They were divided into four groups: group I (control) received no magnesium; group II received 10 mg/kg of magnesium sulfate intravenously before cardiopulmonary bypass (CPB); group III received 10 mg/kg of magnesium soon after CPB; group IV received 10 mg/kg of magnesium before and after CPB. Serum potassium and catecholamine levels, as well as serum and urine magnesium levels, were measured and the incidence and type of arrhythmias were determined. There was a statistically significant difference in the occurrence of arrhythmias between the groups studied. The incidence of arrhythmias was highest in groups I and II and lowest in group IV (12 patients in group I, 14 in group II, 5 in group III; and 1 in group IV). Magnesium levels were higher in group IV than any other group studied after completion of surgery. There was no difference in serum and urine magnesium levels between the hypokalemic and normokalemic patients within each group. Serum magnesium returned to normal in all patients after 48 hours. Therefore, it appears that administration of magnesium during and after cardiac surgery reduces the incidence of arrhythmias in hypokalemic and normokalemic patients.", "Sixty patients undergoing coronary artery bypass surgery were studied prospectively in order to investigate the effect of a cardioselective beta-blocker on the incidence of postoperative supraventricular arrhythmias. Patients with good left ventricular function were randomly divided into two groups: 30 patients treated with atenolol and 30 patients acting as controls. Atrial fibrillation was seen in 11 patients and frequent premature atrial extrasystoles were noted in one. Eleven (37%) patients in the control group experienced arrhythmias whilst atenolol significantly reduced this incidence to 3% (one patient), P = 0.001. There was no significant relationship between the development of supraventricular arrhythmias and the following variables: age, sex, severity of preoperative symptoms, previous myocardial infarction, extent of coronary artery disease, technique of myocardial preservation used, ischaemic time, number and site of saphenous vein grafts, endarterectomies performed and perioperative serum potassium levels. It is concluded that the use of atenolol (started 72 h before operation) is effective in reducing the incidence of supraventricular arrhythmias following elective coronary artery bypass operations in patients with good left ventricular function.", "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." ]

[ "11040177", "16669959", "19891665", "15080848", "17260365" ]

[ "Comparison of heparin and steroids in the treatment of moderate and severe ulcerative colitis.", "Low-molecular-weight heparin (enoxaparin) as adjuvant therapy in the treatment of active ulcerative colitis: a randomized, controlled, comparative study.", "Clinical trial: oral colon-release parnaparin sodium tablets (CB-01-05 MMX) for active left-sided ulcerative colitis.", "Low molecular weight heparin (tinzaparin) vs. placebo in the treatment of mild to moderately active ulcerative colitis.", "Randomized, placebo-controlled trial of low molecular weight heparin in active ulcerative colitis." ]

[ "Unfractionated heparin has been found to reduce symptoms and improve healing as adjuvant therapy in patients with ulcerative colitis. The current study evaluated the efficacy and safety of unfractionated heparin in the treatment of ulcerative colitis in comparison with methylprednisolone.\n A multicenter randomized trial with blinded endpoint evaluation was conducted in patients hospitalized for moderate or severe ulcerative colitis. Patients were randomized to receive heparin as a continuous infusion or methylprednisolone (0.75-1 mg x kg(-1) x day(-1)).\n Twenty-five patients entered the study: 13 received methylprednisolone and 12 received heparin. By day 10, 69% of patients in the methylprednisolone group, but none in the heparin group, achieved significant improvement or remission. C-reactive protein levels significantly decreased in the methylprednisolone group but not in the heparin group. Three patients in the heparin group were withdrawn before day 10 because of an adverse event: rectal bleeding needing transfusion (2 cases) or surgery (1 case). The proportion of patients with persistent rectal bleeding at day 10 was 31% in the methylprednisolone group and 90% in the heparin group (P<0.05).\n Unfractionated heparin as monotherapy is not effective in the treatment of moderate or severe ulcerative colitis and is associated with significant bleeding complications.", "Heparin could be beneficial to the treatment of active ulcerative colitis because of its anticoagulant, anti-inflammatory and immunomodulatory properties.\n To evaluate the tolerability, safety and efficacy of low-molecular-weight heparin as adjuvant therapy in patients with active ulcerative colitis.\n Thirty-four adult patients with active ulcerative colitis were consecutively included in a prospective, randomized, comparative study, and were treated for 12 weeks. Eighteen patients in the 'standard therapy' group were treated with aminosalicylates and weekly tapered corticosteroids. Sixteen patients in the 'heparin therapy' group were treated with standard therapy plus enoxaparin 100 Anti-Xa IU/kg/day subcutaneously.\n Seventeen patients in the 'standard therapy' group and 15 patients in the 'heparin therapy' group completed the study. Tolerability and compliance to therapy were excellent and no withdrawals were noted because of complications. There was a significant improvement in the disease severity in both groups (P<0.001), without any difference between them (P=not significant). Both treatment groups showed similar proportions of disease improvement (65% and 73%, respectively; P=not significant). There were no significant differences in inflammation (fibrinogen, ESR, CRP) and coagulation (thrombin-antithrombin complex, F1+2, D-dimers) parameters during and at the end of the study between treatment groups.\n Adjuvant administration of low-molecular heparin in patients with active ulcerative colitis is safe and well tolerated, but no additive benefit over standard therapy for ulcerative colitis was noted.", "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.", "Heparin has anti-inflammatory and immunomodulatory activity which may be of therapeutic benefit in the treatment of ulcerative colitis.\n To test whether low molecular weight heparin, given subcutaneously, would provide a significant therapeutic response compared with placebo in the treatment of mild to moderate ulcerative colitis.\n A prospective, double-blind, randomized, placebo-controlled, multi-centre trial comparing tinzaparin 175 anti-Xa IU/kg/day (innohep, LEO Pharma) subcutaneously for 14 days followed by tinzaparin 4500 anti-Xa IU/day subcutaneously for 28 days with placebo, administered subcutaneously once daily for up to 42 days. The primary outcome measure was the mean change in colitis activity from baseline to the end of study treatment assessed by the sum of scores of stool frequency, rectal bleeding, sigmoidoscopic appearance and histology. Secondary outcome measures included changes in individual activity indices and laboratory parameters. Patients were assessed at weekly intervals for 6 weeks and within 1 week of completing treatment.\n One hundred patients with active ulcerative colitis (up to six bloody stools per day, no fever, no tachycardia or systemic disturbances) were randomized. Forty-eight received tinzaparin and 52 received placebo. The difference in the mean percentage change in colitis activity from baseline to end of treatment (tinzaparin-placebo) was not statistically significant (P = 0.84). There was no difference between tinzaparin and placebo in any secondary outcome measure. One major bleed (rectal), occurred in a patient receiving placebo.\n This is the largest trial to date of heparin in ulcerative colitis. The results show no benefit of low molecular weight heparin over placebo in mild to moderately active ulcerative colitis.", "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." ]

[ "8473466", "8793522", "8018618", "10374092", "2115379", "8199102", "7672654", "9853762", "7994879", "10733017", "8690106", "7936386", "2533145", "8203435", "7784025", "2509250", "7618457" ]

[ "Pre-operative gonadotrophin-releasing hormone agonist treatment in surgery for uterine leiomyomata.", "The place of Zoladex in deferred surgery for uterine fibroids. Zoladex Myoma Study Group.", "Treatment with the gonadotrophin releasing hormone-agonist goserelin before hysterectomy for uterine fibroids.", "Laparoscopic myomectomy in premenopausal women with and without preoperative treatment using gonadotrophin-releasing hormone analogues.", "Treatment with GnRH agonists before myomectomy and the risk of short-term myoma recurrence.", "Deferred versus immediate surgery for uterine fibroids: clinical trial results.", "[Preoperative management of uterine leiomyomatosis using pituitary gonadotropin-releasing hormone analogues].", "Treatment with a gonadotrophin releasing hormone agonist before hysterectomy for leiomyomas: results of a multicentre, randomised controlled trial.", "Role of goserelin-depot in the clinical management of uterine fibroids.", "Leuprorelin depot 3.75 mg versus lynestrenol in the preoperative treatment of symptomatic uterine myomas: a multicentre randomised trial.", "Zoladex (goserelin acetate) and the anemic patient: results of a multicenter fibroid study.", "[Short-term treatment with leuprolide acetate depot before surgical intervention for uterine leiomyomatosis].", "Mechanism of LHRH analogue action in uterine fibroids.", "Gonadotropin-releasing hormone agonist use before hysterectomy.", "GnRH agonist and iron versus placebo and iron in the anemic patient before surgery for leiomyomas: a randomized controlled trial. Leuprolide Acetate Study Group.", "A randomized, placebo-controlled, double-blind study evaluating leuprolide acetate depot treatment before myomectomy.", "Trial of routine gonadotropin releasing hormone agonist treatment before abdominal hysterectomy for leiomyoma." ]

[ "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.", "Two hundred and forty-seven patients with uterine fibroids were randomized to surgery alone or 3 months' Zoladex (Zeneca, Macclesfield, Ches., UK) followed by surgery. Zoladex significantly reduced uterine and fibroid volumes (p = 0.0001). There was a significantly (p = 0.002) greater mean rise in haemoglobin from entry to preoperation in the Zoladex group (1 g/dl) compared with the surgery-alone group (0.3 g/dl) as well as a tendency towards easier surgery, and reduced operative blood loss. Zoladex-treated patients had a significantly (p = 0.016) shorter hospital stay and pelvic pain and abdominal pressure symptoms were significantly (p < 0.0001) reduced in this group. Zoladex was well tolerated.", "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.", "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.", "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.", "nan", "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 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.", "On 30 women suffering from uterine fibroids, the monthly subcutaneous administration of goserelin depot (3.6 mg) for 6 (n = 22) or 12 months (n = 8) induced an about 50% shrinkage of uterus and fibroid volume, and within 3 months, an increase in the haematocrit value, with no metabolic side effects or detectable bone demineralization, evaluated by single photon absortiometry at distal radius. Both uterine and fibroid volumes reversed to pretreatment values after 3 months of goserelin depot withdrawal. In comparison with untreated subjects, on another 10 patients a three month administration of goserelin depot reduced the loss of blood during the surgical removal of the uterus or fibroids. Present data indicate that goserelin depot is effective and relatively safe in the medical management of uterine fibroids. Although, goserelin depot cannot yet be proposed as a definite medical therapy, it may represent a useful instrument in the presurgical management of uterine fibroids.", "To compare the effect of the gonadotrophin-releasing hormone agonist leuprorelin and progestin lynestrenol, given prior to surgical treatment of symptomatic uterine myomas, on the pre-operative symptoms, tolerance, and operative blood loss.\n Fifty-six women were randomly selected to receive, during 16 weeks, either monthly subcutaneous injections of leuprorelin 3.75 mg sustained release (n=33) or lynestrenol 5 mg two tabs per day (5th to the 25th menstrual cycle) (n=23).\n Intent-to-treat analysis of the main efficacy criterion, namely ultrasonographic reduction of myoma(s) diameter, showed a significant difference in favour of leuprorelin (P=0.02) with a mean decrease of 26.5+/-4.5% (n=29) as opposed to 7.3+/-5% in the lynestrenol group (n=17). Clinical improvement was satisfactory in both groups. Hematocrit decrease between the preoperative value and the value measured 48 h postoperatively was significantly lower in the leuprorelin group than in the lynestrenol one (P=0.02) (for hemoglobin: P=0.07).\n Leuprorelin was more effective than lynestrenol because of its more intense antigonadotropic activity. The tolerance was good, reflecting each drug mechanism of action.", "To compare the effects of goserelin acetate treatment with or without iron with iron alone.\n Multinational, multicenter, prospective, randomized, double-blind study.\n Premenopausal women with menorrhagia or metrorrhagia and anemia associated with uterine leiomyomata awaiting hysterectomy.\n Patients were randomized to one of three 12-week treatment groups namely goserelin acetate 3.6 mg once monthly plus placebo iron; 3.6 mg goserelin acetate once monthly plus 600 mg/d iron; or sham injection once monthly plus 600 mg/d iron.\n Preoperative hemoglobin concentration; preoperative uterine and fibroid volumes and operative blood loss.\n Considering the entry and preoperative hemoglobin concentrations, there was a difference in least square means of just over 1 g/dL between the goserelin acetate plus iron and iron only groups and 2.6 g/dL between the goserelin acetate plus iron and goserelin acetate only group. These differences were both statistically significant. Uterine and fibroid volumes were decreased in the goserelin acetate-treated patients by between 37% and 40% and 44% and 47%, respectively, compared with 7% decreases for both in the iron only group. The differences in absolute changes were statistically significant for both the goserelin acetate-treated groups versus the iron-treated group. The least square geometric mean operative blood loss was greatest in the iron only group.\n In the patient with uterine leiomyomata and anemia, goserelin acetate in combination with iron therapy has shown significant advantages over the iron alone in restoring hematologic normality, decreasing uterine and fibroid volumes, and reducing operative blood loss.", "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\".", "Luteinising hormone-releasing hormone analogues have been found to reduce the size of uterine fibroids. Further studies are required to determine their exact mechanism of action. However, they are known to induce hypo-oestrogenism, which leads to reduction in uterine arterial blood flow, one mechanism by which reduction of fibroid size is thought to occur.", "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.", "To determine the effectiveness of leuprolide acetate depot plus iron compared with iron alone in the preoperative treatment of anemia due to prolonged or excessive bleeding associated with uterine leiomyomas.\n This was a phase III, stratified, randomized, double-blind, placebo-controlled, parallel-group, 12-week multicenter study. Enrolled patients had hemoglobin levels of 10.2 g/dL or less and/or hematocrit values of 30% or less. Patients were entered into one of two strata based on their pre-study hematocrit level: stratum A, hematocrit less than or equal to 28%, and stratum B, hematocrit greater than 28%. Patients within each stratum were randomized to one of three treatment arms: leuprolide acetate depot 7.5 mg, leuprolide acetate depot 3.75 mg, or placebo. All patients received iron orally. Response was defined as a hemoglobin level of 12 g/dL or more and a hematocrit value of 36% or greater.\n Three hundred nine patients were entered into the study, of whom 265 were evaluated. Using our response criteria, a significantly greater number of patients in both leuprolide acetate groups (combined strata) responded to therapy than did those in the placebo group: 74% in each leuprolide acetate group versus 46% in the placebo group (P < .001). Gonadotropin-releasing hormone agonist-treated patients had a significant reduction in uterine and myoma volume when compared with the placebo group (P < .01). Hot flashes and vaginitis were reported significantly more often (P < .001) in the leuprolide acetate-treated groups than in the placebo group.\n Both dosages of GnRH agonist plus iron were more effective than iron alone in treating the anemia of patients with uterine leiomyomas, in reducing uterine-myoma volume, and in alleviating bleeding and other leiomyoma-related symptoms.", "Eighteen premenopausal women with symptomatic leiomyomata uteri were enrolled in a stratified, randomized, double-blind, placebo-controlled study evaluating the efficacy of leuprolide acetate (LA) depot treatment before myomectomy. Stratification was based on pretreatment uterine volume (less than 600 cm3 versus greater than or equal to 600 cm3). Nine women received intramuscular (IM) depot LA 3.75 mg every 4 weeks for 12 weeks (group A); nine women received IM placebo with the same injection schedule (group B). All women underwent myomectomy within 4 weeks of their last injection. Mean total intraoperative blood loss was 213 +/- 44 mL (mean +/- standard error of the mean [SEM]) in group A and 302 +/- 43 mL in group B. When data from patients with large uteri (pretreatment uterine volumes of 600 cm3 or greater) were analyzed, mean total blood loss was 189 +/- 44 mL in group A and 390 +/- 20 mL in group B. These data suggest that leuprolide depot treatment before myomectomy may decrease intraoperative blood loss in women with large leiomyomata uteri.", "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." ]

[ "16698351", "12798892", "15082950", "6601789", "1637766", "3877785", "17364305", "7562226", "3545246", "3872439", "15620492", "12103366" ]

[ "Assessment of efficacy of transcutaneous electrical nerve stimulation for pain management during office-based flexible cystoscopy.", "Suppression of pelvic pain during hysteroscopy with a transcutaneous electrical nerve stimulation device.", "Evaluation of TENS during screening flexible sigmoidoscopy.", "Transcutaneous electrical nerve stimulation (TENS) as compared to placebo TENS for the relief of acute oro-facial pain.", "Is transcutaneous electrical nerve stimulation of any value during cervical laser treatment?", "Effect of transcutaneous electrical nerve stimulation for post-thoracotomic pain.", "A comparison of high- versus low-intensity, high-frequency transcutaneous electric nerve stimulation for painful postpartum uterine contractions.", "Transcutaneous electrical nerve stimulator for procedural pain associated with intravenous needlesticks.", "Transcutaneous electrical nerve stimulation versus oral analgesic: a randomized double-blind controlled study in acute traumatic pain.", "Modification of haemophiliac haemorrhage pain by transcutaneous electrical nerve stimulation.", "Transcutaneous electrical nerve stimulation for neuropathic pain.", "Transcutaneous electrical nerve stimulation for pain management in patients with uncomplicated minor rib fractures." ]

[ "To evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) for its effectiveness in eliminating or minimizing discomfort during office-based flexible cystoscopy.\n A total of 148 patients were prospectively randomized into one of three groups: flexible cystoscopy with no analgesics, a placebo TENS, or an activated TENS. The patient data collected included patient parameters, number of previous flexible cystoscopies, visual analog pain scores during and after the procedure, surgeon's difficulty rating of procedure, and International Prostate Symptom Score before and 24 hours after the procedure.\n No statistically significant difference was found among the three groups regarding patient parameters. The visual analog pain scores were similar before and after the procedure. At 30 seconds, the mean visual analog scale score for the control group, placebo group, and TENS study group was 3.73, 3.65, and 3.52, respectively (control versus placebo, control versus active, and placebo versus active: P = 0.97, 0.29, and 0.53, respectively). At 1 and 5 minutes, the corresponding scores were 3.44, 4.37, and 3.50 (P = 0.88, P = 0.99, and P = 0.99) and 0.86, 1.23, and 0.88 (P = 0.97, P = 0.35, and P = 0.56), respectively. The surgeon's mean difficulty rating for the control procedures was 1.08 and for the placebo group was 2.30 (P = 0.02).\n All patients undergoing flexible cystoscopy in the office setting experienced discomfort. The TENS device provided no significant benefit for pain. The trend toward greater pain scores in the control group could be attributed to the greater degree of difficulty.", "To evaluate the effectiveness of transcutaneous electrical nerve stimulation (TENS) as a pain control method during office hysteroscopy.\n A prospective, randomized study.\n Centre for Minimally Invasive Surgery, Department of Gynecological Science and Perinatology, \"La Sapienza\" University, Rome, Italy.\n One hundred forty-two patients undergoing office hysteroscopy.\n Application of a TENS device on the patient's abdomen before and during office hysteroscopy.\n The level of pain experienced by the patients was assessed using a 10 cm visual analog scale; the side effects and changes in the hemodynamic parameters were evaluated.\n The patients treated with TENS during hysteroscopy (group A, n = 71) were compared with a control group (group B, n = 71) on whom the TENS device was not used. The women in the TENS group experienced a significantly lower level of pain during hysteroscopy. No differences in side effects were observed between both group.\n TENS is a simple, efficient, and safe method of relieve pain during office hysteroscopy.", "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.", "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.", "To assess the value of transcutaneous electrical nerve stimulation (TENS) during cervical laser therapy.\n Randomized three arm controlled clinical trial comparing (i) TENS, (ii) local anaesthetic and (iii) TENS plus local anaesthetic (direct infiltration of 2% lignocaine and 0.03 iu/ml octopressin).\n Colposcopy Unit adapted to run randomized trials.\n 100 women with CIN and no previous experience of cervical surgery.\n Visual linear analogue pain scores.\n The median pain score associated with TENS was greater than the score associated with local anaesthesia (23% compared with 17%; P = 0.1). Combining TENS with local anaesthesia did not further reduce pain scores.\n Although there was considerable consumer satisfaction with TENS it provided no additional pain relieving effect in addition to direct infiltration of lignocaine and it is inferior to lignocaine alone. We are unable to advocate the use of TENS for laser treatment of the cervix.", "nan", "Breast-feeding in the postpartum period is known to induce intense uterine contractions with pain in the lower abdomen.\n The primary aim of this study was to compare the effects of high and low intensity, high frequency Transcutaneous Electric Nerve Stimulation (TENS) on pain and discomfort of postpartum uterine contractions. The secondary aim was to evaluate discomfort experienced from the stimulation itself.\n Twenty-one newly delivered women participated in this single-blind trial, 12 women received high intensity, high-frequency TENS (HI TENS) and 9 women received low intensity, high-frequency TENS (LI TENS). The electrodes were placed abdominally on each side of the uterus. Stimulation was done during one minute. Visual analogue scales were used to evaluate the intensity of the pain before and after stimulation. A verbal scale was used to estimate sensation of discomfort before, during and after stimulation.\n The median decrease in pain ratings before and after treatment by VAS was larger in the HI TENS group -49 mm (95% CI -66.5--33.2) than in the LI TENS group -21 mm (95% CI -39.0--20.0). The reduction of pain was most pronounced in the HI TENS group (median difference 28 (95% CI was 14.0-53.0). Furthermore, the HI TENS group experienced significantly less discomfort of the uterine contractions after stimulation (p<0.01) but they also experienced more discomfort of the stimulation than women in the LI TENS group (p<0.01).\n The women treated with HI TENS, experienced significantly less postpartum pain and discomfort to those treated with LI TENS even though the discomfort from the stimulation with HI TENS was greater.", "Venipuncture continues to be considered a painful and unpleasant experience for those receiving medical treatment. A prospective study investigating whether the application of a transcutaneous electrical nerve stimulator (TENS) decreases the complaints of pain and unpleasantness with i.v. needle insertion was conducted using a group of 71 subjects who were double-blinded and randomized to one of three groups: TENS, placebo-TENS, and control. This article gives an overview of this research and describes its findings.", "A double-blind controlled analgesic study was undertaken in outpatients suffering acute traumatic pain. One hundred patients completed the study and were randomly assigned to four treatment groups, each receiving either functioning transcutaneous electrical nerve stimulators (TENS), placebo TENS, acetaminophen with codeine and a functioning TENS, or acetaminophen with codeine and a placebo TENS. Pain was assessed prior to treatment, at 48 hours, and at one month using a visual analog scale. A statistically significant difference in pain relief occurred between the placebo and functioning TENS groups. The TENS was approximately as effective as acetaminophen (300-600 mg) with codeine (30-60 mg) but had no side effects. Transcutaneous electrical nerve stimulators have been shown to be effective in the management of acute traumatic pain and may be indicated for patients who cannot be given medications.", "Haemophiliacs suffer considerable pain when they bleed into their joints. This study investigated the use of transcutaneous electrical nerve stimulation (TENS) for relief of such pain. Thirty-six haemophiliac patients received either active or placebo TENS treatment. The intensity of pain was assessed before and after treatment using the McGill Pain Questionnaire. After 25 min of active treatment, 71% of the subjects reported at least 50% pain relief as measured by the McGill Pain Questionnaire. This compares with only 25% pain relief experienced by the placebo group.", "This study examined the clinical effectiveness of high-frequency transcutaneous electrical nerve stimulation for reducing hypersensitivity of the hand. Nineteen patients suffering from hand hypersensitivity were randomly assigned into either a treatment or a placebo group. A visual analogue scale and the Downey Hand Centre Hand Sensitivity Test were used to measure the tactile tolerance of the hand. Grip strength was assessed by a grip dynamometer. Daily applications of electrical stimulation were provided for 2 weeks. Significantly lower pain scores were found in the treatment group than in the placebo group by Day 7 and Day 11. The ranking of ten dowel textures of the Downey Hand Centre Hand Sensitivity Test in the treatment group was significantly higher than in the placebo group by Day 7 and Day 11. However, no significant inter-group difference was found in grip strength.", "Few non-surgical conditions are more painful than rib fractures. There are a few methods for pain relief in patients with minor rib fractures.\n We used a non-steroidal anti-inflammatory drug (NSAID, Naproxen sodium) and transcutaneous electrical nerve stimulator (TENS) to control pain of the patients with uncomplicated minor rib fractures. One hundred consecutive patients admitted to Kartal Education and Research Hospital Emergency Service, were randomized into four groups. The patients were assigned to one of the following pain treatments: NSAID, TENS, NSAID plus inactive TENS or placebo. The patients used NSAIDs and placebo four times a day and TENS twice a day for 3 days. All patients were asked to assess their pain level with a scoring system on days 0, 1 and 3.\n The most effective treatment was TENS on days 1 and 3 (P<0.05). Although NSAID and NSAID plus inactive TENS controlled pain better than placebo on day 1 (P<0.05), this superiority did not continue to day 3 (P>0.05). There was no difference between NSAID and NSAID plus inactive TENS in controlling pain on either days 1 or 3.\n We conclude that TENS was more effective than NSAID or placebo in patients with uncomplicated minor rib fractures, because of its prominent and admirable efficacy in reduction of pain." ]

[ "782464", "3067098", "16820790", "16306519", "18596121", "12209517", "1356175", "21912022", "19478041", "10470708", "20605876", "7272867", "7045314", "20169461", "8815753", "16221103", "7920609", "11863119", "3511372", "4695164", "20833738", "15082482", "9886795", "1106277", "1458919", "11036121", "21177013", "309095", "7985937", "9569080", "19369404", "11854810" ]

[ "Prednisone and azathioprine compared to prednisone plus low-dose azathioprine and cyclophosphamide in the treatment of diffuse lupus nephritis.", "Prospective multicentre trial on the short-term effects of plasma exchange versus cytotoxic drugs in steroid-resistant lupus nephritis.", "Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial.", "Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis.", "Successful treatment of class V+IV lupus nephritis with multitarget therapy.", "Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide.", "Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis.", "Comparison of high and low dose of cyclophosphamide in lupus nephritis patients: a long-term randomized controlled trial.", "Is combination rituximab with cyclophosphamide better than rituximab alone in the treatment of lupus nephritis?", "Intravenous immunoglobulin compared with cyclophosphamide for proliferative lupus nephritis.", "Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study.", "Monthly plasmapheresis for systemic lupus erythematosus with diffuse proliferative glomerulonephritis: a pilot study.", "Pulse methylprednisolone therapy in diffuse proliferative lupus nephritis.", "Is mycophenolate mofetil superior to pulse intravenous cyclophosphamide for induction therapy of proliferative lupus nephritis in Egyptian patients?", "Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial.", "Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis.", "A controlled trial of pulse cyclophosphamide versus pulse methylprednisolone in severe lupus nephritis.", "Comparative effects of plasmapheresis and intravenous cyclophosphamide on urinary podocyte excretion in patients with proliferative Lupus nephritis.", "Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs.", "Comparison of azathioprine, prednisone, and heparin alone or combined in treating lupus nephritis.", "Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial.", "EULAR randomised controlled trial of pulse cyclophosphamide and methylprednisolone versus continuous cyclophosphamide and prednisolone followed by azathioprine and prednisolone in lupus nephritis.", "Randomized controlled trial of pulse/synchronization cyclophosphamide/apheresis for proliferative lupus nephritis.", "Azathioprine plus prednisone compared with prednisone alone in the treatment of systemic lupus erythematosus. Report of a prospective controlled trial in 24 patients.", "Ciclosporin plus steroids versus steroids alone in the treatment of lupus nephritis.", "Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group.", "Short-term outcomes of induction therapy with tacrolimus versus cyclophosphamide for active lupus nephritis: A multicenter randomized clinical trial.", "Treatment of diffuse proliferative lupus nephritis with prednisone and combined prednisone and cyclophosphamide.", "Therapy of lupus nephritis. A two-year prospective study.", "Clinical efficacy of cyclosporin a neoral in the treatment of paediatric lupus nephritis with heavy proteinuria.", "Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis.", "Misoprostol and Prednisone Treatment of Lupus Nephritis." ]

[ "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.", "nan", "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.", "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.", "Treatment of class V+IV lupus nephritis remains unsatisfactory despite the progress made in the treatment of diffuse proliferative lupus nephritis. In this prospective study, 40 patients with class V+IV lupus nephritis were randomly assigned to induction therapy with mycophenolate mofetil, tacrolimus, and steroids (multitarget therapy) or intravenous cyclophosphamide (IVCY). Patients were treated for 6 mo unless complete remission was not achieved, in which case treatment was extended to 9 mo. An intention-to-treat analysis revealed a higher rate of complete remission with multitarget therapy at both 6 and 9 mo (50 and 65%, respectively) than with IVCY (5 and 15%, respectively). At 6 mo, eight (40%) patients in each group experienced partial remission, and at 9 mo, six (30%) patients receiving multitarget therapy and eight (40%) patients receiving IVCY experienced partial remission. There were no deaths during this study. Most adverse events were less frequent in the multitarget therapy group. Calcineurin inhibitor nephrotoxicity was not observed, but three patients developed new-onset hypertension with multitarget therapy. In conclusion, multitarget therapy is superior to IVCY for inducing complete remission of class V+IV lupus nephritis and is well tolerated.", "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.", "Pulse cyclophosphamide is more effective than prednisone alone in preventing renal failure in lupus nephritis. We undertook a randomised, controlled trial to find out whether pulse methylprednisolone could equal pulse cyclophosphamide in preserving renal function in patients with lupus nephritis, and whether there was a difference between long and short courses of pulse cyclophosphamide in preventing exacerbations. 65 patients (60 female, 5 male; median [range] age 29 [10-48] years) with severe lupus nephritis were assigned randomly to monthly pulse methylprednisolone for 6 months (25 patients), monthly pulse cyclophosphamide for 6 months (20), or monthly cyclophosphamide for 6 months followed by quarterly pulse cyclophosphamide for 2 additional years (20). Patients treated with pulse methylprednisolone had a higher probability of doubling serum creatinine than those treated with long-course cyclophosphamide (p less than 0.04). Risk of doubling creatinine was not significantly different between short and long course cyclophosphamide. However, patients treated with short-course cyclophosphamide had a higher probability of exacerbations than those treated with long-course cyclophosphamide (p less than 0.01). An extended course of pulse cyclophosphamide is more effective than 6 months of pulse methylprednisolone in preserving renal function in patients with severe lupus nephritis. Addition of a quarterly maintenance regimen to monthly pulse cyclophosphamide reduces the rate of exacerbations.", "To evaluate the outcome of low doses of cyclophosphamide (Cyclo) therapy in lupus nephritis (LN) patients, we studied 117 biopsy-proven, de novo LN WHO class IV patients double-blinded and randomized in December 1997 to receive Cyclo in different doses; Group I (n=73) received Cyclo 10 mg/kg monthly for six months then every two months for 12 months. Group II (n=44) received Cyclo 5 mg/kg monthly for six months then every two months for 36 months. The patients were followed-up till January 2007. Six months post-induction values for creatinine clearance were significantly higher in Group I (67.7 ± 28.6 mL/min) compared with Group II (55.1 ± 30.1 mL/min), P = 0.026. Serum C4 and ANA were not significantly different between the groups (P > 0.05). At the mean follow-up of 6.77 ± 3.3 years, the mean creatinine clearance was 44.74 ± 31.7 mL/min in Group I vs. 49.3 ± 38.8 in Group II. Urinary protein was 1.65 ± 1.8 g/dL in Group I vs. 1.02 ± 1.01 in Group II (P = 0.03). The survival curve showed that kidney survival overtime was comparable in both groups (P = 0.2). Complete remission was observed in 25 (34.2%) patients in Group I vs. 11 (25%) in Group II (P = 0.288), while partial remission was similar in both groups; 43 (58.9%) patients in Group I vs. 26 (59%) patients in Group II. End-stage renal disease was observed in 10 (13.7%) patients in Group I vs. 9 (20.4%) patients in Group II (P = 0.359). Side-effects were more frequent in Group I patients than in Group II patients; gonadal toxicity and malignancy were lower in Group II patients (P = 0.0000). Moreover, different infections occurred in 23 (31.3%) patients vs. six (13.6%), digital infarcts occurred in 1.35% vs. 0%, diabetes in 4.1% vs. 2.27%, and vasculitis in 4.1% vs. 2.27% in Group I vs. Group II, respectively. Sustained amenorrhea without pregnancy was observed in both groups; however, significantly more in Group I patients, P ≤ 0.05. We conclude that low-dose Cyclo therapy is sufficiently effective for WHO class IV LN patients with lower side-effects compared with standard dose.", "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.", "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.", "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)", "Twelve patients with systemic lupus erythematosus and biopsy-proved diffuse proliferative glomerulonephritis were randomly allocated to a control group (to continue receiving conventional therapy only) or to a plasmapheresis group (to receive conventional therapy along with one 4-I plasma exchange a month). The six patients treated with plasmapheresis had better preservation of renal function, reduced disease activity, fewer admissions to hospital and less need for steroid and immunosuppressive therapy than the six control patients. The patients treated with plasmapheresis also showed evidence of reduced immunologic activity and had no side effects attributable to the plasma exchange. These results suggest that monthly plasma exchange should be assessed in a controlled randomized trial as a possible therapeutic adjunct in patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis.", "The prognosis of patients with diffuse proliferative lupus nephritis is generally poor, and the majority of patients with this lesion develop progressive deterioration in renal function. Intravenous \"pulses\" of methylprednisolone have been advocated for the treatment of severe nephritis. In this study, 15 patients with biopsy-proven diffuse proliferative lupus nephritis were treated with oral high-dose prednisone therapy, initially 2 mg/kg/day. They were compared with seven patients with similar renal pathology treated with six daily pulses of methylprednisolone (30 mg/kg/day, not to exceed 1 gm/day), followed by prednisone orally, initially 2 mg/kg/day. There were no deaths in either group and the side effects of therapy were similar in the two groups. Pretreatment GFRs for the pulse and high-dose groups were similar. There was a more rapid improvement in GFR following pulse therapy, but the long-term effects on renal function for the two modes of therapy were the same.", "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.", "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.", "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.", "We carried out a prospective randomized trial comparing pulse cyclophosphamide and pulse methylprednisolone in 29 patients with severe lupus nephritis in activity. Patients were assigned to one of two regimens: monthly pulse cyclophosphamide (0.5-1.0 g/m2 body surface area) for 4 months, followed by bimonthly doses for 4 months and quarterly doses for 6 months (14 patients) or pulse methylprednisolone (10-20 mg/kg weight) initially for 3 consecutive days and thereafter in the same intervals as the alternative regimen (15 patients). The mean follow-up was 15 months. Two patients in the cyclophosphamide group and three in the methylprednisolone group died. Renal failure (doubling of serum creatinine) developed in four patients in the cyclophosphamide group compared with five patients in the methylprednisolone group. Cumulative probability of not doubling serum creatinine was similar for cyclophosphamide and methylprednisolone groups (0.66 vs 0.69, respectively, P > 0.20, after 18 months). Cumulative probability of survival without renal failure was also not significantly different (0.61 and 0.63, respectively, P > 0.20, after 18 months). These results suggest that pulse cyclophosphamide is as effective as pulse methylprednisolone in preserving renal function in patients with severe lupus nephritis.", "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.", "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.", "nan", "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.", "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.", "To assess the efficacy of pulse/synchronization cyclophosphamide/apheresis in patients with proliferative lupus nephritis.\n Eighteen patients with Class III or IV renal biopsies and chronicity indices <6 were prospectively randomized to receive 6 courses of parenteral cyclophosphamide over 8 months along with prednisone. Nine of these patients also received 3 daily plasmaphereses prior to each of the 6 courses of cyclophosphamide. Assessments compiled at 6 and 24 months included serum creatinine, albumin, anti DNA, 24-hour urine protein, and C3 complement along with SLAM scores.\n Two out of nine patients in each group evolved end stage renal disease and 3/9 patients in each group went into a renal remission at 24 months. Serum albumin, C3 complement, and SLAM scores improved in both groups, and anti-DNA improved in the pulse/synchronization patients (P < 0.025). No intergroup comparisons were significant.\n The addition of pulse/synchronization apheresis to cyclophosphamide therapy does not improve the course of patients with proliferative lupus nephritis.", "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.", "nan", "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.", "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 © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.", "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.", "The aim of our study was to compare the efficacy of 3 different therapeutic protocols in the treatment of patients with WHO class IV lupus nephritis and normal renal function. We carried out a randomized prospective trial. The treatment programs consisted of a standard therapy regimen alone (protocol A), plus plasmapheresis (protocol B) or pulse methylprednisolone (protocol C), followed by a slow (protocols A and B) or fast (protocol C) prednisone tapering schedule. Statistical analysis was performed, using univariate survival analysis according to Kaplan Meier and Breslow's test to compare survival curves. Eighteen patients entered the study: 6 protocol A, 5 protocol B and 7 protocol C. No patients developed renal insufficiency. Moreover, no statistical differences in the probability of inducing partial or complete disease remission and in reducing 24-hour urinary protein excretion to < or = 2 g per day were observed among the groups. Protocols A and B were more effective in comparison with protocol C in decreasing 24-hour urinary protein excretion to < or = 0.5 g and < or = 0.2 g per day. In conclusion, a slow prednisone tapering schedule is more effective in reducing 24-hour urinary protein excretion to < or = 0.5 and < or = 0.2 g per day as compared with a fast prednisone tapering schedule, even if it is preceded by methylprednisolone pulse therapy.", "Cyclosporin A (CsA) was introduced in recent years for the treatment of lupus nephritis in patients with steroid resistance or in those with severe corticosteroid toxicity. Our previous study on paediatric patients showed that Neoral (a new microemulsion formulation) had better bioavailability than CsA capsules. To evaluate the clinical efficacy of Neoral in children with lupus nephritis compared with conventional therapy, we performed an open randomized study on 40 children, ranging from 9 to 14 yr old, with class III-V lupus nephritis and heavy proteinuria. They were randomly assigned to either Neoral (5 mg/kg/day), administered q.12.h, or prednisolone (2 mg/kg/day) plus cyclophosphamide (2 mg/kg/day) for 1 yr. Both groups showed a significant decrease in proteinuria (Neoral: 4.62 +/- 1.93 to 0.35 +/- 0.29 g/day, P < 0.05; prednisolone plus cyclophosphamide: 4.52 +/- 1.86 to 0.62 +/- 0.21 g/day, P < 0.01). The CH50 haemolytic assay titre decreased after 1 yr of Neoral treatment (26.5 +/- 0.9 to 21.4 +/- 2.2 U/ml, P < 0.05). Serum C3 and anti-double-stranded (ds) DNA antibody levels also fell with Neoral (C3: 86.2 +/- 6.8 to 76.3 +/- 4.5 mg/dl; anti-ds DNA antibodies: 14.1 +/- 3.2 to 8.2 +/- 1.4 IU/ml, P < 0.05). The Neoral group had a significant increase in growth rate over the prednisolone plus cyclophosphamide group (8.2 +/- 1.1 cm/yr vs 2.7 +/- 0.6 cm/yr, P < 0.01) with improvement of growth status. During the study period, patients tolerated Neoral well with no significant changes in renal function, liver function or lipid profile. Our study implies that Neoral appears to be effective in suppressing proteinuria. Neoral should be regarded as being adjunctive therapy, perhaps with a steroid-sparing effect, in paediatric lupus nephritis. However, its long-term use awaits further studies.", "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.", "Fourteen patients were enrolled in a placebo-controlled double-blind randomized trial of 8 weeks of treatment for active lupus nephritis. Seven patients received prednisone at a dose of 1 mg kg(minus sign1) day(minus sign1) plus misoprostol at a dose of 200 &mgr;g P.O. Q.I.D.; 7 patients received prednisone plus placebo. The patients included 12 females, 2 males; 3 African-Americans, 3 Asians, 5 Hispanics, and 3 Caucasians. There were no serious side effects associated with prednisone or misoprostol treatment during the 8-week study period. Laboratory measures obtained at baseline, 4, 8, and 12 weeks included complete blood count (CBC), ESR, C reactive protein (CRP), serum creatinine, creatinine clearance, 24-h urine protein excretion, C3, C4, and anti-double stranded DNA (anti-dsDNA). Statistical analysis was conducted assessing change in measures over time in the entire study group by paired t-tests. The effect of treatment on change over time was examined by analysis of covariance. Log transformation of the variables was performed prior to statistical analysis. For the entire study group, the mean levels of ESR, CRP, 24-h protein excretion, C3, C4, and anti-dsDNA were improved at 4, 8, and 12 weeks. The mean ESR at baseline was 70 plus minus 8 compared to 42 plus minus 8 at 12 weeks (p < 0.01). The mean CRP at baseline was 0.6 plus minus 0.2 compared to 0.2 plus minus 0.1 at 12 weeks (p < 0.01). The 24-h protein excretion was 4367 plus minus 769 mg at baseline compared to 2512 plus minus 709 mg at 12 weeks (p = 0.02). The mean C3 at baseline was 40 plus minus 4 mg dl(minus sign1) compared to 60 plus minus 4 mg dl(minus sign1) at 12 weeks (p < 0.01). The mean C4 at baseline was 14 plus minus 1 mg dl(minus sign1) compared to 23 plus minus 2 mg dl(minus sign1) at 12 weeks (p < 0.01). The mean anti-dsDNA at baseline was 4268 plus minus 1780 compared to 316 plus minus 111 at 12 weeks (p < 0.001). The baseline serum creatinine (1.12 plus minus.15 mg dl(minus sign1)) and creatinine clearance (82 plus minus 15 ml min(minus sign1)) were not significantly changed at 12 weeks (1.10 plus minus 0.2 mg dl(minus sign1) and 80 plus minus 17 ml min(minus sign1), respectively). Comparing the misoprostol treatment group to the placebo group, there were no statistically significant differences for ESR, CRP, creatinine, creatinine clearance, 24-h protein excretion, C3, C4, or anti-dsDNA at any time points. However, comparing the misoprostol treatment group at 4 weeks to the placebo group, a more rapid decrease in anti-dsDNA (reduction of 3297 plus minus 2374) was observed in the misoprostol treatment group versus 304 plus minus 409 in the placebo group), as well as lower mean anti-dsDNA levels (464 plus minus 140) in the misoprostol treatment group versus 4118 plus minus 3834 in the placebo group). Also, the C3 and C4 levels at 12 weeks in the misoprostol treatment group (67 plus minus 5 and 27 plus minus 3 mg dl(minus sign1), respectively) were greater than levels in the placebo group (52 plus minus 4 and 19 plus minus 3 mg dl(minus sign1), respectively). The data demonstrate that oral prednisone is effective in reducing proteinuria and improving the biological markers of disease activity (i.e., ESR, CRP, C3, C4, and anti-dsDNA) following short-term treatment of active lupus nephritis. Additionally, the more rapid change in anti-dsDNA levels and superior normalization of complement levels in the treatment group, although not statistically significant, are consistent with a biologic effect of misoprostol on lymphocyte function and the production of a pathogenic autoantibodies." ]

[ "19216661", "345174", "16269029", "12755982", "105096", "19647206", "17391302", "105097", "17285269", "19124628", "17438178", "19488646", "20519098", "321087", "16472981", "19926502", "6366166", "342850", "22467697", "105101", "20136677", "19699111", "105098" ]

[ "The effect of beta-glucan on recurrent aphthous stomatitis.", "A randomized double-blind trial of levamisole in the therapy of recurrent aphthous stomatitis.", "Norwegian LongoVital and recurrent aphthous ulceration: a randomized, double-blind, placebo-controlled study.", "Recurrent aphthous stomatitis unresponsive to topical corticosteroids: a study of the comparative therapeutic effects of systemic prednisone and systemic sulodexide.", "Double-blind trial of tetracycline in recurrent aphthous ulceration.", "Homeopathic treatment of minor aphthous ulcer: a randomized, placebo-controlled clinical trial.", "Subantimicrobial dose doxycycline in the treatment of recurrent oral aphthous ulceration: a pilot study.", "Effect of levamisole on the incidence and prevalence of recurrent aphthous stomatitis. A double-blind clinical trial.", "The effect of bee propolis on recurrent aphthous stomatitis: a pilot study.", "Effectiveness of vitamin B12 in treating recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled trial.", "A randomized, double-blind, placebo-controlled trial of pentoxifylline for the treatment of recurrent aphthous stomatitis.", "[Levamisole does not prevent lesions of recurrent aphthous stomatitis: a double-blind placebo-controlled clinical trial].", "Comparison of colchicine versus prednisolone in recurrent aphthous stomatitis: A double-blind randomized clinical trial.", "Levamisole in aphthous stomatitis: evaluation of three regimens.", "Effects of cooking plant oils on recurrent aphthous stomatitis: a randomized, placebo-controlled, double-blind trial.", "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.", "Therapeutic evaluation of levamisole in recurrent aphthous stomatitis. Double-blind comparison of two dosage schedules of levamisole and placebo.", "Levamisole in the treatment of recurrent aphthous stomatitis.", "Multivitamin therapy for recurrent aphthous stomatitis: a randomized, double-masked, placebo-controlled trial.", "Randomized, double-blind study of levamisole in recurrent aphthous stomatitis.", "Effects of camel thorn distillate on recurrent oral aphthous lesions.", "Treatment of recurrent aphthous stomatitis with clofazimine.", "Double-blind study of levamisole therapy in recurrent aphthous stomatitis." ]

[ "nan", "A Controlled, double-blind study was performed to compare the effects of levamisole and placebo in eighteen patients with recurrent aphthous stomatitis. Levamisole is a drug which enhances defective cellular immune responses. It was administered in a flexible dosage schedule: 50 mg. three times daily for three consecutive days at the start of an aphthous lesion but with an interval of at least 2 weeks between courses of therapy. Placebo consisted of pills that were identical in appearance, taken according to the same schedule. Statistical evaluation showed decreased frequency of lesions, shorter duration, and diminished pain of lesions in the group receiving levamisole. Subsequent follow-up in an open trial confirmed these results.", "LongoVital (LV) is a herbal-based tablet enriched with the recommended daily doses of vitamins. The present study was undertaken to investigate possible prevention of recurrent aphthous ulceration (RAU) during 4 months daily intake of the Norwegian LV.\n The study was a placebo-controlled, double-blind, randomized, clinical trial.\n Sixty otherwise healthy patients with at least one attack of minor RAU per 2 months were included in the study.\n After an introduction period (IP) of 60 days, the patients were randomly divided into three groups and given either LV, the herbs of LV only, or placebo. Three test tablets were taken every day together with breakfast for 4 months [tablet period (TP)] and the patients followed up for another 4 months (F-UP). The number of new ulcers (NU) and ulcer-free days (UFD) were observed.\n Fifty-two patients completed the study. Neither NU nor UFD showed any statistical significant differences between any of the groups in any of the periods. All three groups, however, showed a significant increase in UFD during the first 2 months of TP compared to IP. Within the LV group only, there was a further increase in UFD after 2 months intake of the tablets. The number of NU and UFD decreased significantly in both the LV and the herbal group in F-UP compared with TP.\n Neither the Norwegian LV nor the herbal component alone was superior to placebo in the prevention of RAU. The results, however, indicate that neither the LV nor the herbal group benefited from the treatment.", "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.", "A double-blind trial of a tetracycline suspension was carried out in 25 patients with recurrent aphthous oral ulcerations. A combined topical-systemic treatment procedure was used. Both the placebo and tetracycline group experienced reductions in ulcer incidence during the treatment period, whereas only the tetracycline group showed significant reductions in ulcer duration, size, and pain. Tetracylcine treatment apparently alters the severity of the ulcer, but does not appear to affect those factors responsible for recurrences. The side effects recorded in patients taking tetracycline were comparable to those in patients on placebo.", "The objectives of this study were to clinically determine the efficacy of individualised homeopathy in the treatment of minor recurrent aphthous ulceration (MiRAU).\n A randomized, single blind, placebo-controlled clinical trial of individualised homeopathy. One hundred patients with minor aphthous ulcer were treated with individualised homeopathic medicines or placebo and followed up for 6 days. Patients received two doses of individualised homeopathic medicines in the 6C potency as oral liquid at baseline and 12 h later. Pain intensity and ulcer size were recorded at baseline during and at the end of the trial (mornings of days 4 and 6).\n All 100 patients completed treatment. Between group differences for pain intensity and ulcer size were statistically significant at day 4 and at day 6 (P<0.05). No adverse effects were reported.\n The results suggest that homeopathic treatment is an effective and safe method in the treatment of MiRAU.", "Recurrent oral aphthous ulceration (ROAU) is a common problem that can result in considerable pain and distress for patients. The aim of this pilot study was to evaluate the role of subantimicrobial dose doxycycline (SDD - 20 mg doxycycline twice daily) in the management of patients with ROAU.\n 50 patients with ROAU were randomly allocated to treatment with SDD or placebo for 90 days. Daily ulcer diaries were completed by the participants to record the number of new ulcers and the pain associated with the ulcers.\n There were significantly more days with no new ulcers in the SDD group (80.4 +/- 5.9) than the placebo group (69.8 +/- 18.7; P=0.04). Strong trends were observed towards fewer new ulcers per day, fewer new ulcers over the 90-day period, and more days with no pain in the SDD group compared with the placebo group (P=0.06-0.08).\n SDD shows promise as potential therapy in the management of ROAU, though this needs to be confirmed in further studies.", "Twenty patients with severe recurrent aphthous stomatitis were treated with a new drug, levamisole, to determine its effects upon the incidence and prevalence of recurrent aphthous stomatitis. The trial, conducted in a non-crossover, double-blind fashion, did not demonstrate any statistically significant differences when levamisole and placebo groups were compared over time either in the number of ulcers, number of ulcer-days, mean duration of ulcers, or mean number of ulcers per day. Positive subjective results were experienced by the 10 patients receiving levamisole but these were not of sufficient magnitude to affect group mean differences.", "Recurrent aphthous stomatitis (RAS) is a common, painful, and ulcerative disorder of the oral cavity of unknown etiology. No cure exists and medications aim to reduce pain associated with ulcers through topical applications or reduce outbreak frequency with systemic medications, many having serious side effects. The purpose of this pilot study was to evaluate the potential of a product to reduce the number of outbreaks of RAS ulcers. Propolis is a bee product used in some cultures as treatment for mouth ulcers. In this randomized, double-blind, placebo-controlled study, patients were assigned to take 500 mg of propolis or a placebo capsule daily. Subjects reported a baseline ulcer frequency and were contacted biweekly to record recurrences. Data were analyzed to determine if subjects had a decrease of 50% in outbreak frequency. The data indicated a statistically significant reduction of outbreaks in the propolis group (Fisher's exact test, one sided, p = 0.04). Patients in the propolis group also self-reported a significant improvement in their quality of life (p = 0.03). This study has shown propolis to be effective in decreasing the number of recurrences and improve the quality of life in patients who suffer from RAS. Propolis should be evaluated further in a larger sample clinical trial.", "The frequency of recurrent aphthous stomatitis (RAS), the most common oral mucosa lesions seen in primary care, is up to 25% in the general population. However, there has been no optimal therapeutic approach. Our objective was to confirm our previous clinical observation of the beneficial treatment of RAS with vitamin B(12).\n A randomized, double-blind, placebo-controlled trial was done using primary care patients. A sublingual a dose of 1000 mcg of vitamin B(12) was used in patients in the intervention group for 6 months.\n In total, 58 patients suffering from RAS participated in the study: 31 were included in the intervention group and 27 were included in control group. All parameters of RAS among patients in the intervention group were recorded and compared with the control group. The duration of outbreaks, the number of ulcers, and the level of pain were reduced significantly (P < .05) at 5 and 6 months of treatment with vitamin B(12), regardless of initial vitamin B(12) levels in the blood. During the last month of treatment a significant number of participants in the intervention group reached \"no aphthous ulcers status\" (74.1% vs 32.0%; P < .01).\n Vitamin B(12) treatment, which is simple, inexpensive, and low-risk, seems to be effective for patients suffering from RAS, regardless of the serum vitamin B(12) level.", "To evaluate pentoxifylline for the treatment of recurrent aphthous stomatitis.\n A 60-day, randomized, double-blind, placebo-controlled trial with a 60-day no treatment follow-up.\n An oral medicine specialist referral center in Manchester.\n Forty-nine volunteers who passed the initial assessment for recurrent aphthous stomatitis entered a pretrial phase in which their eligibility for the trial phase of the study was assessed. Sixteen subjects were deemed ineligible, and 7 failed to attend or withdrew. The remaining 26 subjects were randomized to placebo or treatment. Six subjects withdrew because of adverse effects, and 1 was unavailable for follow-up.\n Pentoxifylline (also called oxpentifylline), 400 mg 3 times daily, or matching placebo.\n A reduction in the median pain score, ulcer size, number of ulcers, or total number of ulcer episodes.\n Patients taking pentoxifylline had less pain and reported smaller and fewer ulcers compared with baseline. Patients taking placebo reported no improvement in these variables. Patients taking pentoxifylline also reported more ulcer-free days than those taking placebo. However, the differences were small and, with the exception of median ulcer size (P = .05), did not reach statistical significance. Adverse effects were common with pentoxifylline, but not significantly different from those experienced by patients taking placebo.\n Although pentoxifylline may have some benefit in the treatment of recurrent aphthous stomatitis, the benefit is limited. It may have a role in the treatment of patients unresponsive to other treatments, but cannot yet be recommended as a first-line treatment.", "to utilize a double-blind protocol to provide clarification about the safety and effectiveness of levamisole in the treatment of recurrent aphthous stomatitis.\n Fourteen patients took a decreasing dose of oral levamisole for six months (initial dose 150mg three times a week) and ten others were placebo control patients. All were evaluated monthly.\n The number of crises had a tendency to decrease in both groups, but without a difference between groups. The number of lesions diminished significantly in the two groups, but upon comparison the difference was not significant. Duration of the lesions diminished significantly in the placebo, however when compared to the levamisole group, difference was not significant during treatment. The intensity of pain was significantly lower in the two groups, but upon comparison, pain was significantly lower in the placebo group. The final global evaluation showed improvement in 50% of patients of the levamisole group and in 70% of the placebo, without a significant difference between treatments. No difference in the frequency of collateral effects was observed between groups.\n Levamisole, as used in this protocol, is a safe drug. When compared with the placebo, levamisole is not effective in the prophylactic treatment of recurrent aphthous stomatitis. The placebo effect is important in diseases where emotional factors affect recurrence or expression of symptoms.", "Recurrent aphthous stomatitis (RAS) is one of the most common ulcers of the oral cavity with a reported prevalence of 5- 50%. There is still no definitive treatment for RAS; however, immunosuppressive and immunomodulant agents have been proposed. In this study, we compared the therapeutic effects of 5 mg/d prednisolone with 0.5 mg/d colchicine in the treatment of RAS.\n In a double-blind randomized clinical trial, 34 patients with RAS were randomly divided into two groups for treatment with prednisolone or colchicine. All patients took the medication for three months and were assessed at two weeks intervals. The groups were compared for size and number of lesions, severity of pain and burning sensation, duration of pain-free episodes and any side effects of the prescribed medicines. Both colchicine and prednisolone treatments significantly reduced RAS (p < 0.001). No significant differences in size and number of lesions, recurrence and severity of pain and duration of pain-free period were seen between the two treatment groups. Colchicine (52.9%) had significantly more side effects than prednisolone (11.8%).\n Low dose prednisolone and colchicine were both effective in treating RAS. Given that the two therapies had similar efficacy, yet colchicine was associated with more side effects, , 5mg/d of prednisolone seems to be a better alternative in reducing the signs and symptoms of the disease.", "One hundred and twenty-four patients who had had recurrent aphthous stomatitis (RAS) for two to 53 years took part in three studies to assess the effectiveness of levamisole and determine an adequate regimen. In study 1 and the first half of study 2 both of which were double-blind, levamisole 150 mg/day (or placebo) was given on three consecutive days in every fortnight. In the second two months of study 2 and in the open trial (study 3) three-day courses were given only when an episode of RAS occurred. The drug was well tolerated. The signs and symptoms of RAS improved gradually and significantly in those treated with levamisole but not in those on placebo, and intergroup differences were also significantly in favour of the active drug. Improvement occurred earlier in study 3 than in the other two studies. Hence levamisole may prevent new episodes of RAS.", "One-third of the total population seems to develop minor recurrent aphthous stomatitis (RAS) during their lifetime. However, well-controlled dietary intervention studies to prevent minor RAS are very rare. The objective of the present study was to investigate whether the prevalence of RAS decreased with perilla oil (rich in alpha-linolenic acid).\n Thirty subjects (8 men and 22 women) who had minor RAS at least once a month were randomly allocated to a soybean oil group or a perilla oil group in a double-blind manner (experimental phase) after a run-in phase of 4 mo during which subjects used a reference oil, the most popular cooking oil in Japan, or a 50/50 mixture of soybean oil and rapeseed oil. During the experimental phase, subjects were asked to use soybean oil or perilla oil as the sole cooking oil for 8 mo. Blood samples were collected at the start and end of the experimental phase for fatty acid analysis of total plasma phospholipid fraction. Occurrence and needed days for healing of minor RAS were recorded during the two phases and compared.\n alpha-Linolenic acid concentrations in the plasma phospholipid fraction increased significantly in both groups during the experimental phase to a similar extent. The prevalence of minor RAS in the experimental phase decreased significantly in both groups compared with the run-in phase to a similar extent, without intergroup differences.\n Perilla oil, which is rich in alpha-linolenic acid, was not superior to soybean oil in preventing minor RAS. There was a possibility that avoiding rapeseed oil might be beneficial for prevention of minor RAS.", "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.", "nan", "In a pilot study as well as in a double-blind placebo-controlled study, 21 patients suffering from recurrent aphthous stomatitis were treated with the immunotherapeutic agent, levamisole. The results obtained confirm previous studies that levamisole has a beneficial effect on the symptoms of recurrent aphthous stomatitis and is well-tolerated.", "Recurrent aphthous stomatitis (RAS) is a painful condition of unknown etiology, affecting more than 2.5 billion people worldwide. Vitamin deficiencies have been implicated as a possible cause.\n The authors conducted a single-center, randomized, parallel-arm, double-masked, placebo-controlled study to examine the effect of daily multivitamin supplementation on the number and duration of RAS episodes. The authors randomly assigned 160 adults who had a validated history of at least three episodes of idiopathic minor RAS within the previous 12 months to one of two groups: the first group (n = 83) received a once-daily multivitamin containing 100 percent of the U.S. reference daily intake (RDI) of essential vitamins, and the second group (n = 77) received once-daily placebo for up to 365 days.\n The results showed no significant difference in the mean number of new RAS episodes between the multivitamin (4.19 episodes) and placebo (4.60 episodes) arms during the study period (P = .69). The mean duration of new RAS episodes also was similar for the multivitamin (8.66 days) and placebo (8.99 days) arms (P = .60). Furthermore, the authors found no differences between the two arms with regard to mouth pain, normalcy of diet or compliance with the study medication regimen.\n Daily multivitamin supplementation, with the RDI of essential vitamins, did not result in a reduction in the number or duration of RAS episodes.\n Clinicians should not recommend multi-vitamin supplementation routinely as prophylaxis for RAS.", "A randomized double-blind study was designed to evaluate the safety and efficacy of levamisole in the treatment of recurrent aphthous stomatitis (RAS). Thirty patients, aged 9-65 years, were selected, based on a documented history of three or more episodes of RAS. Patients were instructed to take 150 mg of levamisole (or placebo) daily for 3 days at the onset of the first prodromal symptoms of an ulcer. The regimen was to be repeated for each new episode, but not more than once per week. At each episode patients were examined and evaluated as to number and duration of ulcers, interval between episodes, pain associated with ulcers, and side effects. Data on 24 patients were suitable for analysis. Of those patients receiving levamisole, six showed slight improvement and five were unchanged. Of those patients receiving the placebo, one showed a marked improvement, four slight improvement, six were unchanged, and two deteriorated. There was neither a clinical nor a statistically significant difference between the groups. It is concluded that levamisole, in this study protocol, had no effect on the incidence or severity of aphthous ulcers.", "Near 20 % of people suffer from recurrent oral aphthous ulcers. These painful ulcers are found on the oral mucosa. We conducted this study to evaluate the effect of the camel thorn distillate on this condition.\n 93 patients with recurrent aphthous ulcers were selected and divided into two groups. One group was given a placebo (n = 44) and the other was given camel thorn distillate (n = 49). The diameter of the lesions and the severity of the pain were measured 3, 5, 7, 10 and 14 days after initiation of therapy. The lesion diameters and pain scores of the two groups were compared using the t-test.\n Complete resolution time ranged from 3 to 7 days (mean = 4.02) in the group treated with camel thorn distillate, whereas in the control group, complete resolution time ranged from 7 to 14 days (mean = 8.9, p < 0.001).\n The efficacy of camel thorn distillate is comparable to that of other drugs used to treat oral aphthous ulcers. Its therapeutic effect may be due to the flavanones (alhagitin and alhagidin) that are present in this plant.", "The aim was to investigate the safety and efficacy of clofazimine for the treatment of recurrent aphthous stomatitis.\n In this randomized controlled partially blind study, 23 patients received clofazimine 100 mg daily for 30 days and then 100 mg every other day. Twenty-three patients received colchicine 0.5 mg 3 times daily. Twenty patients received 1 placebo pill 2 times daily. All subjects received medications for 6 months. The chi-squared or Fisher exact tests were used to assess drug efficacy with respect to objective findings and symptoms.\n A greater percentage of individuals in the clofazimine group had no further aphthous episodes (17%-44% compared with <or=6% in the other groups). A significantly greater percentage of treatment interruption occurred in the colchicine group because of gastrointestinal effects (23%-45%). Individuals in the clofazimine group who continued to suffer from aphthous stomatitis presented with better results for the evaluated variables.\n Clofazimine should be considered for the treatment of recurrent aphthous stomatitis.", "Forty-eight patients with diagnosed recurrent aphthous stomatitis participated in a randomized double-blind study of levamisole therapy. Each patient's response to treatment was determined by the following criteria: (1) days between attacks, (2) duration of lesions, (3) patient's self-evaluation of pain, (4) investigator's clinical evaluation of patient's subjective treatment response. Statistical analysis of the levamisole and placebo groups of criteria 1 and 2 above revealed no significant difference. In contrast to the above findings, analysis of the investigator's recordings of patient's subjective treatment response showed that 26% of the levamisole patients experienced marked or moderate improvement. None of the placebo patients were recorded as having experienced the same degree of benefit. Fourteen of 15 patients who complained of side effects were taking levamisole. The most common side effects were dysgeusia and hyperosmia." ]

[ "7857353", "7857348", "14498765", "1745846", "9950305", "380912", "7857347", "11399700", "10351117", "10929921", "15265442", "10425883", "17126918", "12475845", "6234240", "3544353", "3068610", "55648", "8414777", "7857356", "14657066", "2687818", "18831749", "12573204", "12718222", "3805711", "3541764", "385400", "7857354", "14687691", "14993078", "7857357", "20052587", "3755127", "15366332", "6752937", "7502900", "11955602", "477676", "2970744", "3244540", "9585823" ]

[ "Role of immunoactivation with pidotimod in recurrent respiratory infections in childhood.", "Pidotimod in the treatment of recurrent respiratory infections in paediatric patients.", "Ribosomal immunostimulation: assessment of studies evaluating its clinical relevance in the prevention of upper and lower respiratory tract infections in children and adults.", "Immunotherapy with an oral bacterial extract (OM-85 BV) for upper respiratory infections.", "Isoprinosine does not protect against frequent respiratory tract infections in childhood.", "Levamisole (R 12564) in the prevention of recurrent upper respiratory tract infections in children: a double-blind, placebo-controlled study.", "Efficacy and safety of pidotimod in the treatment of recurrent respiratory infections in children.", "Safety and efficacy of two courses of OM-85 BV in the prevention of respiratory tract infections in children during 12 months.", "Use of a polyvalent bacterial lysate in patients with recurrent respiratory tract infections: results of a prospective, placebo-controlled, randomized, double-blind study.", "Primary prevention of acute respiratory tract infections in children using a bacterial immunostimulant: a double-masked, placebo-controlled clinical trial.", "[Efficacy of sublingual polyvalent bacterial vaccine (Lantigen B) in children with recurrent respiratory infection: a randomized double-blind controlled clinical trial].", "[Klebsiella pneumoniae glycoproteins as coadjuvants in the prevention of recurrent respiratory infections in children 1-6 years of age].", "Ribosomal therapy in the prophylaxis of recurrent pharyngotonsillitis in children.", "Immunostimulation with OM-85 in children with recurrent infections of the upper respiratory tract: a double-blind, placebo-controlled multicenter study.", "Clinical and immunobiological effects of an orally administered bacterial extract.", "A double-blind clinical trial for the evaluation of the therapeutical effectiveness of a calf thymus derivative (Thymomodulin) in children with recurrent respiratory infections.", "Broncho-Vaxom in children with rhinosinusitis: a double-blind clinical trial.", "Levamisole in prevention of recurrent upper-respiratory-tract infections in children.", "Stimulation of nonspecific immunity to reduce the risk of recurrent infections in children attending day-care centers. The Epicrèche Research Group.", "Immunoactivity of pidotimod against episodes of recurrent tonsillitis in childhood.", "Efficacy and safety of echinacea in treating upper respiratory tract infections in children: a randomized controlled trial.", "[Treatment using immucytal in children with recurrent respiratory infections: an Italian multicenter experience].", "Echinacea purpurea and osteopathic manipulative treatment in children with recurrent otitis media: a randomized controlled trial.", "Use of OM-85 BV in children suffering from recurrent respiratory tract infections and subnormal IgG subclass levels.", "[Effect of long-acting garlic tablets \"allicor\" on the incidence of acute respiratory viral infections in children].", "Bacterial lysate (I.R.S. 19) applied intranasally in the prevention of acute respiratory diseases in children: a randomized double-blind study.", "[Biostim prevention of recurrent respiratory infections in children. A double-blind versus placebo study].", "A placebo controlled, double-blind evaluation of levamisole in the reduction of the frequency, duration and severity of attacks in children suffering from recurrent upper respiratory tract infections.", "Pidotimod in the management of recurrent pharyngotonsillar infections in childhood.", "Short ribosomal prophylaxis in the prevention of clinical recurrences of chronic otitis media in children.", "Effectiveness of an herbal preparation containing echinacea, propolis, and vitamin C in preventing respiratory tract infections in children: a randomized, double-blind, placebo-controlled, multicenter study.", "Immunoactivation by pidotimod in children with recurrent respiratory infections.", "Ribosomal therapy in the treatment of recurrent acute adenoiditis.", "[Prospective placebo-controlled double-blind study using a bacterial lysate in infections of the respiratory tract and ENT region in children].", "Efficacy of Lantigen B in the prevention of bacterial respiratory infections.", "[Clinical study concerning the prevention of infections of the upper respiratory tract of preschool children].", "Reduction of the number and severity of respiratory tract infections in children by oral immunostimulation.", "A preventive measure for otitis media in children with upper respiratory tract infections.", "A double-blind pediatric evaluation of levamisole in the prevention of recurrent upper respiratory tract infections.", "[Prophylactic efficacy of reaferon in viral hepatitis A and acute respiratory infections in children].", "[Evaluation of the effectiveness of thymomodulin in children with recurrent respiratory infections].", "[Safety and efficacy of OM-85-BV plus amoxicillin/clavulanate in the treatment of subacute sinusitis and the prevention of recurrent infections in children]." ]

[ "The efficacy and safety of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl)carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) were rated in a child population with a remote history of recurrent respiratory infections (RRI). This randomized double-blind multicenter clinical trial versus placebo, stratified by age groups, involved 748 children recruited in 69 Medical Centres. The trial consisted of a 60-day treatment period and a 90-day follow-up. At the end of the treatment period the pidotimod group showed a significant decrease in the number of RRI episodes and associated symptoms vs control group. As a consequence, there was a significant decrease in the number of days of absence from kindergarten or school and in the consumption of antibiotics and symptomatic drugs. Safety was good. The effect of the drug persisted after its withdrawal throughout the whole 90-day follow-up period. During this period there was a significantly lower RRI incidence rate in the pidotimod group than in the placebo group (p < 0.01). Because of its efficacy and safety, pidotimod may be rated as an excellent drug in the RRI management in children.", "50 young patients suffering from recurrent respiratory infections (RRI) were treated with pidotimod ((R)-3-[(S)-(5-oxo-2- pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) (one 400 mg ampoule twice a day) or placebo, according to a double-blind experimental design. The treatment period was 20 days and there was then a 60-day follow-up period. Evaluation was both clinical (number and severity of the respiratory infectious episodes) and immunological, investigating the OKT 4 and OKT 8 lymphocyte sub-populations and OKT 4/OKT 8 ratio. The group of children treated with pidotimod showed a decrease in the number of infections. Patients free from RRI episodes, after 20 days of therapy, were 68% of the group treated with pidotimod compared with 8% of the placebo group. In addition, the mean duration of the episodes was lower in treated patients than in patients of the control group. Such differences were statistically significant. It was also observed that administration of the drug potentiated the immune response such that the clinical picture remained improved for a further 60 days after treatment cessation. Furthermore, only in the pidotimod group there were improving changes of OKT 4 and OKT 8 percentages which affected the OKT 4/OKT 8 ratio.", "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 efficacy of Broncho-Vaxom/Imocur (OM-85 BV), an orally administered lyophilized bacterial extract, for recurrent respiratory and ear, nose and throat (ENT) infections was evaluated in 116 children aged 6 months to 19 years by comparing its activity in 61 children with that of a placebo in 55 children. The study was randomized, double-blind, and comprised a 90-day treatment period followed by a 90-day follow-up period without test drugs. Over the 180 days, 39.5% of patients taking OM-85 BV remained free from infection compared with 16.5% on placebo (p less than 0.01). 44% on OM-85 BV did not need antibiotics compared with 23.5% on placebo (p less than 0.05). These differences were even greater in the subgroup of children aged 6 years and less (34 vs. 3.5% for the absence of infections, p less than 0.01 and 37 vs. 10% for the need of antibiotics, p less than 0.05). Tolerance to OM-85 BV was excellent, and laboratory investigations showed no abnormalities attributable to this product. This work confirms that the immunomodulator OM-85 BV is an effective immunotherapy for recurrent respiratory and ENT infections in children.", "Isoprinosine, an in vitro immuno-enhancing agent principally acting by stimulating T-lymphocytes, is one of a number of agents sometimes used in an attempt to prevent recurrent respiratory infections in children, although there are no formal trials for this particular drug. We performed a placebo-controlled double-blind trial to assess the efficacy of isoprinosine (50 mg/kg per day) for 6 weeks followed by 50 mg/kg per day twice weekly for 6 weeks in the prevention of frequent acute respiratory tract infections in 102 children aged 4-8 years. A total of 43 children treated with isoprinosine and 41 with placebo finished the study. Despite a transient increase in the total number of CD3+, CD4+ and CD8+ T-lymphocytes after 6 weeks of daily isoprinosine treatment, there was no difference in the number and length of duration of acute respiratory infections, number of antibiotic courses and number of days with cough, pharyngitis, rhinitis and increased body temperature (> or = 37.0 degrees C and > or = 38.0 degrees C). There were no changes in markers of T- or B-lymphocyte activation (CD25, HLA-DR, CD45RA/RO, CD23).\n Attempts at immunomodulation using isoprinosine in the dose and for the duration used may increase the total numbers of both CD4 and CD8 T-lymphocytes but is ineffective in prevention of respiratory tract infections in childhood.", "A double-blind, placebo-controlled trial was carried out in 33 children suffering from chronic or recurrent upper respiratory tract infections to assess the effectiveness of levamisole in reducing the number, duration, and severity of infective episodes. A weight-related dosage of levamisole was used (2.0 to 2.5 mg per kg body weight), patients taking a single dose on 1 day per week over an autumn-winter period of 4 months. The results showed that patients in the levamisole-treated group had statistically significantly fewer periods of upper respiratory tract infection and when they occurred the episodes were milder and shorter in the levamisole group and required less antibiotics. No side-effects were noted.", "The activity of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) was evaluated in a double-blind, placebo-controlled, randomized, multicentre trial, on 120 pediatric patients affected by recurrent respiratory infections. The clinical course of acute infections was favourable both in placebo and in treatment group, but recovery was quicker with pidotimod than with placebo. Antibiotic therapy and time of hospitalization were shorter in the patients taking pidotimod, and main symptomatic parameters (pharyngalgia, dysphagia, mucous membrane inflammation, adenopathy, anorexia) receded quickly. In patients receiving the drug as well as in placebo group changes in laboratory parameters, indicating recovery from the acute infectious events, were observed. A significant trend to normalization of the immune response, evidenced by chemotaxis and leukocyte phagocytosis index, was found only in patients treated with pidotimod. A significant decrease in the risk of relapses was observed in patients treated with pidotimod (35%), as well as a reduction of hospitalization (86%) and a decreased antibiotic therapy (47%). If a relapse occurred, the response of treated patients was quicker (fever, antibiotic therapy, hospitalization). These findings allow to correlate the individual immune response activation to the resistance to recurrent infections and also to a better response to therapy in case of clinically relevant disease. No side effects were observed. Only in 12 patients (5 pidotimod, 7 placebo) mild reactions were observed, but they were attributed to concomitant antibiotic treatment or other factors. No alterations in main laboratory parameters were seen.(ABSTRACT TRUNCATED AT 250 WORDS)", "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.", "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.", "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.", "nan", "Forty two children with clinical diagnosis of recurrent high and low respiratory infections, were treated with an extract of P1 and F1 glycoproteins; fraction of Klebsiella pneumoniae, 1 g/day for one week a month for three months, according to a double-blind, randomized, parallel group trial.\n Improvement of clinical and laboratory results were compared with 44 control patients with the same age and similar sex distribution, that were treated with placebo. At the end of study, clinical analysis at 6, 9 and 12 months after the initial dose of Klebsiella pneumoniae, decreased in the number of respiratory infections, sick days, and school assistance were observed in the study group when compared with the control group (p < 0.001 in all parameters). There were not statistical significant changes in hemolytic complement, C3, C4 and immunoglobulins (IgA, IgG, IgM and IgE) levels before and after treatment and between groups. There were not observed adverse reactions to oral treatment with this extract of Klebsiella pneumoniae.\n These results suggested that the extract of Klebsiella can be used as a coadjuvant in the treatment of pediatric patients with recurrent high and low respiratory infections.", "Although much has been written on how to manage recurrent pharyngotonsillitis, it remains a controversial topic. The composition of normal commensal oropharynx bacteria may be disrupted by frequently using antimicrobials, by inhibiting sensitive organisms and by allowing resistant organisms to overgrowth. This may cause the recurrence of acute episodes. The aim of this study was to evaluate the efficacy of ribosomal immunotherapy in the prophylaxis of recurrent pharyngotonsillitis.\n A total of 160 children aged between 5 and 14 years with recurrent pharyngotonsillitis were ramdomized to receive either ribosomal immunotherapy (group A one tablet a day, 8 days a month for 3 months) or a placebo (group B same dosage for the same period).\n At the end of the study, each patient treated with Immucytal presented a subjective decrease of symptoms. Compared with group B, group A experienced a significant improvement of some clinical parameters.\n The results show that ribosomal immunotherapy causes a significant improvement of both specific and non-specific immunity and may be effective in the prophylaxis of recurrent pharyngotonsillitis and in preventing recurrences without entailing side effects or bacterial resistance.", "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.", "The effect of a bacterial extract orally administered to 20 children with recurrent infections of the upper respiratory tract, was investigated in a double-blind study. The composition of the peripheral blood mononuclear cells (T and B-lymphocytes, monocytes) and some of their biochemical properties (5'-nucleotidase, beta-N-acetyl-glucosaminidase and non-specific esterase) were unaffected. In contrast, the allogeneic mixed lymphocyte reaction was significantly increased in patients treated with the bacterial extract. In the treated group the number of infectious episodes decreased significantly and the clinical response correlated positively with the mixed lymphocyte reaction. These findings suggest that the bacterial extract has the capacity of restoring depressed immune functions by acting through the gut-associated lymphoid tissue.", "The effectiveness of an orally administrable thymic derivative (Thymomodulin) for the treatment of the recurrent respiratory infections (RRI) in children has been studied in a double-blind clinical trial with historical comparison. In the Thymomodulin treated group a significant decrease of the monthly frequency of RRI has been observed in comparison with the previous year (P less than 0.05) and with the placebo treated group (P less than 0.002). The evaluation of the laboratory data at the beginning of the study didn't show in the two groups typical alterations of the common hematological and immunological parameters, but at the end of the trial a statistically significant increase of the levels of salivary IgA has been noticed only in the Thymomodulin treated group (P less than 0.02).", "Fifty-one children aged 4-12 years, presenting with an acute epidose of chronic rhinosinusitis, were treated for 6 months with either Broncho-Vaxom (BV; marketed in Yugoslavia under the trade mark of Broncho-Munal) or placebo under double-blind randomized conditions. The efficacy of BV was assessed on the basis of clinical symptoms (cough, nasal discharge, congestion of nasal mucosa), number and duration of concomitant treatments (antibiotics, secretolytics, antitussives), number and duration of acute episodes during the trial and serum IgA levels. In BV treated patients the incidence and duration of infectious episodes and the number and duration of concomitant treatments decreased significantly in comparison with the placebo group, and the clinical response correlated positively with an increase in the serum levels of IgA. The results of treatment of acute episodes of chronic rhinosinusitis in children demonstrated the curative and prophylactic efficacy of BV.", "70 children with chronically relapsing mild-to-severe upper-respiratory-tract infections during autumn and winter participated in a six month double-blind placebo-controlled trial: 38 of them received about 1-25 mg/kg of levamisole twice daily for two consecutive days every week, the others were given placebo. During each of the three trial periods, levamisole proved superior to placebo in that it significantly reduced the number, the duration, and the severity of the infections. Moreover, in the group treated with the higher dose (i.e. greater than 2-5 mg/kg/day), the superiority of levamisole to placebo was much more clear-cut. No drug-related side-effects were reported.", "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.", "The therapeutic efficacy of the synthetic immunostimulant pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) was evaluated in a double-blind placebo-controlled study in parallel groups in the management of recurrences in 235 children with recurrent tonsillitis. The ambulant study provided for 15 days of treatment with two oral vials of pidotimod 400 mg or placebo daily, in accordance with a randomisation list, 60 days of treatment with one oral vial of pidotimod 400 mg or placebo daily, and a 90-day follow-up period. The total trial period was 165 days. In addition to evaluating the number of tonsillitis recurrences which occurred during the 75 days of treatment and the 90-day follow-up period, the number of days on which the principal symptoms of the illness were present and on which drugs such as antibiotics or anti-inflammatory agents were used concomitantly, as well as the number of days' absence from school, were analyzed. The findings showed that, taking the treatment phase and the three-month follow-up period together, pidotimod significantly reduces the incidence of inflammatory upper airways episodes. The very low incidence of adverse effects, which was the same as that in the placebo group, confirmed the excellent safety of the product.", "Echinacea is a widely used herbal remedy for treatment of upper respiratory tract infections (URIs). However, there are few data on the efficacy and safety of echinacea in treating URIs in children.\n To determine if Echinacea purpurea is effective in reducing the duration and/or severity of URI symptoms in children and to assess its safety in this population.\n Randomized, double-blind, placebo-controlled trial of healthy children 2 to 11 years old recruited from a regional practice-based network and an alternative medical center in 4-month periods from 2000 through 2002.\n Study patients were randomized to receive either echinacea or placebo for up to 3 URIs over a 4-month period. Study medication was begun at the onset of symptoms and continued throughout the URI, for a maximum of 10 days.\n Primary outcomes were duration and severity of symptoms and adverse events recorded by parents; secondary outcomes included peak severity of symptoms, number of days of peak severity, number of days of fever, and a global assessment of severity of symptoms by parents of study children.\n Data were analyzed on 707 URIs that occurred in 407 children, including 337 URIs treated with echinacea and 370 with placebo. There were 79 children who completed their study period without having a URI. The median duration of URIs was 9 days (95% confidence interval, 8-10 days); there was no difference in duration between URIs treated with echinacea or placebo (P =.89). There was also no difference in the overall estimate of severity of URI symptoms between the 2 treatment groups (median, 33 in both groups; P =.69). In addition, there were no statistically significant differences between the 2 groups for peak severity of symptoms (P =.68), number of days of peak symptoms (1.60 in the echinacea group and 1.64 in the placebo group; P =.97), number of days of fever (0.81 in the echinacea group vs 0.64 in the placebo group; P =.09), or parental global assessment of severity of the URI (P =.67). Overall, there was no difference in the rate of adverse events reported in the 2 treatment groups; however, rash occurred during 7.1% of the URIs treated with echinacea and 2.7% of those treated with placebo (P =.008).\n Echinacea purpurea, as dosed in this study, was not effective in treating URI symptoms in patients 2 to 11 years old, and its use was associated with an increased risk of rash.", "120 children, 71 male and 49 female, aged between 2 years and 15 years (mean 6.15 +/- 3.52 years) with recurrent respiratory infections, were treated with Immucytal, an immunomodulator of bacterial origin, based on membrane proteoglycan fractions plus bacterial ribosomes. The children, selected on the basis of the previous year's clinical score, were treated according to a random design with either Immucytal or placebo, using the same dosage of one puff per nostril plus one puff in the oropharyngeal cavity three times a day, as follows: 1st month: two weeks' treatment, one week wash out, one week's treatment. 2nd, 3rd, 4th months: two weeks' treatment, two week's wash out. Monthly throughout the treatment period the frequency and severity of airway infections episodes were assessed using the same score as for admission. Blood chemistry test, immunological assays (circulating Ig, lymphocyte subpopulations, Merieux Multitest in vivo blastization test) and respiratory tests (spirometry using a pneumotachigraph) were done before and after the treatment. 118/120 children completed treatment; the two dropouts were in the placebo group, one for compliance and the other because of headaches. Respiratory symptoms improved significantly in the actively treated children already from the first month, but not in the placebo group. This improvement consisted of reduction of the respiratory infectious episodes in both the upper and lower airways. No changes were noted in respiratory function parameters. From the immunological viewpoint, there were significant rises in serum IgA and IgM and enhanced skin response tot he Multitest; there was no change in the percentages of different circulating lymphocyte subpopulations.(ABSTRACT TRUNCATED AT 250 WORDS)", "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.", "Recurrent acute respiratory tract infections (RARTIs) in children are related to IgG subclass deficiencies. The aim of the trial was to evaluate the effect of OM-85 BV in the number of RARTIs as well as in the IgG subclass levels.\n This was a randomized, double-blind, placebo-controlled clinical trial. Patients of ages three to six years, having three or more documented ARTIs during the last six months with subnormal IgG subclass levels were included. Patients took either one capsule of OM-85 BV (3.5 mg) or placebo orally every day for ten consecutive days per month during three consecutive months. Patients were followed three further months without drug intake. IgG subclass levels were determined before and after treatment.\n IgG4 levels diminished after the OM-85 BV treatment (-3 [-8.0, -1.0] median difference [95 % CI] p < 0.05 by Wilcoxon test). No other significant changes in IgG subclasses were observed. After six months the patients in the OM-85 BV group (n = 20) experienced 2.8 1.4 (mean SD) ARTIs, while the patients in the placebo group (n = 20) suffered 5.2 1.5 ARTIs (-2.4 [3.3, -1.5] mean difference [95 % CI] p < 0.001 by Student's t test). Three patients with OM-85 BV had gastrointestinal events related to drug administration, as well as three placebo patients.\n This study demonstrated the clinical benefit of OM-85 BV in patients suffering from RARTIs and subnormal levels of IgG subclasses. This trial opens new perspectives in the research of the mechanism of action of OM-85 BV.", "To elucidate the prospects administration of allicor (long-releasing garlic tablets) in prevention of acute respiratory diseases (ARD) in children vs benzimidazole (dibazole).\n At the first stage, tolerance of allicor (600 mg/day) and its effects on ARD morbidity were investigated in an opened 5-month study in 172 children aged 7-16 years compared to 468 controls. As the second stage, the effects of allicor (300 mg/day) on ASRD morbidity were investigated in a double-blind placebo-controlled randomized 5-month trial in 42 children aged 10-12 years in comparison with 41 placebo-treated children and 73 benzimidazole-treated children.\n At the first stage of the study allicor was not observed to induce gastrointestinal side effects in children at any dosage while ARD morbidity was reduced 2-4-fold as compared to the controls. At the second stage of the study allicor reduced ARD morbidity 1.7-fold compared to placebo and 2.4-fold vs benzimidazole. There was no significant difference in ARD morbidity between placebo- and benzimidazole-treated groups. Health index in allicor-treated group was 1.5-fold higher as compared either to placebo- or benzimidazole-treated children.\n Thus, the results of this study have demonstrated that allicor is effective for non-specific prevention of acute respiratory infections in children and has no side effects. ARD prevention with benzimidazole appeared ineffective in placebo-controlled study, so the development of new useful and safe preparations is of ultimate importance.", "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.", "nan", "In a double-blind placebo controlled study of levamisole in the treatment of children with recurrent upper respiratory tract infection (URI) eighty-six patients took part. Medication was given once a week, in a single body-weight adjusted dose. The children treated with levamisole had a statistically significantly reduced incidence of episodes of infection which were severe, less prolonged and required less antibiotics. No side-effects were reported.", "The efficacy and safety of a new synthetic immunostimulant pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) in recurrent infections of the primary airways were assessed in a group of 416 children with a history of recurrent respiratory infections (RRI). This was a double-blind randomized trial of pidotimod vs. placebo, consisting of a treatment period of 60 days and a follow-up period of 3 months. A reduction in the duration and frequency of infectious episodes in the group of children treated with pidotimod (one 400 mg oral bottle daily) was observed which was statistically different from the placebo group. The protective effect produced by pidotimod was also confirmed by a series of recordings made over the five-month observation period, which showed a significant reduction in the number of days of fever, the severity of the signs and symptoms of acute episodes, use of antibiotics and antipyretic drugs and absence from school or nursery school. Safety was excellent.", "The aim of this study was to compare the efficacy and the safety of a short oral ribosomal immunotherapy (Immucytal) in the prevention of chronic otitis media in children. Seventy-two patients were enrolled in this study, 41 males and 31 females, aged between 6 and 14 years, with an history of recurrent otitis media. Patients were randomised to receive Immucytal (group A) or placebo (group B) according to the following protocol: one tablet daily in the morning 8 days per month for three consecutive months. Immucytal and placebo were identical in shape and size, in order to maintain double-blind conditions. The efficacy parameters were (evaluated before, at the end and 6 months after the beginning of the therapy): clinical score; changes in immunological parameters; patient's parents assessment of symptoms on a scale from 0 (much worse) to 4 (much improved) and hearing tests. Patients of group A, had an improvement of clinical items measured, serum concentrations of immunoglobulins, subjective patient's parents assessment of symptoms and hearing tests. For all evaluations, a significant difference between treatment groups was found. Using this dosage and posology (shorter than others) the beneficial effects of Immucytal were maintained until the end of the 6-month study period.", "To evaluate the effectiveness and safety of a preparation containing echinacea, propolis, and vitamin C in the prevention of respiratory tract infections in children during a 12-week winter period.\n Randomized, double-blind, placebo-controlled study.\n Four hundred thirty children, aged 1 to 5 years, were randomized to an herbal extract preparation (n = 215) or a placebo elixir (n = 215).\n Administration of an herbal preparation (Chizukit) containing 50 mg/mL of echinacea, 50 mg/mL of propolis, and 10 mg/mL of vitamin C, or placebo (5.0 mL and 7.5 mL twice daily for ages 1 to 3 years and 4 to 5 years, respectively) for 12 weeks.\n Significant mean +/- SD reductions of illnesses were seen in the Chizukit group in the number of illness episodes, 138 vs 308 (55% reduction); number of episodes per child, 0.9 +/- 1.1 vs 1.8 +/- 1.3 (50% reduction, P<.001); and number of days with fever per child, 2.1 +/- 2.9 vs 5.4 +/- 4.4) (62% reduction, P<.001). The total number of illness days and duration of individual episodes were also significantly lower in the Chizukit group. Adverse drug reactions were rare, mild, and transient.\n A preventive effect of a product containing echinacea, propolis, and vitamin C on the incidence of respiratory tract infections was observed.", "The therapeutic activity and safety of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6), a new synthetic \"biological response modifier\", were examined in a double-blind, placebo-controlled, multicentre trial in 101 children, including 53 boys and 48 girls aged 2-13 years (mean +/- SD: 4.7 +/- 2.1 years) with a history of recurrent respiratory infections (RRI). Pidotimod (400 mg/day) or placebo were administered orally for 60 consecutive days, followed by a further 60-day follow-up period. The trial was completed by 89.1% of patients. The results indicate that pidotimod has a beneficial effect in children with recurrent respiratory infections: the percentage of patients presenting symptoms affecting the upper and lower airways was significantly lower after treatment with the active drug than after treatment with placebo. Relevant side effects were not reported during the trial. An evaluation of the expression of CD25 (after in vitro stimulation of circulating mononuclear cells with PHA) before and after treatment with the two products revealed a significant increase in CD25+ cells in the group treated with pidotimod but not in the group treated with placebo.", "The aim of this study was to evaluate the efficacy of an oral ribosomal immunotherapy in the management of children with recurrent acute adenoiditis (RAA). 60 children with RAA were included and randomly assigned into two groups (group A and B). Group A children underwent ribosomal prophylaxis, while group B received a placebo. Before, at the end and 6 months after start of the therapy, children underwent medical history, ENT examination, plasma levels of immunoglobulins class E, A, G, M (IgE, IgA, IgG, IgM), tympanometry, active anterior rhinomanometry and VAS scores by children' parents. After the treatment and at the end of the study, in the group A, the serum concentration of IgE was significantly (P < 0.05) lower than in group B (77.34 +/- 6.23 vs. 95.49 +/- 7.07 mg/dl; 74.82 +/- 6.26 vs. 94.44 +/- 7.44 mg/dl), IgA titers were significantly (P < 0.05) higher than in group B (312.04 +/- 18.41 vs. 213.20 +/- 11.82; 309.07 +/- 18.33 vs. 211.73 +/- 11.54 mg/dl) as well as serum concentration of IgG (1401.12 +/- 118.81 vs. 1101.81 +/- 109.64 mg/dl; 1412.19 +/- 116.43 vs. 1144.06 +/- 103.58 mg/dl). At the end of the study, comparison between the two groups showed, in group A: 77% of children (n = 23), versus 23% (n = 7) of group B, with a type A tympanogram; significant (P < 0.05) nasal flow decrease at the rhinomanometric measures; VAS scores were significantly (P < 0.05) improved (1.8 +/- 0.22 vs. 5.1 +/- 0.59) and frequency, severity and social impact of RAA episodes were significantly (P < 0.05) lower than group B. Our results show the therapeutic effectiveness of this approach in the prophylaxis of recurrent acute adenoiditis.", "94 children suffering from frequent infections of the respiratory tract and of the ear, nose and throat were treated under double-blind conditions with either a bacterial lysate (n = 45) or a placebo (n = 49). During the 6 months of the trial both treatments brought about a significant decrease in the incidence and duration of these infections as well as in the duration of concomitant antibiotherapy in comparison to the corresponding prior 6-month reference period. As these positive results recorded under the bacterial lysate and the placebo could not be differentiated statistically, the influence of meteorological and epidemiological factors as well as of the age of the children is discussed.", "Respiratory tract infections are among the most common diseases both in adults and children.\n This multicentre study, was carried out in 212 patients (118 adults with chronic respiratory diseases and 94 children with recurrent respiratory infections) at six Italian study centres. It was performed to establish the efficacy of Lantigen B for the prevention of bacterial complications and/or reduction of associated symptoms. Lantigen B is an oral product based on bacterial lysates of six different inactivated strains commonly involved in respiratory tract infections.\n The results of prophylactic treatment with Lantigen B in the population investigated were as follows: - the mean incidence of recurrence in the pediatric patients over the 6-month observation period of the study was 1.643 in the placebo group and 1.211 in the Lantigen B group (a relative reduction of 35.7%); - the mean incidence of recurrence in the adult patients over the 6-month observation period of the study was 0.73 in the placebo group and 0.56 in the Lantigen B group (a relative reduction of 30.4%). The improvement in other important parameters, such as the number of days with a high temperature, cough, and catarrh in the children and objective clinical findings at the lymph nodes of the neck, chest, and pharyngotonsillar region in the adults, provides further evidence of the efficacy of Lantigen B.\n This study demonstrates Lantigen B's effectiveness in the prevention of bacterial complications and suggests that it can be used in patients who are particularly at risk of infection (children, the elderly, diabetics, and immunocompromised patients) or those in whom an infection might aggravate a clinical picture that is already inherently complicated (diabetics again, but also patients with heart, kidney, or liver disease).", "nan", "nan", "Recurrent upper respiratory tract infections (URTI) are very common in patients of all ages. Rhinitis, bronchitis, chronic sinusitis and otitis appear to be the prevalent forms of recurrent respiratory infections in the paediatric population. The aim of treatment is so the solution of the respiratory pathology and the also the prevention of their complications. Antibacterial therapy is still the classical treatment approach in patients both with respiratory tract infections and with otitis media, despite the fact that antibacterials have several well known drawbacks, especially when used to treat recurrent infections. Eighty-four paediatric patients of both sexes (range: 4-14 years) with otitis were enrolled in the study. Patients were included if they had a >2 years' history of recurrent or chronic respiratory infections, and/or had experienced at least three episodes requiring medical consultations and/or treatment during the winter prior to the study. The young patients were randomised to receive Immucytal (group A) or placebo (group B) treatment according to the following protocol: (1) starting therapy (1 month): one tablet daily in the morning 4 days per week for 3 consecutive weeks; (2) maintenance period (5 months): one tablet daily in the morning 4 days per week for 1 week every month. Placebo and Immucytal tablets were identical in shape and size, in order to maintain double-blind conditions. Patients of group A with recurrent URTI had a significantly decreased incidence of ENT infections, fever and shorter duration of illness, decreased requirement for ancillary medications and fewer work-days lost. The reduction in the incidence of infectious episodes became significant vs. placebo. A significantly improved outcome vs. placebo was also observed on the incidence of fever, frequency and duration of infectious episodes, ancillary therapies. Immucytal treatment was associated with significant changes in both immunological and auditory function parameters. Serum concentrations of immunoglobulins were significantly increased in Immucytal. For both evaluations, a significant difference between treatment groups was found (P>0.001). Preventive strategies, such as ribosomal immunotherapy, may represent a valid alternative approach.", "Levamisole was tested double-blind in 106 children with recurrent upper respiratory tract infections. They received either levamisole (n = 53) or placebo (n = 53) 0.5 ml/kg bodyweight b.i.d. for two consecutive days each week for six months. A control examination was performed every two months. Both groups were compared by means of the Fisher-test and the Mann-Whitney U-test (two-tailed probability each). Improvement was observed more frequently in the levamisole group with regard to the number of episodes of infection, and the total duration and severity of the infections. No side-effects, except for some stomach complaints in one levamisole patient, were reported.", "Reaferon, the analog of human alpha 2-interferon obtained by gene engineering techniques, was studied with a view to its use for the prevention of hepatitis A. The study involved children of preschool age in Tashkent. In a strictly controlled trial children aged 2-6 years received the preparation orally in a dose of 1 X 10(6) I. U. or the diluent alone used as placebo. The preparation was administered to 1,100 children and the placebo to 1,078 children. The preparation and placebo were administered twice a week for two months. On the whole, during that period hepatitis A morbidity in both test and control groups of children was the same (5.1% and 4.9% respectively), but among children of nursery age receiving Reaferon the incidence of hepatitis A and acute respiratory viral infections was lower than among those receiving the placebo, though this difference was statistically significant only for cases of acute respiratory infections.", "Numerous trials of prophylaxis of recurrent respiratory infections in children have been performed, even though the only controlled trials providing incontrovertible results were the ones carried out with levamisole and thymostimulin through intramuscular administration. We have experimented a calf-thymic extract administered by oral route (thymomodulin). During the summer we enrolled 40 children aged between 3.5, and 9 years who had suffered from RRI during the previous winter. The patients were randomly divided in two groups and respectively treated with thymomodulin or with placebo; 21 children were given the thymic extract and 19 the placebo. The trial was carried out according to a double-blind schedule for a period of four months, from the beginning of October '84. At the end of the trial we assessed the catharral bouts observed during the research period by the family doctors and the parents evaluation on the clinical state. The difference between the two groups is statistically highly significant both with reference to the reduction of the total number of catharral bouts and to the general clinical state according to the parents opinion. The research clearly demonstrates the protective effect of the thymomodulin, probably due to the \"restorative\" effect on some immunological functions, temporarily compromised during the infection bouts.", "A 6-month double-blind, prospective, randomized, placebo-controlled trial was conducted to establish the safety and efficacy of OM-85-BV in the treatment of subacute sinusitis and in the following prevention of the respiratory tract infections in 56 children from 18 months to 9 years of age. In the subacute phase of the sinusitis the patients were given one OM-85-BV capsule (3.5 mg of bacterial extracts) (n = 26) or placebo (n = 30), daily for ten days; additionally both groups took amoxicillin/clavulanate 40/10 mg/kg daily in three divided doses for 21 days. For the following two months the patients took one OM-85-BV capsule or placebo, ten days a month. In the subacute phase the OM-85-BV group of patients improved sooner (5.56 +/- 4.98 vs 10 +/- 8.49 days) and had a shorter convalescence (15.38 +/- 8.91 vs 20.28 +/- 7.17 days). During the six month follow-up the patients in the OM-85-BV group had a lower number of infections (1.56 +/- 0.3 vs 2.22 +/- 0.43) and required a lower number of drug treatments (1.47 +/- 0.32 vs 1.94 +/- 0.42). One patient treated with OM-85-BV presented a mild rash which disappeared three days after the drug discontinuation. We conclude that OM-85-BV is safe at pediatric ages, as well as accelerates the cure and improvement of subacute sinusitis while it lowers the incidence of respiratory infections." ]

[ "15294086", "19025495", "16135904", "19549342" ]

[ "Adherence to antiretroviral therapy in HIV-infected pediatric patients improves with home-based intensive nursing intervention.", "Virological suppression achieved with suboptimal adherence levels among South African children receiving boosted protease inhibitor-based antiretroviral therapy.", "Evaluation of a peer support group therapy for HIV-infected adolescents.", "Medication diaries do not improve outcomes with highly active antiretroviral therapy in Kenyan children: a randomized clinical trial." ]

[ "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.", "Sixty-six children who were receiving antiretroviral treatment were assessed for treatment adherence and virological outcome to compare boosted protease inhibitor-based regimens with nonnucleoside reverse-transcriptase inhibitor-based regimens. Children who were receiving protease inhibitor-based regimens demonstrated higher rates of virological suppression, even with poor treatment adherence (<80%). In children, boosted protease inhibitors seem to be more forgiving of poor adherence than do nonnucleoside reverse-transcriptase inhibitors.", "To assess the effects of a peer support group therapy on HIV-infected adolescents.\n A prospective study of a cohort of HIV-infected adolescents participating or not participating in a psychodynamic oriented, emotional support group.\n From a group of 30 perinatally HIV-infected adolescents who attended an outpatient clinic, 10 agreed to participate in the peer support group (group 1), 10 declined (group 2) and 10 others who lived too far from the clinic were not invited to participate (group 3). The three groups were compared at baseline and 2 years later using the outcome measures: perceived illness experience scale, perceived treatment inventory, self-esteem inventory.\n At baseline, the three groups had similar characteristics overall. The adolescents' self-esteem was in the normal range. After 2 years, worries about illness had decreased in group 1, whereas the scores had increased or remained the same for the other adolescents (P = 0.026). The adolescents in group 1 had less negative perception of treatment at 2 years than those in groups 2 and 3 (P = 0.030). After intervention, the percentage of adolescents with an undetectable viral load had increased in group 1 from 30 to 80% (P = 0.063) but was unchanged in groups 2 and 3. Considering the three groups altogether, the decrease in the viral load correlated with improvement of the perceived treatment inventory (Spearman R = 0.482 P = 0.015).\n : This pilot study suggests that a peer support group intervention is associated with an improvement in adolescents' emotional well being, and that this can have a positive influence on medical outcomes.", "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." ]

[ "6615094", "8124838", "91836", "18372218", "1973470", "11401128", "18277196", "8296738", "11273502", "10092561", "8105673", "6478567", "10892523", "12707240", "12565088", "2011669", "2271343", "6456960", "8147544", "18654005", "8185448", "12520156", "8970420", "7330986", "9802147", "7050369", "10493846", "1208362", "1617762", "1874262", "2024598", "8790035", "10098823", "6846123", "6972693", "18513526", "7074797", "1349062", "1588521", "14671465", "15605326", "16563893", "12186798" ]

[ "The group counseling v exercise therapy study. A controlled intervention with subjects following myocardial infarction.", "Effects of intensive multiple risk factor reduction on coronary atherosclerosis and clinical cardiac events in men and women with coronary artery disease. The Stanford Coronary Risk Intervention Project (SCRIP).", "Reduction in sudden deaths by a multifactorial intervention programme after acute myocardial infarction.", "Effects of high frequency exercise in patients before and after elective percutaneous coronary intervention.", "Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial.", "Exercise training intervention after coronary angioplasty: the ETICA trial.", "Left ventricular remodelling in patients with moderate systolic dysfunction after myocardial infarction: favourable effects of exercise training and predictive role of N-terminal pro-brain natriuretic peptide.", "Exercise testing and training in physically disabled men with clinical evidence of coronary artery disease.", "Retardation of coronary atherosclerosis with yoga lifestyle intervention.", "Changes in cardiorespiratory fitness, psychological wellbeing, quality of life, and vocational status following a 12 month cardiac exercise rehabilitation programme.", "Secondary prevention after acute myocardial infarction.", "Home versus group exercise training for increasing functional capacity after myocardial infarction.", "Physiologic and related behavioral outcomes from the Women's Lifestyle Heart Trial.", "Improved exercise tolerance and quality of life with cardiac rehabilitation of older patients after myocardial infarction: results of a randomized, controlled trial.", "Long-term changes in exercise capacity, quality of life, body anthropometry, and lipid profiles after a cardiac rehabilitation program in obese patients with coronary heart disease.", "Recovery after myocardial infarction. Effects of a caring rehabilitation programme.", "A controlled trial of community based coronary rehabilitation.", "[Early functional evaluation and physical rehabilitation in patients with wide myocardial infarction (author's transl)].", "A case-management system for coronary risk factor modification after acute myocardial infarction.", "Effects of a phase III cardiac rehabilitation program on physical status and lipid profiles in elderly patients with coronary artery disease: Juntendo Cardiac Rehabilitation Program (J-CARP).", "Training after myocardial infarction: lack of long-term effects on physical capacity and psychological variables.", "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 of five years of cardiac rehabilitation after coronary artery bypass grafting on coronary risk factors.", "[Value of regular supervised physical training after acute myocardial infarction].", "Serum cholesterol, lifestyle, working capacity and quality of life in patients with coronary artery disease. Experiences from a hospital-based secondary prevention programme.", "Exercise after myocardial infarction: a 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 physical training after myocardial infarction. Effects on risk factors, nonfatal reinfarction, and death.", "Regular physical exercise and low-fat diet. Effects on progression of coronary artery disease.", "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.", "Effects on quality of life with comprehensive rehabilitation after acute myocardial infarction.", "Interaction between exercise training and ejection fraction in predicting prognosis after a first myocardial infarction.", "Behavioral effects of a comprehensive, multifactorial program for lifestyle change after percutaneous transluminal coronary angioplasty: a prospective, randomized controlled study.", "Effects of cardiac rehabilitation after myocardial infarction: changes in coronary risk factors and long-term prognosis.", "Effects of a prescribed supervised exercise program on mortality and cardiovascular morbidity in patients after myocardial infarction. The National Exercise and Heart Disease Project.", "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.", "Treadmill test responses to an early exercise program after myocardial infarction: a randomized study.", "Effects of self-help post-myocardial-infarction rehabilitation on psychological adjustment and use of health services.", "Benefits and weaknesses of a cardiac rehabilitation programme.", "Influence on lifestyle measures and five-year coronary risk by a comprehensive lifestyle intervention programme in patients with coronary heart disease.", "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.", "Return to full normal activities including work at two weeks after acute myocardial infarction.", "Exercise-induced increase in baroreflex sensitivity predicts improved prognosis after myocardial infarction." ]

[ "One hundred six postmyocardial infarction subjects who either achieved a mean work load of less than seven mets on treadmill testing, who were rated as anxious and/or depressed, or who met both criteria, participated in a controlled study comparing the rehabilitation effectiveness of exercise therapy and group counseling. Each intervention lasted 12 weeks. Follow-up evaluations were scheduled at three months, six months and one year. Exercise substantially increased mean work capacity, decreased fatigue, lessened anxiety and depression, and promoted independence and sociability. Counseling substantially reduced depression and promoted a sense of friendliness, and decreased interpersonal friction as well as greater independence and sociability. The control group reported no substantial change on any measured factor. Neither counseling nor exercise had an effect on mortality though subjects in the exercise group reported fewer major cardiovascular sequelae.", "Recent clinical trials have shown that modification of plasma lipoprotein concentrations can favorably alter progression of coronary atherosclerosis, but no data exist on the effects of a comprehensive program of risk reduction involving both changes in lifestyle and medications. This study tested the hypothesis that intensive multiple risk factor reduction over 4 years would significantly reduce the rate of progression of atherosclerosis in the coronary arteries of men and women compared with subjects randomly assigned to the usual care of their physician.\n Three hundred men (n = 259) and women (n = 41) (mean age, 56 +/- 7.4 years) with angiographically defined coronary atherosclerosis were randomly assigned to usual care (n = 155) or multifactor risk reduction (n = 145). Patients assigned to risk reduction were provided individualized programs involving a low-fat and -cholesterol diet, exercise, weight loss, smoking cessation, and medications to favorably alter lipoprotein profiles. Computer-assisted quantitative coronary arteriography was performed at baseline and after 4 years. The main angiographic outcome was the rate of change in the minimal diameter of diseased segments. All subjects underwent medical and risk factor evaluations at baseline and yearly for 4 years, and reasons for all hospitalizations and deaths were documented. Of the 300 subjects randomized, 274 (91.3%) completed a follow-up arteriogram, and 246 (82%) had comparative measurements of segments with visible disease at baseline and follow-up. Intensive risk reduction resulted in highly significant improvements in various risk factors, including low-density lipoprotein cholesterol and apolipoprotein B (both, 22%), high-density lipoprotein cholesterol (+12%), plasma triglycerides (-20%), body weight (-4%), exercise capacity (+20%), and intake of dietary fat (-24%) and cholesterol (-40%) compared with relatively small changes in the usual-care group. No change was observed in lipoprotein(a) in either group. The risk-reduction group showed a rate of narrowing of diseased coronary artery segments that was 47% less than that for subjects in the usual-care group (change in minimal diameter, -0.024 +/- 0.066 mm/y versus -0.045 +/- 0.073 mm/y; P < .02, two-tailed). Three deaths occurred in each group. There were 25 hospitalizations in the risk-reduction group initiated by clinical cardiac events compared with 44 in the usual-care group (rate ratio, 0.61; P = .05; 95% confidence interval, 0.4 to 0.9).\n Intensive multifactor risk reduction conducted over 4 years favorably altered the rate of luminal narrowing in coronary arteries of men and women with coronary artery disease and decreased hospitalizations for clinical cardiac events.", "375 consecutive patients below 65 years who had an acute myocardial infarction (AMI) took part in a randomised rehabilitation and secondary prevention trial (part of a W.H.O.-coordinated project) designed to study the effects of a multifactorial intervention programme on morbidity, mortality, return to work, &c. After three years' follow-up the cumulative coronary mortality was significantly smaller in the intervention group than in the controls (18.6% versus 29.4%, p = 0.02). This difference was mainly due to a reduction of sudden deaths in the intervention group (5.8% versus 14.4%, p less than 0.01). The reduction was greatest during the first six months after AMI. 18.1% in the intervention group and 11.2% in the controls (p less than 0.10) presented with non-fatal reinfarctions. The number of patients with new Q-QS findings at the end of the three years was, however, almost the same in both groups. The results suggest that organised aftercare during the first six months after AMI with special emphasis on optimum medical control and health education contributes significantly to a reduction in the number of sudden deaths.", "The aim of this study was to evaluate the effects of high frequency exercise for patients before and after an elective percutaneous coronary intervention (PCI), with special reference to maximal aerobic capacity, muscle function, health related quality of life (HRQoL), waist-hip ratio (WHR) and restenosis.\n A randomised, controlled study was performed in Sweden between 2004 and 2006 in thirty-seven patients (five women) with stable coronary artery disease (CAD), age 63.6+/-6.9 years, randomised to either high frequency exercise or control group. The patients in the training group performed three endurance resistance exercises and trained on a cycle ergometer 30 min, 5 times a week for 8 months at 70% of VO(2max).\n Patients in the training group significantly improved their maximal aerobic capacity (15 (9-46) vs. 8 (0-18)% p<or=0.05), shoulder flexion (p<or=0.01), shoulder abduction (p<or=0.01) and heel-lift (p<or=0.05) compared to the control group. There were no significant differences between the groups in HRQoL, WHR and restenosis.\n High frequency exercise in patients treated with PCI seems to improve maximal aerobic capacity and muscle function, which may reduce the risks of further progression of atherosclerosis. However, further larger studies are needed to fully investigate the effects of exercise in patients with PCI.", "In a prospective, randomised, controlled trial to determine whether comprehensive lifestyle changes affect coronary atherosclerosis after 1 year, 28 patients were assigned to an experimental group (low-fat vegetarian diet, stopping smoking, stress management training, and moderate exercise) and 20 to a usual-care control group. 195 coronary artery lesions were analysed by quantitative coronary angiography. The average percentage diameter stenosis regressed from 40.0 (SD 16.9)% to 37.8 (16.5)% in the experimental group yet progressed from 42.7 (15.5)% to 46.1 (18.5)% in the control group. When only lesions greater than 50% stenosed were analysed, the average percentage diameter stenosis regressed from 61.1 (8.8)% to 55.8 (11.0)% in the experimental group and progressed from 61.7 (9.5)% to 64.4 (16.3)% in the control group. Overall, 82% of experimental-group patients had an average change towards regression. Comprehensive lifestyle changes may be able to bring about regression of even severe coronary atherosclerosis after only 1 year, without use of lipid-lowering drugs.", "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 investigate the effects of exercise training (ET) on left ventricular (LV) volumes, cardiopulmonary functional capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in postinfarction patients with moderate LV dysfunction.\n Sixty-one postinfarction patients were randomized into two groups: group T [n=30, LV ejection fraction (EF) 41.6+/-11.3%, mean+/-SD] entered a 6-month ET programme, whereas group C (n=31, EF 42.0+/-7.6%, P=NS) did not. NT-proBNP assay, Doppler-echocardiography and cardiopulmonary exercise test were performed upon enrolment and at sixth months.\n At sixth months, trained patients showed an improvement in workload (+26%, P<0.001), Vo2peak (+31%, P<0.001), LV end-diastolic volume index (LVEDVI; -9%, P<0.001), a reduction in NT-proBNP (-71%, P<0.001) and a significant correlation between changes in NT-proBNP and in LVEDVI (r=0.858, P<0.001). Baseline NT-proBNP correlated with changes in LVEDVI in both trained (r=0.673, P<0.001) and untrained (r=0.623, P<0.001) patients. Group C showed unfavourable LVEDVI dilation (+8%, P<0.001; T vs. C group, P<0.001) and a smaller reduction in NT-proBNP (-40%, P<0.001; T vs. C group, P<0.001).\n Six month ET induced a favourable LV remodelling and a marked fall in NT-proBNP that could predict LV remodelling in postinfarction patients with moderate LV dysfunction.", "A prospective, randomized, controlled clinical trial in patients with coronary artery disease (CAD) and a concurrent physical disability evaluated the effects of a home exercise training program on cardiovascular function and blood lipids. Eighty-eight men between the ages of 42 and 72 years (mean 62) with documented CAD and a physical disability with functional use of > or = 2 extremities including 1 arm were randomized to either a 6-month home exercise training program using wheelchair ergometry or to a control group that received usual and customary care. Both groups received dietary instructions and were requested to follow a fat-controlled diet. Exercise test variables with echocardiography and blood lipids were measured at baseline and at 6 months. The home exercise training group significantly improved both peak exercise left ventricular ejection fraction (p = 0.007) and fractional shortening (p = 0.01) between baseline to 6 months, whereas the control group showed no significant changes. Exercise training effects of decreased resting heart rate (p = 0.03) and decreased peak rate pressure product (p = 0.03) were also found in the treatment group. No exercise-related cardiac complications occurred. Both groups significantly (p < or = 0.01) increased high-density lipoprotein cholesterol levels. These results indicate that physically disabled men with CAD can safely participate in a home exercise training program which may result in intrinsic cardiac benefits. The metabolic cost of activities of daily living imposed on this disabled population may also have a positive effect on high-density lipoprotein cholesterol levels.", "Yoga has potential for benefit for patients with coronary artery disease though objective, angiographic studies are lacking.\n We evaluated possible role of lifestyle modification incorporating yoga, on retardation of coronary atherosclerotic disease. In this prospective, randomized, controlled trial, 42 men with angiographically proven coronary artery disease (CAD) were randomized to control (n = 21) and yoga intervention group (n = 21) and were followed for one year. The active group was treated with a user-friendly program consisting of yoga, control of risk factors, diet control and moderate aerobic exercise. The control group was managed by conventional methods i.e. risk factor control and American Heart Association step I diet.\n At one year, the yoga groups showed significant reduction in number of anginal episodes per week, improved exercise capacity and decrease in body weight. Serum total cholesterol, LDL cholesterol and triglyceride levels also showed greater reductions as compared with control group. Revascularisation procedures (coronary angioplasty or bypass surgery) were less frequently required in the yoga group (one versus eight patients; relative risk = 5.45; P = 0.01). Coronary angiography repeated at one year showed that significantly more lesions regressed (20% versus 2%) and less lesions progressed (5% versus 37%) in the yoga group (chi-square = 24.9; P < 0.0001). The compliance to the total program was excellent and no side effects were observed.\n Yoga lifestyle intervention retards progression and increases regression of coronary atherosclerosis in patients with severe coronary artery disease. It also improves symptomatic status, functional class and risk factor profile.", "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.", "The hypothesis that 6 months after acute myocardial infarction, adoption of secondary prevention activities would be higher, quality of life better, and blood cholesterol lower in patients randomly allocated to a mail-out intervention program than in those receiving usual care was tested. Patients were aged < 70 years, admitted to hospitals in and around Newcastle, Australia with a suspected heart attack and discharged alive from the hospital. Cluster randomization, based on the patient's family practitioner, was used to allocate consenting patients to an intervention or usual care group. A low-cost mail-out program was designed to help patients reduce dietary fat, obtain regular exercise by walking and (for smokers only) to quit smoking. Supplementary telephone contact was also used. In addition, a letter was sent to the family doctor regarding the benefit of aspirin and beta blockers for secondary prevention. Of eligible patients, 71% participated, and 79% of the 213 intervention subjects and 87% of the 237 usual care ones returned a 6-month follow-up questionnaire. Self-reported fat intake was significantly lower, an \"emotional\" score obtained from a quality-of-life questionnaire was significantly higher in the intervention than in the usual care group, and \"physical\" and \"social\" scores for quality of life were slightly higher. Blood cholesterol level and other variables were not different between the groups at 6 months. Simple low-cost programs providing support and advice on lifestyle change may be beneficial, particularly in improving patients' perceived quality of life.", "To evaluate the efficacy of exercise training for increasing functional capacity in the 6 months after clinically uncomplicated myocardial infarction, 198 men 52 +/- 9 years of age participated in a training study. They were randomly assigned to one of four exercise protocols: 8 to 26 weeks of training at home (group 1, n = 66) or in a group program (group 2, n = 61) following treadmill testing performed 3 weeks after infarction, treadmill testing at 3 weeks without subsequent training (group 3, n = 34), and treadmill testing for the first time at 26 weeks (control, n = 37). At 26 weeks functional capacity was significantly higher in patients training at home or in a group program than that in patients without training or in control patients: 8.1 +/- 1.5, 8.5 +/- 1.3, 7.5 +/- 1.8, and 7.0 +/- 1.7 METs, respectively (p less than .05 and p less than .001). No significant differences in functional capacity were noted between patients training at home and those in a group program. No training-related complications occurred. Home and group training are equally effective in increasing functional capacity of low-risk patients after myocardial infarction.", "The Women's Lifestyle Heart Trial was a small (N = 28) randomized controlled trial to evaluate the effects of a comprehensive lifestyle self-management program (very low-fat vegetarian diet, stress-management training, exercise, group support, and smoking cessation) on reduction of cardiovascular risk factors in postmenopausal women with coronary heart disease (CHD). Women assigned to the treatment condition (Prime Time) participated in a week-long retreat followed by twice-weekly 4-hour meetings. Endpoints were program adherence; changes in lipid profiles, body mass, blood pressure, hypolipidemic and antihypertensive medications; and quality of life. Risk factor and psychosocial evaluations were conducted at baseline and at 4, 12, and 24 months. Repeated measures analyses of covariance revealed that the dietary, stress management, and physical activity changes made by intervention women were dramatic and lasting. There were significantly greater improvements in the Prime Time condition compared to the usual care control group on body mass, angina symptoms, and quality of life, and a tendency for a greater reduction in blood pressure-lowering medications. Similar patterns were seen in lipids, blood pressure, and lipid-lowering medications, but did not reach significance. These results demonstrate that postmenopausal CHD women can make lasting lifestyle changes, and that these changes may reduce the need for cardiac medications and improve CHD risk factors and quality of life.", "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.", "nan", "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.", "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.", "nan", "To evaluate the efficacy of a physician-directed, nurse-managed, home-based case-management system for coronary risk factor modification.\n Randomized clinical trial in which patients received a special intervention (n = 293) or usual medical care (n = 292) during the first year after acute myocardial infarction.\n 5 Kaiser Permanente Medical Centers in the San Francisco Bay area.\n 585 men and women aged 70 years or younger who were hospitalized for acute myocardial infarction.\n In the hospital, specially trained nurses initiated interventions for smoking cessation, exercise training, and diet-drug therapy for hyperlipidemia. Intervention after discharge was implemented primarily by telephone and mail contact with patients in their homes. All medically eligible patients received exercise training; all smokers received the smoking cessation intervention; and all patients received dietary counseling and, if needed, lipid-lowering drug therapy.\n Smoking prevalence and plasma low-density lipoprotein cholesterol (LDL) concentrations were measured 2 months after infarction, and functional capacity was measured 6 months after infarction.\n In the special intervention and usual care groups, the cotinine-confirmed smoking cessation rates were 70% and 53% (P = 0.03), plasma LDL cholesterol levels were 2.77 +/- 0.69 mmol/L and 3.41 +/- 0.90 mmol/L (107 +/- 30 mg/dL and 132 +/- 30 mg/dL) (P = 0.001), and functional capacities were 9.3 +/- 2.4 METS and 8.4 +/- 2.5 METS (P = 0.001), respectively.\n In a large health maintenance organization, a case-management system was considerably more effective than usual medical care for modification of coronary risk factors after myocardial infarction.", "Limited data are available regarding the effects of phase III cardiac rehabilitation on the physical status and risk factors in elderly patients with coronary artery disease (CAD).\n Thirty-four male CAD patients (>65 years old) were randomly assigned to an intervention group (n=18) or a control group (n=16). The intervention group participated in a phase III cardiac rehabilitation program consisting of exercise training, diet therapy, and weekly counseling for 6 months. In the control group, usual outpatient care was provided. In the intervention group, body mass index, waist size and fat weight significantly decreased; peak VO2 and anaerobic threshold VO2 were maintained; isokinetic peak torques of knee extensor and flexor muscles significantly increased; anterior trunk flexibility was significantly improved. In the control group, all parameters were unchanged except for peak VO2, which significantly decreased. In the intervention group, serum total cholesterol levels significantly decreased after cardiac rehabilitation. However, high-density lipoprotein-cholesterol and apoA-I levels also decreased. In the control group, no significant change in lipid profile was observed.\n The results suggest that phase III cardiac rehabilitation could be beneficial for elderly patients with CAD.", "This study evaluated long-term effects of 12 weeks of supervised training, of at least 45 minutes duration with two sessions per week, on physical performance and psychological well-being after myocardial infarction (MI). Sixty-nine patients were randomized to either an exercise or a nonexercise group. Maximum exercise capacity 6 weeks post-MI was inversely related to the acute peak aspartate aminotransferase values in serum, as an index of infarct size. One year post-MI, the increase in level of fitness (10%) in the training group did not significantly exceed (p = .10) that of the controls (2%). No intergroup differences were registered in self-rated psychological well-being and physical scores or in the return to work rate. In the training group, but not in the controls, the change in perceived dyspnoea at leisure-time activities was positively related to the objectively measured peak exercise capacity. We conclude that after MI only marginal improvements in physical performance are achieved 6 months after training is finished, with no long-term psychological benefits apparent versus a usual care program. The adaptive implications of supervised conventional exercise programs post-MI are therefore questioned.", "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.", "Coronary risk factors were studied in 119 patients randomly assigned to cardiac rehabilitation and compared with 109 patients receiving standard care alone after coronary artery bypass grafting. The long-term impact of rehabilitation on risk factors was modest in patients undergoing elective coronary surgery.", "nan", "Coronary artery diseases (CAD) are main causes of morbidity and hospitalisation in western countries and CAD patients are at considerable risk of suffering further cardiac events. The development and evaluation of secondary prevention programmes therefore an important task. This thesis includes investigations on CAD patients admitted to a secondary prevention programme at Malmö University Hospital, Malmö, Sweden. Four weeks after discharge from the hospital, consecutive male and female patients aged 50-70 years with acute myocardial infarction (AMI) or treated with coronary artery bypass grafting (CABG) surgery were randomised to a hospital organised preventive intervention or to usual follow-up at their general practitioners. In the three studies using this randomised design, 87 (study II), 90 (study IV), and 106 (study V) intervention patients were available for evaluation. In addition, without randomisation, lipid levels at four weeks after the event was compared with levels estimated within 24 hours after onset of symptoms in 141 AMI patients (study I), and quality of life (QL) were estimated by questionnaire at one month and at one year after the event in 266 AMI, 94 CABG, and 16 percutaneous transluminal coronary angioplasty (PTCA) patients (study III). The prevention programme was effective in improving food habits but showed no impact on smoking habits or physical exercise in AMI patients (study II). The intervention also did not show any significant improvement in working capacity in AMI and CABG patients. However, working capacity improved in both intervention and reference CABG patients, most probably due to improved coronary circulation from the surgery (study IV). Cholesterol levels decreased significantly in AMI and CABG intervention patients as compared to the corresponding reference patients. This difference most likely was due to a higher frequency of lipid lowering drugs used in the intervention patients (study V). The prevention programme also decreased body mass index significantly in AMI but not in CABG patients (study V). In AMI patients receiving thrombolysis, cholesterol levels estimated within 24 hours after onset of symptoms and at four weeks after the event were virtually equal. In AMI patients not receiving thrombolysis, the lipid estimates from four weeks after the event were slightly, but significantly, above the within 24 hours from onset of symptoms estimates (study I). One month after the event, both somatic and psychological aspects of QL were negatively affected in AMI and CABG patients compared to population controls. One year after the event, patients differed from controls mainly in somatic symptoms (study III). Thus, the intervention programme was most successful in affecting lipid levels and food habits in AMI patients. QL was considerably affected in patients following an cardiac event, especially during the initial recovery phase. In addition, in patients receiving thrombolysis, cholesterol levels estimated four weeks after an AMI are reasonably valid estimates of baseline values and may be used to decide about lipid lowering interventions.", "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.", "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.", "nan", "Significant regression of coronary and femoral atherosclerotic lesions has been documented by angiographic studies using aggressive lipid-lowering treatment. This study tested the applicability and effects of intensive physical exercise and low-fat diet on coronary morphology and myocardial perfusion in nonselected patients with stable angina pectoris.\n Patients were recruited after routine coronary angiography for stable angina pectoris; they were randomized to an intervention group (n = 56) and a control group on \"usual care\" (n = 57). Treatment comprised intensive physical exercise in group training sessions (minimum, 2 hr/wk), daily home exercise periods (20 min/d), and low-fat, low-cholesterol diet (American Heart Association recommendation, phase 3). No lipid-lowering agents were prescribed. After 12 months of participation, repeat coronary angiography was performed; relative and minimal diameter reductions of coronary lesions were measured by digital image processing. Change in myocardial perfusion was assessed by 201Tl scintigraphy. In patients participating in the intervention group, body weight decreased by 5% (p less than 0.001), total cholesterol by 10% (p less than 0.001), and triglycerides by 24% (p less than 0.001); high density lipoproteins increased by 3% (p = NS). Physical work capacity improved by 23% (p less than 0.0001), and myocardial oxygen consumption, as estimated from maximal rate-pressure product, by 10% (p less than 0.05). Stress-induced myocardial ischemia decreased concurrently, indicating improvement of myocardial perfusion. Based on minimal lesion diameter, progression of coronary lesions was noted in nine patients (23%), no change in 18 patients (45%), and regression in 13 patients (32%). In the control group, metabolic and hemodynamic variables remained essentially unchanged, whereas progression of coronary lesions was noted in 25 patients (48%), no change in 18 patients (35%), and regression in nine patients (17%). These changes were significantly different from the intervention group (p less than 0.05).\n In patients participating in regular physical exercise and low-fat diet, coronary artery disease progresses at a slower pace compared with a control group on usual care.", "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.", "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)", "Although recent meta-analysis trials have shown that exercise training may improve survival after myocardial infarction, the mechanism of this beneficial effect is still unknown. The purpose of this study was to detect possible interactions between exercise training and predictors of prognosis after a first myocardial infarction.\n Patients with uneventful clinical courses after a first myocardial infarction were randomly assigned to a 4-week training period (125 patients, group 1) or to a control group (131 patients, group 2). Before randomization, all patients underwent a symptom-limited exercise test (28 +/- 2 days after myocardial infarction), 24-hour Holter monitoring, and coronary arteriography (31 +/- 3 days after the acute episode). After a mean follow-up period of 34.5 months, 18 patients had cardiac deaths (5 in group 1 and 13 in group 2). Multivariate analysis by Cox regression model showed that ejection fraction was the only independent prognostic indicator (P = .03). Evidence existed of an interaction between ejection fraction and exercise training, showing an effect of physical training on survival that depended on the patient's ejection fraction. Among patients with ejection fractions < 41%, the relative risk for an untrained patient was 8.63 times higher than for a trained patient (P = .04), whereas for ejection fractions > 40%, the estimated risks for trained and untrained patients were similar.\n These data show that exercise training may prolong survival in post-myocardial infarction patients with depressed left ventricular function. A randomized trial in such patients seems warranted.", "A group of 93 coronary patients recently treated with percutaneous transluminal coronary angioplasty (PTCA) were randomly assigned to either an intervention or a control group. Subjects in the intervention group participated in a comprehensive behaviorally oriented program aimed at achieving significant long-term changes in risk factor-related lifestyle behavior. Assessments of lifestyle behaviors, psychological factors, biological risk factors, and rehabilitation as well as secondary prevention endpoints were carried out, at inclusion and after 12 months. Results showed that the intervention patients, as compared with controls, improved significantly on measures assessing smoking, exercise, and diet habits. These self-rated changes were confirmed by weight reductions and improved exercise capacity, as well as by between-group differences in subclinical chest pain during an exercise test. However, few effects were found on the different psychological variables, as well as on morbidity or return to work.", "Prognosis during 5 years of follow-up after first myocardial infarction (MI) in a group of men (aged 40 to 55 years) was related to risk factors determined at the time of MI. Progression of coronary artery disease (CAD) was measured by the occurrence of severe angina pectoris, recurrent myocardial infarction, and cardiac death. Only smoking and serum cholesterol level influenced prognosis. It was possible to identify a subgroup (patients smoking less than 20 cigarettes/day and having a cholesterol level of less than 7.0 mmoles/L) with low risk for progression of CAD. A randomly applied 6-week rehabilitation program shortly after MI was associated with a 50% decrease in progressive CAD when compared to the control group. Since only a slight decrease in cholesterol levels was found in the rehabilitation group, a direct effect of the rehabilitation program could thus not be excluded because the second important risk factor, smoking, did not show differences between the two groups. The smoking habits at the time of MI determined the continuation of cigarette smoking and rehabilitation did not influence smoking habits.", "This study enrolled 651 men with myocardial infarction in five participating centers in a randomized 3 year clinical trial of the effects of prescribed supervised exercise. The subjects, aged to 30 to 64 years, were screened for eligibility 2 to 36 months after their qualifying myocardial infarction. The men in the exercise group pursued intensive exercise in the laboratory for 8 weeks and then in a gymnasium for 34 months. The experience of the exercise group was more favorable than that of the control group in most of the comparisons made. The cumulative 3 year total mortality rate was 7.3 percent for the control group and 4.6 percent for the exercise group; the 3 year rate for recurrent myocardial infarction was 7.0 and 5.3 percent, respectively. Mortality rates in the two groups did not differ significantly, but the data were consistent with an assumption of substantial benefit from exercise. Adjustment for small differences in baseline variables by multivariate methods did not materially alter the estimate of effect of exercise. Certain subgroups showed a greater benefit from exercise.", "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 effects of an exercise program started early after myocardial infraction and the added effects of an outpatient teaching-counseling program were studied. At random, 84 patients were allocated to a control group (A), 88 patients to an exercise group (B1) and 86 patients to an exercise and teaching-counseling group (B2). The same exercise program was prescribed for patients in groups B1 and B2 and was started about 4.5 days after myocardial infarction and continued for 3 months. The outpatient teaching-counseling program consisted of eight group sessions pertaining to risk factor reduction and psychosocial adjustment to myocardial infraction. A low-level treadmill test and an exercise test were performed at 3 months and the exercise test was repeated at 6 months. The clinical, hemodynamic and electrocardiographic responses to these tests were not different among the three groups. However, by the end of 3 months, patients in group B1 and B2 reported walking greater distances than patients in group A. The incidence of morbidity and mortality was not different between the groups. No deleterious or beneficial physiologic effects of an exercise program either by itself or combined with a teaching-counseling program were demonstrated. Routine medical care and our interventions were equally effective in permitting the spontaneous hemodynamics improvements after myocardial infraction. More than 3 months after myocardial infarction, the group as a whole manifested spontaneous recovery in the form of a significant decrease in resting heart rate (p less than 0.001) and a significant increase in systolic and diastolic blood pressure at rest and with submaximal exercise (p less than 0.001). No further improvements were observed between 3 and 6 months.", "A home-based exercise programme has been found to be as useful as a hospital-based one in improving cardiovascular fitness after an acute myocardial infarction. To find out whether a comprehensive home-based programme would reduce psychological distress, 176 patients with an acute myocardial infarction were randomly allocated to a self-help rehabilitation programme based on a heart manual or to receive standard care plus a placebo package of information and informal counselling. Psychological adjustment, as assessed by the Hospital Anxiety and Depression Scale, was better in the rehabilitation group at 1 year. They also had significantly less contact with their general practitioners during the following year and significantly fewer were readmitted to hospital in the first 6 months. The improvement was greatest among patients who were clinically anxious or depressed at discharge from hospital. The cost-effectiveness of the home-based programme has yet to be compared with that of a hospital-based programme, but the findings of this study indicate that it might be worth offering such a package to all patients with acute myocardial infarction.", "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.", "Lifestyle measures of coronary heart disease (CHD) prevention have been overshadowed by the efficacy of drug treatments. This is particularly the case in the setting of secondary prevention where the benefits of lipid lowering, anti-platelet and anti-hypertensive drugs have been emphasised in numerous trials. Lifestyle measures address several CHD risk factors at once and are generally free of serious side effects.\n The objective of the present study was to determine whether a comprehensive programme of lifestyle modification could favourably influence dietary and exercise habits in addition to smoking cessation over two years. In addition, an attempt was made to evaluate if this programme could favourably influence the five-year CHD-risk in the male population included in the study.\n A total of 197 patients with proven coronary heart disease were included and randomised to a lifestyle intervention programme or to usual care. Follow-up was after a period of two years.\n Intervention comprised a low fat diet, regular exercise, smoking cessation, psychosocial support and education, delivered by nurses on the rationale for pharmacological and lifestyle measures. Usual care comprised follow-up in the routine outpatient clinic. Both groups were given the same comprehensive medication according to recent guidelines.\n Patients in the lifestyle intervention group reduced the intake of saturated fat, sugar and cholesterol (P<0.001), increased their exercise level (P<0.01) and stopped smoking (P<0.05) when compared with the usual care group. A sub-analysis of the influence of five-year CHD calculated risk in males resulted in a relative risk reduction of 22% (95% confidence intervals 9-35). Although significant, this result must be interpreted with caution due to poor statistical power and reproducibility of the method.\n In the presence of modern drug treatments for secondary cardiovascular disease prevention it remains possible through a favourable diet, exercise and smoking cessation to show an additional reduction in the five-year risk for CHD in males.", "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.", "Patients are generally advised to return to full normal activities, including work, 6 to 8 weeks after acute myocardial infarction (AMI). We assessed the outcomes of early return to normal activities, including work at 2 weeks, after AMI in patients who were stratified to be at a low risk for future cardiac events. Patients were considered for randomization before discharge if they had no angina, had left ventricular ejection fraction >40%, a negative result from a symptom-limited exercise stress test for ischemia (<2 mm ST depression) at 1 week, and achieved >7 METs. Patients with left ventricular ejection fraction <40% were included only if they did not have inducible ventricular tachycardia at electrophysiologic studies. Seventy-two patients were randomized to return to normal activities at 2 weeks and 70 patients to undergo standard cardiac rehabilitation and return to normal activities at 6 weeks after AMI. There were no deaths or heart failure in either group. There was no significant difference in the incidence of reinfarction, revascularization, left ventricular function, lipids, body mass index, smoking, or exercise test results at 6 months. In conclusion, return to full normal activities, including work at 2 weeks, after AMI appears to be safe in patients who are stratified to a low-risk group. This should have significant medical and socioeconomic implications.", "Despite the rational expectation for a survival benefit produced by exercise training among post-myocardial infarction (MI) patients, direct evidence remains elusive. Clinically, changes in autonomic balance toward lower vagal activity have consistently been associated with increased mortality risk; conversely, among both control and post-MI dogs, exercise training improved vagal reflexes and prevented sudden death. Accordingly, we tested the hypothesis that exercise training, if accompanied by a shift toward increased vagal activity of an autonomic marker such as baroreflex sensitivity (BRS), could reduce mortality in post-MI patients.\n Ninety-five consecutive male patients surviving a first uncomplicated MI were randomly assigned to a 4-week endurance training period or to no training. Age (51+/-8 versus 52+/-8 years), site of MI (anterior 41% versus 43%), left ventricular ejection fraction (52+/-13 versus 51+/-14%), and BRS (7.9+/-5.4 versus 7.9+/-3.4 ms/mm Hg) did not differ between the two groups. After 4 weeks, BRS improved by 26% (P=0.04) in trained patients, whereas it did not change in nontrained patients. During a 10-year follow-up, cardiac mortality among the 16 trained patients who had an exercise-induced increase in BRS >or = 3 ms/mm Hg (responders) was strikingly lower compared with that of the trained patients without such a BRS increase (nonresponders) and that of the nontrained patients (0 of 16 versus 18 of 79 [23%], P=0.04). Cardiac mortality was also lower among responders irrespective of training (4% versus 24%, P=0.04).\n Post-MI exercise training can favorably modify long-term survival, provided that it is associated with a clear shift of the autonomic balance toward an increase in vagal activity." ]

[ "2641980" ]

[ "How physical settings affect chronic mental patients." ]

[ "A study was conducted at New York State's Harlem Valley Psychiatric Center of the effects of physical changes in the ward environment on severely regressed psychotic inpatients and on the hospital staff who treat them. Two standard wards were remodeled according to principles in the scientific literature, preferences of those involved, and attempts to facilitate treatment goals. Within 8 months of the inauguration of the redesigned setting, there were selective behavior and attitude changes in both staff (N = 27) and patients (N = 37) as compared to four matched control wards (staff N = 44; patient N = 44): (1) staff mood level was raised significantly on a standard scale; (2) staff unscheduled absence rate was cut in half; (3) staff did not report significant improvement on scales of ward atmosphere and patient functioning; (4) patients themselves reported improvement in their self-images, but not in irritability, isolation, or depression; (5) patients reported significantly more satisfaction with the ward dayroom; (6) rate of patient violence decreased almost 50%." ]

[ "16766588", "8695248", "8708713", "12166338", "10388135", "7738628", "19135415", "8082100", "8608488", "9552067", "9081358", "8589019", "7749165", "8265095", "9391542" ]

[ "A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy.", "An open randomised cross-over study on granisetron versus ondansetron in the prevention of acute emesis induced by moderate dose cisplatin-containing regimens.", "Double-blind, randomized comparison of the antiemetic efficacy of intravenous dolasetron mesylate and intravenous ondansetron in the prevention of acute cisplatin-induced emesis in patients with cancer. Dolasetron Comparative Chemotherapy-induced Emesis Prevention Group.", "Ramosetron for the prevention of cisplatin-induced acute emesis: a prospective randomized comparison with granisetron.", "A Comparison of Oral Ondansetron and Intravenous Granisetron for the Prevention of Nausea and Emesis Associated with Cisplatin-Based Chemotherapy.", "Comparative clinical trial of granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. The Granisetron Study Group.", "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 in the prevention of chemotherapy-induced nausea and vomiting. Results of a prospective randomized trial.", "Comparison of granisetron, ondansetron, and tropisetron in the prophylaxis of acute nausea and vomiting induced by cisplatin for the treatment of head and neck cancer: a randomized controlled trial.", "Single-dose oral granisetron has equivalent antiemetic efficacy to intravenous ondansetron for highly emetogenic cisplatin-based chemotherapy.", "A double-blind, randomised comparison of the anti-emetic efficacy of two intravenous doses of dolasetron mesilate and granisetron in patients receiving high dose cisplatin chemotherapy.", "Ondansetron versus granisetron, both combined with dexamethasone, in the prevention of cisplatin-induced emesis. Italian Group of Antiemetic Research.", "Is Navoban (tropisetron) as effective as Zofran (ondansetron) in cisplatin-induced emesis? The French Navoban Study Group.", "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 comparative study of intravenous granisetron versus intravenous and oral ondansetron in the prevention of nausea and vomiting associated with moderately emetogenic 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.", "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 assess the comparative antiemetic efficacy of single-dose intravenous (IV) dolasetron mesylate and ondansetron in preventing cisplatin-induced nausea and vomiting.\n Cancer patients (n = 609) receiving first-course cisplatin chemotherapy were randomized to one of three treatments: 1.8 or 2.4 mg/kg dolasetron mesylate salt (equivalent to 1.3 and 1.8 mg/kg dolasetron base, respectively) or 32 mg ondansetron. Each treatment was infused over 15 minutes, 30 minutes before cisplatin administration. Patients were stratified to cisplatin doses of > or = 70 and less than 91 mg/m2 (n = 368) or > or = 91 mg/m2 (n = 241), administered over < or = 3 hours. Protocol-defined efficacy criteria included complete response (zero emetic episodes and no rescue medication), major response (1 to 2 emetic episodes and no rescue medication), and patients' report of nausea severity and satisfaction recorded on a 100-mm visual analog scale (VAS).\n The three treatments met protocol-specified criteria for equivalence. Complete response rates for dolasetron mesylate 1.8 mg/kg, 2.4 mg/kg, and ondansetron, respectively, were 49.2%, 45.6%, and 50.4% for patients in the lower cisplatin stratum (mean, 74.7 mg/m2) and 36.8%, 31.3%, and 31.8% in the higher cisplatin stratum (mean, 100.6 mg/m2). No significant differences were observed in the extent of nausea with either dolasetron dose compared with ondansetron. Less nausea was noted with 1.8 mg/kg dolasetron compared with the 2.4 mg/kg dose (P = .044) All three antiemetic treatments were well tolerated. Asymptomatic electrocardiogram changes were recorded with both dolasetron and ondansetron.\n A single IV dose of dolasetron mesylate (1.8 or 2.4 mg/kg) has comparable safety and efficacy to a single 32-mg IV dose of ondansetron in patients receiving cisplatin chemotherapy.", "Control of nausea and vomiting is very important in determining patient compliance with cisplatin chemotherapy. A multicentre, randomized, single-blind study was conducted to compare the tolerability and efficacy of ramosetron with those of granisetron over 24 h following cisplatin administration to cancer patients. In eight study centres, a total of 194 adult patients were randomly assigned to receive either intravenous ramosetron 0.3 mg or intravenous granisetron 3.0 mg. The anti-emetic effect of ramosetron determined from the no-vomiting rate lasted longer, but there was no significant difference in the number of acute vomiting episodes or the severity of nausea between the two groups. In the tolerability evaluation, there were no statistically significant differences between the two groups, except for a higher incidence of dull headache in the granisetron group. Ramosetron and granisetron appear to have equivalent efficacy and tolerability profiles, but the effects of ramosetron on the prevention of acute vomiting in patients undergoing cisplatin chemotherapy were longer lasting.", "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/m&sup2;), 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.", "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.", "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).", "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.", "A single-institution, prospective, randomized, open controlled trial was carried out on head and neck cancer patients to compare granisetron (GRA), ondansetron (OND), and tropisetron (TRO) in the prevention of cisplatin-induced acute nausea and vomiting. All patients were chemotherapy-naive and treated with cisplatin on Day 1 (80 to 100 mg/m2).\n One hundred seventeen patients were treated for a total of 463 cycles of cisplatin-based chemotherapy and randomized to receive 24 mg of OND intravenously (i.v.), 3 mg of GRA i.v., or 5 mg of TRO i.v. for the control of acute nausea and emesis.\n In the GRA group, complete response (CR) was obtained in 119 of 165 cycles (72.1%), major response (MR) in 32 cycles (19.4%), minor response (MiR) in 5 cycles (3%), and a failure (F) in 9 cycles (5.5%). In the OND group, CR was obtained in 110 of 150 cycles (73.3%), MR in 31 cycles (20.7%), MiR in 2 cycles (1.3%), and F in 7 cycles (4.7%). In the TRO group, CR was obtained in 100 of 148 cycles (67.6%), MR in 26 cycles (17.6%), MiR in 15 cycles (10.1%), and F in 7 cycles (4.7%). Major efficacy (CR + MR) was obtained in 151 of 165 cycles (91.5%) for GRA, in 141 of 150 cycles (94.0%) for OND, and in 126 of 148 cycles (85.2%) for TRO. The difference in major efficacy between OND and TRO was statistically significant. When comparing MiR, both GRA and OND were more effective than TRO. No other significant differences were observed among the three antiemetic agents.\n Although our results were achieved in an open trial, they show that GRA and OND are equally effective antiemetic agents in the prevention of cisplatin induced acute nausea and vomiting. TRO provides almost the same protection but is not as effective as OND for major efficacy. All three antiemetics can be administered safely to patients undergoing chemotherapy with cisplatin at doses of 80 mg/m2 or more.", "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 multicentre, double-blind, double-dummy, randomised trial was designed to compare the efficacy and safety of single intravenous doses of dolasetron mesilate and granisetron in the prevention of acute emesis and nausea due to high-dose (> or = 80 mg/m2) cisplatin. Single intravenous doses of 1.8 or 2.4 mg/kg of dolasetron mesilate or 3 mg of granisetron hydrochloride were administered in a volume of 50 ml over a 5-min period, beginning 30 min prior to cisplatin (> or = 80 mg/m2) administration. The number and timing of emetic episodes, time to administration of escape anti-emetic medication, severity of nausea by visual analogue scale (VAS), and safety were monitored for 24 h after the start of cisplatin-containing chemotherapy. Investigators' evaluations of overall efficacy and patients' satisfaction with therapy were recorded at the end of the 24-h study period. Of the 474 patients evaluable for efficacy, complete responses were achieved by 54, 47 and 48% of patients given dolasetron mesilate 1.8 mg/kg, dolasetron mesilate 2.4 mg/kg and granisetron, respectively. Statistically, treatment groups had comparable complete and complete plus major responses, times to first emesis, and use of escape medication; patient maximum nausea severity and treatment satisfaction ratings; and physician nausea severity and overall efficacy assessments. For the majority of efficacy endpoints, 1.8 mg/kg dolasetron mesilate produced numerically superior responses compared with the 2.4 mg/kg dose. Gender and prior chemotherapy were significant predictors of complete response; males and chemotherapy-naive patients had higher responses. The overall incidences of adverse events were comparable among the treatment groups; headache and diarrhoea were most common. In conclusion, 1.8 and 2.4 mg/kg of dolasetron mesilate and granisetron (3 mg) were equally effective in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy. In addition, because no additional benefit was observed with 2.4 mg/kg of dolasetron mesilate and numerically greater responses were observed with the 1.8 mg/kg dose, the lower dose of 1.8 mg/kg is optimal for further clinical development.", "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.", "The purpose of this study was to evaluate and compare the antiemetic effectiveness and tolerability of Navoban (tropisetron) and Zofran (ondansetron) following high-dose (> or = 50 mg/m2) cisplatin chemotherapy. In a randomised, multi-centre, double-blind, double-dummy, parallel group study, 117 evaluable chemotherapy-naive patients who received Navoban were compared with 114 who received Zofran. Patient diary cards were used to assess both acute (Day 1) and delayed (Days 2-6) nausea and vomiting. Total control of acute vomiting was achieved in 54% of Navoban and 65% of Zofran patients (p = 0.052), and total control of acute nausea in 66% and 62% respectively (p = 0.655). Total control of delayed vomiting was achieved in 44% of Navoban patients and 46% of Zofran patients (p = 0.765), and of delayed nausea in 56% and 47% respectively (p = 0.207). Both reactions combined were totally prevented during the entire 6-day trial period in 22% of Navoban and 24% of Zofran patients (NS), while a further 42% of patients in both groups remained largely free from both nausea and emesis. The few adverse reactions (e.g. headache, constipation, diarrhoea) were mainly mild and typical of the 5-HT3-receptor antagonists. In conclusion, there were no significant differences in efficacy and tolerability between Navoban 5 mg once daily and the highest recommended dose of Zofran (32 mg on Day 1, followed by 8 mg three times a day).", "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.", "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." ]

[ "12403254", "10545590", "14608267", "1828205", "15815206", "18252070", "2109432", "10547243", "15357564", "19652108", "18410562", "18701826", "15740542", "19330931" ]

[ "Prevention of antibiotic-associated diarrhea in infants by probiotics.", "Prophylactic Lactobacillus GG reduces antibiotic-associated diarrhea in children with respiratory infections: a randomized study.", "[Prevention of antibiotic-associated diarrhea with Lactobacillus sporogens and fructo-oligosaccharides in children. A multicentric double-blind vs placebo study].", "[Oral bacterial therapy in prevention of antibiotic-induced diarrhea in childhood].", "A randomized formula controlled trial of Bifidobacterium lactis and Streptococcus thermophilus for prevention of antibiotic-associated diarrhea in infants.", "Does eating yogurt prevent antibiotic-associated diarrhoea? A placebo-controlled randomised controlled trial in general practice.", "A double-blind, placebo-controlled study of the efficacy of Lactinex in the prophylaxis of amoxicillin-induced diarrhea.", "Lactobacillus GG in the prevention of antibiotic-associated diarrhea in children.", "The probiotic effect of Saccharomyces boulardii in a pediatric age group.", "A randomized clinical trial measuring the influence of kefir on antibiotic-associated diarrhea: the measuring the influence of Kefir (MILK) Study.", "Clinical trial: effectiveness of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) in the prevention of antibiotic-associated diarrhoea in children.", "Bifidobacterium longum PL03, Lactobacillus rhamnosus KL53A, and Lactobacillus plantarum PL02 in the prevention of antibiotic-associated diarrhea in children: a randomized controlled pilot trial.", "Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a randomized double-blind placebo-controlled trial.", "Randomized, double-blind, placebo-controlled trial: effect of lactobacillus GG supplementation on Helicobacter pylori eradication rates and side effects during treatment in children." ]

[ "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.", "Antimicrobial treatment may disturb the colonization resistance of gastrointestinal microflora, which may induce clinical symptoms, most commonly diarrhea. The severity of antibiotic-associated diarrhea may range from a brief, self-limiting disease to devastating diarrhea with electrolyte disturbances, dehydration, crampy abdominal pain, pseudomembranous colitis, toxic megacolon, or even death. The incidence of diarrhea in children receiving a single antimicrobial treatment is unclear. In addition to more critical use of antimicrobials, adjunctive preventive measures to antibiotic-associated diarrhea are needed. The objective of this study was to evaluate the incidence of diarrhea after antimicrobial treatment in children with no history of antimicrobial use during the previous 3 months. Another aim of this study was to assess the preventive potential of Lactobacillus rhamnosus GG (Lactobacillus GG; American Type Culture Collection 53103), a probiotic strain with a documented safety record and a therapeutic effect in viral gastroenteritis on antibiotic-associated diarrhea.\n Oral antimicrobial agents were prescribed for the treatment of acute respiratory infections at the clinics of the Health Care Center of the City of Tampere or Tampere University Hospital, Finland, to 167 patients who were invited to participate in the study. Of the patients, 48 were lost to follow-up; therefore, the final study population consisted of 119 children from 2 weeks to 12. 8 years of age (mean: 4.5 years). All study subjects met the inclusion criteria: they had not received any antimicrobial medication during the previous 3 months, they did not suffer from gastrointestinal disorders, and they did not need intravenous antimicrobial treatment. The patients were randomized to receive placebo or 2 x 10(10) colony-forming units of Lactobacillus GG in capsules given twice daily during the antimicrobial treatment. Lactobacillus GG and placebo capsules were indistinguishable in appearance and taste. The parents kept a daily symptom diary and recorded stool frequency and consistency at home for 3 months. Diarrhea was defined as at least three watery or loose stools per day for a minimum of 2 consecutive days. In the case of diarrhea, viral (adenovirus, rotavirus, calicivirus and astrovirus) and bacterial (Salmonella, Shigella, Yersinia, Campylobacter, Clostridium difficile, Staphylococcus aureus, and yeasts) analyses were studied in fecal samples. The metabolic activity of the gut microflora was assessed by analysis of fecal urease, beta-glucosidase, and beta-glucuronidase activities. The primary outcome measure was diarrhea during the first 2 weeks after the beginning of the antimicrobial treatment, because this period most likely reflects the effects of antimicrobial use. Secondary outcome measures were the activities of fecal urease, beta-glucuronidase, and beta-glucosidase.\n On the entire follow-up, 80% of any gastrointestinal symptoms were reported during the first 2 weeks after the beginning of the antimicrobial treatment. The incidence of diarrhea was 5% in the Lactobacillus GG group and 16% in the placebo group within 2 weeks of antimicrobial therapy (chi(2) = 3.82). The treatment effect (95% confidence interval) of Lactobacillus GG was -11% (-21%-0%). In diarrheal episodes, the viral and bacterial analyses were positive for Clostridium difficile in 2 cases and for Norwalk-like calicivirus in 3 cases. The age of the patients with diarrhea was between 3 months and 5 years in 75% of cases in both groups. The severity of diarrhea was comparable in the study groups, as evidenced by similar stool frequency (mean: 5 per day; range: 3-6) and the duration of diarrhea (mean: 4 days; range: 2-8). The activities of fecal urease and beta-glucuronidase, but not beta-glucosidase, changed significantly after the beginning of the antimicrobial treatment in the Lactobacillus GG group and in the placebo group alike. (ABSTRACT TRUNCATED)", "The aim of this paper is to determine the efficacy of a fructo-oligosaccharides (FOS)-Lactobacillus sporogenes preparation in the prevention of diarrhea due to antibiotics in childhood.\n A multicentre, randomised, double-blind versus placebo study was carried out. A total of 120 children, with active infections requiring antibiotics, were enrolled in the study and treated for 10 days either in the experimental group (F) or in the placebo one (P). The results of the study were recorded from the patients' diary and from follow-up clinical examinations.\n Out of 98 evaluable patients, 71% in group F had no diarrhea versus 38% in group P. The duration of diarrhea in F and P groups was 0.7 vs 1.6 days (p=0.002), respectively.\n Prophylaxis with Lactobacillus sporogens, associated to FOS, significantly reduced the number of days and duration of events in children with antibiotic-induced diarrhea.", "Amoxycillin is currently the most widely used antibiotic in pediatrics. It is known that this antibiotic, as well as other kinds of antimicrobial treatments, may produce variations in the bowel ecosystem. A controlled randomised clinical trial was performed using commercially available fermented milk products in infants who had received an oral treatment with amoxycillin for an average of ten days. 40 children have been examined, randomly divided into two groups of twenty. Group 1 received treatment with antibiotic plus lactobacilli. Group 2 received only amoxycillin. At the end of the trial infants of group 1 showed a lower frequency of stool passages and more fully-formed feces, while patients of group 2 presented an increased frequency of gastrointestinal disorders. On the basis of the results obtained it is possible to conclude that oral bacterial therapy with lactobacilli is efficacious in preventing diarrhea from amoxycillin in infancy.", "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.", "Probiotic capsules have been shown to reduce the incidence of antibiotic-associated diarrhoea in a number of settings. If probiotic yogurt were equally efficacious then it would provide a simple and cost-effective means of preventing antibiotic-associated diarrhoea.\n To investigate whether eating live bio yogurt at the time of taking oral antibiotics can prevent antibiotic-associated diarrhoea.\n This study was a three-arm (bio yogurt, commercial yogurt, no yogurt) randomised controlled trial with double blinding between the two yogurt arms.\n A single primary care general practice surgery in Hingham, Norfolk. The study population included all ages except babies.\n Patients aged over 1 year who required a 1-week course of antibiotics were included in the study. There was complete follow up for 369 patients. The intervention was the consumption of 150 ml of live strawberry-flavoured yogurt for 12 days, starting on the first day of taking the antibiotic. Diarrhoea was defined as 'three or more loose stools per day over at least 2 consecutive days' within 12 days of starting the antibiotics.\n Of the 120 patients in the no-yogurt group, 17 (14%, 95% confidence interval [CI] = 9.0 to 21.5) developed diarrhoea. Of the 118 given commercial yogurt, 13 (11%, 95% CI = 6.6 to 17.9) developed diarrhoea; nine of the 131 patients (7%; 95% CI = 3.7 to 12.5) given bio yogurt developed diarrhoea (P = 0.17).\n Overall, this study failed to demonstrate that yogurt has any effect on antibiotic-associated diarrhoea.", "The disruption of the natural flora of the gastrointestinal tract (especially Lactobacillus acidophilus) may occur during antibiotic therapy. This may lead to diarrhea, dehydration, and electrolyte imbalances. It has been suggested that replacement of the lactobacilli with a commercially available product may prevent the diarrhea. The efficacy and safety of prophylactically administered Lactinex (culture of L. acidophilus and L. bulgaricus) was compared with placebo for the prevention of amoxicillin-induced diarrhea in pediatric patients. Lactinex or placebo was administered four times a day for ten days to coincide with the antibiotic therapy. The Lactobacillus preparation did not appear to consistently prevent diarrhea in this patient population. Patients' age, diet, and parental definition of diarrhea were factors that may have influenced the results.", "The objective of this study was to determine the efficacy of Lactobacillus casei sps. rhamnosus (Lactobacillus GG) (LGG) in reducing the incidence of antibiotic-associated diarrhea when coadministered with an oral antibiotic in children with acute infectious disorders.\n Two hundred two children between 6 months and 10 years of age were enrolled; 188 completed all phases of the protocol. LGG, 1 x 10(10) - 2 x 10(10) colony forming units per day, or comparable placebo was administered in a double-blind randomized trial to children receiving oral antibiotic therapy in an outpatient setting. The primary caregiver was questioned every 3 days regarding the incidence of gastrointestinal symptoms, predominantly stool frequency and consistency, through telephone contact by blinded investigators.\n Twenty-five placebo-treated but only 7 LGG-treated patients had diarrhea as defined by liquid stools numbering 2 or greater per day. Lactobacillus GG overall significantly reduced stool frequency and increased stool consistency during antibiotic therapy by the tenth day compared with the placebo group.\n Lactobacillus GG reduces the incidence of antibiotic-associated diarrhea in children treated with oral antibiotics for common childhood infections.", "The aim of this study was to determine the efficacy of S. boulardii in diarrhea associated with commonly used antibiotics such as sulbactam-ampicillin (SAM) and azithromycin (AZT). Four hundred and sixty-six patients were assigned to four different groups as follows: group 1:117 patients receiving SAM alone; group 2:117 patients receiving SAM and S. boulardii, group 3:105 patients receiving AZT alone; group 4:127 patients receiving AZT and S. boulardii. Antibiotic-associated diarrhea was seen in 42 of the 222 patients (18.9 per cent) receiving an antibiotic without the probiotic, and in 14 of the 244 patients (5.7 per cent) who received both the probiotic and the antibiotic (p < 0.05). In the group receiving SAM where S. boulardii use was found to be significant, the use of S. boulardii decreased the diarrhea rate from 32.3 to 11.4 per cent in the 1-5 years age group (p < 0.05). This is a pioneering study investigating combined antibiotic and probiotic use in pediatric diarrhea patients.", "To examine the role of commercially available kefir, a fermented milk similar to yogurt but containing different fermentation microbes, in preventing antibiotic-associated diarrhea (AAD). Probiotics have shown some promise in preventing AAD.\n A double-blinded randomized placebo-controlled allocation concealment clinical trial.\n Primary care patients in the Washington, DC, metropolitan area.\n A total of 125 children aged 1 to 5 years presenting to primary care physicians. Intervention Kefir drink or heat-killed matching placebo. Main Outcome Measure The primary outcome was the incidence of diarrhea during the 14-day follow-up period in children receiving antibiotics.\n There were no differences in the rates of diarrhea per group, with 18% in the active group and 21.9% in the placebo group (relative risk, 0.82; 95% confidence interval, 0.54-1.43). Additionally, there were no differences in any secondary outcomes among the groups. However, there were some interesting interactions among initial health at enrollment, age of participants, and sex that require further study.\n In our trial, kefir did not prevent AAD. Further independent research on the potential of kefir needs to be conducted.", "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 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.", "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.", "To determine the effectiveness of Lactobacillus GG (LGG) in children with Helicobacter pylori infection undergoing eradication therapy.\n We conducted a double-blind, placebo-controlled, randomized trial comparing a 7-day, triple eradication regimen consisting of 2 antibiotics (amoxicillin tablets, 25 mg/kg twice per day, and clarithromycin tablets, 10 mg/kg twice per day) plus a proton pump inhibitor (omeprazole capsules, 0.5 mg/kg twice per day) supplemented with LGG (109 colony-forming units) or placebo in 83 children with H pylori infection confirmed by 2 of 3 tests (13C-urea breath test, histopathology, rapid urease test). The primary outcome measure was the H pylori eradication rate. The secondary outcome measure was the proportion of patients who experienced therapy-related adverse effects during anti-H pylori treatment.\n The groups did not differ with respect to H pylori eradication rates. Of the 34 children in the LGG group, 23 (69%) experienced eradication, compared with 22 of 32 children (68%) in the placebo group (RR 0.98, 95% CI 0.7-1.4). The groups did not differ with respect to adverse effects.\n In children with H pylori infection, supplementation of standard triple therapy with LGG did not significantly alter the eradication rate or side effects." ]

[ "17077230", "18398664", "20399951", "12850599", "18307077", "15333602", "16202939", "15050984", "16022849", "15632336" ]

[ "Impact of increased access to emergency contraceptive pills: a randomized controlled trial.", "Computer-assisted provision of emergency contraception a randomized controlled trial.", "A randomized controlled trial of the effect of advanced supply of emergency contraception in postpartum teens: a feasibility study.", "Advance supply of emergency contraception. effect on use and usual contraception--a randomized trial.", "Advance provision of emergency contraceptive pills reduces treatment delay: a randomised controlled trial among Swedish teenage girls.", "Effect of advanced provision of emergency contraception on women's contraceptive behaviour: a randomized controlled trial.", "Advance supply of emergency contraception: a randomized trial in adolescent mothers.", "The effects of advance provision of emergency contraception on adolescent women's sexual and contraceptive behaviors.", "Advanced provision of emergency contraception to postnatal women in China makes no difference in abortion rates: a randomized controlled trial.", "Direct access to emergency contraception through pharmacies and effect on unintended pregnancy and STIs: a randomized controlled trial." ]

[ "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) 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.", "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.", "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.", "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.", "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 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.", "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) 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.", "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." ]

[ "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." ]

[ "2379568", "11008086", "10926126", "12090970", "11889277", "16774462", "15117710", "9917447", "16520528", "9605896", "10638714", "7896983", "7751483", "16894074", "9083601", "16135905", "11030260", "9083598", "12509592", "8634730", "9573435", "12182264", "10425698" ]

[ "Reproductive health counseling for young men: what does it do?", "Postponing sexual intercourse among urban junior high school students-a randomized controlled evaluation.", "The effect of tailoring a model HIV prevention program for local adolescent target audiences.", "Long-term reductions in sexual initiation and sexual activity among urban middle schoolers in the reach for health service learning program.", "Safer choices: reducing teen pregnancy, HIV, and STDs.", "All4You! A randomized trial of an HIV, other STDs, and pregnancy prevention intervention for alternative school students.", "Draw the line/respect the line: a randomized trial of a middle school intervention to reduce sexual risk behaviors.", "A STD/HIV prevention trial among adolescents in managed care.", "Mothers' effectiveness as HIV risk reduction educators for adolescent daughters.", "Abstinence and safer sex HIV risk-reduction interventions for African American adolescents: a randomized controlled trial.", "Parental underestimates of adolescent risk behavior: a randomized, controlled trial of a parental monitoring intervention.", "Comparison of education versus behavioral skills training interventions in lowering sexual HIV-risk behavior of substance-dependent adolescents.", "Cognitive-behavioral intervention to reduce African American adolescents' risk for HIV infection.", "A randomized controlled trial testing an HIV prevention intervention for Latino youth.", "Does parental involvement make a difference? The impact of parent interactive activities on students in a school-based AIDS prevention program.", "Outcomes of a randomized, controlled community-level HIV prevention intervention for adolescents in low-income housing developments.", "Using randomized designs to evaluate client-centered programs to prevent adolescent pregnancy.", "An impact evaluation of project SNAPP: an AIDS and pregnancy prevention middle school program.", "Sustaining and broadening intervention impact: a longitudinal randomized trial of 3 adolescent risk reduction approaches.", "A randomized, controlled effectiveness trial of an AIDS prevention program for low-income African-American youths.", "The Healthy for Life project: sexual risk behavior outcomes.", "Reducing STD and HIV risk behavior of substance-dependent adolescents: a randomized controlled trial.", "Reducing HIV risk-associated sexual behavior among African American adolescents: testing the generality of intervention effects." ]

[ "A reproductive health intervention combining a highly explicit half-hour slide-tape program with a personal health consultation was provided to male patients aged 15-18 at a large health maintenance organization. A test of the consultation's impact against a control group provides no support for the argument that highly explicit instruction in contraception encourages early initiation of intercourse. In fact, the consultation may have reduced pressure to become sexually active among young men who had never had sexual intercourse. There is also some evidence that the consultation helped improve the effectiveness of contraceptive practice among the men who were sexually active at follow-up; those exposed to the consultation were more likely than those who were not to report that their last intercourse was protected by the pill and that their main method of contraception in the previous year was the pill. Compared with those in the control group, patients who received the health consultation scored higher on measures of fertility knowledge and knowledge of the prevention of sexually transmitted diseases, including AIDS. Furthermore, the young men who had the consultation were more likely to have practiced testicular self-examination. In many cases, however, the positive effects of the consultation were stronger or were only statistically significant among those who had not been sexually active at the time of the baseline survey.", "To describe a randomized, controlled evaluation of a school-based intervention to delay sexual intercourse among urban junior high school students.\n Six Washington, D.C., junior high schools were randomly assigned to the intervention or nonintervention control condition for an educational program. During the first school year, seventh graders (n = 582) from the six schools obtained written parental consent to participate. Three health professionals (one per intervention school) implemented the program, which consisted of reproductive health classes, the Postponing Sexual Involvement Curriculum, health risk screening, and \"booster\" educational activities during the following (eighth grade) school year. Cross-sectional surveys were administered at baseline, the end of the seventh grade, and the beginning and end of the eighth grade. Intervention and control group differences in virginity, attitudes toward delayed sex and childbearing, and sexual knowledge and behavior were assessed at all four time points.\n At baseline, 44% of the seventh grade males and 81% of the seventh grade females reported being virgins. At the end of the seventh grade (first follow-up), after controlling for baseline study group differences, intervention-group females were more likely to report virginity, self-efficacy to refuse sex with a boyfriend, and the intention to avoid sexual involvement during the following 6 months. At the end of the eighth grade, significantly more intervention- than control-group females reported virginity, birth control use at last intercourse (for nonvirgins), and knowledge of adolescent reproductive health and confidentiality rights. No changes in virginity, self-efficacy to refuse sex, or sexual intent for the next 6 months were observed among male participants at any time during the study. However, on all three follow-up surveys, intervention-group males scored significantly higher than their control-group counterparts in knowledge of birth control method efficacy. No change in attitudes toward abstinence was observed for either gender at any follow-up point.\n Gender differences in baseline sexual activity rates and in various study outcomes suggest a possible need for separate, gender-specific intervention activities that can adequately address the social and cognitive needs of both sexes.", "In five U.S. sites (Nashville, Tennessee; Newark, New Jersey; northern Virginia; Phoenix, Arizona; and Sacramento, California), HIV risk-reduction workshops were mounted as a part of the Prevention Marketing Initiative (PMI). In four of the five sites, the workshop curriculum was a version of Be Proud! Be Responsible! (Jemmott, Jemmott, & McCaffree, 1996) that had been tailored to fit the needs of local target audiences. This article describes the evaluation of the PMI workshops. Protective effects on several behavioral determinants and behavioral outcome measures were observed 1 month after the workshops. Based on the overall pattern of results, it was concluded that the PMI workshops reduced the likelihood of unprotected sex among participants. The intervention developed by Jemmott and colleagues appears to have retained its effectiveness after it was tailored to meet perceived local needs.", "To evaluate the sustained effectiveness of a middle school service learning intervention on reducing sexual initiation and recent sex among urban African-American and Latino adolescents from 7th grade through the 10th grade.\n During the fall of seventh grade and again in eighth grade, students were randomly assigned by classroom to participate either in community youth service (CYS) or not (controls). Service learning is an educational strategy that couples meaningful service in the community with classroom instruction. Students in both intervention and control conditions received classroom health lessons. Surveys were conducted at seventh grade baseline and at the end of 10th grade, approximately 2 years after intervention. Self-reported sexual behaviors of youths who had participated in CYS were compared with those of controls receiving classroom curriculum alone (n = 195).\n CYS participants were significantly less likely than controls to report sexual initiation (2 years CYS, odds ratio [OR] = 0.32; 1 year, OR = 0.49) as well as recent sex (2 years CYS, OR = 0.39; 1 year CYS, OR = 0.48). Among those who were virgins at seventh grade, 80% of males in the curriculum-only condition had initiated sex, compared with 61.5% who received 1 year of CYS, and 50% who received 2 years. Among females, the figures were 65.2%, 48.3%, and 39.6%, respectively.\n A service learning intervention that combines community involvement with health instruction can have a long-term benefit by reducing sexual risk taking among urban adolescents.", "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.", "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.", "This study evaluated the long-term effectiveness of Draw the Line/Respect the Line, a theoretically based curriculum designed to reduce sexual risk behaviors among middle school adolescents.\n The randomized controlled trial involved 19 schools in northern California. A cohort of 2829 sixth graders was tracked for 36 months.\n The intervention delayed sexual initiation among boys, but not girls. Boys in the intervention condition also exhibited significantly greater knowledge than control students, perceived fewer peer norms supporting sexual intercourse, had more positive attitudes toward not having sex, had stronger sexual limits, and were less likely to be in situations that could lead to sexual behaviors. Psychosocial effects for girls were limited.\n The program was effective for boys, but not for girls.", "To determine if sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection, risk assessment, and education tools provided as part of office-based primary care reduce adolescent risky sexual behaviors.\n A randomized intervention trial with 3- and 9-month follow-up.\n Five staff-model managed care sites in Washington, DC (n = 19 pediatricians).\n Consecutive 12- to 15-year-olds receiving a general health examination; 81% minority. Participation rate = 215/432 (50%). Nine-month follow-up rate = 197/215 (92%).\n Audiotaped STD risk assessment and education about staying safe (safer = condoms, safest = abstinence).\n Adolescent-reported sexual intercourse and condom use.\n More intervention adolescents reported pediatrician discussion on 11/13 sexual topics. Although more vaginal intercourse (odds ratio [OR] = 2.46, 95% confidence interval [CI] = 1.04-5.84) was reported in the intervention group at 3 months, this was not true of overall sexual intercourse (OR = 1.55, 95% CI =.73-3.32). More sexually active adolescents reported condom use in the intervention group at 3 months (OR = 18.05, 95% CI = 1.27-256.03). At 9 months, there were no group differences in sexual behaviors; however, more signs of STD were reported by the control (7/103) than the intervention group (0/94).\n STD risk assessment and education tools administered in a single office visit facilitated STD/HIV prevention education. Any impact on sexual activity and condom use was short-lived. Further research is needed to develop brief, office-based sexual risk reduction for young adolescents.", "Low-income African American inner city adolescent females continue to be at disproportionately high risk for contracting HIV. Though it has been speculated that mothers' involvement in HIV risk reduction may be helpful in the fight against HIV, very few interventions involve mothers. The Mother/Daughter HIV Risk Reduction intervention (MDRR), an innovative community-based intervention, trains mothers to be their daughters' primary HIV educators. A split-plot repeated measures design was used to test the effectiveness of the MDRR in decreasing daughters' sexual activity over a 2-month period. The mediating variables were daughters' HIV transmission knowledge, self-efficacy and intention to refuse sex. The sample consisted of 262 daughters with a mean age of 12.4 years. The results revealed that mothers were effective in increasing the mediating variables and in reducing their daughters' level of sexual activity. Active involvement of mothers is cost-effective and should be integrated into HIV intervention programs.", "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.", "To develop and evaluate an intervention (ImPACT) seeking to increase monitoring (supervision and communication) by parents and guardians of African-American youth regarding high risk and protective behaviors; and to develop an instrument to assess parental monitoring, the Parent-Adolescent Risk Behavior Concordance Scale.\n This research was a randomized, controlled longitudinal study. Baseline (preintervention), and 2 and 6 months postintervention data were obtained via a talking MacIntosh computer regarding youth and parent perceptions of youth involvement in 10 risk behaviors, parental monitoring and youth-parent communication, and condom-use skills. Intervention parents and youth received the ImPACT program and a video emphasizing parental supervision and discussion, followed by a structured discussion and role-play emphasizing key points. Control parents and youth received an attention-control program on goal-setting, which also included an at-home video and discussion.\n A total of 237 parents and one each of their youth (ages 12-16 years) recruited from eight public housing developments located in a city in the mid-Atlantic region.\n Similarity of youth and parental reporting on the Parent-Adolescent Risk Behavior Concordance Scale was positively correlated with protective behaviors, perceived parental monitoring, and good parent-youth communication. At baseline, parents significantly underestimated their youth's risk behaviors. However, 2 and 6 months postintervention, the ImPACT program increased similarity of reports by youth and their parents of youth involvement in risk and protective behaviors. In addition, at 6 months postintervention, intervention (compared to control) youths and parents also demonstrated higher levels of condom-use skills.\n Parental monitoring interventions such as ImPACT should be given to parents in conjunction with more traditional youth-centered risk-reduction interventions.", "Substance-dependent adolescents (N = 34) in a residential drug treatment facility received either a 6-session behavior skills training HIV-risk reduction intervention or standard HIV education. After the intervention, adolescents who received behavior skills training exhibited increased knowledge about HIV-AIDS, more favorable attitudes toward prevention and condom use, more internal locus of control, increased self-efficacy, increased recognition of HIV risk and decreases in high-risk sexual activity. Self-report data were corroborated by records for the treatment of sexually transmitted diseases. The results from this pilot demonstration effort suggest that skills training based on cognitive-behavioral principles may be effective in lowering high-risk adolescents' vulnerability to HIV infection and warrant evaluation in a controlled comparison with a larger sample.", "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.", "To test the efficacy of a prevention intervention to reduce sexual risk behavior among Latino adolescents.\n Randomized controlled trial from April 2000 through March 2003, with data collection before and after intervention and at 3, 6, and 12 months.\n Northeast Philadelphia schools.\n Latinos aged 13 through 18 years (249 males and 304 females); 81.6% retained at 12-month follow-up.\n The HIV and health-promotion control interventions consisted of six 50-minute modules delivered by adult facilitators to small, mixed-gender groups in English or Spanish. Main Outcome Measure Self-reported sexual behavior.\n Analyses using generalized estimation equations over the follow-up period revealed that adolescents in the HIV intervention were less likely to report sexual intercourse (odds ratio, 0.66; 95% confidence interval [CI], 0.46-0.96), multiple partners (odds ratio, 0.53; 95% CI, 0.31-0.90), and days of unprotected intercourse (relative risk, 0.47; 95% CI, 0.26-0.84) and more likely to report using condoms consistently (odds ratio, 1.91; 95% CI, 1.24-2.93). Baseline sexual experience and language use moderated intervention efficacy. Adolescents assigned to the HIV intervention who were sexually inexperienced at baseline reported fewer days of unprotected sex (relative risk, 0.22; 95% CI, 0.08-0.63); Spanish speakers were more likely to have used a condom at last intercourse (odds ratio, 4.73; 95% CI, 1.72-12.97) and had a greater proportion of protected sex (mean difference, 0.35; P<.01) compared with similar adolescents in the health-promotion intervention.\n Results provide evidence for the efficacy of HIV intervention in decreasing sexual activity and increasing condom use among Latino adolescents.", "In this study, we test the effectiveness of involving parents in school-based AIDS education with respect to altering AIDS-related knowledge, attitudes, behavioral intentions, communications patterns, and behavior of students.\n Fifteen high risk school districts (pre-test N = 2,392) were randomly assigned to one of three conditions: parent-interactive (classroom curricula + parent-interactive component); parent non-interactive (classroom curricula only); control (basic AIDS education ordinarily provided by the school). Students were tested over time in grades 7, 8 and 9.\n Results indicate that both treatment conditions (parent-interactive and non-interactive) had a strong positive impact in enhancing student's knowledge, attitudes, communication patterns and behavioral intentions. Further, results indicate that there were no behavioral outcome differences between the treatment groups and the control condition. Results demonstrate few outcome differences between the two experimental conditions.\n In the two treatment groups (parent-interactive and parent non-interactive), the program effects appear to be the result of school-based curricula and of student self-determined intentions and behaviors, rather than the presence or absence of planned parental involvement. Whether or not structured or planned parental involvement becomes part of a school-based educational activity should perhaps be determined by (a) the existing level of parent-school interaction based on the nature of the community, (b) the amount of money readily available to follow through on a program of parent involvement without compromising on student programs, (c) the age of the child and the sensitivity of the issue, and (d) the ability of the parent/family to be involved effectively without extraordinary expense or sacrifice by either parent or school. Our findings speak to the positive role of the school regardless of parent participation.", "Youth are increasingly at risk for contracting HIV infection, and community-level interventions are needed to reduce behavioral risk.\n A randomized, controlled, multi-site community-level intervention trial was undertaken with adolescents living in 15 low-income housing developments in five US cities.\n Baseline (n = 1172), short-term follow-up (n = 865), and long-term follow-up (n = 763) risk assessments were conducted among adolescents, ages 12-17, in all 15 housing developments. The developments were randomly assigned in equal numbers to each of three conditions: experimental community-level intervention (five developments); \"state-of-the-science\" skills training workshops (five developments); and, education-only delayed control intervention (five developments).\n At long-term follow-up, adolescents living in the housing developments receiving the community-level intervention were more likely to delay onset of first intercourse (85%) than those in the control developments (76%), while those in the workshop developments (78%) did not differ from control condition adolescents. Adolescents in both the community-level intervention (77%) and workshop (76%) developments were more likely to use a condom at last intercourse than those in control (62%) developments.\n Community-level interventions that include skills training and engage adolescents in neighborhood-based HIV prevention activities can produce and maintain reductions in sexual risk behavior, including delaying sexual debut and increasing condom use.", "Interventions to prevent adolescent pregnancy (primarily curriculum-based programs) have not produced convincing evidence as to their success. Moreover, many evaluation approaches have been inadequate to assess program effectiveness. Therefore, rigorous evaluation of different kinds of interventions may help identify potentially effective strategies to prevent adolescent pregnancy.\n An experimental design, in which clients were randomized to treatment and control groups, was used to evaluate the effects of a \"client-centered\" approach to reducing pregnancy among high-risk young people in seven communities in Washington State. Four projects served 1,042 youth (clients aged 9-13), and three served 690 teenagers (primarily clients aged 14-17). Projects offered a wide variety of services tailored to individual clients' needs, including counseling, mentoring and advocacy.\n On average, clients in the treatment group at youth sites received 14 hours of service, and their teenage counterparts received 27 hours; controls received only 2-5 hours of service. At one youth site, clients were less likely to intend to have intercourse after the intervention than before; at another, they became less likely to intend to use substances. Clients at one teenage project reported reduced sexual behavior and improved contraceptive use after receiving services; teenagers at another site reported reduced sexual intentions and drug use, and a greater intention to use contraceptives. The programs showed no other effects on factors that place young people at risk of becoming pregnant, including their sexual values and educational aspirations, communication with their parents (measured at youth sites only), and sexual and contraceptive behavior (assessed for teenagers only).\n High-risk clients likely need considerably more intervention time and more intensive services than programs normally provide. Rigorous evaluation designs allow continued assessment that can guide program modifications to maximize effects.", "A theory-based curriculum designed to delay the onset of intercourse and increase use of condoms was implemented in the classrooms of six Los Angeles middle schools.\n The curriculum activities were very interactive, emphasized skill building, and were implemented by well trained peer educators, including young HIV-positive males and teen mothers. To evaluate the impact of the curriculum, 102 classrooms of students were randomly assigned to receive either the existing curriculum or the existing curriculum plus the intervention curriculum. Students completed confidential questionnaires before program implementation, five months later, and 17 months later. A total of 1,657 students completed both the baseline and 17-month follow-up questionnaires.\n Analyses of these data revealed that the curriculum significantly increased knowledge, significantly improved only two out of 21 attitudes or beliefs, and did not significantly change sexual or contraceptive behaviors.\n Well implemented programs that are based on upon theory, use interactive activities, and utilize well-trained peer educators do not always change important sexual attitudes and behaviors among middle school youth.", "To determine whether the addition of a parental monitoring intervention (Informed Parents and Children Together [ImPACT]) alone or with \"boosters\" could enhance (either broaden or sustain or both) the effect of a small group, face-to-face adolescent risk reduction intervention Focus on Kids (FOK).\n A longitudinal, randomized, community-based cohort study was conducted of 35 low-income, community-based, in-town settings. A total of 817 black youths aged 12 to 16 years at baseline were studied. After completion of baseline measures, youths were randomized to receive a face-to-face intervention alone (FOK only), a face-to-face intervention and a parental monitoring intervention (FOK plus ImPACT), or both of the above plus boosters (FOK plus ImPACT plus boosters). Risk and protective behaviors were assessed at 6 and 12 months after intervention.\n At 6 months' follow-up, youths in families that were assigned to FOK plus ImPACT reported significantly lower rates of sexual intercourse, sex without a condom, alcohol use, and cigarette use and marginally lower rates of \"risky sexual behavior\" compared with youths in families that were assigned to FOK only. At 12 months after intervention, rates of alcohol and marijuana use were significantly lower and cigarette use and overall risk intention were marginally lower among FOK plus ImPACT youths compared with FOK only youths. With regard to the boosters delivered at 7 and 10 months, 2 risk behaviors--use of crack/cocaine and drug selling--were significantly lower among the youths who were assigned to receive the additional boosters compared with youths without the boosters. The rates of the other risk behaviors and intentions did not differ significantly.\n The results of this randomized, controlled trial indicate that the inclusion of a parental monitoring intervention affords additional protection from involvement in adolescent risk behaviors 6 and 12 months later compared with the provision of an intervention that targets adolescents only. At the same time, the results of the present study do not provide sufficient evidence that booster sessions further improve targeted behaviors enough to include them in a combined parent and youth intervention.", "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.", "Sexual risk behavior outcome data from the Healthy for Life (HFL) project is presented. Using a social influences model, the intervention was designed to positively affect the health behaviors of middle school students in five related areas: alcohol use, tobacco use, marijuana use, nutrition, and sexuality. The in-school program was supplemented by parent, community and peer components. The research used self-report data on an initial sample of 2,483 middle school students followed from Grade 6 to Grade 10. Twenty-one schools were assigned to three conditions--age appropriate (program taught in Grades 6, 7, and 8), intensive (program taught in Grade 7) and control--using blocked randomization. Attrition was 20% (by Year 4) and 33% (by Year 5). By ninth grade the lifetime intercourse rate among both groups of HFL subjects was significantly higher than for controls (controlling for baseline substance use risk and involvement with the opposite sex), but reported past month intercourse rates and condom use did not differ. At the tenth grade follow-up, the age appropriate subjects reported higher adjusted rates of lifetime and past month intercourse than did the controls. Intensive subjects perceived significantly lower normative rates of intercourse than controls at ninth grade follow-up, but age appropriate subjects perceived significantly higher norms at tenth grade. Our expectation that this approach would be effective in reducing adolescent sexual risk behavior has not been supported. The influence of social and community norms and contextual factors has a far greater influence on the behavior of students (even 6 years later) than this school-based social influences program targeting only one grade cohort.", "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.", "This randomized controlled trial tested the effects of a theory-based culture-sensitive HIV risk-reduction intervention among 496 inner-city African American adolescents (mean age = 13 years) and examined the generality of its effects as a function of the facilitator's race and gender and the gender composition of the intervention group. Adolescents who received the HIV risk-reduction intervention expressed more favorable behavioral beliefs about condoms, greater self-efficacy, and stronger condom-use intentions postintervention than did those who received a control intervention on other health issues. Six-month follow-up data collected on 93% of the adolescents revealed that those who received the HIV risk-reduction intervention reported less HIV risk-associated sexual behavior, including unprotected coitus, than did their counterparts in the control condition. Self-reported sexual behavior and changes in self-reported behavior were unrelated to scores on a standard measure of social desirability response bias. There was strong evidence for the generality of intervention effects. Moderator analyses testing eight specific interaction hypotheses and correlational analyses indicated that the effects of the HIV risk-reduction intervention did not vary as a function of the facilitator's race or gender, participant's gender, or the gender composition of the intervention group." ]

[ "8377159", "6437487", "1998929", "7410783", "8361239", "11509308", "8085511", "14008212", "7660408" ]

[ "Day hospital and home physiotherapy for stroke patients: a comparative cost-effectiveness study.", "Day hospital rehabilitation--effectiveness and cost in the elderly: a randomised controlled trial.", "Effectiveness of a geriatric day hospital.", "Geriatric day care and homemaker services: an experimental study.", "Adult Day Health Care Evaluation Study.", "Stroke rehabilitation after hospital discharge: a randomized trial comparing domiciliary and day-hospital care.", "Cost comparison of domiciliary and hospital-based stroke rehabilitation. DOMINO Study Group.", "The day hospital in the community care of the elderly.", "Outcomes of elderly stroke patients. Day hospital versus conventional medical management." ]

[ "The financial cost of stroke rehabilitation is considerable but few cost-effectiveness studies are available to guide clinical practice. The Bradford community stroke trial was a randomised trial comparing day hospital attendance with home physiotherapy for elderly stroke patients leaving hospital. The outcome measurements used indicated a consistent modest advantage in favour of home physiotherapy. This advantage is now re-examined in conjunction with the quantified costs of the rehabilitation services and community support received by the two patient groups. The results show that the median cost for the day hospital patients over the first eight weeks was 620.00 pounds (interquartile range 555.00-730.00 pounds) and 385.00 pounds for the home physiotherapy group (interquartile range 240.00-510.00 pounds). These costs were significantly different (median difference 265.00 pounds, 95% confidence interval 190.00-340.00 pounds; p < 0.01). There were no significant differences between the two groups for the indirect costs. This cost-effectiveness study supports the clinical trial result that home physiotherapy should be the treatment of choice for stroke aftercare.", "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.", "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 purpose of this study was to examine the impact of geriatric day care and homemaker services on patient outcomes. Patients were randomly assigned to receive the experimental services in three study samples. In comparing outcomes between the experimental and control groups, it was found that there were significant differences in physical functioning and activity level for the day care samples, in physical functioning and contentment level for the homemaker study sample, and in all of these outcome measures for the combined services group. Among users of the experimental services, increased use of the services was associated with improved outcomes of care. Multivariate analysis of data showed that factors other than the use of the experimental services were more effective in explaining variation in outcomes. Significant factors that affected all four outcome measures in both the day care and homemaker study were primary diagnosis, impairment prognosis, and number of inpatient hospital days.", "nan", "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.", "The DOMINO study (DOMiciliary rehabilitation In NOttingham) was a randomized controlled trial comparing domiciliary and hospital-based rehabilitation for stroke patients after discharge from hospital, stratified according to the ward at hospital discharge. The outcomes of these patients have been reported previously. In this paper, we present estimates of health service costs of care. No difference in outcome had been found between the overall services, but we have found the hospital-based costs to be 27% cheaper. However, different cost-effectiveness patterns are observable when the strata are analysed. Patients from geriatric wards had been shown to be 2.4 times less likely to die or become institutionalized by 6 months if allocated to a day hospital service, although the cost of this service was 25% more than that of the domiciliary service. Patients from the Stroke Unit who had received domiciliary rehabilitation had been shown to have greater household and leisure abilities at 6 months than those treated in outpatient departments, but the domiciliary service was found to cost 2.6 times more. Patients from general medical wards had similar outcomes whether treated at home or in outpatient departments, but the cost of the latter service was 56% of the former. Some patients may be best cared for in day hospitals and others may do better if treated at home, but for these groups the clinical advantages are achieved at an expense greater than that incurred by the alternative services. Other patients may do as well if treated in outpatient departments as at home, but the former approach is cheaper. A range of services is required for stroke patients leaving hospital.", "nan", "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." ]

[ "2201431", "7139566", "6344983", "7602342", "135666", "3585441", "8315424" ]

[ "Randomized comparison of doxorubicin and vindesine to doxorubicin for patients with metastatic soft-tissue sarcomas.", "A comparison of adriamycin versus vincristine and adriamycin, and cyclophosphamide versus vincristine, actinomycin-D, and cyclophosphamide for advanced sarcoma.", "A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas.", "Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.", "Combination chemotherapy with adriamycin and streptozotocin. I. Clinical results in patients with advanced sarcoma.", "Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas.", "Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas." ]

[ "Two treatment regimens for metastatic soft-tissue sarcomas were compared in a randomized trial in the cooperative group setting. Histopathologic diagnosis was affirmed by pathology reference panel review in 72% of the 347 patients. In 21% of patients, the reference panel affirmed the diagnosis of soft-tissue sarcoma but disagreed as to type; 7% of patients were ineligible based upon cell type. Of 298 patients evaluable, measurable tumor regression (partial or complete response) occurred in 17% of patients to doxorubicin (70 mg/m2 intravenously) and 18% of patients to doxorubicin (70 mg/m2 intravenously) and vindesine (3 mg/m2 intravenously), each given every 3 weeks. No difference existed in complete response (4% for doxorubicin, 6% for doxorubicin and vindesine) or median survival (9.4 months for doxorubicin, 9.9 months for doxorubicin and vindesine). Overall, 60% of those patients on doxorubicin and vindesine and 46% on doxorubicin experienced a severe or worse toxicity of treatment (P = 0.01). With greater toxicity and lack of any gains in efficacy, the results do not support use of the combination of doxorubicin and vindesine for metastatic soft-tissue sarcomas.", "This randomized study, conducted by the Eastern cooperative Oncology Group, compared Adriamycin (doxorubicin) (70 mg/m2) versus vincristine (1.4 mg/m2) and Adriamycin (50 mg/m2); and cyclophosphamide (750 mg/m2) versus vincristine (1.4 mg/m2), actinomycin-D (0.4 mg/m2), and cyclophosphamide (750 mg/m2) for treatment of metastatic mesenchymal malignancies. The respective response rate seen in 200 evaluable patients to the treatments were, 27, 19, and 11%. The response rate to Adriamycin was significant better than the response to vincristine, actinomycin-D, and cyclophosphamide (P = 0.03, two-sided). The respective median survivals on the three treatments were 37, 34, and 41 weeks and were not significantly different. Moderate or severe vomiting occurred in 60% of patients receiving vincristine-cyclophosphamide-adriamycin, a greater frequency than in Adriamycin alone (P = .09 two-sided) Severe or life-threatening hematologic toxicity (leukocytes less than 2000, platelets less than 50,000) occurred in 30% of patients receiving the Adriamycin combination, a markedly increased frequency when compared to the other two regimens (P equals 0.07, P = 0.02, two-sided). This trial establishes that Adriamycin has a better response rate than the combination of vincristine-actinomycin-D-cyclophosphamide in advanced sarcomas. The combination of vincristine, Adriamycin, and cyclophosphamide increased toxicity and did not add to the therapeutic effect achieved with Adriamycin alone.", "Various drug combinations including Adriamycin have been tested in soft tissue sarcomas, but optimal treatment remains unclear. We have evaluated Adriamycin with and without dimethyl-triazeno-imidazole-carboxamide (DTIC) in the treatment of Stage III or IV and recurrent sarcomas of the uterus. Two hundred and forty cases of these rare tumors were evaluable. Of 146 evaluable patients with measurable disease, 13/80 (16.3%) of Adriamycin-treated patients and 16/66 (24.2%) of patients receiving the combination showed an objective response (P greater than 0.05). Lung metastases responded more frequently (P equal to 0.04) to combination therapy, but there was no survival advantage. For patients with nonmeasurable disease the progression-free interval was similar (10.0 months for Adriamycin and 8.0 months for the combination). Leiomyosarcomas had a significantly longer survival than other cell types (12.1 versus 6.0 months, P less than 0.001) but there was no advantage for either regimen. There was a suggestion that heterologous mixed mesodermal sarcomas were more responsive to the combination (27.3 versus 8.7%). The addition of DTIC produced significantly more hematologic and gastrointestinal toxicity. Other Adriamycin combinations should be evaluated in uterine sarcomas.", "The aim of this trial was to compare the activity and toxicity of single-agent doxorubicin with that of two multidrug regimens in the treatment of patients with adult advanced soft tissue sarcomas.\n This was a prospective randomized phase III trial performed by 35 cancer centers within the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer (EORTC). Six hundred sixty-three eligible patients were randomly allocated to receive either doxorubicin 75 mg/m2 (arm A), cyclophosphamide, vincristine, doxorubicin, and dacarbazine (CYVADIC) (arm B), or ifosfamide 5 g/m2 plus doxorubicin 50 mg/m2 (arm C).\n The overall response rate was 24% (95% confidence interval, 20.7% to 27.3%) among eligible patients and 26% among assessable patients. No statistically significant difference was detected among the three study arms in terms of response rate (arm A, 23.3%; arm B, 28.4%; and arm C, 28.1%), remission duration (median, 46 weeks on arm A, 48 weeks on arm B, and 44 weeks on arm C), or overall survival (median, 52 weeks on arm A, 51 weeks on arm B, and 55 weeks on arm C). The degree of myelosuppression was significantly greater for the combination of ifosfamide and doxorubicin than for the other two regimens. Cardiotoxicity was also more frequent in this arm, but other toxicities were similar.\n In advanced soft tissue sarcomas of adults, single-agent doxorubicin is still the standard chemotherapy against which more intensive or new drug treatments should be compared. Combination chemotherapy cannot be recommended outside a controlled clinical trial with the exclusion of some subsets of sarcoma patients for whom significant tumor volume reduction may be an important end point of a chemotherapy regimen.", "In a prospectively randomized study, 17 evaluable patients treated with adriamycin alone, 60 mg/m2 intravenously every 3 wk, were compared with 14 patients treated with adriamycin in the same dose and schedule plus streptozotocin. 500 mg/m2/day intravenously for 5 days every 3 wk. All patients had advanced sarcomas, but none had previously received either adriamycin or streptozotocin. Objective responses were seen in 9 patients on the single drug arm (4 with more than 50% tumor shrinkage and 5 with stabilization of disease), and in 8 patients given the combination drug arm (2 with more than 50% tumor shrinkage and 6 with stabilization of disease). Duration of response and survival from treatment for both treatment groups were similar. Transient hepatic dysfunction, renal function abnormalities, and nausea with vomiting were additive in the combination drug arm, the last two limiting therapy most. Leukopenia, thrombocytopenia, and mucositis appeared to be synergistically increased in patients receiving both adriamycin and streptozotocin. Patients with abnormal pretreatment renal function were able to tolerate the combination therapy without undue incidence of severity of renal toxicity. Patients who developed transient streptozotocin-related renal dysfunction were able to tolerate further doses of streptozotocin after their renal parameters normalized. Adriamycin in combination with streptozotocin did not offer any therapeutic advantage over adriamycin alone.", "This study addressed two major questions regarding therapeutic use of Adriamycin ([Adr] Adria Laboratories, Columbus, OH) in adult soft tissue sarcomas: the influence of dosing schedule and the value of adding imidazole carboxamide (DTIC) to Adr. Patients with objectively measurable metastatic soft tissue sarcomas were randomized to Adr 70 mg/m2 intravenously (IV) day 1 and every 3 weeks (94 patients); Adr 20 mg/m2 IV day 1, 2, and 3, and 15 mg/m2 IV day 8 and weekly thereafter (89 patients); and Adr 60 mg/m2 IV day 1 and DTIC 250 mg/m2 days 1 to 5, repeated every 3 weeks (92 patients). The regimens using Adr as a single agent resulted in an equivalent response frequency (18% and 16%) and survival (median, 8.0 and 8.4 months). DTIC significantly increased (P less than .02) the overall response frequency of Adr to 30%. However, DTIC did not influence survival (median, 8.0 months) or increase the number of complete responses. The toxicities of the two single-agent regimens differed: Adr weekly resulted in more stomatitis (P = .09) and less hematologic toxicity (P less than .05). DTIC resulted in substantially increased toxicity, primarily gastrointestinal (P less than .002); overall, 98% of patients receiving Adr-DTIC experienced moderate or worse toxicity. To decrease the potential for error in interpretation of treatment results, histopathological confirmation of diagnosis was undertaken by a panel of reference pathologists; pathology slides were submitted on 97% of entered patients. The on-study clinical diagnosis was affirmed in 199 of 316 patients (63%) with a final review. In 23% of patients, the panel agreed with the diagnosis of soft tissue sarcoma, but not with the type. In 14%, the panel concluded that a diagnosis of mesenchymal malignancy could not be affirmed. Final treatment results were based on the 275 pathologically confirmed, eligible patients. The most common histological subtype entered was leiomyosarcoma (99 patients). The response to Adr-DTIC of this subtype was higher (44%) than that of any other subtype. However, this difference alone was not responsible for the overall superiority of the combination. This confirmed that the combination of DTIC plus Adr adds to the response rate of Adr alone in soft tissue sarcomas. Whether the increased response frequency, without an impact on survival, is worth the significantly greater toxicity remains a subjective judgement that must be made within the context of the individual patient.", "This three-armed phase III study in adults with advanced soft tissue sarcomas was planned as a comparison of objective regression rates, toxicity, and survival of patients receiving doxorubicin alone, ifosfamide plus doxorubicin, and mitomycin plus doxorubicin plus cisplatin.\n Between December 1987 and July 1990, 279 patients with histologically confirmed sarcomas were enrolled to receive treatment A (doxorubicin 80 mg/m2), treatment B (ifosfamide 7.5 g/m2 plus doxorubicin 60 mg/m2), or treatment C (mitomycin 8 mg/m2 plus doxorubicin 40 mg/m2 plus cisplatin 60 mg/m2).\n Of 262 assessable patients, 74 (29%) achieved objective tumor regression. Objective regression occurred in 20% of the 90 patients who received doxorubicin alone (complete remission [CR] rate, 2%), in 34% of the 88 who received ifosfamide plus doxorubicin (CR rate, 3%), and in 32% of the 84 who received mitomycin plus doxorubicin plus cisplatin (CR rate, 7%). With grade 3 or greater myelosuppression in 53% of group A, 80% of group B, and 55% of group C, regimen B was significantly more myelosuppressive than either regimen A or C (P = .01) with two, three, and one treatment-related deaths, respectively. Synovial sarcomas were responsive to ifosfamide plus doxorubicin, especially among patients younger than 40 years of age.\n Ifosfamide plus doxorubicin produced a significantly higher regression rate (P = .03) than did doxorubicin alone; however, this was achieved at a level of myelosuppression significantly more intense than that produced by the single agent or by the three-drug combination. Mitomycin, doxorubicin, and cisplatin also appeared to be more active than the single agent; however, at a myelosuppression level similar to that of doxorubicin alone, this trend (P = .07) did not attain the usual level for significance. No significant survival differences were observed." ]

[ "8605558", "8780576", "9723315", "10693639", "7762065", "8475558", "7843707", "8356662" ]

[ "Postoperative intravenous infusion of alprostadil (PGE1) does not improve renal function in hepatic transplant recipients.", "Prostaglandin E1 administration following orthotopic liver transplantation: a randomized prospective multicenter trial.", "Treatment with PGE1 in patients after liver transplantation.", "Administration of prostacyclin after liver transplantation: a placebo controlled randomized trial.", "Enisoprost in liver transplantation.", "Evidence that intraoperative prostaglandin E1 infusion reduces impaired platelet aggregation after reperfusion in orthotopic liver transplantation.", "A double-blind, randomized, placebo-controlled trial of prostaglandin E1 in liver transplantation.", "Failure of PGE1 to prevent liver allograft reperfusion injury in a prospective randomized trial." ]

[ "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.", "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.", "nan", "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.", "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.", "Recent investigations measuring platelet aggregation during 10 orthotopic liver transplantations showed a significant decrease in platelet aggregation immediately after reperfusion and in the perfusate. As prostaglandin E1 has been shown to exhibit a beneficial effect in the treatment of ischemic injury of the liver, we investigated in a prospective, randomized, and open study the effect of PGE1 infusion during OLT on platelet function. Ten patients were randomized to receive a continuous PGE1 infusion (PG group) and another ten patients served as controls. Platelet function was determined ex vivo by measuring the adenosine diphosphate-, collagen-, and ristocetin-induced aggregation in platelet-rich plasma. A significantly higher platelet aggregability was measured in the PG group throughout the whole operation for ADP (1 and 2 mumol/L) and collagen (0.5 micrograms/ml). The same was true for collagen (1 microgram/ml) and ristocetin (1.2 mg/ml) after reperfusion. Not only the postreperfusional decrease in platelet aggregation but also the decline in platelet count that occurred in the control group could be prevented greatly by PGE1 infusion. In the perfusate, released from the liver graft vein by flushing with arterial blood, a significantly lower platelet aggregability was seen in comparison with the systemic circulation before reperfusion in the control group, a difference that was not found when PGE1 infusion was given intraoperatively. However, blood product requirements during OLT were comparable in both groups. In conclusion, PGE1 therapy during OLT preserves platelet function and prevents the drop in platelet count observed in the control group after revascularization.", "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.", "nan" ]

[ "12797881", "19574255" ]

[ "Effort and work of breathing in neonates during assisted patient-triggered ventilation.", "Flow-cycled versus time-cycled sIPPV in preterm babies with RDS: a breath-to-breath randomised cross-over trial." ]

[ "OBJECTIVE: This study compares patient-ventilator synchrony, work of breathing and patient effort in neonates during different modes of patient-triggered ventilation. DESIGN: Clinically stable neonates received intermittent mandatory ventilation (IMV), synchronized intermittent mandatory ventilation (SIMV), pressure assist/control ventilation (A/C), and pressure support ventilation (PSV) in a random order for 20 mins. With each mode patient-ventilator synchrony, work of breathing, and patient effort were evaluated. SETTING: Neonatal level III intensive care unit of a university hospital. Measurements and RESULTS: Seven clinically stable neonates (31.4 +/- 2 wks gestation, weighing 1.49 +/- 0.38 kg) were randomly ventilated with the above four modes using a Bird VIP ventilator. Esophageal pressure, airway pressure, and flow were measured using a CP-100 neonatal monitor (Bicore). Data for five consecutive breaths in each mode were analyzed. Patient effort and work of breathing differed significantly among modes of ventilation. The inspiratory pressure time product was least with A/C (0.54 +/- 0.29 cm H(2)O.sec) and increased with PSV (0.60 +/- 0.39 cm H(2)O.sec), SIMV (1.46 +/- 0.55 cm H(2)O.sec), and IMV (2.74 +/- 1.05 cm H(2)O.sec) (p <.05). A similar trend was observed for work of breathing, with work least during A/C (0.07 +/- 0.04 joules per liter [J/L]), followed by PSV (0.17 +/- 0.14 J/L), SIMV (0.33 +/- 0.13 J/L), and IMV (0.41 +/- 0.16 J/L) (p <.05). Marked dyssynchrony between patient-initiated and ventilator-initiated inspiration occurred only during IMV. CONCLUSION: Asynchrony can be avoided by the use of assisted, patient triggered modes of ventilation and, of the available modes, pressure A/C results in the least effort and work of breathing for clinically stable neonates.", "Few data exist about patient-triggered ventilation techniques in neonatal critical care. Our aim was to compare pressure-limited synchronised intermittent positive pressure (or assist/control) ventilation (sIPPV) in the classical time-cycled (TC-sIPPV) mode against flow-cycled (FC-sIPPV) modality. In this latter, typical sIPPV full respiratory support is provided but both the initiation and the end of inflation are determined by the infant's spontaneous respiratory efforts by using airway flow changes.\n A third-level neonatal intensive care unit.\n Ten preterm babies (<32 weeks' gestation) were randomised to receive 1 h FC-sIPPV followed by 1 h TC-sIPPV or the inverse shift, according to a computer-created randomisation table. Eligible babies had hyaline membrane disease and received 200 mg/kg surfactant at least 6 h before the study period. Respiratory mechanics, ventilatory and vital parameter data were registered real time.\n FC-sIPPV resulted in lower-rate volume ratio, pressure x rate product, mean airway pressure and heart rate; tidal volume and oxygen saturation were higher (all p<0.001). Spontaneous inspiratory time was lower than usually set by the physician and it was directly correlated to birth weight (rho = 0.5, p = 0.001) and gestational age (rho = 0.32, p = 0.001). No differences were noticed in the mechanics and blood gas and vital parameters during the two study phases.\n FC-sIPPV may safely result in a better patient ventilator synchrony. Inspiratory time usually set in neonatal critical care is higher than that decided by the baby during spontaneous effort. This should be considered when establishing time-cycled ventilation." ]

[ "12842060", "11251483" ]

[ "Does perineal suturing make a difference? The SUNS trial.", "Is it necessary to suture all lacerations after a vaginal delivery?" ]

[ "To examine differences in outcome between primiparous women who do and who do not have suturing to first or second degree perineal lacerations sustained during spontaneous vaginal births after 37 weeks of gestation.\n Parallel group randomised controlled trial.\n Bellshill Maternity Hospital, Lanarkshire, and St John's Hospital, Livingston.\n Primigravidae with perineal lacerations following spontaneous birth.\n One thousand and three hundred fourteen women were recruited to the trial antenatally from whom 74 were randomised either to be sutured or not sutured immediately after giving birth. Randomisation was stratified by degree of tear.\n Using standardised measures, perineal pain and healing were measured at 1 and 10 days and 6 weeks postpartum. In addition, postnatal depression was assessed at 10 days and 6 weeks postpartum.\n Findings indicated that there were no significant differences between the groups with regard to pain or depression but there were differences with regard to healing. At six weeks, there remained a significant difference in wound closure between the groups, with women who had not been sutured having poorer wound approximation.\n While acknowledging the small sample size, the results are nonetheless important, showing persistent evidence of poorer wound approximation in those women who had not been sutured. Practitioners need to review the present practices of not suturing perineal lacerations until research examining the longer term implications is undertaken.", "Midwives tend to leave minor perineal lacerations to heal spontaneously, and clinical experience and studies show that women can suffer from their stitched lacerations. The study purpose was to determine any differences in the healing process and experience of minor perineal lacerations when they were sutured or not sutured.\n Eighty term pregnant primiparas with minor perineal lacerations of grades I-II were randomized after childbirth. The experimental group was nonsutured and the control group was sutured. A follow-up examination was performed at 2 to 3 days, 8 weeks, and 6 months after the delivery. Participants were asked about the type of discomfort, and the effect of the laceration on breastfeeding and sexual intercourse.\n No significant differences were found in the healing process. The type of pain differed between the groups, but the amount of discomfort was the same. The sutured group had to visit the midwife more often because of discomfort from the stitches. Sixteen percent of the women in the sutured group, but none in the nonsutured group (p = 0.0385), considered that the laceration had had a negative influence on breastfeeding.\n Minor perineal lacerations can be left to heal spontaneously. The benefits for the woman include the possibility of having a choice, avoiding the discomfort of anesthesia and suturing, providing positive affects on breastfeeding." ]

[ "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." ]

[ "10321661", "9559600", "8823850", "17992396", "15557131", "12426230", "12186604", "6384785", "786190", "17426195", "3306374", "6712466", "3202402", "12133187", "4929896", "16276166", "18184957", "2888017", "20103758" ]

[ "Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study.", "Reversal of late septic shock with supraphysiologic doses of hydrocortisone.", "Randomized, placebo-controlled, double blinded trial of dexamethasone in African children with sepsis.", "Early dexamethasone treatment for septic shock patients: a prospective randomized clinical trial.", "Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study.", "Immunologic and hemodynamic effects of \"low-dose\" hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study.", "Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.", "The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study.", "Steroids in the treatment of clinical septic shock.", "Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial.", "A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock.", "The cardiopulmonary response to massive doses of steroids in patients with septic shock.", "Ineffectiveness of high-dose methylprednisolone in preventing parenchymal lung injury and improving mortality in patients with septic shock.", "Physiological-dose steroid therapy in sepsis [ISRCTN36253388].", "Effectiveness of betamethasone in management of severe infections. A double-blind study.", "Low-dose hydrocortisone improves shock reversal and reduces cytokine levels in early hyperdynamic septic shock.", "Hydrocortisone therapy for patients with septic shock.", "Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. The Veterans Administration Systemic Sepsis Cooperative Study Group.", "Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial." ]

[ "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.", "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.", "To determine the effect of moderate dose dexamethasone administered before antibiotics on the outcome of African children with sepsis.\n The design was a randomized, double blinded, placebo-controlled trial of dexamethasone (0.2 mg/kg) vs. placebo given intravenously before antibiotic therapy. Patients were recruited from the patient populations at two missionary hospitals. Primary outcome variables were determined before analysis of data.\n Seventy-two children with sepsis were enrolled in the study. Treatment with dexamethasone was not associated with improved outcome for any of six outcome variables: survival to discharge (83%, dexamethasone group; 89%, placebo group); hemodynamic stability at 48 h (33%, dexamethasone group; 49%, placebo group); median length of hospital stay (11 days, dexamethasone group; 11 days, placebo group); normal at discharge (90%, dexamethasone group; 75%, placebo group); normal at follow-up (90%, dexamethasone group; 72%, placebo group); and afebrile at 48 to 72 h (61%, dexamethasone group; 44%, placebo group).\n These data indicate that a moderate dose of dexamethasone given before antibiotic therapy did not improve outcome in the pediatric patients with sepsis whom we studied.", "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.", "We hypothesize that hydrocortisone infusion in severe community-acquired pneumonia attenuates systemic inflammation and leads to earlier resolution of pneumonia and a reduction in sepsis-related complications. In a multicenter trial, patients admitted to the Intensive Care Unit (ICU) with severe community-acquired pneumonia received protocol-guided antibiotic treatment and were randomly assigned to hydrocortisone infusion or placebo. Hydrocortisone was given as an intravenous 200-mg bolus followed by infusion at a rate of 10 mg/hour for 7 days. Primary end-points of the study were improvement in Pa(O(2)):FI(O(2)) (Pa(O(2)):FI(O(2)) > 300 or >/= 100 increase from study entry) and multiple organ dysfunction syndrome (MODS) score by Study Day 8 and reduction in delayed septic shock. Forty-six patients entered the study. At study entry, the hydrocortisone group had lower Pa(O(2)):FI(O(2)), and higher chest radiograph score and C-reactive protein level. By Study Day 8, treated patients had, compared with control subjects, a significant improvement in Pa(O(2)):FI(O(2)) (p = 0.002) and chest radiograph score (p < 0.0001), and a significant reduction in C-reactive protein levels (p = 0.01), MODS score (p = 0.003), and delayed septic shock (p = 0.001). Hydrocortisone treatment was associated with a significant reduction in length of hospital stay (p = 0.03) and mortality (p = 0.009).", "Within the last few years, increasing evidence of relative adrenal insufficiency in septic shock evoked a reassessment of hydrocortisone therapy. To evaluate the effects of hydrocortisone on the balance between proinflammatory and antiinflammation, 40 patients with septic shock were randomized in a double-blind crossover study to receive either the first 100 mg of hydrocortisone as a loading dose and 10 mg per hour until Day 3 (n = 20) or placebo (n = 20), followed by the opposite medication until Day 6. Hydrocortisone infusion induced an increase of mean arterial pressure, systemic vascular resistance, and a decline of heart rate, cardiac index, and norepinephrine requirement. A reduction of plasma nitrite/nitrate indicated inhibition of nitric oxide formation and correlated with a reduction of vasopressor support. The inflammatory response (interleukin-6 and interleukin-8), endothelial (soluble E-selectin) and neutrophil activation (expression of CD11b, CD64), and antiinflammatory response (soluble tumor necrosis factor receptors I and II and interleukin-10) were attenuated. In peripheral blood monocytes, human leukocyte antigen-DR expression was only slightly depressed, whereas in vitro phagocytosis and the monocyte-activating cytokine interleukin-12 increased. Hydrocortisone withdrawal induced hemodynamic and immunologic rebound effects. In conclusion, hydrocortisone therapy restored hemodynamic stability and differentially modulated the immunologic response to stress in a way of antiinflammation rather than immunosuppression.", "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.", "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.", "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.", "To determine the effects of low-dose prolonged methylprednisolone infusion on lung function in patients with early severe ARDS.\n Randomized, double-blind, placebo-controlled trial.\n ICUs of five hospitals in Memphis.\n Ninety-one patients with severe early ARDS (</= 72 h), 66% with sepsis.\n Patients were randomized (2:1 fashion) to methylprednisolone infusion (1 mg/kg/d) vs placebo. The duration of treatment was up to 28 days. Infection surveillance and avoidance of paralysis were integral components of the protocol.\n The predefined primary end point was a 1-point reduction in lung injury score (LIS) or successful extubation by day 7.\n In intention-to-treat analysis, the response of the two groups (63 treated and 28 control) clearly diverged by day 7, with twice the proportion of treated patients achieving a 1-point reduction in LIS (69.8% vs 35.7%; p = 0.002) and breathing without assistance (53.9% vs 25.0%; p = 0.01). Treated patients had significant reduction in C-reactive protein levels, and by day 7 had lower LIS and multiple organ dysfunction syndrome scores. Treatment was associated with a reduction in the duration of mechanical ventilation (p = 0.002), ICU stay (p = 0.007), and ICU mortality (20.6% vs 42.9%; p = 0.03). Treated patients had a lower rate of infections (p = 0.0002), and infection surveillance identified 56% of nosocomial infections in patients without fever.\n Methylprednisolone-induced down-regulation of systemic inflammation was associated with significant improvement in pulmonary and extrapulmonary organ dysfunction and reduction in duration of mechanical ventilation and ICU length of stay.", "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.", "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.", "We conducted a prospective, randomized, double-blind study to determine whether high-dose methylprednisolone could prevent parenchymal lung injury, including the adult respiratory distress syndrome (ARDS), or improve mortality when administered early in septic shock. All patients already hospitalized in or newly admitted to the medical and surgical intensive care units at San Francisco General Hospital between September 1, 1983 and August 29, 1986 were eligible for admission to the study if they had either (1) an increase in temperature of 1.5 degrees C and a decrease in systolic blood pressure of 20 mm Hg or more from baseline values (in already hospitalized patients), or (2) a temperature greater than 38.5 degrees C or less than 35.5 degrees C and a systolic blood pressure of less than 90 mm Hg (in newly admitted patients). Patients meeting these criteria were excluded if they (1) had severe immunodeficiency, (2) were less than 18 or greater than 76 yr of age, (3) had multilobar roentgenographic infiltrates, or (4) were already receiving corticosteroids. Eighty-seven patients enrolled in the study received either methylprednisolone, 30 mg/kg per dose, or mannitol placebo for a total of 4 doses every 6 h, following the presumptive diagnosis of septic shock. Of these patients, 75 ultimately were determined on the basis of culture results to have actually had septic shock at the time of entry. Thirteen of the patients who received methylprednisolone developed ARDS, compared to 14 patients who received placebo. Lesser degrees of parenchymal lung injury did not differ between the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)", "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.", "nan", "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.", "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", "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.", "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." ]

[ "15613603", "12019686", "11493843", "15676878", "8433181", "9628709", "10649606", "11607869", "18803093", "17304142", "16845347", "19915206", "9233870", "18408345", "19952790" ]

[ "Intensive education combined with low tech ergonomic intervention does not prevent low back pain in nurses.", "A field trial of back belts to reduce the incidence of acute low back injuries in New York City home attendants.", "A randomized controlled trial to prevent patient lift and transfer injuries of health care workers.", "An evaluation of a weightlifting belt and back injury prevention training class for airline baggage handlers.", "The Back Injury Prevention Project pilot study. Assessing the effectiveness of back attack, an injury prevention program among nurses, aides, and orderlies.", "Lumbar supports and education for the prevention of low back pain in industry: a randomized controlled trial.", "Evaluation of an educational low back pain prevention program for hospital employees.", "[Coordinative treatment and quality of life - a randomised trial of nurses with back pain].", "Little effect of transfer technique instruction and physical fitness training in reducing low back pain among nurses: a cluster randomised intervention study.", "Can a new behaviorally oriented training process to improve lifting technique prevent occupationally related back injuries due to lifting?", "Prevention of low back pain in female eldercare workers: randomized controlled work site trial.", "Effects of a multifaceted minimal-lift environment for nursing staff: pilot results.", "A controlled trial of an educational program to prevent low back injuries.", "Effect of nursing assistance tools on preventing musculoskeletal pain among staff in schools for disabled children.", "The effect of individual job coaching and use of health threat in a job-specific occupational health education program on prevention of work-related musculoskeletal back injury." ]

[ "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.", "To determine the effect of black belt use on the incidence of low back injury in home attendants, a cluster-randomized trial involving employees of nine home attendant agencies in New York City was conducted. Nine agencies employing 12,772 home attendants between June 1997 and September 1999 were randomized into three groups-one group received back belts with use instruction, one group received lifting advice only, and one group served as a control. Low back injury rates per 100 full-time equivalents and rate ratios adjusted for potential confounders were estimated with random-effects Poisson regression. The back-belt group had a lower rate of low back injury than did those in both the advice-only and control groups, though the differences were marginally significant. Age, body mass index, history of back injury, years worked as a home attendant, and level of exercise were associated with risk of low back injury. The findings suggest that use of back belts is associated with some reduction in risk of low back injury.", "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.", "This study evaluated the efficacy of a commercially available weightlifting belt in relation to reduction of lumbar injury incident rate and severity of injuries over an 8-month period. The study used 642 baggage handlers working for a major airline company as participants. Four treatment groups were randomly selected: a group receiving the belt only, a group receiving a 1 h training class only, a group receiving both a belt and a 1 h training class, and a control group receiving nothing. Two treatment groups were added which contained participants who discontinued use of the belt prior to the end of an 8-month study period. Results indicated that there were no significant differences for total lumbar injury incident rate, restricted workday case injury incident rate, lost workdays and restricted workdays rate, and worker's compensation rates. There was, however, a marginal significant difference for lost workday case injury incident rate. Groups with participants who wore the belt for a while then discontinued its use had a higher lost day case injury incident rate than did either the group receiving training only or the control group. Compliance was an overriding factor as the belt questionnaire response indicated that 58% of participants in the belt groups discontinued use of the belt before the end of 8 months. Comments made on the survey forms indicated that the belt was too hot. Similarly, comments suggested that the belt rubbed, pinched, and bruised ribs. Based on these results, the weightlifting belt used for this study cannot be recommended for use in aid of lifting during daily work activities of baggage handlers. Results indicate that use of the belts may, in fact, increase the risk of injury when not wearing a belt following a period of wearing a belt. As industries are experimenting with the use of belts, it is recommended that great care be taken in any further evaluation and close attention directed towards injuries which occur when not wearing the belt following a period of wearing the belt (ie, off-the-job injuries).", "The Back Injury Prevention Project was a pilot study of \"Back Attack,\" an educational program designed to prevent back injuries among nurses, nurses' aides, and orderlies. The pilot tested program feasibility, developed and tested instruments, and generated preliminary data measuring program effectiveness. Fifty-five nurses, aides, and orderlies on two medical/surgical units at two Kaiser Permanente medical centers in Portland, Oregon participated in the study. Intervention group scores on the composite back pain and composite fatigue scales decreased relative to the control group, but this did not reach statistical significance. A 19% improvement in scores for quality of patient transfer was observed for the intervention group (P < .0003), while the control group did not show any significant improvement during the same time period. Results of the pilot suggest that the Back Attack program changes behavior at least in the short term. Further study will be necessary to determine if the behavior change persists and back pain and injury rates are subsequently reduced.", "Low back pain is a frequent and costly health problem. Prevention of low back pain is important both for the individual patient and from an economic perspective.\n To assess the efficacy of lumbar supports and education in the prevention of low back pain in industry.\n A randomized controlled trial with a factorial design.\n The cargo department of an airline company in the Netherlands.\n A total of 312 workers were randomized, of whom 282 were available for the 6-month follow-up.\n Subjects were randomly assigned to 4 groups: (1) education (lifting instructions) and lumbar support, (2) education, (3) lumbar support, and (4) no intervention. Education consisted of 3 group sessions on lifting techniques with a total duration of 5 hours. Lumbar supports were recommended to be used during working hours for 6 months.\n Low back pain incidence and sick leave because of back pain during the 6-month intervention period.\n Compliance with wearing the lumbar support at least half the time was 43%. In the 282 subjects for whom data were available, no statistically significant differences in back pain incidence (48 [36%] of 134 with lumbar support vs 51 [34%] of 148 without, P=.81) or in sick leave because of low back pain (mean, 0.4 days per month with lumbar support vs 0.4 days without, P=.52) were found among the intervention groups. In a subgroup of subjects with low back pain at baseline, lumbar supports reduced the number of days with low back pain per month (median, 1.2 vs 6.5 days per month; P=.03).\n Overall, lumbar supports or education did not lead to a reduction in low back pain incidence or sick leave. The results of the subgroup analysis need to be confirmed by future research. Based on our results, the use of education or lumbar supports cannot be recommended in the prevention of low back pain in industry.", "To evaluate the impact of an educational low back pain prevention program in a cohort of hospital employees.\n A cohort of 136 nonclerical hospital employees attended classes on safe postures and patient handling, then received advice by educators who observed them while they performed their typical workday tasks. Each of the subjects in this intervention group was matched on age, sex, and job category with a control. Musculoskeletal complaints and changes in habits during work and recreational activities were evaluated before the intervention (or the corresponding date in the control group) and after two years.\n In the intervention group, 36% of subjects with low back pain at baseline were free of this symptom at follow-up, whereas only 26% were in the opposite situation. The proportion of subjects with low back pain episodes lasting longer than 30 days increased significantly from baseline to follow-up in the control group (from 30% to 49%) but not in the intervention group. The number of sick leaves longer than 30 days decreased significantly in the intervention group. Only 33% of the intervention group subjects felt the intervention had been helpful; this proportion varied across job categories.\n Our data suggest that differences in job categories should be taken into account when designing educational programs for preventing low back pain. They also indicate that back school programs may be more effective in subjects with a history of low back pain, whereas instruction on safe postures and patient handling may be the best approach in subjects who have not previously experienced low back pain. Observing and providing advice to employees while they are performing their usual duties may be an essential component of low back pain prevention.", "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.", "The aim of this study was to evaluate the effect of a transfer technique education programme (TT) alone or in combination with physical fitness training (TTPT) compared with a control group, who followed their usual routine. Eleven clinical hospital wards were cluster randomised to either intervention (six wards) or to control (five wards). The intervention cluster was individually randomised to TT (55 nurses) and TTPT (50 nurses), control (76 nurses). The transfer technique programme was a 4-d course of train-the-trainers to teach transfer technique to their colleagues. The physical training consisted of supervised physical fitness training 1 h twice per week for 8 weeks. Implementing transfer technique alone or in combination with physical fitness training among a hospital nursing staff did not, when compared to a control group, show any statistical differences according to self-reported low back pain (LBP), pain level, disability and sick leave at a 12-month follow-up. However, the individual randomised intervention subgroup (transfer technique/physical training) significantly improved the LBP-disability (p = 0.001). Although weakened by a high withdrawal rate, teaching transfer technique to nurses in a hospital setting needs to be thoroughly considered. Other priorities such as physical training may be taken into consideration. The current study supports the findings of other studies that introducing transfer technique alone has no effect in targeting LBP. However, physical training seems to have an influence in minimising the LBP consequences and may be important in the discussion of how to prevent LBP or the recurrence of LBP among nursing personnel.", "A prospective randomized control trial.\n To determine the degree to which a new behavior-based lift training program (LiftTrainer; Ascension Technology, Burlington, VT) could reduce the incidence of low back disorder in distribution center jobs that require repetitive lifting.\n Most studies show programs aimed at training lifting techniques to be ineffective in preventing low back disorders, which may be due to their conceptual rather than behavioral learning approach.\n A total of 2144 employees in 19 distribution centers were randomized into either the LiftTrainer program or a video control group. In the LiftTrainer program, participants were individually trained in up to 5, 30-minute sessions while instrumented with motion capture sensors to quantify the L5/S1 moments. Twelve months following the initial training, injury data were obtained from company records.\n Survival analyses (Kaplan-Meier) indicated that there was no difference in injury rates between the 2 training groups. Likewise, there was no difference in the turnover rates. However, those with a low (<30 Nm) average twisting moment at the end of the first session experienced a significantly (P < 0.005) lower rate of low back disorder than controls.\n While overall the LiftTrainer program was not effective, those with twisting moments below 30 Nm reported fewer injuries, suggesting a shift in focus for \"safe\" lifting programs.", "Randomized controlled trial.\n To evaluate the effectiveness of an ergonomic and psychosocial intervention in reducing low back pain (LBP) among health care workers.\n LBP and injuries are reported frequently among health care workers worldwide. Improvement of person-transfer techniques is the preferred tool in the prevention of both. Although popular, to our knowledge, any effect has not been documented in controlled trials.\n Study participants were eldercare workers from 19 eldercare groups randomly assigned to the transfer technique, stress management, or reference arm. A total of 163 individuals (79% of the source population) participated in both baseline and follow-up after 2 years. Outcome was intra-individual change in rating of LBP during the past 3 and 12 months.\n We found no difference in LBP in any of the intervention arms over the study period.\n The study showed no effect of a transfer technique or stress management program targeting LBP. Thus, there is a need for discussing other priorities in the prevention of LBP among health care workers.", "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.", "Low back injuries are common and costly, accounting for 15 to 25 percent of injuries covered by workers' compensation and 30 to 40 percent of the payments made under that program. The high costs of injury, the lack of effective treatment. and the evidence that there are behavioral risk factors have led to widespread use of employee education programs that teach safe lifting and handling. The effectiveness of those programs, however, has received little rigorous evaluation.\n We evaluated an educational program designed to prevent low back injury in a randomized, controlled trial involving about 4000 postal workers. The program, similar to that in wide use in so-called back schools, was taught by experienced physical therapists. Work units of workers and supervisors were trained in a two-session back school (three hours of training), followed by three to four reinforcement sessions over the succeeding few years. Injured subjects (from both the intervention and the control groups) were randomized a second time to receive either training or no training after their return to work.\n Physical therapists trained 2534 postal workers and 134 supervisors. Over 5.5 years of follow-up, 360 workers reported low back injuries, for a rate of 21.2 injuries per 1000 worker-years of risk. The median time off from work per injury was 14 days (range, 0 to 1717); the median cost was $204 (range, zero to $190,380). After their return to work, 75 workers were injured again. Our comparison of the intervention and control groups found that the education program did not reduce the rate of low back injury, the median cost per injury, the time off from work per injury, the rate of related musculoskeletal injuries, or the rate of repeated injury after return to work; only the subjects' knowledge of safe behavior was increased by the training.\n A large-scale, randomized, controlled trial of an educational program to prevent work-associated low back injury found no long-term benefits associated with training.", "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.", "To examine the effect of individual job coaching and use of health threat in a job-specific occupational health education program in preventing work-related musculoskeletal back injuries during manual materials handling in construction laborers.\n Two hundred five laborers were recruited by 3-stage cluster sampling process and randomly assigned to receive different education programs on manual materials handling. Control group was given a conventional program, whereas experimental group received a job-specific program.\n A statistically significant group difference was found in the knowledge and practical skills on manual materials handling after training (P < 0.0001). Furthermore, the results from 1-year cumulative incidence revealed a significantly lesser number of first-time reports of work-related musculoskeletal back injuries in the experimental group.\n These results indicate that job-specific education is an effective preventive strategy for work-related musculoskeletal back injury." ]

[ "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." ]

[ "16267634", "15276691", "12755665", "16585435", "16062094", "16889453", "16797162", "17606657", "16633144", "17728106", "16783811", "16585434" ]

[ "Quetiapine has equivalent efficacy and superior tolerability to risperidone in the treatment of schizophrenia with predominantly negative symptoms.", "Effect of switching to atypical antipsychotics on memory in patients with chronic schizophrenia.", "Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics.", "Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic.", "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.", "A double-blind comparison of risperidone, quetiapine and placebo in patients with schizophrenia experiencing an acute exacerbation requiring hospitalization.", "Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison.", "A 24-week randomized study of olanzapine versus ziprasidone in the treatment of schizophrenia or schizoaffective disorder in patients with prominent depressive symptoms.", "Cognition, functioning and quality of life in schizophrenia treatment: results of a one-year randomized controlled trial of olanzapine and quetiapine.", "Quetiapine versus olanzapine for the treatment of negative symptoms in patients with schizophrenia.", "Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment." ]

[ "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.", "While the usefulness of atypical antipsychotics for improving cognitive function has been proven, the specific effects of these drugs are still unknown. The objective of this study was to investigate changes of the immediate memory and verbal working memory in patients with chronic schizophrenia after switching to one of four atypical antipsychotic agents and cessation of anticholinergic therapy. The subjects included 77 schizophrenic patients who were treated primarily with typical antipsychotics. Treatment was randomly switched to one of four atypical antipsychotics (olanzapine, perospirone, quetiapine, or risperidone) over a 4-week period, and then the drug was continued for another 4 weeks while the patient was taken off anticholinergics. The immediate memory, verbal working memory, and symptoms were evaluated. Significant improvement of immediate memory was only seen with olanzapine and risperidone. Improvement was also seen after switching to perospirone, but immediate memory worsened after treatment with this anticholinergic drug was discontinued. Deterioration was seen after switching to quetiapine, but immediate memory improved and reached the previous level after treatment with anticholinergic drugs was discontinued. Significant improvement of the verbal working memory was only seen during risperidone administration. The findings suggested that switching chronic schizophrenic patients to atypical antipsychotics can improve both the immediate memory and the verbal working memory when risperidone is used, while improvement of immediate memory can be expected with olanzapine. From the viewpoint of improving the memory, quetiapine should not be administered concomitantly with anticholinergic drugs, and caution should be exercised when discontinuing anticholinergic drugs during treatment with perospirone.", "Weight gain is a common adverse effect associated with the use of most antipsychotic drugs. Leptin has been reported to be associated with antipsychotic-induced weight gain. Previous studies have demonstrated a relationship between the atypical antipsychotics clozapine and olanzapine and serum leptin levels. We planned to comparatively investigate the effects of the atypical antipsychotics quetiapine, olanzapine, risperidone, and clozapine on leptin and triglyceride levels and weight gain.\n The study population comprised 56 patients with DSM-IV schizophrenia, who were divided into 4 treatment groups: quetiapine (N = 14), olanzapine (N = 14), risperidone (N = 14), or clozapine (N = 14) monotherapy, and a control group of 11 patients receiving no psychopharmacologic treatment. The patients were evaluated at baseline and at the sixth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight, and fasting serum leptin and triglyceride levels. Data were gathered in 2001 and 2002.\n Olanzapine and clozapine caused a marked increase in weight and serum triglyceride and leptin levels, though increases in these variables were modest in the patients receiving quetiapine and minimal in those receiving risperidone. There were positive correlations between serum leptin levels and BMI and triglyceride levels. Clinical efficacy, as indicated by decrease in total PANSS scores, was associated with leptin levels in all atypical antipsychotic groups.\n Our results suggest that leptin may be associated with olanzapine- and clozapine-induced weight gain and that quetiapine appears to have modest influence and risperidone appears to have minimal influence on leptin and triglyceride levels and weight gain compared with olanzapine and clozapine.", "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.", "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.", "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.", "This 52-week randomized, double-blind, flexible-dose, multicenter study evaluated the overall effectiveness (as measured by treatment discontinuation rates) of olanzapine, quetiapine, and risperidone in patients early in the course of psychotic illness.\n Patients were randomly assigned to treatment with olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day) administered in twice-daily doses. Statistical analyses tested for noninferiority in all-cause treatment discontinuation rates up to 52 weeks (primary outcome measure) based on a prespecified noninferiority margin of 20%.\n A total of 400 patients were randomly assigned to treatment with olanzapine (N=133), quetiapine (N=134), or risperidone (N=133). The mean modal prescribed daily doses were 11.7 mg for olanzapine, 506 mg for quetiapine, and 2.4 mg for risperidone. At week 52, all-cause treatment discontinuation rates were 68.4%, 70.9%, and 71.4% for olanzapine, quetiapine, and risperidone, respectively. Reductions in total score on the Positive and Negative Syndrome Scale (PANSS) were similar for the three treatment groups, but reductions in PANSS positive subscale scores were greater in the olanzapine group (at 12 weeks and at 52 weeks or withdrawal from study) and the risperidone group (at 12 weeks). The most common elicited adverse events for olanzapine were drowsiness (53%), weight gain (51%), and insomnia (38%); for quetiapine, drowsiness (58%), increased sleep hours (42%), and weight gain (40%); and for risperidone, drowsiness (50%), menstrual irregularities in women (47%), and weight gain (41%).\n Olanzapine, quetiapine, and risperidone demonstrated comparable effectiveness in early-psychosis patients, as indicated by similar rates of all-cause treatment discontinuation.", "The objective of this study is to compare olanzapine with ziprasidone therapy in patients with schizophrenia or schizoaffective disorder and experiencing depressive symptoms.\n This randomized, double-blind, 24-week, fixed-dose study compared olanzapine (n = 202) and ziprasidone (n = 192) for patients with schizophrenia or schizoaffective disorder and experiencing prominent depressive symptoms. Outcome measures included change in Calgary Depression Scale for Schizophrenia (CDSS) score from baseline to 8 weeks (primary outcome) and changes in CDSS, Montgomery-Asberg Depression Rating Scales, Positive and Negative Syndrome Scale, and Global Assessment of Functioning (GAF) scores for 24 weeks. Statistical analyses included mixed-effects model repeated measures (primary analysis) and change from baseline to last observation carried forward (LOCF).\n At baseline, patients had moderate depressive symptoms (mean Montgomery-Asberg Depression Rating Scales total score, 27.3). For 8 weeks, patients treated with olanzapine or ziprasidone had significant improvements on CDSS. Treatment group differences were not statistically significant (P = 0.493, mixed-effects model repeated measures; P = 0.497, LOCF). For 24 weeks, olanzapine-treated patients showed significantly greater improvements in depressive symptoms (results varied by depression measure and statistical approach) and GAF (P < 0.017, LOCF). A significantly higher proportion of olanzapine-treated patients completed the study (44.6% vs 29.7%; P = 0.003) and remained longer on medication (median, 163 vs 73 days, P < 0.001), compared with ziprasidone-treated patients. Olanzapine-treated patients experienced significantly (P < 0.05) greater increases in triglycerides, HgbA1c, and weight.\n For 24 weeks, olanzapine-treated patients had greater and more sustained participation in treatment, during which time significantly greater improvements were observed in depressive symptoms and GAF scores, along with increases in weight and certain metabolic parameters as compared with ziprasidone-treated patients.", "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.", "Negative symptoms are considered the most debilitating and refractory aspect of schizophrenia, being associated with poor social, occupational and global outcomes. Conventional antipsychotics have limited efficacy against these symptoms and poor tolerability profiles. Atypical antipsychotics are an alternative treatment, and this 12-week, randomised, flexibly dosed study compared the efficacy, safety and tolerability of quetiapine and olanzapine in this regard. Of the 40 patients who entered the study (32 male; 8 female), 19 were randomised to quetiapine (mean dose 637 mg/day, mean treatment duration 80 days) and 21 to olanzapine (mean dose 16 mg/day, mean treatment duration 78 days). Quetiapine and olanzapine were similarly effective: in each treatment group significant improvements at Week 12 were observed for negative symptom scores on the SANS and the PANSS, and for subscale scores of affective flattening and alogia on the SANS. Both treatments were well tolerated in this patient population, with no worsening of extrapyramidal symptoms in either case. Anxiety and insomnia were the most common adverse events (> or =7% of patients in each group), but were not drug-related. Although this is a small study with limited power, the results support the effectiveness of quetiapine and olanzapine in treating the negative symptoms of schizophrenia.\n Copyright 2006 John Wiley & Sons, Ltd.", "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." ]

[ "16772625", "671684", "9596436", "8350885" ]

[ "Manual chest compression vs use of an automated chest compression device during resuscitation following out-of-hospital cardiac arrest: a randomized trial.", "External cardiac compression. A randomized comparison of mechanical and manual techniques.", "Effectiveness of mechanical versus manual chest compressions in out-of-hospital cardiac arrest resuscitation: a pilot study.", "A preliminary study of cardiopulmonary resuscitation by circumferential compression of the chest with use of a pneumatic vest." ]

[ "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.", "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.", "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.", "More than 300,000 people die each year of cardiac arrest. Studies have shown that raising vascular pressures during cardiopulmonary resuscitation (CPR) can improve survival and that vascular pressures can be raised by increasing intrathoracic pressure.\n To produce periodic increases in intrathoracic pressure, we developed a pneumatically cycled circumferential thoracic vest system and compared the results of the use of this system in CPR (vest CPR) with those of manual CPR. In phase 1 of the study, aortic and right-atrial pressures were measured during both vest CPR (60 inflations per minute) and manual CPR in 15 patients in whom a mean (+/- SD) of 42 +/- 16 minutes of initial manual CPR had been unsuccessful. Vest CPR was also carried out on 14 other patients in whom pressure measurements were not made. In phase 2 of the study, short-term survival was assessed in 34 additional patients randomly assigned to undergo vest CPR (17 patients) or continued manual CPR (17 patients) after initial manual CPR (duration, 11 +/- 4 minutes) had been unsuccessful.\n In phase 1 of the study, vest CPR increased the peak aortic pressure from 78 +/- 26 mm Hg to 138 +/- 28 mm Hg (P < 0.001) and the coronary perfusion pressure from 15 +/- 8 mm Hg to 23 +/- 11 mm Hg (P < 0.003). Despite prolonged unsuccessful manual CPR, spontaneous circulation returned with vest CPR in 4 of the 29 patients. In phase 2 of the study, spontaneous circulation returned in 8 of the 17 patients who underwent vest CPR as compared with only 3 of the 17 patients who received continued manual CPR (P = 0.14). More patients in the vest-CPR group than in the manual-CPR group were alive 6 hours after attempted resuscitation (6 of 17 vs. 1 of 17) and 24 hours after attempted resuscitation (3 of 17 vs. 1 of 17), but none survived to leave the hospital.\n In this preliminary study, vest CPR, despite its late application, successfully increased aortic pressure and coronary perfusion pressure, and there was an insignificant trend toward a greater likelihood of the return of spontaneous circulation with vest CPR than with continued manual CPR. The effect of vest CPR on survival, however, is currently unknown and will require further study." ]

[ "21419770", "10535880", "7493311", "11580151", "19052125" ]

[ "Maintenance therapy with peginterferon alfa-2b does not prevent hepatocellular carcinoma in cirrhotic patients with chronic hepatitis C.", "A randomized, controlled trial of maintenance interferon therapy for patients with chronic hepatitis C virus and persistent viremia.", "Re-treatment of interferon-resistant patients with chronic hepatitis C with interferon-alpha.", "Maintenance therapy with gradual reduction of the interferon dose over one year improves histological response in patients with chronic hepatitis C with biochemical response: results of a randomized trial.", "Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon." ]

[ "Several studies have reported that low doses of interferon can delay the development of hepatocellular carcinoma (HCC) and progression of chronic hepatitis C. We investigated the incidence of clinical events among participants of the Evaluation of PegIntron in Control of Hepatitis C Cirrhosis (EPIC)3 program.\n Data were analyzed from an open-label randomized study of patients with chronic hepatitis C who had failed to respond to interferon alfa plus ribavirin. All patients had compensated cirrhosis with no evidence of HCC. Patients received peginterferon alfa-2b (0.5 μg/kg/week; n=311) or no treatment (controls, n=315) for a maximum period of 5 years or until 98 patients had a clinical event (hepatic decompensation, HCC, death, or liver transplantation). The primary measure of efficacy was time until the first clinical event.\n There was no significant difference in time to first clinical event among patients who received peginterferon alfa-2b compared with controls (hazard ratio [HR], 1.452; 95% confidence interval [CI]: 0.880-2.396). There was no decrease in the development of HCC with therapy. The time to disease progression (clinical events or new or enlarged varices) was significantly longer for patients who received peginterferon alfa-2b compared with controls (HR, 1.564; 95% CI: 1.130-2.166). In a prospectively defined subanalysis of patients with baseline portal hypertension, peginterferon alfa-2b significantly increased the time to first clinical event compared with controls (P=.016). There were no new safety observations.\n Maintenance therapy with peginterferon alfa-2b is not warranted in all patients and does not prevent HCC. However, there is a potential clinical benefit of long-term suppressive therapy in patients with preexisting portal hypertension.\n Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.", ": 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.", "Non-responders to 6-months treatment with recombinant interferon (rIFN)-alpha, 3 MU thrice weekly (primary non-responders) were treated for 6 further months with the same therapy or with a double dose of rIFN-alpha or with a different type of IFN (L-IFN). 112 primary non-responders were randomly enrolled into four groups of 28 patients each over a period of 4 years and were followed up for 6 months: group A continued the same dose of rIFN-alpha, group B was treated with the same rIFN-alpha but received a double dose (6 MU thrice weekly), group C received L-IFN, 3 MU thrice weekly, and group D stopped IFN therapy and did not receive any treatment. Patients were examined at monthly intervals and response was defined as a complete normalization of alanine amino transferase (ALT). The four groups were homogeneous as to age, sex, duration of the disease, probable source of infection, histological diagnosis. ALT and gamma glutamyl transferase (gamma GT) levels. No patient discontinued therapy for side-effects. Further treatment with rIFN-alpha 3 MU thrice weekly (group A) induced normalization of ALT levels in four patients (14%); treatment with double-dosed rIFN-alpha (group B) induced normalization of liver enzymes in six cases (21%); a different type of interferon (L-IFN) (group C) achieved normalization of serum ALT in five patients (18%). None of 28 primary non-responders who did not receive any treatment (group D) showed normalization of ALT levels. None of the patients was anti-HCV negative at the end of the study and no statistically significant difference was noted between responders and non-responders to the second course of IFN therapy as to age, sex, duration of the disease. ALT and gamma GT levels at the end of the trial. Overall at the end of the study the primary non-responders with normal levels of ALT were 15/112 (13%), with a therapeutic advantage of 7%. No statistically significant difference in the response rate was found among patients who continued IFN therapy, but prolongation of rIFN-alpha treatment at double dosage seems to be the best therapeutic regimen.", "Our aim was to assess whether histological response was improved by continuing interferon-alpha (IFN) treatment in patients with chronic hepatitis C (HCV) with a biochemical response and no viral clearance after a usual IFN treatment.\n Fifty-seven patients with normal alanine aminotransferase (ALAT) levels and positive HCV RNA at the end of a 1 year IFN treatment were randomly assigned to either group 1 (n = 28) where IFN was stopped, or group 2 (n = 29) where IFN was continued for 1 more year with gradual reduction of the dose to keep serum ALAT activity below the upper limit of normal. Liver biopsies were obtained before, and then 6 months after the end of treatment.\n Knodell's index improved between paired biopsies in group 2 (8.2+/-2.4 vs. 5.5+/-2.1), but not in group 1 (8+/-2.3 vs. 6.5+/-2). In post-treatment biopsies, the METAVIR activity score was significantly lower in group 2 than in group 1 (0.7+/-0.2 vs. 1.1+/-0.3, P < 0.05). In group 2, an improvement of the METAVIR fibrosis score was observed (1.3+/-0.4 vs. 1.1+/-0.2), whereas fibrosis progressed in group 1 (1.3+/-0.4 vs. 1.6+/-0.4).\n Maintenance therapy by the minimal dose of IFN able to maintain biochemical response prevents histological progression in the sub-group of patients without virological response.", "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" ]

[ "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." ]

[ "17978833", "10362390", "18608847", "19675481", "17654228", "19211945", "12627305", "16558514", "18547863", "17261562", "12972871", "19308790", "19074671", "19401897" ]

[ "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.", "The effect of recovery strategies on physical performance and cumulative fatigue in competitive basketball.", "The effects of recovery interventions on consecutive days of intermittent sprint exercise.", "Influence of cold-water immersion on indices of muscle damage following prolonged intermittent shuttle running.", "Physiological responses to cold water immersion following cycling in the heat.", "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 water immersion methods on post-exercise recovery from simulated team sport exercise.", "Ice-water immersion and delayed-onset muscle soreness: a randomised controlled trial.", "Evaluations of cooling exercised muscle with MR imaging and 31P MR spectroscopy.", "Effects of cold-water immersion on physical performance between successive matches in high-performance junior male soccer players.", "Effect of cold water immersion on postexercise parasympathetic reactivation.", "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." ]

[ "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.", "To evaluate the effectiveness of recovery strategies on physical performance during a 3-day tournament style basketball competition, 29 male players (mean age 19.1 years, s= 2.1; height 1.84 m, s= 0.34; body mass 88.5 kg, s= 14.7) were assigned to one of three treatment groups: carbohydrate+stretching (7.7 g kg(-1) day(-1), s= 1.7; 'n = 9), cold water immersion (11 degrees C, 5 x 1; n = 10) or full leg compression garments (18 mmHg, approximately 18 h; n = 10). Effects of the recovery strategies on pre-post tournament performance tests were expressed as the mean change (% +/- standard deviation of the change score). Changes and differences were standardized for accumulated game time, assessed against the smallest worthwhile change for each test, and reported qualitatively. Accumulated fatigue was evident over the tournament with small to moderate impairments in performance tests. Sprint and agility performance decreased by 0.7% (s = 1.3) and 2.0% (s = 1.9) respectively. Vertical jump decreased substantially after the first day for all treatments, and remained suppressed post-tournament. Cold water immersion was substantially better in maintaining 20-m acceleration with only a 0.5% (s = 1.4) reduction in 20-m time after 3 days compared with a 3.2% (s = 1.6) reduction for compression. Cold water immersion (-1.4%, s = 1.7) and compression (-1.5%, s = 1.7) showed similar substantial benefits in maintaining line-drill performance over the tournament, whereas carbohydrate+stretching elicited a 0.4% (s =1.8) reduction. Sit-and-reach flexibility decreased for all groups, although cold water immersion resulted in the smallest reduction in flexibility. Basketball tournament play elicited small to moderate impairments in physical test performance. In conclusion, cold water immersion appears to promote better restoration of physical performance measures than carbohydrate + stretching routines and compression garments.", "The purpose of this study was to compare four recovery interventions following simulated team sport, intermittent-sprint exercise on consecutive days. Ten female netball players performed four randomized sessions of a simulated netball exercise circuit on consecutive days. Each condition consisted of two identical sessions (Session 1 and 2), with the recovery intervention implemented at the completion of Session 1. Participants performed all interventions involving: passive recovery, active recovery (ACT), cold water immersion (CWI) and contrast water therapy (C(T)WT). No significant differences (p > 0.05) were evident between conditions for exercise performance (vertical jump, 20-m sprint, 10-m sprint, total circuit time) during Session 2. Effect size data indicated trends for an ameliorated decline in 5 x 20-m sprints and vertical jump for C(T)WT and CWI, respectively. C(T)WT demonstrated a significant reduction (p = 0.04) in lactate post-intervention compared to ACT recovery. Further, ACT recovery resulted in a significantly elevated (p < 0.01) heart rate compared to all other conditions postintervention and demonstrated significantly higher (p < 0.01) rating of perceived exertion postintervention and muscle soreness pre-exercise Session 2. It is likely that while interventions may be applicable to team sport practices, the 24-hour recovery period between exercise bouts was sufficient to allow performance to be maintained, regardless of recovery interventions.", "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.", "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.", "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.", "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.", "To investigate the effects of cooling human skeletal muscle after strenuous exercise using 31P MR spectroscopy and MR imaging.\n 14 male subjects (mean age +/- SD, 23.8 +/- 2.3 yr) were randomly assigned to the normal (N = 7) or the cooling group (N = 7). All subjects performed the ankle plantar flexion exercise (12 repetitions, 5 sets). Localized 31P-spectra were collected from the medial gastrocnemius before and after exercise (immediately, 30, 60 min, 24, 48, 96, and 168 h) to determine the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) and intracellular pH. Transaxial T2-weighted MR images of the medial gastrocnemius were obtained to calculate T2 relaxation time (T2), indicative of intramuscular water level, before and after exercise (24, 48, 96, and 168 h). In addition, the muscle soreness level was assessed at the same time as 31P-spectra measurements. Fifteen-minute cold-water immersion was administered to the cooling group after exercise and initial postexercise measurements.\n The control group showed significantly increased T2 from rest at 48 h after exercise (P < 0.05), but the cooling group showed no significant change in T2 throughout this study. Both groups showed a significantly decreased intracellular pH immediately after exercise (P < 0.05). After that, the cooling group showed a significantly greater value than the value at rest or the control group at 60 min after exercise (P < 0.05). For the Pi/PCr, no significant change was observed in both groups throughout this study. The muscle soreness level significantly increased immediately and at 24-48 h after exercise in both groups (P < 0.05).\n The findings of this study suggest that cooling causes an increase in intracellular pH and prevents the delayed muscle edema.", "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 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.", "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." ]

[ "16531621", "17161051", "15860518", "16275869", "17182126", "16507801", "17659916" ]

[ "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.", "Granulocyte colony stimulating factor in patients with large acute myocardial infarction: results of a pilot dose-escalation randomized trial.", "Use of granulocyte-colony stimulating factor during acute myocardial infarction to enhance bone marrow stem cell mobilization in humans: clinical and angiographic safety profile.", "Preservation from left ventricular remodeling by front-integrated revascularization and stem cell liberation in evolving acute myocardial infarction by use of granulocyte-colony-stimulating factor (FIRSTLINE-AMI).", "Feasibility and safety of granulocyte colony-stimulating factor treatment in patients with acute myocardial infarction.", "Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: a randomized controlled trial.", "Usefulness of granulocyte colony-stimulating factor in patients with a large anterior wall acute myocardial infarction to prevent left ventricular remodeling (the rigenera study)." ]

[ "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.", "Preclinical studies suggest that administration of cytokines to mobilize stem cells and alter the postinfarction inflammatory cardiac milieu may enhance left ventricular function and survival.\n Eighteen patients were randomized in a 2:1 double-blind fashion to granulocyte colony stimulating factor (G-CSF) (at 5 escalating to 10 microg/kg per day subcutaneously for 5 days [6 patients in each group]) or matching placebo. Principal safety and efficacy end points were rupture-free survival and recovery of left ventricular function, respectively. Mobilization into the systemic circulation of precursor CD34+ and CD117+ stem cells at 30 days were also assessed.\n Baseline characteristics of the 3 groups were well matched. Mean +/- SD creatine kinase-MB maximum was 349 (169) IU. Follow-up averaged 30 +/- 6, 21 +/- 11, and 11 +/- 6 months in the 3 groups, respectively. Precursor cell mobilization increased by a factor of 5 to 7 in the G-CSF-treated patients. There were no deaths or myocardial ruptures leading to tamponade through 30 days. Baseline and 30-day left ventricular ejection fraction in the placebo, 5-microg, and 10-microg dose groups were 33.7% (1.6) and 41.7% (8.2), 36.8% (7.5) and 41.3% (10.3), and 33.5% (4.8) and 38.7% (7.3), respectively (P = NS for all between-group comparisons). No differences between the G-CSF and placebo groups were noted in any other measure of left ventricular systolic or diastolic function 30 days after infarction.\n Despite demonstrated mobilization of precursor stem cells in a timely fashion, in this small, pilot-scale randomized trial involving patients with large myocardial infarction, we were unable to demonstrate improvement in left ventricular function at 30 days.", "There is increasing evidence that stem cell (SC) mobilization to the heart and their differentiation into cardiac cells is a naturally occurring process. We sought to assess the safety and feasibility of granulocyte-colony stimulating factor (G-CSF) administration in humans to enhance SC mobilization and left ventricle (LV) injury repair during myocardial infarction (MI).\n Twenty patients with STEMI (mean age, 61+/-10 years), of whom 14 were submitted to primary percutaneous coronary intervention, were randomized to G-CSF (5 microg/kg/day s.c. for 4 consecutive days) or placebo. At entry and then at months 3 and 6, (99m)Tc-sestamibi gated-SPECT was performed to estimate extension of perfusion defect (PD) and LV function. The study drug was well tolerated and induced a significant increase of white blood count, CD34(+) cells, and CD34(+) cells coexpressing AC133 and VEGFR-2. At follow-up, treated and placebo groups did not differ for the angiographic coronary late loss and showed a similar pattern of PD recovery, whereas in the former at 6 months LVEF and especially LVEDV tended to be relatively higher (P=0.068) and lower (P=0.054), respectively.\n G-CSF administration in acute MI patients was feasible and did not lead to any clinical or angiographic adverse events and resulted in CD34(+) and CD34(+)AC133(+)VEGFR2(+) cell mobilization.", "Considering experimental evidence that stem cells enhance myocardial regeneration and granulocyte colony-stimulating factor (G-CSF) mediates mobilization of CD34+ mononuclear blood stem cells (MNCCD34+), we tested the impact of G-CSF integrated into primary percutaneous coronary intervention (PCI) management of acute myocardial infarction in man.\n Fifty consecutive patients with ST-segment elevation myocardial infarction were subjected to primary PCI stenting with abciximab and followed up for 6 months; 89+/-35 minutes after successful PCI, 25 patients were randomly assigned in this pilot study (PROBE design) to receive subcutaneous G-CSF at 10 microg/kg body weight for 6 days in addition to standard care, including aspirin, clopidogrel, an ACE inhibitor, beta-blocking agents, and statins. By use of CellQuest software on peripheral blood samples incubated with CD45 and CD34, mobilized MNCCD34+ were quantified on a daily basis. With homogeneous demographics and clinical and infarct-related characteristics, G-CSF stimulation led to mobilization of MNCCD34+ to between 3.17+/-2.93 MNCCD34+/microL at baseline and 64.55+/-37.11 MNCCD34+/microL on day 6 (P<0.001 versus control); there was no indication of leukocytoclastic effects, significant pain, impaired rheology, inflammatory reactions, or accelerated restenosis at 6 months. Within 35 days, G-CSF and MNCCD34+ liberation led to enhanced resting wall thickening in the infarct zone of between 0.29+/-0.22 and 0.99+/-0.32 mm versus 0.49+/-0.29 mm in control subjects (P<0.001); under inotropic challenge with dobutamine (10 microg.kg(-1).min(-1)), wall motion score index showed improvement from 1.66+/-0.23 to 1.41+/-0.21 (P<0.004 versus control) and to 1.35+/-0.24 after 4 months (P<0.001 versus control), respectively, coupled with sustained recovery of wall thickening to 1.24+/-0.31 mm (P<0.001 versus control) at 4 months. Accordingly, resting wall motion score index improved with G-CSF to 1.41+/-0.25 (P<0.001 versus control), left ventricular end-diastolic diameter to 55+/-5 mm (P<0.002 versus control), and ejection fraction to 54+/-8% (P<0.001 versus control) after 4 months. Morphological and functional improvement with G-CSF was corroborated by enhanced metabolic activity and 18F-deoxyglucose uptake in the infarct zone (P<0.001 versus control).\n G-CSF and mobilization of MNC(CD34+) after reperfusion of infarcted myocardium may offer a pragmatic strategy for preservation of myocardium and prevention of remodeling without evidence of aggravated restenosis.", "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.", "Experimental studies and early phase clinical trials suggest that transplantation of blood-derived or bone marrow-derived stem cells may improve cardiac regeneration and neovascularization after acute myocardial infarction. Granulocyte colony-stimulating factor (G-CSF) induces mobilization of bone marrow stem cells.\n To assess the value of stem cell mobilization by G-CSF therapy in patients with acute myocardial infarction.\n Randomized, double-blind, placebo-controlled trial of patients diagnosed with ST-segment elevation acute myocardial infarction who had successful reperfusion by percutaneous coronary intervention within 12 hours after onset of symptoms in Germany between February 24, 2004, and February 2, 2005.\n Patients were randomly assigned to receive subcutaneously either a daily dose of 10 microg/kg of G-CSF or placebo for 5 days.\n The primary end point was reduction of left ventricular infarct size according to technetium Tc 99m sestamibi scintigraphy performed at baseline and at 4 to 6 months after randomization. Secondary end points included improvement of left ventricular ejection fraction measured by magnetic resonance imaging and the incidence of angiographic restenosis.\n Of the 114 patients, 56 were assigned to receive treatment with G-CSF and 58 were assigned to receive placebo. Treatment with G-CSF produced a significant mobilization of stem cells. Between baseline and follow-up, left ventricular infarct size according to scintigraphy was reduced by a mean (SD) of 6.2% (9.1%) in the G-CSF group and 4.9% (8.9%) in the placebo group (P = .56) and left ventricular ejection fraction was improved by 0.5% (3.8%) in the G-CSF group and 2.0% (4.9%) in the placebo group (P = .14). Angiographic restenosis occurred in 19 (35.2%) of 54 patients in the G-CSF group and in 17 (30.9%) of 55 patients in the placebo group (P = .79). The most common adverse event among patients assigned to G-CSF was mild to moderate bone pain and muscle discomfort.\n Stem cell mobilization by G-CSF therapy in patients with acute myocardial infarction and successful mechanical reperfusion has no influence on infarct size, left ventricular function, or coronary restenosis.\n ClinicalTrials.gov Identifier: NCT00126100.", "Intracoronary injection of bone marrow stem cells seems to improve left ventricular (LV) function after acute myocardial infarction (AMI). Granulocyte colony-stimulating factor (G-CSF) could improve myocardial function and perfusion noninvasively through mobilization of stem cells into peripheral blood, although previous clinical trials have produced controversial results. Forty-one patients with large anterior wall AMI at high risk of unfavorable remodeling were randomized 1:2 to G-CSF (10 microg/kg/day for 5 days) or to conventional therapy. All patients underwent successful primary or rescue percutaneous coronary intervention. LV function was assessed by echocardiography before G-CSF administration, > or =5 days after AMI, and at follow-up. Only patients with a LV ejection fraction <50% at baseline were enrolled in the study. After a median follow-up of 5 months (range 4 to 6) patients treated with G-CSF exhibited improvement in LV ejection fraction, from 40 +/- 6% to 45 +/- 6% (p = 0.068) in the absence of LV dilation (LV end-diastolic volume from 147 +/- 33 to 144 +/- 46 ml at follow-up, p = 0.77). In contrast, patients treated conventionally exhibited significant LV dilation (LV end-diastolic volume from 141 +/- 35 to 168 +/- 41 ml, p = 0.002) in the absence of change in LV ejection fraction (from 38 +/- 6% to 38 +/- 8%, p = 0.95). However, when comparing patients treated with G-CSF with controls, variations in these parameters were significantly different at 2-way analysis of variance (p = 0.04 for LV end-diastolic volume, p = 0.02 for LV ejection fraction). In conclusion, G-CSF prevents unfavorable LV remodeling and improves LV function in patients with large anterior wall AMI and decreased LV ejection fraction after successful percutaneous coronary intervention." ]

[ "19670432", "15781825", "18340100" ]

[ "Transcranial ultrasound in clinical sonothrombolysis (TUCSON) trial.", "Sonothrombolysis in acute ischemic stroke for patients ineligible for rt-PA.", "Sonothrombolysis with transcranial color-coded sonography and recombinant tissue-type plasminogen activator in acute middle cerebral artery main stem occlusion: results from a randomized study." ]

[ "Microspheres (microS) reach intracranial occlusions and transmit energy momentum from an ultrasound wave to residual flow to promote recanalization. We report a randomized multicenter phase II trial of microS dose escalation with systemic thrombolysis.\n Stroke patients receiving 0.9mg/kg tissue plasminogen activator (tPA) with pretreatment proximal intracranial occlusions on transcranial Doppler (TCD) were randomized (2:1 ratio) to microS (MRX-801) infusion over 90 minutes (Cohort 1, 1.4ml; Cohort 2, 2.8ml) with continuous TCD insonation, whereas controls received tPA and brief TCD assessments. The primary endpoint was symptomatic intracerebral hemorrhage (sICH) within 36 hours after tPA.\n Among 35 patients (Cohort 1 = 12, Cohort 2 = 11, controls = 12) no sICH occurred in Cohort 1 and controls, whereas 3 (27%, 2 fatal) sICHs occurred in Cohort 2 (p = 0.028). Sustained complete recanalization/clinical recovery rates (end of TCD monitoring/3 month) were 67%/75% for Cohort 1, 46%/50% for Cohort 2, and 33%/36% for controls (p = 0.255/0.167). The median time to any recanalization tended to be shorter in Cohort 1 (30 min; interquartile range [IQR], 6) and Cohort 2 (30 min; IQR, 69) compared to controls (60 min; IQR, 5; p = 0.054). Although patients with sICH had similar screening and pretreatment systolic blood pressure (SBP) levels in comparison to the rest, higher SBP levels were documented in sICH+ patients at 30 minutes, 60 minutes, 90 minutes, and 24-36 hours following tPA bolus.\n Perflutren lipid microS can be safely combined with systemic tPA and ultrasound at a dose of 1.4ml. Safety concerns in the second dose tier may necessitate extended enrollment and further experiments to determine the mechanisms by which microspheres interact with tissues. In both dose tiers, sonothrombolysis with microS and tPA shows a trend toward higher early recanalization and clinical recovery rates compared to standard intravenous tPA therapy. Ann Neurol 2009;66:28-38.", "The authors studied the effect of transcranial ultrasound on patients with acute middle cerebral artery occlusion and contraindications for thrombolysis. Fifteen consecutive subjects were randomized for insonation over 1 hour or for inclusion in a control group. By day 4, recanalization and neurologic improvement occurred more frequently in the target group. Ultrasound-induced acceleration of clot dissolution may be an option for patients with contraindications for recombinant tissue plasminogen activator.", "Sonothrombolysis is a new treatment approach in acute ischemic stroke. The results of a monocenter, randomized clinical study are presented.\n Subjects with acute middle cerebral artery main stem occlusion were randomized into a target group receiving 1-hour transcranial continuous insonation using a 1.8-MHz Doppler ultrasound (US) probe or a control group. All underwent standard thrombolysis with intravenous recombinant tissue-type plasminogen activator.\n Thirty-seven subjects were included; 19 subjects were treated in the target (US) group and 18 in the control (no-US) group, all with no residual flow in the middle cerebral artery main stem occlusion (Thrombolysis in Brain Ischemia recanalization grade 0). Compared with the no-US group, the US group showed greater improvement in National Institutes of Health Stroke Scale values at days 1 and 4 and a higher median Thrombolysis in Brain Ischemia grade 1 hour after recombinant tissue-type plasminogen activator initiation. Recanalization (complete or partial) after 1 hour occurred in 57.9% of the US group and 22.2% of the no-US group (P=0.045). After 90 days, 4 subjects from the US group had a modified Rankin Score <or=1 (none from the no-US group) and 8 had a Barthel Index >or=95 (none from the no US group; P=0.106 and P=0.003, respectively). Three subjects from the US group (15.8%) developed a symptomatic intracranial hemorrhage as did one (5.6%) in the no-US group (P=0.60).\n This small randomized study indicates a beneficial impact of transcranial ultrasound on recanalization and short-term outcome in subjects with middle cerebral artery main stem occlusion and recombinant tissue-type plasminogen activator treatment." ]

[ "17113759", "12684609", "12464464", "17022791", "15578006", "16528136", "10622347", "15076013" ]

[ "A double-blind randomised comparative trial of amisulpride versus olanzapine for 2 months in the treatment of subjects with schizophrenia and comorbid depression.", "Amisulpride versus risperidone in the treatment of schizophrenic patients: a double-blind pilot study in Taiwan.", "Amisulpride vs. risperidone in chronic schizophrenia: results of a 6-month double-blind study.", "The treatment of negative symptoms and deficit states of chronic schizophrenia: olanzapine compared to amisulpride and placebo in a 6-month double-blind controlled clinical trial.", "Cognitive improvement in schizophrenic patients does not require a serotonergic mechanism: randomized controlled trial of olanzapine vs amisulpride.", "Ziprasidone and amisulpride effectively treat negative symptoms of schizophrenia: results of a 12-week, double-blind study.", "Amisulpride vs. risperidone in the treatment of acute exacerbations of schizophrenia. Amisulpride study group.", "A double-blind, randomized comparative trial of amisulpride versus olanzapine for 6 months in the treatment of schizophrenia." ]

[ "To compare the efficacy and safety of amisulpride and olanzapine in subjects with schizophrenia and comorbid depression in a randomised double-blind trial.\n Eighty-five adult patients fulfilling DSM-IV criteria for schizophrenia and presenting a depressive episode were randomised to amisulpride (200-600 mg/day) or olanzapine (5-15 mg/day) for 8 weeks. Primary efficacy variables were change in Calgary Depression Scale (CDS) score and Clinical Global Impression (CGI) of Change. Safety was monitored by adverse event reporting and determination of extrapyramidal function and metabolic variables.\n The mean change from baseline of CDS score was -6.84 in the amisulpride group and -7.36 in the olanzapine group. 65.9% and 61.5% of subjects, respectively, were considered \"much\" or \"very much\" improved. No significant inter-group difference in effect size was observed. The frequency of adverse events was low and emergence of extrapyramidal symptoms was not seen. Four patients in the olanzapine group developed abnormal triglyceride levels. Mean weight gain was 1.45 and 0.5 kg, respectively, in the olanzapine and amisulpride groups.\n Amisulpride and olanzapine are effective in patients with schizophrenia and comorbid depression. Tolerance of both drugs was acceptable, although use of olanzapine was associated with a trend toward greater metabolic side-effects .", "The 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.", "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.", "The aim of the study was to evaluate the efficacy of olanzapine (5 and 20 mg/day) over a 6-month period in chronic schizophrenic patients experiencing predominantly negative symptoms.\n Two hundred and forty-four patients participated in a 6-month multicenter double-blind trial of placebo (n = 34), olanzapine 5 mg/day (n = 70), olanzapine 20 mg/day (n = 70), or amisulpride 150 mg/day (n = 70). Primary measure was the scale for the assessment of negative symptoms.\n Olanzapine 5 mg/day showed significantly greater improvement than placebo in negative symptoms and in the Positive and Negative Syndrome Scale total score. Baseline positive symptoms were low at baseline and changed minimally. The neurological tolerance of olanzapine, amisulpride and placebo were comparable.\n Olanzapine 5 mg/day was effective in treating negative symptoms in a group of schizophrenic with predominantly negative symptoms during the stabilization phase. Improvement in positive symptoms or extrapyramidal symptoms (EPS) was unlikely to explain this result while improvement in depression may have partially contributed.", "Combined serotonin-2A (5-HT(2A)) and dopamine-2 (D2) receptor blockade has been proposed as a candidate mechanism by which second-generation antipsychotics (SGAs) improve both cognition and negative symptoms in schizophrenic patients, in contrast to antipsychotics of the first generation. The SGA amisulpride, however, only binds to D2/D3 receptors, which makes it an interesting tool to test this assumption. In a randomized controlled trial, 52 schizophrenic patients were allocated to treatment with either olanzapine (10-20 mg/day) or amisulpride (400-800 mg/day). A comprehensive neuropsychological test battery and clinical ratings were used to assess participants at inclusion and after 4 and 8 weeks. Cognitive improvements of moderate size were observed, with effect sizes similar to those obtained in previous studies on the cognitive effects of SGAs. Importantly, amisulpride was not inferior to olanzapine for any cognitive domain. Combined 5-HT(2A)/D2 receptor blockade is probably not necessary for cognitive improvement by SGAs.", "We compared the efficacy of ziprasidone and amisulpride in the treatment of negative symptoms and overall psychopathology in subjects who had chronic schizophrenia with predominantly negative symptoms. This multicentre, 12-week, double-blind study randomly assigned subjects with predominantly negative-symptom schizophrenia [i.e. Positive and Negative Syndrome Scale (PANSS) Negative Subscale score >or=6 points greater than Positive Subscale score] to ziprasidone (40-80 mg b.i.d.; n=60) or amisulpride (50-100 mg b.i.d.; n=63). The primary efficacy variable was the change from baseline in PANSS Negative Subscale score. Secondary efficacy variables included change in scores for PANSS Total, Global Assessment of Functioning, Brief Psychiatric Rating Scale derived from PANSS Total and Core, Clinical Global Impression (CGI)-Severity and CGI-Improvement. For the change in PANSS Negative Subscale score, a ratio to assess the equivalence of the treatment groups was calculated from the least squares mean changes from baseline, with equivalence claimed if the lower limit of the 95% confidence interval of the ratio exceeded 0.60. Mean daily dose, adjusted for differential numbers of subjects and differential days between visits, was 118.0 mg for ziprasidone and 144.7 mg for amisulpride. Mean PANSS Negative Subscale scores improved over the 12-week treatment period for intent-to-treat subjects, evaluable subjects (subjects with >or=4 weeks of double-blind treatment and no protocol deviations) and completers in both treatment groups. Ziprasidone demonstrated efficacy comparable to amisulpride in improving negative symptoms and global psychopathology. The groups demonstrated comparable improvements in secondary efficacy variables. Both agents were generally well tolerated, with comparably low incidences of movement disorders. In subjects with negative symptom-prominent schizophrenia, ziprasidone in mean daily doses of 118 mg was equivalent to amisulpride in mean daily doses of 148 mg in ameliorating negative symptoms and comparable in improving overall psychopathology and global illness severity.", "Amisulpride, a substituted benzamide with high selectivity for dopamine D3 and D2 receptors, was compared with the antipsychotic risperidone in patients with acute exacerbations of schizophrenia. The study was double-blind and involved 228 patients allocated, after a 3-6-day wash-out period, to amisulpride 800 mg (n = 115) or risperidone 8 mg (n = 113) for 8 weeks. Both treatments produced a marked improvement in schizophrenic symptomatology. Decreases in mean BPRS total score were 17.7 +/- 14.9 for amisulpride and 15.2 +/- 13.9 for risperidone, and all of the individual factors on the BPRS showed a numerically greater improvement in the amisulpride than in the risperidone patients. Both treatments were equally effective against positive symptoms on the PANSS positive syndrome subscale; however, there was a trend in favor of greater improvement in negative symptoms assessed on the PANSS negative subscale in patients receiving amisulpride with a decrease of 6.9 +/- 7.5 vs. 5.3 +/- 6.6 for risperidone (P = 0.09). Both drugs demonstrated good safety profiles, and scores on neurological scales (SAS, AIMS, and BAS) did not increase during treatment. A comparable proportion of patients received antiparkinsonian medication, 30 and 23% in the amisulpride and risperidone groups, respectively (P = 0.21). Patients receiving risperidone experienced an increase in body weight, which was significantly greater than for amisulpride (P = 0.026).", "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." ]

[ "10748957", "10323611", "1779005", "15993304" ]

[ "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.", "Management of partial thickness facial burns (comparison of topical antibiotics and bio-engineered skin substitutes).", "The role of gentamicin iontophoresis in the treatment of burned ears.", "Treatment of second degree facial burns with allografts--preliminary results." ]

[ "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.", "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.", "Ear cartilage heals slowly, and limited vascularity in cartilage precludes use of systemic antibiotics. Iontophoresis electrically induces drugs in solution to migrate into target tissues. Fifteen patients were randomized to receive gentamicin iontophoresis (n = 7) plus dressing changes every 6 hours and cleaning or routine care alone (n = 8) for treatment of ear burns. There were no differences between the groups in incidence of chondritis (43% vs 50%) or cartilage loss (11% vs 16%). However, gentamicin-resistant organisms developed in 29% of the patients who received iontophoresis, but in none of the patients in the control group (p less than 0.05). To identify the etiology of the resistant organisms, 10 New Zealand white rabbits receive 7 cm2 contact burns to each ear. Gentamicin iontophoresis was performed on one ear, and the other ear served as the control. Serum gentamicin levels were always subtherapeutic. Additionally, gentamicin tissue levels in both the treated and control ears were subtherapeutic. Gentamicin iontophoresis appears to offer no additional salutary effects beyond those that are provided by routine care and may encourage the development of antibiotic resistance.", "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." ]

[ "16531616", "11519503" ]

[ "Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events.", "Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation." ]

[ "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.", "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." ]

[ "10739150", "9046143", "7951964" ]

[ "Interdigital neuroma: intermuscular neuroma transposition compared with resection.", "Surgery of Morton's neuroma: dorsal or plantar approach?", "Effect of pronation and supination orthosis on Morton's neuroma and lower extremity function." ]

[ "This prospective, randomized study compares the treatment of an interdigital neuroma (IDN) by the standard resection operation with a technique in which the IDN is transposed into the inter-muscular space between the adductor hallucis and the interossei muscles after division of the digital nerves distal to the IDN. The resection group contained 22 patients and 22 neuromas and the transposition group contained 22 patients and 23 neuromas. An interviewer, blinded as to the operative technique used, telephoned each patient preoperatively, and at 1 month, 3 months, 6 months, 12 months, and 36-48 months postoperatively. The interviewer recorded the patient's reported pain level on a numerical rating scale of 0 to 100. In the resection group the average pain level was slightly lower through the first 6 month period, but at the 12 month review the resection group had a slightly higher average pain level . At the 36-48 month survey the resection group again reported a greater average pain level and fewer asymptomatic patients. It was concluded that it is unnecessary to excise the IDN to obtain excellent relief of pain. It was also concluded that transposition of the IDN into an intermuscular position between the adductor hallucis and the interossei muscles produced significantly better long term results than did the standard resection operation.", "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.", "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." ]

[ "2213375", "12070950" ]

[ "Normalization of plasma arginine vasopressin concentrations when children with meningitis are given maintenance plus replacement fluid therapy.", "Management of meningitis in children with oral fluid restriction or intravenous fluid at maintenance volumes: a randomised trial." ]

[ "We hypothesized that plasma arginine vasopressin (AVP) concentrations in children with meningitis are appropriate for the children's degree of hypovolemia, even though the concentrations were higher than expected for the serum osmolality. A randomized study was conducted to compare the effect on plasma AVP concentrations of giving maintenance fluid requirements plus replacement of any deficit versus restricting fluids to two thirds of maintenance requirements for 24 hours. Plasma AVP concentrations and serum osmolality were measured before fluid therapy was begun and again after 24 hours. Nineteen children, 2 months to 17 years of age, were studied; 13 had bacterial meningitis (12 with Haemophilus influenzae type b). Ten children (seven with bacterial meningitis) received a mean of 1.42 times the calculated maintenance fluid requirements, and nine (six with bacterial meningitis) were restricted to a mean of 0.65 times maintenance. Children in the maintenance group also received significantly more sodium (mean = 6.3 mEq/kg/24 hr) than children in the fluid-restricted group (mean = 2.0 mEq/kg/24 hr). The two groups were comparable for plasma AVP concentration and serum osmolality before fluid therapy was begun. The plasma AVP concentration was significantly lower after 24 hours of maintenance plus replacement fluids than after fluid restriction (p = 0.005), and the change in AVP concentration correlated with the amount of sodium given (p less than 0.02). This study supports the hypothesis that serum AVP concentrations are elevated in patients with meningitis because of hypovolemia and become normal when sufficient sodium is given to facilitate reabsorption of water by the proximal tubule of the kidney. Patients with meningitis can be given maintenance plus replacement fluids but should be monitored for the development of the syndrome of inappropriate secretion of antidiuretic hormone.", "A multi-centre randomised open trial was done to determine whether moderate oral fluid restriction or intravenous fluid at full maintenance volumes would result in a better outcome for children with bacterial meningitis in Papua New Guinea, and what clinical signs could guide fluid management. Children with clinical signs and cerebrospinal fluid suggestive of bacterial meningitis received either breast milk by nasogastric tube at 60% of normal maintenance volumes (n = 172) or intravenous half-normal saline and 5% dextrose at 100% of normal maintenance volumes (n = 174) for the 1st 48 hrs of treatment. An adverse outcome was death or severe neurological sequelae, and a good outcome was defined as intact survival or survival with at worst mild-to-moderate neurological sequelae. The probability of an adverse outcome was 24.7% in the intravenous group and 33.1% in the oral-restricted group, but the difference was not statistically significant (RR 0.75, 0.53-1.04, p = 0.08). Sunken eyes or reduced skin turgor at presentation were risk factors for an adverse outcome (OR 5.70, 95% CI 2.87-11.29) and were most strongly associated with adverse outcome in the fluid-restricted group. Eyelid oedema during treatment was also a risk factor for an adverse outcome (OR 2.54, 95% CI 1.36-4.75) and eyelid oedema was much more common in the intravenous group (26%) than in the restricted group (5%). For many children with bacterial meningitis in less developed countries, moderate fluid restriction is unnecessary and will be harmful; a normal state of hydration should be achieved but over-hydration should be avoided. Giving 100% of normal maintenance fluids, especially with intravenous hypotonic fluid, will lead to oedema in up to one quarter of children with bacterial meningitis. If additional intravenous fluids are required for children with meningitis, an isotonic solution should be used." ]

[ "6109989", "8285749", "3887165", "1468386" ]

[ "Pancuronium during mechanical ventilation speeds recovery of lungs of infants with hyaline membrane disease.", "Randomised trial of routine versus selective paralysis during ventilation for neonatal respiratory distress syndrome.", "Reduction in intraventricular hemorrhage by elimination of fluctuating cerebral blood-flow velocity in preterm infants with respiratory distress syndrome.", "Effect of morphine and pancuronium on the stress response in ventilated preterm infants." ]

[ "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.", "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.", "In a previous study of preterm infants requiring mechanical ventilation for the respiratory distress syndrome, we demonstrated a striking association of fluctuating cerebral blood-flow velocity in the first day of life with the subsequent occurrence of intraventricular hemorrhage. Because this fluctuating pattern could be eliminated by muscle paralysis, we conducted a prospective study of preterm infants receiving mechanical ventilation for the respiratory distress syndrome in which we evaluated the effect of paralysis and this flow-velocity pattern on the incidence and severity of intraventricular hemorrhage. Twenty-four infants with the fluctuating pattern in the first hours of life were identified and randomly selected to serve as controls (10) or to be subjected to muscle paralysis (14). Intraventricular hemorrhage developed in all 10 control infants but in only 5 of the 14 infants subjected to muscle paralysis. Moreover, in 4 of the 5 paralyzed infants in whom hemorrhage developed, it did so after cessation of the paralysis. Seven of the 10 control infants had Grade III hemorrhage, the most severe variety of intraventricular hemorrhage, whereas none of the paralyzed infants had Grade III hemorrhage. We conclude that elimination of fluctuating cerebral blood-flow velocity in preterm infants with respiratory distress syndrome markedly reduces the incidence and severity of intraventricular hemorrhage.", "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." ]

[ "16314627", "11205200", "17704423", "9440756" ]

[ "Phase III study of fluorouracil, leucovorin, and levamisole in high-risk stage II and III colon cancer: final report of Intergroup 0089.", "Optimum duration of oral adjuvant chemotherapy of HCFU for colorectal cancer; review of 5-year follow-up.", "Phase III study comparing a semimonthly with a monthly regimen of fluorouracil and leucovorin as adjuvant treatment for stage II and III colon cancer patients: final results of GERCOR C96.1.", "Prospectively randomized trial of postoperative adjuvant chemotherapy in patients with high-risk colon cancer." ]

[ "In 1990, fluorouracil (FU) plus levamisole for 1 year became standard adjuvant treatment for patients with high-risk stages II and III colon cancer. Intergroup (INT) 0089 assessed the relative contributions of leucovorin and levamisole in such patients.\n From 1988 to 1992, 3,794 patients were randomly assigned. Experimental treatment consisted of one of three chemotherapy regimens: the low-dose leucovorin plus FU (Mayo Clinic; LDLV) regimen, the high-dose leucovorin plus FU (Roswell Park; HDLV) regimen, and the low-dose leucovorin plus levamisole plus FU (LDLV plus LEV) regimen, each administered for 30 to 32 weeks. The control arm was levamisole plus FU (LEV) for 1 year.\n After a median follow-up of 10 years, of 3,561 eligible patients, 1,691 (47%) have died and 1,330 (37%) have experienced disease recurrence; 137 (10%) of those experiencing recurrence are still alive. A total of 481 patients (13%) died without evidence of recurrence, and 1,723 (48%) are alive and disease free. Although there were toxicity differences among the four arms, none was statistically superior in disease-free or overall survival.\n The 6- to 8-month regimens of LDLV and HDLV without levamisole used in this trial, rather than the previous standard regimen of 12 months of LEV, have become widely used. INT-0089 has long-term follow-up of the largest clinical trial of patients with high-risk colon cancer, documenting not only the durability of the treatment effects, but also the natural history of patients with high-risk colon cancer, and analyses of treatment based on age, race, and comorbid conditions such as obesity, diabetes, and second primary cancers.", "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.", "This randomized, 2 x 2 factorial study compared a semimonthly regimen (fluorouracil [FU] and leucovorin [LV] semi-monthly is LV5FU2) with a monthly regimen of FU and LV (mFU/LV) as well as 24 weeks versus 36 weeks of each regimen as adjuvant treatment of stage II and III colon cancer.\n LV5FU2 was administered semimonthly for 2 days as racemate (dl) or levogyre (l-; 200 or 100 mg/m(2)) as a 2-hour infusion, followed by 400 mg/m(2) FU bolus and a 600-mg/m(2) FU 22-hour continuous infusion. FU and LV were administered monthly (mFU/LV) for 5 days as dl- or l-LV 15-minute infusion, followed by a 400 mg/m(2) FU 15-minute infusion. The primary end point was disease-free survival (DFS).\n Between September 1996 and November 1999, 905 patients with stage II (43%) and III (57%) colon cancer were enrolled. The median follow-up was 6 years. There was no statistically significant difference between mFU/LV and LV5FU2 in terms of DFS (150 v 148 events; hazard ratio [HR],1.01; 95% CI, 0.806 to 1.269; P = .94) and overall survival (OS; 104 v 103 events; HR,1.02; 95% CI, 0.77 to 1.34; P = .91). No statistical difference was observed between 24 or 36 weeks of chemotherapy. Median survival from metastatic relapse was 24 months. The survival of patients with metastatic relapse (n = 243) was significantly longer for patients with a longer time from random assignment to relapse (< 1, 1 to 2, >or= 2 years; log-rank test for trend P, .0497).\n DFS and OS were not statistically different between treatment groups and treatment durations. These data confirm the value of LV5FU2 as control arm in the Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer and Pan-European Trials in Adjuvant Colon Cancer studies.", "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." ]

[ "14988972", "12236277", "9076288", "9686713", "14508426", "10701382", "12236273", "9631159", "9744187", "12236274", "10776366", "2066823", "7963201", "21263970", "9158573", "8259810", "10698242", "11276541", "3093045", "9232713", "18999909", "12433017", "18209107", "11887119", "16883677", "12457048", "10432913", "8047518", "2744287", "11401608", "1996510", "10480825", "1940817", "10625023", "1403212", "3565663", "2910979", "7887759", "9481466" ]

[ "Opportunistic electronic reminders. Improving performance of preventive care in general practice.", "Cluster randomised controlled trial of an educational outreach visit to improve influenza and pneumococcal immunisation rates in primary care.", "A randomised intervention study to examine the effect on immunisation coverage of making influenza vaccine available at no cost.", "Influenza immunization in a managed care organization.", "The influence of health professionals on the uptake of the influenza immunization.", "Effect of preventive home visits by a nurse on the outcomes of frail elderly people in the community: a randomized controlled trial.", "Boosting uptake of influenza immunisation: a randomised controlled trial of telephone appointing in general practice.", "Performance-based physician reimbursement and influenza immunization rates in the elderly. The Primary-Care Physicians of Monroe County.", "Postcard reminders from GPs for influenza vaccine: are they more effective than an ad hoc approach?", "Improving uptake of influenza vaccination among older people: a randomised controlled trial.", "Enhancing influenza immunization. Postcard and telephone reminders and the challenge of immunization site shift.", "A target-based model for increasing influenza immunizations in private practice. Genesee Hospital Medical Staff.", "Improving compliance with immunization in the older adult: results of a randomized cohort study.", "The telephone: an overlooked technology for prevention in family medicine.", "A randomized trial of group outpatient visits for chronically ill older HMO members: the Cooperative Health Care Clinic.", "The impact of a public health nurse intervention on influenza vaccine acceptance.", "Increasing influenza and pneumococcal immunization rates: a randomized controlled study of a senior center-based intervention.", "Evidence to action: a tailored multifaceted approach to changing family physician practice patterns and improving preventive care.", "Comparison of three methods of recalling patients for influenza vaccination.", "Impact of postal invitations and user fee on influenza vaccination rates among the elderly. A randomized controlled trial in general practice.", "Cost and utilization avoidance with mail prompts: a randomized controlled trial.", "The effects of framing and action instructions on whether older adults obtain flu shots.", "Improving prevention in primary care: evaluating the effectiveness of outreach facilitation.", "Impact of physician reminders on the use of influenza vaccinations: a randomized trial.", "[Immunization program against influenza for adults 65 years or older at a community pharmacy in Puerto Rico].", "A randomised, clinical trial comparing the effectiveness of hospital and community-based reminder systems for increasing uptake of influenza and pneumococcal vaccine in hospitalised patients aged 65 years and over.", "Public health in managed care: a randomized controlled trial of the effectiveness of postcard reminders.", "Impact of Medicare reimbursement on influenza vaccination rates in the elderly.", "Improving geriatric preventive care through a patient-held checklist.", "Improving quality improvement using achievable benchmarks for physician feedback: a randomized controlled trial.", "The effect of microcomputer-generated reminders on influenza vaccination rates in a university-based family practice center.", "Improving the health behaviours of elderly people: randomised controlled trial of a general practice education programme.", "Influenza immunization: the impact of notifying patients of high-risk status.", "Physician education and report cards: do they make the grade? results from a randomized controlled trial.", "Computer-generated mailed reminders for influenza immunization: a clinical trial.", "Increasing influenza vaccination among high-risk elderly: a randomized controlled trial of a mail cue in an HMO setting.", "Postcard reminders and influenza vaccination.", "Enhancing physician adoption of practice guidelines. Dissemination of influenza vaccination guideline using a small-group consensus process.", "Randomized controlled study of customized preventive medicine reminder letters in a community practice." ]

[ "Preventive care is an important role for general practitioners, yet opportunities for prevention are often missed.\n We provided an automatic electronic record preventive care reminder system for 12 preventive care activities for one 10 doctor practice. All patients who attended were randomised by the terminal digit of their record number.\n The control uptake of opportunistic prevention was low; ranging from 1.5% (tetanus immunisation) to 27% (influenza immunisation). The reminders increased this by significant but small amounts for four out of 12 activities (immunisation for tetanus and pneumococcus and recording of allergies and weight), insignificant increases for four (mumps, measles and rubella immunisation, recording of smoking, and taking of cervical smears and of blood pressure), and insignificantly decreased influenza immunisation, and screening for diabetes and hyperlipidaemia.\n Opportunistic electronic reminders have the potential to increase preventive care in general practice.", "Improvement in the delivery of influenza and pneumococcal vaccinations to high-risk groups is an important aspect of preventive care for primary healthcare teams.\n To investigate the effect of an educational outreach visit to primary healthcare teams on influenza and pneumococcal vaccination uptake in high-risk patients.\n Cluster randomised controlled trial.\n Thirty general practices in the Trent region, UK.\n Fifteen practices were randomised to intervention and 15 to the control group after stratifying for baseline vaccination rate. All intervention practices were offered and received an educational outreach visit to primary healthcare teams, in addition to audit and feedback directed at improving influenza and pneumococcal vaccination rates in high-risk groups. Control practices received audit and feedback alone. All practices measured influenza and pneumococcal vaccination rates in high-risk groups. Primary outcomes were improvements in vaccination rates in patients aged 65 years and over, and patients with coronary heart disease (CHD), diabetes and a history of splenectomy.\n Improvements in pneumococcal vaccination rates in the intervention practices were significantly greater compared with controls in patients with CHD, 14.8% versus 6.5% (odds ratio [OR] = 1.23, 95% confidence interval [CI] = 1.13 to 1.34) and diabetes, 15.5% versus 6.8% (OR = 1.18, 95% CI = 1.08 to 1.29) but not splenectomy, 6.5% versus 4.7% (OR = 0.96, 95% CI = 0.65 to 1.42). Improvements for influenza vaccination were also usually greater in intervention practices but did not reach statistical significance. The increases for influenza vaccination in intervention versus control practices were for CHD, 18.1% versus 13.1% (OR = 1.06, 95% CI = 0.99 to 1.12); diabetes, 15.5% versus 12.0% (OR = 1.07, 95% CI = 0.99 to 1.16), splenectomy 16.1% versus 2.9% (OR = 1.22, 95% CI = 0.78 to 1.93); and those over 65 years 20.7% versus 25.4% (OR = 0.99, 95% CI = 0.96 to 1.02).\n Practices where primary care teams received an educational outreach visit demonstrated a significantly greater improvement in uptake in high-risk groups for pneumococcal but not influenza vaccine.", "This study aims to assess the effects of two interventions on influenza vaccination coverage: a simple organisational strategy, and making the vaccine available free.\n Sixteen general practitioners in the Auckland region were randomly selected to participate. Patients over 65 years of these general practitioners were randomly allocated to control, letter of invitation for a flu vaccine, or offer of a free flu vaccine. Administration of a flu vaccine for each person in the study was documented in each general practitioner surgery. Vaccine coverage for each of the three groups was measured.\n Results were available for 15 of the 16 participating general practitioners, a total of 2791 subjects. Immunisation coverage rates for control, letter of invitation and vaccine at no cost, were 17%, 27% and 45% respectively. Statistical analysis, allowing for the cluster method used to obtain subjects, showed risk ratios of 1.55 and 2.65 for the two interventions, with p values of < 0.00001.\n A potential source of bias in this study is underreporting of administration of vaccine to people in group 1. Notwithstanding this potential bias, both interventions were highly effective at increasing the uptake of influenza vaccine in the elderly population. General practitioners should be recommended to routinely invite patients over 65 years to have a flu vaccine. Given the commitment of the Ministry of Health to the vaccination against influenza of people over 65, this study would suggest that serious consideration should be given to making the vaccine available at no cost to this age group.", "To compare the effects of different types of computer-generated, mailed reminders on the rate of influenza immunization and to analyze the relative cost-effectiveness of the reminders.\n Randomized controlled trial.\n Multispecialty group practice.\n We studied 24,743 high-risk adult patients aligned with a primary care physician.\n Patients were randomized to one of four interventions: (1) no reminder, which served as control; (2) a generic postcard; (3) a personalized postcard from their physician; and (4) a personalized letter from their physician, tailored to their health risk.\n The immunization rate was measured using billing data. A telephone survey was conducted in a subgroup of patients to measure reactions to the mailed reminders. To evaluate the cost-effectiveness, a model was constructed that integrated the observed effect of the interventions with published data on the effect of immunization on future inpatient health care costs.\n All three of the reminders studied increased the influenza vaccination rate when compared with the control group. The vaccination rate was 40.6% in the control group, 43.5% in the generic postcard group, 44.7% in the personalized postcard group, and 45.2% in the tailored letter group. The rates of immunization increased as the intensity of the intervention increased (p < .0001). Seventy-eight percent of patients in the letter group deemed the intervention useful, and 86% reported that they would like to get reminders in the future. The cost-effectiveness analysis estimated that in a nonepidemic year, the net savings per 100 reminders sent would be $659 for the personalized postcard intervention and $735 for the tailored letter intervention. When these net cost-savings rates were each applied to the entire high-risk cohort of 24,743 patients, the estimated total net savings was $162,940 for the postcard and $181,858 for the tailored letter.\n Although the absolute increase in immunization rates with the use of reminders appeared small, the increases translated into substantial cost savings when applied to a large high-risk population. Personalized reminders were somewhat more effective in increasing immunization, and personalized letters tailored to the patients' condition were deemed useful and important by the individuals who received them and had a beneficial indirect effect on patient satisfaction.", "Influenced by the Department of Health's aim to increase the uptake of the influenza immunization to 70% among those eligible, this study aimed to compare three methods of promoting influenza immunization among over 65 year old patients in a GP practice, and to identify if a particular promotion method was more effective among either of two defined age groups. The sample (n = 90) was randomly allocated into three intervention groups, and then subdivided into two age groups. A different subject experimental design was used to compare the groups. Statistical analysis of the data showed no significant difference in influenza immunization uptake between the three intervention groups, or the age-defined sub-groups. However, although not significant at 5% significance level, participants aged 72 years and over showed a greater uptake among those visited by a health professional. The findings suggest that a larger study using the same interventions would produce significant results.", "Timely recognition and prevention of health problems among elderly people have been shown to improve their health. In this randomized controlled trial the authors examined the impact of preventive home visits by a nurse compared with usual care on the outcomes of frail elderly people living in the community.\n A screening questionnaire identified eligible participants (those aged 70 years or more at risk of sudden deterioration in health). Those randomly assigned to the visiting nurse group were assessed and followed up in their homes for 14 months. The primary outcome measure was the combined rate of deaths and admissions to an institution, and the secondary outcome measure the rate of health services utilization, during the 14 months; these rates were determined through a medical chart audit by a research nurse who was blind to group allocation.\n The questionnaire was mailed to 415 elderly people, of whom 369 (88.9%) responded. Of these, 198 (53.7%) were eligible, and 142 consented to participate and were randomly assigned to either the visiting nurse group (73) or the usual care group (69). The combined rate of deaths and admissions to an institution was 10.0% in the visiting nurse group and 5.8% in the usual care group (p = 0.52). The rate of health services utilization did not differ significantly between the 2 groups. Influenza and pneumonia vaccination rates were significantly higher in the visiting nurse group (90.1% and 81.9%) than in the usual care group (53.0% and 0%) (p < 0.001).\n The trial failed to show any effect of a visiting nurse other than vastly improved vaccination coverage.", "Immunisation against influenza is an effective intervention that reduces serologically confirmed cases by between 60% and 70%. Almost all influenza immunisation in the UK is done within general practice. Current evidence on the effectiveness of patient reminders for all types of immunisation programmes is largely based on North American studies.\n To determine whether telephone appointments offered bygeneral practice receptionists increase the uptake of irfluenza immunisation among the registered population aged over 65 years in east London practices.\n Randomised controlled trial.\n Three research general practices within the East London and Essex network of researchers (ELENoR).\n Participants were 1,820 low-risk patients aged 65 to 74 years who had not previously been in a recall system for influenza immunisation at their general practice. The intervention, during October 2000, was a telephone call from the practice receptionist to intervention group households, offering an appointment for influenza immunisation at a nurse-run. clinic Main outcome measures were the numbers of individuals in each group receiving immunisation, and practice costs of a telephone-appointing programme.\n intention to treat analysis showed an immunisation rate in the control group of 44%, compared with 50% in the intervention group (odds ratio = 1.29, 95% confidence interval = 1.03 to 1.63). Of the patients making a telephone appointment, 88% recieved immunisation, while 22% of those not wanting an appointment went on to be immunised. In the controlgroup, income generated was 11.35 pounds per immunisation, for each additional immunisation in the intervention group the income was 5.20 pounds. The 'number needed to telephone' was 17.\n Uptake of influenza immunisation among the low-risk older population in inner-city areas can be boosted by around 6% using a simple intervention by receptionists. Immunisation rates in this low-risk group fell well short of the 60% government target. Improving immunisation rates will require a sustained public health campaign. Retaining the item-of-service payments to practices should support costs of practice-based interventions.", "To investigate the effect of performance-based financial incentives on the influenza immunization rate in primary care physicians' offices.\n Randomized controlled trial during the 1991 influenza immunization season.\n Rochester, New York, and surrounding Monroe County during the Medicare Influenza Vaccine Demonstration Project.\n A total of 54 solo or group practices that had participated in the 1990 Medicare Demonstration Project.\n All physicians in participating practices agreed to enumerate their ambulatory patients aged 65 or older who had been seen during the 1990 or 1991 calendar years, and to track the immunization rate on a weekly basis using a specially designed poster from September 1991 to January 1, 1992. Additionally, physicians agreed to be randomized, by practice group, to the control group or to the incentive group, which could receive an additional $.80 per shot or $1.60 per shot if an immunization rate of 70% or 85%, respectively, was attained.\n The main outcome measures are the 1991 immunization rate and the improvement in immunization rate from the 1990 to 1991 influenza seasons for each group practice.\n For practices in the incentive group, the mean immunization rate was 68.6% (SD 16.6%) compared with 62.7% (SD 18.0%) in the control group practices (P = .22). The median practice-specific improvement in immunization rate was +10.3% in the incentive group compared with +3.5% in the control group (P = .03).\n Despite high background immunization rates, this modest financial incentive was responsible for approximately 7% increase in immunization rate among the ambulatory elderly.", "All persons 65 years and older are recommended to be immunised against influenza each autumn. As immunisation rates remain low, we conducted a randomised control trial in a three-partner urban general practice to evaluate the differential effectiveness of a single postcard reminder in a general practice setting compared to usual care. All non-residential patients aged 65 years and over were identified from the age/sex/disease register. After exclusions, 325 patients were stratified by sex (125 men and 200 women) and randomised to receive either a postcard reminder in large print mailed in April or usual care. General practitioners (GPs) were blind to the randomisation. A blinded record audit performed in July demonstrated that the postcard was effective in increasing immunisation for men (chi(2)1df = 3.85; p = 0.05) but not for women (chi(2)1df = 0.45; p = 0.50). After adjusting for 1995 immunisation status, the effect of the postcard on immunisation rates was even stronger in men (Wald chi(2)1df = 6.20; p = 0.01) but remained non-significant in women (Wald chi(2)1df = 1.38; p = 0.24). With this adjustment, the odds of having the 1996 flu vaccine for men sent the postcard reminder were three times that of men in the control group (OR = 3.0; 95% CI 1.3-6.9). In a general practice setting, a single postcard reminder appears to be a promising way to boost influenza immunisation rates among ageing men. Replication of the study is recommended.", "The uptake of influenza vaccination among older people is suboptimal. Contact with a doctor or nurse is associated with older people deciding to accept influenza vaccination.\n To compare different forms of approach in improving uptake of influenza vaccination among patients aged 75 years and over in primary care.\n Randomised controlled trial.\n One large rural general practice serving the town and surrounding area of Melton Mowbray, Leicestershire.\n All 2,052 patients aged 75 years and over, registered with the practice and not living in nursing/residential homes or sheltered accommodation, were included in the study. One-third of patients were randomised to receive an offer of influenza vaccination as part of an over-75 health check administered by a practice nurse in the patient's home, and two-thirds of patients were randomised to receive a personal letter of invitation to attend an influenza vaccination clinic held at the surgery. The main outcome measure was uptake of influenza vaccination.\n Six hundred and eighty patients were randomised to the health check arm of the trial and 1,372 were randomised to receive a personal letter. Of those randomised to the health check arm, 468 received the health check from the nurse. Overall, the difference in influenza vaccination uptake was 6.4% (95% confidence interval [CI] = 2.2% to 10.4%) with 67.9% (n = 932) of those who were sent a personal letter actually receiving the vaccine, compared with 74.3% (n = 505) of those offered a combined health check and influenza vaccination (P = 0.003).\n Combining home-based over- 75 health checks with influenza vaccination can improve uptake among older patients. However this intervention is likely to be costly and its effect on influenza vaccination rates is modest. The difference in uptake is greater among those who do not routinely comeforwardfor vaccination and a more viable option may be to target these patients.", "To determine if postcard and telephone reminders increased the rate of influenza immunization of Medicare beneficiaries.\n Before and after trial (postcard reminders) with systematically allocated control group (telephone reminder intervention).\n A semirural family practice residency program.\n All 475 noninstitutionalized persons older than 65 years who had received at least 1 office service in the previous 2 years.\n In September 1996, each of 475 patients received a postcard urging prompt influenza immunization. Those not responding within 1 month were systematically allocated either to a group receiving further telephone contact or to a control group. At the time of telephone contact, any offered information about influenza immunization received outside the Smoky Hill Family Practice Center, Salina, Kan, was recorded.\n We measured the percentage of change in practice-administered influenza immunizations compared with the baseline rate of the preceding 2 years; the difference in immunization rates between the telephone intervention group and controls; and the number of patients contacted by telephone who reported receiving influenza immunization at a site other than the Family Practice Center.\n Twenty-eight percent of patients who received a postcard obtained office influenza immunizations within 1 month, but no additional immunizations could be attributed to the telephone intervention. Thirty-five percent of patients contacted by telephone reported receiving influenza immunization at a site other than the Family Practice Center.\n The postcard intervention was associated with a significant increase in the office immunization rate. This increase may have been confounded by \"site shift\" in which individuals came to the office for an immunization that they might otherwise have received at other community sites.", "To measure the impact of a population-based tracking system on influenza immunization rates.\n Thirteen practices with 45 physicians were randomized to a control and two intervention groups.\n Private practices.\n All patients aged 65 years and over who were seen in participating physicians' practices within the preceding two years.\n In both intervention groups influenza immunization rates for physicians were recorded weekly as cumulative percentages of their target populations, using a specially prepared poster. In addition, postcard reminders were sent to all the patients in one of the intervention groups.\n Immunization rates in the two intervention groups were 30% higher than in the control group; the control group immunized 50% (2,405/4,772) of its target population, while the poster and poster/postcard groups immunized 66% (1,420/2,149) and 67% (2,427/3,604), respectively.\n A population-based strategy that monitors performance can significantly improve rates of influenza immunization in private practices.", "To compare three approaches for improving compliance with influenza and pneumococcal vaccination of elderly patients.\n Randomized controlled trial using three parallel group practices at a public urban teaching hospital.\n Public teaching hospital.\n All patients 65 years of age and older (n = 1202) seen by resident physicians (n = 66) attending three ambulatory medical practices from October 1, 1989 to March 31, 1990.\n All three provider groups received intensive education in immunization standards. The control group received no further intervention. Staff in the second group offered education to patients at their visits. In the third group, the prevention team, a flowsheet was used, patient education offered, and staff had their tasks redefined to facilitate compliance; for vaccinations, eg, nurses could vaccinate independent of MD initiative.\n Medical records were reviewed for the 1202 patients seen, including 756 patients seen during both the 1988-89 and 1989-90 influenza seasons, to determine documented offering and receipt of vaccinations. During the intervention period (1989-90), influenza vaccinations were offered significantly more frequently to prevention team patients (68.3%) than to patients in either the patient education (50.4%) or control (47.6%) groups (P = 0.006), even after adjusting for the patients' prior vaccination status, age, gender, race, and high-risk co-morbidity and for physicians' level of training. Likewise, pneumococcal vaccinations were offered more frequently to previously unvaccinated prevention team patients (28.3%) than to patient education (6.5%) or control (5.4%) group patients (P = 0.001), even after adjusting for the factors using multivariate analysis. Compliance rates did not differ between patient education and control subjects for either vaccine. Pre-intervention physician surveys documented higher perceived than actual compliance for both vaccines, with 89.0% and 52.8% of physicians believing that they complied with influenza and pneumococcal vaccination guidelines, respectively.\n The results of this trial provide strong support for organizational changes that involve non-physician personnel to enhance vaccination rates among older adults.", "Annual influenza vaccination has long been recommended for the elderly population. Despite this recommendation, immunization rates have remained very low. This study measured the effects of two approaches to the provision of influenza immunization to the 65-years-and-over age group in a single family practice. The \"drop-in\" group (N=123) was informed of the availability of the vaccine at visits made during the vaccination period. The \"phone\" group (N=120) was notified of the availability of the vaccine by telephone and was invited to come in for the shot. An immunization rate of 50.8% for the \"phone\" group and 26.8% for the \"drop-in\" group was obtained (P=.0002). These results contrast strongly with the overall immunization rates of 5.9% and 9.5% obtained during the previous two years, when no active immunization policy was in place. The telephone approach was found to benefit the type of patient at greatest risk from influenza: the chronically ill and the aged. It is clear that having a defined immunization policy substantially improves the provision of influenza vaccination. The authors discuss the effectiveness and practicality of these approaches to the delivery of influenza vaccine and their applicability to other forms of prevention in family medicine.", "To compare the impact of group outpatient visits to traditional \"physician-patient dyad\" care among older chronically ill HMO members on health services utilization and cost, self-reported health status, and patient and physician satisfaction.\n A 1-year randomized trial.\n A group model HMO in the Denver Metropolitan area.\n Three hundred twenty-one members aged 65 and older, randomized to a group visit intervention (n = 160) or to usual care (n = 161).\n Patients with high health services utilization and one or more chronic conditions had monthly group visits with their primary care physician and nurse. Visits included health education, prevention measures, opportunities for socialization, mutual support, and for one-to-one consultations with their physician, where necessary.\n Health services utilization and associated cost, health status, and patient and physician satisfaction.\n Outcome measures obtained after a 1-year follow-up period showed that group participants had fewer emergency room visits (P = .009), visits to subspecialists (P = .028), and repeat hospital admissions per patient (P = .051). Group participants made more visits (P = .021) and calls (P = .038) to nurses than control group patients and fewer calls to physicians (P = .019). In addition, a greater percentage of group participants received influenza and pneumonia vaccinations (P < .001). Group participants had greater overall satisfaction with care (P = .019), and participating physicians reported higher levels of satisfaction with the groups than with individual care. No differences were observed between groups on self-reported health and functional status. Cost of care per member per month was $14.79 less for the group participants.\n Group visits for chronically ill patients reduce repeat hospital admissions and emergency care use, reduce cost of care, deliver certain preventive services more effectively, and increase patient and physician satisfaction.", "Public health clients in an Ontario community 65 years of age or older were randomly allocated to receive an intervention by a public health nurse during a home visit promoting either influenza immunization or safety measures. There was no statistically significant differences in influenza immunization rates between these two groups (56.1% vs 56.6%). Men were significantly more likely to receive immunization.", "Immunizations decrease morbidity from influenza and pneumococcal infections. Immunization levels remain below desired levels despite clinic-based and public education efforts. This paper describes a randomized, controlled trial of a senior center-based program, which used peer-to-peer outreach to increase pneumococcal and influenza immunization rates among an urban senior population.\n Seniors were randomized to intervention or control groups. The intervention group received educational brochures mailed with reply cards to report immunization status, telephone calls from senior volunteers to unimmunized participants, and computerized immunization tracking. Immunization rates were obtained before and after the intervention by self-report.\n Among participants without prior pneumococcal immunization, the pneumococcal immunization rate among the intervention group (52.0%; 95% CI = 46.6%-57.4%) was significantly higher than that of the control group (30.9%; 95% CI = 26.6%-35.2%) (rate ratio = 1.68; 95% CI = 1.40-2.03). Among those without influenza immunization in the prior year, significantly more (50.0%; 95% CI = 40.0%-60.0%) were immunized against influenza in the intervention group than in the control group (23.0%; 95% CI = 15.2%-33.3%) (rate ratio = 2.17; 95% CI = 1.42-3.31). Among those with influenza immunization in the prior year, the rate ratio was 1.04 (95% CI = 1.01-1.07).\n The intervention increased both influenza and pneumococcal immunization rates to high levels, suggesting that further progress in increasing adult immunization coverage is possible.", "Although there is much room for improvement in the performance of recommended preventive manoeuvres, many inappropriate preventive interventions are being done. We evaluated a multifaceted intervention, delivered by nurses trained in prevention facilitation, to improve prevention in primary care.\n Forty-six health service organizations (HSOs) were recruited from 100 sites in Ontario. After baseline data were collected, we randomly assigned the practices to either an 18-month (July 1997 to December 1998) multifaceted intervention delivered by 1 of 3 nurse facilitators (23 practices) or no intervention (23 practices). The unit of intervention and analysis was the medical practice. The outcome measure was an overall index of preventive performance, which was calculated as the proportion of eligible patients who received 8 recommended preventive manoeuvres less the proportion of eligible patients who received 5 inappropriate preventive manoeuvres.\n One HSO, in the intervention group, was lost to follow-up. Before the intervention, the index of preventive performance was similar for the intervention and control groups (31.9% [95% confidence interval (CI) 27.3%-36.5%] and 32.1% [95% CI 27.2%-37.0%] respectively). At follow-up the corresponding values were 43.2% (95% CI 38.4%-48.0%) and 31.9% (95% CI 26.8%-37.0%), for an absolute improvement in the intervention group of 11.5% (p < 0.001). The mean proportion of eligible patients who received the recommended manoeuvres was 62.3% (95% CI 58.2%-66.4%) in the intervention group, as compared with 57.4% (95% CI 54.1%-60.7%) in the control group, for an absolute improvement of 7.2% (p = 0.008). The corresponding values for the inappropriate manoeuvres were 19.1% (95% CI 15.6%-22.6%) and 25.5% (95% CI 20.0%-31.0%), for an absolute improvement of 4.4% (p = 0.019).\n The tailored multifaceted intervention delivered by nurse facilitators was effective in modifying physician practice patterns and significantly improved preventive care performance.", "Despite recommendations supporting annual influenza vaccination for people aged 65 years or older, vaccination rates remain low. Several studies have evaluated the effect of sending mailed reminders, but few have compared alternative ways of reminding patients to receive the vaccine. In a randomized trial of 939 patients aged 65 years or older in four family practices carried out between Oct. 23 and Dec. 31, 1984, we compared three ways of reminding elderly patients to receive the vaccine: personal reminder by the physician, telephone reminder by the nurse and reminder by letter. The vaccination rates for the three groups were 22.9%, 37% and 35.1% respectively. No reminder was issued to a control group, and the rate was 9.8%. Some patients could not be reached by telephone, and some did not see the physician during the specified time. Among the patients whom the nurse actually contacted, the vaccination rate was 43.5%; the rate for patients whom the doctor actually saw was 45.1%. Overall, a telephone reminder by the nurse was the most effective method, and at an hourly salary of $16 or less this method would also be the most cost-effective. The reminders used in this study were automatically generated from a computerized medical record system. The study shows how a computerized system can be used to identify patients for whom preventive procedures are due.", "To examine the impact of postal invitations and user fee on influenza vaccination rates.\n A controlled randomized trial in 13 general practices. One third of the participating patients received postal invitations to influenza vaccination free of charge. Another third received postal invitations to influenza vaccination on paying the usual fee (US$ 40-60). The last third served as a control group, being vaccinated at their own request and paying the usual fee.\n General practice in the Counties of Funen and Vejle, Denmark.\n Five hundred and eighty-five patients aged 65 years or older, recognized by their general practitioner (GP) as being in the risk group for whom influenza vaccination is recommended.\n Influenza vaccination rates.\n In the control group 25% (19-31%, 95% confidence interval) of the patients were vaccinated, compared with 49% (42-56%) in the group who received a postal reminder and paid the usual fee, and 72% (65-78%) in the group invited to be vaccinated free of charge.\n It is suggested that GPs send postal invitations to their elderly patients in the risk groups urgently recommending influenza vaccination. Attention should also be given to offering free influenza vaccination to elderly patients who have recognized indications for vaccination.", "To study the medical service utilization changes and return on investment from a health plan's direct mailings that either encouraged members to receive influenza vaccinations or encouraged members to call a nurse advice service.\n Randomized controlled trial with 2 intervention groups and 1 control group consisting of all members over age 65 years who were enrolled in 5 states in the Blue Cross and Blue Shield Government-wide Service Benefit Plan. Sample size was 134,791 individuals.\n Administrative claims-based influenza, pneumonia, heart failure, and respiratory inpatient bed days, emergency department (ED) visits, physician evaluation and management visits, other outpatient visits, and nurse advice call rates were compared between the intervention and control groups.\n The influenza mailing intervention group experienced 2.87% (P = .033) fewer conditionrelated inpatient bed days and 7.25% (P = .101) fewer condition-related ED visits. The nurse advice service mailing intervention group experienced 7.65% (P <.001) fewer condition-related inpatient bed days and 6.75% (P = .125) fewer condition-related ED visits. Per dollar spent, the return on investment was estimated to be $2.51 for the influenza mailing intervention and $24.24 for the nurse advice mailing intervention.\n Administrative claims data suggest that members respond to health plan mailings. By mailing information to their members, health plans can affect rates of medical service utilization and generate cost savings.", "The authors tested the effects of cues to action--messages intended to increase flu immunizations. North Dakota counties were randomly assigned to reminder letters, action letters, or no letters. Within the reminder-letter counties, Medicare recipients received either (a) a reminder from the state peer review organization (PRO) to obtain a flu shot or (b) a reminder from the PRO, framed either in terms of the loss associated with failing to get a shot or (c) the benefits associated with getting a shot. Within the action-letter counties, Medicare recipients leaned where and when to receive a flu shot. Reminder type failed to differentially affect the immunization rate (overall M = 24.5%). However, the action messages worked better (28.2%) than no message (19.6%).", "Out reach facilitation is designed to promote uptake of evidence-based guidelines. There is evidence indicating that outreach facilitation can be effective in improving implementation of preventive care in GPs' offices. In this trial, we test a modified version of an outreach facilitation intervention.\n To evaluate whether a comprehensive preventive intervention program using outreach facilitators improves preventive care delivery.\n Match-paired, cluster-randomized controlled trial.\n Fee-for-service primary care practices in Eastern Ontario, Canada, at a time of physician shortage.\n Volunteer sample of 54 primary care practices.\n Mean difference between trial arms in practices' delivery of preventive manoeuvres, measured by preventive performance indices estimated from chart reviews and patient survey data.\n No difference was detected between the trial's arms for the primary outcome's overall prevention index [2.0%; 95% confidence interval (CI) -3.2 to 7.3; P = 0.44]. A small significant difference between the arms was detected for the secondary outcome's overall prevention index (2.8%; 95% CI 0.7-4.8; P = 0.01).\n In contrast to similar facilitation trials, this outreach facilitation program did not produce improvements in the delivery of preventive care. This lack of effect may be due to differences in the intervention and context, or the practice's limited capacity to change. Our intervention simultaneously facilitated a high number of manoeuvres, blinded facilitators and physicians to the targeted tests and had a relatively short intervention period and large number of practices assigned per facilitator. Changes in the primary care service model in Ontario at the time of the trial could have also washed out the intervention effect.", "To analyze the impact of mailed physician reminders to immunize their patients.\n Randomized trial involving Washington State physiatrists participating in the Medicare program. In 1997, all physiatrists in the state were separated into solo or group practice. Solo physicians and group practices were then separately randomized to receive 4 monthly reminders to have their patients immunized. In 1998, the intervention and control groups were switched.\n The state of Washington.\n A total of 4300 Medicare outpatients seen in Washington State in 1997 and 4025 patients in 1998.\n Repeated mailer.\n By using multivariate analysis, Medicare billing data was analyzed to determine the impact of the physician reminders on influenza vaccination rates.\n Among solo practitioners, patients whose physiatrist received the reminder letters in 1998 were 34% more likely (adjusted relative risk [RR] = 1.34; 95% confidence interval [CI],.96-1.88) to have a vaccination billing. Among group practitioners, those patients whose physiatrist received the reminder letters in 1997 were 26% more likely (RR = 1.26; 95% CI,.98-1.60) to have a vaccination billing. These differences, however, were not statistically significant. The adjusted RRs for the remaining intervention groups, solo practitioners in 1997 (RR =.89; 95% CI,.63-1.26), and group practitioners in 1998 (RR = 1.00; 95% CI,.73-1.36), revealed no increase in vaccination billings for patients whose physiatrist received the intervention.\n Repeated physician reminders did not increase the vaccination rate of Washington State Medicare patients who were seen by physiatrists in 1997 and 1998. These results were consistent whether the physiatrists were in solo or group practice. Other methods should be considered to improve the primary care delivered to this Medicare population.\n Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation", "Evaluate the educational needs of adults over 65 years or more with regards to the vaccine, vaccination and immunization against the influenza, design strategies to assist the educational needs and implant and evaluate an immunization program at an independent community pharmacy. A study divided into three phases: Phase I--evaluation of the educational needs related to the vaccine, vaccination and immunization. Phase II--designing of strategies to assist the needs. Phase III--a random longitudinal controlled study to evaluate an immunization program against the influenza implanted at an independent community pharmacy. One hundred (100) patients participated, randomly assigned to a controlled and experimental group. Three months into the study's Phase III, a 68% of the experimental group had been vaccinated and showed a tendency to improvement in knowledge; in the controlled group, a 32% had been vaccinated and did not show a tendency in improvement of knowledge. A year into the study's Phase III, a 76% of the experimental group had been vaccinated and 24% of the controlled group was vaccinated. The satisfaction average of the experimental group towards the pharmacist was 3.94 +/- 0.18 and, in the controlled group was 3.98 +/- 0.20, whiting a scale of 0-04. People who participated in an educational activity offered by a pharmacist showed: more knowledge, remembered what they learned and an increase in influenza vaccination.", "Hospitalisation represents an opportunity to identify unimmunised people at risk for the complications of influenza and pneumococcal disease. We conducted a randomised controlled trial of two strategies to increase uptake of influenza and pneumococcal vaccines in eligible, hospitalised subjects aged 65 years or more, admitted between May and September 1998 to a Melbourne hospital. Unvaccinated participants were allocated randomly to alert systems for hospital staff or community general practitioners (GPs). Follow-up occurred at 1 and 3 months. The baseline vaccination rates were 70% for influenza (426/606) and 41% (248/606) for pneumococcal disease. For unvaccinated subjects, the hospital alert resulted in 67% uptake compared to 55% following a GP alert for pneumococcal vaccine; and 63% in hospital compared to 53% following a GP alert for influenza vaccine. Although there was a trend toward a higher uptake in hospital, neither of these differences was statistically significant. The majority (75%) of vaccinations following a GP alert occurred within 1 month of discharge. Despite hospital and community-based reminder systems, there are still significant missed opportunities for vaccination. We did not demonstrate significant differences between hospital and GP reminder systems, but there was a trend towards higher uptake with opportunistic vaccination in hospital.\n Copyright 2003 S. Karger AG, Basel", "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.", "Influenza is responsible for significant morbidity, mortality, and medical costs, but immunization rates in the elderly remain low.\n As part of a demonstration project in rural Pennsylvania, 1,989 community-dwelling Medicare beneficiaries, 65-79 years old, completed a health risk appraisal including questions about flu shots. Participants were randomized to two experimental (hospital or physician) or control groups. Experimental groups were offered free flu shots for the 1990-91 flu season. Follow-up interviews to determine vaccination rates were completed about 1 year later.\n Baseline immunization rates were almost identical for the hospital-based (41.2%), physician-based (41.3%), and control group not offered free immunizations (40.6%). Follow-up rates for the groups offered immunizations rose significantly to 63.6 and 69.1% for hospital and physician groups, respectively, while the control group also increased significantly to 54.1%. Individuals who were more educated, were older, and had greater chronic diseases history (myocardial infarction, hypertension, and pulmonary disease) were more likely to be immunized. Male and married elderly were more likely to be immunized as a result of the demonstration.\n Increasing community education and providing immunizations free through Medicare will increase immunization rates among elderly. The elderly are more likely to receive flu shots provided through physicians' offices than through hospital-based clinics.", "Providing preventive services to patients is a priority for most family physicians. In this study, a three-item preventive checklist reminded patients 65 years of age and older to obtain an annual blood pressure check, influenza immunization, and cancer checkup. Over a one-year period, patients who received the checklist (n = 59) obtained 46% of indicated cancer detection services, while those who did not (n = 55) obtained 30%. Both groups had similar rates of obtaining blood pressure measurement (over 90%) and influenza immunization (over 45%). Patients themselves may be an underutilized resource for improving preventive care.", "Performance feedback and benchmarking, common tools for health care improvement, are rarely studied in randomized trials. Achievable Benchmarks of Care (ABCs) are standards of excellence attained by top performers in a peer group and are easily and reproducibly calculated from existing performance data.\n To evaluate the effectiveness of using achievable benchmarks to enhance typical physician performance feedback and improve care.\n Group-randomized controlled trial conducted in December 1996, with follow-up through 1998.\n Seventy community physicians and 2978 fee-for-service Medicare patients with diabetes mellitus who were part of the Ambulatory Care Quality Improvement Project in Alabama.\n Physicians were randomly assigned to receive a multimodal improvement intervention, including chart review and physician-specific feedback (comparison group; n = 35) or an identical intervention plus achievable benchmark feedback (experimental group; n = 35).\n Preintervention (1994-1995) to postintervention (1997-1998) changes in the proportion of patients receiving influenza vaccination; foot examination; and each of 3 blood tests measuring glucose control, cholesterol level, and triglyceride level, compared between the 2 groups.\n The proportion of patients who received influenza vaccine improved from 40% to 58% in the experimental group (P<.001) vs from 40% to 46% in the comparison group (P =.02). Odds ratios (ORs) for patients of achievable benchmark physicians vs comparison physicians who received appropriate care after the intervention, adjusted for preintervention care and nesting of patients within physicians, were 1.57 (95% confidence interval [CI], 1.26-1.96) for influenza vaccination, 1.33 (95% CI, 1.05-1.69) for foot examination, and 1.33 (95% CI, 1.04-1.69) for long-term glucose control measurement. For serum cholesterol and triglycerides, the achievable benchmark effect was statistically significant only after additional adjustment for physician characteristics (OR, 1.40 [95% CI, 1.08-1.82] and OR, 1.40 [95% CI, 1.09-1.79], respectively).\n Use of achievable benchmarks significantly enhances the effectiveness of physician performance feedback in the setting of a multimodal quality improvement intervention.", "Less than 20 percent of elderly and other high-risk persons targeted for annual influenza vaccination are immunized each year. In most busy practice settings, it is difficult for primary care physicians to identify every patient in need of preventive health interventions. The purpose of this study was to assess the effect of microcomputer-generated reminders on influenza vaccination rates in a university-based family practice center. The practice uses an interactive encounter form system from which updated clinical information is routinely entered into a cumulative database. During a 2-month period, 686 patients were identified in the database as eligible to receive influenza vaccine according to accepted criteria. Practice physicians (n = 32) were stratified by level of training and randomized to one of three groups, thereby receiving printed reminders on the encounter forms of all, none, or half of their eligible patients. Patients of physicians who always received reminders were more likely to receive influenza vaccine during the study period than patients of the never-reminded physicians (51 percent versus 30 percent, P less than 0.001). Patients whose physicians received reminders for only half their patients had an intermediate likelihood of receiving a vaccination if a reminder was printed (38 percent) but were less likely than the patients of never-reminded physicians to receive the vaccine if no reminder was printed (20 percent, P less than 0.001). This study suggests that physicians learn to depend on reminders for preventive health activities and that reminders are most effective when they are provided at every patient encounter.", "To establish the effect of an educational intervention for general practitioners on the health behaviours and wellbeing of elderly patients.\n Randomised controlled trial with 1 year follow up.\n Metropolitan general practices in Melbourne, Australia.\n 42 general practitioners and 267 of their patients aged over 65 years.\n Educational and clinical practice audit programme for general practitioners on health promotion for elderly people.\n Patients' physical activity, functional status, self rated health, immunisation status, social contacts, psychological wellbeing, drug usage, and rate of influenza vaccination. Primary efficacy variables were changes in outcome measures over 1 year period.\n Patients in the intervention group had increased (a) walking by an average of 88 minutes per fortnight, (b) frequency of pleasurable activities, and (c) self rated health compared with the control group. No change was seen in drug usage, rate of influenza vaccination, functional status, or psychological wellbeing as a result of the intervention. Extrapolations of the known effect of these changes in behaviour suggest mortality could be reduced by 22% if activity was sustained for 5 years.\n Education of the general practitioners had a positive effect on health outcomes of their elderly patients. General practitioners may have considerable public health impact in promotion of health for elderly patients.", "The influenza immunization rate in the high-risk military and retired military population has not been reported. To determine this rate, and to test whether the rate could be improved by notifying patients of their high-risk status, a clinical trial was conducted using a postcard reminder as an intervention.\n All 1068 high-risk patients enrolled in a large, residency-affiliated, military family practice department were identified. Of these, 519 patients were randomly selected to receive a reminder postcard; the remainder (549) were not sent a card. The immunization rates of each group were compared.\n A significantly higher percentage of those to whom postcards were sent received an influenza immunization (25.2% vs 9.1%, P less than .001). This difference was significant in all demographic groups except in those less than 21 years of age and those 21 to 40 years of age, in which very few patients presented for immunization. In those in the study group aged 65 years and over, 46.7% were immunized vs 20% of controls (P less than .001). Those aged 65 years and older and those in the higher income group had higher immunization rates, while those aged 40 years and under had very low immunization rates.\n The influenza immunization rate among military beneficiaries in high-risk groups is low, but can be significantly improved with a reminder postcard. This intervention may be more effective in the older and higher-income segments of the high-risk population. The low immunization rates of the lower-income group and the younger age groups have significant public health implications and should be studied further.", "We sought to determine whether tailored educational interventions call improve the quality of care, as measured by the provision of preventive care services recommended by the US Preventive Services Task Force, as well as lead to better patient satisfaction.\n We performed a randomized controlled study among 41 primary care physicians who cared for 1,810 randomly selected patients aged 65 to 75 years old at Kaiser Permanente Woodland Hills, a group-model health maintenance organization in southern California. All physicians received ongoing education. Physicians randomly assigned to the comprehensive intervention group also received peer-comparison feedback and academic detailing. Baseline and postintervention (2 to 2.5 years later) surveys examining the provision of preventive care and patient satisfaction were performed and medical records were reviewed.\n Based on the results of patient surveys, there were significant improvements over time in the provision of preventive care in both the education and the comprehensive intervention groups for influenza immunization (79% versus 89%, P <0.01, and 80% versus 91%, P <0.01), pneumococcal immunization (42% versus 73%, P < 0.01 and 34% versus 73%, P < 0.01), and tetanus immunization (64% versus 72%, P <0.01, and 59% versus 79%, P <0.01). Mammography (90% versus 80%, P <0.01) and clinical breast examination (85% versus 79%, P <0.05) scores worsened in the education only group but not in the comprehensive intervention group. However, there were few differences in rates of preventive services between the groups at the end of the study, and the improvements in preventive care were not confirmed by medical record review. Patient satisfaction scores improved significantly in the comprehensive intervention group (by 0.06 points on a 1 to 5 scale, P = 0.02) but not in the education only group (by 0.02 points, P = 0.42); however, the improvement was not significantly greater in the comprehensive intervention group (P = 0.20).\n A physician-targeted approach of education, peer-comparison feedback, and academic detailing has modest effects on patient satisfaction and possibly on the offering of selected preventive care services. The lack of agreement between patient reports and medical records review raises concerns about current methods of ascertaining compliance with guidelines for preventive care.", "A randomized, single-blind, controlled trial was performed at a community health center to measure the impact of computer-generated reminders mailed to patients on the rate of influenza immunization. High-risk patients were randomized to one of three groups: 1) usual care, 2) one reminder letter, offering free influenza immunization without an appointment, or 3) two sequential reminder letters, offering the same. The reminders did not significantly affect rates of influenza immunization. Analysis of the combined groups indicates that an appointment with a primary care provider remains the most reliable method of immunizing high-risk patients at this health center.", "A randomized controlled trial demonstrated that a single mailed influenza vaccination cue increased the vaccination rate among elderly HMO members with high-risk chronic conditions (n = 2217) from 30 per cent to 39 per cent during the fall and winter of 1984/85.", "nan", "A dissemination intervention to facilitate adoption of a preventive practice guideline (influenza vaccination for older adults) in group practices was developed and evaluated. The intervention, small-group consensus process, started with a physician expert presenting the guideline and followed with the group participating in a structured discussion of ways to implement the guideline that culminated in a public commitment (ie, \"buy in\") to adopt the guideline.\n Thirteen group practices and their primary care physicians (mean size, 5) were assigned randomly to intervention or control arms. In each group practice, physicians in the intervention arm met for 1 hour. Control physicians participated in an unrelated discussion (non-steroidal drug use). Guideline adoption was determined by changes in physicians' vaccination rates that were obtained through prechart and postchart reviews of 51 physicians. Prequestionnaires and postquestionnaires measured influenza knowledge and prevention attitudes.\n Using analysis of covariance, the small-group consensus process was found to increase physician vaccination rates by 34% compared with the control arm (F (1,48) = 19.49). All intervention arm physicians increased vaccination rates from before to after compared with 54% of control arm physicians. Attitudes and knowledge did not change and were unrelated to increased vaccination rates.\n A case is made for the small-group consensus process as an effective utilization-focused dissemination method. Interventions based on group dynamics and sensitive to local practice contexts can be useful in facilitating adoption of guidelines by physicians in group practices.", "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." ]

[ "16340187", "11591835", "9880383", "11779900" ]

[ "Diazepam to improve acute stroke outcome: results of the early GABA-Ergic activation study in stroke trial. a randomized double-blind placebo-controlled trial.", "The Clomethiazole Acute Stroke Study in tissue-type plasminogen activator-treated stroke (CLASS-T): final results.", "Clomethiazole acute stroke study (CLASS): results of a randomized, controlled trial of clomethiazole versus placebo in 1360 acute stroke patients.", "Clomethiazole Acute Stroke Study in ischemic stroke (CLASS-I): final results." ]

[ "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.", "To assess the safety of tissue-type plasminogen activator (t-PA) plus clomethiazole in patients with acute ischemic stroke and determine the feasibility of combination stroke therapy.\n Clomethiazole is a neuroprotectant that appeared to improve outcome in patients with clinical deficits of a major stroke (total anterior circulation syndrome [TACS]) in a previous study, the Clomethiazole Acute Stroke Study (CLASS). Combining a neuroprotectant such as clomethiazole with thrombolysis may augment the beneficial effects of the two agents. CLASS-t-PA (CLASS-T) was a pilot study to explore the safety of the combination and the feasibility of performing combination treatment in the setting of acute ischemic stroke.\n In a randomized, double-blind design (stratified for age, severity at admission, and time since onset of stroke), all patients received 0.9 mg/kg t-PA beginning within 3 hours of stroke onset and then either 68 mg/kg clomethiazole (n = 97) IV over 24 hours or placebo (n = 93) beginning within 12 hours of stroke onset. Patients were followed for 90 days. The main measures of safety were mortality and serious adverse events, and the main measure of functional outcome was the Barthel Index.\n The number of serious adverse event reports was 47 in the clomethiazole group and 48 in the placebo group. Death during the 90 days after treatment occurred in 15 clomethiazole and nine placebo patients (p = 0.26). Sedation was reported as an adverse event during therapy in 42% of clomethiazole patients vs 13% of placebo patients. The proportion of patients with TACS was 53% in the clomethiazole group and 41% in the placebo group. In the TACS subgroup, 52.9% of the clomethiazole patients scored a Barthel Index greater than 60 vs 44.7% of placebo patients (odds ratio 1.39; 95% CI 0.60 to 3.23).\n In this pilot study, there were no safety concerns related to the combination of t-PA and clomethiazole. The combination paradigm proved feasible, although many patients received clomethiazole several hours after thrombolysis; future studies must require prompt administration of the neuroprotectant either before or during administration of the thrombolytic. Patients with major strokes (TACS) may have the potential to benefit from the combination of t-PA and clomethiazole.", "The efficacy and safety of the neuroprotective drug clomethiazole was tested in a double blind placebo controlled trial in patients with a clinical diagnosis of acute hemispheric stroke.\n Patients with symptom onset of </=12 hours before the start of treatment were included in the study. Clomethiazole (75 mg/kg) or placebo was given as an intravenous infusion over a 24-hour period. Patients were followed up for 90 days. The primary efficacy variable was the proportion of patients reaching relative functional independence (>/=60 points on the Barthel Index) at 90 days.\n A total of 1360 patients were included. In the main efficacy analysis (n=1353), 56.1% of patients taking clomethiazole and 54.8% of placebo patients reached relative functional independence. The difference was not statistically significant. An analysis of the effect of time since onset of symptoms showed no difference between the treatment groups. Clomethiazole was generally well tolerated and appeared safe in the population studied. Sedation was the most common adverse event, leading to treatment withdrawal that occurred in 15.6% of clomethiazole-treated patients compared with 4.2% of placebo-treated patients. In a subgroup classified before randomization as having total anterior circulation syndrome (TACS) (n=545, or 40% of all randomized patients), the percentage of those reaching relative functional independence was 40.8% on clomethiazole and 29.8% on placebo, a difference of approximately 11 percentage units. TACS patients have clinical symptoms suggesting a \"large\" stroke.\n Clomethiazole had no adverse or beneficial effect on long-term outcome for all patients but produced sedation. The hypothesis that clomethiazole is effective in patients with large strokes will be tested in a further study.", "A previous trial (the Clomethiazole Acute Stroke Study) generated the hypothesis that clomethiazole is effective in patients with a major ischemic stroke (total anterior circulation syndrome), and this was tested in the present study.\n A total of 1198 patients with major ischemic stroke and a combination of limb weakness, higher cortical dysfunction, and visual field deficits were randomly assigned to clomethiazole (68 mg/kg IV over 24 hours) or placebo. The study drug was initiated within 12 hours of symptom onset. Functional outcome and neurological recovery were assessed at days 7, 30, and 90, with the proportion of patients with a Barthel Index > or =60 at last follow-up as the primary outcome measure.\n The patients were randomly assigned equally, and the two treatment groups were well matched for baseline characteristics, including stroke severity (mean National Institutes of Health Stroke Scale score 16.9+/-5.2). Ninety-six percent were classified as total anterior circulation syndrome. The proportion of patients reaching a Barthel Index score of > or =60 was 42% in the clomethiazole-treated group and 46% in the placebo-treated group (odds ratio, 0.81; 95% CI, 0.62 to 1.05; P=0.11). There was no evidence of efficacy on any secondary outcome variables (modified Rankin Score, National Institutes of Health Stroke Scale, Scandinavian Stroke Scale, and 30-day CT infarct volumes) compared with placebo. Subgroup analysis showed a similar lack of treatment effect in patients treated early (<6 hours) and in those treated later (6 to 12 hours). Somnolence was an expected pharmacological effect of clomethiazole, and this occurred during treatment as an adverse event in half of the patients randomly assigned to study drug.\n The target population was selected, and sufficient drug was given to produce the expected pharmacological effect in the brain. Clomethiazole does not improve outcome in patients with major ischemic stroke." ]

[ "10983198", "12600838", "12197996", "12600852", "11976158", "9020271", "9096978", "10731498", "12351467", "15531671", "15277155" ]

[ "A prospective study of whole-grain intake and risk of type 2 diabetes mellitus in US women.", "Whole-grain foods, dietary fiber, and type 2 diabetes: searching for a kernel of truth.", "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.", "Effect of whole grains on insulin sensitivity in overweight hyperinsulinemic adults.", "Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women.", "Dietary fiber, glycemic load, and risk of NIDDM in men.", "Carbohydrates, dietary fiber, and incident type 2 diabetes in older women.", "Dietary fiber intake and glycemic index and incidence of diabetes in African-American and white adults: the ARIC study.", "Changes in whole-grain, bran, and cereal fiber consumption in relation to 8-y weight gain among men.", "Glycemic index, glycemic load, and dietary fiber intake and incidence of type 2 diabetes in younger and middle-aged women." ]

[ "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.", "nan", "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 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.", "To examine prospectively the relationship between glycemic diets, low fiber intake, and risk of non-insulin-dependent diabetes mellitus.\n Cohort study.\n In 1986, a total of 65173 US women 40 to 65 years of age and free from diagnosed cardiovascular disease, cancer, and diabetes completed a detailed dietary questionnaire from which we calculated usual intake of total and specific sources of dietary fiber, dietary glycemic index, and glycemic load.\n Non-insulin-dependent diabetes mellitus.\n During 6 years of follow-up, 915 incident cases of diabetes were documented. The dietary glycemic index was positively associated with risk of diabetes after adjustment for age, body mass index, smoking, physical activity, family history of diabetes, alcohol and cereal fiber intake, and total energy intake. Comparing the highest with the lowest quintile, the relative risk (RR) of diabetes was 1.37 (95% confidence interval [CI], 1.09-1.71, P trend=.005). The glycemic load (an indicator of a global dietary insulin demand) was also positively associated with diabetes (RR= 1.47; 95% CI, 1.16-1.86, P trend=.003). Cereal fiber intake was inversely associated with risk of diabetes when comparing the extreme quintiles (RR=0.72, 95% CI, 0.58-0.90, P trend=.001). The combination of a high glycemic load and a low cereal fiber intake further increased the risk of diabetes (RR=2.50, 95% CI, 1.14-5.51) when compared with a low glycemic load and high cereal fiber intake.\n Our results support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of diabetes in women. Further, they suggest that grains should be consumed in a minimally refined form to reduce the incidence of diabetes.", "Intake of carbohydrates that provide a large glycemic response has been hypothesized to increase the risk of NIDDM, whereas dietary fiber is suspected to reduce incidence. These hypotheses have not been evaluated prospectively.\n We examined the relationship between diet and risk of NIDDM in a cohort of 42,759 men without NIDDM or cardiovascular disease, who were 40-75 years of age in 1986. Diet was assessed at baseline by a validated semiquantitative food frequency questionnaire. During 6-years of follow-up, 523 incident cases of NIDDM were documented.\n The dietary glycemic index (an indicator of carbohydrate's ability to raise blood glucose levels) was positively associated with risk of NIDDM after adjustment for age, BMI, smoking, physical activity, family history of diabetes, alcohol consumption, cereal fiber, and total energy intake. Comparing the highest and lowest quintiles, the relative risk (RR) of NIDDM was 1.37 (95% CI, 1.02-1.83, P trend = 0.03). Cereal fiber was inversely associated with risk of NIDDM (RR = 0.70; 95% CI, 0.51-0.96, P trend = 0.007; for > 8.1 g/day vs. < 3.2 g/day). The combination of a high glycemic load and a low cereal fiber intake further increased the risk of NIDDM (RR = 2.17, 95% CI, 1.04-4.54) when compared with a low glycemic load and high cereal fiber intake.\n These findings support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of NIDDM in men. Further, they suggest that grains should be consumed in a minimally refined form to reduce the incidence of NIDDM.", "Dietary carbohydrates may influence the development of type 2 (non-insulin-dependent) diabetes, for example, through effects on blood glucose and insulin concentrations.\n We examined the relations of baseline intake of carbohydrates, dietary fiber, dietary magnesium, and carbohydrate-rich foods and the glycemic index with incidence of diabetes.\n This was a prospective cohort study of 35988 older Iowa women initially free of diabetes. During 6 y of follow-up, 1141 incident cases of diabetes were reported.\n Total grain, whole-grain, total dietary fiber, cereal fiber, and dietary magnesium intakes showed strong inverse associations with incidence of diabetes after adjustment for potential nondietary confounding variables. Multivariate-adjusted relative risks of diabetes were 1.0, 0.99, 0.98, 0.92, and 0.79 (P for trend: 0.0089) across quintiles of whole-grain intake; 1.0, 1.09, 1.00, 0.94, and 0.78 (P for trend: 0.005) across quintiles of total dietary fiber intake; and 1.0, 0.81, 0.82, 0.81, and 0.67 (P for trend: 0.0003) across quintiles of dietary magnesium intake. Intakes of total carbohydrates, refined grains, fruit and vegetables, and soluble fiber and the glycemic index were unrelated to diabetes risk.\n These data support a protective role for grains (particularly whole grains), cereal fiber, and dietary magnesium in the development of diabetes in older women.", "To determine the association of dietary fiber and glycemic index with incident type 2 diabetes in African-Americans and whites.\n We studied 12,251 adults aged 45-64 years and free of diabetes at baseline (1987-1989). A total of 1,447 cases of diabetes were reported between baseline and 9 years of follow-up. Diabetes status was determined by fasting glucose level > or =126 mg/dl (7.0 mmol/l), nonfasting glucose level > or =200 mg/dl (11.1 mmol/l), self-report of physician diagnosis, or use of diabetes medication. Usual dietary intake over the previous year was obtained at baseline using a 66-item food-frequency questionnaire. Nutrients were energy-adjusted using the residuals method. Proportional hazard regression analysis was used to examine dietary fiber intake and glycemic index as predictors of type 2 diabetes in both ethnic groups.\n After adjustment for age, BMI, education, smoking status, physical activity, sex, and field center, there were no statistically significant associations of intake of total dietary fiber, fruit fiber, legume fiber, glycemic index, or glycemic load with incident diabetes. The hazard ratio for the fifth compared with the first quintile of cereal fiber was 0.75 (95% CI 0.60-0.92) in whites and 0.86 (0.65-1.15) in African-Americans.\n This finding supports a protective role for cereal fiber in the development of diabetes in whites. More studies are needed to determine the role of dietary fiber and glycemic index in diabetes in African-Americans.", "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.", "Increasing evidence suggests an important role of carbohydrate quality in the development of type 2 diabetes.\n Our objective was to prospectively examine the association between glycemic index, glycemic load, and dietary fiber and the risk of type 2 diabetes in a large cohort of young women.\n In 1991, 91249 women completed a semiquantitative food-frequency questionnaire that assessed dietary intake. The women were followed for 8 y for the development of incident type 2 diabetes, and dietary information was updated in 1995.\n We identified 741 incident cases of confirmed type 2 diabetes during 8 y (716 300 person-years) of follow-up. After adjustment for age, body mass index, family history of diabetes, and other potential confounders, glycemic index was significantly associated with an increased risk of diabetes (multivariate relative risks for quintiles 1-5, respectively: 1, 1.15, 1.07, 1.27, and 1.59; 95% CI: 1.21, 2.10; P for trend = 0.001). Conversely, cereal fiber intake was associated with a decreased risk of diabetes (multivariate relative risks for quintiles 1-5, respectively: 1, 0.85, 0.87, 0.82, and 0.64; 95% CI: 0.48, 0.86; P for trend = 0.004). Glycemic load was not significantly associated with risk in the overall cohort (multivariate relative risks for quintiles 1-5, respectively: 1, 1.31, 1.20, 1.14, and 1.33; 95% CI: 0.92, 1.91; P for trend = 0.21).\n A diet high in rapidly absorbed carbohydrates and low in cereal fiber is associated with an increased risk of type 2 diabetes." ]

[ "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." ]

[ "10451130", "11273951", "1642936", "11094664", "16361300", "8291731", "15450559", "12607659", "11132739", "1467074", "8160944", "8109770", "10701031", "9972405", "8836264", "1642935", "9489309", "8010474", "7588670", "11325088", "9609409", "10364998" ]

[ "Rectal indomethacin reduces postoperative pain and morphine use after cardiac surgery.", "Ketorolac is not nephrotoxic in connection with sevoflurane anesthesia in patients undergoing breast surgery.", "Effects of ketorolac trometamol on renal function.", "Tenoxicam i.v. for major gynaecological surgery--effects on renal function.", "Single dose parecoxib significantly improves ventilatory function in early extubation coronary artery bypass surgery: a prospective randomized double blind placebo controlled trial.", "Use of ketorolac after lower abdominal surgery. Effect on analgesic requirement and surgical outcome.", "Postoperative naproxen after coronary artery bypass surgery: a double-blind randomized controlled trial.", "Pain treatment with a COX-2 inhibitor after coronary artery bypass operation: a randomized trial.", "Non-steroidal anti-inflammatory drugs in treatment of postoperative pain after cardiac surgery.", "Effect of diclofenac on renal function and prostacyclin generation after surgery.", "Indomethacin as adjunct analgesia following open cholecystectomy.", "The effects of perioperative ketorolac infusion on postoperative pain and endocrine-metabolic response.", "Morphine-sparing effect of ketoprofen after abdominal surgery.", "Tenoxicam does not alter renal function during anaesthesia in normal individuals.", "Intravenous ketoprofen for pain relief after total hip or knee replacement.", "IV diclofenac in post-thoracotomy pain.", "[Does the preoperative administration of ketorolac improve postoperative analgesia].", "Evaluation of intravenous ketorolac administered by bolus or infusion for treatment of postoperative pain. A double-blind, placebo-controlled, multicenter study.", "Peri-operative administration of rectal diclofenac sodium. The effect on renal function in patients undergoing minor orthopaedic surgery.", "Prospective double-blind study of effect of ketorolac administration after laparoscopic urologic surgery.", "Ibuprofen does not impair renal function in patients undergoing infrarenal aortic surgery with epidural anaesthesia.", "I.v. diclofenac and ketorolac for pain after thoracoscopic surgery." ]

[ "To evaluate the combination of rectal indomethacin with patient controlled intravenous morphine analgesia (PCA) on postoperative pain relief and opioid use after cardiac surgery.\n With institutional ethics approval, 57 consenting adults undergoing elective aortocoronary bypass surgery were randomly assigned preoperatively in a double-blind fashion to receive either placebo (n = 26) or indomethacin 100 mg suppositories (n = 31), 2-3 hr postoperatively, and 12 hr later. Both groups utilized PCA morphine. Pain scores in the two treatment groups were assessed on a 10-cm visual analogue scale (VAS) (at rest and with cough) at 4, 6, 12, 18 and 24 hr after initial dosing, and were analyzed through a 2 x 5 repeated measures of variance. The 24 hr analgesic consumption, 12 and 24 hr chest tube blood loss, and time to tracheal extubation were also recorded, and compared for the two treatment arms through Student's t test on independent samples.\n Postoperative morphine consumption in the first 24 hr was 38% less in the indomethacin group (22.40 +/- 12.55 mg) than the placebo group (35.99 +/- 25.84 mg), P = 0.019. Pain scores, measured with a VAS, were 26% to 66% lower in the indomethacin vs placebo group at rest (P = 0.006), but not with cough, for all times assessed. There was no difference in blood loss (at 12 hr) or time to tracheal extubation for both groups.\n The combination of indomethacin with morphine after cardiac surgery results in reduced postoperative pain scores and opioid use without an increase in side effects.", "Ketorolac, which may cause renal vasoconstriction by cyclooxygenase inhibition, is often administered to patients anesthetized with sevoflurane that is metabolized to inorganic fluoride (F(-)), another potential nephrotoxin. We assessed this possible interaction using urine N-acetyl-beta-D-glucosaminidase indexed to urinary creatinine (U-NAG/crea) as a marker of proximal tubular, beta2-microglobulin as a tubular, urine oxygen tension (P(u)O(2)) as a medullary, and erythropoietin as a marker of tubulointerstitial damage. Thirty women (ASA physical status I-II) undergoing breast surgery were included in our double-blinded study. They were allocated into two groups receiving either ketorolac 30 mg IM (Group K) or saline (Group C) at the time of premedication, at the end of, and 6 h after anesthesia maintained with sevoflurane. Urine output, U-NAG/crea, P(u)O(2,) serum creatinine, urea, and F(-) were assessed. Blood loss was larger in Group K (465 +/- 286 mL vs 240 +/- 149 mL, mean +/- SD, P < 0.05). The MAC-doses of sevoflurane were similar. U-NAG/crea increased during the first 2 h of anesthesia and serum F(-) peaked 2 h after the anesthesia without differences between the groups. There were no statistically significant changes in P(u)O(2), erythropoietin, beta2-microglobulin, serum creatinine, urea, or urine output during anesthesia or the recovery period in either group. Our results indicate that the kidneys are not affected by ketorolac administered in connection with sevoflurane anesthesia.\n The different kinetics of N-acetyl-beta-D-glucosaminidase indexed to urinary creatinine and serum inorganic fluoride during and after sevoflurane anesthesia suggest that the observed mild renal tubular function deterioration is not caused by inorganic fluoride. Administration of ketorolac IM is therefore considered safe in adequately hydrated healthy adult patients given sevoflurane anesthesia.", "We have compared the renal effects of ketorolac trometamol 10 mg administered 4-hourly by intermittent i.m. injection or by continuous i.m. infusion with placebo in a double-blind study in 67 patients who had undergone upper abdominal surgery. Ketorolac was supplemented during the 48-h postoperative study period with bolus doses of morphine delivered by a patient controlled analgesia system. The only significant effect of ketorolac on renal function compared with patients who received placebo was reduced excretion of potassium. The overall changes caused by surgery alone were of much greater magnitude. Bleeding time was increased with ketorolac, but there were no adverse events related to this.", "Thirty women presenting for major gynaecological oncology surgery under a standardized, combined epidural/general anaesthetic technique received either placebo or tenoxicam 20 mg intravenously, in a randomized double-blinded manner prior to surgery. Plasma and urinary electrolytes, creatinine, prostaglandins PgE2 and PgF1 alpha, and thromboxane (TxB2) were collected 12 hours preoperatively and then for four days postoperatively. There were no significant differences in any of the measured parameters between the groups, at any of the measurement times. Mean (SD) creatinine clearance at baseline, 24 h and 48 h was 100.4 (29.7) and 86.9 (27.5), 128.1 (45.9) and 115.0 (40.3), 137.5 (50.7) and 121.6 (38.6) in the placebo and tenoxicam groups respectively (P = 0.28). Both groups required similar amounts of intraoperative ephedrine and intravenous fluids to maintain blood pressure. The minimal changes in plasma and renal parameters reflect predictable responses to major surgery and rehydration rather than any response to cyclooxygenase inhibition. This may underscore the importance of maintenance of blood pressure during the course of surgery and postoperative care, and perhaps the usefulness of a fluid loading regimen to preserve renal function during surgery. The predicted attenuation of renal prostaglandin-mediated protective mechanisms and enhancement of the catecholamine-mediated renal vasoconstriction by the use of a single 20 mg dose of tenoxicam in this study were not seen. Modulation of renal concentrating mechanisms or excretion of sodium and potassium by tenoxicam was not apparent and a large increase in study size would be required to detect a significant difference in these parameters as a consequence of the drug, over and above any changes in response to surgery and epidural anaesthesia.", "Parecoxib, a cyclo oxygenase-2 inhibiting non-steroidal anti-inflammatory drug, has been widely used for postoperative analgesia. Our aim was to quantify the benefit of a single dose after coronary artery bypass grafting.\n The investigation was carried out as a randomized double blind placebo controlled study. A single i.v. dose of parecoxib 40 mg or placebo was given at closure of sternotomy. No opioid other than morphine was given in the first 24 postoperative hours. Pain was assessed using both a Visual Analogue Score (1-10), and the amount of morphine used via a morphine patient controlled analgesia pump. Creatinine clearance was measured before and after operation from 24 h urine collections. After a global announcement by Pfizer that paracoxib was 'contraindicated in patients with ischaemic heart disease' further recruitment was suspended and the collected data from 40 patients were analysed.\n Twenty-one patients received parecoxib and 19 received placebo. Amongst those who received parecoxib, there was a highly significant sparing of rescue medication before tracheal extubation (P=0.004) compared with placebo, and an overall 35% morphine sparing effect during the first 6 h post extubation after correction for the variability in extubation time (P=0.037). Respiration, as measured by arterial carbon dioxide tension at the time of extubation, was significantly better in the parecoxib group (P=0.045). Significantly more furosemide was given for postoperative oliguria in those patients who received parecoxib (P=0.036). After correcting for differences in diuretic usage and fluid balance, parecoxib was associated with a significant increase in plasma creatinine (P=0.041).\n A single dose of parecoxib has a significant opioid sparing effect in the first 6 h after coronary artery bypass grafting which resulted in significantly improved ventilation with mild elevation of plasma creatinine within normal limits.", "Ketorolac is a nonsteroidal antiinflammatory agent with opioid-sparing properties. The effect of ketorolac on postoperative opioid analgesic requirement and surgical outcome was evaluated in 198 women after abdominal hysterectomy procedures using a double-blind protocol design.\n Patients were randomly assigned to receive either 60 mg intravenous (2 ml) ketorolac, followed by 30 mg intravenously (in saline 20 ml) over 30 min every 6 h, or 2 ml intravenous saline, followed by saline 20 ml intravenously over 30 min every 6 h, for up to 72 h. The postoperative opioid analgesic requirement was assessed using a patient-controlled analgesia (PCA) device to self administer either morphine or meperidine. The authors also evaluated pain, sedation (or drowsiness), fatigue, quality of sleep, and postoperative side effects at 2-8-h intervals for up to 72 h after surgery.\n Ketorolac decreased the PCA opioid usage on the night of operation and during the first postoperative day. Ketorolac also improved the quality of sleep during the first night after surgery. Although ketorolac- (vs. saline-) treated patients had a significantly shorter time to passage of bowel gas (50 +/- 24 h vs. 61 +/- 25 h), there were no clinically significant differences in the times to oral intake, unassisted ambulation, or hospital discharge. There were also no differences in the overall incidence of side effects in the ketorolac- (vs. saline-) treated patients. However, the use of ketorolac with opioid PCA was associated with a reduced need for antiemetic therapy on the postsurgical ward.\n The authors conclude that the opioid-sparing effects of ketorolac contributed few clinically significant advantages after abdominal hysterectomy procedures.", "Non-steroidal anti-inflammatory drugs (NSAIDs) are routinely used after coronary artery bypass surgery (CABG), yet their effects have seldom been evaluated in randomized controlled settings. The aim of this study was to examine the efficacy and safety of a commonly used NSAID, naproxen. We hypothesized that naproxen would reduce postoperative pain following CABG without increasing complications.\n Patients (N=98) undergoing primary CABG were randomized to receive naproxen (500 mg q12hX5 doses via suppository started 1h after operation, followed by oral 250 mg q8hX6 doses) or placebo. Standard analgesic and anti-emetic regimens were available to both patient groups. Interventions were double-blinded. Primary end-points were postoperative pain measured before and after chest physiotherapy by visual analog scale and pulmonary slow vital capacity (SVC).\n Baseline characteristics were equivalent between the two groups. Over the first 4 postoperative days, naproxen decreased pain by 47+/-17% on average before chest physiotherapy (P=0.034), and 44+/-13% after chest physiotherapy (P=0.0092). Patients who received naproxen also had better preservation of SVC over the first 4 postoperative days (mean loss of SVC from baseline: 2.1+/-0.1 vs. 2.5+/-0.1l, naproxen vs. placebo, P=0.0032). This was concomitant with a lower white blood cell count observed in naproxen patients (9.2+/-0.3 vs. 12.7+/-1.5x10(9)/l, naproxen vs. placebo, P=0.03). Patients who received naproxen had more chest tube drainage after 4h postoperatively, but there was no difference in the incidence or amount of transfusions. There was no difference in medication use, length of stay, or in the incidence of atrial fibrillation, azotemia, and other complications.\n Naproxen is an effective and low-cost adjunct for optimization of pain control and lung recovery after CABG. Its use may result in increased chest tube drainage, but no apparent increase in other complications.", "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.", "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.", "We have examined the effect of diclofenac on renal function after major surgery in a randomized, double-blind, controlled study of 20 patients undergoing oesophagogastrectomy. Diclofenac 75 mg or placebo was given i.m. 12-hourly for 2 days. I.v. fluid administration was standardized. Renal function was assessed by fluid balance and measurement of serum creatinine and electrolyte concentrations, creatinine and free water clearance, and urinary sodium and potassium excretion. Urinary 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) was measured by radioimmunoassay to assess renal prostacyclin production. After surgery, 6-keto-PGF1 alpha production increased, but this did not occur with diclofenac. On the first day after surgery, use of diclofenac was associated with a decreased urine flow rate, decreased urinary sodium and potassium excretion and a tendency to hyperkalaemia. Frusemide was required more often in the diclofenac group. One patient was withdrawn from the diclofenac group because of impaired renal function. Urine flow rate and blood potassium concentration should be monitored if diclofenac is used after major surgery.", "Fifty patients scheduled for elective cholecystectomy were randomised to receive either indomethacin suppositories 200 mg p.r. at the end of anaesthesia, followed by 100 mg bd for three days, or placebo suppositories according to the same regimen. All patients were given intravenous pethidine via patient-controlled analgesia (PCA) postoperatively. The mean dose of pethidine required by the patients in the indomethacin group was significantly less than that used by the placebo group, the cumulative dose after three days being 530.7 mg (SD 664.0) and 1151.0 mg (682.0) for the indomethacin and placebo groups respectively. At the same time the patients in the indomethacin group had lower pain scores both at rest and with movement, though this was only statistically significant on the first day on movement. There was no statistical difference between the groups with respect to the incidence of nausea, indigestion, proctitis, volume of drainage from the wound drain, or width of bruising around the wounds. Serum creatinine levels were compared pre- and postoperatively where possible and showed no change in either group.", "We designed a randomized, double-blind study to assess the analgesic efficacy and safety of perioperative ketorolac infusion in 95 patients undergoing cholecystectomy. The ketorolac group (n = 48) received premedication, combined with ketorolac 30 mg intramuscularly (IM), followed by a ketorolac continuous infusion (2 mg/h). The control group (n = 47) received an IM bolus of NaCl 0.9% (1 mL) followed by continuous saline infusion (2 mL/h) for 24 h. Operative blood losses, postoperative pain, sedation, and on-demand morphine consumption (patient-controlled analgesia [PCA]) were measured. The effects on plasma catecholamines, cortisol, potassium, creatinine, skin bleeding time, prothrombin time (PT), and partial thromboplastin time (PTT) were also evaluated. Ketorolac improved pain scores (P < 0.05) and reduced plasma cortisol concentrations between 2 and 6 h (P < 0.05). No significant differences were observed concerning operative blood losses, glucose concentration, and renal and hemostatic functions. The ketorolac group required less morphine (not significant [NS]) than the control group and had less adverse effects (P = 0.002). Thus, perioperative ketorolac infusion improved the quality of postoperative pain relief, and had no major influence on endocrine-metabolic response and no negative influences on hemostatic and renal functions. This study suggests that preventive ketorolac administration, followed by a continuous infusion, is an easy, useful, and safe method for pain control after abdominal surgery.", "In a double-blind, placebo-controlled clinical trial (power of 80% to detect a 30% reduction in morphine consumption, P < 0.05), we have determined that the administration of two doses of intravenous ketoprofen 100 mg, one at the end of surgery and the second 12 hours postoperatively, was associated with a significant reduction in morphine consumption at eight (P = 0.028), 12 (P = 0.013) and 24 hours (P = 0.013) but not four hours (P = 0.065) postoperatively, as compared to placebo, when assessed by patient-controlled analgesia. There was no difference between the groups in pain scores or in the incidence of nausea and vomiting. One patient in the placebo group suffered from excessive sedation while one patient from the ketoprofen group suffered from transient oliguric renal failure. There were no other adverse effects. The results of this study show that ketoprofen does provide a morphine-sparing effect in the management of postoperative pain after abdominal surgery.", "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.", "There are few studies in which ketoprofen, a propionic acid derivate NSAID, has been tested as an intravenous postoperative analgesic. The aim of this double-blind, randomized, placebo-controlled work was to study the tolerability and efficacy of intravenous ketoprofen in seventy-six patients undergoing hip or knee total endoprothesis surgery using three different doses.\n The patients received either ketoprofen 50 mg, 100 mg or 150 mg, or placebo as an initial intravenous loading, followed by an infusion containing 50 mg, 100 mg or 150 mg or placebo, respectively, over the following eleven and a half hours. The consumption of fentanyl was recorded and the patients assessed their pain intensity on a 10-cm visual analogue scale (VAS) at 0, 2, 4 and 12 hours. Possible side-effects were recorded at the same intervals.\n Patients receiving ketoprofen showed significantly lower total fentanyl consumption and significantly better pain relief at 12 hours was achieved by a 300 mg dose of ketoprofen than by placebo. Side-effects were minimal, with no differences between the groups.\n A bolus of ketoprofen following continuous infusion of ketoprofen, coupled with a PCA-system, was an effective and safe approach for the relief of postoperative pain.", "We have studied the efficacy of a continuous i.v. infusion of diclofenac 2 mg kg-1/24 h given for 2 days after major thoracic surgery in 30 patients in a double-blind, placebo-controlled, parallel-group design. The patients were able to obtain additional pain relief as on demand morphine boluses. In the diclofenac group, the consumption of morphine was reduced by 60% during the first and by 76% during the second day after operation compared with the control group. Overall, analgesia was also superior in the diclofenac group. Arterial oxygenation was significantly greater and the arterial PCO2 increased less during the first day after operation in the diclofenac group compared with the control group. Diclofenac had no significant effect compared with placebo on blood loss or on any bleeding or platelet test. Urine output was significantly less during the first day after operation in the diclofenac group compared with the control group, but was normal on the second day after operation; plasma creatinine concentrations were unchanged. I.v. diclofenac infusion combined with opioids delivered via a patient-controlled analgesia device seems a valuable method of pain relief after thoracic surgery in patients in whom more invasive techniques, such as extradural local anaesthetics and opioids, cannot be used. However, non-steroidal anti-inflammatory drugs should be used cautiously, if at all, in patients who are at risk of acute renal failure.", "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.", "Ketorolac is a nonsteroidal analgesic that may provide postoperative analgesia without opioid-related side effects. This double-blind, randomized, multicenter study evaluated the analgesic efficacy and safety of intravenous ketorolac in 207 patients during the first 24 h after major surgery.\n Subjects were assigned to receive one of three analgesic regimens: a ketorolac infusion, ketorolac boluses, or placebo. All subjects had access to intravenous morphine via patient-controlled analgesia (PCA). Evaluations included PCA morphine used, pain assessment (categorical pain intensity scores and visual analogue pain scores), pain relief (categorical pain relief scores), sedation, presence of adverse events, and overall rating of regimens by study observers and patients.\n Patients in the ketorolac infusion group (but not the ketorolac bolus group) used less morphine (average 33 mg) than did the placebo group (44 mg) (P = 0.009). Significant differences favoring both ketorolac groups were seen in the pain intensity and the categorical pain relief scores at various time points during the study. At the termination of the study, compared with the placebo group, categorical pain intensity scores were lower in the ketorolac bolus group; visual analogue pain scores were lower in both ketorolac groups; and pain relief scores were higher in the ketorolac bolus group. The incidence of vomiting was significantly greater in the placebo group (27%) than in the ketorolac infusion group (12%) or bolus group (9%) (P = 0.032 and P = 0.005, respectively). The incidence of postoperative fever was 10% in the ketorolac bolus group and 25% in the placebo group (P = 0.013). Study observers noted less nursing difficulty while caring for patients in the ketorolac infusion group (P = 0.015). Study observers and patients in both ketorolac groups reported statistically significant overall drug superiority compared with placebo.\n It is concluded that intravenous boluses or infusions of ketorolac in conjunction with PCA morphine provide effective, safe analgesia after major surgery and improve on the response to PCA morphine alone.", "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.", "To decrease postoperative dependence on narcotics for analgesia, we have evaluated ketorolac as an adjunct to perioperative pain control in patients undergoing laparoscopic urologic surgery.\n Sixty-five patients (34 male, 31 female) were randomized to receive either ketorolac tromethamine (15-30 mg IV q 6 h) or placebo prior to laparoscopic surgery. Patient-controlled analgesia in the form of morphine sulfate was provided. Operative factors such as the type of surgery, operative time, and estimated blood loss were recorded. Postoperative factors such as analog pain score (range 0-10), narcotic usage, and length of stay were evaluated.\n Fifty-five patients completed the study. The average pain score was 2.2 and 4.5 for the ketorolac and placebo groups, respectively (P < 0.005). The mean amounts of total morphine used were 39.2 mg (ketorolac) and 62.5 mg (placebo) (P = 0.077). The length of stay was not significantly different in the ketorolac (2.5 days) and placebo (2.6 days) groups (P = 0.74). Operative times (P = 0.21) and estimated blood loss (P = 0.60) were not significantly different in the two groups. Ketorolac did not adversely affect renal function; serum creatinine changes were not significantly different from those in the patients receiving placebo (P = 0.50). Laparoscopic pyeloplasty necessitated more narcotic analgesia than did other laparoscopic procedures (P = 0.05).\n Ketorolac decreases the subjective perception of pain after laparoscopic urologic surgery. It is suggested that ketorolac administration decreases the amount of narcotic usage as well. Time to resumption of oral intake and length of hospital stay were not influenced by use of ketorolac.", "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.", "We studied intensity of pain, cumulative morphine consumption, ventilatory and renal function, and haemostasis in patients undergoing video-assisted thoracoscopic surgery and receiving a 2-day i.v. infusion of diclofenac, ketorolac or saline. Plasma concentrations of the two NSAID were also measured. The study was randomized, double-blind and placebo-controlled, with 10 patients in each group. Patients experienced mainly moderate pain. Mean consumption of i.v. morphine during the first day after operation was 57 (SEM 11) mg in the placebo group. Diclofenac and ketorolac were equally effective in reducing total morphine consumption (61% and 52%, respectively). Adverse events were similar and minor. Greater variability in plasma concentrations of ketorolac were detected compared with diclofenac." ]

[ "2842677", "14551893", "9359740", "11803060", "4325804", "14575762", "2561722" ]

[ "Protection against Japanese encephalitis by inactivated vaccines.", "Chimeric live, attenuated vaccine against Japanese encephalitis (ChimeriVax-JE): phase 2 clinical trials for safety and immunogenicity, effect of vaccine dose and schedule, and memory response to challenge with inactivated Japanese encephalitis antigen.", "Short-term safety of live attenuated Japanese encephalitis vaccine (SA14-14-2): results of a randomized trial with 26,239 subjects.", "Clinical proof of principle for ChimeriVax: recombinant live, attenuated vaccines against flavivirus infections.", "A controlled field trial for an evaluation of effectiveness of mouse-brain Japanese encephalitis vaccine.", "Non-clinical and phase I clinical trials of a Vero cell-derived inactivated Japanese encephalitis vaccine.", "A field trial of Japanese encephalitis vaccine produced in Thailand." ]

[ "Encephalitis caused by Japanese encephalitis virus occurs in annual epidemics throughout Asia, making it the principal cause of epidemic viral encephalitis in the world. No currently available vaccine has demonstrated efficacy in preventing this disease in a controlled trial. We performed a placebo-controlled, blinded, randomized trial in a northern Thai province, with two doses of monovalent (Nakayama strain) or bivalent (Nakayama plus Beijing strains) inactivated, purified Japanese encephalitis vaccine made from whole virus derived from mouse brain. We examined the effect of these vaccines on the incidence and severity of Japanese encephalitis and dengue hemorrhagic fever, a disease caused by a closely related flavivirus. Between November 1984 and March 1985, 65,224 children received two doses of monovalent Japanese encephalitis vaccine (n = 21,628), bivalent Japanese encephalitis vaccine (n = 22,080), or tetanus toxoid placebo (n = 21,516), with only minor side effects. The cumulative attack rate for encephalitis due to Japanese encephalitis virus was 51 per 100,000 in the placebo group and 5 per 100,000 in each vaccine group. The efficacy in both vaccine groups combined was 91 percent (95 percent confidence interval, 70 to 97 percent). Attack rates for dengue hemorrhagic fever declined, but not significantly. The severity of cases of dengue was also reduced. We conclude that two doses of inactivated Japanese encephalitis vaccine, either monovalent or bivalent, protect against encephalitis due to Japanese encephalitis virus and may have a limited beneficial effect on the severity of dengue hemorrhagic fever.", "ChimeriVax-JE is a live, attenuated vaccine against Japanese encephalitis, using yellow fever (YF) 17D vaccine as a vector. In a double-blind phase 2 trial, 99 adults received vaccine, placebo, or YF 17D vaccine (YF-VAX). ChimeriVax-JE was well tolerated, with no differences in adverse events between treatment groups. Viremias resulting from administration of ChimeriVax-JE and YF-VAX were of short duration and low titer; 82 (94%) of 87 subjects administered graded doses (1.8-5.8 log(10)) of ChimeriVax-JE developed neutralizing antibodies. A second dose, administered 30 days later, had no booster effect. Previous inoculation with YF did not interfere with ChimeriVax-JE, but there was a suggestion (not statistically significant) that ChimeriVax-JE interfered with YF-VAX administered 30 days later. A separate study explored immunological memory both in subjects who had received ChimeriVax-JE 9 months before and in ChimeriVax-JE-naive subjects challenged with inactivated mouse-brain vaccine (JE-VAX). Anamnestic responses were observed in preimmune individuals. ChimeriVax-JE appears to be a safe vaccine that provides protective levels of neutralizing antibody after a single dose.", "The short-term safety of an effective and inexpensive new live attenuated Japanese encephalitis vaccine (SA14-14-2) was studied in a randomized trial, using block randomization. Of 26,239 children who were enrolled, half received the vaccine and half served as controls. Subjects were prospectively followed for 30 days for severe adverse events, such as encephalitis, meningitis, and \"all-cause\" hospitalization. No cases of encephalitis or meningitis occurred in either group. The upper 95% confidence limit for adverse events not occurring among subjects receiving their first dose was 4.1/10,000. Risk ratios and 95% confidence intervals for other adverse events were 0.70 (0.43-1.15) for all-cause hospitalization, 0.91 (0.37-2.22) for seizure, and 0.79 (0.56-1.11) for fever lasting > or = 3 days. These data attest to the short-term safety of the SA14-14-2 virus strain and the hamster kidney cell substrate.", "ChimeriVax is a live, attenuated recombinant virus constructed from yellow fever (YF) 17D in which the envelope protein genes of YF 17D are replaced with the corresponding genes of another flavivirus. A ChimeriVax vaccine was developed against Japanese encephalitis (JE). A randomized, double-blind, outpatient study was conducted to compare the safety and immunogenicity of ChimeriVax-JE and YF 17D. Six YF immune and six non-immune adults were randomized to receive a single SC inoculation of ChimeriVax-JE (5log(10)PFU), ChimeriVax-JE (4log(10)PFU) or YF-VAX((R)) (5log(10)PFU). Mild, transient injection site reactions and flu-like symptoms were noted in all treatment groups, with no significant difference between the groups. Nearly all subjects inoculated with ChimeriVax-JE at both dose levels developed a transient, low-level viremia which was similar in magnitude and duration to that following YF-VAX). Neutralizing antibody seroconversion rates to ChimeriVax-JE was 100% in the high and low dose groups in both naïve and YF immune subjects; seroconversion to wild-type JE strains was similar or lower than to the homologous (vaccine) virus. Mean neutralizing antibody responses were higher in the ChimeriVax-JE high dose groups (naïve subjects LNI 1.55, PRNT(50) 254; YF immune subjects LNI 2.23, PRNT(50) 327) than in the low dose groups (naïve subjects 1.38, PRNT(50) 128; YF immune subjects LNI 1.62, PRNT(50) 270). JE antibody levels were higher in YF immune than in naïve subjects, dispelling concerns about anti-vector immunity. The safety and immunogenicity profile of ChimeriVax-JE vaccine appears to be similar to that of YF 17D. The new vaccine holds promise for prevention of JE in travelers and residents of endemic countries. The ChimeriVax technology platform is being exploited for development of new vaccines against dengue and West Nile.", "nan", "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.", "nan" ]

[ "8895624", "18442423", "9007770", "15902862", "1537158", "1512910", "16445331", "3188866", "11307132", "2743665", "9802665", "8615108", "3430154" ]

[ "Rehabilitation after total knee arthroplasty: a comparison of 2 rehabilitation techniques.", "Effectiveness of prolonged use of continuous passive motion (CPM), as an adjunct to physiotherapy, after total knee arthroplasty.", "The effect of continuous passive motion duration and increment on range of motion in total knee arthroplasty patients.", "A comparison of 2 continuous passive motion protocols after total knee arthroplasty: a controlled and randomized study.", "The influence of continuous passive motion on the results of total knee arthroplasty.", "A controlled evaluation of continuous passive motion in patients undergoing total knee arthroplasty.", "Effectiveness of continuous passive motion and conventional physical therapy after total knee arthroplasty: a randomized clinical trial.", "No effect of continuous passive motion after arthroplasty of the knee.", "Use of continuous passive motion after total knee arthroplasty.", "Continuous passive motion versus physical therapy in total knee arthroplasty.", "Home continuous passive motion machine versus professional physical therapy following total knee replacement.", "Continuous passive motion compared to active physical therapy after knee arthroplasty: similar hospitalization times in a randomized study of 68 patients.", "Continuous passive motion after total knee arthroplasty." ]

[ "This study was conducted to compare postoperative total knee arthroplasty rehabilitation protocols. The hypothesis of this study was that patients undergoing total knee arthroplasty could achieve range of motion and hospital discharge in the same period using a postoperative rehabilitation protocol that did not use a continuous passive motion machine. This randomized prospective study compared 46 total knee arthroplasties in which a continuous passive motion machine was used with 37 total knees that were rehabilitated with early passive flexion of the knee (named drop and dangle protocol). Postoperative physical therapy regimens were otherwise the same for both groups. Surgical technique was the same for both groups except for closure which was performed in the drop and dangle group with the knee at 90 degrees to 95 degrees flexion. Only patients with osteoarthritis were included in the study, and in both groups of patients received the same prosthetic components. Patients in the drop and dangle group were discharged from the hospital 1 day earlier (p = 0.01) and had a statistically better extension range of 2.8 degrees at 6 months (p = 0.03). Knees in the drop and dangle group had less drainage (p = 0.06). Range of motion and hospital discharge can be achieved in a similar time interval with the drop and dangle technique as with using a continuous passive motion device, and that such a device is not required for postoperative knee rehabilitation.", "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.", "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.", "Effect of continuous passive motion (CPM) protocols on outcomes after total knee arthroplasty. In this prospective randomized controlled study, 147 patients were assigned to 1 of 3 treatment groups: CPM from 0 degrees to 40 degrees and increased by 10 degrees per day, CPM from 90 degrees to 50 degrees (early flexion) and gradually progressed into full extension over a 3-day period, and a no-CPM group. The CPM was administered twice a day for 3 hours over a 5-day period. All patients participated in the same postoperative physiotherapy program. Patients were assessed preoperatively, day 5, 3 months, and 1 year postoperatively. The early flexion group had significantly more range of flexion than both the standard and control groups at day 5. There was no significant difference between the groups for any other variable tested at any time frame. Key words: total knee arthroplasty, CPM, rehabilitation, outcomes.", "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.", "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.", "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.", "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.", "Sixty primary total knee arthroplasties in 43 Chinese patients were included into a prospective study. Twenty-six patients who had unilateral knee arthroplasty were randomized to receive continuous passive motion (CPM) or immobilization in the first week. The 2 groups of patients were comparable in demographic data and preoperative knee range of motion (ROM). In 17 patients who had 1-stage sequential bilateral arthroplasties, one side had CPM and the other side was immobilized. The active knee ROM was assessed regularly until 1 year after the operation. For all patients, the early active knee ROM in the CPM group was significantly better than the immobilization group. There was no difference after 7 days, however. For patients who had 1-stage bilateral total knee arthroplasties, the active knee ROM was significantly better on the CPM side until day 28. After 4 weeks, there was no difference between the CPM group and the immobilization group. Immobilization after total knee arthroplasty does not preclude good ROM.", "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.", "A vigorous rehabilitation program following discharge from the hospital is necessary for patients having a total knee arthroplasty to maintain and improve range of motion and function. To compare the effectiveness of the continuous passive motion (CPM) machine as a home therapy program versus professional physical therapy, a prospective, comparative, randomized clinical study of 103 consecutive primary total knee arthroplasties in 80 patients (23 bilateral) was performed. The CPM group consisted of 37 patients (49 knees), and the physical therapy group consisted of 43 patients (54 knees). At 2 weeks, knee flexion was similar in the two groups, but a flexion contracture was noted in the CPM group (4.2 degrees). This difference is felt by the authors to be clinically insignificant. At 6 months, there were no differences in knee scores, knee flexion, presence of flexion contracture, or extensor lag between the two groups. The cost for the CPM machine group was $10,582 ($286 per patient), and the cost for professional therapy was $23,994 ($558 per patient). We conclude that the CPM machine after the hospital discharge of patients having total knee replacement is an adequate rehabilitation alternative with lower cost and with no difference in results compared with professional therapy.", "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.", "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." ]

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[ "Selective decontamination of the digestive tract in neurosurgical intensive care unit patients: a double-blind, randomized, placebo-controlled study.", "Selective intestinal decontamination in multiple trauma patients: prospective, controlled trial.", "Prevention of infection in critically ill patients by selective decontamination of the digestive tract.", "Utility of selective digestive decontamination in mechanically ventilated patients.", "Randomized, controlled trial of selective digestive decontamination in 600 mechanically ventilated patients in a multidisciplinary intensive care unit.", "Selective decontamination of the digestive tract in multiple trauma patients. A prospective double-blind, randomized, placebo-controlled study.", "Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study.", "Selective decontamination of the digestive tract with norfloxacin in the prevention of ICU-acquired infections: a prospective randomized study.", "Oropharyngeal decontamination with gentamicin for long-term ventilated patients on stress ulcer prophylaxis with sucralfate?", "Intestinal decontamination for control of nosocomial multiresistant gram-negative bacilli. Study of an outbreak in an intensive care unit.", "Prevention of colonization and respiratory infections in long-term ventilated patients by local antimicrobial prophylaxis.", "Antibiotic prophylaxis of respiratory tract infection in mechanically ventilated patients. A prospective, blinded, randomized trial of the effect of a novel regimen.", "The effect of selective decontamination of the digestive tract on colonisation and infection rate in multiple trauma patients.", "Prevention of nosocomial lung infection in ventilated patients: use of an antimicrobial pharyngeal nonabsorbable paste.", "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.", "Effectiveness and cost of selective decontamination of the digestive tract in critically ill intubated patients. A randomized, double-blind, placebo-controlled, multicenter trial.", "Prevention of nosocomial infection in critically ill patients by selective decontamination of the digestive tract. A randomized, double blind, placebo-controlled study.", "Selective decontamination of subglottic area in mechanically ventilated patients with multiple trauma.", "The effect of selective decontamination of the digestive tract on mortality in multiple trauma patients: a multicenter randomized controlled trial.", "Prevention of acquired infections in intubated patients with the combination of two decontamination regimens.", "Decrease in nosocomial pneumonia in ventilated patients by selective oropharyngeal decontamination (SOD).", "Prevention of colonization and infection in critically ill patients: a prospective randomized study.", "Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled 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.", "Selective gut decontamination reduces nosocomial infections and length of stay but not mortality or organ failure in surgical intensive care unit patients.", "Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia. A randomized, placebo-controlled, double-blind clinical trial." ]

[ "The aim of this study was to assess, in a selected population, the effects of selective decontamination of the digestive tract on colonization of the oropharynx, trachea, stomach and rectum, and on the infection rate. An economical assessment was also performed.\n A prospective, double-blind, randomized, placebo-controlled, dual-center trial.\n Two neurosurgical intensive care units.\n A total of 191 comatose patients admitted emergently and intubated within < 24 hrs were enrolled. Of these patients, 68 were excluded because they either died, got an early infection, or were extubated within the first 5 days. A total of 123 patients were analyzed: 63 treated and 60 placebo patients.\n Topical antibiotics (tobramycin, polymyxin E, amphotericin B) were applied in the oropharynx and in the stomach. Vancomycin was added in the oropharyngeal paste. Placebo patients received the same regimen (i.e., a suspension of fluid and a paste) but without antibiotics. No parenteral antibiotics were given during the study period.\n Bronchopneumonia episodes were diagnosed with protected specimen brush or plugged telescoping catheter and other infections were diagnosed according to the Center for Disease Control of Atlanta criteria. Antibiotic costs and cost per survivor were calculated. Selective decontamination of the digestive tract significantly reduced Gram-negative bacilli colonization as well as the number of episodes of bronchopneumonia, urinary tract infections, and sinusitis. Despite the addition of vancomycin, Staphylococcus aureus remained the main potential pathogen causing tracheal colonization and subsequent bronchopneumonia. The reduction in bronchopneumonia rate was observed in head-trauma patients only. We were able to show that: a) the trachea was the main reservoir of microorganisms responsible for pneumonia; b) pneumonia developed after tracheal colonization. Total charges for antibiotics were 2.8 times higher in the treated group than in the placebo group; in calculating the cost per survivor, selective decontamination of the digestive tract might be beneficial due to the reduced length of stay.\n Selective decontamination of the digestive tract is an effective technique in reducing infectious morbidity in comatose neurosurgical patients. Because of its cost, this technique should be used only in selected populations.", "Reduction of potential pathogens by selective intestinal decontamination has been proposed to improve intensive care. Despite large scientific interest in this method, little is known about its benefit in homogeneous trauma populations.\n In a prospective, controlled study, we enrolled non-infected trauma patients (age over 18 years, mechanical ventilation > or = 48 hours, intensive care for more than 3 days) who primarily were admitted to our university medical center. We randomized patients to be treated with two different topical regimens (polymyxin, tobramycin, and amphotericin (PTA) or polymyxin, ciprofloxin, amphotericin (PCA)) or the carrier only (placebo), administered four times daily both to the oropharynx and to the gastrointestinal tract. All patients received intravenous ciprofloxacin (200 mg, bd) for 4 days.\n Of 357 enrolled patients, 310 (age 38.0 +/- 16.5 years, Injury Severity Score 35.2 +/- 12.7) met all inclusion criteria. Selective decontamination successfully reduced intestinal bacterial colonization. However, we did not identify significant differences between groups regarding pneumonia (PTA 47.5%, PCA 39.0%, placebo 45.3%), sepsis (PTA 47.5%, PCA 37.8%, placebo 42.6%), multiple organ failure (PTA 56.3%; PCA 52.4%, placebo 58.1%), and death (PTA 11.3%, PCA 12.2%, placebo 10.8%). Total costs per patient were highest with the PTA regimen.\n We found no benefit of selective decontamination in trauma patients. Apparently, bacterial overgrowth in the intestinal tract is not the sole link between trauma, sepsis, and organ failure.", "To determine whether selective decontamination of the digestive tract using oral and nonabsorbable antimicrobial agents and parenteral cefotaxime prevents infection in critically ill patients.\n Randomized, controlled trial without blinding.\n Surgical trauma and medical intensive care units in a tertiary referral hospital.\n One hundred fifty patients admitted to surgical trauma and medical intensive care units during a 3-year interval, whose condition suggested a prolonged stay (greater than 3 days).\n Patients were randomly allocated to an experimental group (n = 75) that received cefotaxime, 1 g intravenously every 8 hours for the first 3 days only, and oral, nonabsorbable antibiotics (gentamicin, polymyxin, and nystatin by oral paste and oral liquid) for the entire stay in the intensive care unit. Control patients (n = 75) received usual care.\n The number of infections, total hospital days, and deaths, as well as the number of days in intensive care unit, were recorded.\n Control patients experienced more infections (36 compared with 12, P = 0.04), including bacteremias (14 compared with 4, P = 0.05) and pulmonary infections (14 compared with 4, P = 0.03). Although total hospital days, days in intensive care, and the overall death rate all were lower in the treatment group, these differences were not statistically significant. Clinically important complications of selective decontamination of the digestive tract were not encountered.\n Selective decontamination of the digestive tract decreases subsequent infection rates, especially by gram-negative bacilli, in selected patients during long-term stays in the intensive care unit.", "To assess selective digestive decontamination for preventing nosocomial pneumonia and mortality in mechanically ventilated patients.\n Prospective, randomized, placebo-controlled, double-blind study.\n Respiratory intensive care unit of a 1000-bed teaching hospital.\n 80 patients receiving mechanical ventilation for more than 72 hours.\n Patients received selective digestive decontamination using polymyxin E, tobramycin, and amphotericin B through a nasogastric tube and also topically in the oropharynx; control patients received placebo. All patients received intravenous cefotaxime for 4 days or other systemic antibiotics if required.\n Bacteriologic surveillance (three times a week) was done by quantitatively culturing tracheal aspirates, pharyngeal swabs, and gastric juice. The diagnosis of pneumonia was based on quantitative cultures of protected specimen brush samples (> or = 10(3) CFU/mL [colony forming units/mL]) or bronchoalveolar lavage fluid (> or = 10(4) CFU/mL) and autopsy findings.\n Bronchial, oropharyngeal, and gastric colonization by gram-negative bacilli and Candida species was lower in the selective digestive decontamination group compared with the placebo group. Nonsignificant differences were found in the incidence of nosocomial infections (28% compared with 37%; odds ratio, 0.66; 95% CI, 0.35 to 1.25) and nosocomial pneumonia (18% compared with 24%; odds ratio, 0.7; CI, 0.33 to 1.46) and in the crude mortality rate (31% compared with 27%; odds ratio, 1.21; CI, 0.63 to 2.34) when comparing digestive decontamination with placebo, respectively.\n Selective digestive decontamination in our mechanically ventilated patients significantly decreased the colonization rate of gram-negative bacilli and of Candida species but not of Staphylococcus aureus. It did not decrease the incidence of nosocomial pneumonia, mortality, length of stay, or the duration of mechanical ventilation.", "To evaluate the efficacy of two regimens of selective decontamination of the digestive tract in mechanically ventilated patients.\n Prospective, randomized, concurrent trial.\n Multidisciplinary intensive care unit (ICU) in a 1,800-bed university hospital.\n Consecutive patients (n = 660) who were likely to require mechanical ventilation for at least 48 hrs were randomized to one of three groups: conventional antibiotic regimen (control group A); oral and enteral ofloxacin-amphotericin B (group B); and oral and enteral polymyxin E-tobramycin-amphotericin B (group C). Both treatment groups received systemic antibiotics for 4 days (ofloxacin in group B and cefotaxime in group C).\n Patients were randomized to receive standard treatment (control group A, n = 220), selective decontamination regimen B (group B, n = 220), and selective decontamination regimen C (group C, n = 220). After early deaths and exclusions from the study, 185 controls (group A) and 193 (group B)/200 (group C) selective decontamination regimen patients were available for analysis.\n Measurements included colonization and primary/secondary infection rate, ICU mortality rate, emergence of antibiotic resistance, length of ICU stay, and antimicrobial agent costs. The study duration was 19 months. The patient groups were fully comparable for age, diagnostic category, and severity of illness. One third of patients in each group suffered a nosocomial infection at the time of admission. There was a significant difference between treatment group B and control group A in the number of infected patients (odds ratio of 0.42, 95% confidence interval of 0.27 to 0.64), secondary lower respiratory tract infection (odds ratio of 0.47, 95% confidence interval of 0.26 to 0.82), and urinary tract infection (odds ratio of 0.47, 95% confidence interval of 0.27 to 0.81). Significantly more Gram-positive bacteremias occurred in treatment group C vs. group A (odds ratio of 1.22, 95% confidence interval 0.72 to 2.08). Infection at the time of admission proved to be the most significant risk factor for subsequent infection in control and both treatment groups. ICU mortality rate was almost identical (group A 16.8%, group B 17.6%, and group C 15.5%) and was not significantly related to primary or secondary infection. Increased antimicrobial resistance was recorded in both treatment groups: tobramycin-resistant enterobacteriaceae (group C 48% vs. group A 14%, p < .01), ofloxacin-resistant enterobacteriaceae (group B 50% vs. group A 11%, p < .02), ofloxacin-resistant nonfermenters (group B 81% vs. group A 52%, p < .02), and methicillin-resistant Staphylococcus aureus (group C 83% vs. group A 55%, p < .05). Antimicrobial agent costs were comparable in control and group C patients; one third less was spent for group B patients.\n In cases of high colonization and infection rates at the time of ICU admission, the preventive benefit of selective decontamination is highly debatable. Emergence of multiple antibiotic-resistant microorganisms creates a clinical problem and a definite change in the ecology of environmental, colonizing, and infecting bacteria. The selection of multiple antibiotic-resistant Gram-positive cocci is particularly hazardous. No beneficial effect on survival is observed. Moreover, selective decontamination adds substantially to the cost of ICU care.", "Study objective: The aims of the study were to evaluate the technique of selective digestion decontamination (SDD) in preventing the development of nosocomial infections in a selected population and to assess the effects on colonization of the oropharynx, nares, and bronchi. A financial assessment was also performed. Design: Prospective, double-blind, randomized placebo-controlled trial using amphotericin B, colistin sulfate (polymixin E), and gentamicin applied to the nares, the oropharynx, and enterally; no parenteral antibiotics were given during the study period. The SDD was applied every 6 h during the study period. Setting: Multidisciplinary ICU in a university hospital. Patients: A total of 148 trauma patients admitted emergently and intubated within less than 24 h were enrolled. Seventy-two patients who received placebo and 76 treated patients were analyzed on an \"intention-to-treat\" basis. Interventions: Microbiologic surveillance samples of oropharyngeal and bronchial secretions, urine, and any other potentially infected sites were taken at the time of ICU admission and twice weekly thereafter until discharge from the unit. Measurements and results: With the use of SDD, colonization was significantly reduced in the oropharynx and nares (<0.05) but not in bronchi. However, episodes of bronchopneumonia were significantly reduced (19 in the active group vs 37 in the placebo group; p,0.01). Staphylococcus aureus remained the main potential pathogen causing bronchial colonization and subsequent bronchopneumonia. There was no reduction in the incidence of other infections. Days in the ICU, duration of mechanical ventilation, and mortality rate were unchanged. After the use of SDD, Gram-positive colonization tended to increase and this was mainly due to methicillin-resistant coagulase-negative staphylococci. The total cost of antibiotic therapy ($62,117 [US] in the placebo group and $36,008 in the SDD group) was decreased by 42% with the use of SDD. Clinically important complications of SDD were not encountered. Conclusions: The use of SDD in this population of trauma patients reduced the incidence of bronchopneumonia and the total charge for antibiotics. Stay in the ICU, mechanical ventilation, and mortality rate were unchanged. Methicillin-resistant coagulase-negative staphylococci were selected by SDD in some patients and the clinical relevance of this colonization needs further evaluation.", "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", "The efficacy of a relatively cheap regimen of selective decontamination (SDD) was evaluated in a diverse population of ICU patients. Patients requiring prolonged ICU stay (greater than 5 days) were randomly allocated to a treatment group or control group. Control patients (n = 52) received perioperative antimicrobial prophylaxis and antibiotic treatment was instituted only on sound clinical and bacteriological criteria. Treated patients (n = 48) received gastro-intestinal and oro-pharyngeal decontamination with polymyxin E, norfloxacin, amphotericin B and systemic antibiotic prophylaxis with trimethoprim until decontamination was achieved. The rate of gram-positive infections was not altered by SDD. The incidence of gram-negative respiratory tract, urinary tract and line infections was significantly reduced from 44%, 27% and 15% respectively in the control group to 6%, 4% and 0% in the treatment group. Mortality from nosocomial sepsis and overall mortality were also significantly reduced from 15% and 54% to 0% and 31% respectively. The ICU stay was not reduced by SDD, nor was time on the ventilator or use of therapeutic antibiotics. The reduction in morbidity and mortality was achieved at a relatively low cost.", "The incidence of nosocomial pneumonia in long-term ventilated patients has been reduced by stress ulcer prophylaxis with sucralfate. In a double-blind trial we studied whether gentamicin administered topically to the oropharynx (OPG) had additional clinical benefits in these patients. 67 critically ill adult patients fulfilled entry criteria for > or = 5 days on ventilation. The OPG group received 40 mg gentamicin, the control group received 5% dextrose topically administered to the oropharynx 4 times a day. During OPG, pharyngeal colonization rate (21 vs 44%) and tracheal secretion colonization rate (12 vs 41%) were significantly lower than during placebo (p < 0.05). Despite these differences nosocomial pneumonia rate (3 vs 12%), duration of mechanical ventilation [15.8 +/- 11.1 vs 19.9 +/- 37.5 days (means +/- SD)] and mortality (27 vs 41%) were not significantly affected by OPG. Moreover, 13 of 15 bacteria (87%) that occurred during OPG were resistant to gentamicin. Despite its reduction of bacterial colonization rates of pharyngeal and tracheal secretions, OPG did not seem to offer additional clinical benefits in long-term mechanically ventilated patients on stress ulcer prophylaxis with sucralfate.", "To study the efficacy of intestinal decontamination by oral nonabsorbable antibiotic agents to control a nosocomial outbreak of intestinal colonization and infection with multiresistant Enterobacteriaceae, and to examine its effects on endemic nosocomial infection rates.\n A 10-week prospective incidence study (group 1), and then an 8-week randomized, open trial of intestinal decontamination (groups 2 and 3).\n A medical intensive care unit of a tertiary care university hospital.\n Consecutive patients with unit stay of over 2 days and a severity score at admission of more than 2; 124 patients were included in group 1, 50 in group 2 (control), and 36 in group 3 (intestinal decontamination).\n Neomycin, polymyxin E, and nalidixic acid were given to group 3 patients throughout their stay in the unit.\n Intestinal colonization with multiresistant strains occurred in 19.6% of patients in group 1, at a mean of 16 days after admission, and preceded detection in clinical samples by a mean of 11 days. During the decontamination trial, intestinal colonization rates decreased to 10% (group 2), and 3% (group 3) (P = 0.12 and P less than 0.01, compared with group 1, respectively). Corresponding infection rates were 9% (group 1), 3% (group 2), and 0 (group 3). No new cases were detected in the following 4 months. The intestinal colonization rate with gram-positive cocci was higher in group 3 than group 2 (P less than 0.001). The overall rate of nosocomial infections was at 28% (group 1), 33% (group 2), and 32% (group 3).\n Intestinal decontamination can help to control an outbreak of intestinal colonization and infection with multiresistant gram-negative bacilli in the intensive care unit, but should not be recommended for routine prevention of endemic nosocomial infections.", "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.", "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.", "122 multiple trauma patients staying in the ICU for 5 or more days and needing mechanical ventilation were investigated to determine the effect of selective decontamination of the digestive tract on prevention of infection. The (retrospectively studied) control group of 59 patients received no antibiotic prophylaxis. The infection rate during ICU-stay was 81%. Most infections were caused by potentially pathogenic microorganisms (PPM) from the oral cavity or the intestines (i.e. endogenous infections). The oropharynx and the intestines were rapidly colonised with ICU-associated gram-negative bacilli. After 2 weeks more than 80% of patients were found colonised. This secondary colonisation of the digestive tract is a very important stage in the pathogenesis of infections. Sixty-three patients were selectively decontaminated with nonabsorbable antibiotics, administered through the gastric tube even if peristalsis was absent. Emphasis was laid on the selective decontamination of the oral cavity, using topical application of an antibiotic paste. With this technique the oral cavity was free of PPM within 3 days in most patients. No secondary colonisation was found. Rectal colonisation decreased significantly after 5 days. Secondary colonisation occurred in 9 patients with PPM sensitive to the antibiotics used. The prophylactic regimen included systemic cefotaxim, directed against early endogenous infection. The suppression and after some time the absence of the endogenous source of PPM resulted in a significant reduction of colonisation and infection. The total infection rate decreased to 16%.", "A comparative, prospective study was made of the incidence of infection in the lower airway (purulent tracheobronchitis and pneumonia) in long-term patients who were mechanically ventilated due to respiratory failure of noninfectious origin. Twenty-eight patients were randomly allocated into a study group (A, n = 13) in which a nonabsorbable paste containing 2% tobramycin, 2% amphotericin B, and 2% polymyxin E was administered locally to decontaminate the oropharynx, and a control group (B, n = 15) in which a paste without antibiotics was also applied to the oropharynx. We studied the effectiveness of the prophylactic technique in decontaminating the oropharynx and trachea of organisms potentially pathogenic for the respiratory system. Decontamination was successful in ten of 13 patients in group A vs. one of 15 patients in group B (p less than .001). The results demonstrated a lower rate of infection in the lower respiratory tract in the study group (three patients with tracheobronchitis and no pneumonias) than in the control group (three patients with tracheobronchitis and 11 with pneumonia), the difference between both being highly significant (p less than .001). Two (15%) patients in group B developed sepsis of pulmonary origin. None of the patients on prophylactic treatment developed this complication. Although the overall mortality was similar in both groups (group A, 30% vs. group B, 33%), we believe that infection contributed to a great extent to the death of two of five patients in group B. We conclude that nosocomial pneumonia, which is a frequent complication in critically ill patients on mechanical ventilation, could be prevented by local application of nonabsorbable antibiotics to the oropharynx.", "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.", "We evaluated the effect of selective decontamination of the digestive tract (SDD) on the incidence of ventilator-associated pneumonia (VAP) and its associated morbidity and cost in a mixed population of intubated patients. Two hundred seventy-one consecutive patients admitted to the intensive care units (ICUs) of five teaching hospitals and who had an expected need for intubation exceeding 48 h were enrolled and received topical antibiotics or placebo. Uninfected patients additionally received ceftriaxone or placebo for 3 d. VAP occurred in 11.4% of SDD-treated and 29.3% of control-group patients (p < 0.001; 95% confidence interval [CI]: 7.8 to 27.9). The incidence of nonrespiratory infections in the two groups was 19.1% and 30.7%, respectively (p = 0.04; 95% CI: 0.7 to 22.7). Among survivors, the median length of ICU stay was 11 d (interquartile range: 7 to 21.5 d) for the SDD-treated group and 16. 5 d (10 to 30 d) for the control group (p = 0.006). Mean cost per survivor was $11,926 for treated and $16,296 for control-group patients. Mortality was 38.9% and 47.1%, respectively (p = 0.57). In decontaminated patients, the prevalence of gram-negative bacilli fell within 7 d from 47.4% to 13.0% (p < 0.001), whereas colonization with resistant gram-positive strains was higher (p < 0. 05) than in the placebo group. In a mixed population of intubated patients, SDD was associated with a significant reduction of morbidity at a reduced cost. Our findings support the use of SDD in this high-risk group.", "To evaluate the effect of a method of Selective Decontamination of the Digestive Tract (SDD) on colonization, nosocomial infection (NI), bacterial resistance, mortality and economic costs.\n Randomized, double blind, placebo controlled study.\n Polyvalent intensive care unit (ICU) of a tertiary care hospital with 27 beds.\n 101 patients with > 3 days of mechanical ventilation and > 5 days of stay, without infection at the start of the study. 47 belonged to the Treated Group (TG) and 54 to the Placebo Group (PG).\n The TG was given Cefotaxime i.v. (6 g/day) for the first four days and an association of Polymyxin E, Tobramycin and Amphotericin B at the oropharyngeal and gastrointestinal level throughout the whole stay.\n In the TG, colonization by gram-negative agents at oropharyngeal, tracheal and gastrointestinal level fell significantly. There was a significant drop in the overall, respiratory and urinary NI (26% vs 63%, p < 0.001; 15% vs 46%, p < 0.001; 9% vs 31%, p < 0.01). The overall mortality and NI related mortality was less in the TG (21% vs 44%, p < 0.05; 2% vs 20%, p < 0.01). The economic costs, mechanical ventilation time and length of stay were similar. The percentage of bacterial isolations resistant to Cefotaxime and Tobramycin was greater in the TG (38% vs 15% and 38% vs 9%, p < 0.001).\n colonization by gram-negative bacilli, NI and the mortality related to it can be modified by SDD. Continuous bacteriological surveillance is necessary.", "To determine whether selective decontamination locally in the subglottic area (SDSA) reduces tracheal colonization and prevents ventilator-associated pneumonia (VAP) in patients with multiple trauma.\n A prospective randomized, controlled, clinical study in a 14-bed general intensive care unit of a university hospital.\n 79 consecutive multiple trauma patients admitted to the ICU who were expected to be mechanically ventilated for more than 5 days; 61 patients completed the protocol.\n Patients were randomly assigned to receive SDSA using a continuous infusion of a suspension containing three nonabsorbable antibiotics (polymyxin, tombramycin, and amphotericin B; n=30) or placebo ( n=31).\n The incidence of bronchial and gastric colonization and the number of cases of VAP were recorded. Gastric fluid and tracheal secretion cultures were obtained soon after intubation and thereafter every 4 days. Etiological diagnosis of VAP was based on samples taken by a specific protected double catheter set.\n VAP developed in 5 of 30 (16.6%) patients receiving SDSA and 16 of 31 (51.6%) patients receiving placebo. Negative bronchial secretion cultures were found in 14 of 30 (46.6%) patients in the SDSA group and in only 3 of 31 (9.6%) patients in the control group. No patient with negative bronchial secretion culture developed VAP. No significant differences in outcome were found.\n The SDSA is an effective and safe type of chemoprophylaxis against tracheal colonization and can significantly reduce the incidence of VAP in mechanically ventilated patients with multiple trauma.", "Evaluation of selective decontamination of the digestive tract (SDD) on late mortality in ventilated trauma patients in an intensive care unit (ICU).\n A multicenter, randomized controlled trial was undertaken in 401 trauma patients with Hospital Trauma Index-Injury Severity Score of 16 or higher. Patients were randomized to control (n=200) or SDD (n=201), using polymyxin E, tobramycin, and amphotericin B in throat and gut throughout ICU treatment combined with cefotaxime for 4 days. Primary endpoint was late mortality excluding early death from hemorrhage or craniocerebral injury. Secondary endpoints were infection and organ dysfunction.\n Mortality was 20.9% with SDD and 22.0% in controls. Overall late mortality was 15.3% (57/372) as 29 patients died from cerebral injury, 16 SDD and 13 control. The odds ratio (95% confidence intervals) of late mortality for SDD relative to control was 0.75 (0.40-1.37), corresponding to estimates of 13.4% SDD and 17.2% control. The overall infection rate was reduced in the test group (48.8% vs. 61.0%). SDD reduced lower airway infections (30.9% vs. 50.0%) and bloodstream infections due to aerobic Gram-negative bacilli (2.5% vs. 7.5%). No difference in organ dysfunction was found.\n This study demonstrates that SDD significantly reduces infection in multiple trauma, although this RCT in 401 patients was underpowered to detect a mortality benefit.", "The use of topical polymyxin and tobramycin to prevent intensive care infections is controversial. Moreover, these antibiotics are ineffective against methicillin-resistant Staphylococcus aureus. A decontamination regimen using mupirocin and chlorhexidine could prevent acquired infections, including those involving S. aureus. Because these two regimens could have a complementary role, we evaluated their effects when given both alone and combined.\n The authors conducted a multiple-center, placebo-controlled, randomized, double-blind study performed according to a 2 x 2 factorial design.\n The study was conducted at three polyvalent medical intensive care units at university-affiliated hospitals in France.\n Adult patients (age, > or =18 yrs) intubated for <48 hrs who were likely to be ventilated for >48 hrs.\n Two regimens were used: topical administration of polymyxin/tobramycin (or placebo) and nasal mupirocin with chlorhexidine body washing (or nasal placebo with liquid soap). The patients (n = 515) received polymyxin/tobramycin alone (n = 130), mupirocin/chlorhexidine alone (n = 130), both regimens (n = 129), or all placebos (n = 126) for the period of mechanical ventilation plus 24 hrs.\n The incidence of total infections acquired from the date of randomization until the termination date of study treatments plus 48 hrs was assessed. There were fewer acquired infections with both regimens than with polymyxin/tobramycin alone (odds ratio, 0.44; 95% confidence interval, 0.26-0.75; p = .003), mupirocin/chlorhexidine alone (0.43; 0.25-0.73; p = .002), or all placebos (0.42; 0.25-0.72; p = .001). There were no differences between polymyxin/tobramycin alone (0.95; 0.59-1.54; p = .84) and mupirocin/chlorhexidine alone (0.98; 0.60-1.58; p = .92) vs. all placebos. The probability of freedom from infection was higher with both regimens than with polymyxin/tobramycin alone (p = .002), mupirocin/chlorhexidine alone (p < .001), or all placebos (p < .001). Infection rates were also significantly lower with both regimens than with polymyxin/tobramycin alone (p = .017), mupirocin/chlorhexidine alone (p < .001), or all placebos (p < .001).\n Acquired infections were substantially reduced by mupirocin/chlorhexidine plus polymyxin/tobramycin, whereas each regimen given alone was ineffective. Whether both regimens could increase Candida infections deserves further investigation.", "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.", "In a prospective randomized study to determine whether prevention of colonization of Gram-negative bacteria results in prevention of Gram-negative bacterial infections, 96 intensive care patients were randomly allocated into a control group and a study group. The study group received oral nonabsorbable antimicrobial agents (i.e., tobramycin, amphotericin B, and polymyxin E) in addition to parenteral antibiotics. Colonization with Gram-negative microorganisms in the oropharynx, and respiratory and digestive tracts increased in the control group during their stay, while the study group did not tend to colonize with Gram-negative bacteria. In the control group, 107 nosocomial infections were diagnosed, vs. 42 nosocomial infections in the study group. Nosocomial infections caused by Gram-negative bacteria were significantly less frequent in the study group. Mortality due to an acquired infection was significantly less frequent in the study group. We conclude that colonization, infection, and subsequent mortality by nosocomial Gram-negative bacteria can be prevented by a regime of topically applied nonabsorbable antibiotics.", "Selective decontamination of the digestive tract (SDD) is an infection-prevention regimen used in critically ill patients. We assessed the effects of SDD on intensive-care-unit (ICU) and hospital mortality, and on the acquisition of resistant bacteria in adult patients admitted to intensive care.\n We did a prospective, controlled, randomised, unblinded clinical trial. 934 patients admitted to a surgical and medical ICU were randomly assigned oral and enteral polymyxin E, tobramycin, and amphotericin B combined with an initial 4-day course of intravenous cefotaxime (SDD group n=466), or standard treatment (controls n=468). Primary endpoints were ICU and hospital mortality and the acquisition of resistant bacteria.\n In the SDD group 69 (15%) patients died in the ICU compared with 107 (23%) in the control group (p=0.002). Hospital mortality was lower in the SDD groups than in the control group (113 [24%] vs 146 [31%], p=0.02). During their stay in intensive care, colonisation with gram-negative bacteria resistant to ceftazidime, ciprofloxacin, imipenem, polymyxin E, or tobramycin occurred in 61 (16%) of 378 SDD patients and in 104 (26%) of 395 patients in the control group (p=0.001). Colonisation with vancomycin-resistant enterococcus occurred in five (1%) SDD patients and in four (1%) controls (p=1.0). No patient in either group was colonised with meticillin-resistant Staphylococcus aureus.\n In a setting with low prevalence of vancomycin-resistant enterococcus and meticillin-resistant S aureus, SDD can decrease ICU and hospital mortality and colonisation with resistant gram-negative aerobic bacteria.", "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.", "Suppression of the gut luminal aerobic flora to reduce nosocomial infections was tested in a prospective, randomized, double-blind, placebo-controlled clinical trial in patients in a surgical intensive care unit who had persistent hypermetabolism. Forty-six patients were randomized to receive either norfloxacin, 500-mg suspension every 8 hours, together with nystatin, 1 million units every 6 hours, or matching placebo solutions administered through a nasogastric tube within 48 hours of surgical intensive care unit admission. Selective gut decontamination with the experimental therapy or placebo solutions continued for at least 5 days or until the time of surgical intensive care unit discharge. Patients were monitored with routine surveillance cultures for the development of nosocomial infections, as defined by criteria from the Centers for Disease Control. All other therapy was given as clinically indicated, including systemic antibiotics. The selective gut decontamination group experienced a significant reduction in the incidence of nosocomial infections and a reduced length of stay. However, these results were not associated with a concomitant decrease in progressive multiple organ failure syndrome, adult respiratory distress syndrome, or mortality.", "Secondary pneumonia in patients requiring mechanical ventilation has a high morbidity and mortality. Diagnosis is difficult and treatment failure common; therefore, preventive measures are important. In a double-blind, placebo-controlled trial, we evaluated selective decontamination of the oropharynx with polymyxin B sulfate, neomycin sulfate, and vancomycin hydrochloride (PNV) in 52 patients requiring mechanical ventilation during a 3- to 34-day period (mean, 10 days). Either PNV or placebo was administered six times daily in the oropharynx. During the first 12 days of intubation, tracheobronchial colonization by gram-negative bacteria and Staphylococcus aureus, as well as pneumonia, occurred less frequently in the PNV than in the placebo group (16% vs 78%; P less than .0001). Hospital mortality was not different, but systemic antibiotics were prescribed less often in the PNV group and no resistant microorganism emerged. In these critically ill patients, topical oropharyngeal antibiotic application lowered the rate of ventilator-associated pneumonia by a factor of 5, probably by interrupting the stomach-to-trachea route of infection, and decreased the requirement for intravenous antibiotics." ]

[ "15556258", "11806295", "16167789", "11231856", "17665244", "9875644", "16710858", "17175424", "10400458", "9684133", "12520569", "12143204", "8799402", "11103179" ]

[ "Pilot study on the effect of parenteral vitamin E on ischemia and reperfusion induced liver injury: a double blind, randomized, placebo-controlled trial.", "[Trimetazidine prevents ischemia-reperfusion injury in hepatic surgery under vascular clamping].", "[Reevaluation of protective effects of alprostadil on hepatic function in patients undergoing hepatectomy].", "Effects of preoperative steroid administration on surgical stress in hepatic resection: prospective randomized trial.", "Hepatocellular glycogen in alleviation of liver ischemia-reperfusion injury during partial hepatectomy.", "Protective effect of prostaglandin E1 against ischemia/reperfusion-induced liver injury: results of a prospective, randomized study in cirrhotic patients undergoing subsegmentectomy.", "Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: a prospective randomized study.", "Effects of mannitol in the prevention of lipid peroxidation during liver resection with hepatic vascular exclusion.", "Normothermic liver ischemia and antioxidant treatment during hepatic resections.", "Antioxidant treatment during liver resection for alleviation of ischemia-reperfusion injury.", "Prospective randomized study of steroids in the prevention of ischaemic injury during hepatic resection with pedicle clamping.", "The role of allopurinol in human liver ischemia/reperfusion injury: a prospective randomized clinical trial.", "The role of prostanoid in hepatic damage during hepatectomy.", "Effects of amrinone on ischaemia-reperfusion injury in cirrhotic patients undergoing hepatectomy: a comparative study with prostaglandin E1." ]

[ "Liver surgery usually involves ischemia and reperfusion (I/R) which results in oxidative stress and cell damage. The administration of antioxidants should diminish or prevent this damage. The purpose of this study was to investigate the effect of the antioxidant vitamin E on I/R injury.\n We carried out a placebo-controlled double-blind study on 68 patients undergoing elective, tumor-related, partial liver resection. 47 patients were qualified for the per protocol population based evaluation. The patients were randomly assigned to two groups. The day before surgery one group received three infusions containing vitamin E (600 IU=540 mg vitamin E emulsion). The other group received three infusions of placebo.\n Length of stay in the intensive care unit (ICU) was significantly shorter in the verum group than in the placebo group (P<0.05). There were signs of improvement for AUC AST (P<0.05), ALT and GLDH in the verum group after surgery. Serum vitamin E concentration increased after administration of vitamin E infusion and declined in both treatment groups after surgery (P<0.01). In the verum group vitamin E deficiency was prevented while vitamin E concentration remained low in the placebo group (P<0.01).\n The findings from this study indicate that preoperative administration of vitamin E is safe and that this treatment may have beneficial effects by reducing the impact of I/R injury in liver surgery.", "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.", "The protective effect of alprostadil (PGE1), used during hepatectomy, on hepatic function has not been clearly proven. We reevaluated this effect by measuring serum alpha-glutathione S-transferase (aGST), which detects liver injury sensitively.\n Thirty hepatocellular carcinoma patients scheduled for hepatectomy were randomly assigned to control (n=12) and PGE1 (n=10) groups. In the latter group, PGE1 was administered intravenously at a rate of 0.05 microg x kg(-1) x min(-1) during surgery. For measuring alphaGST, arterial blood samples were obtained before anesthesia, following laparotomy, and immediately, 2, 4, and 6 hrs after liver resection.\n The alphaGST concentrations after liver resection were significantly higher, while mean arterial pressures were significantly lower in the PGE1 group.\n Our findings suggest that PGE1 medication during hepatectomy cannot protect hepatic function during and after liver resection.", "Preoperative administration of methylprednisolone sodium succinate can control surgical stress in patients undergoing hepatic resection.\n A prospective randomized trial.\n A university hospital department of surgery.\n Thirty-three patients who underwent hepatic resection were classified into 2 groups: a control group (n = 16) and a steroid group (n = 17) in which patients were intravenously administered 500 mg of methylprednisolone 2 hours before surgery.\n Perioperative levels of interleukin (IL)-6 and IL-10 (serum and peritoneal), immunosuppressive acidic protein, Candida antigen, and other laboratory and clinical variables were measured.\n Postoperative levels of serum and peritoneal IL-6 and levels of C-reactive protein were significantly lower in the steroid group than in controls. Furthermore, serum and peritoneal IL-10 levels were significantly higher in the steroid group. The total bilirubin value on postoperative day 1 was significantly lower in the steroid group than in controls. Postoperative immunosuppressive acidic protein levels were also significantly lower in the steroid group, as was the positive rate of serum Candida antigen. No differences were found in the incidence of postoperative complications.\n Preoperative steroid administration significantly elevated anti-inflammatory cytokine IL-10 levels, suppressed the levels of inflammatory cytokines IL-6 and C-reactive protein, and prevented postoperative elevation of total bilirubin values. Furthermore, postoperative elevation of immunosuppressive acidic protein levels and the positive rate of Candida antigen were suppressed, indicating that the immune response was maintained by preoperative steroid administration.", "Temporary occlusion of liver blood supply for complex liver operation is common in liver surgery. However, hepatic vascular occlusion will undoubtedly impair liver function. This study was designed to elucidate the effect of hepatocellular glycogen in alleviation of liver ischemia-reperfusion injury during hepatic vascular occlusion for partial hepatectomy.\n Fifty-seven patients were randomly divided into an experimental group (n = 29) and a control group (n = 28). In the experimental group, patients were given high-concentration glucose intravenously during 24 h before the operation. The hepatic lesion was resected after portal triad clamping in the two groups. Noncancer liver tissue was biopsied to measure hepatic tissue ATP content and change of malondialdehyde (MDA) and superoxide dismutase (SOD). Liver function of all patients was assessed by using an automatic biochemical analysis apparatus before the operation and the first and fifth days after operation.\n The mean hepatic vascular occlusion time in the experimental group was 19.21 +/- 4.54 min and in the control group it was 21.04 +/- 5.11 min. Hepatic tissue ATP content of the experimental group was significantly higher than that of the control group at the end of hepatic vascular occlusion (2.15 +/- 0.39 mumol/g wet tissue vs. 1.33 +/- 0.44, p < 0.01) and at the point of 1-h reperfusion (2.19 +/- 0.29 mumol/g wet tissue vs. 1.57 +/- 0.35, p < 0.01). There was significant difference in SOD activity between the two groups at the end of hepatic vascular occlusion (130.69 +/- 30.49 NU/mg pr vs. 97.83 +/- 26.23, p < 0.01) and at the point of 1-h reperfusion (139.55 +/- 39.88 NU/mg pr vs. 114.74 +/- 25.93, p < 0.01). Significant difference was shown in MDA content between the two groups at the end of hepatic vascular occlusion (3.02 +/- 0.30 nmol/mg pr vs. 3.99 +/- 0.49, p < 0.01) and at the point of 1-h reperfusion (3.81 +/- 0.69 nmol/mg pr vs. 5.75 +/- 1.17, p < 0.01). In addition, the liver function of the experimental group was significantly better than that of the control group the first and fifth days after the operation (p < 0.01).\n Abundant intracellular glycogen may reduce liver ischemia-reperfusion injury caused by hepatic vascular occlusion. It is beneficial to give a large amount of glucose before a complex liver operation during which temporary occlusion of hepatic blood flow is necessary.", "The cytoprotective effects of prostaglandin E1 on livers suffering from ischemia/reperfusion injury in the clinical setting are unproved. These effects were examined, focusing on inflammatory cytokine and nitric oxide metabolism.\n Twenty-four cirrhotic patients with hepatocellular carcinoma undergoing subsegmentectomy under ischemia induced only by Pringle's maneuver were divided into two groups (patients given prostaglandin E1 by injection and untreated controls) and postoperative results were compared. Peripheral blood was taken perioperatively and the plasma aminotransferase, cytokines and nitrate/nitrite levels of the two groups were compared. Two liver specimens were taken from each patient, one before ischemia and the other after hepatectomy, and the levels of inducible nitric oxide synthase and cytokine mRNAs and proteins were analyzed.\n Although no apparent differences were recognized in postoperative complications or duration of postoperative hospital stay between the groups, the perioperative plasma aminotransferase level was significantly lower in the prostaglandin E1 group. Significant differences were also seen in interleukin-6 and nitrate plasma levels during the observation period and the interleukin-6 protein levels in the liver supernatants after hepatectomy in the two groups. In contrast, no significant differences were apparent between the interleukin-1 beta and tumor necrosis factor-alpha plasma levels of the two groups. The corrected fluorescence activities of interleukin-6 and inducible nitric oxide synthase mRNAs in the liver after hepatectomy correlated significantly. No interleukin-1 beta or tumor necrosis factor-alpha mRNAs or proteins were detected.\n Prostaglandin E1 exerted hepatoprotective effects on livers suffering from ischemia/reperfusion injury, and interleukin-6 might play an important role in these effects.", "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.", "To examine the efficacy of mannitol in the prevention of lipid peroxidation during major liver resections performed during hepatic inflow occlusion.\n Prospective, randomized, open-label study.\n Aretaieion Hospital, a university-affiliated hospital.\n 30 ASA physical status II and III patients, less than 75 years of age, scheduled for elective liver resection.\n All patients received combined general and epidural anesthesia. Laparotomy was performed through a bilateral subcostal incision, and hepatectomy was performed by inflow vascular exclusion (Pringle's maneuver). Before this maneuver, and if the patients were hemodynamically stable, they were randomized to receive either mannitol 20% 1.5 mL kg(-1) (group M) or normal saline 1.5 mL kg(-1) (group S) intravenously for 30 minutes.\n Venous blood malondialdehyde (MDA) concentration, as an index of lipid peroxidation, was measured spectrophotometrically at selected time points.\n Patients in both groups presented with raised MDA values (P < 0.05) for the period starting before the release of vascular occlusion until 6 days postoperatively. In patients receiving mannitol, lower MDA values were observed (P < 0.05) compared with group S at the end of operation.\n Mannitol has an antioxidant activity, but we were unable to confirm a positive impact on the postoperative clinical course.", "The purpose of our study was to evaluate the clinical impact of reperfusion injury after normothermic ischemia during major liver resections and the effect of an intraoperative antioxidant infusion. This prospective randomized study comprised 50 patients; half of them (treatment group) were given an antioxidant infusion containing tocopherol and ascorbate immediately prior to reperfusion onset. Venous blood samples for the determination of MDA-TBARS (malondialdehyde-thiobarbituric acid reactive substances) by a HPLC-based test as a marker of lipid peroxidation were taken prior to ischemia, 30 min after reperfusion onset and at the end of the operation. In the control group there was a significant increase of MDA-TBARS (p = 0.001) at 30 min after reperfusion onset. At the end of the operation the values had returned to the initial level. The treatment group showed only a marginal increase (p-value for the difference between the two groups: 0.007). After exclusion of the patients with histologically proven advanced cirrhosis the increase in the control group (p < 0.001) and the difference between the increase in the two groups (p = 0.001) became more significant. Prothrombin time was also significantly better in the treatment group (p = 0.003). Postoperative complications such as prolonged liver failure, bleeding disorders and infections were seen more often in the control group. In our study MDA-TBARS was increased after liver ischemia, but in patients with advanced cirrhosis the effect was smaller or even absent. This increase and possible clinical consequences of reperfusion injury could be reduced by intraoperative administration of an antioxidant infusion.", "Many experimental studies on ischemia-reperfusion injury in animals suggest a preventive effect of antioxidants, but the clinical significance of these findings is still unclear. The aim of our study was to evaluate the effect of antioxidant treatment with vitamins on liver function parameters during liver resection.\n Our prospective randomized study comprised 58 patients undergoing major liver surgery, including the Pringle maneuver. In the treatment group 32 patients received a multivitamin infusion (Omnibionta) which included 10 mg of alpha-tocopherol acetate, 2 mg of DL-alpha-tocopherol and 1 g of ascorbate. The control group consisted of 26 patients. Various parameters associated with liver function, such as transaminases, lactate, ammonia, bilirubin, cholinesterase and clotting parameters were measured preoperatively, at the beginning of liver ischemia, 15, 30 and 60 minutes after reperfusion onset and every 12 hours after the operation.\n The Mann-Whitney-Wilcoxon-Test showed statistically significant differences in the postischemic changes between the treatment group and the control group for the Quick test (prothrombin time): p = 0.01. The transaminases were also markedly better in the treatment group (splitting-up slightly more delayed than with the Quick test). A smaller effect was seen with cholinesterase. Lactate, however, increased intraoperatively with a strong correlation to the duration of ischemia and returned quickly to baseline values without any remarkable influence of the antioxidant treatment.\n In our study, antioxidant treatment with a multivitamin infusion showed a positive effect on postischemic liver function parameters.", "The major drawback of hepatic pedicle clamping is ischaemia-reperfusion injury with impairment of liver function. Perioperative steroid administration has been advocated to reduce liver damage. The aim of this prospective, randomized study was to determine whether steroid administration can reduce liver injury and improve short-term outcome.\n Fifty-three patients undergoing liver resection were randomized to a steroid group (group 1) or to a control group (group 2); patients in group 1 received methylprednisolone 30 mg/kg 30 min before liver resection whereas those in group 2 did not. Serum levels of interleukin (IL) 6, total bilirubin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and prothrombin time (PT) were measured. Length of stay, and type and number of complications were recorded.\n Serum IL-6 levels were significantly lower in the steroid group than in the control group 24 h after surgery. Steroid administration significantly modified AST, ALT and PT levels only in patients with chronic liver disease. Overall and lung-related morbidity were not significantly different between the two groups.\n Steroid administration suppresses serum IL-6 levels, but has no effect on short-term outcome.\n Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd", "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.", "The aim of this study in hepatectomy is to investigate whether or not hepatic ischemia elevates the serum prostanoid levels, and whether or not thromboxane A2 (TXA2) synthetase inhibitor (OKY 046) improves hepatic damage.\n The prostanoid levels were measured in 22 hepatectomy cases. The beneficial effects of thromboxane A2 synthetase inhibitor were examined in cases who underwent hepatectomy under hemihepatic vascular control. The total prostanoid levels (6-keto PG Fla+ PGE2 + TXB2) were measured in 22 cases before and after hepatectomy. The hepatic ischemic time (HIT) was defined as the time required to perform a hepatic mobilization plus the right hemihepatic vascular control technique.\n The total prostanoid levels increased after hepatectomy (P < 0.01). The changes in the total prostanoid levels positively correlated with the HIT (P < 0.01). The 17 cases who underwent hepatectomy with the HIT were randomly divided into 2 groups; the OKY group (n = 9), OKY 046 (0.2 mg/kg/hr), the control group (n = 8); no drug was given. The OKY 046 administration reduced the TXB2 levels (P < 0.01), without any changes in the PGE2, or 6-keto PGF1a levels. The serum glutamic oxaloacetic transaminase levels after operation were lower, and the hepaplastin tests were higher in the OKY group than those of the control (P < 0.05).\n These results demonstrated that hepatectomy under ischemia elevated the prostanoid levels. OKY 046 significantly reduced the TXB2 levels and the degree of hepatic damage in hepatectomy under ischemia.", "The effects of amrinone, a selective phosphodiesterase III inhibitor, on liver ischaemia reperfusion injury have not yet been clarified. Forty-five patients with hepatocellular carcinoma who underwent partial liver resection using Pringle's manoeuvre were studied. Patients were divided into three groups: those given amrinone, those given prostaglandin E1 (PGE1) and those not treated (controls). An indocyanine green (ICG) clearance test was performed before the operation and three times during surgery: just before induction of liver ischaemia, just after liver resection and 60 min after reperfusion. Blood lactate and base excess were measured at the same times. Systolic and diastolic arterial pressure, heart rate, cardiac index and oesophageal temperature were monitored. Aminotransferase levels were recorded the day before surgery, 1 h after operation and on the first and third postoperative days. These data were compared between groups. The ICG elimination rate, lactate and base excess in the amrinone group differed significantly from those in controls during the observation period (P = 0.03, P = 0.04 and P = 0.03, respectively). The differences between the PGE1 and control groups were not significant. There were no significant differences between the groups in perioperative vital signs, cardiac index or postoperative aminotransferase. Amrinone enhanced intraoperative ICG elimination in cirrhotic patients who underwent liver resection." ]

[ "6770731", "11874817", "10379017", "12826636", "8924134", "2920584" ]

[ "Controlled clinical trial of methylprednisolone in patients with chronic bronchitis and acute respiratory insufficiency.", "Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial.", "Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group.", "Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease.", "Early corticosteroid use in acute exacerbations of chronic airflow obstruction.", "A randomized controlled trial of methylprednisolone in the emergency treatment of acute exacerbations of COPD." ]

[ "To evaluate the role of corticosteroids as treatment for acute exacerbations of chronic obstructive pulmonary disease, we conducted a double-blind, randomized, placebo-controlled trial in 44 consecutive patients with chronic bronchitis and severe airflow obstruction. All were hospitalized with acute respiratory insufficiency from acute bronchitis. Patients with asthma, atopy, or pneumonia were excluded. Treatment consisted of intravenous aminophylline, inhaled isoproterenol, antibiotics, and either methylprednisolone, 0.5 mg/kg of body weight, or placebo every 6 h intravenously for 72 h. Bedside spirometry was done before and after bronchodilator inhalation three times daily. The methylprednisolone-treated group had a greater improvement in both prebronchodilator and postbronchodilator forced expiratory volume in 1 second (P less than 0.001). More patients with large improvements in their prebronchodilator or postbronchodilator flow rates, or both (greater than or equal to 40% by 72 h), received methylprednisolone (P less than 0.01). Methylprednisolone improved airflow more than placebo when added to standard therapy in patients with chronic bronchitis and acute respiratory insufficiency.", "Nebulized budesonide has been used successfully to treat acute asthma exacerbation, and we hypothesized that it could also be effective for exacerbations of chronic obstructive pulmonary disease (COPD). In this multicenter, double-blind, randomized, placebo-controlled trial, the efficacy of nebulized budesonide (Pulmicort Respules/Nebuamp), oral prednisolone, and placebo was compared in 199 patients with acute exacerbations of COPD requiring hospitalization. Patients received from randomization (H(0)) to 72 h (H(72)), 2 mg of budesonide every 6 h (n = 71), 30 mg of oral prednisolone every 12 h (n = 62), or placebo (n = 66). All received standard treatment, including nebulized beta(2)-agonists, ipratropium bromide, oral antibiotics, and supplemental oxygen. The mean change (95% confidence interval) in postbronchodilator FEV(1) from H(0) to H(72) was greater with active treatments than with placebo: budesonide versus placebo, 0.10 L (0.02 to 0.18 L); prednisolone versus placebo, 0.16 L (0.08 to 0.24 L). The difference in FEV(1) between budesonide and prednisolone was not significant, -0.06 L (-0.14 to 0.02 L). The occurrence of serious adverse events was similar for all groups. Budesonide had less systemic activity than prednisolone as indicated by a higher incidence of hyperglycemia observed with prednisolone. Both budesonide and prednisolone improved airflow in COPD patients with acute exacerbations when compared with placebo. Nebulized budesonide may be an alternative to oral prednisolone in the treatment of nonacidotic exacerbations of COPD but further studies should be done to evaluate its long-term impact on clinical outcomes after an initial episode of COPD exacerbation.", "Although their clinical efficacy is unclear and they may cause serious adverse effects, systemic glucocorticoids are a standard treatment for patients hospitalized with exacerbations of chronic obstructive pulmonary disease (COPD). We conducted a double-blind, randomized trial of systemic glucocorticoids (given for two or eight weeks) or placebo in addition to other therapies, for exacerbations of COPD. Most other care was standardized over the six-month period of follow-up. The primary end point was treatment failure, defined as death from any cause or the need for intubation and mechanical ventilation, readmission to the hospital for COPD, or intensification of drug therapy.\n Of 1840 potential study participants at 25 Veterans Affairs medical centers, 271 were eligible for participation and were enrolled; 80 received an eight-week course of glucocorticoid therapy, 80 received a two-week course, and 111 received placebo. About half the potential participants were ineligible because they had received systemic glucocorticoids in the previous 30 days. Rates of treatment failure were significantly higher in the placebo group than in the two glucocorticoid groups combined at 30 days (33 percent vs. 23 percent, P=0.04) and at 90 days (48 percent vs. 37 percent, P=0.04). Systemic glucocorticoids (in both groups combined) were associated with a shorter initial hospital stay (8.5 days, vs. 9.7 days for placebo, P=0.03) and with a forced expiratory volume in one second that was about 0.10 liter higher than that in the placebo group by the first day after enrollment. Significant treatment benefits were no longer evident at six months. The eight-week regimen of therapy was not superior to the two-week regimen. The patients who received glucocorticoid therapy were more likely to have hyperglycemia requiring therapy than those who received placebo (15 percent vs. 4 percent, P=0.002).\n Treatment with systemic glucocorticoids results in moderate improvement in clinical outcomes among patients hospitalized for exacerbations of COPD. The maximal benefit is obtained during the first two weeks of therapy. Hyperglycemia of sufficient severity to warrant treatment is the most frequent complication.", "In this randomized, double-blind, placebo-controlled trial, we studied the effectiveness of prednisone in reducing the risk of relapse after outpatient exacerbations of chronic obstructive pulmonary disease (COPD).\n We enrolled 147 patients who were being discharged from the emergency department after an exacerbation of COPD and randomly assigned them to 10 days of treatment with 40 mg of oral prednisone once daily or identical-appearing placebo. All patients received oral antibiotics for 10 days, plus inhaled bronchodilators. The primary end point was relapse, defined as an unscheduled visit to a physician's office or a return to the emergency department because of worsening dyspnea, within 30 days after randomization.\n The overall rate of relapse at 30 days was lower in the prednisone group than in the placebo group (27 percent vs. 43 percent, P=0.05), and the time to relapse was prolonged in those taking prednisone (P=0.04). After 10 days of therapy, patients in the prednisone group had greater improvements in forced expiratory volume in one second than did patients in the placebo group (mean [+/-SD] increase from base line, 34+/-42 percent vs. 15+/-31 percent; P=0.007). Patients in the prednisone group also had significant improvements in dyspnea, as measured by the transitional dyspnea index (P=0.04) and by the dyspnea domain of the Chronic Respiratory Disease Index Questionnaire (P=0.02), but not in health-related quality of life (P=0.14).\n Outpatient treatment with oral prednisone offers a small advantage over placebo in treating patients who are discharged from the emergency department with an exacerbation of COPD.\n Copyright 2003 Massachusetts Medical Society", "To determine the benefit of early steroid use in acute exacerbations of chronic airflow obstruction in the ED, 113 patients with an average age of 66 years, acute or chronic dyspnea, an FEV1 of < 60% and FEV1/FVC ratio of < 60% were included in a randomized, double-blinded, interventional clinical trial. All patients received the same bronchodilator treatment. At 6 hours the steroid- treated group showed a 21.71 L/min improvement in PEFR (P < .05) and 0.14 L improvement in FEV1 (P < .05), while the nonsteroid group showed insignificant improvements of 5.52 L/min and 0.02 L, respectively. Of those patients receiving steroids, 22 achieved > 40% improvements in PEFR by 6 hours and 17 achieved similar results in FEV1, whereas of those not receiving steroids, 13 and 8, respectively, achieved improvements. Within 24 hours of observation in the ED, 16 patients receiving steroids were discharged and none relapsed within 2 weeks. Of those not receiving steroids, only 10 were discharged and 3 returned with exacerbations. Although early response to steroids in chronic airflow obstruction is variable, the overall medical and cost benefits justify their early use in acute exacerbations.", "We conducted a randomized, controlled double-blind study to determine whether intravenous administration of methylprednisolone early in the therapy for acute exacerbations of COPD would improve pulmonary function in the Emergency Department and reduce the need for hospitalization. Ninety-six patients completed the study. All were at least 50 years of age and had no history of asthma. Patients received aminophylline and hourly administration of aerosolized isoetharine. Methylprednisolone (100 mg) or physiologic saline solution was given within one-half hour of arrival in the Emergency Department. Spirometry was performed initially and after the third and fifth aerosol treatments. We found no greater improvement in FEV1 in the group receiving the steroid (37 percent) than in the control group (43 percent; NS). There was also no difference in the rate of hospitalization (33 percent in the steroid-treated group vs 30 percent in the control group; NS). We conclude that early administration of methylprednisolone does not affect the emergency phase of treatment for acute exacerbations of COPD." ]

[ "11989986", "9589759", "2091459", "12693432", "7498892", "7552558", "16452695", "16543298", "10353452", "8590112", "7956109", "2836295", "7953033", "11016522", "11111259", "1398563", "9117472", "9534826", "12027240", "9366661", "17650271", "7953035", "11256724", "2361668", "7788458", "8689371", "10357291", "16897413", "9068775" ]

[ "Heavy users of acute psychiatric beds: randomized controlled trial of enhanced community management in an outer London borough.", "Assertive community treatment for patients with co-occurring severe mental illness and substance use disorder: a clinical trial.", "Assertive community treatment for frequent users of psychiatric hospitals in a large city: a controlled study.", "The relationship of clinical factors and environmental opportunities to social functioning in young adults with schizophrenia.", "Toward managed care for persons with severe mental illness: implications from a cost-effectiveness study.", "Implementing assertive community treatment teams.", "Comparison of ACT and standard case management for delivering integrated treatment for co-occurring disorders.", "The REACT study: randomised evaluation of assertive community treatment in north London.", "Intensive case management in Australia: a randomized controlled trial.", "Two-year outcome of team-based intensive case management for patients with schizophrenia.", "The role of case management within a community support system: partnership with psychosocial rehabilitation.", "Assertive case management in three CMHCs: a controlled study.", "Home-based versus out-patient/in-patient care for people with serious mental illness. Phase II of a controlled study.", "Early detection and assertive community treatment of young psychotics: the Opus Study Rationale and design of the trial.", "Serving street-dwelling individuals with psychiatric disabilities: outcomes of a psychiatric rehabilitation clinical trial.", "Experimental comparison of the effects of three treatment programs for homeless mentally ill people.", "Client outcomes in a three-year controlled study of an integrated service agency model.", "Intensive case management for the severely mentally ill. Controlled trial.", "Outcome of case management based on the strengths model compared to standard care. A randomised controlled trial.", "A randomized trial of assertive community treatment for homeless persons with severe mental illness.", "Assertive community treatment in the Netherlands: a randomized controlled trial.", "Community psychiatric nurse teams: cost-effectiveness of intensive support versus generic care.", "Psychiatric hospitalizations, arrests, emergency room visits, and homelessness of clients with serious and persistent mental illness: findings from a randomized trial of two ACT programs vs. usual care.", "Operation outreach: intensive case management for severely psychiatrically disabled adults.", "Service utilization and costs of care for severely mentally ill clients in an intensive case management program.", "Deaths among former psychiatric inpatients in an outreach case management program.", "Assertive community treatment for people with severe mental illness: the effect on hospital use and costs.", "Treating homeless clients with severe mental illness and substance use disorders: costs and outcomes.", "Problems in conducting economic evaluations alongside clinical trials. Lessons from a study of case management for people with mental disorders." ]

[ "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.", "Integrated mental health and substance abuse treatment within an assertive community treatment (ACT) approach was compared to that within a standard case management approach for 223 patients with dual disorders over three years. ACT patients showed greater improvements on some measures of substance abuse and quality of life, but the groups were equivalent on most measures, including stable community days, hospital days, psychiatric symptoms, and remission of substance use disorder.", "Evaluated a large-city adaptation of the assertive community treatment (ACT) model (Stein & Test, 1980). Outcomes were examined after 1 year for 82 clients, averaging over 17 lifetime psychiatric hospitalizations, randomly assigned either to ACT or to a drop-in (DI) center. After 1 year, 76% of the ACT clients and only 7% of DI clients were involved in the respective programs. The ACT team averaged 2 home and community visits per week to each client. ACT clients averaged significantly fewer state hospital admissions and state hospital days than did DI clients. ACT clients reported greater satisfaction with program services, fewer contacts with the police, and less difficulty with practical problems associated with psychiatric readmission. More ACT clients were known to have stable community housing. Annual per-client treatment costs for ACT were estimated to be $1,500 less than for DI.", "This study used data from the long-term experimental evaluation of the Program of Assertive Community Treatment (PACT) to examine the clinical and situational contributors to social functioning in people with schizophrenia. Subjects were 87 young adults with schizophrenia spectrum disorders. Data from two time points, 6 months apart, were used to test models predicting five social outcomes (network size, network reciprocity, sociosexual contact, satisfaction with social relationships, and loneliness) from positive symptoms, work involvement, living situation, and residential mobility. Results indicated that (1) work involvement was associated with larger network sizes over a 6-month period; (2) experiencing an increase in positive symptoms over a 6-month period was associated with the loss of reciprocal network ties, a lessening of satisfaction with social relationships, and an increase in loneliness; and (3) neither living situation nor moving frequently was associated with later social outcomes. These findings suggest strong support for the role of short-term changes in positive symptoms and modest support for the role of work involvement in social outcome.", "Over the past two decades various models of community-based care for persons with severe mental illness have been developed. This study, which represents the first comparison of the most successful care approach (Program of Assertive Community Treatment or PACT adaptation model) with other, less intensive approaches (clinical team and intensive broker models) in a community service system, indicates that client outcomes were more positive in the PACT adaptation model in terms of enhanced psychosocial functioning and reduced acute and subacute care costs. The PACT model was not significantly more expensive in terms of the costs of providing supportive services compared with the clinical team approach and the intensive broker model of care.", "The Connecticut Department of Mental Health began creating assertive community treatment teams in 1987. The authors describe the approach taken by the department in defining the assertive community treatment model, in creating new assertive community treatment teams, and in monitoring the creation and functioning of these teams to ensure that fidelity to the assertive community treatment model is maintained. Assertive community treatment teams can be created even in the absence of funding for new staff by reconfiguring current community-based staff and by moving staff from state hospitals to the community. Preliminary data from a randomized trial in Connecticut comparing assertive community treatment with high-quality case management in areas with an array of community services indicated that the intended models were replicated, with variations in practice style across programs. Clients in assertive community treatment were in the hospital about half as often as clients in standard services and were also less likely to be without a permanent residence. Training and ongoing monitoring of assertive community treatment teams are necessary to detect practices that diverge from the intervention model so that corrective action can be taken.", "Clients with co-occurring severe mental and substance use disorders are at high risk of institutionalization and other adverse outcomes. Although integrated mental health and substance abuse treatment is becoming a standard clinical approach for such clients, the optimal method for delivering integrated treatment remains unclear.\n This study compared integrated treatment delivered within two different models of community-based case management (assertive community treatment and standard clinical case management). A total of 198 clients in two urban sites who had co-occurring disorders and were homeless or unstably housed were randomly assigned to one of two treatment conditions and were followed for three years.\n Participants in both treatment conditions improved over time in multiple outcome domains, and few differences were found between the two models. Decreases in substance use were greater than would be expected given time alone. At the site that had higher rates of institutionalization, clients who received standard case management were more likely to be institutionalized. However, in the site that had lower rates of institutionalization, no differences in the rate of institutionalization were found between the two treatment conditions.\n Integrated treatment can be successfully delivered either by assertive community treatment or by standard clinical case management.", "To compare outcomes of care from assertive community treatment teams with care by community mental health teams for people with serious mental illnesses.\n Non-blind randomised controlled trial.\n Two inner London boroughs.\n 251 men and women under the care of adult secondary mental health services with recent high use of inpatient care and difficulties engaging with community services.\n Treatment from assertive community treatment team (127 participants) or continuation of care from community mental health team (124 participants).\n Primary outcome was inpatient bed use 18 months after randomisation. Secondary outcomes included symptoms, social function, client satisfaction, and engagement with services.\n No significant differences were found in inpatient bed use (median difference 1, 95% confidence interval -16 to 38) or in clinical or social outcomes for the two treatment groups. Clients who received care from the assertive community treatment team seemed better engaged (adapted homeless engagement acceptance schedule: difference in means 1.1, 1.0 to 1.9), and those who agreed to be interviewed were more satisfied with services (adapted client satisfaction questionnaire: difference in means 7.14, 0.9 to 13.4).\n Community mental health teams are able to support people with serious mental illnesses as effectively as assertive community treatment teams, but assertive community treatment may be better at engaging clients and may lead to greater satisfaction with services.", "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.", "Two-year outcomes of patients with schizophrenic disorders who were assigned to an intensive, team-based case management program and patients who received standard psychiatric services were assessed. The case management model featured increased staff contact time with patients, rehabilitation plans based on patients' expressed needs, and patients' attendance at team meetings where their rehabilitation plan was discussed.\n Forty patients were randomly assigned to either the case management group or the control group that received standard services. Patients' use of emergency and inpatient services, their quality of life, the size of their social networks, and their relatives' burden of care were assessed at assignment to the study groups and at two-year follow-up.\n Patients in the case management group had significantly fewer emergency visits compared with the two years before the study, and their relatives reported significantly reduced burden of care associated with relationships with psychiatric services over the two-year period. The size of patients' social networks increased for the case management group and decreased for the control group.\n A team-based intensive case management model is an effective intervention in the rehabilitation of patients with chronic schizophrenia.", "The Strengths model of team case management was assessed relative to an existing high quality psychosocial rehabilitation program that informally provided many services typical of case management (e.g., service linkage, monitoring, and consumer advocacy). The experimental evaluation triangulated consumer and family member responses with mental health professional reports and consumer records of hospitalization and crisis center contacts. An analysis of data from these four sources revealed that one year after full program implementation, consumers who received case management in conjunction with psychosocial rehabilitation functioned at a higher level of competency and experienced significantly lower psychiatric symptomatology than consumers who received only psychosocial rehabilitation. Implications for the successful integration of case management into an existing community support program are discussed.", "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.", "The effect of a randomised controlled withdrawal of home-based care was studied for half of a sample of seriously mentally ill (SMI) patients from an inner London catchment area, compared with the effects of continuing home-based care.\n Patients, aged 18-64, had entered the trial at month 0 when facing emergency admission for SMI. After at least 20 months home-based care (Phase I), patients were randomised at month 30 into Phase II (months 30-45) to have either further home-based care (DLPII, n = 33) or be transferred to out-/in-patient care (DLP-control, n = 33). They were assessed at 30, 34, and 45 months. Phase I control patients (n = 70) were assessed again at month 45. Measures used were number and duration of in-patient admissions, independent ratings of clinical and social function, and patients' and relatives' satisfaction.\n The slim clinical and social gains from home-based v. out-/in-patient care during Phase I were largely lost in Phase II. Duration of crisis admissions increased from Phase I to Phase II in both DLPII and DLP-control patients. During Phase II, patients' and relatives' satisfaction remained greater for home-based than out-/in-patient care patients. At 45 months, compared with the Phase I controls, DLPII patients and relatives were more satisfied with care. Such satisfaction was independent of clinical/social gains.\n The loss of Phase I gains were perhaps due to attenuation of home-based care quality and to benefits of Phase I home-based care lingering into Phase II in DLP-controls. The Phase II home-based care team suffered from low morale.", "Recent research indicates that early detection of young persons suffering from psychosis and subsequent intensive intervention enhances treatment response and prognosis, but the data are only preliminary and suggestive.\n We present the rationale and design of the largest study to date to evaluate two major issues in the field of secondary prevention: (1) Does education and intensified collaboration with general practice, social services etc. reduce the duration of untreated psychosis? and (2) Can modified assertive community treatment improve the course and outcome in young persons suffering from psychosis as compared to treatment in community mental health centres? The article aims additionally to put the study in context and assist in designing future studies.\n Preliminary experiences are described. The findings of the first 312 patients show that modified assertive community treatment results in patients adhering to treatment significantly better than standard treatment in community mental health centres.\n The surge of interest in preventively oriented detection and treatment models for untreated psychosis in young people calls for research programmes and evidence. The obstacles to this are manifold. The initial findings of the OPUS study suggest, however, that better adherence to treatment is possible.", "This study tested a psychiatric rehabilitation approach for organizing and delivering services to street-dwelling persons with severe mental illness.\n Street-dwelling persons with severe mental illness were randomly assigned to the experimental program (called Choices) or to standard treatment in New York City. We assessed study participants at baseline and at 6-month intervals over 24 months, using measures of service use, quality of life, health, mental health, and social psychological status. The average deviation from baseline summary statistic was employed to assess change.\n Compared with persons in standard treatment (n = 77), members of the experimental group (n = 91) were more likely to attend a day program (53% vs 27%), had less difficulty in meeting their basic needs, spent less time on the streets (55% vs 28% reduction), and spent more time in community housing (21% vs 9% increase). They showed greater improvement in life satisfaction and experienced a greater reduction in psychiatric symptoms.\n With an appropriate service model, it is possible to engage disaffiliated populations, expand their use of human services, and improve their housing conditions, quality of life, and mental health status.", "A longitudinal experimental design was used to compare the effectiveness of three community-based treatment programs serving homeless mentally ill people: traditional outpatient treatment offered by a mental health clinic, a daytime drop-in center, and a continuous treatment team program that included assertive outreach, a high staff-to-client ratio, and intensive case management. At 12-month follow-up, clients in all three treatment programs spent fewer days per month homeless, showed fewer psychiatric symptoms, and had increased income, interpersonal adjustment, and self-esteem. Clients in the continuous treatment program had more contact with their treatment program, were more satisfied with their program, spent fewer days homeless, and used more community services and resources than clients in the other two programs.", "In a three-year controlled study, two California integrated service agency demonstration programs that combined structural and program reforms were tested to see if they produced improved outcomes for a cross-section of clients with severe and persistent mental illness.\n Clients at an urban site and a rural site were randomly assigned to an integrated service agency program or to a comparison group who received the usual services. Data on client outcomes, were drawn from databases and client and family interviews.\n Compared with the comparison groups, clients served by the integrated service agencies had less hospital care, greater workforce participation, fewer group and institutional housing arrangements, less use of conservatorship, greater social support, more leisure activity, less family burden, and greater client and family satisfaction. Clients in the urban demonstration program, but not those in the rural program, did better than the comparison group on measures of financial stability, personal well-being, and friendship. At the urban site, 72.6 percent of clients participated in the work force during the three-year study period, compared with 14.6 percent of the clients in the comparison group. No differences were found at either site in rates of arrest and conviction and in self-reported ratings of self-esteem, symptoms, medication compliance, homelessness, and criminal victimization. The capitated costs for demonstration clients were much higher than the costs for services used by comparison clients.\n Three-year outcomes for a cross-section of clients with severe mental illness in the integrated service agencies were broadly favorable, but costs of services for those clients were high relative to costs for clients receiving the current standard of care.", "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.", "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.", "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.", "Assertive community treatment is rapidly implemented by many European mental health services, but recently the evidence base has been questioned. Positive results of randomized trials in the USA were not replicated in the UK. The question is whether the UK findings are representative for other European countries with modern mental health services.\n Open randomized controlled trial of long-term severely mentally ill patients [Health of the Nation Outcome Scales (HoNOS) total score >or=15], assigned to assertive community treatment (n = 59) or to standard community mental health care (n = 59). Primary outcome: sustained contact; housing stability and admission days. This trial is registered as an International Standard Randomized Clinical Trial, number ISRCTN 11281756.\n Assertive community treatment was significantly better in sustaining contact with patients, but not in reducing admission days. No differences in housing stability, psychopathology, social functioning or quality of life were found.\n The results are in agreement with UK studies. However, the sustained contact potential of assertive community treatment is important, as too many patients are lost in standard care.", "Part of the community psychiatric nurse (CPN) service was reorganised into a community support team (CST), with staff acting as case managers. An economic evaluation ran parallel to the comparison with generic CPN care.\n Eighty-two clients were randomly allocated to experimental and control groups. Costs were comprehensively measured over a pre-referral period (three months), and then at 6, 12, and 18 months.\n The economic evaluation found a cost difference between the groups. Generic group costs averaged 89 pounds per patient per week more than CST group costs. The difference was only significant for the first six months. Changes in the burden of cost across agencies were observed.\n Although CPN inputs and costs were higher for the CST group, there was a significant short-term reduction in total cost. Beyond the short term, the CST did not confer cost or cost-effectiveness advantages.", "This investigation examined several adverse outcomes in clients with serious mental illness in a randomized trial of Assertive Community Treatment (ACT) versus usual care.\n 163 subjects were randomized to one of two ACT experimental conditions (staffed by consumers or non-consumers) or usual community care. Conditions were compared on psychiatric hospitalization, emergency room visit, arrest, and homelessness, within the two-year study period. Demographic, program, and client variables were examined for significant associations with outcomes.\n Significant differences were found between ACT and usual care in time to first arrest, but not hospitalization, homelessness or ER visits. Shorter time to first hospitalization was associated with male gender, diagnoses other than schizophrenia, high psychiatric symptomatology and lower provider case load. ER visits were associated with increased client symptomatology. Shorter times to homelessness were predicted by poorer therapeutic alliance between case manager and clients. Shorter time to first arrest was predicted by client minority status and enrollment in usual care.\n The paucity of significant main effects may have been due to a prolonged \"start-up\" phase of the ACT programs, poor ACT implementation, restricted availability of psychiatric hospital beds, or changes in usual care services delivered over the study period.", "Twenty-eight severely mentally ill adults in an inner-city area of Atlanta participated in a study to determine if intensive outreach by case managers would result in decreased use of mental hospitals and improved community living. The experimental group of 14 clients received intensive support from case managers in the community who helped them anticipate and prevent crises, maintain medication schedules, and address problems in living. Fourteen clients in the control group received some of these same services but at a less intensive level and only at the offices of the case managers. Compared with control clients, experimental clients had an average of ten fewer hospital days and better adherence to medication regimens and agreed-upon service plans during the project.", "The study evaluated the effects of an intensive case management model on clients' use of inpatient and outpatient psychiatric care and on the costs of care.\n Ninety clients of a county mental health system who were frequent users of inpatient services were randomly assigned to either an intensive case management group, a traditional case management group, or a control group who received no particular services. Outcome variables measured over a two-year period were number of units used by clients and costs of inpatient care in county and private facilities and various types of outpatient care, including day treatment and use of an emergency psychiatric unit.\n Clients who received intensive case management had fewer inpatient days and reduced overall costs for mental health services.\n Assertive outreach and intensive case management can reduce hospitalizations of clients who are frequent users of inpatient care and can reduce overall mental health care costs. Mental health consumers employed as case management aides can play an important role in the delivery of mental health services, particularly with frequent users of inpatient care.", "The mortality rate of discharged psychiatric inpatients has long been known to be higher than that of persons in the general population. This study assessed the effectiveness of outreach case management in reducing the mortality rate of recently discharged psychiatric inpatients in New York City.\n A sample of 292 patients discharged from an inpatient psychiatry service at an urban general hospital were randomly assigned either to an intervention group (N = 147), which received intensive outreach case management for periods ranging from 15 to 52 months after discharge, or to a control group (N = 145), which received standard aftercare services. Both groups were offered and received regular aftercare and other services during the study period. Both groups were followed for comparable periods of time to determine their rate of mortality.\n The overall mortality rate for the total group of 292 patients was 7.2 percent, 2.25 times higher than among persons in the general population matched for age, sex, and race. The mortality rates for the intervention group and the control group were 7.5 percent and 6.9 percent, respectively, not a significant difference.\n Discharged psychiatric inpatients who received outreach case management did not have a lower mortality rate than similar patients who did not receive this intervention.", "To determine the effect of the Program for Assertive Community Treatment (PACT) model on psychiatric inpatient service use in a population of non-emergency psychiatric patients with severe chronic mental illness, and to test for variations in this effect with program staffing levels and patient characteristics such as race and age.\n Data are taken from a randomized trial of PACT in Charleston, South Carolina for 144 patients recruited from August 1989 through July 1991.\n Subjects were randomly assigned either to one of two PACT programs or to usual care at a local mental health center. Effects on hospital use were measured over an 18-month follow-up period via multiple regression analysis.\n Data were obtained from Medicaid claims, chart reviews, subject, case manager, and family interviews; searches of the computerized patient and financial databases of the South Carolina Department of Mental Health and relevant hospitals; and searches of the hard copy and computerized financial databases of the two major local hospitals providing inpatient psychiatric care.\n PACT participants were about 40 percent less likely to be hospitalized during the follow-up period. The effect was stronger for older patients. Lower PACT client/staff ratios also reduced the risk of hospitalization. No evidence of differential race effects was found. Given some hospital use, PACT did not influence the number of days of use.\n Controlling for other covariates, PACT significantly reduces hospitalizations but the size of this effect varies with patient and program characteristics. This study shows that previous results on PACT can be applied to non-emergency patients even when the control condition is an up-to-date CMHC office-based case management program.", "This study compared the costs and outcomes associated with three treatment programs that served 149 individuals with dual disorders (i.e., individuals with co-occurring severe mental illness and substance use disorders) who were homeless at baseline. The three treatment programs were: Integrated Assertive Community Treatment (IACT), Assertive Community Treatment only (ACTO), and standard care (Control). Participants were randomly assigned to treatment and followed for a period of 24 months. Clients in the IACT and ACTO programs were more satisfied with their treatment program and reported more days in stable housing than clients in the Control condition. There were no significant differences between treatment groups on psychiatric symptoms and substance use. The average total costs associated with the IACT and Control conditions were significantly less than the average total costs for the ACTO condition.", "Case management has become the statutory basis of community care in the UK for people with long-term mental disorders, although a randomised controlled trial found no important improvements over standard care. Here we compare the costs and cost consequences of this intervention with standard care.\n Resource-use data were collected over a six-month baseline period and for 14 months after randomisation on all patients in the trial.\n At 14 months the ratio of control group to treatment group weekly costs was 1.09 (95% CI 0.86-1.38) for total costs; 1.12 (0.76-1.65) for state benefits, and 1.21 (0.61-2.42) for health care costs. Costs were thus lower in the treatment group, but these differences were not significant.\n Retrospective power calculations indicated that the trial could have detected differences of 30% in total cost, but would have required 700 patients per arm to detect a 20% difference in health care costs. Hence this study, which had adequate power to detect clinically meaningful differences, was found to be far too small to detect large differences in costs. Funding agencies increasingly request that clinical trials include economic alongside clinical end-points: these findings may have important lessons for that policy." ]

[ "15143088", "19726226", "7908358", "21282540", "15304029", "12888870", "16770976", "20598077" ]

[ "Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS).", "Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study.", "Double-blind randomised trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer.", "Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial.", "A randomized clinical trial of combination chemotherapy with and without low-molecular-weight heparin in small cell lung cancer.", "Trend to efficacy and safety using antithrombin concentrate in prevention of thrombosis in children receiving l-asparaginase for acute lymphoblastic leukemia. Results of the PAARKA study.", "Low-molecular-weight heparin in patients with advanced cancer: a phase 3 clinical trial.", "PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma." ]

[ "In experimental systems, interference with coagulation can affect tumor biology. Furthermore, it has been suggested that low molecular weight heparin therapy may prolong survival in patients with cancer. The primary aim of this study was to assess survival at 1 year of patients with advanced cancer.\n Patients with advanced malignancy (N = 385) were randomly assigned to receive either a once-daily subcutaneous injection of dalteparin (5,000 IU), a low molecular weight heparin, or placebo for 1 year.\n The Kaplan-Meier survival estimates at 1, 2, and 3 years after randomization for patients receiving dalteparin were 46%, 27%, and 21%, respectively, compared with 41%, 18%, and 12%, respectively, for patients receiving placebo (P =.19). In an analysis not specified a priori, survival was examined in a subgroup of patients (dalteparin, n = 55; and placebo, n = 47) who had a better prognosis and who were alive 17 months after randomization. In these patients, Kaplan-Meier survival estimates at 2 and 3 years from randomization were significantly improved for patients receiving dalteparin versus placebo (78% v 55% and 60% v 36%, respectively, P =.03). The rates of symptomatic venous thromboembolism were 2.4% and 3.3% for dalteparin and placebo, respectively, with bleeding rates of 4.7% and 2.7%, respectively.\n Dalteparin administration did not significantly improve 1-year survival rates in patients with advanced malignancy. However, the observed improved survival in a subgroup of patients with a better prognosis suggests a potential modifying effect of dalteparin on tumor biology.", "Clinical trials are needed to assess the clinical benefit of antithrombotic prophylaxis in patients with cancer who are receiving chemotherapy, since these patients are at an increased risk of developing a thromboembolism. We did a trial to assess the clinical benefit of the low-molecular-weight heparin nadroparin for the prophylaxis of thromboembolic events in ambulatory patients receiving chemotherapy for metastatic or locally advanced solid cancer.\n Between October, 2003, and May, 2007, ambulatory patients with lung, gastrointestinal, pancreatic, breast, ovarian, or head and neck cancer were randomly assigned in a double-blind manner to receive subcutaneous injections of nadroparin (3800 IU anti-Xa once a day, n=779) or placebo (n=387), in a 2:1 ratio. Study treatment was given for the duration of chemotherapy up to a maximum of 4 months. The primary study outcome was the composite of symptomatic venous or arterial thromboembolic events, as assessed by an independent adjudication committee. All randomised patients who received at least one dose of study treatment were included in the efficacy and safety analyses (modified intention-to-treat population). The study is registered with ClinicalTrials.gov, NCT 00951574.\n 1150 patients were included in the primary efficacy and safety analyses: 769 patients in the nadroparin group and 381 patients in the placebo group. 15 (2.0%) of 769 patients treated with nadroparin and 15 (3.9%) of 381 patients treated with placebo had a thromboembolic event (single-sided p=0.02). Five (0.7%) of 769 patients in the nadroparin group and no patients in the placebo group had a major bleeding event (two-sided p=0.18). The incidences of minor bleeding were 7.4% (57 of 769) with nadroparin and 7.9% (30 of 381) with placebo. There were 121 (15.7%) serious adverse events in the nadroparin goup and 67 (17.6%) serious adverse events in the placebo group.\n Nadroparin reduces the incidence of thromboembolic events in ambulatory patients with metastatic or locally advanced cancer who are receiving chemotherapy. Future studies should focus on patients who are at a high risk for thromboembolic events.\n Italfarmaco SpA, Milan, Italy.", "Patients receiving chemotherapy for metastatic breast cancer are at high risk of thromboembolic disease. Long-term oral anticoagulant therapy is needed but increases the risk of haemorrhagic complications. We have assessed the safety and efficacy of warfarin in very low doses as prophylaxis. Women receiving chemotherapy for metastatic breast cancer were randomly assigned either very-low-dose warfarin (152 patients) or placebo (159). The warfarin dose was 1 mg daily for 6 weeks and was then adjusted to maintain the prothrombin time at an international normalised ratio (INR) of 1.3 to 1.9. Study treatment continued until 1 week after the end of chemotherapy. The average daily dose from initiation of titration was 2.6 (SD 1.2) mg for the warfarin group and the mean INR was 1.52. The mean time at risk of thrombosis was 199 (126) days for warfarin-treated patients and 188 (137) days for placebo recipients (p = 0.45). There were 7 thromboembolic events (6 deep-vein thrombosis, 1 pulmonary embolism) in the placebo group and 1 (pulmonary embolism) in the warfarin group, a relative risk reduction of about 85% (p = 0.031). Major bleeding occurred in 2 placebo recipients and 1 warfarin-treated patient. There was no detectable difference in survival between the treatment groups. Very-low-dose warfarin is a safe and effective method for prevention of thromboembolism in patients with metastatic breast cancer who are receiving chemotherapy.", "In patients with myeloma, thalidomide significantly improves outcomes but increases the risk of thromboembolic events. In this randomized, open-label, multicenter trial, we compared aspirin (ASA) or fixed low-dose warfarin (WAR) versus low molecular weight heparin (LMWH) for preventing thromboembolism in patients with myeloma treated with thalidomide-based regimens.\n A total of 667 patients with previously untreated myeloma who received thalidomide-containing regimens and had no clinical indication or contraindication for a specific antiplatelet or anticoagulant therapy were randomly assigned to receive ASA (100 mg/d), WAR (1.25 mg/d), or LMWH (enoxaparin 40 mg/d). A composite primary end point included serious thromboembolic events, acute cardiovascular events, or sudden deaths during the first 6 months of treatment.\n Of 659 analyzed patients, 43 (6.5%) had serious thromboembolic events, acute cardiovascular events, or sudden death during the first 6 months (6.4% in the ASA group, 8.2% in the WAR group, and 5.0% in the LMWH group). Compared with LMWH, the absolute differences were +1.3% (95% CI, -3.0% to 5.7%; P = .544) in the ASA group and +3.2% (95% CI, -1.5% to 7.8%; P = .183) in the WAR group. The risk of thromboembolism was 1.38 times higher in patients treated with thalidomide without bortezomib. Three major (0.5%) and 10 minor (1.5%) bleeding episodes were recorded.\n In patients with myeloma treated with thalidomide-based regimens, ASA and WAR showed similar efficacy in reducing serious thromboembolic events, acute cardiovascular events, and sudden deaths compared with LMWH, except in elderly patients where WAR showed less efficacy than LMWH.", "Small cell lung cancer (SCLC) is a chemotherapy-responsive tumor type but most patients ultimately experience disease progression. SCLC is associated with alterations in the coagulation system. The present randomized clinical trial (RCT) was designed to determine whether addition of low-molecular-weight heparin (LMWH) to combination chemotherapy (CT) would improve SCLC outcome compared with CT alone.\n Combination CT consisted of cyclophosphamide, epirubicine and vincristine (CEV) given at 3-weekly intervals for six cycles. Eighty-four patients were randomized to receive either CT alone (n = 42) or CT plus LMWH (n = 42). LMWH consisted of dalteparin given at a dose of 5000 U once daily during the 18 weeks of CT. Results Overall tumor response rates were 42.5% with CT alone and 69.2% with CT plus LMWH (P = 0.07). Median progression-free survival was 6.0 months with CT alone and 10.0 months with CT plus LMWH (P = 0.01). Median overall survival was 8.0 months with CT alone and 13.0 months with CT plus LMWH (P = 0.01). Similar improvement in survival with LMWH treatment occurred in patients with both limited and extensive disease stages. The risk of death in the CT + LMWH group relative to that in the CT group was 0.56 (95% confidence interval 0.30, 0.86) (P = 0.012 by log rank test). Toxicity from the experimental treatment was minimal and there were no treatment-related deaths.\n These results support the concept that anticoagulants, and particularly LMWH, may improve clinical outcomes in SCLC. Further clinical trials of this relatively non-toxic treatment approach are indicated.", "An association has been reported between thrombotic events and the use of L-asparaginase (ASP) in children with acute lymphoblastic leukaemia (ALL). The mechanism for thrombosis is likely related to an acquired antithrombin deficiency. Since a primary prophylaxis using antithrombin concentrates may prevent thrombosis, the PARKAA (Prophylactic Antithrombin replacement in kids with ALL treated with L-asparaginase) study was performed. The objectives of PARKAA were to determine if there was a trend to efficacy and safety of antithrombin treatment as assessed by 1) incidence of thrombosis 2) incidence of bleeding and 3) plasma markers of endogenous thrombin generation as surrogate outcomes for thrombosis. The study was not powered to answer the question of efficacy and safety, but rather to detect a trend. PARKAA was an open, randomised, controlled study in children with ALL being treated with ASP. Children were randomised to receive antithrombin infusions or no antithrombin treatment. All thrombotic events were confirmed using bilateral venography, ultrasound, echocardiography and MRI. The incidence of thrombosis in patients treated with antithrombin was 28% (95% CI 10-46%), compared to 37% (95% CI 24-49%) in the non treated arm. Two minor bleeds occurred in patients in the treated arm, but were not considered to be related to antithrombin. No significant differences were seen in plasma markers by the treatment group. In conclusion, treatment with antithrombin concentrate shows a trend to efficacy and safety. In contrast, there was no difference in surrogate markers for thrombosis. Carefully designed clinical trials are needed to test the efficacy and safety of antithrombin in this population.", "To prospectively assess whether low-molecular-weight heparin (LMWH) provides a survival benefit in patients with advanced cancer.\n Between December 1998 and June 2001, we performed a randomized controlled study of patients with advanced cancer. Initially, the study was double blinded and placebo controlled, with the patients receiving daily injections of 5000 U of LMWH or saline. However, because of low accrual midway through the study, the placebo injection arm was eliminated, and the study became open labeled, with patients receiving either LMWH injections plus standard clinical care or standard clinical care alone. The primary study end point was overall survival.\n Of 141 patients randomized to this clinical trial, 3 dropped out, leaving 138 patients. The median survival time was 10.5 months (95% confidence interval, 7.6-12.2 months) for the combined standard care and placebo groups. The median survival time for the combined LMWH arms was 7.3 months (95% confidence interval, 4.8-12.2 months). These median survival times were not significantly different (log-rank P = .46). The median survival times for the blinded and unblinded LMWH groups were 6.2 months and 9.0 months, respectively. The median survival times were 10.3 months for the blinded placebo arm and 10.5 months for the standard care arm. The rate of severe or life-threatening venous thromboembolism was 6% in the LMWH arms and 7% in the control arms. The rate of severe or life-threatening bleeding was 3% in the LMWH arms and 7% in the control arms.", "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." ]

[ "22472744", "15329362", "17900321", "11560298", "17604300", "18840110", "18949181", "17356555", "16572062", "19727002", "22371721", "18410562", "16292090", "10545590", "2494098", "17669103", "7872284", "18026577", "2184848", "19138244", "9570649", "11864087", "15179608", "20145608", "18402597", "16437727", "15740542" ]

[ "Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized, double-blind, placebo-controlled trial.", "Effect of Lactobacillus F19 on the emergence of antibiotic-resistant microorganisms in the intestinal microflora.", "The effect of a multispecies probiotic on the intestinal microbiota and bowel movements in healthy volunteers taking the antibiotic amoxycillin.", "Lack of effect of Lactobacillus GG on antibiotic-associated diarrhea: a randomized, placebo-controlled trial.", "Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial.", "Lactobacillus plantarum 299v reduces colonisation of Clostridium difficile in critically ill patients treated with antibiotics.", "[Effect of probiotic Saccharomyces boulardii on prevention of antibiotic-associated diarrhea in adult outpatients with amoxicillin treatment].", "Prevention of antibiotic-associated diarrhoea by a fermented probiotic milk drink.", "Prophylactic Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea: a prospective study.", "Intake of Lactobacillus plantarum reduces certain gastrointestinal symptoms during treatment with antibiotics.", "Efficacy of BIO K+ CL1285 in the reduction of antibiotic-associated diarrhea - a placebo controlled double-blind randomized, multi-center study.", "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.", "Prophylactic Lactobacillus GG reduces antibiotic-associated diarrhea in children with respiratory infections: a randomized study.", "Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: a prospective study.", "Efficacy and safety of Saccharomyces boulardii in the 14-day triple anti-Helicobacter pylori therapy: a prospective randomized placebo-controlled double-blind study.", "Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo.", "Effect of a fermented milk combining Lactobacillus acidophilus Cl1285 and Lactobacillus casei in the prevention of antibiotic-associated diarrhea: a randomized, double-blind, placebo-controlled trial.", "Effect of Lactobacillus GG yoghurt in prevention of antibiotic associated diarrhoea.", "Feasibility and tolerability of probiotics for prevention of antibiotic-associated diarrhoea in hospitalized US military veterans.", "The lack of therapeutic effect of Saccharomyces boulardii in the prevention of antibiotic-related diarrhoea in elderly patients.", "Oral supplementation with lactic acid-producing bacteria during intake of clindamycin.", "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.", "Efficacy of Clostridium butyricum preparation concomitantly with Helicobacter pylori eradication therapy in relation to changes in the intestinal microbiota.", "Effect of Clostridium butyricum on fecal flora in Helicobacter pylori eradication therapy.", "Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a randomized double-blind placebo-controlled trial." ]

[ "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.", "Probiotic lactic-acid-producing bacteria have been used for prevention of gastrointestinal diseases. The aim of the present study was to examine whether Lactobacillus F19 in conjunction with treatment with penicillin, ciprofloxacin or norfloxacin prevents establishment of resistant bacteria in the gastrointestinal tract.\n Twenty patients admitted to hospital due for treatment with penicillin and 16 patients due for treatment with ciprofloxacin or norfloxacin were included in the study. In either group, the patients were randomized into two groups, receiving placebo or an active probiotic product. Faecal samples were collected before treatment, on day 10 and 1 month after the start of the treatment. Isolates of enterococci, enterobacteria and Bacteroides fragilis species were screened for resistance to penicillin and ciprofloxacin, respectively.\n Administration of penicillin did not influence resistance in enterococci while quinolone resistance increased during quinolone treatment. Susceptibility to ampicillin and piperacillin/tazobactam decreased in enterobacteria during penicillin treatment and ciprofloxacin resistance increased in the quinolone group. Penicillin and quinolones did not influence the resistance rates of Bacteroides isolates. No major differences were observed between the probiotic- and placebo-supplemented groups.\n There was a limited effect of Lactobacillus F19 on the emergence of resistant isolates during treatment with penicillin and quinolones.", "One of the side effects of antimicrobial therapy is a disturbance of the intestinal microbiota potentially resulting in antibiotic-associated diarrhea (AAD). In this placebo-controlled double-blind study, the effect of a multispecies probiotic on the composition and metabolic activity of the intestinal microbiota and bowel habits was studied in healthy volunteers taking amoxycillin.\n Forty-one healthy volunteers were given 500 mg amoxycillin twice daily for 7 days and were randomized to either 5 g of a multispecies probiotic, Ecologic AAD (10(9) cfu/g), or placebo, twice daily for 14 days. Feces and questionnaires were collected on day 0, 7, 14, and 63. Feces was analyzed as to the composition of the intestinal microbiota, and beta-glucosidase activity, endotoxin concentration, Clostridium difficile toxin A, short chain fatty acids (SCFAs), and pH were determined. Bowel movements were scored according to the Bristol stool form scale.\n Mean number of enterococci increased significantly from log 4.1 at day 0 to log 5.8 (day 7) and log 6.9 (day 14) cfu/g feces (P < 0.05) during probiotic intake. Although no other significant differences were observed between both intervention groups, within each group significant changes were found over time in both microbial composition and metabolic activity. Moreover, bowel movements with a frequency >or=3 per day for at least 2 days and/or a consistency >or=5 for at least 2 days were reported less frequently in the probiotic compared to the placebo group (48%vs 79%, P < 0.05).\n Apart from an increase in enterococci no significant differences in microbial composition and metabolic activity were observed in the probiotic compared with the placebo group. However, changes over time were present in both groups, which differed significantly between the probiotic and the placebo arm, suggesting that the amoxycillin effect was modulated by probiotic intake. Moreover, the intake of a multispecies probiotic significantly reduced diarrhea-like bowel movements in healthy volunteers receiving amoxycillin.", "To assess the efficacy of Lactobacillus GG in preventing antibiotic-associated diarrhea (AAD) in adults and, secondarily, to assess the effect of coadministered Lactobacillus GG on the number of tests performed to determine the cause of diarrhea.\n In this prospective, randomized, double-blind, placebo-controlled trial conducted from July 1998 to October 1999, 302 hospitalized patients receiving antibiotics were randomized to receive Lactobacillus GG, 20 x 10(9) CFU/d, or placebo for 14 days. Subjects recorded the number of stools and their consistency daily for 21 days. The primary outcome was the proportion of patients who developed diarrhea in the first 21 days after enrollment. Weekly telephone follow-up was also performed. Results were analyzed in an intention-to-treat fashion.\n Diarrhea developed in 39 (29.3%) of 133 patients randomized to receive Lactobacillus GG and in 40 (29.9%) of 134 patients randomized to receive placebo (P=.93). No additional difference in the rate of occurrence of diarrhea was found between treatment and placebo patients in a subgroup analysis of those treated with beta-lactam vs non-beta-lactam antibiotics. Too few patients had stool cultures, additional laboratory tests for diarrhea, or a positive diagnosis of Clostridium difficile infection to assess between-group differences.\n Lactobacillus GG in a dose of 20 x 10(9) CFU/d did not reduce the rate of occurrence of diarrhea in this sample of 267 adult patients taking antibiotics initially administered in the hospital setting.", "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.", "The incidence of Clostridium difficile-associated disease (CDAD) in hospitalised patients is increasing. Critically ill patients are often treated with antibiotics and are at a high risk of developing CDAD. Lactobacillus plantarum 299v (Lp299v) has been found to reduce recurrence of CDAD. We investigated intensive care unit (ICU) patients with respect to the impact of Lp299v on C. difficile colonisation and on gut permeability and parameters of inflammation and infection in that context.\n Twenty-two ICU patients were given a fermented oatmeal gruel containing Lp299v, and 22 received an equivalent product without the bacteria. Faecal samples for analyses of C. difficile and Lp299v were taken at inclusion and then twice a week during the ICU stay. Other cultures were performed on clinical indication. Infection and inflammation parameters were analysed daily. Gut permeability was assessed using a sugar probe technique.\n Colonisation with C. difficile was detected in 19% (4/21) of controls but in none of the Lp299v-treated patients (P<0.05).\n Enteral administration of the probiotic bacterium Lp299v to critically ill patients treated with antibiotics reduced colonisation with C. difficile.", "Antibiotic-associated diarrhea is one of the most common adverse effects of antimicrobials. Any antimicrobial can potentially produce diarrhea but beta-lactamics have a higher risk. Among these, amoxicillin is widely indicated in ambulatory practice. One of the alternatives suggested to prevent antibiotic-associated diarrhea, is the use of the probiotic Saccharomyces boulardii.\n To evaluate whether the concomitant use of Saccharomyces boulardii and amoxicillin can prevent antibiotic associated diarrhea in ambulatory adults with acute infections diseases, without provoking other adverse effects.\n Eighty six adults (aged 15 to 81 years) with acute infectious diseases, excluding those arising in the gastrointestinal tract, that received a prescription of oral amoxicillin for 5 to 10 days, were included. In a controlled randomized, double blind trial, 41 patients were assigned to receive lyophilized Saccharomyces boulardii (500 mg/day) during 12 days, and 45 patients were assigned to placebo for the same period.\n Ten percent of patients (9/86) reported acute diarrhea, 9,8% (4/41) in the experimental group and 11.196 (5/45) in the control group (p = 100). No adverse effects were associated to the use of the probiotic.\n Saccharomyces boulardii (500 mg/day) did not prevent diarrhea related to amoxicillin.", "To study the preventive effect of a milk drink fermented with multistrain probiotics on antibiotic associated diarrhoea (AAD).\n Double-blind placebo controlled study.\n University Hospital of North Norway.\n Of 853 patients treated with antibiotics, 87 met the inclusion criteria, and were randomized to ingestion of a fermented milk drink containing LGG, La-5 and Bb-12 (n=46) or placebo with heat-killed bacteria (n=41), during a period of 14 days. A diary was recorded, and stool samples were collected for microbiological analyses.\n Sixty-three patients completed the study according to the protocol; two patients (5.9%) in the treatment group and eight (27.6%) in the placebo group developed AAD (P=0.035). The relative risk of developing AAD was 0.21 (95% confidence interval: 0.05-0.93) when given probiotic milk drink.\n A fermented multistrain probiotic milk drink may prevent four of five cases of AAD in adult hospitalized patients.\n TINE BA, Oslo, Norway.", "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.", "To examine if intake of Lactobacillus plantarum can prevent gastrointestinal side effects in antibiotic-treated patients.\n Diarrhea is a common side effect of treatment with antibiotics. Some studies indicate that the risk of antibiotic-associated diarrhea can be reduced by administration of certain probiotic microorganisms.\n Patients treated for infections at a university hospital infectious diseases clinic were randomized to daily intake of either a fruit drink with L. plantarum 299v (10(10) colony forming units/d) or a placebo drink, until a week after termination of antibiotic treatment. Subjects recorded the number and consistency of stools as well as gastrointestinal symptoms until up to 3 weeks after last intake of test drink. Fecal samples were collected before the first intake of test drink and after termination of antibiotic therapy and analyzed for Clostridium difficile toxin.\n Clinical characteristics on admission were similar in the 2 groups. The overall risk of developing loose or watery stools was significantly lower among those receiving L. plantarum [odds ratio (OR), 0.69; 95% confidence interval (CI), 0.52-0.92; P=0.012], as was development of nausea (OR, 0.51; 95% CI, 0.30-0.85; P=0.0097). Diarrhea defined as > or =3 loose stools/24 h for > or =2 consecutive days was unaffected by the treatment (OR, 1.4; 95% CI, 0.33-6.0; P=0.86). No significant differences regarding carriage of toxin producing C. difficile were observed between the groups.\n Our results indicate that intake of L. plantarum could have a preventive effect on milder gastrointestinal symptoms during treatment with antibiotics.", "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.", "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.", "Antimicrobial treatment may disturb the colonization resistance of gastrointestinal microflora, which may induce clinical symptoms, most commonly diarrhea. The severity of antibiotic-associated diarrhea may range from a brief, self-limiting disease to devastating diarrhea with electrolyte disturbances, dehydration, crampy abdominal pain, pseudomembranous colitis, toxic megacolon, or even death. The incidence of diarrhea in children receiving a single antimicrobial treatment is unclear. In addition to more critical use of antimicrobials, adjunctive preventive measures to antibiotic-associated diarrhea are needed. The objective of this study was to evaluate the incidence of diarrhea after antimicrobial treatment in children with no history of antimicrobial use during the previous 3 months. Another aim of this study was to assess the preventive potential of Lactobacillus rhamnosus GG (Lactobacillus GG; American Type Culture Collection 53103), a probiotic strain with a documented safety record and a therapeutic effect in viral gastroenteritis on antibiotic-associated diarrhea.\n Oral antimicrobial agents were prescribed for the treatment of acute respiratory infections at the clinics of the Health Care Center of the City of Tampere or Tampere University Hospital, Finland, to 167 patients who were invited to participate in the study. Of the patients, 48 were lost to follow-up; therefore, the final study population consisted of 119 children from 2 weeks to 12. 8 years of age (mean: 4.5 years). All study subjects met the inclusion criteria: they had not received any antimicrobial medication during the previous 3 months, they did not suffer from gastrointestinal disorders, and they did not need intravenous antimicrobial treatment. The patients were randomized to receive placebo or 2 x 10(10) colony-forming units of Lactobacillus GG in capsules given twice daily during the antimicrobial treatment. Lactobacillus GG and placebo capsules were indistinguishable in appearance and taste. The parents kept a daily symptom diary and recorded stool frequency and consistency at home for 3 months. Diarrhea was defined as at least three watery or loose stools per day for a minimum of 2 consecutive days. In the case of diarrhea, viral (adenovirus, rotavirus, calicivirus and astrovirus) and bacterial (Salmonella, Shigella, Yersinia, Campylobacter, Clostridium difficile, Staphylococcus aureus, and yeasts) analyses were studied in fecal samples. The metabolic activity of the gut microflora was assessed by analysis of fecal urease, beta-glucosidase, and beta-glucuronidase activities. The primary outcome measure was diarrhea during the first 2 weeks after the beginning of the antimicrobial treatment, because this period most likely reflects the effects of antimicrobial use. Secondary outcome measures were the activities of fecal urease, beta-glucuronidase, and beta-glucosidase.\n On the entire follow-up, 80% of any gastrointestinal symptoms were reported during the first 2 weeks after the beginning of the antimicrobial treatment. The incidence of diarrhea was 5% in the Lactobacillus GG group and 16% in the placebo group within 2 weeks of antimicrobial therapy (chi(2) = 3.82). The treatment effect (95% confidence interval) of Lactobacillus GG was -11% (-21%-0%). In diarrheal episodes, the viral and bacterial analyses were positive for Clostridium difficile in 2 cases and for Norwalk-like calicivirus in 3 cases. The age of the patients with diarrhea was between 3 months and 5 years in 75% of cases in both groups. The severity of diarrhea was comparable in the study groups, as evidenced by similar stool frequency (mean: 5 per day; range: 3-6) and the duration of diarrhea (mean: 4 days; range: 2-8). The activities of fecal urease and beta-glucuronidase, but not beta-glucosidase, changed significantly after the beginning of the antimicrobial treatment in the Lactobacillus GG group and in the placebo group alike. (ABSTRACT TRUNCATED)", "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.", "Recent studies indicate a potential role of Saccharomyces boulardii in the prevention of Helicobacter pylori treatment-related side-effects and also in improvement of eradication rate. Our aim is to investigate the efficacy and safety of S. boulardii in the prevention of side-effects related to H. pylori eradication. The secondary aim of the study was to define the effect of S. boulardii on the eradication success of anti-H. pylori therapy.\n One hundred and twenty-four patients with H. pylori infection (male/female: 44/80, mean age: 48 +/- 14.25 year) receiving 14 days of triple therapy (clarithromycin 500 mg b.i.d., amoxicillin 1000 mg b.i.d., and lansoprazole 30 mg b.i.d.) were randomly assigned to S. boulardii or placebo. Dyspeptic symptoms were recorded by using modified Glasgow Dyspepsia Questionnaire (GDQ). Side-effect profile and tolerability were assessed using a symptom-based questionnaire. H. pylori status was rechecked after 6 weeks after completion of eradication therapy.\n H. pylori eradication rate, although higher in the treatment group, was statistically similar in treatment and control groups: 71% (44/62) versus 59.7% (37/62), respectively (p > .05). Nine (14.5%) patients in the treatment group and 19 (30.6%) patients in the placebo group experienced diarrhea (p < .05). Epigastric discomfort was more frequent in the control group [9 (14.5%) versus 27 (43.5%), respectively (p < .01)]. Diffuse abdominal pain, abdominal gas, taste disturbance, urticaria, nausea symptoms were similar in both groups. GDQ scores after treatment were significantly better for treatment group (mean +/- SD, range: 1.38 +/- 1.25 (0-5) vs. 2.22 +/- 1.44 (0-6), respectively; p < .01).\n S. boulardii improved anti-H. pylori antibiotherapy-associated diarrhea, epigastric discomfort, and treatment tolerability. In addition, S. boulardii supplement decreased post-treatment dyspepsia symptoms independent of H. pylori status. However, S. boulardii had no significant affect on the rate of H. pylori eradication.", "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.", "Antibiotic-associated diarrhea is an important problem in hospitalized patients. The use of probiotics is gaining interest in the scientific community as a potential measure to prevent this complication. The main objective of the present study was to assess the efficacy and safety of a fermented milk combining Lactobacillus acidophilus and Lactobacillus casei that is widely available in Canada, in the prevention of antibiotic-associated diarrhea.\n In this double-blind, randomized study, hospitalized patients were randomly assigned to receive either a lactobacilli-fermented milk or a placebo on a daily basis.\n Among 89 randomized patients, antibiotic-associated diarrhea occurred in seven of 44 patients (15.9%) in the lactobacilli group and in 16 of 45 patients (35.6%) in the placebo group (OR 0.34, 95% CI 0.125 to 0.944; P=0.05). The median hospitalization duration was eight days in the lactobacilli group, compared with 10 days in the placebo group (P=0.09). Overall, the lactobacilli-fermented milk was well tolerated.\n The daily administration of a lactobacilli-fermented milk was safe and effective in the prevention of antibiotic-associated diarrhea in hospitalized patients.", "The efficacy of Lactobacillus GG yoghurt in preventing erythromycin associated diarrhoea was studied. Sixteen healthy volunteers were given erythromycin acistrate 400 mg t.i.d for a week. The volunteers were randomly assigned into two groups taking twice daily 125 ml of either Lactobacillus GG fermented yoghurt or pasteurized regular yoghurt as placebo during the drug treatment. Subjects receiving Lactobacillus GG yoghurt with erythromycin had less diarrhoea than those taking pasteurized yoghurt. Other side effects of erythromycin, such as abdominal distress, stomach pain and flatulence, were less common in the GG yoghurt group than in the placebo yoghurt group. The subjects receiving Lactobacillus GG yoghurt were colonized with these bacteria even during erythromycin treatment as measured by faecal counts of total Lactobacillus GG. No Lactobacillus GG was found in the faecal samples of volunteers in the group taking pasteurized yoghurt.", "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.", "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.", "OBJECTIVE: To study the effect of administration of clindamycin with or without supplementation of the intestinal microflora with Bifidobacterium bifidum and Lactobacillus acidophilus. METHODS: Twenty-three healthy subjects received clindamycin by mouth for 7 days. Eleven of the subjects also received capsules containing lyophilized L. acidophilus and B. bifidum for 14 days. The other 12 subjects received placebo. RESULTS: There was a marked decrease in total numbers of anaerobic bacteria during the administration of clindamycin. In the lactic acid bacteria-supplemented group, a tendency towards delayed reduction and earlier increase in bifidobacteria was observed, and two of 11 subjects (18%) were colonized with Clostridium difficile, in comparison with five of 12 (41%) in the placebo group. The total number of microorganisms was significantly higher in the lactic acid bacteria-supplemented group than in the placebo group (p=0.02) 4 days after the end of clindamycin administration. The difference was mainly due to higher counts of Escherichia coli and enterococci. Mean levels of other enterobacteria increased less in the lactic acid bacteria-supplemented group than in the placebo group between days 0 and 14. CONCLUSIONS: The recolonization with aerobic and anaerobic microorganisms was faster in the lactic acid bacteria-supplemented group than in the placebo group. This may be of importance in preventing colonization with C. difficile.", "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 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.", "To investigate the effect of probiotic bacterium, Clostridium butyricum MIYAIRI 588 strain (CBM) on the changes of the fecal flora in Helicobacter pylori (H. pylori) treatment.\n Thirty-five patients with gastric or duodenal ulcers positive for H. pylori were randomized either to 1 wk amoxicillin, clarithromycin, lansoprazole (Group 1) or to the same regimen supplemented with CBM 7 d ahead of the triple therapy (Group 2). Stool samples were collected before and 2, 4, 7, 15, and 22 d after the starting eradication therapy, and were examined intestinal flora. Patients were required to keep a diary record of their condition.\n Obligate anaerobes decreased significantly on d 2, 4, 8 and 15 in Group 1. On the other hand, they did not decrease significantly in Group 2. The Escherichia coli was dominant bacterium in Enterobacteriaceae, but that was replaced by other species such as Klebsiella and Enterobacter after eradication in Group 1. The change was suppressed in Group 2. Abdominal symptoms were less frequent in Group 2 than in Group 1.\n The combined use of CBM reduced the changes in the intestinal flora and decreased the incidence of gastrointestinal side effects.", "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." ]

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[ "Dynamics and significance of placebo response in primary dysmenorrhea.", "Effects of naproxen sodium on menstrual prostaglandins and primary dysmenorrhea.", "Piroxicam in primary dysmenorrhea.", "Comparison of ketoprofen and naproxen in the treatment of dysmenorrhoea, with special regard to the time of onset of pain relief.", "The treatment of dysmenorrhea with naproxen sodium: a report on two independent double-blind trials.", "Feldene in the symptomatic treatment of primary dysmenorrhoea.", "Primary dysmenorrhea treated with indomethacin.", "Double-blind crossover comparison of ketoprofen, naproxen, and placebo in patients with primary dysmenorrhea.", "Comparison of fenoprofen calcium, ibuprofen and placebo in primary dysmenorrhea.", "Alterations in intrauterine pressure, menstrual fluid prostaglandin F levels, and pain in dysmenorrheic women treated with nimesulide.", "Efficacy of indomethacin suppository in primary dysmenorrhoea.", "Indomethacin in the treatment of primary dysmenorrhoea.", "An attempt at real prophylaxis of primary dysmenorrhea: comparison between meclofenamate sodium and naproxen sodium.", "[Piroxicam versus naproxen in primary dysmenorrhea].", "Diflunisal compared with naproxen in the treatment of dysmenorrhea.", "Treatment of primary dysmenorrhea with diclofenac sodium.", "Comparative efficacy of diclofenac dispersible 50 mg and ibuprofen 400 mg in patients with primary dysmenorrhea. A randomized, double-blind, within-patient, placebo-controlled study.", "Efficacy of ketoprofen in treating primary dysmenorrhea.", "Efficacy and tolerability of lumiracoxib in the treatment of primary dysmenorrhoea.", "Ibuprofen and naproxen-sodium in the treatment of primary dysmenorrhea: a double-blind cross-over study.", "A double-blind, placebo-controlled study comparing three single-dose regimens of piroxicam with ibuprofen in patients with primary dysmenorrhea.", "A crossover comparison of bromfenac sodium, naproxen sodium, and placebo for relief of pain from primary dysmenorrhea.", "Piroxicam in the treatment of primary dysmenorrhea.", "Analgesic efficacy of ibuprofen for treatment of primary dysmenorrhea.", "Indomethacin in the treatment of primary dysmenorrhoea.", "Comparison of the efficacy and tolerability of dexketoprofen and ketoprofen in the treatment of primary dysmenorrhea.", "Efficacy and tolerability of lumiracoxib 200 mg once daily for treatment of primary dysmenorrhea: results from two randomized controlled trials.", "Mefenamic acid therapy in dysmenorrhea.", "[Menstrual prostaglandin and dysmenorrhea: modulation by non-steroidal antiinflammatory drugs].", "[Nimesulide in the treatment of primary dysmenorrhea. Comparative clinical evaluation with mefenamic acid and fentiazac].", "Diclofenac potassium attenuates dysmenorrhea and restores exercise performance in women with primary dysmenorrhea.", "Analgesic efficacy of etoricoxib in primary dysmenorrhea: results of a randomized, controlled trial.", "The effect of three cyclo-oxygenase inhibitors on intensity of primary dysmenorrheic pain.", "[A new pharmacologic treatment of primary dysmenorrhea].", "Clinical experience of naproxen in the treatment of primary dysmenorrhea.", "Flufenamic acid in treatment of primary spasmodic dysmenorrhoea. A double-blind crossover study.", "Naproxen in dysmenorrhoea.", "Severe, primary dysmenorrhea treated with naproxen. A prospective, double-blind, crossover investigation.", "An objective evaluation of flurbiprofen and tranexamic acid in the treatment of idiopathic menorrhagia.", "[Treatment of primary dysmenorrhea. Comparative study of ibuprofen and mefenamic acid].", "The efficacy and safety of aceclofenac versus placebo and naproxen in women with primary dysmenorrhoea.", "Valdecoxib, a cyclooxygenase-2-specific inhibitor, is effective in treating primary dysmenorrhea.", "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.", "Treating dysmenorrhea with anti-inflammatory agents: a double-blind trial with naproxen sodium.", "Naproxen sodium in dysmenorrhea. Its influence in allowing continuation of work/school activities.", "Rofecoxib, a specific cyclooxygenase-2 inhibitor, in primary dysmenorrhea: a randomized controlled trial." ]

[ "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.", "Prostaglandins E2 and F2 alpha in the menstrual fluid from 12 patients with primary dysmenorrhea were measured by radioimmunoassay (RIA). Each patient was studied for 3 cycles, using vaginal tampons issued for this study. All tampons were collected individually for prostaglandin extraction and RIA. Severity of dysmenorrhea and clinical response to treatment were evaluated by a scoring method and by the patients' self-assessment. Each patient in this double-blind cross-over study had a control cycle and 2 treatment cycles with naproxen sodium tablets (275 mg) or placebo in random order. The treatment regimen was 2 tablets at the first sign of menses followed by one tablet 4 times daily for 3 days. Nine patients obtained good to excellent relief from naproxen sodium, but no relief from the placebo. Two patients had moderate to good response to both naproxen and placebo, and one patient showed no response. Naproxen therapy but not placebo therapy sharply reduced menstrual prostaglandin F2 alpha and prostaglandin E2 release. There was a positive correlation between menstrual prostaglandin levels and the severity of dysmenorrhea. Symptomatically, naproxen sodium was most effective in alleviating severe menstrual cramps but had little effect on mild cramps. It was also effective in ameliorating many but not all of the subjective symptoms such as dizziness, nausea, and vomiting. Relief of dysmenorrhea was apparent within one hour after the initial dose, attained maximum level in 2 hours, and was maintained throughout therapy.", "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.", "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.", "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.", "nan", "Primary dysmenorrhea is a difficult entity to treat, and therapy is usually directed at relieving symptoms. There is some indication that this disorder is caused by an increase in prostaglandin F2alpha. Therefore, logically the treatment may include antiprostaglandin agents. We have studied 32 women with the diagnosis of primary dysmenorrhea in a randomized double-blind fashion using a placebo and indomethacin. Both agents were taken three times a day over four cycles, and therapy was begun two days before the usual onset of pelvic pain. Only two of 16 patients in the placebo group were significantly improved in the four-month treatment cycles while all 16 in the treatment group showed some improvement, 11 having cessation of pain. In the six months following the study period, all patients were given indomethacin. The original treatment group did not change significantly. However, all in the placebo group when switched to indomethacin had some relief, 12 of the 16 showing complete cessation of pain. Gastric irritation was the main side effect and was present in 18% of the treatment group and 12% in the placebo group. Indomethacin appears to effectively relieve primary dysmenorrhea and does not appear to be associated with a high incidence of side effects.", "Sixty-three women, aged 18 to 39 years, with primary dysmenorrhea received 25 mg, 50 mg, or 75 mg of ketoprofen, 500 mg of naproxen, or placebo as a first dose at the onset of moderate or severe pain. Each patient received three treatments and each treatment was tested in 36 patients. Mean pain relief scores (on a five-point scale) indicated a significant analgesic response for all active treatments; superiority over placebo was shown by ketoprofen 50 mg for six hours, by ketoprofen 75 mg for five hours, by ketoprofen 25 mg for four hours, and by naproxen for four hours. The onset of pain relief and peak relief were reached faster and pain relief lasted longer after 75 mg and 50 mg of ketoprofen than after 25 mg of ketoprofen or 500 mg of naproxen, which in turn were superior to placebo. Treatment was rated good to excellent by 20 patients after 25 mg of ketoprofen, by 26 after 50 mg, and by 28 after 75 mg, and by 22 after naproxen and 11 after placebo. The incidence of side effects was similar in the ketoprofen-treated and naproxen-treated patients.", "This prospective, double-blind, parallel, two clinic study compared fenoprofen calcium, 200 mg; ibuprofen, 400 mg; and placebo in the treatment of pain due to primary dysmenorrhea. By various criteria, the treatment groups, prior to treatment, were not significantly different (P greater than 0.05) in paired comparisons. However, after oral administration of the study medications, the pain scores were significantly greater (P less than 0.05) for the placebo group than for either other group. The posttreatment pain scores for the fenoprofen and ibuprofen treated groups were not significantly different (P greater than 0.05).", "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.", "The efficacy of indomethacin suppositories (100 mg 1-3 times a day) in the treatment of primary dysmenorrhoea was investigated in a double-blind, crossover study involving 40 patients, in comparison to placebo. The patients were treated for four menstrual periods-two periods with placebo and two periods with indomethacin suppositories. A dysmenorrhoeic score based on subjective estimations of nine symptoms was used, the symptoms including pelvic pain, backache, headache, dizziness, nausea, vomiting, diarrhoea, nervousness and incapacitation. As compared to placebo, indomethacin suppositories led to a insignificant decrease in the frequency and severity of the associated symptoms, as evaluated by subjective rating (P less than 0.05). Indomethacin suppositories were well tolerated and there was no drop-out. No side effects were reported except for a mild burning sensation in the rectal region experienced by 3 patients on indomethacin suppositories.", "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.", "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.", "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.", "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.", "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.", "Sixty female out-patients suffering from moderate to severe primary dysmenorrhea, aged 14-40 years (mean 27 years), entered this randomized, double-blind, 3-period, within-patient study, evaluating the efficacy and tolerability of diclofenac dispersible 46.5 mg (equivalent to 50 mg of diclofenac sodium), ibuprofen 400 mg and placebo taken up to 4 times daily for a maximum of 3 days. Pain relief was evaluated on a verbal rating scale (0 = none, 1 = slight, 2 = moderate, 3 = considerable, 4 = complete) at 0.5, 1,2,3,4,5 and 6 hours after the first dose; the weighted sum of pain relief scores over the 6-hour observation period was also investigated (TOTPAR-6). Pain intensity was assessed on a verbal rating scale (0 = nil, 1 = mild, 2 = moderate, 3 = severe) at baseline and at the above mentioned time points; the weighted sum of pain intensity differences at each time point was also analyzed (SPID-6). A rescue medication was permitted 1 hour or more after the intake of the test drug: in such cases the last value of pain intensity/relief scores was carried forward and used for the analysis. A global evaluation of efficacy and of trial medication as compared to her usual medication was performed by the patient at the end of each treatment period. Finally, adverse experiences were recorded throughout the study period. Analysis of covariance and Koch's adaptation of the Wilcoxon-Mann-Whitney rank sum test were used, where appropriate, for statistical analysis. Mean TOTPAR-6 values for diclofenac dispersible, ibuprofen and placebo were 16.5, 17.8 and 14.7, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)", "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.", "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.", "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.", "Sixty-eight women with primary dysmenorrhea were randomly assigned to one of five four-times-daily treatment groups for a minimum of three days and a maximum of five days. Three of the groups received different initial single-daily doses of piroxicam, which were followed on each treatment day with placebo for the second through fourth doses, namely, piroxicam 20 mg daily for five days (piroxicam 20 mg for five days); piroxicam 40 mg on Day 1, followed by piroxicam 20 mg on Days 2 through 5 (piroxicam 40 mg for one day); and piroxicam 40 mg on Days 1 and 2, followed by piroxicam 20 mg on Days 3 through 5 (piroxicam 40 mg for two days). The fourth group received ibuprofen 400 mg four times per day, and the fifth group received placebo four times per day. Patients determined the severity of overall discomfort and pelvic-abdominal pain at baseline and prior to each dose using a four-point numerical scale. Supplemental ibuprofen, 400 mg four times per day, was provided for those patients requiring additional pain relief. Patients also made a global determination of overall relief at the end of the study. At 24 hours, the results revealed that piroxicam 40 mg for two days, piroxicam 20 mg for five days, and ibuprofen provided significantly more relief of overall discomfort compared with placebo (p = 0.003, p = 0.018, and p = 0.026, respectively). All four active treatment groups also experienced significantly more relief of pelvic-abdominal pain compared with placebo: piroxicam 40 mg for two days followed by three days of 20 mg (p = 0.002), piroxicam 40 mg for one day followed by four days of 20 mg (p = 0.023), piroxicam 20 mg for five days (p = 0.012), and ibuprofen (p = 0.011). A significantly smaller percentage of patients treated with piroxicam 40 mg for two days required supplemental medication as compared with those treated with piroxicam 20 mg for five days (p = 0.035) and patients treated with placebo (p = 0.010). A greater amount of overall relief was obtained by patients treated with piroxicam 40 mg for two days compared with patients treated with piroxicam 40 mg for one day (p = 0.041) and placebo-treated patients (p = 0.001). It was concluded that single daily doses of piroxicam 20 mg and 40 mg were as effective as ibuprofen, 400 mg four times per day, for the relief of primary dysmenorrhea.", "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.", "In double-blind, crossover studies, piroxicam was compared with naproxen sodium and with placebo. The different parameters studied were pain intensity, patient's opinion of the drugs tested, complementary pharmacological treatment, ability to work, overall effect, treatment preference, and side effects. It was concluded that piroxicam was comparable to naproxen sodium and that piroxicam was significantly better than placebo, as regards these parameters. It was also concluded that piroxicam has an effect equivalent to that of naproxen sodium, an accepted treatment for dysmenorrhea.", "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 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.", "Dexketoprofen, the pure S(+)-enantiomer of ketoprofen, is a promising new analgesic, but few clinical trials have yet examined its efficacy and tolerability. In this study, patients with a history of primary dysmenorrhea were treated with dexketoprofen doses of 12.5 and 25 mg, ketoprofen 50 mg, and placebo using a randomized, four-way crossover design. Efficacy analyses showed that dexketoprofen 12.5 and 25 mg and racemic ketoprofen 50 mg significantly reduced pain intensity compared with placebo from 1 h after dose to 4-6 h after dose. Interestingly, dexketoprofen at 12.5 mg was significantly superior to placebo at 30 min after dose. Mean pain relief scores also demonstrated that both doses of dexketoprofen and racemic ketoprofen were significantly superior to placebo at 1-6 h after the first dose. No indices of analgesic efficacy showed any significant differences between the two doses of dexketoprofen or between dexketoprofen and ketoprofen. After repeated dose administration, similar results were obtained. There were no significant effects of any treatment on activities of daily living, menstrual flow, or associated symptoms. Dexketoprofen was effective, well tolerated, and had no difference in the incidence of adverse events compared to ketoprofen or placebo.", "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.", "nan", "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).", "Sixty patients with primary dismenorrhea were treated: 20 with nimesulide, 20 with fentiazac and 20 with mefenamic acid during three consecutive cycles under double blind design. The doses used in each group were: nimesulide or fentiazac 100 mg, every 12 hrs., mefenamic acid 500 mg. every 8 hrs. in all cases during 5 days, beginning a day before the beginning, of the menstruation. The pain evolution and the symptoms were evaluated three times a day using a scale from 0 to 10, so measure its intensity. Concluding, the nimesulide is useful in the treatment of pain associated with primary dismenorrhea, answering with little statistical advantage over the fentiazac and with bigger statistical advantage over the mefenamic acid. The tolerance was excellent with the three drugs studied.", "We assessed the efficacy of diclofenac potassium, a nonsteroidal anti-inflammatory drug, in alleviating menstrual pain and restoring exercise performance to that measured in the late-follicular phase of the menstrual cycle. Twelve healthy young women with a history of primary dysmenorrhea completed, in a random order, laboratory exercise-testing sessions when they were in the late-follicular (no menstruation, no pain) phase of the menstrual cycle and when they were experiencing dysmenorrhea and receiving, in a double-blinded fashion, either 100 mg of diclofenac potassium or placebo. We assessed the women's leg strength (1-repetition maximum test), aerobic capacity (treadmill walking test), and ability to perform a functional test (task-specific test). Compared with placebo, diclofenac potassium significantly decreased dysmenorrhea on the day of administration (Visual Analog Scale, P < .001 at all times). When receiving placebo for menstrual pain, the women's performance in the tests was decreased significantly, compared with when they were receiving diclofenac potassium for menstrual pain (P < .05) and compared with when they were in the late-follicular phase of the menstrual cycle (P < .05 for treadmill test, P < .01 for task-specific test and 1-repetition maximum test). Administration of diclofenac potassium for menstrual pain restored exercise performance to a level not different from that achieved in the late-follicular phase of the cycle.\n In women with primary dysmenorrhea, menstrual pain, if untreated, decreases laboratory-assessed exercise performance. A recommended daily dose of a readily available nonsteroidal anti-inflammatory drug, diclofenac potassium, is effective in relieving menstrual pain and restoring physical performance to levels achieved when the women were in the late-follicular (no menstruation, no pain) phase of the menstrual cycle.", "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", "To determine the effect of 3 different cyclo-oxygenase (COX) inhibitors on primary dysmenorrheic pain.\n Eleven female patients self-medicated with either placebo (sugar), 25 mg of the COX-2 specific inhibitor rofecoxib, 50 mg of the nonselective COX inhibitor diclofenac potassium, or 7.5 mg of the COX-2 selective inhibitor meloxicam, over 4 menstrual cycles. Pain was assessed using the McGill Pain Questionnaire and a visual analog scale.\n The pain response index, present pain index, and visual analog scale were highly correlated as measures of intensity of pain (r=0.81 to 0.96, P<0.0001). Rofecoxib and diclofenac potassium both decreased the duration of dysmenorrheic pain compared with placebo (P<0.001) and with meloxicam (P<0.01), and were equally effective in improving pain, compared with placebo, after each capsule (P<0.001). When compared with placebo, both drugs also provided 50% or more pain relief, after each capsule (P<0.0048). Meloxicam, although superior to placebo, was not as effective as rofecoxib and diclofenac potassium in reducing pain, and when compared with placebo, was associated with providing 50% or more of pain relief only after the third and fourth capsules (P=0.016).\n Rofecoxib and diclofenac potassium, when taken in recommended doses, were equally effective in alleviating pain associated with primary dysmenorrhea.", "nan", "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.", "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.", "nan", "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.", "The effect of flurbiprofen (100 mg x 2 for 5 days) was compared with tranexamic acid (1.5 g x 3 for 3 days, 1 g x 2 days 4 and 5) in the treatment of 15 women with idiopathic menorrhagia. The mean blood loss during two medication-free periods was 295 +/- 52 ml. A significant (p less than 0.01) reduction in menstrual blood loss was recorded during treatment with both flurbiprofen and tranexamic acid. The menstrual blood loss was significantly (p less than 0.01) lower during treatment with tranexamic acid (155 +/- 33 ml) than with flurbiprofen (223 +/- 44 ml). Various side effects were recorded by 7 of 15 women during treatment with tranexamic acid and by 4 women of 15 during treatment with flurbiprofen. Many women with menorrhagia suffer simultaneously from dysmenorrhea. Thus although tranexamic acid was generally more effective in reducing menstrual blood loss, flurbiprofen provides an important therapeutic alternative to antifibrinolytic agents, especially in patients with concomitant dysmenorrhea.", "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.", "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.", "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.", "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.", "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.", "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.", "To determine whether rofecoxib is effective for treating primary dysmenorrhea and whether cyclooxygenase-2 is involved in the pathophysiology of primary dysmenorrhea.\n A double-masked, randomized, placebo and active-comparator-controlled clinical trial including 127 subjects with histories of primary dysmenorrhea was conducted in an outpatient clinical research center. Subjects were randomly assigned to placebo, rofecoxib 25 or 50 mg followed by 25 mg every 24 hours as needed, or naproxen sodium 550 mg every 12 hours as needed for up to 3 days. Subjects took all four treatments in a balanced, complete-block, crossover design. Measurements included self-administered questionnaires of analgesic efficacy, spontaneous reports of adverse experiences, physical examinations, and laboratory safety tests.\n Rofecoxib 25 and 50 mg provided analgesic efficacy greater than placebo (P < or = .006) for the primary endpoint of total pain relief over the first 8 hours. For other efficacy endpoints (sum of the pain intensity difference over the first 8 hours, subject's global evaluation, peak pain relief, peak pain intensity difference, and time to remedication) both doses of rofecoxib were better than placebo (P < or = .006) and were not distinguishable from naproxen sodium for all efficacy endpoints. All treatments were well tolerated.\n Rofecoxib effectively treated primary dysmenorrhea, and cyclooxygenase-2-derived prostanoids play a role in the pathophysiology of primary dysmenorrhea." ]

[ "20005647", "2437967", "15731312", "20007011" ]

[ "Dydrogesterone in threatened miscarriage: a Malaysian experience.", "Double-blind controlled trial of progesterone substitution in threatened abortion.", "Effects of vaginal progesterone on pain and uterine contractility in patients with threatened abortion before twelve weeks of pregnancy.", "Dydrogesterone support in 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.", "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)", "Fifty women with previous diagnosis of inadequate luteal phase and threatened abortion underwent a prospective, randomized, double-blind study in one medical center carried out with a parallel trial. The primary objective was to establish the effects of vaginal progesterone (Crinone 8%) in reducing both pain and uterine contractions (UCs). The gel with or without (placebo) vaginal progesterone was administered once a day since the diagnosis of threatened abortion and for 5 days. The efficacy on pain symptom amelioration was evaluated by a 5-score intensity gradation, while the UCs were evaluated by ultrasound. The secondary objective of the study was to evaluate the outcome of the pregnancies. The use of progesterone was effective both on pain relief and on the frequency of the UCs that decreased after 5 days of vaginal progesterone administration (P < 0.005). The evaluation of the ongoing pregnancy and spontaneous abortion in both study groups after 60 days showed that 4 patients of group A and 8 patients of group B miscarried (P < 0.05). In conclusion, patients with threatened abortion benefit from vaginal progesterone by a reduction of UCs and pain. The use of vaginal progesterone improved the outcome of pregnancies complicated by threatened abortion and previous diagnosis of inadequate luteal phase.", "The aim of this study was to determine whether dydrogesterone helps to preserve pregnancy in women with threatened miscarriage.\n 146 women who presented with mild or moderate vaginal bleeding during the first trimester of pregnancy were randomised to receive oral dydrogesterone (10mg b.i.d.) (n=86) or no treatment (n=60). Dydrogesterone was continued until 1 week after the bleeding had stopped. All women received standard supportive care.\n The incidence of miscarriage was significantly lower in the dydrogesterone group than in the untreated group (17.5% vs. 25%; p<0.05). There were no statistically significant differences between the groups with respect to pregnancy complications or congenital abnormalities.\n Dydrogesterone appears to have beneficial effects in women with threatened miscarriage.\n Copyright 2009 Elsevier Ireland Ltd. All rights reserved." ]

[ "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." ]

[ "12698153", "22554673", "17919621" ]

[ "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.", "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.", "A randomized controlled trial of tacrolimus versus cyclosporine after lung transplantation." ]

[ "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.", "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.", "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." ]

[ "8783954", "15121569", "7646610", "1290441", "11166751", "15288222", "16241013", "12635758", "10426243", "11576573", "9883403", "12678150", "12660281", "8602315", "4913514" ]

[ "Simplified care of women with prolonged or persistent retention of the placenta: the use of paracervical block.", "Paracervical block in incomplete abortion using manual vacuum aspiration: randomized clinical trial.", "Paracervical anesthesia for outpatient hysteroscopy.", "Outpatient hysteroscopy: a comparison of 2 methods of local analgesia.", "Comparison of paracervical block techniques during first trimester pregnancy termination.", "The role and comparison of two techniques of paracervical block for pain relief during suction evacuation for first-trimester pregnancy termination.", "Randomized controlled trial of mefenamic acid vs paracervical block for relief of pain for outpatient uterine curettage.", "Pain relief using paracervical block in patients undergoing manual vacuum aspiration of uterus.", "Paracervical anaesthesia in outpatient hysteroscopy: a randomised double-blind placebo-controlled trial.", "Lidocaine versus plain saline for pain relief in fractional curettage: a randomized controlled trial.", "Paracervical anesthesia for hysteroscopy and endometrial biopsy in postmenopausal women. A randomized, double-blind, placebo-controlled study.", "Double-blind randomized comparison of xylocaine and saline in paracervical block for diagnostic fractional curettage.", "Outpatient operative hysteroscopy with bipolar electrode: a prospective multicentre randomized study between local anaesthesia and conscious sedation.", "A double-blind randomized comparison of lidocaine and saline for cervical anesthesia.", "Paracervical block anaesthesia for the evacuation of incomplete abortion--a controlled trial." ]

[ "Thirty patients with prolonged or persistent retention of the placenta were randomized to either paracervical block or intravenous cocktail of pethidine and diazepam. When paracervical block worked, the analgesia produced was better than that usually achieved with intravenous cocktail of pethidine and diazepam. From a cost-benefit point of view paracervical block is preferable to intravenous cocktail. No significant side-effects occurred during the trial.", "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.", "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.", "A prospective, randomized study was undertaken to objectively compare pain tolerance of 2 methods of local analgesia for outpatient hysteroscopy. Patients in group 1 received a paracervical block using 20 ml of 1% lignocaine. Patients in group 2 received a uterosacral block using 2 ml of 2% lignocaine. There was no statistical difference between the 2 groups (p = < 0.65) in efficacy of pain relief. The method used for patients in group 2 reduces time and costs for outpatient hysteroscopy.", "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.", "This prospective study assessed the role and compared two techniques of paracervical block (PCB) for pain relief during suction evacuation for first-trimester termination of pregnancy following cervical priming with misoprostol. One-hundred and thirty-five women undergoing suction evacuation up to 12 weeks of gestation were randomized into three groups: (a) 5 mL of 1% lignocaine injected at the 4 and 8 o'clock positions of the vaginal vault; (b) 5 mL of 1% lignocaine injected at the 4 and 8 o'clock positions of the cervix and (c) no PCB. Pain scores during PCB, cervical dilatation and during and after suction evacuation were compared among the three groups. The sedation and satisfaction levels were also compared. There were no statistically significant differences in the pain levels during PCB, cervical dilatation and suction evacuation and in the satisfaction levels among the three groups. Patients with a lighter sedation level experienced more pain. In conclusion, PCB did not improve the pain levels during first-trimester suction termination of pregnancy after cervical priming with misoprostol and use of intravenous sedation, regardless of whether the local anaesthetic was injected into the cervix or the vaginal vault.", "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 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 evaluate the efficacy and safety of paracervical anaesthesia in reducing pain during outpatient hysteroscopy and endometrial biopsy.\n Prospective, randomised, placebo-controlled, double-blind study.\n One hundred women undergoing outpatient hysteroscopy and endometrial biopsy for abnormal uterine bleeding.\n Paracervical block using 10 mL of either 2% lignocaine or normal saline before the procedure.\n Evaluation of pain at different stages of hysteroscopy using a visual analogue scale together with blood pressure and heart rate monitoring.\n Compared with placebo, paracervical anaesthesia significantly reduced the pain only at the time of insertion of the hysteroscope, but not at the subsequent stages of the procedure. However, paracervical injection of lignocaine resulted in a higher incidence of bradycardia and hypotension.\n Paracervical anaesthesia not only fails to reduce pain during outpatient hysteroscopy and endometrial biopsy, but also carries a risk of inducing bradycardia and hypotension, which is probably a result of inadvertent intravascular injection.", "To compare the efficiency of lidocaine with that of plain saline for paracervical pain relief during fractional curettage.\n This double-blind, randomized, controlled trial included 140 women who underwent fractional curettage. Seventy women were allocated to the lidocaine group and 70 to the plain saline group. The main outcome measure was the intensity of pain measured by visual analog scale during and after the procedure.\n The intensity of pain was significantly lower in the lidocaine group than in the plain saline group over the course of the procedure (P = .02), especially during fractional curettage. There were no serious adverse effects in this study.\n Lidocaine is more effective than plain saline for paracervical pain relief during fractional curettage. The anesthetic mechanisms of lidocaine are mechanical distention of tissue and peripheral nerve block.", "To evaluate the efficiency of paracervical anesthesia in reducing pain and the incidence of vasovagal reactions during diagnostic hysteroscopy with endometrial biopsy in postmenopausal women.\n A randomized, placebo-controlled, double-blind study. Seventy-two postmenopausal women underwent diagnostic hysteroscopy and endometrial biopsy. Hysteroscopies were performed by using a lens-based endoscope with a diameter of < 4 mm and endometrial biopsies by using a 3-mm Novak's curette. Ten milliliters of 1.5 mepivacaine or saline solution was injected at the junction of the cervix and vagina (at the 4 and 8 o'clock positions) by means of an appropriate needle before performing the intrauterine procedures. Referred pain was evaluated by means of a visual analogue scale; continuous monitoring of heart rate and blood pressure was also performed.\n Paracervical anesthesia significantly reduced pain at hysteroscopy and biopsy. The incidence of vasovagal reactions was also significantly lower in the anesthetized group.\n Paracervical anesthesia is effective for hysteroscopy and endometrial biopsy in postmenopausal women and may be indicated particularly for patients with cervical stenosis, for very anxious subjects and in all situations where pain stimulation could trigger threatening side effects due to systemic pathologies.", "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.", "The study was designed to compare local anaesthesia and conscious sedation for outpatient bipolar operative hysteroscopy in terms of pain control and patients' satisfaction.\n A prospective multicentre randomized study was carried out in university hospitals and in a private endoscopy unit. A total of 166 women with surgically treatable lesions associated with infertility or abnormal uterine bleeding was considered eligible for the study. Patients were randomized, using a computer-generated randomization list, into two groups. Group A (82 patients) underwent operative hysteroscopy with local anaesthesia. Group B (84 patients) received conscious sedation. Operative hysteroscopy was performed with a bipolar electrosurgical device to cut, vaporize and coagulate. Main outcome measures were pain control during the procedure, the post-operative pain score at 15 and 60 min, and at 24 h after the procedure, and patients' satisfaction rate.\n All procedures were completed within 35 min, the amount of saline used varied from 400-1200 ml. There were no significant differences between local anaesthesia and conscious sedation in terms of pain control during the procedure and in postoperative pain at different intervals. Satisfaction rate was similar in the two groups.\n Both local anaesthesia and conscious sedation can be used for operative hysteroscopy using a bipolar electrosurgical system without significant differences in terms of pain control and patients' satisfaction.", "To compare bacteriostatic saline and buffered lidocaine for cervical anesthesia to blunt the reported pain during brief suction curettage.\n A double-blind randomized clinical trial was conducted on women presenting for pregnancy termination procedures. Participants received either paracervical submucosal injections of bacteriostatic saline or 1% buffered lidocaine just before cervical dilation. Self-reported pain intensity was assessed at three time points during and 30 minutes after the procedure.\n Fifty-two of 135 eligible women presenting for pregnancy termination procedures participated in the study. Pain intensity ratings in lidocaine and saline treatment subjects did not differ significantly at any point. Our study had a power of 0.94 to detect more than a 15% difference on the 21-point box scale between the two solutions. Only one patient requested her block be repeated, and she had received lidocaine originally. Furthermore, of those women receiving lidocaine, 11% reported mild toxicity symptoms.\n To minimize lidocaine toxicity for a brief suction curettage procedure, bacteriostatic saline or very dilute lidocaine could be considered for the paracervical injection solution. The local anesthetic mechanism may be distention rather than blockage of specific autonomic nerves when there is no waiting period. This would mean that the term paracervical block could be changed to cervical anesthesia.", "nan" ]

[ "2082953", "6379022", "6228938", "406875", "2651014", "4204090", "4198303", "13251096" ]

[ "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.", "[Dihydroergotoxine mesylate in the treatment of senile cerebral insufficiency. Result of a long-term multicenter double-blind clinical trial with a placebo].", "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.", "A clinical trial comparing 'Hydergine' with placebo in the treatment of cerebrovascular insufficiency in elderly patients.", "Influence of treatment on symptomatology and correlated electroencephalographic (EEG) changes in the aged.", "Combined hydrogenated alkaloids of ergot in mental and nervous disorders associated with old age." ]

[ "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.", "Many controlled double-blind clinical trials against placebo and other drugs have clearly demonstrated the activity of dihydroergotoxine mesylate (DHT) on some symptoms of chronic senile cerebral insufficiency (CSCI). In spite of this, there is still some controversy about the usefulness of DHT for treatment of CSCI, as it seems to be hard to transpose the results of these studies to treatment of a population with DHT. Trying to overcome this criticism, a multicenter double-blind, placebo-controlled long-term (1 year) clinical trial has been planned, using very simple criteria for patient selection and easy to use assessment devices. Fifty two centres distributed throughout Italy were invited and 40 took active part in the study. The present report deals with data collected for analysis on Aug. 31, 1982. On this date 559 patients entered the study and 458 were under treatment (229 on DHT 1.5 mg t.i.d. and 229 on placebo). 101 patients dropped out (48 on DHT and 53 on placebo). 388 patients (195 on DHT and 193 on placebo) had completed 6 months and 204 (111 on DHT and 93 on placebo) had completed 1 year of treatment. The data from patients who completed 6 and 12 months of treatment period were analyzed statistically using Student t tests for paired and unpaired data, the large number of patients being adequate protection against any non normality in the distribution of the data. Differences with 2P values of 0.01 or less were considered significant.(ABSTRACT TRUNCATED AT 250 WORDS)", "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.", "nan", "nan", "nan" ]

[ "3052064" ]

[ "A controlled trial of stimulant medication in children with the fragile X syndrome." ]

[ "Attentional deficits and hyperactivity frequently are major problems for fra(X) boys. This study evaluated the effectiveness of 2 stimulant medications, methylphenidate and dextroamphetamine compared to placebo in 15 children (13 males, 2 females) with the fra(X) syndrome. A double-blind crossover design was used with outcome measures which included parent and teacher behavior checklists, a controlled observation period, continuous performance tasks and an actometer measure of movement. When the children were treated with methylphenidate only, improvement was seen in socialization skills and attention span according to teacher checklists. Ten children were clinically considered responders and treatment was continued after the study was completed." ]