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[ "7021067", "347921", "3285638", "7841729", "6754899", "4579587", "1734400" ]

[ "Radiographic tracheal diameter measurements in acute infectious croup: an objective scoring system.", "Nebulized racemic epinephrine by IPPB for the treatment of croup: a double-blind study.", "A randomized double-blind, placebo-controlled trial of dexamethasone and racemic epinephrine in the treatment of croup.", "Inhalation of racemic adrenaline in the treatment of mild and moderately severe croup. Clinical symptom score and oxygen saturation measurements for evaluation of treatment effects.", "Racemic epinephrine in the treatment of croup: nebulization alone versus nebulization with intermittent positive pressure breathing.", "The evaluation of racemic epinephrine in the treatment of infectious croup.", "Prospective randomized double-blind study comparing L-epinephrine and racemic epinephrine aerosols in the treatment of laryngotracheitis (croup)." ]

[ "The percentage of change in tracheal diameter (TD% change), as assessed by an objective radiological measurement, was used along with a simple subjective clinical score to assess response to therapy in upper airway obstruction in 14 patients with acute infectious croup. Studies were performed on the 14 patients, each of whom was randomly assigned to one of two treatment groups: distilled water or racemic epinephrine (RE), both being nebulized and delivered by manual IPPB. The objective radiological assessment and the subjective clinical score both confirmed that RE is significantly (p less than 0.005) more effective than distilled water in the acute relief of upper airway obstruction. The more precise radiological assessment may be of value in determining objectively better drug therapy for infectious croup.", "Racemic epinephrine has been advocated for the treatment of croup, but controlled studies have not proved it more effective than saline. Twenty patients (aged 4 months to 5 years) hospitalized with acute croup and persistent inspiratory stridor at rest were randomly assigned to one of two treatment groups: saline or racemic epinephrine, both nebulized and delivered by intermittent positive pressure breathing. Clinical scores were significantly improved (P less than .01) at ten and 30 minutes following the treatment with racemic epinephrine but not at 120 minutes. Racemic epinephrine was significantly more effective than saline at 10 (P less than .01) and 30 minutes (P less than .05) but not at 120 minutes after the treatment. We conclude that nebulized racemic epinephrine is effective treatment for the acute signs of croup.", "Seventy-two children hospitalized for croup received on admission a single dose of either 0.6 mg/kg dexamethasone or an equivalent placebo intramuscularly from randomized ampules; subsequently the same patients were randomized to receive either nebulized racemic epinephrine or saline by intermittent positive pressure breathing. Of the four treatment groups those receiving a placebo injection and nebulized saline had the slowest recovery by all criteria. Dexamethasone and nebulized epinephrine reduced the symptoms and hastened recovery, but dexamethasone was more effective by clinical evaluation at 6 and 12 hours post admission. The patients given dexamethasone had a significantly shorter hospital stay than those receiving placebo. We conclude that a single injection of a potent corticosteroid is beneficial in acute spasmodic croup. Nebulized racemic epinephrine given with an appropriate device is also effective, but the effect of epinephrine is less remarkable in patients treated with dexamethasone.", "The aim of this study was to evaluate the immediate effect of inhaling racemic adrenaline to treat croup and to evaluate a scoring system. Two groups were investigated. One group inhaled a racemic adrenaline solution and the other group received the same solution with no racemic adrenaline. The study was double-blinded and placebo-controlled. Fifty-four children (0.4-10.8 years) with mild to moderately severe croup were included in the study after clinical evaluation. The clinical score was useful when evaluating the treatment effects in mild to moderately severe croup and may be used as a quality assurance tool when treatment protocols are re-evaluated. Oxygen saturation before and after treatment did not change significantly in either group and therefore its measurement did not provide additional information on the effect of treatment. In both groups, a significant improvement in total mean clinical scores was seen 30 min after inhalation, compared with before inhalation (p < 0.001). However, racemic adrenaline was significantly better than placebo in terms of improvement in total clinical score, inspiratory stridor, retractions and air entry, and should therefore be used as first-line treatment.", "nan", "nan", "Aerosolized racemic epinephrine, but not L-epinephrine, is commonly used in treating croup. The efficacy and adverse effects of nebulized racemic and L-epinephrine in the treatment of laryngotracheitis were compared. Children 6 months to 6 years of age with a croup score of 6 or above were assigned in a randomized double-blind fashion to receive either racemic (n = 16) or L-epinephrine (n = 15) aerosols. Croup score, heart rate, blood pressure, respiratory rate, fraction of inspired oxygen, and oxygen saturation were recorded before treatment and at 5, 15, 30, 60, 90, and 120 minutes after the aerosol. Patients in both groups showed significant transient reduction of the croup score and respiratory rate following the aerosol (P less than .001), but there were no differences between treatment groups when croup score, heart rate, blood pressure, and respiratory rate were assessed over time. It is concluded that L-epinephrine is at least as effective as racemic epinephrine in the treatment of laryngotracheitis and does not carry the risk of additional adverse effects. L-Epinephrine is also more readily available worldwide, is less expensive, and can be recommended for this purpose." ]

[ "9074574", "15313740", "11570939", "11054217" ]

[ "Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis.", "Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial.", "Prevention and treatment of postphlebitic syndrome: results of a 3-part study.", "Compression and walking versus bed rest in the treatment of proximal deep venous thrombosis with low molecular weight heparin." ]

[ "Post-thrombotic syndrome varies from mild oedema to incapacitating swelling with pain and ulceration. We investigated the rate of post-thrombotic syndrome after a first episode of deep-vein thrombosis and assessed the preventive effect of direct application of a sized-to-fit graded compression stocking.\n Patients with a first episode of venogram-proven proximal deep-vein thrombosis were randomly assigned no stockings (the control group) or made-to-measure graded compression elastic stockings for at least 2 years. Post-thrombotic syndrome was assessed with a standard scoring system that combined clinical characteristics and objective leg measurements. Patients were assessed every 3 months during the first 2 years, and every 6 months thereafter for at least 5 years. The cumulative incidence of mild-to-moderate post-thrombotic syndrome was the primary outcome measure.\n Of the 315 consecutive outpatients considered for inclusion, 44 were excluded and 77 did not consent to take part. 194 patients were randomly assigned compression stockings (n = 96) or no stockings (n = 98). The median follow-up was 76 months (range 60-96) in both groups. Mild-to-moderate post-thrombotic syndrome (score > or = 3 plus one clinical sign) occurred in 19 (20%) patients in the stocking group and in 46 (47%) control-group patients (p < 0.001). 11 (11%) patients in the stocking group developed severe post-thrombotic syndrome (score > or = 4), compared with 23 (23%) patients in the control group (p < 0.001). In both groups, most cases of post-thrombotic syndrome occurred within 24 months of the acute thrombotic event.\n About 60% of patients with a first episode of proximal deep-vein thrombosis develop post-thrombotic syndrome within 2 years. A sized-to-fit compression stocking reduced this rate by about 50%.", "Because only limited evidence suggests that elastic stockings prevent the post-thrombotic syndrome in patients with symptomatic deep venous thrombosis (DVT), these stockings are not widely used.\n To evaluate the efficacy of compression elastic stockings for prevention of the post-thrombotic syndrome in patients with proximal DVT.\n Randomized, controlled clinical trial.\n University hospital.\n 180 consecutive patients with a first episode of symptomatic proximal DVT who received conventional anticoagulant treatment.\n Before discharge, patients were randomly assigned to wear or not wear below-knee compression elastic stockings (30 to 40 mm Hg at the ankle) for 2 years. Follow-up was performed for up to 5 years.\n The presence and severity of the post-thrombotic syndrome were scored by using a standardized scale.\n Post-thrombotic sequelae developed in 44 of 90 controls (severe in 10) and in 23 of 90 patients wearing elastic stockings (severe in 3). All but 1 event developed in the first 2 years. The cumulative incidence of the post-thrombotic syndrome in the control group versus the elastic stockings group was 40.0% (95% CI, 29.9% to 50.1%) versus 21.1% (CI, 12.7% to 29.5%) after 6 months, 46.7% (CI, 36.4% to 57.0%) versus 22.2% (CI, 13.8% to 30.7%) after 1 year, and 49.1% (CI, 38.7% to 59.4%) versus 24.5% (CI, 15.6% to 33.4%) after 2 years. After adjustment for baseline characteristics, the hazard ratio for the post-thrombotic syndrome in the elastic stockings group compared with controls was 0.49 (CI, 0.29 to 0.84; P = 0.011).\n This study lacked a double-blind design.\n Post-thrombotic sequelae develop in almost half of patients with proximal DVT. Below-knee compression elastic stockings reduce this rate by approximately 50%.", "The true incidence of postphlebitic syndrome (PPS) following proximal deep venous thrombosis (DVT) and the efficacy of graduated compression stockings in preventing and treating PPS are unknown.\n A 3-part study of 202 patients evaluated 1 year after proximal DVT: 2 randomized placebo-controlled trials of stockings and 1 prospective cohort of untreated patients. Patients were evaluated for PPS, using a standardized questionnaire, and for venous valvular incompetence, using photoplethysmography and venous Doppler. They were enrolled in study 1 or study 2 if they did not have symptomatic PPS and did not have or had venous valvular incompetence, respectively, and into study 3 if they had symptomatic PPS. Study 1 patients were left untreated and followed up for development of PPS every 6 months for a mean of 55 months. Study 2 patients were randomized to a below-knee stocking (20-30 mm Hg) or a matched placebo stocking, and followed up for development of PPS every 6 months for a mean of 57 months. Study 3 patients were randomized to an active stocking (30-40 mm Hg) or a matched placebo stocking and followed up every 3 months for treatment failure, defined a priori.\n In study 1, 6 (5.0%) of 120 patients were categorized as treatment failures, a rate similar to placebo-treated study 2 patients (P =.10). In study 2, 0 (0%) of 24 active and 1 (4.3%) of 23 placebo-treated patients were categorized as treatment failures (P =.49). In study 3, 11 (61.1%) of 18 active and 10 (58.8%) of 17 placebo-treated patients were categorized as treatment failures (P>.99).\n Most patients do not have PPS 1 year after proximal DVT, and do not require stockings. We failed to show a benefit of stockings in patients with PPS, but the small numbers preclude definitive conclusions.", "The purpose of this randomized controlled trial was to evaluate the benefits of compression and walking exercises in comparison with bed rest in the acute stage of proximal deep venous thrombosis (DVT).\n Forty-five patients with proximal DVT that was proved with compression ultrasound scan or phlebography were randomized into three groups. Group A consisted of 15 patients who received inelastic compression bandages (Unna boots on the lower leg, adhesive bandages on the thigh), and group B consisted of 15 patients who received thigh-length compression stockings, class II. Group C consisted of 15 patients who underwent bed rest and no compression. All patients received dalteparin, 200 IU/kg per body weight, subcutaneously every 24 hours. The clinical characteristics of the three groups were comparable. Primary end points were the reduction of pain assessed daily with the Visual Analogue Scale and the Lowenberg test, the reduction of leg circumference at the ankle and calf levels, and the improvement of clinical scores. The daily walking distance was measured with a pedometer. Safety parameters were ventilation-perfusion scans and duplex ultrasound scans performed on days 0 and 9.\n The daily walking distance was between 600 and 12,000 m in the compression groups and averaged 66 m in the bed rest group. The pain level showed a statistically significant reduction starting after the second day in the compression groups (A and B) and after 9 days in the bed rest group C (P <.05). The same was true for the measurement of leg circumference. Improvement of the clinical scores was significantly better in the compression groups compared with the bed rest group (P <.01). There was no significant difference concerning the occurrence of new pulmonary emboli and regression of thrombus diameter. Progression of thrombi in the femoral vein was greater and occurred more frequently in the bed rest group than in the other two groups (P = not significant).\n Mobile patients with acute proximal DVT treated with low molecular weight heparin should be encouraged to walk with compression bandages or medical compression stockings. The rate of resolution of pain and swelling is significantly faster when the patient ambulates with compression. The risk of pulmonary embolism is not significantly increased by this approach." ]

[ "12556780", "9468416", "2466520", "10625787", "10673303", "8519239", "12783344", "9865556", "12838221", "11144946", "16733114", "1281903", "11868008", "7996958", "14648409", "2475392", "18277888", "12776028", "15082593", "16897286", "10625790" ]

[ "Plastic or metal stents for malignant stricture of the common bile duct? Results of a randomized prospective study.", "A randomized trial of endoscopic drainage methods for inoperable malignant strictures of the common bile duct.", "Endoscopic biliary endoprosthesis in the palliation of malignant obstruction of the distal common bile duct: a randomized trial.", "Hydrophilic hydromer-coated polyurethane stents versus uncoated stents in malignant biliary obstruction: a randomized trial.", "A prospective randomised multicentre trial comparing 10 Fr Teflon Tannenbaum stents with 10 Fr polyethylene Cotton-Leung stents in patients with malignant common duct strictures.", "A prospective, randomized, controlled trial of metal stents for malignant obstruction of the common bile duct.", "A prospective randomized study of hydrophilic polymer-coated polyurethane versus polyethylene stents in distal malignant biliary obstruction.", "A prospective randomized trial of Teflon versus polyethylene stents for distal malignant biliary obstruction.", "Prospective, randomized, single-center trial comparing 3 different 10F plastic stents in malignant mid and distal bile duct strictures.", "[Randomized prospective study to compare the efficiency between standard plastic and polyurethane stents in biliary tract malignant obstruction].", "Covered metal versus plastic stents for malignant common bile duct stenosis: a prospective, randomized, controlled trial.", "Randomised trial of self-expanding metal stents versus polyethylene stents for distal malignant biliary obstruction.", "\"Tannenbaum\" Teflon stents versus traditional polyethylene stents for treatment of malignant biliary stricture.", "Randomised trial of endoscopic stenting versus surgical bypass in malignant low bileduct obstruction.", "A prospective, randomized multicenter trial comparing DoubleLayer and polyethylene stents for malignant distal common bile duct strictures.", "Randomised trial of endoscopic endoprosthesis versus operative bypass in malignant obstructive jaundice.", "Uncovered Hanaro Versus Luminex metal stents for palliation of malignant biliary strictures.", "Multicenter randomized trial of the spiral Z-stent compared with the Wallstent for malignant biliary obstruction.", "A prospective randomised study of \"covered\" versus \"uncovered\" diamond stents for the management of distal malignant biliary obstruction.", "Tannenbaum and metal stents in the palliative treatment of malignant distal bile duct obstruction: a comparative study of patency and cost effectiveness.", "Prospective randomized trial comparing Tannenbaum Teflon and standard polyethylene stents in distal malignant biliary stenosis." ]

[ "The systematic use of metal stents to treat biliary obstruction is restricted by high cost compared with plastic stents. The aims of this study were to compare cost and efficacy of plastic stents and metal stents in the treatment of patients with malignant common bile duct strictures and to define factors that predict survival of these patients.\n One hundred eighteen patients (mean age 75 years) with malignant strictures of the common bile duct were randomized to placement of a plastic stent or metal stent. Comparisons were made with the Mann-Whitney or chi-square test as indicated; survival rates were compared with a Cox proportional hazards model.\n There was no significant difference in survival between the two groups. Time to first obstruction was longer for patients in the metal stent group (metal stent, median not reached vs. plastic stent, 5 months; p = 0.007). The number of additional days of hospitalization, days of antibiotic therapy, and the numbers of ERCPs and transabdominal US procedures was significantly higher in the plastic stent group. After multivariate analysis, only the presence of liver metastases was independently related to survival (p < 0.0005; OR = 2.25). This variable defined a group with a shorter survival. Median survival of patients with hepatic metastasis at diagnosis was 2.7 months compared with 5.3 months for patients without liver metastasis; in the latter group, the overall cost associated with metal stents was lower than for plastic stents.\n Metal stent placement is the most effective treatment of inoperable malignant common bile duct stricture. Placement of a metal stent is cost effective in patients without hepatic metastases, whereas a plastic stent should be placed in patients with spread of the tumor to the liver.", "Although metallic stents remain patent longer than plastic stents, the optimal palliation of inoperable malignant biliary strictures remains controversial because of the high cost of metallic stents and short patient survival.\n A total of 101 patients (mean age 72.5+/-12.9 years) with malignant strictures of the common bile duct were included in this study, after three exclusions for technical failure (n = 3) and one for noncompliance with study design. The etiology of the strictures included pancreatic cancer (65), cholangiocarcinoma (21), ampullary tumor (3), and metastatic lymph nodes (12). Patients were randomized to receive either an 11.5F polyethylene stent to be exchanged in case of dysfunction (group 1, n = 33), an 11.5F stent to be exchanged every 3 months (group 2, n = 34), or a self-expanding metallic Wallstent (group 3, n = 34).\n Endoscopic procedures were successful (including complete relief of jaundice) in 97.1 % of cases. Procedure-related morbidity was 11.9%, and mortality was 2.9%. Bilirubinemia after 48 hours (37.2%+/-21.7% decrease from the preoperative level) did not differ between groups. Patients were followed for a mean of 166 days (median 143, range 0 to 596 days). Overall survivals were not different between groups, but complication-free survival for groups 2 and 3 was longer than that of group 1 (p < 0.05). Cumulated hospital days were 7.4+/-1.5, 10.6+/-1.7, and 5.5+/-1.4 (groups 1, 2, and 3, respectively) (p < 0.05; analysis of variance). Cost analysis showed that metallic stents were advantageous in patients surviving more than 6 months, whereas a plastic stent was advantageous in patients surviving 6 months or less.\n Metallic stents and plastic stents exchanged every 3 months are valuable alternatives for increasing complication-free survival in patients with malignant strictures of the common bile duct. Metal stents are advantageous in patients with the longest life expectancy.", "A total of 52 jaundiced elderly patients who had malignant obstruction of the distal common bile duct and who required palliative biliary decompression were randomized to receive either an endoscopically placed biliary endoprosthesis (10 French gauge) or conventional surgical bypass. Patients within the two treatment groups were well matched and 51 were followed until their death. Patients treated with endoprosthesis had a significantly shorter initial hospital stay than those treated surgically. In the long term, overall survival in the two groups was similar and jaundice was relieved in over 90 per cent of patients. Despite more re-admissions to hospital for those patients treated endoscopically, the total time spent in hospital still remained significantly shorter in this treatment group compared with those subjected to surgery. The endoscopically placed biliary endoprosthesis is a valuable alternative to conventional surgical bypass in the palliation of extrahepatic biliary obstruction.", "Hydromer-coated polyurethane stents (HCPS) have a low coefficient of friction that may reduce sludge formation and potentially increase stent longevity.\n Eighty-three patients (39 men, mean age 69.3 years) with malignant mid or distal bile duct strictures were prospectively randomized to receive either 10F HCPS (n = 40) or standard polyethylene stents (n = 43).\n Fifteen patients (18.1%) underwent surgery after stent insertion. Six patients were lost to follow-up (7.2%), whereas 34 died of the underlying disease without evidence of stent occlusion (15 HCPS group and 19 polyethylene group). Median survival was 75 days (range 15 to 372 days) and 108 days (range 25 to 325 days) in the HCPS and polyethylene stent groups, respectively (p = not significant). Stent occlusion was observed in 25 patients (42%), 16 with HCPS stents and 9 with polyethylene stents, with a median patency of 103 days (range 40 to 280 days) and 68 days (range 32 to 175 days), respectively (p = not significant).\n HCPS do not appear to provide significant clinical advantages in terms of stent longevity over standard plastic prostheses.", "Stent blockage is a multifactorial process in which stent design and materials, bacteria, proteins, and bile viscosity play a role.\n To compare the patency of the 10 Fr Teflon Tannenbaum (TT) stent to that of the 10 Fr Cotton-Leung (CL) polyethylene stent with sideholes, in patients with malignant obstructive jaundice.\n Patients were recruited to this prospective multicentre randomised study if they had a newly diagnosed malignant bile duct stricture below the hilum of the liver suitable for stenting with a 10 Fr stent. Data were collected and monitored by a professional monitoring company. Primary patency was the interval between stent placement and first exchange or death without recurrent jaundice.\n 134 consecutive patients were recruited between November 1994 and June 1997; 65 were randomised to the TT stent and 69 to the CL stent. Median patency and 95% confidence intervals were 181 (59, 303) days for the TT stent and 133 (92, 174) days for the CL stent, with no significant difference between the two stents (p=0.49). Median survival and 95% confidence intervals were 115 (71, 159) days for the TT stent and 151 (112, 190) days for the CL stent, with no significant difference between the two stents (p=0.765).\n Neither Teflon as a stent material nor the Tannenbaum design prolong the patency of plastic stents.", "Endoscopic insertion of biliary stents is the preferred method of palliation for inoperable malignant biliary obstruction; however, migration and clogging are frequent problems with conventional endoprostheses. We sought to determine if expandable metal stents offer improved palliation compared to conventional stents. Sixty-two patients with common bile duct lesions were randomized to receive polyethylene or metal stents. Stents were placed endoscopically or by the combined percutaneous-endoscopic route. Early results (< 1 month) were similar in both groups. Long-term follow-up (n = 28 polyethylene, median: 5 months; n = 27 metal, median: 5 months) showed a higher stent failure rate in the polyethylene (n = 12; 43%) compared to the metal group (n = 6; 22%). The incidence of cholangitis was significantly higher (p < 0.05) in the polyethylene (n = 10; 36%) compared to the metal group (n = 4; 15%). Life-table analysis showed a significantly reduced incidence of stent failure (p = 0.0035) in the metal stent compared to the polyethylene group. The total duration of hospital stay for treatment of stent related problems was significantly higher in the polyethylene (11.8 +/- 3 days) compared to the metal group (4 +/- 1.9 days; p = 0.02). The costs for retreatment because of stent failure were significantly higher in the plastic (DM 5900 +/- 1516) compared to the metal group (DM 2070 +/- 977). As a result, the overall costs (treatment of stent related complications & stents) were higher in the polyethylene group (DM 6000 +/- 1500).(ABSTRACT TRUNCATED AT 250 WORDS)", "Hydrophilic polymer-coated polyurethane (HPCP) stents have a low friction coefficient and a hydrophilic layer, which may reduce biofilm formation and increase the period of stent patency. We compared the patency rates with this new stent with the standard Amsterdam-type polyethylene (PE) stent in a prospective randomized trial.\n One hundred patients with an unresectable distal malignant bile duct stricture without a previous drainage procedure were randomly assigned to receive either a HPCP stent or a PE stent. The diameter (10 Fr), length (9 cm) and stent design (Amsterdam type) were similar in both stents. Nine patients were excluded. Forty-four patients received an HPCP stent and 47 patients a PE stent. The diagnoses included carcinoma of the pancreas (n = 78), papilla (n = 1), bile duct (n = 10), and metastases (n = 2).\n Stent insertion was successful in all patients. Stent dysfunction occurred in 27 of the HPCP stents and 20 of the PE stents, with median stent patency periods of 77 days (95 % CI, 53-101 days) for HPCP stents and 105 days (95 % CI, 42-168 days) for PE stents. The patency period was significantly longer for the PE stent (P = 0.04). Early complications occurred in four patients (4%), one in the HPCP group and three in the PE group.\n Hydrophilic polymer-coated polyurethane stents do not prolong the patency period of biliary stents. In fact, the current standard treatment using polyethylene stents in patients with distal malignant biliary obstruction showed a significantly longer patency period.", "Clogging of biliary stents continues to be a major clinical problem. Different polymer materials may have different effects on clogging. In vitro studies have shown a direct relation between the frictional coefficient of a polymer and the amount of encrusted material. Teflon appeared to be the best polymer for biliary stents. Two different types of stents made of Teflon have been tested in clinical practice and showed favourable patency rates. However, a randomized trial has never been performed. We compared the patency of an Amsterdam-type polyethylene stent with a Teflon stent in a prospective randomized trial.\n Between September 1995 and November 1996, 42 patients received a Teflon stent and 42 patients a polyethylene stent. All patients had a distal malignant biliary stricture without a previous drainage procedure. Diagnoses included carcinoma of the pancreas (n = 76), papilla (n = 1), bile duct (n = 5) and metastases (n = 2). The internal and external diameter (10 Fr), length (9 cm) and stent design (a straight stent with two side flaps and one side hole at each end) were similar for both stents.\n A reduction in bilirubin of more than 20% within one week was seen in 91% of the patients. Early complication rates were similar in both groups (10%). The median follow-up was 142 days. Stent dysfunction occurred in 28 Teflon and 29 polyethylene stents. The thirty-day mortality was 14% in both groups. Patient survival did not differ significantly between the groups (median survival: Teflon 165 days, polyethylene 140 days). The median stent patency was 83 days for Teflon and 80 days for polyethylene stents, and was not significantly different either.\n Teflon material did not improve patency in biliary stents with an Amsterdam-type design.", "The aim of this study was to determine whether patency rates differ with respect to the material, design, and surface texture of 3 different plastic stents.\n A total of 120 patients (median age 70.5 years; interquartile range 62-78 years) with malignant mid or distal bile duct strictures, seen between March 1996 and May 1999, were prospectively randomized to receive a 10F polyurethane stent, a Teflon Tannenbaum stent, or a hydrophilic hydromer-coated polyurethane stent. The primary study outcome measure was the interval between stent insertion and the first episode of clogging (or the presence of jaundice at death without stent exchange). All 3 types of stent were studied by scanning electron microscopy before insertion.\n A total of 19 patients were excluded from long-term follow-up. Median duration of stent patency was 76 days overall (interquartile range 29-150 days) and 76 (interquartile range 30-110) days for hydrophilic hydromer-coated polyurethane, 108 (interquartile range 33-186) days for 10F polyurethane, and 58 (interquartile range 21-188) days for Teflon Tannenbaum stents. There were no statistically significant differences among stent types. The hydrophilic hydromer-coated stent had the smoothest surface, as visualized by scanning electron microscopy.\n No significant differences in the patency of 3 types of stents were detected in this randomized trial. In particular, the hydrophilic hydromer-coated plastic stent did not provide clinical advantages despite its smooth surface.", "The aim of this paper is to compare the efficiency between standard plastic stents and polyurethane stents used in biliary tract malignant obstruction. The main problem of the plastic prosthesis is their early occlusion. On the other hand there is the hypothesis that due to the less porousness of the polyurethane surface, there might be lesser adherence and consequently a late occlusion. Thirty-eight patients in two groups of 19 were evaluated prospectively and at random in the Jerusalem Hadassah Hospital and the HIGA San Martín La Plata. They had biliary tract obstruction due to inoperable tumors. Biliary endoprosthesis (plastic standard or polyurethane 10 French diameter) were placed, according to the randomization, after a previous staging with clinical examination, laboratory analysis and images. The follow-up with the same parameters was monthly done. Twelve of the 38 patients were female and 26 male; age average 62.73 (range 81-49). The stents were placed in 17 patients with biliary cancer, 14 pancreatic cancer, 2 papila cancer, 2 gallbladder cancer with bile duct invasion and 3 liver metastasis with biliary tract compression. The clinical and laboratory parameters in 36 patients at 30 days improved. On the contrary, 2 (1 plastic standard and 1 polyurethane stent) did not improve. There were 29 deaths due to the basic illness and not related to the endoscopic method. The mean obstruction occurred at 12.76 weeks (range 32-4) in the standard stents and 12.05 (range 24-2) in the polyurethane ones.\n There were no significant differences in the two groups patients.", "Most patients with malignant common bile duct strictures are suited only for palliation of jaundice by placement of a polyethylene (PE) stent using an endoscopic retrograde cholangiographic technique. Occlusion of these stents occurs after 3 to 4 months, whereas uncovered self-expanding metal stents (SEMS) remain open twice as long. The initial higher cost of the latter might be balanced by a decreased need for repeat intervention.\n To compare the patency of 10F PE stents and covered 30F steel SEMS (Wallstent; Boston Scientific Nordic AB, Helsingborg, Sweden).\n Single-center, prospective, randomized, controlled trial.\n General hospital in Stockholm, Sweden, which has a catchment area of 0.6 million people.\n Non-referred, unresectable malignant common bile duct strictures.\n Endoscopic retrograde cholangiography with plastic stents or covered SEMS.\n Time to stent failure, requiring a new stent.\n Similar setting and patients, and costs in Scandinavia.\n Fifty-one and 49 patients were allocated to the PE stent and SEMS groups, respectively. Fifty-six patients died without stent failure within 10 months (median, 2.6 months). Twenty-two PE stent and 9 SEMS patients (P = .009) developed failure after a median of 1.1 and 3.5 months, respectively (P = .007). Median patency times were 1.8 and 3.6 months in the PE and SEMS groups, respectively (P = .002). Median survival was 4.5 months; in 35 patients with distant metastases, the median survival was 2.5 months (P = .002)(PE group, 1.9 months).\n The more-effective SEMS are recommended in unresectable patients with malignant common bile duct strictures, who survive a median of 4.5 months. Less costly plastic stents are preferable in the one third of patients who have distant metastases. In our study, the cost was equal.", "Self-expanding metal stents are claimed to prolong biliary-stent patency, although no formal comparative trial between plastic and expandable stents has been done. In a prospective randomised trial, we assigned 105 patients with irresectable distal bile-duct malignancy to receive either a metal stent (49) or a straight polyethylene stent (56). Median patency of the first stent was significantly prolonged in patients with a metal stent compared with those with a polyethylene stent (273 vs 126 days; p = 0.006). The major cause of stent dysfunction was tumour ingrowth in the metal-stent group and sludge deposition in the polyethylene-stent group. Treatment after any occlusion included placement of a polyethylene stent. In the metal-stent group none of 14 second stents occluded, whereas 11 of 23 (48%) second stents clogged in the polyethylene-stent group (p = 0.002). Overall median survival was 149 days and did not differ significantly between treatment groups. Incremental cost-effectiveness analysis showed that initial placement of a metal stent results in a 28% decrease of endoscopic procedures. Self-expanding metal stents have a longer patency than polyethylene stents and offer adequate palliation in patients with irresectable malignant distal bile-duct obstruction.", "Premature stent clogging is the major limitation with plastic stents used in the treatment of malignant biliary structures. A pilot study suggested improved duration of patency of the Tannenbaum stent compared with polyethylene stents. The aim of this prospective, multicenter randomized trial was to compare the Tannenbaum Teflon stent with a conventional polyethylene endoprosthesis (Cotton-Leung biliary stent set) for the treatment of malignant biliary strictures.\n Patients over age 18 years with symptoms caused by nonhilar malignant biliary strictures were enrolled. Patients were randomized to receive a 10F Tannenbaum or polyethylene stent after a guidewire was passed beyond the stricture. One hundred six patients (mean age 72 years and 71 years, respectively) were enrolled (54 Tannenbaum, mean age 72 years; 52 polyethylene, mean age 71 years).\n Tannenbaum and polyethylene stent placement was successful in, respectively, 100% and 96% of procedures without complications. The mean (SD) 90-day stent patency of the Tannenbaum stent was 67% (7%) compared with 73% (7%) for the polyethylene stents.\n The present study demonstrated no difference in ease of implantation or stent patency between Tannenbaum and polyethylene stents.", "The development of non-surgical techniques for the relief of malignant low bileduct obstruction has cast doubt on the best way of relieving jaundice, particularly in patients fit for surgery whose life expectancy is more than a few weeks. We did a randomised prospective controlled trial comparing endoscopic stent insertion and surgical biliary bypass in patients with malignant low bileduct obstruction. 204 patients were randomised (surgery 103, stent 101); 3 subsequently proved to have benign disease and were excluded, leaving 101 surgical and 100 stented patients for assessment. Technical success was achieved in 94 surgical and 95 stented patients, with functional biliary decompression obtained in 92 patients in both groups. In stented patients, there was a lower procedure-related mortality (3% vs 14%, p = 0.01), major complication rate (11% vs 29%, p = 0.02), and median total hospital stay (20 vs 26 days, p = 0.001). Recurrent jaundice occurred in 36 stented patients and 2 surgical patients. Late gastric outlet obstruction occurred in 17% of stented patients and 7% of the surgical group. Despite the early benefits of stenting there was no significant difference in overall survival between the two groups (median survival: surgical 26 weeks; stented 21 weeks; p = 0.065). Endoscopic stenting and surgery are effective palliative treatments with the former having fewer early treatment-related complications and the latter fewer late complications.", "Endoscopic biliary stenting is an established treatment for malignant obstructive jaundice. Stent clogging continues to be a major problem with plastic stents. The aim of this study was to carry out a prospective comparison of two stents with different materials and shapes: the Olympus DoubleLayer stent (DLS; perfluoro alkoxy, without sideholes) and the standard polyethylene (PE) stent (with sideholes).\n A total of 120 patients (70 women; mean age 71, range 36 - 91) with jaundice due to malignant strictures of the middle to distal third of the common bile duct were randomly assigned to receive either DLS (n = 60) or PE (n = 60) biliary stents. Patients with cholangitis, hemobilia, previous biliary drainage, hilar stricture, or ampullary cancer were excluded.\n In all, 28 DLS patients (47 %) and 17 PE stent patients (29 %) died without clinical evidence of stent occlusion after a mean of 114 and 105 days, respectively ( P < 0.05). Twenty-six DLS patients (43 %) and 38 PE stent patients (63 %) had symptoms of stent clogging after a mean of 144 and 99 days, respectively ( P < 0.05). Stent dysfunction (stent orifice impacted on the bile duct or duodenal wall, stent migration) was recorded in six DLS patients (10 %) and five PE patients (8 %) (n. s.). Kaplan-Meier analysis of DLS and PE stent clogging-free survival showed a significantly longer patency period with the DLS stents (P = 0.0005).\n These results show that DoubleLayer stents have a longer patency period than PE stents. Patients who received PE stents had a higher risk of stent occlusion (relative risk 3.05; 95 % CI, 1.57 - 5.89) before death than DLS patients.", "In patients with obstructive jaundice caused by malignant stricture of the extrahepatic bile duct we compared survival time, complication rates, hospitalisation requirements, and quality of life after palliation by endoscopic endoprosthesis or bypass surgery. During diagnostic endoscopic cholangiography 50 patients were randomised to the two treatment alternatives. All 25 patients randomised to endoprosthesis were treated by this procedure, whereas only 19 of 25 patients randomised to bypass surgery underwent operative biliary-digestive anastomosis. Life table analysis revealed no difference in survival between treatment groups or randomisation groups. No differences were found when other variables were compared. We conclude, that palliation of obstructive jaundice in malignant bile duct obstruction with endoscopically introduced endoprosthesis is as effective as operative bypass.", "Endoscopic stent insertion is the optimum method of palliation for malignant biliary obstruction. Various types of self-expanding metal stents have been introduced in the market. Whether one type of stents is superior to the others in terms of stent patency remains undefined.\n This randomized trial compared 2 uncovered metal stents with similar technical characteristics, but significant cost difference, in the palliation of inoperable malignant biliary strictures.\n Ninety-two patients with inoperable biliary obstruction were randomized to receive either a 10-mm diameter Hanaro or Luminex uncovered metal stent. The duration of stent patency, the overall patient survival, the mechanism of stent occlusion, and the adverse events were analyzed.\n Eighty-nine patients were included in the analysis; 44 received Hanaro stents and 45 Luminex stents. The overall median patency rates between the 2 stents did not differ (328 d for the Hanaro vs. 289 d for the Luminex stent; P=0.815). Similarly, no difference was found between the overall median survival rates by the 2 stents (347 d for the Hanaro vs. 307 d for the Luminex stent; P=0.654). Two major procedure-related complications occurred, perforation (Hanaro stent) and proximal stent migration (Luminex stent). Stent occlusion requiring reintervention occurred in 25 patients (11 with the Hanaro vs. 14 with the Luminex stent; P=0.521).\n The 2 uncovered metal stents are comparable in terms of placement, occlusion rates, overall stent patency, and patient survival; Hanaro stent insertion, however, seems to be a cost-saving strategy at least in Greece.", "The industry standard since 1990 for self-expanding biliary metallic stents has been the Wallstent. In 1998 the Spiral Z-stent was released. This randomized trial compared the Z-stent with the Wallstent in the treatment of malignant biliary obstruction.\n Patients with unresectable malignant biliary obstruction distal to the bile duct bifurcation were randomized to receive a 10-mm diameter Wallstent or a 10-mm diameter Z-stent.\n A total of 145 patients were randomized; 13 were excluded. Sixty-four patients who received a Z-stent and 68 who had a Wallstent are included in the analysis. Tumors responsible for bile duct obstruction were pancreatic cancer (108), cholangiocarcinoma (15), metastatic cancer (6), and papillary cancer (3). Metallic stents were successfully placed in all patients. Seven technical problems were encountered during placement of the Z-stent and 5 with the Wallstent. There were 21 occlusions requiring reintervention (8 Z-stent, 13 Wallstent; p = 0.30). Median time to reintervention was the following: Z-stent, 162 days; Wallstent, 150 days (p = 0.22). A total of 104 patients died of progressive disease or other cause; 7 patients remain alive with patent stents. The overall calculated median patency rates were: Z-stent, 152 days; Wallstent, 154 days (p = 0.90).\n The Spiral Z-stent is comparable with the Wallstent in terms of placement, occlusion rates, and overall patency. Occasional early occlusion of both stents suggests tumor characteristics instead of the size of the mesh openings in the stents as important factors.", "Covered self-expandable metal stents (EMS) were recently developed to overcome tumour ingrowth in conventional EMS. However, supporting evidence for the efficacy of covered EMS is lacking.\n We enrolled 112 patients with unresectable distal biliary malignancies. They were randomly assigned to polyurethane covered (n = 57) or original diamond stent (n = 55).\n Stent occlusion occurred in eight patients (14%) after a mean of 304 days in the covered group, and in 21 patients (38%) after a mean of 166 days in the uncovered group. The incidence of covered EMS occlusion was significantly lower than that of uncovered EMS (p = 0.0032). The cumulative stent patency of covered stents was significantly higher than that of uncovered stents (p = 0.0066). No tumour ingrowth occurred in the covered group while it was observed in 15 patients in the uncovered group. In subgroup analysis, the cumulative patency of the covered EMS was significantly higher in pancreatic cancer (p = 0.0363) and metastatic lymph nodes (p = 0.0354). There was no significant difference in survival between the two groups. Acute cholecystitis was observed in two of the covered group and in none of the uncovered group. Mild pancreatitis occurred in five of the covered group and in one of the uncovered group.\n Covered diamond stents successfully prevented tumour ingrowth and were significantly superior to uncovered stents for the treatment of patients with distal malignant biliary obstruction. However, careful attention must be paid to complications specific to covered self-expandable metal stents, such as acute cholecystitis and pancreatitis.", "Stent clogging is the major limitation of palliative treatment for malignant biliary obstruction. Metal stents have much better patency than plastic stents, but are more expensive. Preliminary data suggest that the recently designed plastic (Tannenbaum) stent has better duration of patency than the polyethylene stent. This study aimed to compare the efficacy and cost effectiveness between the Tannenbaum stent without side holes and the uncovered metal stent for patients with malignant distal common bile duct obstruction.\n In this study, 47 patients (median age, 73 years, range, 56-86 years) with inoperable malignant distal common bile duct strictures were prospectively randomized to receive either a Tannenbaum stent (n = 24) or an uncovered self-expandable metal stent (n = 23). The patients were clinically evaluated, and biochemical tests were analyzed if necessary until their death or surgery for gastric outlet obstruction. Cumulative first stent patency and patient survival were compared between the two groups. Cost-effectiveness analysis also was performed for the two study groups.\n The two groups were comparable in terms of age, gender, and diagnosis. The median first stent patency was longer in the metal group than in the Tannenbaum stent group (255 vs 123.5 days; p = 0.002). There was no significant difference in survival between the two groups. The total cost associated with the Tannenbaum stents was lower than for the metal stents (17,700 vs 30,100 euros; p = 0.001), especially for patients with liver metastases (3,000 vs 6,900 euros; p < 0.001).\n Metal stent placement is an effective treatment for inoperable malignant distal common bile duct obstruction, but Tannenbaum stent placement is a cost-saving strategy, as compared with metal stent placement, especially for patients with liver metastases and expected short survival time.", "Our aim was to compare the clinical efficacy of the Tannenbaum (TB) biliary prostheses, a recently designed Teflon stent without side holes, with the Cotton-Huibregtse (CH) polyethylene stent.\n Fifty-seven patients (26 men, mean age 75.5 years) with unresectable malignant tumors and distal biliary stenosis were included (38 pancreatic head cancer, 17 cholangiocarcinoma, 2 ampullary cancer). Patients were prospectively randomized to have a 10F, 7 cm long TB (29 patients) or CH (28 patients) stent inserted endoscopically. Four patients (2 TB and 2 CH) were excluded: 3 because of the failure of stent insertion and 1 because of a protocol violation. The patients were evaluated clinically and, if necessary, with biochemical tests every month until death or until they needed surgery for symptoms of gastric outlet obstruction. When occlusion or dislocation occurred, the stent was replaced with one of the same type. Cumulative stent patency and patient survival were estimated with the Kaplan-Meier life-table analysis and compared by log-rank chi-square test.\n The two groups were comparable in mean age, gender, and diagnosis. The patients were followed for a mean of 145.5 days (range 24 to 613); by the end of the study 47 patients (81%) had died or developed symptoms of gastric outlet obstruction. Median survival was 88 days (range 24 to 613) in the TB group and 75.6 days (23 to 486) in the CH group. Stent exchange (occlusion 16, dislocation 3) was necessary for 5 patients in the TB group and 7 in the CH group. No statistical difference was found on comparing the mean duration of function of the first, second, and third stents (analysis of variance, p = 0.80). The median duration of stent function was 96 days (range 11 to 613) in the TB group and 75.5 days (range 23 to 323) in the CH group. No significant difference was found in either survival time (p = 0.48) or stent patency (p = 0.12).\n This study found no significant advantage of the Tannenbaum prostheses over the standard polyethylene stent in the palliation for patients with distal malignant biliary stenosis with regard to survival or length of stent patency." ]

[ "8463521", "1904354", "1638171", "2109658", "9152715", "1773423", "1592575", "8369100", "10805059", "1288668", "9581210" ]

[ "L-deprenyl in the treatment of mild dementia of the Alzheimer type: preliminary results.", "Effects of a MAO-B inhibitor in the treatment of Alzheimer disease.", "CBF and cognitive evaluation of Alzheimer type patients before and after IMAO-B treatment: a pilot study.", "Neuropsychological effects of L-deprenyl in Alzheimer's type dementia.", "Selegiline in the treatment of behavioural disturbance in Alzheimer's disease.", "L-deprenyl therapy improves verbal memory in amnesic Alzheimer patients.", "Alzheimer-type dementia and verbal memory performances: influence of selegiline therapy.", "Effects of monoamine oxidase inhibition by selegiline on concentrations of noradrenaline and monoamine metabolites in CSF of patients with Alzheimer's disease.", "Selegiline treatment and the extent of degenerative changes in brain tissue of patients with Alzheimer's disease.", "A strategy of \"combination chemotherapy\" in Alzheimer's disease: rationale and preliminary results with physostigmine plus deprenyl.", "Short-term administration of selegiline for mild-to-moderate dementia of the Alzheimer's type." ]

[ "To examine the short-term cognitive and behavioral effects of L-deprenyl in persons with mild dementia of the Alzheimer type (DAT) over a 2-month period.\n A 15-month randomized, double-blind, placebo-controlled trial using a parallel-group design. This report deals with the first 2 months of the trial.\n 39 subjects with mild DAT (CDR 1) selected using NINCDS-ADRDA criteria.\n A battery of neuropsychological tests and clinical rating scales.\n The placebo and L-deprenyl subjects were similar at baseline on the clinical and neuropsychological tests. There was no evidence of a L-deprenyl effect on any clinical or neuropsychological measures after 2 months.\n L-deprenyl did not have a measurable impact on behavior or cognitive function over a 2-month period in this group of subjects with mild DAT.", "119 patients were enrolled in a double-blind randomized parallel study versus placebo carried out to assess both the efficacy and tolerability of L-deprenyl (10 mg/day) for treatment of patients with organic mental disorders of the Alzheimer type (DAT). The treatments were given for 3 months, starting after a run-in period of 15 days to evaluate efficacy. A complete neuropsychological battery was administered monthly after the start of treatment whereas tolerability was assessed by checking, recording and classifying all the unfavorable experiences occurring. According to the results, L-deprenyl would seem to be a useful and reliable tool for the treatment of DAT patients in an attempt to improve their cognitive functions and reduce behavioral alterations, without frequent or severe side effects.", "Ten patients diagnosed as affected by primary degenerative dementia of the Alzheimer type, with a mild to moderate cognitive and behavioral impairment, were studied in a double blind design when taking for 60 days 5 mg twice a day of L-deprenyl or placebo. Cognitive functions and cerebral blood flow were assessed at the beginning and at the end of treatment by a wide array of memory, attention, and language efficiency measures and by SPECT-99TcHMPAO procedure. Reduced CBF on the parietal lobes was demonstrated in the patients at baseline together with a reduction of memory and cognitive efficiency. At the end of the treatment patients who received L-deprenyl showed an improvement in cognitive efficiency and no changes in CBF, while patients treated with placebo showed a worsening of cognitive efficiency and further reduction of parietal lobe CBF.", "The monoaminergic neurotransmission defect seen in dementia of the Alzheimer type (DAT) is linked to a known increased activity of type B cerebral monoamine oxidases (MAO-Bs). The use of drugs that are able to block this abnormal activity could therefore be useful in the treatment of some cognitive deficits that characterize DAT. Twenty patients with a clinical diagnosis of DAT and with a slight-moderate mental deterioration were treated with 10 mg/day of L-deprenyl, a selective MAO-B inhibitor, according to a double-blind crossover design vs. placebo. Initial treatment (drug or placebo) was randomly assigned. The patients' cognitive functions were evaluated at baseline and then after 3 and 6 months of treatment with drug or placebo. The patients crossed over treatment after 3 months, without a washout interval. The results of the study show the higher and statistically significant effects of L-deprenyl on memory and attention that seem to be due to an improved function of the monoaminergic systems involved in the process of neuronal degeneration.", "The purpose of this study was to examine the behavioural and cognitive effects of selegiline in a group of moderately behaviourally disturbed AD patients.\n This was a 14-week randomized double-blind placebo-controlled study of selegiline (10 mg) and placebo.\n An outpatient clinic in an urban-based tertiary referral centre in the USA.\n Twenty-five outpatients meeting NINCDS criteria for probable Alzheimer's disease with associated behavioural disturbance.\n The Brief Psychiatric Rating Scale (BPRS), the Dementia Mood Assessment Scale (DMAS) and the Alzheimer Disease Assessment Scale (Cognitive) (ADAS-COG).\n In the primary analysis, improvement on the BPRS and DMAS scores with selegeline treatment did not. reach statistical significance. A secondary analysis using a parallel design showed a significant benefit of drug treatment on BPRS scores with a trend towards improvement on the DMAS. Among the 10 subjects who could be tested, there was a significant improvement in cognitive function on the ADAS-COG with selegiline compared to placebo.\n Short-term selegiline treatment produced an improvement in behaviour and had a significant effect on cognition in a subset of testable patients.", "Altered monoaminergic neurotransmission could play an important role in the cognitive dysfunctions typical of dementia of the Alzheimer type (DAT). DAT is not, however, a homogenous phenomenon inasmuch as two forms are distinguishable: early onset (EO) and late onset (LO). Moreover, focal patterns of neuropsychological deterioration fall into various subgroups. According to our hypothesis, DAT patients, who at the onset of the disease mainly manifest memory disorders, also represent a specific subgroup characterized by impaired cortically projecting catecholaminergic pathways. In a 6-month randomized, double-blind, cross-over study versus placebo we analysed the influence of L-deprenyl on the verbal memory of 19 amnesic EO-DAT patients. Verbal memory was assessed by means of the Rey Auditory Verbal Learning Test. The results obtained show significantly better performances for L-deprenyl treated patients in learning and long-term memory skills. We suggest that L-deprenyl, through selective inhibition of MAO-B and by increasing the activity of the catecholaminergic systems, positively influences cognitive functions and behaviour founded on memory efficiency.", "In a double blind randomized crossover trial lasting 6 months selegiline, a selective MAO-B inhibitor, was tested against placebo for activity on verbal memory performances in Alzheimer-type dementia (DAT). Verbal memory was assessed with the Rey-Auditory-Verbal Learning Test at the start of treatment, at the time scheduled for crossover (90 days) and at the end of the trial (180 days). The results suggest that selegiline possesses significant activity on some memory parameters, which seems to depend on an improvement both in information processing abilities and in learning strategies at the moment of acquisition.", "A double-blind, cross-over trial with 12 patients with Alzheimer's disease (AD) was carried out primarily to test the suitability of this design in the investigation of the clinical effects of selegiline (10 mg/day) in AD. Cerebrospinal fluid (CSF) samples for the determination of concentrations of noradrenaline (NA) and several monoamine metabolites were collected at baseline and at the end of both four-week treatment periods (placebo and selegiline). The severity of dementia was assessed using Ferm's and Gottfries-Bråne-Steen (GBS) dementia scales. The concentrations of the dopamine metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and the NA metabolites, 3,4-dihydroxyphenylglycol (DHPG), and 3-methoxy-4-hydroxyphenyl glycol (MHPG) decreased significantly during selegiline treatment. There was a clear trend of reduction in concentrations of homovanillic acid (HVA) during selegiline treatment, whereas the concentrations of NA, 5-hydroxyindoleacetic acid (5-HIAA), and tryptophan did not differ significantly. The study design was not suitable for the analysis of the clinical results as there was a significant carry-over effect in both scales. As only the first period data could be used in the analysis, there were no significant differences in the scores of Ferm's or GBS scales, but clear positive trends could be detected in favour of selegiline.", "A beneficial effect of selegiline (L-deprenyl) in Alzheimer's disease (AD) has been reported in several clinical studies.\n The brain tissue from 17 deceased patients, members of a double-blind clinical trial to assess the potential benefit of selegiline in AD, were analysed.\n In our study, the decrease in the Mini-Mental State Examination (MMSE) scores during the progress of the disease had been significantly influenced by selegiline treatment. Prior to death, the MMSE scores were significantly higher in those patients receiving selegiline than in those receiving placebo. However, according to our results, none of the lesions critical for AD diagnosis, such as counts of senile/neuritic plaques, neurofibrillary tangles or beta-A4 load, were influenced by the selegiline treatment.\n In conclusion, according to our study, mechanisms other than neuronal degeneration seen as lesions critical for AD diagnosis are influenced by selegiline treatment, leading to the functional benefit found in AD.", "Although the central cholinergic deficits are still considered to be of primary importance in Alzheimer's disease, there is great need for an expansion of the pharmacological approach in this illness beyond the simple cholinergic replacement hypothesis. This report focuses on the concept of \"combination chemotherapy\" in Alzheimer's disease as the next generation of therapeutic strategies. Based on earlier positive findings in Alzheimer patients with the monoamine oxidase B inhibitor, 1-deprenyl, the authors speculate that a combination of physostigmine, the short-acting cholinesterase inhibitor, and 1-deprenyl might be more beneficial than either agent alone. The authors outline a sample paradigm for such combination studies, report preliminary data on the first 16 Alzheimer subjects to have received an initial combination of physostigmine and deprenyl, and point to other possible \"combination chemotherapy\" strategies for future study.", "As a follow-up to an earlier study showing short-term benefit in inpatients with more severe dementia, the authors studied the short-term cognitive, functional, and behavioral effects of selegiline in outpatients with mild-to-moderate dementia of the Alzheimer type (DAT) by means of a double-blind, randomized, crossover study of placebo vs. selegiline. Fifty outpatients with mild-to-moderate DAT and no behavioral disturbances were given selegiline in two 8-week treatment periods separated by a 4-week washout. Outcome was assessed with standardized measures of dementia severity, daily functioning, behavior, and cognition. There was no drug-placebo difference in any outcome measure. Selegiline did not show short-term benefit in this study, contrary to the earlier study, perhaps because the patients were studied less intensively and/or lacked behavioral problems that could show response, although the medication was well tolerated." ]

[ "18362256", "16631910", "21542934", "9135895" ]

[ "Treatment success in cancer: new cancer treatment successes identified in phase 3 randomized controlled trials conducted by the National Cancer Institute-sponsored cooperative oncology groups, 1955 to 2006.", "Effect of a US National Institutes of Health programme of clinical trials on public health and costs.", "Treatment success in pragmatic randomised controlled trials: a review of trials funded by the UK Health Technology Assessment programme.", "Thirty years of Medical Research Council randomized trials in solid tumours." ]

[ "The evaluation of research output, such as estimation of the proportion of treatment successes, is of ethical, scientific, and public importance but has rarely been evaluated systematically. We assessed how often experimental cancer treatments that undergo testing in randomized clinical trials (RCTs) result in discovery of successful new interventions.\n We extracted data from all completed (published and unpublished) phase 3 RCTs conducted by the National Cancer Institute cooperative groups since their inception in 1955. Therapeutic successes were determined by (1) assessing the proportion of statistically significant trials favoring new or standard treatments, (2) determining the proportion of the trials in which new treatments were considered superior to standard treatments according to the original researchers, and (3) quantitatively synthesizing data for main clinical outcomes (overall and event-free survival).\n Data from 624 trials (781 randomized comparisons) involving 216 451 patients were analyzed. In all, 30% of trials had statistically significant results, of which new interventions were superior to established treatments in 80% of trials. The original researchers judged that the risk-benefit profile favored new treatments in 41% of comparisons (316 of 766). Hazard ratios for overall and event-free survival, available for 614 comparisons, were 0.95 (99% confidence interval [CI], 0.93-0.98) and 0.90 (99% CI, 0.87- 0.93), respectively, slightly favoring new treatments. Breakthrough interventions were discovered in 15% of trials.\n Approximately 25% to 50% of new cancer treatments that reach the stage of assessment in RCTs will prove successful. The pattern of successes has become more stable over time. The results are consistent with the hypothesis that the ethical principle of equipoise defines limits of discoverability in clinical research and ultimately drives therapeutic advances in clinical medicine.", "Few attempts have been made to estimate the public return on investment in medical research. The total costs and benefits to society of a clinical trial, the final step in testing an intervention, can be estimated by evaluating the effect of trial results on medical care and health.\n All phase III randomised trials funded by the US National Institute of Neurological Disorders and Stroke before Jan 1, 2000, were included. Pertinent publications on use, cost to society, and health effects for each studied intervention were identified by systematic review, supplemented with data from other public and proprietary sources. Regardless of whether a trial was positive or negative, information on use of tested therapies was integrated with published per-use data on costs and health effect (converted to 2004 US dollars) to generate 10-year projections for the US population.\n 28 trials with a total cost of 335 million dollars were included. Six trials (21%) resulted in measurable improvements in health, and four (14%) resulted in cost savings to society. At 10 years, the programme of trials resulted in an estimated additional 470,000 quality-adjusted life years at a total cost of 3.6 billion dollars (including costs of all trials and additional health-care and other expenditures). Valuing a quality-adjusted life year at per-head gross domestic product, the projected net benefit to society at 10-years was 15.2 billion dollars. 95% CIs did not include a net loss at 10 years.\n For this institute, the public return on investment in clinical trials has been substantial. Although results led to increases in health-care expenditures, health gains were large and valuable.", "Previous research reviewed treatment success and whether the collective uncertainty principle is met in RCTs in the US National Cancer Institute portfolio. This paper classifies clinical trials funded by the UK HTA programme by results using the method applied to the US Cancer Institute trials, and compares the two portfolios.\n Data on all completed randomised controlled trials funded by the HTA programme 1993-2008 were extracted. Each trial's primary results was classified into six categories; 1) statistically significant in favour of the new treatment, 2) statistically significant in favour of the control treatment 3) true negative, 4) truly inconclusive, 5) inconclusive in favour of new treatment or 6) inconclusive in favour of control treatment. Trials were classified by comparing the 95% confidence interval for the difference in primary outcome to the difference specified in the sample size calculation. The results were compared with Djulbegovic's analysis of NCI trials.\n Data from 51 superiority trials were included, involving over 48,000 participants and a range of diseases and interventions. 85 primary comparisons were available because some trials had more than two randomised arms or had several primary outcomes. The new treatment had superior results (whether significant or not) in 61% of the comparisons (52/85 95% CI 49.9% to 71.6%). The results were conclusive in 46% of the comparisons (19% statistically significant in favour of the new treatment, 5% statistically significant in favour of the control and 22% true negative). The results were classified as truly inconclusive (i.e. failed to answer the question asked) for 24% of comparisons (20/85). HTA trials included fewer truly inconclusive and statistically significant results and more results rated as true negative than NCI trials.\n The pattern of results in HTA trials is similar to that of the National Cancer Institute portfolio. Differences that existed were plausible given the differences in the types of trials -HTA trials are more pragmatic. The results indicate HTA trials are compatible with equipoise. This classification usefully summarises the results from clinical trials and enables comparisons of different portfolios of trials.", "This paper reviews the survival outcome from the randomized Phase III trials in solid tumours published on behalf of, or in collaboration with, the Cancer Therapy Committee (CTC) of the British Medical Research Council over a 30-year period to 31 December 1995. We review briefly the innovations in statistical methodology that have occurred over the period. We also note the ways in which standards of reporting the trials have improved, with more recent publications including, for example, estimates of the size of effect and confidence intervals. In all, 32 trials, involving over 5000 deaths in more than 8000 patients, have been published. Tumour types have included bladder, bone, brain, cervix, colon and rectum, head and neck, kidney, lung, ovary, prostate and skin. This paper presents a bibliography of these trials and gives details of the treatment comparisons made, the numbers of patients randomized and included in the analysis for each treatment arm, the observed numbers of deaths, and an estimate of the hazard ratio with associated 95% confidence intervals. The bibliography also indicates the main endpoint of each trial, whether recurrence-free survival or survival, and whether the trial was aimed at finding a difference or showing equivalence. The MRC trials have made an impact on both clinical practice and research activities. For example, the lung cancer programme has helped to establish the role of chemotherapy in small cell lung cancer and has developed better palliative treatment for non-small cell lung cancer. Trials of the radiosensitizer misonidazole have demonstrated that it has no role in the treatment of a number of cancers, trials of hyperbaric oxygen have defined the biological activity of this approach, and the appropriate dose of radiotherapy in patients with brain tumours has been found. The individual trials recruited between 44 and 824 patients (median 213). A better measure of the information in a trial is the number of deaths reported, which varied from 28 to 661 (median 145). A large proportion of the comparisons (8/29 or 28%) anticipating a survival difference, demonstrated such a difference at the 5% level of significance. Despite this, it is concluded that some of the trials should have been larger. In such cases, hindsight suggests either that an overoptimistic view of the anticipated survival benefit was taken at the design stage, or, for equivalence trials, the planned confidence interval was too wide for definitive statements to be made. As a consequence, the current CTC profolio of ongoing randomized trials open to patient accrual at 1 January 1996 have a projected median size of 600 and range from 120 to 2000 patients." ]

[ "2880213", "8011819", "2659679", "2405727", "1311351", "12135285", "2166429", "9466205", "2994500", "9314461", "15741547", "7886779", "1738379", "9114142", "10515844", "15127339", "15569787", "15844060", "9027276", "2827242", "9309267", "16274713", "11982640", "15234664", "8059918", "11716099", "1651060", "9373659", "7886777", "17304449", "15499535", "9455509", "17556623" ]

[ "Immunotherapy versus chemotherapy in localised cutaneous leishmaniasis.", "Efficacy of a short course (10 days) of high-dose meglumine antimonate with or without interferon-gamma in treating cutaneous leishmaniasis in Guatemala.", "Immunotherapy of localized, intermediate, and diffuse forms of American cutaneous leishmaniasis.", "Placebo-controlled clinical trial of meglumine antimonate (glucantime) vs. localized controlled heat in the treatment of cutaneous leishmaniasis in Guatemala.", "Placebo-controlled clinical trial of sodium stibogluconate (Pentostam) versus ketoconazole for treating cutaneous leishmaniasis in Guatemala.", "Treatment of cutaneous leishmaniasis with a topical antileishmanial drug (WR279396): phase 2 pilot study.", "Efficacy of ketoconazole against Leishmania braziliensis panamensis cutaneous leishmaniasis.", "Evaluating the efficacy of allopurinol for the treatment of cutaneous leishmaniasis.", "American cutaneous leishmaniasis: a comparison of three sodium stibogluconate treatment schedules.", "Efficacy of sodium stibogluconate alone and in combination with allopurinol for treatment of mucocutaneous leishmaniasis.", "Comparison of meglumine antimoniate and pentamidine for peruvian cutaneous leishmaniasis.", "Aminosidine (paromomycin) versus sodium stibogluconate for the treatment of American cutaneous leishmaniasis.", "Allopurinol in the treatment of American cutaneous leishmaniasis.", "Treatment of cutaneous leishmaniasis with allopurinol and stibogluconate.", "Randomized, double-blind study of stibogluconate plus human granulocyte macrophage colony-stimulating factor versus stibogluconate alone in the treatment of cutaneous Leishmaniasis.", "Miltefosine for new world cutaneous leishmaniasis.", "Comparison of generic to branded pentavalent antimony for treatment of new world cutaneous leishmaniasis.", "Randomized, double-blind clinical trial of topical imiquimod 5% with parenteral meglumine antimoniate in the treatment of cutaneous leishmaniasis in Peru.", "Inefficacy of allopurinol as monotherapy for Colombian cutaneous leishmaniasis. A randomized, controlled trial.", "[Evaluation of the effectiveness and toxicity of pentostam and glucantime in the treatment of cutaneous leishmaniasis].", "Treatment of American cutaneous leishmaniasis: a comparison between low dosage (5 mg/kg/day) and high dosage (20 mg/kg/day) antimony regimens.", "Heat therapy for cutaneous leishmaniasis elicits a systemic cytokine response similar to that of antimonial (Glucantime) therapy.", "Immunochemotherapy for cutaneous leishmaniasis: a controlled trial using killed Leishmania (Leishmania) amazonensis vaccine plus antimonial.", "Comparison of the effectiveness of two topical paromomycin treatments versus meglumine antimoniate for New World cutaneous leishmaniasis.", "Efficacy of 28-day and 40-day regimens of sodium stibogluconate (Pentostam) in the treatment of mucosal leishmaniasis.", "Randomized, controlled, double-blind trial of topical treatment of cutaneous leishmaniasis with paromomycin plus methylbenzethonium chloride ointment in Guatemala.", "Placebo controlled treatment of Ecuadorian cutaneous leishmaniasis.", "Non-ulcerative cutaneous leishmaniasis in Honduras fails to respond to topical paromomycin.", "Limited efficacy of injectable aminosidine as single-agent therapy for Colombian cutaneous leishmaniasis.", "Oral pentoxifylline combined with pentavalent antimony: a randomized trial for mucosal leishmaniasis.", "Antimony plus recombinant human granulocyte-macrophage colony-stimulating factor applied topically in low doses enhances healing of cutaneous Leishmaniasis ulcers: a randomized, double-blind, placebo-controlled study.", "Topical paromomycin/methylbenzethonium chloride plus parenteral meglumine antimonate as treatment for American cutaneous leishmaniasis: controlled study.", "Parenteral aminosidine is not effective for Peruvian mucocutaneous leishmaniasis." ]

[ "In a randomised trial a combination vaccine consisting of live BCG together with killed leishmania promastigotes was compared with a standard antimonial regimen in 94 patients with localised cutaneous leishmaniasis. Three vaccinations over 32 weeks gave a similar cure rate (94%) to three 20-day courses of meglumine antimonate. In the immunotherapy group side-effects were few (5.8%) and slight whereas in the chemotherapy group they were frequent (52.4%) and often serious. Immunotherapy is a low-cost, low-risk alternative to chemotherapy in localised cutaneous leishmaniasis, applicable by primary health services in rural areas.", "Sixty-six Guatemalan men with parasitologically confirmed cutaneous leishmaniasis, due most commonly to Leishmania braziliensis, were randomly assigned to receive one of three treatment regimens: meglumine antimonate (meglumine) for 20 days; meglumine for 10 days; and meglumine for 10 days plus alternate-day injections of interferon-gamma. In each group, meglumine was given intravenously as 20 mg of antimony/(kg of body weight.d). All treatment regimens were associated with similar response rates: the lesions of 19 (90%) of 21 patients who received meglumine for 20 days, 18 (90%) of 20 patients who received meglumine for 10 days, and all 22 patients who received meglumine plus interferon-gamma were completely reepithelialized by 13 weeks. In addition, for patients receiving all treatment regimens, test-of-cure cultures for Leishmania were negative and reactivation of lesions did not occur during 12 months of follow-up. The high efficacy of our 10-day course of meglumine indicates that the currently recommended duration of 20 days may be unnecessary for infections caused by L. braziliensis and suggests that a 10-day course of high-dose antimony should be tested as therapy for cutaneous leishmaniasis in other geographic areas.", "The clinical efficacy of immunotherapy for localized American cutaneous leishmaniasis with a combination of heat-killed Leishmania mexicana amazonensis promastigotes and viable BCG (bacille Calmette Guérin) has been compared with meglumine antimoniate chemotherapy and with BCG alone in a controlled clinical study in 217 patients. The results in the first two groups were comparable, with greater than 90% clinical cures with an average time of 16-18 w required for healing. The cure rate was considerably lower (42%) and more prolonged in the group receiving BCG alone. Secondary effects were observed in less than 5% of the patients receiving combined immunotherapy or BCG alone. In contrast, 49% of the patients receiving chemotherapy showed side effects. High therapeutic efficacy was also observed using combined immunotherapy in patients with intermediate and diffuse cutaneous leishmaniasis who were previously unresponsive to chemotherapy. Cure or clinical improvement was seen in all 11 patients with intermediate forms of the disease, and marked clinical improvement was observed in 9 of 10 patients with diffuse disease. The results on the efficacy of the combined vaccine in immunotherapy for American cutaneous leishmaniasis provide a strong rationale for studying its effectiveness in prophylactic trials.", "Sixty-six Guatemalans with parasitologically proven cutaneous leishmaniasis were randomly and equally divided into 3 treatment groups: those receiving meglumine antimonate (Glucantime), 850 mg antimony/day im for 15 days; those receiving localized controlled heat from a radio-frequency generator, 50 degrees C for 30 sec, 3 treatments at 7 day intervals; and those receiving treatment with a placebo. Of 53 isolates identified, 40 were Leishmania braziliensis braziliensis and 13 were L. mexicana mexicana. Thirteen weeks after beginning treatment, the number of patients from each group with completely healed and parasitologically negative lesions were as follows: meglumine antimonate, 16 (73%); localized heat, 16 (73%); and placebo, 6 (27%). The cure rate for those with infections due to L. b. braziliensis in each group was as follows: meglumine antimonate, 11 out of 14 (79%); controlled heat, 9 out of 14 (64%); and placebo, 0 out of 11.", "To determine the relative efficacy and toxicity of stibogluconate and ketoconazole for the treatment of cutaneous leishmaniasis, a comparative trial was conducted in which 120 Guatemalan men with parasitologically proven cutaneous leishmaniasis were randomly divided into three treatment groups: sodium stibogluconate (20 mg of antimony per kilogram per day intravenously for 20 days), ketoconazole (600 mg per day orally for 28 days), and placebo. Treatment outcome was influenced by species. Among patients infected with Leishmania braziliensis, 24 (96%) of 25 in the stibogluconate group but only 7 (30%) of 23 in the ketoconazole group responded. Among Leishmania mexicana-infected patients, only 4 (57%) of 7 in the stibogluconate group but 8 (89%) of 9 in the ketoconazole group responded. These differences emphasize the importance of speciation in the treatment of leishmaniasis.", "We studied the efficacy of WR279396, a topical formulation of aminoglycosides that cures 100% of cutaneous leishmaniasis lesions in mice. We conducted what is to our knowledge the first controlled study of WR279396 therapy for clinical cutaneous leishmaniasis. A total of 45 Colombian soldiers, all men, were randomly assigned to treatment with WR279396 (33 patients) or placebo (12 patients). Each lesion was treated twice daily for 20 days. Lesions were measured at the end of therapy and at 45, 90, and 180 days after treatment began. A total of 17 (61%) of 28 assessable WR279396-treated patients were cured, and 5 (55%) of 9 assessable placebo-treated patients were cured (P = 0.9). For the 36 lesions treated with WR279396 that were cured, cure took a mean of 35 days, whereas for the 6 lesions that were cured in the group of patients receiving placebo, cure time took a mean of 56 days (P = 0.04). WR279396 is a nontoxic topical formulation that significantly accelerated cure time in patients with Leishmania panamensis cutaneous leishmaniasis.", "The classic agent for cutaneous leishmaniasis is pentavalent antimony. However, there are no reports of the efficacy of antimony versus placebo or of the efficacy of any alternative therapy versus either antimony or placebo. In the present report, the oral antifungal agent ketoconazole (600 mg/day for 28 days) was compared to a recommended regimen of intramuscular Pentostam (20 mg antimony/kg, with a maximum of 850 mg antimony/day, for 20 days) in a randomized study of the treatment of Panamanian cutaneous leishmaniasis due to Leishmania braziliensis panamensis. A separate group of patients with this disease was administered placebo.\n Ketoconazole clinically cured 16 of 21 (76%) patients. The lesions on nine patients healed by 1 month after therapy, and the lesions healed by 3 months after therapy on the other seven patients. Side effects were limited to a 27% incidence of mild, reversible hepatocellular enzyme elevation and an asymptomatic, reversible, approximately 70% decrease in serum testosterone in all patients. Pentostam cured 13 of 19 (68%) patients; the lesions on seven patients healed by the end of therapy, and the lesions on four other patients healed by 1 month after the end of therapy. Side effects were a 47% incidence of mild, reversible hepatocellular enzyme elevation and the morbidity due to 20 intramuscular injections in almost all patients. The placebo group of 11 patients had a 0% cure rate. By 1 month after therapy, all placebo-treated patients demonstrated new lesions or one lesion that was 23% to 875% larger than before therapy.\n Both ketoconazole and Pentostam were more effective than placebo against L. braziliensis panamensis cutaneous leishmaniasis. Oral ketoconazole is comparable in efficacy to this parenteral Pentostam regimen and can be recommended as initial treatment for this disease.", "nan", "Thirty-six patients with American cutaneous leishmaniasis were randomized to receive intravenous sodium stibogluconate for 10 days at a dose of 600 mg antimony (Sb) per day by one of three schedules: once daily by rapid infusion (A), by continuous 24 hr infusion (B), or in divided doses every eight hours by rapid infusion (C). Patients not cured after initial treatment were rerandomized to one of the other treatment schedules. An additional 19 patients who were not part of the randomized study received standard (STD) sodium stibogluconate treatment (600 mg Sb once daily by rapid infusion for 10 days, identical with schedule A). In the randomized study, the overall cure rate after the first course of treatment was 64%, but was higher for schedule A (100%) than for B (50%) or C (42%) (P less than 0.01). Considering all courses of treatment, schedule A was more effective (94%) than B (53%) or C (43%) (P less than 0.01). Paradoxically, patients in group A had a higher cure rate than patients in group STD (42% after the first course of treatment and 51% when all courses of treatment were considered). Side effects were mild and well tolerated. Total side effects were more frequent in groups B + C (52%) than A + STD (23%) due to an increased incidence of subjective complaints (26% vs. 10%, P less than 0.05) in patients receiving other than once daily rapid infusion. We conclude that giving the same total amount of sodium stibogluconate in three divided doses or by continuous infusion offers no advantage over standard, once daily treatment of American cutaneous leishmaniasis.", "A randomized, open, controlled clinical trial was designed to evaluate the efficacy, tolerance, and safety of sodium stibogluconate plus allopurinol and sodium stibogluconate alone as treatment of patients with mucocutaneous leishmaniasis. In phase 1 of the study, all 22 patients with severe disease had improvement of their lesions, but only two had clinical cure (both of these patients received sodium stibogluconate alone). In phase 2, which included 59 patients with moderate disease, the cure rate among sodium stibogluconate recipients was 75% (21 of 28) compared with 63.6% (14 of 22) among the sodium stibogluconate plus allopurinol recipients. The rates of clinical adverse events were similar among both groups. Thrombocytopenia was more frequent in the sodium stibogluconate plus allopurinol recipients, but the difference was not statistically significant. Eight patients (two sodium stibogluconate recipients and six sodium stibogluconate plus allopurinol recipients) withdrew from the study because of severe thrombocytopenia. In this study, the addition of allopurinol to sodium stibogluconate provided no clinical benefit as treatment of mucocutaneous leishmaniasis.", "Pentamidine was compared with meglumine antimoniate (Glucantime) for 80 patients with cutaneous leishmaniasis due to Leishmania braziliensis in Peru. Of the 40 patients administered Glucantime (20 mg of antimony [Sb]/kg/day intravenously for 20 days), 31 cured (78%), 6 failed (15%), of which 5 were due to relapse, and 3 were lost to follow-up (7%). Of the 40 patients administered pentamidine (2 mg/kg every other day for seven injections), 14 were cured (35%), 23 failed (58%), and 3 were lost to follow-up (7%). Five pentamidine failures were due to relapse, and 14 failures were due to the presence of parasites two weeks after therapy. Both regimens were well tolerated. Gastrointestinal, musculoskeletal, and total adverse events were not statistically different in either group. Elevations in levels of liver enzymes and pancreatic enzymes were statistically higher in the Glucantime group, but no patient terminated therapy prematurely. In this study, Glucantime was more effective than pentamidine for treatment of L. braziliensis cutaneous leishmaniasis in Peru based on parasitologic as well as clinical criteria.", "The efficacy of aminosidine was compared with sodium stibogluconate in an open, randomized study of parasitologically-proven cutaneous leishmaniasis in Belize. Aminosidine, 14 mg/kg/d (max. 1 g daily) for 20 d, healed 10 of 17 lesions and sodium stibogluconate, 20 mg/kg/d for 20 d, healed 15 of 17 lesions. Lesions caused by Leishmania braziliensis were relatively unresponsive to aminosidine. Aminosidine was well tolerated and toxicity was not observed. Sodium stibogluconate was not well tolerated and treatment was associated with bone marrow suppression and elevation of serum aminotransferases.", "Pentavalent antimony, the generally accepted treatment for leishmaniasis, is given parenterally, and it is expensive and not readily available in developing countries. An inexpensive, orally administered compound would be a substantial advance in treatment. Previous studies in vitro have shown synergism between allopurinol and pentavalent antimony in tissue-culture systems. We designed this clinical study to determine whether synergism could be demonstrated in patients.\n We performed a randomized, controlled study of the efficacy of allopurinol plus meglumine antimoniate (Glucantime), as compared with meglumine antimoniate alone, in patients with cutaneous leishmaniasis, who were recruited from a village in southeastern Colombia. In addition, those who declined injections were treated with allopurinol alone, and those who declined any treatment were considered controls. All the patients were followed for one year after the completion of treatment. Lesions that healed completely at three months and remained healed during follow-up were considered to be cured.\n The cure rate for patients treated with meglumine antimoniate was 36 percent; the addition of allopurinol increased the rate to 74 percent (P less than 0.001). Treatment with allopurinol alone yielded a cure rate of 80 percent (P less than 0.001). There were no cures among the untreated patients. There was no significant difference between the cure rate with allopurinol plus meglumine antimoniate and that with allopurinol alone. No major toxic effects were observed.\n For the treatment of American cutaneous leishmaniasis, the combination of allopurinol and meglumine antimoniate is significantly more effective than meglumine antimoniate alone, probably because of the efficacy of allopurinol alone, which appears to be as good as the combination.", "We conducted a randomized, controlled study in southern Colombia to determine if the addition of allopurinol to stibogluconate was superior to stibogluconate alone in the treatment of cutaneous leishmaniasis. Lesions that healed after a 3-month course of therapy and remained so during a 1-year period of follow-up were considered cured. The cure rate for patients treated with stibogluconate was 39%; the addition of allopurinol increased this rate to 71% (P = .005). For the treatment of cutaneous leishmaniasis, the combination of allopurinol and stibogluconate is significantly more effective than is stibogluconate alone. These results support those of other clinical studies in which allopurinol and stibogluconate were shown to be superior to stibogluconate alone. The aggregate data support the use of allopurinol as an inexpensive, orally administered agent that can be used as an adjunct to stibogluconate or, perhaps, other oral agents in the treatment of cutaneous leishmaniasis.", "The response to recombinant human granulocyte macrophage colony-stimulating factor (GM-CSF) in the treatment of cutaneous leishmaniasis was evaluated. Twenty patients with cutaneous leishmaniasis who had lesions for 60 days were enrolled in a double-blind placebo trial of GM-CSF with standard parenteral sodium stibogluconate (20 mg/kg-1/day-1) for 20 days. Ten patients were randomized to receive intralesionally injected GM-CSF (200 microgram) at enrollment and 1 week after, and 10 patients received saline as placebo. GM-CSF- and antimony-treated patients healed faster than patients who received antimony alone (49+/-32.8 vs. 110+/-61.6 days, P<.05). Seven of 10 patients were healed of their lesions before 40 days after therapy in the GM-CSF group, compared with only 1 of 10 patients in the placebo group (relative risk, 7; 95% confidence interval, 1.04-47.00). Thus, GM-CSF plus antimony significantly increased the chance of lesion healing in 40 days.", "The oral agent miltefosine has demonstrated a >95% cure rate in Indian visceral leishmaniasis. We performed a large, placebo-controlled study of miltefosine therapy (2.5 mg/kg per day orally for 28 days) against cutaneous leishmaniasis in Colombia and Guatemala. In regions in Colombia where Leishmania vianna panamensis is common, the per-protocol cure rates for miltefosine and placebo were 91% (40 of 44 patients) and 38% (9 of 24). These values are similar to historic values for the antimony standard of care and placebo. In regions in Guatemala where L. v. braziliensis and L. mexicana mexicana are common, the per-protocol cure rates were 53% (20 of 38) for miltefosine and 21% (4 of 19) for placebo. The miltefosine rate was lower than historic antimony cure rates of >90%. Miltefosine was well tolerated. Miltefosine is a useful oral agent against cutaneous leishmaniasis due to L. v. panamensis in Colombia but not against leishmaniasis due to L. v. braziliensis in Guatemala.", "The cost of generic pentavalent antimony (generic stibogluconate) is approximately one-sixth that of branded pentavalent antimony (stibogluconate in the form of Pentostam or meglumine antimoniate in the form of Glucantime. We compared generic stibogluconate to Pentostam and Glucantime for the treatment of cutaneous leishmaniasis patients in Bolivia and Colombia. For all 114 patients, the per-protocol cure rates were 83-91% and the intent-to-treat cure rates were 75-83%. The highest values were in the generic stibogluconate group. The incidence of pancreatic enzyme abnormalities was 48-88% and the incidence of liver enzyme abnormalities was 48-87%. The lowest incidences were in the generic stibogluconate group. The efficacy and tolerance of inexpensive generic stibogluconate appears comparable to branded formulations for the treatment of cutaneous leishmaniasis in these endemic regions.", "Current treatments for cutaneous leishmaniasis are limited by their toxicity, high cost, and discomfort and the emergence of drug resistance. New approaches, including combination therapies, are urgently needed. We performed a double-blind, randomized trial of therapy with parenteral antimony plus topical imiquimod, an innate immune-response modulator, versus therapy with antimony alone, in subjects with cutaneous leishmaniasis for whom an initial course of antimony therapy had failed.\n Forty subjects with clinical resistance to antimony were recruited in Lima, Peru, between February 2001 and December 2002. All subjects received meglumine antimoniate (20 mg/kg/day im or iv) and were randomized to receive either topical imiquimod 5% cream (Aldara; 3M Pharmaceuticals) or vehicle control every other day for 20 days. Lesions and adverse events were evaluated during treatment and at 1, 2, 3, 6, and 12 months after the treatment period.\n The mean number of lesions was 1.2 per person; 71% of the lesions were facial and 76% were ulcerative. There were no major differences between the groups, and all but 2 subjects completed therapy. Mild adverse events were reported by 73% of the subjects, but only erythema occurred more commonly in the imiquimod group (P < or = .02). Lesions resolved more rapidly in the imiquimod group: 50% of the imiquimod group achieved cure at 1 month after the treatment period versus 15% of the vehicle cream group (P < or = .02); 61% of the imiquimod group at 2 months versus 25% of the vehicle cream group (P < or = .03); and 72% of the imiquimod group at 3 months versus 35% of the vehicle cream group (P < or = .02). Residual scarring in the imiquimod group was less prominent than in the vehicle cream group.\n Combined antimony plus imiquimod treatment was well tolerated, accelerated healing of lesions, and improved scar quality. This therapy may have particular advantages for subjects with facial lesions.", "Hundreds of thousands of cases of cutaneous leishmaniasis occur each year worldwide. Available therapies are parenteral, moderately toxic, and costly.\n To determine the efficacy of and tolerance for oral allopurinol as monotherapy for cutaneous leishmaniasis.\n Randomized, controlled trial.\n Outpatient clinics in 11 regions of Colombia in which cutaneous leishmaniasis is endemic.\n 187 otherwise healthy adults with cutaneous leishmaniasis. Eighty-four percent of patients were infected with or were from regions with Leishmania panamensis; 16% were infected or were from regions with L. braziliensis.\n Patients were randomly assigned to one of three treatment groups. The first group received allopurinol, three 100-mg tablets four times daily (20 mg/kg of body weight per day) for 28 days. The second group received three placebo tablets four times daily for 28 days. The third group received Glucantime, 20 mg of intramuscular antimony/kg per day for 20 days.\n Complete cure was defined as complete clinical reepithelialization of all lesions at 3 months and no relapse during 12 months of follow-up.\n Of 182 patients whose data could be analyzed, 157 (86%) were evaluated. In the allopurinol group, 18 of 55 (33% [95% CI, 21% to 47%]) patients were cured; in the placebo group, 17 of 46 patients (37% [CI, 23% to 52%]) were cured (difference, 4% [CI, -14% to 22%]; P = 0.68); and in the Glucantime group, 52 of 56 patients (93% [CI, 83% to 98%]) were cured (P < 0.001 compared with the allopurinol and placebo groups combined). In most cases, therapy was considered to have failed because the lesion did not reepithelialize by 1.5 months after the end of therapy. Three cases of relapse (two in the allopurinol group and one in the placebo group) at the nasal mucosa (mucosal leishmaniasis) had occurred by the end of 12 months of follow-up.\n Allopurinol monotherapy has no effect on Colombian cutaneous disease primarily caused by L. panamensis and therefore is unlikely to be effective against cutaneous leishmaniasis in other endemic regions.", "nan", "Twenty-three patients from Rio de Janeiro, Brazil-an area of Leishmania (Viannia) braziliensis transmission-were randomly assigned to receive either a high dose (20 mg/kg/day) of antimony or a lower one (5 mg/kg/day) in a 30 days series. The two treatment regimens showed similar responses. In 10 out of 12 patients receiving a dose of 5 mg/kg/day and 9 out of 11 patients with a dosage of 20 mg/kg/day a complete epithelization was noted by the end of treatment. In addition patients were followed for up to 7 years. No reactivation or development of mucosal lesions were observed in both groups during the extensive follow-up. We think that a low dosage of antimony could be equally effective than a higher one, at least in the presence of the clinical picture usually seen in Rio de Janeiro.", "Controlled heat delivered as radio waves has been used successfully in the treatment of cutaneous leishmaniasis (CL). Here we investigated whether local heat therapy has systemic effects, as measured by the modulation of cytokine production following heat therapy of CL lesions compared with antimonial (Glucantime) treatment. Patients with CL were randomly assigned into this study. Heat (50 degrees C for 30s) was applied once. The control group received Glucantime therapy for 20 d. Cytokine production by peripheral blood mononuclear cells was assayed on days 0, 14 and 28 after onset of treatment. At the end of 28 d, 75% of lesions were healing or healed in the heat therapy group and 90% in the control group (P=0.1261). There was a decrease in IFN-gamma, IL-5 and TNF-alpha levels comparing day 0 with day 28 in both groups, but no difference between the two therapy groups. In patients with only one of several lesions treated with heat therapy, the untreated lesions also healed. Local heat therapy in CL lesions leads to systemic cytokine responses similar to that induced by systemic Glucantime therapy.", "Leishmaniasis is endemic in 88 countries in the world, and 350 million individuals are at risk of acquiring the disease. Treatment for American cutaneous leishmaniasis (ACL) is long, expensive, and associated with important side-effects.\n In this double-blind, placebo-controlled study, we treated 102 patients with ACL using either a combination of a single-strain Leishmania amazonensis killed promastigote vaccine plus a half dose of meglumine antimoniate, or placebo plus the same half dose regimen of meglumine antimoniate, in 10-day series followed by 10-day intervals.\n Of the 47 patients in the experimental arm, 47 (100%) were cured after four series of treatment, compared to four of 49 (8.2%) in the control group (P < 0.0001). Six patients were lost to follow-up.\n The combination of a single-strain Leishmania (Leishmania) amazonensis killed promastigote vaccine with a half dose regimen of antimonial is highly effective for the treatment of ACL.", "The randomized, controlled study compared the therapeutic efficacy and safety of two paromomycin-containing topical preparations with the gold treatment standard, meglumine antimoniate, and with each other in 120 Ecuadorian patients with ulcerated lesions. The two paromomycin treatment comparisons were double-blinded. Group 1 (n = 14) received 15% paromomycin plus 12% methylbenzonium chloride (PR-MBCL) dissolved in a soft white paraffin base, applied twice daily for 30 days. Group 2 (n = 40) was also treated for 30 days with 15% paromomycin plus 10% urea (PR-U) dissolved in the same paraffin base. Group 3 (n = 40) received 20mg/kg/day of IM meglumine antimoniate (MA) for 10 days as per Ecuadorian Ministry of Public Health recommendations at the time of the study. The 10-day treatment was completed by 90% of the MA group compared to 72.5% of the PR-MBCL (X2 = 4.0, P = 0.045) and 75% of the PM-U (X2 = 3.1, P > 0.05) groups whose treatment regime lasted 20 days longer than the MA treatment. Post-treatment lesion burning, redness, inflammation, and soreness were more common in the two paromomycin groups compared to MA group (P < 0.05). The frequency of treatment-related side effects in the two paromomycin groups was similar. Six weeks after the start of treatment, 80.6% of MA subjects were clinically cured compared to 48.3% in the PR-MBCL (X2 = 6.1, P = 0.014) and 40% in the PM-U groups (X2 = 12.6, P = 0.002). By 12 weeks, the proportion of clinically cured subjects in the MA (91.7%) compared to PM-MBCL (79.3%) or PM-U (70%) groups was not significantly different (P > 0.05). MA-treated subjects clinically cured by 12 weeks had a faster mean healing time (29.5 +/- 12.2 days) compared to those in the PM-MBCL (versus 43.1 +/- 14.4 days, t = -3.7, P = 0.001) or PR-U groups (43.5 +/- 17 days; t = -3.2, P = 0.002). During the 48-week post-treatment follow-up period, infection reactivation was observed in 15.2% of the MA subjects compared to 17.4% in the PM-MBCL and 10.5% PM-U of subjects diagnosed as clinically healed by 12 weeks (P > 0.05). The results suggest that although the time required for the clinical healing of ulcerated lesions takes longer, topical paromomycin may be an acceptable therapeutic alternative in endemic areas where meglumine antimoniate is not available, is too costly or medically contraindicated.", "The efficacy and toxicity of two regimens of antimony, 28 and 40 days of 20 mg of antimony/kg/day, were compared in the treatment of culture-positive mucosal leishmaniasis involving more than one anatomic site. Forty consecutive eligible Peruvians with infiltrative or ulcerative mucosal disease of the lips, nose, palate-uvula-pharynx, or larynx-epiglottis were randomized to receive either 28 days (P28) or 40 days (P40) of sodium stibogluconate (Pentostam). Treatment was prematurely terminated due to thrombocytopenia in three patients and two patients did not complete six months of follow-up. At one month post-treatment, 13% (2 of 16) of the P28 patients and 16% (3 of 19) of the P40 patients no longer had infiltrates or ulcers and were initially considered cured. During a further 11 months of follow-up, infiltrated lesions healed in eight more P28 patients and in 10 more P40 patients. The cure rate after 12 months of follow-up was therefore 63% for both groups (10 of 16 in the P28 group and 12 of 19 in the P40 group). The total of 13 patients who had infiltrates or ulcers at the 9-12-month follow-up were considered failures. All seven patients (three in the P28 group and four in the P40 group) whose lesions were culture-positive for Leishmania at some point in the 12 months after treatment, and who were thereby parasitologic failures, were also clinical failures.(ABSTRACT TRUNCATED AT 250 WORDS)", "A double-blind, randomized trial was undertaken in Guatemala to determine the therapeutic efficacy of an ointment for the treatment of cutaneous leishmaniasis that contained 15% paromomycin and 12% methylbenzethonium chloride and that was applied twice a day for 20 days. The treatment group included 35 patients, and the placebo group included 33 patients. The initial clinical response rate (13 weeks after completing the treatment) was 91.4% in the treatment group and 39.4% in the placebo group. The final clinical response rate at the 12-month follow-up examination was 85.7% (31 of 35) in the treatment group and 39.4% (13 of 33) in the placebo group (P < or = 0.001). In general, the treatment was well tolerated and was never interrupted because of adverse effects. The number of adverse effects reported in the placebo group was lower than in the treatment group (16 events versus 30 events). All adverse effects reported by patients disappeared within 1 week of completing the treatment. Our findings show that the combination of paromomycin with methylbenzethonium chloride for 20 days is a good alternative for antimonial treatments of cutaneous leishmaniasis in Guatemala.", "Pentavalent antimony has been considered to be the standard treatment for leishmaniasis, but more recently, the orally administrable agent allopurinol ribonucleoside has been the subject of several clinical trials. In this study, these two agents were evaluated in patients with Ecuadorian cutaneous leishmaniasis. Patients were randomly assigned to the two treatment groups. The mean reduction in lesion size for the 28 patients treated with Pentostam (20 mg Sb/kg/day intramuscularly for 20 days) was 61%, 23%, and 11% after one, two, and three weeks, respectively. There was a wide range in the individual values, and some lesions markedly enlarged in the first week of therapy. An initially healed lesion was defined as one that had greater than 80% re-epithelialized by the 1.5-month post-treatment followup. All Pentostam patients demonstrated this degree of lesion resolution (100% initial healing rate), but one patient showed evidence of relapse at the three month followup resulting in a 96% complete healing rate for the 12 month observation period. Patients in the untreated control group demonstrated a strikingly high rate of healing with 9 of 12 patients having re-epithelialized all lesions after 1.5 months observation (75% initial healing rate). The mean reduction in lesion size for the untreated patients was 56%, 29%, and 25% after one, two, and three weeks, respectively. Twenty-one patients received allopurinol ribonucleoside (1,500 mg QID) plus probenecid (500 mg QID) for 28 days. Lesions in nine of these patients were healed at the time of the 1.5 month followup (41% healing rate).(ABSTRACT TRUNCATED AT 250 WORDS)", "A double-'blind', placebo-controlled trial of topical therapy with 15% paromomycin (aminosidine) and 10% urea in white paraffin was carried out on 53 patients with non-ulcerating cutaneous leishmaniasis in Honduras. Although the treatment was not effective, several unexpected findings emerged from the trial. Leishmania mexicana was found to be the cause of many of the skin lesions in one of the 2 study sites. These lesions were clinically indistinguishable from those caused by L. chagasi, the aetiologic agent previously found for this form of leishmaniasis. This is the first documented report of L. mexicana in Honduras.", "Ninety military patients with cutaneous leishmaniasis in Colombia were randomly allocated to 3 treatment regimens of parenteral aminosidine sulphate: (i) 12 mg aminosidine base/kg/d for 7 d, (ii) 12 mg/kg/d for 14 d, and (iii) 18 mg/kg/d for 14 d. With the 89 evaluable patients, the cure rates 12 months after the end of treatment were 10%, 45%, and 50%, respectively. Fifty-eight of the 66 patients who were not cured had lesions that enlarged or were unchanged by 1.5 months after treatment follow up. The other 8 patients had lesions that relapsed between 3 and 12 months after therapy. Even in group (iii) the cure rate was inferior to that (> 90%) with antimony or pentamidine previously reported in this patient population. This study indicates that parenteral aminosidine alone is less likely to be successful in the treatment of cutaneous lesihmaniasis than visceral leishmaniasis, for which a 74% cure rate has been reported. Further trials might consider the combination of aminosidine with other antileishmanial drugs.", "Mucosal leishmaniasis is associated with intense tissue damage and high tumor necrosis factor-alpha production. Therapeutic failure occurs in up to 42% of cases; patients who experience treatment failure will require >1 pentavalent antimony (Sb(v)) course or alternative drugs to achieve a cure. We previously showed that an inhibitor of tumor necrosis factor-alpha (pentoxifylline) combined with Sb(v) cured 90% patients refractory to monotherapy with Sb(v).\n A double-blind, placebo-controlled trial involving 23 patients with mucosal leishmaniasis evaluated the efficacy of pentoxifylline when administered in association with Sb(v), compared with Sb(v) treatment alone. Eleven patients were randomized to receive Sb(v) plus oral pentoxifylline for 30 days, and 12 patients received Sb(v) plus oral placebo. The criterion for cure was a complete healing of lesions.\n All patients in the pentoxifylline group experienced a cure with 1 course of Sb(v), whereas 5 (41.6%) of 12 patients in the placebo group required a second course of Sb(v) (P=.037). The healing time +/- standard deviation in the pentoxifylline group was 83+/-36 days, compared with 145+/-99 days in the placebo group (P=.049). No relapses were documented in either group at the 2-year follow-up visit.\n The addition of pentoxifylline to Sb(v) in mucosal leishmaniasis reduces the healing time significantly and prevents the need for further courses of Sb(v).", "Cutaneous leishmaniasis (CL) requires 2-6 months to heal. In an effort to reduce this healing time, we studied topically applied granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjunct to antimonial therapy. Ten patients received antimony plus topical GM-CSF, and 10 patients received antimony plus placebo (saline). GM-CSF was diluted for topical use and was applied 3 times weekly for 3 weeks (1-2 microg/cm2/lesion). The mean +/- SD healing time was 43 +/- 14 days in the GM-CSF group and was 104+/-79 days in the placebo group (P=.043). Ten (100%) of 10 patients in the GM-CSF group healed within 60 days, compared with 5 (50%) of 10 patients in the placebo group. Two of the patients in the placebo group required retreatment with antimony. In conclusion, topically applied GM-CSF is effective in the management of CL.", "We determined the efficacy of the combination of the topical formulation 15% paromomycin sulfate/12% methylbenzethonium chloride (MBCL) and a short course (7 days) of parenteral meglumine antimonate (pentavalent antimony [Sb]) as treatment of American cutaneous leishmaniasis in Colombian patients. Patients were randomly assigned in unequal allocation (2:1:1:1) to group 1 (topical paromomycin/MBCL plus injectable Sb for 7 days), group 2 (topical placebo plus injectable Sb for 7 days), group 3 (topical paromomycin/MBCL plus injectable Sb for 3 days), and group 4 (injectable Sb for 20 days). Cure was defined as complete reepithelialization of all lesions without relapse. Cure rates among groups were as follows: 58% (34 of 59), group 1; 53% (16 of 30), group 2; 20% (6 of 30), group 3; and 84% (26 of 31), group 4. Seventy-one percent of the organisms identified to the species level were Leishmania braziliensis panamensis. We conclude that 10 days of therapy with paromomycin/MBCL does not augment the response of cutaneous leishmaniasis (predominately due to L. braziliensis panamensis) to a short course of treatment with meglumine antimonate.", "Few therapeutic options are available for mucocutaneous leishmaniasis (MCL). We conducted a randomized open trial to evaluate the efficacy, safety, and tolerance of parenteral aminosidine sulphate (AS) 14 mg/kg/d for 21 days compared with intravenous meglumine antimonate (MA) 20 mg/kg/d for 28 days in patients with moderate MCL in Cuzco, Peru. Cure was defined as complete healing with re-epithelialization within 1 year of follow-up. The trial was stopped after 38 patients were enrolled (17 in the MA group and 21 in the AS group) because of marked differences in response. Study groups were comparable in baseline characteristics. Cure rates were 0/21 in the AS group compared with 8/17 (47%, 95% confidence interval: 23-71%) in the MA group (P < 0.001). Side effects and laboratory abnormalities were mild in both groups. We conclude that parenteral AS given on its own is not effective for MCL in Peru." ]

[ "8181328", "9404747", "10786204", "8610712", "8610720", "9782217", "8610715", "8610716", "8681667" ]

[ "In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more effective than either agent alone. An 85-day multicenter trial. COMBIVENT Inhalation Aerosol Study Group.", "Routine nebulized ipratropium and albuterol together are better than either alone in COPD. The COMBIVENT Inhalation Solution Study Group.", "Individual results of treatment of COPD with low doses of fenoterol compared with treatment with ipratropium bromide.", "Nebulized bronchodilators for outpatient management of stable chronic obstructive pulmonary disease.", "Results of a multicenter study of nebulized inhalant bronchodilator solutions.", "Inhalation by nebulization of albuterol-ipratropium combination (Dey combination) is superior to either agent alone in the treatment of chronic obstructive pulmonary disease. Dey Combination Solution Study Group.", "A multicenter study of nebulized bronchodilator solutions in chronic obstructive pulmonary disease.", "Addition of anticholinergic solution prolongs bronchodilator effect of beta 2 agonists in patients with chronic obstructive pulmonary disease.", "Extended therapy with ipratropium is associated with improved lung function in patients with COPD. A retrospective analysis of data from seven clinical trials." ]

[ "Combination bronchodilator therapy for chronic obstructive pulmonary disease (COPD) is available widely throughout the world except in North America. Previous studies have yielded conflicting results regarding the advantages of combining anticholinergic therapy with sympathomimetic therapy in COPD. We report the results of a 12-week prospective, double-blind, parallel-group evaluation of the use of the following: albuterol, a beta-adrenergic agent; ipratropium, an anticholinergic agent; or a combination of the two, administered by metered-dose inhaler to patients with moderately severe stable COPD. Following baseline studies, 534 patients were given one of the three test bronchodilator preparations to be used at home four times daily in addition to oral theophylline and corticosteroids as required. The doses of the latter two drugs were kept stable. Subjects were tested on days 1, 29, 57, and 85. Analysis of 1-s forced expiratory volume (FEV1) curves on those test days indicated that the combination was superior to either single agent alone in peak effect, in the effect during the first 4 h after dosing, and in the total area under the curve of the FEV1 response. The mean peak percent increases in FEV1 over baseline on the four test days were 31 to 33 percent for the combination, 24 to 25 percent for ipratropium, and 24 to 27 percent for albuterol. The differences between the combination and its components were statistically significant on all test days. The AUC0-4 means for the combination were 21 to 44 percent greater than the ipratropium means and 30 to 46 percent greater than the albuterol means. Similar changes were noted in the forced vital capacity curves. Symptom scores did not change over time and did not differ among the treatment groups. We conclude that the combination of ipratropium and albuterol, when given by metered-dose inhaler to patients with COPD, is more effective than either of the two agents alone. The advantage of the combination is apparent primarily during the first 4 h after administration. The availability of combination therapy by metered-dose inhaler should help to improve patient compliance.", "We compared the long-term safety and efficacy of the combination ipratropium bromide (IB) and albuterol sulfate (ALB) inhalation solution with that of each separate component using three-times-daily administration.\n Using a parallel design, we randomized patients to receive 3.0 mg ALB, 0.5 mg IB, or the combination by small-volume nebulizer (SVN) for 85 days. Subjects were allowed to use up to two extra doses of study medication daily for control of symptoms on an as-needed basis. The main efficacy evaluation was the acute pulmonary function response to an aerosol of the maintenance study medication over the course of the investigation. Physician global evaluation, subject quality of life assessments, COPD symptom scores, and twice-daily peak expiratory flow rate (PEFR) were also assessed over the study period.\n Twenty-five centers participated in the investigation.\n We studied 652 patients with moderate to severe COPD.\n Over the course of the study, the acute spirometric response and evening PEFR values with the SVN combination of IB plus ALB were statistically significantly better compared to ALB or IB alone. The quality of life scores, physician global evaluations, symptom scores, and morning PEFR scores were unchanged over the duration of the study in all treatment groups. There was no significant difference in adverse events in the three treatment groups.\n In patients with COPD, maintenance SVN therapy with IB and ALB provides better bronchodilation than either therapy alone without increasing side effects.", "We compared the effects of 30-day treatments with fenoterol in low doses (4 x 100 mcg) and ipratropium bromide (4 x 40 mcg) on the lung function parameters (LFP), dyspnea and physical capacity of patients with severe chronic obstructive pulmonary disease (COPD) (FEV1 < 35% pred.) and analysed the individual response of patients to the administered therapy. The study included two groups of patients treated with fenoterol (n = 22) and ipratropium bromide (n = 22). The patients were matched by functional characteristics (age: 60 +/- 7 and 57 +/- 9 years; ATS Dyspnea Scale: 2.7 +/- 0.8 and 2.4 +/- 0.9; FEV1%: 25 +/- 7% and 23 +/- 6%; pO2: 62.4 +/- 5.3 mm Hg and 61.0 +/- 9.5 mm Hg; all values mean +/- SD). After 30 days of treatment we measured the lung function parameters (FEV1, FVC), dyspnea indices (ATS dyspnea scale, Borg scale) and the physical capacity of the patients (6-minute walking distance test). The results showed that in an open experiment fenoterol (4 x 100 mcg daily), unlike ipratropium bromide (4 x 40 mcg daily), cannot improve statistically and clinically significantly the lung function parameters, dyspnea and the physical capacity of the group as a whole. However, when the findings were assessed for each patient individually, 32% of the patients proved to have responded positively to the treatment. Therefore efficaciousness of fenoterol in low doses should be determined by assessing the lung function parameters, dyspnea and the physical capacity individually for each patient.", "The bronchodilator efficacy, safety, and persistence of effect of the anticholinergic agent ipratropium bromide and the beta-adrenergic agonist albuterol, both given by nebulization, were compared in 223 patients with stable, severe chronic obstructive pulmonary disease (COPD). The study was a randomized, double-blind, parallel group trial conducted over 85 days. Patients took the study drugs (either 500 micrograms of ipratropium bromide or 2.5 mg of albuterol) three times daily on an outpatient basis throughout the study. The acute bronchodilator responses to nebulized ipratropium bromide and albuterol were studied on days 1, 43, and 85. The forced expiratory volume in 1 second (FEV1) response was similar for both drugs on day 1 (33% peak increase after ipratropium bromide and 36% peak increase after albuterol). However, albuterol's effect on FEV1 decreased over time. Clinical improvement was noted in both study groups, but the ipratropium bromide group had a greater symptomatic benefit. Patients receiving ipratropium bromide scored higher on a quality-of-life questionnaire evaluating dyspnea, fatigue, emotional function, and mastery. Side effects were relatively infrequent and generally mild for both study drugs. These results show that ipratropium bromide, given by nebulization, is safe and effective in the outpatient treatment of COPD.", "The efficacy, persistence of bronchodilator action, and safety of the quaternary ammonium anticholinergic agent, ipratropium bromide (500 microgram), and placebo were compared when each was added in solution form to the beta-adrenergic agonist solution, metaproterenol sulfate (15 mg), and administered three times daily for 12 weeks to a total of 213 patients with chronic obstructive pulmonary disease (COPD). Subjects had a mean forced expiratory volume in 1 second (FEV1) of approximately 1 liter (37% of predicted) and were permitted to use nonanticholinergic therapy for COPD throughout the trial. The study was a randomized, double-blind, 85-day, parallel-group, eight-center study. On a 3 test days, 1, 43, and 85, mean peak responses for FEV1 and forced vital capacity and mean area under the curve were significantly higher for the iprathropium bromide-metaproterenol combination than for metaproterenol only. Duration of action was also significantly longer for the combination therapy than for the beta-agonist alone on test days 1 and 43. Neither treatment regimen produced an demonstrable effect on daily morning peak expiratory flow rates, reported respiratory symptoms, or quality of life. Both treatment regimens were similarly well tolerated with a comparable frequency of adverse events. These results suggest that the combination of iprathropium bromide and metaproterenol inhalation solutions offers a potential therapeutic advantage to patients with symptomatic COPD over nebulized metaproterenol alone without the risk of increased side effects.", "Combination bronchodilator therapy for chronic obstructive pulmonary disease (COPD) potentially can provide increased benefit over single-agent therapy. The objective of this double-blind, randomized, positive-control trial was to determine the effectiveness of an albuterol-ipratropium solution aerosol combination (Dey combination solution, Dey LP, Napa, Calif., USA) compared with solution aerosols of both component medications administered alone in patients with COPD. The trial consisted of a 6-week, 3-period crossover phase followed by a 6-week parallel phase during which patients self-administered study medications by inhalation from a nebulizer. A total of 863 patients were initially randomized to each of the six possible treatment sequences of the three study medications in the crossover phase and received each study medication in turn for a 2-week period. Patients continued to receive the same treatment administered during the last 2-week period of the crossover phase for an additional 6 weeks in the parallel phase. Assessment of 1-second forced expiratory volume (FEV1) curves before and after dosing on the last day of each 2-week period indicated that the combination was superior to either single agent in peak effect and area under the curve up to 8 h after dosing (FEV1-AUC0-8), in both phases of the trial. The use of Dey combination during the crossover phase resulted in 24% more improvement in peak FEV1 than was seen with albuterol alone (p < 0.001), and 37% more than was seen with ipratropium alone (p < 0.001). Similarly, when examining FEV1-AUC0-8, Dey combination resulted in 30% more improvement than was seen with albuterol alone (p < 0.001), and 32% more than was seen with ipratropium alone (p < 0.001). The combination affords a convenient dosing regimen and incorporates enhanced benefit without compromising the safety profile of either component agent.", "A multicenter, 85-day, double-blind, randomized study was conducted to compare the effects of a single-dose and chronic inhalation of ipratropium bromide solution (500 micrograms) to the beta-adrenergic agonist metaproterenol (5% solution, 15 mg) in patients with chronic obstructive pulmonary disease (COPD). Patients were required to have a relatively stable, moderately severe COPD, forced expiratory volume in 1 second (FEV1) < 65% of predicted normal, FEV1 <70% of forced vital capacity (FVC), and a smoking history of > 10 pack-years. Following a 2-week baseline period, patients were randomized into either the ipratropium bromide (106 patients) or metaproterenol (107 patients) study groups. Pulmonary function testing was performed on days 1, 43, and 85. Secondary efficacy variables examined included peak expiratory flow rates, physician's global evaluation, quality of life, COPD symptom score, and use of concomitant medications. FEV1 was comparable between the two groups on day 1 (1.00 and 1.02 liters, ipratropium bromide vs metaproterenol, respectively; p = nonsignificant). The baseline FEV1 increased significantly in the ipratropium bromide group between day 1 and 43 by 10% (from 1.00 to 1.10 liters, p < 0.002) and remained 7% elevated on day 85 (1.07 liters) compared to day 1 (p < 0.02); it did not change in the metaproterenol group across all three test days. A clinically significant (> 15%) mean FEV1 response was observed on each of the 3 test days following drug inhalation in both treatment groups. The median duration of action was similar between groups (5 hours) on test day 1, but on day 85 the median duration for ipratropium bromide was r.5 hours compared to 3.0 hours for metaproterenol (p < 0.04). The secondary efficacy variables were uniformly better in the ipratropium bromide than the metaproterenol group. Side effects were infrequent and generally mild in both groups. These data suggest that the availability of a high-dose ipratropium bromide solution offers a safe and effective means of producing prolonged bronchodilation in patients with COPD.", "A randomized, double-blind placebo-controlled clinical trial was designed to assess the safety, efficacy, and duration of the bronchodilation resulting from the addition of 500 micrograms of ipratropium bromide (Atrovent; Boehringer Ingelheim, CT) inhalation solution to standard small volume nebulizer treatments with 2.5 mg albuterol inhalation solution. A total of 195 patients (63% men, average age 64 years) with > 10 pack-year smoking histories and stable, moderate-to- severe chronic obstructive pulmonary disease (COPD; forced expiratory volume in 1 second [FEV1] 1.02 liter, 38.8% predicted) from eight university-affiliated chest clinics in seven U.S. cities were enrolled into the study. Asthma, rhinitis, and eosinophilia were exclusions, as was daily use of > 10 mg of prednisone (or 20 mg on alternate days). There was a 2-week stabilization period during which the patients were instructed in the use of the small volume nebulizers, which they used three times daily with albuterol alone. They were asked to keep daily logs of peak flow rates, pulmonary symptoms, and additional medication usage. On their test day 1 the subjects came to the pulmonary function laboratory having been off theophylline for 24 hours and beta 2-agonists for 12 hours and performed a baseline spirometry. They then received their morning small volume nebulizer treatment of albuterol to which was added either 500 micrograms if ipratropium bromide or a saline placebo. Spirometry was repeated at 15, 30, and 60 minutes, and then hourly for 8 hours. Subjects then took home a 2-week supply of albuterol and test drug for thrice daily use in their small volume nebulizer. They were evaluated for pulmonary symptoms and adverse effects every 14 days. The 8-hour spirometry was repeated on test day 43 and finally on test day 85. Primary data evaluated were the peak increase in FEV1 and the area between the FEV1 baseline value and the 8-hour FEV1 curve. Similar calculations were made for forced vital capacity (FVC) and 25-75% forced expiratory flow (FEF25-75%). On test day 1 the peak increase in FEV1 for the ipratropium bromide + albuterol subjects was 26% greater than those on placebo + albuterol (p < 0.003). The area under the 8-hour FEV1 curve was 64% greater in those given ipratropium bromide on test day 1 (p < 0.0002). Similar increases were seen in FVC and FEF25-75%. The peak improvements in FEV1 and FVC with the addition of ipratropium bromide to albuterol were maintained on test days 43 and 85. Considering the safety and efficacy profiles of this combination, the data would suggest that ipratropium bromide inhalation solution should be considered first-line therapy for those patients with COPD requiring small volume nebulizer treatments.", "Bronchodilators are routinely used in the long-term therapy of patients with COPD. These drugs are generally evaluated for their short-term bronchodilatory effects. Long-term and short-term benefits, however, are not necessarily equivalent. We evaluated, therefore, the effects of extended therapy with inhaled bronchodilators in patients with COPD.\n Data were obtained from seven clinical trials in which ipratropium was compared with a beta-agonist over a 90-day treatment interval. This comprised all the available data from clinical trials performed for registration of ipratropium and included 1,445 evaluable patients. Results of pulmonary function tests were evaluated prior to and after short-term administration of bronchodilator both before and after the 90-day treatment period. In addition, data were analyzed after stratification for smoking status and for lung function.\n Long-term therapy with ipratropium resulted in improvement in baseline (ie, before short-term administration of bronchodilator) FEV1 (28 mL; p < 0.01) and FVC (131 mL; p < 0.01), while long-term therapy with beta-agonist resulted in no significant change in FEV1 (1-mL decline; p > 0.2) or in FVC (20-mL improvement; p > 0.2). The improvement in baseline function in the ipratropium-treated patients was most marked in ex-smokers (average duration of abstinence, 9 years). Short-term administration of ipratropium following the 90-day treatment interval resulted in similar response in average FEV1 (6 mL more improvement after the extended therapy; p > 0.2) and an increased response in average FVC (44 mL more improvement after extended therapy; p < 0.01). In contrast, extended therapy with beta-agonist resulted in significantly less response to the short-term administration of beta-agonist for both FEV1 (49 mL less response; p < 0.0001) and FVC (74 mL less response; p < 0.0001). Assessed as the percentage of patients who achieved a 15% improvement in lung function, most patients responded to both treatments both before and after extended therapy. There was, however, a significant decline in the number of patients who responded after extended therapy, and this was more marked for the beta-agonist treated group.\n Long-term benefits of bronchodilator therapy appear to differ from short-term effects. Extended administration of ipratropium appears to be associated with improved baseline lung function and perhaps with improvement in the response to acute bronchodilation. Extended administration of beta-agonist, in contrast, appears to have little effect on baseline lung function, but may decrease response to acute bronchodilation." ]

[ "2728887", "14630841", "12475511", "11954842", "2323137", "12027488", "10990311", "10191737", "8636175", "16766978" ]

[ "Bone cement for redislocated Colles' fracture. A prospective comparison with closed treatment.", "Norian SRS cement compared with conventional fixation in distal radial fractures. A randomized study.", "Norian SRS versus functional treatment in redisplaced distal radial fractures: a randomized study in 20 patients.", "Primary bone grafting does not improve the results in severely displaced distal radius fractures.", "External skeletal fixation versus cement fixation in the treatment of redislocated Colles' fracture.", "Controlled trial of distal radial fractures treated with a resorbable bone mineral substitute.", "Treatment of fractures of the distal radius with a remodellable bone cement: a prospective, randomised study using Norian SRS.", "Norian SRS versus external fixation in redisplaced distal radial fractures. A randomized study in 40 patients.", "Redisplaced unstable fractures of the distal radius: a prospective randomised comparison of four methods of treatment.", "Cancellous allograft versus autologous bone grafting for repair of comminuted distal radius fractures: a prospective, randomized trial." ]

[ "Colles' fractures (not comminuted or intraarticular) that redislocated after two closed reductions were randomized into two groups. In one group the dorsal bone deficiency was filled with bone cement (methylmethacrylate) at operation; in the other, the fractures were rereduced and immobilized in a plaster cast. All the patients were followed for 2 years and examined with respect to anatomy of the fracture, wrist movement, strength, appearance, pain, and function. The operated on group were better with regard to all objectively measurable characteristics; all operated on fractures had healed radiographically, and the cement was surrounded by cortical bone.", "A prospective, randomized multicenter study was conducted to evaluate closed reduction and immobilization with and without Norian SRS (Skeletal Repair System) cement in the management of distal radial fractures. Norian SRS is a calcium-phosphate bone cement that is injectable, hardens in situ, and cures by a crystallization reaction to form dahllite, a carbonated apatite equivalent to bone mineral.\n A total of 323 patients with a distal radial fracture were randomized to treatment with or without Norian SRS cement. Stratification factors included fracture type (intra-articular or extra-articular), hand dominance, bone density, and the surgeon's preferred conventional treatment (cast or external fixator). The subjects receiving Norian SRS underwent a closed reduction followed by injection of the cement percutaneously or through a limited open approach. Wrist motion, beginning two weeks postoperatively, was encouraged. Control subjects, who had not received a Norian SRS injection, underwent closed reduction and application of a cast or external fixator for six to eight weeks. Supplemental Kirschner wires were used in specific instances in both groups. Patients were followed clinically and radiographically at one, two, four, and between six and eight weeks and at three, six, and twelve months. Patients rated pain and the function of the hand with use of a visual analog scale. Quality of life was assessed with use of the Short Form-36 (SF-36) health status questionnaire. Complications were recorded.\n Significant clinical differences were seen at six to eight weeks postoperatively, with better grip strength, wrist range of motion, digital motion, use of the hand, and social and emotional function, and less swelling in the patients treated with Norian SRS than in the control group (p < 0.05). By three months, these differences had normalized except for digital motion, which remained significantly better in the group treated with Norian SRS (p = 0.015). At one year, no clinical differences were detected. Radiographically, the average change in ulnar variance was greater in the patients treated with Norian SRS (+2.0 mm) than in the control group (+1.4 mm) (p < 0.02). No differences were seen in the total number of complications, including loss of reduction. The infection rate, however, was significantly higher (p < 0.001) in the control group (16.7%) than in the group treated with Norian SRS (2.5%) and the infections were always related to external fixator pins or Kirschner wires. Four patients with intra-articular extravasation of cement were identified; no sequelae were observed at twenty-four months. Cement was seen in extraosseous locations in 112 (70%) of the SRS-treated patients; loss of reduction was highest in this subgroup (37%). The extraosseous material had disappeared in eighty-three of the 112 patients by twelve months.\n Our results indicate that fixation of a distal radial fracture with Norian SRS cement may allow for accelerated rehabilitation. A limited open approach and supplemental fixation with Kirschner wires are recommended. Additional or alternate fixation is necessary for complex articular fractures.", "We compared the use of Norian SRS, an injectable calcium phosphate bone cement, with functional treatment of redisplaced distal radial fractures in a prospective randomized study of 20 patients. The redisplaced fractures were either rereduced and stabilized by Norian SRS, or the displaced position was accepted and was not rereduced. All wrists were immobilized in a short-arm dorsal splint for 1 week, followed by a removable splint for another 3 weeks. The chosen primary effect variable was grip strength at 7 weeks, and this did not differ between the two treatment groups. The clinical results at 6 months in both groups were similar. We conclude that aggressive treatment of redisplaced fractures of the distal radius may be unnecessary in most women aged 50 years or more.", "We prospectively randomised 45 patients ages 20-70 years with distal radius fractures of Older type III and IV to one of two treatment groups. One group was treated with closed reduction, primary bone grafting, and external fixation for 3 weeks, followed by a plaster cast that allowed volar flexion, for an additional 3 weeks. The other group was treated with closed reduction and external fixation for 6 weeks. The functional and radiographic results were evaluated. There was no difference between the two groups in either clinical or radiographic outcome. We do not recommend external fixation and primary bone grafting as a routine method in these fractures.", "In a prospective investigation in 1984 and 1985, all Colles' fractures (not comminuted or intraarticular) that redisplaced after two closed reductions were allocated at random to one of two groups: Group I (n = 23), in which the dorsal bone deficiency was filled with bone cement (methylmethacrylate), and Group II (n = 25), in which the fracture was treated with external fixation. All were followed for one year and examined with respect to anatomy of the fracture, wrist movement, strength, appearance, pain, function, and complications. Roentgenograms, 12 months after treatment, showed that all fractures had healed and that the cement was enveloped in cortical bone. The final results were equal in the two groups, but Group I improved earlier and had no complications.", "This randomized trial compared the use of hydroxyapatite cement with Kapandji wiring in distal radial fractures. Two groups of nine patients with distal radial fractures were either treated by reduction and fixation with wires or insertion of the cement into the fracture void. There was no difference between the groups before operation, on reduction or at day 1. Dorsal angle in the hydroxyapatite group was significantly worse at 6, 12 and 26 weeks. Grip strength and palmar flexion were poor in the hydroxyapatite cement group. All the clinical parameters and X-ray variables were worse at 12 and 26 weeks in the hydroxyapatite cement group. We conclude from this trial that there is nothing to support the use of this hydroxyapatite cement, without the use of additional fixation, in distal radial fractures.\n Copyright 2001 The British Society for Surgery of the Hand.", "We performed a prospective, randomised study on 110 patients more than 50 years old with fractures of the distal radius to compare the outcome of conservative treatment with that using remodellable bone cement (Norian skeletal repair system, SRS) and immobilisation in a cast for two weeks. Patients treated with SRS had less pain and earlier restoration of movement and grip strength. The results at one year were satisfactory in 81.54% of the SRS patients and 55.55% of the control group. The rates of malunion were 18.2% and 41.8%, respectively. There was a significant relationship between the functional and radiological results. Soft-tissue extrusion was present initially in 69.1% of the SRS patients; most deposits disappeared progressively, but persisted in 32.73% at one year. We conclude that the injection of a remodellable bone cement into the trabecular defect of fractures of the distal radius provides a better clinical and radiological result than conventional treatment.", "We compared Norian SRS, an injectable calcium phosphate bone cement, with external fixation in the treatment of redisplaced distal radial fractures by a prospective randomized study in 40 patients (women 50-80 years or men 60-80 years). After rereduction, the fracture was either stabilized by injection of SRS and immobilized with a cast for 2 weeks, or externally fixed with Hoffman's bar for 5 weeks. Each patient was evaluated at 2, 5, 7 weeks and at 3, 6 and 12 months. Functional parameters were grip strength, range of motion and pain. Radiographic parameters were radial angle, ulnar variance and dorsal tilt. The chosen primary effect variable was grip strength at 7 weeks. Patients treated by injection of SRS apatite had better grip strength, wrist extension and forearm supination at 7 weeks. There was no difference in functional parameters at 3 months or later. None of the methods could fully stabilize the fracture: radiographs showed a progressive redislocation over time. The results indicate that SRS can be used in the treatment of unstable distal radial fractures. The more rapid recovery of grip strength and wrist mobility in the SRS group appears to be due to the shorter immobilization time.", "We performed a prospective, randomised trial on 120 patients with redisplaced fractures of the distal radius comparing four methods of treatment. The four treatment groups, each containing 30 patients, were remanipulation and plaster, open reduction and bone grafting, and closed external fixation with and without mobilisation of the wrist at three weeks. The radiological results showed improvement in angulation of the distal radius for the open reduction and bone grafting group. Functional results at six weeks, three and six months and at one year, however, showed no difference between any of the four groups. The main influence on final outcome was carpal malalignment which had a statistically significant negative effect on function.", "Distal radius fractures with a large metaphyseal defect often need defect filling. We assessed the reliability of a new allogenic transplant as a bone-graft substitute in comparison to autologous iliac crest bone-grafting.\n This prospective, randomized study included 90 patients. Fracture-osteosynthesis was done with 2.7 mm quarter-tube plates. Tutoplast-cancellous-chips were used as allografts. Clinical and radiologic parameters were determined at three and 12 months after surgery.\n Overall outcomes were assessed according to the Demerit Point System: There were 71% good-to-excellent results in the \"Tutoplast\"; group and 75% good-to-excellent in the \"iliac crest\" group. Radiologic parameters were comparable and within normal range. Complications deriving from iliac bone harvesting were notably more frequent in the iliac crest group. Operation time was significantly shorter in the Tutoplast group.\n By the use of the investigated allograft no adverse effects were detected on the outcome of the treated radius fractures. Therefore, this new allograft could be a desirable alternative to autologous bone grafting from the iliac crest, as operating and anesthetics times are shortened and complications of iliac crest bone grafting avoided." ]

[ "15743283", "20501583", "22503739", "20482476", "22544817", "20598577", "16088114", "22330025", "11812553" ]

[ "Exercise leads to faster postural reflexes, improved balance and mobility, and fewer falls in older persons with chronic stroke.", "Effect on falls of providing single lens distance vision glasses to multifocal glasses wearers: VISIBLE randomised controlled trial.", "Effects of a multifactorial falls prevention program for people with stroke returning home after rehabilitation: a randomized controlled trial.", "Treadmill walking with body weight support in subacute non-ambulatory stroke improves walking capacity more than overground walking: a randomised trial.", "Exercise to enhance mobility and prevent falls after stroke: the community stroke club randomized trial.", "An open-label trial comparing alendronate and alphacalcidol in reducing falls and hip fractures in disabled stroke patients.", "Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial.", "Whole-body vibration has no effect on neuromotor function and falls in chronic stroke.", "Physiotherapy for patients with mobility problems more than 1 year after stroke: a randomised controlled trial." ]

[ "To determine the effect of two different community-based group exercise programs on functional balance, mobility, postural reflexes, and falls in older adults with chronic stroke.\n A randomized, clinical trial.\n Community center.\n Sixty-one community-dwelling older adults with chronic stroke.\n Participants were randomly assigned to an agility (n=30) or stretching/weight-shifting (n=31) exercise group. Both groups exercised three times a week for 10 weeks.\n Participants were assessed before, immediately after, and 1 month after the intervention for Berg Balance, Timed Up and Go, step reaction time, Activities-specific Balance Confidence, and Nottingham Health Profile. Testing of standing postural reflexes and induced falls evoked by a translating platform was also performed. In addition, falls in the community were tracked for 1 year from the start of the interventions.\n Although exercise led to improvements in all clinical outcome measures for both groups, the agility group demonstrated greater improvement in step reaction time and paretic rectus femoris postural reflex onset latency than the stretching/weight-shifting group. In addition, the agility group experienced fewer induced falls on the platform.\n Group exercise programs that include agility or stretching/weight shifting exercises improve postural reflexes, functional balance, and mobility and may lead to a reduction of falls in older adults with stroke.", "To determine whether the provision of single lens distance glasses to older wearers of multifocal glasses reduces falls.\n Parallel randomised controlled trial stratified by recruitment site and source of referral, with 13 months' follow-up and outcome assessors blinded to group allocation.\n Community recruitment and treatment room assessments in Sydney and Illawarra regions of NSW, Australia.\n 606 regular wearers of multifocal glasses (mean age 80 (SD 7) years). Inclusion criteria included increased risk of falls (fall in previous year or timed up and go test >15 seconds) and outdoor use of multifocal glasses at least three times a week.\n Provision of single lens distance glasses with recommendations for wearing them for walking and outdoor activities compared with usual care.\n Number of falls and injuries resulting from falls during follow-up.\n Single lens glasses were provided to 275 (90%) of the 305 intervention group participants within two months; 162 (54%) of the intervention group reported satisfactory use of distance glasses for walking and outdoor activities for at least 7/12 months after dispensing. In the 299 intervention and 298 control participants available to follow-up, the intervention resulted in an 8% reduction in falls (incidence rate ratio 0.92, 95% confidence interval 0.73 to 1.16). Pre-planned sub-group analyses showed that the intervention was effective in significantly reducing all falls (incidence rate ratio 0.60, 0.42 to 0.87), outside falls, and injurious falls in people who regularly took part in outside activities. A significant increase in outside falls occurred in people in the intervention group who took part in little outside activity.\n With appropriate counselling, provision of single lens glasses for older wearers of multifocal glasses who take part in regular outdoor activities is an effective falls prevention strategy. The intervention may be harmful, however, in multifocal glasses wearers with low levels of outdoor activity.\n Clinical trials NCT00350855.", "To determine whether a multifactorial falls prevention program reduces falls in people with stroke at risk of recurrent falls and whether this program leads to improvements in gait, balance, strength, and fall-related efficacy.\n A single blind, multicenter, randomized controlled trial with 12-month follow-up.\n Participants were recruited after discharge from rehabilitation and followed up in the community.\n Participants (N=156) were people with stroke at risk of recurrent falls being discharged home from rehabilitation.\n Tailored multifactorial falls prevention program and usual care (n=71) or control (usual care, n=85).\n Primary outcomes were rate of falls and proportion of fallers. Secondary outcomes included injurious falls, falls risk, participation, activity, leg strength, gait speed, balance, and falls efficacy.\n There was no significant difference in fall rate (intervention: 1.89 falls/person-year, control: 1.76 falls/person-year, incidence rate ratio=1.10, P=.74) or the proportion of fallers between the groups (risk ratio=.83, 95% confidence interval=.60-1.14). There was no significant difference in injurious fall rate (intervention: .74 injurious falls/person-year, control: .49 injurious falls/person-year, incidence rate ratio=1.57, P=.25), and there were no significant differences between groups on any other secondary outcome.\n This multifactorial falls prevention program was not effective in reducing falls in people with stroke who are at risk of falls nor was it more effective than usual care in improving gait, balance, and strength in people with stroke. Further research is required to identify effective interventions for this high-risk group.\n Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.", "Is treadmill walking with body weight support during inpatient rehabilitation detrimental to walking quality compared with assisted overground walking? Does it result in better walking capacity, perception of walking or community participation?\n Analysis of secondary outcomes of a randomised trial with concealed allocation, assessor blinding and intention-to-treat analysis.\n 126 patients unable to walk within 4 weeks of a stroke who were undergoing inpatient rehabilitation.\n The experimental group undertook up to 30 minutes of treadmill walking with body weight support via an overhead harness per day while the control group undertook up to 30 minutes of overground walking.\n The secondary outcomes were walking quality and capacity, walking perception, community participation and falls.\n Six months after entering the study, there was no difference between the groups of independent walkers in terms of speed (MD 0.10 m/s, 95% CI -0.06 to 0.26) or stride (MD 6 cm, 95% CI -7 to 19). The independent walkers in the experimental group walked 57 m further (95% CI 1 to 113) in the 6 min walk than those in the control group. The experimental group (walkers and non-walkers) rated their walking 1 point out of 10 (95% CI 0.1 to 1.9) higher than the control group. There was no difference between the groups in community participation or number of falls.\n Treadmill training with body weight support results in better walking capacity and perception of walking compared to overground walking without deleterious effects on walking quality.", "Exercise interventions can enhance mobility after stroke as well as prevent falls in elderly persons.\n Investigate whether an exercise intervention can enhance mobility, prevent falls, and increase physical activity among community-dwelling people after stroke.\n A randomized trial with blinding of physical outcome assessment was conducted through local stroke clubs. Both groups, on average 5.9 years poststroke, received exercise classes, advice, and a home program for 12 months. The experimental group (EG) program (n = 76) aimed to improve walking, prevent falls and increase physical activity. The control group (CG) program (n = 75) aimed to improve upper-limb and cognitive functions. The primary outcomes were walking capacity, walking speed measured before and after the intervention, and fall rates monitored monthly.\n At 12 months, the EG walked 34 m further in 6 minutes (95% confidence interval [CI] = 19-50; P < .001) and 0.07 m/s faster over 10 m (95% CI = 0.01-0.14; P = .03) than the CG. The EG had 129 falls, and the CG had 133. There were no differences in proportion of fallers (relative risk = 1.22; 95% CI = 0.91-1.62; P = .19) or the rate of falls between groups (incidence rate ratio = 0.96; 95% CI = 0.59-1.51; P = .88).\n The experimental intervention delivered through stroke clubs enhanced aspects of mobility but had no effect on falls.", "Although vitamin D supplementation has been suggested to reduce the risk of falling in ambulatory or institutionalized elderly persons, no study has examined whether it reduces the frequency of falling in immobilized stroke patients who have immobilization-induced hypercalcemia reflecting increased bone resorption leading to inhibited renal synthesis of 1, 25-dihydroxyvitamin D (1, 25-[OH]2D). Bisphosphonate is known to reduce immobilization-induced hypercalcemia by inhibiting bone resorption of calcium. This study compared the efficacy of 2 drugs in reducing the risk of falling in patients with long-standing stroke. Eighty-two elderly patients with poststroke hemiparesis were followed for 1 year. The patients were randomly assigned to one of 2 groups; 41 patients received alendronate 35 mg once weekly, and 41 patients received alphacalcidiol 1 μg daily. The number of falls per person and incidence of hip fracture in the 2 groups were compared. At baseline, all patients had a low serum 1, 25-[OH]2D level. Alphacalcidol therapy enhanced immobilization-induced hypercalcemia by increasing intestinal calcium absorption, leading to a reduction of serum 1, 25-[OH]2D level, while alendronate therapy enhanced 1, 25-[OH]2D production by decreasing hypercalcemia. Alendronate treatment accounted for a 55% reduction in falls (95% confidence interval [CI]=25-72%; P=.0021). During the 1-year study period, hip fracture occurred in 1 of 41 subjects in the alphacalcidol group and in no subjects in the alendronate group. Bone mineral density was increased by 3.2% in the alendronate group and decreased by 0.1% in the alphacalcidol group (P<.0001). Alendronate therapy increased serum 1, 25-[OH]2D levels by improving immobilization-induced hypercalcemia, which may lead to decreased falling and subsequent hip fractures.\n Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.", "Vitamin D supplementation is suggested to reduce the risk of falls among ambulatory or institutionalized elderly subjects. The present study was undertaken to address the reduced risk of falls and hip fractures in patients with long-standing stroke by vitamin D supplementation.\n Ninety-six elderly women with poststroke hemiplegia were followed for two years. Patients were randomly assigned to one of the two groups, and 48 patients received 1,000 IU ergocalciferol daily, and the remaining 48 received placebo. The number of falls per person and incidence of hip fractures were compared between the two groups. Strength and tissue ATPase of skeletal muscles on the nonparetic side were assessed before and after the study.\n At baseline, serum 25-hydroxyvitamin D levels were in the deficient range (<10 ng/ml) in all patients; and vitamin D treatment enhanced serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels. Vitamin D treatment accounted for a 59% reduction in falls (95% CI, 28-81%; p = 0.003). There were increases in the relative number and size of type II muscle fibers and improved muscle strength in the vitamin D-treated group. Hip fractures occurred in 4 of 48 placebo group and 0 in 48 vitamin D2 group during the 2-year study period (log-rank, p = 0.049).\n Vitamin D may increase muscle strength by improving atrophy of type II muscle fibers, which may lead to decreased falls and hip fractures.\n Copyright (c) 2005 S. Karger AG, Basel.", "Whole-body vibration therapy has gained increasing popularity in enhancing neuromotor function in various patient populations. It remains uncertain, however, whether whole-body vibration is beneficial when used in stroke patients. The aim of this randomized controlled trial was to examine the efficacy of whole-body vibration in optimizing neuromotor performance and reducing falls in chronic stroke patients.\n Eighty-two chronic stroke patients were randomly assigned to either the experimental group or control group. The experimental group received 9-15 min of whole-body vibration (vertical vibration; frequency = 20-30 Hz. amplitude = 0.44-0.60 mm, peak acceleration = 9.5-15.8 m·s or 0.97-1.61 U of Earth gravitational acceleration (g) while performing a variety of dynamic leg exercises on the vibration platform. The control group performed the same exercises without vibration. The subjects underwent their respective training three times a week for 8 wk. Balance (Berg balance scale), mobility (10-m walk test and 6-min walk test), knee muscle strength (isokinetic dynamometry), and fall-related self-efficacy (activities-specific balance confidence scale) were assessed at baseline, immediately after the 8-wk training and at a 1-month follow-up. The incidence of falls was recorded until 6 months after the termination of training.\n Intention-to-treat analysis revealed similar significant improvement in all balance, mobility, muscle strength, and fall-related self-efficacy measures in both groups after the 8-wk treatment period (P < 0.001), and these were maintained at the 1-month follow-up. The incidence of falls did not differ significantly between the two groups (P > 0.05).\n The addition of the presently used whole-body vibration paradigm to a leg exercise protocol was no more effective in improving neuromotor performance and reducing the incidence of falls than leg exercises alone in chronic stroke patients who have mild to moderate motor impairments.", "Community physiotherapy is often prescribed for stroke patients with long-term mobility problems. We aimed to assess the effectiveness of this treatment in patients who had mobility problems 1 year after stroke.\n We screened 359 patients older than 50 years for a single-masked, randomised controlled trial to assess the effects of community physiotherapy. Assessments were made at baseline, 3, 6, and 9 months in 170 eligible patients assigned treatment or no intervention. The primary outcome measure was mobility measured by the Rivermead mobility index. Secondary outcome measures were gait speed, number of falls, daily activity (Barthel index scores), social activity (Frenchay activities index), hospital anxiety and depression scale, and emotional stress of carers (general health questionnaire 28). Analyses were by intention to treat.\n Follow-up was available for 146 patients (86%). Changes in scores on the Rivermead mobility index (score range 0-15) differed significantly between treatment and control groups at 3 months (p=0.018), but only by a median of 1 point (95% CI 0-1), with an interpolated value of 0.55 (0.08-1.04). Gait speed was 2.6 m/min (0.30-4.95) higher in the treatment group at 3 months. Neither treatment effect persisted at 6-months' and 9-months' follow-up. Treatment had no effect on patients' daily activity, social activity, anxiety, depression, and number of falls, or on emotional stress of carers.\n Community physiotherapy treatment for patients with mobility problems 1 year after stroke leads to significant, but clinically small, improvements in mobility and gait speed that are not sustained after treatment ends." ]

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[ "Hospital volume and surgical outcomes for elderly patients with colorectal cancer in the United States.", "The influence of hospital and surgeon volume on in-hospital mortality for colectomy, gastrectomy, and lung lobectomy in patients with cancer.", "Association of hospital procedure volume and outcomes in patients with colon cancer at high risk for recurrence.", "Impact of surgeon volume and specialization on short-term outcomes in colorectal cancer surgery.", "Lothian and Borders large bowel cancer project: immediate outcome after surgery. The consultant surgeons and pathologists of the Lothian and Borders Health Boards.", "Subspecialisation and its effect on the management of rectal cancer.", "Hospital volume and inpatient mortality after cancer-related gastrointestinal resections: the experience of an Asian country.", "Surgeon volume does not predict outcomes in the setting of technical credentialing: results from a randomized trial in colon cancer.", "Surgical volume and long-term survival following surgery for colorectal cancer in the Veterans Affairs Health-Care System.", "Hospital volume can serve as a surrogate for surgeon volume for achieving excellent outcomes in colorectal resection.", "Colon cancer management and outcome in relation to individual hospitals in a defined population.", "Does it matter what a hospital is \"high volume\" for? Specificity of hospital volume-outcome associations for surgical procedures: analysis of administrative data.", "Volume-outcome analysis of colorectal cancer-related outcomes.", "Hospital procedure volume and teaching status do not influence treatment and outcome measures of rectal cancer surgery in a large general population.", "Influence of hospital volume on the frequency of abdominoperineal resection and long-term oncological outcomes in low rectal cancer.", "Actionable indicators for short and long term outcomes in rectal cancer.", "Elective resection of colon cancer by high-volume surgeons is associated with decreased morbidity and mortality.", "Effect of hospital caseload on long-term outcome after standardization of rectal cancer surgery at a national level.", "Influence of volume of work on the outcome of treatment for patients with colorectal cancer.", "Variability in the quality of rectal cancer care in public hospitals in Catalonia (Spain): clinical audit as a basis for action.", "Population-based audit of colorectal cancer management in two UK health regions. Colorectal Cancer Working Group, Royal College of Surgeons of England Clinical Epidemiology and Audit Unit.", "Surgeon and hospital volume and the management of colorectal cancer patients in Australia.", "Hospital volume and surgical mortality in the United States.", "The rate of abdominoperineal resections for rectal cancer in the state of Victoria, Australia: a population-based study.", "Impact of hospital case volume on the quality of laparoscopic colectomy in Japan.", "Effect of surgeon specialty interest on patient outcome after potentially curative colorectal cancer surgery.", "Influence of volume and specialization on survival following surgery for colorectal cancer.", "Hospital and surgeon procedure volume as predictors of outcome following rectal cancer resection.", "Surgeon volume compared to hospital volume as a predictor of outcome following primary colon cancer resection.", "Hospital volume and outcome of rectal cancer surgery in Denmark 1994-99.", "The surgeon as a prognostic factor after the introduction of total mesorectal excision in the treatment of rectal cancer.", "The impact of hospital volume on surgical outcome in patients with rectal cancer.", "Relationship between surgeon caseload and sphincter preservation in patients with rectal cancer.", "Effect of caseload on the short-term outcome of colon surgery: results of a multicenter study.", "Curative rectal cancer surgery in a low-volume hospital: a quality assessment.", "Hospital caseload and the results achieved in patients with rectal cancer.", "Variation in treatment and outcome of patients with rectal cancer by region, hospital type and volume in the Netherlands.", "Impact of hospital case volume on short-term outcome after laparoscopic operation for colonic cancer.", "Relation of hospital volume to colostomy rates and survival for patients with rectal cancer.", "Evidence of the effect of 'specialization' on the management, surgical outcome and survival from colorectal cancer in Wessex.", "Disparities in quality of care for colon cancer between hospitals in the Netherlands.", "Surgeon and hospital characteristics as predictors of major adverse outcomes following colon cancer surgery: understanding the volume-outcome relationship.", "Surgical volume influences survival in patients undergoing resections for stage II colon cancers.", "Influence of hospital volume on local recurrence and survival in a population sample of rectal cancer patients.", "Operative mortality after colorectal resection in the Netherlands.", "Relation of surgeon and hospital volume to processes and outcomes of colorectal cancer surgery." ]

[ "Recent emphasis has been placed on the quality of surgical care in the United States. As such, patients, providers, and payers are increasingly aware of the outcomes of surgical care as a marker of quality. The objective of this study was to determine the impact of hospital volume on mortality for patients of different age groups to determine whether elderly patients would derive more benefit from selective referral policies.\n Data from the Nationwide Inpatient Sample for all patients undergoing surgery for colorectal cancer during 1997 were obtained (N = 20,862). Differences in mortality associated with increasing age and hospital volume quartiles were determined. Risk-adjusted analyses of mortality were performed using multiple logistic regression.\n The overall mortality rate was 3.1% for the 842 hospitals included. Patient age breakdown was the following: age <50, 7%; age 50 to 64, 19%; age 65 to 80, 51%; and age >80, 22%. Increasing age was associated with higher mortality rates: age <50, 0.8%; age 51 to 65, 1.3%; age 66 to 80, 2.9%; and >80, 6.9%. Overall, the highest volume hospitals (HVH) (>150/year) had lower mortality than the lowest volume hospitals (LVH) (<55/year) (2.5% vs. 3.7%; P = 0.006). However, the effect of volume on mortality was primarily due to differences in older patients. For patients greater than 65 years old, the mortality rate was 3.1% at HVH and 4.5% at LVH (P = 0.03). For patients greater than 80 years old, the mortality rate was 4.6% at HVH and 7.3% at LVH (P = 0.04). The results were unchanged after adjustment for patient demographics, comorbid disease, site of cancer, and type of resection.\n The majority of deaths after surgery for colorectal cancer occur in older patients. Hospitals that perform higher volumes of colorectal resection have lower mortality rates, especially for older patients. In the absence of other information about the quality of surgical care, provider volumes are a useful marker of postoperative outcomes for older patients in need of surgery for colorectal cancer.", "This study explores the volume-mortality relationship for 3 groups of cancer procedures to determine whether higher-volume hospitals, higher-volume surgeons, or both are associated with lower in-hospital mortality.\n New York's Statewide Planning and Research Cooperative System was used to identify more than 32,000 hospital inpatients with a cancer diagnosis who underwent colectomy, lobectomy of the lung, or gastrectomy between January 1, 1994, and December 31, 1997. The association of in-hospital mortality rates with provider (hospital and surgeon) volume was examined after adjusting for differences in age, demographics, organ metastasis, socioeconomic status, and comorbidities.\n For hospital volume for gastrectomy, the highest-volume quartile had an absolute risk-adjusted mortality rate that was 7.1% lower (P <.0001) than the lowest-volume quartile, although the overall mortality rate for the procedure was only 6.2%. For surgeon volume for colectomy, the highest- and lowest- volume quartiles differed by 1.9% (P <.0001), although the procedure mortality rate was only 3.5%. For hospital volume for lung lobectomy, the absolute difference in mortality was 1.7%. Patients undergoing operations performed by high-volume surgeons in high-volume hospitals usually had significantly lower risk-adjusted mortality rates than did patients who had low-volume surgeons or who were in low-volume hospitals, or both.\n For all 3 procedure groups, the risk-adjusted in-hospital mortality is significantly lower when the procedures are performed by high-volume providers.", "Studies that use registry data have demonstrated superior long-term overall survival after curative surgical resection of colon cancer at hospitals where the volume of such surgeries is high. However, because such administrative data lack information on cancer recurrence, the true nature of this relation remains uncertain.\n To determine whether hospital procedure volume predicts long-term outcomes of colon cancer surgery.\n Nested cohort study within a randomized clinical trial.\n Intergroup 0089 national adjuvant colon cancer study conducted between 1988 and 1992.\n 3161 patients with high-risk stage II and stage III colon cancer.\n Overall survival and recurrence-free survival, by hospital procedure volume as defined by Medicare claims data.\n With a median follow-up of 9.4 years, 5-year overall survival significantly differed across tertiles of hospital procedure volume (63.8% for patients who had resection at low-volume hospitals compared with 67.3% at high-volume hospitals; P = 0.04). After adjustment for other predictors of colon cancer outcome, the hazard ratio for overall mortality in patients treated at low-volume centers was 1.16 (95% CI, 1.03 to 1.32). However, the risk for cancer recurrence was not associated with hospital procedure volume. Five-year recurrence-free survival was 63.9% for patients who had resection at low-volume hospitals compared with 63.0% at high-volume hospitals (adjusted hazard ratio, 1.03 [CI, 0.89 to 1.18]). These findings did not materially change after stratification by other potential demographic and clinical predictors of outcome.\n According to prospectively recorded data from a large clinical trial, patients whose colon cancer was resected at low-volume hospitals experienced a higher risk for long-term mortality; however, this increased mortality was not attributable to differences in colon cancer recurrences.", "Several studies have shown a relationship between surgeon volume and outcomes in colorectal cancer surgery. The aim of this study was to determine the impact of surgeon volume and specialization on primary tumour resection rate, restoration of bowel continuity following rectal cancer resection, anastomotic leakage and perioperative mortality.\n The Northern Region Colorectal Cancer Audit Group conducts a population-based audit of patients with colorectal cancer managed by surgeons. This study examined 8219 patients treated between 1998 and 2002. Outcomes were modelled using multivariate logistic regression analysis.\n Tumour resection was performed in 6949 (93.8 per cent) of 7411 patients. High-volume surgeons with an annual caseload of at least 18.5 (odds ratio (OR) 1.53 (95 per cent confidence interval (c.i.) 1.10 to 2.12); P = 0.012) and colorectal specialists (OR 1.42 (95 per cent c.i. 1.06 to 1.90); P = 0.018) were more likely to perform elective sphincter-saving rectal surgery. In elective surgery, the risk of perioperative death was lower for high-volume surgeons (OR 0.58 (95 per cent c.i. 0.44 to 0.76); P < 0.001), but this was not the case in emergency surgery.\n High-volume surgeons had lower perioperative mortality rates for elective surgery, and were more likely to use restorative rectal procedures.\n Copyright (c) 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.", "A prospective audit of all large bowel cancer resections is being conducted in the adjacent Health Boards of Lothian and Borders. The results of surgery in 750 consecutive patients recruited during the first 2 years are presented. In this time, 249 (33.2 per cent) patients presented as an emergency, 490 (65.3 per cent) had resection of a colonic cancer, and 36 (4.8 per cent) patients died within 30 days. Abdominal resection was performed in 741 patients and intestinal continuity was restored in 646 (87.2 per cent). Of all anastomoses performed, 31 (4.8 per cent) leaked (15 of 467 (3.2 per cent) and 16 of 179 (8.9 per cent) after resection of colonic and rectal cancers, respectively). Of the patients presenting with a rectal cancer, 251 (96.5 per cent) underwent abdominal resection and intestinal continuity was restored in 179 (71.3 per cent). Five of 28 consultants were responsible for half of these patients. Patients treated by these five consultants were no more likely to undergo anastomosis, but when an anastomosis was performed it was less likely to leak (four of 95 (4.2 per cent) versus 12 of 84 (14.3 per cent) (chi 2 = 4.63, P < 0.05)). The overall outcome of surgery appears to be improved when compared to previous similar audits. Considerable intersurgeon variation remains in the results of resection of rectal cancer.", "To assess the impact of subspecialisation on surgical and oncological outcomes after rectal cancer surgery in a single surgical unit within a district general hospital.\n A total of 207 patients with rectal cancer treated surgically by two colorectal surgeons and four experienced general surgeons at the Royal Berkshire Hospital, Reading, England between January 1995 and December 1999 were studied. A retrospective case-note review of each patient's personal details, operative and histological findings, their subsequent clinical progress and oncological outcomes, including 5-year survival were recorded.\n In the study group, 127 patients were treated by a colorectal surgeon and 80 by general surgeons. Pre-operative radiotherapy was more likely to be given to patients treated by a colorectal surgeon. Fewer permanent stomas were performed by colorectal surgeons. Postoperative morbidity, transfusion requirements, anastomotic leak rates and 30-day mortality were not significantly different. Tumour-involved circumferential resection margins, local recurrence rates and risk of distant metastases were similar between the two groups of surgeons.\n Colorectal subspecialisation has resulted in an increased use of pre-operative radiotherapy and fewer permanent stomas. No significant improvement in surgical or oncological outcomes after rectal cancer surgery have been observed.", "Using 4-year nationwide population-based data for Taiwan, this study compared in-hospital surgical mortality rates with hospital volume for five cancer-related gastrointestinal resections.\n The study sample was drawn from the Taiwan National Health Insurance Research Database. A total of 34,715 patients, each of whom had undergone a cancer-related colectomy, gastrectomy, esophagectomy, pancreatic resection, or liver lobectomy between 2000 and 2003, were selected as the study sample. The outcome measure was in-hospital mortality. The study sample was categorized into five patient groups for each procedure, and logistic regression analyses were performed for each procedure after adjustment for hospital and patient characteristics to assess the independent association between hospital volume and in-hospital mortality.\n The adjusted odds ratios showed a steady decline in mortality rates for colectomy, gastrectomy, esophagectomy, and liver lobectomy with increasing hospital volume. The adjusted mortality odds for these four procedures in very-high-volume hospitals, relative to very-low-volume hospitals, ranged from .65 to .05. As regards pancreatic resection, after adjustment for patient, clinical, and hospital factors, no statistically significant association was discernible between hospital volume and the likelihood of mortality.\n After adjustment for hospital and physician characteristics, in four of the five procedures, patients treated at higher-volume hospitals had lower in-hospital mortality rates than those treated at lower-volume hospitals. Our findings confirm, for the most part, the hypothesis that better outcomes are associated with higher-volume hospitals.", "To test the hypothesis that surgeon volume would not predict short- and long-term outcomes when evaluated in the setting of technical credentialing.\n Surgical volume is a known predictor of outcomes; the importance of technical credentialing has not been evaluated.\n Fifty-three credentialed surgeons operated on 871 patients in the Clinical Outcomes of Surgical Therapy Study (NCT00002575), investigating laparoscopic versus open surgery for colon cancer. Credentialing required that each surgeon document performance of at least 20 laparoscopic colon cases and demonstrate oncologic techniques on a video-recorded case. Surgeons were separated based on volume entered into the trial (low, < or =5 cases (n = 39); medium, 6-10 cases (n = 9); or high, >10 cases (n = 5)) and compared by outcomes.\n Patients treated by high volume compared with medium or low volume surgeons were older (70, 66, and 68 years; P < 0.001), more often had right-sided tumors (63%, 46%, and 53%; P < 0.001) and had more previous operations (48%, 38% and 45%; P < 0.004), respectively. Mean operative times were shorter (123, 147 and 145 minutes; P < 0.001), distal margins longer (13.4, 12.4 and 11.6 cm; P = 0.005), and lymph node harvest greater (14.8, 12.8, 12.6; P = 0.05) for high versus medium versus low volume surgeons. However, rates of conversion, complications, 5-year survival, and disease-free survival showed no significant differences.\n When tested in a randomized controlled trial with case-specific surgical technical credentialing and auditing, surgeon volume did not predict differences in rates of conversion, complications, or long-term cancer outcomes. Case-specific technical credentialing should be further studied specific to the role it could play in creating consistent, high quality outcomes.", "The objective of this study was to examine the relationship between hospital surgical volume and long-term survival in patients with a new diagnosis of colorectal cancer who underwent surgical resection during fiscal years 1991-2000 in the Veterans Affairs (VA) health-care system.\n This research was a cohort study of patients admitted to all VA hospitals with a new diagnosis of colorectal cancer who underwent surgical resection between October 1990 and September 2000 and followed through September 2001. Overall 5-yr cumulative survival was calculated from Kaplan-Meier estimates, while adjusted risk of death was estimated using a Cox proportional hazards model. Adjustment was made for differences in patient characteristics including comorbidity, receipt of therapy, and year of surgery.\n We identified 34,888 individuals with a new diagnosis of colorectal cancer in VA hospitals during fiscal years 1991-2000, of whom 22,633 (65%) underwent surgical resection. The majority (98.5%) were men, the mean age was 68 yr, and the two largest race/ethnic groups were whites (75%) and blacks (17%). The 5-yr cumulative survival was greater among those who received surgery in high surgical volume hospitals as defined by 25 or more procedures per year (52.1%) than among those who received surgery in low volume hospitals (48.3%). After adjusting for differences in patient characteristics, comorbidity, receipt of adjuvant therapy, and year of surgery, we found 7% and 11% increases in 5-yr survival for patients with colon and rectal cancers, respectively, who underwent surgical resection in high volume hospitals compared with those who had surgery in low volume hospitals.\n Greater hospital surgical volume is an independent predictor of prolonged long-term survival following surgery for both colon and rectal cancer in the VA health-care system. The volume-long-term mortality relationship is greater for rectal than for colon cancer patients, perhaps reflecting the fact that surgery for rectal cancer is more technically demanding. Future studies are needed to discover what aspects of clinical management explain these differences.", "To examine the association of surgeon and hospital case volumes with the short-term outcomes of in-hospital death, total hospital charges, and length of stay for resection of colorectal carcinoma.\n The study design was a cross-sectional analysis of all adult patients who underwent resection for colorectal cancer using Maryland state discharge data from 1992 to 1996. Cases were divided into three groups based on annual surgeon case volume--low (< or =5), medium (5 to 10), and high (>10)--and hospital volume--low (<40), medium (40 to 70), and high (> or =70). Poisson and multiple linear regression analyses were used to identify differences in outcomes among volume groups while adjusting for variations in type of resections performed, cancer stage, patient comorbidities, urgency of admission, and patient demographic variables.\n During the 5-year period, 9739 resections were performed by 812 surgeons at 50 hospitals. The majority of surgeons (81%) and hospitals (58%) were in the low-volume group. The low-volume surgeons operated on 3461 of the 9739 total patients (36%) at an average rate of 1.8 cases per year. Higher surgeon volume was associated with significant improvement in all three outcomes (in-hospital death, length of stay, and cost). Medium-volume surgeons achieved results equivalent to high-volume surgeons when they operated in high- or medium-volume hospitals.\n A skewed distribution of case volumes by surgeon was found in this study of patients who underwent resection for large bowel cancer in Maryland. The majority of these surgeons performed very few operations for colorectal cancer per year, whereas a minority performed >10 cases per year. Medium-volume surgeons achieved excellent outcomes similar to high-volume surgeons when operating in medium-volume or high-volume hospitals, but not in low-volume hospitals. The results of low-volume surgeons improved with increasing hospital volume but never equaled those of the high-volume surgeons.", "The Stockholm and Gotland region in Sweden has a common management protocol for the treatment of colon cancer. The aim of this study was to assess the management and treatment of colon cancer in the region and to try to identify ways to improve the outcome further.\n Clinical data on all patients diagnosed with colon cancer in the region's nine hospitals between January 1996 and December 2000 were prospectively collected. Patients were followed until December 2004, and their management and outcome analysed.\n Colon cancer was diagnosed in 2775 patients. An elective operation was performed in 2116 (76.3 per cent) patients and an emergency procedure in 590 (21.3 per cent). Emergency surgery was an independent risk factor for death. The crude overall cumulative 5-year survival was 46.2 per cent. A multivariable analysis of risk of dying and risk of local recurrence showed significant differences between hospitals. The number of lymph nodes examined in the specimens also differed between hospitals.\n Differences in the management and outcome of colon cancer in the nine hospitals, despite a common management protocol, indicate a need for improving collaboration between hospitals and multidisciplinary management.", "To determine whether the improved outcome of a surgical procedure in high volume hospitals is specific to the volume of the same procedure.\n Analysis of secondary data in Ontario, Canada.\n Patients having an oesophagectomy, colorectal resection for cancer, pancreaticoduodenectomy, major lung resection for cancer, or repair of an unruptured abdominal aortic aneurysm between 1994 and 1999.\n Odds ratio for death within 30 days of surgery in relation to the hospital volume of the same surgical procedure and the hospital volume of the other four procedures. Estimates were adjusted for age, sex, and comorbidity and accounted for hospital level clustering.\n With the exception of colorectal resection, 30 day mortality seemed to be inversely related not only to the hospital volume of the same procedure but also to the hospital volume of most of the other procedures. In some cases the effect of the volume of a different procedure was stronger than the effect of the volume of the same procedure. For example, the association of mortality from pancreaticoduodenectomy with hospital volume of lung resection (odds ratio for death in hospitals with a high volume of lung resection compared with low volume 0.36, 95% confidence interval 0.23 to 0.57) was much stronger than the association of mortality from pancreaticoduodenectomy with hospital volume of pancreaticoduodenectomy (0.76, 0.44 to 1.32).\n The inverse association between high volume of procedure and risk of operative death is not specific to the volume of the procedure being studied.", "Significant associations between caseload and surgical outcomes highlight the conflict between local cancer care and the need for centralization. This study examined the effect of hospital volume on short-term outcomes and survival, adjusting for the effect of surgeon caseload.\n Between 1998 and 2002, 8219 patients with colorectal cancer were identified in a regional population-based audit. Outcomes were assessed using univariable and multivariable analysis to allow case mix adjustment. Surgeons were categorized as low (26 or fewer operations annually), medium (27-40) or high (more than 40) volume. Hospitals were categorized as low (86 or fewer), medium (87-109) or high (more than 109) volume.\n Some 7411 (90.2 per cent) of 8219 patients underwent surgery with an anastomotic leak rate of 2.9 per cent (162 of 5581), perioperative mortality rate of 8.0 per cent (591 of 7411) and 5-year survival rate of 46.8 per cent. Medium- and high-volume surgeons were associated with significantly better operative mortality (odds ratio (OR) 0.74, P = 0.010 and OR 0.66, P = 0.002 respectively) and survival (hazard ratio (HR) 0.88, P = 0.003 and HR 0.93, P = 0.090 respectively) than low-volume surgeons. Rectal cancer survival was significantly better in high-volume versus low-volume hospitals (HR 0.85, P = 0.036), with no difference between medium- and low-volume hospitals (HR 0.96, P = 0.505).\n This study has confirmed the relevance of minimum volume standards for individual surgeons. Organization of services in high-volume units may improve survival in patients with rectal cancer.\n Copyright 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.", "A clear benefit of increased hospital procedure volume or teaching hospital status on outcomes of rectal cancer surgery has yet to be shown. Few have examined treatment differences that may lead to varying outcomes. This study assessed the impact of hospital procedure volume and teaching status on both treatment and outcome measures of rectal cancer surgery in a large general population. Data were obtained for 1072 incident cases of rectal adenocarcinoma diagnosed in 1990 from Ontario, Canada, and treated with a major resection. Hospitals were classified by teaching status and procedure volume. Pathology reports were examined for 418 procedures. Abdominoperineal resections accounted for 31.0% of all procedures. There were no clinically significant differences in treatment measures, operative mortality, and long-term survival among the hospital groups according to both univariate and multivariate analyses. In conclusion, the absence of a hospital volume or teaching status effect on treatment and outcome measures suggests that for rectal cancer surgery in Ontario, centralization of procedures into high-volume or teaching centers is unlikely to improve surgical quality.", "Studies analysing the outcome after resection of low rectal cancer that has not infiltrated the anal sphincter reveal poorer long-term outcomes after abdominoperineal resections (APR) in comparison with low anterior resections (LAR). Further, a relationship between the frequency of APR and LAR for low rectal cancer and hospital volume is known. Our aim was to investigate the independent impact of hospital volume and type of resection on oncological outcomes after resection of low rectal cancer.\n In a prospective multi-centre observational study of 1557 patients with low rectal cancer undergoing LAR or APR, the long-term oncological outcomes were analysed for their dependence on hospital volume and type of procedure.\n Univariate analysis revealed that patients undergoing APR had a higher local recurrence rate (p = 0.022) and shorter disease-free survival (p < 0.001) than patients undergoing LAR, while hospital volume showed merely a tendency to impact the local recurrence rate (p = 0.060). With regard to disease-free survival, no dependence on hospital volume was to be found (p = 0.201). The rate of APR was significantly associated with hospital volume (p < 0.001). Multivariate analysis revealed an independent impact of hospital volume on local recurrence rate, while disease-free survival was influenced by the type of surgical procedure performed.\n In the surgical treatment of low rectal cancer the hospital volume has a major impact on outcome. The type of procedure does not affect the local recurrence rate but the disease free survival.", "Although patient and tumour characteristics are the most important determinants for outcomes in rectal cancer care, actionable factors for improving these are still unclear. Therefore, the purpose of this study was to assess the impact of surgeon and hospital factors which can actually be influenced to improve on postoperative complications, disease-free survival (DFS) and relative survival (RS) in rectal cancer.\n For 819 curatively operated rectal cancer patients, staged I-III and diagnosed between 2001 and 2005, data were derived from the population-based Cancer Registry of the Comprehensive Cancer Centre North East and supplemented by medical record examination. (Multilevel) Logistic regression analysis was performed to examine the influence of relevant factors on postoperative complications and time from diagnosis to first treatment. Besides, Cox regression analysis for DFS and relative survival analysis was performed.\n Postoperative complications were dependent on type of surgery (p=0.024) and hospital volume (p=0.029). DFS was mainly influenced by stage (p<0.001) and time to treatment (p=0.018). Actionable indicators related to RS were type of surgery (p=0.011) and time to treatment (p=0.048). Time to treatment was found to be related to co-morbidity (p=0.007), preoperative radiotherapy (p=0.003) and referral for operation (p=0.048). Nevertheless, 18.2% unexplained variation in time to treatment remained on hospital level.\n We conclude that optimal outcomes for rectal cancer care can be achieved by focusing on early detection and timely diagnosis, as well as adequate choice and timeliness of treatment in hospitals with optimal logistics for rectal cancer patients.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "The purpose of this study was to determine whether morbidity and mortality in patients undergoing elective resection of colon cancer are associated with surgeon or hospital volume.\n Using the Nationwide Inpatient Sample database, we identified all adult patients who underwent elective resection for colon cancer as their primary procedure between 2003 and 2007. Cases were divided into three groups according to the mean number of resections performed annually by each surgeon: low volume (≤4/year), intermediate volume (5-9/year), or high volume (≥10/year). Annual hospital case-load was also categorized as low volume (≤30/year), intermediate volume (31-60/year), and high volume (≥61/year). Multiple logistic regression models were used to identify differences in morbidity and mortality.\n A total of 54,000 patients underwent resection of colon cancer by 7,313 surgeons in 1,398 hospitals. After adjusting for important covariates including hospital volume, colon cancer resection by high-volume surgeons was an independent predictor of decreased morbidity (odds ratio [OR], 0.91; 95% CI, 0.85-0.97) and mortality (OR, 0.75; 95% CI, 0.65-0.86). Mortality was lowest among patients operated on by high-volume surgeons in high-volume hospitals (2.2% vs. 3.9%; OR, 0.56; 95% CI, 0.46-0.68).\n In patients undergoing elective resection of colon cancer, procedures done by high-volume surgeons are associated with decreased morbidity and mortality.", "The purpose of this prospective study was to examine the influence of hospital caseload on long-term outcome following standardization of rectal cancer surgery at a national level.\n Data relating to all 3388 Norwegian patients with rectal cancer treated for cure between November 1993 and December 1999 were recorded in a national database. Treating hospitals were divided into four groups according to their annual caseload: hospitals in group 1 (n = 4) carried out 30 or more procedures, those in group 2 (n = 6) performed 20-29 procedures, group 3 (n = 16) 10-19 procedures and group 4 (n = 28) fewer than ten procedures.\n The 5-year local recurrence rates were 9.2, 14.7, 12.5 and 17.5 per cent (P = 0.003) and 5-year overall survival rates were 64.4, 64.0, 60.8 and 57.8 per cent (P = 0.105) respectively in the four hospital caseload groups. An annual hospital caseload of less than ten procedures increased the risk of local recurrence compared with that in hospitals where 30 or more procedures were performed each year (hazard ratio 1.9 (95 per cent confidence interval (c.i.) 1.3 to 2.7); P < 0.001). Overall survival was lower for patients treated at hospitals with an annual caseload of less than ten versus hospitals with 30 or more (hazard ratio 1.2 (95 per cent c.i. 1.0 to 1.5); P = 0.023).\n The rate of local recurrence was higher for hospitals with a low annual caseload of less than ten procedures than for hospitals with a high treatment volume of 30 or more. Patients treated in small hospitals also had a shorter long-term survival than those treated in large hospitals.", "Recent recommendations for the reorganization of cancer services emphasize the importance of a 'minimal acceptable volume of work'. The influence of both hospital and surgical workload has been examined using a population-based series of patients with colorectal cancer.\n Nine hundred and twenty-seven patients with primary colorectal cancer diagnosed during the period 1 January to 30 June 1993 were identified from the North Western Regional Cancer Registry. Case notes were reviewed for information on patient age and sex, histological diagnosis, disease stage, degree of tumour differentiation, mode of admission, identity of operating surgeon, timing of operative procedure, and use of radiotherapy and/or chemotherapy. A multivariate Cox proportional hazards model was then constructed to examine, simultaneously, the effects of patient-, disease- and health service-related variables on survival.\n Age, tumour stage and differentiation, and mode of admission were revealed as significant independent prognostic variables. After adjusting for these variables, neither operator grade (consultant versus junior), consultant workload nor hospital throughput were identified as independently influencing patient survival.\n The results of this study do not support an association between volume of work and patient outcome.", "Clinical practice guidelines in cancer are a relevant component of Catalonian Cancer Strategy aimed at promoting equity of access to therapy and quality of cancer care. The colorectal cancer (CRC) guideline was first published in 2003 and subsequently updated in 2008. This study examined the quality of therapy administered to patients with rectal cancer in public hospitals in Catalonia (Spain) in 2005 and 2007, according to CRC guideline recommendations.\n We conducted a multicentre retrospective cohort study of patients who underwent curative-intent surgery for primary rectal cancer at Catalonian public hospitals in 2005 and 2007. Data were drawn from clinical records.\n The study covered 1831 patients with rectal cancer. Performance of total mesorectal excision (TME) was poorly reported by surgeons (46.4%) and pathologists (36.2%). Pre-operative radiotherapy was performed on 52% of stage-II and -III patients. Compared to high-caseload hospitals, those with a low caseload (≤11 cases/year) registered more Hartman's procedures, worse TME quality, a higher rate of post-operative complications and lower adherence to recommended pre-operative radio-chemotherapy.\n Reporting quality of care is essential for ascertaining current performance status and opportunities for improvement. In our case, there is a need for the quality of the information included in clinical records to be improved, and variability in adherence to guideline recommendations to be reduced. In view of the fact that heterogeneity in the quality of the health care process was linked to hospital caseload, the health authorities have decided to reorganise the provision of rectal cancer care.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "To obtain information on the contemporary management of colorectal cancer in the UK to assist in the development of management guidelines, an independent, 1-year population audit was carried out in Trent Region and Wales.\n Data were collected on all patients admitted to hospital with a new diagnosis of colorectal cancer in a 1-year period.\n Of 3520 patients, 3221 (91.5 per cent) had surgery. Emergency/urgent operations were carried out as the first procedure in 552 (17.1 per cent). Resection of the primary disease was achieved in 2859 (81.2 per cent) and this was deemed curative in 2070 (58.8 per cent). Twenty-one per cent of all patients had metastatic disease at presentation. Overall, 30-day operative mortality was 7.6 per cent (21.7 per cent for emergency/urgent and 5.5 per cent for scheduled/elective procedures). Anastomotic dehiscence occurred in 105 patients (4.9 per cent); this was 3.9 per cent after colonic resections and 7.9 per cent after anterior rectal resections. Elective rectal excision resulted in a permanent stoma in 486 of 1054 patients (46 per cent).\n This initial report from a comprehensive, independent audit of colorectal cancer management shows improvement in some aspects of treatment as evidenced by improved anastomotic dehiscence and stoma rates when compared with previous studies. However, there has been little improvement in the proportion of patients presenting with advanced disease, and curative resection rates remain low.", "The evidence for a relationship between patient outcomes and clinician and hospital volume is increasing. The National Colorectal Cancer Care Survey was undertaken to determine the management patterns in Australia for individuals newly diagnosed with colorectal cancer in a 3 month period in the year 2000.\n All new cases of colorectal cancer registered at each Australian State Cancer Registry were entered into the survey. This generated a questionnaire that was sent to the treating surgeon. Chi-squared tests and logistic regression analyses were used to determine levels of statistical significance.\n Of 2,383 surgical questionnaires generated, 2,015 (85%) were completed. The majority (58%) of surgeons treated one or two patients with colorectal cancer over the 3 months of the survey. There was variation across surgeon cohorts for preoperative measures including the use of deep vein thrombosis prophylaxis. Patients seen by low volume surgeons were most likely to be given a permanent stoma (P < 0.0001). Patients with rectal cancer who were operated on by high volume surgeons were significantly more likely to receive a colonic pouch (P < 0.0001).\n This nationwide population-based survey of the treatment of colorectal cancer patients suggests that the delivery of care by surgeons (the majority) who treat patients with rectal cancer infrequently should be evaluated.", "Although numerous studies suggest that there is an inverse relation between hospital volume of surgical procedures and surgical mortality, the relative importance of hospital volume in various surgical procedures is disputed.\n Using information from the national Medicare claims data base and the Nationwide Inpatient Sample, we examined the mortality associated with six different types of cardiovascular procedures and eight types of major cancer resections between 1994 and 1999 (total number of procedures, 2.5 million). Regression techniques were used to describe relations between hospital volume (total number of procedures performed per year) and mortality (in-hospital or within 30 days), with adjustment for characteristics of the patients.\n Mortality decreased as volume increased for all 14 types of procedures, but the relative importance of volume varied markedly according to the type of procedure. Absolute differences in adjusted mortality rates between very-low-volume hospitals and very-high-volume hospitals ranged from over 12 percent (for pancreatic resection, 16.3 percent vs. 3.8 percent) to only 0.2 percent (for carotid endarterectomy, 1.7 percent vs. 1.5 percent). The absolute differences in adjusted mortality rates between very-low-volume hospitals and very-high-volume hospitals were greater than 5 percent for esophagectomy and pneumonectomy, 2 to 5 percent for gastrectomy, cystectomy, repair of a nonruptured abdominal aneurysm, and replacement of an aortic or mitral valve, and less than 2 percent for coronary-artery bypass grafting, lower-extremity bypass, colectomy, lobectomy, and nephrectomy.\n In the absence of other information about the quality of surgery at the hospitals near them, Medicare patients undergoing selected cardiovascular or cancer procedures can significantly reduce their risk of operative death by selecting a high-volume hospital.", "The aim of this study was to document a population-based rate of abdominoperineal resections for adenocarcinoma of the rectum in the state of Victoria, Australia. It also determined whether surgeon caseload or specialist colorectal training affects this rate.\n All resections for adenocarcinoma of the rectum (International Classification of Diseases for Oncology, 3rd edition C20) that were performed in Victoria in the year 2005 were included. Procedures for rectosigmoid or colon cancer were excluded. The sample was taken from the Victorian Cancer Registry. The rate of abdominoperineal resections was calculated by dividing the total number of abdominoperineal resections by the total number of procedures for rectal cancer. Mixed-effects logistic regression was used to estimate the odds ratio for surgeon caseload and specialist colorectal training.\n There were 582 resections available for analysis. Patients were mostly males (66%) and over 60 years of age (67.7%). The overall rate of abdominoperineal resection was 23.4%. The rate of abdominoperineal resections for low rectal cancers was lower (42.8%) among surgeons who had specialist colorectal training compared with those who did not (60.6%) (OR = 2.06; 95% CI, 1.24-3.42).\n The rate of abdominoperineal resection in Victoria for 2005 was 23.4%. Patients with low rectal cancer operated on by surgeons who had had specialist colorectal training were significantly less likely to undergo an abdominoperineal resection compared with patients undergoing an operation by surgeons who did not have specialist colorectal training.", "The increased use of laparoscopic colectomy for colon cancer requires the evaluation of hospital case volume, quality care, and training systems, considering the difficulty of this surgery for various tumor locations.\n We assessed the quality of this procedure in Japan, based on hospital case volume and tumor location. A total of 3,765 patients were enrolled across 567 hospitals between July and December 2007. We analyzed patient characteristics, postoperative surgical complications, the administration of stapling devices or chemotherapy, hospital volume and teaching status, postoperative length of stay, total charges, and operating room time. Hospitals were classified into four case-volume categories: high (> or =5 cases per month), intermediate to high (3-4), low to intermediate (1-2), and low (<1). Multivariate analysis was used to test the impact of hospital category and tumor location.\n Ten high-volume hospitals performed 401 cases, while 355 low-volume hospitals did 903. Hospital case volume, operating time, and complications affected postoperative stay and total costs. Longer procedural time was an independent predictor of complications. Tumor location, case volume, and teaching status explained the variations in procedural time individually but not complications. Training systems highlighting the applicability of techniques are important to promote the quality of laparoscopic colectomy.", "There are significant differences in patient outcome after potentially curative surgery for colorectal cancer that relate to the surgeon performing the procedure. The reasons for these differences remain obscure. The aim of this study was to examine the effect of the surgeon's specialty on patient outcome after potentially curative colorectal cancer surgery and to identify factors that may help explain differences in outcome among specialty groups.\n Between 1990 and 1993, 378 patients underwent potentially curative surgery for colorectal cancer by surgeons with different specialty interests, vascular or transplant, general, and colorectal surgeons, in a large teaching hospital. Information on operative details, including the length of the resection specimen, resection margins, whether the tumor was removed with en bloc resection of adjacent clinically involved organs, number of lymph nodes removed, and stage was collected. Factors affecting both local and overall recurrence rates were analyzed using logistic regression analysis at both univariate and multivariate levels.\n At a median follow-up of 45 months the only factors associated with a significantly reduced local recurrence rate were the length of the resection specimen (odds ratio, 0.56; 95 percent confidence interval, 0.31-0.99) and colorectal specialty (P = 0.04). Patients operated on by a general surgeon were 3.42 times (95 percent confidence interval, 1.32-8.9) more likely to develop a local recurrence than those operated on by a colorectal surgeon. For overall recurrence, early stage disease (P < 0.0001), absence of vascular invasion (0.005), and colorectal specialty (0.025) were the only factors associated with significantly improved outcome at multivariate analysis.\n These data show that surgeons with an interest in colorectal cancer achieve lower local and overall recurrence rates compared with vascular or transplant or general surgeons. Differences in local recurrence rates seem to be predominantly related to the extent of resection performed and demonstrate the need to remove an adequate specimen when performing potentially curative colorectal cancer surgery.", "Previous studies have shown that significant surgeon-related differences in survival exist following surgery for colorectal cancer. It is not clear whether these differences were due to differences in caseload or degree of specialization.\n Outcome in 3200 patients who underwent resection for colorectal cancer between 1991 and 1994 was analysed on the basis of caseload and degree of specialization of individual surgeons. Five-year survival rates, and the corresponding hazard ratios adjusted for case mix, were calculated.\n Cancer-specific survival rate at 5 years following curative resection varied among surgeons from 53.4 to 84.6 per cent; the adjusted hazard ratios varied from 0.48 to 1.55. Cancer-specific survival rate at 5 years following curative resection was 70.2, 62.0 and 65.9 per cent for surgeons with a high, medium and low case volume respectively. There were no consistent differences in the adjusted hazard ratios by volume. Cancer-specific survival rate at 5 years following curative resection was 72.7 per cent for those treated by specialists and 63.8 per cent for those treated by non-specialists; the adjusted hazard ratio for non-specialists was 1.35 (95 per cent confidence interval 1.13 to 1.62; P = 0.001).\n The differences in outcome following apparently curative resection for colorectal cancer among surgeons appear to reflect the degree of specialization rather than case volume. It is likely that increased specialization will lead to further improvements in survival.\n Copyright 2004 British Journal of Surgery Society Ltd.", "To compare surgeon and hospital procedure volume as predictors of outcomes for patients with rectal cancer.\n Although a \"volume-outcome\" relationship exists for several major cancer operations, the impact of procedure volume on outcomes following rectal cancer surgery remains uncertain, and it has not been determined whether hospital or surgeon volume is a more important predictor of outcomes.\n A retrospective population-based cohort study utilizing the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database identified 2,815 rectal cancer patients aged 65 and older who had surgery for a primary tumor diagnosed in 1992-1996 in a SEER area. Hospital- and surgeon-specific procedure volume was ascertained based on the number of claims submitted over the 5-year study period. Outcome measures were mortality at 30 days and 2 years, overall survival, and the rate of abdominoperineal resections. Age, sex, race, comorbid illness, cancer stage, and socioeconomic status were used to adjust for differences in case mix.\n Neither hospital- nor surgeon-specific procedure volume was significantly associated with 30-day postoperative mortality or rates of rectal sphincter-sparing operations. Although an association between hospital volume and mortality at 2 years was evident, this finding was no longer significant once surgeon-specific volume was controlled for. In contrast, surgeon-specific volume was associated with 2-year mortality and remained an important predictor even after adjustment for hospital volume. Surgeon volume was also better than hospital procedure volume at predicting long-term survival.\n Surgeon-specific experience as measured by procedure volume can have a significant impact on survival for patients with rectal cancer.", "A strong association between high hospital procedure volume and survival following colon cancer resection has been demonstrated. However, the importance of surgeon case volume as a determinant of outcome has been less well studied, and it is unclear whether hospital or surgeon volume is the more powerful predictor of outcomes.\n A retrospective population-based cohort study utilizing the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database identified 24,166 colon cancer patients aged 65 years and older who had surgery for a primary tumor diagnosed in 1991-1996 in a SEER area. Hospital and surgeon-specific procedure volume was ascertained based on the number of claims submitted over the 6-year study period. Outcome measures were mortality at 30 days and 2 years, overall survival, and the frequency of operations requiring an intestinal stoma. Age, sex, race, comorbid illness, cancer stage, socioeconomic status, emergent hospitalization, and the presence of obstruction/perforation were used to adjust for differences in case-mix.\n After adjusting for surgeon procedure volume, high hospital procedure volume remained a strong predictor of low post-operative mortality rates (P < 0.001 for each outcome with and without adjustment for surgeon procedure volume). Surgeon-specific procedure volume was also an important predictor of surgical outcomes (P = 0.002 for 30-day mortality, P = 0.001 for 2-year mortality), although this effect was attenuated after adjusting for hospital volume (P = 0.03 for 30-day mortality, P = 0.02 for 2-year mortality). Hospital volume and surgeon volume were each an important predictor of the ostomy rate. Among high volume institutions and surgeons, individual providers with unusually high ostomy rates could be identified.\n Both hospital and surgeon-specific procedure volume predict outcomes following colon cancer resection; but hospital volume may exert a stronger effect. Therefore, efforts to optimize the quality of colon cancer surgery should focus on multidisciplinary aspects of hospital care rather than solely on intraoperative technique.\n Copyright 2003 Wiley-Liss, Inc.", "The association between hospital volumen and outcome of major cancer surgery is being debated at present. We analysed the outcome of rectal cancer surgery in Denmark during the period 1994-99.\n All patients with a first-time rectal cancer were registered in a national database during the 5-year period. In this observational cohort study, the influence of hospital case volume on resectional procedure, complications, 30-day mortality and 5-year mortality was analysed.\n The register comprised 5021 patients. Surgery was performed in 27 hospitals with <15 operations per year, 15 hospitals with 15-30 operations per year and 11 hospitals with >30 operations per year. In a multivariate model, the risk of permanent colostomy was significantly increased in the group of low-volume hospitals. On the contrary, volume did not influence the risk of anastomotic leakage, 30-day mortality and 5-year mortality. However, a large variation in 5-year mortality was observed particularly within the low-volume group of hospitals.\n In this study, only risk of having a permanent colostomy during surgery for rectal cancer was significantly related to hospital case volume. When individual hospitals were analysed, a large variation in 5-year mortality was observed within the low-volume group of hospitals.", "With conventional blunt surgical resection of rectal cancer, local recurrence rates are high and the individual surgeon putatively influences patient outcome. With total mesorectal excision (TME) local recurrence rates have been reduced and intersurgeon variability may be less important. The 'TME project' was a collaborative project that included surgical workshops in Stockholm between 1994 and 1997. The aim of this study was to assess the impact of the project on the practice of rectal cancer surgery in Stockholm and to analyse whether surgeon case volume and participation in the workshops influenced patient outcome.\n All 652 patients who had an abdominal resection for rectal cancer in Stockholm between 1995 and 1997 were included. Outcome was compared in patients operated on by teams that included high-volume surgeons (more than 12 operations per year) with teams that included low-volume surgeons (12 operations or fewer per year), as well as between teams that including workshop participants and non-participants.\n Forty-six surgeons operated on the 652 patients. Five high-volume surgeons operated on 48 per cent of the patients. In these, outcome was significantly better than in patients treated by low-volume surgeons (local recurrence rate 4 versus 10 per cent (P = 0.02); rate of rectal cancer death 11 versus 18 per cent (P = 0.007)). Twenty-six surgeons were workshop participants and performed 93 per cent of the operations. Radiotherapy, TME and sphincter-preserving surgery were more common among patients treated by workshop participants.\n The TME project has had an impact on rectal cancer surgical practice in Stockholm. Variability in patient outcome was mainly related to case volume, with better results obtained in patients treated by high-volume surgeons.", "This study was designed to investigate, in a population-based setting, the surgical outcome in patients with rectal cancer according to the hospital volume.\n Since 1995 all patients with rectal cancer have been registered in the Swedish Rectal Cancer Registry. Hospitals were classified, according to number treated per year, as low-volume, intermediate-volume, or high-volume hospitals (<11, 11-25, or >25 procedures per year). Postoperative mortality, reoperation rate within 30 days, local recurrence rate, and overall five-year survival were studied. For postoperative morbidity and mortality the whole cohort from 1995 to 2003 (n = 10,425) was used. For cancer-related outcome only, those with five-year follow-ups, from 1995 to 1998, were used (n = 4,355).\n In this registry setting the postoperative mortality rate was 3.6% in low-volume hospitals, and 2.2% in intermediate-volume and high-volume hospitals (P = 0.002). The reoperation rate was 10%, with no differences according to volume. The overall local recurrence rates were 9.4%, 9.3%, and 7.5%, respectively (P = 0.06). Significant difference was found among the nonirradiated patients (P = 0.004), but not among the irradiated patients (P = 0.45). No differences were found according to volume in the absolute five-year survival.\n Postoperative mortality and local recurrence in nonirradiated patients were lower in high-volume hospitals. No difference was seen between volumes in reoperation rates, overall local recurrence, or absolute five-year survival.", "The aim of this study was to determine by means of a national database whether higher surgeon caseload correlates with greater utilization of sphincter-sparing procedures than of abdominoperineal resections in treatment of patients with rectal cancer.\n Patients with a primary International Classification of Diseases-9 diagnosis code of rectal cancer who underwent a sphincter-sparing procedure or abdominoperineal resection were selected from the 1997 Nationwide Inpatient Sample, a database that represents 20 percent of all U.S. community hospital discharges. Multivariable logistic regression models were used on a 20 percent sample of this database to estimate the risk-adjusted relationship between surgeon caseload volume and the odds of receiving a sphincter-sparing procedure. All models were adjusted for age, gender, race, hospital region, and patient comorbidity.\n The study population (n = 477) was 70.4 percent white and 57.9 percent male with an average age of 67.6 years. The mean Deyo comorbidity score was 7.0. Patients treated by surgeons in the highest-volume category (> or =10 rectal cancer surgeries per year) compared with those treated by surgeons in the lowest-volume category (1-3 rectal cancer surgeries per year) were significantly more likely to undergo a sphincter-sparing procedure, after adjustment for other covariates (odds ratio = 5.05; 95 percent confidence interval, 2.5-10.22).\n This analysis suggests that rectal cancer patients treated by high-volume surgeons are five times more likely to undergo sphincter-sparing procedures than those treated by low-volume surgeon. This has significant implications for those seeking a sphincter-preserving option for the treatment of their rectal cancer.", "This prospective multicenter study investigated the effect of hospital caseload on early postoperative outcome of surgery for carcinoma of the colon in 75 German hospitals and included 2293 patients. The hospitals were divided into those with a caseload of 1-30 (group A), 31-60 (group B), and more than 60 (group C) operations. Increasing caseload was associated only with fewer general postoperative complications. It was also associated with significantly greater use of antibiotic prophylaxis. No significant differences between the groups were found in resection rates, intraoperative complications, specific postoperative complications, overall postoperative morbidity, hospital mortality, or 30-day mortality. The significance of hospital caseload for the short-term postoperative outcome following surgery on the colon should not be overestimated. Basing conclusions about the results to be expected simply on the case volume is impermissible. On the basis of the available data it is not possible to establish a threshold value, that is, a minimum number of required operations.", "Hospital volume or caseload is often used as a surrogate measure for quality of care in rectal cancer treatment. The aim of this study was to assess outcome in a low-volume hospital and secondly to examine the impact of surgeon volume on the results.\n A retrospective review of 131 patients' charts identified 102 patients receiving apparently curative resections for rectal cancer in the period 1993-2002. Our study population did not differ significantly from the national average except for shift towards more advanced Dukes stage (p=0.00) and a higher rate of node positive patients at time of diagnosis (p=0.00).\n There were no significant differences from the national outcome results, neither in perioperative mortality or complications, nor 5-year survival or local recurrences. Thirteen different on-staff surgeons performed rectal cancer surgery in our hospital in the decade, and median annual caseload was four. We detect a difference in 5-year survival when grouping the surgeons by annual caseload, but the significance is inconclusive. It is, however, interesting that in 85% of the resections, two or more certified gastrointestinal surgeons with specific training were involved. A relatively high number (9%) of discrepancies between the Norwegian Rectal Cancer Registry (NRCR) database and the local hospital database were identified.\n Adequate results for surgical outcome can be achieved in a low-volume hospital. Surgeon volume showed inconclusive impact for our results of outcome. A local quality initiative is justified in addition to national registries.", "The aim of the study was to investigate the impact of hospital caseload on the short-term postoperative outcome of patients with rectal carcinoma.\n A multicentre study involving 75 German hospitals was carried out between January and December 1999. Some 1463 patients with rectal carcinoma were studied.\n The hospitals were divided into three groups by annual caseload as follows: less than 20 (group 1), 20-40 (group 2) and more than 40 (group 3). The groups were identical in terms of age, gender, height, weight, tumour stage, risk factors and American Society of Anesthesiologists classification. Postoperative morbidity was less in hospitals with a case volume of more than 20 patients per year (41.7 per cent in group 2 versus 49.9 per cent in group 1). The proportion of patients undergoing abdominoperineal resection with a permanent stoma was less in hospitals with a case volume of more than 40 patients per year (26.4 per cent in group 3 versus 34.0 per cent in group 2).\n A large caseload in rectal surgery results in a significant reduction in permanent stoma formation and postoperative morbidity.", "Aim of this study was to describe treatment patterns and outcome according to region and hospital type and volume among patients with rectal cancer in the Netherlands.\n All patients with rectal carcinoma diagnosed in the period 2001-2006 were selected from the Netherlands Cancer Registry. Logistic regression analyses were performed to examine the influence of relevant factors on the odds of receiving preoperative radiotherapy and on the odds of postoperative mortality. Relative survival analysis was used to estimate relative excess risk of dying according to hospital type and volume.\n In total, 16 039 patients were selected. Patients diagnosed in a teaching or university hospital had a lower odds (OR 0.85; 95% CI 0.73-0.99 and OR 0.70; 95% CI 0.52-0.92) and patients diagnosed in a hospital performing >50 resections per year had a higher odds (OR 1.95; 95% CI 1.09-1.76) of receiving preoperative radiotherapy. A large variation between individual hospitals in rates of preoperative radiotherapy and between Comprehensive Cancer Centre-regions in the administration of preoperative chemoradiation was revealed. Postoperative mortality was not correlated to hospital type or volume. Patients with T1-M0 tumours diagnosed in a hospital with >50 resections per year had a better survival compared to patients diagnosed in a hospital with <25 resections per year (RER 0.11; 95% CI 0.02-0.78).\n This study demonstrated variation in treatment and outcome of patients with rectal cancer in the Netherlands, with differences related to hospital volume and hospitals teaching or academic status. However, variation in treatment patterns between individual hospitals proved to be much larger than could be explained by the investigated characteristics. Future studies should focus on the reasons behind these differences, which could lead to a higher proportion of patients receiving optimal treatment for their stage of the disease.\n Copyright (c) 2010 Elsevier Ltd. All rights reserved.", "High hospital case volume has been associated with improved outcome after open operation for colorectal malignancies.\n To assess the impact of hospital case volume on short-term outcome after laparoscopic operation for colon cancer, we conducted an analysis of patients who underwent laparoscopic colon resection within the COlon Cancer Laparoscopic or Open Resection (COLOR) trial.\n A total of 536 patients with adenocarcinoma of the colon were included in the analysis. Median operating time was 240, 210 and 188 min in centers with low, medium, and high case volumes, respectively (p < 0.001). A significant difference in conversion rate was observed among low, medium, and high case volume hospitals (24% vs 24% vs 9%; p < 0.001). A higher number of lymph nodes were harvested at high case volume hospitals (p < 0.001). After operation, fewer complications (p = 0.006) and a shorter hospital stay (p < 0.001) were observed in patients treated at hospitals with high caseloads.\n Laparoscopic operation for colon cancer at hospitals with high caseloads appears to be associated with improved short-term results.", "Postoperative mortality after some types of cancer surgery is inversely related to the number of operations performed at a hospital (i.e., hospital volume). This study assessed the association of hospital volume with colostomy rates and survival for patients with rectal cancer in a large representative cohort identified from the California Cancer Registry.\n We identified 7257 patients diagnosed from January 1, 1994, through December 31, 1997, with stage I-III rectal cancer who underwent surgical resection. Registry data were linked to hospital discharge abstracts and ZIP-code-level data from the 1990 U.S. Census. Associations of hospital volume with permanent colostomy and 30-day mortality were assessed with the Mantel-Haenszel trend test and logistic regression. Overall survival was examined with the Kaplan-Meier method and a multivariable Cox proportional hazards model. Multivariable analyses adjusted for demographic and clinical variables and patient clustering within hospitals. All tests of statistical significance were two-sided.\n In unadjusted analyses across decreasing quartiles of hospital volume, we observed statistically significant increases in colostomy rates (29.5%, 31.8%, 35.2%, and 36.6%; P<.001) and in 30-day postoperative mortality (1.6%, 1.6%, 2.9%, and 4.8%; P<.001) and a decrease in 2-year survival (83.7%, 83.2%, 80.9%, and 76.6%; P<.001). The adjusted risks of permanent colostomy (odds ratio [OR] = 1.37, 95% confidence interval [CI] = 1.10 to 1.70), 30-day mortality (OR = 2.64, 95% CI = 1.41 to 4.93), and 2-year mortality (hazard ratio = 1.28, 95% CI = 1.15 to 1.44) were greater for patients at hospitals in the lowest volume quartile than for patients at hospitals in the highest volume quartile. Stratification by tumor stage and comorbidity index did not appreciably affect the results. Adjusted colostomy rates varied statistically significantly (P<.001) among individual hospitals independent of volume.\n Rectal cancer patients who underwent surgery at high-volume hospitals were less likely to have a permanent colostomy and had better survival rates than those treated in low-volume hospitals. Identifying processes of care that contribute to these differences may improve patients' outcomes in all hospitals.", "A prospective audit of the management of colorectal cancer was established to investigate factors associated with variation in survival observed within the former Wessex region (population three million).\n Some 5173 patients (4562 surgically treated) with colorectal cancer diagnosed between 1991 and 1994 were followed for 5 years. Details of referral, diagnosis, surgical treatment, postoperative complications and outcomes were collected. The association between surgical outcomes and survival and both case volume and specialization (defined to include membership of the Association of Coloproctology of Great Britain and Ireland) was explored, accounting for variables with prognostic significance.\n There was a statistically significant association between high-volume operators (more than 50 operations per year) and specialization. The greatest benefit was observed with respect to specialists versus non-specialists, in terms of a lower postoperative mortality rate (odds ratio 0.67 (95 per cent confidence interval (c.i. 0.53 to 0.84)), lower anastomotic leak rates (odds ratio 0.46 (c.i. 0.31 to 0.66)), higher local recurrence-free survival (hazard ratio 0.56 (0.44 to 0.71)) and better long-term survival (hazard ratio 0.76 (c.i. 0.71 to 0.83)).\n There is a stronger association between surgical specialization in coloproctology and beneficial outcome than with high-volume caseloads. This is not entirely accounted for by case-mix or patient population, and is seen following colonic and rectal surgery and among patients with advanced disease.\n Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.", "Aim of this study was to describe treatment patterns and outcome according to region, and according to hospital types and volumes among patients with colon cancer in the Netherlands.\n All patients with invasive colon carcinoma diagnosed in the period 2001-2006 were selected from the Netherlands Cancer Registry. Logistic regression analyses were performed to examine the influence of relevant factors on the odds of having adequate lymph node evaluation, receiving adjuvant chemotherapy and postoperative mortality. Relative survival analysis was used to estimate relative excess risk of dying according to hospital type and volume.\n In total, 39 907 patients were selected. Patients diagnosed in a university hospital had a higher odds (OR 2.47; 95% CI 2.19-2.78) and patients diagnosed in a hospital with >100 colon carcinoma diagnoses annually had a lower odds (OR 0.70; 95% CI 0.64-0.77) of having >/=10 lymph nodes evaluated. The odds of receiving adjuvant chemotherapy was lower in patients diagnosed in teaching hospitals (OR 0.85; 95% CI 0.73-0.98) and university hospitals (OR 0.56; 95% CI 0.45-0.70) compared to patients diagnosed in non-teaching hospitals. Funnel plots showed large variation in these two outcome measures between individual hospitals. No differences in postoperative mortality were found between hospital types or volumes. Patients diagnosed in university hospitals and patients diagnosed in hospitals with >50 diagnoses of colon carcinoma per year had a better survival.\n Variation in treatment and outcome of patients with colon cancer in the Netherlands was revealed, with differences between hospital types and volumes. However, variation seemed mainly based on the level of the individual hospital.\n Copyright (c) 2010 Elsevier Ltd. All rights reserved.", "Although numerous studies have demonstrated an association between surgical volume and improved outcome in cancer surgery, the specific structures and mechanisms of care that are associated with volume and lead to improved outcomes remain poorly defined. We hypothesize that there are modifiable surgeon and hospital characteristics that explain observed volume-outcome relationships.\n Retrospective cohort study.\n Surveillance, Epidemiology, and End Results cancer registry areas.\n Patients aged 66 years and older, diagnosed and surgically treated for stage I, II, or III colon cancer between 1992 and 1996 (n = 22 672).\n Thirty-day postoperative mortality and 30-day postoperative procedural interventions, including reoperation and image-guided percutaneous procedures.\n Surgeon volume, but not hospital volume, is a significant predictor of postoperative procedural intervention (adjusted odds ratio for very high-volume surgeons vs low-volume surgeons, 0.79; 95% confidence interval, 0.64-0.98). In the unadjusted analyses, high hospital volume (odds ratio, 0.67; 95% confidence interval, 0.56-0.81) and very high hospital volume (odds ratio, 0.65; 95% confidence interval, 0.54-0.79) is associated with lower postoperative mortality. Postoperative procedural intervention is not a significant mediator of the relationship between hospital volume and mortality. A single variable-the presence of sophisticated clinical services-was the most important explanatory variable underlying the relationship between hospital volume and mortality.\n Very high surgeon volume is associated with a reduction in surgical complications. However, the association between increasing hospital volume and postoperative mortality appears to derive mainly from a full spectrum of clinical services that may facilitate the prompt recognition and treatment of complications.", "There is current interest in the correlation between surgical volume and outcomes. Survival in patients with rectal cancer appears to improve when carried out by surgeons who do high volumes of procedures. A similar correlation for patients with colon cancer has never been clearly established. The aim of this study was to determine whether surgical volume was an independent predictor for survival in patients undergoing surgery for stage II colon cancer.\n Population-based findings were collected from all patients diagnosed with stage II colon cancer in Western Australia between 1993 and 2003. The Kaplan-Meier product limit estimate of survival was used to calculate overall and cancer-specific survival. The Cox proportional hazards model was used to define the correlation between a number of covariates and survival. The results are recorded as hazard ratio (HR) with 95% confidence intervals (CI).\n From 1993 to 2003, 1467 patients underwent resections for stage II colon cancers. Significant independent predictors for overall survival were surgeon carrying out more than 25 procedures (P = 0.0001, HR 0.657, 95%CI 0.532-0.811), surgery in a private hospital (P = 0.0001, HR 0.487, 95%CI 0.400-0.594), use of chemotherapy (P = 0.001, HR 0.664, 95%CI 0.496-0.837), age at diagnosis (P = 0.0001, HR 1.014, 95%CI 1.027-1.044) and T staging and vascular invasion (T4 and vascular positive P = 0.001, HR 1.850, 95%CI 1.294-2.645).\n Surgical volume was a significant independent predictor for survival in patients undergoing resections for stage II colon cancers. Surgeons carrying out only 25 procedures over a 10-year period outperformed surgeons doing fewer cases.", "To investigate the role of hospital volume and individual hospitals on long term outcomes (local recurrence and survival) of rectal cancer patients.\n One thousand thirty-eight patients with rectal cancer were diagnosed between 1996 and 1998. From these, we analysed 884 patients with a resected invasive primary rectal cancer. Median follow-up was 5.7 years. The impact of hospital volume (<10, 10-30 and >30 rectal cancer patients annually) on local recurrence and survival was examined in a Cox model. Differences between the four largest clinics in the high volume group were also investigated.\n In the multivariate model predicting survival the following variables were significant: UICC stage, grade, age, local recurrence, and (neo-) adjuvant therapy treatment. In the multivariate model predicting local recurrence UICC stage, tumour localisation, and neoadjuvant therapy treatment were significant variables. Hospital volume was not a significant factor for survival or local recurrence. Within the high volume category one hospital showed significantly worse local recurrence rates than all other hospitals, but no survival difference could be seen between the four largest hospitals of the high volume group.\n This analysis of a rectal cancer population found that hospital volume did not determine survival or local recurrence. Detailed clinical data with long term follow-up from cancer registries are vital to demonstrate the quality of routine care.", "The aim of this study was to quantify factors related to operative mortality after colorectal resection in the Netherlands.\n Multilevel logistic regression modelling was used. Institutional effects were calculated with and without adjustment for specific patient (age, sex, urgency of operation) and hospital (number of procedures, type of hospital) characteristics. All adult Dutch patients who underwent primary colorectal resection between 1994 and 1999 were included, except those who had (sub)total colectomy or local rectal resection.\n A total of 67 594 patients underwent colorectal resection. The in-hospital mortality rate was 7.0 per cent (elective 3.9 per cent, acute 14.3 per cent). Acute operation (odds ratio 3.89) and age (odds ratios 2.63, 5.23 and 10.13 for patients aged 50-69, 70-79 and 80 or more years respectively compared with those aged less than 50 years) had the strongest effects, followed by male sex (odds ratio 1.48) and type of hospital. There was no difference in operative mortality rate between low-, medium- and high-volume hospitals.\n In the Netherlands, advanced age and acute operation are by far the most important factors related to operative mortality after colorectal resection. Male sex and type of hospital have only a modest effect, and there is no discernible effect of hospital volume.\n Copyright (c) 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.", "Greater hospital volume has been associated with lower mortality after colorectal cancer surgery. The contribution of surgeon volume to processes and outcomes of care is less well understood. We assessed the relation of surgeon and hospital volume to postoperative and overall mortality, colostomy rates, and use of adjuvant radiation therapy.\n From the California Cancer Registry, we studied 28,644 patients who underwent surgical resection of stage I to III colorectal cancer during 1996 to 1999 and were followed up to 6 years after surgery to assess 30-day postoperative mortality, overall long-term mortality, permanent colostomy, and use of adjuvant radiation therapy.\n Across decreasing quartiles of hospital and surgeon volume, 30-day postoperative mortality ranged from 2.7% to 4.2% (P < 0.001). Adjusting for age, stage, comorbidity, and median income among patients with colorectal cancer who survived at least 30 days, patients in the lowest quartile of surgeon volume had a higher adjusted overall mortality rate than those in the highest quartile (hazard ratio, 1.16; 95% confidence interval, 1.09-1.24), as did patients in the lowest quartile of hospital volume relative to those treated in the highest quartile (hazard ratio, 1.11; 95% confidence interval, 1.05-1.19). For rectal cancer, adjusted colostomy rates were significantly higher for low-volume surgeons, and the use of adjuvant radiation therapy was significantly lower for low-volume hospitals.\n Greater surgeon and hospital volumes were associated with improved outcomes for patients undergoing surgery for colorectal cancer. Further study of processes that led to these differences may improve the quality of colorectal cancer care." ]

[ "14615440", "18481713", "10437260" ]

[ "Analgesic effect of auricular acupuncture for cancer pain: a randomized, blinded, controlled trial.", "[Observation on the therapeutic effect of acupuncture at pain points on cancer pain].", "Clinical study on acupuncture treatment of stomach carcinoma pain." ]

[ "During the last 30 years, auricular acupuncture has been used as complementary treatment of cancer pain when analgesic drugs do not suffice. The purpose of this study is to examine the efficacy of auricular acupuncture in decreasing pain intensity in cancer patients.\n Ninety patients were randomly divided in three groups; one group received two courses of auricular acupuncture at points where an electrodermal signal had been detected, and two placebo groups received auricular acupuncture at points with no electrodermal signal (placebo points) and one with auricular seeds fixed at placebo points. Patients had to be in pain, attaining a visual analog score (VAS) of 30 mm or more after having received analgesic treatment adapted to both intensity and type of pain, for at least 1 month of therapy. Treatment efficacy was based on the absolute decrease in pain intensity measured 2 months after randomization using the VAS.\n The main outcome was pain assessed at 2 months, with the assessment at 1 month carried over to 2 months for the eight patients who interrupted treatment after 1 month. For three patients, no data were available because they withdrew from the study during the first month. Pain intensity decreased by 36% at 2 months from baseline in the group receiving acupuncture; there was little change for patients receiving placebo (2%). The difference between groups was statistically significant (P <.0001).\n The observed reduction in pain intensity measured on the VAS represents a clear benefit from auricular acupuncture for these cancer patients who are in pain, despite stable analgesic treatment.", "To search for a safe and effective method for alleviating cancer pain.\n Sixty-six cases of late cancer with pain were first divided into 3 different degrees of pain, mild, moderate and severe, and then the patients with pain of each same degree were randomly divided into an acupuncture group treated by acupuncture at 3-5 of the most severe tender points, and a medication group treated with oral administration according to the WHO Three Step Administration Principle, i.e. the patients with mild pain took aspirin, moderate pain took codeine and severe pain took morphine.\n Both two methods could effectively control cancer pain. The total effective rate of 94.1% in the acupuncture group was significantly better than 87.5% in the medication group (P<0.05).\n The analgesic effect of acupuncture treatment is better than that of the Three Step Administration, with no adverse effect and addiction of analgesics.", "Clinical observation on 48 cases of stomach carcinoma pain indicated that acupuncture including filiform needle group and point-injection group had better therapeutic effects in treatment of stomach carcinoma pain when patient's mind was concentrated at the site of disease. After treatment for 2 months, the long-term effective rates of analgesia in both the filiform needle group and the point-injection group were similar to that in the western medicine group, all being about 81%. While the long-term markedly effective rates in the two groups were superior to that in the western medicine group. Life quality of the patients in all the groups were improved. The toxic action and side effects caused by chemotherapy were prevented, the high viscous state showed by indexes of blood rheology was improved, and the lowered Cu-Zu-SOD activity in erythrocytes in patients of stomach carcinoma was increased in the filiform needle group and the point-injection group. Based on the results of clinical study, we consider that acupuncture analgesic effect on stomach carcinoma is related to the increase of PLEK, improvement of cellular immune function and the elevation of life quality after acupuncture." ]

[ "16245220", "12792701", "14999696", "15505596" ]

[ "Management of fatty liver disease with vitamin E and C compared to ursodeoxycholic acid treatment.", "A randomized double-blind study of the short-time treatment of obese patients with nonalcoholic fatty liver disease with ursodeoxycholic acid.", "Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial.", "Weight reduction and ursodeoxycholic acid in subjects with nonalcoholic fatty liver disease. A double-blind, placebo-controlled trial." ]

[ "Despite a proposed role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis, antioxidant approaches have not been investigated sufficiently in the therapy of nonalcoholic steatohepatitis. Our aim was to determine whether vitamin E plus C therapy is effective in normalization of liver enzymes compared to ursodeoxycholic acid treatment in patients with fatty liver disease.\n This was an open-labeled, prospective, randomized study enrolling patients with histologically proven fatty liver disease who had chronically elevated alanine aminotransferase, despite a three-month reducing diet. Patients consuming alcohol (more than 20 g/day) were excluded. The patients were randomly prescribed either oral vitamin E (600 IU/day) plus vitamin C (500 mg/day) or ursodeoxycholic acid (10 mg/kg/day). Patients were randomized as two groups to receive vitamin E plus vitamin C combination (28 patients, 10 F) or ursodeoxycholic acid treatment (29 patients, 13 F).\n There was no significant change in body mass index before and after the treatment in both groups. At the end of six months of therapy, serum aspartate aminotransferase and aminotransferase levels significantly decreased in both treatment options. Vitamin E and C combination was more efficacious on serum aminotransferase levels than ursodeoxycholic acid, but the difference was not significant. Alanine aminotransferase decreased to normal levels in 17 of 27 (63%) and in 16 of 29 patients (55%), respectively, in the two groups. Gamma-glutamyl transpeptidase decreased in patients receiving ursodeoxycholic acid, but no change was obtained in the vitamin-treated patients.\n Vitamin E plus C combination treatment is a safe, inexpensive and effective treatment option in patients with fatty liver disease, with results comparable to those obtained with ursodeoxycholic acid. Since more effective new therapeutic options are lacking, patients with fatty liver disease should be encouraged to take vitamin E and C supplements, which are safe and affordable.", "In order to determine the effect of ursodeoxycholic acid on nonalcoholic fatty liver disease, 30 patients with body mass indices higher than 25, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or gamma-glutamyltransferase (gamma-GT) at least more than 1.5 times the upper limit of normality, and hepatic steatosis demonstrated by ultrasonography were randomized into two groups of 15 patients to receive placebo or 10 mg kg-1 day-1 ursodeoxycholic acid for three months. Abdominal computed tomography was performed to quantify hepatic fat content, which was significantly correlated with histological grading of steatosis (r s = -0.83, P < 0.01). Patient body mass index remained stable for both groups throughout the study, but a significant reduction in mean ( +/- SEM) serum levels of ALT, AST and gamma-GT was observed only in the treated group (ALT = 81.2 +/- 9.7, 44.8 +/- 7.7, 48.1 +/- 7.7 and 52.2 +/- 6.3 IU/l at the beginning and after the first, second and third months, respectively, N = 14, P < 0.05). For the placebo group ALT values were 66.4 +/- 9.8, 54.5 +/- 7, 60 +/- 7.6 and 43.7 5 IU/l, respectively. No alterations in hepatic lipid content were observed in these patients by computed tomography examination (50.2 +/- 4.2 Hounsfield units (HU) at the beginning versus 51.1 +/- 4.1 HU at the third month). These results show that ursodeoxycholic acid is able to reduce serum levels of hepatic enzymes in patients with nonalcoholic fatty liver disease, but this effect is not related to modifications in liver fat content.", "No effective medical therapy is available for all patients with nonalcoholic steatohepatitis (NASH). Ursodeoxycholic acid (UDCA) has been suggested to be of benefit based on open label clinical studies. We randomized 166 patients with liver biopsy-proven NASH to receive between 13 and 15 mg/kg/d of UDCA or placebo for 2 years. End points included changes in liver test results and liver histology at 2 years of therapy. The treatment groups were comparable at entry with regard to age, gender, risk factors for NASH, serum liver biochemistries, and baseline liver histology. A total of 126 patients completed 2 years of therapy. Pre- and posttreatment liver biopsies were available in 107 patients for review at the end of the study. UDCA was well tolerated and body weight was stable during the study duration. Serum liver biochemistries were stable or improved in both the UDCA and placebo-treated groups. Changes in the degree of steatosis, necroinflammation, or fibrosis that occurred with therapy were not significantly different between the UDCA and placebo groups. In conclusion, 2 years of therapy with UDCA at a dose of 13 to 15 mg/kg/d, although safe and well tolerated, is not better than placebo for patients with NASH.", "Nonalcoholic fatty liver disease is an increasingly recognized condition that may progress to end-stage liver disease. We investigated the effects of weight reduction and ursodeoxycholic acid administration in patients with this disease.\n A double-blind, placebo-controlled trial. Twenty-seven women with a body mass index of >30 kg/m2 and willing to participate in the diet plan for six weeks were studied were assigned to one of two treatment groups (ursodeoxycholic acid, n = 14: placebo n = 13). Both groups received a normal diet (1,200 kcal/d) plus 1200 mg/d of ursodeoxycholic acid or placebo. Hepatic steatosis, was assessed by abdominal ultrasound. Fasting glucose, cholesterol, triglycerides, and aminotransferases levels were determined before and after treatment.\n Body mass index decreases significantly from 34.2 +/- 4.2 kg/m2 and 33.3 +/- 1.6 kg/m2 to 31.8 +/- 4.5 kg/m2 and 30.6 +/- 2.6 kg/m2 in the ursodeoxycholic acid and placebo groups, p < 0.001. The hepatic steatosis index decreased from 2.3 +/- 0.7 to 1.0 +/- 0.6 and 2.2 +/- 0.7 to 1.1 +/- 0.7 in the ursodeoxycholic acid and placebo groups, p<0.003. Serum AST decreased significantly from 41.2 +/- 5.6 to 34.5 +/- 3.4 in the ursodeoxycholic acid group, p <0.001, and from 43.6 +/- 4.2 to 35.3 +/- 2.9 in the placebo group, p <0.001. Serum ALT decreased from 62.9 +/- 6.5 to 44.0 +/- 3.5 in the ursodeoxycholic acid group, p <0.001, and from 63.5 +/- 4.5 to 44.0 +/- 3.5 in the placebo group. We did not find any differences in all variables studied between groups.\n The present study shows beneficial effect of weight reduction, producing improvements in biochemical and imaging markers of liver disease." ]

[ "3119286", "12290800", "6765331", "4844514", "4396", "4613534", "12305415", "4587643", "3955685" ]

[ "Postcoital contraception with levonorgestrel during the peri-ovulatory phase of the menstrual cycle. Task Force on Post-ovulatory Methods for Fertility Regulation.", "Prospective study of contraception with levonorgestrel.", "Results of a multicentre trial of Postinor.", "The use of progestogens as postcoital oral contraceptives.", "Evaluation of d-norgestrel 1.0 mg as a post-coital contraceptive.", "Further experience with quingestanol acetate as a postcoital oral contraceptive.", "Post-coital contraception with dienoestrol.", "Low-dosage oral progestogens to control fertility. I. clinical investigation.", "[Postcoital contraception]." ]

[ "The contraceptive efficacy and side effects of postcoital levonorgestrel used repeatedly during the peri-ovulatory period of one cycle was examined in 259 women. All subjects were of proven fertility in their present union and had ovulatory cycles as assessed from pre-treatment BBT charts. The mean number of coital acts during the treatment cycle was 7.5 (SD:2.6) and the mean number of 0.75 mg levonorgestrel tablets taken during the peri-ovulatory period was 4.0 (SD:1.2). Two pregnancies, both considered to be method failures, occurred, giving a failure rate of 0.8% per treated cycle. Although the overall effect of levonorgestrel on menstrual cycle length was small and insignificant, menstrual cycle disturbances were not uncommon. Intermenstrual bleeding or spotting occurred in 8.5% of the treated cycles and 12.5% of the cycles were less than 20 or more than 35 days. Other side effects, mainly nausea, headache and dizziness, were reported by about 20% of the subjects but the apparent incidence of these complaints varied markedly between the nine participating centres from 0% to just over 50%. The data suggest that repeated postcoital use of levonorgestrel is probably not a viable approach to fertility regulation for the majority of women who have regular intercourse and wish to limit the number of their pregnancies.", "nan", "nan", "nan", "Two hundred and ninety-eight women were followed for 2578 months (2739 'bleeding intervals') of treatment with d-Norgestrel 1.0 mg given as a post-coital oral contraceptive. Fourteen pregnancies were recorded (general failure rate, 6.5 per 100 woman/years); at least 6 of these patients did not miss any tablet (corrected failure rate, 2.8). The acceptability rates (life table method) were 0.58 and 0.40 after 6 and 12 months of follow-up. The most important medical reason for drop-out was cycle irregularities. The cycle pattern is deeply disturbed by this method of oral contraception.", "nan", "nan", "nan", "nan" ]

[ "19406981", "19345831", "18230244", "16675781", "9597244" ]

[ "Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis.", "Moxifloxacin versus ethambutol in the initial treatment of tuberculosis: a double-blind, randomised, controlled phase II trial.", "A Phase II study of the sterilising activities of ofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis.", "Moxifloxacin versus ethambutol in the first 2 months of treatment for pulmonary tuberculosis.", "Evaluation of an intensive intermittent-induction regimen and duration of short-course treatment for human immunodeficiency virus-related pulmonary tuberculosis. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) and the AIDS Clinical Trials Group (ACTG)." ]

[ "Moxifloxacin has potent activity against Mycobacterium tuberculosis in vitro and in a mouse model of antituberculosis (TB) chemotherapy, but data regarding its activity in humans are limited.\n Our objective was to compare the antimicrobial activity and safety of moxifloxacin versus isoniazid during the first 8 weeks of combination therapy for pulmonary TB.\n Adults with sputum smear-positive pulmonary TB were randomly assigned to receive either moxifloxacin 400 mg plus isoniazid placebo, or isoniazid 300 mg plus moxifloxacin placebo, administered 5 days/week for 8 weeks, in addition to rifampin, pyrazinamide, and ethambutol. All doses were directly observed. Sputum was collected for culture every 2 weeks. The primary outcome was negative sputum culture at completion of 8 weeks of treatment.\n Of 433 participants enrolled, 328 were eligible for the primary efficacy analysis. Of these, 35 (11%) were HIV positive, 248 (76%) had cavitation on baseline chest radiograph, and 213 (65%) were enrolled at African sites. Negative cultures at Week 8 were observed in 90/164 (54.9%) participants in the isoniazid arm, and 99/164 (60.4%) in the moxifloxacin arm (P = 0.37). In multivariate analysis, cavitation and enrollment at an African site were associated with lower likelihood of Week-8 culture negativity. The proportion of participants who discontinued assigned treatment was 31/214 (14.5%) for the moxifloxacin group versus 22/205 (10.7%) for the isoniazid group (RR, 1.35; 95% CI, 0.81, 2.25).\n Substitution of moxifloxacin for isoniazid resulted in a small but statistically nonsignificant increase in Week-8 culture negativity.", "New treatments are needed to shorten the time required to cure tuberculosis and to treat drug-resistant strains. The fluoroquinolone moxifloxacin is a promising new agent that might have additive activity to existing antituberculosis agents. We assessed the activity and safety of moxifloxacin in the initial stage of tuberculosis treatment.\n We undertook a phase II, double-blind, randomised controlled trial of a regimen that included moxifloxacin in adults with sputum smear-positive tuberculosis at one hospital in Rio de Janeiro, Brazil. 170 participants received isoniazid, rifampicin, and pyrazinamide at standard doses and were assigned by permuted block randomisation to receive either moxifloxacin (400 mg) with an ethambutol placebo (n=85) or ethambutol (15-20 mg/kg) plus moxifloxacin placebo (n=85) 5 days per week for 8 weeks. The primary endpoint was the proportion of patients whose sputum culture had converted to negative by week 8. Analysis was by modified intention to treat (ITT); patients whose baseline cultures were negative, contaminated, or contained drug-resistant Mycobacterium tuberculosis were excluded from the analysis. Additionally, all missing 8-week results were deemed treatment failures. This study is registered with ClinicalTrials.gov, number NCT00082173.\n 74 patients assigned to the moxifloxacin group and 72 in the ethambutol group were included in the modified ITT population. 125 patients had 8-week data (moxifloxacin n=64, ethambutol n=61); the main reason for absence of data was culture contamination. At 8 weeks, culture conversion to negative had occurred in 59 (80%) of 74 patients in the moxifloxacin group compared with 45 (63%) of 72 in the ethambutol group (difference 17.2%, 95% CI 2.8-31.7; p=0.03). There were 16 adverse events (eight in each group) in 12 patients. Only one event was judged related to study drug (grade 3 cutaneous reaction in the ethambutol group).\n Moxifloxacin improved culture conversion in the initial phase of tuberculosis treatment. Trials to assess whether moxifloxacin can be used to shorten the duration of tuberculosis treatment are justified.", "Current treatment for pulmonary tuberculosis (TB) might be shortened by the incorporation of fluoroquinolones (FQs).\n A Phase II study aimed to assess the sterilising activities of three novel regimens containing FQs before a Phase III trial of a 4-month regimen containing gatifloxacin (GFX).\n A total of 217 newly diagnosed smear-positive patients were randomly allocated to one of four regimens: isoniazid (INH), pyrazinamide and rifampicin (RMP) with either ethambutol, GFX, moxifloxacin (MFX) or ofloxacin (OFX) for 2 months. At the end of the study, RMP and INH were given for 4 months. The rates of elimination of Mycobacterium tuberculosis were compared in the regimens using non-linear mixed effects modelling of the serial sputum colony counts (SSCC) during the first 8 weeks.\n After adjustment for covariates, MFX substitution appeared superior during the early phase of a bi-exponential fall in colony counts, but significant and similar acceleration of bacillary elimination during the late phase occurred with both GFX and MFX (P = 0.002). Substitution of OFX had no effect. These findings were supported by estimates of time to conversion, using Cox regression, but there were no significant differences in proportions culture-negative at 8 weeks.\n GFX and MFX improve the sterilising activity of regimens and might shorten treatment; their progression into Phase III trials therefore seems warranted.", "Moxifloxacin has promising preclinical activity against Mycobacterium tuberculosis, but has not been evaluated in multidrug treatment of tuberculosis in humans.\n To compare the impact of moxifloxacin versus ethambutol, both in combination with isoniazid, rifampin, and pyrazinamide, on sputum culture conversion at 2 mo as a measure of the potential sterilizing activity of alternate induction regimens.\n Adults with smear-positive pulmonary tuberculosis were randomized in a factorial design to receive moxifloxacin (400 mg) versus ethambutol given 5 d/wk versus 3 d/wk (after 2 wk of daily therapy). All doses were directly observed.\n The primary endpoint was sputum culture status at 2 mo of treatment.\n Of 336 patients enrolled, 277 (82%) were eligible for the efficacy analysis, 186 (67%) were male, 175 (63%) were enrolled at African sites, 206 (74%) had cavitation on chest radiograph, and 60 (22%) had HIV infection. Two-month cultures were negative in 71% of patients (99 of 139) treated with moxifloxacin versus 71% (98 of 138) treated with ethambutol (p = 0.97). Patients receiving moxifloxacin, however, more often had negative cultures after 4 wk of treatment. Patients treated with moxifloxacin more often reported nausea (22 vs. 9%, p = 0.002), but similar proportions completed study treatment (88 vs. 89%). Dosing frequency had little effect on 2-mo culture status or tolerability of therapy.\n The addition of moxifloxacin to isoniazid, rifampin, and pyrazinamide did not affect 2-mo sputum culture status but did show increased activity at earlier time points.", "This study examined whether adding levofloxacin to a standard four-drug regimen improved the 8-week culture response and compared effectiveness of 9 versus 6 months of intermittent therapy for human immunodeficiency virus-related pansusceptible pulmonary tuberculosis. Patients were randomized to receive either four or five drugs, the fifth being levofloxacin. Patients who completed induction therapy were randomized to complete 9 versus 6 months of intermittent therapy with isoniazid and rifampin. In the randomized induction phase, 97.3% of patients in the four-drug group and 95.8% in the five-drug group had sputum culture conversion at 8 weeks (P = 1.00). In the continuation phase, one patient (2%) assigned to 9 months and two patients (3.9%) assigned to 6 months of therapy had treatment failure/relapse (P = 1.00). In conclusion, this study showed that levofloxacin added no benefit to a highly effective, largely intermittent, four-drug induction regimen. Both 9 and 6 months of intermittent therapy were associated with low treatment failure/relapse rates." ]

[ "17166313", "17565167", "2378683", "1930765", "16019280", "17117398", "16807197", "12425704", "15374371", "15980656", "4031404", "12215960", "11827617", "3075181", "3505872", "17530622", "16888038", "2630380", "8872082", "18653001", "2317292" ]

[ "Cognitive rehabilitation in the elderly: effects on strategic behavior in relation to goal management.", "Do self-monitoring interventions improve older adult learning?", "Supplemental group discussions in memory training for older adults.", "Stories as a mnemonic aid for older learners.", "The impact of speed of processing training on cognitive and everyday performance.", "Efficacy of cognitive rehabilitation in patients with mild cognitive impairment treated with cholinesterase inhibitors.", "In-home cognitive training with older married couples: individual versus collaborative learning.", "Effects of cognitive training interventions with older adults: a randomized controlled trial.", "The effects of a rehabilitation program with mnemotechniques on the institutionalized elderly subject.", "Forgetting numbers in old age: strategy and learning speed matter.", "Memory-skills training, memory complaints, and depression in older adults.", "Improvement of cognitive function by mental and/or individualized aerobic training in healthy elderly subjects.", "Memory enhancement training for older adults with mild cognitive impairment: a preliminary study.", "Pretraining enhances mnemonic training in elderly adults.", "The effect of mnemonic training on perceived recall confidence in the elderly.", "A randomized, two-year study of the efficacy of cognitive intervention on elderly people: the Donostia Longitudinal Study.", "Memory enhancement in healthy older adults using a brain plasticity-based training program: a randomized, controlled study.", "Multifactorial memory training with older adults: how to foster maintenance of improved performance.", "Memory enhancement program for community-based older adults: development and evaluation.", "Memory training and drug therapy act differently on memory and metamemory functioning: evidence from a pilot study.", "Learning mnemonics: roles of aging and subtle cognitive impairment." ]

[ "Executive functions are highly sensitive to the effects of aging and other conditions affecting frontal lobe function. Yet there are few validated interventions specifically designed to address executive functions, and, to our knowledge, none validated in a healthy aging sample. As part of a large-scale cognitive rehabilitation randomized trial in 49 healthy older adults, a modified Goal Management Training program was included to address the real-life deficits caused by executive dysfunction. This program emphasized periodic suspension of ongoing activity to establish goal hierarchies and monitor behavioral output. Tabletop simulated real-life tasks (SRLTs) were developed to measure the processes targeted by this intervention. Participants were randomized to two groups, one of which received the intervention immediately and the other of which was wait-listed prior to rehabilitation. Results indicated improvements in SRLT performance and self-rated executive deficits coinciding with the training in both groups. These gains were maintained at long-term follow-up. Future research will assess the specificity of these effects in patient groups.", "We describe a self-monitoring approach for improving older adult learning that older adults can use in conjunction with more traditional mnemonic-based interventions. According to the self-monitoring approach, older adults can improve the effectiveness of learning by accurately monitoring their progress toward a learning goal and by using the output from such monitoring to allocate study time and to inform strategy selection. We review current evidence, which includes outcomes from two previously unpublished interventions, relevant to the efficacy of this approach. Both interventions demonstrated performance gains in memory performance after self-monitoring training, although these training gains did not exceed gains obtained through standard mnemonic training. Our discussion highlights both successes and failures of self-monitoring to enhance learning as well as challenges for future research.", "Memory training was compared in adults aged 60-80. Groups 1 and 2 studied a self-instructional memory training manual; Group 2 also attended supplementary group discussions of typical problems of later life, related coping methods, and the techniques in the self-instructional manuals. Group 3 was a wait-list control group. Memory performance on 2 word lists significantly improved in the supplemental discussion group but not in the group that only studied the self-instructional manual. Enhanced performances were maintained at a 1-month follow-up. Bibliotherapy alone may be inferior to treatment involving a group component, although the mechanisms of such enhancement remain unexplored with respect to memory training. Neither treated group improved their digit span or recall of names and a brief prose passage; teaching older adults the strategies of chunking and use of imagery may not be beneficial.", "The effectiveness of a story mnemonic for free-recall learning was assessed in 71 community-dwelling elderly adults. Participants received 1 of 3 memory-training programs: (a) narrative story, (b) method of loci, or (c) placebo training. The stimuli consisted of 26 nouns chosen for being highly imagible and concrete. Recall was examined immediately following study of the words, after 1 hr, and after 3 days. At each testing interval, both mnemonic condition groups outperformed the placebo group. The results suggest that a story mnemonic can enhance word retention on a free-recall task.", "The purpose of the present investigation was to examine the impact of speed of processing training on the cognitive and everyday abilities of older adults with initial processing speed or processing difficulty. Participants were randomized to either a speed of processing intervention or a social- and computer-contact control group. Results indicate that speed of processing training not only improves processing speed, as indicated by performance on the Useful Field of View test (UFOV), but also transfers to certain everyday functions, as indicated by improved performance on Timed Instrumental Activities of Daily Living (Timed IADL). Transfer of speed of processing training to other cognitive domains was not evident. This study provides additional evidence that speed of processing training has the potential to enhance everyday functions that maintain independence and quality of life, particularly when the training is targeted toward individuals who most need it. Further study is needed to learn about the long-term effects of such training in relation to everyday abilities.", "Individuals who have Mild Cognitive Impairment (MCI) may be in a transitional stage between aging and Alzheimer's disease (AD). The high rate of conversion from MCI to AD makes early treatment an important clinical issue. Recent evidence suggests that cognitive training intervention may reduce the rate of progression to AD.\n To evaluate the efficacy of a NeuroPsychological Training (TNP) in patients with MCI who are treated with cholinesterase inhibitors (ChEIs), compared with patients MCI treated only with ChEIs and patients not treated, in a longitudinal, one year follow-up study.\n One year longitudinal and retrospective comparison study of neuropsychological performances in 59 subjects affected by Mild Cognitive Impairment (MCI) according to Petersen's criteria. Fifteen subjects were randomised to receive TNP plus cholinesterase inhibitors; 22 subjects cholinesterase inhibitors alone and 22 subjects no treatment. All the subjects referring memory complaints, corroborated by an informant, underwent a multidimensional assessment concerning neuropsychological, behavioural and functional characteristics, at baseline and after one year follow-up.\n Subjects without treatment maintained their cognitive, functional and behavioural status after one year; patients treated only with ChEIs improved in depressive symptoms whereas subjects treated with TNP and ChEIs showed significant improvements in different cognitive areas, such as memory, abstract reasoning and in behavioural disturbances, particularly depressive symptoms.\n A long-term TNP in ChEIs-treated MCI subjects induces additional cognitive and mood benefits.", "Research has demonstrated that older adults' cognitive performance can be enhanced via formal intervention, as well as more informal intervention including collaboration or working with a partner. The current study investigated the effects of an inductive reasoning training program adapted for in-home use among older adults assigned to individual training (n = 30), collaborative training (n = 34), or a no-treatment control group (n = 34). The training consisted of 10 sessions, and all participants completed a pretest followed by a post-test 6 weeks later. Findings suggest that older adults could effectively \"train themselves\" without the guidance of a formal instructor. The results, however, did not indicate immediate added benefit in reasoning performance for collaborative versus individual training using the current reasoning program.", "Cognitive function in older adults is related to independent living and need for care. However, few studies have addressed whether improving cognitive functions might have short- or long-term effects on activities related to living independently.\n To evaluate whether 3 cognitive training interventions improve mental abilities and daily functioning in older, independent-living adults.\n Randomized, controlled, single-blind trial with recruitment conducted from March 1998 to October 1999 and 2-year follow-up through December 2001.\n Volunteer sample of 2832 persons aged 65 to 94 years recruited from senior housing, community centers, and hospital/clinics in 6 metropolitan areas in the United States.\n Participants were randomly assigned to 1 of 4 groups: 10-session group training for memory (verbal episodic memory; n = 711), or reasoning (ability to solve problems that follow a serial pattern; n = 705), or speed of processing (visual search and identification; n = 712); or a no-contact control group (n = 704). For the 3 treatment groups, 4-session booster training was offered to a 60% random sample 11 months later.\n Cognitive function and cognitively demanding everyday functioning.\n Thirty participants were incorrectly randomized and were excluded from the analysis. Each intervention improved the targeted cognitive ability compared with baseline, durable to 2 years (P<.001 for all). Eighty-seven percent of speed-, 74% of reasoning-, and 26% of memory-trained participants demonstrated reliable cognitive improvement immediately after the intervention period. Booster training enhanced training gains in speed (P<.001) and reasoning (P<.001) interventions (speed booster, 92%; no booster, 68%; reasoning booster, 72%; no booster, 49%), which were maintained at 2-year follow-up (P<.001 for both). No training effects on everyday functioning were detected at 2 years.\n Results support the effectiveness and durability of the cognitive training interventions in improving targeted cognitive abilities. Training effects were of a magnitude equivalent to the amount of decline expected in elderly persons without dementia over 7- to 14-year intervals. Because of minimal functional decline across all groups, longer follow-up is likely required to observe training effects on everyday function.", "After having screened the cognitive functions in 103 institutionalized elderly subjects in Terni, a sample affected by mnemic deficit was obtained so as to verify the use of mnemotechniques on the same. Generally the findings show an improvement in cognitive performance in those treated which leads to suppose that our patients were affected by apparent cognitive deficits rather than real ones, supporting in any case the use of neuropsychological rehabilitative treatment in institutionalized subjects.", "Memory intervention research with older adults has primarily focused on immediate effects of training. Little is known about whether memory training can prevent forgetting of a learned material over time.\n The main purpose of this study was to investigate the effects of memory training on forgetting of numerical information in old age. In addition, the effect of speed of learning on forgetting rate was examined.\n Two training programs were employed contrasting a number-consonant mnemonic strategy with a self-generated strategy. A non-practice control group was also included. There were 20 participants in each group (age range=60-83 years). Following completion of training, participants memorized six 4-digit numbers to perfection. Retention was tested after 30 min, 24 h, 7 weeks, and 8 months.\n The three groups showed equal rates of forgetting across the first two follow-up assessments. A different picture emerged for the last two occasions, with the self-generated strategy group remembering more items relative to the two other groups. Moreover, participants reaching the criterion in few trials exhibited less forgetting than slow learners.\n These data indicate that self-generated strategy training may have advantages over learning a classical mnemonic for preventing long-term forgetting of numeric materials in old age.\n Copyright (c) 2005 S. Karger AG, Basel.", "This study examined the effectiveness of a self-taught program of memory-skills training for older adults complaining of memory difficulties in an immediate-treatment/waiting-list design. Analyses of covariance of measures of memory performance, memory evaluation (complaints), and a self-rating depression scale revealed a significant impact of training on memory performance but not on memory complaints or symptoms of depression. Subsequent evaluation of the waiting-list group, which was provided training after participation in the initial portion of the study, provided a partial replication of the design. The pattern of results was remarkably consistent with that obtained in the controlled evaluation of the training program. Finally, those complaining of memory problems were compared with a group of noncomplaining older adults. The two groups were comparable in memory performance and depression scores. Thus, memory complaints do not appear to reflect, systematically, memory problems or depression.", "The aim of this study was to compare the effects of aerobic and mental training on cognitive function and to determine if the association of the two techniques shows better results. Thirty-two healthy elderly subjects (60 - 76 years) were assigned to one of four groups: aerobic training, mental training, combined aerobic and mental training and a control group. All subjects took two cognitive tests and an incremental exercise test before and after the training period. The intensity of exercise was individualized at the heart rate corresponding to the ventilatory threshold of each subject. After two months, the control group showed no alteration in physiological and cognitive variables. After the training period, the results showed a significant improvement in VO(2)max (F = 4.45, DF = 1, p < 0.05) of 12 % and 11 % in aerobic training and combined aerobic and mental training groups, respectively. Logical memory (F = 4.31, DF = 1, p < 0.05), as well as paired associates learning scores (F = 5.47, DF = 1, p < 0.05) and memory quotient (F = 6.52, DF = 1, p < 0.01) were significantly improved in the three trained groups. The mean difference in memory quotient between pre and post training was significantly higher in the combined aerobic and mental training group compared to aerobic training or mental training groups (F = 11.60, DF = 3, p < 0.001). We conclude that the specific aerobic training and mental training used in this study could induce the same degree of improvement in cognitive function and that combined training seemed to lead to greater effects than either technique alone.", "'Mild cognitive impairment' (MCI) in older adults refers to a significant decline in memory function but not other cognitive functions. Pharmacological and non-pharmacological treatments for MCI are needed. The present randomized clinical trial tests the efficacy of a cognitive and behavioral treatment to improve memory performance and participants' attitudes about their memory. A multi-faceted intervention that included education about memory loss, relaxation training, memory skills training, and cognitive restructuring for memory-related beliefs was compared to a no-treatment control condition. Outcomes included memory performance and appraisals of memory function and control. Results indicate that the treated group had significantly better memory appraisals than controls at the end of treatment and at a six-month follow-up. There were no differences between groups on memory performance at post-test but at follow-up the trained individuals showed a trend toward better word list recall than controls. Findings suggest that individuals with MCI can benefit from multi-component memory enhancement training. Further development of such training programs and tests of their efficacy alone and in combination with medications are needed.", "One hundred twenty-eight elderly adults were recruited to assess the effects of affective judgment, imagery, and relaxation pretraining on mnemonic training. Participants were assigned to one of the following conditions: (1) visual imagery and affective judgment pretraining plus mnemonic training, (2) visual imagery pretraining only plus mnemonic training, (3) relaxation pretraining plus mnemonic training, (4) nonspecific pretraining plus mnemonic training, (5) nonspecific pretraining only, and (6) wait list. Subjects were tested at three times: prior to training (Time 1), following pretraining (Time 2), and at the conclusion of mnemonic training (Time 3). Although those receiving active pretraining plus mnemonics did not differ from one another at Time 3, they recalled more than those with no active pretraining. The results suggest that for mnemonics to be effective they should be coupled with active pretraining techniques.", "This study examined the effects of memory training on the relationship between perceived recall confidence and recall performance. The sample consisted of 76 elderly, community dwelling volunteers. Fifty-nine individuals received eight hours of memory training; the remaining 17 were wait-list controls. Participants were tested at pre- and post-intervention, and rated their confidence for recall of name-face pairs prior to each testing. The results showed a significant improvement in name-face recall at post test, favoring the group receiving mnemonic training. There was a significant association found between confidence ratings and recall performance at post-test. A closer examination of standardized regression residuals (confidence ratings and number of name-face pairs recalled) revealed that with mnemonic training, there was an improvement in the relationship between perceived confidence and recall performance following mnemonic training. The results suggest that the ability to assess changes in recall capacity and to judge future memory performance is enhanced by exposure to mnemonic training.", "Research on non-pharmacological therapies (cognitive rehabilitation) in old age has been very limited, and most has not considered the effect of interventions of this type over extended periods of time.\n To investigate a new cognitive therapy in a randomized study with elderly people who did not suffer cognitive impairment.\n The efficacy of this therapy was evaluated by means of post-hoc analysis of 238 people using biomedical, cognitive, behavioural, quality of life (QoL), subjective memory, and affective assessments.\n Scores for learning potential and different types of memory (working memory, immediate memory, logic memory) for the treatment group improved significantly relative to the untreated controls.\n The most significant finding in this study was that learning potential continued at enhanced levels in trained subjects over an intervention period lasting two years, thereby increasing rehabilitation potential and contributing to successful ageing.", "Normal aging is associated with progressive functional losses in perception, cognition, and memory. Although the root causes of age-related cognitive decline are incompletely understood, psychophysical and neuropsychological evidence suggests that a significant contribution stems from poorer signal-to-noise conditions and down-regulated neuromodulatory system function in older brains. Because the brain retains a lifelong capacity for plasticity and adaptive reorganization, dimensions of negative reorganization should be at least partially reversible through the use of an appropriately designed training program. We report here results from such a training program targeting age-related cognitive decline. Data from a randomized, controlled trial using standardized measures of neuropsychological function as outcomes are presented. Significant improvements in assessments directly related to the training tasks and significant generalization of improvements to nonrelated standardized neuropsychological measures of memory (effect size of 0.25) were documented in the group using the training program. Memory enhancement appeared to be sustained after a 3-month no-contact follow-up period. Matched active control and no-contact control groups showed no significant change in memory function after training or at the 3-month follow-up. This study demonstrates that intensive, plasticity-engaging training can result in an enhancement of cognitive function in normal mature adults.", "The purpose of this study was to examine the effects of a multifactorial memory training program designed for normal older adults. The multifactorial program involved the training of three components that are critical to memory functioning: recoding operations, attentional functions and relaxation. Two controls groups were used. One control group took part in a general cognitive activation program involving training in problem solving, logical thinking, and visuospatial skills, whereas the other received no training. Three types of tasks were administered to assess potential effects of training: (a) free recall of words within the Buschke selective reminding paradigm, (b) digit span, and (c) the Benton visual retention test. Results indicated that the multifactorial group improved performance following training on several measures of the selective reminding task, and that this improvement was maintained 6 months after completion of training. In addition, the two other groups did not show any improvement of memory performance, and no effects occurred in the digit span and visual retention tasks. This pattern of results suggests that multifactorial training may be an effective way of achieving long-term benefits of training for older people, and that effects of memory training may be relatively task-specific.", "The purpose of the study was to develop a multifactorial memory enhancement program for community-dwelling older adults aimed at encouraging positive beliefs and behaviors about memory function and abilities in later life. The study evaluated the effectiveness of cognitive restructuring techniques (56 subjects) as compared to traditional memory training techniques (61 subjects) for purposes of enhancing memory performance. Posttest assessments were conducted after 10 weeks of memory training. Follow-up assessments were conducted 9 weeks later to assess maintenance of memory performance and memory beliefs. Three 2 x 3 (Treatment x Time) repeated measures multivariate analyses of variance were conducted to evaluate the effects of two types of intervention on memory performance, memory perception, and affective symptomatology over time. Results suggest that cognitive restructuring techniques may help community-dwelling older adults gain control over their beliefs about memory and thereby enhance their memory performance.", "The aim of this study was to assess the influence of drug therapy (DT) with pramiracetam and memory training (MT), each alone, and in combination (DTMT), on both the objective memory and metamemory performance. Thirty-five non-depressed, non-demented healthy elderly (mean age: 64.8 years) with objective (story recall) and/or subjective (cognitive difficulties scale) memory loss were randomly included in four open-label conditions: an MT condition (n = 10), a DT condition (n = 8), a DTMT condition (n = 10), and a control (CTR) condition (n = 7). MT and DTMT subjects participated in 12 real-life tutor-guided MT sessions, once weekly, each lasting 1.5 hrs. The subjects were tested for objective (Randt memory test) and subjective (Sehulster metamemory scale; memory functioning questionnaire) memory proficiency prior to (t(0)) and shortly after treatment (t(1)). Results showed that objective memory gains of the two groups receiving pramiracetam were significantly larger than that of the MT and CTR groups. The ranking order in terms of decreasing score improvements was DTMT - DT - MT - CTR. Metamemory, on the other hand, displayed only a trend to between-group differences with opposite patterns for the DT and DTMT groups. In the DT group, the level of depression, negatively interfered with metamemory but not with actual memory performance. The present findings stress, once again, the complex relationships between memory, metamemory and affective status, which may be differently modified by DT and MT.", "Previously validated methods of memory training were used in conjunction with the Folstein Mini-Mental State Examination (MMSE) to explore the relationship between complexity of learned mnemonic, aging, and subtle cognitive impairment. Subjects were 218 community-dwelling elderly. Treatment included imagery mnemonics for remembering names and faces and lists. There was a significant interaction among age, type of learning task (face-name vs. list), and improvement when controlling for MMSE score. There was also a significant interaction among MMSE score, type of learning task, and improvement when controlling for age. Scores on the more complex list-learning mnemonic were more affected by age and MMSE scores than were scores on the face-name mnemonic. Implications of the findings for cognitive training of the old old and the impaired are discussed." ]

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[ "Sublingual versus vaginal misoprostol (400 microg) for cervical priming in first-trimester abortion: a randomized trial.", "Intracervical administration of prostaglandin E2-gel prior to therapeutic abortion: a prospective randomized double-blind study.", "Cervagem/Dilapan for preoperative cervical dilatation prior to vacuum aspiration for termination of first trimester pregnancy. A prospective randomized study.", "A randomized double blind study of a new ready-for use prostaglandin gel (Org 2436) for cervical ripening prior to first trimester pregnancy termination.", "Efficacy of progesterone antagonist RU486 (mifepristone) for pre-operative cervical dilatation during first trimester abortion.", "A randomized controlled comparison of sublingual and vaginal administration of misoprostol for cervical priming before first-trimester surgical abortion.", "A randomized controlled trial of laminaria, oral misoprostol, and vaginal misoprostol before abortion.", "Sublingual misoprostol before first trimester abortion: a comparative study using two dose regimens.", "A randomized study comparing the use of sublingual to vaginal misoprostol for pre-operative cervical priming prior to surgical termination of pregnancy in the first trimester.", "The effect of oral versus vaginal misoprostol on cervical dilatation in first-trimester abortion: a double-blind, randomized study.", "The use of misoprostol for pre-operative cervical dilatation prior to vacuum aspiration: a randomized trial.", "Randomized comparison of different prostaglandin analogues and laminaria tent for preoperative cervical dilatation. World Health Organization Special Programme of Research, Development and Research Training in Human Reproduction: Task Force on Prostaglandins for Fertility Regulation.", "Cervical dilatation with sulprostone prior to vacuum aspiration. A two-dose, randomized study.", "Cervical dilatation with 16,16-dimethyl-trans-delta 2-PGE1 methyl ester (Cervagem) prior to vacuum aspiration. A double-blind, placebo-controlled randomized study.", "The cervix-ripening effect of 15-methyl-prostaglandin F2 alpha methyl ester before vacuum aspiration for termination of early pregnancy in primigravidae.", "Oral misoprostol versus placebo for cervical dilatation before vacuum aspiration in first trimester pregnancy.", "A randomized trial of laminaria tents versus vaginal misoprostol for cervical ripening in first trimester surgical abortion.", "Preoperative cervical priming by intracervical application of a new sulprostone gel.", "Comparative study of various intracervically administered PG gel preparations for termination of first trimester pregnancies.", "Sublingual compared with oral misoprostol for cervical dilatation prior to vacuum aspiration: a randomized comparison.", "The use of oral misoprostol for pre-abortion cervical priming: a randomised controlled trial of 400 versus 200 microg in first trimester pregnancies.", "Oral versus self-administered vaginal misoprostol at home before surgical termination of pregnancy: a randomised controlled trial.", "Magnesium sulphate and cervical ripening (a biomechanical double-blind, randomized comparison between a synthetic polyvinyl sponge with and without magnesium sulphate).", "Preoperative cervical dilatation: a trial of laminaria tents and prostaglandin F2 alpha gel.", "Cervical priming with prostaglandin E1 analogues, misoprostol and gemeprost.", "Oral misoprostol versus vaginal gemeprost for cervical dilatation prior to vacuum aspiration in women in the sixth to twelfth week of gestation.", "Oral versus vaginal misoprostol administered one hour before surgical termination of pregnancy: a randomised controlled trial.", "[Use of a new vaginal suppository: prostaglandin E1 analog Gemeprost for cervix maturation prior to abortion in the 1st trimester].", "Effect of misoprostol for cervical ripening prior to pregnancy interruption before twelve weeks of gestation.", "Cervical priming with sublingual misoprostol vs. 15-methyl-prostaglandin F2alpha prior to surgical abortion.", "Sublingual misoprostol for preabortion cervical ripening in first-trimester pregnancy termination.", "Induced cervical ripening with Mifepristone in first trimester abortion. A double-blind randomized biomechanical study.", "Cervical priming before first trimester aspiration abortion: a single blind study comparing gemeprost 1 mg and prostaglandin E2 10 mg pessaries.", "Vaginal misoprostol for pre-abortion cervical priming: is there an optimal evacuation time interval?", "Preoperative cervical dilatation with 15 (S) 15 methyl prostaglandin E2 methyl ester in first trimester nulliparae. A double blind study.", "Randomised controlled study comparing oral and vaginal misoprostol for cervical priming prior to surgical termination of pregnancy.", "Effect of mifepristone on dilatation of the pregnant and non-pregnant cervix.", "Mifepristone versus vaginally administered misoprostol for cervical priming before first-trimester termination of pregnancy: a randomized, controlled study.", "Pre-operative cervical dilatation in termination of first trimester pregnancies using 16, 16-dimethyl-trans-delta 2 PGE1 methyl ester vaginal pessaries.", "A comparison of osmotic dilators, Lamicel and Dilapan, and a prostaglandin E1 analogue, gemeprost, for ripening the cervix before legal abortion.", "A randomized comparison of sublingual and vaginal misoprostol for cervical priming before suction termination of first-trimester pregnancy.", "Comparison of vaginal misoprostol and gemeprost as pre-treatment in first trimester pregnancy interruption.", "Comparison of oral and vaginal misoprostol for cervical ripening before manual vacuum aspiration of first trimester pregnancy under local anesthesia: a randomized placebo-controlled study.", "Oral versus vaginal misoprostol for cervical priming in first-trimester abortion: a randomized trial.", "Gemeprost versus misoprostol for cervical priming before first-trimester abortion: a randomized controlled trial.", "Randomised controlled trial of the efficacy of misoprostol used as a cervical ripening agent prior to termination of pregnancy in the first trimester.", "Preoperative administration of prostaglandin to avoid dilatation-induced damage in first-trimester pregnancy terminations." ]

[ "Our objective was to compare the sublingual administration and the vaginal administration of misoprostol for cervical priming before first-trimester surgical abortion.\n We used an open, multicenter, randomized trial.\n We conducted the study in four clinics (in Valencia, Castelló, Murcia and Murcia Capital) in Spain.\n A total of 1424 healthy pregnant women with amenorrhea of <or=84 days who voluntarily decided to terminate their pregnancy participated in the study.\n Women were randomly assigned to receive a single dose of 400 microg of misoprostol either sublingually or vaginally 1-3 h before aspiration.\n The outcome measures assessed were cervical dilation before surgery and surgical time needed for aspiration. The incidence of side effects, such as nausea, vomiting, diarrhea, fever/chills and paresthesia, was evaluated.\n The mean cervical dilation achieved was 6.8+/-0.8 and 6.7+/-0.9 mm for the sublingual and vaginal groups, respectively. The mean surgical time was 7.0+/-2.8 and 7.4+/-2.5 min for the sublingual and vaginal groups, respectively. Nausea, vomiting and diarrhea were more frequent in the sublingual group.\n Both regimens had equal efficacy; however, the sublingual route caused more side effects.", "Forty primigravid women due to undergo first trimester termination of pregnancy were randomly selected for intracervical application of 1 mg prostaglandin E2 in gel or gel only as placebo. In the PGE2-gel group, a marked dilatation of the cervical canal was obtained, with post-gel treatment mean Hegar dilatation of 11.18 mm in that group, compared to 4.4 mm in the control group (P 0.001). Moreover, 16 (80%) patients in the PGE2-gel group had a complete abortion, one (5%) patient had an incomplete abortion and in the remaining three (15%) patients, fetal demise was observed. The mean induction-abortion interval in this group was 7.5 h. In the placebo group, none of the above effects were observed. The only side effect noted was vomiting, which occurred in five (25%) of the patients in the PGE2-gel group. Termination of pregnancy was found to be easier in the PGE2-gel group, compared to the placebo group.", "The present study included 40 healthy nulliparous women admitted to the hospital for termination of first trimester pregnancy. The patients were randomly allocated to two study groups. One group was treated for 4 hours with one 1 mg Cervagem vaginal suppository prior to vacuum aspiration, the other was treated 4 hours with a Dilapan osmotic dilator intracervically. The patients were continuously supervised during treatment and after operation. Side effects and analgesic consumption were recorded. At operation the degree of cervical dilatation, blood loss and operative complications was registered. Dilapan was more effective and more uniform in dilating the cervix (p less than 0.05) and eventual further dilatation was easier (p less than 0.05). The blood loss was higher in the Dilapan-treated group (p less than 0.05). Side effects of postoperative pain and use of analgesic injections were higher in the Cervagem group (p less than 0.05). It is concluded that both methods are effective in dilating the cervix prior to vacuum aspiration, with Dilapan being the more effective dilator with the lower frequency of side effects.", "In a placebo-controlled double-blind randomized study involving 50 primigravidae scheduled for termination of first trimester pregnancy 500 micrograms PGE2 gel or placebo gel were applied intracervically 6 hours before curettage. The priming effect was verified in all patients by means of comparative examinations with a special tonometer before application of the gel and immediately before the surgical procedure. No abortion or vaginal bleeding occurred in any of the patients. After 500 micrograms PGE2 gel the mean free passability (i.e. force less than or equal to 1 Newton) was 7.8 (+/- 2.0) mm, the corresponding value for the placebo group 5.2 (+/- 1.2) mm (p less than 0.0001). The prostaglandin pretreatment led to a significant increase in dilation of 5.9 +/- 2.3 mm versus 2.0 +/- 1.2 mm in the placebo group (p less than 0.0001). 17 of the 25 PGE2-treated patients complained of lower abdominal pain, gastrointestinal side effects were observed in one of these patients. In the placebo group there were no undesired concomitant symptoms. No intra- or postoperative complications occurred in the PGE2 gel-treated group. After application of the placebo gel cervical lesions and incomplete curettages were demonstrated in 4 cases. According to this preliminary experience, the intracervical application of the new ready-for-use-PGE2 gel represents a practicable and efficient method for preoperative cervical priming. In view of the intraoperative complications in the placebo group the frequency of side effects after PG application are within tolerable limits.", "A randomized double-blind study (RU486 versus placebo) was carried out in order to investigate whether a progesterone antagonist facilitated surgical abortion in the first trimester of pregnancy. The consistency of the cervix changed significantly after RU486 (P less than 0.02). We conclude that this effect may facilitate cervical dilatation, making first trimester abortion under local anaesthesia more comfortable and less dangerous.", "The purpose of this study was to compare the effectiveness of the sublingual and vaginal administration of misoprostol for cervical priming before surgical termination of pregnancy.\n In a randomized controlled trial, 74 primigravid women who were undergoing surgical abortion were assigned randomly to receive misoprostol (400 microg) sublingually or vaginally.\n There was no statistically significant difference in the cumulative force that was required to dilate the cervix to 9 mm, for baseline cervical dilatation, for priming to abortion interval, for operating time, or for intraoperative blood loss between the two groups. Women in the sublingual group had more nausea (P=.008), vomiting (P=.01), diarrhea (P=.01), and unpleasant mouth taste (P=.0001) compared with the women in the vaginal group. In the sublingual group, 65% of women were satisfied with the route of misoprostol administration compared with 78% in the vaginal group (P=.11). Most of the staff members (84%) said that they would recommend the sublingual administration of misoprostol (P=.0001).\n The sublingual administration of misoprostol is an effective alternative to vaginal administration for cervical priming before surgical abortion; despite a higher incidence of side effects, there was high patient and staff acceptability.", "To compare the efficacy and acceptability of oral misoprostol, vaginal misoprostol, and laminaria tents for cervical dilation before surgical abortion.\n We conducted a randomized, double-blind, placebo-controlled trial comparing oral misoprostol 400 microg, vaginal misoprostol 400 microg, and one medium laminaria for dilating the cervix over 4 hours before surgical abortion. The study sample consisted of 106 women at 7-14 weeks' gestation who presented to San Francisco General Hospital requesting abortion. The primary outcome was the amount of cervical dilation measured by Pratt dilators. Secondary outcomes were the proportion of subjects needing further manual dilation, difficulty of dilation, duration of the procedure, blood loss, and side effects.\n The vaginal-misoprostol group had a significantly greater mean dilation (28.0 mm) than the oral misoprostol group (24.2 mm; P < .05) and a greater mean dilation than the laminaria group (25.9 mm), although this difference did not reach significance. Women who received laminaria reported significantly more pain at the time of placement (85.7% reported at least \"a little\" pain) compared with women who received misoprostol by either route (28.9% of oral-misoprostol and 34.0% of vaginal-misoprostol subjects reported \"a little\" pain; P < .01). The proportion of subjects who required further manual dilation, ease of dilation, duration of the procedure, and blood loss were not significantly different among the groups. There was no difference in side effects during the 4-hour waiting period among the three groups, and gastrointestinal side effects were rare in all groups.\n Vaginal misoprostol is superior to oral misoprostol and is an acceptable alternative to laminaria tents for cervical dilation before surgical abortion in pregnancies of 7-14 weeks' gestation. It is inexpensive and easy to administer, and achieves equal or greater dilation with less pain on insertion and no increase in side effects compared with laminaria.", "Various methods have been described for preoperative cervical priming prior to vacuum aspiration (VA) in first trimester pregnancy termination, to facilitate cervical dilatation and shorten the abortion procedure. Recently misoprostol a prostaglandin E1 analogue has been shown to be effective in facilitating cervical dilatation prior to VA. Misoprostol offers several advantages over the other prostagland in analogues including stability at room temperature, ease of administration and minimal side effects.\n To determine the optimal dosage and dosing interval for the use of misoprostol administered sublingually for pre-abortion cervical dilatation.\n This was a prospective randomised study conducted at Comprehensive Rural Health Project, Ballabgarh the rural health centre under Centre for Community Medicine, AIIMS, New Delhi.\n One hundred and twenty pregnant women between 6-11 weeks of gestation opting for voluntary medical termination of pregnancy were (MTP) randomly allocated to either 200 microg or the 400 microg misoprostol group. Vacuum aspiration was performed either two or three hours after administration of sublingual misoprostol. Using Hegar's dilators, degree of cervical dilatation before vacuum aspiration was measured. Other parameters assessed included the amount of additional dilatation required, intra-operative blood loss and associated side effects.\n Statistical analysis was conducted using chisquare, the student's t and the Mann-Whitney U tests to examine the difference between the two groups.\n In the 200 microg misoprostol group 33% achieved a dilatation of > or = 8 mm compared with 71% of women in the 400 microg misoprostol group. The odds ratio was 95.8 (95% CI 10.2-842.9) for 400 microg misoprostol for successful preoperative cervical dilatation of > or = 8 mm. The mean baseline cervical dilatation for 400 microg and 200 microg misoprostol was 8.2 mm and 6.0 mm respectively (P < 0.001). The use of 400 mg misoprostol with an evacuation interval of two hours appears to be the optimal dosage and evacuation interval. Increasing the time interval beyond two hours did not confer any additional advantage on the rate of successful cervical dilatation but was instead associated with an increased incidence of side effects such as preoperative vaginal bleeding, abdominal pain and shivering.\n Our study has shown that Sublingual administration of 400 microg of misoprostol at least two hours before procedure is effective for preoperative cervical dilatation before vacuum aspiration in first trimester pregnancy termination. There is no additional advantages of increasing the dosing interval upto three hours.", "Misoprostol is an effective agent for pre-operative cervical priming before surgical termination of pregnancy in the first trimester. Previous studies have shown that both oral and vaginal routes are equally effective for such a purpose. This study aimed to compare a new route of sublingual administration to the vaginal route of administration for pre-operative cervical priming in first trimester surgical abortion.\n Eighty women with gestational age <12 weeks were randomized by a computer-generated model to receive 400 micro g of misoprostol either sublingually or vaginally 3 h prior to vacuum aspiration. The primary outcome measure was the degree of cervical dilatation, and secondary outcomes included the force required to dilate the cervix from 3 to 8 mm, intra-operative blood loss and incidence of pre-operative side-effects.\n There was no significant difference in the baseline cervical dilatation (sublingual: 7.6 +/- 1.3 mm; vaginal: 7.7 +/- 0.73 mm), cumulative force required to dilate the cervix from 3 to 8 mm (sublingual: 9.0 +/- 9.8 N; vaginal: 6.6 +/- 5.4 N) and total blood loss (sublingual: 52.1 +/- 20.2 ml; vaginal: 48.3 +/- 12.3 ml). Pre-operative side-effects were also similar.\n Both sublingual and vaginal misoprostol are effective in cervical priming before surgical termination of pregnancy in the first trimester. Sublingual misoprostol has the advantage of being more convenient to administer and may be more suitable for day surgery.", "To determine the effect of oral versus vaginal misoprostol on cervical dilatation in first-trimester intrauterine evacuation or menstrual regulation (MR).\n A total of 120 patients were randomly assigned to a double-blind prestudy. Four groups, each consisting of 30 cases, were administered one of four regimens: 200 microg misoprostol orally, 200 microg misoprostol intravaginally, placebo orally, or placebo intravaginally, 10 h before MR, respectively. Age, number of births and abortions, birth methods, date of last delivery and last abortion were recorded. The gestational age was determined by ultrasonography. Prior to MR, data regarding the time of the application of the drug, the presence of placenta in the cervical canal, the degree of cervical dilatation, the duration of MR and patients' complaints were recorded. The MRs were performed by the same physician. The statistical analyses were evaluated with the chi(2) test and Fisher's exact test in the Aegean University Science Faculty Department of Statistics.\n In the oral misoprostol group, four patients had cervical bleeding and one had intracervical placenta. In the intravaginal misoprostol group, cervical bleeding was observed in seven patients and intracervical placenta was recorded in four cases. Cervical bleeding was observed in one case and intracervical placenta was also observed in one case in the oral placebo group. Cervical dilatation reached 8 mm in seven patients in the oral misoprostol group and in three patients in the intravaginal group, with none in the placebo group. Symptoms such as pelvic pain, headache and nausea were observed in 11 cases in the oral and 14 cases in the vaginal misoprostol groups.\n Different methods of misoprostol administration may not be equivalent in terms of efficacy and side-effects. Therefore, we decided to extend the study to include more patients so as to achieve statistically significant results.", "Misoprostol is effective for cervical priming prior to vacuum aspiration for first trimester termination of pregnancy. Previous studies showed that the oral route was more acceptable to patients but there were higher incidences of side-effects when compared with the vaginal route. This study is to determine the optimal dosage and route of administration of misoprostol for pre-operative cervical dilatation. A double-blind, randomized trial was undertaken for 225 nulliparous women with 8-12 weeks amenorrhoea. They were randomly assigned to groups given 0 (placebo), 200 or 400 microg oral or vaginal misoprostol 3 h prior to vacuum aspiration. In misoprostol-treated groups the baseline cervical dilatation was significantly increased when compared with the placebo group; the effect was dose-related in the oral but not in the vaginal group. The cumulative force and blood loss was significantly decreased in the misoprostol-treated groups. The incidences of side-effects were more frequent in misoprostol groups but were not related to the route and dosage of medication. The duration of procedure, incidences of post-operative complications, the duration of post-operative bleeding and the interval to the first period were similar in the five treatment groups. We conclude that a 3 h pre-treatment interval is effective for both oral and vaginal routes. When given orally, 400 microg is more effective than 200 microg. The efficacy was otherwise similar when compared with the vaginal route. We recommend 400 microg oral misoprostol 3 h prior to vacuum aspiration for cervical dilatation.", "In an eleven-centre study, 627 nulliparous subjects in the 8th to 12th week of gestation admitted for termination of pregnancy were allocated to one of five treatments to induce pre-operative cervical dilatation. The treatments were: 0.5 mg PGE2 methyl sulphonylamide; 1.0 mg PGE1 methyl ester; 30 mg 9-methylene PGE2 free acid, 0.5 mg 15-methyl PGF2 alpha; a single medium-sized laminaria tent. The results indicate that the three PGE analogues are at least equally effective as one medium sized laminaria tent and more effective than 0.5 mg 15-methyl PGF2 alpha in producing adequate pre-operative cervical dilatation prior to vacuum aspiration. It is concluded that both pre-treatment with prostaglandin analogues and laminaria tent are effective methods for preoperative cervical dilatation and both types of treatment are associated with a low incidence of side effects. Prostaglandin analogue treatment can be administered by paramedical personnel but laminaria tent insertion has to be performed by medical staff.", "In the article are presented the results of a randomized study comparing the efficiency and tolerance of 250 micrograms or 500 micrograms of 16-phenoxy-omega-17, 18,19,20-tetranor-PGE2 methyl sulfonylamide (Sulprostone) as a pretreatment to vacuum aspiration for termination of pregnancy in the 8th to 12th week of gestation. Two-hundred patients, mainly nulliparous, received either 250 micrograms or 500 micrograms Sulprostone intramuscularly three hours prior to vacuum aspiration. The patients were continuously supervised during treatment and during at least three hours after the operation. Side-effects and analgesic injections administered were recorded. At operation the degree of cervical dilatation, amount of blood loss and other operative complications were registered. Both doses of Sulprostone administered three hours prior to vacuum aspiration were equally effective in dilating the cervix and controlling the peroperative blood loss in late first trimester abortion patients. When the dose was doubled from 250 to 500 micrograms, no significant further dilatation of the cervix was achieved. Instead, there was an increase in the frequency of gastro-intestinal side-effects and the need for analgesic injection for relief of painful uterine contractions.", "In the article are presented the results of a randomized double-blind study comparing the efficacy and tolerance of vaginal administration of 1.0 mg 16,16-dimethyl-trans-delta 2-PGE1 methyl ester and placebo as a pretreatment to vacuum aspiration for termination of pregnancy in nulliparae in the 8th to 12th weeks of gestation. One-hundred and-twenty-six patients fulfilled all the criteria for acceptance in the study and received either 1 mg of the E analogue or placebo three hours prior to vacuum aspiration. The mean cervical dilation at operation was following treatment with the E analogue 6.5 mm and with placebo 4.9 mm (p less than 0.001). The number of patients requiring no further mechanical dilation or the dilatation was considered easy was significantly higher in the prostaglandin-treated group than in the placebo group (p less than 0.001). The mean blood loss at operation was also higher in the placebo group (p less than 0.001). Uterine pain was slightly more common following prostaglandin treatment (p less than 0.05) while gastrointestinal side effects occurred equally often in both groups. In two patients the uterine wall was perforated, both perforations occurring in the placebo group. Late complication rates were comparable between the two groups. It can be concluded that pretreatment with the E analogue accomplishes sufficient dilatation and softening of the cervix in most patients. The efficacy of the procedure and its low frequency of side effects and complications make the procedure useful for cervical dilatation prior to vacuum aspiration in late first trimester pregnancy.", "A double blind clinical trial on prostaglandin for cervix ripening prior to vacuum aspiration for termination of early pregnancy in primigravidae was carried out in 68 patients with 6-11 week's gestation. The patients were randomly treated with either 1.0 mg of 15-methyl-prostaglandin F2 alpha methyl ester vaginal suppository or a placebo suppository. A mean cervical dilation to 6.6 mm was achieved with minimal side effects in the prostaglandin group as against 4.3 mm in the placebo group. The 15-methyl-prostaglandin F2 alpha methyl ester suppository technique seems to be effective, safe and simple in ripening the cervix for termination of early pregnancy in primigravidae.", "Intravaginal misoprostol has been shown to be effective for cervical priming before a surgically induced abortion. The objective was to investigate the effectiveness of oral misoprostol in cervical dilatation prior to vacuum aspiration between the 6th and 12th weeks of pregnancy. The results showed that in nulliparous patients, the median cervical dilatation in the treatment group (7.8 mm) was significantly greater than that in the placebo group (3.7 mm). In multiparous patients, the difference was also statistically significant (9.8 versus 6.0 mm). The ease of dilatation, assessed subjectively by the operating surgeons, was significantly improved in the treatment group. There was also a significant reduction in the duration of the operation and in the mean blood loss in the treatment group. The side-effects encountered in the treatment group were mild and well accepted by the women. Oral misoprostol is an effective and safe method for cervical dilatation prior to vacuum aspiration in first trimester pregnancy.", "To compare the use of laminaria tents with misoprostol for cervical ripening prior to first trimester surgical abortion.\n In a prospective, open-label, randomized trial, 70 women were assigned to have either insertion of a 3 mm intracervical laminaria tent or vaginal misoprostol 200 microg on the day prior to suction dilatation and curettage (D and C). Cervical dilatation and operating time were measured at the time of D and C; the surgeon subjectively rated the ease of dilatation. The women were interviewed just prior to the D and C with regard to pain, vaginal bleeding, and dilator preference.\n Laminaria produced significantly (P < 0.001) greater pre-abortion dilatation of the cervix (34.8 Pratt +/- 6.2) than did misoprostol (28.4 Pratt +/- 5.8). There was no demonstrable difference in ease of dilatation or operating time. Women randomized to use of laminaria reported significantly more pain on insertion than did those who received misoprostol (P < 0.001). Conversely, misoprostol was associated with more vaginal bleeding (P < 0.01). Pain following insertion was similar in each group. Two patients aborted completely after misoprostol alone. Overall, the stated patient preference for cervical dilator was more likely to be misoprostol (P < 0.01).\n Laminaria tents are more effective cervical dilators than vaginal misoprostol when inserted the day prior to suction D and C. Vaginal misoprostol insertion is more comfortable, although it is associated with an increased risk of vaginal bleeding and may abort the pregnancy. Patient preference favours misoprostol. In patient-centred care, both laminaria and misoprostol are suitable options for cervical preparation prior to suction D and C.", "In a prospective, randomised dose-finding study involving 60 women scheduled for termination of 1st trimester pregnancy, 25 micrograms, 50 micrograms or 100 micrograms of a sulprostone gel with a constant injection volume of 2.5 ml were applied intracervically 6-8 hours before curettage. The gelatinising agent was Pluronic F 127, which is liquid at temperatures less than 20 degrees C but gelatinises immediately at body temperature. A sterile, ready-to-use gel can be produced within a minute by mixing the active substance with the gelatinising agent; this rules out any loss of activity due to storage of the substances. The priming effect was verified in 30 patients by means of comparative examinations with a special tonometer before application of the gel and immediately before the surgical procedure. The 100-micrograms dosage proved to be the most effective method in nulliparae, achieving a mean free patency (i.e. force less than 1 Newton) of 8.7 mm. In primiparae and multiparae, a comparable good effect was achieved with the 50-micrograms dose. After application of 25 micrograms sulprostone gel, the mean free patency was only 5.3 mm in the nulliparae and 8.5 mm in the primiparae and multiparae. The results of the tonometric studies agreed with the clinical documentation of the priming effect, which was assessed by means of a special score. The efficiency of the cervical priming correlated with the rate of vaginal bleeding and with the frequency of contraction-related lower abdominal pain. According to the present results, local application of this sulprostone gel represents a practicable and promising method for preoperative cervical priming because of its special electromechanical properties.", "In a randomized, double-blind study, 30 healthy, nulliparous women of similar gestational age were given intracervical applications of 0.5mg PGE2, 0.05mg Sulprostone or 0.1mg Sulprostone gel in order to soften the cervix prior to curettage for first trimester termination of pregnancy. The preparations were administered 8 hours before curettage. The number of complete and incomplete abortions, ease of passage through the cervical canal, as measured by a tonometer before and 8 hours after the administration of prostaglandin, the degree of pain experienced and the quantity of analgesics required, plus the frequency of systemic side effects were all always assessed by one trialist. With regard to the rate of abortion and cervical softening, the administration of 0.1mg Sulprostone gel proved the most effective method. However, in comparison with the others, it also caused the greatest degree of pain and necessitated the greatest use of analgesics. The softening effect of the prostaglandin E2 gel was significantly less and in this group there were two cases of cervical lesion due to tenaculum laceration. The intracervical application of 0.05mg Sulprostone gel is to be recommended for pre-operative ripening of the cervix before termination of pregnancy in the first trimester, as it effectively dilates the cervix and does not cause systemic side effects or pain in the lower abdomen, enough to make treatment necessary.", "The aim of the study was to compare the effect of oral and sublingual administration of misoprostol for cervical priming prior to vacuum aspiration. Thirty-two first-time-pregnant women with 8-12 weeks amenorrhea were randomly assigned to receive 400 microg misoprostol either orally or sublingually 3 h prior to surgery. The degree of baseline dilatation and the cumulative force needed for dilatation of the cervical canal did not differ between the two treatment groups. However, the number of patients in whom a strong force was needed was significantly higher following oral than following sublingual treatment. It was shown that sublingual administration is more effective than oral administration of misoprostol for cervical priming and is associated with less blood loss but a higher frequency of side effects.", "To compare the impact of 200 and 400 microg oral misoprostol on pre-operative cervical priming in both primi- and multigravidae prior to first trimester termination of pregnancy. Pre-operative cervical dilatation and bleeding were assessed.\n Randomised controlled trial.\n Norwegian university teaching hospital.\n Five hundred and fifty-one women undergoing surgical termination of pregnancy between 7 and 12 weeks of gestation.\n Patients were randomised to either 200 or 400 microg of oral misoprostol 10-16 hours before vacuum aspiration. The degree of cervical dilatation prior to abortion by vacuum aspiration was measured. Pre-operative bleeding and pain were recorded and vaginal bleeding was measured.\n Degree of pre-operative cervical dilatation and pre-operative bleeding.\n The mean cervical dilatation was 5.8 mm (SD 1.7) for the women who received 400 microg misoprostol and 5.4 mm (SD 1.4) for those who received 200 microg (P= 0.004). The pre-operative dilatation was larger in multigravidae than in primigravidae in both dosage groups. The odds ratio (OR) of pre-operative bleeding was 3.3 (95% confidence interval [CI] 2.1-5.0) in the 400 microg dosage group, as compared with the group receiving 200 microg misoprostol. The occurrence of bleeding was dose-dependent. Frequency of bleeding was similar in multigravidae compared with primigravidae in the 400 microg dosage group, whereas the occurrence of bleeding was less in primigravidae than multigravidae in the 200 microg dosage group. Only 89 out of 551 patients bled one or more grams. The volumes measured were not statistically significantly different. Complications were minor, and were distributed equally between the two dosage groups.\n The 200 microg oral misoprostol compared with the 400 microg oral misoprostol given 10-16 hours before first trimester surgical abortions results in less pre-operative vaginal bleeding and in a statistically, although not clinically significant reduction in cervical dilatation.", "To compare the impact of 400 mug oral versus self-administered vaginal misoprostol at home on pre-operative cervical priming in both primigravid and multigravid women prior to first trimester surgical abortion.\n Randomised controlled trial.\n Norwegian University Teaching Hospital.\n Three hundred and thirty-eight women undergoing surgical abortion between 7 and 12 weeks of gestation.\n The women were randomised to either 400 microg of oral misoprostol the evening before or 400-microg of self-administered vaginal misoprostol at home the same day as vacuum aspiration. Main outcome measures Pre-operative cervical dilatation, complications and acceptability.\n The median cervical dilatation was 6.2 mm (range 0-11 mm) for the women in the 400 mug oral misoprostol and 6.5 mm (range 0-11 mm) in the 400-microg vaginal misoprostol groups. The median pre-operative dilatation was larger in multigravidae (6.4 and 6.7 mm for the oral and vaginal routes, respectively) than in primigravidae (5.8 and 6.0 mm, respectively). In primigravidae, 19% achieved a pre-operative dilatation of > or = 7 mm, with no significant difference between oral and vaginal dosage. In multigravidae, 52% achieved a pre-operative dilatation of > or = 7 mm with vaginal dosage, compared with 36% with oral dosage (P = 0.03). There was no difference between non-immigrant versus immigrant women in pre-operative cervical dilatation. The 400-microg oral dosage group had a higher risk of bleeding, compared with the group receiving 400-microg vaginal misoprostol [odds ratio (OR) = 10.4; confidence interval (CI) 5.2-20.8]. There was no difference between non-immigrant and immigrant women in acceptability of self-administered vaginal misoprostol; almost all women found this administration route acceptable. Complications were minor and were distributed equally between the two dosage groups.\n The vaginal route will result in a satisfactory dilatation in about half of multigravidae but is much less effective in primigravidae. The oral route does not lead to satisfactory dilatation in either group and is associated with a higher occurrence of pre-operative bleeding. Self-administered vaginal misoprostol at home is highly acceptable.", "Lamicel is a commercially available synthetic polyvinyl sponge impregnated with magnesium sulphate (MgSO4), used to soften and dilate the cervix. To investigate whether magnesium sulphate contributes to the effect of Lamicel, forty-one pregnant nulliparous patients who underwent a first trimester abortion were allocated to three to four hours preoperative treatment with either Lamicel or the same type of tent without magnesium sulphate. The ripening effect on the cervix was measured biomechanically. Lamicel produced a cervical dilatation and ripeness equal to the syntetic tent without MgSO4. The two pretreated groups together showed a significantly (p less than 0.05) more favourable cervix compared to a control group of 40 patient.", "Surgical damage to the cervix in patients undergoing termination of pregnancy may be responsible for serious complications in subsequent pregnancies. Sixty nulliparous women undergoing first trimester termination of pregnancy were randomly allocated to 3 treatment groups, one using laminaria tents preoperatively, one using intracervical PGF2 alpha gel preoperatively and one using no pretreatment. Results showed clear benefits in the laminaria group, in terms of achieving preoperative cervical dilatation and ease of further operative dilatation. Laminaria tents were superior to PGF2 alpha gel which was, in turn, superior to no pretreatment. There were no differences in blood loss or postoperative complications among the 3 groups. Laminaria tents provide a cheap, effective and safe method of reducing the risk of cervical damage in women undergoing surgical termination of pregnancy.", "Although it is well established that cervical priming before surgically induced abortion reduces the incidence of complications, its use is infrequent and confined to groups perceived to be at high risk. We compared the effect of prostaglandin E1 analogues, gemeprost and misoprostol, on the cervix. Both induced clinical and histochemical changes that were significantly different from controls and were likely to have therapeutic value. Misoprostol, however, is cheap, easily stored, and associated with few side-effects. Cervical pre-dilation with misoprostol may be considered in all women having surgically induced abortions.", "The effectiveness of oral misoprostol versus vaginal gemeprost for cervical dilatation prior to vacuum aspiration was compared in women in the 6th to 12th week of pregnancy. Sixty-four nulliparous women requesting termination of pregnancy between 6th to 12th weeks of gestation were randomized to receive either 400 micrograms misoprostol orally or 1 mg vaginal gemeprost at 12 hr or 3 hr prior to vacuum aspiration, respectively. The cervical dilatation at vacuum aspiration, the ease of the subsequent surgical procedure, and the incidence of complications and side effects were compared between these two methods of cervical priming. The median cervical dilatation at vacuum aspiration in the misoprostol group was significantly greater than that in the gemeprost group (8.0 mm versus 7.0 mm, p < 0.02). Preoperative side effects were significantly less frequent in the misoprostol group (p < 0.01). The ease of dilatation assessed subjectively by the operating surgeons was also improved significantly in the misoprostol group (p < 0.01). However, the duration of operation and blood loss were similar in both groups. Since misoprostol is also much cheaper and more convenient to use, we conclude that oral misoprostol is better than vaginal gemeprost for cervical dilatation prior to vacuum aspiration in first trimester pregnancy.", "To assess the efficacy of oral and vaginal misoprostol as cervical priming agents administered 1 hour before first trimester surgical termination of pregnancy.\n A randomised controlled trial.\n Chelsea and Westminster Hospital, London.\n Pregnant women of 10 weeks or less gestation attending the termination of pregnancy clinic.\n Ninety eligible women were recruited to the study during September 2001 and September 2002. Women were randomised to one of the three groups: misoprostol administered orally (400 microg), misoprostol administered vaginally (800 microg) and standard care (no cervical priming agent) administered prior to surgical termination of pregnancy. Under general anaesthesia, and prior to the operation, a cervical tonometer was used to determine the main outcome measures.\n Baseline cervical dilatation and the cumulative force required to dilate the cervix from 3 to 9 mm.\n There was no significant difference in the mean baseline cervical dilation (P= 0.16) or the cumulative force required to dilate the cervix (P= 0.12) between the three randomised groups.\n No cervical priming effects were detectable with oral or vaginal misoprostol administered 1 hour before first trimester surgical termination of pregnancy.", "This double-blind study is concerned with the efficacy and safety of a new prostaglandin E1-analogue (16,16'-dimethyl-trans-delta 2PGE1-methylester) (Gemeprost) (ONO-802), which was administered as a single 1 mg vaginal pessary three hours prior to legal abortion. The efficacy of the prostaglandin was assessed by the largest size of the dilator meeting no resistance when inserted in the cervical channel. Furthermore, the quality of the cervix and the effort needed for further dilatation was evaluated. The average size of the cervix prior to dilatation was found to be 10 mm, in comparison to only 7 mm in the placebo-group (p less than 0.001). 80% of the patients of the Gemeprost group did not need any further dilatation, i.e. the dilatation procedure of the cervix was easier than in the group without treatment (19%). The incidence of uterine pain was more frequent in the Gemeprost group (40%) than in the Placebo group (7%). Analgesics were not required. The frequency of gastrointestinal side effects was rare in the Gemeprost group (13%) and in the Placebo group (11%) compared with other prostaglandins. By the preoperative application of a new prostaglandin E1-analogue (1 mg) prior to vacuum aspiration in the first trimenon of pregnancy sufficient softening of the cervix and a dilatation of the cervix was achieved. It significantly reduces the need for further mechanical dilatation of the cervix as well as the force needed to perform this dilatation. These effects reduce the trauma associated with mechanical dilatation and therefore diminish the risk of subsequent complications.", "Liberalization of the law in respect of legal abortions has led to a search for an appropriate technique for termination of pregnancy. The technique should be cheap, easy to perform and have minimal or no complications.\n To evaluate the effectiveness of performing manual vacuum aspiration (MVA) with and without the use of misoprostol to the procedure.\n Randomised control study.\n Obstetrics and Gynaecology Department, University of Natal Medical School, South Africa.\n One hundred and thirty six women were recruited; 70 women were assigned to the misoprostol group. Of these, 11 (15%) did not show any change in cervical score. Their mean cervical dilatation was similar to the control group (3.3 versus 31; p > 0.06). In the group whose gestational age was less than eight weeks, the time taken to complete the procedure, quantity of products of conception and cervical dilatation, were different from that of the control group, and this reached statistical significance except quantity of products of conception in primigravidae. In pregnancies greater than eight weeks gestation, all parameters assessed, such as cervical dilatation, quantity of products of conception was significantly different from the control group, in both multi- and primigravidae. Pain score was similar for all gestations.\n Misoprostol is of specific value during MVA for voluntary interruption of pregnancy.", "To compare the efficacy and tolerability of sublingual misoprostol with those of intramuscular 15-methyl-prostaglandin F2alpha (15-M-PG F2alpha) for cervical dilation prior to vacuum aspiration (VA) in first-trimester pregnancy termination.\n Sixty pregnant women requesting pregnancy termination between the 9th and 12th week were randomized to receive 400 microg of sublingual misoprostol or an intramuscular injection of 125 microg of 15-M-PG F2alpha 2 h prior to vacuum aspiration. Baseline cervical dilation prior to vacuum aspiration was measured using Hegar's dilators. Other variables assessed included procedure duration, intraoperative blood loss, and associated adverse effects. Patient acceptability was assessed by questionnaires completed at the time of discharge from the hospital.\n Mean cervical dilation at vacuum aspiration was significantly greater in the misoprostol group than in the 15-M-PG F2alpha group (8.8 vs. 7.6 mm; P<0.01), and preoperative adverse effects were significantly less frequent in the sublingual misoprostol group (P<0.05). However, procedure duration and intraoperative blood loss were similar in both groups. The acceptability rates were 93.3% in the sublingual misoprostol group and 76.6% in the 15-M-PG F2alpha group, respectively; however, 6.6% patients in the sublingual misoprostol group thought that the tablets had an unpleasant taste.\n Sublingual misoprostol appears to be an effective alternative to intramuscular 15-M-PG F2alpha for cervical dilation prior to vacuum aspiration in first trimester pregnancy. In addition, misoprostol is inexpensive and convenient to use and has higher patient acceptability rates.", "The objective of this prospective randomized placebo-controlled study was to determine the efficacy of sublingual misoprostol in facilitating cervical dilatation before surgical abortion in first trimester pregnancy. Sixty healthy pregnant women between 6 and 11 weeks of gestation opting for voluntary medical termination of pregnancy at All India Institute of Medical Sciences hospital were included in this study. Women were randomized to two groups, the study group (n = 30) received 400 micro g of sublingual misoprostol and the control group (n = 30) received placebo, 2 h prior to surgical abortion. Using Hegar's dilators, cervical dilatation prior to vacuum aspiration was measured. Other parameters assessed included the total time required for the procedure, intraoperative blood loss and associated side effects. The mean cervical dilatation in the misoprostol group was 7.7 mm as compared to 3.4 mm for placebo group. The average time required for pregnancy termination was significantly shorter (p < 0.001) in the misoprostol group. The procedure-related blood loss was also significantly decreased in the misoprostol group. However, side effects including pre-evacuation vaginal bleeding, lower abdominal pain, nausea and vomiting were significantly higher in the misoprostol group than in placebo group (p < 0.005). There was no case of hemorrhage or uterine perforation in either group. Sublingual misoprostol is effective in facilitating cervical dilatation prior to surgical abortion. Its usage significantly decreased the time of surgical evacuation and minimized blood loss during the procedure.", "Mifepristone (RU 486; Roussel-Uclaf, Paris, France) is an antiprogesterone used for termination of very early pregnancy. The ripening effect of Mifepristone on the human pregnant cervix was studied in 42 healthy women from 7 to 11 weeks gestation. The women were randomly allocated to oral treatment of either 100 mg Mifepristone or placebo for 24 and 12 hours before vacuum aspiration. An objective method has been designed to measure the force necessary to step-wise dilate the cervix from 4 to 11 mm. Significant (p less than 0.05) changes in the stiffness of the cervix were demonstrated in patients treated with Mifepristone, reflecting ripeness. The treatment was simple and had no side effects.", "nan", "To determine the optimal evacuation time interval in the use of vaginal misoprostol for cervical priming before first trimester termination of pregnancy.\n Prospective double-blind randomised study.\n Fertility Control Centre, National University Hospital, Singapore.\n Sixty healthy nulliparous women requesting legal termination of pregnancy between 6 and 11 weeks of gestation were randomly allocated to either the 400 microg or 600 microg misoprostol group. Vacuum aspiration was performed after three hours in the 400 microg group and at the end of two hours in the women given 600 microg misoprostol. Using Hegar's dilator, degree of cervical dilatation before operation was measured. Other parameters assessed included the amount of additional dilatation required (if < Hegar 8), pre-operative and intra-operative blood loss, and associated side effects.\n For the 600 microg group, only five women (16.7%) achieved a cervical dilatation of > or = 8 mm, compared with 28 women (93.3%) in the 400 microg group. Using the 400 microg misoprostol group as a baseline, the odds ratio was 0.014 (95% CI 0.003-0.080) for 600 microg for successful pre-operative cervical dilatation of > or = 8 mm. The mean cervical dilatation for 400 and 600 microg misoprostol was 8.1 mm and 6.6 mm, respectively (P < 0.001). Despite the shorter evacuation time interval of two hours, the 600 microg dose was associated with an increase in side effects such as vaginal bleeding, abdominal pain and a fever of > 38.0 degrees C. However, other than abdominal pain, no significant differences in the frequency of these side effects were shown.\n Use of 400 microg misoprostol with a minimal evacuation time interval of three hours still appears the optimal dosage and evacuation time for cervical priming before first trimester termination of pregnancy.", "nan", "To compare the effectiveness of oral misoprostol with vaginal misoprostol as a cervical priming agent prior to first trimester vacuum aspiration.\n Randomised study.\n Scottish teaching hospital.\n Primigravid women at gestations up to 91 days requesting surgical abortion under the 1967 Abortion Act.\n Sixty-four women were randomised to receive misoprostol 400 microg orally at home or vaginally in hospital 2-4 hours pre-operatively for cervical priming.\n The main outcome measures were cumulative force required to dilate the cervix to 9 mm, baseline cervical dilatation, intra-operative blood loss and patient and staff acceptability.\n There was no significant difference in baseline cervical dilatation, peak force required to dilate the cervix at 8 and 9 mm and cumulative force required between the two groups. Operating time and intra-operative blood loss were not significantly different between the two groups. The priming to abortion interval was significantly longer with oral misoprostol when compared with the vaginal group (P < 0.0001). Women receiving oral misoprostol were significantly more likely to experience nausea (OR: 3.9, 95% CI: 1.3 to 11.2), while women receiving vaginal misoprostol were more likely to complain of tiredness (OR: 0.2, 95% CI: 0.1 to 0.7) with no significant differences in other side effects between the two groups. There was no significant difference in patient acceptability in relation to the priming agent between the two groups (P = 0.96). However, majority of the nursing staff (83%) admitting women preferred the oral route of administration.\n Cervical priming with oral misoprostol at home is effective with high patient and staff acceptability.", "The effect of the progesterone antagonist mifepristone on the cervix was investigated in two randomised double-blind placebo-controlled trials, the first in 30 women undergoing first trimester surgical termination of pregnancy and the second in 30 non-pregnant premenopausal women. 600 mg mifepristone, given orally 48 h before surgery, increased the mean preoperative cervical dilatation in both pregnant and non-pregnant treatment groups and also reduced the force required to dilate the pregnant and non-pregnant cervix.", "This study was undertaken to compare the effectiveness of mifepristone orally administered at 24 or 48 hours before first-trimester vacuum aspiration abortion with that of vaginally administered misoprostol as a cervical priming agent.\n In a randomized comparative trial 90 women who requested surgical termination of pregnancy were randomly assigned to receive 200 mg mifepristone orally 24 or 48 hours before the operation or 800 microg misoprostol vaginally 2 to 4 hours before the operation. The main outcome measures were baseline cervical dilatation, cumulative force required to dilate the cervix to 9 mm, and intraoperative blood loss.\n The baseline cervical dilatation was significantly greater among women who received mifepristone 48 hours before the operation (P =.02). This group also required the least mechanical force to dilate the cervix (P =.06). There were no significant differences among the 3 groups in the intraoperative blood loss, in the operating time, or in patient acceptability. Side effects such as hot flushes and headaches were significantly higher among women who received mifepristone 24 or 48 hours before the operation than among those who received misoprostol (P =.01 and P =. 002, respectively).\n Mifepristone is an effective cervical priming agent when orally administered 48 hours before vacuum aspiration for termination of first-trimester pregnancy. Because of its cost and availability in comparison with misoprostol, however, selective use may have to be considered.", "The effect of a prostaglandin E1 analogue on the cervix prior to termination of first trimester pregnancy was studied in a double-blind placebo-controlled trial with 70 primigravid and 125 multigravid patients in the Hong Kong University Gynaecological Unit. One mg of 16, 16-dimethyl-trans-delta 2-prostaglandin E1 methyl ester (ONO 802) in the form of vaginal pessary was inserted 3 hours before vacuum aspiration. The cervical dilatation in patients receiving ONO 802 pessaries was significantly greater than that in patients who received no treatment or placebo pessaries but the difference in dilatation between patients who received no treatment or placebo was not significant. The blood loss during operation in patients receiving ONO 802 pessaries was also significantly less than that in patients receiving placebo pessaries. The side effects due to ONO 802 pessaries were mild and infrequent.", "66 primigravid women were allocated at random to receive either intravaginal application of the prostaglandin El analogue, gemeprost, or intracervical insertion of 1 of 2 osmotic dilators, Lamicel or Dilapan, 3 hours before legal abortion at 7-14 weeks gestation. Insertion of the dilators was not possible in 5 patients. All 3 methods were otherwise equally effective in achieving cervical dilatation and there was no difference in the need for or resistance to further dilatation between the 3 groups. Gemeprost was the most easily administered, and would be the most appropriate for routine preoperative use.", "This randomized trial compares the efficacy and side effects of sublingual and vaginal misoprostol for cervical priming before first-trimester pregnancy termination. One-hundred pregnant women between 6 and 12 weeks of gestation opting for termination of pregnancy by suction evacuation were included in this study. The women were randomly allocated into two groups. Group 1 received 400 microg of sublingual misoprostol and group 2 received 400 microg of vaginal misoprostol 2 h prior to suction evacuation. The abortion was carried out by suction evacuation using a Karman's cannula attached to an electrically operated suction machine under intravenous analgesia. Baseline cervical dilatation, duration of the procedure, operative blood loss, side effects and complications were noted in both groups. There was a significant difference between the sublingual and vaginal misoprostol groups with respect to mean cervical dilatation (8.6 mm vs. 6.8 mm, p < 0.05). However, the duration of the procedure (3.03 min vs. 3.16 min) and the amount of blood loss (29 mL vs. 31.2 mL) were not significantly different between the two groups. The women in the sublingual group experienced significantly more shivering and preoperative vaginal bleeding (68% vs. 56%, p < 0.05). None of the women in the two groups had either uterine perforation or excessive hemorrhage. In our study, sublingual misoprostol (400 microg) was significantly more effective in facilitating cervical dilation prior to surgical abortion than vaginal misoprostol.", "To compare the effectiveness of vaginal misoprostol pre-treatment with standard gemeprost pre-treatment in first trimester pregnancy termination.\n A prospective randomised study.\n One hundred and ninety-nine women scheduled for day case termination of pregnancy during the first trimester.\n Cervical priming with a vaginally applied 200 microg tablet of misoprostol for at least four hours, compared with a 1.0 mg vaginal suppository of gemeprost for at least three hours before vacuum aspiration.\n The prostaglandin effect on baseline cervical dilatation was the main outcome. Others were occurrence of pre-operative pain and need for analgesia, pre-operative side effects such as nausea, vomiting and diarrhoea, presence of blood in the vagina and blood loss during the operation.\n There was no significant difference in the dilatation ability of misoprostol or gemeprost, nor in the pre-operative use of analgesics. The frequency of nausea and diarrhoea was significantly less common in the misoprostol treated women.\n Vaginally applied misoprostol is as effective as gemeprost in cervical priming prior to first trimester vacuum aspiration. Misoprostol was associated with fewer side effects than gemeprost.", "The objective of this prospective randomized placebo-controlled study was to determine the effectiveness of 400 mug oral and 400 mug vaginal misoprostol administration for cervical priming 3 h prior to manual vacuum aspiration (MVA) under local anesthesia for voluntary termination of pregnancy before 10 weeks of gestation in comparison with placebo oral or placebo vaginal administration (n=40 in each group). Postmedication cervical dilatation was similar in the oral (mean, 6.6+/-1.5) and vaginal (mean, 7.2+/-0.8) misoprostol groups but significantly higher compared with the oral (mean, 3.4+/-0.2) and vaginal (mean, 3.6+/-1.9) placebo groups. Duration of the procedure was also significantly shorter in the misoprostol groups in comparison with their placebo counterparts. Preoperative bleeding and side effects were more common in the misoprostol groups, but none required medical intervention. Intraoperative bleeding was less in the vaginal misoprostol group compared with the placebo groups. There was no significant difference in terms of visual analogue scores during the procedure, patient satisfaction, days of postoperative bleeding and rate of postoperative complications among the groups. Cervical priming with misoprostol administered orally or vaginally 3 h before MVA for termination of pregnancy under local anesthesia facilitates the procedure by decreasing the need for cervical dilatation and by shortening its duration without improving patients' pain perception and satisfaction mainly due to side effects.", "The objective of this study was to compare the oral and vaginal administration of misoprostol for cervical priming before surgical abortion up to 63 days' gestation. A total of 900 pregnant women, with ages ranging from 18 to 42 years, who asked for pregnancy termination, were included in this study. Women were randomly allocated to one of the following groups: oral administration of 400 microg misoprostol, 8 h before aspiration; and vaginal self-administration of 400 microg misoprostol, 4 h before aspiration. During admission, all subjects were checked on a 15-min basis. The preoperative cervical dilatation achieved was the main outcome assessed. The cervix was dilated (Hegar > or = 8) in 348 (78%) subjects from the oral treatment group and in 391 (87%) women from the vaginal treatment group; this difference was statistically significant (p = 0.0004). The mean dilatation achieved in the oral treatment group was 8.1 mm (SD 1.6 mm) and it was 8.5 mm (SD 1.5 mm) in the vaginal treatment group; this difference was statistically significant (p = 0.0001). The frequencies of side-effects such as nausea, vomiting, diarrhea and chills reported by women from the vaginal misoprostol group were 10, 8, 18 and 4 times lower, respectively, than those reported by subjects from the oral misoprostol group. In conclusion, vaginal self-administration of misoprostol was the best administration route, as it obtained the same or greater priming effectiveness of the cervix in half the time with a much lower frequency of side-effects.", "To compare the efficacy of 400 microg of misoprostol with that of 1 mg of gemeprost as cervical priming agents when administered vaginally 3 to 4 hours before first-trimester vacuum aspiration abortion.\n In a prospective controlled trial 90 nulliparous women who requested termination of pregnancy before 12 weeks' gestation were randomized to receive vaginally either misoprostol or gemeprost for cervical priming. The force to dilate the cervix was measured by the use of a cervical tonometer connected to Hegar dilators from 3 to 10 mm. The main outcome measures were baseline cervical dilation; the peak force to dilate the cervix at 8, 9, and 10 mm; and the cumulative force to dilate the cervix to 10 mm.\n Baseline cervical dilation did not differ significantly between the women who received misoprostol and those who were treated with gemeprost. Neither the peak force required to dilate the cervix at 8, 9, and 10 mm nor the cumulative force to dilate the cervix to 10 mm showed any significant difference between the two groups.\n Vaginally administered misoprostol (400 microg) is as effective as gemeprost (1 mg) for cervical priming 3 to 4 hours before surgical termination of first-trimester pregnancies.", "Misoprostol is being used increasingly in clinical practice for cervical ripening in first-trimester abortions, but because of lack of good evidence of its effectiveness, administration consensus has not been reached on dosage, route of administration, time of administration pre-operatively and gestational age group. In this study we tested the hypothesis that self-administration of 600 micrograms vaginal misoprostol is feasible and when used 2-4 hours pre-operatively results in sufficient cervical dilatation to make suction curettage easier.\n A double-blind, randomised, placebo-controlled trial was undertaken. Two hundred and seventy-eight women scheduled for termination of pregnancy of up to 12 weeks' duration by manual vacuum aspiration were assigned to receive either 600 micrograms misoprostol pre-operatively, or placebo. The achievement of 'satisfactory' (> or = 7 mm) baseline cervical dilatation after 2-4 hours was evaluated as the primary outcome. Secondary outcome measurements included ease and duration of the procedure. Side-effects such as pre-operative bleeding, gastro-intestinal complaints and pain as well as adverse events were noted in all cases.\n Self-administration of vaginal misoprostol was successful in all women and 273 women were evaluated for main end-points. A significantly larger proportion of patients in the treatment group reached cervical dilatation of > or = 7 mm (67.3% v. 30.9%, P < 0.0001). The side-effects were minimal and comparable in the two groups. In the treatment group the mean procedure duration was significantly shorter (220 seconds v. 321 seconds, P = 0.0013) and the procedure was more likely to be rated by the operator as 'easy' (81.8% v. 63.3%, P = 0.0082). This resulted in a significant reduction in treatment failure in the < 70-day gestation group (5.0% v. 14.7%, P = 0.005).\n It is feasible, safe and effective for 600 micrograms misoprostol to be self-administered vaginally 2-4 hours pre-operatively for cervical priming prior to manual vacuum aspiration. Further research is needed to establish optimal use in the first trimester and to determine patient acceptance.", "A prospective, randomized, controlled study was carried out to investigate the dilating and softening effect on the cervix of prostaglandin F2-alpha gel administered intracervically and of prostaglandin E2 tablets administered orally. A total of 581 patients were included in the study: 149 received 2.5 mg prostaglandin F2-alpha in gel form intracervically, 150 received 1 mg prostaglandin E2 in tablet form orally, 138 were given placebo gel and 144 no medication at all. In the group given prostaglandin F2-alpha gel intracervically, success was achieved in 85.8% of patients and partial success in 8.8%. In the group given prostaglandin E2 tablets orally, the results were successful in 29.4% and partially successful in 40.6%. The incidence of side effects in the group given prostaglandin F2-alpha gel was rather high - 53%. The results show that prostaglandin can bring about a certain softening of the cervix, but side effects cannot be ruled out. Nevertheless, priming of the cervix is to be recommended in young primigravidas." ]

[ "6397454", "10592922", "1432432" ]

[ "The use of dopamine for the prevention of the renal side effects of indomethacin in premature infants with patent ductus arteriosus.", "Can dopamine prevent the renal side effects of indomethacin? A prospective randomized clinical study.", "Effect of dopamine on failure of indomethacin to close the patent ductus arteriosus." ]

[ "To determine if dopamine would prevent the renal side effects of indomethacin, fifteen preterm infants were randomized into two groups: seven received indomethacin alone, and eight received indomethacin together with low dose dopamine infusion. Infants who received indomethacin together with dopamine had significantly higher UV (p less than 0.005), CNa (p less than 0.005), Cosm (p less than 0.005) and FENA (p less than 0.005) than those of infants who received indomethacin alone. There was, however, no significant difference in Ccr and FNa between the groups. These data indicate that dopamine overcomes indomethacins renal side effects of tubular origin, but it cannot prevent the renal vasoconstrictive action of vasoconstrictor hormones following the inhibition of prostaglandin synthesis by indomethacin. Considering that RBF and GFR turn to normal approximately 12 hours after the last dose of indomethacin, and that with the use of dopamine systemic blood pressure and peripheral circulation can also be normalized and to some extent myocardiac contractility improved, low doses of dopamine can be used instead of furosemide in the sick preterm infant with PDA when indomethacin therapy is indicated.", "Indomethacin therapy for closure of a patent ductus arteriosus in preterm neonates is responsible for transient renal insufficiency. Dopamine theoretically reduces the renal side effects of indomethacin therapy.\n 33 neonates with a mean gestational age of 28.5 weeks who received indomethacin for treatment of a symptomatic PDA were included in a prospective randomized controlled clinical study.\n 15 patients were treated with indomethacin alone (control group), 18 patients with indomethacin and dopamine (study group). Indomethacin was given in a dose of 0.2 mg/kg/dose intravenously, all patients received three doses with intervall of 12 hours. The dose of dopamine was in all patients 4 micrograms/kg per minute commencing 2 hours prior to the first dose of indomethacin and continuing for 12 hours after the third dose.\n Indomethacin induced a significant increase in serum creatinin (76.3 mumol/l vs 99.7 mumol/l for the control group, and 70.7 mumol/l vs 93.0 mumol/l for the study group), and weight (1259 g vs 1316 g for the control group, and 1187 g vs 1221 g for the study group). The increase systolic blood pressure (61 mmHg vs 65.7 mmHg) in the study group was significant (p < 0.05) but remained unchanged in the control group. The changes between the study group and the control group were not significant either in serum creatinin, fractional excretion of sodium, or weight gain. The failure rate of ductal closure was not different between the two groups.\n The additional use of dopamine does not reduce the renal side effects of indomethacin.", "To test the hypotheses that administering dopamine before and concurrently with indomethacin therapy would (1) increase successful ductal closure rate, (2) act by maintaining a diuresis, and (3) prevent oliguria or high serum creatinine concentrations, we conducted a randomized, controlled trial in infants whose gestational age was <36 weeks and who had hemodynamically significant ductus arteriosus. Thirty-six infants were selected to receive a continuous infusion of either placebo or dopamine at either a low dosage of 2 micrograms/kg per minute or a higher dosage of 5 micrograms/kg per minute, beginning 6 hours before the use of indomethacin and continuing until 12 hours after the third dose of indomethacin. A total of 12 patients were selected to receive placebo, 14 were selected to receive \"low dopamine,\" and 10 were selected to receive \"high dopamine.\" The three groups were similar in their initial characteristics. Serum creatinine concentrations, urine output, and fractional excretion of sodium were not different in the three groups after indomethacin treatment. Two patients receiving placebo required a second course of indomethacin compared with four patients in the low-dopamine group and one in the high-dopamine group. The proportion of failures of medical treatment was not statistically different among the three groups. We conclude that concomitant dopamine therapy neither decreases the failure rate in indomethacin-treated infants nor reduces the magnitude of the indomethacin-induced oliguria." ]

[ "10428523", "17178185", "2972171", "9720832", "17434511", "8005305", "9389816", "10992178", "15656211", "10325289", "11679528", "17005086", "7977520" ]

[ "A gonadotrophin-releasing hormone agonist compared with expectant management after conservative surgery for symptomatic endometriosis.", "A randomized study comparing triptorelin or expectant management following conservative laparoscopic surgery for symptomatic stage III-IV endometriosis.", "Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis after conservative surgery.", "Pre or post-operative medical treatment with nafarelin in stage III-IV endometriosis: a French multicenter study.", "Hormonal suppression treatment or dietary therapy versus placebo in the control of painful symptoms after conservative surgery for endometriosis stage III-IV. A randomized comparative trial.", "Ovarian endometrial cysts: the role of gonadotropin-releasing hormone agonist and/or drainage.", "Use of nafarelin versus placebo after reductive laparoscopic surgery for endometriosis.", "Postoperative administration of monophasic combined oral contraceptives after laparoscopic treatment of ovarian endometriomas: a prospective, randomized trial.", "Short-term postoperative GnRH analogue or danazol treatment after conservative surgery for stage III or IV endometriosis before ovarian stimulation: a prospective, randomized study.", "Effects of 3 month therapy with danazol after laparoscopic surgery for stage III/IV endometriosis: a randomized study.", "Post-operative GnRH analogue treatment after conservative surgery for symptomatic endometriosis stage III-IV: a randomized controlled trial.", "Comparative study on the efficacy of Yiweining and Gestrinone for post-operational treatment of stage III endometriosis.", "Postsurgical medical treatment of advanced endometriosis: results of a randomized clinical trial." ]

[ "To ascertain whether the frequency of pelvic pain recurrence is reduced and time to symptoms recurrence is prolonged in women with symptomatic endometriosis undergoing conservative surgery and post-operative hormonal therapy compared with women treated with surgery only. Pregnancy rates and time to conception in women wanting children were also evaluated.\n A multicentre, prospective, randomised controlled study.\n Nineteen Italian academic departments and teaching hospitals specialising in reparative and reconstructive surgery.\n A total of 269 women undergoing conservative surgery for mild to severe symptomatic endometriosis.\n After surgery the women were assigned to treatment with subcutaneous goserelin depot injections for six months or to expectant management. Dysmenorrhoea, deep dyspareunia, nonmenstrual pain and general discomfort were graded according to a verbal rating scale from 0 (absent) to 3 (severe) and the scores summed to give a total symptoms score. Only patients with at least one preoperative moderate or severe symptom were enrolled. The women were evaluated regularly for two years.\n Post-operative pain recurrences (total symptoms scores > or = 5), time to recurrence, pregnancy rates and time to conception in the two study groups.\n At one- and two-year follow up visits, 14/107 (13.1%) and 19/81 (23.5%) patients had moderate or severe symptoms recurrence in the goserelin group compared with, respectively, 22/103 (21.4%) and 27/74 (36.5%) in the expectant management group (P = 0.143 at 1 year and 0.082 at 2 years). Time to symptoms recurrence was significantly longer in the goserelin group according to survival analysis (Wilcoxon test, P = 0.041). Among women wanting children, few conceptions occurred in both the goserelin (8/69, 11.6%) and the expectant management group (14/76, 18.4%). There was no significant difference at survival analysis (Wilcoxon test, P = 0.427).\n Post-operative treatment with goserelin significantly prolonged the pain-free interval after conservative surgery for symptomatic endometriosis and did not influence reproductive prognosis.", "To investigate the role of adjuvant treatment with gonadotropin-releasing-hormone agonist (GnRHa) following conservative surgical treatment of endometriosis.\n Sixty patients in the reproductive age (mean age 28.6 years), with symptomatic stages III and IV endometriosis following laparoscopic surgery and without previous hormonal treatment were enrolled in a prospective, randomized, controlled trial to compare the effects of 3-month treatment with triptorelin depot-3.75 i.m. (30 patients) versus expectant management using placebo injection (30 patients).\n Six patients (one in triptorelin group and five in placebo group) were lost at follow-up, the remaining 54 were suitable for analysis. Pelvic pain persistence or recurrence, endometrioma relapses and pregnancy rate were evaluated during a 5-year follow-up. The results of 29 cases treated with triptorelin and 25 that received placebo did not show significant differences in pain recurrence (P=1, RR=0.94, 95% CI=0.57-1.55), endometrioma relapse (P=0.67, RR=1.29, 95% CI=0.66-2.50), and pregnancy rate in infertile women (P=0.80, RR=0.81, 95% CI=0.37-1.80). Curves of time of pain recurrence and pregnancy during 5-year follow-up did not show significant differences between the two groups (P=0.79 and P=0.51, respectively, using Mantel-Haenzsel logrank test).\n Triptorelin treatment after operative laparoscopy for stage III/IV endometriosis does not appear to be superior to expectant management in terms of prevention of symptoms recurrence and endometrioma relapse, and has no influence on pregnancy rate in endometriosis-associated infertility.", "To evaluate the clinical value of postoperative hormone therapy in endometriosis, 60 patients with advanced disease were randomized to receive in a double-blind study danazol (200 mg, 3 times daily), medroxyprogesterone acetate (MPA) (100 mg daily) or placebo post-operatively for 6 months. Treatment efficacy was evaluated clinically and at laparoscopy 6 months after medication. In relation to placebo, danazol and high-dose MPA treatments, which did not differ from each other in efficacy, significantly alleviated pelvic pain. In addition, the peritoneal endometriosis lesions found at 6-months laparoscopy were significantly smaller in the MPA and danazol groups than in the placebo group. Breakthrough bleeding, weight gain and acne complicated danazol treatment but only breakthrough bleeding complicated MPA treatment. These data suggest that postoperative treatment of advanced endometriosis with high-dose MPA or danazol is clinically beneficial.", "To determine the effectiveness of a 6-month course of nafarelin in the treatment of stage III-IV endometriosis and to determine if pre-operative use of nafarelin facilitates surgery.\n Prospective, multicenter, clinical trial.\n Eight university hospitals and two private practice institutions in France.\n Fifty-five patients with stage III and IV endometriosis. Two were excluded.\n The severity of endometriosis was assessed at the time of laparoscopy and patients were randomized to have either laparosopic surgery at that time following 6 months of nafarelin therapy (n=28), or laparoscopic surgery following 6 months of nafarelin therapy (n=25). All had 200 microg intranasal nafarelin twice a day for 6 months and a second look laparoscopy.\n Clinical efficacy, tolerance to the treatment.\n Efficacy and tolerance to the treatment were the same in both groups. AFS scores compared on both laparoscopies were significantly better if nafarelin was given prior to surgery (P=0.007).\n This preliminary study shows that in cases of combined medico-surgical treatment for stage III-IV endometriosis, preoperative medical treatment with GnRH-a gives a better AFS score improvement, but no conclusion was possible whether preoperative treatment facilitates surgery.", "To evaluate the effectiveness for the outcomes of endometriosis-related pain and quality of life of conservative surgery plus placebo compared with conservative surgery plus hormonal suppression treatment or dietary therapy.\n Randomized comparative trial.\n University hospital.\n Two hundred twenty-two consecutive women who underwent conservative pelvic surgery for symptomatic endometriosis stage III-IV (r-AFS).\n Six months of placebo (n = 110) versus GnRH-a (tryptorelin or leuprorelin, 3.75 mg every 28 days) (n = 39) or continuous estroprogestin (ethynilestradiol, 0.03 mg plus gestoden, 0.75 mg) (n = 38) versus dietary therapy (vitamins, minerals salts, lactic ferments, fish oil) (n = 35).\n Painful symptoms (visual analogue scale score) and quality-of-life endometriosis-related symptoms (SF-36 score) at 12 months' follow-up.\n Patients treated with postoperative hormonal suppression therapy showed less visual analogue scale scores for dysmenorrhoea than patients of the other groups. Hormonal suppression therapy and dietary supplementation were equally effective in reducing nonmenstrual pelvic pain. Surgery plus placebo showed significative decrease in dyspareunia scores. Postoperative medical and dietary therapy allowed a better quality of life than placebo.\n Postoperative hormonal suppression treatment or dietary therapy are more effective than surgery plus placebo to obtain relief of pain associated with endometriosis stage III-IV and improvement of quality of life.", "To evaluate the role of GnRH agonist (GnRH-a) and/or drainage in the management of large endometriomas.\n This prospective clinical study was conducted in a parallel and randomized design.\n Department of Gynecology, Cliniques Universitaires St. Luc, Brussels, Belgium.\n Eight infertile women with laparoscopically confirmed ovarian endometriotic cysts. After laparoscopic drainage of the ovarian cyst, patients were randomized. Patients in group I (n = 40) received no therapy. Patients in group II (n = 40) received GnRH-a therapy for 12 weeks. A second-look laparoscopy was performed after 12 weeks in each woman.\n After drainage, a quick recurrence of the endometrial cyst was observed in only group I. Indeed, the score and the cyst size were similar to the values observed before the first laparoscopy. In group II, a significant decrease in score and cyst diameter was observed. Ovarian biopsies revealed significant reduction in the stromal vascularization and a significant reduction in the mitotic activity in the group of women treated with GnRH-a.\n The quick recurrence of the ovarian cyst after drainage proved that drainage alone is ineffective. Drainage followed by GnRH-a was effective in the reduction of cyst size and the glandular mitotic activity.", "To evaluate the efficacy of the GnRH agonist (GnRH-a) nafarelin compared with placebo administered for 6 months after reductive laparoscopic surgery for symptomatic endometriosis.\n Randomized, prospective, placebo-controlled, multicenter clinical trial.\n Thirteen clinics including private practice and university centers.\n One hundred nine women aged 18-47 with laparoscopically proven endometriosis and pelvic pain who had undergone reductive laparoscopic surgery for endometriosis.\n Patients were randomized to receive either the GnRH-a nafarelin (200 micrograms twice daily) or placebo for 6 months.\n Time to initiation of alternative treatment (the length of time from beginning study medication to receiving alternative therapy or to deeming that the study drug was ineffective) and patient-reported and physician-assessed pelvic pain scores.\n The median time to initiation of alternative treatment was > 24 months in the nafarelin group versus 11.7 months in the placebo group. Fifteen (31%) of 49 nafarelin-treated patients required alternative therapy, compared with 25 (57%) of 44 placebo-treated patients. The patients' pelvic pain scores dropped significantly in the nafarelin and placebo groups after 6 months of treatment. Physician summary ratings showed significant improvement in the nafarelin group and no significant changes in the placebo group after 6 months of treatment.\n Compared with placebo, nafarelin administered after reductive laparoscopic surgery for endometriosis significantly delays the return of endometriosis symptoms requiring further treatment.", "We sought to evaluate the efficacy of postoperative administration of monophasic, combined, low-dose oral contraceptives on endometrioma recurrence and on persistence-recurrence of associated pain symptoms after laparoscopic treatment of moderate-to-severe endometriosis.\n In a prospective, randomized trial 70 patients who were not attempting to conceive, aged 20 to 35 years, underwent laparoscopic excision of ovarian endometriomas, followed by either postoperative administration of low-dose cyclic oral contraceptives for 6 months or no treatment on the basis of a computer-generated sequence. At 3 and 6 months after surgery and then at 6-month intervals, both groups underwent ultrasonographic examination for possible evidence of endometrioma recurrence and for evaluation of the absence, persistence, or recurrence of pain symptoms.\n Two patients in the oral contraceptive group did not complete the study. After a mean follow-up of 22 months (range, 12-48 months), there were 2 (6.1%) endometrioma recurrences in the 33 patients who received postoperative oral contraceptives versus 1 (2.9%) recurrence in the 35 patients in the control group (not significant). The moderate-to-severe pain recurrence rate was 9.1% in the oral contraceptive group versus 17.1% in the control group (not significant). The mean time to recurrence of either symptoms or endometriomas was 18.2 months in the oral contraceptive group versus 12.7 months in the control group. The 12-month cumulative recurrence rate at life-table analysis was significantly lower for patients receiving oral contraceptives versus control subjects, whereas no significant difference was evident at 24 and 36 months.\n Postoperative administration of low-dose cyclic oral contraceptives does not significantly affect the long-term recurrence rate of endometriosis after surgical treatment. A delay in recurrence is evident at life-table analysis.", "To assess the effect of short-term use of a gonadotropin releasing hormone (GnRH) analogue for 3 months before ovarian stimulation in patients with stage III and IV endometriosis after conservative surgery.\n Eleven patients were randomly selected to receive intramuscular injections of GnRH analogue, leuprolide acetate (3.75 mg), every 28 days, or 400 mg danazol orally 2 times per day for 3 months before ovarian stimulation after conservative laparoscopic or laparotomy surgeryfor stage III and IV symptomatic endometriosis (group 1), as compared with 30 patients who had received no postoperative treatment with GnRH analogue or danazol but underwent ovarian stimulation immediately after thefirst menses within 3 months postoperatively (group 2).\n Although the number of oocytes retrieved and number of embryos per cycle were significantly higher in group 1, the pregnancy rate per cycle in group 1 was not significantly different from that in group 2 (18% vs. 20%). The cumulative pregnancy rate at 12 months was 54.5% and 56.7% in group 1 and group 2, respectively. With regard to recurrence of disease after 24 months of follow-up, group 2 had a statistically significantly higher recurrence rate (13.3%) than did group 1 (0%).\n Short-term use of GnRH analogue before ovarian stimulation in women with stage III or IV endometriosis confers no definite benefits on pregnancy rates per cycle when compared with patients who received ovarian stimulation within 3 months after conservative surgery.", "The effect of treatment with danazol was evaluated with respect to expectant management after laparoscopic conservative surgery. All patients conservatively operated at laparoscopy for stage III-IV endometriosis from July 1994 to October 1996 were requested to enter the study. Patients who underwent surgery for recurrent endometriosis were excluded from the study, as well as patients who had taken hormonal therapies before laparoscopy. Informed consent was obtained from 77 women who were randomized after surgery to treatment with danazol 600 mg daily for 3 months (n = 36) or to expectant management (n = 41). All patients were regularly followed up every 6 months for evaluation of fertility, recurrence of pain symptoms and disease. During the follow-up, six (55%) of the 11 infertile women allocated to danazol and eight (50%) of the 16 given no treatment became pregnant (not significant). Moderate/severe pelvic pain recurred during follow-up in seven (23%) of the 31 women with pelvic pain allocated to the danazol group and nine (31%) of the 29 allocated to no treatment; the respective cumulative pain recurrence rates at 12 months were 26 and 34% (log rank test, not significant). Three women (8.3%) treated with danazol and six (15%) who received no treatment had disease recurrence as demonstrated by gynaecological examination and/or pelvic ultrasonography (not significant). Our results do not demonstrate a significant advantage of 3 month danazol therapy after laparoscopic surgery for stage III-IV endometriosis with respect to postoperative expectant management.", "In order to decrease endometriosis recurrence after surgical therapy, it has been proposed to use a post-surgical oestrogen-lowering medical treatment. Results from previous trials on this topic are contradictory.\n A total of 89 women were randomized, by computer-generated list, after laparoscopic conservative surgery for symptomatic endometriosis stage III-IV to receive monthly i.m. injections of gonadotrophin-releasing hormone (GnRH) analogue, leuprolide acetate depot (3.75 mg) for 3 months (n = 44) or to an expectant management (n = 45). All patients were followed up every 6 months for evaluation of pain symptoms, fertility and objective disease recurrence.\n During the follow-up, which ranged from 6-36 months, five (33%) of the 15 women who wanted children and who were allocated the GnRH analogue and six (40%) of the 15 given no treatment became pregnant (not significant). Moderate/severe pelvic pain recurred during the follow-up in 10 (23%) of the women allocated the GnRH analogue and 11 (24%) of those allocated no treatment; the cumulative pain recurrence rates at 18 months were 23 and 29% respectively (not significant). Four women (9%) treated with GnRH analogue and four women (9%) who received no treatment had objective disease recurrence as demonstrated by gynaecological examination and/or pelvic ultrasonography.\n This study does not support the routine post-operative use of a 3 month course of GnRH analogue in women with symptomatic endometriosis stage III-IV.", "To observe the clinical efficacy and safety of Yiweining (YWN) and gestrinone (GT) in treating post-operational patients of stage III endometriosis (EM-III).\n Fifty-two patients of EM-III after operation were randomly assigned into three groups, the YWN group (20 patients) was treated through oral intake of YWN 200 ml, twice a day; the GT group (19 patients) treated with gestrinone 2.5 mg, twice every week, with the medication starting from the 7th post-operational day and lasting for 6 months. The control group (13 patients) was untreated. Six months was one therapeutic course, and follow-up study was carried out in the 6 - 30 months after the end of the medication.\n The recurrence rate in the YWN group and the GT group were 5.0% and 5.3% respectively, showing insignificant difference between the two groups, but they were lower than that in the control group (30.7%, P < 0.05). Besides, the adverse reaction rate in the YWN group was lower than that in the GT group (10.0% vs 31.6%, P < 0.05).\n Application of YWN to prevent the post-operational recurrence of endometriosis is effective and safe, and its efficacy is similar to that of GT.", "Our purpose was to investigate the efficacy of postsurgical treatment with nafarelin in women with advanced endometriosis.\n Eligible for trial were women < or = 38 years old with unexplained infertility with or without chronic pelvic pain and stage III or IV endometriosis according to the American Fertility Society, revised, classification who underwent laparotomy as first surgical treatment for debulking or radical surgery of endometriotic lesions. Patients were assigned according to a randomization list to nasal nafarelin, 400 micrograms/day (36 subjects) or placebo nasal spray (39 subjects) for 3 months. Pelvic pain was assessed before first surgery and at the 12-month follow-up visit in women with pelvic pain by means of a multidimensional score system and a 10-point linear pain scale.\n No marked differences in pain scores emerged among women allocated to different treatments. The mean reduction of the multidimensional score was 3.6 and 4.0, respectively, in women allocated to nafarelin and placebo and of the 10-point linear scale scores was 7.0 and 6.9. These differences were not statistically significant. Within 1 year from randomization, of the 36 women allocated to nafarelin and the 39 allocated to placebo, seven (19%) and seven (18%), respectively, became pregnant.\n This study suggests that medical treatment with nafarelin does not markedly improve pelvic pain and short-term reproductive prognosis in women with stages III and IV endometriosis." ]

[ "15738537", "18421054", "12506171", "17442997", "15175435" ]

[ "Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial.", "Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study.", "Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer.", "Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200.", "Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer." ]

[ "Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, increases survival when combined with irinotecan-based chemotherapy in first-line treatment of metastatic colorectal cancer (CRC). This randomized, phase II trial compared bevacizumab plus fluorouracil and leucovorin (FU/LV) versus placebo plus FU/LV as first-line therapy in patients considered nonoptimal candidates for first-line irinotecan.\n Patients had metastatic CRC and one of the following characteristics: age > or = 65 years, Eastern Cooperative Oncology Group performance status 1 or 2, serum albumin < or = 3.5 g/dL, or prior abdominal/pelvic radiotherapy. Patients were randomly assigned to FU/LV/placebo (n = 105) or FU/LV/bevacizumab (n = 104). The primary end point was overall survival. Secondary end points were progression-free survival, response rate, response duration, and quality of life. Safety was also assessed.\n Median survival was 16.6 months for the FU/LV/bevacizumab group and 12.9 months for the FU/LV/placebo group (hazard ratio, 0.79; P = .16). Median progression-free survival was 9.2 months (FU/LV/bevacizumab) and 5.5 months (FU/LV/placebo); hazard ratio was 0.50; P = .0002. Response rates were 26.0% (FU/LV/bevacizumab) and 15.2% (FU/LV/placebo) (P = .055); duration of response was 9.2 months (FU/LV/bevacizumab) and 6.8 months (FU/LV/placebo); hazard ratio was 0.42; P = .088. Grade 3 hypertension was more common with bevacizumab treatment (16% v 3%) but was controlled with oral medication and did not cause study drug discontinuation.\n Addition of bevacizumab to FU/LV as first-line therapy in CRC patients who were not considered optimal candidates for first-line irinotecan treatment provided clinically significant patient benefit, including statistically significant improvement in progression-free survival.", "To evaluate the efficacy and safety of bevacizumab when added to first-line oxaliplatin-based chemotherapy (either capecitabine plus oxaliplatin [XELOX] or fluorouracil/folinic acid plus oxaliplatin [FOLFOX-4]) in patients with metastatic colorectal cancer (MCRC).\n Patients with MCRC were randomly assigned, in a 2 x 2 factorial design, to XELOX versus FOLFOX-4, and then to bevacizumab versus placebo. The primary end point was progression-free survival (PFS).\n A total of 1,401 patients were randomly assigned in this 2 x 2 analysis. Median progression-free survival (PFS) was 9.4 months in the bevacizumab group and 8.0 months in the placebo group (hazard ratio [HR], 0.83; 97.5% CI, 0.72 to 0.95; P = .0023). Median overall survival was 21.3 months in the bevacizumab group and 19.9 months in the placebo group (HR, 0.89; 97.5% CI, 0.76 to 1.03; P = .077). Response rates were similar in both arms. Analysis of treatment withdrawals showed that, despite protocol allowance of treatment continuation until disease progression, only 29% and 47% of bevacizumab and placebo recipients, respectively, were treated until progression. The toxicity profile of bevacizumab was consistent with that documented in previous trials.\n The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved PFS in this first-line trial in patients with MCRC. Overall survival differences did not reach statistical significance, and response rate was not improved by the addition of bevacizumab. Treatment continuation until disease progression may be necessary in order to optimize the contribution of bevacizumab to therapy.", "This phase II trial investigated the safety and efficacy of two doses of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, plus fluorouracil (FU)/leucovorin (LV) versus FU/LV alone in patients with metastatic colorectal cancer.\n One hundred four previously untreated patients with measurable metastatic colorectal cancer were randomly assigned to one of the following three treatment groups: 36 to FU (500 mg/m(2))/LV (500 mg/m(2)) alone, 35 to FU/LV + low-dose bevacizumab (5 mg/kg every 2 weeks), and 33 to FU/LV + high-dose bevacizumab (10 mg/kg every 2 weeks). FU/LV was given weekly for the first 6 weeks of each 8-week cycle.\n Compared with the FU/LV control arm, treatment with bevacizumab (at both dose levels) plus FU/LV resulted in higher response rates (control arm, 17%, 95% confidence interval [CI], 7% to 34%; low-dose arm, 40%, 95% CI, 24% to 58%; high-dose arm, 24%, 95% CI, 12% to 43%), longer median time to disease progression (control arm, 5.2 months, 95% CI, 3.5 to 5.6 months; low-dose arm, 9.0 months, 95% CI, 5.8 to 10.9 months; high-dose arm, 7.2 months, 95% CI, 3.8 to 9.2 months), and longer median survival (control arm, 13.8 months; 95% CI, 9.1 to 23.0 months; low-dose arm, 21.5 months, 95% CI, 17.3 to undetermined; high-dose arm, 16.1 months; 95% CI, 11.0 to 20.7 months). After cross-over, two of 22 patients had a partial response to bevacizumab alone. Thrombosis was the most significant adverse event and was fatal in one patient. Hypertension, proteinuria, and epistaxis were other potential safety concerns.\n The encouraging results of this randomized trial support further study of bevacizumab 5 mg/kg plus chemotherapy as first-line therapy for metastatic colorectal cancer.", "Colorectal cancer is the second leading cause of cancer mortality in the United States. Antiangiogenic therapy with bevacizumab combined with chemotherapy improves survival in previously untreated metastatic colorectal cancer. This study was conducted to determine the effect of bevacizumab (at 10 mg/kg) on survival duration for oxaliplatin-based chemotherapy in patients with previously treated metastatic colorectal cancer.\n Eight hundred twenty-nine metastatic colorectal cancer patients previously treated with a fluoropyrimidine and irinotecan were randomly assigned to one of three treatment groups: oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) with bevacizumab; FOLFOX4 without bevacizumab; or bevacizumab alone. The primary end point was overall survival, with additional determinations of progression-free survival, response, and toxicity.\n The median duration of survival for the group treated with FOLFOX4 and bevacizumab was 12.9 months compared with 10.8 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for death = 0.75; P = .0011), and 10.2 months for those treated with bevacizumab alone. The median progression-free survival for the group treated with FOLFOX4 in combination with bevacizumab was 7.3 months, compared with 4.7 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for progression = 0.61; P < .0001), and 2.7 months for those treated with bevacizumab alone. The corresponding overall response rates were 22.7%, 8.6%, and 3.3%, respectively (P < .0001 for FOLFOX4 with bevacizumab v FOLFOX4 comparison). Bevacizumab was associated with hypertension, bleeding, and vomiting.\n The addition of bevacizumab to oxaliplatin, fluorouracil, and leucovorin improves survival duration for patients with previously treated metastatic colorectal.", "Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promising preclinical and clinical activity against metastatic colorectal cancer, particularly in combination with chemotherapy.\n Of 813 patients with previously untreated metastatic colorectal cancer, we randomly assigned 402 to receive irinotecan, bolus fluorouracil, and leucovorin (IFL) plus bevacizumab (5 mg per kilogram of body weight every two weeks) and 411 to receive IFL plus placebo. The primary end point was overall survival. Secondary end points were progression-free survival, the response rate, the duration of the response, safety, and the quality of life.\n The median duration of survival was 20.3 months in the group given IFL plus bevacizumab, as compared with 15.6 months in the group given IFL plus placebo, corresponding to a hazard ratio for death of 0.66 (P<0.001). The median duration of progression-free survival was 10.6 months in the group given IFL plus bevacizumab, as compared with 6.2 months in the group given IFL plus placebo (hazard ratio for disease progression, 0.54; P<0.001); the corresponding rates of response were 44.8 percent and 34.8 percent (P=0.004). The median duration of the response was 10.4 months in the group given IFL plus bevacizumab, as compared with 7.1 months in the group given IFL plus placebo (hazard ratio for progression, 0.62; P=0.001). Grade 3 hypertension was more common during treatment with IFL plus bevacizumab than with IFL plus placebo (11.0 percent vs. 2.3 percent) but was easily managed.\n The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival among patients with metastatic colorectal cancer.\n Copyright 2004 Massachusetts Medical Society" ]

[ "7589769", "1306646", "10102158" ]

[ "High-dose intravenous immunoglobulin therapy for rhesus haemolytic disease.", "High-dose intravenous immune globulin therapy for hyperbilirubinemia caused by Rh hemolytic disease.", "High-dose intravenous immunoglobulin therapy in neonatal immune haemolytic jaundice." ]

[ "Rhesus haemolytic disease is a continuing problem in the newborn especially in countries where the use of anti-D immunoglobulin is not prevalent. The fetuses may need intrauterine transfusions to prevent hydrops faetalis and they also may need exchange transfusions to treat the hyperbilirubinaemia that develops after birth. These interventions expose the baby to several blood donors, hence the risk of infection and exchange transfusions. This study was performed to test whether the use of high-dose intravenous immunoglobulin soon after the birth of these infants reduced the need for exchange transfusions. After randomization, intravenous immunoglobulin was given at a dose of 500 mg/kg to 22 infants in the treatment group. Nothing was given to the 19 controls. The number of exchange transfusions needed decreased significantly in the treatment group. No side-effects of intravenous immunoglobulins were seen.", "We conducted a multicenter controlled trial to test the hypothesis that high-dose intravenous immune globulin (HDivIG) therapy can modulate bilirubin production and reduce the frequency of exchange transfusions in newborn infants with Rh hemolytic disease. Thirty-four patients with Rh incompatibility proved by positive direct antiglobulin test (Coombs test) results were randomly assigned to receive conventional treatment including phototherapy, with or without additional HDivIG therapy at 500 mg/kg given for a 2-hour period as soon as the diagnosis was established. Exchange transfusions were performed if serum bilirubin concentrations exceeded the modified curves of Polácek by more than 2 mg/dl. Two patients were excluded because of protocol violations. The results in 32 infants were analyzed. In the HDivIG group, 2 (12.5%) of 16 children required exchange transfusions, whereas it became necessary in 11 (69%) of 16 children in the control group (p less than 0.005). Bilirubin levels in the HDivIG group were lower despite reduced frequency of exchange transfusions. No side effects of HDivIG treatment were observed. We conclude that HDivIG therapy by a yet unknown mechanism reduces serum bilirubin levels and the need for blood exchange transfusions in children with Rh hemolytic disease.", "A controlled study was conducted to assess the role of high-dose i.v. immunoglobulin (HDIVIG) therapy in neonatal immune haemolytic jaundice. Patients with ABO and/or Rh incompatibilities proved by significant hyperbilirubinaemia (>204 mmol l(-1)), positive direct antiglobulin test and high reticulocyte count (> or =10%) were randomly assigned to receive either conventional phototherapy alone or phototherapy with high-dose i.v. immunoglobulin (1 g kg(-1), over 4 h) as soon as the diagnosis was established. Exchange transfusions were performed if serum bilirubin concentrations exceeded 290 mmol l(-1) and increased by more than 17 mmol l(-1) per h despite both treatment manoeuvres. Eight of 58 patients in the HDIVIG group required exchange transfusions, whereas it became necessary in 22 of 58 patients in the control group (p<0.001). The durations of phototherapy and hospitalization in terms of hours were significantly shorter in the HDIVIG group (p<0.05). No side effects of HDIVIG therapy were observed. In conclusion, HDIVIG therapy in newborns with ABO or Rh haemolytic diseases reduces haemolysis, serum bilirubin levels and the need for blood exchange transfusion, a procedure which has potential complications and carries a risk of mortality." ]

[ "7714648", "10421182", "15855919", "14598411", "15457363", "16452735", "11451974", "16049250", "8703169", "9452837", "8331703" ]

[ "Effectiveness of pneumatic leg compression devices for the prevention of thromboembolic disease in orthopaedic trauma patients: a prospective, randomized study of compression alone versus no prophylaxis.", "Calf-thigh sequential pneumatic compression compared with plantar venous pneumatic compression to prevent deep-vein thrombosis after non-lower extremity trauma.", "Electrostimulation for the prevention of deep venous thrombosis in patients with major trauma: a prospective randomized study.", "Randomized clinical trial of intermittent pneumatic compression and low molecular weight heparin in trauma.", "Venous thromboembolism prophylaxis after head and spinal trauma: intermittent pneumatic compression devices versus low molecular weight heparin.", "Prophylaxis against deep-vein thrombosis following trauma: a prospective, randomized comparison of mechanical and pharmacologic prophylaxis.", "Mechanical prophylaxis against deep-vein thrombosis after pelvic and acetabular fractures.", "Continuous passive motion in the prevention of deep-vein thrombosis: a randomised comparison in trauma patients.", "A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma.", "A randomized comparison of sequential-gradient calf compression with intermittent plantar compression for prevention of venous thrombosis in orthopedic trauma patients: preliminary results.", "Efficacy of deep venous thrombosis prophylaxis in trauma patients and identification of high-risk groups." ]

[ "A prospective, randomized clinical trial in 304 orthopaedic trauma patients with hip and pelvic fractures was conducted to investigated the effectiveness of pneumatic sequential leg compression devices (PSLCDs) for the prevention of thromboembolic disease. The control group received no specific form of prophylaxis. Patients were followed by venous Doppler, duplex can, and ventilation perfusion lung scans. The study end-point was documented pulmonary embolism and/or deep vein thrombosis. The incidence of a venous thromboembolic event in the control group was 11% and in the experimental group 4%. This difference was statistically significant (p = 0.02). These patients were also stratified into hip and pelvic fracture groups. In the hip fracture patients, the control group had a thromboembolic event incidence of 12% and the experimental group 4%. This difference was also statistically significant (p = 0.03). In the pelvic fracture group there was a thromboembolic incidence of 11% in the controls, demonstrating this patient population to be at significant risk. In this group, the PSLCDs were not statistically shown to be effective. Pneumatic leg compression devices are effective in reducing the incidence of thromboembolic events in patients with hip fractures.", "To compare the effectiveness of calf-thigh sequential pneumatic compression devices with the effectiveness of plantar venous intermittent pneumatic compression devices in prevention of venous thrombosis after major trauma.\n We evaluated 181 consecutive patients after major trauma without lower extremity injuries that precluded the use of pneumatic compression devices. We randomly assigned 149 patients to either calf-thigh sequential pneumatic compression or plantar venous pneumatic compression. After blinding the observers to the method of prophylaxis against deep-vein thrombosis, we performed bilateral compression ultrasonography on or before day 8 after randomization.\n Among 149 randomized patients, 62 who received calf-thigh sequential pneumatic compression and 62 who received plantar venous intermittent pneumatic compression devices completed the trial. Thirteen patients randomized to plantar venous intermittent pneumatic compression (21.0%) and 4 patients randomized to calf-thigh sequential pneumatic compression (6.5%) had deep-vein thrombosis (p = 0.009). Seven of 13 patients with deep-vein thrombosis after prophylaxis with plantar venous intermittent pneumatic compression had bilateral deep-vein thromboses, whereas all 4 patients with deep-vein thrombosis after prophylaxis with calf-thigh sequential pneumatic compression had unilateral deep-vein thrombosis.\n Calf-thigh sequential pneumatic compression prevents deep-vein thrombosis more effectively than plantar venous intermittent pneumatic compression after major trauma without lower extremity injuries.", "Current methods of posttraumatic thromboprophylaxis (heparins and sequential compression devices) are inadequate. New methods should be tested. Muscle electrostimulation (MEST) has been used over the years with mixed-but predominantly encouraging-results for a variety of conditions, including prevention of deep venous thrombosis (DVT). It has not been tested in multiple trauma patients.\n Trauma patients with Injury Severity Score higher than 9 who were admitted to the intensive care unit and had a contraindication for prophylactic heparinization were randomized to groups MEST and control. MEST patients received 30-minute MEST sessions twice daily for 7 to 14 days. Venous flow velocity and venous diameter were measured by duplex venous scan. Venography-or, if not available, duplex-was used to evaluate the presence of proximal and peripheral DVT between days 7 and 15.\n After exclusions, 26 MEST and 21 control patients completed the study and received outcome evaluation by venography (25) or duplex (22). Three patients in each group developed proximal DVT (11.5% vs 14%, P = .79), and an additional 4 (15%) MEST group and 3 (14%) control group patients developed peripheral DVT ( P = .96). There was no difference in venous flow velocity or venous diameter between the groups.\n MEST was not effective in decreasing DVT rates in major trauma patients.", "After trauma, up to 60 per cent of immobilized patients have been reported to develop a silent deep vein thrombosis (DVT). No large, prospective randomized trials have tested the efficacy of intermittent pneumatic compression (IPC) devices in these patients.\n A prospective randomized trial was performed of 442 patients who received thromboprophylaxis using either an IPC device or low molecular weight heparin (LMWH). Duplex imaging was performed on both legs on admission, and was repeated weekly thereafter until discharge, at 30 days or when there was a thrombotic event, whichever occurred first.\n There were no significant differences in time spent in intensive care, or the proportion of patients with pelvic fractures, spinal cord or head injuries between the two groups. Six patients (2.7 per cent) developed a DVT in the IPC group and one (0.5 per cent) in the LMWH group (P = 0.122). Pulmonary embolism occurred in one patient in each group. There were 13 minor bleeding episodes (four in the IPC group and nine in the LMWH group) and eight major bleeding episodes (four in each group), none of which required operative intervention.\n The low rate of thromboembolic complications and the cost savings suggest that IPC might be used safely and effectively for thromboprophylaxis in trauma patients.\n Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.", "Although there are alternative methods and drugs for preventing venous thromboembolism (VTE), it is not clear which modality is most suitable and efficacious for patients with severe (stable or unstable) head/spinal injures. The aim of this study was to compare intermittent pneumatic compression devices (IPC) with low-molecular-weight heparin (LMWH) for preventing VTE. We prospectively randomized 120 head/spinal traumatized patients for comparison of IPC with LMWH as a prophylaxis modality against VTE. Venous duplex color-flow Doppler sonography of the lower extremities was performed each week of hospitalization and 1 week after discharge. When there was a suspicion of pulmonary embolism (PE), patients were evaluated with spiral computed tomography. Patients were analyzed for demographic features, injury severity scores, associated injuries, type of head/spinal trauma, complications, transfusion, and incidence of deep venous thrombosis (DVT) and PE. Two patients (3.33%) from the IPC group and 4 patients (6.66%) from the LMWH group died, with their deaths due to PE. Nine other patients also succumbed, unrelated to PE. DVT developed in 4 patients (6.66%) in the IPC group and in 3 patients (5%) in the LMWH group. There was no statistically significant difference regarding a reduction in DVT, PE, or mortality between groups ( p = 0.04, p > 0.05, p > 0.05, respectively). IPC can be used safely for prophylaxis of VTE in head/spinal trauma patients.", "Deep-vein thrombosis following skeletal trauma is an important yet poorly studied issue. The purpose of the present study was to evaluate the efficacy of two different strategies for prophylaxis against deep-vein thrombosis and pulmonary embolus following blunt skeletal trauma.\n Two hundred and twenty-four inpatients were enrolled in a prospective, randomized study investigating venous thromboembolic disease following trauma. Two hundred patients completed the study, which compared two different regimens of prophylaxis. The patients in Group A received enoxaparin (30 mg, administered subcutaneously twice a day) starting twenty-four to forty-eight hours after blunt trauma. The patients in Group B were managed with pulsatile foot pumps at the time of admission combined with enoxaparin on a delayed basis. All patients were screened with magnetic resonance venography and ultrasonography before discharge.\n There were ninety-seven patients in Group A and 103 patients in Group B. Twenty-two patients (including thirteen in Group A and nine in Group B) had development of deep-vein thrombosis, with two (both in Group A) also having development of pulmonary embolism. The prevalence of deep-vein thrombosis was 11% for the whole series, 13.4% for Group A, and 8.7% for Group B; the difference between Groups A and B was not significant. There were eleven large or occlusive clots (prevalence, 11.3%) in Group A, compared with only three (prevalence, 2.9%) in Group B (p = 0.025). The prevalence of pulmonary embolism was 2.1% in Group A and 0% in Group B. Wound complications occurred in twenty-one patients in Group A, compared with twenty patients in Group B. Patients who had development of deep-vein thrombosis during the inpatient portion of the study required a mean of 7.4 units of blood during hospitalization, compared with 3.9 units of blood for those who did not (p < 0.05).\n Our results indicate that early mechanical prophylaxis with foot pumps and the addition of enoxaparin on a delayed basis is a very successful strategy for prophylaxis against venous thromboembolic disease following serious musculoskeletal injury. The prevalence of large or occlusive deep-vein thromboses among patients who had been managed with this protocol was significantly less than that among patients who had been managed with enoxaparin alone.", "Deep-vein thrombosis is a common complication following pelvic and acetabular fractures. The hypothesis of this study was that pulsatile mechanical compression is superior to standard sequential mechanical compression for decreasing the prevalence of deep-vein thrombosis in patients with pelvic or acetabular fracture.\n A prospective, randomized, blinded study of two methods of mechanical prophylaxis against deep-vein thrombosis was conducted. One hundred and seven patients were randomized into either Group A (fifty-four patients), in which a thigh-calf low-pressure sequential-compression device was used, or Group B (fifty-three patients), in which a calf-foot high-pressure pulsatile-compression pump was used. All patients underwent duplex ultrasonography and magnetic resonance venography. The two groups were comparable with regard to demographics, fracture type, fracture treatment, time from the injury to the prophylaxis, and patient compliance.\n Deep-vein thrombosis developed in ten patients (19%) in Group A, with seven (13%) having a large or occlusive clot and one (2%) having a documented pulmonary embolism. Deep-vein thrombosis developed in five patients (9%) in Group B, with two (4%) having a large or occlusive clot and none having a documented pulmonary embolism. Nine of the nineteen detected thromboses were in the deep pelvic veins. The difference in the prevalence of large or occlusive clots between the two groups demonstrated a trend but, with the numbers available, was not significant (p = 0.16). Increased patient age and the time elapsed from the injury to the surgery were found to be associated with higher rates of thrombosis.\n Pulsatile compression was associated with fewer deep-vein thromboses than was standard compression, with the difference representing a trend but not reaching significance with the number of patients studied.", "There is a high risk of venous thromboembolism when patients are immobilised following trauma. The combination of low-molecular-weight heparin (LMWH) with graduated compression stockings is frequently used in orthopaedic surgery to try and prevent this, but a relatively high incidence of thromboembolic events remains. Mechanical devices which perform continuous passive motion imitate contractions and increase the volume and velocity of venous flow. In this study 227 trauma patients were randomised to receive either treatment with the Arthroflow device and LMWH or only with the latter. The Arthroflow device passively extends and plantarflexes the feet. Patients were assessed initially by venous-occlusion plethysmography, compression ultrasonography and continuous wave Doppler, which were repeated weekly without knowledge of the category of randomisation. Those who showed evidence of deep-vein thrombosis underwent venography for confirmation. The incidence of deep-vein thrombosis was 25% in the LMWH group compared with 3.6% in those who had additional treatment with the Arthroflow device (p < 0.001). There were no substantial complications or problems of non-compliance with the Arthroflow device. Logistic regression analysis of the risk factors of deep-vein thrombosis showed high odds ratios for operation (4.1), immobilisation (4.3), older than 40 years of age (2.8) and obesity (2.2).", "Patients who have had major trauma are at very high risk for venous thromboembolism if they do not receive thromboprophylaxis. We compared low-dose heparin and a low-molecular-weight heparin with regard to efficacy and safety in a randomized clinical trial in patients with trauma.\n Consecutive adult patients admitted to a trauma center who had Injury Severity Scores of at least 9 and no intracranial bleeding were randomly assigned to heparin (5000 units) or enoxaprin (30 mg), each given subcutaneously every 12 hours in a double-blind manner, beginning within 36 hours after the injury. The primary outcome was deep-vein thrombosis as assessed by contrast venography performed on or before day 14 after randomization.\n Among 344 randomized patients, 136 who received low-dose heparin and 129 who received enoxaparin had venograms adequate for analysis. Sixty patients given heparin (44 percent) and 40 patients given enoxaparin (31 percent) had deep-vein thrombosis (P=0.014). The rates of proximal-vein thrombosis were 15 percent and 6 percent, respectively (P=0.012). The reductions in risk with enoxaparin as compared with heparin were 30 percent (95 percent confidence interval, 4 to 50 percent) for all deep-vein thrombosis and 58 percent (95 percent confidence interval, 12 to 87 percent) for proximal-vein thrombosis. Only six patients (1.7 percent) had major bleeding (one in the heparin group and five in the enoxaparin group, P=0.12). Conclusions: Low-molecular-weight heparin was more effective than low-dose heparin in preventing venous thromboembolism after major trauma. Both interventions were safe.", "Trauma patients with fractures of the pelvis, acetabulum, or femur are at risk for deep venous thrombosis complicating the treatment of their injuries. This risk can be lessened with anticoagulant medications or with mechanical methods such as sequential pneumatic compression. However, many patients in this population group have contraindications to systemic anticoagulation and cannot use sequential limb compression devices because of leg injuries or appliances. Intermittent pneumatic compression of the plantar venous plexus is able to provide prophylaxis against deep venous thrombosis in many of these patients. We performed a prospective, randomized, controlled comparison between plantar compression and leg compression for prevention of deep venous thrombosis in an orthopedic trauma population of 124 patients. Patients were evaluated with duplex ultrasonagraphy at intervals after surgery. Both methods proved protective in comparison with reported rates in patients not given prophylaxis, and although the numbers were too small to give statistically meaningful results, we observed no significant difference in the thrombosis rate (4% for plantar compression versus 0% for leg compression). We conclude that foot pumps are an effective alternative to calf compression for prevention of deep venous thrombosis after a lower extremity fracture.", "The incidence of deep venous thrombosis (DVT) and the efficacy of prophylactic measures were prospectively evaluated in all patients admitted to a level I trauma center during 1991. Patients with Injury Severity Scores (ISS) > 9 who survived a minimum of 48 hours (n = 395) were monitored using venous Doppler and ultrasound studies during hospitalization (total, 1308 studies). Two hundred eighty-one patients (71%) were randomly assigned to low-dose heparin or sequential compression devices. There were 18 cases of lower extremity DVT (4.6%) and four cases (1.0%) of pulmonary emboli (PE), three of which were fatal. Eight patients (2.9%) on prophylaxis and 10 (8.8%) without prophylaxis developed DVT (p < 0.02 by Chi-square). There were two PEs in each group. Fourteen of these 18 patients sustained blunt trauma and included seven spinal fractures or subluxations (four paraplegic) and four severe head injuries. This represented 14.0% of 50 patients admitted with spinal injuries and 4.3% of 92 patients with severe head injuries. Compared with those with no neurologic injury (7 of 253 or 2.7%), the risk of DVT is significantly higher in the spinal injury patients (p < 0.001, Chi-square) and twice as high as in the head injury group, although not statistically significant (p = 0.4, Chi-square). Three of the four patients with penetrating trauma and DVT had venous injuries. We conclude that DVT prophylaxis can significantly reduce the incidence of DVT in trauma patients with ISS > 9. Patients with severe neurologic injuries (particularly spinal cord) are at high risk for DVT and PE and may be considered for a prophylactic Greenfield filter." ]

[ "22275296" ]

[ "Effects of skim milk powder enriched with glycomacropeptide and G600 milk fat extract on frequency of gout flares: a proof-of-concept randomised controlled trial." ]

[ "Previous laboratory studies have identified two dairy fractions, glycomacropeptide (GMP) and G600 milk fat extract (G600), with anti-inflammatory effects in models of acute gout. The aim of this proof-of-concept clinical trial was to test the hypothesis that daily intake of skim milk powder (SMP) enriched with GMP and G600 can prevent gout flares.\n This was a 3-month randomised double-blind controlled trial of milk products for prevention of gout flares. One hundred and twenty patients with recurrent gout flares were randomised to one of three arms: lactose powder control, SMP control and SMP enriched with GMP and G600 (SMP/GMP/G600). The primary end point was change in the frequency of gout flares using a daily flare diary measured monthly for 3 months.\n The frequency of gout flares reduced in all three groups over the 3-month study period compared with baseline. Over the 3-month study period there was a significantly greater reduction in gout flares in the SMP/GMP/G600 group (analysis of covariance p(group)=0.031, Tukey post hoc test compared with lactose control, p=0.044). Following treatment with SMP/GMP/G600 over the 3-month period, greater improvements were also observed in pain and fractional excretion of uric acid, with trends to greater improvement in tender joint count. Similar adverse event rates and discontinuation rates were observed between the three groups.\n This is the first reported controlled trial of dietary intervention in patients with gout, and suggests that SMP enriched with GMP and G600 may reduce the frequency of gout flares." ]

[ "3050179", "15349113" ]

[ "Impact of a medical journal club on house-staff reading habits, knowledge, and critical appraisal skills. A randomized control trial.", "Teaching practicing surgeons critical appraisal skills with an Internet-based journal club: A randomized, controlled trial." ]

[ "The journal club is an established teaching modality in many house-staff training programs. To determine if a journal club improves house-staff reading habits, knowledge of epidemiology and biostatistics, and critical appraisal skills, we randomized 44 medical interns to receive either a journal club or a control seminar series. A test instrument developed by the Delphi method was administered before and after the interventions (mean, five journal club sessions). By self-report, 86% of the house staff in the journal club group improved their reading habits vs 0% in the control group. Knowledge scores increased more in the journal club group than in the control group, and a trend was found toward more knowledge gained as more sessions were attended. Ability to appraise critically a test article increased slightly in each group, but there was no significant difference between the groups. We conclude that a journal club is a powerful motivator of critical house-staff reading behavior and can help teach epidemiology and biostatistics to physicians-in-training.", "The effectiveness of interventions for developing critical appraisal skills in practicing physicians has not been studied, despite the documented importance of reading the literature in caring for patients and in continuing professional development. The objective of this study was to evaluate whether an Internet-based intervention would lead to enhanced critical appraisal skills in practicing surgeons.\n General surgeons who agreed to participate were randomized into 2 groups. The intervention was a curriculum in critical appraisal skills that included a clinical and methodologic article, a listserve discussion, and clinical and methodologic critiques. The control group received only the clinical articles. The primary outcome measure was a previously validated 2-hour test of critical appraisal.\n Of the 55 surgeons who completed the examination, subjects in the intervention group performed better on the test of critical appraisal skills than those in the control group (mean score: intervention group, 58% +/- 8 vs control group, 50% +/- 8), with a large effect size of 1.06 standard deviation units (t+3.92, P <.0001). Training conditions accounted for 22% of the variance in total scores.\n A multifaceted, Internet-based intervention resulted in improved critical appraisal skills of practicing general surgeons." ]

[ "12195253", "17493557", "10653081", "19559369", "15889022", "16203880", "19651956" ]

[ "Cemented polyethylene versus uncemented metal-backed glenoid components in total shoulder arthroplasty: a prospective, double-blind, randomized study.", "A study of the micromovement of pegged and keeled glenoid components compared using radiostereometric analysis.", "Shoulder arthroplasty with or without resurfacing of the glenoid in patients who have osteoarthritis.", "Improved accuracy of glenoid positioning in total shoulder arthroplasty with intraoperative navigation: a prospective-randomized clinical study.", "Radiographic comparison of pegged and keeled glenoid components.", "Quality-of-life outcome following hemiarthroplasty or total shoulder arthroplasty in patients with osteoarthritis. A prospective, randomized trial.", "Stability of cemented in-line pegged glenoid compared with keeled glenoid components in total shoulder arthroplasty." ]

[ "Thirty-nine patients (forty shoulders) with primary osteoarthritis consented to be randomized to receive either a cemented all-polyethylene glenoid component or a cementless metal-backed component at the time of total shoulder arthroplasty. Their mean age was 69 years. Preoperative and postoperative evaluations were completed at 3, 6, 12, 24, and 36 months by history, physical examination, radiographs, and Constant scoring system. The presence of periprosthetic radiolucent lines was significantly greater with polyethylene than with metal-backed glenoids (85% vs 25%, P <.01). Of 20 radiolucent lines, 12 (60%) around polyethylene glenoids were present on immediate postoperative radiographs and 25% were progressive. No significant correlation was found between the presence of radiolucent lines around polyethylene glenoids and functional results (P =.3). By contrast, periprosthetic radiolucent lines around metal-backed glenoids were rare but progressive when present. The incidence of loosening of metal-backed implants (4 cases, 20%) was significantly higher than that observed with polyethylene glenoids (0%, P <.001) and was associated with component shift and severe osteolysis. Metal-backed glenoid loosening significantly correlated with deteriorating functional results and increasing pain (P <.05). Revision surgery was required for 4 patients in the metal-backed group (P =.02), for a subscapularis tear (1 case) and metal-backed glenoid component loosening (3 cases). Computed tomography scan analysis and revision surgery revealed that preoperative posterior humeral subluxation may recur with time despite glenoid reorientation and may cause asymmetric accelerated polyethylene wear, resulting in metal-on-metal contact and severe osteolysis. Reimplantation of a stable cemented glenoid component was possible in 1 case, whereas the cavitary defect was packed with cancellous bone in the 2 other cases. At a minimum of 3 years' follow-up, the results of this study clearly show that (1) the survival rate of cementless, metal-backed glenoid components is inferior to cemented all-polyethylene components and (2) the incidence of radiolucency at the glenoid-cement interface with all-polyethylene components is high and remains a concern. The high rate of loosening, because of the absence of ingrowth and/or the accelerated polyethylene wear, has led us to abandon the use of metal-backed glenoids. Efforts must continue to improve glenoid component design and fixation.", "In a prospective, randomized study between 2000 and 2004, 20 patients with primary osteoarthritis of the shoulder had a total shoulder arthroplasty with radiostereometric analysis, 10 with keeled and 10 with pegged glenoid components. The relative movement of the glenoid component with respect to the scapula was measured over a 24-month period. Three keeled and five pegged glenoids needed reaming for erosion. The largest translations occurred along the longitudinal axis (mean of 1.35 mm for keeled eroded components) (P = .017 for keeled vs pegged components and P = .013 for eroded vs non-eroded components). Both of the other translation axes showed no significant differences. The highest maximum total point movement at 24 months was 2.57 mm for keeled eroded components and 1.64 mm for pegged eroded components (P = .029 for keeled vs pegged components and P = .023 for eroded vs non-eroded components). The largest rotation was anteversion, with mean values of 5.5 degrees for keeled eroded components and 4.8 degrees for pegged eroded components (P = .658 for keeled vs pegged components and P = .90 for eroded vs non-eroded components). The mean varus tilt was 4.5 degrees for keeled eroded components compared with 2.3 degrees for pegged eroded components (P = .004 for keeled vs pegged components and P = .016 for eroded vs non-eroded components), and finally, anterior-posterior rotation mean values were 3.5 degrees for keeled eroded components and 1.1 degrees for pegged eroded components (P = .022 for keeled vs pegged components and P = .04 for eroded vs non-eroded components). In conclusion, whereas all components moved, radiostereometric analysis revealed increased migration with keeled components, exacerbated by glenoid erosion. Furthermore, a distinctive pattern of migration was identified over the 2-year period.", "The indications for resurfacing of the glenoid in patients who have osteoarthritis of the shoulder are not clearly defined; some investigators routinely perform hemiarthroplasty whereas others perform total shoulder arthroplasty.\n Forty-seven patients (fifty-one shoulders) who were scheduled to have a shoulder arthroplasty for the treatment of degenerative osteoarthritis were randomly assigned, according to a random-numbers table, to one of two groups: replacement of the humeral head with resurfacing of the glenoid with a polyethylene component with cement (total shoulder arthroplasty [twenty-seven shoulders]) or replacement of the humeral head without resurfacing of the glenoid (hemiarthroplasty [twenty-four shoulders]). All patients received the same type of humeral component, and all operations were performed by or under the direct supervision of the same surgeon. The patients were followed for a mean of thirty-five months (range, twenty-four to seventy-two months) postoperatively. Evaluation was performed with use of the scoring systems of the University of California at Los Angeles and the American Shoulder and Elbow Surgeons.\n No difference was observed between the preoperative scores for the two groups of patients. Postoperatively, the mean scores with use of the University of California at Los Angeles system and the American Shoulder and Elbow Surgeons system were 23.2 points (range, 10 to 31 points) and 65.2 points (range, 15 to 94 points), respectively, after hemiarthroplasty and 27.4 points (range, 9 to 34 points) and 77.3 points (range, 3 to 100 points), respectively, after total shoulder arthroplasty. With the numbers available for study, no significant difference was found between the two operative groups with respect to the postoperative score. (Thirty-five subjects per group would be needed, assuming an effect size of 0.60 and a power of 0.80.) Total shoulder arthroplasty provided significantly greater pain relief (p = 0.002) and internal rotation (p = 0.003) than hemiarthroplasty did. Total shoulder arthroplasty also provided superior results in the specific areas of patient satisfaction, function, and strength, although none of these differences were found to be significant, with the numbers available. Total shoulder arthroplasty was associated with increased cost ($1177), operative time (thirty-five minutes), and blood loss (150 milliliters) per patient compared with hemiarthroplasty. To date, none of the total shoulder arthroplasties in the study group have been revised. Hemiarthroplasty yielded equivalent results for elevation and external rotation. Three of the twenty-five patients who had had a hemiarthroplasty needed a subsequent operation for resurfacing of the glenoid. The mean cost for the revision operations was $15,998.\n Total shoulder arthroplasty provided superior pain relief compared with hemiarthroplasty in patients who had glenohumeral osteoarthritis, but it was associated with an increased cost of $1177 per patient.", "The correct implantation of the glenoid component is of paramount importance in total shoulder arthroplasty (TSA). We hypothesized that the accuracy of the glenoid positioning in the transverse plane can be improved using intraoperative navigation.\n This prospective, randomized clinical study comprised 2 groups of 10 patients each with osteoarthritis of the shoulder TSA, with or without intraoperative navigation. Glenoid version was measured on axial computed tomography scans preoperatively and 6 weeks postoperatively.\n The operating time was significantly longer in the navigation group (169.5 +/- 15.2 vs 138 +/- 18.4 min). We found an average change of retroversion from 15.4 degrees +/- 5.8 degrees (range, 3.0 degrees -24.0 degrees) preoperatively to 3.7 degrees +/- 6.3 degrees (range, -8.0 degrees to 15.0 degrees) postoperatively in the navigation group compared with 14.4 degrees +/- 6.1 degrees (range, 2.0 degrees -24.0 degrees) preoperatively to 10.9 degrees +/- 6.8 degrees (range, 0.0 degrees -19.0 degrees) postoperatively in the group without navigation (P = .021).\n We found an improved accuracy in glenoid positioning in the transverse plane using intraoperative navigation. The validity of the study is limited by the small number, which advocates continuation with more patients and longer follow-up.\n Level 2; Therapeutic study.", "Glenoid loosening is one reason for failure of total shoulder arthroplasty. Several factors, including radiographic lucency, have been shown to be associated with glenoid loosening. The purpose of this study was to assess the correlation between glenoid design and immediate radiographic lucency in a prospective randomized clinical trial. Total shoulder arthroplasty was performed in 43 patients over a 2-year period. Twenty-three patients were randomized into the keel group and twenty patients into the pegged group. Postoperative radiographs obtained within 6 weeks of surgery were evaluated by 3 raters to determine glenoid lucency. On a scale from 0 (no lucency) to 5 (gross lucency and component loosening), the rate of lucency was 39% (9/23) in the keeled components, which was significantly higher than the rate of 5% (1/20) observed in the pegged components (P = .026). Patient age, gender, and glenoid size did not significantly affect glenoid component lucency (P > .05). The consistency reliability among raters (Cronbach alpha) was 0.87, and the intertester reliability was 0.87. Pegged glenoid components have less radiographic lucency when compared with keeled glenoid components in the immediate postoperative period.", "Both total shoulder arthroplasty and hemiarthroplasty have been used commonly to treat severe osteoarthritis of the shoulder; however, their effect on disease-specific quality-of-life outcome is unknown. The purpose of this study was to compare the quality-of-life outcome following hemiarthroplasty with that following total shoulder arthroplasty in patients with osteoarthritis of the shoulder.\n Forty-two patients with a diagnosis of osteoarthritis of the shoulder were randomized to receive a hemiarthroplasty or a total shoulder arthroplasty. One patient died, and all others were evaluated preoperatively and at six weeks and three, six, twelve, eighteen, and twenty-four months postoperatively with use of a standardized format including a disease-specific quality-of-life measurement tool (Western Ontario Osteoarthritis of the Shoulder [WOOS] index), general shoulder rating scales (University of California at Los Angeles [UCLA] shoulder scale, Constant score, and American Shoulder and Elbow Surgeons [ASES] evaluation form), general pain scales (McGill pain score and visual analogue scale), and a global health measure (Short Form-36 [SF-36]). When a patient required revision of a hemiarthroplasty to a total shoulder arthroplasty, the last score before he or she \"crossed over\" was used for the analysis.\n Significant improvements in disease-specific quality of life were seen two years after both the total shoulder arthroplasties and the hemiarthroplasties. There were no significant differences in quality of life (WOOS score) between the group treated with total shoulder arthroplasty and that treated with hemiarthroplasty (90.6 +/- 13.2 and 81.5 +/- 24.1 points, respectively; p = 0.18). The other outcome measures demonstrated similar findings. Two patients in the hemiarthroplasty group crossed over to the other group by undergoing a revision to a total shoulder arthroplasty because of glenoid arthrosis.\n Both total shoulder arthroplasty and hemiarthroplasty improve disease-specific and general quality-of-life measurements. With the small number of patients in our study, we found no significant differences in these measurements between the two treatment groups.\n Therapeutic Level I.", "Considerable interest has been focused on the design of the glenoid component used in total shoulder arthroplasty in order to reduce the risk of loosening. One design-related feature that has attracted attention is whether to use pegged or keeled cemented glenoid components. The main purpose of this study was to compare the fixation of cemented keeled glenoid components with that of cemented in-line pegged glenoid components.\n In a prospective randomized study, we compared the stability of cemented, all-polyethylene, keeled glenoid components and cemented, all-polyethylene, in-line three-pegged glenoid components by radiostereometric analysis. Twenty-seven shoulders in twenty-five patients with osteoarthritis (twenty-two shoulders had primary and five shoulders had secondary osteoarthritis) were included. There were sixteen women and nine men, and the mean age was sixty-four years. Radiostereometric analysis and conventional radiographs were carried out at five days, at four months, and at one and two years postoperatively.\n The mean Constant and Murley score preoperatively and two years postoperatively was 25 and 70, respectively, for shoulders with the keeled glenoid component and 22 and 70 for the shoulders with a pegged component. No significant difference was detected between groups with regard to the average micromigration of the glenoid components at any of the time points. The average translation was <1 mm, while the median value was <0.3 mm at two years, with no significant difference between the different axes. In five shoulders (three with the keeled component and two with the pegged component), translation at two years was >1 mm. In fourteen shoulders (eight with the keeled and six with the pegged component), the rotation around one or several axes was >2 degrees . We were not able to detect any specific pattern with regard to movement for either type of component nor were we able to detect any difference between the two types of components in the way they migrated, if migration occurred.\n Cemented all-polyethylene keeled or in-line three-pegged glenoid components appear to have similar stability during the first two years after surgery. Studies with a longer follow-up period are needed to relate these findings to long-term clinical and radiographic outcomes." ]

[ "7042126", "10194586", "3610515", "5553582" ]

[ "Use of topical benzydamine in gynecology.", "Prevention of vaginal stenosis in patients following vaginal brachytherapy.", "Topical benzydamine in the treatment of vaginal radiomucositis.", "Postirradiation vaginitis. An evaluation of prophylaxis with topical estrogen." ]

[ "To evaluate the topical anti-inflammatory activity of benzydamine when used as 0.1% solution for vaginal douche, a double blind, parallel group, randomized clinical trial was carried out on 30 patients with vaginitis following internal radiotherapy for carcinoma of the uterus. The patients were divided into 3 groups, one being treated with 0.1% benzydamine plus tricetol as preservative, one with 0.1% benzydamine alone, and one with placebo. Treatment began 12-24 hours after radiotherapy. Benzydamine was found to be significantly superior to placebo in its overall topical anti-inflammatory activity both after 5 and 15 days of treatment. Tricetol did not interfere with the therapeutic effect of benzydamine.", "The assessment of patients following intracavitary irradiation administered as part of the treatment of gynaecological malignancy reveals vaginal stenosis in the majority. Vaginal dilators are available for daily insertion in an attempt to prevent the formation of adhesions. However, the design of the dilator neglects the fact that the vagina is the most distensible in the upper third and hence many patients develop stenosis of the upper vagina. Many clinicians have abandoned the use of dilators and instead advise patients to have sexual intercourse to prevent the problem. In 1994, we designed a new vaginal stent, which was given to all patients who had received intracavitary irradiation with full instructions about its use. This stent was designed to suit better the true anatomy of the vagina and hence, with correct use, should prevent vaginal stenosis. A retrospective study was undertaken to look at the incidence of vaginal stenosis and this was compared with the incidence in patients using the new stent. The study revealed that 57% of the patients who were advised to have sexual intercourse had stenosis, whereas 11% of the patients using the stent had evidence of stenosis, which, however, was related to their incorrect use of the stent. In those who used the stent correctly there was no evidence of vaginal stenosis. Details of the design of the stent and the problems relating to those who used the stent incorrectly are presented. The findings of this study strongly support the continued use of this vaginal stent in patients who have undergone intracavitary irradiation as a means of preventing this common complication.", "Radiotherapy for invasive cervical cancer involves a high risk of local complications. Classically, the critical structures are the rectum, the bladder and the bony ring of the pelvis. However, endocavitary curietherapy is an important component in the radiological treatment since it delivers the highest dose to the vaginal mucosa. The anti-inflammatory efficacy of benzydamine in gynaecology, already well documented, was investigated in our controlled clinical study (benzydamine vs. placebo) involving 32 consecutive unselected patients treated by endocavitary curietherapy with 137caesium sources, alone, after radical surgery, or in association with megavoltage external irradiation. In the group with topical benzydamine, we have observed a statistically significant improvement of subjective symptomatology and colposcopic view. On the contrary in the placebo group a worsening of all the clinical parameters considered became evident.", "nan" ]

[ "21349913", "12454299", "19748761", "17174082", "11923552", "21552662", "14720530", "11237275", "22116795", "16778272", "12853536" ]

[ "Skeletal muscle effects of electrostimulation after COPD exacerbation: a pilot study.", "Randomised controlled trial of transcutaneous electrical muscle stimulation of the lower extremities in patients with chronic obstructive pulmonary disease.", "Randomized controlled pilot study of neuromuscular electrical stimulation of the quadriceps in patients with non-small cell lung cancer.", "Skeletal muscle structure and function in response to electrical stimulation in moderately impaired COPD patients.", "Home based neuromuscular electrical stimulation as a new rehabilitative strategy for severely disabled patients with chronic obstructive pulmonary disease (COPD).", "Neuromuscular electrical stimulation improves exercise tolerance in chronic obstructive pulmonary disease patients with better preserved fat-free mass.", "Beneficial effects of chronic low-frequency stimulation of thigh muscles in patients with advanced chronic heart failure.", "Improvement of thigh muscles by neuromuscular electrical stimulation in patients with refractory heart failure: a single-blind, randomized, controlled trial.", "Functional and muscular effects of neuromuscular electrical stimulation in patients with severe COPD: a randomized clinical trial.", "Improvement in quadriceps strength and dyspnea in daily tasks after 1 month of electrical stimulation in severely deconditioned and malnourished COPD.", "Peripheral muscle strength training in bed-bound patients with COPD receiving mechanical ventilation: effect of electrical stimulation." ]

[ "Muscle dysfunction is a major problem in chronic obstructive pulmonary disease (COPD), particularly after exacerbations. We thus asked whether neuromuscular electrostimulation (NMES) might be directly useful following an acute exacerbation and if such a therapy decreases muscular oxidative stress and/or alters muscle fibre distribution. A pilot randomised controlled study of NMES lasting 6 weeks was carried out in 15 in-patients (n=9 NMES; n=6 sham) following a COPD exacerbation. Stimulation was delivered to the quadriceps and hamstring muscles (35 Hz). Primary outcomes were quadriceps force and muscle oxidative stress. At the end of the study, quadriceps force improvement was statistically different between groups (p=0.02), with a significant increase only in the NMES group (median (interquartile range) 10 (4.7-11.5) kg; p=0.01). Changes in the 6-min walking distance were statistically different between groups (p=0.008), with a significant increase in the NMES group (165 (125-203) m; p=0.003). NMES did not lead to higher muscle oxidative stress, as indicated by the decrease in total protein carbonylation (p=0.02) and myosin heavy chain carbonylation (p=0.01) levels. Finally, we observed a significant increase in type I fibre proportion in the NMES group. Our study shows that following COPD exacerbation, NMES is effective in counteracting muscle dysfunction and decreases muscle oxidative stress.", "Although exercise training improves exercise tolerance in most patients with chronic obstructive pulmonary disease (COPD), some patients with severe disease may not be able to tolerate exercise training due to incapacitating breathlessness. Transcutaneous electrical muscle stimulation (TCEMS) has been shown to improve muscle strength, muscle mass, and performance in paraplegics, patients with knee ligament injury, and patients with peripheral vascular disease. We hypothesised that TCEMS of the lower extremities can improve muscle strength and exercise tolerance in patients with moderate to severe COPD.\n A randomised controlled trial of TCEMS of the lower extremities was performed in 18 medically stable patients of mean (SD) age 60.0 (1.5) years with a mean forced expiratory volume in 1 second (FEV(1)) of 1.03 (0.10) l (38% predicted) and residual volume/total lung capacity (RV/TLC) of 59 (2)%. Stimulation of the lower extremities was performed three times a week, 20 minutes each session, for six continuous weeks. Quadriceps and hamstring muscle strength, exercise capacity, and peak oxygen uptake were measured at baseline and after 6 weeks of stimulation.\n TCEMS improved both the quadriceps strength (by 39.0 (20.4)% v 9.0 (8.1)%, p=0.046) and hamstring muscle strength (by 33.9 (13.0)% v 2.9 (4.7)%, p=0.038) in the treated (n=9) and sham treated (n=9) groups, respectively. The improvement in muscle strength carried over to better performance in the shuttle walk test in the treated group (36.1% v 1.6% in the treated and sham groups respectively, p=0.007, Mann-Whitney U test). There was no significant change in lung function, peak workload, or peak oxygen consumption in either group. Muscle stimulation was well tolerated by the patients with no dropouts and better than 95% compliance with the protocol.\n TCEMS of peripheral muscles can be a useful adjunct to the comprehensive pulmonary rehabilitation of patients with COPD.", "Patients with lung cancer experience muscle wasting and weakness. Therapeutic exercise may be beneficial but is not always practical. An alternative approach may be neuromuscular electrical stimulation (NMES) of the quadriceps muscles, but this has not been formally examined in patients with cancer. Thus, we have undertaken this pilot study to assess feasibility and inform the design of future studies. Sixteen patients were randomized to receive usual care (control group) or usual care plus NMES for four weeks. NMES consisted of daily stimulation to both thighs for up to 30minutes (frequency 50Hz, \"on\" cycle 11%-25%). Adherence was assessed by a self-report diary and a semistructured evaluation form. Quadriceps muscle strength, exercise endurance, and free-living physical activity were assessed using a Cybex NORM dynamometer, an endurance shuttle walk test, and an ActivPAL accelerometer (mean daily step count), respectively. Changes in outcome from baseline were compared between groups by mean differences and their 95% confidence intervals using independent t-test (P=0.05). Median (range) adherence to the program was 80% (69%-100%). All patients found the NMES device easy to use. Changes in outcome favored the NMES group, with mean differences of 9.4 Nm (21%) in quadriceps muscle strength, 768 steps (15%) in free-living activity, and 138 m (8%) in exercise endurance, but none of the differences were statistically significant. In conclusion, NMES warrants further study in patients with lung cancer.", "To determine the structural and functional consequences of high-frequency neuromuscular electrical stimulation (hf-NMES) in a group of moderately impaired outpatients with chronic obstructive pulmonary disease (COPD).\n A prospective, cross-over randomized trial.\n An university-based, tertiary center.\n Seventeen patients (FEV(1)=49.6+/-13.4% predicted, Medical Research Council dyspnoea grades II-III) underwent 6-weeks hf-NMES (50Hz) and sham stimulation of the quadriceps femoris in a randomized, cross-over design. Knee strength was measured by isokinetic dynamometry (peak torque) and leg muscle mass (LMM) by DEXA; in addition, median cross-sectional area (CSA) of type I and II fibres and capillary-fibre ratio were evaluated in the vastus lateralis. The 6-min walking distance (6MWD) was also determined.\n At baseline, patients presented with well-preserved functional capacity, muscle strength and mass: there was a significant relationship between strength and type II CSA (P<0.05). NMES was not associated with significant changes in peak torque, LMM or 6MWD as compared to sham (P>0.05). At micro-structural level, however, electrical stimulation increased type II, but decreased type I, CSA; no change, however, was found in the relative fibre distribution or capillary:fibre ratio (P<0.05). There was no significant association between individual changes in structure and function with training (P>0.05). Post-NMES increase in type II CSA was inversely related to baseline mass and strength (P<0.05).\n NMES may promote a modest degree of type II muscle fibre hypertrophy in COPD patients with well-preserved functional status. These micro-structural changes, however, were not translated into increased volitional strength in this sub-population.", "Passive training of specific locomotor muscle groups by means of neuromuscular electrical stimulation (NMES) might be better tolerated than whole body exercise in patients with severe chronic obstructive pulmonary disease (COPD). It was hypothesised that this novel strategy would be particularly effective in improving functional impairment and the consequent disability which characterises patients with end stage COPD.\n Fifteen patients with advanced COPD (nine men) were randomly assigned to either a home based 6 week quadriceps femoris NMES training programme (group 1, n=9, FEV(1)=38.0 (9.6)% of predicted) or a 6 week control period before receiving NMES (group 2, n=6, FEV(1)=39.5 (13.3)% of predicted). Knee extensor strength and endurance, whole body exercise capacity, and health related quality of life (Chronic Respiratory Disease Questionnaire, CRDQ) were assessed.\n All patients were able to complete the NMES training programme successfully, even in the presence of exacerbations (n=4). Training was associated with significant improvements in muscle function, maximal and endurance exercise tolerance, and the dyspnoea domain of the CRDQ (p<0.05). Improvements in muscle performance and exercise capacity after NMES correlated well with a reduction in perception of leg effort corrected for exercise intensity (p<0.01).\n For severely disabled COPD patients with incapacitating dyspnoea, short term electrical stimulation of selected lower limb muscles involved in ambulation can improve muscle strength and endurance, whole body exercise tolerance, and breathlessness during activities of daily living.", "High-frequency neuromuscular electrical stimulation increases exercise tolerance in patients with advanced chronic obstructive pulmonary disease (COPD patients). However, it is conceivable that its benefits are more prominent in patients with better-preserved peripheral muscle function and structure.\n To investigate the effects of high-frequency neuromuscular electrical stimulation in COPD patients with better-preserved peripheral muscle function. Design: Prospective and cross-over study.\n Thirty COPD patients were randomly assigned to either home-based, high-frequency neuromuscular electrical stimulation or sham stimulation for six weeks. The training intensity was adjusted according to each subject's tolerance. Fat-free mass, isometric strength, six-minute walking distance and time to exercise intolerance (Tlim) were assessed.\n Thirteen (46.4%) patients responded to high-frequency neuromuscular electrical stimulation; that is, they had a post/pre Δ Tlim >10% after stimulation (unimproved after sham stimulation). Responders had a higher baseline fat-free mass and six-minute walking distance than their seventeen (53.6%) non-responding counterparts. Responders trained at higher stimulation intensities; their mean amplitude of stimulation during training was significantly related to their fat-free mass (r = 0.65; p<0.01). Logistic regression revealed that fat-free mass was the single independent predictor of Tlim improvement (odds ratio [95% CI] = 1.15 [1.04-1.26]; p<0.05).\n We conclude that high-frequency neuromuscular electrical stimulation improved the exercise capacity of COPD patients with better-preserved fat-free mass because they tolerated higher training stimulus levels. These data suggest that early training with high-frequency neuromuscular electrical stimulation before tissue wasting begins might enhance exercise tolerance in patients with less advanced COPD.", "Patients with chronic heart failure (CHF) exhibit detrimental changes in skeletal muscle that contribute to their impaired physical performance. This study investigates the possibility of counteracting these changes by chronic low-frequency electrical stimulation (CLFS) of left and right thigh muscles.\n (mean+/-SD) 32 CHF patients (53+/-10 years) with an LVEF of 22+/-5%, NYHA II-IV, undergoing optimized drug therapy, were randomized in a CLFS group (CLFSG) or a control group (controls). The groups differed in terms of the intensity of stimulation, which elicited strong muscle contractions only in the CLFSG, whereas the controls received current input up to the sensory threshold without muscle contractions. Functional capacity was assessed by peak VO(2), work capacity, and a 6-min-walk (6-MW). Muscle biopsies were analyzed for myosin heavy chain (MHC) isoforms, citrate synthase (CS) and glyceraldehydephosphate dehydrogenase (GAPDH) activities. Peak VO(2)(mlmin(-1)kg -1) increased from 9.6+/-3.5 to 11.6+/-2.8 (P<0.001) in the CLFSG, and decreased from 10.6+/-2.8 to 9.4+/-3.2 (P<0.05) in the controls. The increase in the CLFSG was paralleled by increases in maximal workload (P<0.05) and oxygen uptake at the anaerobic threshold (P<0.01). The corresponding values of the controls were unchanged, as also the 6-MW values, the MHC isoform distribution, and both CS and GAPDH activities. In the CLFSG, the 6-MW values increased (P<0.001), CS activity was elevated (P<0.05), GAPDH activity decreased (P<0.01), and the MHC isoforms were shifted in the slow direction with increases in MHCI at the expense of MHCIId/x (P<0.01).\n Our results suggest that CLFS is a suitable treatment to counteract detrimental changes in skeletal muscle and to increase exercise capacity in patients with severe CHF.", "To determine the impact of an 8-wk neuromuscular stimulation program of thigh muscles on strength and cross-sectional area in patients with refractory heart failure listed for transplantation.\n Forty-two patients with a stable disease course were assigned randomly to a stimulation group (SG) or a control group (CG). The stimulation protocol consisted of biphasic symmetric impulses with a frequency of 50 Hz and an on/off regime of 2/6 sec.\n Primary outcome measures were isometric and isokinetic thigh muscle strength and muscle cross-sectional area. Our results showed an increase of muscle strength by mean 22.7 for knee extensor and by 35.4 for knee flexor muscles. The CG remained unchanged or decreased by -8.4 in extensor strength. Cross-sectional area increased in the SG by 15.5 and in the CG by 1.7.\n Activities of daily living as well as quality of life increased in the SG but not in the CG. Subscales of the SF-36 increased significantly in the SG, especially concerning physical functioning by +7.5 (1.3-30.0), emotional role by +33.3 (0-66.6), and social functioning by +18.8 (0-46.9), all P < 0.05. Neither a change nor a decrease was observed in the CG. Neuromuscular electrical stimulation of thigh muscles in patients with refractory heart failure is effective in increasing muscle strength and bulk and positively affects the perception of quality of life and activities of daily living.", "The mechanisms through which neuromuscular electrical stimulation (NMES) training may improve limb muscle function and exercise tolerance in COPD are poorly understood. We investigated the functional and muscular effects of NMES in advanced COPD.\n Twenty of 22 patients with COPD were randomly assigned to NMES (n = 12) or sham (n = 8) training in a double-blind controlled study. NMES was performed on quadriceps and calf muscles, at home, 5 days per week for 6 weeks. Quadriceps and calf muscle cross-sectional area (CSA), quadriceps force and endurance, and the shuttle-walking distance with cardiorespiratory measurements were assessed before and after training. Quadriceps biopsy specimens were obtained to explore the insulin-like growth factor-1/AKT signaling pathway (70-kDa ribosomal S6 kinase [p70S6K] , atrogin-1).\n NMES training improved muscle CSA (P < .05), force, and endurance (P < .03) when compared with sham training. Phosphorylated p70S6K levels (anabolism) were increased after NMES as compared with sham (P = .03), whereas atrogin-1 levels (catabolism) were reduced (P = .01). Changes in quadriceps strength and ventilation during walking contributed independently to variations in walking distance after training (r = 0.77, P < .001). Gains in walking distance were related to the ability to tolerate increasing current intensities during training (r = 0.95, P < .001).\n In patients with severe COPD, NMES improved muscle CSA. This was associated with a more favorable muscle anabolic to catabolic balance. Improvement in walking distance after NMES training was associated with gains in muscle strength, reduced ventilation during walking, and the ability to tolerate higher stimulation intensity. Trial registry: ClinicalTrials.gov; No.: NCT00874965; URL: www.clinicaltrials.gov.", "Low body weight in COPD patients is associated with worsening dyspnea, reduced leg strength, and poor prognosis. Classical rehabilitation strategies are then limited by reduced exercise tolerance. Thus, we proposed to evaluate whether electrostimulation (ES) was a beneficial technique in the rehabilitation programs for severely deconditioned COPD patients after an acute exacerbation.\n Randomized, controlled study.\n Pulmonary rehabilitation center.\n Seventeen patients with severe COPD (mean [ +/- SD] FEV(1), 30 +/- 3% predicted) and low body mass index (BMI) [18 +/- 2.5 kg/m(2)].\n Patients were randomly assigned either to usual rehabilitation (UR) alone or to a UR-plus-ES program for 4 weeks. Quadriceps muscle strength, total muscle mass (MM), exercise capacity, and health-related quality of life were measured before and after rehabilitation.\n The training with ES plus UR induced a significant twofold improvement in the mean number of maximal voluntary contraction (MVC) compared to UR alone (97 +/- 71 vs 36 +/- 34 contractions, respectively; p = 0.03) and resulted in a more significant improvement in dyspnea when performing daily tasks (decrease in the dyspnea domain score of the 28-item Maugeri Foundation Respiratory Failure questionnaire, -1.7 +/- 1.0 vs -0.2 +/- 1.2 points, respectively; p = 0.05). There was also a significant increase in walking distance (63 +/- 40 m; p = 0.01) and BMI (0.6 +/- 0.5 kg/m(2); p = 0.02) after training in the ES + UR group. A significant relationship was found between changes in MVC and changes in MM after training in the ES + UR group (r = 0.94; p = 0.03).\n The combination of ES and UR was associated with greater improvement in quadriceps strength and dyspnea during the performance of daily tasks than UR alone in severely disabled COPD patients with low BMI. In this population, ES has been revealed as a useful procedure, complementing the usual pulmonary rehabilitation.", "To compare the effects of active limb mobilization (ALM) with or without electrical stimulation (ES) on muscle strength, respiratory rate (RR), heart rate, oxygen saturation, and time needed to transfer from bed to chair in two groups of patients with COPD.\n Randomized, controlled study.\n Respiratory high-dependency care unit.\n Twenty-four bed-bound patients with chronic hypercapnic respiratory failure due to COPD who were receiving mechanical ventilation, with marked peripheral muscle hypotonia and atrophy.\n Patients were randomly assigned either to ALM alone or to ALM plus ES (ALM/ES). ES was applied using square-wave alternate, symmetric, and compensated impulses for 30 min bid. The duration of treatment was 28 days for all patients.\n Muscle strength improved significantly in the overall group of patients (from 1.75 +/- 0.73 to 3.44 +/- 0.65, p < 0.05). Comparing the change (end minus beginning) of the analyzed variables, ALM/ES significantly improved muscle strength (2.16 +/- 1.02 vs 1.25 +/- 0.75, p = 0.02) and RR (- 1.91 +/- 1.72 vs 0.41 +/- 1.88, p = 0.004), and decreased the number of days needed to transfer from bed to chair (10.75 +/- 2.41 days vs 14.33 +/- 2.53 days, p = 0.001).\n In bed-bound patients with COPD receiving mechanical ventilation, with marked peripheral muscle hypotonia and atrophy, application of ES in addition to classical ALM significantly improved muscle strength and decreased the number of days needed to transfer from bed to chair." ]

[ "10333127", "333077" ]

[ "Comparison of albumin versus bicarbonate treatment for neonatal metabolic acidosis.", "Controlled trial of bicarbonate therapy in high-risk premature newborn infants." ]

[ "In this study the effectiveness of 4.5% human albumin was compared with 4.2% sodium bicarbonate for neonatal metabolic acidosis, using a randomised controlled trial. The change in median pH following bicarbonate was more than twice that in the albumin group. This was statistically significant.\n In normotensive infants, use of bicarbonate to correct metabolic acidosis may be more effective than use of albumin.", "Sixty-two high-risk acidemic premature newborn infants, given maintenance intravascular infusions of 10% glucose, were assigned to liberal or restricted sodium bicarbonate treatment groups. Those infants in the liberal group received 5 to 15 mEq bicarbonate/dl 10% glucose, depending on the degree of acidosis. Among infants given bicarbonate, correction of pH was not more rapid and mortality was not decreased. Instead, there was a small increase in the number of deaths, but the incidence of intraventricular hemorrhage was similar to that in infants not given bicarbonate." ]

[ "15599837", "12695272", "18995174", "10493325", "16061499", "11738225", "16499299", "14564327", "10683133", "18790668", "11911726", "16624687", "18936502", "17942364", "16533388", "17802984", "18222552", "15492340", "18776075", "18337049", "17402355" ]

[ "A multicenter disease management program for hospitalized patients with heart failure.", "Case management in a heterogeneous congestive heart failure population: a randomized controlled trial.", "A randomized clinical trial of the clinical effects of enhanced heart failure monitoring using a computer-based telephonic monitoring system in older minorities and women.", "Reduction in heart failure events by the addition of a clinical pharmacist to the heart failure management team: results of the Pharmacist in Heart Failure Assessment Recommendation and Monitoring (PHARM) Study.", "Randomised trial of telephone intervention in chronic heart failure: DIAL trial.", "Compliance and effectiveness of 1 year's home telemonitoring. The report of a pilot study of patients with chronic heart failure.", "[The telemonitoring service].", "Randomized trial of a daily electronic home monitoring system in patients with advanced heart failure: the Weight Monitoring in Heart Failure (WHARF) trial.", "Impact of pharmacist interventions on hospital readmissions for heart failure.", "Tele-guidance of chronic heart failure patients enhances knowledge about the disease. A multi-centre, randomised controlled study.", "Effect of a standardized nurse case-management telephone intervention on resource use in patients with chronic heart failure.", "Randomized controlled trial of telephone case management in Hispanics of Mexican origin with heart failure.", "Cost-effectiveness of nurse-led disease management for heart failure in an ethnically diverse urban community.", "Adherence, adaptation and acceptance of elderly chronic heart failure patients to receiving healthcare via telephone-monitoring.", "A heart failure self-management program for patients of all literacy levels: a randomized, controlled trial [ISRCTN11535170].", "Impact of a comprehensive telephone-based disease management programme on quality-of-life in patients with heart failure.", "Multicenter randomised trial on home-based telemanagement to prevent hospital readmission of patients with chronic heart failure.", "Care management for low-risk patients with heart failure: a randomized, controlled trial.", "Impact of telemonitoring at home on the management of elderly patients with congestive heart failure.", "Nurse and patient communication profiles in a home-based telehealth intervention for heart failure management.", "[Disease management for heart failure patients: role of wireless technologies for telemedicine. The ICAROS project]." ]

[ "Despite the availability of proven therapies, outcomes in patients with heart failure (HF) remain poor. In this 2-stage, multicenter trial, we evaluated the effect of a disease management program on clinical and economic outcomes in patients with HF.\n In Stage 1, a pharmacist or nurse assessed each patient and made recommendations to the physician to add or adjust angiotensin-converting enzyme (ACE) inhibitors and other HF medications. Before discharge (Stage 2), patients were randomized to a patient support program (PSP) (education about HF, self-monitoring, adherence aids, newsletters, telephone hotline, and follow-up at 2 weeks, then monthly for 6 months after discharge) or usual care. In Stage 1 (766 patients) ACE inhibitor use increased from 58% on admission to 83% at discharge (P < .0001), and the daily dose (in enalapril equivalents) increased from 11.3 +/- 8.8 mg to 14.5 +/- 8.8 mg (P < .0001). In Stage 2 (276 patients) there was no difference in ACE inhibitor adherence, but a reduction in cardiovascular-related emergency room visits (49 versus 20, P = .030), hospitalization days (812 versus 341, P = .003), and cost of care (2,531 Canadian dollars less per patient) in favor of the PSP.\n Simple interventions can improve ACE inhibitor use and patient outcomes.", "Both randomized and nonrandomized controlled studies have linked congestive heart failure (CHF) case management (CM) to decreased readmissions and improved outcomes in mostly homogeneous settings. The objective of this randomized controlled trial was to test the effect of CHF CM on the 90-day readmission rate in a more heterogeneous setting.\n A total of 287 patients admitted to the hospital with the primary or secondary diagnosis of CHF, left ventricular dysfunction of less than 40%, or radiologic evidence of pulmonary edema for which they underwent diuresis were randomized. The intervention consisted of 4 major components: early discharge planning, patient and family CHF education, 12 weeks of telephone follow-up, and promotion of optimal CHF medications.\n The 90-day readmission rates were equal for the CM and usual care groups (37%). Total inpatient and outpatient median costs and readmission median cost were reduced 14% and 26%, respectively, for the intervention group. Patients in the CM group were more likely to be taking CHF medication at target doses, but dosages did not increase significantly throughout 12 weeks. Although both groups took their medications as prescribed equally well, the rest of the adherence to treatment plan was significantly better in the CM group. Subgroup analysis of patients who lived locally and saw a cardiologist showed a significant decrease in CHF readmissions for the intervention group (P =.03).\n These results suggest several limitations to the generalizability of the CHF CM-improved outcome link in a heterogeneous setting. One explanation is that the lack of coordinated system supports and varied accessibility to care in an extended, nonnetworked physician setting limits the effectiveness of the CM.", "Prior studies suggest that disease management programs may be effective in improving clinical outcomes in patients with heart failure (HF). However, the use of these programs in settings with limited sources and among diverse population is not know. Thus the present study was designed to assess the impact of a computer-based home disease management program (Alere DayLink HF Monitoring System [HFMS]) on the clinical outcomes of Medicare beneficiaries with HF who were elderly, women, and non-white males who received the care from a community-based primary care practitioner.\n The Heart Failure Home Care (HFHC) trial was a multicenter, randomized, controlled trial of HFMS versus standard heart failure care (SC: enhanced patient education, education to clinicians, and follow-up). The primary study end point was treatment failure, defined as a composite of cardiovascular death or rehospitalization for heart failure within 6 months of enrollment. Among patients rehospitalized for HF, length of hospital stay was also considered a primary end point. A total of 315 patients were randomized: 160 to HFMS and 155 to SC. Although the incidence of the primary outcome was somewhat higher in the SC arm (28.8% versus 21.2%, P = .15), the difference was not statistically different. The length of hospital stay was also similar in both groups.\n Our study results suggest that enhanced patient education and follow-up is as successful as a sophisticated home monitoring device with an interactive program in patients with HF who are elderly, women and non-Caucasian males and receive the care from a community-based primary care practitioner.", "The multidisciplinary approach to managing heart failure has been shown to improve outcomes. The role of a clinical pharmacist in treating heart failure has not been evaluated.\n One hundred eighty-one patients with heart failure and left ventricular dysfunction (ejection fraction <45) undergoing evaluation in clinic were randomized to an intervention or a control group. Patients in the intervention group received clinical pharmacist evaluation, which included medication evaluation, therapeutic recommendations to the attending physician, patient education, and follow-up telemonitoring. The control group received usual care. The primary end point was combined all-cause mortality and heart failure clinical events. All clinical events were adjudicated by a blinded end point committee.\n Baseline characteristics were similar except for slightly higher age in the intervention group. Median follow-up was 6 months. All-cause mortality and heart failure events were significantly lower in the intervention group compared with the control group (4 vs 16; P= .005). In addition, patients in the intervention group received higher angiotensin-converting enzyme inhibitor doses as reflected by the median fraction of target reached (25th and 75th percentiles), 1.0 (0.5 and 1) and 0.5 (0.1875 and 1) in the intervention and control groups, respectively (P<.001). The use of other vasodilators in angiotensin-converting enzyme inhibitor-intolerant patients was higher in the intervention group (75% vs 26%; P= .02).\n Outcomes in heart failure can be improved with a clinical pharmacist as a member of the multidisciplinary heart failure team. This observation may be due to higher doses of angiotensin-converting enzyme inhibitors and/or closer follow-up.", "To determine whether a centralised telephone intervention reduces the incidence of death or admission for worsening heart failure in outpatients with chronic heart failure.\n Multicentre randomised controlled trial.\n 51 centres in Argentina (public and private hospitals and ambulatory settings).\n 1518 outpatients with stable chronic heart failure and optimal drug treatment randomised, stratified by attending cardiologist, to telephone intervention or usual care.\n Education, counselling, and monitoring by nurses through frequent telephone follow-up in addition to usual care, delivered from a single centre.\n All cause mortality or admission to hospital for worsening heart failure.\n Complete follow-up was available in 99.5% of patients. The 758 patients in the usual care group were more likely to be admitted for worsening heart failure or to die (235 events, 31%) than the 760 patients who received the telephone intervention (200 events, 26.3%) (relative risk reduction = 20%, 95% confidence interval 3 to 34, P = 0.026). This benefit was mostly due to a significant reduction in admissions for heart failure (relative risk reduction = 29%, P = 0.005). Mortality was similar in both groups. At the end of the study the intervention group had a better quality of life than the usual care group (mean total score on Minnesota living with heart failure questionnaire 30.6 v 35, P = 0.001).\n This simple, centralised heart failure programme was effective in reducing the primary end point through a significant reduction in admissions to hospital for heart failure.", "Patients with a diagnosis of heart failure, registered at the study practice, were recruited into the study. First, they had a cardiologist's assessment. They were then randomised into telemonitored patients who measured pulse, BP, weight and video consulted, and controls.\n To examine the acceptability, effectiveness and reliability of home telemonitoring.\n A high proportion of those invited took part (n=20/24). Compliance with measuring weight, pulse and BP remained high throughout the study. The data collection system and secure web-server were reliable. The telemonitoring group complied better with collecting prescriptions for their cardiac drugs. Video consulting started with enthusiasm, but became less useful. There were no significant differences in the quality of life (GHQ) and Chronic Heart Failure (Guyatt) questionnaire scores between the telemonitored group and the controls.\n Home telemonitoring is an acceptable reliable intervention. Baseline rates for compliance with self-monitoring are set out in this study. Benefit in terms of compliance with medication and self-monitoring is still seen after 1 year. Video consulting over ordinary telephone lines did not show sustained benefit, and was not complied with.", "nan", "Heart failure treatment guidelines emphasize daily weight monitoring for patients with heart failure, but data to support this practice are lacking. Using a technology-based heart failure monitoring system, we determined whether daily reporting of weight and symptoms in patients with advanced heart failure would reduce rehospitalization and mortality rates despite aggressive guideline-driven heart failure care.\n This was a randomized, controlled trial. Patients hospitalized with New York Heart Association class III or IV heart failure, with a left ventricular ejection fraction < or =35% were randomized to receive heart failure program care or heart failure program care plus the AlereNet system (Alere Medical, Reno, Nev) and followed-up for 6 months. The primary end point was 6-month hospital readmission rate. Secondary end points included mortality, heart failure hospitalization readmission rate, emergency room visitation rate, and quality of life.\n Two hundred eighty patients from 16 heart failure centers across the United States were randomized: 138 received the AlereNet system and 142 received standard care. Mean age was 59 +/- 15 years and 68% were male. The population had very advanced heart failure, New York Heart Association class III (75%) or IV (25%), as evidenced by serum norepinepherine levels, 6-minute walk distance and outcomes. No differences in hospitalization rates were observed. There was a 56.2% reduction in mortality (P <.003) for patients randomized to the AlereNet group.\n This is the largest multicenter, randomized trial of a technology-based daily weight and symptom-monitoring system for patients with advanced heart failure. Despite no difference in the primary end point of rehospitalization rates, mortality was significantly reduced for patients randomized to the AlereNet system without an increase in utilization, despite specialized and aggressive heart failure care in both groups.", "nan", "New strategies are required to optimize care in increasing numbers of chronic heart failure patients. The aim of this randomised trial was to evaluate a remote guidance system.\n Intervention group patients received a home TV-channel providing educational materials. Tele-guidance was performed by a Medical Service Centre. Control group patients were followed by cardiologists and HF-nurses. Primary endpoints were total days in hospital for all causes and days alive and out of hospital. Secondary endpoints were: quality of life and knowledge of disease and self care.\n 214 patients were enrolled, median age was 66 years, 89% had systolic LV dysfunction, and 90% were in NYHA class II or III. The mean LVEF was 31%. Over a mean follow-up duration of 288 days, there were 199 hospital admissions in 105 patients. Comparison of the groups revealed no differences for the primary outcomes or for QoL or self care behaviour. Knowledge about heart failure however, increased significantly more in the Intervention group (p<0.001).\n Tele-guidance may play a role in the management of heart failure patients since it takes over some of the tasks of HF-nurses. This may facilitate delivery of optimal care to more patients with the same level of experienced staff.", "Case management is believed to promote continuity of care and decrease hospitalization rates, although few controlled trials have tested this approach.\n To assess the effectiveness of a standardized telephonic case-management intervention in decreasing resource use in patients with chronic heart failure.\n A randomized controlled clinical trial was used to assess the effect of telephonic case management on resource use. Patients were identified at hospitalization and assigned to receive 6 months of intervention (n = 130) or usual care (n = 228) based on the group to which their physician was randomized. Hospitalization rates, readmission rates, hospital days, days to first rehospitalization, multiple readmissions, emergency department visits, inpatient costs, outpatient resource use, and patient satisfaction were measured at 3 and 6 months.\n The heart failure hospitalization rate was 45.7% lower in the intervention group at 3 months (P =.03) and 47.8% lower at 6 months (P =.01). Heart failure hospital days (P =.03) and multiple readmissions (P =.03) were significantly lower in the intervention group at 6 months. Inpatient heart failure costs were 45.5% lower at 6 months (P =.04). A cost saving was realized even after intervention costs were deducted. There was no evidence of cost shifting to the outpatient setting. Patient satisfaction with care was higher in the intervention group.\n The reduction in hospitalizations, costs, and other resource use achieved using standardized telephonic case management in the early months after a heart failure admission is greater than that usually achieved with pharmaceutical therapy and comparable with other disease management approaches.", "Disease management is effective in the general population, but it has not been tested prospectively in a sample of solely Hispanics with heart failure (HF). We tested the effectiveness of telephone case management in decreasing hospitalizations and improving health-related quality of life (HRQL) and depression in Hispanics of Mexican origin with HF.\n Hospitalized Hispanics with chronic HF (n = 134) were enrolled and randomized to intervention (n = 69) or usual care (n = 65). The sample was elderly (72 +/- 11 years), New York Heart Association class III/IV (81.3%), and poorly educated (78.4% less than high school education). Most (55%) were unacculturated into US society. Bilingual/bicultural Mexican-American registered nurses provided 6 months of standardized telephone case management. Data on hospitalizations were collected from automated systems at 1, 3, and 6 months after the index hospital discharge. Health-related quality of life and depression were measured by self-report at enrollment, 3, and 6 months. Intention to treat analysis was used. No significant group differences were found in HF hospitalizations, the primary outcome variable (usual care: 0.49 +/- 0.81 [CI 0.25-0.73]; intervention: 0.55 +/- 1.1 [CI 0.32-0.78] at 6 months). No significant group differences were found in HF readmission rate, HF days in the hospital, HF cost of care, all-cause hospitalizations or cost, mortality, HRQL, or depression.\n These results have important implications because of the current widespread enthusiasm for disease management. Although disease management is effective in the mainstream HF patient population, in Hispanics this ill, elderly, and poorly educated, a different approach may be needed.", "Randomized, controlled trials have shown that nurse-led disease management for patients with heart failure can reduce hospitalizations. Less is known about the cost-effectiveness of these interventions.\n To estimate the cost-effectiveness of a nurse-led disease management intervention over 12 months, implemented in a randomized, controlled effectiveness trial.\n Cost-effectiveness analysis conducted alongside a randomized trial.\n Medical costs from administrative records, and self-reported quality of life and nonmedical costs from patient surveys.\n Patients with systolic dysfunction recruited from ambulatory clinics in Harlem, New York.\n 12 months. Perspective: Societal and payer.\n 12-month program that involved 1 face-to-face encounter with a nurse and regular telephone follow-up.\n Quality of life as measured by the Health Utilities Index Mark 3 and EuroQol-5D and cost-effectiveness as measured by the incremental cost-effectiveness ratio (ICER).\n Costs and quality of life were higher in the nurse-managed group than the usual care group. The ICERs over 12 months were $17,543 per EuroQol-5D-based quality-adjusted life-year (QALY) and $15,169 per Health Utilities Index Mark 3-based QALY (in 2001 U.S. dollars).\n From a payer perspective, the ICER ranged from $3673 to $4495 per QALY. Applying national prices in place of New York City prices yielded a societal ICER of $13,460 to $15,556 per QALY. Cost-effectiveness acceptability curves suggest that the intervention was most likely cost-effective for patients with less severe (New York Heart Association classes I to II) heart failure.\n The trial was conducted in an ethnically diverse, inner-city neighborhood; thus, results may not be generalizable to other communities.\n Over 12 months, the nurse-led disease management program was a reasonably cost-effective way to reduce the burden of heart failure in this community.", "Although the potential to reduce hospitalisation and mortality in chronic heart failure (CHF) is well reported, the feasibility of receiving healthcare by structured telephone support or telemonitoring is not.\n To determine; adherence, adaptation and acceptability to a national nurse-coordinated telephone-monitoring CHF management strategy. The Chronic Heart Failure Assistance by Telephone Study (CHAT).\n Triangulation of descriptive statistics, feedback surveys and qualitative analysis of clinical notes. Cohort comprised of standard care plus intervention (SC+I) participants who completed the first year of the study.\n 30 GPs (70% rural) randomised to SC+I recruited 79 eligible participants, of whom 60 (76%) completed the full 12 month follow-up period. During this time 3619 calls were made into the CHAT system (mean 45.81 SD+/-79.26, range 0-369), Overall there was an adherence to the study protocol of 65.8% (95% CI 0.54-0.75; p=0.001) however, of the 60 participants who completed the 12 month follow-up period the adherence was significantly higher at 92.3% (95% CI 0.82-0.97, p<or=0.001). Only 3% of this elderly group (mean age 74.7+/-9.3 years) were unable to learn or competently use the technology. Participants rated CHAT with a total acceptability rate of 76.45%.\n This study shows that elderly CHF patients can adapt quickly, find telephone-monitoring an acceptable part of their healthcare routine, and are able to maintain good adherence for a least 12 months.", "Self-management programs for patients with heart failure can reduce hospitalizations and mortality. However, no programs have analyzed their usefulness for patients with low literacy. We compared the efficacy of a heart failure self-management program designed for patients with low literacy versus usual care.\n We performed a 12-month randomized controlled trial. From November 2001 to April 2003, we enrolled participants aged 30-80, who had heart failure and took furosemide. Intervention patients received education on self-care emphasizing daily weight measurement, diuretic dose self-adjustment, and symptom recognition and response. Picture-based educational materials, a digital scale, and scheduled telephone follow-up were provided to reinforce adherence. Control patients received a generic heart failure brochure and usual care. Primary outcomes were combined hospitalization or death, and heart failure-related quality of life.\n 123 patients (64 control, 59 intervention) participated; 41% had inadequate literacy. Patients in the intervention group had a lower rate of hospitalization or death (crude incidence rate ratio (IRR) = 0.69; CI 0.4, 1.2; adjusted IRR = 0.53; CI 0.32, 0.89). This difference was larger for patients with low literacy (IRR = 0.39; CI 0.16, 0.91) than for higher literacy (IRR = 0.56; CI 0.3, 1.04), but the interaction was not statistically significant. At 12 months, more patients in the intervention group reported monitoring weights daily (79% vs. 29%, p < 0.0001). After adjusting for baseline demographic and treatment differences, we found no difference in heart failure-related quality of life at 12 months (difference = -2; CI -5, +9).\n A primary care-based heart failure self-management program designed for patients with low literacy reduces the risk of hospitalizations or death.", "Disease management programmes for patients with heart failure have improving the quality-of-life (QOL) of patients with heart failure.\n Patients attending the heart failure clinic were randomized into 2 groups of 25 patients each. The control group was managed in the heart failure clinic and the intervention group underwent the following additional interventions: (i) interactive sessions with the patient and spouse informing them about the disease, drugs, and self-management of fluid intake and diuretic dose; (ii) a telephonic helpline was established and regular telephone calls made to reinforce the information and modify drug dosages. The QOL was assessed using the Kansas City Cardiomyopathy questionnaire. Functional capacity was assessed by the 6-minute walk test. Continuous variables were compared with the Student t-test (paired or unpaired).\n There was significant improvement in the QOL and functional capacity of patients in the intervention group compared with controls over a 6-month period. The mean (SD) QOL scores in the intervention group improved from 60.0 (23.6) to 76.3 (17.3) but did not change significantly in the control group (62.2 [22.6] to 63.4 [21.9]). There was a similar improvement in the functional capacity measured by the 6-minute walk test in the intervention group (from 202.2 [81.5] to 238.1 [100.9] metres, p < 0.05) but not in the control group (193.8 [81.5] to 179.7 [112.0] metres). In the intervention group, the use of beta-blockers and angiotensin-converting enzyme inhibitors was similar but in the intervention group patients were placed on higher doses. There was no significant difference in the number of emergency room visits or admissions in either group. For every 20 patients in the intervention group, 14 patients improved by 1 functional class while in the control group this was observed in only 3 patients for every 20 treated.\n This study demonstrates that in the setting of a developing country, improvement in QOL by intensive management of heart failure patients through a heart failure programme with telephonic reinforcement and a helpline is greater than that usually achieved with drug therapy in a routine heart failure clinic.", "Chronic heart failure (CHF) remains a common cause of disability, death and hospital admission. Several investigations support the usefulness of programs of disease management for improving clinical outcomes. However, the effect of home-based telemanagement programs on the rate of hospital readmission is still unclear and the cost-effectiveness ratio of such programs is unknown. The aim of the study was to determine whether a home-based telemanagement (HBT) programme in CHF patients decreased hospital readmissions and hospital costs in comparison with the usual care (UC) follow-up programme over a one-year period.\n Four hundred-sixty CHF patients (pts), aged 57+/-10 years were randomised to two management strategies: 230 pts to HBT programme and 230 pts to UC programme. The HBT pts received a portable device, transferring, by telephone, a one-lead trace to a receiving station where a nurse was available for interactive teleconsultation. The UC pts were referred to their primary care physicians and cardiologists. The primary objective of the study was one-year hospital readmission for cardiovascular reasons. During one-year follow-up 55 pts (24%) in HBT group and 83 pts (36%) in UC group had at least one readmission (RR=0.56; 95% CI: 0.38-0.82; p=0.01). After adjusting for clinical and demographic characteristics, the HBT group had a significantly lower risk of readmission compared with the UC group (HR=0.50, 95% CI: 0.34-0.73; p=0.01). The intervention was associated with a 36% decrease in the total number of hospital readmissions (HBT group: 91 readmissions; UC group: 142 readmissions) and a 31% decrease in the total number of episodes of hemodynamic instability (101 in HBT group vs 147 in UC group). The rate of hearth failure-related readmission was 19% (43 pts) in HBT group and 32% (73 pts) in UC group (RR=0.49, 95% [CI]: 0.31-0.76; p=0.0001). No significant difference was found on cardiovascular mortality between groups. Mean cost for hospital readmission was significantly lower in HBT group (euro 843+/-1733) than in UC group (euro 1298+/-2322), (-35%, p<0.01).\n This study suggests that one-year HBT programme reduce hospital readmissions and costs in CHF patients.", "Nurse care management programs for patients with chronic illness have been shown to be safe and effective.\n To determine whether a telephone-mediated nurse care management program for heart failure reduced the rate of rehospitalization for heart failure and for all causes over a 1-year period.\n Randomized, controlled trial of usual care with nurse management versus usual care alone in patients hospitalized for heart failure from May 1998 through October 2001.\n 5 northern California hospitals in a large health maintenance organization.\n Of 2786 patients screened, 462 met clinical criteria for heart failure and were randomly assigned (228 to intervention and 234 to usual care).\n Nurse care management provided structured telephone surveillance and treatment for heart failure and coordination of patients' care with primary care physicians.\n Time to first rehospitalization for heart failure or for any cause and time to a combined end point of first rehospitalization, emergency department visit, or death.\n At 1 year, half of the patients had been rehospitalized at least once and 11% had died. Only one third of rehospitalizations were for heart failure. The rate of first rehospitalization for heart failure was similar in both groups (proportional hazard, 0.85 [95% CI, 0.46 to 1.57]). The rate of all-cause rehospitalization was similar (proportional hazard, 0.98 [CI, 0.76 to 1.27]).\n The findings of this study, conducted in a single health care system, may not be generalizable to other health care systems. The overall effect of the intervention was minor.\n Among patients with heart failure at low risk on the basis of sociodemographic and medical attributes, nurse care management did not statistically significantly reduce rehospitalizations for heart failure or for any cause. Such programs may be less effective for patients at low risk than those at high risk.", "We studied the effects of home telemonitoring in elderly patients with congestive heart failure (CHF) on mortality and rate of hospitalization, compliance with treatment, quality of life and costs of CHF management, by comparison with a group receiving usual care. Fifty-seven elderly CHF patients were randomized to standard care or to home telemonitoring-based care and followed for 12 months. In the subjects who were monitored, weekly reports on their clinical status were obtained and their management was modified accordingly. Home telemonitoring was associated with improvements in the composite endpoint of mortality and rate of hospitalizations (P = 0.006), a better compliance with therapy, more frequent use of beta-blockers and statins, lower total cholesterol level and a better reported health perception score. The improved results with home telemonitoring in CHF were probably due to better compliance and to closer monitoring of the patients.", "This study compared differences in nurse and patient communication profiles between two telehealth modes: telephone and videophone, and evaluated longitudinal changes in communication, nurse perceptions, and patient satisfaction.\n Subjects were enrolled in a randomized controlled clinical trial evaluating a 90-day home-based intervention for heart failure. Telephone (n=14) and videophone (n=14) interactions were audio taped and analyzed using the Roter Interaction Analysis System.\n Nurses were more likely to use open-ended questions, back-channel responses, friendly jokes, and checks for understanding on the telephone compared to videophone. Compliments given and partnership were more common on the videophone. Patients were more likely to give lifestyle information and approval comments on the telephone, and used more closed-ended questions on the videophone. Nurses perceptions of the interactions were not different between the telephone and videophone, nor did their perceptions change significantly over the course of the intervention. There were no significant differences in patient satisfaction between the telephone and videophone.\n The results of this study did not support use of a videophone over the telephone.\n It is critical to match technologies to patient needs and use the least complex technology possible. When considering use a videophone, health care providers should critically examine the trade-offs between additional complexities with the added value of the visual interaction.", "Healthcare costs for heart failure are increasing. The need for a better care, however, has to be matched with a policy of cost containment. A way to improve the cost-effectiveness of heart failure care is the disease management approach, in which therapy, education and follow-up are tailored for each patient by a multidisciplinary team. Such a complex intervention can be facilitated by the use of telemedicine, which allows the remote control of considerable amounts of clinical data. In Italy, a few studies with telemedicine have been reported. A recent development in this field is represented by the ICAROS project (Integrated Care vs Conventional Intervention in Cardiac Failure Patients: Randomized Open Label Study), whose aim is to improve the clinical and psychological care of heart failure patients employing advanced wireless telecommunication technology. So far, we randomized 60 patients: 30 in usual ambulatory care, 30 in an intensive treatment group. The latter patients were instructed to use a portable computer to get in touch daily with the heart failure clinic and receive feedback instruction for the management of drug therapy and daily problems. At the first year of follow-up, the treatment group showed good compliance to drug prescriptions, and could easily handle the portable computer. The preliminary results of this ongoing study support the feasibility and appropriateness of new technologies for the management of heart failure, even in elderly patients in whom a limited expertise with these appliances could have been anticipated." ]

[ "2536911" ]

[ "A prospective randomized comparison of methotrexate, dactinomycin, and chlorambucil versus methotrexate, dactinomycin, cyclophosphamide, doxorubicin, melphalan, hydroxyurea, and vincristine in \"poor prognosis\" metastatic gestational trophoblastic disease: a Gynecologic Oncology Group study." ]

[ "In 1981, the Gynecologic Oncology Group initiated a prospective randomized study in which patients with poor-prognosis gestational trophoblastic disease received either standard MAC chemotherapy (methotrexate, dactinomycin, and chlorambucil) or the modified CHAMOMA regimen (methotrexate, dactinomycin, cyclophosphamide, doxorubicin, melphalan, hydroxyurea, and vincristine). The protocol was closed in May 1986 because the modified CHAMOMA regimen was significantly more toxic and possibly less effective. There were 42 patients entered, with 22 receiving MAC and 20 receiving modified CHAMOMA. There have been six deaths due to disease in the modified CHAMOMA group and none in the MAC group. Five MAC failures and one modified CHAMOMA failure have been rescued by surgery and/or chemotherapy. All six of the patients who died on the modified CHAMOMA regimen had developed disease following a previous term pregnancy, but none had prior chemotherapy. All seven patients who were treated for gestational trophoblastic disease after term pregnancy in the MAC group were cured of disease. With the modified CHAMOMA regimen, 44% of patients had life-threatening hematologic toxicity, as compared with only 9% of the MAC patients. Thus, the standard MAC regimen appears to be at least equally effective and much less toxic than the modified CHAMOMA regimen, indicating a more favorable therapeutic index." ]

[ "16868976", "17614270", "17617808", "19141327" ]

[ "A comparative study of inhaled ciclesonide 160 microg/day and fluticasone propionate 176 microg/day in children with asthma.", "Randomized comparison of the efficacy and safety of ciclesonide and budesonide in adolescents with severe asthma.", "Comparison of the efficacy and safety of ciclesonide 160 microg once daily vs. budesonide 400 microg once daily in children with asthma.", "Efficacy and safety of ciclesonide once daily and fluticasone propionate twice daily in children with asthma." ]

[ "Ciclesonide (CIC) is an inhaled corticosteroid (ICS) with high anti-inflammatory activity and low incidence of local and systemic adverse effects. The objective of this study was to compare the efficacy and safety of CIC with fluticasone propionate (FP) in children and adolescents with persistent asthma. This was a 12-week, randomized, double blind, parallel-group study. After a 2-to 4-week baseline period, a total of 556 children (ages 6-15 years) with asthma (forced expiratory volume in 1 sec [FEV(1)], 50% to 90% predicted) were treated twice daily with CIC 80 microg (ex-actuator, equivalent to 100 microg ex-valve) or FP 88 microg (ex-actuator, equivalent to 100 microg ex-valve) administered via a hydrofluoroalkane-propelled metered-dose inhaler. A statistically significant increase from baseline was observed in FEV(1) for both CIC (285 +/- 16 ml) and FP (285 +/- 15 ml) (P < 0.0001 for both) and in morning and evening peak expiratory flow (P < 0.0001 for both). Significant improvements were seen in asthma symptoms, use of rescue medication, and asthma symptom-free days in both treatment groups, without any differences between the treatment groups in changes from baseline. Two FP-treated patients experienced oral candidiasis and one patient experienced voice alteration. Creatinine-adjusted 24-hr urine cortisol levels increased from baseline levels by 10% in the CIC group (P < 0.05) and by 6% in the FP group (not significant). The efficacy and safety of CIC 160 microg/day were comparable to those of FP 176 microg/day in children with asthma.\n (c) 2006 Wiley-Liss, Inc.", "The aim of the study was to investigate the efficacy and safety of ciclesonide compared with budesonide in adolescents with severe asthma.\n In this randomized, double-blind, double-dummy, parallel-group study, patients aged 12-17 years with severe asthma were treated with budesonide 400 microg once daily (QD) in a 2-week run-in period. At randomization, eligible patients were assigned 2:1 to ciclesonide 320 microg QD (ex-actuator) or budesonide 800 microg QD (metered dose), respectively, in the evening. Forced expiratory volume in 1s (FEV(1)) was the primary variable. Patients recorded asthma symptom score and rescue medication use in diaries. Safety assessments included adverse events (AEs) and 24-h urine cortisol.\n Four hundred and three patients were randomized. Ciclesonide 320 microg QD and budesonide 800 microg QD significantly increased FEV(1) (least-squares mean: 505 and 536 mL, respectively; both p<0.0001 versus baseline) in the intention-to-treat (ITT) population. Lower limits of the 95% confidence intervals (ITT: -138 mL; per-protocol: -122 mL) were above the non-inferiority limit (-150 mL). Median percentage of days without asthma symptoms and without rescue medication use was 84% with ciclesonide and 85% with budesonide. AEs were unremarkable, with no cases of confirmed candidiasis. Median creatinine-adjusted urine cortisol significantly decreased with budesonide treatment (15.9-13.7 nmol cortisol/mmol creatinine; p=0.0086 versus baseline), but not with ciclesonide (p=0.1125).\n Ciclesonide 320 microg QD showed similar efficacy to budesonide 800 microg QD in adolescents with severe asthma. Ciclesonide was well tolerated and, unlike budesonide, had no effect on urine cortisol levels.\n EudraCT No.: 2004-001233-41.", "Ciclesonide is an onsite-activated inhaled corticosteroid (ICS) for the treatment of asthma. This study compared the efficacy, safety and effect on quality of life (QOL) of ciclesonide 160 microg (ex-actuator; nominal dose 200 microg) vs. budesonide 400 microg (nominal dose) in children with asthma. Six hundred and twenty-one children (aged 6-11 yr) with asthma were randomized to receive ciclesonide 160 microg (ex-actuator) once daily (via hydrofluoroalkane metered-dose inhaler and AeroChamber Plus spacer) or budesonide 400 microg once daily (via Turbohaler) both given in the evening for 12 wk. The primary efficacy end-point was change in forced expiratory volume in 1 s (FEV1). Additional measurements included change in daily peak expiratory flow (PEF), change in asthma symptom score sum, change in use of rescue medication, paediatric and caregiver asthma QOL questionnaire [PAQLQ(S) and PACQLQ, respectively] scores, change in body height assessed by stadiometry, change in 24-h urinary cortisol adjusted for creatinine and adverse events. Both ciclesonide and budesonide increased FEV1, morning PEF and PAQLQ(S) and PACQLQ scores, and improved asthma symptom score sums and the need for rescue medication after 12 wk vs. baseline. The non-inferiority of ciclesonide vs. budesonide was demonstrated for the change in FEV1 (95% confidence interval: -75, 10 ml, p = 0.0009, one-sided non-inferiority, per-protocol). In addition, ciclesonide and budesonide showed similar efficacy in improving asthma symptoms, morning PEF, use of rescue medication and QOL. Ciclesonide was superior to budesonide with regard to increases in body height (p = 0.003, two-sided). The effect on the hypothalamic-pituitary-adrenal axis was significantly different in favor of ciclesonide treatment (p < 0.001, one-sided). Both ciclesonide and budesonide were well tolerated. Ciclesonide 160 microg once daily and budesonide 400 microg once daily were effective in children with asthma. In addition, in children treated with ciclesonide there was significantly less reduction in body height and suppression of 24-h urinary cortisol excretion compared with children treated with budesonide after 12 wk.", "Ciclesonide is a new inhaled corticosteroid (ICS). Information about its clinical efficacy and safety in relation to other ICS in children is needed for clinical positioning.\n This 12-week, randomized, double-blind, double-dummy, three-arm, parallel-group study compared the efficacy and safety of ciclesonide with fluticasone propionate in children with mainly moderate and severe persistent asthma.\n Seven hundred and forty-four patients (aged 6-11 years) were randomized to ciclesonide (80 or 160 microg once daily) or fluticasone propionate (88 microg twice daily), following a 2-4-week run-in. Efficacy measurements included forced expiratory flow in 1s (FEV(1)), morning peak expiratory flow (PEF), asthma symptom scores, rescue medication use and quality of life. Systemic effect was assessed by 24-hour urine free cortisol adjusted for creatinine.\n FEV(1) and morning PEF increased from baseline in all groups (p<0.0001). Ciclesonide 160 microg was not inferior to fluticasone propionate 176 microg for FEV(1) (p=0.0030, one-sided). In all groups, asthma symptom score sums and rescue medication use significantly improved (p<0.0001). The percentages of asthma symptom-, rescue medication- and nocturnal awakening-free days were high, with no significant differences between treatments. Quality of life scores improved with all treatments (p<0.0001). A significant dose-response occurred between low and higher doses of ciclesonide for exacerbations and asthma control definitions. The incidences of adverse events were comparable across treatments. Urine free cortisol levels decreased significantly with fluticasone propionate (p=0.0103), but not with ciclesonide.\n Once-daily ciclesonide has a clinical effect similar to that of fluticasone propionate, but does not suppress cortisol excretion, in children with moderate and severe asthma." ]

[ "2634614", "3397040" ]

[ "Postnatal triiodothyronine replacement and respiratory distress syndrome of the preterm infant.", "Postnatal thyroxine administration for idiopathic respiratory distress syndrome in preterm infants." ]

[ "Improvements in the management of respiratory distress syndrome (RDS) include pre- and postnatal stimulation of pulmonary maturity, and triiodothyronine (T3) is believed to influence directly surfactant production. Its circulating levels are low in premature infants with RDS probably due to a low thyroxine T4-T3 hepatic conversion mechanism. While a state of hypotriiodothyroninemia exists at birth, we studied the influence of postnatal intravenous T3 administration on the course of RDS in preterm infants of less than 32 weeks' gestation. Fifty preterm infants with RDS were studied (mean gestational age 30.4 +/- 1.2 weeks and birth weight 1,180 +/- 220 g). They were at random assigned to treatment with 50 micrograms L-T3 (Thyrotardin) or to the control group. Mortality rate, peak oxygen concentrations, duration of artificial ventilation and development of major complications of RDS were the criteria to estimate the influence of T3 treatment on RDS. We failed to detect a statistically significant difference between the two groups in all of the mentioned criteria except for FiO2 concentrations required to maintain PaO2 between 50 and 60 mm Hg (p less than 0.05). These observations suggest a relative beneficial effect of T3 replacement on the course of RDS in preterm infants of less than 32 weeks of gestation.", "Thirty-six preterm infants of less than 34 weeks of gestation with idiopathic respiratory distress syndrome (IRDS) were studied. Eighteen of them were treated with intravenous thyroxine (T4) and compared with 18 control prematures to evaluate the effect of postnatal T4 administration on the course of IRDS. After treatment, serum T4 levels were similar to those of healthy term infants. No statistically significant effect on mortality rate, duration of mechanical ventilation (p greater than 0.3), need of high oxygen environment (p greater than 0.05) and development of bronchopulmonary dysplasia (p greater than 0.2) was observed between the two groups. These observations show that postnatal use of T4 does not carry any benefit for preterm infants with IRDS." ]

[ "9679876" ]

[ "Treatment of male urethral strictures: is repeated dilation or internal urethrotomy useful?" ]

[ "We evaluate the efficacy of repeated dilation or urethrotomy as treatment of male urethral strictures.\n Between January 1991 and January 1994, 210 men with proved urethral strictures were prospectively randomized to undergo filiform dilation (106) or internal urethrotomy (104). Followup was scheduled at 3, 6, 9, 12, 24, 36 and 48 months. Dilation or internal urethrotomy was repeated at the first and second stricture recurrence. The Kaplan-Meier method was used to estimate survivor function for the treatment methods (survival time being the time to first stricture recurrence) and the log rank test was used to compare the efficacy of different treatments.\n Followup (mean 24 months, range 2 to 63) was available in 163 patients (78%). After a single dilation or urethrotomy not followed by re-stricturing at 3 months, the estimated stricture-free rate was 55 to 60% at 24 months and 50 to 60% at 48 months. After a second dilation or urethrotomy for stricture recurrence at 3 months the stricture-free rate was 30 to 50% at 24 months and 0 to 40% at 48 months. After a third dilation or urethrotomy for stricture recurrence at 3 and 6 months the stricture-free rate at 24 months was 0 (p <0.0001).\n Dilation and internal urethrotomy are useful in a select group (approximately 70% of all patients) who are stricture-free at 3 months, and of whom 50 to 60% will remain stricture-free up to 48 months. A second dilation or urethrotomy for early stricture recurrence (at 3 months) is of limited value in the short term (24 months) but of no value in the long term (48 months), whereas a third repeated dilation or urethrotomy is of no value." ]

[ "10972216", "7482844", "7878817", "9838320", "8709353", "15882713" ]

[ "Is routine ureteric stenting needed in kidney transplantation? A randomized trial.", "Renal transplantation using ureteral stents.", "Urologic complications after renal transplantation: a prospective randomized trial comparing different techniques of ureteric anastomosis and the use of prophylactic ureteric stents.", "Significance of routine JJ stenting in living related renal transplantation: a prospective randomised study.", "Insertion of a double pigtail ureteral stent for the prevention of urological complications in renal transplantation: a prospective randomized study.", "Routine insertion of ureteral stent in live-donor renal transplantation: is it worthwhile?" ]

[ "Whether routine ureteric stenting in low-urological-risk patients reduces the risk of urological complications in kidney transplantation is not established.\n Eligible patients were recipients of single-organ renal transplants with normal lower urinary tracts. Patients were randomized intraoperatively to receive either routine stenting or stenting only in the event of technical difficulties with the anastomosis. All patients underwent Lich-Gregoire ureteroneocystostomy.\n Between June 1994 and December 1997, 331 kidney transplants were performed at a single center, 305 patients were eligible, and 280 patients were enrolled and randomized. Donor and recipient age, sex, donor source, whether first or subsequent grafts, ureteric length, native renal disease, and immunosuppression were similar in each group. In the no-routine-stenting group 6 of 137 patients (4.4%) received stents after randomization for intraoperative events that in the surgeon's opinion required use of a stent. In an intention-to-treat analysis there was no difference between groups in the primary outcome cluster of obstruction or leak [routine stenting 5 of 143 (3.5%) vs. no routine stenting 9 of 137 (6.6%); P=0.23], or in either of these complications analyzed separately. All urological complications were successfully managed without major morbidity. Living donor organs and shorter ureteric length (after trimming) were univariate risk factors for leaks, although increasing donor age was associated with obstruction.\n Routine ureteric stenting is unnecessary in kidney transplantation in patients at low risk for urological complications. Careful surgical technique with selective stenting of problematic anastomoses yields similar results.", "nan", "nan", "nan", "Urologists successfully use ureteral stents to protect the ureterovesical anastomosis in nontransplant patients.\n We determined the value of ureteral stents in transplant patients. The frequency of urological complications (leaks, obstructions and urinary tract infections) was compared in a prospective randomized series of 194 kidney transplantations (97 with and 97 without a double pigtail ureteral stent).\n In the stent group 1 patient had a urinary leak and 35 had urinary tract infections (including 2 cases of Corynebacterium cystitis). In the no stent group 6 patients had urinary leaks, 4 had obstructions and 32 had urinary tract infections. The 1-year patient and graft survival rates were similar in both groups, and renal function at 1 year was also similar (229 versus 208 mumol./l. creatinine in the stent and no stent groups, respectively). A small number of stent related complications occurred (2 stent breakages and 1 stent migration). No stones formed in any case.\n Ureteral stent insertion significantly decreases the rate of vesicoureteral leakage and obstruction in renal transplantation.", "To evaluate the impact of the routine use of double-J stents in live-donor renal transplantation at a single institute from a prospective randomized study.\n A total of 100 patients were prospectively randomized into two groups of 50 patients each. Group 1 received a routine double-J silicone ureteral stent and group 2 did not. A standard Lich-Gregoir ureteroneocystostomy was performed in both groups. In group 1, the patients were scheduled for stent removal after 2 weeks.\n Both groups were comparable in terms of age, sex, ischemia time, number of renal arteries, and time to diuresis. In group 1, two grafts were lost in the early postoperative period and those patients were excluded from the final analysis. None of our patients in either group had developed a ureteral stricture at a mean follow-up of 10.8 +/- 3.6 months. In the stented group, 2 patients developed a urinary leak, but no leakage was reported in the nonstented group (P = 0.14). Although 19 patients in group 1 (39.6%) had a urinary tract infection, only 9 in group 2 (18%) showed evidence of a positive urine culture (P = 0.02). The presence of a ureteral stent and female sex were the independent predictors of postoperative urinary tract infection on multivariate analysis. The mean serum creatinine at discharge was 1.2 +/- 0.3 mg% and 1.2 +/- 0.4 mg% in groups 1 and 2, respectively (P = 0.2).\n The results of our study have shown that routine ureteral stent insertion has no impact on the rate of vesicoureteral leakage or obstruction in live-donor renal transplantation, whereas it is significantly associated with an increased incidence of urinary tract infection. Stenting should be limited to patients with a pathologic and/or defunctionalized bladder." ]

[ "10683058", "12668296", "3720391" ]

[ "Effect of out-of-hospital pediatric endotracheal intubation on survival and neurological outcome: a controlled clinical trial.", "Comparison of a conventional tracheal airway with the Combitube in an urban emergency medical services system run by physicians.", "Esophageal gastric tube airway vs endotracheal tube in prehospital cardiopulmonary arrest." ]

[ "Endotracheal intubation (ETI) is widely used for airway management of children in the out-of-hospital setting, despite a lack of controlled trials demonstrating a positive effect on survival or neurological outcome.\n To compare the survival and neurological outcomes of pediatric patients treated with bag-valve-mask ventilation (BVM) with those of patients treated with BVM followed by ETI.\n Controlled clinical trial, in which patients were assigned to interventions by calendar day from March 15, 1994, through January 1, 1997.\n Two large, urban, rapid-transport emergency medical services (EMS) systems.\n A total of 830 consecutive patients aged 12 years or younger or estimated to weigh less than 40 kg who required airway management; 820 were available for follow-up.\n Patients were assigned to receive either BVM (odd days; n = 410) or BVM followed by ETI (even days; n = 420).\n Survival to hospital discharge and neurological status at discharge from an acute care hospital compared by treatment group.\n There was no significant difference in survival between the BVM group (123/404 [30%]) and the ETI group (110/416 [26%]) (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.61-1.11) or in the rate of achieving a good neurological outcome (BVM, 92/404 [23%] vs ETI, 85/416 [20%]) (OR, 0.87; 95% CI, 0.62-1.22).\n These results indicate that the addition of out-of-hospital ETI to a paramedic scope of practice that already includes BVM did not improve survival or neurological outcome of pediatric patients treated in an urban EMS system.", "This prospective randomised study was performed to compare the use of the Esophageal-Tracheal Combitube(R) (ETC; Tyco Healthcare, Mansfield, MA; http://www.combitube.org) with a conventional tracheal airway (ETA) for airway management by experienced physicians of the Emergency Medical Services System of the City of Vienna in the prehospital setting. Access to the patient's head, time of arrival of the ambulance, ease of insertion, time of insertion, potential substitution by the alternate airway, efficacy of adrenaline (epinephrine) administered via the airway, survival to the intensive care unit (ICU) ward and survival to discharge from the hospital were evaluated. One hundred and seventy-two non-traumatic cardiac arrest patients (131 males, 41 females) were enrolled in this study during a 12 months period. In 83 patients (48.3%), the conventional ETA (group 1) was used for the initial intubation attempt which was successful in 78 patients (94%). The remaining five patients of group 1 could not be intubated with an ETA, but were successfully managed with the ETC. Eighty-nine patients (51.7%) were intubated with the ETC (group 2) as first choice (79 in oesophageal position (89%); eight in tracheal position: (9%)), which was successful in 87 (98%) patients. The remaining two patients in group 2 (2%) were successfully managed with the ETA. Success of intubation and ventilation with ETC was comparable to the ETA. Recorded time of insertion was shorter with the ETC versus ETA (P<0.05). The Combitube worked well in cases of difficult access to the patient's head and in bleeding and vomiting patients. Both devices served as successful substitutes for each other. Adrenaline (epinephrine) applied via ETC with a 10-fold dosage was as effective as via the conventional ETA. To our knowledge this is the first study using physicians comparing ETC and ETA in the prehospital setting.", "We evaluated the efficacy of the esophageal airway (EA) by prospectively randomizing 175 prehospital cardiopulmonary arrest patients to receive either an esophageal gastric tube airway (EGTA) or an endotracheal tube (ET). If attempts with the initial airway failed, the alternate airway was attempted. The cost of training paramedics in EA use was considerably less than the ET ($80 vs $1,000). Survival to the emergency room, to hospitalization and to discharge in ET and EGTA groups were 64.4 percent, 25.6 percent, 11.1 percent, and 54.1 percent, 27.1 percent, 12.9 percent, respectively--differences not statistically significant. The incidence of neurologic residual (ET 50 percent, EGTA 36.4 percent) and congestive heart failure (ET 40 percent, EGTA 45.5 percent) in surviving ET and EGTA patients did not differ (NS). An additional 125 consecutive patients with only the opportunity to receive an EA were also evaluated and did not differ in mortality, neurologic residual, or congestive heart failure from ET patients. We conclude that the EA is a satisfactory alternative to the ET for short-term prehospital use in cardiopulmonary arrest patients." ]

[ "14744821", "16336365", "6567853" ]

[ "Randomised controlled trial of effect of hands and knees posturing on incidence of occiput posterior position at birth.", "Randomized controlled trial of hands-and-knees positioning for occipitoposterior position in labor.", "Nursing, maternal postures, and fetal position." ]

[ "To evaluate the efficacy of hands and knees position and pelvic rocking exercises on the incidence of fetal occiput posterior position at birth.\n Multicentre randomised controlled trial.\n Seven maternity units in New South Wales, Australia, encompassing teaching hospitals and district general hospitals.\n 2547 pregnant women at 37 weeks' gestation; 1292 randomised to the intervention group and 1255 to the control group.\n Hands and knees position and pelvic rocking exercises from 37 weeks' gestation until the onset of labour.\n Incidence of fetal occiput posterior position at birth.\n 1046 women in the intervention group and 1209 women in the control group remained in the study until they went into labour. No significant difference existed between the groups for the incidence of occiput posterior position at birth: 105 (8.1%) women in the intervention group and 98 (7.8%) in the control group had a baby in a posterior position at delivery (difference in risk 0.3%, 95% confidence interval -1.8 to 2.4). The incidence of fetal transverse arrest was 3.4% (44 women) in the intervention group and 3.0% (38 women) in the control group (difference in risk 0.4, -1 to 1.7). No differences occurred between intervention and control groups for induction of labour, use of epidural, duration of labour, mode of delivery, use of episiotomy, or Apgar score.\n Hands and knees exercise with pelvic rocking from 37 weeks' gestation to the onset of labour did not reduce the incidence of persistent occiput posterior position at birth.", "Hands-and-knees positioning during labor has been recommended on the theory that gravity and buoyancy may promote fetal head rotation to the anterior position and reduce persistent back pain. A Cochrane review found insufficient evidence to support the effectiveness of this intervention during labor. The purpose of this study was to evaluate the effect of maternal hands-and-knees positioning on fetal head rotation from occipitoposterior to occipitoanterior position, persistent back pain, and other perinatal outcomes.\n Thirteen labor units in university-affiliated hospitals participated in this multicenter randomized, controlled trial. Study participants were 147 women laboring with a fetus at >or=37 weeks' gestation and confirmed by ultrasound to be in occipitoposterior position. Seventy women were randomized to the intervention group (hands-and-knees positioning for at least 30 minutes over a 1-hour period during labor) and 77 to the control group (no hands-and-knees positioning). The primary outcome was occipitoanterior position determined by ultrasound following the 1-hour study period and the secondary outcome was persistent back pain. Other outcomes included operative delivery, fetal head position at delivery, perineal trauma, Apgar scores, length of labor, and women's views with respect to positioning.\n Women randomized to the intervention group had significant reductions in persistent back pain. Eleven women (16%) allocated to use hands-and-knees positioning had fetal heads in occipitoanterior position following the 1-hour study period compared with 5 (7%) in the control group (relative risk 2.4; 95% CI 0.88-6.62; number needed to treat 11). Trends toward benefit for the intervention group were seen for several other outcomes, including operative delivery, fetal head position at delivery, 1-minute Apgar scores, and time to delivery.\n Maternal hands-and-knees positioning during labor with a fetus in occipitoposterior position reduces persistent back pain and is acceptable to laboring women. Given this evidence, hands-and-knees positioning should be offered to women laboring with a fetus in occipitoposterior position in the first stage of labor to reduce persistent back pain. Although this study demonstrates trends toward improved birth outcomes, further trials are needed to determine if hands-and-knees positioning promotes fetal head rotation to occipitoanterior and reduces operative delivery.", "The objectives of this study were to (a) determine if a safe, simple, and economic nursing procedure--maternal posturing--would result in the rotation of a fetus in the posterior or transverse position to the optimal anterior position and (b) evaluate the relative effectiveness of a series of maternal postures for facilitating anterior fetal rotation. One hundred healthy women at term pregnancy were randomly assigned to four treatment and one control posture for a 10-minute period. At two nurse-midwifery clinics, one certified nurse-midwife postured the subjects and one midwife measured the dependent variable (fetal position) with Leopold's maneuvers. Hypotheses I-IV, which predicted that the four rotation postures would have a greater proportion of anterior fetal rotations than the control posture, were supported (p less than .000). Essentially all four postures were effective and there was little difference between the treatment postures. A second posturing was performed to determine if an additional 10 minutes in a treatment posture would result in an anterior fetal position. There was a greater proportion of anterior fetal rotations with the four rotation postures than the control posture. The Sims posture was used as a maintenance posture for anterior positions, and was successful when done on the opposite side of the fetal back. The theoretical explication of how maternal postures effect fetal rotation remains sound." ]

[ "11152924", "15863540", "20207251", "21627422" ]

[ "Vaginal preparation with povidone iodine and postcesarean infectious morbidity: a randomized controlled trial.", "Preoperative vaginal preparation with povidone-iodine and the risk of postcesarean endometritis.", "Vaginal cleansing before cesarean delivery to reduce postoperative infectious morbidity: a randomized, controlled trial.", "Preoperative vaginal preparation with povidone-iodine on post-caesarean infectious morbidity." ]

[ "To determine whether vaginal preparation with povidone iodine before cesarean decreased the incidence of postpartum infectious morbidity.\n Participants were randomly assigned to vaginal preparation with povidone iodine (n = 247) or no preparation (n = 251). Postpartum infectious morbidity included fever, defined as temperature of 38C or greater after the day of surgery; endometritis, defined as fever with abdominal or uterine tenderness and initiation of intravenous antibiotics; and wound separation, defined as disruption of the abdominal incision that required wound care. We calculated overall rates of postpartum infectious morbidity, relative risks (RR), and 95% confidence intervals (CI) for the effect of vaginal preparation. As designed and reported, the trial had at least 80% power to detect a 10% or greater absolute difference in rates of overall infectious morbidity, fever, and endometritis (two-tailed, alpha = 0.05).\n There was no difference between groups in maternal age, parity, race, education, prior cesarean, type of anesthesia, labor before current cesarean, number of vaginal examinations during labor, internal monitoring, prophylactic antibiotic use, gestational age at delivery, or payment status. Excluding 68 women with chorioamnionitis, incidence of postoperative fever was 19.3%, endometritis 7.2%, and wound separation 7.0%. Vaginal preparation with povidone iodine before cesarean had no effect on risk for fever (RR 1.1, 95% CI 0.8, 1.6), endometritis (RR 1.6, 95% CI 0.8, 3.1), or wound separation (RR 0.6, 95% CI 0.3, 1.3).\n Vaginal preparation with povidone iodine before cesarean had no effect on the incidence of fever, endometritis, or wound infection.", "Postcesarean endometritis and wound infection remain significant morbidities, despite use of strategies to prevent these complications. We investigated the effect of preoperative vaginal preparation with povidone-iodine as a preventive intervention against postcesarean endometritis and wound infection.\n A randomized controlled study was performed in 308 women undergoing nonemergent cesarean delivery. Subjects received either standard abdominal scrub alone or abdominal scrub with an additional vaginal preparation with povidone-iodine solution. All subjects received prophylactic antibiotic at the time of umbilical cord clamping. Each subject's postoperative course was reviewed for development of febrile morbidity (temperature > 38.0 degrees C), endometritis (temperature > 38.4 degrees C accompanied by fundal tenderness occurring beyond the first postoperative day, in the absence of evidence of other infection), and wound infection.\n Postcesarean endometritis occurred in 7.0% of subjects who received a preoperative vaginal preparation and 14.5% of controls (P < .05). There was no measurable effect of a vaginal scrub on the development of postoperative fever or wound infection. The adjusted odds ratio for developing endometritis after a vaginal preparation was 0.44 (95% confidence interval [CI] 0.193-0.997). Multivariate analysis showed an increased risk of developing endometritis in association with severe anemia (adjusted OR 4.26, 95% CI 1.568-11.582), use of intrapartum internal monitors (adjusted OR 2.84, 95% CI 1.311-6.136), or history of antenatal genitourinary infection (adjusted OR 2.9, 95% CI 1.265-6.596).\n Preoperative vaginal scrub with povidone-iodine decreases the incidence of postcesarean endometritis. This intervention does not seem to decrease the overall risk of postoperative fever or wound infection.", "The objective of the study was to determine whether vaginal preparation with povidone iodine before cesarean delivery decreased the risk of postoperative maternal morbidities.\n The design of the study was a randomized, controlled trial in women undergoing cesarean delivery with subjects assigned to have a preoperative vaginal cleansing with povidone iodine or to a standard care group (no vaginal wash). The primary outcome was a composite of postoperative fever, endometritis, sepsis, readmission, wound infection, or complication.\n There were 155 vaginal cleansing subjects and 145 control subjects. Overall, 9.0% developed the composite outcome, with fewer women in the cleansing group (6.5%) compared with the control group (11.7%), although the difference was not statistically significant (relative risk, 0.55; 95% confidence interval, 0.26-1.11; P = .11). Length of surgery, being in labor, and having a dilated cervix were all associated with the composite morbidity outcome.\n Vaginal cleansing with povidone iodine before cesarean delivery may decrease postoperative morbidities, although the reduction is not statistically significant.\n Copyright 2010 Mosby, Inc. All rights reserved.", "The commonest complication associated with caesarean section is infection. The aim of this study is to investigate the effect of vaginal preparation with povidone-iodine on post-caesarean infection. In this clinical trial, 568 patients were selected for two groups: a treatment group and a control group, each with 284 patients. A vaginal scrub was performed before the routine abdominal scrub, with two 4 × 4 cm sponge sticks saturated with povidone-iodine solution, rotated in the vagina for about 30 s. In the control group, only the abdominal scrub was performed. Patients received a single dose of prophylactic antibiotics, and were reviewed for 6 weeks to look for predefined variables. Post-caesarean endometritis occurred less frequently in the treatment group than in the control group (2.5% vs 1.4%). There was no significant difference for febrile morbidity and wound infection in the two groups. The adjusted odds ratio for endometritis after vaginal preparation was 0.03 (95% CI: 0.008-0.7). Vaginal preparation with povidone-iodine may decrease the risk of post-caesarean endometritis." ]

[ "15336467", "10792154", "20970066", "11342895", "3895410", "11454106", "9776013", "15990220", "15936869", "16698176", "9666761", "15842558", "17651893", "2005707", "14678372", "11516807", "10543335", "15967567", "3959249", "9638316", "20132103", "12175392", "17135784", "11176403", "9144906", "3516295", "12934777", "12811500", "11248608", "11435842", "17669143", "10332441", "11696741", "20860717", "16834644", "2667633", "9353802", "17162046", "15808387", "17937959", "20109997", "15540755", "9467475", "15041104", "16096831", "15548447", "12201616", "16469019", "10510109", "8578271", "7788255", "14764127", "14616458", "10775736", "17825137", "10210394", "19143854", "12060436", "12893326", "19389083", "18637156", "16532466", "20303119", "17190372" ]

[ "A randomized, double-blind, parallel-group comparison of controlled- and immediate-release oxybutynin chloride in urge urinary incontinence.", "A randomized controlled trial comparing the efficacy of controlled-release oxybutynin tablets (10 mg once daily) with conventional oxybutynin tablets (5 mg twice daily) in patients whose symptoms were stabilized on 5 mg twice daily of oxybutynin.", "Solifenacin and tolterodine are equally effective in the treatment of overactive bladder symptoms.", "Tolterodine: superior tolerability than and comparable efficacy to oxybutynin in individuals 50 years old or older with overactive bladder: a randomized controlled trial.", "Emepronium carrageenate: clinical effects and urinary excretion in treatment of female urge incontinence.", "Tolterodine: a safe and effective treatment for older patients with overactive bladder.", "Dose-ranging study of tolterodine in patients with detrusor hyperreflexia.", "A comparison of the efficacy and tolerability of solifenacin succinate and extended release tolterodine at treating overactive bladder syndrome: results of the STAR trial.", "Comparison of darifenacin and oxybutynin in patients with overactive bladder: assessment of ambulatory urodynamics and impact on salivary flow.", "Propiverine compared to oxybutynin in neurogenic detrusor overactivity--results of a randomized, double-blind, multicenter clinical study.", "Tolterodine, a new antimuscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder.", "Ocular side-effects of tolterodine and oxybutynin, a single-blind prospective randomized trial.", "Clinical efficacy, safety, and tolerability of once-daily fesoterodine in subjects with overactive bladder.", "Randomized, double-blind, multicenter trial on treatment of frequency, urgency and incontinence related to detrusor hyperactivity: oxybutynin versus propantheline versus placebo.", "Solifenacin appears effective and well tolerated in patients with symptomatic idiopathic detrusor overactivity in a placebo- and tolterodine-controlled phase 2 dose-finding study.", "Tolterodine reduces the number of urge incontinence episodes in patients with an overactive bladder.", "Clinical efficacy and safety of tolterodine compared to oxybutynin and placebo in patients with overactive bladder.", "Propiverine versus tolterodine: efficacy and tolerability in patients with overactive bladder.", "Oxybutynin versus propantheline in patients with multiple sclerosis and detrusor hyperreflexia.", "[Intravesical instillation of trospium chloride, oxybutynin and verapamil for relaxation of the bladder detrusor muscle. A placebo controlled, randomized clinical test].", "Comparison of fesoterodine and tolterodine extended release for the treatment of overactive bladder: a head-to-head placebo-controlled trial.", "A randomized controlled trial of tolterodine and oxybutynin on tolerability and clinical efficacy for treating Chinese women with an overactive bladder.", "Propiverine hydrochloride immediate and extended release: comparison of efficacy and tolerability in patients with overactive bladder.", "Intravesical electromotive administration of oxybutynin in patients with detrusor hyperreflexia unresponsive to standard anticholinergic regimens.", "Efficacy and safety of two doses of tolterodine versus placebo in patients with detrusor overactivity and symptoms of frequency, urge incontinence, and urgency: urodynamic evaluation. The International Study Group.", "Dose titration in clinical trials. An example using emepronium carrageenate in detrusor instability.", "Prospective, randomized, double-blind study of the efficacy and tolerability of the extended-release formulations of oxybutynin and tolterodine for overactive bladder: results of the OPERA trial.", "Controlled, double-blind, multicentre clinical trial to investigate long-term tolerability and efficacy of trospium chloride in patients with detrusor instability.", "Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder.", "A short-term, multicenter, randomized double-blind dose titration study of the efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence.", "Randomized, double-blind, placebo- and propiverine-controlled trial of the once-daily antimuscarinic agent solifenacin in Japanese patients with overactive bladder.", "Once daily controlled versus immediate release oxybutynin chloride for urge urinary incontinence. OROS Oxybutynin Study Group.", "Intravesical oxybutynin: mode of action assessed by passive diffusion and electromotive administration with pharmacokinetics of oxybutynin and N-desethyl oxybutynin.", "Superior efficacy of fesoterodine over tolterodine extended release with rapid onset: a prospective, head-to-head, placebo-controlled trial.", "Comparison of the efficacy, safety, and tolerability of propiverine and oxybutynin for the treatment of overactive bladder syndrome.", "Oxybutinin versus propantheline in the management of detrusor instability. A patient-regulated variable dose trial.", "Comparison of a 10-mg controlled release oxybutynin tablet with a 5-mg oxybutynin tablet in urge incontinent patients.", "Intravesical atropine compared to oral oxybutynin for neurogenic detrusor overactivity: a double-blind, randomized crossover trial.", "Long-term prospective randomized study comparing two different regimens of oxybutynin as a treatment for detrusor overactivity.", "Efficacy, safety and tolerability of fesoterodine for overactive bladder syndrome.", "Trospium chloride and oxybutynin hydrochloride in a german study of adults with urinary urge incontinence: results of a 12-week, multicenter, randomized, double-blind, parallel-group, flexible-dose noninferiority trial.", "Randomized, double-blind placebo controlled trial of the once daily antimuscarinic agent solifenacin succinate in patients with overactive bladder.", "Efficacy and safety of tolterodine in patients with detrusor instability: a dose-ranging study.", "Darifenacin, an M3 selective receptor antagonist, is an effective and well-tolerated once-daily treatment for overactive bladder.", "Efficacy and tolerability of darifenacin, a muscarinic M3 selective receptor antagonist (M3 SRA), compared with oxybutynin in the treatment of patients with overactive bladder.", "Comparison of the efficacy of tolterodine and oxybutynin in different urodynamic severity grades of idiopathic detrusor overactivity.", "Treatment of overactive bladder with once-daily extended-release tolterodine or oxybutynin: the antimuscarinic clinical effectiveness trial (ACET).", "A double-blind randomized dose-response study comparing daily doses of 5, 10 and 15 mg controlled-release oxybutynin: balancing efficacy with severity of dry mouth.", "A placebo-controlled, multicentre study comparing the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence.", "Clinical and urodynamic effects of propiverine in patients suffering from urgency and urge incontinence. A multicentre dose-optimizing study.", "Trospium chloride versus oxybutynin: a randomized, double-blind, multicentre trial in the treatment of detrusor hyper-reflexia.", "Randomized, double-blind placebo- and tolterodine-controlled trial of the once-daily antimuscarinic agent solifenacin in patients with symptomatic overactive bladder.", "Clinical efficacy and tolerability of extended-release tolterodine and immediate-release oxybutynin in Japanese and Korean patients with an overactive bladder: a randomized, placebo-controlled trial.", "Dry mouth with conventional and controlled-release oxybutynin in urinary incontinence. The Ditropan XL Study Group.", "Randomized trial of oxybutynin extended versus immediate release for women aged 65 and older with overactive bladder: lessons learned from conducting a trial.", "Clinical efficacy and safety of tolterodine compared to placebo in detrusor overactivity.", "Efficacy and safety of solifenacin succinate in Korean patients with overactive bladder: a randomised, prospective, double-blind, multicentre study.", "Tolterodine: as effective but better tolerated than oxybutynin in Asian patients with symptoms of overactive bladder.", "Comparative efficacy and safety of transdermal oxybutynin and oral tolterodine versus placebo in previously treated patients with urge and mixed urinary incontinence.", "A randomized, double-blind, placebo- and propiverine-controlled trial of the novel antimuscarinic agent imidafenacin in Japanese patients with overactive bladder.", "A randomized, double-blind, placebo-controlled phase II dose-finding study of the novel anti-muscarinic agent imidafenacin in Japanese patients with overactive bladder.", "Minimal clinically important change in urinary incontinence detected by a quality of life assessment tool in overactive bladder syndrome with urge incontinence.", "Tolerability of 5 mg solifenacin once daily versus 5 mg oxybutynin immediate release 3 times daily: results of the VECTOR trial.", "Trospium chloride in patients with neurogenic detrusor overactivity: is dose titration of benefit to the patients?" ]

[ "The aim of this study was to evaluate the efficacy and safety of a new PO controlled-release (CR) QD oxybutynin tablet relative to PO immediate-release (IR) TID oxybutynin in patients with urge urinary incontinence (UI).\n In this multicenter, double-blind trial, patients with UI (> or = 7 episode/wk) and frequency (> or = 8 micturitions/d) were randomized to CR or IR oxybutynin for 6 weeks. Patients initiated treatment at 15 mg/d and the dose was adjusted (in 5-mg/d increments) over 2 weeks according to tolerability. Efficacy (UI episodes, voids, absorbent pads used, urgency, and volume voided per micturition) was assessed during the final 2 weeks of treatment. Tolerability was assessed by evaluating adverse events and treatment withdrawals.\n Of the 125 patients randomized, 94 (75%) were evaluable for efficacy; tolerability was assessed in all patients. In the CR group, 48 patients (91%) were women and 5 (9%) were men; the mean (SD) age was 58.0 (12.4) years (range, 26-78 years). In the IR group, 37 patients (90%) were women and 4 (10%) were men; the mean (SD) age was 60.6 (14.8) years (range, 26-83 years). Both CR and IR oxybutynin significantly reduced the mean number of total UI episodes per week (both P < 0.001 vs baseline). Both treatments produced equivalent reductions in mean voiding frequency and urinary urgency (all P < 0.001 vs. baseline). Significantly more patients rated CR oxybutynin tolerable on the initial dose of 15 mg/d (P = 0.020) and completed the study at a dose of > or = 15 mg/d (P = 0.018). Dry mouth was the most common adverse event, reported by 68% and 72% of patients in the CR and IR oxybutynin groups, respectively.\n Among the patients with urge UI included in this study, CR oxybutynin was as effective as IR oxybutynin for improving primary symptoms, with the additional benefit of QD administration.", "To compare the efficacy of a controlled-release (CR) formulation of oxybutynin with that of conventional oxybutynin in patients with detrusor instability or detrusor hyper-reflexia whose symptoms were stabilized on conventional oral oxybutynin tablets.\n The study comprised a randomized, double-blind, parallel-group trial involving 130 patients drawn from 15 centres in the UK. The study was of 6 weeks' duration, i.e. 2 weeks of screening whilst taking conventional oxybutynin tablets (5 mg twice daily) followed by 4 weeks of double-blind treatment with either CR oxybutynin tablets (10 mg once daily) or conventional oxybutynin tablets (5 mg twice daily). Outcome measures were changes in 24-h frequency and 24-h incontinence episodes recorded throughout the study on diary charts. Adverse events were recorded by patients in their diary charts and serum concentrations of oxybutynin and its active metabolite, N-desethyloxybutynin, were measured at baseline and at completion of the study to detect possible drug accumulation.\n The treatments did not differ significantly in any of the outcome measures. The primary efficacy criterion was the daytime continence at completion of the study; 53% and 58% of patients were continent on CR and conventional oxybutynin treatments, respectively (the 95% confidence interval of the difference in the proportion being - 22% to 13%; P = 0.62). The total number of side-effects experienced by those patients receiving treatment with the CR formulation was 57% of that for patients receiving treatment with conventional oxybutynin. Individual side-effects showed a similar distribution within treatment groups. There was no evidence of the accumulation of oxybutynin or N-desethyloxybutynin during the multiple dosing of CR or conventional oxybutynin tablets.\n The CR and conventional formulations of oxybutynin did not differ in their efficacy, and the CR formulation was associated with fewer side-effects. In addition, CR oxybutynin appeared to maintain therapeutic blood levels over the 24 h dosing interval with no accumulation of oxybutynin or its active metabolite. Once-daily dosing with a CR tablet is seen as convenient for the patient and is expected to result in improved compliance in patients already stabilized on conventional oxybutynin treatment.", "Various antimuscarinic agents have been developed for the treatment of overactive bladder (OAB). More data comparing these agents are still required. This study evaluated the efficacy and safety of solifenacin and tolterodine in Taiwanese patients with OAB symptoms.\n This was a prospective, randomized, open-label study. A total of 75 patients (25 men and 50 women) with OAB symptoms were randomized to treatment with solifenacin (n = 39) or tolterodine (n = 36). Efficacy and safety variables were assessed and compared with the baseline and between the two groups.\n At week 12, solifenacin and tolterodine demonstrated equal efficacy in reducing the number of micturition (-2.56 ±3.31 vs. -2.44 ± 4.56, p = 0.58), urgency (-1.70 ± 3.07 vs. -1.15 ± 2.68, p =0.37) and incontinence (-2.79 ± 2.82 vs. -4.67 ± 9.29, p =0.28) episodes per 24 hours. There was no difference in improvement of the quality of life. The patient and physician assessments of treatment benefit were not statistically different for solifenacin and tolterodine (p = 0.23 and p = 0.52, respectively), with the majority showing benefits in both groups. The incidence of major adverse events, including dry mouth (18.0%vs. 8.3%, p = 0.31) and constipation (12.8%vs. 2.8%, p = 0.20) was not significantly different. Compared with baseline, the severity of dry mouth did not increase in either group.\n Both solifenacin and tolterodine are effective in treating key OAB symptoms, including urinary frequency, urgency and incontinence in the Taiwanese population. Both medications are comparably effective and safe, with the most common adverse effects being dry mouth and constipation.\n Copyright © 2010 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.", "We compared the tolerability and clinical efficacy of tolterodine with those of oxybutynin in patients with an overactive bladder using an upward oxybutynin dose titration strategy analogous to that used in routine clinical practice in the United Kingdom and Republic of Ireland.\n In a randomized double-blind trial 378 male and female patients 50 years old or older with symptoms of overactive bladder (a urinary frequency of 8 or more voids per 24 hours with urgency and/or urge incontinence, that is 1 or more urge incontinence episodes per 24 hours) received 10 weeks of treatment with 2 mg. tolterodine twice daily/or an initial dose of 2.5 mg. oxybutynin twice daily, increasing to 5 mg. twice daily after 2 weeks of treatment. The main outcome measures were changes in voiding diary variables combined with detailed tolerability-safety assessments.\n Patients treated with tolterodine had significantly fewer adverse events (69% versus 81%, p = 0.01), notably dry mouth (37% versus 61%, p <0.0001), as well as a lower incidence of dose reduction (6% versus 25%, p <0.0001) than those in the oxybutynin group. Each agent had comparable efficacy for improving urinary symptoms. Tolterodine and oxybutynin caused a significant decrease (p = 0.0001) in the mean number of voids per 24 hours (-1.7 or -15% and -1.7 or -15%, respectively), urge incontinence episodes per 24 hours (-1.3 or -54% and -1.8 or -62%, respectively) and mean voided volume per void (33 ml. or 22% and 34 ml. or 23%) after 10 weeks of treatment.\n Tolterodine is as effective as oxybutynin for improving the symptoms of overactive bladder but it has superior tolerability. The combination of these qualities makes tolterodine the preferred pharmacological therapy for the long-term treatment of this condition.", "Eighteen women (median age 54 years, 36-79) with urinary motor urge (n = 13) or sensory urge (n = 5) incontinence were treated for three 2-week periods with emepronium carrageenate (EC) (Cetiprin Novum) in daily doses of 500 and 1000 mg and placebo. Subjectively the women experienced an increased ability to control micturition, i.e. less urge, during EC treatment. Only mild and mainly anticholinergic side effects were recorded, most frequently dryness of the mouth. As regards side effects, the evaluation of objective effects were complicated by a tendency towards carry-over effect to placebo. Placebo in the first treatment periods were analysed solely; no effects of placebo could be demonstrated. Compared with the reference period, decreases in the total number of micturitions (approx. 20%) and in the number of urge incontinence episodes (approx. 75%) were seen. As compared with placebo, a significant increase (approx. 25%) in the average micturition volume could be demonstrated. The percentage urinary excretion of emepronium decreased with increasing oral intake and with advancing age. Probably, an initial daily dosage of 500 mg EC will do well in younger women (less than 50 years), whereas elder patients may need 1000 mg. Further dosage recommendations are given.", "To investigate the clinical safety and efficacy of two dosages of tolterodine in older patients with symptoms attributable to overactive bladder.\n Randomized, double-blind, placebo-controlled, parallel-group, multinational, phase III study.\n Incontinence, older care, urological, and urogynecological clinics in the United Kingdom, France, and the Republic of Ireland.\n One hundred and seventy-seven older patients (age > or =65 years) with symptoms of urinary urgency, increased frequency of micturition (> or =8 micturitions/24 hours), and/or urge incontinence (> or =1 episode/24 hours).\n Tolterodine 1 mg or 2 mg twice daily (bid), or placebo, for 4 weeks.\n Safety and tolerability were evaluated through spontaneously reported adverse events, electrocardiogram, and blood pressure measurements. Efficacy was assessed using micturition diary variables: mean change from baseline in frequency of micturition and number of incontinence episodes/24 hours.\n The mean age of the patient population was 75 years. Overall, > or =87% of patients completed the study. Neither dosage of tolterodine was associated with serious drug-related adverse events during the study. No cardiac arrythmogenic events were noted. Dry mouth (mild to moderate intensity) was the most common adverse event in both the placebo and tolterodine treatment groups. Three percent of patients in the tolterodine 2 mg bid group discontinued treatment because of dry mouth, compared with 2% of placebo-treated patients. Compared with placebo, statistically significant decreases in micturition frequency were apparent in both tolterodine treatment groups. Furthermore, patients treated with tolterodine 2 mg bid had statistically significant decreases in urge incontinence episodes/24 hours and increases in volume voided per micturition compared with placebo.\n Tolterodine (taken for 4 weeks) is safe and shows efficacy, particularly at a dosage of 2 mg bid, in the treatment of older patients with urinary symptoms attributable to overactive bladder.", "Tolterodine is a potent antimuscarinic agent specifically developed for the treatment of urinary urge incontinence and other symptoms related to the overactive bladder. In order to assess the optimum dosage for use in future clinical studies, a double-blind, randomized, placebo-controlled, parallel-group, multicenter study was performed in 90 patients with detrusor hyperreflexia and symptoms of urinary urgency, frequency, and/or urge incontinence. Urodynamic variables, micturition diary variables, and subjective urinary symptoms were measured before and after 2 weeks' treatment with either placebo or tolterodine 0.5, 1, 2, or 4 mg twice daily (bd). Serum drug concentrations, electrocardiogram recordings, blood pressure, and incidence of adverse events were also assessed. Linear regression analysis showed a significant dose-response relationship for several clinically relevant urodynamic variables, while there was a trend towards an improvement in micturition diary variables and subjective assessment of symptoms with increasing dosages of tolterodine. There were no safety or tolerability concerns regarding any of the dosages of tolterodine investigated, although 2 patients treated with a dosage of 4 mg bd experienced urinary retention that necessitated dosage reduction. The results of this study suggest that tolterodine is well-tolerated and exerts a dose-dependent effect on bladder function in patients with detrusor hyperreflexia. The optimum dosage of tolterodine for use in future studies is 1-2 mg bd.", "To compare two new generation antimuscarinics at their recommended doses for treatment of overactive bladder syndrome (OAB).\n A prospective, double blind, double-dummy, two-arm, parallel-group, 12-week study was conducted to compare the efficacy and safety of solifenacin 5 or 10 mg and tolterodine extended release (ER) 4 mg once daily in OAB patients. After 4 weeks of treatment patients had the option to request a dose increase but were dummied throughout as approved product labelling only allowed an increase for those on solifenacin.\n Solifenacin, with a flexible dosing regimen, showed greater efficacy to tolterodine in decreasing urgency episodes, incontinence, urge incontinence and pad usage and increasing the volume voided per micturition. More solifenacin treated patients became continent and reported improvements in perception of bladder condition assessments. The majority of side effects were mild to moderate in nature, and discontinuations were comparable and low in both groups.\n Solifenacin, with a flexible dosing regimen, was found to be superior to tolterodine ER with respect to the majority of the efficacy variables.", "To evaluate the effects of darifenacin, an M3 selective receptor antagonist, compared with oxybutynin, on ambulatory urodynamics, salivary flow, heart rate and visual nearpoint in patients with overactive bladder (OAB).\n A double-blind, randomized, crossover study (n=65) with three treatment cohorts: darifenacin immediate release (IR) 2.5 mg three times a day (t.i.d.) or oxybutynin 2.5 mg t.i.d.; darifenacin controlled release (CR) 15 mg once daily (q.d.) or oxybutynin 5 mg t.i.d.; darifenacin CR 30 mg q.d. or oxybutynin 5 mg t.i.d. Within cohorts, patients received 7 days' treatment with each agent separated by 14 days' washout.\n All active treatments improved urodynamic parameters. Both darifenacin CR doses had significantly less effect on salivary flow than oxybutynin. Effects on urodynamic parameters, heart rate and visual nearpoint were comparable.\n Ambulatory urodynamics appears to be an innovative and potentially useful investigative tool in the evaluation of the efficacy of new therapeutic agents. Darifenacin CR is an efficacious therapy for OAB with comparable effects on urodynamic parameters but producing significantly less dry mouth than oxybutynin.", "To compare the efficacy and tolerability of propiverine and oxybutynin in patients with neurogenic detrusor overactivity.\n Patients were eligible, if at least 18 years of age and suffering from neurogenic detrusor overactivity. Eligibility also required a maximum cystometric capacity less than 300 ml. After a one-week run-in period, propiverine 15 mg t.i.d. or oxybutynin 5mg t.i.d. were administered for 21 days. As primary efficacy outcomes urodynamic parameters were assessed. As tolerability outcome the percentage of patients with newly manifesting anticholinergic adverse events was taken.\n 131 patients were recruited at 20 study centers. The maximum cystometric capacity (ml) was increased significantly in the propiverine group from 198 (+/-110) to 309 (+/-166), and in the oxybutynin group from 164 (+/-64) to 298 (+/-125). Similarly, maximum detrusor pressure during the filling phase (cm H(2)O) was lowered significantly in the propiverine group from 56.8 (+/-36.2) to 37.8 (+/-31.6), and in the oxybutynin group from 68.6 (+/-34.5) to 43.1 (+/-29.2). No significant differences resulted between treatment groups. Anticholinergic adverse events were reported less frequently in the propiverine compared to the oxybutynin group (63.0% versus 77.8%). Dryness of the mouth, the most frequent adverse event, was reported significantly less (47.1% versus 67.2%; p=0.02) in the propiverine compared to the oxybutynin group.\n Propiverine and oxybutynin are equally effective in increasing bladder capacity and lowering bladder pressure in patients with neurogenic detrusor overactivity. The trend for better tolerability of propiverine compared to oxybutynin achieved significance for dryness of the mouth.", "To compare the efficacy and tolerability of tolterodine with that of oxybutynin in patients with an overactive bladder.\n A randomized, double-blind, placebo-controlled, parallel group, multinational phase-III study was conducted in urology and gynaecology clinics in the UK, Republic of Ireland and Sweden. The study enrolled 293 patients with urodynamically confirmed bladder overactivity, increased frequency of micturition (> or = micturitions/24 h) and symptoms of urgency and/or urge incontinence (> or = 1 episode/24 h). Patients received either tolterodine (2 mg twice daily) or oxybutynin (5 mg three times daily) or placebo. Doses could be reduced, to prevent withdrawal, to 1 mg or 2.5 mg, respectively. The main outcome measures were the mean change from baseline in frequency of micturition/24 h, the number of incontinent episodes/24 h and volume voided per micturition.\n After 12 weeks' treatment, the mean frequency of micturition decreased by 21% and 19.5% in those receiving tolterodine (n = 118) and oxybutynin (n = 118), respectively, and by 10.5% in those on placebo (n = 57). Among those with urge incontinence at baseline (75% of patients), the mean number of incontinent episodes decreased by 47%, 71% and 19%, respectively, in those receiving tolterodine, oxybutynin and placebo. The effect of tolterodine and oxybutynin on these two micturition variables was statistically equivalent. There was also a comparable increase in mean volume voided per micturition in the tolterodine (27%) and oxybutynin groups (31%), compared with 7% in the placebo group. Dry mouth was the most common adverse event and was reported with greater frequency and intensity among patients receiving oxybutynin than among those receiving either tolterodine or placebo. In the oxybutynin group, more patients also withdrew because of adverse events and a greater proportion required dose reduction as a result of adverse events. Despite dose reduction, the frequency of adverse events and the intensity of dry mouth remained higher among those receiving oxybutynin (2.5 mg three times daily) than in patients who remained on tolterodine 2 mg twice daily.\n Tolterodine 2 mg twice daily is effective and well tolerated in the treatment of bladder overactivity. Tolterodine was better tolerated than oxybutynin, particularly with respect to the frequency and intensity of dry mouth, but had comparable clinical efficacy. The superior tolerability of tolterodine therefore allows more patients to remain on effective therapy than the current most commonly prescribed agent for the treatment of the overactive bladder.", "To evaluate the effects of tolterodine and oxybutynin on visual accommodation, pupillary diameter, intraocular pressure and tear secretion in women with overactive bladder.\n One hundred and four eyes from 52 consecutive female patients (age range: 22-60 years) with a urodynamic diagnosis of overactive bladder were prospectively investigated. Patients with a history of ocular disease or surgery were excluded. The subjects were randomly assigned to one of two groups: Group I received 2 mg tolterodine bid and Group II received 5 mg oxybutynin tid. All patients were evaluated at baseline (day 0) and after 1 month of treatment (day 28) by an ophthalmologist who was blinded to the medication. At each time point, a complete ophthalmic examination was performed and accommodation amplitude (AA), and pupillary diameter (PD) in dim and bright light were recorded. As well, tear secretion was assessed based on tear film break-up time and Schirmer I-test results. Statistical comparisons were made using the chi-square test, Student's t-test and Mann-Whitney U-test, as appropriate.\n Twenty-eight patients (56 eyes) received tolterodine and 24 patients (48 eyes) received oxybutynin. The mean ages of the two groups were similar (P = 0.523). After 4 weeks of treatment, AA was significantly lower in the oxybutynin treated group (P = 0.003, 95% CI 0.15, 0.62) whereas there was no significant change in AA in the tolterodine treated group (P = 0.155, 95% CI -0.042, 0.86). At day 28, PD in dim light was significantly larger in the tolterodine treated group (P = 0.031, 95% CI -0.82, -0.06), whereas no significant change in PD in dim light was noted in the oxybutynin treated group (P = 0.330, 95% CI -0.38, 0.18). Neither group showed a significant change in PD in bright light values on day 28 (P > 0.05 for both). In each group, the differences from day 0 to day 28 for intraocular pressure, and Schirmer-I results were insignificant (P > 0.05 for all). Both groups had significantly shorter tear film break-up time after 1 month of therapy (P = 0.014 (95% CI 0.47, 3.81) and P = 0.02 (95% CI 1.14, 4.61) for the tolterodine and oxybutynin treated groups, respectively).\n Four weeks of standard-dose oxybutynin treatment in women with overactive bladder decreases AA significantly, whereas the same duration of standard-dose tolterodine does not have this effect. However, tolterodine seemed to affect PD in dim light. One month of treatment with either of these anticholinergic drugs shortens tear film break-up time significantly. Concerning ocular side-effects, tolterodine seems to offer an advantage over oxybutynin because it does not affect AA, however, the shorter tear film break-up time with both agents suggests potential problems for patients who already have dry eye.", "To determine the efficacy, tolerability, and safety of fesoterodine in subjects with overactive bladder (OAB).\n This was a multicentre, randomised, double-blind, placebo- and active-controlled trial with tolterodine extended release (ER) to assess the efficacy and safety of fesoterodine. Eligible subjects (> or =18 yr) with increased micturition frequency and urgency and/or urgency urinary incontinence (UUI) were randomised to placebo, fesoterodine 4 mg, fesoterodine 8 mg, or tolterodine ER 4 mg for 12 wk. The primary efficacy variable was a change from baseline to week 12 in micturitions per 24 h. Co-primary end points included change from baseline to week 12 in UUI episodes per 24 h and Treatment Response (\"yes\" or \"no,\" based on four-point treatment benefit scale). Secondary efficacy variables included mean volume voided per micturition, continent days per week, and number of urgency episodes.\n At the end of treatment, subjects taking fesoterodine 4 and 8 mg had significant (p<0.05) and clinically relevant improvements versus placebo in the primary, co-primary, and most secondary efficacy variables. Tolterodine ER (active control) also provided significantly greater improvement than placebo for most efficacy variables, confirming the sensitivity of the study design. A more pronounced effect was observed with fesoterodine 8 mg at most end points.\n Both doses of fesoterodine were significantly better than placebo in improving the symptoms of OAB and produced a significantly greater Treatment Response versus placebo. Efficacy was more pronounced with fesoterodine 8 mg compared with the other treatments. Active treatments were well tolerated.", "Clinical efficacy and adverse effects of oxybutynin and propantheline in the treatment of symptoms related to detrusor hyperactivity were studied in a randomized, controlled, double-blind multicenter trial. Of 169 patients entered into the study 154 were evaluable for statistical analysis. Mean grade of improvement (visual analogue scale) was significantly higher with oxybutynin (58.2%) versus propantheline (44.7%) and placebo (43.4%). Mean bladder volume at first involuntary cystometric contraction was significantly increased with oxybutynin (+57.0 ml.) versus placebo (-9.7 ml.). Mean maximum cystometric bladder capacity was also significantly increased with oxybutynin (+80.1 ml.) versus placebo (+22.5 ml.). Rate of inquired possible adverse effects was significantly higher for oxybutynin (63%) versus propantheline (44%) and placebo (33%). However, only 5 patients dropped out of the study because of adverse effects (oxybutynin 2 and propantheline 3). No serious or lasting adverse effects were encountered with dryness of the mouth being the major complaint. Oxybutynin has statistically significant effects on subjective symptoms and objective urodynamic parameters in patients with detrusor hyperactivity compared to propantheline.", "To evaluate the dose-response relationship and safety/tolerability of solifenacin succinate (YM905) in the treatment of overactive bladder (OAB), and to compare its efficacy and safety/tolerability with tolterodine 2 mg twice daily.\n This multicentre study included a 2-week single-blind placebo run-in, a 4-week double-blind placebo-controlled active treatment phase, and a 2-week follow-up. Men and women with an OAB and urodynamic evidence of detrusor overactivity were randomized to placebo or solifenacin 2.5, 5, 10 or 20 mg once daily, or tolterodine 2 mg twice daily.\n Of 265 patients enrolled, 225 were randomized and 192 completed the study. Solifenacin 5, 10 and 20 mg produced statistically significant (P < 0.05) improvements in voids/24 h vs placebo, whereas tolterodine did not; the mean change with tolterodine was between those with solifenacin 2.5 and 5 mg. The outcome was similar for the mean change from baseline to endpoint in mean volume voided/void. For incontinence and urgency episodes/24 h the solifenacin dose groups showed numerically superior changes vs placebo; the mean effects with tolterodine were generally smaller than with solifenacin. Most of the efficacy effect of solifenacin was evident at 2 weeks. Quality-of-life outcomes supported the efficacy results. Solifenacin 5 and 10 mg were well tolerated; there were no serious treatment-related adverse events. The incidence of dry mouth was 14% for solifenacin 5 and 10 mg, 2.6% for placebo and 24% for tolterodine.\n In this study, the 5- and 10-mg doses of solifenacin appeared to be the most clinically effective for treating OAB, considering the balance between efficacy, quality of life and tolerability. From the results of this study solifenacin 5 and 10 mg were selected for further evaluation in large-scale phase 3 studies.", "To evaluate the efficacy, safety and tolerability of tolterodine compared to placebo in patients with an overactive bladder.\n A double-blind, multi-centre phase III study in France and Belgium 251 patients with overactive bladder symptoms, and urodynamically verified detrusor overactivity, were randomised to receive 4-week treatment with either placebo or tolterodine 1 or 2mg twice daily (bd). Efficacy was evaluated from patient micturition diaries. Safety and tolerability endpoints were also evaluated.\n After 4-week treatment, the number of incontinence episodes/24h decreased significantly relative to placebo in the tolterodine 1 and 2 mgbd groups (P=0.045 and P=0.0089, respectively). Both dosages of tolterodine increased volume voided per micturition compared with placebo (P=0.055 and P=0.056, respectively), although significant decreases in micturition frequency were not apparent. Tolterodine was safe and well tolerated, few patients were withdrawn due to adverse events. Dry mouth, mainly of mild-to-moderate intensity, was the most common adverse event. No clinically relevant changes in blood pressure or laboratory safety variables were reported.\n Tolterodine is effective, safe and well tolerated for the treatment of symptoms of an overactive bladder, particularly urge incontinence.", "This study compared the clinical efficacy (determined from micturition diaries) and safety of 12 weeks' treatment with either tolterodine 2 mg twice daily, oxybutynin 5 mg three times daily or placebo in patients with an overactive bladder. A total of 277 patients were randomized and treated at 25 centers. Both tolterodine and oxybutynin significantly increased volume voided/micturition compared to placebo. Both treatment groups evoked greater decreases in micturitions per 24 hours and incontinence episodes per 24 hours compared to placebo; however, only tolterodine was significantly better than placebo in reducing micturition frequency. Tolterodine and oxybutynin were equivalent in their effectiveness. Tolterodine was significantly better tolerated than oxybutynin when adverse events (particularly frequency and intensity of dry mouth), dose reduction and patient withdrawals were considered. Oxybutynin is an effective drug whose frequent adverse effects limit its clinical usefulness. Tolterodine has equivalent efficacy to oxybutynin, but with less severe adverse effects. This will allow patients to receive more effective treatment for their condition, with better compliance.", "Propiverine and tolterodine were compared with respect to efficacy, tolerability and impact on the quality of life in the treatment of patients with idiopathic detrusor overactivity.\n In a randomised, double-blind, multicentre clinical trial, patients with idiopathic detrusor overactivity were treated with 15 mg propiverine twice daily or 2mg tolterodine twice daily over a period of 28 days. The maximum cystometric capacity was determined at baseline and after 4 weeks of therapy. The difference of both values was used as the primary endpoint. Secondary endpoints were voided volume per micturition, evaluation of efficacy (by the investigator), tolerability, post void residual urine, and quality of life.\n The mean maximum cystometric capacity increased significantly (p < 0.01) in both groups. The volume at first urge and the frequency/volume chart parameters also showed relevant improvements during treatment. 42/100 patients in the propiverine group and 43/102 in the tolterodine group experienced adverse events. The most common adverse event, dry mouth, occurred in 20 patients in the propiverine group and in 19 patients in the tolterodine group. The scores for the quality of life improved comparably in both groups.\n The study demonstrates comparable efficacy, tolerability, and improvement in the quality of life of 15 mg propiverine twice-daily and 2mg tolterodine twice-daily in the treatment of the symptoms of idiopathic detrusor overactivity.", "Hyperreflexia is the most common urological finding in patients with multiple sclerosis. A prospective randomized study was done to compare the effectiveness of 2 commonly used drugs, oxybutynin and propantheline. Of the 34 patients entered into the trial 19 were treated with oxybutynin and 15 with propantheline. The urological symptoms (frequency, nocturia, hesitancy, urgency and urge incontinence) were graded according to severity from 0 to 3. Patients with urinary infection were excluded. Urodynamic examination, consisting of cystometrography and electromyography, was performed in all patients before treatment. Both groups of patients had comparable neurological, urological and urodynamic status before treatment. In 4 patients (21 per cent) treated with oxybutynin and in 4 (27 per cent) treated with propantheline side effects were so severe that the treatment had to be discontinued. Symptomatic response to oxybutynin was good in 10 patients (67 per cent), fair in 2 (13 per cent) and poor in 3 (20 per cent). Propantheline produced good symptomatic results in 4 patients (36 per cent), fair in 1 (9 per cent) and poor in 6 (55 per cent). The mean increase in maximum cystometric capacity on cystometrography was significantly larger in the oxybutynin group than in the propantheline group (144 +/- 115 versus 35 +/- 101). Our results indicate that oxybutynin is more effective than propantheline in the treatment of detrusor hyperreflexia in patients with multiple sclerosis.", "Therapy of detrusor hyperactivity with anticholinergic agents often is followed by adverse drug reactions. Intravesical application may be an interesting alternative. A randomised, single-blind, placebo-controlled, mono-centre clinical trial was carried out in 84 patients with urgency or urge incontinence. Due to intravesical administration of oxybutynin (CAS 5633-20-5) (n = 21) and trospium chloride (CAS 10405-02-4) (n = 21), respectively, a significant increase in maximum bladder capacity and decrease of detrusor pressure accompanied by an increase of residual urine were found in comparison to placebo in urodynamical investigations. Improvement of uninhibited bladder contractions occurred leading to higher filling volume. Under verapamil (CAS 152-11-4) (n = 21) no marked changes in the efficacy variables were found compared with placebo. All patients completed the study and were assessed with regard to efficacy and safety. No adverse events or marked changes in the vital signs were reported. The immediate onset of effect and the lack of adverse drug reactions suggest that treatment with topical oxybutynin or trospium chloride is an effective alternative in patients with intolerable side effects when orally treated. In addition, intravesical administration may be indicated in patients with bladder spasms due to indwelling catheter or in order to increase bladder capacity before percutaneous cystostomy.", "To compare the efficacy and tolerability of fesoterodine 8 mg with tolterodine extended-release (ER) 4 mg and placebo in a randomized clinical trial of patients with an overactive bladder (OAB).\n In this 12-week double-blind, double-dummy, placebo-controlled, randomized clinical trial, eligible patients reported OAB symptoms for > or = 3 months and recorded > or = 8 voids and > or = 1 urgency urinary incontinence (UUI) episode per 24 h in 3-day bladder diaries at baseline. Patients were randomized in a 2:2:1 ratio to fesoterodine (4 mg for 1 week then 8 mg for 11 weeks); tolterodine ER 4 mg; or placebo (with sham dose escalation for tolterodine ER and placebo). Endpoints were changes from baseline to week 12 in UUI episodes (primary endpoint), total and nocturnal voids, urgency episodes, severe urgency episodes, and frequency-urgency sum per 24 h; mean voided volume per void (MVV); and the OAB questionnaire (OAB-q), Patient Perception of Bladder Condition (PPBC), and Urgency Perception Scale (UPS). Safety and tolerability were assessed and summarized over the 12-week study period.\n Fesoterodine (636 patients) significantly improved UUI episodes at week 12 (primary endpoint) compared with tolterodine ER (641 patients; P = 0.017) and placebo (313 patients; P < 0.001). Fesoterodine also produced significantly greater improvements than tolterodine ER in MVV (P = 0.005). Fesoterodine significantly improved all diary endpoints compared with placebo (P < 0.001), except for nocturnal voids (P = 0.327). Tolterodine ER significantly improved all diary endpoints vs placebo (P < 0.001), except for nocturnal voids (P = 0.506) and MVV (P = 0.103). Diary dry rates (the proportion of patients reporting no UUI episodes at endpoint among those with one or more UUI episodes at baseline) were significantly higher with fesoterodine (64%) than with tolterodine ER (57%; P = 0.015) and placebo (45%; P < 0.001). Improvements in PPBC, UPS and OAB-q scale and domain scores at week 12 were all significantly better with fesoterodine than placebo (all P < 0.001) and tolterodine ER (all P < 0.05) except for the OAB-q Sleep domain vs tolterodine ER (P = 0.081). Dry mouth and constipation rates were 28% and 5% in the fesoterodine group, 16% and 4% in the tolterodine ER group, and 6% and 3% with placebo, respectively. Discontinuations due to treatment-emergent adverse events were 6%, 4% and 2% in the fesoterodine, tolterodine ER, and placebo groups, respectively.\n In patients with OAB, fesoterodine 8 mg showed superior efficacy over tolterodine ER 4 mg and placebo in reducing UUI episodes (primary endpoint) and in improving most patient-reported outcome measures. Both active treatments were well tolerated.", "Objective To compare the tolerability and clinical efficacy of tolterodine and oxybutynin in the treatment of Hong Kong Chinese women with an overactive bladder. Patients and methods A randomized controlled trial was conducted at two urogynaecology centres in Hong Kong. In all, 106 women with urodynamically confirmed detrusor instability were recruited. Baseline severity assessments included a visual analogue scale (VAS), urinary diary and urinary pad-test. The women were randomized to receive either oral tolterodine 2 mg or oxybutynin 5 mg twice daily for 10 weeks. Treatment responses were assessed at 4 and 10 weeks using the VAS and urinary diary. Treatment tolerability was assessed at baseline, 4 and 10 weeks using the Xerostomia Questionnaire. A urinary pad-test was repeated at 10 weeks. Results The perceived change from baseline VAS was better in the tolterodine than the oxybutynin group after 10 weeks of treatment (per-protocol analysis, P = 0.043). The two drugs were effective in reducing the symptoms of frequency (P < 0.001). Tolterodine was significantly better than oxybutynin in reducing urinary leakage (urinary pad-test; median change - 5.00 g vs 0 g, P = 0.019). Both drugs caused a significant worsening of dry mouth (overall dryness, P < 0.005; discomfort, P < 0.005; sleep, P = 0.021; speaking, P = 0.045; swallowing, P = 0.004; and liquid consumption, P = 0.017). Conclusions Both oxybutynin and tolterodine were effective in ameliorating the severity of the symptoms of detrusor instability. Tolterodine was better than oxybutynin in both subjective and objective outcome measures, but both drugs caused similar worsening of dry mouth that may limit the tolerability of these medications.", "This study aims to compare the efficacy of propiverine hydrochloride immediate release (IR), propiverine hydrochloride extended release (ER) and placebo for the treatment of overactive bladder syndrome. The primary outcome measure is incontinence episode frequency, with secondary outcome measures including mean volume per void and quality of life as assessed on King's Health Questionnaire.\n The double-blind, double-dummy, randomized study compared IR 15 mg twice daily, ER 30 mg once daily and placebo in 3 parallel groups. After a run-in period of 7 days, the patients were treated for 32 days. Nine hundred and eighty-eight patients were randomized, and 910 patients completed the protocol without major violations.\n The number of incontinence episodes/24 h decreased by 2.26 in the IR group (p < 0.001 vs. placebo), by 2.46 in the ER group (p < 0.0001 vs. placebo) and by 1.75 in the placebo group. The most frequent adverse event was dry mouth with 22.8% of the patients in the IR group, 21.7% in the ER group and 6.4% in the placebo group. The overall tolerability was rated 'very good' or 'good' by more than 80% of the investigators and patients in all 3 groups.\n Propiverine ER 30 mg once daily and propiverine IR 15 mg twice daily significantly reduce the number of incontinence episodes/24 h within a treatment period of 32 days. Both formulations are safe and well tolerated. The extended release formulation of propiverine is a suitable new option for the treatment of the overactive bladder.\n Copyright (c) 2006 S. Karger AG, Basel.", "About 15% to 20% of patients with detrusor hyperreflexia do not benefit from oral oxybutynin regimens, frequently because of unpleasant side effects. Several reports indicate that intravesical oxybutynin is effective in many of these patients but there are some who still fail to respond.\n A select group of 10 adults with detrusor hyperreflexia unresponsive to standard oral and intravesical oxybutynin regimens were treated at weekly intervals with 5 mg. oxybutynin orally, or 5 mg. oxybutynin in 100 ml. intravesically for 60 minutes of passive diffusion and for 30 minutes with 5 mA. electrical current. Each treatment (plus oral placebo and 2 intravesical controls) was associated with an 8-hour, full urodynamic monitoring session, and periodic blood and bladder content sampling.\n There was no significant objective improvement with oral or intravesical passive diffusion oxybutynin. Conversely there was significant improvement in 5 of 6 objective urodynamic measurements with intravesical electromotive oxybutynin. Plasma profiles were a single peak and decay following oral oxybutynin and 2 distinct peaks with intravesical passive diffusion and electromotive oxybutynin. Area under the curve for intravesical passive diffusion were 709 ng. per 8 hours versus oral 1,485 (p <0.05) versus intravesical electromotive 2,781 (p <0.001). Bladder content samples confirmed oxybutynin absorption. Oral oxybutynin caused anticholinergic side effects in 7 of 10 patients. There were no side effects with intravesical passive diffusion or electromotive administrations.\n Accelerated intravesical administration results in greater bioavailability and increased objective benefits without side effects in previously unresponsive patients compared with oral and intravesical passive diffusion oxybutynin administration.", "Tolterodine is a new competitive muscarinic receptor antagonist developed for the treatment of the unstable bladder. A total of 242 patients were enrolled in a multicenter, multinational, randomized, double-blind, placebo-controlled study conducted over a period of 4 weeks in patients with detrusor overactivity and symptoms of frequency, urgency, and urge incontinence. The objective of the study was to compare the efficacy and safety of tolterodine given at 1 or 2 mg b.i.d. versus placebo. At week 4 a statistically significant increase in the volume at first contraction (p = 0.030) and maximal cystometric capacity (p = 0.034) was only in the tolterodine 2 mg b.i.d. group. Tolterodine was safe and generally well tolerated. The incidence of dry mouth, as the most commonly reported adverse event, was only 9% and of mild to moderate intensity.", "Seventy-two women with proven detrusor instability completed a novel clinical trial of the new anticholinergic emepronium carrageenate (Cetiprin novum), which allowed for dose titration. The tolerated dose has been shown to correlate with the severity of symptoms. Statistically significant improvement was achieved in symptomatic and urodynamic parameters without serious side effects.", "To compare the efficacy and tolerability of extended-release formulations of oxybutynin chloride and tolterodine tartrate in women with overactive bladder.\n The OPERA (Overactive bladder: Performance of Extended Release Agents) trial was a randomized, double-blind, active-control study performed at 71 US study centers from November 21, 2000, to October 18,2001. Extended-release formulations of oxybutynin at 10 mg/d or tolterodine at 4 mg/d were given for 12 weeks to women with 21 to 60 urge urinary incontinence (UUI) episodes per week and an average of 10 or more voids per 24 hours. Episodes of UUI (primary end point), total (urge and nonurge) incontinence, and micturition were recorded in 24-hour urinary diaries at baseline and at weeks 2, 4, 8, and 12 and compared. Adverse events were also evaluated.\n Improvements in weekly UUI episodes were similar for the 790 women who received extended-release formulations of oxybutynin (n = 391) or tolterodine (n = 399). Oxybutynin was significantly more effective than tolterodine in reducing micturition frequency (P = .003), and 23.0% of women taking oxybutynin reported no episodes of urinary incontinence compared with 16.8% of women taking tolterodine (P = .03). Dry mouth, usually mild, was more common with oxybutynin (P = .02). Adverse events were generally mild and occurred at low rates, with both groups having similar discontinuation of treatment due to adverse events.\n Reductions in weekly UUI and total incontinence episodes were similar with extended-release formulations of oxybutynin and tolterodine. In the oxybutynin group, micturition frequency was significantly lower, and the percentage of women reporting no urinary incontinence episodes was significantly higher compared with the tolterodine group. Dry mouth was more common with oxybutynin, but tolerability was otherwise comparable, including adverse events involving the central nervous system.", "Our objectives were to ascertain the tolerability and efficacy of trospium chloride in doses of 20 mg twice daily for long-term therapy (52 weeks) in patients with urge syndrome. The trial comprised a total of 358 patients with urge syndrome or urge incontinence. After randomisation in the ratio of 3:1, participants were treated continuously for 52 weeks with either trospium chloride (20 mg twice daily) or oxybutynin (5 mg twice daily). At intervals of 4-8 weeks, patients were physically examined with measurements of blood pressure and pulse rate, were questioned about any adverse events, checked for compliance and underwent relevant laboratory tests. As an additional safety measure, an ECG was made at 26 and 52 weeks. Urodynamic measurements were performed at the beginning, and at 26 and 52 weeks to determine the maximal cystometric bladder capacity. Among others things, the frequencies of micturition, incontinence and number of urgency events were recorded in patient diary protocols in weeks 0, 2, 26 and 52. The evaluation of vital parameters, laboratory results and ECGs did not show any relevant changes attributable to the action of the anticholinergics. Analysis of the micturition diary clearly indicated a reduction of the micturition frequency, incontinence frequency, and a reduction of the number of urgencies in both treatment groups. Mean maximum cystometric bladder capacity increased during treatment with trospium chloride by 92 ml after 26 weeks and 115 ml after 52 weeks (P=0.001). Further comparison with oxybutynin did not reveal any statistically significant differences in urodynamic variables between the drugs. Adverse events occurred in 64.8% of the patients treated with trospium chloride and 76.7% of those treated with oxybutynin. The main symptom encountered in both treatment group was dryness of the mouth. For patients on trospium chloride, the estimated risk of an unexpected adverse event was 0.027 per patient per week for all adverse events and 0.009 for dryness of the mouth, resulting in a considerably lower risk during treatment given with trospium chloride than with oxybutynin (0.045 and 0.021, respectively). An overall assessment for each of the drugs reveals a comparable efficacy level and a better benefit-risk ratio for trospium chloride than for oxybutynin due to better tolerability.", "To evaluate the efficacy and tolerability of a new extended-release (ER), once-daily, capsule formulation of tolterodine, relative to placebo and the existing immediate-release (IR), twice-daily, tablet formulation, for treatment of the overactive bladder.\n This was a double-blind, multicenter, randomized, placebo-controlled trial. One thousand five hundred twenty-nine patients (81% women) with urinary frequency (eight or more micturitions every 24 hours) and urge incontinence (five or more episodes per week) were randomized to oral therapy with tolterodine ER 4 mg once daily (n = 507), tolterodine IR 2 mg twice daily (n = 514), or placebo (n = 508) for 12 weeks. Efficacy was assessed at the end of the treatment period on the basis of the micturition diary variables. Tolerability and safety were assessed by evaluating the adverse events, electrocardiogram parameters, laboratory values, and treatment withdrawals.\n Tolterodine ER 4 mg once daily (P = 0.0001) and tolterodine IR 2 mg twice daily (P = 0.0005) both significantly reduced the mean number of urge incontinence episodes per week compared with placebo. The median reduction in these episodes as a percentage of the baseline values was 71% for tolterodine ER, 60% for tolterodine IR, and 33% for placebo. The ER formulation was 18% more effective than the IR formulation (P <0.05). Treatment with both formulations of tolterodine was also associated with statistically significant improvements in all other micturition diary variables compared with placebo. For both formulations, the mean decreases in micturition frequency (P <0.0079) and pad usage (P <0.0145) were significant, and the mean volume voided per micturition increased (P = 0.0001). The rate of dry mouth (of any severity) was 23% for tolterodine ER, 30% for tolterodine IR, and 8% for placebo. The overall dry mouth rate for patients taking tolterodine ER was 23% lower than for tolterodine IR (P <0.02), and the rate of severe dry mouth in the ER group was only 1.8%. The rates of withdrawal were comparable for the two active groups and the placebo group. No safety concerns were noted.\n Tolterodine ER 4 mg once daily is effective and well tolerated in the treatment of overactive bladder with no safety concerns. Tolterodine ER demonstrated an improved efficacy for reducing urge incontinence episodes and a lower frequency of dry mouth compared with the existing IR twice-daily formulation.", "We compared the short-term efficacy, safety and tolerability of transdermal versus oral oxybutynin in adults with urge urinary incontinence.\n Volunteers with detrusor instability currently responding to oral immediate release oxybutynin were enrolled in our study. Those patients presenting with recurrence of incontinent symptoms after a 2-week washout underwent confirmatory cystometrogram with subsequent randomization to transdermal or oral treatment. Matching active and placebo medications included matrix patches applied twice weekly and capsules taken 2 or 3 times daily. Dose titration was based on anticholinergic symptoms. Outcome measures included comparison of baseline to 6 week changes in incontinence episodes on a 3 day urinary diary, a visual analog scale for efficacy and anticholinergic symptoms reported on a questionnaire. Safety monitoring included adverse events and skin tolerability of the transdermal system.\n A total of 76 patients were enrolled and 74 completed at least 4 weeks of treatment. Mean age in the transdermal and oral groups was 64 and 63 years, and 87% and 97% were female, respectively. Daily incontinent episodes decreased in the transdermal and oral groups (7.3 to 2.4 [66%] and 7.4 to 2.6 [72%], respectively, p = 0.39). The visual analog scale reduction in urinary leakage improved from washout in both groups (p <0.0001) with no difference between them (p = 0.9). Dry mouth occurred in significantly fewer patients in the transdermal (38%) compared with those in the oral group (94%, p <0.001). Of the patients in the transdermal group 67% noticed a reduction in dry mouth severity compared with previous oral treatment, and 90% had none or mild skin erythema.\n Transdermal delivery of oxybutynin resulted in comparable efficacy and a significantly improved anticholinergic side effect profile compared with oral administration in adults with urge urinary incontinence.", "To compare solifenacin succinate (5 and 10 mg once-daily) to placebo and propiverine hydrochloride (20 mg once-daily), respectively, in Japanese patients with overactive bladder syndrome (OAB).\n A multicentre, 12-week, double-blind phase III trial randomized men and women aged > or = 20 years with OAB to solifenacin 5 or 10 mg, propiverine 20 mg, or placebo. Changes at endpoint in number of voids/24 h, urgency, incontinence, urgency incontinence and nocturia episodes, volume voided/void, restoration of continence and quality of life (QoL) were examined.\n Of 1593 patients randomized, 1584 were treated; at the endpoint there were greater reductions in mean (sd) voids/24 h with solifenacin 5 mg, at -1.93 (1.97), and 10 mg, at -2.19 (2.09), and propiverine 20 mg, at -1.87 (2.70), than with placebo, at -0.94 (2.29) (P < 0.001 for all). Solifenacin (5 and 10 mg) was superior to placebo, and no worse than propiverine 20 mg, for this variable. There were significantly fewer mean (sd) urgency, incontinence and urgency incontinence episodes with solifenacin and propiverine than with placebo, with respective changes on placebo of - 1.28 (2.90), - 0.72 (1.95) and - 0.69 (2.00); solifenacin 5 mg, - 2.41 (2.88), -1.59 (2.12) and -1.45 (1.89) (P < 0.001 for all), and 10 mg, -2.78 (2.82), - 1.60 (1.81) and - 1.52 (1.77) (P < 0.001 for all), and propiverine 20 mg, -2.30 (3.08), -1.25 (2.79) and - 1.19 (2.20) (P < 0.001, = 0.002 and = 0.002 respectively). All active treatments vs placebo improved the volume voided (P < 0.001 for all) and QoL; solifenacin 10 mg reduced nocturia episodes (P = 0.021) and significantly improved urgency episodes (P = 0.012) and volume voided (P = 0.009) vs propiverine 20 mg, and solifenacin 5 mg caused less dry mouth (P = 0.003). Solifenacin 10 mg caused more dry mouth (P = 0.012) and occurrences of constipation (P = 0.004) than propiverine 20 mg, but discontinuation rates between both treatment groups were similar. Continence was restored at endpoint in more than half of the patients on active treatment.\n Solifenacin 5 and 10 mg once daily significantly improved the symptoms of OAB compared with placebo. Solifenacin therapy at 5 mg once daily is well-tolerated; 10 mg can be given if additional efficacy is required.", "We compared the efficacy and safety of once daily controlled and immediate release oxybutynin for incontinence.\n This multicenter, randomized, double-blind, active control, parallel study was designed to evaluate urge urinary incontinence episodes using a 7-day diary.\n A total of 97 women and 8 men 34 to 76 years old with urge incontinence or mixed incontinence with a clinically significant urge component were enrolled in the study. The number of weekly urge incontinence episodes decreased from 27.4 to 4.8 after controlled and from 23.4 to 3.1 after immediate release oxybutynin (p = 0.56), and total incontinence episodes decreased from 29.3 to 6 and from 26.3 to 3.8, respectively (p = 0.6). Weekly urge incontinence episodes from baseline to end of study also decreased to 84% after controlled and 88% after immediate release oxybutynin (p = 0.7). Continence was achieved in 41% of the controlled and 40% of the immediate release group (p = 0.9). Dry mouth of any severity was reported by 68 and 87% of the controlled and immediate release groups, respectively (p = 0.04), and moderate or severe dry mouth occurred in 25 and 46%, respectively (p = 0.03).\n Participants taking a single daily does of controlled release oxybutynin had similar reductions in urge incontinence and total incontinence episodes compared to those taking oxybutynin 1 to 4 times daily. A lower incidence of dry mouth was reported for controlled release oxybutynin.", "A proportion of patients with detrusor hyperreflexia who are unresponsive to oral oxybutynin often benefit from intravesical oxybutynin instillation. To our knowledge the precise mode of action of this method is obscure.\n In 12 patients with detrusor hyperreflexia who were previously unresponsive to oral and intravesical passive diffusion of 5 mg. oxybutynin we administered 5 mg. oxybutynin orally as well as increased doses of 15 mg. oxybutynin intravesically with passive diffusion and with 15 mA. associated electric current. Each administration mode per patient was associated with an 8-hour urodynamic monitoring session during which oxybutynin and N-desethyl oxybutynin plasma levels, and intravesical oxybutynin uptake were measured.\n A dose of 5 mg. oxybutynin orally induced no urodynamic improvement with an area under the plasma concentration time curve of combined N-desethyl oxybutynin plus oxybutynin of 16,297 ng./8 hours and an area under the curve ratio of N-desethyl oxybutynin-to-oxybutynin of 11:1. Passive diffusion oxybutynin resulted in 12 mg. oxybutynin intravesical uptake and significant improvement in 3 of 8 urodynamic measurements, although the area under the curve of combined N-desethyl oxybutynin plus oxybutynin was only 2,123 ng./8 hours and the N-desethyl oxybutynin-to-oxybutynin ratio was 1.1:1.0. Electromotive administration of oxybutynin resulted in almost complete intravesical uptake of the 15 mg. dose, significant improvement in all 8 urodynamic measurements and an increased oxybutynin level versus oral and passive diffusion, although the area under the curve of combined N-desethyl oxybutynin plus oxybutynin was 4,574 ng./8 hours and the N-desethyl oxybutynin-to-oxybutynin ratio was inverted at 1.0:1.4. The oral dose of 5 mg. oxybutynin caused anticholinergic side effects in 8 of the 12 patients. Neither intravesical passive diffusion nor electromotive administration caused side effects with an uptake of 12 and 15 mg., respectively.\n A large proportion of intravesical oxybutynin is sequestered, probably in the urothelium. Intravesical oxybutynin administration confers therapeutic benefits via localized direct action within the bladder wall.", "• To show the superior efficacy of fesoterodine over tolterodine extended release (ER) in a placebo-controlled overactive bladder (OAB) trial with predefined treatment comparisons for both diary measures and patient-reported outcomes.\n • In this 12-week, double-blind, double-dummy trial, subjects reporting >1 urgency urinary incontinence (UUI) episode and ≥8 micturitions per 24 h at baseline were randomized to fesoterodine (4 mg for 1 week, 8 mg for 11 weeks), tolterodine ER 4 mg, or placebo. • Subjects completed 3-day bladder diaries, the Patient Perception of Bladder Condition (PPBC) and the Urgency Perception Scale (UPS) at baseline and weeks 1, 4 and 12 and the OAB Questionnaire at baseline and week 12.\n • A total of 2417 subjects were randomized. At week 12, fesoterodine 8 mg showed superiority over tolterodine ER 4 mg and placebo on UUI episodes (primary endpoint), micturitions, urgency and most other diary endpoints, and on the PPBC, UPS and all OAB Questionnaire scales and domains (all P < 0.05). • Superiority of fesoterodine 8 mg over tolterodine ER 4 mg was seen as early as week 4 (3 weeks after escalation to fesoterodine 8 mg). At week 1, fesoterodine 4 mg was superior to placebo on most diary variables, the PPBC and the UPS (all P < 0.05). Dry mouth and constipation rates were 28% and 4% with fesoterodine, 13% and 3% with tolterodine ER, and 5% and 2% with placebo. • Discontinuation rates as a result of adverse events were 5%, 3% and 2% for fesoterodine, tolterodine ER and placebo, respectively.\n • In this randomized study, which is the largest to compare antimuscarinic efficacy performed to date, fesoterodine 8 mg was superior to tolterodine ER 4 mg for UUI episodes, micturitions and urgency episodes, as well as for self-reported patient assessments of bladder-related problems, urgency, symptom bother and health-related quality of life. • The superiority of fesoterodine 8 mg over tolterodine ER 4 mg was observed as early as 3 weeks after escalation from fesoterodine 4 mg for most outcomes. These data may have important implications for the clinical management of OAB patients previously treated with tolterodine ER.\n © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.", "To compare the effects of propiverine and oxybutynin on ambulatory urodynamic monitoring (AUM) parameters, safety, and tolerability in patients with overactive bladder.\n This was a randomized, double-blind, placebo-controlled, multicentre, crossover study. Patients (n = 77) received two of the following treatments during two 2-week periods: propiverine 20 mg once daily, propiverine 15 mg three times daily, oxybutynin 5 mg three times daily, and placebo. AUM parameters, salivary flow, visual near point, and heart rate were assessed.\n A consistent order in the efficacy between active treatment groups was observed for the reduction in mean involuntary detrusor contractions (IDCs; oxybutynin 15 mg </= propiverine 45 mg </= propiverine 20 mg). Differences between the oxybutynin and propiverine 20 mg groups were statistically significant for several AUM endpoints. Statistically significant differences between the oxybutynin and both propiverine groups were also noted in salivary flow rate and heart rate (oxybutynin 15 mg < both propiverine regimens) and in heart rate variability (both propiverine regimens < oxybutynin 15 mg). All active treatments lengthened visual near point. The incidence of dry mouth was significantly more pronounced in the oxybutynin group than in either propiverine group. Treatment with propiverine 45 mg resulted in the highest rates of constipation, lengthening of the visual near point, and effects on heart rate.\n Oxybutynin 15 mg was more effective than propiverine 20 mg in reducing symptomatic and asymptomatic IDCs in ambulatory patients. The primary differences between the two drugs were the incidence and type of adverse events, which varied with the antimuscarinic receptor specificity of each agent.", "Two of the principal drugs used to treat detrusor instability, oxybutinin hydrochloride and propantheline bromide, were compared using clinical and urodynamic outcome measures in a randomized crossover trial with a patient-regulated variable dose regimen. Of the 23 women in the trial, 14 reported subjective improvement during treatment with oxybutinin hydrochloride compared with 11 during treatment with propantheline bromide. Apart from a greater increase in the maximum cystometric capacity with oxybutinin, there were no other objective differences between the two drugs. Oxybutinin significantly delayed the first desire to void, increased the maximum cystometric capacity and reduced the maximum detrusor pressure rise on filling. Propantheline significantly increased the maximum cystometric capacity and reduced the maximum detrusor pressure rise on filling. Three patients stopped treatment due to side-effects.", "Oxybutynin has long been used for the treatment of patients with detrusor overactivity and urinary urge incontinence. The short half-life of oxybutynin administered as a conventional tablet formulation or syrup requires 2-3 times daily dosage to be effective. A new controlled release (CR) tablet for once-daily administration has been developed. The efficacy and tolerability of this new controlled release tablet was compared to that of a 5-mg conventional oxybutynin tablet administered twice daily. Seventeen female incontinent patients were studied in a double-dummy crossover trial. Efficacy and tolerability were assessed by using a voiding diary, pad-weighing test, visual-analogue scale (VAS), and questionnaire. Adverse events were recorded spontaneously on a questionnaire by the patients themselves throughout the study. Serum concentrations of oxybutynin and its active metabolite N-desethyloxybutynin were studied after both a single dose and multiple dosage. There was no difference in efficacy between the two formulations. Depending on the parameters tested, the change from baseline values in a positive direction ranged from 15 to 53%. The incidence of adverse events was similar with both formulations. Oxybutynin or its metabolite showed no cumulation during the multiple dosage with a 10-mg CR tablet. The controlled release tablet formulation is as effective and as well-tolerated as the conventional one, but has the advantage of only once-a-day dosage, enhancing treatment compliance.", "We tested the efficacy and side effect profiles of intravesical atropine compared to oxybutynin immediate release when used by individuals with multiple sclerosis.\n We performed a study to determine the most effective dose of atropine. Eight participants used increasing doses of intravesical atropine during a 12-day period. Bladder diary data showed that the instillation of 6 mg atropine 4 times daily was most effective for increasing bladder capacity (voided/catheter volumes). We then did a randomized, double-blind crossover trial. Participants received 14 days of treatment with oral oxybutynin or with intravesical atropine, followed by 14 days of alternative treatment. Participants recorded a bladder diary and rated side effects and quality of life. The primary outcome variable was bladder capacity.\n A total of 57 participants with multiple sclerosis completed the study. Average change in bladder capacity was higher in the atropine arm. The mean +/- SD oxybutynin change was 55.5 +/- 67.2 ml, the mean atropine change was 79.6 +/- 89.6 ml and the mean difference between arms was 24.1 ml (95% CI -0.4, 49.7; p = 0.053). Changes in incontinence events and voiding frequency were not statistically different between the arms. Changes in total side effect and dry mouth scores were significantly better in the atropine treatment arm.\n Intravesical atropine was as effective as oxybutynin immediate release for increasing bladder capacity and it was probably better with less antimuscarinic side effects. We recommend that intravesical atropine should be made available to patients with neurogenic detrusor overactivity and voiding problems requiring intermittent catheterization as an alternative to oral therapy, which often has troublesome side effects.", "Prospective randomized trial to compare two low starting doses of oxybutynin, using an incremental regimen to assess patient compliance and treatment efficacy in the long-term.\n Women with detrusor overactivity were included. Oxybutynin was randomly prescribed with a starting dose of either 2.5 mg bd or 5 mg nocte. Instructions were given to increase oxybutynin up to 5 mg tds over a period of 6 weeks fortnightly. After two years we re-contacted all the women, using a specific questionnaire to assess the efficacy, acceptability and compliance with these two different regimens. Twenty-two women in each group were calculated to show a 5% difference with a significance of 0.05 and a power of 0.9. The chi2-test was used to compare the two groups and a P-value < 0.05 was considered significant.\n Ninety-six women were included; 66 (68.75%) (mean age 57.5 years) responded to our questionnaire. Twenty-seven had a starting dose of 2.5 mg oxybutynin twice a day and 39 of 5 mg nocte. 34.8% complained of side effects. Only 19 (43.2%) out of the 44, not on medication anymore abandoned oxybutynin for adverse reactions. Most of the patients stopped oxybutynin within 4 months. 53.0% reported improvement or cure. 39.4% denied any benefit and 7.6% (none still on oxybutynin) did not answer. The two groups did not differ for duration of treatment, improvement with oxybutynin, maximum dose they reached, the present dose, and the present urinary symptoms.\n This study did not show any advantage in efficacy or compliance with oxybutynin when two different regimens of low starting were used. Two-thirds of patients discontinued the therapy within 4-6 months. Therefore, patients on anticholinergics should be reassessed after 6 months in clinical practice.", "We evaluated the efficacy, tolerability and safety of the new antimuscarinic agent fesoterodine relative to placebo for overactive bladder syndrome.\n This was a randomized, double-blind, placebo controlled, multicenter trial performed in the United States. Overall 836 subjects with urinary frequency, urinary urgency or urgency urinary incontinence were randomized to placebo (274), 4 mg fesoterodine (283) or 8 mg fesoterodine (279) once daily for 12 weeks. The primary efficacy end point was the change in the number of micturitions per 24 hours. Co-primary end points were the change in the number of urgency urinary incontinence episodes per 24 hours and the treatment response. Secondary efficacy end points were other bladder diary variables, such as the change in mean voided volume per micturition, number of continent days and number of urgency episodes per 24 hours. Tolerability and safety were assessed by evaluating adverse events, electrocardiograms, post-void residual urine volume, laboratory parameters and treatment withdrawals.\n Treatment with 4 or 8 mg fesoterodine resulted in statistically significant and clinically relevant improvements from baseline to end of treatment for the primary and co-primary end points compared with placebo (p <0.05). Results for most secondary end points, including mean voided volume per micturition, number of continent days and number of urgency episodes per 24 hours, were also significantly improved vs placebo. The adverse events reported more frequently with fesoterodine than with placebo were dry mouth, constipation and urinary tract infection.\n The 2 doses of fesoterodine were well tolerated and they statistically significantly improved overactive bladder symptoms.", "The aims of this study were to determine whether oral trospium chloride is noninferior to oxy-butynin for urinary urge incontinence and to evaluate its efficacy, tolerability, and health-related quality of life parameters.\n In this randomized, double-blind, active-controlled, parallel-group, multicenter, Phase IIIb trial conducted in Germany, male and female outpatients aged >or=18 years with documented urinary frequency (>or=8 micturitions/24 hours) plus urge incontinence (>or=5 episodes/week) were randomized to receive oral treatment with trospium chloride 15 mg TID or oxybutynin hydrochloride 2.5 mg TID for 12 weeks. Daily doses could be adjusted upward after 4 weeks, to 90 mg of trospium (30 mg TID) and 15 mg of oxybutynin (5 mg TID), respectively, if needed. The absolute reduction in weekly episodes of urinary urge incontinence was evaluated as the primary efficacy variable. Secondary variables included the absolute reduction of micturitions per 24 hours, intensity of urgency, and mean voided volume. Qualitative symptom changes were recorded from the patients' entries in their micturition diaries at baseline, at week 4, and at week 12 of treatment. Subjective treatment outcome was assessed by patient ratings on a visual analog scale (VAS), the King's Health Questionnaire (KHQ), and the 36-Item Medical Outcomes Study Short-Form General Health Survey (SF-36); intensity of dry mouth was also recorded on a scale. Adverse events (AEs) were assessed.\n Of the 1658 patients treated, 828 patients (49.9%) received trospium 45 mg/d and 830 patients (50.1%) received oxybutynin 7.5 mg/d. After 4 weeks, daily doses were doubled in 29.2% (242/828) of patients in the trospium chloride group, and in 23.3% (193/830) of patients in the oxybutynin group, until the end of treatment. No clinically relevant differences in demographic characteristics were observed between the treatment groups. Trospium was noninferior to oxybutynin hydrochloride in terms of the reduction in the number of weekly urge incontinence episodes after 4 and 12 weeks of treatment. In the per-protocol population, the median change after 12 weeks was -11.0 in both groups. In the full analysis set, the median change was -10.42 with trospium chloride and -10.00 with oxybutynin (P < 0.001 for the noninferiority hypothesis, for both the per-protocol and the full analysis set calculations). There was also no indication of a difference between groups concerning the observed reductions of daily micturitions and intensity of urgency as well as the increase in micturition volume at the end of 12 weeks. VAS, KHQ, and SF-36 scores were improved to a similar extent in both treatment groups at the end of treatment. Worsening of dry mouth was less common in the trospium group than in the oxybutynin group after 4 and 12 weeks (46.9% vs 63.9% and 51.2% vs 64.4%, respectively; bothtime points, P < 0.001 between groups). Treatment-related AEs were reported by 22.7% (188/828) of the trospium chloride group and 26.5% (220/830) of the oxybutynin group. Dry mouth was the most frequently occurring AE, reported by 4.1% (34/828) of patients in the trospium group and 7.7% (64/830) of the oxybutynin group.\n Our findings indicate that trospium chloride was noninferior to oxybutynin hydrochloride, both with flexible dosing, over 12 weeks in these patients with urinary urge incontinence. Both drugs were generally well tolerated in the population studied, but fewer patients who received trospium reported worsening of dry mouth than those who received oxybutynin. German Federal Institute for Drugs and Medical Devices Registration Number 4022383.\n Copyright 2009 Excerpta Medica Inc. All rights reserved.", "In this phase 3 trial we assessed the efficacy of solifenacin 5 mg and 10 mg daily in patients with symptoms related to overactive bladder. In addition, we assessed the safety and acceptability of solifenacin.\n The study was a multicenter, multinational, randomized, double-blind, placebo controlled trial. Patients were randomized to 12-week once daily treatment with solifenacin 5 mg, solifenacin 10 mg or placebo. The primary efficacy variable was changed from baseline to study end point in mean number of micturitions per 24 hours. Secondary efficacy variables included changes from baseline in mean number of urgency, nocturia and incontinence episodes per 24 hours, and mean volume voided per micturition.\n Compared with changes obtained with placebo (-1.59), micturitions per 24 hours were statistically significantly decreased with solifenacin 5 mg (-2.37, p = 0.0018) and solifenacin 10 mg (-2.81, p = 0.0001). A statistically significant decrease was observed in the number of incontinence episodes with both solifenacin doses (5 mg, p = 0.002 and 10 mg, p = 0.016). This effect was also seen for episodes of urge incontinence (5 mg, p = 0.014 and 10 mg, p = 0.042). Of patients reporting incontinence at baseline, fully 50% achieved continence after treatment with solifenacin. Episodes of nocturia were statistically significantly decreased in patients treated with solifenacin 10 mg (-0.71, -38.5%) versus placebo (-0.52, -16.4%, p = 0.036). Episodes of urgency were statistically significantly reduced with solifenacin 5 mg (-2.84, -51%, p = 0.003) and solifenacin 10 mg (-2.90, -52%, p = 0.002). Mean volume voided per micturition was statistically significantly increased with both solifenacin doses (p = 0.0001). Treatment with solifenacin was well tolerated. Dry mouth, mostly mild in severity, was reported in 7.7% of patients receiving solifenacin 5 mg and 23% receiving solifenacin 10 mg (vs 2.3% with placebo).\n In this study treatment with solifenacin 5 mg and 10 mg once daily significantly improved all the major symptoms of overactive bladder including frequency, urgency and incontinence. Solifenacin 10 mg also decreased the frequency of nocturia. Solifenacin therapy was associated with a favorable tolerability profile and a low incidence of dry mouth, especially at the 5 mg starting dose.", "To investigate the efficacy and safety of tolterodine, a new antimuscarinic agent, and define the optimum dosage in patients with symptoms of detrusor instability (urgency, increased frequency of micturition and/or urge incontinence).\n A double-blind, placebo-controlled, multicentre study was carried out; after a 1-week run-in period to establish baseline values, 81 patients were randomized to receive placebo or tolterodine 0.5, 1, 2 or 4 mg twice daily for 2 weeks. Micturition (diary) variables, urodynamics and subjective urinary symptoms were assessed after 2 weeks' treatment.\n A per-protocol analysis of efficacy in 64 patients showed dose-related improvements in recorded micturition and urodynamic variables, e.g. at a dosage of 2 mg twice daily, the frequency of micturition, episodes of incontinence and pad use were reduced by 20%, 46% and 29%, respectively, while the volume at first contraction increased by 89 mL. The 4 mg dosage was associated with a large increase in residual urinary volume and an increased incidence of dry mouth. The incidence of adverse events (mainly mild or moderate antimuscarinic effects) was comparable with placebo at tolterodine dosages of < or = 2 mg. No serious adverse events were observed and tolterodine had no clinically significant impact on electrocardiographic or laboratory findings.\n The results indicate that tolterodine offers an effective treatment for the symptoms of detrusor instability. The optimum dosage appears to be 1-2 mg twice daily.", "To evaluate the efficacy, tolerability and safety of darifenacin, a once-daily M3) selective receptor antagonist (M3 SRA), in patients with overactive bladder (OAB).\n This multicentre, double-blind, placebo-controlled, parallel-group study enrolled 561 patients (19-88 years; 85% female) with OAB symptoms for >6 months, and included some patients with prior exposure to antimuscarinic agents. After washout and a 2-week placebo run-in, patients were randomised (1:4:2:3) to once-daily oral darifenacin controlled-release tablets (3.75 mg [n=53], 7.5 mg [229] or 15 mg [n=115]) or matching placebo (n=164) for 12 weeks. Patients recorded daily incontinence episodes, micturition frequency, bladder capacity (mean volume voided), frequency of urgency, severity of urgency, incontinence episodes resulting in change of clothing or pads and nocturnal awakenings due to OAB using an electronic diary during weeks 2, 6 and 12 (directly preceding clinic visits). Tolerability data were evaluated from adverse event reports.\n Darifenacin 7.5 mg and 15 mg had a rapid onset of effect, with significant improvement compared with placebo being seen for most parameters at the first clinic visit (week 2). This effect was sustained through week 12. At this time the number of incontinence episodes per week was reduced from baseline by 67.7% with darifenacin 7.5 mg and 72.8% with darifenacin 15 mg compared with 55.9% with placebo (p=0.010 and p=0.017, respectively, versus placebo). The 3.75 mg group (null dose arm) was included for proof of concept of dose flexibility, therefore formal sample sizing and statistical analysis were not performed for this group. Darifenacin 7.5 mg and 15 mg, respectively, were significantly superior to placebo for improvements in micturition frequency (p<0.001, p<0.001), bladder capacity (p<0.040, p<0.001), frequency of urgency (p<0.001, p=0.005), severity of urgency (p<0.001, p=0.002) and number of incontinence episodes leading to a change in clothing or pads (p<0.001, p=0.002). There was no significant reduction in nocturnal awakenings due to OAB. The most common adverse events were mild-to-moderate dry mouth and constipation. However, no patients withdrew from the study as a result of dry mouth and discontinuation related to constipation was rare (0.6% placebo versus 0.9% darifenacin). In addition, there was a low need for laxative use, with no difference between the darifenacin groups and those taking placebo. There were no reports of blurred vision and the CNS and cardiac safety profile was comparable to placebo.\n Darifenacin significantly improves the major symptoms of OAB. No significant CNS (primarily M1-receptor mediated) adverse events or cardiac (primarily M2-receptor mediated) adverse events were identified in this study, as may be predicted from the M3 selective receptor profile of darifenacin.", "A randomized, double-blind, placebo-controlled, four-way crossover, safety study of darifenacin versus oxybutynin was carried out on 76 patients with overactive bladder (OAB). Adults with OAB received 2 weeks each of darifenacin 15 and 30 mg once daily (q.d.), oxybutynin 5 mg three times daily (t.i.d.) and placebo, in random sequence at 10-day intervals. Darifenacin and oxybutynin significantly reduced incontinence episodes, and the number/severity of urgency episodes (all P<0.05 versus placebo). Improvements in OAB symptoms with darifenacin were dose-dependent. Dry mouth was less common with darifenacin 15 mg than oxybutynin (13% and 36%; P<0.05), while constipation was comparable (10% and 8%, respectively). Corresponding rates for darifenacin 30 mg were 34% and 21%, respectively. Patients only reported blurred vision or dizziness with oxybutynin (3% and 2%, respectively). Darifenacin (15 mg q.d.) provides comparable efficacy with improved tolerability versus oxybutynin (5 mg t.i.d.) in the treatment of patients with OAB.", "To compare the efficacy of tolterodine and oxybutynin in the treatment of specific, according to their urodynamic grade of severity, populations with overactive detrusor.\n In this open, randomized, two-way crossover study 128 women with urodynamically confirmed, idiopathic detrusor overactivity were recruited. Patients were categorized in 4 grades of severity groups, according to the characteristics of the first overactive detrusor contraction during filling cystometrogram: high volume-low pressure (grade-group I), high volume-high pressure (grade-group II), low volume-low pressure (grade-group III) and low volume-high pressure (grade-group IV). The primary outcome measure was average volume of voided urine per micturition.\n 107 patients successfully completed the study protocol and were included in the analyses: 40 in group IV, 36 in III, 25 in II and 6 in group I. In groups IV and III both oxybutynin and tolterodine significantly increased the average volume of voided urine per micturition but the differences between the drugs were not significant (p > 0.05). In group II neither of the drugs achieved significant changes in the outcome measure (p > 0.05).\n Tolterodine and oxybutynin are clinically equipotent in treating detrusor overactivity in specific severity groups of patients, although urodynamic effects are somewhat different.", "Treatment with the antimuscarinic agents tolterodine and oxybutynin is the mainstay of therapy for overactive bladder, a chronic and debilitating condition characterized by urinary urgency with or without urge incontinence, usually in combination with urinary frequency and nocturia. This study consisted of two trials; in one, patients with overactive bladder were randomized to 8 weeks of open-label treatment with either 2 mg or 4 mg of once-daily extended-release tolterodine (TER), and in the other to 5 mg or 10 mg of extended-release oxybutynin (OER). The study protocol and design were identical for the two trials and site selection ensured that there was no bias in either trial for the tendency of investigators to prescribe one drug rather than the other, or for geographical location. A total of 1289 patients were enrolled, 669 in the tolterodine trial (TER 2 mg, n = 333; TER 4 mg, n = 336) and 620 in the oxybutynin trial (OER 5 mg, n = 313; OER 10 mg, n = 307). Fewer patients prematurely withdrew from the trial in the TER 4 mg group (12%) than either the OER 5 mg (19%; p = 0.01) or OER 10 mg groups (21%; p = 0.002). More patients in the OER 10 mg group than the TER 4 mg group withdrew because of poor tolerability (13% vs 6%; p = 0.001). After 8 weeks, 70% of patients in the TER 4 mg group perceived an improved bladder condition, compared with 60% in the TER 2 mg group, 59% in the OER 5 mg group and 60% in the OER 10 mg group (all p < 0.01 vs TER 4 mg). Response to therapy was greater in a subgroup of patients whose perception of bladder condition was moderate to severe at baseline (TER 4 mg 77% vs OER 10 mg 65%; p < 0.01). Dry mouth was dose-dependent with both agents, although differences between doses only reached statistical significance in the oxybutynin trial (OER 5 mg vs OER 10 mg; p = 0.05). Patients treated with TER 4 mg reported a significantly lower severity of dry mouth compared with OER 10 mg. In conclusion, the greater efficacy and tolerability of tolterodine ER 4 mg suggests improved clinical effectiveness compared with oxybutynin ER 10 mg.", "To assess the efficacy, incidence of dry mouth and overall satisfaction with initial doses of 5, 10 and 15 mg of a new, once-daily, controlled-release (CR) form of oxybutynin for treating urge urinary incontinence (UUI).\n Patients who reported urinary incontinence (UI) (one or more episodes/diary) and voiding frequency (eight or more voids/day) or urgency (one or more episodes/diary) during a 2-week baseline were randomized to once-daily 5, 10 or 15 mg CR oxybutynin for 4 weeks. Daily episodes of UI, voids, urgency, adverse events, dry mouth and satisfaction were recorded in a 3-day diary at baseline and after 4 weeks of treatment. In all, 237 patients were randomized and evaluated.\n Episodes of UI, voids and urgency were significantly reduced over the study period at all doses. Daily UI episodes were significantly lower with 15 mg/day than 5 and 10 mg/day. Dry mouth symptoms were similar in the 10 and 15 mg/day groups, and higher than in the 5 mg/day group. However, significantly greater overall satisfaction was reported with 15 than 5 mg/day.\n There were significant dose-response relationships with CR oxybutynin for both UI episodes and dry mouth. The greatest satisfaction was with 15 mg/day, and the severity of dry mouth was comparable at 10 mg/day, indicating that greater efficacy at the higher dose did not compromise tolerability.", "To assess the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence in a randomized, double-blind placebo-controlled clinical trial.\n In all, 366 patients (149 on propiverine, 145 oxybutynin and 72 placebo, ratio 2:2:1) with urgency and urge incontinence were recruited in 32 study centres. Propiverine (group 1, 15 mg three times daily), oxybutynin (group 2, 5 mg twice daily) or placebo (group 3) were administered for 4 weeks, using the double-dummy technique. The dosages were selected specifically to compare the tolerability profile of propiverine with the commonly used therapeutic dosage of oxybutynin. Tolerability was assessed by directly questioning the patients about adverse events at four visits (V-1 before and V0 after a 1-week 'washout' period, V1 after 1 week and V4 after 4 weeks of treatment) during a 5-week surveillance period, and by tolerability ratings of the physicians. Efficacy was assessed using urodynamics at V0 and V4, evaluating the cystometric bladder capacity at maximal and first desire to void, and postvoid residual urine, according to the criteria of the International Continence Society. Additionally, a voiding protocol, overall assessment of clinical symptomatology and efficacy ratings by the physicians were documented.\n A remarkably high percentage of adverse events was reported in the washout period (VO: 13%, 16% and 18% in groups 1-3, respectively). At V4, the clinically most relevant symptom (dry mouth) occurred in 53% of patients in group 1, in 67% of group 2 and in 28% of group 3. Furthermore, dry mouth was less severe in group 1 than group 2. In contrast to groups 2 and 3, only patients in group 1 showed increasing tolerability during the treatment (from V1 to V4). These tolerability results were further supported by the overall tolerability assessment ('very good' or 'good' tolerability in 67% of group 1, in 59% of group 2 and in 83% of group 3). The urodynamic assessment of efficacy (comparing V0 and V4) showed a statistically significant increase in the mean (sd) maximal cystometric bladder capacity in group 1, being 222 (77) mL at V0 and 311 (125) mL at V4, an increase of 89 (108) mL, and in group 2, at 226 (75) mL and 322 (123) mL, an increase of 96 (106) mL, compared with group 3, at 211 (77) mL and 263 (93) mL, an increase of only 52 (92) mL. The cystometric bladder capacity at first desire to void also increased in group 1 (93 to 160 mL) and group 2 (89 to 160 mL), whereas in group 3 there were only minor changes (93 to 120 mL). Changes in the residual urine volume within and between the treatment groups were minimal and clinically irrelevant. The overall assessment of efficacy showed significant differences between the drugs when compared with placebo.\n Propiverine is a safe and effective drug in the treatment of urgency and urge incontinence; it is as effective as oxybutynin, but the incidence of dry mouth and its severity is less with propiverine than with oxybutynin. The availability of alternative pharmacotherapeutics such as propiverine should reduce the therapeutic failure rate and improves the success rate in the treatment of patients suffering from urgency and urge incontinence.", "The efficacy and tolerability of propiverine hydrochloride (15, off 45, 60 mg/d) were evaluated in the treatment of 185 patients suffering from urgency/urge incontinence in an open, randomized, multicentre parallel-group trial lasting 21 days. The effects on bladder volume and pressure were assessed on the basis of urodynamics and micturition frequency. Subjective adverse reactions were recorded. The bladder capacity and compliance increased and bladder pressure decreased in a dose dependent manner following therapy with 15, 30, 45 and 60 mg/d. In 70% of the patients a decrease in micturition frequency was observed after 15 mg/d, and in 80% after 30 to 60 mg/d. Subjective anticholinergic symptoms were reported by 21, 40 and 28% of the patients following therapy with 30, 45 and 60 mg/d. 15 and 30 mg were the daily doses with the most favourable ratio of efficacy in micturition frequency to tolerability. The results suggest that propiverine is a safe and effective drug for the treatment of urgency and urge incontinence. Individual treatment with an initial dosage of 30 mg/d should be recommended.", "To compare trospium chloride (TCl), a quaternary ammonium derivative with atropine-like effects and predominantly antispasmodic activity, with oxybutynin (Oxy) in terms of efficacy and adverse effects.\n In a randomized, double-blind, multicentre trial, 95 patients with spinal cord injuries and detrusor hyper-reflexia were studied. Treatment consisted of three doses per day over a 2 week period, with either Oxy (5 mg three times daily) or with TCl (20 mg twice daily) with an additional placebo at midday. The results were evaluated with regard to changes in objective (urodynamic) data and subjective symptoms as well as the incidence/severity of adverse effects.\n With both drugs there was a significant increase in maximum bladder capacity, a significant decrease in maximum voiding detrusor pressure and a significant increase in compliance and residual urine; there were no statistically significant differences between the treatment groups. The percentage of patients who reported severe dryness of the mouth was considerably lower (4%) in those receiving TCl 2 x 20 mg/day than in those receiving Oxy (23%) 3 x 5 mg/day. Withdrawal from treatment was also less frequent in those receiving TCl (6%) than in those receiving Oxy (16%).\n Trospium chloride and oxybutynin, judged in terms of objective urodynamic parameters, are of substantially equal value as parasympathetic antagonists. However, assessment of tolerance in terms of adverse drug effects showed that TCl had certain advantages.", "To assess in a phase 3a trial the efficacy of solifenacin succinate, a once-daily oral antimuscarinic agent in development at 5-mg and 10-mg dosage strengths, for the treatment of overactive bladder (OAB) (Yamanouchi Pharmaceutical Co. Ltd, Tokyo, Japan) compared with placebo in patients with symptoms of OAB, i.e. urgency, incontinence, and frequency, with additional objectives being to assess the safety and tolerability of solifenacin and to compare the efficacy and safety of solifenacin with tolterodine 2 mg twice daily.\n The study was an international, multicentre, randomized, double-blind, tolterodine- and placebo-controlled trial conducted at 98 centres. Adult patients with symptomatic OAB for > or = 3 months were eligible; after a single-blind 2-week placebo run-in period patients were randomized equally to a 12-week double-blind treatment with either tolterodine 2 mg twice daily, placebo, solifenacin 5 mg or 10 mg once daily. Efficacy variables included change from baseline in the mean number of urgency, incontinence and urge incontinence episodes, and change from baseline in voids/24 h and mean volume voided/void.\n In all, 1281 patients were enrolled, 1081 randomized and 1077 treated; 1033 were evaluated for efficacy. Compared with placebo, the change from baseline (-1.41, -32.7%) in the mean number of urgency episodes per 24 h was statistically significantly lower with solifenacin 5 mg (-2.85, -51.9%) and 10 mg (-3.07, -54.7%; both P < 0.001), but not with tolterodine (-2.05, -37.9%; P = 0.0511). There was a statistically insignificant decrease in episodes of incontinence with tolterodine (-1.14; P = 0.1122) but a significant decrease in patients treated with solifenacin 5 (-1.42; P = 0.008) and 10 mg (-1.45; P = 0.0038). Compared with placebo (-1.20, -8.1%) the mean number of voids/24 h was significantly lower in patients receiving tolterodine (-1.88, -15%; P = 0.0145), solifenacin 5 (-2.19, -17%) and 10 mg (-2.61, -20%; both P < 0.001). The mean volume voided/void was also significantly higher with all three active treatments (P < 0.001). Solifenacin was well tolerated; compared with placebo (4.9%), dry mouth (the most common side-effect), mostly mild, was reported in 18.6% of patients receiving tolterodine, 14.0% receiving 5 mg and 21.3% receiving 10 mg solifenacin.\n Solifenacin 5 and 10 mg once daily improved urgency and other symptoms of OAB, and was associated with an acceptable level of anticholinergic side-effects. Solifenacin demonstrated significantly favourable efficacy to side-effect ratio in treating symptomatic OAB.", "To compare extended-release (ER) tolterodine and immediate-release (IR) oxybutynin with placebo in Japanese and Korean patients with an overactive bladder (OAB).\n Men and women aged >or= 20 years with symptoms of urinary urgency, urinary frequency (>or= 8 micturitions/24 h), urge incontinence (>or= 5 episodes/week) and symptoms of OAB for >or= 6 months were randomized to double-blind treatment with tolterodine ER 4 mg once daily, oxybutynin IR 3 mg three times daily or placebo for 12 weeks. Efficacy assessments included changes from baseline in numbers of incontinence episodes per week, voids/24 h and mean volume voided/void. Patient perceptions of bladder condition, urgency and treatment benefit were also assessed.\n In all, 608 patients were randomized to treatment with tolterodine (240), oxybutynin (246) or placebo (122). More patients prematurely withdrew on oxybutynin (23%) than with tolterodine (10.4%) or placebo (16.4%). After 12 weeks of treatment, the median number of incontinence episodes/week was reduced significantly more in the tolterodine (79%; P= 0.0027) and oxybutynin groups (76.5%; P= 0.0168) than on placebo (46.4%). There were also significantly greater improvements in the number of voids/24 h and volume voided/void with tolterodine and oxybutynin than with placebo. More patients in the tolterodine and oxybutynin than in the placebo groups reported improvements in perceived bladder condition, ability to hold urine and treatment benefit. Patients treated with oxybutynin reported more adverse events than those treated with tolterodine or placebo. Dry mouth was significantly more common with oxybutynin than with tolterodine (53.7% vs. 33.5%; P < 0.001), and occurred in 9.8% of placebo patients.\n Tolterodine ER has similar efficacy but is better tolerated than oxybutynin IR in Japanese and Korean patients with OAB.", "To compare the efficacy and safety of controlled-release oxybutynin with conventional, immediate-release oxybutynin and determine rates of dry mouth.\n Patients (n = 226) who were known to be responsive to anticholinergic therapy and who had seven or more urge incontinence episodes per week were randomized to receive controlled-release oxybutynin or immediate-release oxybutynin. After an initial placebo run-in period, dosing in each began at 5 mg per day and increased weekly by 5 mg per day to a maximum of 20 mg per day or when a balance between improvement of incontinence symptoms and tolerability of side effects was achieved. Rates of urge incontinence and dry mouth were compared. Post hoc Kaplan-Meier survival analysis was used to describe elimination of incontinence episodes by dose and to analyze dry mouth risk by dose.\n Reductions in urge urinary incontinence episodes from baseline to the end of treatment were 18.6 to 2.9 per week (83% mean decrease) and 19.8 to 4.4 per week (76% mean decrease) in the controlled- and immediate-release oxybutynin groups (P =.36), respectively. At equal doses, comparable proportions of patients in both groups reported the absence of urge incontinence (P =.85). The incidence of dry mouth increased with dose in both groups, but there was no difference in dry mouth rates between the groups: 47.7% and 59.1% for the controlled- and immediate-release oxybutynin (P =.09), respectively. However, Kaplan-Meier analysis to examine first report of dry mouth at a given dose revealed that a significantly lower proportion of patients taking controlled-release oxybutynin had moderate to severe dry mouth (P =.007) or any dry mouth (P =.003) compared with those taking immediate-release oxybutynin.\n At the same daily dose, controlled- and immediate-release oxybutynin demonstrated comparable efficacy in reduction of urge incontinence episodes. The incidence of dry mouth was dose dependent but equal in both groups; first report of moderate to severe dry mouth was significantly lower in the controlled-release group.", "This trial was designed to investigate the effectiveness of extended release versus immediate release oxybutynin in reducing symptoms of overactive bladder in a community-dwelling female population over the age of 65.\n This was a prospective randomized 12-week, open-label study. The primary outcome was number of micturitions per 24 hours, 12 weeks after treatment. The a priori sample size estimate was 60 patients per group.\n Of the 318 women approached, only 72 women (23%) were enrolled over 34 months (33 in the immediate release group, and 39 in the extended release group). The study was stopped prematurely because of recruitment difficulties and an interim analysis revealing the need for a much larger sample than had been estimated to show a significant difference between treatments. After 12 weeks of treatment, there was no difference between the oxybutynin extended release and immediate release groups in the number of micturitions per 24 hours or in other outcomes.\n This study did not demonstrate differences between oxybutynin extended release and immediate release and in reducing symptoms of overactive bladder or quality of life, possibly because the study did not reach the necessary sample size. The difficulty in recruiting subjects for the trial likely resulted from the onerous study requirements (4 study visits required over 12 weeks) and the downtown location of the study centres: these factors would cause particular difficulties for women over age 65 with overactive bladder, for whom travelling may be a problem. Evidence is needed to guide prescribing for older patients, but designing research to obtain adequate sample sizes is difficult. Studies in older subjects should ensure that a much larger budget is allocated for recruitment than would be allocated for studies in younger subjects, that meticulous attention is paid to issues of transport and access, and that support is provided for subjects who agree to take part research.", "We evaluated the efficacy, patient acceptability and side effect profile of tolterodine, a new antimuscarinic agent for treating bladder overactivity.\n In our randomized, placebo controlled, parallel group study 123, 129 and 64 patients 18 years old or older with proved detrusor overactivity (idiopathic detrusor instability or detrusor hyperreflexia) were randomized to receive 1 or 2 mg. tolterodine, or placebo, respectively, twice daily for 12 weeks. Main outcome measures were number of voids per 24 hours, urine volume per void and episodes of urge incontinence per 24 hours on a frequency-volume chart with detailed recording of side effects.\n After 12 weeks of treatment mean number of voids per 24 hours plus or minus standard deviation decreased from 11.2 +/- 3.1 to 9.0 +/- 2.6 with the 2 mg. dosage (p = 0.0045 versus placebo). At this dose mean urine volume per void increased from 155 +/- 52 to 190 +/- 70 ml. (p <0.0001 versus placebo), while mean number of incontinence episodes per 24 hours decreased from 3.6 +/- 4.0 to 1.8 +/- 3.1 (p = 0.19 versus placebo). Similar efficacy was observed in patients receiving the 1 mg. dose. Severe dry mouth was reported by only 2, 1 and 2% of patients given the 1 and 2 mg. dose, and placebo, respectively. There was no clinical or electrocardiographic evidence of significant cardiac adverse events.\n Tolterodine administration resulted in a significant decrease in the frequency of voiding and improved voided volume but it was seldom associated with troublesome or severe side effects.", "We assessed the efficacy and safety of solifenacin compared with tolterodine for treatment of overactive bladder (OAB) in Korean patients.\n The study was randomised, double-blind, tolterodine-controlled trial in Korea. Patients had average frequency of >or= 8 voids per 24 h and episodes of urgency or urgency incontinence >or= 3 during 3-day voiding diary period. Patients were randomised to 12-week double-blind treatment with either tolterodine immediate release (IR) 2 mg twice daily (TOL4) or solifenacin 5 mg (SOL5) or 10 mg (SOL10) once daily. The outcome measure was mean change in daily micturition frequency, volume, daily frequency of urgency incontinence, urgency and nocturia from baseline to week 12. Quality of life was assessed using the King's Health Questionnaire.\n A total of 357 were randomised and 329 were evaluated for efficacy. All voiding parameters recorded in micturition diary improved after treatment in all three groups. Mean changes in volume voided were 19.30 ml (26.69%) in TOL4, 30.37 ml (25.89%) in SOL5 and 37.12 ml (33.36%) in SOL10 group (p = 0.03). Speed of onset of SOL10 efficacy on urgency incontinence was faster than that of SOL5 and TOL4. Quality of life improved in all three groups. Dry mouth was the most common adverse event; its incidence was the lowest in SOL5 group (7.63%, compared with 19.49% and 18.64% in SOL10 and TOL4 groups respectively).\n Solifenacin succinate 5 and 10 mg once daily improve OAB symptoms with acceptable tolerability levels compared with tolterodine IR 4 mg. Solifenacin 5 mg is a recommended starting dose in Korean patients with OAB.", "This double-blind, multicenter study compared the efficacy and tolerability of tolterodine (Pharmacia, Los Angeles, USA) with that of oxybutynin (Alza, Palo Alto, USA) in Asian patients with overactive bladder.\n Two-hundred-and-twenty-eight adults with overactive bladder symptoms were randomized to receive tolterodine 2 mg twice daily (bid) (n = 112) or oxybutynin 5 mg bid (n = 116). After 8 weeks' treatment, changes in micturition diary variables, patients' perception of treatment benefit, and tolerability endpoints were determined.\n The mean (+/- SD) number of micturitions/24 h decreased by 2.6 +/- 2.9 (-21%) with tolterodine and 1.8 +/- 4.2 (-15%) with oxybutynin (both P = 0.0001 vs baseline). The mean number of incontinence episodes/24 h decreased by 2.2 +/- 2.3 (-85%) in the tolterodine group and by 1.4 +/- 1.8 (-58%) in the oxybutynin group (both P = 0.0001 vs baseline). Patient perception of treatment benefit was over 70% in each treatment group. Adverse events were significantly lower in the tolterodine group compared with oxybutynin-treated patients (55% vs 82%; P = 0.001). Dry mouth was reported by significantly fewer patients on tolterodine, compared with oxybutynin (35% vs 63%; P = 0.001) and withdrawals due to adverse events were lower in the tolterodine group than with those treated with oxybutynin (10% vs 16%). There were no safety concerns.\n Tolterodine 2 mg bid is equally or more effective than oxybutynin 5 mg bid in the treatment of Asian patients with overactive bladder, and shows significantly better tolerability. This may enhance compliance during long-term treatment.", "To compare the efficacy and safety of an oxybutynin transdermal delivery system (OXY-TDS) and oral, long-acting tolterodine (TOL-LA) with placebo in previously treated patients with urge or mixed urinary incontinence.\n After withdrawal of their current antimuscarinic therapy, 361 adult patients were randomized to 12 weeks of double-blind, double-dummy treatment with twice weekly OXY-TDS 3.9 mg/day, daily TOL-LA 4 mg, or placebo. Evaluations included change from baseline in patient urinary diary symptoms, incontinence-specific quality of life, and safety.\n OXY-TDS 3.9 mg/day and TOL-LA 4 mg/day significantly reduced the number of daily incontinence episodes (median change -3 OXY-TDS and -3 TOL-LA versus -2 placebo; P <0.05), increased the average void volume (median change 24 and 29 mL versus 5.5 mL, P <0.01), and improved quality of life (incontinence impact questionnaire [IIQ] total score, P <0.05; Urogenital Distress Inventory Irritative Symptom subscale, P <0.05) compared with placebo. The most common adverse event for OXY-TDS was localized application site pruritus (14% versus 4% placebo) accompanied by a low incidence of systemic side effects (eg, dry mouth 4.1%). Anticholinergic adverse events occurred with greatest frequency during TOL-LA treatment (dry mouth 7.3% versus 1.7% placebo, P <0.05).\n OXY-TDS and TOL-LA are effective and comparable treatments for patients with urge and mixed incontinence. OXY-TDS improves systemic safety with regard to anticholinergic side effects. Local skin irritation occurs in some OXY-TDS patients.", "To compare the efficacy and tolerability of imidafenacin, a novel antimuscarinic agent, with propiverine and a placebo in Japanese patients with overactive bladder (OAB).\n Men and women having OAB symptoms were randomized to double-blind treatment with 0.1 mg of imidafenacin twice daily, 20 mg of propiverine once daily, or a placebo for 12 weeks, and assessed for efficacy and safety.\n Overall, 781 patients were randomized to imidafenacin (324), propiverine (310), or a placebo (147). After 12 weeks of treatment, a significantly larger reduction in the mean number of incontinence episodes was observed in the imidafenacin group than in the placebo group (P < 0.0001). The non-inferiority of imidafenacin compared with propiverine was confirmed for the reduction in using incontinence episodes (P = 0.0014, non-inferiority margin: 14.5%). Imidafenacin was well tolerated. The incidence of adverse events with imidafenacin was significantly lower than with propiverine (P = 0.0101). Dry mouth, the most common adverse event, was significantly more common in the propiverine group than in the imidafenacin group (P = 0.0302). There were no significant increases in either the imidafenacin or placebo group in the mean QTc interval, whereas there was a significant increase in the mean QTc interval in the propiverine group (P < 0.0001), but there were no clinical arrhythmia and clinical arrhythmic events in any of the treatment groups.\n The novel antimuscarinic agent imidafenacin at a dose of 0.1 mg twice daily was not inferior to propiverine for the reduction of incontinence episodes, and well tolerated for the treatment of OAB symptoms.", "To evaluate the efficacy, safety/tolerability, and dose-response relationship of imidafenacin in Japanese patients with overactive bladder.\n Men and women who had overactive bladder symptoms were randomized equally to double-blind treatment with 0.05, 0.1, or 0.25 mg of imidafenacin twice daily or a placebo for 12 weeks, and assessed for efficacy and safety.\n Overall, 401 patients were enrolled and randomized for treatment with 0.1 mg of imidafenacin/day (99 patients), 0.2 mg of imidafenacin/day (100), 0.5 mg of imidafenacin/day (101), or a placebo (101). After 12 weeks of treatment, the number of incontinence episodes was reduced in a dose-dependent manner, and a significant difference between the imidafenacin treatment and the placebo was observed (P < 0.0001). Compared with the placebo, imidafenacin caused significant reductions in urgency incontinence, voiding frequency, and urinary urgency, and a significant increase in the urine volume voided per micturition. Imidafenacin was also well tolerated. The incidence of dry mouth in the imidafenacin groups increased dose-dependently. Even though the percentage of patients receiving 0.5 mg/day who discontinued treatment due to dry mouth was high (8.9%), the percentages in the 0.1 mg/day and 0.2 mg/day groups (1.0% and 0.0%, respectively) were comparable with that in the placebo group (0.0%).\n Considering the balance between efficacy and safety, 0.1 mg of imidafenacin twice daily appeared to be a clinically appropriate dose for treating overactive bladder. This dose was therefore selected for further evaluation in large-scale phase III studies.", "The objective of this research was to detect a minimal clinically important change (MCIC) in frequency of incontinence episodes in Japanese patients with overactive bladder syndrome (OAB) based on the change in domain scores of health-related quality of life (HRQoL).\n The patients (n = 659) enrolled for the 8 weeks, randomized, double-blind, placebo-controlled study of an oxybutynin transdermal patch were used for the analysis. The endpoints of the study were the change in frequency of incontinence episodes and the domain scores of King's health questionnaire (KHQ) from baseline to the end of treatment. To search a threshold of the change of incontinence frequency that apparently improves patient's quality of life (QOL), we calculated mean changes of selected five KHQ domain scores for nine patient groups divided by the amount of change of incontinence frequency. A minimum value of the change of incontinence frequency in the groups with apparent improvement in the QOL scores was defined as an MCIC of incontinence frequency.\n The apparent improvement of KHQ domain scores was seen in the patient groups whose incontinence episodes decreased more than three times per week (/w) after treatment. This result was common in almost all domain scores, but more relevant for the domains related to patients' life limitations.\n Japanese OAB patients can feel their QOL improved if their incontinence episodes decrease more than 3 times/w. This suggests that the reduction of '3 times /w' is an MCIC of incontinence frequency for Japanese OAB patients.", "Although antimuscarinic treatment is indicated for overactive bladder, many patients discontinue it because of dry mouth. Of available antimuscarinics oxybutynin is associated with the highest dry mouth rate. We compared the safety and tolerability of 5 mg solifenacin vs 15 mg oxybutynin immediate release.\n At 12 Canadian centers a total of 132 patients with overactive bladder symptoms (greater than 1 urgency episode per 24 hours, and 8 or greater micturitions per 24 hours) were randomized to 5 mg solifenacin once daily or 5 mg oxybutynin 3 times daily for 8 weeks. The primary end point was the incidence and severity of dry mouth reported after direct questioning. Efficacy end points (3-day diary documented changes in urgency, frequency, incontinence, nocturia and voided volume), and changes on the Patient Perception of Bladder Condition scale and the Overactive Bladder Questionnaire were evaluated secondarily.\n Of patients on solifenacin vs oxybutynin immediate release 35% vs 83% reported dry mouth (p <0.0001). Of patients reporting dry mouth severity was graded moderate by 13% and 42% of those on solifenacin and oxybutynin immediate release, and severe by 13% and 28%, respectively (p = 0.001). Patients in each group showed improvements in efficacy end points, and Patient Perception of Bladder Condition scale and Overactive Bladder Questionnaire scores from baseline to treatment end.\n Significantly fewer patients on 5 mg solifenacin once daily reported dry mouth vs those receiving 5 mg oxybutynin immediate release 3 times daily. Significantly fewer patients on solifenacin reported moderate/severe dry mouth. Significantly fewer patients on solifenacin withdrew from study due to dry mouth and there were significantly fewer overall adverse events. Solifenacin and oxybutynin immediate release were efficacious in decreasing efficacy end points, and improved Patient Perception of Bladder Condition scale and Overactive Bladder Questionnaire results from baseline to treatment end.\n 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.", "To determine whether dose titration based on therapeutic response is superior to standard dosing of oral trospium chloride in patients with neurogenic detrusor overactivity and, moreover, to investigate the possible underlying causes of differences in efficacy at equal doses in some patients.\n Using a double-blind approach, two groups (standard dose and adjustable dose) with a total of 80 patients were treated with trospium chloride coated tablets for a period of 3 - 5 weeks. Treatment duration and daily doses varied depending on change ofurodynamic parameters defined as therapeutic response. In Week 1, both groups started on 45 mg/day (3 x 15 mg). In the adjustable dose group, it was permissible to increase the daily dose to 90 or 135 mg/day depending on the urodynamic treatment response. In contrast, doses remained unchanged in the standard dose group although a need for dose adjustment had been recognized under the double-blind conditions. Therapeutic response was defined as improvement of at least two of the following three urodynamic parameters: bladder compliance 2 20 ml/cmH20, maximum cystometric capacity > 250 ml and maximum detrusor pressure < 40 cmH20. Changes in individual urodynamic parameters were defined as secondary efficacy variables. Primary and secondary parameters were assessed by comparing baseline values with those at the end of treatment. Therapeutic response was analyzed by using the Fisher-Yates test, and the Mann-Whitney U-test was used for secondary parameters. Trospium plasma concentration was measured to assess patient's compliance and as a tool to elucidate possible factors influencing treatment efficacy. Safety and tolerability were evaluated based on withdrawal rates and adverse events.\n Both dose groups had comparable baseline characteristics. Therapeutic response was achieved in 58% of patients in the adjustable dose group (ADG) and in 72% of those in the standard dose group (SDG, p -0.23). Clinically relevant increases in maximum cystometric capacity and bladder compliance were observed, and there was a clear decrease in detrusor pressure. After Day 7, the daily dose was increased in 52.8% of all patients in the adjustable dose group and (seemingly) in 32.5% of those of the standard dose group. Further dose escalation after Day 14 was assessed as necessary in 15% of the standard dose group and 22% of the adjustable dose group. The main changes in urodynamic parameters occurred during the first 7 days of treatment, but in some patients it takes a longer time. No statistically significant differences between plasma trospium chloride levels in the two dose groups were observed at any time, but increase of plasma concentration with higher doses became obvious when patients were differentiated to individual dose stages. In both groups, the most common treatment-related adverse event was dry mouth (ADG 35%, SDG 37%), which never led to discontinuation of treatment. Rates of other adverse events such as dry skin, dysopia, increased heart rate and gastrointestinal disorders were much lower.\n Generally, in patients with neurogenic detrusor overactivity daily doses of 45 mg trospium chloride can be considered as being the standard dose, and dose adjustment, e.g. due to increased body weight, might usually not be necessary. However, increased daily doses of up to 135 mg appear to be safe when prescribed in individual patients less responsive to the drug." ]

[ "8774298", "8425628", "8747045", "1740198" ]

[ "Intrauterine insemination with frozen sperm increases pregnancy rates in donor insemination cycles under gonadotropin stimulation.", "Comparison of intracervical, intrauterine, and intratubal techniques for donor insemination.", "Prospective randomized comparison of intrauterine and intracervical insemination with donor spermatozoa.", "Intrauterine insemination outperforms intracervical insemination in a randomized, controlled study with frozen, donor semen." ]

[ "To compare the efficacy of IUI donor and pericervical insemination donor in frozen sperm insemination cycles under gonadotropin stimulation.\n Couples where infertility was caused by male conditions were randomized into two groups: IUI and pericervical insemination. Semen samples, gonadotropin stimulation, and ovarian monitoring were the same in both groups. One IUI was performed per cycle as against two pericervical inseminations.\n The donor insemination program at the Human Reproduction Unit at the Hospital of Cruces, Pais Vasco University.\n Eighty-eight women (47 IUI and 41 pericervical insemination) with at least one patent fallopian tube and < 40 years of age.\n Intrauterine gestational sac observed by transvaginal ultrasound.\n Per woman pregnancy rate (PR) was higher in IUI than in pericervical insemination (65.96% versus 41.46%, odds ratio [OR] = 2.73, confidence interval [CI] = 1.06 to 7.2). Pregnancy rates were always higher in IUI irrespective of woman and husband's status, but statistical significance was not reached in any subgroups analyzed independently. Per cycle PR was also significantly higher in IUI than in pericervical insemination: 24.03% (31/129) versus 11.89% (17/143) (OR = 2.34, CI = 1.17 to 4.71). Moreover, cumulative PR was higher in IUI (86% versus 49.5%) (OR = 6, CI = 1.98 to 18.80).\n Per woman and per cycle PRs were significantly higher in IUI.", "To compare the efficacy of intracervical insemination (ICI), intrauterine insemination (IUI), and a combination of intratubal and intrauterine insemination (ITI/IUI) for donor insemination.\n Prospective randomized clinical trial.\n The University of Michigan donor insemination program.\n Forty-one women undergoing donor insemination with cryopreserved sperm for either isolated male factor or male factor plus ovulatory dysfunction corrected by clomiphene citrate.\n Each patient was randomly assigned to receive each of the three insemination techniques in consecutive cycles until pregnancy occurred or the patient dropped from the study.\n Cycle fecundity rates were compared using the chi 2 test, and cumulative pregnancy rates (PRs) determined by life table analysis were compared using a log-rank test.\n Cycle fecundity rate was significantly higher for IUI (18.3%) than for ICI (3.9%) or ITI/IUI (7.3%). By life table analysis, the cumulative PR for IUI was significantly higher than for ICI, but the PR for ITI/IUI was not.\n For donor insemination with cryopreserved sperm, IUI increases cycle fecundity compared with ICI. The addition of ITI to IUI, however, interferes with the apparent beneficial effect of IUI alone.", "From March 1990 to September 1993, 20 women underwent a total of 89 cycles of intracervical inseminations with donor semen (ICI) and 23 women underwent 67 cycles of intrauterine inseminations with donor semen (IUI). The women were assigned to the two groups randomly, but ensuring that the ages of the women and pathologies of the male partner (azoospermia or severe oligozoospermia) were similar in the two groups. There was no significant difference between the characteristics of the two groups and the method used to induce ovulation (HMG/HCG) was identical. Two semen straws were used for each insemination cycle. Semen was prepared for IUI on a Percoll gradient. Thirteen clinical pregnancies were obtained in the IUI group (19.4% of the attempts) and six in the ICI group (6.75%). After six cycles of insemination, 75.4% of the women of the IUI group obtained a pregnancy, as compared to 35% in the ICI group. These good results may be due to the method of induction of ovulation, but also to the technique itself, increasing the number of motile spermatozoa at the site of fertilization. The time taken to obtain a pregnancy is thus shorter with IUI than with ICI, and the number of semen straws required is smaller. In-vitro fertilization (IVF) should be proposed after six failures by IUI.", "To assess the efficacy of intrauterine insemination (IUI) in a donor insemination program.\n Prospective randomized clinical trial.\n Donor insemination program.\n Women undergoing insemination were randomly assigned to receive either IUI or intracervical insemination for a maximum of six cycles.\n None.\n Cycle fecundity rates between the two routes were compared.\n The monthly fecundity rate for intracervical insemination was 5.1% compared with 23% by IUI. By life table analysis, pregnancy rates for IUI were significantly higher than intracervical insemination (P = 0.02).\n Intrauterine insemination with quarantined donor sperm is superior to intracervical insemination." ]

[ "358755", "5072717", "796755", "4868797" ]

[ "Clinical effects and drug concentrations in plasma and cerebrospinal fluid in psychotic patients treated with fixed doses of chlorpromazine.", "Chlorpromazine in chronic schizophrenia. The effect of age and hospitalization on behavioral dose-response relationships.", "Alpha-methyldopa-chlorpromazine combination in schizophrenic patients.", "Prien RF, Cole JO: High dose chlorpromazine therapy in chronic schizophrenia. Report of National Institute of Mental Health--psychopharmacology research branch collaborative study group." ]

[ "The clinical effects of chlorpromazine (CPZ) administered in accordance with a double-blind design in one of three doses (200, 400 or 600 mg) were examined in 44 psychotic patients. The relationships between the effects and the CPZ concentrations in plasma and cerebrospinal fluid (CSF) were analyzed. The antipsychotic and side effects were rated according to the CPRS and the Simpson and Angus scale. CPZ concentrations were measured by a mass fragmentographic method. Treatment with CPZ resulted in a significant reduction of morbidity scores, without any clear dose relation. The final outcome was more favourable in women than in men. Extrapyramidal side effects but not somnolence were positively dose related. The antipsychotic effects tended to be positively related to the dose of CPZ in mg/kg as well as the CPZ concentrations in plasma and CSF. The greatest number of significant correlations between the CPZ concentration in CSF and the morbidity scores were seen after 2 weeks of treatment. The results indicated marked clinical improvement with CPZ concentrations above 1 ng/ml in CSF and 40 ng/ml in plasma. After 4 weeks of treatment the correlations between the CPZ concentrations and the clinical improvement were still positive but the coefficients were lower than at 2 weeks and only occasionaly significant. Extrapyramidal symptoms were significantly related to the CPZ concentrations in plasma and CSF. Somnolence was significantly related to the CPZ concentrations in CSF.", "nan", "In a double-blind, controlled clinical study, lasting 8 weeks, 55 hospitalized schizophrenic patients were randomly assigned to one of the five drug treatments: 600 mg chlorpromazine/day, 300 mg chlorpromazine/day, 300 mg chlorpromazine--250 mg alpha-methyldopa/day, 300 mg chlorpromazine--500 mg alpha-methyldopa/day, 300 mg chlorpromazine--750 mg alpha-methyldopa/day. The results showed that all five treatments were significantly effective in treating schizophrenic behavior. The dose-response relationship for the different doses of alpha-methyldopa in combination with chlorpromazine, suggested an optimal response to 300 mg chlorpromazine--500 mg alpha-methyldopa.", "nan" ]

[ "12930331", "19120324", "16536811", "15761427", "15004830" ]

[ "Prospective study of pulsed dye laser in conjunction with cryogen spray cooling for treatment of port wine stains in Chinese patients.", "Pulsed dye laser vs. intense pulsed light for port-wine stains: a randomized side-by-side trial with blinded response evaluation.", "The treatment of port-wine stains with the pulsed-dye laser at 2-week and 6-week intervals: a comparative study.", "Long-pulsed neodymium:yttrium-aluminum-garnet laser treatment for port-wine stains.", "Prospective study of port wine stain treatment with dye laser: comparison of two wavelengths (585 nm vs. 595 nm) and two pulse durations (0.5 milliseconds vs. 20 milliseconds)." ]

[ "Pulsed dye laser (PDL) in conjunction with cryogen spray cooling (CSC) is effective in improving efficacy and safety for treatment of port wine stains (PWSs) in whites. However, for dark-skinned patients such as Chinese, only retrospective studies have been performed.\n To compare prospectively clinical efficacy in terms of blanching and acute and long-term adverse effects of PDL alone and PDL-CSC for treatment of PWSs in Chinese patients.\n Thirty-five Chinese patients (13 males and 22 females) were recruited, and 131 treatments were performed. Half of the test area on the PWS was treated with PDL alone, and the contralateral half was treated with PDL-CSC. The degree of PWS blanching was objectively assessed by spectrophotometer. Skin textural changes were detected by cutometer. All measurements were taken at baseline and before each subsequent laser treatment. Patients were interviewed immediately after treatment and again the following week using a visual analog scale questionnaire to assess the degree of pain and swelling. Occurrence of blisters was noted during each follow-up visit. Patients were evaluated for evidence of long-term adverse effects such as dyspigmentation and scarring after three treatments.\n Statistically significant higher fluences were used on the PDL-CSC-treated group. The percentage change in the spectrophotometer a* value was significantly greater using PDL-CSC, indicating that there was more PWS blanching after treatment. There was no significant difference in the incidence of skin textural changes after three treatments with PDL alone or PDL-CSC. The immediate pain scores were significantly higher for PDL alone than with PDL-CSC. Blisters were significantly more common on the area treated using PDL alone than PDL-CSC. The overall incidence of long-term adverse effects was not significantly different between the PDL alone and PDL-CSC treatments. PDL-CSC was also the preferred treatment modality for most patients.\n PDL-CSC was more effective than PDL alone for blanching of PWS in Chinese patients. Moreover, PDL-CSC was better tolerated and resulted in a lower incidence of acute adverse effects such as blistering.", "Pulsed dye lasers (PDLs) are considered the treatment of choice for port-wine stains (PWS). Studies have suggested broadband intense pulsed light (IPL) to be efficient as well. So far, no studies have directly compared the PDL with IPL in a randomized clinical trial.\n To compare efficacy and adverse events of PDL and IPL in an intraindividual randomized clinical trial.\n Twenty patients with PWS (face, trunk, extremities; pink, red and purple colours; skin types I-III) received one side-by-side treatment with PDL (V-beam Perfecta, 595 nm, 0.45-1.5 ms; Candela Laser Corporation, Wayland, MA, U.S.A.) and IPL (StarLux, Lux G prototype handpiece, 500-670 and 870-1400 nm, 5-10 ms; Palomar Medical Technologies, Burlington, MA, U.S.A.). Settings depended on the preoperative lesional colour. Treatment outcome was evaluated by blinded, clinical evaluations and by skin reflectance measurements.\n Both PDL and IPL lightened PWS. Median clinical improvements were significantly better for PDL (65%) than IPL (30%) (P = 0.0004). A higher proportion of patients obtained good or excellent clearance rates with the PDL (75%) compared with IPL (30%) (P = 0.0104). Skin reflectance also documented better results after PDL (33% lightening) than IPL (12% lightening) (P = 0.002). Eighteen of 20 patients preferred to receive continued treatments with PDL (P = 0.0004). No adverse events were observed with PDL or IPL.\n Both the specific PDL and IPL types of equipment used in this study lightened PWS and both were safe with no adverse events. However, the PDL conveyed the advantages of better efficacy and higher patient preference.", "The pulsed-dye laser (PDL) is the treatment of choice for port-wine stains (PWS). Multiple treatments are usually necessary, with standard treatment intervals ranging between 6 and 12 weeks. However, there are no studies on the effect of treating PWS at different time intervals, and the ideal time interval between treatments has not yet been agreed. It is uncertain whether treatment is more effective if administered at shorter time intervals.\n To establish whether the treatment of PWS with the variable pulse width 595-nm (V-beam) PDL at 2-week intervals achieves better results, with no difference in the complication rate, than treatment given at 6-week intervals.\n We prospectively investigated 15 patients with PWS. Each patient had the whole PWS treated at initial visit. Half of the PWS was randomly allocated to be treated at 2 weeks and the other half at 6 weeks from initial visit. Both halves of the PWS thus were treated twice in total, once at the initial visit and the second treatment either at 2 weeks or 6 weeks from initial visit. At 12 weeks an observer blinded to treatment allocation clinically evaluated the results. The outcome measure was lightening of the PWS as measured with a reflectance spectrophotometer. Complications were recorded throughout the study period.\n Of the 15 patients, 13 completed the study. Three patients had two PWS each treated separately, giving a total of 16 treated PWS sites. In 11 sites (69%), the 2-week interval treatment resulted in greater reduction in reflectance than the 6-week interval treatment. Using the nonparametric Wilcoxon matched-pair signed rank test, the 2-week treatment interval site resulted in greater reduction in reflectance measurements compared with the 6-week treatment interval site (P < 0.01). This agreed closely with independent observer assessment judging that the 2-week treatment interval resulted in better lightening of the PWS than the 6-week treatment interval (P = 0.003). There were no adverse reactions from the treatments.\n Preliminary data suggest that a treatment interval of 2 weeks is well tolerated by patients and resulted in greater lightening of the PWS in the majority, compared with a standard 6-week interval. It also has the potential to reduce the total duration of a course of treatment significantly.", "Laser treatment of port-wine stain (PWS) might be improved using a deeply penetrating wavelength.\n PWSs in 17 patients were treated 3 times with a 595-nm pulsed dye laser (PDL) and a 1064-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. Fluences of 1.0, 0.8, and 0.6 times the minimum purpura dose (MPD) were used for Nd:YAG laser. Posttreatment biopsy specimens were taken. Blind assessment and quantitative analysis of PWS clearing were performed from digital photographs.\n MPD for Nd:YAG laser varied widely, from 40 to 250 J/cm 2 . Purpura lasted longer after PDL. Treatment achieved similar 50% to 75% clearing with both PDL and Nd:YAG laser at 1 MPD. Nd:YAG caused greater perivascular and epidermal injury. Scarring occurred in the only patient treated with a Nd:YAG fluence greater than 1 MPD. Patients preferred Nd:YAG laser because of their faster recovery.\n Nd:YAG laser used at MPD is as effective as PDL for treating PWS. Nd:YAG laser fluences higher than MPD may cause scarring.", "The conventional pulsed-dye laser (wavelength 585 nm, pulse duration 0.5 milliseconds) is seen as the standard treatment for port wine stains (PWS). Using the pulsed-dye laser at wavelengths of 590, 595, and 600 nm and at varying pulse durations of 1.5-40 milliseconds is one of the newest developments in the field, the therapeutic value of which has been examined in only a few studies. Treatment of PWS with short- and long-pulse dye lasers. Comparison of two wavelengths (585 nm vs. 595 nm) and two pulse durations (0.5 milliseconds vs. 20 milliseconds).\n Fifteen patients with untreated PWS were included in a randomized prospective study with three different laser settings. Patients underwent one treatment session. The following treatment parameters were chosen at a uniform spot size of 7 mm: (1) 585 nm/0.5 milliseconds/5.5 J/cm(2), (2) 595 nm/0.5 milliseconds/5.5 J/cm(2), and (3) 595 nm/20 milliseconds/13 J/cm(2). The clearance as well as side effects was evaluated. All treatments were performed with cold air-cooling. Follow-up took place immediately, 2 days and 4 weeks after the treatment. The PWS was assigned a clearance score (CS) from 1 to 4 (1 = poor to 4 = excellent).\n Descriptively, 585 nm/0.5 milliseconds generated the best average CS of 2.7, followed by 595 nm/20 milliseconds (2.5) and 595 nm/0.5 milliseconds (1.6)); statistically, there is no difference between the CS of 585 nm/0.5 milliseconds and 595 nm/20 milliseconds. The best lightening rates overall were achieved in purple PWS (CS = 3.5) versus red (CS = 2.5) and pink (CS = 2.0). Purple PWS responded best to 585 nm/0.5 milliseconds; red and pink PWS yielded similar results with 585 nm/0.5 milliseconds and 595 nm/20 milliseconds. The setting, 595 nm/0.5 milliseconds was clearly not as effective as the other laser settings. Purpura, pain, and crusting were most commonly reported after treatments with 585 nm/0.5 milliseconds (93%/93%/33%), closely followed by treatments at 595 nm/20 milliseconds (86%/93%/20%). The settings 595 nm/0.5 milliseconds yielded the lowest rate of adverse effects (67%/60%/0%). Hypopigmentation only occurred in one case (585 nm/0.5 milliseconds), and there were no reports of hyperpigmentation or scarring.\n With respect to treating PWS, the conventional pulsed-dye laser set to 585 nm/0.5 milliseconds yields a significantly greater clearance rate than it does at a setting of 595 nm (with the same pulse duration, fluence, and spot size), although the former also entails the highest spectrum of adverse effects. In this study, purple PWS treated at these parameters showed the best results. In dealing with pink PWS, the results were similar to those of the conventional pulsed-dye laser when the pulse duration was increased to 20 milliseconds and fluence was increased. As a rule, the clearance rate corresponded to the extent of the postoperative purpura.\n Copyright 2004 Wiley-Liss, Inc." ]

[ "1279169", "2449871", "2454140", "7506013", "7538285", "1279170" ]

[ "Placebo controlled study showing therapeutic benefit of iloprost in the treatment of Raynaud's phenomenon.", "Infusion of iloprost, a prostacyclin analogue, for treatment of Raynaud's phenomenon in systemic sclerosis.", "Successful treatment of Raynaud's syndrome with Iloprost, a chemically stable prostacyclin analogue.", "Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study.", "Oral iloprost as a treatment for Raynaud's syndrome: a double blind multicentre placebo controlled study.", "Intravenous iloprost treatment of Raynaud's phenomenon and ischemic ulcers secondary to systemic sclerosis." ]

[ "Iloprost is a chemically stable analog of prostaglandin I2 showing the same properties as the naturally occurring substance, but with advantages of ease of handling and administration to patients. A double blind within patient comparison of intravenous iloprost and placebo was undertaken in 13 patients with Raynaud's phenomenon severe enough to warrant short term hospitalization for intravenous dilator therapy; thermography was used as one form of assessment. Our results, while showing improvements in frequency of Raynaud's attacks after iloprost compared with placebo, show no significant effects on other variables.", "Iloprost, a stable prostacyclin analogue, was given by intravenous infusion to 29 patients with severe Raynaud's phenomenon, 26 of whom had systemic sclerosis (SS), and compared with placebo infusion in a double blind crossover trial. Iloprost significantly lessened the number and the severity of attacks compared with placebo. Nine patients expressed a preference for effectiveness of treatment, eight of these in favour of Iloprost. Thermography failed to show any long term effect of Iloprost. Side effects of headache, flushing, nausea, and vomiting were common, and the inconvenience of intravenous administration may limit its routine use.", "Twelve female patients with severe secondary Raynaud's phenomenon were treated in a randomized order with both placebo and Iloprost infusions. Infusions were for 5 hours on 3 consecutive days and Iloprost was administered at variable dosage from 1.0 to 3.0 ng/kg/min. A 6-week follow-up period was used between the two sets of infusions. A significant number of patients reported Iloprost had improved Raynaud's symptomatology compared with placebo and this effect lasted for up to 6 weeks. The number of attacks of Raynaud's as recorded by patients in diary books was similarly reduced after Iloprost. Digital and nail-bed blood flows measured by laser-Doppler methods were increased for up to 6 weeks after Iloprost, but not after placebo infusions. Iloprost may be a useful therapeutic agent in the treatment of severe secondary Raynaud's syndrome.", "To evaluate the efficacy and safety of iloprost, a prostacyclin analog, administered intravenously in patients with Raynaud phenomenon secondary to systemic sclerosis.\n Multicenter, randomized, parallel placebo-controlled, double-blind study.\n University medical centers.\n 131 patients with systemic sclerosis (101 women, 30 men) ages 20 to 79 years.\n Patients were randomly assigned to receive one of two parallel treatments of five daily sequential, 6-hour intravenous infusions of iloprost (0.5 to 2.0 ng/kg per min) or to receive a similar volume of placebo.\n Frequency of Raynaud attacks, Raynaud severity score, physician's overall rating of treatment effect, and digital cutaneous lesion healing.\n Of the 131 patients enrolled, 126 completed the 5-day infusion and 114 (87%) completed at least 6 weeks of follow-up. Sixty-four patients were randomly assigned to receive iloprost and 67 patients, to receive placebo. The mean weekly number of Raynaud attacks decreased 39.1% with iloprost and 22.2% with placebo (P = 0.005). In addition, the mean percentage of improvement in a global Raynaud severity score during the entire 9-week follow-up was greater in patients given iloprost (34.8%) than in those receiving placebo (19.7%) (P = 0.011). The physician's overall rating of treatment effect showed greater improvement with iloprost than with placebo at week 6 (52.4% compared with 27.4%; P = 0.008) and week 9 (60.9% compared with 26.9%; P < 0.001). At week 3, 14.6% more patients receiving iloprost had 50% or more lesions heal compared with those given placebo (95% CI, 0.9% to 30%). During the infusion, 59 (92%) of the patients receiving iloprost had one or more side effects compared with 38 (57%) of the patients receiving placebo.\n Iloprost is effective for the short-term palliation of severe Raynaud phenomenon in patients with systemic sclerosis.", "To compare the efficacy, tolerance and safety of 50-150 micrograms orally administered iloprost given twice a day versus placebo in patients with Raynaud's syndrome.\n The study was multicentre (n = 3), double blind and placebo controlled. Sixty three patients who had eight or more vasospastic attacks per week were enrolled. After a one week run-in period, all patients received either iloprost or placebo treatment to a maximum tolerated dose of 150 micrograms twice a day for 10 days. Diary cards assessed the duration and severity of the vasospastic attacks. Side effects were monitored by direct questioning. A global assessment of treatment efficacy was made by the patient at the end of treatment and two weeks later.\n Patient opinion tended to favour iloprost at the end of the 10 day treatment phase (p = 0.09) and this was significant at day 24 (the follow up visit) (p = 0.011). Although the duration and severity of attacks tended to decrease in the iloprost treated group, these results tended not to reach statistical significance (for severity p = 0.06 at end of treatment, p = 0.09 on day 24).\n Iloprost administered intravenously has been shown to be of benefit in the treatment of the Raynaud's syndrome associated with systemic sclerosis, but this route of administration is inconvenient. This study evaluated the use of iloprost administered orally to patients with Raynaud's syndrome. Patient documented improvement was significantly improved by iloprost. Diary card analysis showed a trend in favour of iloprost, but these results did not reach statistical significance.", "We conducted this study to assess the clinical usefulness and physiologic effects of intravenous iloprost in patients with Raynaud's phenomenon secondary to systemic sclerosis.\n Thirty-five patients with Raynaud's phenomenon secondary to systemic sclerosis, including 11 with digital ischemic ulcerations, were enrolled in a double blind placebo controlled parallel study in 2 centers. Following a 2 week washout, subjects received intravenous iloprost (0.5-2.0 ng/kg/min) or saline by continuous infusion for 6 h on 5 consecutive days. Clinical assessments, status of digital ulcers, measures of in vivo platelet activation and detailed studies of peripheral vascular response to cold challenge, were performed at entry, at 5 days of therapy and at biweekly intervals for 10 weeks.\n Complete healing of all cutaneous lesions (ulcers, fissures, and paronychia) was observed 10 weeks after treatment in 6 of 7 patients receiving iloprost versus none of 4 receiving placebo (p = 0.015). Ischemic digital tip ulcers completely healed in all 4 patients with ulcers in the iloprost group, but none in the placebo group (p = 0.029). Patient diaries of frequency, duration and symptoms of Raynaud's phenomenon showed improvement in both groups. Critical ischemic temperature (finger temperature during controlled cold challenge at which Raynaud's or loss of detectable digital blood flow occurred) progressively decreased in the iloprost group from 21.3 +/- 7.3 degrees C at baseline to a minimum of 16.1 +/- 3.2 degrees C at 8 weeks after treatment (p = 0.076), whereas no consistent changes were observed in the placebo group. Treatment was associated with improvement in the rate of skin temperature recovery following cold challenge. No changes were noted in ambient digital skin temperature, total digital blood flow, finger systolic pressure or in measures of in vivo platelet activation. One subject dropped out with chest pain, but adverse effects of nausea, vomiting, headache and jaw pain were otherwise limited to the 5 days of drug infusion.\n Iloprost appears useful for the treatment of digital ulcers in systemic sclerosis and is associated with evidence of prolonged physiologic improvement although the mechanism of this effect remains unclear." ]

[ "11585273", "11343530", "17513815", "11742045", "16967054", "20658835", "9885092", "17385190", "2571815", "10607980" ]

[ "Difference in patient's acceptance of early versus late initiation of psychosocial support in breast cancer.", "Supportive-expressive group therapy and distress in patients with metastatic breast cancer: a randomized clinical intervention trial.", "Impact of a peer-delivered telephone intervention for women experiencing a breast cancer recurrence.", "The effect of group psychosocial support on survival in metastatic breast cancer.", "Meeting the support and information needs of women with advanced breast cancer: a randomised controlled trial.", "A randomized controlled trial of emotionally expressive writing for women with metastatic breast cancer.", "A randomized controlled trial of the effects of group psychological therapy on survival in women with metastatic breast cancer.", "Supportive-expressive group therapy for women with metastatic breast cancer: survival and psychosocial outcome from a randomized controlled trial.", "Effect of psychosocial treatment on survival of patients with metastatic breast cancer.", "Effects of group CBT on the survival time of patients with metastatic breast cancer." ]

[ "The present study was performed to assess the difference in acceptance of psychosocial counseling and resulting benefits between patients with breast cancer with early or late onset. In a prospective randomized controlled study conducted over 6 months, 41 women with a new diagnosis of early breast cancer (group 1) and 43 patients with advanced breast cancer (group 2) received individually tailored psychosocial support and were compared against controls. This therapy was free of charge, and the duration of support was determined by the patients' wishes and needs. Among the patients with new onset of disease acceptance of the psychosocial counseling was high, and these patients experienced significant improvements in their quality of life. In contrast, acceptance of psychosocial counseling was low in the advanced breast cancer group and the therapy did not improve quality of life over the observation period of 6 months. Early psychosocial support in patients with breast cancer meets with a high acceptance rate and improves quality of life.", "Metastatic breast cancer carries with it considerable psychosocial morbidity. Studies have shown that some patients with metastatic breast cancer experience clinically significant anxiety and depression and traumatic stress symptoms. Supportive-expressive group psychotherapy was developed to help patients with cancer face and adjust to their existential concerns, express and manage disease-related emotions, increase social support, enhance relationships with family and physicians, and improve symptom control.\n Of 125 women with metastatic breast cancer recruited into the study, 64 were randomized to the intervention and 61 to the control condition. Intervention women were offered 1 year of weekly supportive-expressive group therapy and educational materials. Control women received educational materials only. Participants were assessed at baseline and every 4 months during the first year. Data at baseline and from at least 1 assessment were collected from 102 participants during this 12-month period, and these participants compose the study population.\n Primary analyses based on all available data indicated that participants in the treatment condition showed a significantly greater decline in traumatic stress symptoms on the Impact of Event Scale (effect size, 0.25) compared with the control condition, but there was no difference in Profile of Mood States total mood disturbance. However, when the final assessment occurring within a year of death was removed, a secondary analysis showed a significantly greater decline in total mood disturbance (effect size, 0.25) and traumatic stress symptoms (effect size, 0.33) for the treatment condition compared with the control condition.\n Supportive-expressive therapy, with its emphasis on providing support and helping patients face and deal with their disease-related stress, can help reduce distress in patients with metastatic breast cancer.", "A first breast cancer recurrence creates considerable distress, yet few psychosocial interventions directed at this population have been reported. The Southwest Oncology Group conducted a phase III randomized trial to evaluate the effectiveness of a brief telephone intervention.\n Three hundred five women experiencing a first recurrence of breast cancer were randomly assigned to standard care or intervention. The intervention consisted of four to eight telephone calls delivered over a 1-month period. The calls were conducted by trained peer counselors at a breast cancer advocacy organization, the Y-ME National Breast Cancer Organization, and followed a standard curriculum. Psychosocial distress (Cancer Rehabilitation Evaluation System-Short Form [CARES-SF]) and depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D]) outcomes were assessed at baseline and 3 and 6 months. The 3-month assessment was the primary end point and is the focus of this article.\n Analysis revealed no differences in distress or depressive symptoms at 3 months between the intervention and control groups; at 3 months, 70% of control patients and 66% of intervention patients reported psychosocial distress, and 40% of control patients and 47% of intervention patients exhibited depressive symptoms.\n Telephone peer counseling did not lead to better psychosocial outcomes. The persistent distress in these women supports the urgent need for the development and testing of more intensive or different supportive interventions for this group of patients.", "Supportive-expressive group therapy has been reported to prolong survival among women with metastatic breast cancer. However, in recent studies, various psychosocial interventions have not prolonged survival.\n In a multicenter trial, we randomly assigned 235 women with metastatic breast cancer who were expected to survive at least three months in a 2:1 ratio to an intervention group that participated in weekly supportive-expressive group therapy (158 women) or to a control group that received no such intervention (77 women). All the women received educational materials and any medical or psychosocial care that was deemed necessary. The primary outcome was survival; psychosocial function was assessed by self-reported questionnaires.\n Women assigned to supportive-expressive therapy had greater improvement in psychological symptoms and reported less pain (P=0.04) than women in the control group. A significant interaction of treatment-group assignment with base-line psychological score was found (P</=0.003 for the comparison of mood variables; P=0.04 for the comparison of pain); women who were more distressed benefited, whereas those who were less distressed did not. The psychological intervention did not prolong survival (median survival, 17.9 months in the intervention group and 17.6 months in the control group; hazard ratio for death according to the univariate analysis, 1.06 [95 percent confidence interval, 0.78 to 1.45]; hazard ratio according to the multivariate analysis, 1.23 [95 percent confidence interval, 0.88 to 1.72]).\n Supportive-expressive group therapy does not prolong survival in women with metastatic breast cancer. It improves mood and the perception of pain, particularly in women who are initially more distressed.", "Addressing psychosocial and quality of life needs is central to provision of excellent care for people with advanced cancer. This study tested a brief nurse-delivered intervention to address the needs of urban women with advanced breast cancer. This study was conducted at four large urban hospitals in Australia. One hundred and five women with advanced breast cancer were recruited and randomised to receive the intervention or usual care, then asked to complete the European Organisation of Research and Treatment of Quality of life Q-C30 version (2.0) (EORTC Q-C30) (version 2) and Supportive Care Needs Survey (SCNS) at 1 month and 3 months postrecruitment. No significant differences were detected between intervention and usual care groups in the SCNS or the EORTC Q-C30 subscale scores. However, when the groups were divided into high needs (score of above 50) and low baseline needs (score of 50 or below) for each SCNS subscale, a significant difference between intervention and usual care groups was found in the psychological/emotional subscale among women with high baseline needs. In conclusions, this study demonstrated that a face-to-face session and follow-up phone call with a breast care nurse significantly reduced the psychological and emotional needs of those with high initial needs. There was no evidence of the intervention influencing the quality of life; or perceived needs of women with low initial psychological/emotional needs or perceived needs in other domains. Possibly, the intervention was not sufficiently intense to achieve an effect.", "To test the effects of emotionally expressive writing in a randomized controlled trial of metastatic breast cancer patients and to determine whether effects of the intervention varied as a function of perceived social support or time since metastatic diagnosis.\n Women (N = 62) living with Stage IV breast cancer were randomly assigned to write about cancer-related emotions (EMO; n = 31) or the facts of their diagnosis and treatment (CTL; n = 31). Participants wrote at home for four 20-min sessions within a 3-week interval.\n Depressive symptoms, cancer-related intrusive thoughts, somatic symptoms, and sleep quality at 3 months postintervention.\n No significant main effects of experimental condition were observed. A significant condition x social support interaction emerged on intrusive thoughts; EMO writing was associated with reduced intrusive thoughts for women reporting low emotional support (eta2 = .15). Significant condition x time since metastatic diagnosis interactions were also observed for somatic symptoms and sleep disturbances. Relative to CTL, EMO participants who were more recently diagnosed had fewer somatic symptoms (eta2 = .10), whereas EMO participants with longer diagnosis duration exhibited increases in sleep disturbances (eta2 = .09).\n Although there was no main effect of expressive writing on health among the current metastatic breast cancer sample, expressive writing may be beneficial for a subset of metastatic patients (including women with low levels of emotional support or who have been recently diagnosed) and contraindicated for others (i.e., those who have been living with the diagnosis for years).\n PsycINFO Database Record (c) 2010 APA, all rights reserved.", "In order to test the effect of a psychological intervention on survival from cancer, 66 women with metastatic breast cancer, all receiving standard medical care, were randomly assigned into two groups; one group (n = 30) attended the psychological intervention, consisting of 35 weekly, 2 h sessions of supportive plus cognitive behavioral therapy; the control group (n = 36) received only a home study cognitive behavioral package. No significant difference was found in survival post-randomization between the groups as assessed by a log rank test 5 years after the commencement of the study. As expected, several prognostic factors were significant predictors of survival: metastatic site, hormonal receptor status, and chemotherapy prior to randomization. While many personal and demographic variables did not influence survival, there was a significant effect of self-reported exercise (possibly due to better health). A small subgroup of intervention subjects who attended outside support groups also survived significantly longer than those who did not. The strengths and limitations of the present study are discussed, and the results contrasted with those of a well known study by Spiegel et al. (Spiegel, D., Bloom, J.R., Kraemer, H.C. and Gottheil, E. (1989) Lancet ii, 888-891). We propose that a different experimental design (correlative) may be needed to show any effect of self-help behaviors and psychological attributes in a small minority of patients.", "Mixed reports exist about the impact of supportive-expressive group therapy (SEGT) on survival.\n From 485 women with advanced breast cancer recruited between 1996-2002, 227 (47%) consented and were randomized within an average 10 months of cancer recurrence in a 2:1 ratio to intervention with 1 year or more of weekly SEGT plus three classes of relaxation therapy (147 women) or to control receiving three classes of relaxation therapy (80 women). The primary outcome was survival; psychosocial well-being was appraised secondarily. Analysis was by intention-to-treat.\n SEGT did not prolong survival (median survival 24.0 months in SEGT and 18.3 in controls; univariate hazard ratio for death 0.92 [95% CI, 0.69-1.26]; multivariate hazard ratio, 1.06 [95% CI, 0.74-1.51]). Significant predictors of survival were treatment with chemotherapy and hormone therapy (p<0.001), visceral metastases (p<0.001) and advanced disease at first diagnosis (p<0.05). SEGT ameliorated and prevented new DSM-IV depressive disorders (p = 0.002), reduced hopeless-helplessness (p = 0.004), trauma symptoms (p = 0.04) and improved social functioning (p = 0.03).\n SEGT did not prolong survival. It improved quality of life, including treatment of and protection against depression.\n Copyright (c) 2007 John Wiley & Sons, Ltd.", "The effect of psychosocial intervention on time of survival of 86 patients with metastatic breast cancer was studied prospectively. The 1 year intervention consisted of weekly supportive group therapy with self-hypnosis for pain. Both the treatment (n = 50) and control groups (n = 36) had routine oncological care. At 10 year follow-up, only 3 of the patients were alive, and death records were obtained for the other 83. Survival from time of randomisation and onset of intervention was a mean 36.6 (SD 37.6) months in the intervention group compared with 18.9 (10.8) months in the control group, a significant difference. Survival plots indicated that divergence in survival began at 20 months after entry, or 8 months after intervention ended.", "We have recently reported the psychological outcome of a group Cognitive Behaviour Therapy (CBT) intervention with patients who had metastatic breast cancer. The data of 92 patients who were retained at the first follow-up assessment revealed short-term improvements on measures of mood and self-esteem amongst therapy participants. These changes were not sustained at the 3- and 6-month follow-up assessments. This report describes a survival analysis of 121 patients who entered the study, at 5 years after its commencement. The analysis, based on the Cox Proportional Hazards Regression model, revealed no survival advantage associated with the intervention. Only medical prognostic factors such as Eastern Cooperative Oncology Group (ECOG) performance status, visceral metastases and chemotherapy treatment significantly predicted patients' survival time. The findings of this study are compared with those of two earlier studies which also examined the survival effects of a group psychological intervention with metastatic breast cancer patients.\n Copyright 1999 John Wiley & Sons, Ltd." ]

[ "20074264", "14664880", "19900131", "12962924", "16681474", "20799571", "18338177", "12397189" ]

[ "Short-term recovery after subtotal and total abdominal hysterectomy--a randomised clinical trial.", "Randomised controlled trial of total compared with subtotal hysterectomy with one-year follow up results.", "A randomized trial comparing changes in sexual health and psychological well-being after subtotal and total hysterectomies.", "A randomized comparison of total or supracervical hysterectomy: surgical complications and clinical outcomes.", "The psychosocial outcomes of total and subtotal hysterectomy: A randomized controlled trial.", "Outcomes of total versus subtotal abdominal hysterectomy.", "Hysterectomy and women satisfaction: total versus subtotal technique.", "Outcomes after total versus subtotal abdominal hysterectomy." ]

[ "To determine whether the day-by-day postoperative recovery differs between women undergoing subtotal and total abdominal hysterectomy, and to analyse factors associated with postoperative recovery and sick leave.\n A prospective, open, randomised multicentre trial.\n Seven hospitals and one private clinic in the south-east of Sweden.\n Two-hundred women scheduled for hysterectomy for benign conditions were enrolled in the study, and 178 women completed the study. Ninety-four women were randomised to subtotal abdominal hysterectomy; 84 women were randomised to total abdominal hysterectomy.\n The day-by-day recovery of general wellbeing was measured on a visual analogue scale in a diary 7 days preoperatively and 35 days postoperatively. Psychometric measurements included depression, anxiety and general psychological wellbeing.\n Effects of operating method and preoperative wellbeing on the day-by-day recovery and duration of sick leave.\n No significant difference was found in the day-by-day recovery between operating methods. The day-by-day recovery of general wellbeing and duration of sick leave was strongly associated with the occurrence of minor complications, but not with major complications. The level of psychological wellbeing preoperatively was strongly associated with the day-by-day recovery of general wellbeing and duration of sick leave.\n Day-by-day recovery of general wellbeing is no faster in subtotal versus total abdominal hysterectomy. Independent of operation method there is an interaction between preoperative psychological wellbeing, postoperative recovery of general wellbeing and the duration of sick leave. Postoperative complications and preoperative psychological wellbeing are strong determinants for the duration of sick leave. There is a need for intervention studies with a focus on complications and preoperative wellbeing.", "To compare total abdominal hysterectomy and subtotal abdominal hysterectomy performed for benign uterine diseases.\n Randomised, controlled, unblinded trial with central, computer-generated randomisation.\n Danish trial performed in 11 departments of gynaecology.\n Women referred for benign uterine diseases were randomised to total abdominal hysterectomy (n = 158) or subtotal abdominal hysterectomy (n = 161). One-year follow up questionnaires had a response rate of 87%.\n Patients were followed by strict data collection procedures, including postal questionnaires. The results after one year of follow up were analysed by intention-to-treat analyses.\n (1) Primary: urinary incontinence and (2) secondary: post-operative complications, quality of life (SF-36), constipation, prolapse of the vaginal vault/cervical stump, satisfaction with sexual life, pelvic pain and vaginal bleeding.\n A significantly (P = 0.043) smaller proportion of women had urinary incontinence one year after total abdominal hysterectomy compared with subtotal abdominal hysterectomy [9% vs 18% (OR 2.08, 95% CI 1.01-4.29)]. The lower proportion of incontinent women in the total abdominal hysterectomy group was a result of a higher proportion of symptom relief (total abdominal hysterectomy: 20/140, subtotal abdominal hysterectomy: 14/136) as well as a lower proportion of women with new symptoms (total abdominal hysterectomy: 3/140, subtotal abdominal hysterectomy: 10/137). Twenty-seven women (20%) from the subtotal abdominal hysterectomy group had vaginal bleeding and two of them had to have their cervix removed. No other clinically important differences were found between the two hysterectomy methods.\n A smaller proportion of women suffered from urinary incontinence after total abdominal hysterectomy than after subtotal abdominal hysterectomy one year post-operatively.", "To evaluate changes in sexual health and psychological well-being one year after subtotal and total hysterectomies.\n Prospective randomized controlled trial.\n One hundred and thirty-two premenopausal patients scheduled for hysterectomy without planned oophorectomy for benign disorders and without a history of cervical dysplasia or symptomatic prolapse were randomized to total (n = 66) or subtotal hysterectomy (n = 66). The McCoy Female Sexuality Questionnaire was used to evaluate changes in sexual health and the Psychological General Well-Being index was used to evaluate changes in psychological well-being. Differences in outcome before and one year after the hysterectomy were calculated for each individual, and changes compared between the groups.\n Women who had subtotal hysterectomy (SH) reported a significantly greater positive change in frequency of orgasm and sexual pleasure as compared with women who had total hysterectomy (TH) (mean values +/- standard deviation (SD), orgasm: SH: 0.4 +/- 1.1; TH: -0.2 +/- 0.9, p = 0.012, sexual enjoyment: SH 0.3 +/- 1.5; TH: -0.3 +/- 1.3, p = 0.039). There was a significantly greater general health gain for the women who underwent subtotal hysterectomy as compared with total hysterectomy (mean values +/- SD SH: 1.2 +/- 2.3; TH: 0.3 +/- 1.6, p = 0.03). The total score did not show a difference.\n Women undergoing subtotal hysterectomy experience a greater positive change in the frequency of orgasm and extent of sexual pleasure after surgery than women undergoing total hysterectomy, but the results must be interpreted with caution.", "To compare surgical complications and clinical outcomes after total versus supracervical abdominal hysterectomy for control of abnormal uterine bleeding, symptomatic uterine leiomyomata, or both.\n We conducted a randomized intervention trial in four US clinical centers among 135 patients who had abdominal hysterectomy for symptomatic uterine leiomyomata, abnormal uterine bleeding refractory to hormonal treatment, or both. Patients were randomly assigned to receive a total or supracervical hysterectomy performed using the surgeon's customary technique. Using an intention-to-treat approach, we compared surgical complications and clinical outcomes for 2 years after randomization.\n Sixty-eight participants were assigned to supracervical hysterectomy (SCH) and 67 to total abdominal hysterectomy (TAH). Hysterectomy by either technique led to statistically significant reductions in most symptoms, including pelvic pain or pressure, back pain, urinary incontinence, and voiding dysfunction. Patients randomly assigned to (SCH) tended to have more hospital readmissions than those randomized to TAH, but this difference was not statistically significant. There were no statistically significant differences in the rate of complications, degree of symptom improvement, or activity limitation. Participants weighing more than 100 kg at study entry were twice as likely to be readmitted to the hospital during the 2-year follow-up period (relative risk [RR] 2.18, 95% confidence interval [CI] 1.06, 4.48, P=.034).\n We found no statistically significant differences between (SCH) and TAH in surgical complications and clinical outcomes during 2 years of follow-up.", "Current controversies involve the adverse effects of hysterectomy on women's psychosocial functioning and whether subtotal as opposed to total hysterectomy mitigates these effects.\n To investigate the psychosocial effects of hysterectomy by examining sexual, pain, and psychological outcomes of total vs. subtotal hysterectomy in a randomized controlled trial.\n Patients suffering from benign gynecological conditions were randomly assigned to one of two groups: (i) total hysterectomy, that is, laparoscopic assisted vaginal hysterectomy (TOT, N = 32); or (ii) subtotal hysterectomy, that is, supracervical laparoscopic hysterectomy (SUB, N = 31). Both groups were premenopausal and underwent hysterectomy without concurrent oophorectomy. Two premenopausal control groups: (i) minor gynecological surgery (SURG-CON, N = 30); and (ii) healthy nonsurgical controls (NORM-CON, N = 40), were also tested. All surgical groups were assessed 2-3 weeks before surgery and then 6-7 months afterward; the nonsurgical control group was assessed at the time of recruitment and 6-7 months later.\n Assessments included semistructured interviews, standardized questionnaires, and standardized gynecological examinations.\n For the TOT group, sexual drive, arousal, and sexual behavior significantly improved postoperatively. For the SUB group, sexual behavior and overall sexual functioning significantly improved. For both TOT and SUB groups, unprovoked pain in the abdomen and pain in the abdomen during gynecological examinations was significantly reduced. For both TOT and SUB groups, overall psychological functioning did not significantly change postoperatively. Although between 3% and 16% of women undergoing hysterectomy reported adverse changes in psychosocial well-being after surgery, similar percentages of women in the control groups reported such effects.\n Hysterectomy resulted in a consistent reduction in abdominal pain, some improvement in sexual functioning, but no change in overall psychological functioning. There was no evidence supporting the idea that subtotal hysterectomy produced more favorable psychosocial outcomes than total hysterectomy nor was there any evidence that either type of hysterectomy resulted in adverse effects.", "There is still controversy about the best technique for hysterectomy to reduce postoperative adverse effects. This randomized clinical study in Babol, Islamic Republic of Iran, compared some clinical complications and sexual functioning following subtotal (SAH) and total abdominal hysterectomy (TAH). A total of 150 women (50 allocated to SAH and 100 to TAH) were followed up at 6 months postoperatively. Length of hospitalization was 4.40 (SD 1.90) days after SAH and 4.48 (SD 1.67) days after TAH. Haemoglobin level, postoperative fever, symptoms of dyspareunia and frequency of sexual intercourse were not significantly different between the 2 groups of women. SAH did not show any significant benefits over TAH.", "The impact of different surgical procedures on women's satisfaction after hysterectomy is a topical issue. The aim of this study was to investigate the impact of sub-total and total hysterectomy on women's satisfaction, evaluated with questionnaire assessment of sexual activity, body image, and health status.\n A prospective, randomized, non-blind study was conducted. In the study period of 3 years, 105 women were enrolled and completed the questionnaires [EuroQol (EQ-5D), body image scale (BIS), sexual activity questionnaire] 2 weeks before and 1 year after surgery.\n Both total and sub-total hysterectomy resulted with improvements in the women's sexual satisfaction (1 year after surgery), but no statistically significant differences were reached between the two groups. A highly significant difference (P < 0.001) in the perception of the body image between total and sub-total hysterectomy, at 1 year after surgery, was underlined. The health-related quality of life resulted significantly better in the \"sub-total hysterectomy\" group 1 year after surgery (P < 0.05).\n Considering these results, why should a total hysterectomy be performed, if the women's satisfaction seems to be higher using the sub-total technique? In our opinion, the woman undergoing hysterectomy for benign conditions must be counseled regarding the differences between the two techniques and, when possible, a choice must be offered to the woman.", "It is uncertain whether subtotal abdominal hysterectomy results in better bladder, bowel, or sexual function than total abdominal hysterectomy.\n We conducted a randomized, double-blind trial comparing total and subtotal abdominal hysterectomy in 279 women referred for hysterectomy because of benign disease; most of the women were premenopausal. The main outcomes were measures of bladder, bowel, and sexual function at 12 months. We also evaluated postoperative complications.\n The rates of urinary frequency (urination more than seven times during the day) were 33 percent in the subtotal-hysterectomy group and 31 percent in the total-hysterectomy group before surgery, and they fell to 24 percent and 20 percent, respectively, at 12 months (P=0.03 for the change over time within each group; P=0.84 for the interaction between the treatment assignment and time). The reduction in nocturia and stress incontinence and the improvement in bladder capacity were similar in the two groups. The frequency of bowel symptoms (as indicated by reported constipation and use of laxatives) and measures of sexual function (including the frequency of intercourse and orgasm and the rating of the sexual relationship with a partner) did not change significantly in either group after surgery. The women in the subtotal-hysterectomy group had a shorter hospital stay (5.2 days, vs. 6.0 in the total-hysterectomy group; P=0.04) and a lower rate of fever (6 percent vs. 19 percent, P<0.001). After subtotal abdominal hysterectomy, 7 percent of women had cyclical bleeding and 2 percent had cervical prolapse.\n Neither subtotal nor total abdominal hysterectomy adversely affects pelvic organ function at 12 months. Subtotal abdominal hysterectomy results in more rapid recovery and fewer short-term complications but infrequently causes cyclical bleeding or cervical prolapse.\n Copyright 2002 Massachusetts Medical Society" ]

[ "3881447", "3090049", "11380123" ]

[ "A prospective, randomized study of the management of severe ankle fractures.", "A prospective trial comparing operative and manipulative treatment of ankle fractures.", "Conservative versus operative treatment for displaced ankle fractures in patients over 55 years of age. A prospective, randomised study." ]

[ "One hundred and thirty-eight patients with a closed grade-4 supination-external rotation or pronation-external rotation ankle fracture (Lauge-Hansen classification) who were seen in the emergency room of the University of Chicago Hospitals were entered into a randomized study of the results of various methods of treatment. Ninety-six patients with satisfactory initial closed reduction were randomized between continued closed treatment in a plaster cast and open reduction with rigid internal fixation according to the techniques of the Association for the Study of Internal Fixation (ASIF). Forty-two patients with unsatisfactory closed reduction were randomized between open reduction with internal fixation of only the medial malleolus and open reduction with rigid internal fixation according to the ASIF techniques. Of the 138 patients who were admitted to the study, only seventy-one (51 per cent) could be followed for an average of 3.5 years (a typical return rate of urban trauma centers). The outcomes were evaluated by a scoring system that included clinical, anatomical, and arthritis scores. Statistical analysis of the data showed that, of the patients with initial satisfactory closed reduction, the ones treated by open reduction and rigid internal fixation had significantly higher total scores, particularly the patients who were more than fifty years old and those with a medial malleolar fracture. The small number of patients with unsatisfactory closed reduction who were treated by one of the two types of open reduction and internal fixation and were available for follow-up precluded drawing any conclusions about the superiority of one method of internal fixation over the other in that group. The difference in the talocrural angle between the injured and normal sides was the only statistically significant radiographic indicator of a good prognosis.", "A series of 42 ankle fractures have been randomised into two groups respectively undergoing either open reduction and internal fixation or manipulative reduction and plaster. Their progress after removal of all external splintage has been followed using simple gait analysis techniques. There appears to be no difference in the outcome of treatment of the two groups in the early recovery period (up to 20 weeks).", "Forty-seven patients over the age of 55 years with a displaced fracture of the ankle were entered into a prospective, randomised study in order to compare open reduction and internal fixation with closed treatment in a plaster cast; 36 were reviewed after a mean of 27 months. The outcome was assessed clinically, radiologically and functionally using the Olerud score. The results showed that anatomical reduction was significantly less reliable (p = 0.03) and loss of reduction significantly more common (p = 0.001) in the group with closed treatment. Those managed by open reduction and internal fixation had a significantly higher functional outcome score (p = 0.03) and a significantly better range of movement of the ankle (p = 0.044) at review." ]

[ "7600346", "17352751", "19349934", "9341430", "1302331", "16240623", "12066081", "15545697" ]

[ "Comparison of two dressings in the treatment of venous leg ulcers.", "Randomized trial of two foam dressings in the management of chronic venous ulceration.", "Monitoring the microcirculation to evaluate dressing performance in patients with venous leg ulcers.", "A comparison of two dressings in the management of chronic wounds.", "[A comparative study of the hydrocellular dressing Allevyn and the hydrocolloid dressing Duoderm in the local treatment of leg ulcers].", "Use of a hydrocapillary dressing in the management of highly exuding ulcers: a comparative study.", "Randomised, comparative study of three primary dressings for the treatment of venous ulcers.", "Comparing a foam composite to a hydrocellular foam dressing in the management of venous leg ulcers: a controlled clinical study." ]

[ "nan", "A multicenter prospective randomized clinical trial was undertaken to compare two foam dressings (Allevyn Hydrocellular, Smith & Nephew and Mepilex, Molnlycke Health Care AB) in the management of chronic venous leg ulceration. Patients were also randomized to two compression bandage systems (4-layer vs. cohesive short stretch) as a factorial design. Those with causes of ulceration other than venous disease were excluded. In all, 156 patients met the entry criteria and were randomized from the 12 clinical centers with a median (range) ulcer size of 4.33 (0.33-123.10) cm(2). After 24 weeks a total of 100 (64.1%) patients had complete ulcer closure, 46 (29.5%) had withdrawn from the trial, nine (5.8%) remained unhealed and one patient died. Of the patients randomized to Mepilex, 50/75 (66.7%) had complete ulcer healing compared with 50/81 (61.7%) on Allevyn. The hazard ratio for healing after adjustment for bandage type and trial center was 1.48 (95% C.I. 0.87-2.54, p=0.15), which only marginally changed following adjustment for baseline variables, neither of which achieved statistical significance (p=0.16). Withdrawal rates were similar between groups (23, 30.7% Mepilex vs. 23, 28.4% Allevyn). Pain improved following treatment with both dressings (p<0.001), but with no difference between dressings.", "To compare the effect on the microcirculation in venous leg ulcers (VLUs) of two treatment regimens that promote a moist wound environment versus paraffin gauze. The hypothesis is that moist wound dressings are more likely to stimulate the microcirculation and therefore angiogenesis.\n Patients with non-healing VLUs were randomised to receive either a foam dressing (Suprasorb P), a collagen dressing (Suprasorb C) plus the foam dressing, or paraffin gauze (control). All patients wore short-stretch high compression bandages. Parameters used to measure the effects of the treatments on the microcirculation were: TcPO2 measurements, video laser Doppler measurements and the number of capillaries in the wound bed. The progression towards healing was measured by the reduction in ulcer area and formation of granulation tissue. The treatment period was four weeks.\n Significant increases in TcPO2 values were reported between baseline and week 4 for patients receiving the foam dressing only or the collagen plus foam dressing combination (p<0.008 versus p<0.003 respectively). There was also a significant increase in the number of capillaries for the collagen plus foam treatment only (p<0.002).\n This pilot study suggests that a moist wound environment stimulates perfusion of blood and oxygen to the wound tissue, thereby promoting angiogenesis. The collagen and foam dressing combination demonstrated superior results to the control and the foam dressing only. Monitoring the microcirculation may help to assess the effect of dressings on VLU healing, although more research is needed.\n This pilot study was supported by a limited grant from Lohmann & Rauscher GmbH, Germany.", "A hydropolymer dressing (Tielle) and a hydrocolloid dressing (Granuflex) were compared in a randomised controlled clinical study involving 100 patients with leg ulcers and 99 patients with pressure sores in the community. Statistically significant differences in favour of the hydropolymer dressing were detected for dressing leakage and odour production, but no statistically significant differences were recorded in the number of patients with either leg ulcers or pressure sores who healed in each treatment group.", "nan", "To evaluate the safety and performance of Alione Hydrocapillary dressing (Coloplast A/S) in the management of highly exuding chronic venous leg ulcers and compare it with two hydropolymer dressings,Tielle and Tielle Plus (Johnson & Johnson).\n A comparative clinical trial was conducted on 97 patients with an ankle brachial pressure index > or = 0.8 and a highly exuding leg ulcer. Ulcer duration was at least four weeks. Treatment continued until healing or for a maximum of 12 months.\n There was no statistically significant difference in healing time or wound area reduction between the two treatment protocols. The test dressing (Alione Hydrocapillary) had better absorption capacity and was more comfortable for the patients than the comparator dressings (Tielle/Tielle Plus) and adhered less to the wound bed.Also, more patients preferred the test dressing to their previous treatment. Although severe leakage and maceration were observed more frequently in the comparator group compared with the test group, this was not statistically significant.\n Both treatment protocols were safe and effective in treating highly exuding chronic venous leg ulcers. The test dressing performed as well as or better than the comparator dressings for all study parameters and more patients preferred the test dressing to their previous dressing compared with the comparator dressings.", "In this article, we describe a randomised trial in which two established primary dressings - Comfeel (Coloplast, UK) and Granuflex improved formulation (Convatec, UK) - were compared to Cutinova foam (Beiersdorf Medical, UK) in the management of venous leg ulcers. Patients that met the study trial criteria were randomised to receive one of the three primary dressings. All ulcers were secondarily bandaged with Comprilan (Beiersdorf Medical, UK) short-stretch compression. The three dressings were compared in terms of their ability to promote ulcer healing (closure rate and healing rate) and reduce the prevalence and severity of ulcer-associated pain, over a 12-week period. The ease with which dressings could be used in a busy outpatient clinic setting was also considered. On enrollment, groups were well matched in terms of all of the patient and ulcer parameters studies. Six patients were withdrawn for reasons unrelated to study dressings or trial procedures. Following non-parametric analysis of the study data, the three dressings were found to be equally effective at promoting ulcer healing and alleviating ulcer-associated pain. Study personnel rated Cutinova Foam as easy, if not easier, to use than Comfeel or Granuflex. This study suggests that Cutinova Foam is as safe and effective as both Comfeel and Granuflex, in the treatment of venous leg ulcers.", "Venous leg ulcers are the most prevalent form of chronic wounds in the Western world. The principles of moist wound healing coupled with the use of graduated compression bandaging have become the cornerstone of treatment for venous leg ulcers but not all moist dressings are alike. To compare the attributes of a foam composite dressing with those of a hydrocellular foam dressing in the management of venous leg ulcers, a prospective, randomized, comparative 12-week study was conducted in 15 centers in the US, Canada, France, Germany, and the UK. Dressings were changed and compression bandages applied per manufacturer recommendations and dressing performance was assessed at every dressing change and at the final evaluation. Patients with venous ulcers were randomized to treatment for 12 weeks with either hydrocellular foam (n = 52) or foam composite (n = 55) dressing. Healing differences between the groups were not statistically significant, with 36% of patients using foam composite dressing healed in a mean of 66 days and 39% of patients using hydrocellular foam dressing healed in a mean of 73 days. However, the foam composite dressing performed significantly better than the hydrocellular foam dressing with regard to condition of the periwound skin - 55% of patients in the foam composite group having healed or markedly improved surrounding skin compared to 37% of patients using hydrocellular foam (P = 0.03). The foam composite dressing was rated significantly better than the hydrocellular foam dressing (\"very good\" to \"excellent\") in level of satisfaction with conformability (87% and 75%, respectively, P = 0.05); being non-sensitizing (73% and 52%, respectively, P = 0.02); and ease of application (93% and 81%, respectively, P = 0.01). The findings reported in this study suggest that the foam composite dressing offers significant improvements in the quality of life of patients with venous leg ulcers as well as for their caregivers." ]

[ "17023435", "11021553", "11825813" ]

[ "Effect of beta radiation on success of glaucoma drainage surgery in South Africa: randomised controlled trial.", "Beta radiation as an adjunct to low-risk trabeculectomy.", "Randomized controlled clinical trial of beta irradiation as an adjunct to trabeculectomy in open-angle glaucoma." ]

[ "To evaluate whether beta radiation may offer a practical method of improving surgical success for glaucoma drainage surgery in South Africa.\n Double blind, randomised controlled trial.\n Three public hospitals in South Africa.\n 450 black Africans with primary glaucoma.\n Trabeculectomy with 1000 cGy beta radiation or standard trabeculectomy without beta radiation (placebo).\n Primary outcome measure was surgical failure within 12 months (intraocular pressure > 21 mm Hg while receiving no treatment for ocular hypotension). Secondary outcomes were visual acuity, surgical reintervention for cataract, and intraoperative and postoperative complications.\n 320 people were recruited. beta radiation was given to 164; 20 (6%) were not seen again after surgery. One year after surgery the estimated risk of surgical failure was 30% (95% confidence interval 22% to 38%) in the placebo arm compared with 5% (2% to 10%) in the radiation arm. The radiation group experienced a higher incidence of operable cataract (18 participants) than the placebo group (five participants; P = 0.01). At two years the estimated risks with placebo and beta radiation were, respectively, 2.8% (0.9% to 8.3%) and 16.7% (10.0% to 27.3%).\n beta radiation substantially reduced the risk of surgical failure after glaucoma surgery. Some evidence was, however, found of an increased risk for cataract surgery (a known complication of trabeculectomy) in the beta radiation arm during the two years after surgery.\n ISRCTN62430622 [controlled-trials.com].", "To assess a single dose of intraoperative beta radiation used to enhance the success rate of trabeculectomy in a population of low-risk glaucoma patients in whom antimetabolites might not be indicated.\n A prospective randomized trial of 65 eyes was designed, with 31 eyes receiving 750 rads of intraoperative beta radiation (group 1), and 34 eyes receiving no supplementation (group 2).\n Mean follow-up time was 24 months. Mean postoperative intraocular pressure was 12.2 mmHg in group 1, and 13.7 mmHg in group 2 (P = 0.16). Mean decrease in intraocular pressure was 10.3 mmHg in group 1, and 9.3 mmHg in group 2 (P = 0.49). The two groups were not significantly different in terms of surgical complications.\n For this population of low-risk patients, there was no significant difference in outcome after applications of a single intraoperative dose of beta radiation.", "To assess the effect of a single intraoperative application of 750 cGy of beta irradiation on the outcome of trabeculectomy for uncontrolled open-angle glaucoma.\n A prospective, randomized, double-blind, placebo-controlled clinical trial.\n Sixty-one eyes of 61 Caucasian patients at low risk of filtering surgery failure, with poorly controlled primary or secondary open-angle glaucoma undergoing routine trabeculectomy.\n Patients were randomly assigned to control or beta irradiation groups. All patients underwent standard trabeculectomy with fornix-based conjunctival incision. Eyes assigned to beta irradiation received 750 cGy of beta irradiation directly over the sclerostomy site on completion of conjunctival suturing. An identical but inactive applicator was applied to control eyes, delivering no radiation. Both operator and patient remained masked to the assignment for the 12-month follow-up period.\n The main outcome measure was intraocular pressure (IOP) control. Complete success of IOP control was defined as an IOP less than 21 mmHg at 12 months without need for additional medication. Qualified success was defined as an IOP less than 21 mmHg at 12 months where additional medication was required.\n Complete success of IOP control was achieved in 19 (86%) control eyes and 35 (90%) irradiated eyes (P = 1.0). Qualified success of IOP control was achieved in 21 (95%) control eyes and 39 (100%) irradiated eyes at 12 months follow-up (P = 1.0)\n We experienced a very high success rate of filtration surgery in this select population without adjunctive irradiation. Our sample size was too small to show any improvement in success with use of beta irradiation in this group. Other studies would have to be done to determine whether it may have measurable benefit in cases with a high risk of filtration failure." ]

[ "18158176", "18951617", "21055664", "21481024" ]

[ "Specific oral tolerance induction in children with very severe cow's milk-induced reactions.", "A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy.", "Oral immunotherapy for cow's milk allergy with a weekly up-dosing regimen: a randomized single-blind controlled study.", "Oral desensitization as a useful treatment in 2-year-old children with cow's milk allergy." ]

[ "Some children allergic to cow's milk proteins (CMPs) experience exceptionally severe reactions after ingesting only trace amounts of antigen. Avoiding the food and carrying self-injectable epinephrine are the current strategies for their management.\n The aim of this study was to evaluate the safety and efficacy of specific oral tolerance induction (SOTI) for children with severe CMP-induced systemic reactions.\n Ninety-seven children aged 5 years or older with a history of severe allergic reactions and very high CMP-specific IgE levels were selected for a double-blind, placebo-controlled food challenge. Sixty had positive test results to very small amounts of milk and were randomly divided in 2 different groups. Thirty children (group A) immediately began SOTI, whereas the remaining 30 (group B) were kept on a milk-free diet and followed for 1 year.\n After 1 year, 11 (36%) of 30 children in group A had become completely tolerant, 16 (54%) could take limited amounts of milk (5-150 mL), and 3 (10%) were not able to complete the protocol because of persistent respiratory or abdominal complaints. In group B the result of the double-blind, placebo-controlled food challenge performed after a year was positive in all 30 cases (P < .001).\n In this study SOTI was effective in a significant percentage of cases.", "Orally administered, food-specific immunotherapy appears effective in desensitizing and potentially permanently tolerizing allergic individuals.\n We sought to determine whether milk oral immunotherapy (OIT) is safe and efficacious in desensitizing children with cow's milk allergy.\n Twenty children were randomized to milk or placebo OIT (2:1 ratio). Dosing included 3 phases: the build-up day (initial dose, 0.4 mg of milk protein; final dose, 50 mg), daily doses with 8 weekly in-office dose increases to a maximum of 500 mg, and continued daily maintenance doses for 3 to 4 months. Double-blind, placebo-controlled food challenges; end-point titration skin prick tests; and milk protein serologic studies were performed before and after OIT.\n Nineteen patients, 6 to 17 years of age, completed treatment: 12 in the active group and 7 in the placebo group. One dropped out because of persistent eczema during dose escalation. Baseline median milk IgE levels in the active (n = 13) versus placebo (n = 7) groups were 34.8 kUa/L (range, 4.86-314 kUa/L) versus 14.6 kUa/L (range, 0.93-133.4 kUa/L). The median milk threshold dose in both groups was 40 mg at the baseline challenge. After OIT, the median cumulative dose inducing a reaction in the active treatment group was 5140 mg (range 2540-8140 mg), whereas all patients in the placebo group reacted at 40 mg (P = .0003). Among 2437 active OIT doses versus 1193 placebo doses, there were 1107 (45.4%) versus 134 (11.2%) total reactions, with local symptoms being most common. Milk-specific IgE levels did not change significantly in either group. Milk IgG levels increased significantly in the active treatment group, with a predominant milk IgG4 level increase.\n Milk OIT appears to be efficacious in the treatment of cow's milk allergy. The side-effect profile appears acceptable but requires further study.", "Cow's milk allergy (CMA) in children is a important problem in medical practice. Oral desensitization has been proposed as a therapeutic approach, but current protocols are time-consuming and impractical.\n To establish a patient-friendly desensitization regimen with weekly up-dosing and to evaluate it in a randomized controlled trial.\n Thirty children with IgE-mediated CMA confirmed by double-blind placebo-controlled food challenge were equally randomized to desensitization with CM or soy milk as control. The weekly up-dosing lasted 18 weeks. The occurrence and severity of reactions after each dose was evaluated, and the desensitization was stopped if severe reactions occurred. Specific IgE and IgG4 levels to CM were measured at baseline, after 8 weeks, and at the end of the study. The double-blind food challenge was repeated once the desensitization was completed or after premature discontinuation.\n Two active and 1 control patient dropped out. Full tolerance to CM (200 mL) was achieved in 10 active patients and partial tolerance in 1. Two active patients discontinued the desensitization after experiencing severe reactions, whereas no reactions occurred in controls, whose sensitivity to CM remained unchanged. A significant increase in specific IgG4 levels was found only in the active group.\n This weekly up-dosing desensitization protocol for CMA performed under medical supervision was effective and reasonably safe and induced consistent immunologic changes.\n Copyright © 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.", "Limited published evidence shows oral desensitization to be a potential intervention option for cow's milk protein (CMPs) allergy.\n The aim of this study was to evaluate the safety and efficacy of oral desensitization in 2-year-old children with cow's milk allergy, as a treatment alternative to elimination diet.\n A total of 60 children aged 24-36 months with IgE-mediated allergy to CMPs were included in this multi-center study and were randomized into two groups. Thirty children (group A: treatment group) began oral desensitization immediately, whereas the remaining 30 (group B: control group) were kept on a milk-free diet and followed-up for 1 year.\n After 1-year follow-up period, 90% of the children in group A had become completely tolerant vs. 23% of the children in group B. In group A, cow's milk skin reactivity and serum-specific IgE to milk and casein decreased significantly from the initial assessment, whereas group B showed no significant change after 1 year of follow-up. Twenty-four patients (80%) developed some reaction during the treatment period: 14 children developed moderate reaction (47%) and 10 mild reaction (33%). The most common manifestations were urticaria-angioedema, followed by cough.\n In this study, oral desensitization was found to be effective in a significant percentage of 2-year-old children with cow's milk allergy. Oral desensitization appears to be efficacious as an alternative to elimination diet in the treatment of 2-year-old children with cow's milk allergy. The side-effect profile appears acceptable but requires further study.\n © 2011 Blackwell Publishing Ltd." ]

[ "16123483" ]

[ "Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes." ]

[ "To assess the application of autologous transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (PBMNCs) in the treatment of critical limb ischemia (CLI) of diabetic patients and to evaluate the safety, efficacy, and feasibility of this novel therapeutic approach.\n Twenty-eight diabetic patients with CLI were enrolled and randomized to either the transplant group or the control group. In the transplant group, the patients received subcutaneous injections of recombinant human G-CSF (600 microg/day) for 5 days to mobilize stem/progenitor cells, and their PBMNCs were collected and transplanted by multiple intramuscular injections into ischemic limbs. All of the patients were followed up after at least 3 months.\n At the end of the 3-month follow-up, the main manifestations, including lower limb pain and ulcers, were significantly improved in the patients of the transplant group. Their laser Doppler blood perfusion of lower limbs increased from 0.44 +/- 0.11 to 0.57 +/- 0.14 perfusion units (P < 0.001). Mean ankle-brachial pressure index increased from 0.50 +/- 0.21 to 0.63 +/- 0.25 (P < 0.001). A total of 14 of 18 limb ulcers (77.8%) of transplanted patients were completely healed after cell transplantation, whereas only 38.9% of limb ulcers (7 of 18) were healed in the control patients (P = 0.016 vs. the transplant group). No adverse effects specifically due to cell transplantation were observed, and no lower limb amputation occurred in the transplanted patients. In contrast, five control patients had to receive a lower limb amputation (P = 0.007, transplant vs. control group). Angiographic scores were significantly improved in the transplant group when compared with the control group (P = 0.003).\n These results provide pilot evidence indicating that the autologous transplantation of G-CSF-mobilized PBMNCs represents a simple, safe, effective, and novel therapeutic approach for diabetic CLI." ]

[ "16947782", "18358926", "17485422", "18821691", "18625622", "15188351", "18979150" ]

[ "Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate.", "Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial.", "Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab.", "Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study.", "IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial.", "Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial.", "Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate (SATORI): significant reduction in disease activity and serum vascular endothelial growth factor by IL-6 receptor inhibition therapy." ]

[ "To establish the safety and efficacy of repeat infusions of tocilizumab (previously known as MRA), a humanized anti-interleukin-6 (IL-6) receptor antibody, alone and in combination with methotrexate (MTX), for the treatment of rheumatoid arthritis (RA).\n The study group comprised 359 patients with active RA in whom the response to MTX was inadequate. During a stabilization period, these patients received their current dose of MTX for at least 4 weeks. Following stabilization, they were randomized to 1 of 7 treatment arms, as follows: tocilizumab at doses of 2 mg/kg, 4 mg/kg, or 8 mg/kg either as monotherapy or in combination with MTX, or MTX plus placebo.\n A 20% response (improvement) according to the American College of Rheumatology criteria (ACR20 response) was achieved by 61% and 63% of patients receiving 4 mg/kg and 8 mg/kg of tocilizumab as monotherapy, respectively, and by 63% and 74% of patients receiving those doses of tocilizumab plus MTX, respectively, compared with 41% of patients receiving placebo plus MTX. Statistically significant ACR50 and ACR70 responses were observed in patients receiving combination therapy with either 4 mg/kg or 8 mg/kg of tocilizumab plus MTX (P < 0.05). A dose-related reduction in the Disease Activity Score in 28 joints was observed from week 4 onward, in all patients except those receiving monotherapy with 2 mg/kg of tocilizumab. In the majority of patients who received 8 mg/kg of tocilizumab, the C-reactive protein level/erythrocyte sedimentation rate normalized, while placebo plus MTX had little effect on these laboratory parameters. Tocilizumab was mostly well tolerated, with a safety profile similar to that of other biologic and immunosuppressive therapies. Alanine transaminase and aspartate transaminase levels followed a sawtooth pattern (rising and falling between infusions). There were moderate but reversible increases in the nonfasting total cholesterol and triglyceride levels and reversible reductions in the high-density lipoprotein cholesterol and neutrophil levels. There were 2 cases of sepsis, both of which occurred in patients who were receiving combination therapy with 8 mg/kg of tocilizumab plus MTX.\n These results indicate that targeted blockade of IL-6 signaling is a highly efficacious and promising means of decreasing disease activity in RA.", "Interleukin 6 is involved in the pathogenesis of rheumatoid arthritis via its broad effects on immune and inflammatory responses. Our aim was to assess the therapeutic effects of blocking interleukin 6 by inhibition of the interleukin-6 receptor with tocilizumab in patients with rheumatoid arthritis.\n In this double-blind, randomised, placebo-controlled, parallel group phase III study, 623 patients with moderate to severe active rheumatoid arthritis were randomly assigned with an interactive voice response system, stratified by site with a randomisation list provided by the study sponsor, to receive tocilizumab 8 mg/kg (n=205), tocilizumab 4 mg/kg (214), or placebo (204) intravenously every 4 weeks, with methotrexate at stable pre-study doses (10-25 mg/week). Rescue therapy with tocilizumab 8 mg/kg was offered at week 16 to patients with less than 20% improvement in both swollen and tender joint counts. The primary endpoint was the proportion of patients with 20% improvement in signs and symptoms of rheumatoid arthritis according to American College of Rheumatology criteria (ACR20 response) at week 24. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00106548.\n The intention-to-treat analysis population consisted of 622 patients: one patient in the 4 mg/kg group did not receive study treatment and was thus excluded. At 24 weeks, ACR20 responses were seen in more patients receiving tocilizumab than in those receiving placebo (120 [59%] patients in the 8 mg/kg group, 102 [48%] in the 4 mg/kg group, 54 [26%] in the placebo group; odds ratio 4.0 [95% CI 2.6-6.1], p<0.0001 for 8 mg/kg vs placebo; and 2.6 [1.7-3.9], p<0.0001 for 4 mg/kg vs placebo). More people receiving tocilizumab than those receiving placebo had at least one adverse event (143 [69%] in the 8 mg/kg group; 151 [71%] in the 4 mg/kg group; 129 [63%] in the placebo group). The most common serious adverse events were serious infections or infestations, reported by six patients in the 8 mg/kg group, three in the 4 mg/kg group, and two in the placebo group.\n Tocilizumab could be an effective therapeutic approach in patients with moderate to severe active rheumatoid arthritis.\n F Hoffmann-La Roche, Chugai Pharmaceutical.", "To evaluate the ability of tocilizumab (a humanised anti-IL-6 receptor antibody) monotherapy to inhibit progression of structural joint damage in patients with RA.\n In a multi-centre, x ray reader-blinded, randomised, controlled trial, 306 patients with active RA of <5 years' duration were allocated to receive either tocilizumab monotherapy at 8 mg/kg intravenously every 4 weeks or conventional disease-modifying antirheumatic drugs (DMARDs) for 52 weeks. Radiographs of hands and forefeet were scored by the van der Heijde modified Sharp method.\n Patients had a mean disease duration of 2.3 years and a disease activity score in 28 joints of 6.5 at baseline. Mean total modified Sharp score (TSS) was 29.4, which was very high despite the relatively short disease duration. At week 52, the tocilizumab group showed statistically significantly less radiographic change in TSS (mean 2.3; 95% CI 1.5 to 3.2) than the DMARD group (mean 6.1; 95% CI 4.2 to 8.0; p<0.01). Tocilizumab monotherapy also improved signs and symptoms. The overall incidences of AEs were 89% and 82% (serious AEs: 18% and 13%; serious infections: 7.6% and 4.1%) in the tocilizumab and DMARD groups, respectively.\n Tocilizumab monotherapy was generally well tolerated and provided radiographic benefit in patients with RA.", "To examine the efficacy and safety of the humanized anti-interleukin-6 receptor antibody tocilizumab combined with conventional disease-modifying antirheumatic drugs (DMARDs) in patients with active rheumatoid arthritis (RA).\n A total of 1,220 patients were randomized (2:1 ratio) in the phase III, double-blind, placebo-controlled, multicenter TOWARD (Tocilizumab in Combination With Traditional DMARD Therapy) study. Patients remained on stable doses of DMARDs and received tocilizumab 8 mg/kg or placebo (control group) every 4 weeks for 24 weeks.\n At week 24, the proportion of patients achieving a response according to the American College of Rheumatology criteria for 20% improvement (ACR20) was significantly greater in the tocilizumab plus DMARD group than in the control group (61% versus 25%; P<0.0001). Secondary end points including 50% or 70% improvement (ACR50/70), the Disease Activity Score in 28 joints (DAS28), DAS28 remission responses (DAS28<2.6), European League Against Rheumatism responses, and systemic markers such as the C-reactive protein and hemoglobin levels showed superiority of tocilizumab plus DMARDs over DMARDs alone. Seventy-three percent of patients in the tocilizumab group had >or=1 adverse event (AE), compared with 61% of patients in the control group. AEs leading to withdrawal from the study were infrequent (4% of patients in the tocilizumab group and 2% of those in the control group). Serious AEs occurred in 6.7% and 4.3% of patients in the tocilizumab and control groups, respectively, and serious infections occurred in 2.7% and 1.9%, respectively. Elevations in the alanine aminotransferase level, from normal at baseline to >3-fold the upper limit of normal, occurred in 4% of patients in the tocilizumab group and 1% of those in the control group, and elevated total cholesterol levels were observed in 23% and 6% of patients, respectively. Sixteen patients started lipid-lowering therapy during the study. Grade 3 neutropenia occurred in 3.7% of patients receiving tocilizumab and none of the patients in the control group, and no grade 4 neutropenia was reported.\n Tocilizumab combined with any of the DMARDs evaluated was safe and effective in reducing articular and systemic symptoms in patients with an inadequate response to these agents.", "The phase III RADIATE study examined the efficacy and safety of tocilizumab, an anti-IL-6 receptor monoclonal antibody in patients with rheumatoid arthritis (RA) refractory to tumour necrosis factor (TNF) antagonist therapy.\n 499 patients with inadequate response to one or more TNF antagonists were randomly assigned to receive 8 mg/kg or 4 mg/kg tocilizumab or placebo (control) intravenously every 4 weeks with stable methotrexate for 24 weeks. ACR20 responses, secondary efficacy and safety endpoints were assessed.\n ACR20 was achieved at 24 weeks by 50.0%, 30.4% and 10.1% of patients in the 8 mg/kg, 4 mg/kg and control groups, respectively (less than p<0.001 both tocilizumab groups versus control). At week 4 more patients achieved ACR20 in 8 mg/kg tocilizumab versus controls (less than p = 0.001). Patients responded regardless of most recently failed anti-TNF or the number of failed treatments. DAS28 remission (DAS28 <2.6) rates at week 24 were clearly dose related, being achieved by 30.1%, 7.6% and 1.6% of 8 mg/kg, 4 mg/kg and control groups (less than p = 0.001 for 8 mg/kg and p = 0.053 for 4 mg/kg versus control). Most adverse events were mild or moderate with overall incidences of 84.0%, 87.1% and 80.6%, respectively. The most common adverse events with higher incidence in tocilizumab groups were infections, gastrointestinal symptoms, rash and headache. The incidence of serious adverse events was higher in controls (11.3%) than in the 8 mg/kg (6.3%) and 4 mg/kg (7.4%) groups.\n Tocilizumab plus methotrexate is effective in achieving rapid and sustained improvements in signs and symptoms of RA in patients with inadequate response to TNF antagonists and has a manageable safety profile.\n NCT00106522.", "Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates the immune response, inflammation, and hematopoiesis. Overproduction of IL-6 plays pathologic roles in rheumatoid arthritis (RA), and the blockade of IL-6 may be therapeutically effective for the disease. This study was undertaken to evaluate the safety and efficacy of a humanized anti-IL-6 receptor antibody, MRA, in patients with RA.\n In a multicenter, double-blind, placebo-controlled trial, 164 patients with refractory RA were randomized to receive either MRA (4 mg/kg body weight or 8 mg/kg body weight) or placebo. MRA was administered intravenously every 4 weeks for a total of 3 months. The clinical responses were measured using the American College of Rheumatology (ACR) criteria.\n Treatment with MRA reduced disease activity in a dose-dependent manner. At 3 months, 78% of patients in the 8-mg group, 57% in the 4-mg group, and 11% in the placebo group achieved at least a 20% improvement in disease activity according to the ACR criteria (an ACR20 response) (P < 0.001 for 8-mg group versus placebo). Forty percent of patients in the 8-mg group and 1.9% in the placebo group achieved an ACR50 response (P < 0.001). The overall incidences of adverse events were 56%, 59%, and 51% in the placebo, 4-mg, and 8-mg groups, respectively, and the adverse events were not dose dependent. A blood cholesterol increase was observed in 44.0% of the patients. Liver function disorders and decreases in white blood cell counts were also observed, but these were mild and transient. There was no increase in antinuclear antibodies or anti-DNA antibodies. Anti-MRA antibodies were detected in 2 patients.\n Treatment with MRA was generally well tolerated and significantly reduced the disease activity of RA.", "We investigated the clinical efficacy and safety of tocilizumab (a humanized anti-IL-6 receptor antibody) monotherapy in active rheumatoid arthritis (RA) patients with an inadequate response to low dose methotrexate (MTX). In a multicenter, double-blind, randomized, controlled trial, 125 patients were allocated to receive either tocilizumab 8 mg/kg every 4 weeks plus MTX placebo (tocilizumab group) or tocilizumab placebo plus MTX 8 mg/week (control group) for 24 weeks. The clinical responses were measured using the American College of Rheumatology (ACR) criteria and the Disease Activity Score in 28 joints. Serum vascular endothelial growth factor (VEGF) levels were also monitored. At week 24, 25.0% in the control group and 80.3% in the tocilizumab group achieved ACR20 response. The tocilizumab group showed superior ACR response criteria over control at all time points. Additionally, serum VEGF levels were significantly decreased by tocilizumab treatment. The overall incidences of adverse events (AEs) were 72 and 92% (serious AEs: 4.7 and 6.6%; serious infections: 1.6 and 3.3%) in the control and the tocilizumab groups, respectively. All serious adverse events improved by adequate treatment. Tocilizumab monotherapy was well tolerated and provided an excellent clinical benefit in active RA patients with an inadequate response to low dose MTX." ]

[ "6342396", "7377243", "11052579" ]

[ "Randomized management of the nonfrank breech presentation at term: a preliminary report.", "The randomized management of term frank breech presentation: a study of 208 cases.", "Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial. Term Breech Trial Collaborative Group." ]

[ "Cesarean section has become the standard management used by many clinicians for breech presentation in labor. Proof of the superiority of routine cesarean section has been largely circumstantial. Concern over rising cesarean section rates has led to renewed interest in possible alternatives. Protocols have been developed to select which patients may be allowed a trial of labor with frank breech presentation at term. We undertook a prospective clinical trial comparing elective cesarean section with a selective management protocol for the nonfrank breech presentation at term. One hundred five patients with nonfrank breech presentations at term in labor were studied. Seventy (67%) were randomized to a trial of labor and 35 (33%) to elective cesarean section. Of the patients allowed a trial of labor, 31 (44%) were delivered vaginally, and 39 (56%) required cesarean section. The largest single cause of a \"failed\" trial of labor was inadequate pelvic dimensions on x-ray pelvimetry (23 patients, 59%). Neonatal morbidity assessed by Apgar scores, cord gases, birth injury, and hospital stay was not different for those delivered vaginally or by cesarean section. Maternal morbidity in terms of febrile morbidity, blood transfusion, wound infections, and hospital stay was significantly greater among women delivered by cesarean section. Two of three neonatal deaths occurred in infants with major congenital anomalies. The third infant, apparently normal, died after vaginal delivery. Extensive evaluation suggests the death was attributable to inadequate resuscitation. We conclude that the use of a selective management protocol under controlled conditions is a reasonable alternative to elective cesarean section. Approximately one half of patients allowed a trial of labor may be expected to deliver vaginally with neonatal morbidity comparable to that seen with cesarean section.", "A prospective study of 208 women in labor at term with singleton fetuses in a frank breech presentation was carried out. One hundred fifteen patients were randomized to a vaginal delivery group and 93 to an elective cesarean section group. Of the 93 women scheduled for cesarean section, 88 were delivered according to protocol. Five women progressed rapidly in labor and were delivered vaginally without complications. Of the 115 women scheduled for vaginal delivery, x-ray pelvimetry was obtained on 112. Three women were delivered vaginally without incident before x-ray pelvimetry could be obtained. One of these women was delivered of an infant who died shortly after birth of lethal congenital anomalies. Of the 112 women with x-ray pelvimetry, 52 had one or more inadequate pelvic measurements and were scheduled for indicated cesarean section. Three women, however, were delivered vaginally without incident before operation could be performed. Of the remaining 60 patients in this group, 49 were delivered vaginally without a perinatal death. Eleven women required cesarean section for difficulties during labor. There were no maternal deaths, but 73 (49.3%) of the 148 women who were delivered by cesarean section in this study experienced postpartum morbidity. Only four (6.7%) of the 60 women delivered vaginally had postpartum complications. Based on the data, it seems resonable to allow vaginal delivery in carefully selected cases of term frank breech presentation.", "For 3-4% of pregnancies, the fetus will be in the breech presentation at term. For most of these women, the approach to delivery is controversial. We did a randomised trial to compare a policy of planned caesarean section with a policy of planned vaginal birth for selected breech-presentation pregnancies.\n At 121 centres in 26 countries, 2088 women with a singleton fetus in a frank or complete breech presentation were randomly assigned planned caesarean section or planned vaginal birth. Women having a vaginal breech delivery had an experienced clinician at the birth. Mothers and infants were followed-up to 6 weeks post partum. The primary outcomes were perinatal mortality, neonatal mortality, or serious neonatal morbidity; and maternal mortality or serious maternal morbidity. Analysis was by intention to treat.\n Data were received for 2083 women. Of the 1041 women assigned planned caesarean section, 941 (90.4%) were delivered by caesarean section. Of the 1042 women assigned planned vaginal birth, 591 (56.7%) delivered vaginally. Perinatal mortality, neonatal mortality, or serious neonatal morbidity was significantly lower for the planned caesarean section group than for the planned vaginal birth group (17 of 1039 [1.6%] vs 52 of 1039 [5.0%]; relative risk 0.33 [95% CI 0.19-0.56]; p<0.0001). There were no differences between groups in terms of maternal mortality or serious maternal morbidity (41 of 1041 [3.9%] vs 33 of 1042 [3.2%]; 1.24 [0.79-1.95]; p=0.35).\n Planned caesarean section is better than planned vaginal birth for the term fetus in the breech presentation; serious maternal complications are similar between the groups." ]

[ "3312207", "2190933", "4283753", "624766", "718402", "3673526", "4585947", "3551643", "8609746", "10905679", "2193477", "7064681", "8419392", "8588960", "8169699", "3334628", "2037323", "8687089", "7364818" ]

[ "Perioperative cefamandole prophylaxis against infections.", "Antibiotic prophylaxis in proximal femoral fracture.", "Cloxacillin in the prophylaxis of postoperative infections of the hip.", "Antibiotic prophylaxis in operations on trochanteric femoral fractures.", "Prophylactic use of cephradine against postoperative infections of petrochanteric fractures.", "Cefuroxime prophylaxis in trochanteric hip fracture operations.", "A double-blind clinical trial of prophylactic antibiotics in hip fractures.", "Antibiotic prophylaxis of 1,036 patients undergoing elective surgical procedures. A prospective, randomized comparative trial of cefazolin, cefoxitin, and cefotaxime in a prepaid medical practice.", "Randomised controlled trial of single-dose antibiotic prophylaxis in surgical treatment of closed fractures: the Dutch Trauma Trial.", "Single-dose antibiotic prophylaxis in osteosynthesis for hip fractures. A clinical multicentre study in Finland.", "Antibiotic prophylaxis in surgery for hip fractures.", "Antibiotic prophylaxis in open and closed fractures: a controlled clinical trial.", "Antibiotic prophylaxis with two doses of cephalosporin in patients managed with internal fixation for a fracture of the hip.", "Prophylaxis with oral cefadroxil versus intravenous cefuroxime in trochanteric fracture surgery. A clinical multicentre study.", "Double-blind randomized prospective study of the efficacy of antibiotic prophylaxis for open reduction and internal fixation of closed ankle fractures.", "Single-dose prophylaxis of ceftriaxone versus standard dosage of cefotaxime in the prophylaxis of bacterial complications in orthopedic surgery.", "Is antibiotic prophylaxis necessary for internal fixation of low-energy fractures?", "One dose cefuroxime prophylaxis in hip fracture surgery.", "Prophylactic antibiotics in hip fractures. A double-blind, prospective study." ]

[ "Seven hundred and seventeen patients were included in a prospective randomized double-blind trial comparing the efficacy of five doses of cefamandole (group I, 335 patients) with that of a single preoperative dose (group II, 382 patients) for prophylaxis against sepsis in patients who had an operation using either a Moore prosthesis, Ender or Küntscher nails, a bone plate, or another internal-fixation device. Patients who had an open fracture or total joint replacement were not included in the study. The two groups were similar in terms of mean age, sex ratio, duration of preoperative hospital stay, underlying risk factors, and type of surgical procedure. A wound infection developed in none of the seventy-four patients in group I and in five (6.6 per cent) of the seventy-six in group II (p = 0.03) who required a Moore prosthesis. A wound infection developed in three patients (1 per cent) in group I and in fifteen (5 per cent) in group II (p = 0.006) who required an internal fixation device other than a Moore prosthesis. Staphylococcus aureus, Staphylococcus epidermidis, and gram-negative bacilli were the most common infecting organisms. The rate of mortality was similar in both groups, while the percentage of postoperative urinary-tract infections was lower in group I (p = 0.04). No adverse side effects of the drug were encountered.", "A prospective randomized double-blind trial was carried out to assess the effectiveness of one dose of prophylactic cefuroxime versus placebo in 502 patients who underwent surgery for a proximal femoral fracture. With an overall deep infection rate of 2.2 per cent there was no significant difference in the superficial or deep wound infection rate between the two groups. However, there was a significant reduction in the incidence of postoperative bacteriuria in the cefuroxime group. A study of three doses of cefuroxime versus placebo is now proposed.", "nan", "Short-term prophylaxis against infection using cephalothin and cephalexin was studied in 140 patients operated on for trochanteric fractures of the femur. The group given the drug during preparation for anesthesia, intraoperatively, and for two days postoperatively had an infection rate of 1.8 per cent (one patient), whereas the group without prophylaxis had a rate of 16.9 per cent (twelve patients). The two groups were similar with regard to factors that may have influenced the infection rate, for example, age, time required for surgery, and blood loss. Staphylococcus aureus was the most common infecting organism, but several patients had mixed infections with intestinal bacteria.", "nan", "In a double-blind randomized study of antibiotic prophylaxis in trochanteric fractures operated on with a nail and plate, a 24-hour intravenous administration of cefuroxime 0.75 grams thrice daily (Group B) was compared with the previous regimen of cefuroxime for 24 hours plus 6 days of oral cephalexin (Group A). In each group, 56 (Group A) and 65 (Group B) patients could be evaluated. One deep infection occurred in Group B with growth of Staphylococcus aureus, and another 4 patients had discharge and cultures of which 2 showed S. aureus. In Group A, 6 patients had signs of an infection, and in 3 patients cultures were taken but were negative. There were no differences between the groups. We concluded that the prophylaxis time need not be longer than 3 days.", "nan", "nan", "The efficacy of prophylactic antibiotics in fracture surgery remains controversial for lack of well-documented prospective studies. We report here the findings of the Dutch Trauma Trial, a prospective, randomised, double-blind, placebo-controlled study of antibiotic prophylaxis in the primary operative treatment of limb fractures. Ceftriaxone was chosen because of its pharmacokinetic profile, including high serum levels, high tissue penetration, and long elimination half-life, makes it suitable for single-dose prophylaxis.\n Patients aged 18 years or more, attending one of fourteen Dutch centres for acute treatment of closed fractures, were randomly allocated to a single preoperative dose of ceftriaxone 2 g or placebo, and evaluated for development of wound infection and nosocomial infection at 10 days, 30 days, and 120 days. To assess the effects of drop-outs and withdrawals, best-case and worst-case analyses were performed.\n A total of 2195 patients were included. The incidence of superficial and deep wound infections after placebo was 8.3%, compared with 3.6% in the ceftriaxone group (p < 0.001, Pearson chi 2-test). The rate of nosocomial infection in the first month was 10.2% with placebo and 2.3% with ceftriaxone (p < 0.001, Pearson chi 2-test). Gram-positive bacteria were found in 74.5% of wound infections and 13.4% of nosocomial infections.\n Adequate single-dose prophylaxis with a long-acting broad-spectrum antibiotic substantially reduces the incidence of wound infection and early nosocomial infection after surgery for closed fractures.", "The use of antibiotic prophylaxis in open reduction and osteosynthesis of closed hip fractures is still controversial. The aim of this study was to demonstrate the effect of antibiotic prophylaxis in osteosynthesis of these fractures.\n A total of 224 patients operated on between November 1994 and February 1998 in six hospitals by internal fixation for a fresh hip fracture were prospectively and randomly allocated to either a ceftriaxone antibiotic prophylaxis or no prophylaxis group and followed for one year.\n Within 6 weeks after the operation, 2.6% wound infections were recorded in the antibiotic group and 4.7% in the control group. Two (1.9%) of the five infections in the control group were deep infections (both sensitive to ceftriaxone). There were no statistically significant differences between the infection rates in both groups. However, when analyzing all complications recorded within 6 weeks, significantly more complications were found in the control group (p < 0.01). In the multivariate analysis the most important factor predicting postoperative complications was the lack of antibiotic prophylaxis.\n In this study the antibiotic prophylaxis group had significantly less postoperative complications than the control group within 6 weeks after the operation.", "Totally, 185 patients, operated on for a fresh hip fracture, were randomly allocated to either methicillin antibiotic prophylaxis or no prophylaxis and followed for 1 month. Two superficial wound infections were recorded in the prophylaxis group and one in the control group. Prophylactic use of antibiotics in surgery for hip fractures seems unnecessary provided strict aseptic routines in the operating room are followed.", "The value of prophylactic antibiotics in fracture surgery was studied in a series of 90 patients with open fractures of various bones and 180 patients with closed malleolar fractures treated by open surgery. Dicloxacillin and benzyl penicillin were compared to saline (placebo). The soft tissue lesions of the open fractures were divided into Grade I wounds and Grade II & III wounds. Of the patients with Grade I wounds, 17 received dicloxacillin, 21 benzyl penicillin and 17 saline. No major infections occurred. Twelve patients with Grade II & III wounds were treated with dicloxacillin, 10 with benzyl penicillin and 13 with saline. In the saline group, 2 patients developed a deep infection. Fifty-eight patients with closed malleolar fractures received dicloxacillin, 59 benzyl penicillin and 63 saline. Two infections developed in the placebo group. A statistically significant difference was found between the number of infections in the antibiotic groups and the number in the placebo group. Superficial thromboplebitis following the antibiotic infusion occurred in 16 per cent of the dicloxacillin treated patients and in 1 per cent of those treated with benzyl penicillin or placebo.", "A prospective, randomized, double-blind study was performed to evaluate the effects of antibiotic prophylaxis on the development of a wound infection in 239 patients who had immediate stabilization of a fracture of the proximal part of the femur with a dynamic hip screw. The effects of two perioperative doses of cefotiam, given twelve hours apart, were compared with those of two doses of a placebo. Sixteen perioperative risk factors were evaluated to determine whether it was possible to identify patients who were at risk for a wound infection. All patients were followed for a minimum of six weeks. Antibiotic prophylaxis significantly reduced the prevalence of wound infection (p < 0.05): the rate of major wound infection decreased from 5 to 1 per cent and the rate of minor wound infection, from 11 to 4 per cent. The most powerful predictors of major wound infection were the duration of the operation, the interval between the accident and admission to the hospital, and the duration of postoperative urinary catheterization. The preoperative level of serum albumin and the absolute lymphocyte count were significant predictors (p < 0.05) of minor wound infection and systemic infection, respectively.", "A prospective, randomized study was performed in 559 patients to compare two doses of oral cefadroxil with three doses of intravenous cefuorxime as antibiotic prophylaxis in intra- and subtrochanteric hip fracture surgery. Antibiotic concentrations in the wound fluid were determined at the start and at the end of the operation. The first dose of cefadroxil was given about 2 h before surgery and cefuroxime about 30 min before operation. In 226/242 (93%) patients randomized to oral cefadroxil, the concentration in the wound during surgery was on average 15 micrograms/ml, i.e., well above the minimum inhibitory concentration (MIC-90) for Staphylococcus aureus. In the cefuroxime group, antibiotic levels in the wound exceeded the MIC-90 for S. aureus in 204/210 (97%) of the patients at the start and/or at the end of surgery. All patients were followed up for 4 months. One deep and five superficial infections occurred in the cefuroxime group and no deep but one superficial infection in the cefadroxil group (P = 0.07). S. aureus was cultured in three of the infected cases while cultures were negative in four patients. Four of the seven infected patients had adequate levels of antibiotic in the wound during surgery, and in three patients no antibiotic assay was performed. The infected patients did not differ in age, sex, operation time, bleeding or any other basic variable compared with patients who healed without complications. Two doses of cefadroxil seems to be practical and as effective as intravenously administered cefuroxime as antibiotic prophylaxis in trochanteric hip fracture surgery.", "Antibioprophylaxis has been proven to be efficient for some orthopaedic procedures. However, its efficacy for clean limited procedures with metallic implants is not clear. One hundred twenty-two closed ankle fracture patients undergoing open reduction and internal fixation were randomized, double-blindly, to receive either cephalothin (1 g i.v. every 6 h x four doses) or a placebo starting before tourniquet application. Mean trauma-surgery delay was 30.2 h, and average tourniquet duration was 65.4 min. Four patients (three of 62 on placebo and one of 60 on cephalothin) developed a superficial wound infection. One of the patients in the placebo group was hospitalized and treated with i.v. antibiotics. However, there was no osteomyelitis or premature hardware removal. The difference between the two groups was not statistically significant (chi 2 test of appreciation p = 0.33, two-tailed probabilities). Therefore, cephalothin prophylaxis does not seem justified in this patient population. A larger series is needed to avoid a type II error.", "nan", "A series of 54 patients who had low-energy, closed fractures requiring internal fixation were entered into a randomized prospective study comparing prophylactic antibiotics with no treatment. In five patients who did not have antibiotics a superficial wound infection or fever was recorded. In those who received antibiotics, no infection or fever was detected. However, there was no statistical difference between the two groups, and it is concluded that there is no need for prophylactic antibiotics when internally fixing low-energy fractures.", "One 3 g intravenous dose of cefuroxime during the induction of anaesthesia was administered randomly in a series of 162 consecutive hip fractures. The overall infection rate was 8.0%, and 2.4% for deep infections. The number of infections was seven in the prophylaxis group and six in the control group. The percentage of deep infections was 3.9 and 1.4, correspondingly. Antibiotic prophylaxis given did not seem to have an effect on the infection rate.", "Three hundred and seven patients, each of whom had a fracture of the proximal part of the femur, were studied in a randomized, double-blind fashion to determine whether perioperative administration of cephalothin would prevent postoperative infection. Major postoperative wound infections were significantly reduced in the cephalothin-treated group (4.7 per cent versus 0.7 per cent; p less than 0.05). There also was a reduction in the incidence of postoperative urinary-tract infections and a reduction in mean peak body temperatures. The duration of hospitalization was not affected and no hospital stay was prolonged by complications of antibiotic administration. However, in the cephalothin-treated group, a strong trend toward colonization by cephalothin-resistant organisms was noted." ]

[ "20451294" ]

[ "Cluster randomised controlled trial of an infection control education and training intervention programme focusing on meticillin-resistant Staphylococcus aureus in nursing homes for older people." ]

[ "The aim of this cluster randomised controlled trial was to test the impact of an infection control education and training programme on meticillin-resistant Staphylococcus aureus (MRSA) prevalence in nursing homes. Nursing homes were randomised to intervention (infection control education and training programme; N=16) or control (usual practice continued; N=16). Staff in intervention homes were educated and trained (0, 3 and 6 months) in the principles and implementation of good infection control practice with infection control audits conducted in all sites (0, 3, 6 and 12 months) to assess compliance with good practice. Audit scores were fed back to nursing home managers in intervention homes, together with a written report indicating where practice could be improved. Nasal swabs were taken from all consenting residents and staff at 0, 3, 6 and 12 months. The primary outcome was MRSA prevalence in residents and staff, and the secondary outcome was a change in infection control audit scores. In all, 793 residents and 338 staff were recruited at baseline. MRSA prevalence did not change during the study in residents or staff. The relative risk of a resident being colonised with MRSA in an intervention home compared with a control home at 12 months was 0.99 (95% confidence interval: 0.69, 1.42) after adjustment for clustering. Mean infection control audit scores were significantly higher in the intervention homes (82%) compared with the control homes (64%) at 12 months (P<0.0001). Consideration should be given to other approaches which may help to reduce MRSA in this setting.\n Copyright 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved." ]

[ "16822111" ]

[ "Internet-based health information consumer skills intervention for people living with HIV/AIDS." ]

[ "Medical information can improve health, and there is an enormous amount of health information available on the Internet. A randomized clinical trial tested the effectiveness of an intervention based on social- cognitive theory to improve information use among people living with HIV/AIDS. Men and women (N = 448) were placed in either (a) an 8-session intervention that focused on Internet information consumer skills or (b) a time-matched support group and were followed to 9 months postintervention. The Internet skills group demonstrated greater Internet use for health, information coping, and social support compared with the control group. The authors conclude that people with HIV infection may benefit from increased access to health information on the Internet and that vulnerability to misinformation and fraud can be reduced through behavioral interventions.\n Copyright 2006 APA, all rights reserved." ]

[ "7814828", "1103575", "5325240", "9672054", "3900796", "4573494", "2861874", "7417923" ]

[ "Eltoprazine in aggressive mentally handicapped patients: a double-blind, placebo- and baseline-controlled multi-centre study. The Eltoprazine Aggression Research Group.", "Pipamperone (Dipiperon, R3345) in troublesome mental retardates: a double-blind placebo controlled cross-over study with long-term follow-up.", "A controlled trial of prothipendyl (tolnate) in mentally subnormal patients.", "A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders.", "The effect of milenperone on the aggressive behavior of oligophrenic patients. A double-blind placebo-controlled study.", "Penfluridol (R 16341). A long-acting oral neuroleptic, as maintenance therapy for schizophrenic and mentally retarded patients. A placebo-controlled double-blind trial.", "Pipothiazine palmitate in the management of aggressive mentally handicapped patients.", "Comparison of SCH-12679 and thioridazine in aggressive mental retardates." ]

[ "The efficacy of eltoprazine, a mixed 5-HT1 agonist, in treating aggressive behaviour in mentally handicapped patients was evaluated in a double-blind, placebo- and baseline-controlled study. In the total sample of 160 patients who entered the 8 week double-blind treatment phase, efficacy was not demonstrated. Also in a 28 week double-blind follow-up study, efficacy could not be demonstrated. Post-hoc exploratory analyses suggested eltoprazine was significantly better than placebo in reducing aggression scores of a subgroup of severely aggressive patients. There was no evident relationship between the plasma level of eltoprazine and therapeutic effect or safety and tolerance. The overall safety and tolerance of chronic eltoprazine treatment was good. In the discussion, several issues and pitfalls of aggression research are dealt with.", "A 6-week double-blind cross-over study comparing pipamperone with placebo was conducted in 20 female mental retardates with behavioural disorders. The ages of the patients ranged between 22 and 42 years. After a 2-week washout period, patients were randomly allocated to either pipamperone or placebo treatment. The initial dosage of pipamperone was 40 mg b.i.d., which was gradually increased to 80 mg b.i.d. within 5 days. Patients were assessed using a ten-item rating scale before and after each week of treatment. For six of the ten items, patients showed a better response during the pipamperone than during the placebo period. When pre-trial scores were compared with those at the end of the trial, seven items had significantly improved with pipamperone. The nursing staff considered the patients more alert and amenable during pipamperone treatment.", "nan", "Neurobiological research has implicated the dopamine and serotonin systems in the pathogenesis of autism. Open-label reports suggest that the serotonin2A-dopamine D2 antagonist risperidone may be safe and effective in reducing the interfering symptoms of patients with autism.\n Thirty-one adults (age [mean+/-SD], 28.1+/-7.3 years) with autistic disorder (n=17) or pervasive developmental disorder not otherwise specified (n=14) participated in a 12-week double-blind, placebo-controlled trial of risperidone. Patients treated with placebo subsequently received a 12-week open-label trial of risperidone.\n For persons completing the study, 8 (57%) of 14 patients treated with risperidone were categorized as responders (daily dose [mean+/-SD], 2.9+/-1.4 mg) compared with none of 16 in the placebo group (P<.002). Risperidone was superior to placebo in reducing repetitive behavior (P<.001), aggression (P<.001), anxiety or nervousness (P<.02), depression (P<.03), irritability (P<.01), and the overall behavioral symptoms of autism (P<.02). Objective, measurable change in social behavior and language did not occur. Nine (60%) of 15 patients who received treatment with open-label risperidone following the double-blind placebo phase responded. Other than mild, transient sedation, risperidone was well tolerated, with no evidence of extrapyramidal effects, cardiac events, or seizures.\n Risperidone is more effective than placebo in the short-term treatment of symptoms of autism in adults.", "The antiaggressive action and the side effects of a new neuroleptic, milenperone, were evaluated in 21 oligophrenic patients by means of a double-blind randomized pilot study in comparison with placebo. Only 3 patients appeared to be psychotic, 2 from the milenperone group and 1 from the placebo group. In this study, milenperone was added to the existing psychotropic medication as an adjuvant. The test substance was administered in a dose of 2 X 10 mg daily for 6 weeks. The results were evaluated by means of the Paranoid Belligerence Scale and the improvement of the target symptoms were visualized on the Visual Analogue Line. Although, in the last 3 weeks of the study, the aggressiveness scores had decreased more in the milenperone group than in the placebo group, the difference between both studied groups was not significant. This lack of clear result may probably be ascribed to the high standard deviations, together with the small number of patients per group. The severity and frequency of the side effects remained almost unchanged during the investigation and were independent of the substance administered: milenperone or placebo.", "nan", "The efficacy of intramuscular pipothiazine palmitate (PP) in the management of aggressive mentally handicapped patients was examined in a double-blind, placebo-controlled, cross-over study, in which 30 patients received each treatment for 13 weeks. A target symptom scale of aggressiveness (TSA) and a clinical global impression scale of efficacy were rated at monthly intervals, and an extra-pyramidal side-effects scale weekly. The patients showed marked improvement during treatment with PP, which was assessed as superior to placebo. Individual and total TSA scores were also reduced compared to placebo.", "SCH-12679, a benzazepine derivative, was compared to thioridazine and to placebo on the aggressive behaviour of mentally retarded patients. After a three-week chlorpromazine (100 mg t.i.d.) standardizaton period, no significant differences between the three treatment groups were observed in their abnormal behaviour. During the comparative phase, patients treated with SCH-12679 became less hyperative and less agitated while those treated with thioridazine became more violent, more choleric and more provocative. The clinical investigator and the nursing staff found significant differences between the active drugs. As compared to the placebo, SCH-12679 improved the behaviour of the patients while thioridazine aggravated their condition. No important adverse reaction was found and the drugs did not interact with the sex of the patients and the presence of epilepsy. The results suggest that, in mental retardation, physical restraint of hyperactivity might induce aggressivity and that one should be cautious in using neuroleptics in nonpsychotic patients." ]

[ "12377958", "6387059", "2741218", "10597744", "10334524", "2066763", "9552036", "3890307" ]

[ "Time to progression in metastatic breast cancer patients treated with epirubicin is not improved by the addition of either cisplatin or lonidamine: final results of a phase III study with a factorial design.", "A phase III clinical trial comparing the combination cyclophosphamide, adriamycin, cisplatin with cyclophosphamide, 5-fluorouracil, prednisone in patients with advanced breast cancer.", "Combination of cyclophosphamide, adriamycin and platinum (CAP) versus 5-fluorouracil, adriamycin and cyclophosphamide (FAC) as primary treatment in metastatic breast cancer: results of a prospective randomized study.", "Comparison of CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) with a rotational crossing and a sequential intensification regimen in advanced breast cancer: a prospective randomized study.", "Safety and efficacy of using a single agent or a phase II agent before instituting standard combination chemotherapy in previously untreated metastatic breast cancer patients: report of a randomized study--Cancer and Leukemia Group B 8642.", "Cisplatin and etoposide as first-line chemotherapy for metastatic breast carcinoma: a prospective randomized trial of the Italian Oncology Group for Clinical Research.", "Randomized phase II trial of infusional fluorouracil, epirubicin, and cyclophosphamide versus infusional fluorouracil, epirubicin, and cisplatin in patients with advanced breast cancer.", "Cyclophosphamide, adriamycin and platinum (CAP) combination chemotherapy, a new effective approach in the treatment of disseminated breast cancer. Preliminary report." ]

[ "To investigate the value of the addition of either cisplatin (CDDP) or lonidamine (LND) to epirubicin (EPI) in the first-line treatment of advanced breast cancer.\n Three hundred seventy-one metastatic breast cancer patients with no prior systemic chemotherapy for advanced disease were randomized to receive either EPI alone (60 mg/m(2) on days 1 and 2 every 21 days), EPI and CDDP (30 mg/m(2) on days 1 and 2 every 21 days), EPI and LND (450 mg orally daily, given continuously), or EPI, CDDP, and LND. Time to progression, response rates, side effects, and survival were compared according to the 2 x 2 factorial design of this study.\n The groups were well balanced with respect to prognostic factors. Time to progression did not differ in the comparison between CDDP arms and non-CDDP arms (median, 10.9 months v 9.4 months, respectively; P =.10) or between that of LND arms and non-LND arms (median, 10.8 months v 9.9 months, respectively; P =.47), nor did overall survival. The response rate did not significantly differ in the comparison between LND arms and non-LND arms (62.9% v 54.0%, P =.08). No difference in treatment activity was observed between CDDP arms and non-CDDP arms. Toxicity was significantly higher in the CDDP arms, leading to CDDP dose adjustment in 40% of cases. The most frequent side effects were of a hematologic and gastrointestinal nature. The addition of LND produced more myalgias and fatigue.\n Neither CDDP nor LND was able to significantly improve the time to progression obtained by EPI. CDDP, however, significantly worsened the drug's tolerability.", "We assessed the efficacy of a regimen consisting of four cycles of cyclophosphamide, Adriamycin (Adria Laboratories, Inc, Columbus, Ohio), cisplatin (CAP) followed by maintenance with cyclophosphamide, 5-fluorouracil, prednisone (CFP) compared with CFP alone in a randomized trial of 86 patients with advanced breast cancer. The objective regression rates were 46% (CFP) and 49% (CAP with CFP) which included complete regression rates of 7% (CFP) and 4% (CAP with CFP). The median time to progression was nine months for CFP and six months for CAP with CFP. Median survival in the CFP group was 18 months v 11 months in the CAP recipients. Due to the therapeutic trend in favor of patients receiving CFP, we terminated the study before achieving our initially projected accrual. We observed over a twofold excess of substantial nausea and vomiting among patients receiving the platinum-based regimen. In our view, the CAP followed by the CFP regimen is a more toxic program that offers no clinically meaningful improvement over CFP to patients with advanced breast cancer.", "Based on favorable results we reported earlier with the CAP regimen in breast cancer (CAP vs CMFVP), the present study compared the CAP with the FAC regimen, which is so far one of the most active adriamycin containing chemotherapy regimens in breast cancer. The aim of the study was to find the optimal first line treatment and possibly evaluate the role of cis platinum in breast cancer chemotherapy. The CAP schedule consisted of cyclophosphamide 200 mg/m2 i.v. days 1, 3 and 5, adriamycin 40 mg/m2 i.v. day 1, and platinum 30 mg/m2 i.v. day 1, 3 and 5. The FAC schedule included 5-FU 500 mg/m2 days 1 and 8, adriamycin 50 mg/m2 day 1, and cyclophosphamide 500 mg/m2 day 1. One hundred and twenty-six previously untreated patients received greater than 2 cycles and were evaluated. In the CAP arm 15 complete (26%) and 24 partial remissions were observed, resulting in a 67% overall response rate (39/58). The response in soft tissue and visceral organs was notable (78% - 22/28, 71% - 15/21) with an important complete response rate (32%). In the FAC arm there was an overall response in 41% (28/68) of patients, with 8 complete (12%) and 20 partial responses. The difference in overall response, complete response, and response in soft tissue and visceral organs, was statistically significant in favor of the CAP arm (P less than 0.005). Concerning bone metastases there was no difference between the two schedules in response rate, nor in the median remission duration (CAP 11, FAC 10 months). In spite of a somewhat longer median survival in the CAP group, the difference (13 months vs 9 months) was not statistically significant (P = 0.10). Toxicity was moderate and tolerable in both regimens with more pronounced myelosuppression and vomiting in the CAP group. Compared with the FAC schedule the platinum containing combination chemotherapy (CAP) showed higher antitumor activity with no reflection on remission duration and survival.", "The Italian Oncology Group for Clinical Research tested two experimental chemotherapy strategies in an attempt to improve the results achievable with conventional chemotherapy in metastatic breast cancer. One hundred sixty-two patients were randomly allocated as follows: (a) to the conventional cyclophosphamide, methotrexate, 5-fluorouracil chemotherapy regimen (CMF); (b) to a rotational crossing program (ROT-CROSS); or (c) to a sequential intensification program (SEQ-INT). The same single agents (C, M, F, cisplatin, etoposide, and doxorubicin) were administered in both experimental arms, but following a different policy. The SEQ-INT program induced a significantly higher complete response (32% vs. 6%, p = 0.0006) and objective response rate (72% vs. 42%, p = 0.0047) than CMF did. There were no differences in survival between CMF and either experimental arm. A number of side effects were significantly more with both experimental chemotherapies than with CMF, but the treatments were generally tolerable. Although some caution is required when interpreting a significant advantage found between an entire chemotherapeutic strategy and a single conventional combination, this study documents the potential therapeutic advantage of administering different sequential chemotherapies, and changing each at the time of maximum result without waiting for a progression. The impressive cytoreductive effects achievable with this policy (SEQ-INT) in metastatic disease merit further investigation in the adjuvant setting.", "We undertook a prospective, randomized phase III trial to evaluate the safety and efficacy of using a phase II agent before initiating therapy with standard combination chemotherapy in metastatic breast cancer patients.\n A total of 365 women with measurable metastatic breast cancer, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either immediate chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) or up to four cycles of one of five sequential cohorts of single-agent drugs: trimetrexate, melphalan, amonafide, carboplatin, or elsamitrucin, followed by CAF.\n The toxicity of each single agent followed by CAF was comparable to that of CAF alone. The cumulative response rates for the single agent followed by CAF were not statistically different from those of CAF alone (44% v 52%; P = .24). However, in the multivariate analysis, patients with visceral disease had a trend toward lower response rates on the phase II agent plus CAF arm (P = .078). Although survival and response duration also were not statistically significantly different between the two study arms (P = .074 and P = .069, respectively), there was a suggestion of benefit for the CAF-only arm.\n The brief use of a phase II agent, regardless of its efficacy, followed by CAF resulted in response rates, toxicities, durations of response, and survival statistically equivalent to those seen with the use of CAF alone. These findings support the use of a new paradigm for the evaluation of phase II agents in the treatment of patients with metastatic breast cancer.", "In this prospective randomized study, first-line treatment with the combination of cisplatin (P) and etoposide (E) was compared with the standard cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in 140 patients. Complete remissions were obtained in 11% of 65 assessable patients on CMF and in 12% of 65 assessable patients on PE. Complete plus partial remission rates were 48% on CMF and 63% on PE (P = .08). Time to progression (median, 32 v 31 weeks), duration of response (48 v 39 weeks), and survival (75 v 76 weeks) were not different. Hematologic toxicity was significantly higher with PE, and gastrointestinal side effects were frequent with this treatment. This study demonstrated that the PE combination is effective as front-line chemotherapy. As far as response rate is concerned, a trend of superiority over CMF was observed, which was of borderline significance. Due to the lack of survival advantage and to toxicity, this combination is not recommended for routine clinical use. However, its high level of activity should be taken into account for further research.", "We previously developed an inpatient regimen that consisted of infusional fluorouracil (5-FU), epirubicin, and cisplatin (ECisF), with a response rate of 86% in advanced breast cancer. The current phase II 2:1 randomized study investigated whether cyclophosphamide can be substituted for cisplatin (ECycloF) to reduce toxicity and allow the regimen to be administered on an outpatient basis without loss of efficacy.\n Ninety-six women (median age, 49 years; range, 28 to 73) with breast cancer (59 metastatic, 37 locally advanced) received continuous infusional 5-FU (200 mg/m2/d via Hickman line) and six cycles of epirubicin (60 mg/m2 every 21 days) with either cyclophosphamide 600 mg/m2 every 21 days (38 metastatic, 24 locally advanced) or cisplatin 60 mg/m2 every 21 days (21 metastatic, 13 locally advanced). There were no significant differences in patient characteristics between these groups.\n ECycloF was better tolerated than ECisF in terms of lethargy (P = .005), stomatitis (P = .008), plantar palmar erythema (P = .02), constipation (P < .001), thrombosis (P = .0014), and nausea and vomiting (P = .05). Although there was a trend toward more anemia and leukopenia with ECisF (P =. 1), there was no significant difference in the rates of infection. Efficacy was comparable in terms of overall response (69% v 68%), complete response (CR; 13% v 15%), and median progression-free survival (9 v 8 months).\n ECycloF is an outpatient regimen with a lower incidence of severe nonhematologic toxicity than inpatient ECisF; it has comparable efficacy and is considerably more economical.", "The prospective controlled Phase III clinical trial tested the therapeutic value of the cis-platinum-adriamycin-cyclophosphamide combination (CAP), compared with the combination including cyclophosphamide, methotrexate, 5-fluorouracil, vincristine and prednisolone (CMFVP), in untreated metastatic breast cancer. One hundred and twenty-three patients (greater than 2 cycles) were evaluated: 61 on the CAP, and 62 on the CMFVP schedule. An objective response (CR + PR) to CAP combination chemotherapy was achieved in 72% of patients (43/61), with a high rate (36%) of complete remissions. In terms of metastatic site, the response rate appeared to be particularly high in soft tissue and visceral organ (lung, liver) metastases. In the CMFVP group, an objective response was noted in 26 of 62 patients (42%), with 16% complete remissions. The difference in overall therapeutic response - and in the complete remission rate as well - was statistically significant to the advantage of the CAP regimen (P less than 0.01). The duration of remissions was 6-28 + months (means = 14) for the CAP, and 4-15 + months (mean = 9) for the CMFVP schedule. Toxic side effects were more pronounced in the CAP group, particularly myelosuppression, with anemia prevailing. Side effects of CMFVP treatment were moderate. In 39 CMFVP previously treated cases, CAP was administered as second-line treatment, and an objective response was observed in 51% of cases (20/39). Results of this controlled trial showed the advantage of the CAP combination chemotherapy in the treatment of metastatic breast cancer." ]

[ "8334339" ]

[ "[Effects of baoshen pill in treating chronic renal failure with long-term hemodialysis]." ]

[ "A clinical trial, to evaluate the effects of Baoshen Pill (Rheum palmatum extract, RPE) on hemodialytic patients was conducted. 42 cases with terminal stage of renal failure (Scr < 10 ml/min) on HD were divided at random into RPE treated group and control group. The results showed there were no statistically significant differences between two groups for Scr or BUN. Serum levels of TC, LDL-c, apo B and apo B/apo A1 dropped down and HDL-c, apo A1, albumin, pro-albumin and fibrinectin increased during the follow-up period (P < 0.05) in the treated patients. It is considered that the mechanisms of RPE in preventing chronic renal failure were not the action of whole body. Improving serum levels of albumin, lipoprotein, apolipoproteins might play important role in treatment." ]

[ "483371", "2644815", "4893958", "5346629", "18077809", "10401941", "2626285", "7636936", "18077808", "7667053", "3047581", "7603807", "12432041", "22346503", "17921553", "9014599", "2027357", "17968821", "23054852", "12133656", "8102428" ]

[ "Prednisolone in the treatment of pneumococcal meningitis.", "Magnetic resonance imaging and dexamethasone therapy for bacterial meningitis.", "Corticosteroids as an adjunct to treatment in bacterial meningitis. A controlled clinical trial.", "Dexamethasone in the treatment of acute bacterial meningitis: the effect of study design on the interpretation of results.", "Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa.", "Trial of dexamethasone treatment for severe bacterial meningitis in adults. Adult Meningitis Steroid Group.", "Dexamethasone treatment for bacterial meningitis in children and adults.", "Effectiveness of adjunctive treatment with steroids in reducing short-term mortality in a high-risk population of children with bacterial meningitis.", "Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis.", "Beneficial effects of dexamethasone in children with pneumococcal meningitis.", "Dexamethasone therapy for bacterial meningitis. Results of two double-blind, placebo-controlled trials.", "Oral glycerol and intravenous dexamethasone in preventing neurologic and audiologic sequelae of childhood bacterial meningitis. The Finnish Study Group.", "Dexamethasone in adults with bacterial meningitis.", "Dexamethasone therapy for bacterial meningitis: Better never than late?", "Role of dexamethasone and oral glycerol in reducing hearing and neurological sequelae in children with bacterial meningitis.", "Dexamethasone and bacterial meningitis in Pakistan.", "The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis.", "Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled trial.", "Role of dexamethasone in neonatal meningitis: a randomized controlled trial.", "Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial.", "Dexamethasone therapy for bacterial meningitis in children. Swiss Meningitis Study Group." ]

[ "The results of a steroid on 52 Nigerians (27 males, 25 females, aged 10 to 59 years) with bacteriologically proven pneumococcal meningitis are presented. Twenty-four of the patients were treated with steroids in addition to a standard regime. The clinical features on admission in the two groups were comparable and management other than steroid administration identical. Personality change with impairment of intellect was more frequent and mortality higher in the steroid-treated group although the differences wre not statistically significant. It is concluded that steroids apparently have no beneficial effect and may worsen the prognosis in pneumococcal meningitis.", "We conducted a third placebo-controlled, double-blind study of dexamethasone as adjunctive therapy for bacterial meningitis. Thirty-one patients received cefuroxime sodium (300 mg/kg per day in 3 doses) and dexamethasone phosphate (0.6 mg/kg per day in 4 doses for 4 days), and 29 received cefuroxime and placebo. The groups were comparable at the beginning of therapy. Magnetic resonance imaging performed between days 2 and 5 of therapy was used to assess brain water content indirectly. There were no differences between the 2 treatment groups with respect to the T1- or T2-weighted images. Fifty-two patients (88%) had normal magnetic resonance images; 5 patients had parietal or bifrontal extra-axial fluid collections, and 2 children had areas of abnormal signal intensity in the brain on T2-weighted images. Abnormal findings on magnetic resonance imaging did not alter clinical management, and there was no correlation between the results of magnetic resonance imaging and the outcome of meningitis. The number of patients in this study was too small to determine any statistically significant differences in rates of hearing impairment; however, the cerebrospinal fluid findings and clinical outcome in dexamethasone-treated patients further support the previously reported beneficial effect of corticosteroid treatment in patients with bacterial meningitis.", "nan", "nan", "In sub-Saharan Africa, bacterial meningitis is common and is associated with a high mortality. Adjuvant therapy with corticosteroids reduces mortality among adults in the developed world, but it has not been adequately tested in developing countries or in the context of advanced human immunodeficiency virus (HIV) infection.\n We conducted a randomized, double-blind, placebo-controlled trial of dexamethasone (16 mg twice daily for 4 days) and an open-label trial of intramuscular versus intravenous ceftriaxone (2 g twice daily for 10 days) in adults with an admission diagnosis of bacterial meningitis in Blantyre, Malawi. The primary outcome was death at 40 days after randomization.\n A total of 465 patients, 90% of whom were HIV-positive, were randomly assigned to receive dexamethasone (233 patients) or placebo (232 patients) plus intramuscular ceftriaxone (230 patients) or intravenous ceftriaxone (235 patients). There was no significant difference in mortality at 40 days in the corticosteroid group (129 of 231 patients) as compared with the placebo group (120 of 228 patients) by intention-to-treat analysis (odds ratio, 1.14; 95% confidence interval [CI], 0.79 to 1.64) or when the analysis was restricted to patients with proven pneumococcal meningitis (68 of 129 patients receiving corticosteroids vs. 72 of 143 patients receiving placebo) (odds ratio, 1.10; 95% CI, 0.68 to 1.77). There were no significant differences between groups in the outcomes of disability and death combined, hearing impairment, and adverse events. There was no difference in mortality with intravenous ceftriaxone (121 of 230 patients) as compared with intramuscular ceftriaxone (128 of 229 patients) (odds ratio, 0.88; 95% CI, 0.61 to 1.27).\n Adjuvant therapy with dexamethasone for bacterial meningitis in adults from an area with a high prevalence of HIV did not reduce mortality or morbidity. In this setting, intramuscular administration was not inferior to intravenous administration of ceftriaxone for bacterial meningitis. (Current Controlled Trials number, ISRCTN31371499 [controlled-trials.com].).\n Copyright 2007 Massachusetts Medical Society.", "To evaluate the clinical benefit of early adjunctive dexamethasone therapy for severe bacterial meningitis in adults.\n Multicenter, double-blind, randomized trial initiated in emergency or intensive care units in France and Switzerland. Within 3 h after initiation of an aminopenicillin therapy, patients received dexamethasone (10 mg q.i.d.) or placebo for 3 days. The primary end-point was the rate of patients cured without any neurologic sequelae on day 30.\n Sixty patients were enrolled, predominantly with a severe form since 85% required ICU stay and 43% mechanical ventilation. Streptococcus pneumoniae accounted for 31 cases and Neisseria meningitidis for 18 cases. The study had to be stopped prematurely because of a new national recommendation of experts to use third generation cephalosporin and vancomycin as a result of the increasing rate of penicillin-resistant S. pneumoniae in France. After the third sequential analysis by the triangular statistical test, the difference of rate of cured patients without any neurologic sequelae was not statistically significant (p = 0.0711) between the dexamethasone group (74.2%; n = 31) and the placebo group (51.7%; n = 29). Furthermore, the former group was younger and less sick at inclusion.\n Bacterial meningitis is still a severe disease in adults, since the overall observed rate of death or severe neurologic sequelae was 26.7%. The reported data are inconclusive regarding a systematic use of dexamethasone as an adjunctive therapy for bacterial meningitis in adults. Moreover this treatment impairs antibiotic penetration into the cerebrospinal fluid (CSF) that can lead to therapeutic failure, particularly in areas with high or increasing rates of penicillin-resistant S. pneumoniae.", "Four hundred twenty-nine patients with bacterial meningitis were assigned on a nonselective alternating basis into one of two therapeutic regimens. Patients in Group I received dexamethasone in addition to standard antibacterial chemotherapy of ampicillin and chloramphenicol whereas those in Group II received antibacterial chemotherapy alone. Dexamethasone was given intramuscularly (8 mg to children younger than 12 years and 12 mg to adults every 12 hours for 3 days). Both treatment groups were comparable with regard to age, sex, duration of symptoms and state of consciousness at the time of hospitalization. A significant reduction in the case fatality rate (P less than 0.01) was observed in patients with pneumococcal meningitis receiving dexamethasone; only 7 of 52 patients died compared with 22 of 54 patients not receiving dexamethasone. A reduction in the overall neurologic sequelae (hearing impairment and paresis) was observed in patients receiving dexamethasone. This reduction was significant only in patients with Streptococcus pneumoniae meningitis; none of the 45 surviving patients receiving steroids had hearing loss whereas 4 of 32 patients not receiving dexamethasone had severe hearing loss (P less than 0.05). No significant difference was observed between the two groups with regard to time for patients to become afebrile or to regain consciousness or in the mean admission and 24- to 36-hour cerebrospinal fluid leukocyte count, glucose or protein content.", "Bacterial meningitis is still an important cause of death and/or persistent nervous system damage in children living in developing countries. The aim of the study was to evaluate the effectiveness of steroids in reducing mortality and neurologic sequelae in children affected by bacterial meningitis within the context of a developing country (Mozambique), where the case-fatality rate of this disease is over 30 per cent. Seventy children with bacterial meningitis were randomized to receive either conventional antibiotic therapy or antibiotic therapy plus dexamethasone. On hospital admission there were no statistically significant differences between the two groups with regard to clinical and laboratoristic features. When dexamethasone was used early mortality, within 24 h, was significantly reduced (1/34 v. 8/36, P < 0.05). Total mortality among steroid treated patients, including those who were comatose on admission, was also reduced even if the difference did not reach statistical significance. A favourable trend in terms of fewer serious neurologic abnormalities was also observed among survivors in the steroid treated patients (5/26 v. 7/24). Fever and CSF abnormalities also disappeared more rapidly in patients receiving dexamethasone (P < 0.05). This study showed that the beneficial effect of adjunctive steroid therapy in children with bacterial meningitis can be even more important in areas where the case-fatality rate of this disease is still very high.", "It is uncertain whether all adults with bacterial meningitis benefit from treatment with adjunctive dexamethasone.\n We conducted a randomized, double-blind, placebo-controlled trial of dexamethasone in 435 patients over the age of 14 years who had suspected bacterial meningitis. The goal was to determine whether dexamethasone reduced the risk of death at 1 month and the risk of death or disability at 6 months.\n A total of 217 patients were assigned to the dexamethasone group, and 218 to the placebo group. Bacterial meningitis was confirmed in 300 patients (69.0%), probable meningitis was diagnosed in 123 patients (28.3%), and an alternative diagnosis was made in 12 patients (2.8%). An intention-to-treat analysis of all the patients showed that dexamethasone was not associated with a significant reduction in the risk of death at 1 month (relative risk, 0.79; 95% confidence interval [CI], 0.45 to 1.39) or the risk of death or disability at 6 months (odds ratio, 0.74; 95% CI, 0.47 to 1.17). In patients with confirmed bacterial meningitis, however, there was a significant reduction in the risk of death at 1 month (relative risk, 0.43; 95% CI, 0.20 to 0.94) and in the risk of death or disability at 6 months (odds ratio, 0.56; 95% CI, 0.32 to 0.98). These effects were not found in patients with probable bacterial meningitis. Results of multivariate analysis indicated that dexamethasone treatment for patients with probable bacterial meningitis was significantly associated with an increased risk of death at 1 month, an observation that may be explained by cases of tuberculous meningitis in the treatment group.\n Dexamethasone does not improve the outcome in all adolescents and adults with suspected bacterial meningitis; a beneficial effect appears to be confined to patients with microbiologically proven disease, including those who have received prior treatment with antibiotics. (Current Controlled Trials number, ISRCTN42986828 [controlled-trials.com] .).\n Copyright 2007 Massachusetts Medical Society.", "Fifty-six children older than 2 years with meningitis caused by Streptococcus pneumoniae were enrolled in a prospective, double blind, placebo-controlled trial to evaluate the efficacy of dexamethasone therapy in addition to antimicrobial therapy. Twenty-nine of 56 received dexamethasone (0.6 mg/kg/day iv, divided into 4 daily doses for 4 days) and the remaining 27 received placebo. At the beginning of therapy the clinical and laboratory characteristics of the patients in the treatment groups were comparable, except for the Glasgow coma score (P = 0.004), which was lower in the dexamethasone group. Patients were examined daily during hospitalization and 6 weeks after discharge from the hospital. Hearing was assessed 6 weeks after discharge by means of pure tone audiometry. Two patients in the dexamethasone group and one patient in the placebo group died. There were no differences between the two groups with regard to the duration of fever, the incidence of secondary fever and electrolyte imbalance, seizure activities occurring during hospitalization and rash. Although the differences were statistically insignificant, moderate or severe unilateral or bilateral sensorineural hearing loss at 6 weeks and the overall neurologic sequelae, including hearing loss, at 1 year were higher in the placebo group, at 23% vs. 7.4% (P = 0.11) and 26.9% vs. 7.4% (P = 0.062), respectively. At 3 months after discharge, because of the improvement in hearing loss in one dexamethasone-treated patient the incidence of hearing impairment was significantly less than that in the placebo group, at 3.7% vs. 23%, respectively (P = 0.044). No improvement in hearing loss was observed after 3 months.(ABSTRACT TRUNCATED AT 250 WORDS)", "We enrolled 200 infants and older children with bacterial meningitis in two prospective double-blind, placebo-controlled trials to evaluate the efficacy of dexamethasone therapy in addition to either cefuroxime (Study 1) or ceftriaxone (Study 2). Altogether, 98 patients received placebo and 102 received dexamethasone (0.15 mg per kilogram of body weight every six hours for four days). At the beginning of therapy, the clinical and demographic characteristics of the patients in the treatment groups were comparable. The mean increase in the cerebrospinal fluid concentration of glucose and the decreases in lactate and protein levels after 24 hours of therapy were significantly greater in those who received dexamethasone than in those who received placebo (glucose, 2.0 vs. 0.4 mmol per liter [36.0 vs. 6.9 mg per deciliter], P less than 0.001; lactate, 4.0 vs. 2.1 mmol per liter [38.3 vs. 19.8 mg per deciliter], P less than 0.001; and protein, 0.64 vs. 0.25 g per liter [64.0 vs. 25.3 mg per deciliter], P less than 0.05). One patient in the placebo group in Study 1 died. As compared with those who received placebo, the patients who received dexamethasone became afebrile earlier (1.6 vs. 5.0 days; P less than 0.001) and were less likely to acquire moderate or more severe bilateral sensorineural hearing loss (15.5 vs. 3.3 percent; P less than 0.01). Twelve patients in the two placebo groups (14 percent) had severe or profound bilateral hearing loss requiring the use of a hearing aid, as compared with 1 (1 percent) in the two dexamethasone groups (P less than 0.001). We conclude that dexamethasone is beneficial in the treatment of infants and children with bacterial meningitis, particularly in preventing deafness.", "To assess the value of adjunctive intravenous dexamethasone (DXM) and oral glycerol (GLY) for the treatment of bacteriologically proved bacterial meningitis, 122 infants and children with bacterial meningitis were randomly assigned to receive DXM intravenously (n = 32), GLY orally (n = 30), DXM plus GLY (n = 34) or neither (n = 26) of these drugs. All patients were treated with the same antimicrobial agent, ceftriaxone. The patients were followed neurologically for as long as 6 months. A thorough hearing evaluation was performed routinely 2 months or more after discharge from hospital. Overall 4 (7%) of the GLY-treated patients, compared with 11 (19%) of those not given GLY, developed audiologic or neurologic sequelae (P = 0.052), the relative risk of sequelae being 2.94 (95% confidence interval, 0.99 to 8.72). The patients who had received GLY showed less severe or profound bilateral hearing impairment than those not given GLY (0 vs. 7%, P = 0.049), and none of them had other neurologic abnormalities 3 or 6 months after discharge, compared with 5 (9%) of those not treated with GLY (P = 0.024). The DXM recipients showed only a tendency to less severe hearing impairment than those not given DXM. In conclusion oral GLY prevented neurologic sequelae in infants and children with bacterial meningitis more effectively than intravenous DXM.", "Mortality and morbidity rates are high among adults with acute bacterial meningitis, especially those with pneumococcal meningitis. In studies of bacterial meningitis in animals, adjuvant treatment with corticosteroids has beneficial effects.\n We conducted a prospective, randomized, double-blind, multicenter trial of adjuvant treatment with dexamethasone, as compared with placebo, in adults with acute bacterial meningitis. Dexamethasone (10 mg) or placebo was administered 15 to 20 minutes before or with the first dose of antibiotic and was given every 6 hours for four days. The primary outcome measure was the score on the Glasgow Outcome Scale at eight weeks (a score of 5, indicating a favorable outcome, vs. a score of 1 to 4, indicating an unfavorable outcome). A subgroup analysis according to the causative organism was performed. Analyses were performed on an intention-to-treat basis.\n A total of 301 patients were randomly assigned to a treatment group: 157 to the dexamethasone group and 144 to the placebo group. The base-line characteristics of the two groups were similar. Treatment with dexamethasone was associated with a reduction in the risk of an unfavorable outcome (relative risk, 0.59; 95 percent confidence interval, 0.37 to 0.94; P=0.03). Treatment with dexamethasone was also associated with a reduction in mortality (relative risk of death, 0.48; 95 percent confidence interval, 0.24 to 0.96; P=0.04). Among the patients with pneumococcal meningitis, there were unfavorable outcomes in 26 percent of the dexamethasone group, as compared with 52 percent of the placebo group (relative risk, 0.50; 95 percent confidence interval, 0.30 to 0.83; P=0.006). Gastrointestinal bleeding occurred in two patients in the dexamethasone group and in five patients in the placebo group.\n Early treatment with dexamethasone improves the outcome in adults with acute bacterial meningitis and does not increase the risk of gastrointestinal bleeding.\n Copyright 2002 Massachusetts Medical Society", "A multicentre randomized controlled trial was conducted in children with bacterial meningitis using dexamethasone or placebo for four days within 24 h of starting antibiotics. Primary outcomes were hearing loss and neurological abnormalities at 12 months after meningitis. The dexamethasone (n=50) and placebo (n=51) groups were similar in age, severity of illness and etiological agent. Hearing loss occurred in 10% and 11% of the dexamethasone and placebo groups and neurological deficits occurred in 20% and 18% of patients, respectively. Duodenal perforation occurred in one dexamethasone-treated child. In conclusion, there was no significant benefit in those receiving dexamethasone. The lack of benefit may have been due to the delay in administration of dexamethasone (median delay of 11 h after antibiotics). Therefore, if dexamethasone is used for meningitis it should be given immediately with the antibiotic.", "To investigate the efficacy of dexamethasone and oral glycerol in reducing hearing and neurological sequelae in children with acute bacterial meningitis (ABM).\n Prospective double blind, placebo controlled randomized study.\n Pediatric services of a tertiary care teaching and referral hospital.\n Children 2 months to 12 years with a diagnosis of acute bacterial meningitis admitted between June 2002 to September 2003.\n Subjects were assigned randomly to receive dexamethasone, glycerol, dexamethasone+glycerol or placebo. Neurological and hearing impairment was assessed at discharge and after 1 month.\n 58 children (48 boys, 10 girls), mean age 50.2 +/- 41.0 months, were studied. Twelve patients received dexamethasone, 13 glycerol, 20 dexamethasone + glycerol and 13 placebo. Bacterial etiology was ascertained in 24 patients: Streptococcus pneumoniae-10, H influenzae b-7, Staph. aureus-5 and others-2. Three (5.2%) children died during hospital stay and 55 survived. Seven (12%) patients had neurological sequelae (3 in glycerol, 3 in dexamethasone+glycerol, 1 in placebo group, P = 0.29), and 10 patients (17%) had hearing sequelae (2 in glycerol, 3 in dexamethasone, 2 dexamethasone + glycerol and 3 in placebo group, P = 0.68).\n No significant difference was seen in neurological or hearing outcome with use of either glycerol or dexamethasone in children with acute bacterial meningitis.", "The objective of this study was to assess, in a developing country setting, the effect of dexamethasone therapy on bacterial meningitis outcomes. A prospective double blind placebo controlled trial was conducted in 89 children aged from 2 months to 12 years suffering from bacterial meningitis. Neurological, developmental, and hearing assessments were conducted at one, four, and 12 months after discharge. Forty eight patients received dexamethasone and 41 placebo. Initial antimicrobial drugs used were ampicillin and chloramphenicol. For all patients at the time of admission the mean duration of illness was 5.7 days; 47% had had seizures and 56% had impaired consciousness. Seventeen of 89 (19%) patients died. The mortality for the dexamethasone group was 25% as compared with 12% in the group receiving placebo. Presentation to the hospital after four days of symptoms and with impaired conscious state were independent predictors of death. Of the dexamethasone group survivors, 26.5% had neurological sequelae and 42.3% had hearing impairment, whereas in the placebo group it was 24% and 30% respectively. Altered state of consciousness was a predictor of neurological sequelae. The presence of neurological sequelae and high cerebrospinal fluid protein independently predicted hearing loss. No beneficial effect of dexamethasone was observed on morbidity or mortality of this group of patients with bacterial meningitis. Dexamethasone is therefore not useful in developing countries as adjunctive treatment in patients seriously ill with bacterial meningitis, who present late for treatment and have been partially treated.", "In experimental models of meningitis and in children with meningitis, dexamethasone has been shown to reduce meningeal inflammation and to improve the outcome of disease.\n We conducted a placebo-controlled, double-blind trial of dexamethasone therapy in 101 infants and children admitted to the National Children's Hospital, San José, Costa Rica, who had culture-proved bacterial meningitis or clinical signs of meningitis and findings characteristic of bacterial infection on examination of the cerebrospinal fluid. The patients were randomly assigned to receive either dexamethasone and cefotaxime (n = 52) or cefotaxime plus placebo (n = 49). Dexamethasone (0.15 mg per kilogram of body weight) was given 15 to 20 minutes before the first dose of cefotaxime and was continued every 6 hours thereafter for four days.\n The demographic, clinical, and laboratory profiles were similar for the patients in the two treatment groups. By 12 hours after the beginning of therapy, the mean opening cerebrospinal pressure and the estimated cerebral perfusion pressure had improved significantly in the dexamethasone-treated children but worsened in the children treated only with cefotaxime (controls). At 12 hours meningeal inflammation and the concentrations of two cytokines (tumor necrosis factor alpha and platelet-activating factor) in the cerebrospinal fluid had decreased in the dexamethasone-treated children, whereas in the controls the inflammatory response in the cerebrospinal fluid had increased. At 24 hours the clinical condition and mean prognostic score were significantly better among those treated with dexamethasone than among the controls. At follow-up examination after a mean of 15 months, 7 of the surviving 51 dexamethasone-treated children (14 percent) and 18 of 48 surviving controls (38 percent) had one or more neurologic or audiologic sequelae (P = 0.007); the relative risk of sequelae for a child receiving placebo as compared with a child receiving dexamethasone was 3.8 (95 percent confidence interval, 1.3 to 11.5).\n The results of this study, in which dexamethasone administration began before the initiation of cefotaxime therapy, provide additional evidence of a beneficial effect of dexamethasone therapy in infants and children with bacterial meningitis.", "Despite favorable meta-analyses, no study involving third-generation cephalosporins for the treatment of childhood bacterial meningitis has documented a benefit of adjuvant dexamethasone therapy if the outcomes are examined individually.\n We conducted a prospective, randomized, double-blind trial comparing adjuvant dexamethasone or glycerol with placebo in children aged from 2 months through 16 years in Latin America. Ceftriaxone was administered to all children; children were randomized to also receive dexamethasone intravenously, glycerol orally, both agents, or neither agent. Primary end points were death, severe neurological sequelae, or deafness, with the first 2 end points forming a composite end point. A subgroup analysis for Haemophilus influenzae type b meningitis was undertaken. Intention-to-treat analysis was performed using binary logistic regression models.\n H. influenzae type b, pneumococci, and meningococci were the main agents found among 654 patients; dexamethasone was given to 166, dexamethasone and glycerol were given to 159, glycerol was given to 166, and placebo was given to 163. No adjuvant therapy significantly affected death or deafness. In contrast, glycerol and dexamethasone plus glycerol reduced severe neurological sequelae, compared with placebo; the odds ratios were 0.31 (95% confidence interval [95% CI], 0.13-0.76; P=.010) and 0.39 (95% CI, 0.17-0.93; P=.033), respectively. For neurological sequelae and death, the odds ratios were 0.44 (95% CI, 0.25-0.76; P=.003) and 0.55 (95% CI, 0.32-0.93; P=.027), respectively. Dexamethasone therapy prevented deafness in patients with H. influenzae type b meningitis only if patients were divided grossly into dexamethasone recipients and nonrecipients and if timing between dexamethasone and ceftriaxone administration was not taken into account (odds ratio, 0.27; 95% CI, 0.09-0.77; P=.014).\n Oral glycerol therapy prevents severe neurological sequelae in patients with childhood meningitis. Safety, availability, low cost, and oral administration also add to its usefulness, especially in resource-limited settings.", "To evaluate the role of dexamethasone therapy in neonatal meningitis in a randomized placebo controlled trial.\n The participants were eighty neonates with meningitis randomized to receive dexamethasone or saline placebo. Dexamethasone was started prior to the first dose of antibiotics in the dose of 0.15 mg/kg intravenous 6 hourly for 2 d. Primary outcome measure was mortality. Secondary outcome measures included progression of systemic inflammatory response syndrome (SIRS) up to 48 h, differences in cerebrospinal fluid (CSF) cytokines between baseline levels and 24 h after enrolment and brain stem auditory evoked response (BAER) after 4 to 6 wk of discharge.\n Baseline variables were comparable in both the groups. Mortality was significantly decreased in dexamethasone group (p = 0.005) and the absolute risk difference was 27.5 % (95 % CI 9.5-45.8 %). There was a significant reduction in cells per mm(3) (62.5 vs. 100) and proteins (162 vs. 217.5 mg/dl) after 24 h of treatment in the dexamethasone group. IL-1β was significantly reduced after 24 h in dexamethasone group (290 vs 665 pg/ml). TNF- α was significantly lower (157.5 vs 427.5 pg/ml) and sugar significantly higher (50 vs 38 mg/dl) in the dexamethasone group after 24 h. Significant difference was noted between dexamethasone and saline groups in the progression of SIRS.\n Dexamethasone significantly reduced fatality, progression of SIRS and CSF inflammatory indices.", "Steroids are used as adjuvant treatment in childhood pyogenic meningitis to attenuate host inflammatory responses to bacterial invasion. We aimed to assess the effectiveness of dexamethasone in management of acute bacterial meningitis in a developing country.\n In a double-blind, placebo controlled trial, we included 598 children with pyogenic meningitis who had been admitted to the children's wards of the Queen Elizabeth Central Hospital, Blantyre, Malawi. We did physical, neurological, developmental, and hearing assessments at 1 and 6 months after discharge. The primary outcome was overall death. Secondary outcomes included sequelae, in-hospital deaths, and death after discharge. Analysis was done by intention to treat.\n Of the 598 included children, 307 (51%) were assigned to dexamethasone and 295 (49%) to placebo. 338 (40%) of 598 patients had Streptococcus pneumoniae, 170 (28%) Haemophilus influenzae type b, 66 (11%) Neisseria meningitidis, and 29 (5%) Salmonella spp. 78 (13%) patients had no growth on culture. The number of overall deaths was the same in the two treatment groups (relative risk 1.00 [95% CI 0.8-1.25], p=0.93). At final outcome, sequelae were identified in 84 (28%) of children on steroids and in 81 (28%) on placebo (relative risk 0.99 [95% CI 0.78-1.27], p=0.97). The number of children dying in hospital did not differ between groups.\n Steroids are not an effective adjuvant treatment in children with acute bacterial meningitis in developing countries.", "Routine use of steroids as adjunctive treatment of bacterial meningitis remains controversial. We have carried out a prospective, placebo-controlled, double-blind study of dexamethasone in 115 children with acute bacterial meningitis in Switzerland. The patients were randomly assigned to receive either placebo (n = 55) or dexamethasone (n = 60) in addition to optimum antibiotic treatment (100 mg/kg daily ceftriaxone). Dexamethasone therapy (0.4 mg/kg) was started 10 min before the first dose of ceftriaxone and given every 12 h for 2 days. Baseline demographic, clinical, and laboratory features of the two groups were similar. After 24 h treatment meningeal inflammation as shown by cerebrospinal fluid (CSF) glucose concentration was significantly less with dexamethasone than with placebo (mean increase in glucose 63 [76] vs 40 [75]%, p = 0.008). However, other indices of inflammation showed similar changes in both groups. Addition of dexamethasone did not affect the rate at which CSF became sterile. Both groups showed prompt clinical responses and similar frequencies of complications (15 vs 12%). Monitoring for possible adverse effects of dexamethasone revealed no abnormalities. At follow-up examinations 3, 9, and 15 months after hospital discharge, 9 (16%) of 55 placebo recipients and 3 (5%) of 60 dexamethasone recipients had one or more neurological or audiological sequelae (p = 0.066); the relative risk of sequelae was 3.27 (95% CI 0.93-11.47). Our results and those of similarly designed studies lead us to believe that adjunctive dexamethasone therapy improves outcome from bacterial meningitis in infants and children. We recommend its use, preferably in the dose regimen used in this study." ]

[ "9892331", "11777865", "10390264", "11529382", "2196152", "11177086", "15494842", "2525996", "11450886", "2691478", "7675380" ]

[ "Oral vs intravenous ciprofloxacin in the initial empirical management of severe pyelonephritis or complicated urinary tract infections: a prospective randomized clinical trial.", "Short-term effectiveness of ceftriaxone single dose in the initial treatment of acute uncomplicated pyelonephritis in women. A randomised controlled trial.", "Oral versus initial intravenous therapy for urinary tract infections in young febrile children.", "Oral ceftibuten switch therapy for acute pyelonephritis in children.", "Intravenous and oral ciprofloxacin versus intravenous ceftazidime for the treatment of severe urinary tract infections.", "The addition of ceftriaxone to oral therapy does not improve outcome in febrile children with urinary tract infections.", "Comparison of intravenous aminoglycoside therapy with switch therapy to cefixime in urinary tract infections.", "[Aztreonam vs norfloxacin: a comparative study of the treatment of urinary tract infections in ambulatory and hospitalized patients].", "Comparative study of cefixime alone versus intramuscular ceftizoxime followed by cefixime in the treatment of urinary tract infections in children.", "Urinary tract infections with tissue penetration in children: cefotaxime compared with amoxycillin/clavulanate.", "Outpatient treatment of pyelonephritis in pregnancy: a randomized controlled trial." ]

[ "There are few data on the efficacy of oral antibiotics in the initial empirical management of severe forms of urinary tract infection (UTI).\n In a multicenter, prospective, randomized trial we compared oral (500 mg twice daily) vs intravenous ciprofloxacin (200 mg twice daily) in the initial empirical management of hospitalized patients with serious forms of UTI. Exclusion criteria were severe sepsis, inability to take oral medication, or the presence of obstruction or renal foci of suppuration. The study population included 66 women with pyelonephritis, 43 patients with community-acquired UTIs, and 32 patients with hospital-acquired UTIs. The frequency of bacteremia was 28 (42%) of 66 in the patients with pyelonephritis and 25 (33%) of 75 in those with complicated UTIs. Seventy-two patients were randomized to treatment with oral and 69 to intravenous ciprofloxacin.\n There were no infection-related deaths and no patients required an early change of antibiotics because of worsening clinical status during the initial empirical phase of treatment. The mean duration of fever was 1.7 days in patients treated by the oral vs 1.9 days in patients treated by the intravenous route (P = .15). The rates of microbiological failure (3% in the oral vs 2% in the intravenous treatment group) and of unsatisfactory clinical response (4% oral vs 3% intravenous) were low. A treatment change was eventually required in 14% of the patients assigned to the oral and 7% of the patients assigned to the intravenous regimen, mainly because of the isolation of enterococci or ciprofloxacin-resistant organisms in pretherapy urine specimens.\n In the hospital setting, oral ciprofloxacin is as effective as the intravenous regimen in the initial empirical management of serious UTIs, including bacteremic forms, in patients without severe sepsis, obstruction, or renal foci of suppuration. The efficacy of the oral regimen indicates a potential use for ciprofloxacin in outpatient treatment of a subset of patients currently hospitalized on account of disease severity.", "To compare the short-term effectiveness of ceftriaxone single dose followed by cefixime with a standard treatment of acute uncomplicated pyelonephritis in women.\n An open, prospective, and randomised trial of women with acute uncomplicated pyelonephritis was performed. Group A were given a daily intravenous dose of 1 g ceftriaxone; group B: ceftriaxone 1 g intravenous single dose followed by oral cefixime. When urine culture was received, both groups completed a 10 day treatment based in sensitivity studies. Only women with positive initial urine culture were included. After three days of treatment, clinical and bacteriological efficacy was assessed. Clinical response was classified as \"cured\" if acute symptoms (fever, urinary syndrome and flank pain) were settled. Bacteriological response was classified as: eradication, or no eradication.\n Of 144 eligible patients, urine culture was positive in 54 of 72 (75%) women in group A and 51 of 72 (71%) in group B. There were no significant differences between groups in resolution of acute symptoms. Clinical cure was observed in 49 of 54 (91%) patients in the group A and in 47 of 51 (92%) patients in the group B (p = 0.68). After three days of treatment urine culture was negative for all patients. No adverse effects were observed in either of the groups.\n These data suggest that a intravenous single dose of ceftriaxone followed by oral cefixime is both effective and safe for the initial treatment of acute uncomplicated pyelonephritis in women. This regimen could be useful in managing selected patients with pyelonephritis as outpatients.", "The standard recommendation for treatment of young, febrile children with urinary tract infection has been hospitalization for intravenous antimicrobials. The availability of potent, oral, third-generation cephalosporins as well as interest in cost containment and avoidance of nosocomial risks prompted evaluation of the safety and efficacy of outpatient therapy.\n In a multicenter, randomized clinical trial, we evaluated the efficacy of oral versus initial intravenous therapy in 306 children 1 to 24 months old with fever and urinary tract infection, in terms of short-term clinical outcomes (sterilization of the urine and defervescence) and long-term morbidity (incidence of reinfection and incidence and extent of renal scarring documented at 6 months by 99mTc-dimercaptosuccinic acid renal scans). Children received either oral cefixime for 14 days (double dose on day 1) or initial intravenous cefotaxime for 3 days followed by oral cefixime for 11 days.\n Treatment groups were comparable regarding demographic, clinical, and laboratory characteristics. Bacteremia was present in 3.4% of children treated orally and 5.3% of children treated intravenously. Of the short-term outcomes, 1) repeat urine cultures were sterile within 24 hours in all children, and 2) mean time to defervescence was 25 and 24 hours for children treated orally and intravenously, respectively. Of the long-term outcomes, 1) symptomatic reinfections occurred in 4.6% of children treated orally and 7.2% of children treated intravenously, 2) renal scarring at 6 months was noted in 9.8% children treated orally versus 7.2% of children treated intravenously, and 3) mean extent of scarring was approximately 8% in both treatment groups. Mean costs were at least twofold higher for children treated intravenously ($3577 vs $1473) compared with those treated orally.\n Oral cefixime can be recommended as a safe and effective treatment for children with fever and urinary tract infection. Use of cefixime will result in substantial reductions of health care expenditures.", "The available oral third generation of cephalosporin, \"ceftibuten\" was used to substitute the intravenous drug after defervescence in acute pyelonephritis in children. This randomized controlled study compared the efficacy of an oral ceftibuten switch therapy with a ceftriaxone in both short-term and long-term outcomes. 36 99mTc-dimercaptosuccinic acid (DMSA) scan proved pyelonephritis patients were randomized into the study group, \"ceftibuten\" (N=18) and the control group, \"ceftriaxone\" (N=18). Ceftriaxone (75 mg/kg/day) was the initial antibiotic in both groups. After defervescence for 24-48 hours, oral ceftibuten (9 mg/kg/day) was substituted in the study group and continued for 10 days. The subject characteristics and laboratory data were not different between the two groups. The urine culture at D14 was sterilized in both groups. The incidence of renal scarring was 66.6 per cent and 61.1 per cent in the study group and the control group respectively. The rate of recurrent infection showed no statistical significance. The duration of hospitalization was shorter in the study group than in the control. In conclusion, oral ceftibuten switch therapy can be recommended as a safe and effective treatment for acute pyelonephritis in children. The use of oral therapy may result in a significant reduction of health care expenditure.", "nan", "To determine whether the addition of a single dose of ceftriaxone sodium to a 10-day course of trimethoprim and sulfamethoxazole hastens urine sterilization or resolution of clinical symptoms in febrile children with urinary tract infections.\n Prospective, single-blind, randomized study.\n Tertiary care children's hospital emergency department.\n Febrile children aged 6 months to 12 years with a presumptive urinary tract infection based on history, physical examination, and urinalysis findings.\n A history was taken, a physical examination and urinalysis and culture were performed, and a white blood cell count and erythrocyte sedimentation rate were obtained. Children were randomized to receive an intramuscular dose of ceftriaxone then 10 days of trimethoprim-sulfamethoxazole (IM + PO group) or oral trimethoprim-sulfamethoxazole alone (PO group). After receiving study medication, patients were discharged from the hospital to return in 48 hours for a follow-up evaluation and urine culture. Treatment failure was defined as the persistence of a positive culture at 48 hours or the need for hospital admission for intravenous rehydration or antibiotic therapy.\n Sixty-nine children were enrolled, 34 in the IM + PO group and 35 in the PO group. The 2 groups were similar at the initial visit with respect to age, sex, clinical degrees of illness, white blood cell count, and erythrocyte sedimentation rate (P>.05). At the 48-hour follow-up visit, there were no differences between the 2 treatment groups in resolution of vomiting, fever, general appearance, abdominal tenderness, and hydration state (P>.05). There were 9 treatment failures, 4 in the IM + PO group and 5 in the PO group (P =.93).\n The addition of a single dose of intramuscular ceftriaxone to a 10-day course of oral trimethoprim-sulfamethoxazole for urinary tract infection with fever resulted in no difference at 48 hours in the urine sterilization rate, degree of clinical improvement, or subsequent hospital admission rate.", "nan", "Eighty-two evaluable patients suffering from UTI were randomly treated with parenteral Aztreonam (1 g OD in cystitis and 1 g BID in pyelonephritis) or oral Norfloxacin (400 mg BID). Predisposing urological conditions were present in 75% and 78.5% respectively. Microbiological cultures at the end of treatment and at a follow-up visit after 4 weeks showed significantly better results among Aztreonam treated patients (microbiological cure: 97.5% vs 71.4%-p less than or equal to 0.005). Clinical cure was achieved in 97.5% and 71.4% respectively (p less than or equal to 0.001). A statistically significant difference was present only in patients treated for pyelonephritis (microbiological cure-AZT: 100%; NOR: 50%-p less than or equal to 0.0005) and not in those with cystitis (AZT: 95.0%; NOR: 83.3%). Side effects were rare in both treatments. Aztreonam seems to offer major advantages, when compared to Norfloxacin, in the treatment of UTI, especially when upper urinary tract is involved.", "Urinary tract infections (UTI) can cause acute morbidity and may result in severe problems, including hypertension and reduced renal function. Diagnosis of UTI is extremely important since prompt treatment may prevent damage. In the present study we compared the efficacy of oral cefixime to initial intramuscular ceftizoxime followed by cefixime for the treatment of UTI in children. Fifty-four children were studied. They were randomized to receive either oral cefixime 8 mg/kg/day for 10 days or initial intramuscular ceftizoxime (Cefizox) 50 mg/kg twice a day for 2 days followed by oral cefixime for 8 days. Treatment groups were comparable regarding age, sex, clinical, and laboratory findings. Escherichia coli was isolated from 80% of patients. Repeat urine cultures were sterile within 24 hours in all children. Cure rates were comparable in both groups (92% vs 86% at the end of treatment). No serious adverse effects were observed. We concluded that oral cefixime is a safe and effective alternative treatment.", "In children, the site of urinary tract infection (acute pyelonephritis or cystitis) cannot usually be accurately determined from the clinical presentation. The severity of the urinary tract infection (risk of renal scars) is best correlated with its estimated degree of tissue penetration clinically (fever, general condition) and on laboratory tests (sedimentation rate, C-reactive protein). The duration of parenteral antibiotic therapy, especially in children (taking account of difficult venous access and the cost of hospitalization) needs to be specified beyond the initial period required for sterilization of the urine (usually less than 48 h). We conducted a study in children older than one year to compare the efficacy and tolerance of two treatment regimens for urinary tract infection with tissue penetration: cefotaxime 100 mg/kg/d in four divided iv doses for 14 days (group I) and amoxycillin/clavulanate 100 mg/kg/d in four divided iv doses for seven days with conversion to the oral route at a dosage of 50 mg/kg/d for seven days (group II). The randomised protocol included ten patients in each group, comparable with respect to sex, age and history. Clinical efficacy (time until the patient became afebrile), bacteriological efficacy (sterilization of the urine), and biological efficacy (time to normalization of the indices of the acute inflammatory response) were identical for both groups regardless of the duration of iv antibiotic treatment (seven days for amoxycillin/clavulanate; 14 days for cefotaxime). The only side effect was diarrhoea, which affected three patients and did not require modification of the oral treatment regimen.(ABSTRACT TRUNCATED AT 250 WORDS)", "To compare the safety and efficacy of outpatient and inpatient treatment of pyelonephritis in pregnancy.\n We performed a randomized controlled trial of pregnant women with pyelonephritis before 24 weeks' estimated gestational age, comparing inpatient and outpatient treatment. Sixty inpatients received cefazolin intravenously until afebrile for 48 hours, and 60 outpatients received two injections of ceftriaxone intramuscularly. All patients completed a 10-day course of oral cephalexin. We performed a urine culture 5-14 days after completion of therapy.\n The two groups were similar with respect to age, parity, temperature, estimated gestational age, initial white blood cell count, and incidence of bacteremia. Escherichia coli was the major uropathogen isolated (86% of cultures, 95 of 111). Twelve percent (13 of 111) of bacteria were resistant to cefazolin. Eleven outpatients and 12 inpatients had positive urine cultures after therapy (relative risk 0.9, 95% confidence interval 0.4-1.9). Three patients in each group had recurrent pyelonephritis. We switched six inpatients to gentamicin because of a worsening clinical picture (two) or a prolonged febrile course (four); no outpatients required a change in antibiotic (Fisher exact test, P = .03). One preterm delivery occurred in an inpatient with recurrent pyelonephritis.\n Outpatient antibiotic therapy is effective and safe in selected pregnant women with pyelonephritis." ]

[ "9704717", "1954179", "7993833", "12839848", "8080680", "7881965", "1782080", "9862047", "11432629", "11709566" ]

[ "Effect of preoperative chemotherapy on the outcome of women with operable breast cancer.", "Effects of primary chemotherapy in conservative treatment of breast cancer patients with operable tumors larger than 3 cm. Results of a randomized trial in a single centre.", "Primary (neoadjuvant) chemotherapy and radiotherapy compared with primary radiotherapy alone in stage IIb-IIIa breast cancer.", "Preoperative FLAC/granulocyte-colony-stimulating factor chemotherapy for stage II breast cancer: a prospective randomized trial.", "Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast conserving surgery: preliminary results of a randomised trial: S6.", "Prospective randomized study of surgical morbidity following primary systemic therapy for breast cancer.", "Neoadjuvant chemotherapy in operable breast cancer.", "A reduction in the requirements for mastectomy in a randomized trial of neoadjuvant chemoendocrine therapy in primary breast cancer.", "Estrogen-receptor-directed neoadjuvant therapy for breast cancer: results of a randomised trial using formestane and methotrexate, mitozantrone and mitomycin C (MMM) chemotherapy.", "Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902." ]

[ "To determine, in women with primary operable breast cancer, if preoperative doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan; AC) therapy yields a better outcome than postoperative AC therapy, if a relationship exists between outcome and tumor response to preoperative chemotherapy, and if such therapy results in the performance of more lumpectomies.\n Women (1,523) enrolled onto National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 were randomly assigned to preoperative or postoperative AC therapy. Clinical tumor response to preoperative therapy was graded as complete (cCR), partial (cPR), or no response (cNR). Tumors with a cCR were further categorized as either pathologic complete response (pCR) or invasive cells (pINV). Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were estimated through 5 years and compared between treatment groups. In the preoperative arm, proportional-hazards models were used to investigate the relationship between outcome and tumor response.\n There was no significant difference in DFS, DDFS, or survival (P = .99, .70, and .83, respectively) among patients in either group. More patients treated preoperatively than postoperatively underwent lumpectomy and radiation therapy (67.8% v 59.8%, respectively). Rates of ipsilateral breast tumor recurrence (IBTR) after lumpectomy were similar in both groups (7.9% and 5.8%, respectively; P = .23). Outcome was better in women whose tumors showed a pCR than in those with a pINV, cPR, or cNR (relapse-free survival [RFS] rates, 85.7%, 76.9%, 68.1%, and 63.9%, respectively; P < .0001), even when baseline prognostic variables were controlled. When prognostic models were compared for each treatment group, the preoperative model, which included breast tumor response as a variable, discriminated outcome among patients to about the same degree as the postoperative model.\n Preoperative chemotherapy is as effective as postoperative chemotherapy, permits more lumpectomies, is appropriate for the treatment of certain patients with stages I and II disease, and can be used to study breast cancer biology. Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases; however, knowledge of such a response provided little prognostic information beyond that which resulted from postoperative therapy.", "272 women with operable breast adenocarcinomas larger than 3 cm were included in a randomized trial. The patients in group A (n = 138) with histological nodal involvement (N+) or a lack of estrogen and progesterone receptors (EPR-) were treated by initial mastectomy and axillary node dissection + adjuvant chemotherapy. Those in group B (n = 134) were treated by initial chemotherapy (the same as in group A) followed by loco-regional treatment, adjusted according to their response to chemotherapy. Prognostic factors were identical in the two groups. In group A, 32 patients received no adjuvant treatment (N- and EPR+), while 104 were given adjuvant chemotherapy (N+ and/or EPR-). Two patients were lost to follow-up. In group B, all patients received initial chemotherapy; 44 were in complete clinical remission and were treated with radiotherapy only; 40 with residual tumor (less than 20 mm) were treated with tumorectomy + axillary node dissection + radiotherapy; 49 with residual tumors (greater than 20 mm) had mastectomies. Conservative treatment was administered to 84 patients in group B (62.6%). EPR-tumors responded better to chemotherapy than did EPR+ ones (p = .003). After a median follow-up of 34 months, isolated local recurrences were more frequent in the group with initial chemotherapy, which, however, experienced a better overall survival (p = 0.04).", "A phase III randomized trial was activated to evaluate the efficacy of preoperative combined chemotherapy and radiotherapy as compared to preoperative radiation therapy alone, in patients with breast cancer presenting with a clinical stage of IIb-IIIa (TNM classification).\n From 1985 to 1990, 271 patients, aged 27-55 years, with stage IIb-IIIa breast cancer were randomized to receive either one or two courses of thiotepa 20 mg (i.m. injection) on the days 1, 3, 5, 7, 9, 11 (total dose per course 120 mg), methotrexate 40 mg/m2, i.v. on days 1 and 8, and 5-fluorouracil 500 mg/m2, i.v. on days 1 and 8 (TMF regimen) plus radiotherapy (Group I, 137 patients), or preoperative radiation therapy only (Group II, 134 patients). After the preoperative treatment all patients underwent mastectomy and complete axillary clearance, and then received 4-6 courses of TMF. The trial was conducted in a single institution (N.N. Petrov Research Institute of Oncology, St. Petersburg).\n Histopathological assessment of the mastectomy specimens showed complete regression of the tumour in 29.1% of the patients in group I and in 19.4% of the patients e.c. in group II. The estimated 5-year overall survival percentages were 86.1% for group I, and 78.3% for group II (P > 0.05). 5-year disease-free survival percentages were 81.0% and 71.6%, respectively (p < 0.05).\n Despite the low number of the patients included in the trial, we were able to detect a significant improvement in treatment results with a combination of chemotherapy and radiation therapy given prior to mastectomy over those of local therapy alone with radiation therapy followed by mastectomy, for average- and high-risk patients with operable breast cancer.", "Preoperative chemotherapy for stage II breast cancer may reduce locoregional tumors and provides initial treatment for systemic micrometastases. We conducted a prospective, randomized trial to evaluate the ability of intensive preoperative chemotherapy to enhance the outcome of this approach.\n Patients with clinical stage II breast cancer (T2N0, T1N1, and T2N1) were prospectively randomized to receive either preoperative or postoperative chemotherapy with five 21-day cycles of fluorouracil, leucovorin calcium, doxorubicin, and cyclophosphamide (FLAC)/granulocyte-colony-stimulating factor. Local therapy consisted of modified radical mastectomy or segmentectomy/axillary dissection/breast radiotherapy, according to patient preference.\n Fifty-three women were randomized (26 preoperative chemotherapy and 27 postoperative chemotherapy). The objective clinical response rate of the primary tumor to preoperative chemotherapy was 80%, and the pathologic complete response rate was 20%. Preoperative chemotherapy reduced the overall incidence and number of axillary lymph node metastases. There was no difference in the use of breast-conserving local therapy between the two treatment arms. There were 20 local/regional or distant recurrences (9 preoperative and 11 postoperative). There was no difference in the overall or disease-free survival between the preoperative and postoperative chemotherapy arms.\n Preoperative FLAC/granulocyte-colony-stimulating factor chemotherapy was effective against local/regional tumors in stage II breast cancer but was otherwise comparable to postoperative chemotherapy.", "The aim of this study was to assess a potential advantage in survival by neoadjuvant as compared to adjuvant chemotherapy. 414 premenopausal patients with T2-T3 N0-N1 M0 breast cancer were randomised to receive either four cycles of neoadjuvant chemotherapy (cyclophosphamide, doxorubicin, 5-fluorouracil), followed by local-regional treatment (group I) or four cycles of adjuvant chemotherapy after primary irradiation +/- surgery (group II). Surgery was limited to those patients with a persisting mass after irradiation, and aimed to be as conservative as possible. 390 patients were evaluable. With a median follow-up of 54 months, we observed a statistically significant difference (P = 0.039) in survival in favour of the neoadjuvant chemotherapy group. A similar trend was seen when the time to metastatic recurrence was evaluated (P = 0.09). At this stage, no difference in disease-free interval or local recurrence between these two groups could be observed. The mean total dose of chemotherapy administered was similar in both groups. On average, group I had more intensive chemotherapy regimes (doxorubicin P = 0.02) but fewer treatment courses (P = 0.008) as compared to the treated patients in group II. Haematological tolerance was reduced when chemotherapy succeeded to exclusive irradiation. Breast conservation was identical for both groups at the end of primary treatment (82 and 77% for groups I and II, respectively). Of the 191 evaluable patients in the neoadjuvant treatment arm, 65% had an objective response (> 50% regression) following four cycles of chemotherapy. The objective response rate to primary irradiation (55 Gy) was 85%. Improved survival figures in the neoadjuvant treatment arm could be the result of the early initiation of chemotherapy, but we cannot exclude that this difference might be attributable to a slightly more aggressive treatment. So far, the trend in favour of decreased metastases was not statistically significant. The local control appeared similar in both subgroups.", "The influence of primary systemic therapy in treating operable breast cancer on postmastectomy morbidity rates was investigated. The contribution of other risk factors was assessed by multiple logistic regression. Seventy-nine eligible patients were randomly allocated, 39 to undergo immediate modified radical mastectomy, and 40 to receive initial cytotoxic or endocrine treatment followed by mastectomy. Postoperative wound seroma, infection and necrosis were recorded prospectively. Fourteen minor and six major complications occurred in 17 patients treated conventionally, while 14 patients developed 11 minor and six major complications after systemic therapy (P > 0.4). Median hospital stay was 8 days for both groups. Age, smoking, immediate breast reconstruction and the type of primary systemic treatment given were not independent predictors of complication risk. Obesity emerged as a significant risk factor for postmastectomy complications (P = 0.015). Primary systemic therapy does not increase the rate of morbidity after mastectomy.", "Primary chemotherapy in localised breast cancer may prevent tumour spread during surgical treatment and reduce proliferation of micrometastases. A randomised clinical trial, in 196 premenopausal and postmenopausal patients with operable (T2-3, N0-1b) breast cancer, was started in November 1983 at the Institut Curie to compare neoadjuvant and adjuvant regimens of chemotherapy with radiotherapy with or without surgery. The patients have been followed up for 35-70 months (median 54). A neoadjuvant group received two monthly cycles of intravenous doxorubicin/cyclophosphamide/5-fluorouracil before locoregional therapy and four cycles subsequently. Six monthly cycles following locoregional therapy were administered to the adjuvant group. Because of inclusion of postmenopausal and/or node-negative patients, compliance was less than optimal in 39 patients who were analysed separately according to actual dose received. Tumour response, evaluated after two cycles of neoadjuvant chemotherapy, was significantly associated with dose (P = 0.003). Survival showed a slight non-significant advantage for the neoadjuvant group. Survival plotted by actual dose was also similar. Neoadjuvant chemotherapy was safe and at least as effective as the adjuvant regimen. Patients have been accrued to a subsequent larger trial of chemotherapy as first-line treatment.", "A prospective randomised trial was undertaken to evaluate the role of neoadjuvant chemoendocrine therapy prior to surgery in primary operable breast cancer.\n Three hundred nine women (median age 56 years, range 27-70) with primary operable breast cancer confirmed on fine needle aspiration (FNA) cytology were recruited to this study. They were treated with a combination of mitozantrone and methotrexate (+/- mitomycin-C) combined with tamoxifen (2MT). Patients received eight cycles of 2MT (four prior to surgery in the neoadjuvant group) and tamoxifen for five years with appropriate surgery and radiotherapy. The two groups were comparable for age, menopausal status, stage and surgical requirements.\n The clinical response rates to neoadjuvant therapy were as follows: 22% complete response (CR), 29% minimal residual disease (MRD), 33% partial response (PR), 15% no change (NC) and only two patients had clinical evidence of progressive disease. Surgical requirements were reduced from 31 patients (22%) of the adjuvant group having mastectomy to 14 (10%) in the neoadjuvant group (P < 0.003). At a median follow-up of 48 months (range 10-70 months) there is no statistically significant difference between the two groups in terms of local relapse, metastatic relapse or overall survival. Symptomatic and haematologic acute toxicity was low and similar for adjuvant and neoadjuvant therapy.\n This randomised trial has shown a significant reduction in the surgical requirements for mastectomy, after treatment with neoadjuvant chemoendocrine therapy, with no deterioration in local or distal relapse.", "We wanted to determine whether neoadjuvant systemic chemoendocrine therapy guided by the estrogen receptor (ER) status of the primary breast cancer, followed by conventional surgery and/or radiotherapy, reduces local and distant recurrence and improves survival compared with adjuvant treatment given conventionally postoperatively.\n Two hundred ten patients with primary breast cancer (T1-T4, N0, N1-2) were randomised to receive treatment with neoadjuvant chemoendocrine therapy or conventional post-operative chemoendocrine therapy. Systemic therapy was based on the estrogen receptor (ER) status of the primary tumour obtained by trucut core biopsy. ER-negative patients received MMM chemotherapy (methotrexate (30 mg/m2), mitozantrone (7 mg/m2) and mitomycin (7 mg/m2) three-weekly for three months and ER-positive patients who were premenopausal received goserelin (3.75 mg monthly), and post menopausal women formestane (250 mg every two weeks) over three months.\n With a minimum of five years follow-up, there is no evidence of any survival benefit from the pretreatment neoadjuvant therapy regimen, with five year overall survival being 79% +/- 4.7% (neoadjuvant) and 87% +/- 3.4% (adjuvant). Similarly, there was no apparent benefit in terms of disease-free survival. There was, however, a significant reduction in the incidence of distant metastases in responders (4 of 51; 8%) compared with non-responders (17 of 49; 35%) (P < 0.01). There was a reduction in the need for surgery in responding patients with T1 and T2 tumours, since 10 of 74 (14%) had no detectable residual tumour, without any apparent increase in the risk of local or distant recurrence.\n In this study neoadjuvant treatment with endocrine or chemotherapy provided no obvious survival benefit to women with breast cancer. However, it does allow avoidance of surgery in some cases. Also, the patients whose tumours respond to neoadjuvant systemic therapy have a lower incidence of distant metastases after five year follow-up compared to those whose tumours fail to respond.", "To evaluate whether preoperative neoadjuvant chemotherapy in patients with primary operable breast cancer results in better overall survival (OS) and relapse-free survival rates and whether preoperative chemotherapy permits more breast-conserving surgery procedures than postoperative chemotherapy.\n Six hundred ninety-eight breast cancer patients (T1c, T2, T3, T4b, N0 to 1, and M0) were enrolled onto a randomized phase III trial that compared four cycles of fluorouracil, epirubicin, and cyclophosphamide administered preoperatively versus the same regimen administered postoperatively (the first cycle administered within 36 hours after surgery). Patients were followed up for OS, progression-free survival (PFS), and locoregional recurrence (LRR).\n At a median follow-up of 56 months, there was no significant difference in terms of OS (hazards ratio, 1.16; P =.38), PFS (hazards ratio, 1.15; P =.27), and time to LRR (hazards ratio, 1.13; P =.61). Fifty-seven patients (23%) were downstaged by the preoperative chemotherapy, whereas 14 patients (18%) underwent mastectomy and not the planned breast-conserving therapy.\n The use of preoperative chemotherapy yields similar results in terms of PFS, OS, and locoregional control compared with conventional postoperative chemotherapy. In addition, preoperative chemotherapy enables more patients to be treated with breast-conserving surgery. Because preoperative chemotherapy does not improve disease outcome compared with postoperative chemotherapy, future trials should involve quality-of-life studies to investigate whether patients will benefit from this treatment modality." ]

[ "19124807", "19704068" ]

[ "ABVD compared with BEACOPP compared with CEC for the initial treatment of patients with advanced Hodgkin's lymphoma: results from the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial.", "Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study." ]

[ "To compare doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) versus bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) versus cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxirubicin, vincristine, procarbazine, vinblastine, and bleomycin (COPPEBVCAD; CEC) for advanced Hodgkin's lymphoma (HL).\n Three hundred seven patients with advanced HL (stage IIB, III, and IV) were randomly assigned to receive six courses of ABVD, four escalated plus two standard courses of BEACOPP, or six courses of CEC, plus a limited radiation therapy program.\n After a median follow-up of 41 months, BEACOPP resulted in a superior progression-free survival (PFS), with a significant reduction in risk of progression (hazard ratio [HR] = 0.50) compared with ABVD. No differences between BEACOPP and CEC, or CEC and ABVD were observed. The 5-year PFS was 68% (95% CI, 56% to 78%), 81% (95% CI, 70% to 89%), and 78% (95% CI, 68% to 86%), for ABVD, BEACOPP, and CEC, respectively (BEACOPP v ABVD, P = .038; CEC v ABVD and BEACOPP v CEC, P = not significant [NS]). The 5-year overall survival was 84% (95% CI, 69% to 92%), 92% (95% CI, 84% to 96%), and 91% (95% CI, 81% to 96%) for ABVD, BEACOPP, and CEC, respectively (P = NS). BEACOPP and CEC resulted in higher rates of grade 3-4 neutropenia than ABVD (P = .016); BEACOPP was associated with higher rates of severe infections than ABVD and CEC (P = .003).\n As adopted in this study BEACOPP is associated with a significantly improved PFS compared with ABVD, with a predictable higher acute toxicity.", "The HD9 trial of the German Hodgkin Study Group compared two different doses (baseline and escalated) of the bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) chemotherapy regimen in 1,196 patients with advanced-stage Hodgkin's lymphoma (HL). The previous analysis with 5 years median follow-up had indicated improved tumor control with BEACOPP escalated. Since the long-term safety and efficacy of this regimen has been debated, we report the 10-year follow-up.\n Patients received one of three chemotherapy regimens: eight cycles of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); eight cycles of BEACOPP baseline; or eight cycles of BEACOPP escalated.\n Median follow-up was 111 months. At 10 years, freedom from treatment failure (FFTF) was 64%, 70%, and 82% with OS rates of 75%, 80%, and 86% for patients treated with COPP/ABVD (arm A), BEACOPP baseline (arm B), and BEACOPP escalated (arm C), respectively (P < .001). BEACOPP escalated was significantly better than BEACOPP baseline in terms of FFTF (P < .0001) and OS (P = .0053). A total of 74 second malignancies (6.2%) were documented, including acute myeloid leukemia (0.4%, 1.5%, and 3.0%), non-Hodgkin's lymphoma (2.7%, 1.7%, and 1.0%), and solid tumors (2.7%, 3.4%, and 1.9%). The corresponding overall secondary malignancy rates were 5.7%, 6.6%, and 6.0%, respectively.\n The 10-year follow-up of the HD9 trial demonstrates a stabilized significant improvement in long-term FFTF and OS for BEACOPP escalated in advanced-stage HL. These results challenge ABVD as standard of care for this patient population." ]

[ "9457092", "9635947" ]

[ "Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. The Medical Research Council's General Practice Research Framework.", "Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group." ]

[ "We aimed to evaluate low intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease (IHD).\n 5499 men aged between 45 years and 69 years at high risk of IHD were recruited from 108 practices in the UK that belong to the Medical Research Council's General Practice Research Framework. Initially, warfarin or placebo was randomly allocated to 1427 men; 1013 of these men later moved to a factorial stage of the trial, retaining their warfarin or placebo warfarin allocation and adding randomly allocated active or placebo aspirin. Another 4072 men entered directly into the factorial stage making a total of 5085 men. The four factorial treatment groups were: active warfarin and active aspirin (WA, n = 1277), active warfarin and placebo aspirin (W, n = 1268), and placebo warfarin and active aspirin (A, n = 1268), and placebo warfarin and placebo aspirin (P, n = 1272). The primary end-point was all IHD defined as the sum of coronary death and fatal and non-fatal myocardial infarction (MI).\n The mean International Normalised Ratio (INR) of those on active warfarin was 1.47. The mean warfarin dose was 4.1 mg a day (range 0.5 mg-12.5 mg). There were 410 IHD events (142 fatal, 268 non-fatal). The main effect of warfarin (i.e., WA and W vs A and P) was a reduction in all IHD of 21% (95% CI 4-35, p = 0.02) chiefly due to a 39% reduction (15-57, p = 0.003) in fatal events so that warfarin reduced the death rate from all causes by 17% (1-30, p = 0.04). The main effect of aspirin (i.e., WA and A vs W and P) was a reduction in all IHD of 20% (1-35, p = 0.04) almost entirely due to a 32% reduction (12-48, p = 0.004) in non-fatal events. Absolute reductions in all IHD due to warfarin or aspirin were 2.6 and 2.3 per 1000 person years, respectively. WA reduced all IHD by 34% (11-51, p = 0.006) compared with P. WA increased haemorrhagic and fatal strokes. Ruptured aortic or dissecting aneurysms occurred in 15 of those who were or had been on warfarin compared with three of those who had not (p = 0.01).\n These results add to evidence that aspirin reduces non-fatal IHD. Warfarin reduced all IHD chiefly because of an effect on fatal events. Combined treatment with warfarin and aspirin is more effective in the reduction of IHD than either agent on its own.", "Despite treatment, there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals. Inadequate reduction of their blood pressure is a likely cause, but the optimum target blood pressure is not known. The impact of acetylsalicylic acid (aspirin) has never been investigated in patients with hypertension. We aimed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension.\n 18790 patients, from 26 countries, aged 50-80 years (mean 61.5 years) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg (mean 105 mm Hg) were randomly assigned a target diastolic blood pressure. 6264 patients were allocated to the target pressure < or =90 mm Hg, 6264 to < or =85 mm Hg, and 6262 to < or =80 mm Hg. Felodipine was given as baseline therapy with the addition of other agents, according to a five-step regimen. In addition, 9399 patients were randomly assigned 75 mg/day acetylsalicylic acid (Bamycor, Astra) and 9391 patients were assigned placebo.\n Diastolic blood pressure was reduced by 20.3 mm Hg, 22.3 mm Hg, and 24.3 mm Hg, in the < or =90 mm Hg, < or =85 mm Hg, and < or =80 mm Hg target groups, respectively. The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg. Further reduction below these blood pressures was safe. In patients with diabetes mellitus there was a 51% reduction in major cardiovascular events in target group < or =80 mm Hg compared with target group < or =90 mm Hg (p for trend=0.005). Acetylsalicylic acid reduced major cardiovascular events by 15% (p=0.03) and all myocardial infarction by 36% (p=0.002), with no effect on stroke. There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group, and 129 versus 70 non-fatal major bleeds in the two groups, respectively (p<0.001).\n Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events. The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg. Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infarction. There was no effect on the incidence of stroke or fatal bleeds, but non-fatal major bleeds were twice as common." ]

[ "48347", "2458059", "1704089", "2438965", "7533484", "1705938", "8610865", "1281625", "9313274", "11702324", "9083166", "4177607", "8773867", "16857467", "1693762", "7541310", "7514506", "10447905", "11707825", "8917240", "2465709", "4181148", "1384397", "1378707", "11190708", "2425315", "2457710", "10439568", "14286207", "7686279", "15963867", "9848042", "7521784", "8547554", "8622092" ]

[ "Relative analgesic potencies of morphine and hydromorphone in postoperative pain.", "Patient-controlled analgesia: a comparison of intravenous versus subcutaneous hydromorphone.", "Comparison of continuous subcutaneous and intravenous hydromorphone infusions for management of cancer pain.", "Epidural hydromorphone: a double-blind comparison with intramuscular hydromorphone for postcesarean section analgesia.", "Intravenous versus epidural administration of hydromorphone. Effects on analgesia and recovery after radical retropubic prostatectomy.", "Spinal narcotics for postoperative analgesia in total joint arthroplasty. A prospective study.", "A multidimensional comparison of morphine and hydromorphone patient-controlled analgesia.", "Morphine and hydromorphone epidural analgesia. A prospective, randomized comparison.", "Comparative efficacy of patient-controlled administration of morphine, hydromorphone, or sufentanil for the treatment of oral mucositis pain following bone marrow transplantation.", "[Postoperative pain therapy with hydromorphone and metamizole. A prospective randomized study in intravenous patient-controlled analgesia (PCA)].", "Comparative clinical efficacy and safety of a novel controlled-release oxycodone formulation and controlled-release hydromorphone in the treatment of cancer pain.", "Postoperative analgesia with hydromorphone and meperidine: a double-blind comparison.", "Epidural morphine vs hydromorphone in post-caesarean section patients.", "Safety and efficacy of hydromorphone as an analgesic alternative to morphine in acute pain: a randomized clinical trial.", "Clinical analgesic assay of repeated and single doses of heroin and hydromorphone.", "Comparison of hydromorphone and meperidine for ureteral colic.", "Hydromorphone patient-controlled analgesia (PCA) after coronary artery bypass surgery.", "Comparison of epidural morphine, hydromorphone and fentanyl for postoperative pain control in children undergoing orthopaedic surgery.", "A randomized, placebo-controlled study of outpatient premedication for bone marrow biopsy in adults with lymphoma.", "Patient-controlled analgesia for mucositis pain in children: a three-period crossover study comparing morphine and hydromorphone.", "Epidural hydromorphone with and without epinephrine for post-operative analgesia after cesarean delivery.", "Dental evaluation of hydromorphone (Dilaudid) for oral and maxillo-facial surgery.", "Epidural patient-controlled analgesia: influence of bupivacaine and hydromorphone basal infusion on pain control after cesarean delivery.", "Epidural patient-controlled analgesia: an alternative to intravenous patient-controlled analgesia for pain relief after cesarean delivery.", "Effect of pre-emptive hydromorphone administration on postoperative pain relief--a randomized controlled trial.", "Epidural hydromorphone for postcesarean analgesia.", "Patient-controlled subcutaneous hydromorphone versus continuous subcutaneous infusion for the treatment of cancer pain.", "Continuous subcutaneous infusion of morphine vs. hydromorphone: a controlled trial.", "ORAL HYDROMORPHONE IN TRAUMA.", "Comparison of hydromorphone continuous subcutaneous infusion and basal rate subcutaneous infusion plus PCA in cancer pain: a pilot study.", "Comparative efficacy of oral extended-release hydromorphone and immediate-release hydromorphone in patients with persistent moderate to severe pain: two randomized controlled trials.", "A comparison of oral transmucosal fentanyl citrate and oral hydromorphone for inpatient pediatric burn wound care analgesia.", "Comparative clinical efficacy and safety of immediate release and controlled release hydromorphone for chronic severe cancer pain.", "Pain outcomes after thoracotomy: lumbar epidural hydromorphone versus intrapleural bupivacaine.", "A randomized, double-blind, double-dummy, crossover trial comparing the safety and efficacy of oral sustained-release hydromorphone with immediate-release hydromorphone in patients with cancer pain. Canadian Palliative Care Clinical Trials Group." ]

[ "Because of discrepancies in the estimates of the relative analgesic potencies of hydromorphone and morphine, the drugs were compared in two four-point, double-blind bioassays. In the first study, hydromorphone, 1 and 2 mg, was compared with morphine, 5 and 10 mg, in 31 postoperative patients; in the second, hydromorphone, 0.5 and 1 mg, was compared with morphine, 5 and 10 mg, in 112 postoperative patients. Subjective responses to nurse-observer questions were used to quantitate analgesia for postoperative pain. Hydromorphone is more potent than commonly believed: approximately 0.9 to 1.2 mg is equianalgesic with 10 mg of morphine, with a similar incidence of side effects.", "nan", "To compare the safety and efficacy of subcutaneous and intravenous infusion of opioid analgesics, a randomised, double-blind, crossover trial was carried out in inpatients. 15 patients with severe cancer pain received two 48 h infusions of hydromorphone--one subcutaneously and one intravenously in randomly allocated order. The study was made double-blind by the use of two infusion pumps throughout; during the active subcutaneous infusion the intravenous pump delivered saline and vice versa. Serial measurements of pain intensity, pain relief, mood, and sedation by means of visual analogue scales showed no clinically or statistically significant difference between the two infusion routes. Side-effects were slight, and the mean number of morphine injections for breakthrough pain did not differ significantly between the routes (4.8 [SD 4.5] for intravenous vs 5.3 [5.6] for subcutaneous). Plasma hydromorphone concentrations measured at 24 h and 48 h of infusion showed stable steady-state pharmacokinetics; the mean bioavailability from subcutaneous infusion was 78% of that with intravenous infusion. Because of the simplicity, technical advantages, and cost-effectiveness of continuous subcutaneous opioid infusion into the chest wall or trunk, intravenous opioid infusion for the management of severe cancer pain should be abandoned.", "nan", "It remains unclear whether epidural administration of hydromorphone results in spinal analgesia or clinical benefit when compared with intravenous administration. Therefore, we undertook this study to determine whether epidural administration of hydromorphone resulted in decreased opioid requirement, improved analgesia, reduced side effects, more rapid return of gastrointestinal function, or shorter duration of hospital stay than intravenous administration.\n Sixteen patients undergoing radical retropubic prostatectomy were randomized in a double-blind manner to receive either intravenous or epidural hydromorphone via patient-controlled analgesia (PCA) for postoperative analgesia. All patients underwent a standardized combined epidural and general anesthetic and all received ketorolac for 72 h postoperatively. To decrease variability, patients were cared for according to a standardized protocol and were deemed ready for discharge according to prospectively defined criteria.\n Patients in the intravenous PCA group required approximately twice as much opioid than the epidural PCA group (P < 0.008), but there were no differences between groups in pain scores or patient satisfaction. Epidural administration resulted in a greater incidence of pruritus (P = 0.02). Gastrointestinal function recovered quickly in all patients with little variation, and there were no differences between groups. All patients were deemed ready for discharge by the third postoperative day, and removal of surgical drains was the last discharge criterion reached in all patients.\n Our results indicate that epidural administration of hydromorphone results in spinally mediated analgesia. However, epidural administration did not provide significant benefits in terms of postoperative analgesia, recovery of gastrointestinal function, or duration of hospitalization. Furthermore, we suggest that radical retropubic prostatectomy no longer be used as a model to assess the effects of analgesic technique on postoperative recovery, because control of discharge criteria revealed that hospital discharge was primarily dependent on removal of surgical drains.", "Sixty patients who were scheduled to have an elective total hip or knee arthroplasty were randomly assigned to one of three groups of twenty patients each before operation with spinal anesthesia. A double-blind technique was used throughout the study. The patients in Group I (control group) received hyperbaric 1 per cent tetracaine with epinephrine as the subarachnoid spinal anesthetic; the patients in Group II (morphine group), hyperbaric 1 per cent tetracaine with epinephrine and a single subarachnoid dose of Duramorph (morphine sulphate), 0.5 milligram; and those in Group III (Dilaudid group), hyperbaric 1 per cent tetracaine with epinephrine and a single subarachnoid dose of Dilaudid (hydromorphone hydrochloride), 0.002 milligram per kilogram of body weight. During the first twenty-four hours after the operation, the patients in Group II and Group III had significantly less pain compared with those in Group I. This was shown by the use of a visual linear-analog pain scale (p less than 0.05), the patients' ratings of the quality of relief of pain (p less than 0.02), and comparative measurements of the pain-altering medications that were used (p less than 0.05). The patients in Group II and Group III did not have any more complications or side effects than those in Group I. There was no significant difference in the quality and duration of analgesia between Group II and Group III.", "Although patient-controlled analgesia (PCA) pumps have been in use for more than a decade, the optimal PCA analgesic has yet to be identified. Many drugs are used; however, morphine remains the \"gold standard\" of opioid analgesics worldwide. The present study evaluated morphine and hydromorphone (Dilaudid) PCA with respect to analgesic efficacy, side effects, mood, and cognitive function. Sixty-one opioid naive patients undergoing lower abdominal surgery participated in the double-blind protocol. Verbal rating scores, use of medication, and side effects for the two medications were recorded. Cognitive functioning was assessed by computation of Digit Symbol and Trails Making B Tests. Self-reported affective state (mood) was measured by Profile of Mood States (POMS) inventory. Both medications provided adequate analgesia without a difference in side effects. Cognitive performance was poorer in the hydromorphone group (P < 0.05). Patients receiving hydromorphone reported less anger/hostility (P < 0.01) and generally better mood elevations on the other subscales than those receiving morphine. A similar incidence of side effects and dose medication can be anticipated with morphine and hydromorphone. When considering cognitive effects, morphine had less adverse consequences, while hydromorphone appeared to result in improved mood. We conclude that hydromorphone may provide a suitable alternative to morphine.", "Because evidence from uncontrolled, unblinded studies suggested fewer side effects from epidural hydromorphone than from epidural morphine, we employed a randomized, blinded study design to compare the side effects of lumbar epidural morphine and hydromorphone in 55 adult, non-obstetric patients undergoing major surgical procedures. A bolus dose of epidural study drug was given at least 1 h prior to the conclusion of surgery, followed by a continuous infusion of the same drug for two postoperative days. Infusions were titrated to patient comfort. Visual analog scale (VAS) pain scores, VAS sedation scores, and subjective ratings of nausea and pruritus were assessed twice daily. The two treatments provided equivalent analgesia. Sedation scores and prevalence of nausea did not differ significantly between groups. Prevalence of pruritus, however, differed significantly on postoperative day 1, with moderate to severe pruritus reported by 44.4% of patients in the morphine group versus 11.5% in the hydromorphone group (P < .01). On post-operative day 2, reports of pruritus by patients receiving morphine remained higher than those among the hydromorphone-treated subjects, although this difference was no longer statistically significant (32% vs. 16.7%, P = .18). We conclude that lumbar epidural morphine and hydromorphone afford comparable analgesia, but the occurrence of moderate to severe pruritus on the first postoperative day is reduced by the use of hydromorphone.", "A total of 119 bone marrow transplant patients suffering from oral mucositis pain were enrolled in a randomized, double-blind, parallel-group trial comparing the efficacy of patient-controlled analgesia with morphine, hydromorphone and sufentanil. Patient ratings of pain and side-effects on visual analog scales were gathered daily from the start of patient-controlled analgesia (PCA) therapy until the discontinuation of opioid treatment either because of resolution of oral mucositis pain, intolerable side-effects, inadequate pain control, or complications related to transplantation. Of the 119 enrolled subjects, 100 met the evaluable criteria of developing oral mucositis and remaining on the study for at least 2 days. Multivariate analysis of the outcome measures indicated that the analgesia achieved in all three opioid groups was nearly equivalent, while measures of side-effects, especially for the combination of sedation, sleep and mood disturbances, were statistically lower in the morphine group than in hydromorphone or sufentanil groups. Patients in the hydromorphone group exhibited the most variability in pain control. Event analysis also indicated significant differences in time to treatment failure between the three groups, with the morphine arm exhibiting clear superiority. The proportion of patients discontinued because of inadequate pain relief was much higher in the sufentanil group (7/36) as compared to the hydromorphone (0/34) or the morphine group (1/30). The daily opioid consumption pattern showed a continual dose escalation during the first week of therapy for all groups, coincident with worsening mucositis. Morphine consumption reached a plateau by day 5, whereas hydromorphone and sufentanil consumption continued to rise until days 7 and 9, respectively. Sufentanil dose requirement increased by approximately 10-fold compared to morphine and hydromorphone, whose requirements increased only 5-fold, suggesting the possibility of development of acute pharmacological tolerance in some patients with this phenylpiperidine opioid. This study provides support for the recommendation that morphine is the opioid of first choice when patient-controlled analgesia is employed for the treatment of severe oropharyngeal pain in bone marrow transplantation (BMT) patients.", "Most potent opioid analgesics available in Germany have been investigated for use in postoperative patient-controlled analgesia (PCA). To conclude an older comparative series, it was the aim of the present study to define analgesic potency, side effects and patient acceptance of hydromorphone and its interaction with the non-opioid analgesic metamizole. A total of 120 patients recovering from elective abdominal or orthopaedic surgery, performed under standardised general anaesthesia, were randomised into 3 double-blind treatment groups to receive intravenous PCA demand doses of hydromorphone 283 micrograms (low dose, LD), 566 micrograms (high dose, HD) or a combination of hydromorphone 283 micrograms and metamizole 50 mg (low dose hydromorphone + metamizole, LM). Demand-independent low-dose background infusions were added to deliver hydromorphone at 67.9 micrograms/h in all groups, with additional metamizole at 12 mg/h in group LM. Lockout times were set to 2 min. After an average observation time of 24.5 +/- 2.6 h (mean, SD) since start of PCA, cumulative PCA hydromorphone doses in groups LD, HD and LM were 7.8 +/- 3.3, 12.1 +/- 4.8 and 7.5 +/- 2.0 mg, respectively, with the well known large inter-individual variability in all groups. Although hydromorphone consumption was significantly higher in group HD, self-reported pain intensities (VAS, retrospective pain scores) were quite comparable between the groups. Low dose, PCA bolus-linked metamizole did not significantly reduce hydromorphone consumption nor improve patient acceptance. Side-effects were typical for potent postoperative opioids, but never required special treatment; haemodynamic or respiratory complications were not observed in any patient. It can be concluded by comparison with other PCA opioid investigations performed under the same study protocol that hydromorphone is about 3-4 times as potent an analgesic as morphine under the conditions of intravenous postoperative PCA. Due to a favourable patient acceptance, hydromorphone can be recommended as a suitable alternative to other opioids for the treatment of postoperative pain.", "The use of oxycodone to treat chronic cancer pain has been hampered by its short elimination half-life, which necessitates administration every 4 hours. This study compared the clinical efficacy and safety of a novel oxycodone formulation with that of hydromorphone in the treatment of cancer pain.\n In a double-blind crossover study, 44 patients with stable cancer pain were randomized to controlled-release oxycodone or controlled-release hydromorphone, each given every 12 hours for 7 days. Pain intensity, nausea, and sedation were assessed by patients four times daily, and breakthrough analgesia was recorded.\n Thirty-one patients completed the study (18 women, 13 men; mean age, 56 +/- 3 years) and received a final controlled-release oxycodone dose of 124 +/- 22 mg per day and a final controlled-release hydromorphone dose of 30 +/- 6 mg per day. There were no significant differences between treatments in overall Visual Analogue Scale (VAS) pain intensity (VAS 28 +/- 4 mm vs. 31 +/- 4 mm), categorical pain intensity (1.4 +/- 0.1 vs. 1.5 +/- 0.1), daily rescue analgesic consumption (1.4 +/- 0.3 vs. 1.6 +/- 0.3), sedation scores (24 +/- 4 mm vs. 18 +/- 3 mm), nausea scores (15 +/- 3 mm vs. 13 +/- 3 mm), or patient preference. Two patients experienced hallucinations on controlled-release hydromorphone, but none did while receiving controlled-release oxycodone.\n Controlled-release oxycodone demonstrated excellent pharmacodynamic characteristics, analgesic efficacy, and safety as compared with controlled-release hydromorphone and represents an important new therapeutic option for cancer pain management.", "nan", "The purpose of this randomized controlled double blind study was to compare the efficacy of pain relief and the side effects of epidural hydromorphone and morphine in post-Caesarean patients.\n In all patients, epidural anaesthesia was induced using carbonated lidocaine 2% with 1:200,000 epinephrine and 50 micrograms fentanyl, given in incremental doses. Patients in Group 1 (n = 24) received 0.6 mg hydromorphone and patients in Group 2 (n = 22) received 3 mg morphine after delivery of the infant. Pain, pruritus and nausea were measured using a visual analog scale (at times: baseline, on admission to the recovery room, 3, 6, 12, 18 and 24 hr postoperatively), by the number of requests for additional medications and by an overall satisfaction score.\n There was no difference between the groups in pain relief of in the incidence and severity of side effects. Pruritus was more pronounced within the first six hours in Group 1 and at 18 hr in Group 2.\n Hydromorphone provides no clinical benefit over epidural morphine for post operative analgesia following Caesarean section.", "We compare a standard weight-based dose of intravenous hydromorphone (Dilaudid) to a standard weight-based dose of intravenous morphine in adults presenting to the ED with acute severe pain.\n This was a prospective, randomized, double-blind, clinical trial conducted in an academic medical center. Of the 198 adult patients presenting to the ED with acute severe pain who were randomized to receive either intravenous hydromorphone at 0.015 mg/kg or intravenous morphine at 0.1 mg/kg, 191 patients had sufficient data for analysis. The main outcome measure was the difference between the 2 groups in pain reduction at 30 minutes as measured on a validated numeric rating scale. Adverse effects, pain reduction at 5 minutes and 2 hours postbaseline, and additional analgesics and antiemetics were tracked as secondary outcome measures.\n The mean change of pain from baseline to 30 minutes postbaseline in patients allocated to intravenous hydromorphone was -5.5 numeric rating scale units versus -4.1 in patients allocated to intravenous morphine (difference -1.3; 95% confidence interval -2.2 to -0.5). Adverse effects were similar in both groups, with the exception of pruritus, which did not occur in patients receiving hydromorphone (0% versus 6% [difference -6%; 95% confidence interval -11% to -1%]). No patient required naloxone.\n For the treatment of acute, severe pain in the emergency department, intravenous hydromorphone at 0.015 mg/kg represents a feasible alternative to intravenous morphine at 0.1 mg/kg.", "A direct comparison of the analgesic activities of heroin and hydromorphone was carried out in cancer patients with postsurgical pain. Intramuscular doses of 5 and 10 mg of heroin were compared with 1 and 2 mg of hydromorphone in a randomized, double-blind, 4-point parallel group assay. Design innovations in the study provided that about half the patients would receive prior repeated doses of the same drug as the test medication, and half would receive the alternate medication. Both test drugs were found to be potent, relatively short acting analgesics with similar profiles of action. Hydromorphone was about 5 times as potent as heroin on a milligram basis. The comparison of those patients who had repeated doses of the same treatment prior to the test dose and those who had repeated doses of the alternate drug demonstrated no significant effect on the relative potency estimates. Side effect occurrence was similar for both drugs, with sleepiness the most prominent effect. The study supports the view that hydromorphone and heroin produce similar clinical effects, and that either drug may adequately substitute for the other. Covariate analysis indicated that time since last analgesic was positively related to analgesia, and amount of prior opioid had a negative relationship. To a lesser extent, increase in patient age was associated with an increase in analgesic scores. Taking these covariates into account served to increase the sensitivity of the analysis.", "To compare the efficacies of meperidine and hydromorphone in the treatment for ureteral colic in the emergency department (ED).\n A prospective, double-blind, randomized clinical trial was conducted over six months at a tertiary referral center with 93,000 annual ED visits. Seventy-three patients completed the study. The patients received either 1 mg of hydromorphone or 50 mg of meperidine IV at t = 0. Pain intensity was determined using a 10-cm visual analog scale at t = 0, 15, 30, 60, and 120 minutes. A second dose of the study drug could be given between t = 15 and t = 120 minutes when the clinician believed the initial dose was ineffective. Patients requiring more than one additional dose of analgesia were treated as nonresponders and were removed from the study.\n Thirty-six patients received hydromorphone and 37 received meperidine. The initial pain intensities (hydromorphone group = 8.4 +/- 1.5; meperidine group = 8.5 +/- 2.1), age distributions, sex distributions, and side effects of the two groups were comparable. Pain relief was better (p < 0.05) with hydromorphone at t = 15, 30, 60, and 120 minutes. The hydromorphone group required rescue analgesia less often (31% vs 68%, p < 0.01), had fewer IV pyelographies (IVPs) (28% vs 54%, p < 0.05), and had a lower proportion of hospital admissions (25% vs 49%, p = 0.08).\n For the fixed doses used in this study, the adult ureteral colic patients receiving hydromorphone achieved more pain relief, required less rescue medication, underwent fewer IVPs, and avoided hospital admission more frequently than did those receiving meperidine.", "We conducted a study to compare the effectiveness of patient-controlled analgesia (PCA) technique to conventional analgesic therapy (CAT) after coronary artery bypass graft (CABG). The PCA group received hydromorphone 0.1 mg.hr-1 basal infusion and bolus doses of 0.2 mg Q 5 min (maximum 1.2 mg.hr-1) while the CAT group received morphine 2.5 mg iv Q 30 min prn until extubation followed by prn meperidine 1 mg.kg-1 im Q 4 hr or acetaminophen 325 mg with codeine 30 mg po (1 or 2 tablets) when oral intake was possible. The degree of pain was assessed using a Visual Analogue Scale (VAS) starting after extubation and every 6-8 hr for the next 60 hr. Holter monitoring was initiated one hour after patient arrival in the Intensive Care Unit (ICU) and continued for 72 hr. Other measured variables were pulmonary function, sedation, side effects and total opioid requirements. Results show that the day-to-day VAS pain score decreased in the PCA group (P < 0.001) while it remained unchanged in CAT patients. The PCA patients had lower VAS pain scores at extubation (P < 0.05). During the third postoperative day, the PCA group had a lower VAS pain score, a lower incidence of severe pain defined as a score > 5 on the VAS scale, and a reduced incidence of myocardial ischaemia (P < 0.01). However, there was no difference in the duration, severity, area under the curve (AUC), or heart rate during ischaemic events. Postoperative pulmonary function was abnormal in both groups (NS) with minimal recovery by the fourth day.(ABSTRACT TRUNCATED AT 250 WORDS)", "The safety and side-effects profile of epidural administration of a hydrophilic (morphine), highly lipophilic (fentanyl) and a drug with intermediate hydrophilic and lipophilic activity (hydromorphone) were compared in 90 children undergoing orthopaedic procedures. Ninety patients were randomly assigned (30 in each group) to receive epidural morphine, hydromorphone, or fentanyl for postoperative analgesia. Respiratory effects, nausea, somnolence, urinary retention, pruritus and visual pain scales were evaluated and compared during a 30-h period following surgery. In the morphine group, 25% showed respiratory depression with oxygen saturation below 90% but there was no incidence of respiratory depression in the fentanyl or hydromorphone groups. Somnolence was prominent in some of the patients in all the groups, but was more prolonged in the morphine group. Statistically, there was no significant difference in nausea between the groups, but pruritus was more severe and frequent in the morphine group. The incidence of urinary retention in the morphine group was higher compared with the fentanyl and hydromorphone groups. In conclusion, epidural hydromorphone, demonstrating less side-effects, is preferable to morphine and fentanyl for epidural analgesia in children.", "The outpatient bone marrow biopsy and aspiration (BMBA) procedure performed with local anesthetic is often poorly tolerated in adults. This prospective, randomized, placebo-controlled, double-blind trial was designed to determine whether oral (p.o.) lorazepam and hydromorphone reduces pain and anxiety during BMBA. Eligible patients had lymphoma, had no prior BMBA, and were > or = 18 years old. Since patients had bilateral BMBA, each served as their own control. Patients were stratified by anxiety level using the Spielberger Trait Anxiety Scale and randomized to: A) placebo for the first BMBA and 2 mg lorazepam and 2 mg hydromorphone p.o. for the contralateral BMBA, or B) placebo for both BMBAS. Changes in pain and anxiety experienced between the first and second BMBA were measured by the Visual Analogue Scale (VAS) and the Spielberger State Anxiety Scale at the time of the BMBA and 24 hours later. Twenty-seven patients were enrolled and 25 were evaluable; there were 17 males and eight females. The median age was 57 years (range, 28-79 years). Overall, BMBA was reported as painful in both arms, with a median VAS pain score after the second BMBA of 3.9 (scale, 0-10) for arm A and 5.8 for arm B (P = 0.21). There was no difference in the change in pain, anxiety, or recalled anxiety between treatment arms (all P values > 0.05). The difference in the change in recalled pain was of borderline significance (P = 0.07) and consistent with benzodiazepine-induced anterograde amnesia.", "(1) To test the safety and efficacy of a clinical protocol for administering opioid by using patient-controlled analgesia (PCA) for the management of mucositis pain in children after bone marrow transplantation, (2) to compare the efficacy, side-effect profile, and potency ratio of morphine with those of hydromorphone by using PCA as the method of opioid administration, and (3) to obtain pharmacokinetic data on hydromorphone and morphine in this population of children.\n In this double-blind, three-period crossover study, patients were randomly assigned to receive either morphine (group 1) or hydromorphone (group 2) initially by means of PCA on days 1, 2, and 3 (period 1), to be followed on days 4, 5, and 6 (period 2) with the alternative opioid, followed by the opioid used at the commencement of the study on days 7, 8, and 9 (period 3). A clinical protocol for calculating the PCA commencement opioid dose and subsequent opioid-dose escalation was tested by measures of safety and efficacy. Measures of pain intensity and opioid side effects were made during the three periods. On the last study day (day 10), patients received a continuous infusion of opioid derived from the previous 24-hour PCA opioid requirement, and blood specimens were collected and stored for subsequent opioid analysis.\n Ten patients were enrolled in this study. Rapid escalation in opioid requirement commonly occurred at the commencement of PCA, followed by a variable plateau phase and then deescalation of opioid requirement after mucositis resolution. The measures demonstrated the safety and efficacy of the clinical protocol. In the concentrations used, there was no statistical difference between the mean daily pain, sedation, nausea and vomiting, and pruritus scores for both opioids (Friedman test). The analysis of variance of the log-total opioid doses per patient during periods 1, 2, and 3 indicated that patients used 27% more hydromorphone than expected from its presumed 7:1 ratio relative to morphine potency used in the PCA infusions. The mean plasma hydromorphone concentration was 4.7 ng/ml (range, 1.9 to 8.9 ng/ml), and the mean clearance was 51.7 ml/min per kilogram of body weight (range, 28.6 to 98.2 ml/min per kilogram). The mean plasma morphine, morphine-6-glucuronide, and morphine-3-glucuronide concentrations were 40.0 ng/ml (range, 15 to 62.5), 168.2 ng/ml (range, 54.4 to 231.9), and 391.0 ng/ml (range, 149.4 to 921.7), respectively. The mean morphine clearance was 34.3 ml/min per kilogram of body weight (range, 19.3 to 58.3). The mean molar ratios of morphine-6-glucuronide/morphine, morphine-3-glucoronide/morphine, and morphine-3-glucuronide/morphine-6-glucuronide were 2.48 (range, 1.4 to 3.3), 5.82 (range, 3.4 to 9.1), and 2.46 (range, 1.1 to 3.3), respectively.\n The safety and efficacy of a clinical protocol for the administration of opioids by means of PCA for mucositis pain after bone marrow transplantation was demonstrated. In this small study, hydromorphone was not superior to morphine in terms of analgesia or the side-effect profile: a larger study would be needed to show a difference. The clearances of hydromorphone and morphine in the children studied were generally greater than those previously recorded, but this finding may be related to disease or treatment variables. Apart from clearance, the morphine pharmacokinetics in the study population were similar to those previously recorded. Hydromorphone may be less potent in this population of children than indicated by adult equipotency tables.", "The efficacy of epidural hydromorphone alone or in combination with epinephrine for postoperative analgesia was evaluated in 30 healthy women who underwent cesarean delivery with epidural anesthesia. They were assigned randomly to receive either 1.5 mg hydromorphone alone (N = 15) or 1.5 mg hydromorphone with 1/200,000 epinephrine (N = 15). Duration of analgesia (mean +/- SD) was 24.3 +/- 9.4 hours after the epidural injection of hydromorphone plus epinephrine. This was significantly greater (p less than 0.01) than the duration of 18.2 +/- 5.9 hours after the same dose of plain hydromorphone. Analgesia was more rapid in onset and significantly better at the 0.5, 1, 3, and 12 hours postoperatively in the hydromorphone-epinephrine group. Side effects including pruritus (73%), nausea (20%), and vomiting (15%) were of similar frequency with and without epinephrine. Although mean venous PCO2 (PvCO2) levels three and six hours after the hydromorphone-epinephrine dose were elevated significantly over the pre-drug PvCO2 levels, no respiratory depression was detected by an apnea monitor to which all patients were connected. The addition of epinephrine to epidural hydromorphone hastened onset and prolonged the duration of analgesia after cesarean section.", "nan", "Epidural administration of hydromorphone was evaluated using a patient-controlled analgesia (PCA) delivery system in 170 healthy women undergoing elective cesarean delivery with epidural bupivacaine who were randomly assigned to one of four epidural PCA treatment groups: group I, hydromorphone alone by bolus administration; group II, hydromorphone, with a continuous (basal) infusion; group III, hydromorphone in combination with 0.08% bupivacaine by bolus administration; or group IV, hydromorphone and bupivacaine, with a concurrent infusion of both drugs. Patients in group I required significantly less opioid medication (2.1 +/- 1.1 mg [mean +/- SD]) during the first 24 h than patients in group II (3.3 +/- 1.3 mg). Similarly, patients in group III self-administered significantly less hydromorphone (2.0 +/- 1.0 mg) and bupivacaine (23.3 +/- 11.4 mg) during the first 24 h of PCA therapy, compared with patients in group IV (hydromorphone [2.7 +/- 1.1 mg] and bupivacaine [31.5 +/- 11.6 mg]). The concomitant use of a local anesthetic or basal opioid infusion with hydromorphone via epidural PCA did not decrease the number of PCA demands or delivered doses. In addition, patients in all four groups had similar pain, sedation, discomfort, fatigue, and anxiety scores. The frequency of awakening at night to self-administer analgesic medication was not decreased when a basal infusion was used.(ABSTRACT TRUNCATED AT 250 WORDS)", "Epidural administration of an opioid analgesic by means of a patient-controlled analgesia (PCA) system was compared with conventional intravenous PCA for pain relief after cesarean delivery. One hundred seventeen healthy women were randomly assigned to receive hydromorphone either intravenously (IV-PCA) or epidurally (EPI-PCA) after cesarean delivery with epidural bupivacaine for operative anesthesia. The hydromorphone requirements were 3.4 and 4.2 times more in the IV-PCA group on the first (P less than 0.01) and second (P less than 0.01) postoperative days, respectively. The mean number (+/- SD) of PCA demands during the first 24 h after the operation was 105 (+/- 88) for the IV-PCA group and 33 (+/- 48) for the EPI-PCA group (P less than 0.01). This difference was also significant 24-48 h after surgery. Although the EPI-PCA group utilized significantly less opioid medication, pain and sedation scores were similar in the two treatment groups; however, a significantly larger percentage of patients in the IV-PCA group (46% vs 22%) stated that they felt drowsy during the first postoperative day. Pruritus was reported more frequently in the EPI-PCA (67%) than in the IV-PCA (33%) group. Nausea was experienced by only 10% of patients in the IV-PCA and 6% in the EPI-PCA group. There was no evidence of postoperative respiratory depression, with minimal oxygen saturation values of 93% (+/- 3%) and 94% (+/- 1%) in the IV-PCA and EPI-PCA groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)", "Pre-emptive analgesia represents a treatment strategy which tries to prevent the development of pain by inhibiting central reactions to peripheral sensory stimuli. In a prospective randomized double-blind placebo-controlled study, the effect of oral premedication with 4 mg of a slow-release hydromorphone preparation on postoperative piritramide consumption and subjective pain perception is being evaluated.\n 96 women undergoing hysterectomy were randomly assigned to four study groups. Patients from groups 1 and 2 received hydromorphone and placebo respectively two hours before surgery, while those from groups 3 and 4 were given the same substances one hour after the end of the operation. Postoperative pain relief was provided by a patient-controlled infusion pump with piritramide. The intensity of postoperative pain as perceived by the patients was quantified on a visual analogue scale. Piritramide consumption and pain scores were recorded at 1 and 24 hours after surgery. Approval of the local Ethics Committee had been obtained beforehand as well as written informed consent from the patients.\n No significant differences in piritramide consumption were observed in between the four study groups. Visual analogue scale (VAS) ratings at 1 and 24 hours after surgery did not show any significant differences either--irrespective of whether the patients had received hydromorphone or placebo preoperatively or postoperatively.\n In our study, oral administration of 4 mg of slow-release hydromorphone did not show any greater pre-emptive analgesic effect than placebo.", "The efficacy of epidurally administered hydromorphone for postcesarean analgesia was evaluated in a prospective, randomized, double-blind study. Patients in group H (N = 26) received 1.0 mg of hydromorphone in preservative-free saline (total volume = 10 mL), administered epidurally. Patients in group B (N = 26) received 10 mL of 0.25% bupivacaine, administered epidurally. Both groups subsequently received intramuscular injections of hydromorphone as needed. There were significant differences between the two groups in pain score, patient assessment of analgesia quality, time to first analgesic intervention, and total dosage of hydromorphone during the first 24 hours. Nausea/vomiting and pruritus occurred more frequently in group H. No patient had a respiratory rate less than or equal to 10. There were no statistically significant differences between groups in mean times to first ambulation, first void, first passage of flatus, or hospital discharge.", "Twenty-five patients with pain due to advanced cancer were randomized to receive patient-controlled sc injections (PCIs) of hydromorphone (HM) versus continuous sc infusion (CSCI) of HM by means of a Pharmacia 5200 pump. Each self-injection of HM during PCI was equivalent to 4 hours of CSCI. After 3 days, a crossover occurred, and patients received the alternate treatment for 3 days. During both phases of the study, patients could request extra doses of HM from their nurses. In 22 patients able to be evaluated, pain intensity (visual analogue, 0-100 mm) at 9:00 a.m. and 4:00 p.m. was 31 +/- 23 and 28 +/- 18 mm, respectively, on PCI versus 28 +/- 18 and 27 +/- 17 mm, respectively, on CSCI [P = not significant (NS)]. The total dose of HM was 168 +/- 197 and 181 +/- 234 mg on PCI and CSCI, respectively (P = NS). No significant difference was found in nausea, drowsiness, or number of hours of sleep. The total number of extra doses of HM was 6 +/- 7 on CSCI versus 2 +/- 3 on PCI (P = .007). At the end of the study, patients chose PCI and CSCI in seven and 10 cases, respectively (P = NS; 5 patients expressed no preference). We conclude that both methods were similar in regard to effectiveness and toxic effects in short-term hospital use.", "Seventy-four patients were included in a double-blind, randomized, controlled trial comparing the analgesic efficacy and adverse effects of hydromorphone and morphine delivered by continuous subcutaneous infusion. Patients completed the Memorial Pain Assessment Card and a checklist of opioid-related adverse effects immediately before commencing subcutaneous infusion and 24, 48, and 72 hours later. An assessment tool was developed for the 60 patients who were too ill to complete their own questionnaire. The tool demonstrated excellent inter-rater reliability. Thirty-four percent of patients in the hydromorphone group and 27% of those in the morphine group died before completion of the study (P = 0.66). The hydromorphone group required more analgesia for breakthrough pain in the first 24 hours of the study (P = 0.03) and had a greater improvement in the behavior of frowning on movement and the comfort visual analogue scale (P = 0.08) over the course of the study. Adverse effects were rare and similar in both groups. This study found hydromorphone to be at least as effective as morphine when delivered by continuous subcutaneous infusion.", "nan", "In this pilot randomized, double-blind, cross-over study, the effectiveness and safety of hydromorphone administration by continuous subcutaneous (s.c.) infusion (mode A) and by continuous basal rate s.c. infusion + PCA (mode B) were compared in 8 cancer patients. Patients experimented with each infusion mode during 48 h. Statistical analysis was performed on data collected in 7 patients during 36 h from 22:00 h on day 1 to 10:00 h on day 3 and from 22:00 h on day 3 to 10:00 h on day 5. Mean hydromorphone dose +/- S.D. was 56.6 +/- 30.1 and 40.4 +/- 24.5 mg/36 h for modes A and B, respectively. There was no statistically significant difference observed in mean pain intensity, but the absence of significant difference may be related to the small sample size and high individual variability. Both methods provided adequate overall pain control in most patients. However, a large interindividual variation was detected. Indeed, some patients reported in the subjective questionnaire that they felt marked discomfort during hydromorphone administration with mode B. Only 2 patients chose mode B at the end of the study, but it was interesting to note that those 2 patients were the youngest of the group. This study demonstrated the effectiveness and safety of both modes of hydromorphone administration. The data suggest that it may be possible to identify particular cancer patients which can really benefit from an association of a basal rate infusion and PCA for opiate administration.", "Two multicenter, randomized, double-blind, crossover studies with identical designs evaluated the efficacy of oral extended-release hydromorphone (HHER) administered q24h compared with immediate-release hydromorphone (HHIR) dosed four times daily in patients with persistent moderate to severe pain. Patients titrated to a stable HHER dose were randomized to individualized doses of HHER or HHIR for 3 to 7 days before crossover to the second treatment. Primary efficacy end point was the mean of average pain intensity (API) scores, rated on a 0- to 10-point numeric scale, over the last 2 days before the pharmacokinetics/pharmacodynamics day of each double-blind period. Difference between treatments (HHER - HHIR) in study 1 was 0.17 with a 90% confidence interval (CI) (-0.01, 0.34); in study 2, difference was 0.07 with a 90% CI (-0.12, 0.26). There were no significant differences between treatments in API scores or amount of rescue medication used at any time interval within the 24-hour dosing period. No reduction in pain control occurred in patients administered HHER at the end of the 24-hour dosing period. Most treatment-emergent adverse events were opioid-related. In these studies, HHER administered q24h and HHIR dosed four times daily provided comparable analgesia at an equivalent total daily dose.", "The ideal oral wound care analgesic for children should be palatable, provide potent analgesia of rapid onset and short duration, and require minimal, yet appropriate, monitoring. With use of a double-blinded crossover design, we compared the efficacy and safety of oral transmucosal fentanyl citrate (OTFC) (approximately 10 micrograms/kg) with the efficacy and safety of oral hydromorphone (60 micrograms/kg) in 14 pediatric inpatients (ages 4 to 17 years) undergoing daily burn wound care in a ward setting. Pulse oximetry, vital signs, side effects, patient pain scores, and observer scores for cooperation, anxiety, and sedation were recorded. Pulse oximetry, vital signs, cooperation, sedation, incidence of nausea or vomiting, and the amount of time it took to resume normal activities were similar in both treatment groups. OTFC resulted in improved pain scores before wound care and improved anxiolysis during wound care, but at other points it was similar in effect to hydromorphone. We conclude that OTFC is a safe and effective analgesic, that it may provide minor improvements in analgesia and anxiolysis compared with hydromorphone, and that it offers a palatable alternative route of opioid administration without intravenous access for wound care procedures in children.", "The short elimination half-life of hydromorphone necessitates 4-hourly dosing to maintain optimal levels of analgesia in patients with chronic cancer pain. The purpose of this study was to compare the clinical efficacy and safety of controlled release hydromorphone administered every 12 hours and immediate release hydromorphone administered every 4 hours in patients with chronic severe cancer pain.\n Forty-eight patients with stable chronic severe cancer pain were randomized, in a double-masked crossover study, to controlled release hydromorphone every 12 hours or immediate release hydromorphone every 4 hours for 7 days each. Pain intensity was assessed using a visual analog scale (VAS) and the Present Pain Intensity Index of the McGill Pain Questionnaire. Nausea and sedation were also assessed using a VAS. Assessments were made by the patient four times a day at 7:00 a.m., 11:00 a.m., 3:00 p.m., and 7:00 p.m. Use of rescue hydromorphone also was recorded by the patient.\n Forty-five patients completed the study (26 women, 19 men; mean age, 57.1 +/- 13.6 years) and received a mean daily dose of 76 +/- 133 mg (range, 6-768 mg). There were no significant differences between controlled release hydromorphone and immediate release hydromorphone in overall VAS pain intensity scores (19 +/- 14 vs. 20 +/- 14 mm), ordinal pain intensity scores (1.2 +/- 0.8 vs. 1.2 +/- 0.8) and pain scores by day of treatment or time of day. The daily rescue analgesic consumption during controlled release hydromorphone and immediate release hydromorphone did not differ significantly overall (1.1 +/- 1.1 vs. 1.0 +/- 1.1 doses per day) or with respect to time of day. There were no significant differences in overall VAS sedation scores (18 +/- 18 mm vs. 19 +/- 18 mm) and in overall mean VAS nausea scores (12 +/- 15 mm vs. 11 +/- 14 mm) between controlled release hydromorphone and immediate release hydromorphone.\n Controlled release hydromorphone administered every 12 hours is as effective as immediate release hydromorphone administered every 4 hours in the management of patients with chronic severe cancer pain. The benefits of controlled release hydromorphone lie in the convenience of its capsule formulation, which can be sprinkled on soft food, and its 12-hour duration of action, which allows patients uninterrupted sleep and improved compliance.", "To evaluate postthoractomy analgesia in patients receiving lumbar epidural hydromorphone versus intrapleural bupivacaine.\n A randomized, prospective, double-blind study.\n A university-affiliated medical center.\n Twenty patients undergoing lateral thoracotomy for either pulmonary wedge resection, lobectomy, or pneumonectomy.\n Nine patients received epidural hydromorphone, and 11 patients received intrapleural bupivacaine in the postoperative period.\n Severity of pain was assessed using a visual analog pain scale (VAPS) (0 to 100 mm) at 1, 3, and 5 hours. Patients receiving epidural hydromorphone had a statistically significant improvement in VAPS scores. Patients who received intrapleural bupivacaine did not achieve a significant reduction in pain scores. Nine of 11 patients in the intrapleural bupivacaine group had \"failed\" postoperative analgesia as defined by a VAPS greater than 30. Only 3 of 9 patients in the continuous epidural hydromorphone group had \"failed\" analgesia.\n Epidural hydromorphone is superior to intrapleural bupivacaine in achieving satisfactory pain outcomes during the first 5 hours after thoracotomy.", "To evaluate the safety and efficacy of a new slow-release preparation of hydromorphone (SRH) in the treatment of cancer pain.\n Ninety-five adult patients from three Canadian Palliative Care Centers with no evidence of mental impairment received treatment for cancer pain with an oral opioid analgesic. After informed consent was obtained, patients underwent titration to a stable dose of immediate-release hydromorphone (IRH) for 48 hours, and were then randomized to receive IRH or SRH for 5 days in a double-blind basis. During day 6, a crossover took place, and patients received the alternate drug for 5 days. Pain intensity was assessed using a visual analog scale (VAS) and ordinal scale (OS). Side effects were assessed using VAS. Patients and investigators made a blinded global rating of efficacy a blinded final choice between SRH and IRH.\n In 75 assessable patients, pain intensity of the VAS and OS were (mean +/- SD) 27 +/- 21 and 1.3 +/- 0.6 on IRH, versus 29 +/- 21 (P = .13) and 1.3 +/- 0.6 (P = .19) on SRH, respectively. The total number of extra doses of opioids, global rating, and final blinded choice by both patients and investigators were not significantly different between IRH and SRH. Differences in side effects were not significant.\n Our findings suggest that SRH is as safe and effective as IRH in the treatment of cancer pain." ]

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[ "Double-blind, multicenter comparison of sertraline and amitriptyline in elderly depressed patients.", "Amoxapine and amitriptyline: serum levels and clinical response in patients with primary unipolar depression.", "Double-blind multicenter study of paroxetine and amitriptyline in depressed inpatients.", "Is anxious-agitated major depression responsive to fluoxetine? A double-blind comparison with amitriptyline.", "Double-blind, multicenter comparative study of sertraline and amitriptyline in hospitalized patients with major depression.", "Amitriptyline in depressive states:a controlled trial.", "Double-blind comparison of nortriptyline and amitriptyline in depressive illness.", "A multicentre double blind trial of fluoxetine versus amitriptyline in the treatment of depressive illness.", "A comparison of two drug treatments in depressive illness.", "A double-blind study to compare trazodone with amitriptyline in depressed patients.", "A controlled comparison of trimipramine and amitriptyline.", "Viloxazine and amitriptyline in depressive illness. A double blind controlled trial in general practice.", "Fluoxetine compared with amitriptyline in elderly depression: a controlled clinical trial.", "Clomipramine and amitriptyline in depressed outpatients. A controlled study.", "[A new antidepressive agent: C 34,276-Ba or maprotyline, 1st tetracyclic thymoanaleptic. Clinical study].", "Costs and outcomes of use of amitriptyline, citalopram and fluoxetine in major depression: exploratory study.", "A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression.", "Treatment of anxiety/depressive conditions in the elderly: a double-blind comparative study of Motival and amitriptyline.", "Amoxapine versus amitriptyline for continuation therapy of depression.", "[Lofepramine: a comparative clinical study with amitriptyline].", "Perspectives in clinical psychopharmacology of amitriptyline and fluvoxamine. A double-blind study in depressed inpatients.", "Doxepin and amitriptyline-perphenazine in mixed anxious-depressed neurotic outpatients: a collaborative controlled study.", "A comparison of maprotiline and amitriptyline in the treatment of depression in general practice.", "Tricyclic antidepressants in the treatment of depressions. A double-blind clinical comparison of clomipramine (Anafranil) and amitriptyline.", "A multinational, double-blind trial with a new antidepressant maprotiline (Ludiomil) and amitriptyline.", "[Monitoring of the treatment of endogenous depression with imipramine and amitriptyline (preliminary report)].", "A comparison study of amitriptyline and nortriptyline with plasma levels.", "A multicenter double-blind trial of paroxetine versus amitriptyline in depressed inpatients.", "A controlled trial of maprotiline (Ludiomil) in depressed outpatients.", "A double-blind comparison of dothiepin and amitriptyline in patients with primary affective disorder: serum levels and clinical response.", "A re-examination of the clinical effects of imipramine and amitriptyline in depressive illness.", "Preliminary double-blind clinical trial with a new antidepressive doxepin.", "Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice.", "Viloxazine in the treatment of endogenous depression. A standard (amitriptyline) controlled clinical study.", "Tianeptine and amitriptyline. Controlled double-blind trial in depressed alcoholic patients.", "A controlled trial of maprotiline (Ludiomil) and amitriptyline in general practice.", "Fluoxetine vs amitriptyline in the treatment of depressed out-patients.", "Trazodone in the treatment of neurotic depression.", "A comparison of the onset of action and therapeutic efficacy of amoxapine and amitriptyline.", "Comparison of the efficacy of sustained-release amitriptyline with maprotiline in the treatment of depressive illness.", "A double-blind sequential comparison of doxepin with amitriptyline in depressed patients.", "Trazodone and amitriptyline in treatment of depressed inpatients. A double-blind study.", "A comparison of amitriptyline and a fluphenazine/nortriptyline preparation in anxiety-depressive states.", "[Comparative clinical study of nomifensine and amitriptyline in the treatment of endogenous depression].", "COMPARATIVE TRIAL OF NORTRIPTYLINE AND AMITRIPTYLINE.", "Hypothalamic-pituitary-adrenal axis activity and tricyclic response in major depression.", "Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression.", "Controlled clinical trial of a new antidepressant (Org. GB 94) of novel chemical formulation.", "Trazodone in depressed outpatients.", "The efficacy and safety of tianeptine in the treatment of depressive disorder: results of a controlled double-blind multicentre study vs. amitriptyline.", "A comparison of maprotiline (Ludiomil) and amitriptyline (1).", "A double-blind comparison of a new antidepressant, protryptiline, with imipramine and amitryptiline.", "A double-blind, placebo-controlled study comparing mianserin and amitriptyline in moderately depressed outpatients.", "Double-blind, multicenter comparative study of sertraline versus amitriptyline in outpatients with major depression.", "Clinical evaluation of the antidepressants: maprotiline and amitriptyline. A double-blind controlled trial.", "Does lofepramine have fewer side effects than amitriptyline? Results of a comparative trial.", "Double-blind comparative study of the antidepressant, unwanted and cardiac effects of minaprine and amitriptyline.", "A controlled trial of antidepressant medication in elderly in-patients.", "Minaprine in depression. A controlled trial with amitriptyline.", "Treatment of severe depressive illness: a double-blind comparison of mianserin and long-acting amitriptyline.", "Antidepressant response to tricyclics and urinary MHPG in unipolar patients. Clinical response to imipramine or amitriptyline.", "A double-blind comparative trial with mianserin and amitriptyline in outpatients with major depressive disorders.", "Comparative effects of amitriptyline and amineptine in patients affected by anxious depression.", "A double-blind trial with amitriptyline and lofepramine in the treatment of endogenous depression.", "Comparative effects of fluoxetine and amitriptyline on cardiac function.", "Dopaminergic agonist nomifensine compared with amitriptyline: a double-blind clinical trial in acute primary depressions.", "Doxepin versus amitriptyline in depression: a sequential double-blind study.", "A comparison of desipramine and amitriptyline plasma levels and therapeutic response.", "Paroxetine in the treatment of elderly depressed patients in general practice: a double-blind comparison with amitriptyline.", "[Psychotropic drugs in medical practice. Double-blind studies of lofepramine against amitriptyline].", "A general practitioner double-blind study of dothiepin hydrochloride ('Prothiaden') and amitriptyline in depression.", "A double blind comparative trial of viloxazine and amitriptyline in patients suffering from endogenous depression.", "Blood levels of mianserin and amitriptyline and clinical response in aged depressed patients.", "The comparative antidepressant value of lofepramine and amitriptyline. Results of a controlled trial with comments on the scales used.", "A double-blind study of dothiepin hydrochloride (Prothiaden) and amitriptyline in out-patients with masked depression.", "A comparative double-blind controlled study of trimipramine and amitriptyline in major depression: lack of correlation with 5-hydroxytryptamine reuptake blockade.", "Urinary MHPG excretion and treatment with desipramine or amitriptyline: prediction of response, effect of treatment, and methodological hazards.", "Efficacy of tianeptine in anxious-depressed patients: results of a controlled multicenter trial versus amitriptyline.", "A double-blind multicentre study of paroxetine and amitriptyline in depressed outpatients. Italian Paroxetine Study Group.", "Clinical activity and tolerability of trazodone, mianserin, and amitriptyline in elderly subjects with major depression: a controlled multicenter trial.", "Double-blind clinical trial of the antidepressant action of amineptine.", "Amoxapine and amitriptyline in the outpatient treatment of endogenous depression.", "Double-blind trial of sustained-release amitriptyline compared with viloxazine in moderate to severe depressive illness.", "A comparative study of amoxapine and amitriptyline for depressive illness.", "d-AMPHETAMINE AS A PREDICTOR FOR RESPONSE TO IMIPRAMINE AND AMITRIPTYLINE.", "A comparison of nortriptyline and amitriptyline in depression.", "[Single-blind comparative study between patients with ludiomil (Ciba 34,276-Ba) and its evaluation with Hamilton's scale].", "Paroxetine and amitriptyline in the treatment of depression in general practice.", "A behavioral and clinical evaluation of two psychotropic agents: doxepin-hydrochloride and perphenazine-amitriptylin hydrochloride.", "Acute, subchronic and withdrawal sleep EEG changes during treatment with paroxetine and amitriptyline: a double-blind randomized trial in major depression.", "A comparative trial of doxepin and amitriptyline in depressive illness.", "Experimental comparison between the effect of standardized trazodone-amitriptyline and placebo treatment in vitalized depressive patients.", "A double-blind trial of maprotiline (Ludiomil) and amitriptyline in depressed outpatients.", "Amitriptyline and nortriptyline response profiles in unipolar depressed patients.", "Comparison of effects of desipramine and amitriptyline on EEG sleep of depressed patients.", "Multicenter double blind study of paroxetine and amitriptyline in elderly depressed inpatients.", "A comparative clinical trial of mianserin (Norval) and amitriptyline in the treatment of depression in general practice.", "A double-blind, comparative clinical trial with ludiomil (CIBA 34,276-Ba) and amitriptyline in newly admitted depressed patients.", "Mianserin versus amitriptyline for depression: a double-blind 6-week trial.", "Imipramine and amitriptyline plasma concentrations and clinical response in major depression.", "An evaluation of fluphenazine with nortriptyline in anxiety and depression.", "A comparative trial of amitriptyline and trimipramine in the treatment of depression.", "A double-blind, multicentre study to assess the tolerability and efficacy of paroxetine compared with amitriptyline in the treatment of depressed patients in Australian general practice.", "A double-blind comparative clinical study of amoxapine and amitriptyline in depressed, hospitalised patients.", "A double-blind comparison of dothiepin and amitriptyline for the treatment of depression with anxiety.", "A comparison of the antidepressant action of citalopram and amitriptyline.", "Clinical comparative evaluation of maprotiline, a new antidepressant drug. A multicentre study.", "Amoxapine versus amitriptyline combined with perphenazine in the treatment of psychotic depression.", "Three double-blind comparative trials of mianserine (ORG GB 94) and amitriptyline in the treatment of depressive illness.", "A double-blind controlled study of clinical efficacy of maprotiline and amitriptyline in depression.", "A comparison of fluoxetine and amitriptyline in the treatment of major depression.", "Dexamethasone suppression test status does not predict differential response to nortriptyline versus amitriptyline.", "Reduced REM latency predicts response to tricyclic medication in depressed outpatients.", "The drug treatment of depression in general practice: a comparison of nocte administration of trazodone with mianserin, dothiepin and amitriptyline.", "A controlled study of mianserin in moderately to severely depressed outpatients.", "Mianserin in the treatment of depressive illness: a comparison with amitriptyline.", "[Comparative clinical study of the association of chlordiazepoxide-amitriptyline and maprotiline in patients suffering from depression with anxiety components].", "[Clinical and comparative trial of dosulepin and amitriptyline].", "A controlled study of the efficacy and safety of mianserin and amitriptyline in depressive inpatients.", "Once-daily treatment for mixed anxiety/depressive states: a comparison of slow release amitriptyline and fluphenazine with nortriptyline.", "Clinical evaluation of doxepin and amitriptyline in depressed patients.", "Clinical assessment and performance tasks in depression: a comparison of amitriptyline and trazodone.", "Pharmacokinetics and efficacy of maprotiline and amitriptyline in endogenous depression: a double-blind controlled trial.", "An evaluation of trazodone in the treatment of depression.", "A comparison of maprotiline (Ludiomil) and amitriptyline (2).", "A single-blind comparative study of once daily dothiepin (\"Prothiaden\") and divided daily doses of amitriptyline.", "A double-blind study of the comparative antidepressant effect of paroxetine and amitriptyline.", "[Therapy of elderly depressive patients. Lofepramine and amitriptyline under double-blind conditions].", "A COMPARATIVE TRIAL OF IMIPRAMINE, AMITRIPTYLINE, ISOCARBOXAZID AND TRANYLCYPROMINE IN OUT-PATIENT DEPRESSIVE ILLNESS.", "Clinical evaluation of doxepin in anxious depressed outpatients.", "Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression.", "Amitriptyline-perphenazine and doxepin in depressed outpatients: a controlled double-blind study.", "Trazodone. A comparative clinical and predictive study.", "Which tricyclic for depressed outpatients, imipramine pamoate or amitriptyline?", "Double-bind comparison of maprotiline with amitriptyline in the treatment of depressive illness.", "A controlled double-blind clinical trial between maprotiline and amitriptyline in depressive illness.", "Amoxapine versus amitriptyline in endogenous depression. A double-blind study.", "Maprotiline-a double-blind study of a new tetracyclic antidepressant in severe depression.", "A double-blind study of minaprine versus amitriptyline in major depression.", "A double-blind evaluation of trazodone in the treatment of depression in the elderly.", "A double-blind comparison of citalopram (Lu 10-171) and amitriptyline in depressed patients.", "Paroxetine in the treatment of depression--a randomized comparison with amitriptyline.", "A double-blind clinical trial of mianserin versus amitriptyline: differentiation by adverse symptomatology.", "Double-blind comparative study of paroxetine and amitriptyline in depressed patients of a university psychiatric outpatient clinic (pilot study).", "Fluoxetine versus amitriptyline in the treatment of major depression with associated anxiety (anxious depression): a double-blind comparison." ]

[ "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)", "Amoxapine, a new antidepressant of the dibenzoxazepine class, was compared with amitriptyline in 80 patients with primary unipolar depressive disorders. In a four-week double-blind trial, the two medications were equally effective and had similar onsets of therapeutic action. The range of side effects was similar, although there was a trend for fewer side effects in the amoxapine group. Serum levels were not related to therapeutic response for either medication.", "Paroxetine is a new compound in the group of the selective serotonin-reuptake inhibitors. The results of several open and double-blind control-group studies demonstrate clear antidepressive efficacy of paroxetine. However, most data were collected in samples of outpatients. To overcome this restriction, a six-week double-blind control-group study, comparing 30 mg paroxetine with 150 mg amitriptyline per day, was performed in a sample of inpatients suffering from major depression. Generally speaking, the efficacy analysis of 160 patients was not able to demonstrate statistically significant differences in the antidepressive activity of paroxetine or amitriptyline, either with respect to the total score on the Hamilton Depression Scale (HAMD) and the Clinical Global Impressions or with respect to the subscores of the HAMD. One exception was the retardation subscore, in which amitriptyline showed a greater degree of reduction. Both drugs had a characteristic side-effect profile. Paroxetine was characterized by a lack of anticholinergic side-effects and a higher rate of nausea.", "Whether fluoxetine (FX) is effective in the treatment of anxious depression is still debated. In the present study, after one week of placebo (single blind), 142 outpatients affected by major depression with relevant anxiety and agitation were randomly assigned (double blind) to either FX (20 mg/day) (n. 67) or amitriptyline (AM) (daily dose: 115+/-39.2mg) (n.75) for a period of 10 weeks. Between groups, the mean score of Hamilton Rating Scale for Depression (HRSD) was significantly different only after 3 weeks of treatment (AM 14.7+/-5.7 vs FX 17.3+/-6.2 (p = 0.02), whereas at the end of the trial it was similar (AM 8.15+/-6.9; FX 8.96+/-6.6). At each visit, no significant difference between groups was found regarding the scores of the HRSD items \"psychic anxiety\", \"somatic anxiety\", \"agitation\". Furthermore, the FIX treatment did not increase the scores of the items \"suicide\", \"psychic anxiety\", \"somatic anxiety\", \"agitation\" and \"insomnia\". These findings suggest that patients affected by major depression with anxiety and/or agitation were effectively and safely treated with FX without increasing risks.", "Sertraline is a selective serotonin reuptake inhibitor (SSRI) for which marketing approval has been obtained recently in Germany. The results of several double-blind, placebo-controlled studies have demonstrated that sertraline has a clear antidepressive effect. However these studies have been conducted in outpatient populations. In the context of this multicenter study, a total of 160 inpatients were treated with sertraline 50-150 mg or amitriptyline 75-225 mg over a period of 6 weeks in a double-blind fashion. Sixty-two patients in the sertraline and 59 patients in the amitriptyline group were evaluated for efficacy in the according-to-protocol (ATP) population; 80 sertraline and 75 amitriptyline patients were evaluated for safety in the Intention-to-treat population (ITT). No statistically significant differences were detected between the two groups in the efficacy analysis performed on the basis of the Hamilton Depression Scale (HAM-D) total score and Clinical Global Impression (CGI). Due to its sedating properties, amitriptyline was found to be significantly more effective with regard to the HAM-D factor \"sleep disturbance\". The safety analysis, which was based on the CGI, the global assessment at the end of study and a score for somatic adverse events (FSUCL) revealed statistically significant advantages of sertraline over amitriptyline. Amitriptyline was associated with more autonomic and circulatory side effects, while epigastric complaints occurred more often with sertraline. The incidence of nausea - a typical SSRI side effect - was the same in both groups.", "nan", "nan", "The antidepressant efficacy and side effect profile of a fixed dose of 20 mg/day of fluoxetine, a specific serotonin reuptake inhibitor, were compared to those of amitriptyline. Fifty-eight patients with DSM-III-R depression were randomly assigned to receive either fluoxetine or amitriptyline. Fifty-six patients (fluoxetine N = 23, amitriptyline N = 23) completed the 6 week study. Comparable antidepressant efficacy was demonstrated for the two drugs. Patients taking fluoxetine reported less side-effects than those taking amitriptyline.", "nan", "nan", "Depressed patients seen in a private psychiatric practice (N = 41) were randomly assigned to receive trimipramine or amitriptyline over a study period of at least 4 weeks. Patients in both groups showed significant improvement over time on measures of mood and depression, and on psychological scales. Only one variable, the global improvement rating, showed a significant overall between-groups difference, which favored amitriptyline treatment. This difference may reflect the presence of significantly less baseline symptomatology in the amitriptyline group. Trimipramine patients were more seriously ill on initial diagnosis and showed significantly more improvement at week 2 than amitriptyline patients and a trend toward fewer side effects. Thus, trimipramine may be useful for patients particularly sensitive to side effects in whom evidence of early response is important.", "nan", "Twenty-eight elderly inpatients suffering from major depressive episodes (diagnosed according to DSM III) received randomly, on a double-blind basis, amitriptyline (75 mg/die) or fluoxetine (20 mg/die) for five weeks. There were four drop-outs in the amitriptyline group and two drop-outs in the fluoxetine group. Both groups showed a significant amelioration at the end point for Hamilton Rating Scale of Depression scores compared to the baseline value. Anticholinergic side-effects were significantly more severe in the amitriptyline group. Weight gain was detected only in patients receiving amitriptyline.", "nan", "nan", "The increasing cost of pharmaceuticals in the Czech Republic has led to the restriction on prescriptions of expensive new antidepressants. The aim of the study was to compare the costs and outcomes of using amitriptyline, citalopram and fluoxetine in the treatment of major depression.\n Ninety patients (69 women) with a mean age of 44.5 years (S.D. = 14.3) suffering from major depression were treated with amitriptyline (N = 31), citalopram (N = 29) and fluoxetine (N = 30). Direct medical costs and effectiveness (indicated by the number of hospitalization-free days) were assessed in a prospective, open, intent-to-treat study.\n Neither cost nor effectiveness were significantly different among the treatment groups.\n Amitriptyline treatment is not less expensive nor more effective than citalopram or fluoxetine therapies. There is no advantage in restricting patients from treatment with SSRIs, which have fewer adverse effects and a decreased risk of a lethal overdosage in comparison with tricyclic antidepressants.", "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.", "A double-blind two-group comparison of fluphenazine/nortriptyline (F/N) with amitriptyline in 72 patients aged 65 or over suffering from mixed states of anxiety and depression, each treated for four weeks, showed F/N to be significantly superior to amitriptyline by Day 7 in terms of patients' self-ratings and clinicians' ratings. Patients' preference for F/N was even more pronounced by Day 28 (P less than 0.001), when the improvement in symptoms relating to depression was rated by the clinicians as significantly greater for the patients receiving F/N (P less than 0.025). The incidence of drowsiness was significantly greater (P less than 0.05) in the amitriptyline group than the F/N group. The implications of these results for the treatment of emotional disturbances in the elderly are discussed.", "The efficacy of continuation therapy with tricyclic antidepressants has been established in a number of controlled trials. This study investigated the efficacy of continuation therapy with a relatively new antidepressant, amoxapine, using a double-blind controlled comparison with amitriptyline. Subjects met DSM-III criteria for major depressive disorder and were randomized to treatment with either amoxapine 400 mg (N = 47) or amitriptyline 300 mg (N = 45). The acute phase lasted up to 8 weeks. Responders were continued on the same drug at the same dose for a 16-week continuation phase. Some measures found more rapid onset for amitriptyline, which is inconsistent with findings from some prior studies. Amitriptyline was more effective in inducing full recovery. There was a trend for higher relapse rates on amoxapine, perhaps related to the fact that there were more partial responders entering continuation therapy from this group. Side effect rates were equivalent in the two drugs. However, physicians rated amoxapine's side effects as more frequently interfering with its therapeutic effect. These data suggest that amoxapine does not offer any clear advantage over amitriptyline for continuation therapy in patients who have major depressive disorder. Of potential clinical relevance is the finding that achieving full recovery in the acute phase may reduce the likelihood of relapse in the continuation phase, regardless of the type of antidepressant medication prescribed.", "Lofepramine, a new tricycle antidepressant, is compared with amitriptyline in a double-blind study. A brief pharmacological description of the drug is made emphasizing its low toxicity and anticholinergic peripheral effects, high plasmatic concentration levels and good tolerance and elimination in comparison with some other known tricycle antidepressants. Sixty depressive outpatients of a Mental Health Service in Lima, 5 male and 55 female, aging 16 to 65, 29 endogenous and 31 neurotic were studied with both drugs in a equimolar dosage. Through the chi square test, no statistical significance was found in maximal therapeutic response, Hamilton Depression Rating Scale scores, type of depression, and side-effects xerostomy which is lesser with lofepramine. A discussion of these results is made and it is concluded that in the present study lofepramine compared with amitriptyline has a similar therapeutic effect. Though not statistically significant, lofepramine seems to be better for neurotic depression and patients sensitive to anticholinergic side-effects.", "The efficacy of fluvoxamine was compared to that of amitriptyline in a double-blind 6-week fixed-dose trial of 56 inpatients with major depressive episode. The two drugs were comparable in their antidepressant efficacy. We tested the percentage of improvement in Hamilton-D scores during the first and the second weeks of treatment as predictors of efficacy for the last week. Improvement rates during the second week significantly predicted the outcome. We also investigated whether or not some symptomatological characteristics would permit prior prediction of the outcome with amitriptyline or fluvoxamine, dividing our sample into responders and nonresponders to the two drugs. The four groups showed differences in their symptomatological profiles.", "nan", "nan", "The clinical efficacy of oral clomipramine and amitriptyline treatment (50--125 mg/day) was compared over a period of 2 months in 72 depressive patients visiting a psychiatric out-patient clinic. Both drugs were equally effective as measured by the Hamilton Rating Scale for Depression. According to a nurse's independent evaluation of 13 items the two drugs were equipotent in relieving depressive symptoms and no statistically significant differences between the treatment groups were found in the global evaluation by the investigator and the patient. A trend in favour of clomipramine was, however, seen in several parameters. The declines in the Hamilton Rating Scale scores and the nurse's evaluation scores were highly significant during the first 2 weeks of treatment (P less than 0.001) in both groups and the scores continued to decrease during the 2nd month of the study. The most common unwanted effects were dryness of the mouth and fatigue. The frequency of side effects was 51% in the clomipramine group and 43% in the amitriptyline group. The side effects were generally mild and transient and called for discontinuation of treatment in only one case in each group.", "nan", "Monitored treatment of a depressed phase of unipolar affective disorder was conducted in 11 female patients receiving imipramine and in 12 females taking amitriptyline. Patients were randomly assigned to one of the drug and in 6 patients the drugs were switched because of the lack of response to the first used compound. In the imipramine treated group a satisfactory response after 4 weeks of management (less than 6 points on Hamilton's depression scale) was observed in 6 patients and in amitriptyline treated group in 5 patients. Patients displaying a satisfactory response to amitryptyline had significantly higher--as compared to remaining patients in the group--plasma levels of the drug after two and four weeks of treatment. Such an association was not observed in patients treated wtih imipramine. Severity of depression and motor retardation before the treatment was similar both in patients with satisfactory and with poor response to imipramine as well as to amitriptyline. However the intensity of anxiety symptoms was higher in patients exhibiting poor response to treatment with amitriptyline and imipramine as well.", "Forty-one depressed outpatients were treated for six weeks after random assignment to amitriptyline hydrochloride (N = 22) or nortriptyline hydrochloride (N = 19). On a mean daily dose of 119 mg, amitriptyline-treated patients had a mean tricyclic level (amitriptyline plus nortriptyline) of 120 ng/ml. Nortriptyline-treated patients on a mean dose of 117 mg/day had a mean nortriptyline level of 141 ng/ml. The two drugs were equally effective in the treatment of depression. The correlation between the Hamilton Score and the mean tricyclic level was negative in the amitriptyline-treated patients (r = -0.54, P less than .025) and positive in the nortriptyline-treated patients (r = -0.49, P less than .05). Patients treated with amitriptyline or nortriptyline with plasma levels within the therapeutic range, defined in other laboratories, had a better response, as measured by the Hamilton Score (P less than .001), Zung Score (P less than .01), and percent recovered (P less than .001), than those above or below the therapeutic range.", "The phenylpiperidine derivative paroxetine is a selective serotonin reuptake inhibitor. In a double-blind 6-week trial, paroxetine was compared with amitriptyline in hospitalized patients suffering from major depression (DSM-III). One hundred fifty-three patients were enrolled in the study in seven centers in Austria and Germany. Results showed similar efficacy of both drugs after 6 weeks. The differences between groups in Montgomery-Asberg Depression Rating Scale and Clinical Global Impression ratings did not reach statistical significance at any time. Side effects were distributed similarly but with a significantly higher incidence of anticholinergic effects in patients treated with amitriptyline (p < or = 0.001), whereas agitation and insomnia were registered more often in the paroxetine group. This study supports the antidepressive efficacy of paroxetine in a sample of severely depressed inpatients.", "A double blind comparison is reported of a new tetracyclic antidepressant, maprotiline, with amitriptyline and placebo in psychiatric outpatients. Amitriptyline was significantly more effective than placebo in its global effect on depression. Maprotiline emerged as neither inferior to amitriptyline nor superior to placebo. Methodological difficulties prevented an adequate assessment of the anxiolytic activity of maprotiline.", "In a double-blind parallel group study, thirty-two patients suffering from a primary affective disorder received either dothiepin or amitriptyline. Serum concentrations of total dothiepin plus northiaden or amitriptyline and nortriptyline were estimated. A similar therapeutic response was seen with both drugs but there was no correlation with serum concentrations of amitriptyline or nortriptyline, whereas serum dothiepin correlated positively with clinical response.", "A double-blind trial of amitriptyline and imipramine was conducted in patients suffering from depressive illness. The results failed to confirm the prevalent belief that amitriptyline has a greater sedative effect and superior anxiolytic properties than imipramine. The therapeutic effect of these drugs was not shown to be related to their sedative properties and with regard to anxiety the reverse appeared to be true.", "nan", "The enhanced sensitivity of the elderly to the side effects produced by tricyclic antidepressants (TCAs), and the frequency and type of adverse events, have made the treatment of depression in this group difficult. The selective serotonin reuptake inhibitors (SSRIs) have been reported to produce significantly fewer undesirable side effects and display better tolerance than TCAs. We compared the therapeutic actions and side effects produced by citalopram, the most selective SSRI available, with amitriptyline in a group of elderly patients (aged 65 and older) diagnosed with major depression. In a double-blind, double-dummy, parallel-group, multicenter comparison of citalopram (20 or 40 mg/day) and amitriptyline (50 or 100 mg/day), patients who did not respond to placebo during a 1-week single-blind phase were randomly assigned to receive citalopram or amitriptyline for 8 weeks. Efficacy measures included the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Scale (HAMD), and Clinical Global Impressions. Both drug treatments produced equivalent time-related declines in severity of depression, so that by 8 weeks slightly more than 50% of the patients in each group experienced marked recovery, defined as MADRS scores < or = 12. Amitriptyline produced a greater overall incidence of adverse events, including a significantly higher (P < 0.001) percentage of patients reporting dry mouth (34% vs. 7%), as well as a significantly higher (P < 0.02) incidence of somnolence. Constipation and fatigue also occurred more frequently in the amitriptyline than in the citalopram group. For only one event (nausea) did the citalopram group report a significantly greater (P = 0.012) incidence (12.8% vs. 4.8%). On the basis of these results, it was concluded that citalopram is as effective an antidepressant as amitriptyline in the treatment of the depressed elderly. Because of its low incidence and low magnitude of side effects, citalopram seems especially useful in private practice.", "In a double-blind clinical trial with 20 patients suffering from endogenous depression statistically significant changes (improvement) were present in the scores of all assessment instruments. Although no statistically significant differences occurred between the groups, significant improvement on the HAM-D occurred earlier for amitriptyline and significant improvement occurred earlier on HAM-A for viloxazine. 2 patients were discontinued due to adverse reactions; one for nausea and vomiting while receiving viloxazine and one for paroxysmal atrial tachycardia while receiving amitriptyline. The same number of TES occurred for each group with seven unique to viloxazine (numbness, tingling, palpitation, ejaculation difficulty, nausea/vomiting, diarrhea, epigastric pain and gustatory disturbances) and seven unique to amitriptyline (insomnia, irritability, syncope, tremor, nasal congestion, orthostatic hypertension and paroxysmal atrial tachycardia). Other than for 1 patient who developed syncope and orthostatic hypotension and the patient who developed paroxysmal atrial tachycardia, there were no clinically significant changes in pulse rate, blood pressure and weight. There were no clinical laboratory findings with either drug that were judged to be pathological.", "129 chronic alcoholic patients, withdrawn from alcohol and presenting major depression or dysthymic disorder, were treated for 4-8 weeks under double-blind conditions either with a new antidepressant, tianeptine (37.5 mg per day), or with amitriptyline (75 mg per day). Both groups presented steady improvement of the symptoms of depression during treatment, as scored on the Montgomery and Asberg Depression Rating Scale and the Hopkins Symptom Checklist self-evaluation; for the latter scale, the improvement was significantly greater in the tianeptine group. In addition to the improvement of mood, tianeptine also produced significant reduction of the somatic complaints of the depressed patients. Furthermore, tianeptine possesses anxiolytic activity, as shown by the change of the Hamilton Anxiety Rating Scale global score, similar to that produced by amitriptyline. The anxiolytic activity of tianeptine was not accompanied by any impairment of vigilance, unlike that of amitriptyline. Tianeptine produced rare, mild anticholinergic effects. The results obtained show that tianeptine is an effective anxiolytic antidepressant, with better safety than amitriptyline, suitable for use in the treatment of mood disorders following alcohol withdrawal.", "nan", "nan", "A double-blind study was conducted to determine the efficacy and safety of trazodone vs. amitriptyline and placebo in 184 patients suffering from neurotic depression. All patients were evaluated for safety and 127 patients who completed 12 to 42 days' therapy were evaluated for efficacy. Trazodone was found to be significantly better than placebo on almost every rating scale, particularly on those items or factors related to depression and associated anxiety. Trazodone was superior to amitriptyline in some patients while amitriptyline was only occasionally better than placebo. Significant improvement was noted in trazodone patients within the first seven days of therapy. Trazodone produced a low level of side effects compared to amitriptyline.", "A total of 61 moderately to severely depressed outpatients were treated for four weeks with either amoxapine (a dibenzoxapine tricyclic) or amitriptyline. This double blind study showed that amoxapine was as effective as amitriptyline and had an earlier onset of action. Maximum doses used were 300 mg of amoxapine and 150 mg of amitriptyline. Side effects were similar for the two drugs, except for impotence or loss of libido in eight male amoxapine, as against three amitriptyline patients. Laboratory, EKG, and vital signs findings showed no pathological trends.", "Forty consecutive psychiatric patients referred to hospital with a diagnosis of depressive illness were randomly allocated to double-blind treatment with either 50 mg sustained-release amitriptyline or 75 mg maprotiline in night-time dosage. The dosage was doubled after 1 week. Rating scale assessments were carried out regularly over a 5-week period. The results indicated that there was a significant improvement with both drugs which occurred at approximately the same speed and to the same extent. Side-effects were complained of by approximately as many patients on both forms of treatment.", "nan", "Trazodone (TZ), a 'new generation' antidepressant and amitriptyline (AMT) were administered in a double-blind controlled study to 43 depressed inpatients. The Hamilton Depression Rating Scale (HAM-D), the AMDP-system and the Bf-s self-rating questionnaire were used for documentation of psychopathological changes and autonomic side effects. The Newcastle-Scale for definition of a neurotic and an endogenous subgroup of depression was retrospectively applied. No significant improvement was noticed on the Bf-s self-rating questionnaire in the TZ group as compared to the AMT group (p less than 0.001). The global HAM-D score decreased significantly in the TZ group (p less than 0.05) as well as in the AMT group difference (p less than 0.01) emerged during the trial in favour of AMT. Core symptoms of depression were significantly improved in the AMT group but not in the TZ group: depressed mood (p less than 0.001), psychic anxiety (p less than 0.001) and retardation (p less than 0.05). TZ was faster actin than AMT in controlling agitation. Results of this clinical study demonstrate TZ to have sedative and some anxiolytic properties but only negligible antidepressant efficacy.", "Patients suffering from mixed anxiety/depressive reactions, referred to the out-patient department of a large psychiatric hospital, were treated with either amitriptyline tablets or fluphenazine with nortriptyline (f/n) tablets for a period of four weeks. The study utilized a double-blind, completely randomised design, and patients' progress was assessed by means of the Wing Present State Examination, the Wakefield Self-Assessment Depression Inventory, and a side effects inventory. Both the symptom rating scales showed that purely depressive symptomatology improved significantly in each treatment group, but the patients' self-ratings showed that only f/n produced a significant alleviation of anxiety symptoms and panic attacks. The patients receiving f/n rated themselves as significantly (p less than 0.05) less irritable, as well as less anxious, after 4 weeks treatment, than those receiving amitriptyline. The PSE schedule did not differentiate between the 2 treatment groups, but self-rating, which is a more sensitive method of eliciting drug effectiveness in patients suffering from mild psychiatric disorders, did demonstrate patient preference for f/n. This should have important implications for compliance with treatment.", "nan", "nan", "Hypothalamic-pituitary-adrenal (HPA) axis activity was studied in 28 endogenously depressed, hospitalized patients. Measures of HPA activity obtained were baseline serum cortisol level, 24-hour urinary free cortisol excretion, and an overnight 2-mg dexamethasone suppression test. The patients then received double-blind and randomized treatment with imipramine hydrochloride, 150 mg daily, or amitriptyline hydrochloride, 150 mg daily, for four weeks. Four-week treatment response of all patients was compared with pretreatment HPA axis variables, and higher cortisol values after dexamethasone administration were found to be significantly correlated with greater improvement. There were no significant differences between imipramine and amitriptyline response, however, when improvement with each drug was compared with the pretreatment HPA variables.", "Five hundred four outpatients suffering from a major depressive episode were randomly assigned to receive either amitriptyline, doxepin, alprazolam, or placebo. The study was conducted in three treatment centers during a six-week period. All three active medications produced significantly more clinical improvement than did placebo, irrespective of the patient's initial anxiety, depression, and psychomotor retardation and irrespective of the patient's assignment to various subtypes of depression, including the DSM-III melancholia subtype. Compared with placebo, sedation was reported more frequently with all three medications, whereas anticholinergic effects were reported more frequently only for the two tricyclic antidepressants, but not for alprazolam.", "nan", "The authors compared the nontricyclic antidepressant trazodone with amitriptyline and placebo in a double-blind study of 202 unipolar depressed outpatients. Trazodone's clinical efficacy was similar to that of amitriptyline, with both active drugs producing significantly more clinical improvement than placebo. The incidence of anticholinergic side effects was lower for the patients taking trazodone than for those taking amitriptyline.", "Three hundred in- and outpatients suffering from depressive disorder, as diagnosed using DSM-III criteria were treated for 6 weeks under double-blind conditions in a multicenter controlled study of tianeptine vs. amitriptyline. Both groups presented steady improvement of depressive syndrome from day 7 up to the end of the treatment, as shown by all evaluation scales: HDRS, SAD, CGI. Furthermore, anxiety linked to the depressive syndrome decreased equally in both groups, as shown by the HARS measurements. In addition to the improvement of mood, the tianeptine-treated patients presented less somatic complaints and side effects when compared to the reference antidepressant. These results confirm previous findings that tianeptine is an effective antidepressant with a lower side effect profile than amitriptyline.", "The study described here was designed to see if it was possible to show an earlier onset of action for maprotiline (Ludiomil) compared with amitriptyline while at the same time demonstrating equal long-term effectiveness and certainly no greater side-effects. A between-patient double-blind trial with 40 patients supported these aims and was statistically significant (p less than 0.001) with regard to early onset of antidepressant effect.", "Protryptiline, a new antidepressant, was evaluated in a double-blind study. Results were compared with those obtained in similar groups of patients treated with imipramine and amitryptiline. After full psychiatric and medical assessment, patients were rated on a \"target-symptom\" scale, were assessed weekly and underwent a number of tests before and after treatment, including a hemogram and estimations of serum bilirubin, cephalin flocculation and serum protein values. Observations were made over four to six weeks. The starting dosage was 10 mg. protryptiline three times daily with a maximum of 60 mg. daily. Beneficial responses occurred in 13 of 20 patients (65%). Protryptiline-treated patients had the earliest response to drug treatment, 11 showing some improvement within the first week. Twelve patients (60%) had side effects, mainly minor, indicative of anticholinergic activity. One developed leukopenia which was reversible, and one showed increased excitement; in both, therapy was discontinued. Protryptiline gave clinical results that compared favourably with those of antidepressants of established value. While toxic effects should be carefully watched for, further trials are warranted to decide whether protryptiline possesses special or new advantages in psychopharmacotherapy.", "We report on the results of a study comparing mianserin with amitriptyline and placebo, in outpatients with major depression (DSM-III 296.2 or 296.3). One hundred and forty-nine patients were randomized to mianserin (n = 50), amitriptyline (n = 50) or placebo (n = 49). Medication was taken in a nightly (qhs) dose. During Week 1, the maximum dose was 60 mg mianserin, 120 mg amitriptyline or two placebo capsules. Beginning at Day 7 (through Day 42) maximum dosages were 150 mg mianserin, 300 mg amitriptyline or five placebo capsules. At multiple weeks and endpoint, statistically significant reductions in the Hamilton Depression Scale (HAM-D) 17- and 21-item scores were recorded for both active drugs compared with placebo. Positive results with the HAM-D were corroborated by other measures of efficacy. There were no statistically significant differences between mianserin and amitriptyline in terms of efficacy; however, the results do suggest a more rapid therapeutic response for mianserin compared with amitriptyline, in terms of percentage of patients showing > or = 50% improvement at Weeks 2 (30% vs 23%) and 4 (61% vs 44%). The most common adverse experiences were somnolence (amitriptyline and mianserin 60%, placebo 31%) and dry mouth (amitriptyline 76%, mianserin 30% and placebo 20%). Our results indicate that mianserin is clearly superior to placebo, compares favorably with amitriptyline, and is a safe, well-tolerated, effective medication in the treatment of depressed outpatients.", "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.", "nan", "A double blind trial was carried out comparing the tricyclic antidepressant lofepramine with amitriptyline in the treatment of patients suffering from moderate to markedly severe depression. No difference was demonstrated between the two drugs in terms of their antidepressant effect, but patients treated with lofepramine suffered from significantly less side effects than patients treated with amitriptyline. Both groups of patients had a high drop out rate but this was less marked in the groups of patients treated with lofepramine.", "1. A double-blind, multicentre study comparing the efficacy and safety of minaprine and amitriptyline in patients with major depression was carried out. Five hundred and thirty-one patients were randomly assigned to treatment with either minaprine 100 mg, 200 mg or 300 mg day-1 or with amitriptyline 150 mg day-1 (75 mg during the first week). The medication was administered for 6 weeks. 2. Efficacy was assessed using the Hamilton rating scale for depression (HDRS), the Montgomery-Asberg depression rating scale (MADRS) and visual analogue assessments of depression carried out by both the investigators and patients. Unwanted effects were assessed by a questionnaire and spontaneous reporting. In a subgroup of patients cardiovascular effects were investigated by high speed ECG and systolic time intervals. 3. Patients in each treatment group showed a significant clinical improvement (P < 0.01) from baseline. The mean HDRS and MADRS scores adjusted for baseline differences, showed significantly less improvement in the minaprine 100 mg once daily (P < 0.01) and the minaprine 300 mg daily (P < 0.01) groups than in the amitriptyline group at both week 4 and week 6. The MADRS score at week 4 suggested that 200 mg day-1 minaprine was less effective than amitriptyline (P < 0.05), but there was no difference between the two groups at week 6 on either the HDRS or the MADRS. 4. Both drugs were well tolerated and there were no significant differences between treatment groups in any of the safety and tolerance assessments. In the ECG, amitriptyline produced a significant increase in the heart rate and PR interval while minaprine had no effect on electrocardiographic measurements. Neither drug produced changes in the systolic time intervals.", "A multi-centre controlled trial of amitriptyline, dothiepin and mianserin in the treatment of depressive illness was undertaken in psychiatric inpatients over the age of 65. Despite the co-operation of many of the leading practitioners in this field in Great Britain, it proved impossible to recruit sufficient patients for firm conclusions to be drawn. Forty-five patients were entered into the trial, 13 withdrew because of lack of improvement, 4 because of intercurrent physical illness, 3 because of adverse effects of trial medication and 2 because of lack of compliance. Only 11 of the 23 patients completing had a final score on the Hamilton Depression Rating Scale of 10 or less. No treatment showed a significant superiority over the others, nor was there any difference in tolerance.", "Minaprine (200 mg daily, either once or divided b.d.) was compared with amitriptyline (25-50 mg t.d.s.) over six weeks in 144 patients with major depression. Significant reductions in HRSD scores at the end of six weeks' treatment were recorded with both dose regimes of minaprine and with amitriptyline, with no significant differences between them. There was a significantly greater incidence of drowsiness and dry mouth with amitriptyline than with minaprine.", "nan", "The urinary excretion of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) was measured in unipolar depressed patients before and during the fourth week of treatment with either imipramine hydrocloride or amitriptyline hydroxhloride. On the basis of strict rating criteria, 24 patients were selected as either unequivocal responders or nonresponders. In the imipramine group the mean pretreatment MHPG was significantly lower in the nine responders in the seven nonresponders; the converse was found with the amitriptyline patients. Of particular interest is that there was no overlap in individual values between the responders and nonresponders to either drug. Treatment with eigher imipramine or amitriptyline was associated with a significant decrease in MHPG excretion, which was independent of clinical response.", "1 A double-blind trial with parallel treatment groups was conducted to compare the safety and efficacy of mianserin with amitriptyline. 2 This was a six week trial with weekly visits. Measurements at each visit included: 21 item Hamilton Depression (HAMD) Scale. Clinical Global Impression (CGI) Scale and Treatment Emergent Symptom Scale (TESS). 3 Mianserin and amitriptyline were comparable with respect to efficacy. 4 More adverse experiences were reported by amitriptyline patients. The predominant amitriptyline adverse experiences were of the anticholinergic type; the predominant mianserin adverse experience was drowsiness/fatigue. 5 The Efficacy Index (EI), a scale combining efficacy and adverse experiences, clearly demonstrated the superiority of mianserin over amitriptyline.", "In a double-blind, placebo-controlled study, the therapeutic efficacy of two antidepressants with different neurochemical mechanisms of action, amitriptyline and amineptine, was investigated in patients affected by anxious depression. Sixty-six patients with the primary diagnosis of major depression or bipolar affective disorder (DSM-III-R) and meeting additional operational clinical criteria such as anxiety, trepidation, restlessness, early and/or late insomnia, impulsivity, hostility, dysphoria, compulsivity, hyperperspiration, palpitation, pollakiuria and phobias were included. They were randomly assigned to three groups (n = 22) and treated either with placebo, amitriptyline (up to 100 mg/day) or amineptine (up to 200 mg/day) for 6 weeks. Patients showed better response to amitriptyline, a preferential inhibitor of serotonin reuptake, than to amineptine, a selective inhibitor of dopamine reuptake. The present results suggest that alterations in serotonergic rather than dopaminergic transmission contribute to the pathophysiology of anxious depression.", "A double-blind trial was undertaken to compare the antidepressant efficacy and the side effects of Lofepramine with those of Amitriptyline in the treatment of endogenous depression. The study involves 22 acutely ill endogenously depressive patients. 11 patients were treated with Lofepramine and the remaining 11 with Amitriptyline. The results demonstrate that both substances are effective in the treatment of depression. However, the therapeutical efficacy of Lofepramine is significantly greater than that of Amitriptyline. Furthermore, the tolerance of Lofepramine is better than that of Amitriptyline, and the side effects of Amitriptyline, especially in blood pressure dysregulation, are greater than those of Lofepramine.", "1. The effects of fluoxetine and amitriptyline on the electrocardiogram (ECG) and systolic time intervals (STIs) were measured during a double-blind parallel-group study in depressed patients. 2. ECGs and STIs were measured after a 1 week placebo run-in, following 1 week's treatment with fluoxetine 40 mg daily or amitriptyline 100 mg daily, and then after 3 weeks' treatment with fluoxetine 60-80 mg daily or amitriptyline 150-200 mg daily. 3. Fluoxetine had no effect on the ECG or STIs at any dose. Amitriptyline 150-200 mg daily shortened the sinus cycle length by a mean of 12%, prolonged the PR interval by 8% and the QRS duration by 10%. Amitriptyline did not significantly alter the STIs.", "1. Nomifensine (8-amino-2-methyl-4-phenyl-1,2,3,4,-tetrahydroisoquinoline) is a new antidepressant which displays an interesting pharmacological profile and acts as a potent dopaminergic agonist. 2. In a double-blind clinical trialnomifensine was compared with a standard and widely tested antidepressant amitriptyline. A total of 24 patients with primary acute depressions, defined by research criteria, were treated for 8 weeks and their clinical condition and laboratory values monitored at regular intervals. The dosage schedule was a flexible one, with a daily dose range from 50-200 mg for nomifensine and 50-225 mg for amitriptyline. 3. Nomifensine and amitriptyline were found to be equivalent in their antidepressant efficacy. Nomifensine, however, showed a trend towards more rapid effect and was relatively free of side-effects. 4. As nomifensine combined antidepressant activity with low frequency of adverse effects, it would seem to be suitable for wider use in the treatment of primary depressions. The results of our study have to be generalized with caution because of the limited sample size.", "nan", "nan", "A total of 101 patients entered a double-blind, parallel-group study in general practice, comparing the efficacy and tolerability of paroxetine and amitriptyline in elderly depressed patients. All patients received placebo for 1 week followed by active therapy for a total of 6 weeks. Medication was randomly allocated, two-thirds of the patients took paroxetine (20 mg daily) and one-third received amitriptyline (50 mg daily); this dose was increased to 30 mg and 100 mg, respectively, after 1 week. Of the patients who entered the placebo run-in, 90 took active treatment and were evaluable on an intention-to-treat basis (56 paroxetine, 32 amitriptyline). The mean age of the patients was 72 years. Significant reductions in Hamilton Depression Rating Scale (HAMD) from baseline to the end of treatment were seen for both groups (p < 0.01), with no difference between treatments. The HAMD score was reduced by half, or more, for 76% of patients taking paroxetine and 86% taking amitriptyline. Significant improvement was observed in the investigators' Clinical Global Impression (CGI) score for 57% of patients taking paroxetine and 52% on amitriptyline. Improvements after treatment were also observed in the Leeds Sleep Evaluation Questionnaire (LSEQ) scores. Significantly fewer patients taking paroxetine reported adverse events (34% vs 63% taking amitriptyline, p = 0.02). Those taking paroxetine experienced significantly fewer anticholinergic side effects (7% vs 25% taking amitriptyline, p = 0.04). Overall, this study confirmed the effectiveness of paroxetine as an antidepressant drug.(ABSTRACT TRUNCATED AT 250 WORDS)", "nan", "nan", "nan", "Steady-state plasma levels of mianserin, amitriptyline, and nortriptyline were determined by HPLC in two groups of elderly depressed patients who underwent a 5-week treatment with mianserin (60 mg/day in three oral doses) or amitriptyline (75 mg/day in three oral doses). Both treatments proved to be effective in reducing depressive symptoms. In the mianserin group, responder patients had steady-state plasma concentrations of mianserin higher than nonresponders. No relationship was found between amitriptyline, nortriptyline, or amitriptyline+nortriptyline plasma levels and clinical response in amitriptyline treated patients.", "A double-blind controlled trial comparing the antidepressant activity of amitriptyline with lofepramine is reported. Forty-six patients entered the 4-week trial. Analysis of the Hamilton Depression Rating Scale scores at the beginning and end of the trial showed no significant difference between the therapeutic efficacy of lofepramine and amitriptyline. However, patients with endogenous depression responded significantly more rapidly to lofepramine as measured by Visual Analogue Scales and showed a significantly greater degree of clinical improvement after 4 weeks' treatment, as measured by Global Assessment. Adverse effects were similar in the two treatment groups. The use of rating scales in trials of depressive illnesses is discussed. The Visual Analogue Scale for depression was found to be a simple, useful and valid measure.", "A group of forty patients who presented to their general practitioner with depression or somatic complaints, which were considered to be due to depression, were included in a double-blind trial of dothiepin and amitriptyline. Patient improvement as judged by the Hamilton Rating Scale (HRS) and the Comprehensive Psychopathological Rating Scale (CPRS) indicated that both groups significantly improved over the 6 week period. Only in one comparison, CPRS after 1 week, was there any statistical difference between the groups and in this case dothiepin produced a better response than amitriptyline (p less than 0.05). Statistical analysis of side-effects indicated that the frequency and severity of certain individual side-effects, hypotension, tiredness/sleepiness and dry mouth were significantly less with dothiepin than with amitriptyline at Week 1 (p less than 0.05). The overall incidence and severity of side-effects was also less with dothiepin at all assessments during the trial.", "Thirty-four hospitalized patients with major depression were enrolled in a 3-week double-blind parallel comparative study of trimipramine and amitriptyline. Following a 1-week washout period, patients randomly received one of the two drugs up to 100 mg twice daily on a fixed increment dosage schedule. Both treatments produced a rapid significant clinical improvement that occurred in a predominantly linear fashion. The pattern of improvement was very similar with both drugs. There was no significant correlation between plasma levels of trimipramine and desmethyl-trimipramine and clinical improvement. A negative correlation between amitriptyline plasma levels and clinical improvement was found, whereas a positive correlation occurred with the nortriptyline levels. Amitriptyline, and to a lesser extent trimipramine, prolonged intracardiac conduction. In the amitriptyline group only, this effect was accompanied by significant increases of heart rate and blood pressure. Platelet serotonin content was decreased by 57% by the amitriptyline treatment but remained unchanged in the trimipramine group. This finding constitutes the first clinical evidence that trimipramine does not exert its antidepressant effect through 5-hydroxytryptamine reuptake blockade. It is proposed that neuronal sensitization to 5-hydroxytryptamine might mediate the therapeutic effect of tricyclic antidepressant drugs.", "Urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion was measured in 49 unipolar depressed outpatients to examine the relationship between pretreatment MHPG levels and therapeutic response to desipramine and amitriptyline and to determine the effects of these agents on MHPG excretion. Pretreatment MHPG excretion was greater in amitriptyline responders than amitriptyline nonresponders, but no different in desipramine responders compared to desipramine nonresponders. Pretreatment MHPG excretion did not differentiate desipramine from amitriptyline responders. Treatment for 3 weeks was associated with a decrement in MHPG excretion, particularly in the desipramine responders and combined desipramine and amitriptyline responders. Among patients within the postulated optimal desipramine plasma level range and patients with plasma amitriptyline plus nortriptyline levels greater than 70 ng/ml, high pretreatment MHPG excretion predicted therapeutic response and response was accompanied by a reduction in MHPG excretion. The interpretation of these findings is possibly confounded by the demonstration of a poor correlation (r = 0.61) between duplicate MHPG samples analyzed by a widely employed gas chromatography method and a gas chromatography/mass spectrometry technique. The methodological pitfalls encountered in the course of this investigation and their possible implications for similar studies are discussed.", "265 adult outpatients with dysthymic disorder (DSM-III) associated with clinically manifest anxiety (according to FDA criteria) were included in a multicenter, randomized double-blind study. The trial consisted of three phases: placebo pretreatment phase and inclusion in the trial, treatment phase, placebo posttreatment phase. Patients were treated in monotherapy for 42 days with a mean dosage of 3 tablets per day corresponding to 37.5 mg/day of tianeptine or 75 mg/day of amitriptyline respectively. The following assessment instruments were used: the Montgomery and Asberg Depression Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HARS), and the Check-List for the Evaluation of Somatic Symptoms of J.D. Guelfi and C.B. Pull (CHESS 82). Analysis of MADRS total scores showed an important and rapid improvement in tianeptine and amitriptyline groups, reaching statistical significance as soon as D7. At the end of the 6-week treatment period the tianeptine group reached a decrease of 64% in the initial MADRS total score versus 69% in the amitriptyline group. 78% of patients treated with tianeptine and 83% of patients treated with amitriptyline were considered as treatment responders. There was no difference in drop-out rates between the two groups. HARS scores showed a decrease in psychic as well as somatic anxiety in both groups. The action of tianeptine on anxious-depressive symptomatology was confirmed by the concomitant improvement of global clinical rating and patients' self-rating (HSCL). Statistical comparison of all clinical rating-scale scores in patients having completed the trial failed to show any significant group differences.(ABSTRACT TRUNCATED AT 250 WORDS)", "A comparative double-blind study of paroxetine and amitriptyline in the treatment of depressed hospital outpatients was undertaken at 15 centres in Italy. Three hundred and nine patients of either sex were admitted to the study. The starting dose of paroxetine was 20 mg daily and of amitriptyline 75 mg daily in divided doses; at week 3 these doses could be increased at the investigators' discretion. Efficacy was measured on the Hamilton Depression Rating Scale and on Clinical Global Impression. Both treatment groups showed significant improvement at week 6 with no significant between-group differences. Significantly fewer patients receiving paroxetine reported adverse events compared with those on amitriptyline (44% vs 62%; p < 0.01 in favour of paroxetine).", "The aim of this multicenter study was to compare trazodone (TRA) with two reference drugs, amitriptyline (AMI) and mianserin (MIA), under double-blind conditions, in an elderly population, to ascertain age-related patterns for efficacy and tolerability. One hundred six elderly depressed inpatients, ranging in age from 60 to 83 years, diagnosed as having major depression according to DSM-III, were treated with 75 mg AMI (37 patients), 60 mg MIA (33 patients) or 150 mg TRA (36 patients) p.o.t.i.d. for 5 weeks. There were no differences in the clinical outcome among the three groups of patients at the end of the trial, with a significant amelioration (p less than 0.01) for the Hamilton Rating Scale for Depression (HRS-D) and the Geriatric Depression Scale (GDS). TRA showed a lower overall prevalence of side effects than AMI or MIA, particularly for anticholinergic (p = 0.03 vs. AMI) and cardiovascular (p = 0.05 vs. MIA) effects. For these data GDS seems to be most reliable in detecting changes in elderly depressive symptomatology; moreover a comparable therapeutic response (among the three drugs) but a better tolerance for atypical antidepressants, particularly TRA, make advisable the use of the latter drug in the elderly population.", "A double-blind controlled study was carried out in 51 patients with moderate to severe depression to compare the effectiveness and tolerability of amineptine (200 mg per day) with that of amitriptyline (75 mg per day) given over a period of 6 weeks. Assessments of overall response to treatment, judged clinically, taking into account the patients' views, and also comparing total scores on the Hamilton Rating Scale, showed that amineptine was equally as effective as amitryptyline in producing a marked improvement in most patients. The results suggest, however, that amineptine was more rapid in action as well as being better tolerated. Analysis of the scores for individual items on the rating scale showed up differences between the two drugs in their influence on a number of the items and in the time of onset of improvement.", "This double-blind investigation compared onset of action, efficacy, and safety of amoxapine and amitriptyline in 46 endogenously depressed outpatients. Statistical analysis demonstrated relatively few significant differences in improvement between the two groups. Most of the differences favored amoxapine, however, and on all measures there were clear trends favoring amoxapine for more rapid onset of action or greater overall efficacy or both.", "nan", "nan", "Patients with endogenous depression fulfilling Feighner's criteria were included in the trial. All had pretrial scores above 20 on Hamilton's depression rating scale.Drugs were divided into groups A and B. Group A comprised of placebo and d-amphetamine. It was found that all patients who improved with d-amphetamine also improved with tricyclics. Two who did not improve with d-amphetamine did not improve with tricyclics.", "nan", "nan", "A total of 144 outpatients in general practice in Denmark, aged 18-65 years and diagnosed as suffering from depression with a HAMD-17 score of 15 or more, were included in this 8-week double-blind, randomised, multicentre, controlled, parallel group comparison of paroxetine versus amitriptyline. The purpose of the study was primarily to evaluate efficacy and tolerance of treatment. In addition, focus was added on weight change and subjective well-being. The efficacy results showed equal effect of both drugs. However, paroxetine was tolerated better than amitriptyline, and this difference reached the level of significance when four non-evaluable patients were taken out of the analysis. Moreover, there was a significant weight increase in the amitriptyline group and no significant weight change in the paroxetine group. There was no difference between the groups as regards subjective well-being as measured by the VAS. In conclusion, paroxetine is an effective and well-tolerated antidepressant, and well-suited for the treatment of depression in general practice.", "nan", "Paroxetine (30 mg), a selective serotonin (5-HT) reuptake inhibitor, was compared in a double-blind trial to amitriptyline (150 mg) in a sample of 40 inpatients aged 18-65 years who fulfilled Research Diagnostic Criteria for major depression. Patients were studied after a placebo drug washout period of 10 days and after an active 4-week treatment period. Sleep EEG recordings were performed before and at the end of the study as well as during acute treatment (first 2 days) and following withdrawal of active medication. Paroxetine shows an antidepressant effect similar to amitriptyline with a different side-effect profile typical of 5-HT reuptake inhibition. Paroxetine and amitriptyline decreased the amount of REM sleep, a well-known effect of classical antidepressants. Paroxetine also shared with other 5-HT reuptake inhibitors an alerting effect on sleep that was not shown to be detrimental on subjective sleep quality.", "nan", "We are performing a double-blind trial with inward psychiatric patients. The indication for our psychotropic or psychotherapeutic intervention is mainly severe depression (= major depressive disorders DSM III). For a 3-week trial course trazodone (400 mg daily), amitriptyline (150 mg/die) or placebo capsules were given at random. All patients received the same type of cognitive behaviour therapy. The test battery consists of CGI, BPRS, HAMD, HAMA and AMDP; adverse drug reactions are documented as \"free reports\" (= freier Nebenwirkungsbericht). The interim results (until March 1987) will be presented. Our investigation indicates that it is probable that the trazodone treatment we used is equivalent to corresponding amitriptyline treatment.", "The results of a double-blind trial of a tetracyclic antidepressant, maprotiline (Ludiomil) and a conventional tricyclic, amitriptyline (Elavil), in 67 ambulatory depressives are reported. Hamilton's Rating Scale for Depression was the main outcome criterion. No statistically significant differences were found between the drugs in onset of action, efficacy, side effects or predictors of response. Patients on either drug showed a significant reduction in symptoms after 1 week of treatment and at the end of the trial. Both drugs were tolerated well. A review of double-blind comparisons of maprotiline and tricyclic antidepressants, spanning 13 countries, and including over 900 patients, both ambulatory and inpatient, shows essentially similar results. The main outcome criterion in all these studies was manifest psychopathology assessed on the Hamilton Rating Scale for Depression by the treating physician. The absence of additional types of outcome criteria or assessment techniques, which may have detected differences in motor activity or drive as originally postulated, may have obscured results which were expected to be subtle.", "The relationship between steady-state plasma concentration and clinical response was studied in 22 hospitalized unipolar depressed patients. In a double-blind format the patients were randomly assigned to receive amitriptyline or nortriptyline. Dosage was adjusted based on plasma level with the aim of achieving a concentration of 60-180 ng/ml. By week 4 of treatment, 83% of amitriptyline patients and all nortriptyline patients were within the targeted plasma range. Based on final ratings of clinical state, the drug level adjustment improved the outcome for nortriptyline-treated patients, but not amitriptyline-treated patients. Nortriptyline patients with plasma levels of 60-230 ng/ml had lower Hamilton Rating Scale depression scores than patients outside that range. By contrast, amitriptyline plasma levels were not associated with depression ratings. After 1 week, patients treated with nortriptyline had a significantly greater mean reduction in Hamilton depression score, i.e., 55% compared to 25% for amitriptyline patients.", "Despite their widespread use, there are few data concerning the effects of tricyclic antidepressants on EEG sleep in depression. The present study documented the effects of desipramine (DMI, n = 17) and amitriptyline (AT, n = 16) upon EEG sleep in hospitalized depressed patients as part of a double-blind protocol involving 28 days of active treatment. Compared to placebo, patients receiving DMI showed somewhat worsened sleep continuity, particularly after 1 week of administration when the dose was 150 mg/day. On the other hand, sleep architecture and REM measures showed a rapid suppression of REM sleep, and then partial tolerance for this effect was observed with continued administration of DMI for 3 weeks. DMI was a more potent suppressor of REM sleep, while AT was more sedative. Based on these differences in effects upon EEG sleep, a discriminant function was derived and resulted in a correct classification of 87.5% of AT cases and 76.5% of DMI cases. These results are discussed in terms of the differences in pharmacological profiles for uptake blockade and anticholinergic potency for these two compounds.", "Paroxetine is a phenylpiperidine compound which is a selective serotonin reuptake inhibitor (SSRI). Ninety-one hospitalised patients with a major depression (DSM-III) aged 65 and over from six Austrian and one German center were entered into the study, which compared the efficacy and tolerability of paroxetine versus amitriptyline. After 6 weeks both groups showed similarly good therapeutic results. In the paroxetine group, 64.3% of the patients had a 50% or more reduction of the HAMD total score compared to 58.1% in the amitriptyline group. Side effects were distributed similarly in both groups. Patients in the paroxetine group showed a higher incidence of anxiety and agitation; anticholinergic side effects were registered more often in the amitriptyline group.", "A double-blind controlled comparative trial of mianserin (Norval) and amitriptyline was conducted in general practice. Fifty-one patients were treated with amitriptyline and fifty-five with mianserin. The dosage for the first week was 25 mg t.d.s. for amitriptyline and 10 mg t.d.s. for mianserin, increasing to 50 mg t.d.s. and 20 mg t.d.s. respectively for the subsequent three weeks. Both drugs proved equally effective in relieving the symptoms of primary depression but mianserin showed a reduced incidence of side-effects which was statistically significant.", "nan", "34 patients who met the research diagnostic criteria for major depressive disorder as defined by Spitzer et al. [Archs gen. Psychiat. 35: 773-782, 1978] completed a double-blind 6-week trial of mianserin versus amitriptyline following 1 week of single-blind placebo washout. After 2 weeks of dose build-up, patients took 150 mg/day of mianserin or 300 mg/day of amitriptyline throughout the next 4 weeks. At week 6, 63% of mianserin patients and 73% of amitriptyline patients were rated as responders; this difference is not statistically significant. No clinically meaningful differences between drugs were observed with respect to number or severity of side effects as reported by either patient or physician. Overall, mianserin was found to be equivalent to amitriptyline in terms of efficacy, patient tolerance and ease of administration.", "Plasma drug concentrations and clinical response were measured in two groups of hospitalised depressed patients, who received amitriptyline or imipramine double-blind, in a dosage of 250 mg for four weeks. Virtually no significant linear or curvilinear relationships were found between any plasma measure and any measure of clinical response. Modest but significant direct relationships were found between age and concentration of parent drugs but not demethylated metabolites. Blood drug level measurement therefore appears to be of little value in monitoring drug treatment of depressed in-patients.", "nan", "nan", "This study compared the tolerability and efficacy of paroxetine and amitriptyline in the treatment of depression in general practice.\n In this double-blind, multicentre study conducted in the general practice, patients with depression (Montgomery Asberg Depression Rating Scale [MADRS] score > or = 20) who were regarded as requiring antidepressant therapy were randomly assigned to receive paroxetine (20 mg, n = 184) or amitriptyline (50-100 mg, n = 191) once daily for 9 weeks.\n More patients completed treatment with paroxetine than with amitriptyline (71.1% vs 56.1%, p = 0.009). Depression rating scores (MADRS and Clinical Global Impression [CGI]) were improved with both agents, but at week 9, paroxetine achieved more favourable scores compared with amitriptyline on MADRS (p=0.019), CGI severity of depression (p=0.044), and CGI efficacy index (p = 0.038).\n Depressed patients treated in general practice respond more quickly and are more likely to complete the treatment regimen with paroxetine than with amitriptyline.", "A double blind controlled trial involving 37 inpatients whose depression was judged clinically to require antidepressant medication revealed that amoxapine and amitriptyline was approximately equal in efficacy. In average daily doses of 139.7 mg and 123 mg respectively, there seemed little difference in speed of action, or in the frequency of side effects, though amoxapine had less central nervous system stimulating consequences (tremors and restlessness) than did amitriptyline.", "nan", "The response of patients with major depressive illness to citalopram of amitriptyline was compared in a double-blind multi-centre trial. No differences in efficacy were observed, but citalopram had less hypnotic effect, and a remarkably lower profile of side-effects.", "nan", "In a double-blind study lasting for 4 weeks, the authors compared the effectiveness of amoxapine, an antidepressant with potential antipsychotic properties, with a combination of amitriptyline plus perphenazine in the treatment of 38 patients who had the diagnosis of major depression with psychotic features (psychotic or delusional depression). Patients in each group showed similar improvement in depression and psychosis. There was a tendency for the patients treated with amitriptyline plus perphenazine to have higher global response rates. However, the patients given amoxapine had significantly fewer extrapyramidal side effects.", "The results of double-blind comparative trials carried out simultaneously in three Finnish hospitals are presented. The antidepressant activity and side-effects of mianserine (ORG GB 94) and amitriptyline were compared. No statistically significant differences were found between the two treatments. It was found, however, that mianserine had clearly less anticholinergic side-effects than amitriptyline.", "A multiclinic double-blind controlled study was performed on the effects of MAP in both inpatients and outpatients with AMT as control drug. 1. Subjects consisted of 41 male and 45 female patients suffering from various types of depression. MAP was assigned to 42 cases and AMT to 44 cases. Of these patients, 14 MAP cases and 10 AMT cases were subsequently dropped for a variety of reasons to obtain 28 MAP cases and 34 AMT cases as evaluable. 2. The global improvement ratings were compared and found not significantly different for any week between the two treatments. 3. The global improvement ratings by the characteristic features of patients did not show any significant difference in any items studied between the two treatments. 4. The symptomatic improvement ratings (on the Hamilton R.S. for assessment by the physician) indicated that AMT was more effective on \"anxiety (psychic).\" 5. The symptomatic improvement ratings (on the Beck self-assessment scale by the patient) indicated that MAP was more effective on \"work\" and AMT on \"pathos\", \"feeling of satisfaction\", \"withdrawal\" and \"loss of libido.\" 6. During the treament period, 74.3 percent of the MAP group and 76.9 percent of the AMT group of patients showed some side effects of accompanying symptoms, with no significant difference recognized between the two treatments. Itemwise, however, the incidence of tremor was significantly lower (p-=0.06) in the MAP group. Moreover, the MAP group tended to be less liable to such anticholinergic side effects as dry mouth, constipation, trouble of accomodation, urinary disturbance and palpitation. 7. On the basis of the above findings, it is concluded that MAP is as effective against depression as AMT and less liable to the anticholinergic side effects. It is, therefore, a very useful antidepressant.", "Fluoxetine, a new serotonin uptake blocking antidepressant, was compared with amitriptyline in a double-blind study. Patients were diagnosed as having major depression, according to DSM-III criteria, when interviewed with the Diagnostic Interview Schedule. There was significant improvement in patient and observer ratings of depression in both groups, with no difference between groups. Recent memory improved significantly in the fluoxetine group but not in the amitriptyline group. Numbers of patients reporting side-effects were similar but the profiles of side-effects were different, with more patients on amitriptyline reporting anticholinergic and intolerable side-effects.", "Thirty-five (35) inpatients with nonpsychotic major depression were randomly assigned to either amitriptyline or nortriptyline on a double-blind basis, following a 4- to 10-day placebo run-in period. Thirty-two patients completed at least 3 weeks of active medication. The 1.0-mg dexamethasone suppression test (DST) was performed before treatment. Twelve of 32 patients were DST nonsuppressors. Both medications were equally effective. Pretreatment DST status failed to predict overall response to both medications combined. DST status also did not predict differential medication response. These data argue, along with several other studies, that pretreatment DST status may be of limited value in selecting a particular tricyclic antidepressant compound.", "Forty-two outpatients with major depressive disorder entered a double-blind, randomized trial of either desipramine or amitriptyline for a minimum of 6 weeks. Pretreatment polysomnographic and clinical measures were used to predict response. Response was defined as a 17-item Hamilton Rating Scale for Depression score less than or equal to 9 at the end of treatment. There was a 61.1% response rate for patients treated with amitriptyline and a 66.7% response rate for patients treated with desipramine. Reduced REM latency (2-night mean less than or equal to 65.0 min) predicted a positive response to these tricyclic antidepressants. REM latency did not differentiate between desipramine or amitriptyline responders. More patients with reduced REM latency (80%) responded to treatment compared with patients with nonreduced REM latency (50%). The 80% response rate in reduced REM latency depressed patients confirms our previous findings in a mixed inpatient and outpatient sample. Contrary to our hypothesis, in this sample, endogenous depression was not associated with a good response to tricyclic medication.", "This 6-week, double-blind, randomised, multicentre study was performed to assess the efficacy and tolerability of evening administration of 150 mg trazodone as an initial and maintenance therapy and to compare this regimen with recommended dosages of mianserin, dothiepin and amitriptyline in the treatment of depressed, adult, general practice patients. A total of 227 eligible depressed patients were recruited into the study by a panel of general practitioners. One hundred and twelve patients were randomised to receive trazodone therapy, 36 received mianserin, 35 received dothiepin and 44 received amitriptyline. Trazodone was administered as a single daily dose of 150 mg. Mianserin was given at a dose of 30 mg for the first 7 days followed by 60 mg daily for the remaining 5 weeks. Dothiepin and amitriptyline were both given at a dosage of 75 mg daily for the 1st week; this was then increased to 150 mg and 100 mg, respectively, for the final 5 weeks of the study. Efficacy of the four treatments was assessed using the modified Hamilton depression rating scale scores and by the Investigator's judgment of both the global severity and improvement of the condition. No significant differences were shown, using any measure of efficacy, between trazodone and any of the three comparator drugs. All treatments resulted in significant improvement in both Ham-D scores and global measures over the period of the study. Using a total side-effect score to assess the incidence and severity of adverse events and adjusting for baseline differences, the four treatments were found to differ.(ABSTRACT TRUNCATED AT 250 WORDS)", "Following a 1-week, single-blind placebo washout, 150 patients were randomized to double-blind treatment with daily doses of either mianserin, 30 mg to 150 mg; amitriptyline, 60 mg to 300 mg; or placebo, 1 to 5 capsules taken at bedtime (qhs). Mianserin and amitriptyline were found to be comparable in efficacy, and both significantly more effective than placebo in the treatment of major depressive illness. Rating instruments, all of which showed significant improvement in the active drug groups over the placebo, included the 17- and 21-item Hamilton Rating Scale for Depression (HAM-D), Montgomery and Asberg Depression Rating Scale (MADRS), Self-rating Depression Scale (SDS) index, and the Clinical Global Impressions (CGI) Severity of Illness and Improvement rating scales. Furthermore, for most efficacy parameters in the efficacy-evaluable group, the earliest statistically significant difference vs. placebo could be observed at Visit 1 for the mianserin patients and at Visit 3 for the amitriptyline patients. The safety profile for mianserin was comparable with placebo with respect to laboratory values, electrocardiogram changes, vital signs, ophthalmologic evaluations, and most adverse clinical experiences. Complaints of somnolence and weight gain were comparable in the amitriptyline and mianserin groups. Mianserin was superior to amitriptyline in terms of vital signs; anticholinergic effects; and complaints of dizziness, dyspepsia, and tremor.", "nan", "nan", "nan", "As with other second-generation antidepressants, the antidepressive efficacy of mianserin was investigated in double-blind control group studies, mostly under outpatient conditions. This study tested the antidepressive efficacy and safety of mianserin as compared to amitriptyline in a sample of 51 depressed inpatients suffering from major depression. No statistically significant difference was found with regard to the main efficacy outcome criterion, the HAMD. The tolerability results demonstrated a superiority of mianserin with respect to vegetative symptoms and especially with respect to dryness of the mouth.", "Patients suffering from mixed anxiety/depressive states referred to a psychiatric out-patient clinic completed a four course of either a once-daily table of 30 mg nortriptyline with 1-5 mag fluphenazine, or a sustained release capsule of 50 mg amitriptyline once daily, on a double-blind basis. Depression improved satisfactorily on either treatment, but there was a greater reduction of anxiety on fluphenazine/nortriptyline, Drowsiness, however, occurred more frequently among the patients on amitriptyline, suggesting the sedative properties of this drug did not substitute adequately for a specific anxiolytic effect. Dry mouth was also noticeably more frequent with amitriptyline. As might be expected on pharmacokinetic and phsyological grounds, the results suggest that the sustained release characteristics of the amitriptyline preparation lead to a maximization of side-effects during the day without conferring any therapeutic advantage.", "nan", "Depression, anxiety and psychomotor performance were assessed in 20 depressed patients during double-blind treatment with amitriptyline or trazodone. There was no difference in onset of antidepressant or anxiolytic action. No decrement or improvement on computerised tasks was found. Dry mouth was significantly more frequent and severe with amitriptyline.", "nan", "nan", "Seventy-five patients were admitted to a double-blind multicentre trial of maprotiline (Ludiomil) and amitriptyline in the management of depression in general practice. Forty-seven patients, twenty-one on maprotiline and twenty-six on amitriptyline completed the study. Statistical analysis of admission data showed that the groups were not strictly comparable in that the maprotiline group contained many more males and had a greater average age. Nevertheless, although there was a suggestion that amitriptyline was faster-acting in the younger age group that received it, there were no statistically significant differences between the two treatment groups as regards onset of effect, clinical efficacy or tolerability.", "Forty-eight patients took part in a single-blind clinical trial comparing a once daily dose of dothiepin (75 mg) and 25 mg 3-times a day of amitriptyline. The results showed that dothiepin caused a greater improvement than amitriptyline after 4 weeks of treatment as judged by depression scores, total scores and global assessments. The incidence of side-effects was less with dothiepin and in those patients who actually reported side-effects the severity was much less with dothiepin than with amitriptyline.", "nan", "nan", "nan", "nan", "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.", "Amitriptyline-perphenazine (100/8-150/12 mg/day) and doxepin (100-150 mg/day) were compared for clinical efficacy and safety in a sample of 130 nonpsychotic depressed outpatients. Maximum study duration was 4 weeks; 19 amitriptyline-perphenazine and 29 doxepin patients completed less than or equal to 3 weeks of treatment and 45 amitriptyline-perphenazine and 37 doxepin patients completed 4 weeks of treatment. Patients in both groups showed significant improvement in depression, but amitriptyline-perphenazine produced greater improvement than doxepin on several measures of depressive symptomatology. The incidence of anticholinergic and sedative side effects was higher in the amitriptyline-perphenazine treated group.", "The clinical efficacy and tolerability of trazodone and amitriptyline were compared in 74 hospital patients suffering from depressive illness. The daily doses of trazodone and amitriptyline were 150-300 mg and 75-225 mg, respectively, with half-strength capsules for patients over the age of 65 years. Twenty-five and 29 patients receiving trazodone and amitriptyline, respectively, completed the 6 week treatment period. Antidepressant activity was measured using the Hamilton Depression Rating Scale (HDRS), the Zung Scale of Depression, visual analogue scales and a Global Assessment Scale. Trazodone and amitriptyline were both effective but not statistically different from each other in terms of antidepressant action. Moreover, patients with neurotic or endogenous depression responded equally well on either treatment. Trazodone was less troublesome in respect of the persistent dry mouth and severe adverse psychiatric reactions which occurred with amitriptyline. Patients should be advised to take trazodone after meals.", "Fifty-seven neurotically depressed outpatients with sleep disturbance were randomly assigned to treatment with either imipramine pamoate or amitriptyline given in a single dose at bedtime in a double-blind study for four weeks. The results indicate that both imipramine pamoate and amitriptyline are equally effective in treating neurotic depression. The clinical lore that imipramine is more effective for retarded depression and amitriptyline for anxious, agitated depression was not supported by this study. Of special interest is the fact that the imipramine pamoate group had significantly earlier rising times, and a trend toward better quality of sleep. The side effect profiles of the two drugs were also remarkably similar in this population though more patients complained of side effects on amitriptyline than on imipramine.", "Thirty patients closely matched for age, sex and duration of illness were treated with either amitriptyline or maprotiline in a double-blind, between-patient trial. Within limits of the small number of patients in the trial, maprotiline produced a significantly quicker improvement during the first 2 weeks as judged by the scores on the Hamilton Rating Scale. Maprotiline showed better tolerability than amitriptyline overall, especially as far as trial drop-out rates were concerned.", "nan", "A new antidepressant, amoxapine, which is a dibenzoxazepine deprivative, was compared with amitriptyline in a randomised double-blind trial. Forty-eight patients were included and 41 completed a 4-week treatment. Most of the patients were maintained on 150 mg daily. Assessments were made by the Hamilton Psychiatric Rating Scale for Depression (HAM-D), Nurses' Observation Scale for Inpatient Evaluation (NOSIE), Clinical Global Impression (CGI) scale and Patient's Self-Evaluation. The total HAM-D score was considerably reduced in the majority of the patients. Amitriptyline was the most effective with regard to symptoms included in the factor Sleep Disturbances and-secondary maybe-towards some items included in the factor Somatization. For the remaining items,including the items of the factors Anxiety/Depression and Apathy, the last score was lower in the amoxapine group than in those treated with amitriptyline. Among the unipolar cases the amoxapine treated patients were more satisfied with regard to efficacy (P = 6.3%). The frequency of side effects such as tremor and dizziness was considerably lower in the amoxapine group. In total, the side effects lasted longer in the amitriptyline group. We conclude that amoxapine seems to be an effective antidepressant with a low frequency of side effects.", "A double-blind study was carried out comparing the antidepressant properties of maptotiline (a new tetracyclic antidepressant) and amitriptyline. Twenty-one hospitalized severely depressed patients, selected on the basis of clinical and psychometric criteria, completed the trial period of 28 days. The new drug was found to have an order of effectiveness similar to that of amitriptyline and both drugs were effective in agitated as well as retarded forms of depression. For both, the \"day of effect\", intended as the timing of sharp clinical improvement, tended to occur during the second week of treatment. Both drugs were well tolerated by most patients but one of the maprotiline patients presented a generalized rash which resolved after discontinuation of the drug. In conclusion, maprotiline is seen as an interesting addition to the group of major antidepressant drugs.", "This study was designed to compare the antidepressant effects of minaprine and amitriptyline in a group of 60 outpatients suffering from a major depressive episode as defined by the DSM III. The 6-week study was double-blind with a random allocation of treatment. Patients were treated with flexible daily doses of 200-300 mg of minaprine and 50-75 mg of amitriptyline. Both drugs showed significant global antidepressant efficacy with no significant difference between the two treatment groups. The Hamilton item 'psychomotor retardation' improved earlier with minaprine than amitriptyline. The incidence of anticholinergic adverse effects was significantly higher in the amitriptyline treatment group.", "nan", "In a controlled, clinical, multicentre trial comprising a total of 43 patients (17 men and 26 women) citalopram was compared double-blindly with amitriptyline. Nineteen patients of each group were classified as endogeneously depressed, whereas four patients of the citalopram group and one of the amitriptyline group were classified as non-endogenously depressed. The patients were seriously ill with a high frequency of previous depressive episodes and of mental disorders among their closest relatives. Thirteen of the patients in either group had received antidepressants without satisfactory effect before entry into the trial. Each patient was treated for a period of at least 3 weeks with daily citalopram doses of 30-60 mg or daily amitriptyline doses of 75-225 mg. A statistically significant reduction of MADRS scores (total scores as well as each of the 10 individual items) was recorded in both groups. The only difference between the groups was a trend towards a better effect on sleep disturbances in the amitriptyline group. Side-effects were recorded more frequently in the amitriptyline group than in the citalopram group, global assessment of side effects being significantly different in favour of citalopram. It is concluded that citalopram is an effective and safe drug in the treatment of endogenous depression - probably as efficacious as amitriptyline, but with fewer side effects.", "Paroxetine is a new antidepressant drug with potent serotonin (5HT) uptake inhibitory properties. In this double-blind comparative study, the antidepressant effect of paroxetine and amitriptyline has been compared in 44 patients with depressive illnesses of an endogenous nature. Each drug was given for 6 weeks. The 17-item Hamilton Depression Scale was used to measure the antidepressant effect. Reported events were assessed applying a 22-item check list. Non-parametric statistical analyses were applied in the evaluation of treatment outcome for the 30 patients who completed the study. The results showed no significant differences in overall antidepressant efficacy between paroxetine and amitriptyline and that paroxetine displayed significantly fewer instances of dry mouth and orthostatic dizziness than amitriptyline. No obvious relationship was demonstrated between the plasma levels of the drugs and their clinical effects.", "A 6-week double-blind comparison of mianserin, a new antidepressant, and amitriptyline allowed us to explore the problem of demonstrating main effect differences in drug/drug trials when the focus is primarily only upon efficacy or upon common adverse symptomatology. Statistical analyses of standard psychiatric rating scales revealed no significant treatment differences, while both treatment groups exhibited significant parallel improvement across time. Examination of treatment emergent symptoms indicated that, while it evoked fewer anticholinergic symptoms than amitriptyline, mianserin exhibited a different profile of adverse symptomatology. The usefulness of a measure of the benefit/risk ratio was described as a means of clarifying drug/drug comparisons.", "21 depressed patients of the Basle University Psychiatric Outpatient Clinic were treated in a double-blind study with paroxetine and amitriptyline. 11 of these patients did not continue the trial until the end of the 7th week. There was a significant difference in the number of dropouts between the two groups: 80% of the amitriptyline group did not continue until the end, while in the paroxetine group we found only 30% dropouts. The patients of both groups showed a gradual decrease of the median total scores on the Hamilton and the Montgomery and Asberg Depression Rating Scales. Although the number of patients who stayed in the trial for at least 4 weeks (8 with paroxetine, 6 with amitriptyline) is quite small, we see from the results of the clinical global impression that the members of the paroxetine group improved most of all in the somatic symptoms, while considering their moods we found no differences between the groups. Patients of both groups complained about side effects, most of all about dry mouth and tiredness. From the high rate of dropouts under amitriptyline we found that the side effects under this drug were more severe and therefore led to the dropouts.", "Although common in clinical settings, major depressive disorder with associated anxious symptoms ('anxious depression') has not been well studied in antidepressant clinical trials. The aim of this study was to compare the effects of fluoxetine versus amitriptyline in this group of patients. After a single-blind placebo run-in period of 2 weeks, patients were treated on a double-blind basis with fluoxetine or amitriptyline for 8 weeks. Assessment instruments included: 21-item Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Clinical Global Impressions, Raskin Depression Scale and Covi Anxiety Scale. A total of 157 patients were randomized to either fluoxetine or amitriptyline. Fluoxetine was given at a fixed dose of 20 mg/day and amitriptyline was given in a range of 50-250 mg/day (mean of 138.1 mg/day). Fluoxetine was comparable to amitriptyline in all efficacy measures except the HAMD sleep factor. Unwanted effects were more frequent and more severe in the amitriptyline-treated patients. Fluoxetine was comparably efficacious to amitriptyline in the treatment of major depression with associated anxiety. Since fluoxetine was far better tolerated, it is a promising alternative for this frequent and disabling condition." ]

[ "8038542", "17015530", "8014707", "1863121", "8618177", "9363656", "16143747", "10634835", "10634832", "7014814", "1473544" ]

[ "Comparison of weaning by patient triggered ventilation or synchronous intermittent mandatory ventilation in preterm infants.", "Randomized, controlled trial comparing synchronized intermittent mandatory ventilation and synchronized intermittent mandatory ventilation plus pressure support in preterm infants.", "Flow-synchronized ventilation of preterm infants with respiratory distress syndrome.", "Multicentre randomised controlled trial of high against low frequency positive pressure ventilation. Oxford Region Controlled Trial of Artificial Ventilation OCTAVE Study Group.", "Randomized multicenter trial comparing synchronized and conventional intermittent mandatory ventilation in neonates.", "Comparison of synchronized and conventional intermittent mandatory ventilation in neonates.", "Pressure-regulated volume control ventilation vs synchronized intermittent mandatory ventilation for very low-birth-weight infants: a randomized controlled trial.", "Randomised controlled trial of patient triggered and conventional fast rate ventilation in neonatal respiratory distress syndrome.", "International randomised controlled trial of patient triggered ventilation in neonatal respiratory distress syndrome.", "Prospective clinical comparison of two methods for mechanical ventilation of neonates: rapid rate and short inspiratory time versus slow rate and long inspiratory time.", "Decreased incidence of extra-alveolar air leakage or death prior to air leakage in high versus low rate positive pressure ventilation: results of a randomised seven-centre trial in preterm infants." ]

[ "Forty preterm infants were entered into a randomized controlled trial to compare the efficacy and duration of weaning by patient triggered ventilation (PTV) to that of synchronous intermittent mandatory ventilation (SIMV). Infants were randomized during recovery from respiratory distress once ventilator rate had been reduced to 40 breaths per minute; weaning during PTV was by reduction in ventilator pressure only, whereas infants randomized to SIMV were weaned by reduction in rate only. Weaning failed in 12 infants, 6 from each group, the 12 infants were more immature than those in whom weaning succeeded (p < 0.01). Overall, the duration of weaning did not differ significantly between the PTV and SIMV groups.", "Prolonged mechanical ventilation is associated with lung injury in preterm infants. In these infants, weaning from synchronized intermittent mandatory ventilation may be delayed by their inability to cope with increased respiratory loads. The addition of pressure support to synchronized intermittent mandatory ventilation can offset these loads and may facilitate weaning.\n The purpose of this work was to compare synchronized intermittent mandatory ventilation and synchronized intermittent mandatory ventilation plus pressure support in weaning from mechanical ventilation and the duration of supplemental oxygen dependency in preterm infants with respiratory failure.\n Preterm infants weighing 500 to 1000 g at birth who required mechanical ventilation during the first postnatal week were randomly assigned to synchronized intermittent mandatory ventilation or synchronized intermittent mandatory ventilation plus pressure support. In both groups, weaning followed a set protocol during the first 28 days. Outcomes were assessed during the first 28 days and until discharge or death.\n There were 107 infants enrolled (53 synchronized intermittent mandatory ventilation plus pressure support and 54 synchronized intermittent mandatory ventilation). Demographic and perinatal data, mortality, and morbidity did not differ between groups. During the first 28 days, infants in the synchronized intermittent mandatory ventilation plus pressure support group reached minimal ventilator settings and were extubated earlier than infants in the synchronized intermittent mandatory ventilation group. Total duration of mechanical ventilation, duration of oxygen dependency, and oxygen need at 36 weeks' postmenstrual age alone or combined with death did not differ between groups. However, infants in synchronized intermittent mandatory ventilation plus pressure support within the 700- to 1000-g birth weight strata had a shorter oxygen dependency.\n The results of this study suggest that the addition of pressure support as a supplement to synchronized intermittent mandatory ventilation during the first 28 days may play a role in reducing the duration of mechanical ventilation in extremely low birth-weight infants, and it may lead to a reduced oxygen dependency in the 700- to 1000-g birth weight strata.", "Asynchrony of delivered and spontaneous breaths in mechanically ventilated infants may impair gas exchange and prolong the need for assisted ventilation. We conducted a randomized, controlled trial of a patient-triggered, flow-synchronized ventilator on 30 preterm infants with respiratory distress syndrome who weighed between 1100 and 1500 gm at birth. Entry criteria included radiographic evidence of respiratory distress syndrome and the need for mechanical ventilation and surfactant replacement therapy. Patients were assigned to either conventional time-cycled, pressure-limited ventilation or patient-triggered, flow-synchronized ventilation in an assist/control mode. Otherwise clinical management was identical. Time to extubation was the primary outcome measure. Patients treated with flow-synchronized ventilation were weaned more rapidly and had a significantly shorter mean time to extubation than those treated with time-cycled, pressure-limited ventilation, 119 versus 271 hours, p = 0.0152. In addition, there was no difference in the rate of complications between the two groups. There were, however, considerable reductions in patient charges of $4344 per patient in the flow-synchronized ventilation group.", "A total of 346 infants aged less than 72 hours were randomly allocated to be treated either by high frequency positive pressure ventilation (HFPPV; rate fixed at 60/minute throughout treatment and initial inspiratory:expiratory (I:E) ratio 1:2, increased to 1:1 if necessary) or by low frequency positive pressure ventilation (LFPPV; rate less than or equal to 40/minute and initial I:E ratio usually 1:1, both decreasing during weaning). The main hypotheses were that HFPPV reduces pneumothorax, chronic lung disease and death before discharge in all infants, as well as those with hyaline membrane disease, and that it reduces the incidence of later neurodevelopmental complications in infants of less than 33 weeks' gestation. Among all the infants the rate of pneumothorax was 19% in the HFPPV group and 26% in the LFPPV group (p = 0.13; odds ratio 0.7, 95% confidence intervals (CI) 0.4 to 1.1); there was no difference in mortality or the incidence of chronic lung disease. In infants of less than 33 weeks' gestation there were no differences in adverse neurodevelopmental outcomes. Among the subgroup of 237 infants with hyaline membrane disease, median fractional inspired oxygen at the time of entry to the trial was 0.6 in the HFPPV group and 0.7 in the LFPPV group, indicating that many had moderately severe disease. In patients with hyaline membrane disease HFPPV was associated with a lower rate of pneumothorax (18% in the HFPPV group compared with 33% in the LFPPV group, p = 0.013, odds ratio 0.5, 95% CI 0.3 to 0.8, with no differences in mortality, or in duration of intubation or supplementary oxygen in survivors. As used in this study, HFPPV was the preferred ventilator regimen for infants with hyaline membrane disease.", "To compare synchronized intermittent mandatory ventilation (SIMV) and conventional intermittent mandatory ventilation (IMV) in neonates.\n Prospective, multicenter, randomized clinical trial.\n Level III neonatal intensive care units at six university or children's hospitals.\n Three hundred twenty-seven infants receiving conventional IMV for respiratory distress syndrome, pneumonia, or meconium aspiration pneumonitis were randomly assigned a 7.5 +/- 6 hours of age to either continue with IMV or change to SIMV. Infants assigned to each mode of ventilation had similar birth weight (BW), gestational age, and Apgar scores at birth, and similar oxygenation indexes at randomization. They received similar surfactant therapy and had similar incidence of sepsis, seizures, secondary pneumonia, and necrotizing enterocolitis. In the infants with BW less than 1000 gm, more infants receiving IMV had surgical ligation of their patent ductus arteriosus than did those receiving SIMV (27 vs. 7 %; p = 0.02).\n Data was analyzed overall for all infants and also separately within three BW groups: less than 1000 gm, 1000 to 2000 gm, and more than 2000 gm. The 1000 to 2000 gm BW group was further analyzed in subgroups weighing 1000 to 1499 gm and 1500 to 2000 gm.\n In all infants, at 1 hour after randomization, the infants receiving SIMV had a lower mean airway pressure than those receiving IMV (8.08 +/- 2.15 vs. 8.63 +/- 2.59; p<0.05), with similar fractions of inspired oxygen and oxygenation indexes. Infants whose BW was 1000 to 2000 gm at 0.5 hour required a lower fraction of inspired oxygen with SIMV than with IMV (0.52 +/- 0.20 vs. 0.62 +/- 0.27; p<0.05) and had better oxygenation at 1 hour, as shown by lower oxygenation indexes with SIMV than with IMV (6.14 +/- 4.17 vs. 9.42 +/- 8.41; p = 0.01). Infants whose BW was 1000 to 2000 gm received a lower number of unit doses of sedative/analgesic drugs per infant during the first 4 days of SIMV than did infants receiving IMV (3.8 +/- 3.4 vs 6.3 +/- 5.5 unit doses; p = 0.02). Infants whose BW was more than 2000 gm had a shorter duration of mechanical ventilation with SIMV than with IMV (median, 72 vs 93 hours; p = 0.02). Three of the forty-six infants receiving IMV but none of the 47 infants receiving SIMV required extracorporeal membrane oxygenation. In the infants with BW less than 1000 gm, fewer infants treated with SIMV required supplemental oxygen at 36 weeks of postconceptional age than did those treated with IMV (47 vs 72%; p<0.05). In 83 infants whose lungs were mechanically ventilated for 14 days or longer, all with BW less than 2000 gm, those treated with SIMV regained their BW earlier than those treated with IMV (median, 21.5 vs 29 days; p<0.01). There were no differences in the rates of death, intraventricular hemorrhage (grades III and IV), air leak, need for pharmacologic paralysis, or need for supplemental oxygen at 28 days.\n We found that SIMV was at least as efficacious as conventional IMV, and may have improved certain outcomes in BW-specific groups.", "Between October 1993 and April 1995, a total of 77 neonates requiring mechanical ventilation were enrolled in this study and were randomly divided into two groups. Group A consisted of 31 premature infants (mean birthweight 1.36 +/- 0.29 kg) with respiratory distress syndrome (RDS) and seven neonates (mean birthweight 3.2 +/- 0.5 kg) with meconium aspiration syndrome (MAS). Group B consisted of 31 premature infants (mean birthweight 1.31 +/- 0.3 kg) with RDS and eight neonates (mean birthweight 3.3 +/- 0.5 kg) with MAS. Infants in group A received synchronized intermittent mandatory ventilation (SIMV) and infants in group B received conventional intermittent mandatory ventilation (CIMV) therapy. In premature infants with RDS, our data showed: (i) the duration of ventilation was significantly shorter (P < 0.05) in the synchronized group (156 +/- 122 h) compared to the conventional group (242 +/- 175 h); (ii) significantly fewer (P < 0.05) patients required reintubation in the synchronized group than in the conventional group (three vs 11 patients); (iii) incidence of severe intraventricular hemorrhage (grades 3 and 4) was significantly lower (P < 0.05) in the synchronized group compared to the conventional group (one vs seven patients); (iv) incidence of bronchopulmonary dysplasia was significantly lower (P < 0.05) in the synchronized group than in the control group (one vs seven patients). In neonates with MAS, our data showed no significant difference (P < 0.05) on duration of ventilation, incidence of reintubation, incidence of pneumothorax or mortality rate between synchronized and control groups.", "To test the hypothesis that pressure-regulated volume control (PRVC), an assist/control mode of ventilation, would increase the proportion of very low-birth-weight infants who were alive and extubated at 14 days of age as compared with synchronized intermittent mandatory ventilation (SIMV).\n Ventilated infants with birth weight of 500 to 1249 g were randomized at less than 6 hours of age either to pressure-limited SIMV or to PRVC on the Servo 300 ventilator (Siemens Electromedical Group, Danvers, Mass). Infants received their assigned mode of ventilation until extubation, death, or meeting predetermined failure criteria.\n Mean +/- SD birth weights were similar in the SIMV (888 +/- 199 g, n = 108) and PRVC (884 +/- 203 g, n = 104) groups. No differences were detected between SIMV and PRVC groups in the proportion of infants alive and extubated at 14 days (41% vs 37%, respectively), length of mechanical ventilation in survivors (median, 24 days vs 33 days, respectively), or the proportion of infants alive without a supplemental oxygen requirement at 36 weeks' postmenstrual age (57% vs 63%, respectively). More infants receiving SIMV (33%) failed their assigned ventilator mode than did infants receiving PRVC (20%). Including failure as an adverse outcome did not alter the overall outcome (39% of infants in the SIMV group vs 35% of infants in the PRVC group were alive, extubated, and had not failed at 14 days).\n In mechanically ventilated infants with birth weights of 500 to 1249 g, using PRVC ventilation from birth did not alter time to extubation.", "To compare patient triggered, with conventional fast rate, ventilation in a randomised controlled trial using the incidence of chronic lung disease as the primary outcome measure.\n Three hundred and eighty six preterm infants with birthweights from 1000 to 2000 g, and requiring ventilation for respiratory distress syndrome within 24 hours of birth, were randomised to receive either conventional or trigger ventilation with the SLE 2000 ventilator.\n There were no significant differences in the incidence of chronic lung disease (28 day and 36 week definitions), death, pneumothorax, intraventricular haemorrhage, number of ventilator days, or length of oxygen dependency between groups.\n Patient triggered ventilation in preterm infants with respiratory distress syndrome is feasible. No significant differences, when compared with conventional fast rate ventilation in important medium and longer term outcome measures, were evident.", "To compare the effects of patient triggered ventilation (PTV) with conventional ventilation (IMV) in preterm infants ventilated for respiratory distress syndrome (RDS).\n Nine hundred and twenty four babies from 22 neonatal intensive care units were assessed. They were under 32 weeks of gestation and had been ventilated for respiratory distress syndrome (RDS) for less than 6 hours within 72 hours of birth. The infants were randomly allocated to receive either PTV or IMV. Analysis was on an \"intention to treat\" basis. Death before discharge home or oxygen therapy at 36 weeks of gestation; pneumothorax while ventilated; cerebral ultrasound abnormality nearest to 6 weeks; and duration of ventilation in survivors were the main outcome measures.\n There was no significant difference in outcome between the two groups. Unadjusted rates for death or oxygen dependency at 36 weeks of gestation were 47.4% and 48.7%, for PTV and IMV, respectively; for pneumothorax these were 13.4% and 10.3%; and for cerebral ultrasound abnormality nearest to 6 weeks these were 35.4% and 36.9%. Median duration of ventilation for survivors in both groups was 6 days. Overall, 79% of babies received only their assigned ventilation. PTV babies were more likely to depart from their intended ventilation (27% vs 15%). The trend towards higher pneumothorax rates with PTV occurred only in infants below 28 weeks of gestation (18.8% vs 11.8%).\n There was no observed benefit from the use of PTV, with a trend towards a higher rate of pneumothorax under 28 weeks of gestation. Although PTV has a similar outcome to IMV for treatment of RDS in infants of 28 weeks or more gestation, within 72 hours of birth, it was abandoned more often. It cannot be recommended for infants of less than 28 weeks' gestation with the ventilators used in this study.", "A prospective comparison was made of the clinical courses of two groups of neonates ventilated according to different protocols: one group at rates of 20 to 40/minute with a one-second IT, and the other at a rate of 60/minute and 0.5 second IT. Other ventilator settings were adjusted within protocol limits to maintain desired blood gas values. Mean starting and highest PIP were lower in the rapid rate group. The results showed no difference in mortality, failure to remain within protocol limits, time requiring respiratory treatment or FiO2 more than 0.6, and incidence of PDA or chronic lung disease. There was a difference (P = 0.011) in number of infants developing pneumothoraces (14% in the rapid group vs 35% in the slow group). Rapid rate ventilation can be used to decrease the incidence of pneumothorax, reserving long IT and higher PIP for infants who cannot be oxygenated or ventilated without them.", "Two different ventilation techniques were compared in a seven-centre, randomised trial with 181 preterm infants up to and including 32 completed weeks gestational age, who needed mechanical ventilation because of lung disease of any type. Technique A used a constant rate (60 cycles/min), inspiratory time (IT) (0.33s) and inspiratory: expiratory ratio (I:E) (1:2). The tidal and minute volume was only changed by varying peak inspiratory pressure until weaning via continuous positive airway pressure. Technique B used a lower rate (30 cycles/min) with longer IT (1.0 s). The I:E ratio could be changed from 1:1 to 2:1 in case of hypoxaemia. Chest X-rays taken at fixed intervals were evaluated by a paediatric radiologist and a neonatologist unaware of the type of ventilation used in the patients. A reduction of at least 20% in extra-alveolar air leakage (EAL) or death prior to EAL was supposed in infants ventilated by method A. A sequential design was used to test this hypothesis. The null hypothesis was rejected (P = 0.05) when the 22nd untied pair was completed. The largest reduction in EAL (-55%) was observed in the subgroup 31-32 weeks of gestation and none in the most immature group (< 28 weeks). We conclude that in preterm infants requiring mechanical ventilation for any reason of lung insufficiency, ventilation at 60 cycles/min and short IT (0.33 s) significantly reduces EAL or prior death compared with 30 cycles/min and a longer IT of 1 s. We speculate that a further increase in rate and reduction of IT would also lower the risk of barotrauma in the most immature and susceptible infants." ]

[ "6437366", "4916294", "1108832", "4194439", "6810839", "4562449", "4112185", "9004053", "6791193", "4177227", "9493481" ]

[ "Drug therapy in the prevention of recurrences in unipolar and bipolar affective disorders. Report of the NIMH Collaborative Study Group comparing lithium carbonate, imipramine, and a lithium carbonate-imipramine combination.", "Prophylactic lithium: a double-blind trial in recurrent affective disorders.", "Lithium carbonate and affective disorders. V: A double-blind study of prophylaxis of depression in bipolar illness.", "Prophylactic lithium: double blind discontinuation in manic-depressive and recurrent-depressive disorders.", "Lithium carbonate and imipramine in the prophylaxis of unipolar and bipolar II illness: a prospective, placebo-controlled comparison.", "A controlled evaluation of lithium prophylaxis in affective disorders.", "Prophylactic lithium in recurrent affective disorders.", "Gradual discontinuation of lithium augmentation in elderly patients with unipolar depression.", "Continuation therapy with lithium and amitriptyline in unipolar depressive illness: a controlled clinical trial. A report by the Medical Research Council Drug Trials Subcommittee.", "Prophylactic lithium?", "Maintenance clinical trials in bipolar disorder: design implications of the divalproex-lithium-placebo study." ]

[ "In a double-blind, long-term follow-up study, 117 bipolar patients received lithium carbonate, imipramine hydrochloride, or both and 150 unipolar patients received lithium carbonate, imipramine, both lithium carbonate and imipramine, or placebo. With bipolar patients, lithium carbonate and the combination treatment were superior to imipramine in preventing manic recurrences and were as effective as imipramine in preventing manic recurrences and were as effective as imipramine in preventing depressive episodes. The combination treatment provided no advantage over lithium carbonate alone. With unipolar patients, imipramine and the combination treatment were more effective than lithium carbonate and placebo in preventing depressive recurrences. The combination treatment provided no advantage over imipramine alone. The lithium carbonate-treated group had fewer manic episodes than the other groups. Treatment outcome, which was evaluated primarily in terms of the occurrence of major depression or manic episodes, was significantly related to characteristics of the index episode, ie, the episode that brought the patient into the study.", "nan", "The efficacy of lithium carbonate as a prophylactic drug against depression in bipolar manic depressive patients was assessed through a double-blind, placebo-controlled study of patients who had histories of recurrent depressions and hypomanias (\"bipolar II\"). The results revealed that treatment with lithium carbonate resulted in a reduction in the frequency of depressive attacks was observed with lithium carbonate treatment during the study (mean length of study, approximately 16 months), although there was a suggestion that the depressive attacks that occurred during treatment with lithium carbonate might be less severe than with placebo treatment.", "nan", "Twenty-seven patients with recurrent unipolar depression and 22 with bipolar II illness in remission for at least six months were randomly assigned on a double-blind basis to treatment regimens using lithium carbonate, imipramine hydrochloride, lithium carbonate plus imipramine, or placebo. Lithium carbonate was found to help prevent depressive relapse among patients with unipolar disease, and relapse of any type among those with bipolar II disease. No effect or interaction of imipramine was found in either group. These results add to a growing body of data that suggest the usefulness of lithium carbonate in the prophylaxis of unipolar depressive illness. The relative usefulness of lithium carbonate and imipramine requires further study.", "nan", "nan", "Recently, the therapeutic benefit of lithium augmentation in old age has come into question. These data, in light of the documented high incidence of side effects after lithium use in elderly patients, resulted in the design of a prospective, placebo-controlled lithium augmentation withdrawal study in elderly patients with unipolar depression. Twelve eligible geriatric patients (10 women and 2 men; mean [+/-SD] age, 76.2 +/- 5.7 years) with DSM-III-R unipolar depression receiving adjunct lithium therapy were randomized to receive continued lithium augmentation or matching placebo (withdrawal rate 150 mg/day/wk). At each clinic visit, patients were assessed for depression (Montgomery-Asberg Depression Rating Scale and Geriatric Depression Rating Scale) and lithium-induced toxicities (a 21-item side-effect checklist, renal and thyroid biochemistry). Over the 2-year observation period, the placebo group reported a decrease in composite 21-item side-effect score and specific lithium toxicities (e.g., urinary urgency, hand tremor, and renal/thyroid abnormalities). Two patients in the lithium maintenance group had a recurrence of depression at 61 and 96 weeks, respectively, immediately after a stressful life event (cerebrovascular accident [CVA] or death of spouse), and two patients had a recurrence in the placebo group at 7 and 92 weeks, respectively, without any apparent changes in life stresses. No other prognostic risk factors for recurrence were identified. Depression that recurred in patients who were receiving placebo was relatively resistant to reinstitution of lithium augmentation therapy. In otherwise stable geriatric patients with unipolar depression, the documented benefits of reduced side effects should be weighed against the risk of recurrence and subsequent lithium resistance before withdrawal of lithium augmentation.", "nan", "nan", "Maintenance studies in bipolar disorder have received increased attention in recent years. The interest is driven by apparent contradictions between results of early placebo-controlled trials of lithium and recent open studies, as well as interest in a new group of drugs with mood-stabilizing properties. The multiple outcome indices that require attention in prophylactic bipolar disorder studies add a dimension not present in acute studies of bipolar disorder. We present the methodology of a recently completed randomized, double-blind, placebo-controlled, parallel-group comparison of divalproex and lithium. We examine the consequences of salient design features, along with their implications for future studies. A fundamental conclusion is that such maintenance studies should be designed and executed to emphasize enrollment of patients with relatively active, severe forms of the illness. This goal is not achieved simply, as inherent features of long-term, placebo-controlled studies drive recruitment and enrollment in the direction of patients with milder forms of bipolar disorder. Attention to the frequency of both manic and depressive episodes and the severity of an index manic episode may aid in the selection of patients most suitable for studies designed to achieve adequate statistical power." ]

[ "19836904", "9692270", "12084138" ]

[ "Effect of motivational interviewing on reduction of alcohol use.", "Treatment of cocaine and alcohol dependence with psychotherapy and disulfiram.", "A randomized trial of a brief alcohol intervention for needle exchangers (BRAINE)." ]

[ "Methadone-maintained (MM) clients who engage in excessive alcohol use are at high risk for HIV and hepatitis B virus (HBV) infection. Nurse-led hepatitis health promotion (HHP) may be one strategy to decrease alcohol use in this population.\n To evaluate the impact of nurse-led HHP, delivered by nurses compared to motivational interviewing (MI), delivered by trained therapists in group sessions or one-on-one on reduction of alcohol use.\n A three-arm randomized, controlled trial, conducted with 256 MM adults attending one of five MM outpatient clinics in the Los Angeles area. Within each site, moderate-to-heavy alcohol-using MM participants were randomized into one of three conditions: (1) nurse-led hepatitis health promotion group sessions (n=87); (2) MI delivered in group sessions (MI-group; n=79), or (3) MI delivered one-on-one sessions (MI-single, n=90).\n Self-reported alcohol use was reduced from a median of 90 drinks/month at baseline to 60 drinks/month at 6-month follow-up. A Wilcoxon sign-rank test indicated a significant reduction in alcohol use in the total sample (p<.05). In multiple logistic regression analysis controlling for alcohol consumption at baseline and other covariates, no differences by condition were found.\n As compared to two programs delivered by MI specialists, a culturally-sensitive and easy to implement nurse-led HHP program produced similar reductions in alcohol use over 6 months. Employing nurse-led programs may allow cost savings for treatment programs as well as a greater integration of alcohol reduction counseling along with a more comprehensive focus on general health-related issues than previously conducted.\n Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.", "To evaluate disulfiram and three forms of manual guided psychotherapy for individuals with cocaine dependence and concurrent alcohol abuse or dependence.\n Randomized controlled trial.\n Urban substance abuse treatment center.\n One hundred and twenty-two cocaine/alcohol abusers (27% female; 61% African-American or Hispanic).\n One of five treatments delivered over 12 weeks: cognitive behavioral treatment (CBT) plus disulfiram; Twelve Step facilitation (TSF) plus disulfiram; clinical management (CM) plus disulfiram; CBT plus no medication; TSF plus no medication.\n Duration of continuous abstinence from cocaine or alcohol; frequency and quantity of cocaine and alcohol use by week, verified by urine toxicology and breathalyzer screens.\n Disulfiram treatment was associated with significantly better retention in treatment, as well as longer duration of abstinence from alcohol and cocaine use. The two active psychotherapies (CBT and TSF) were associated with reduced cocaine use over time compared with supportive psychotherapy (CM). Cocaine and alcohol use were strongly related throughout treatment, particularly for subjects treated with disulfiram.\n For the large proportion of cocaine-dependent individuals who also abuse alcohol, disulfiram combined with outpatient psychotherapy may be a promising treatment strategy. This study underlines (a) the significance of alcohol use among treatment-seeking cocaine abusers, (b) the promise of the strategy of treating co-morbid disorders among drug-dependent individuals, and (c) the importance of combining psychotherapy and pharmacotherapy in the treatment of drug use disorders.", "To test motivational interviewing (MI) as a brief intervention for reducing alcohol use among needle exchange clients.\n Randomized clinical trial.\n Needle exchange program-Providence, Rhode Island, USA.\n Between 2/98 and 10/99, we recruited 187 AUDIT-positive (>8) active injection drug users.\n Those assigned to a brief motivational intervention (MI) condition received two 1-hour therapist sessions following assessment visits, 1 month apart, focusing on alcohol use and HIV risk-taking.\n Control and MI subjects received identical research assessments at baseline, 1 and 6 months following study enrollment. At 6 months, study outcomes included days of alcohol use measured using the time-line follow-back method.\n Study retention was 96.8% at 6 months. Participants reported an average of 12.0 drinking days at baseline and 8.3 at 6 months. Significant reductions in drinking days were observed in both treatment conditions. We found significant treatment x baseline drinking day interaction effects. Tests for simple main effects were significant for subjects with above median (>9) baseline drinking day frequency, but not for those with below median baseline drinking frequency. Comparisons on dichotomous outcomes provided supporting evidence of treatment efficacy; those in MI were over two times more likely than controls to report reductions of 7 days or more (P < 0.05).\n This study provides the first direct evidence that brief MI can decrease alcohol use among active injection drug users with drinking problems. Heavier drinkers seem best suited for this intervention, but the optimal intensity of treatments and which components of brief intervention are most effective deserve further study." ]

[ "2995279", "4570522" ]

[ "Constipation during pregnancy: dietary fibre intake and the effect of fibre supplementation.", "Laxatives in the treatment of constipation in pregnant and breast-feeding mothers." ]

[ "Forty women who complained of constipation during the third trimester of pregnancy completed 14-day weighed diet records and bowel function charts over a 4-week period. After 2 weeks of baseline observation the women were randomly allocated into three groups which were asked to take 10 g dietary fibre supplements per day in the form of either a corn-based biscuit (Group A), or as wheat bran (Gp B), or to continue without intervention (Gp C). Mean (+/- s.e.m.) daily dietary fibre intake in the first 2 weeks was similar to that in the general population, at 20.4 +/- 1.2 g, for the whole group, and 21.1 +/- 1.6 g for the 26 women who said they had already increased their dietary fibre intakes in attempts to relieve their symptoms. In the final 2 weeks changes in fibre intakes were: Gp A, mean increase 7.2 +/- 1.0 g per day (P less than 0.001); Gp B, mean increase 9.1 +/- 1.6 g per day (P less than 0.001); Gp C mean decrease 3.50 +/- 1.6 g per day (P less than 0.005). These changes were accompanied by an increase in the number of bowel movements and a change to a softer stool consistency in Gps A and B, with no changes in number of bowel movements or stool consistency in Gp C.", "nan" ]

[ "9926482", "9546538", "7769899", "2180472" ]

[ "Magnesium sulphate versus diazepam in the management of eclampsia.", "Magnesium sulphate in eclampsia.", "Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial.", "Magnesium sulphate versus diazepam in the management of eclampsia: a randomized controlled trial." ]

[ "This clinical trial was conducted to compare the anticonvulsant response of magnesium sulphate and diazepam in the management of eclampsia. The study was carried out at the eclampsia unit of Dhaka Medical College Hospital during the period from October, 1995 to January, 1996. Two hundred consecutive admitted patients were recruited for the study and randomly assigned to two treatment groups: magnesium sulphate and diazepam. One hundred patients received injection magnesium sulphate and another one hundred received injection diazepam. All patients of both the group were matched for baseline characteristics. Convulsion was controlled in 95% of the patients of magnesium sulphate group and 74% of the patients of diazepam group (p < .0005). The mean controlling time is also significantly lower in magnesium sulphate group than diazepam group (8.50 hours vs 9.39 hours). Patients of magnesium sulphate group regain consciousness much earlier (mean time 20.62 hrs.) than the patients of diazepam group (mean time 40.62 hrs.). No significant difference was observed in controlling blood pressure and foetal outcome. The study finding shows that magnesium sulphate has some advantage over diazepam in controlling convulsion and regaining consciousness. If magnesium sulphate can be made available in the market by local production it may be recommended to use this drug in the primary health care without any hazzard before referring to other hospital.", "nan", "Eclampsia, the occurrence of a seizure in association with pre-eclampsia, remains an important cause of maternal mortality. Although it is standard practice to use an anticonvulsant for management of eclampsia, the choice of agent is controversial and there has been little properly controlled evidence to support any of the options. 1687 women with eclampsia were recruited into an international multicentre randomised trial comparing standard anticonvulsant regimens. Primary measures of outcome were recurrence of convulsions and maternal death. Data are available for 1680 (99.6%) women: 453 allocated magnesium sulphate versus 452 allocated diazepam, and 388 allocated magnesium sulphate versus 387 allocated phenytoin. Most women (99%) received the anticonvulsant that they had been allocated. Women allocated magnesium sulphate had a 52% lower risk of recurrent convulsions (95% CI 64% to 37% reduction) than those allocated diazepam (60 [13.2%] vs 126 [27.9%]; ie, 14.7 [SD 2.6] fewer women with recurrent convulsions per 100 women; 2p < 0.00001). Maternal mortality was non-significantly lower among women allocated magnesium sulphate. There were no significant differences in other measures of serious maternal morbidity, or in perinatal morbidity or mortality. Women allocated magnesium sulphate had a 67% lower risk of recurrent convulsions (95% CI 79% to 47% reduction) than those allocated phenytoin (22 [5.7%] vs 66 [17.1%] ie, 11.4 [SD 2.2] fewer women with recurrent convulsions per 100 women; 2p < 0.00001). Maternal mortality was nonsignificantly lower among women allocated magnesium sulphate. Women allocated magnesium sulphate were also less likely to be ventilated, to develop pneumonia, and to be admitted to intensive care facilities than those allocated phenytoin. The babies of women who had been allocated magnesium sulphate before delivery were significantly less likely to be intubated at the place of delivery, and to be admitted to a special care nursery, than the babies of mothers who had been allocated phenytoin. There is now compelling evidence in favour of magnesium sulphate, rather than diazepam or phenytoin, for the treatment of eclampsia.", "This randomized controlled trial compared the use of magnesium sulphate with diazepam as anticonvulsant in 51 eclamptic women. The use of magnesium sulphate was associated with less serious morbidity (in terms of recurrence of convulsions, cardiopulmonary problems, disseminated intravascular coagulopathy, and acute renal failure) but the difference was not statistically significant (relative risk 0.6; 95% CI 0.3 to 1.2). The one maternal death occurred in the magnesium sulphate group. Convulsions recurred in five (21%) women in the magnesium sulphate group and seven (26%) women in the diazepam group. Urine output poor enough to prompt diuretic stimulation was less frequent in the magnesium sulphate group than in the diazepam group (RR 0.3; 95% CI 0.1 to 0.9). Significantly fewer infants born in the magnesium sulphate group had low Apgar scores (less than 7 at 1 min) compared with those in the diazepam group (RR 0.6; 95% CI 0.4 to 0.9). There were two early neonatal deaths in the magnesium sulphate group, and three stillbirths in the diazepam group. This study suggests that magnesium sulphate has advantages over diazepam for the mother and the infant in the treatment of eclampsia, but the trial is small and should be replicated on a larger scale." ]

[ "12181088" ]

[ "[Treatment of chronic hepatitis C by bicyclum, a randomized double-blind placebo controlled trial]." ]

[ "To evaluate the efficacy and safety of bicyclum, a China made new hepatocyte protecting agent, in the treatment of chronic hepatitis C (CHC).\n Thirty-nine CHC patients matched demographically and clinically were randomized into two groups: bicyclum group (group A, n = 20) and placebo/bicyclum crossovergroup (group B, n = 19). Bicyclum 75mg/d or placebo was administered to these two groups respectively for 3 months. Then the patients in group A received bicyclum for further 3 months and were observed for 3 months after the treatment discontinued; and the patients in group B received bicyclum 75mg/d for six months and were observed for 3 months after the treatment discontinued. Investigation items included clinical manifestations,liver function, serum HCV RNA and anti-HCV.\n In group A, the serum ALT was 120 +/- 43 U/L before treatment and was 57 +/- 32 U/L after treatment ( P < 0.01) In group B the baseline serum ALT was 126 U/L +/- 48 U/L. After the placebo administration the serum ALT was 127 U/L +/- 97 U/L (P > 0.05) and the clinical feature showed no improvement. After bicyclum treatment for 6 months, the serum ALT in group B was 68 +/- 45 U/L, significantly lower than that before bicyclum treatment ( P < 0.01) and clinical symptoms improved. The overall ALT normalization response rate were 64.1% and 48.7% at the end of bicyclum treatment and 3 months after the treatment discontinued respectively for the total 39 patients. The serum HCV-RNA became negative in 5 and 2 patients at end of treatment and 3 months after the treatment discontinued. Adverse drug reactions were mild and uncommon. Mild dizziness occurred in 1 patient in each group.\n Bicyclum is effective in improving ALT and clinical manifestations of CHC patients. It is safe and well tolerated and shows few adverse reactions." ]

[ "16261757", "1526044", "8365006", "1540344", "12589843", "335005" ]

[ "Nonsurgical home treatment of middle ear effusion and associated hearing loss in children. Part I: clinical trial.", "Autoinflation in the treatment of glue ear in children.", "Conservative treatment of otitis media with effusion by autoinflation of the middle ear.", "Autoinflation as a treatment of secretory otitis media. A randomized controlled study.", "Factors affecting the results of nonsurgical treatment of secretory otitis media in adults.", "The medical treatment of secretory otitis media. A clinical trial of three commonly used regimes." ]

[ "We conducted a randomized, controlled clinical trial to investigate the efficacy of treatment of persistent middle ear effusion (MEE) and associated hearing loss with a modified Politzer device used in the home setting over a 7-week period. Efficacy was determined by comparing pre-and posttherapy air-conduction thresholds, tympanometric peak pressures, and otoscopic findings. The study group was made up of 94 children (174 ears), aged 4 to 11 years, who had at least a 2-month history of MEE and associated hearing loss. At study's end, patients in the treatment group experienced statistically significant improvements in all measured outcomes; no significant improvements were seen in the control group in all measured outcomes. At study's end, the hearing sensitivity of 73.9% of the treated ears was within normal limits, compared with only 26.7% of the control ears. These findings demonstrate that home treatment of children with persistent MEE and associated hearing loss with the modified Politzer device is highly efficacious.", "The use of autoinflation in the treatment of glue ear has been widely recommended. In order to assess its efficacy, 40 children were studied. 21 children practised nasal autoinflation of a toy balloon 3 times daily for 3 weeks and 19 children had no treatment. In the autoinflation group only 4 glue ears improved, while in the untreated group 10 glue ears improved. This study suggests that autoinflation has no part to play in the treatment of glue ear in children.", "A total of 85 children on the waiting list for grommet insertion aged between 3 and 10 years with bilateral chronic otitis media with effusion (OME) were assigned at random to an observation or treatment group. Those in the treatment group were given the Otovent device to use three times a day for the duration of the study and both groups were then seen at monthly intervals for 3 months for pneumatic otoscopy and tympanometry. Statistically significant improvement was seen in those using the treatment with a compliance of more than 70%. This was detected on the outcome measures of tympanometry and pneumatic otoscopy after 1, 2 and 3 months. No side effects were demonstrated. We conclude that autoinflation is an effective short-term treatment for children with OME when used regularly under supervision.", "This study was undertaken to evaluate the effect of a new method of autoinflation as an alternative treatment of secretory otitis media. Up to 80% of all children experience one or more episodes of eustachian tube dysfunction and secretory otitis media before school age. Common treatment of this condition is insertion of a ventilation tube in the tympanic membrane. Because of the very high incidence of secretory otitis media in childhood, insertion of ventilation tubes is the most frequently performed operation under general anesthesia in children. In addition to possible anesthetic complications, insertion of ventilation tubes may be associated with purulent suppuration, pathologic findings in the eardrum, and hearing impairment. One hundred children were consecutively randomized to undergo either autoinflation, using a new device, or placed in a control group. The children were between 3 and 10 years of age and were entered into the study after having had secretory otitis media for at least 3 months, as verified by tympanometric findings. Tympanometry was repeated at 2 weeks and at 1, 2, and 3 months after the children were entered into the study. After 2 weeks of autoinflation, the tympanometric conditions were improved in 64% of ears, unchanged in 34%, and deteriorated in the remaining 2%. In the control group, tympanometric findings were improved in 15% of ears, unchanged in 71%, and deteriorated in the remaining 14%.", "There is only limited knowledge of the factors influencing the results of nonsurgical treatment of secretory otitis media (SOM) in adults. The present study was carried out to determine the effect of the middle ear (ME) inflation and to clear up the factors affecting the results of conservative treatment of SOM.\n A total of 198 adult patients were randomized to either a group receiving treatment with ME inflation for 10 days or to a group receiving ME inflation and antibiotics (oral Amoxicillin 500 mg 3/day) for 10 days or to a control group. A wide variety of anamnestic and clinical pre-treatment variables were assessed by administered questionnaires. Pneumo-otoscopy, tympanometry and pure-tone audiometry were performed before the treatment and at the 3-5th, 10th+/-2 and 60th+/-5 day of the study. For the prognostic factors, univariate analyses were first performed to determine the significant predictors, which were afterwards entered into a stepwise logistic regression model.\n The effectiveness of treatment was 50.6% in Group A and 58.7% in Group B (control group-11%, P<0.001). The results of treatment were stable and were found unchanged 6 weeks after the treatment. The most important prognostic criteria were defined by analyzing the dynamics of tympanometry (OR, 2.17) and audiometry (OR, 10.27) during conservative treatment. The results of the treatment were related to the mastoid pneumatization, the pathology of paranasal sinuses, the previous history of SOM, the age, and the pre-treatment otoscopic data.\n The results suggest, that daily ME inflation can be effective treatment for adults patients with SOM having regard to the factors significant for the prognosis of treatment.", "A clinical trial was undertaken to evaluate three medical treatments commonly used for chronic secretory otitis media. The treatments compared were Ephedrine nose drops, an oral antihistamine and decongestant (Dimotapp) and autoinflation of the middle ear. Changes in middle ear compliance and pressure were used as objective criteria of the efficacy of treatment in addition to changes in pure-tone threshold and to clinical assessment. Symptoms and abnormal signs tended to remit during the trial but there was no evidence from pure-tone audiometry and tympanometry that any of the treatments was beneficial. The period of observation enabled 28% of the children to avoid surgical treatment. Good and bad prognostic features are described which should help in deciding whether to manage a case conservatively or whether to proceed directly to surgery." ]

[ "17667498", "9449446", "19333040", "6822175", "19102343" ]

[ "Defunctioning stoma reduces symptomatic anastomotic leakage after low anterior resection of the rectum for cancer: a randomized multicenter trial.", "A randomised study of colostomies in low colorectal anastomoses.", "Diverting stoma after low anterior resection: more arguments in favor.", "Protective colostomy in low anterior resection of the rectum using the EEA stapling instrument. A randomized study.", "Defunctioning loop ileostomy with low anterior resection for distal rectal cancer: should we make an ileostomy as a routine procedure? A prospective randomized study." ]

[ "The aim of this randomized multicenter trial was to assess the rate of symptomatic anastomotic leakage in patients operated on with low anterior resection for rectal cancer and who were intraoperatively randomized to a defunctioning stoma or not.\n The introduction of total mesorectal excision surgery as the surgical technique of choice for carcinoma in the lower and mid rectum has led to decreased local recurrence and improved oncological results. Despite these advances, perioperative morbidity remains a major issue, and the most feared complication is symptomatic anastomotic leakage. The role of the defunctioning stoma in regard to anastomotic leakage is controversial and has not been assessed in any randomized trial of sufficient size.\n From December 1999 to June 2005, a total of 234 patients were randomized to a defunctioning loop stoma or no loop stoma. Loop ileostomy or loop transverse colostomy was at the choice of the surgeon. Inclusion criteria for randomization were expected survival >6 months, informed consent, anastomosis < or =7 cm above the anal verge, negative air leakage test, intact anastomotic rings, and absence of major intraoperative adverse events.\n The overall rate of symptomatic leakage was 19.2% (45 of 234). Patients randomized to a defunctioning stoma (n = 116) had leakage in 10.3% (12 of 116) and those without stoma (n = 118) in 28.0% (33 of 118) (odds ratio = 3.4; 95% confidence interval, 1.6-6.9; P < 0.001). The need for urgent abdominal reoperation was 8.6% (10 of 116) in those randomized to stoma and 25.4% (30 of 118) in those without (P < 0.001). After a follow-up of median 42 months (range, 6-72 months), 13.8% (16 of 116) of the initially defunctioned patients still had a stoma of any kind, compared with 16.9% (20 of 118) those not defunctioned (not significant). The 30-day mortality after anterior resection was 0.4% (1 of 234) and after elective reversal a defunctioning stoma 0.9% (1 of 111). Median age was 68 years (range, 32-86 years), 45.3% (106 of 234) were females, 79.1% (185 of 234) had preoperative radiotherapy, the level of anastomosis was median 5 cm, and intraoperative blood loss 550 mL, without differences between the groups.\n Defunctioning loop stoma decreased the rate of symptomatic anastomotic leakage and is therefore recommended in low anterior resection for rectal cancer.", "To assess the value of covering colostomy for patients undergoing low anterior resection for rectal neoplasms.\n Prospective randomised study.\n Two university hospitals, Finland.\n 38 patients with air-tight stapled end-to-end anastomoses and complete anastomotic tissue rings were randomly allocated to have a covering colostomy (n = 19) or not.\n Postoperative mortality, anastomotic leaks, reoperations for leaks.\n The clinical leak rate was 24% (9/38) and six patients (16%) had radiological leaks. The total number of leaks (clinical and radiological together) was similar in the two groups, 7/19 compared with 8/19, respectively. There were fewer clinical leaks in the colostomy group (3/19; 16% compared with 6/19; 32%), but the difference was not significant. Reoperations for leaks were necessary more often in patients who did not have a covering colostomy (6/19; 32% compared with 1/19; 5%, p = 0.09). Two patients who did not have a stoma died from the infective complications of their leaks and one died of heart failure in the colostomy group. One patient who had not been given a stoma initially was left with a permanent colostomy after a leak.\n Our results suggest that a covering colostomy does not reduce the leak rate after low anterior resection, but prevents most of the severe infective consequences of the leaks.", "The necessity of a protective stoma in patients undergoing low anterior resection with total mesorectal excision for primary rectal cancer is discussed controversially. We conducted a randomized, controlled, pilot-study to evaluate the need for diverting ileostomy in patients undergoing low anterior resection [NCT00457327].\n Forty patients after elective sphincter-saving low anterior resection were eligible for intraoperative randomization. The primary objective of this trial was to demonstrate similar risks after the resection with both techniques. A priori stopping rules were defined for early termination of the trial.\n Between July 4, 2006 and March 12, 2007, a total of 41 patients were screened and 34 patients were randomized. Eighteen patients were randomized to the stoma group and 16 patients to the nonstoma group The symptomatic anastomotic leakage rate was significantly higher in the nonstoma group (37.5 percent) than in the stoma group (5.5 percent, P = 0.02). In all six cases in the nonstoma group, reoperations were necessary. The study was stopped after 34 patients were included. A meta-analysis of the available data confirmed the value of a protective ostomy for patients undergoing low anterior resection.\n The data demonstrate a high risk for patients undergoing low anterior resection without diverting ileostomy.", "The need for protective transverse colostomy in low anterior resection using the EEA stapler was tested in a randomized series of 50 patients, half of whom received peroperative protective colostomy. Gastrografin enema on the tenth postoperative day showed a leakage frequency of 30 per cent in both groups. Clinical leakage was noted in 4 per cent (one patient) in the colostomy group and 12 per cent (three patients) in the noncolostomy group. Protective colostomy was followed by stenosis in nine instances, compared with only two in the noncolostomy group (2 alpha = 0.05). Routine protective colostomy should not be used in low anterior resection when the EEA stapling instrument is used. The occasional clinical leakage, which may appear in the postoperative period, can be revealed by close observation and successfully treated by an emergency colostomy. The majority of patients with anterior resection of the rectum, therefore, can be spared the inconvenience and cost of temporary colostomy.", "Anastomotic leakage is a major problem in colorectal surgery particularly in low rectal cancer. The defunctioning loop ileostomy was introduced as a technique to create a manageable stoma that would divert the fecal stream from a more distal anastomosis in order to reduce the consequences of any anastomotic leakage. Therefore, the use of a defunctioning stoma has been suggested, but limited data exist to clearly determine the necessity of routine diversion. This study was designed to evaluate early morbidity, mortality and hospital stay in patients undergoing lower rectal cancer surgery concerned with or without loop ileostomy.\n This is a prospective randomized study that was performed between May 2001 and March 2008. There were 256 patients who underwent elective low anterior resection and stapler anastomosis. They were divided into two groups. Group A consisted of 120 patients who underwent straight anastomosis without ileostomy and group B consisted of 136 patients who underwent straight anastomosis with loop ileostomy. Data regarding patient demographics, underlying pathology, anastomotic problems, and ileostomy-related problems were gathered. The patients were all monitored closely after surgery for an anastomotic leak and all stoma-related complications were recorded. Inclusion criteria consisted of biopsy proven adenocarcinoma of the rectum located at < or = 5 cm above the anal verge, age > or = 22 years, and informed consent. Exclusion criteria included age more than 90 years, associated co morbid conditions Stage IV with disease spread to liver and peritoneum.\n Indications for surgery were lower rectal cancer (n=256). Mean age 55.5 years (range 22-90 years) and a male: female ratio of 1.1:1. All patients were undergoing elective surgery for lower rectal cancer. In our study 12 patients in group A developed anastomotic leak, two of them were re-explored for anastomotic leak and Hartman's colostomy was carried out. There were two deaths in Group A. In group B anastomotic leak was seen in three patients. In all three, anastomotic healing took place at a later period of time on the 18th, 20th, and 25th postoperative day respectively without any additional morbidity and mortality. Ileostomy-related problems were minor and limited to the stoma and complaints requiring stoma nurse evaluation (n=8), dehydration requiring outpatient care (n=3), bleeding at the stoma closure site (n=l). No stoma site hernias have been identified so far.\n The use of defunctioning loop ileostomy in all patients undergoing lower rectal surgery with stapler anastomosis is beneficial and safe. Defunctioning loop ileostomy use has resulted in no anastomotic leak rate and considerable low morbidity. So according to our study, we strongly recommend defunctioning loop ileostomy as a routine procedure in patients undergoing lower rectal cancer surgery." ]

[ "2658897", "3310282", "7620002", "9377880", "3948539", "3334576", "9721959", "2856601", "4048752", "8967707", "9868662", "1433118", "3888810", "3899005", "3302868", "9096584", "3056255", "3652280", "2341068", "9532327", "434682", "7990255", "6460730", "9181655", "7041654", "1288967", "6550482", "1907758", "9699761", "1425726", "8256189", "2139940", "4073086", "3616496", "8543490", "3547357", "10898671", "6089633", "3305464", "6221388", "12041767", "8256188", "6384945", "6751182", "2218831", "11233804", "4569296", "8092830", "6524903", "4697065", "8151910", "9593156", "7676242", "2897559" ]

[ "Prospective randomized comparison of mezlocillin therapy alone with combined ampicillin and gentamicin therapy for patients with cholangitis.", "Antibiotics in infections of the biliary tract.", "Ceftazidime monotherapy vs. ceftriaxone/tobramycin for serious hospital-acquired gram-negative infections. Antibiotic Study Group.", "Empiric treatment of hospital-acquired lower respiratory tract infections with meropenem or ceftazidime with tobramycin: a randomized study. Meropenem Lower Respiratory Infection Group.", "Treatment of serious urological infections with cefotaxime compared to ampicillin plus netilmicin.", "Cefotaxime (C) vs cefotaxime + amikacin (C + A) in the treatment of septicemia due to enterobacteria: a multicenter study.", "Efficacy, safety, and tolerance of piperacillin/tazobactam compared to co-amoxiclav plus an aminoglycoside in the treatment of severe pneumonia.", "Ceftazidime versus a combination of amikacin and ticarcillin in the treatment of severe infections.", "[Comparative clinical trial of cefoperazone versus ampicillin + tobramycin in severe bronchopulmonary and pleural infectious pathology].", "Effectiveness of cloxacillin with and without gentamicin in short-term therapy for right-sided Staphylococcus aureus endocarditis. A randomized, controlled trial.", "Ceftriaxone once daily for four weeks compared with ceftriaxone plus gentamicin once daily for two weeks for treatment of endocarditis due to penicillin-susceptible streptococci. Endocarditis Treatment Consortium Group.", "Ceftazidime versus aminoglycoside and (ureido)penicillin combination in the empirical treatment of serious infection.", "Cefotaxime is more effective than is ampicillin-tobramycin in cirrhotics with severe infections.", "Ceftazidime versus tobramycin-ticarcillin in the treatment of pneumonia and bacteremia.", "[Comparison of the efficacy of cefotaxime alone and the combination cefazolin-tobramycin in the treatment of enterobacterial septicemia].", "A prospective randomized trial of ceftazidime versus netilmicin plus mezlocillin in the empirical therapy of presumed sepsis in cirrhotic patients.", "Cefoperazone compared with ampicillin plus tobramycin for severe biliary tract infections.", "Azlocillin versus azlocillin plus amikacin in the treatment of severe infections in intensive care unit patients.", "[Ceftriaxone or combined cefazolin-gentamicin for complicated urinary tract infections].", "[Multicenter open randomized trial of meropenem in comparison to ceftazidime and amikacin used in combination in severe hospital infections].", "Single or combination therapy of staphylococcal endocarditis in intravenous drug abusers.", "[Imipenem/cilastatin sodium alone or combined with amikacin sulfate in respiratory infections].", "Effectiveness of mezlocillin and endotracheally administered sisomicin with or without parenteral sisomicin in the treatment of Gram-negative bronchopneumonia.", "Aminoglycosides do not improve the efficacy of cephalosporins for treatment of acute pyelonephritis in women.", "A comparative study of two antibiotic regimens for the treatment of operative site infections.", "Randomized comparison of ceftriaxone versus ceftriaxone plus amikacin for the empirical treatment of infections in patients with altered host defense: microbiological and clinical evaluation.", "Therapy of staphylococcal infections with cefamandole or vancomycin alone or with a combination of cefamandole and tobramycin.", "[Efficacy and costs of treatment with ceftriaxone compared to ampicillin-gentamycin in acute pyelonephritis].", "A randomized trial of three antibiotic regimens for the treatment of pyelonephritis in pregnancy.", "Randomized multicenter clinical trial with imipenem/cilastatin versus cefotaxime/gentamicin in the treatment of patients with non-life-threatening infections. German and Austrian Imipenem/Cilastatin Study Group.", "Cefepime for infections of the biliary tract.", "[Prospective, randomized, controlled study of imipenem-cilastatin versus cefotaxime-amikacin in the treatment of lower respiratory tract infection and septicemia at intensive care units].", "Treatment of infections in hospitalized patients with ticarcillin plus clavulanic acid. A comparative study.", "A prospective randomised comparison of cefotaxime vs. netilmicin vs. cefotaxime plus netilmicin in the treatment of hospitalised patients with serious sepsis.", "Empirical monotherapy with meropenem in serious bacterial infections. Meropenem Study Group.", "[Clinical evaluation of ceftazidime and the combined administration of cefotaxime and tobramycin in the treatment of urinary tract infections. Prospective and randomized studies].", "Monotherapy with a broad-spectrum beta-lactam is as effective as its combination with an aminoglycoside in treatment of severe generalized peritonitis: a multicenter randomized controlled trial. The Severe Generalized Peritonitis Study Group.", "Cefotaxime compared with nafcillin plus tobramycin for serious bacterial infections. A randomized, double-blind trial.", "A prospective randomized trial of ceftazidime versus cefazolin/tobramycin in the treatment of hospitalized patients with pneumonia.", "A randomized, controlled trial of cefoperazone vs. cefamandole-tobramycin in the treatment of putative, severe infections with gram-negative bacilli.", "Imipenem/cilastatin as empirical treatment of severe infections in compromised patients.", "A randomized study of cefepime versus the combination of gentamicin and mezlocillin as an adjunct to surgical treatment in patients with acute cholecystitis.", "Ceftazidime versus tobramycin/ticarcillin in treating hospital acquired pneumonia and bacteremia.", "Combination antimicrobial therapy for Staphylococcus aureus endocarditis in patients addicted to parenteral drugs and in nonaddicts: A prospective study.", "Broad spectrum penicillin as an adequate therapy for acute cholangitis.", "Efficacy of meropenem as monotherapy in the treatment of ventilator-associated pneumonia.", "Therapy with carbenicillin and gentamicin for patients with cancer and severe infections caused by gram-negative rods.", "Prospective randomized comparison of imipenem monotherapy with imipenem plus netilmicin for treatment of severe infections in nonneutropenic patients.", "Single-drug versus combination empirical therapy for gram-negative bacillary infections in febrile cancer patients with and without granulocytopenia.", "Effect of ampicillin, chloramphenicol, and penicillin-streptomycin in acute cholecystitis.", "[Clinical evaluation of combination therapy of sulbactam/cefoperazone and aminoglycoside in respiratory tract infections].", "Meropenem versus cefuroxime plus gentamicin for treatment of serious infections in elderly patients.", "[Amoxicillin and clavulanic acid versus amoxicillin plus gentamicin in the empirical initial treatment of urinary tract infections in hospitalized patients].", "Comparison of once daily ceftriaxone with gentamicin plus cefuroxime for treatment of serious bacterial infections." ]

[ "Forty-six patients with cholangitis were randomized to receive therapy with mezlocillin sodium (24 patients) or a combination of ampicillin sodium--gentamicin sulfate (22 patients). The biliary concentration of mezlocillin was 112 times higher than that of ampicillin and 778 times higher than that of gentamicin. The ratio of the concentration in serum or bile over the minimum inhibitory concentration against aerobic gram-negative bacilli (therapeutic index) was higher for mezlocillin than for either ampicillin or gentamicin. Twenty (83%) of 24 patients were cured following mezlocillin therapy compared with 9 (41%) of 22 patients after ampicillin-gentamicin therapy. The 3 patients with superinfection were in the ampicillin-gentamicin arm of the study. Fewer toxic or adverse effects occurred in association with mezlocillin treatment than with ampicillin-gentamicin treatment. Mezlocillin therapy was more effective, less toxic, and less expensive than treatment with ampicillin and gentamicin for patients with cholangitis.", "The combination of a penicillin and an aminoglycoside has been recommended as the initial treatment of choice for patients with infections of the biliary tract. However, elderly, septic, patients with jaundice have a high incidence of renal problems. For this reason, amingolycoside treatment of these patients must be reevaluated as newer less nephrotoxic agents become available. We, therefore, performed a prospective, randomized trial of ampicillin plus tobramycin, cefoperazone and piperacillin in patients with biliary tract infections. During a 20 month period, 106 patients with acute cholecystitis (53) or cholangitis (53), or both, received one of these antibiotic regimens for a minimum of five days. In patients with acute cholecystitis, ampicillin plus tobramycin, cefoperazone and piperacillin had clinical cure rates of 85, 95 and 95 per cent, respectively. In patients with cholangitis, however, cure rates for the three regimens were 85, 56 (p less than 0.05 versus ampicillin plus tobramycin) and 60 per cent (not significant versus ampicillin plus tobramycin), respectively. Moreover, 13 per cent of the patients receiving cefoperazone had an increased prothrombin time and three of 39 patients receiving this antibiotic had clinical problems with bleeding. Nephrotoxicity was greatest in patients with cholangitis receiving ampicillin plus tobramycin, 10 per cent, as compared with 3 per cent in those who did not receive an aminoglycoside. This difference, however, was not statistically significant. It was concluded that piperacillin should be considered for antibiotic management of patients with acute cholecystitis and that further studies are necessary in patients with cholangitis to determine whether or not newer agents should replace penicillin and aminoglycoside combinations.", "We compared ceftazidime monotherapy with ceftriaxone/tobramycin in a prospective, randomized clinical trial that included 580 patients with serious hospital-acquired infections. One-half of the patients had an underlying disease with a rapidly or ultimately fatal prognosis; 40% were nursed in intensive care units. Clinical response among patients with pneumonia (73% in the ceftazidime group vs. 65% in the ceftriaxone/tobramycin group), septicemia (73% vs. 59%), and complicated urinary tract infections (80% vs. 76%) showed that there were no significant differences in efficacy between the two regimens. Pseudomonas aeruginosa was the most prevalent pathogen and was effectively eradicated by both treatments. The odds of bacteriologic cure with either study regimen were equal. Mortality was similar in both treatment groups. Ceftazidime monotherapy was not associated with a higher incidence of development of resistance or superinfection. Both regimens were well tolerated; no patients receiving ceftazidime evidenced nephrotoxicity, compared with nine who received the combination. We conclude that ceftazidime may be used as monotherapy in the empirical treatment of patients with serious nosocomial infections.", "To evaluate the efficacy and tolerability of intravenous empiric treatment with meropenem compared with ceftazidime-tobramycin in patients with hospital-acquired lower respiratory tract infections.\n Prospective, nonblind, randomized trial.\n Multicenter trial conducted at 22 centers.\n Two hundred eleven patients were enrolled and 121 were evaluable for the analysis of both clinical and bacteriologic efficacy.\n One hundred four patients were randomized to receive intravenous meropenem (1000 mg) every 8 hrs and 107 patients were randomized to receive intravenous ceftazidime (2000 mg) plus tobramycin (1 mg/kg) every 8 hrs. Sixty-three meropenem-treated patients and 58 ceftazidime-tobramycin-treated patients were eligible for the analysis of clinical and bacteriologic efficacy. In the ceftazidime-tobramycin group, 32 (55%) evaluable patients received more than six doses of tobramycin, 24 (41%) received six doses or fewer, and two (3%) did not receive any tobramycin.\n The analysis of efficacy was based on the clinical and bacteriologic responses at the end of treatment. Satisfactory clinical responses occurred in 56 (89%) of 63 of the meropenem-treated patients and in 42 (72%) of 58 of the ceftazidime-tobramycin-treated patients (p = .04). Corresponding bacteriologic response rates were 89% and 67%, respectively (p = .006). The frequency and profile of drug-related adverse events was similar across treatment groups. Seizures were reported in three meropenem-treated patients, but these seizures were considered by the investigator to be unrelated to treatment.\n Meropenem is well tolerated and more efficacious than the combination of ceftazidime and tobramycin for the initial empiric treatment of hospital-acquired bacterial pneumonia.", "Fifty-nine patients with severe urinary tract infections were treated with either cefotaxime or ampicillin plus netilmicin in a controlled, open randomised study of the clinical and bacteriological effects. The patients responded favourably in both groups. The minimum inhibitory concentrations of cefotaxime against the isolates from blood were low for all bacterial strains except one (Streptococcus faecalis). Time to normalisation of temperature was significantly shorter in the cefotaxime group. The results suggest that cefotaxime is an effective and well-tolerated agent in the treatment of serious infections. However, the difference between the two groups was too small to allow preference of one procedure over the other.", "nan", "An open, randomized, multicenter study was conducted to compare the efficacy and safety of piperacillin/tazobactam and co-amoxiclav plus aminoglycoside in the treatment of hospitalized patients with severe community-acquired or nosocomial pneumonia. Of the 89 patients who entered the study, 84 (94%) were clinically evaluable. A favorable clinical response was observed in 90% of the piperacillin/ tazobactam group and in 84% of the co-amoxiclav/aminoglycoside group (not significant). The bacteriological efficacy was comparable in both groups (96% vs. 92%; not significant). There was only one fatal outcome in the piperacillin/tazobactam group compared to six in the co-amoxiclav/aminoglycoside group regimen (P=0.058). The adverse event rate was non-significantly lower in the piperacillin/ tazobactam group compared to the co-amoxiclav/aminoglycoside group (2% vs. 7%; P=0.32). Piperacillin/tazobactam is safe and highly efficacious in the treatment of serious pneumonia in hospitalized patients. It compares favorably with the combination of co-amoxiclav/aminoglycoside.", "Hospital patients with severe gram-negative bacterial infections were randomly assigned to treatment with ceftazidime (2 gm every eight or 12 hours) or a combination of amikacin (500 mg every 12 hours) and ticarcillin (3 gm every six or eight hours). The clinical and bacteriological responses to treatment were satisfactory in most of the patients in both treatment groups. Clinical cure was achieved in 18 of the 20 patients treated with ceftazidime and in 17 of the 20 treated with amikacin-ticarcillin. The bacterial eradication rate was 19 of 21 pathogens in the ceftazidime group and 17 of 20 pathogens in the amikacin-ticarcillin group.", "This study involved an open trial with parallel randomised series receiving either cefoperazone (2 g/d) or a combination of ampicillin (6 g/d) and tobramycin (3 to 4 mg/kg/d). The 30 patients included were of both sexes (male predominance), hospitalised, aged 62 +/- 11,5 years and suffering from a severe bronchopulmonary or pleural infection. Underlying pathology was serious (neoplasm, C.O.D.L., bronchiectasis, cardiac pathology). No significant difference was seen in the sampling of the two populations. Cefoperazone was prescribed in 2 infusions per 24 hours. Ampicillin was given as 3 infusions, followed by tobramycin administered by a similar number of injections. The duration of treatment was 16.8 +/- 9 days (cefoperazone) and 11,8 +/- 6,5 days (ampicillin + tobramycin). Overall evaluation (clinical, radiological and laboratory criteria) showed 88% (cefoperazone group) and 71% (ampicillin + tobramycin group) recovery and improvement rates. There were two failures in the cefoperazone group and 6 failures in the other group. These results were not statistically different. Three of the 6 failures could be attributed to resistance of the initial bacteria or selected by one or other type of treatment. None of the antibiotics prescribed raised any acceptability problems.", "It is often difficult to administer extended antibiotic therapy in the hospital for right-sided Staphylococcus aureus endocarditis. Although the effectiveness of single-drug therapy given for 4 to 6 weeks and that of two-drug therapy given for 2 weeks have been shown, no data are available on the effectiveness of short-course single-drug therapy.\n To compare the efficacy of cloxacillin alone with that of cloxacillin plus gentamicin for the 2-week treatment of right-sided S. aureus endocarditis in intravenous drug users.\n Open, randomized study.\n An academic tertiary care hospital in Barcelona, Spain.\n 90 consecutive intravenous drug users who had isolated tricuspid valve endocarditis caused by methicillin-susceptible S. aureus, had no allergy to study medications, and had no systemic infectious complications that required prolonged therapy. An efficacy subset consisted of 74 of these patients who did not meet an exclusion criterion.\n Cloxacillin (2 g intravenously every 4 hours for 14 days) alone or combined with gentamicin (1 mg/kg of body weight intravenously every 8 hours for 7 days).\n Clinical or microbiological evidence of active infection after 2 weeks of therapy, relapse of staphylococcal infection, or death.\n In an analysis of the efficacy subset, treatment was successful in 34 of the 38 patients who received cloxacillin alone (89% [95% CI, 75% to 97%]) and 31 of the 36 patients who received cloxacillin plus gentamicin (86% [CI, 71% to 95%]). Three patients died: one in the cloxacillin group and two in the combination therapy group. Of the 37 patients who completed 2-week treatment with cloxacillin, 34 (92%) were cured, and 3 (8%) needed prolonged treatment to cure the infection. Of the 34 patients who completed 2-week treatment with cloxacillin plus gentamicin, 32 (94%) were cured and 2 (6%) required treatment for 4 weeks. One patient in the combination group had relapse.\n A penicillinase-resistant penicillin used as single-agent therapy for 2 weeks was effective for most patients with isolated tricuspid endocarditis caused by methicillin-susceptible S. aureus. Adding gentamicin did not appear to provide any therapeutic advantages. Additional studies to confirm the therapeutic equivalence of short-course therapy with penicillinase-resistant penicillin alone and therapy with combined regimens are warranted.", "This randomized, multicenter, open-label study compared the efficacy and safety of monotherapy with 2 g of intravenous ceftriaxone once daily for 4 weeks with those of combination therapy with 2 g of intravenous ceftriaxone and 3 mg of intravenous gentamicin/kg once daily for 2 weeks as therapy for endocarditis due to penicillin-susceptible streptococci. Sixty-one patients were enrolled in the study. Clinical cure was observed for 51 evaluable patients both at termination of therapy and at the 3-month follow-up: 25 (96.2%) of 26 monotherapy recipients and 24 (96%) of 25 combination therapy recipients. Of the 23 patients in each treatment group who were microbiologically evaluable, 22 (95.7%) in each group were considered cured. No patient had evidence of relapse. Fourteen patients (27.5%) required cardiac surgery after initiation of treatment, including five monotherapy recipients and nine combination therapy recipients. Adverse effects were minimal in both treatment groups. We conclude that 2 g of ceftriaxone once daily for 4 weeks and 2 g of ceftriaxone in combination with 3 mg of gentamicin/kg once daily for 2 weeks are both effective and safe for the treatment of streptococcal endocarditis.", "Urgent treatment of serious infections with broad spectrum antibiotics usually starts before bacteriological evidence of the infective organism(s) becomes available. In this study 471 patients with a clinical diagnosis of sepsis were treated empirically with ceftazidime (CAZ) monotherapy (249 patients), or with an aminoglycoside+(ureido)penicillin combination (AG+PEN) (222 patients) to establish clinical outcome and bacteriological response. Up to 72 h post-treatment 94.5% of patients in the CAZ group and 93.8% in the AG+PEN group were treated successfully (treatment difference 0.7%, P < 0.01, 95% confidence interval -3.8%, 5.2%); 2-4 weeks after treatment neither regimen proved clinically superior. The differences in bacteriological response up to 72 h, and at 2-4 weeks after treatment, were 5.6% and 12.4% in favour of CAZ, however, these were not statistically significant. Overall, 56 patients reported 72 adverse events in the CAZ group, compared with 33 patients reporting 41 adverse events in the AG+PEN group. Deaths, 40 on CAZ and 21 on AG+PEN, were mainly related to their underlying condition. The two regimens were shown to be clinically equivalent in seriously ill patients treated empirically.", "We compared the effectiveness and incidence of nephrotoxicity of ampicillin-tobramycin and cefotaxime in 73 cirrhotics who had severe bacterial infection. Most of these patients had spontaneous peritonitis and/or bacteremia. Patients were randomly allocated into two groups. Group I included 36 patients treated with ampicillin-tobramycin and Group II comprised 37 patients treated with cefotaxime. Patients from both groups were similar with respect to clinical data, standard liver and renal function tests, types of infection and isolated organisms. Ninety-two per cent of bacteria isolated in Group I and 98% of those isolated in Group II were susceptible in vitro to ampicillin-tobramycin and to cefotaxime, respectively. Ampicillin-tobramycin cured the infection in 56% of Group I patients, and cefotaxime in 85% of Group II patients (p less than 0.02). Five patients treated with ampicillin-tobramycin, and none treated with cefotaxime developed superinfections (p = 0.024). Nephrotoxicity (impairment of renal function associated with an increase of urinary beta 2-microglobulin to over 2,000 micrograms per liter) occurred in two patients in Group I and none in Group II. These results suggest that broad-spectrum cephalosporins should be considered as first choice antibiotics in cirrhotic patients with severe infections.", "A prospective, randomized study was undertaken to compare the efficacy and safety of ceftazidime with those of a combination of ticarcillin and tobramycin in the treatment of 40 nonneutropenic patients with pneumonia or bacteremia. Altogether, 93% of the patients receiving ceftazidime for pneumonia were cured, and 87% of those with bacteremia responded favorably. Of the subjects who were treated with ticarcillin and tobramycin ceftazidime developed significant superinfection, and one individual treated with the aminoglycoside and carboxypenicillin developed reversible azotemia. Ceftazidime appears to be as efficacious as the ticarcillin-tobramycin combination and is probably safer with regard to oto-and nephrotoxicity; however, superinfections did occur more frequently in the group treated with ceftazidime.", "In a prospective, randomized study we compared cefotaxime (C) with tobramycin plus cefazolin (C + T) in the treatment of Enterobacterial septicemia. Twenty-five patients received C and twenty two C + T. There are 8 treatment failures, in C + T group, 3 in C group. We observed 5 adverse effects, 2 in the C group (1 reversible collapse and 1 Pseudomonas aeruginosa superinfection) and 3 in the C + T group (acute renal failures). We conclude that C may be more effective and less toxic than cefazolin plus tobramycin for patients with Enterobacterial septicemia.", "Aminoglycosides are frequently used to treat sepsis in patients with liver disease. However, it has been suggested that cirrhotic patients are particularly sensitive to aminoglycoside-induced renal dysfunction. We investigated the efficacy and incidence of renal impairment with netilmicin plus mezlocillin compared with ceftazidime in 128 cirrhotic patients who required empirical treatment for sepsis. Renal impairment developed in 8 of 63 (13%) patients receiving netilmicin compared with 2 of 65 (3%) patients receiving ceftazidime (P < .05); it occurred despite regular monitoring of trough netilmicin levels. Renal impairment was present at the time of death in 1 of 13 (8%) patients treated with ceftazidime compared with 5 of 9 (56%) of the netilmicin patients (P < .05). Mortality rates were similar in the two groups (ceftazidime 20%, aminoglycoside 14%; P = NS). Renal dysfunction is significantly more frequent in cirrhotic patients treated with netilmicin but with careful attention to dosage and fluid management the clinical effect is likely to be relatively modest.", "In a prospective, randomized, multicenter study, the efficacy and safety of cefoperazone and the combination ampicillin-tobramycin as initial therapy for patients with severe acute biliary tract infections were compared. Of 77 patients initially entered in the study, definite severe biliary tract infection was confirmed in 67. Sixty-four patients completed treatment. At the end of treatment, 35 of 36 (97%) patients given cefoperazone and 23 of 28 (82%) given ampicillin-tobramycin were cured of their infection (P = 0.07). Pathogens were recovered from the bile in 32 patients; microbiological cures were observed in 18 of 19 (94%) patients receiving cefoperazone and 8 of 13 (62%) receiving ampicillin-tobramycin (P = 0.03). Thirteen patients had septicemia. None (0%) of the eight septicemic patients from the cefoperazone group, but two of five (40%) from the ampicillin-tobramycin group, were clinical failures. Of the isolated pathogens, 51% were resistant to ampicillin, while the resistance rate was 4% for tobramycin and 1% for cefoperazone (P less than 0.001). Biliary concentrations of cefoperazone were maintained at high levels--236 +/- 87 micrograms/ml up to 12 h after administration. Even in the presence of severe obstruction, cefoperazone levels in the bile and gallbladder wall were above MICs for most pathogens. Cefoperazone may be considered as an excellent alternative in the therapy of severe biliary tract infections.", "The authors wanted to verify if in clinical practice (Intensive Care Unit patients), the association of azlocillin with an aminoglycoside offers substantial advantages compared to use of azlocillin alone. Their results show that azlocillin alone is potent enough to be used in the treatment of severe infections.", "40 seriously ill patients with complicated urinary tract infections were randomly assigned to receive either a single daily dose of ceftriaxone or combined therapy with cefazolin and gentamicin administered every 8 hours. The groups were of equal size, similar in age (both averaged 75 years) and the sex ratio was about 1:1 in each group. 32.5% had proven bacteremia and the overall mortality was 17.5%. Both regimens were similarly effective in terms of mortality, duration of fever (3.0-3.1 days), and sterilization of the urine prior to discharge from hospital. However, the single daily dose of ceftriaxone was much more convenient to administer.", "Clinical efficacy and tolerance of meropenem were estimated by comparison with those of ceftazidime and amikacin used in combination in the therapy of hospital infections of the lower respiratory tract, skin and soft tissues, intraabdominal and gynecologic infections, urinary tract infection and sepsis. 48 patients were given meropenem in a dose of 1 g every 8 hours for 3-14 days (the average of 9 days). 47 patients were subjected to the routine combined therapy: ceftazidime in a dose of 1 g every 8 hours and amikacin in a dose of 0.5 g every 12 hours for 2-14 days (the average of 9 days). The patient groups were comparable by the age, nature and severity of the infection and the condition (the mean APACHE II of 9.1 and 8.9). By the end of the treatment a positive clinical effect (recovery and improvement) was observed in 47 patients (97.9 per cent) treated with meropenem and in 41 patients (89.1 per cent) subjected to the combined therapy. The infection relapse within 4 weeks after the treatment completion was recorded in 3 patients in every group. Before the treatment 133 microbial strains were isolated from the patients. 121 of them were susceptible to meropenem (91.1 per cent), 111 to amikacin (83.4 per cent) and 90 to ceftazidime (67.7 per cent). The difference between meropenem and ceftazidime was significant (p = 0.0005). Eradication of the primary pathogens at the background of the meropenem therapy was stated in 41 out of 44 patients (93.2 per cent) and that of the combined therapy in 38 out of 43 patients (88.4 per cent). The microbiological relapse after the treatment completion was recorded in 3 and 2 patients, respectively. Side effects were observed in 8.3 per cent of the patients treated with meropenem and in 10.6 per cent of the patients subjected to the combined therapy. The trial results were indicative of the meropenem high efficacy and good tolerance and of the possible use of the drug in the monotherapy as an alternative of the routine combined therapy of severe hospital infections.", "Staphylococcus aureus is the commonest cause of acute endocarditis in intravenous drug abusers. In-vitro and in-vivo animal studies have found increased killing of organisms with the combination of a beta-lactam antibiotic and an aminoglycoside. These findings have created a controversy about the use of such combination therapy. We randomly treated 25 episodes of S. aureus endocarditis in intravenous drug abusers with either single or combination antibiotic regimens. Mean days to defervescence were similar in both groups: 6.3 d (SEM, 1.49 d) for the single drug group and 6.6 d (SEM, 1.02 d) for the group treated in combination with an aminoglycoside. There were no bacteriologic failures or relapses in either group. No patients needed valvular surgery, and the mortality rate was zero. Thus, it appears that single drug therapy with an appropriate beta-lactam antibiotic is adequate and appropriate in intravenous drug abusers with S. aureus endocarditis.", "In the present study, we used the envelope method to divide patients with respiratory infections into two groups: a monotherapy group given imipenem/cilastatin sodium (IPM/CS) and a combination therapy group given imipenem/cilastatin sodium plus amikacin sulfate (AMK). We then compared the clinical efficacy and safety between groups. 1. Safety was evaluated in 83 patients in the IPM/CS group and 88 in the IPM/CS + AMK group while clinical efficacy was evaluated in 77 and 80 patients in the respective groups. 2. The overall efficacy rate was 84.4% in the IPM/CS group. Among the main infections, the efficacy rates were 82.7% in 52 cases of pneumonia (including lung abscess), 100% in cases of infected bronchiectasis, 66.7% in six cases of secondary infection of chronic respiratory disease, and 100% in four cases of chronic bronchitis. The overall efficacy rate was 83.8% in the IPM/CS + AMK group. Among the main infections, the efficacy rates were 88.1% in 59 cases of pneumonia (including lung abscess), 83.3% in 12 cases of infected bronchiectasis, and 60.0% in five cases of secondary infection of chronic respiratory disease. No significant differences in efficacies were seen between groups. 3. In the IPM/CS group, the efficacy rates were 92.3% for patients without prior antibiotic therapy in the IPM/CS group and 68.0% for those with prior therapy; in the IPM/CS + AMK group, the respective rates were 83.7% and 83.9%. In the IPM/CS group, there was a significant difference in the responses of patients with and without prior antibiotic therapy (P < 0.05). 4. Side effects were observed in six patients in the IPM/CS group (7.2%) and two patients in the IPM/CS + AMK group (2.3%). Abnormal laboratory test results were noted in 5 patients in the IPM/CS group (6.0%) and in 10 in the IPM/CS + f1p4group (11.4%). There was no significant difference in the incidence of side effects between groups and no severe adverse reactions in either group. These results indicate that IPM/CS alone produces of good response in moderate to severe respiratory infections while IPM/CS combined with AMK is useful in intractable respiratory infections.", "nan", "A prospective, coordinated, randomized multicentre trial was conducted to determine whether tobramycin 160 mg intravenously (i.v.) once daily for 2 days would improve the efficacy of cefotaxime 1 g i.v. twice daily for 2 days followed by a 10-day course of oral cefadroxil 1 g twice daily, in the treatment of community-acquired acute pyelonephritis in women. Of 73 patients enrolled in the study, 51 could be evaluated according to the protocol. There were no significant differences in bacteriological cure rates between the combined treatment with tobramycin/cefotaxime and cefotaxime alone, either at short-term follow-up (63.0% vs 59.1%; 95% confidence interval (CI) for difference in proportions -23.4% to 31.2%), or up to 7 weeks after cessation of treatment (42.9% vs 52.2%; 95% CI, -18.0% to 36.6%). A modified intention-to-treat analysis showed no difference in clinical efficacy between the two regimens (68.6% vs 69.2%; 95% CI, -22.9% to 24.1%). Tobramycin seemed to enhance the resolution of inflammation by a more rapid decline in C-reactive protein levels. The high recurrence rates after treatment with beta-lactam antibiotics in this and previous studies of acute pyelonephritis may be explained by adverse ecological effects rather than failure to eradicate the infection.", "This prospective study was designed to compare the relative efficacy of two antibiotic regimens for the treatment of operative site infections subsequent to pelvic operations. Patients with endomyoparametritis after delivery or pelvic cellulitis subsequent to hysterectomy were randomized to treatment with the combination of penicillin-gentamicin or the single agent cefoxitin. Seventeen of the 26 patients (65%) with endomyoparametritis who were treated with penicillin-gentamicin were cured by antibiotic therapy alone, in comparison to 15 of 23 (65%) patients treated with cefoxitin. Fifty-eight percent of the patients with pelvic cellulitis who were treated with penicillin-gentamicin responded favorably, in comparison to 50% of the patients treated with cefoxitin. None of these differences was statistically significant. In this study, neither antibiotic regimen provided satisfactory initial treatment for surgically induced soft tissue pelvic infection. Moreover, 11 of the 28 patients with treatment failures (40%) developed serious sequelae of their primary infection.", "Two hundred and eighty-four febrile episodes in immunocompromised patients were treated with ceftriaxone alone or in combination with amikacin. In the ceftriaxone-treated group, 60 out of 143 febrile episodes were microbiologically documented, while in the group receiving the combination therapy, there were 32 out of 140 (p = 0.0007). Gram-positive microorganisms were more common than gram-negative ones, accounting for 59 of the 101 isolated bacteria. The ceftriaxone regimen appeared to have a response rate comparable to the combination regimen (73.91 vs. 78.88%). Superinfections occurred under both regimens.", "Eighty adult patients with microbiologically demonstrated staphylococcal infections were included in a comparative trial of cefamandole and cefamandole plus tobramycin. Patients with cefamandole-resistant pathogens were treated with vancomycin, if the initial therapy consisted of cefamandole, but were continued on cefamandole plus tobramycin if already started on that combination. Of the patients infected with cefamandole-susceptible strains, 91% (20/22) responded favorably to treatment with cefamandole alone, and 88% (30/34) responded favorably to cefamandole plus tobramycin. Of the patients infected with cefamandole-resistant staphylococci, 70% (7/10) responded to treatment with cefamandole plus tobramycin, and 86% (12/14) responded to treatment with vancomycin, even though vancomycin therapy was started 24 to 48 h later than cefamandole-plus-tobramycin therapy. No major side effects were observed; however, cefamandole plus tobramycin was associated with a rise in the serum creatinine level in 11% (4/44) of the patients. The bactericidal activity of the serum in cefamandole-treated patients and in cefamandole-plus-tobramycin-treated patients was identical against cefamandole-susceptible strains. Against cefamandole-resistant strains, 87% of the vancomycin-containing sera were bactericidal at a dilution of 1:8, whereas only 57% of the cefamandole-plus-tobramycin-containing sera were active at that dilution.", "nan", "To compare the effectiveness of three antibiotic regimens for the treatment of acute pyelonephritis in pregnancy.\n One hundred seventy-nine pregnant women earlier than 24 weeks' gestation who had acute pyelonephritis were randomized to 1) intravenous (i.v.) ampicillin and gentamicin, 2) i.v. cefazolin, or 3) intramuscular ceftriaxone. All participants then completed 10-day courses of oral cephalexin after primary treatment. A urine culture was performed on admission and 5-14 days after completion of therapy. Surveillance for persistent or recurrent infection and obstetric complications continued until delivery. On the basis of a two-sided hypothesis test and with alpha = .025, 60 subjects were needed in each group for statistical power greater than 80% to detect a difference between ceftriaxone and other antibiotics if hospital length of stay differed by 1 or more days.\n The treatment groups were similar in age, parity, temperature, gestational age, and initial white blood cell count. There were no statistically significant differences in length of hospitalization, hours until becoming afebrile, days until resolution of costovertebral angle tenderness, or infecting organism. There were no statistically significant differences in birth outcomes between the three groups. The average (standard deviation) age at delivery was 38.8 +/- 3.6 weeks. The average birth weight was 3274 +/- 523 g. Eleven (6.9%) of 159 subjects delivered prematurely. Escherichia coli was the most common uropathogen isolated (137 of 179, 76.5%). Blood cultures were positive for organisms in 15 cases (8.4%). At follow-up examination within 2 weeks of initial therapy, eight (5.0%) of 159 subjects had urine cultures positive for organisms. Ten women (6.3%) had cultures positive for organisms later in their antepartum course, and 10 other participants (6.3%) developed recurrent pyelonephritis.\n There are no significant differences in clinical response to antimicrobial therapy or birth outcomes among subjects treated with ampicillin and gentamicin, cefazolin, or ceftriaxone for acute pyelonephritis in pregnancy before 24 weeks' gestation.", "In an open, controlled, randomized study the safety and efficacy of imipenem/cilastatin was compared with that of the combination cefotaxime/gentamicin (plus metronidazole in patients with suspected anaerobe infection) in the treatment of 337 patients from 12 German and 5 Austrian centers who had non-life-threatening infections. The evaluation was done on an intention-to-treat basis (i.e. all patients including protocol violators) and according to the protocol (144 patients in the imipenem/cilastatin group and 124 in the cefotaxime/gentamicin group). No significant differences were seen between the two treatment groups in terms of the clinical and bacteriological outcome. The frequency of infusion intolerance and thrombophlebitis was low in both groups (< 2%). The overall rate of adverse events was comparable in the two groups, nausea, vomiting and diarrhea being the most frequent events. Nephrotoxicity, indicated by an increase in serum creatinine, was significantly higher in the cefotaxime/gentamicin group. Imipenem/cilastatin was shown to be as effective as cefotaxime/gentamicin (metronidazole) and appears to be well tolerated.", "Antibiotic treatment of biliary tract infections is widely accepted. An open, prospective, randomized, multicenter trial comparing cefepime (2 grams every 12 hours) with gentamicin (1.5 milligrams per kilograms every eight hours) plus mezlocillin (3 grams every four hours) for a minimum of five days was undertaken. Of the 149 patients enrolled, 120 were evaluable; 80 were randomized to receive cefepime and 40 were randomized to receive gentamicin plus mezlocillin (two to one randomization schedule). The diagnosis was acute cholecystitis in 101 patients and acute cholangitis in the remainder. There were no differences between the two treatment groups with regard to gender, age, disease, signs and symptoms, admitting temperature or laboratory values. All patients (100 percent) treated with gentamicin and mezlocillin were cured of the infection, as were 78 (97.5 percent) of the patients treated with cefepime (difference not significant). The incidence and spectrum of adverse events and complications were similar between the two groups (8.8 percent for cefepime versus 10 percent for gentamicin and mezlocillin). Our data show that the efficacy and safety of cefepime administered every 12 hours is equivalent to that of gentamicin and mezlocillin combination for treating patients with acute infections of the biliary tract. In addition, twice-daily administration of cefepime may be more cost-effective than the aminoglycoside-based combination.", "In a multicentre, prospective, controlled trial 211 patients with suspected septicaemia or pneumonia were allocated at random to either imipenem-cilastatin 500 mg 8-hourly or cefotaxime 1 g 6-hourly combined with amikacin 5 mg/kg 8-hourly. The treatments were administered for at least 5 days. Seventy patients on imipenem and 70 patients on cefotaxime-amikacin were assessable for comparison. There were no statistically significant differences between the two groups in underlying pathology and in the clinical results obtained: septicaemia 20/26 patients of the imipenem group and 20/25 patients of the cefotaxime-amikacin group were cured; pneumonia 38/44 patients of the imipenem group and 34/45 patients of the cefotaxime-amikacin group were cured. There were also no differences in the initial organisms and in the bacteriological cure rate, except for Pseudomonas aeruginosa. At the moment, imipenem administered alone is as effective as the cefotaxime-amikacin combination in the treatment of septicaemia or pneumonia in intensive care patients, with the exception of P. aeruginosa pneumonia in patients under assisted ventilation.", "Ninety patients at the Wilmington Medical Center were enrolled in a comparative study to evaluate the efficacy and toxicity of ticarcillin plus clavulanic acid in the treatment of a variety of infections. Forty-seven women with obstetric or gynecologic infections were randomly assigned to receive ticarcillin plus clavulanic acid or cefoxitin. Forty-three patients with gram-negative septicemia or lower respiratory tract infection were given ticarcillin plus clavulanic acid or tobramycin plus piperacillin in a randomized fashion. Of the 47 women with obstetric or gynecologic infections, 23 were randomly assigned to receive ticarcillin plus clavulanic acid, and 24 were randomly assigned to receive cefoxitin. Several patients in each group had underlying diseases such as diabetes, obesity, and hypertension. Of the 27 pathogens isolated in the group receiving ticarcillin plus clavulanic acid, 26 (96 percent) were eradicated, including all three ticarcillin-resistant pathogens. In the cefoxitin-treated group, 31 of the 33 (94 percent) pathogens were eliminated, including all four ticarcillin-resistant organisms. Three reinfections or superinfections occurred, and cefoxitin therapy failed to eliminate an enterococcus isolate from the endometrium in one patient. The clinical response in both treatment groups was excellent. Either cure or clinical improvement was achieved for all 18 sites of infection in the ticarcillin plus clavulanic acid-treated group and for all 22 sites in the cefoxitin-treated group. There were no systemic drug reactions in either treatment group. In one patient in the cefoxitin-treated group, local phlebitis developed at the infusion site. This reaction responded to local therapy. There were no local reactions among the patients receiving ticarcillin plus clavulanic acid. Of the 43 patients with gram-negative septicemia or lower respiratory tract infection, 21 were randomly assigned to receive ticarcillin plus clavulanic acid and 22 were assigned to receive tobramycin plus piperacillin. Thirty-six patients had gram-negative sepsis, and seven patients had lower respiratory tract infection. Nine of the 36 patients suspected of having gram-negative sepsis were not evaluable because no pathogen was isolated prior to treatment. Twenty-two of the 27 patients treated for septicemia had good clinical and microbiologic responses. Three of the seven patients with pneumonia were not evaluable. Of the four evaluable patients, two had pneumococcus pneumonia; one was treated with tobramycin plus piperacillin and one with ticarcillin plus clavulanic acid. In both instances, the clinical and bacteriologic responses were considered good.", "93 patients were enrolled into a prospective randomised study to determine the efficacy and safety of netilmicin, cefotaxime or their combination in the treatment of sepsis caused by susceptible strains of Enterobacteriaceae or staphylococci. 83 patients were evaluable for safety, 74 for clinical efficacy and 63 for microbiological response including 36 patients (57%) with positive blood cultures. There were significantly more clinical failures with cefotaxime than with netilmicin even when urinary tract sepsis was excluded. Microbiological failures occurred more frequently in the cefotaxime arm and were associated with Klebsiella and Enterobacter spp. Four cefotaxime failures were subsequently successfully treated with netilmicin. More mixed infections were however enrolled by chance into the cefotaxime arm. The statistical difference between netilmicin and cefotaxime is not significant if mixed infections are excluded. There was no difference in efficacy between the netilmicin and combination groups although superinfection was seen in the latter group. The incidence of nephrotoxicity was greater in the netilmicin group but not significantly so. Only one minor case of ototoxicity was detected in the 41 patients receiving netilmicin who had serial audiograms. The results suggest that netilmicin is a more effective agent than cefotaxime for treating life-threatening infections with susceptible Enterobacteriaceae or staphylococci particularly with infections in non-urinary tract sites. If dosage of netilmicin is closely monitored by measuring serum concentrations, toxicity is minimal.", "A multicentre, open, randomised, parallel group study was carried out to assess the efficacy and safety of meropenem monotherapy versus the combination of ceftazidime plus amikacin in the treatment of serious bacterial infections. Adult, hospitalised patients (n = 237) were included if they had infections at one or more of the following sites: lower respiratory tract (89 community-acquired; 84 hospital-acquired), urinary tract (59 complicated; 3 uncomplicated), skin and skin structures (n = 8), or septicaemia (n = 29). Patients were randomised to receive either iv meropenem (1 g every 8 h) as monotherapy or iv ceftazidime (2 g every 8 h) plus iv amikacin (15 mg/kg/day in two or three divided doses). Meropenem had comparable clinical efficacy to ceftazidime plus amikacin in: community-acquired lower respiratory tract infection (LRTI) (40/43, 93% vs 31/39, 79% cured or improved); hospital-acquired LRTI (30/37, 81% vs 23/32, 72%); septicaemia (10/12, 83% vs 16/17, 94%) and complicated urinary tract infection (UTI) (13/15, 87% vs 25/25, 100%). A similar proportion of patients in each treatment group experienced adverse events, the most frequent being transient elevations in serum transaminases. Seven patients in the meropenem group and eight patients in the ceftazidime plus amikacin group died during the study period from reasons unrelated to study medication, and seven patients (five meropenem, two ceftazidime plus amikacin) were withdrawn due to adverse events. Empirical monotherapy with meropenem is as well tolerated and as effective as the combination of ceftazidime plus amikacin in the treatment of serious infections.", "nan", "In a randomized trial conducted in 35 centers, we compared the clinical efficacy and safety of piperacillin plus tazobactam (TAZ) alone (monotherapy [MT]) versus those of TAZ combined with amikacin (AMK) (combined therapy [CT]) for the treatment of severe generalized peritonitis (SGP). Primary analysis consisted of blind assessment by an independent committee of the failure rate 30 days after the end of treatment in the modified intent-to-treat (ITT) analysis (mITT) population. Of the 241 patients with suspected SGP randomized into the study, 227 were eligible for ITT analysis, including 204 (99 in the MT group and 105 in the CT group) with confirmed SGP (mITT population). A total of 159 patients were eligible for per-protocol (PP) analysis. The clinical failure rates were equivalent in the mITT and PP populations (MT versus CT): 56 versus 52%, (odds ratio [OR] 0.87, 90% confidence interval [CI] = 0. 6 to 1.27) for mITT and 49 versus 49% (OR = 1.03, 90% CI = 0.67 to 1. 59) for PP analysis. Mortality rates (ITT population, 19%; PP population, 21%) and overall adverse event rates (ITT population, 55%; PP population, 54%) were also similar. Six patients (three in MT group and three in the CT group) developed acute renal failure. In conclusion, the addition of AMK to TAZ does not seem to be necessary for the treatment of SGP, even after adjustment for the simplified acute physiology score (SAPS II) and type of SGP.", "In a prospective, randomized, double-blind study, we compared cefotaxime with nafcillin plus tobramycin in the treatment of serious bacterial infections. Of 195 patients with suspected or proven infections who were not neutropenic, definite bacterial infections were identified in 81; 34 of 38 patients given cefotaxime and 26 of 43 given nafcillin plus tobramycin (p less than 0.01) responded to treatment. The difference in response rates occurred primarily in patients with rapidly fatal underlying disease or with an infection outside the urinary tract. A logistic regression analysis showed that treatment with cefotaxime was still associated with a higher response rate after adjusting for several potential confounding factors. Among patients treated for 3 days or more, our criteria for nephrotoxicity were met in 2 of 68 (2.9%) given cefotaxime and 16 of 57 (28.1%) given nafcillin plus tobramycin (p less than 0.001). Prolongation of the prothrombin time and enterococcal colonization did not occur more frequently with cefotaxime. We conclude that cefotaxime may be more effective and less toxic than nafcillin plus tobramycin for patients with serious bacterial infections.", "Ceftazidime and cefazolin/tobramycin were compared in the treatment of hospitalized patients with pneumonia. Iv doses 8-hourly were: ceftazidime--2 g, cefazolin--1.5 g, tobramycin--1.7 mg/kg. For patients with pseudomonas infection randomized to cefazolin/tobramycin, ticarcillin (3 g iv 4-hourly) was used instead of cefazolin. One hundred and ten of 129 patients were evaluable (ceftazidime = 52, cefazolin/tobramycin = 58). Seventy five cases (68%) had documented pathogens of which 81% were aerobic Gram-negative bacilli. Analysis of clinical response showed no difference in overall results (P = 0.77), or separate outcomes: cured (P = 0.85), improved (P = 0.62), failed (P = 0.53), or relapsed (P = 0.50). No differences in bacteriological response were noted either: eradication (P greater than 0.10), elimination with recurrence (P greater than 0.10), persistence (P greater than 0.10). The incidence of enterococcal and fungal colonization and superinfection was the same for both regimens. There was a greater incidence of Coombs' test positivity with ceftazidime (P less than 0.01) but greater nephrotoxicity with cefazolin/tobramycin (P less than 0.02). Ceftazidime appears to be as efficacious as cefazolin/tobramycin in the treatment of hospitalized patients with pneumonia, and is less nephrotoxic.", "Cefoperazone was compared with the combination of cefamandole and tobramycin in a prospective, randomized study of putative, severe, gram-negative bacillary infections. We attempted to exclude patients with granulocytopenia or infections due to Pseudomonas species. A total of 118 isolates (94 gram-negative bacilli and 24 gram-positive cocci) caused infection in 99 of the 120 patients studied. Cefoperazone (16 micrograms/ml) was active against 93% of the organisms tested; cefamandole (16 micrograms/ml) and/or tobramycin (4 micrograms/ml) was active against 95%. Infection was cured or improved in 77% of cefoperazone-treated patients and 81% of cefamandole-tobramycin-treated patients. Bacteremia was cured or improved in 61% of cefoperazone-treated patients and in 63% of cefamandole-tobramycin-treated patients. Adverse reactions included five cases of probable antibiotic-associated nephrotoxicity in the cefamandole-tobramycin group; there were no such cases in the cefoperazone group. One patient given cefoperazone plus eight other drugs became granulocytopenic, but the condition resolved when all medications were stopped. This analysis suggests that cefoperazone alone may be as effective as cefamandole plus tobramycin in the treatment of severe infections with gram-negative bacilli and is less nephrotoxic. The role of cefoperazone in patients with granulocytopenia or infections due to Pseudomonas aeruginosa was not evaluated.", "Imipenem/cilastatin was administered as empirical treatment to 22 patients with severe infections, at dosages of 2 or 4 g/day, either alone or in combination with an aminoglycoside. The majority of patients had underlying diseases causing various degrees of immune system dysfunction. The overall cure rate was 77.2%, without significant differences according to the type of pathogen or dosage schedule; however one of the two observed failures was due to a resistant Pseudomonas aeruginosa. Strains recovered from improved patients were all sensitive to the drug. Only mild adverse effects were evidenced, without any alteration of laboratory parameters. Imipenem/cilastatin may be useful as monotherapy in empirical treatment of severe infections in compromised patients.", "In patients with acute cholecystitis, antibiotics are used as an adjunct to cholecystectomy to reduce the incidence of postoperative septic complications thought to be related to bactibilia. Combinations of penicillins, or cephalosporins or aminoglycosides, or both, are often used. Cefepime is a fourth-generation cephalosporin with excellent activity against gram-positive and gram-negative bacteria, including Pseudomonas species. It has a prolonged serum half-life, allowing twice-daily dosing, and is not nephrotoxic. This study was undertaken to determine whether or not cefepime was as effective as the combination of gentamicin and mezlocillin in patients with acute cholecystitis. One hundred and forty-nine patients were randomized, two to one, to receive cefepime or gentamicin and mezlocillin. Cefepime was given intravenously at 2 grams every 12 hours; gentamicin, 1.0 to 1.5 milligrams per kilograms every eight hours, and mezlocillin, 3 to 4 grams every four to six hours. All patients underwent cholecystectomy. Bile cultures were obtained, and concentrations of cefepime in blood, bile, peritoneal fluid and gallbladder were determined in a subset of patients. There were 56 evaluable cefepime-treated and 34 evaluable gentamicin and mezlocillin-treated patients. Bactibilia was present in 17 of 56 cefepime-treated patients (30.4 percent) and ten of 34 gentamicin and mezlocillin-treated patients (29.4 percent). Enterococci were recovered in six cefepime-treated patients. Clinical and bacteriologic responses were similar for the cefepime-treated and gentamicin and mezlocillin-treated groups, with one failure in each group, a wound infection in a patient receiving cefepime and a subhepatic abscess in a patients receiving gentamicin and mezlocillin. Other measures of outcome, such as the number of days of fever, days nothing by mouth, days of hospitalization and days of antibiotic therapy were similar in both groups. Cefepime, with every 12 hour dosing, achieved extremely high concentrations in all tissues assayed at the time of the operation, a mean of eight hours after administration. Adverse clinical events were similar in both treatment groups. Cefepime is as effective as gentamicin and mezlocillin in preventing septic complications after cholecystectomy for acute cholecystitis. Cefepime requires fewer doses, does not require drug monitoring, is not associated with nephrotoxicity and may therefore prove to be a cost-effective alternative to combination therapy that uses an aminoglycoside.", "Thirty-five patients in a neurosurgical intensive care unit who had nosocomial pneumonia and bacteremia were randomly assigned to receive either ceftazidime (Cef) or the combination of ticarcillin and pharmacokinetically adjusted doses of tobramycin (T/T). Fifteen of 17 patients (88%) who received Cef were cured or improved compared to 15 of 18 (83%) who received T/T. The original pathogen was eradicated from the respiratory secretion in 10 of 15 patients receiving Cef compared to only 6 of 18 patients receiving T/T (p = 0.12). All patients in both treatment groups who had positive blood cultures cleared the organism from the bloodstream. No cases of drug toxicity, including renal toxicity, were seen in either group. Cef used as a single agent in nosocomial pneumonias and bacteremias performed at least as well as T/T.", "Single (nafcillin for 6 weeks) and combined (nafcillin for 6 weeks plus gentamicin for 2 weeks) drug regimens were compared in two separate multicenter prospective randomized trials. Forty-eight parenteral drug addicts and 30 nonaddicts with clinically and bacteriologically documented Staphylococcus aureus endocarditis were studied. In the addicts, combined therapy effected a more rapid mean clinical response (defervescence and normalization of leukocyte count) and a reduced duration of bacteremia in patients with right-sided endocarditis. In the nonaddicts, combined therapy effected more rapid clearance of bacteremia, but was associated with a higher incidence of azotemia. The addition of gentamicin did not alter morbidity or mortality in either group.", "In a previous study of patients with acute cholecystitis, we demonstrated equal efficacy with a broad spectrum penicillin (piperacillin) and a penicillin plus amino-glycoside combination. Whether a single agent broad spectrum penicillin is adequate treatment for more severe infections, such as acute cholangitis, however, is still unclear. We, therefore, conducted a three center, prospective, randomized trial to determine whether or not a broad spectrum penicillin alone is adequate therapy for patients with acute cholangitis. During a 36 month period, 96 patients with sepsis and biliary obstruction were randomly assigned to receive either piperacillin (n = 49) or ampicillin plus tobramycin (n = 47). The two groups receiving antibiotics were similar with respect to all clinical and laboratory parameters. The incidence of blood cultures with positive results (20 versus 21 per cent) and underlying malignant lesions (51 versus 62 per cent) was also similar between the two groups. The percentage of patients with a clinical cure or significant improvement was the same in the two groups (69 versus 70 per cent). However, there was a significant difference in the cure rate between patients with benign and malignant biliary obstructions (83 versus 59 per cent, p less than 0.01). No significant differences were noted between the two antibiotic groups with respect to drug toxicity, but patients with malignant conditions were more prone to antibiotic related toxicities (2 versus 19 per cent, p less than 0.05). These data suggest that outcome of treatment in patients with acute cholangitis is similar with either a broad spectrum penicillin or a penicillin plus aminoglycoside combination and is dependent upon the nature of the biliary obstruction.", "We performed a prospective, open label, randomized study in intensive care unit patients with ventilator-associated pneumonia (VAP) to determine the efficacy and safety of empiric intravenous (i.v.) meropenem monotherapy compared with the combination of ceftazidime plus amikacin. A total of 140 patients receiving mechanical ventilation and diagnosed with pneumonia were included in the study. Patients were randomized to receive either 1 g meropenem i.v. every 8 hours or 2 g ceftazidime i.v. every 8 hours plus 15 mg/kg amikacin daily, administered to patients with normal renal function as two daily doses. Satisfactory clinical responses (cure or improvement) were achieved at the end of treatment in 68.1% of meropenem-treated patients and 54.9% in the ceftazidime/amikacin-treated group (relative risk 1.25; 95% confidence interval >1.00, 1.55). When non-evaluable patients were excluded from the analysis, the satisfactory clinical response was 82.5% and 66.1% for the meropenem and ceftazidime/amikacin patients, respectively (p = 0.044). Logistic regression demonstrated that treatment with meropenem and both the basic traumatic and medical pathologies were significantly associated with a satisfactory response. Adverse events judged to be possibly or probably related to treatment were reported by seven (10.1%) patients in the meropenem group and by eight patients (11.3%) in the ceftazidime/amikacin group. The results of this study confirm that monotherapy with meropenem is well tolerated and provides superior efficacy to the conventional combination of ceftazidime and amikacin in combating VAP.", "nan", "Nosocomial pneumonia and sepsis, as well as severe diffuse peritonitis, must be treated early in order to prevent complications such as septic shock and organ dysfunctions. With the availability of new broad-spectrum and highly bactericidal antibiotics, the need of combining beta-lactams with aminoglycosides for the treatment of severe infections should be reassessed. A prospective randomized controlled study was performed to compare imipenem monotherapy with a combination of imipenem plus netilmicin in the empiric treatment of nosocomial pneumonia, nosocomial sepsis, and severe diffuse peritonitis. A total of 313 patients were enrolled, and 280 were assessable. The antibiotic treatment was successful in 113 of 142 patients (80%) given the monotherapy and in 119 of 138 patients (86%) given the combination (P = 0.19). The failure rates for the most important type of infection, i.e., pneumonia, were similar in the two groups, as well as the number of superinfections. While creatinine increase was associated with factors not related to antibiotic therapy for all eight patients of the monotherapy group, no factor other than the antibiotics could be found for 6 of the 14 cases of nephrotoxicity observed in the combination group (P = 0.014). Finally, the emergence of Pseudomonas aeruginosa resistant to imipenem occurred in 8 monotherapy patients and in 13 combination therapy patients. In conclusion, imipenem monotherapy appeared as effective as the combination of imipenem plus netilmicin for the treatment of severe infection. The addition of netilmicin increased nephrotoxicity, and it did not prevent the emergence of P. aeruginosa resistant to imipenem.", "Empirical therapy with cefoperazone was compared with cefoperazone plus amikacin in granulocytopenic and nongranulocytopenic febrile patients. In nonneutropenic patients the overall response rate to cefoperazone was 88%; 10 of 12 gram-negative bacteremic patients were cured. Cefoperazone plus amikacin resulted in an 88% overall response rate and cured 14 of 15 patients with bacteremia. In neutropenic patients the overall response rate was 77% with cefoperazone alone and 73% with cefoperazone plus amikacin; the cure rates for gram-negative bacteremias were 8 of 11 and 6 of 12 patients, respectively. Our findings support the concept of single-drug empirical therapy with cefoperazone in febrile cancer patients, whether granulocytopenic or not, especially when gram-negative bacteremias are predominantly caused by Escherichia coli or Klebsiella species. The issue of Pseudomonas spp. and other more resistant pathogens needs further assessment with a larger number of patients.", "nan", "We compared clinical efficacy and safety of sulbactam/cefoperazone (SBT/CPZ) with those of SBT/CPZ combined with aminoglycoside (amikacin (AMK), tobramycin (TOB), etc.) in treatment of respiratory tract infections in patients with underlying respiratory diseases, with cancer, or with acute exacerbation of chronic respiratory infections. Clinical evaluations of monotherapy with SBT/CPZ in a total of 30 patients showed excellent results in 5, good results in 17. Clinical effects of combined therapy of SBT/CPZ plus different aminoglycosides in a total of 33 patients were excellent in 18, good in 5. The efficacy rates (excellent plus good) were 73.3% in the monotherapy and 69.7% in the combined therapy. AMK was used concomitantly with SBT/CPZ in 16 of 33 patients. Clinical effects of SBT/CPZ plus AMK were excellent in 10, good in 3, and the efficacy rate was 81.3%. Bacteriological effects were evaluable against 11 strains in the monotherapy group, and against 17 strains in the combined therapy group. The eradication rates were 54.5% in the monotherapy group, and 81.3% in the combination therapy group. Diarrhea was observed in a patient who received the monotherapy. Abnormal laboratory test results were observed on in 5 patients who received the monotherapy, and in 4 patients who received one of the combined therapies. All abnormalities disappeared after the completion or discontinuation of therapies. We considered SBT/CPZ combined with an aminoglycoside is a useful chemotherapy for respiratory tract infections in patients with underlying diseases and acute exacerbation of chronic respiratory tract infections.", "In this multicenter study, the efficacy of and tolerability for meropenem were compared with those for the combination of cefuroxime-gentamicin (+/- metronidazole) for the treatment of serious bacterial infections in patients > or = 65 years of age. A total of 79 patients were randomized; thirty-nine received meropenem (1 g/8 h), and 40 received cefuroxime (1.5 g/8 h) plus gentamicin (4 mg/kg of body weight daily) for 5 to 10 days. Metronidazole (500 mg/6 h) could be added to the cefuroxime-gentamicin regimen for the treatment of intra-abdominal infections (n = 10). Seventy patients were evaluable for clinical efficacy; the primary diagnoses were as follows: pneumonia in 41 patients (20 treated with meropenem, 21 treated with cefuroxime-gentamicin), intra-abdominal infection in 10 patients (7 meropenem, 3 cefuroxime-gentamicin-metronidazole), urinary tract infection (UTI) in 11 patients (6 meropenem, 5 cefuroxime-gentamicin), sepsis syndrome in 7 patients (4 meropenem, 3 cefuroxime-gentamicin), and \"other\" in 1 patient (cefuroxime-gentamicin). The pathogens isolated from 18 patients with bacteremia were as follows: Staphylococcus spp. (n = 2), Streptococcus spp. (n = 2), members of the family Enterobacteriaceae (n = 11), and Bacteroides spp. (n = 3). A satisfactory clinical response at the end of therapy was achieved in 26 of 37 (70%) and 24 of 33 (73%) evaluable patients treated with meropenem and combination therapy, respectively. Clinical success was achieved in 23 of 31 (74%) and 21 of 28 (75%) evaluable patients with infections other than UTIs, respectively. A satisfactory microbiological response occurred in 15 of 22 (68%) patients in the meropenem group compared with 12 of 19 (63%) treated with combination therapy. Renal failure occurred during therapy in 2 of 39 (5%) meropenem recipients compared with 5 of 40 (13%) of those treated with combination therapy. The findings in this small study indicate that meropenem is as efficacious for and as well tolerated by elderly patients as the combination of cefuroxime-gentamicin (+/- metronidazole).", "We compared the fixed combination amoxicillin plus clavulanic acid with that of amoxicillin plus gentamicin in the empirical initial treatment of severe urinary tract infections. The study included 87 hospitalized patients (51 women and 36 men, mean age 58 +/- 22 years) with acute uncomplicated pyelonephritis (n = 48) or with complicated urinary tract infections (n = 39). 80 patients (92%) had fever and 31 patients (36%) positive blood cultures. 45 patients were randomly assigned to amoxicillin plus clavulanic acid and 42 to amoxicillin plus gentamicin. Overall, 18 patients (21%) were infected with organisms resistant in vitro to amoxicillin plus clavulanic acid, whereas no pathogen was isolated with resistance to amoxicillin plus gentamicin (p < 0.0001). At the end of the empirical treatment (4.2 +/- 1.5 days after the start), significant bacteriuria was present in 6/39 patients (15%) assigned to amoxicillin plus clavulanic acid, compared to 0/34 patients assigned to amoxicillin plus gentamicin (p < 0.05). The clinical response was satisfactory in both groups, and the time from start of therapy to resolution of fever was 2.2 +/- 1.4 days in the amoxicillin plus clavulanic acid group and 2.3 +/- 1.7 days in the amoxicillin plus gentamicin group. Although the in-vitro resistance did not result in a lower clinical efficacy of amoxicillin plus clavulanic acid compared to amoxicillin plus gentamicin in our relatively small sample of patients, the data indicate that the antimicrobial activity of amoxicillin plus clavulanic acid is inadequate to cover the spectrum of causative agents in hospitalized patients with pyelonephritis or complicated urinary tract infections. Amoxicillin plus clavulanic acid should therefore not be used in the initial empirical treatment of these infections.", "To compare the efficacy of once daily monotherapy with that of standard combination antibiotic therapy for the initial management of patients suspected of serious bacterial infections, 105 patients were randomised to treatment with ceftriaxone alone (53 patients) or to a combination of cefuroxime and gentamicin (52 patients). There was no difference between the groups in proportions responding to therapy or proportions dying from infection, except when non-evaluable patients were excluded from the group with definite bacterial infection, in which case response was better among those treated with ceftriaxone. The groups did not differ in number of side-effects, but therapy had to be discontinued because of treatment failure, an adverse effect, or death in 1 of 53 patients given ceftriaxone and in 11 of 34 given the combination. Use of ceftriaxone was 107.36 pounds ($182.51) cheaper per patient, and saved 40 minutes of nursing and drug administration time per patient per day. Thus 2 g ceftriaxone given once a day is at least as effective and costs less in time and money than gentamicin plus cefuroxime for the initial treatment of patients with serious systemic bacterial infections." ]

[ "1997509", "10379018", "11254817", "8317785", "1918724" ]

[ "Differential effects of inhaled budesonide and oral prednisolone on serum osteocalcin.", "Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease.", "Bone mineral density in subjects with mild asthma randomised to treatment with inhaled corticosteroids or non-corticosteroid treatment for two years.", "Effects of short-term inhaled budesonide and beclomethasone dipropionate on serum osteocalcin in premenopausal women.", "Effects of dose and dosing schedule of inhaled budesonide on bone turnover." ]

[ "Inhaled glucocorticosteroids have been developed for the treatment of asthma in an attempt to minimize the suppression of endogenous adrenal function that complicates oral or injected steroid usage, but it is unclear whether this strategy leads to reduced systemic complications in other areas, such as the skeleton. In this study we evaluated serum osteocalcin levels as a marker of skeletal metabolism in healthy volunteers treated with oral and inhaled steroids alone and in response to an oral calcitriol stimulation test. Forty subjects, aged 33 +/- 9 (mean +/- SD) yr were randomized to receive either high or low dose oral prednisolone (40 vs. 10 mg/day) or inhaled budesonide (3.2 vs. 0.8 mg/day). Each dose of budesonide is known to have a greater antiasthmatic potency than the dose of prednisolone with which it was compared. In addition 10 control subjects received placebos containing no active steroid drugs. During the second week of treatment, half of the subjects in each of the 4 steroid-treated groups and all subjects in the control group received oral calcitriol (2.0 micrograms/day). There was a marked dose-dependent reduction in serum cortisol levels, but this reduction was significantly less pronounced during budesonide treatment, such that low dose budesonide was without effect. During the first week of steroid therapy there were significant dose-dependent reductions in serum osteocalcin (P = 0.003), but this reduction was not significantly different between budesonide and prednisolone treatments. In response to calcitriol, serum osteocalcin increased by 35% in the control group (P = 0.06). Osteocalcin levels increased by 56% and 50% in the low dose budesonide and prednisolone groups and by 106% in the high dose budesonide group, but did not change in the high dose prednisolone group. The osteocalcin response to calcitriol was significantly higher in the budesonide groups (P = 0.03, by analysis of variance). High dose prednisolone caused increases in serum 1,25-dihydroxyvitamin D3 (P less than 0.02), urinary calcium excretion (P = 0.07), and urinary hydroxyproline (P less than 0.01). None of these changes was seen during budesonide therapy. There are as yet no data for these variables after long term use of inhaled budesonide in asthmatic patients, but our acute studies suggest that this potent topical glucocorticoid may have considerably less impact on the skeleton than oral prednisolone, even if used at doses high enough to suppress endogenous adrenal function.", "Although patients with chronic obstructive pulmonary disease (COPD) should stop smoking, some do not. In a double-blind, placebo-controlled study, we evaluated the effect of the inhaled glucocorticoid budesonide in patients with mild COPD who continued smoking. After a six-month run-in period, we randomly assigned 1277 subjects (mean age, 52 years; mean forced expiratory volume in one second [FEV1], 77 percent of the predicted value; 73 percent men) to twice-daily treatment with 400 microg of budesonide or placebo, inhaled from a dry-powder inhaler, for three years.\n Of the 1277 subjects, 912 (71 percent) completed the study. Among these subjects, the median decline in the FEV1 after the use of a bronchodilator over the three-year period was 140 ml in the budesonide group and 180 ml in the placebo group (P=0.05), or 4.3 percent and 5.3 percent of the predicted value, respectively. During the first six months of the study, the FEV1 improved at the rate of 17 ml per year in the budesonide group, as compared with a decline of 81 ml per year in the placebo group (P<0.001). From nine months to the end of treatment, the FEV1 declined at similar rates in the two groups (P=0.39). Ten percent of the subjects in the budesonide group and 4 percent of those in the placebo group had skin bruising (P<0.001). Newly diagnosed hypertension, bone fractures, postcapsular cataracts, myopathy, and diabetes occurred in less than 5 percent of the subjects, and the diagnoses were equally distributed between the groups.\n In patients with mild COPD who continue smoking, the use of inhaled budesonide is associated with a small one-time improvement in lung function but does not appreciably affect the long-term progressive decline.", "Inhaled corticosteroids are clearly beneficial for patients with asthma of moderate severity, but the risks and benefits of using them in patients with milder asthma are less clear. We have compared the change in bone mineral density over 2 years in adults with mild asthma randomised to receive an inhaled corticosteroid or non-corticosteroid treatment.\n Subjects with mild asthma (mean forced expiratory volume in one second (FEV(1)) 86% predicted, mean age 35 years, taking beta agonists only) were randomised to receive inhaled budesonide, inhaled beclomethasone dipropionate, or non-corticosteroid treatment for 2 years in a prospective randomised open study in 19 centres in France, New Zealand, Spain, and the UK. The corticosteroid dose was adjusted according to a written self-management plan. The main outcome measure-change in bone mineral density after 6, 12, and 24 months-was measured \"blind\". Secondary outcomes included lung function, the relation between change in bone density and inhaled steroid dose and change in biochemical markers of bone metabolism.\n Of 374 subjects randomised, 239 (64%) completed the study and were included in the analysis. The median daily doses of inhaled budesonide (n=87) and beclomethasone (n=74) were 389 microg and 499 microg, respectively. Subjects treated with an inhaled corticosteroid had better asthma control than those in the reference group (n=78). Change in bone mineral density did not differ between the three groups over the 2 years, nor did it correlate with changes in markers of bone metabolism. The mean change in bone mineral density over 2 years in the budesonide, beclomethasone dipropionate, and reference groups was 0.1%, -0.4%, and 0.4% for the lumbar spine and -0.9%, -0.9%, and -0.4% for neck of the femur. Mean daily dose of inhaled steroid was related to reduction in bone mineral density at the lumbar spine but not at the femoral neck.\n In subjects with mild asthma an inhaled corticosteroid provided better asthma control than alternative non-corticosteroid treatment with no difference in change in bone mineral density over 2 years. The relation between dose of inhaled corticosteroid and change in bone density at the lumbar spine may be due to a direct effect of inhaled corticosteroids on bone. Since inhaled steroid dose is also related inversely to lung function, an effect of asthma severity on bone density was also possible.", "Serum osteocalcin, a marker of bone osteoblast function, has been shown to be sensitive to even low doses of oral glucocorticoids. The effect of 1 wk of inhaled glucocorticoid therapy with budesonide (200 micrograms/puff), beclomethasone dipropionate (250 micrograms/puff), and placebo at two puffs b.i.d. and four puffs b.i.d. on 0900 serum osteocalcin were compared in a double-blind randomized fashion. A two-way repeated-measures analysis of variance showed no main effect of drug or dosage but a significant drug-dose interaction (p = 0.023). Post hoc investigation of this interaction demonstrated that the serum osteocalcin level while taking four puffs b.i.d. (2,000 micrograms) of beclomethasone dipropionate was significantly lower than that of placebo or budesonide at four puffs b.i.d. (1,600 micrograms). These results suggest that at lower doses no acute measurable effect of inhaled glucocorticoids on serum osteocalcin can be appreciated but that at higher doses inhaled beclomethasone dipropionate has a depressant effect on bone osteoblast function.", "To assess whether the use of larger than usual doses of inhaled steroid to treat severe asthma may adversely affect bone turnover and whether such an effect may be mitigated by altering the dose schedule, we investigated the effects of budesonide (BUD) on serum osteocalcin and the urinary output of hydroxyproline and calcium. Healthy adults were administered 1.2 or 2.4 mg of BUD per day (N = 40) or placebo (N = 8) in a crossover, double-blind comparison of morning versus diurnal dosing schedules for 1 month each. Both BUD doses reduced the 24-hour urinary free-cortisol output (p less than 0.001) and serum osteocalcin (p less than 0.001). The larger dose reduced the morning serum cortisol levels (p = 0.002). Neither dose increased the 8 AM urinary calcium or hydroxyproline output. Osteocalcin and plasma cortisol levels were higher on morning than on diurnal dosing (p = 0.01). The 24-hour urinary free-cortisol output was the same with either schedule (p = 0.96). Additional study is required to assess the clinical importance of the inhibitory effect of BUD on bone formation, as evidenced by the reduction in osteocalcin levels. Of concern is the possibility of serious bone complications resulting from the long-term use of inhaled steroid, particularly in growing children or patients in whom other risk factors for osteoporosis are present. The clinical advantage, if any, of morning dosing remains questionable." ]

[ "16697324", "11597664", "12706935", "15358690", "16801459", "18506008", "18572079", "11907289", "20175775", "15750042" ]

[ "Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan.", "Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study.", "Effects of the oral endothelin-receptor antagonist bosentan on echocardiographic and doppler measures in patients with pulmonary arterial hypertension.", "Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2.", "Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study.", "Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2.", "Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial.", "Bosentan therapy for pulmonary arterial hypertension.", "Exercise capacity and haemodynamics in patients with sickle cell disease with pulmonary hypertension treated with bosentan: results of the ASSET studies.", "Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension (SERAPH) study." ]

[ "We sought to determine the optimal dose of the selective endothelin A (ET(A)) receptor antagonist sitaxsentan for the treatment of pulmonary arterial hypertension (PAH); for observation only, an open-label (OL) bosentan arm was included.\n Endothelin is a mediator of PAH. In a preliminary PAH study, the selective ET(A) receptor antagonist sitaxsentan improved six-min walk (6MW) distance, World Health Organization (WHO) functional class (FC), and hemodynamics.\n In this double-blind, placebo-controlled 18-week study, 247 PAH patients (idiopathic, or associated with connective tissue disease or congenital heart disease) were randomized; 245 patients were treated: placebo (n = 62), sitaxsentan 50 mg (n = 62) or 100 mg (n = 61), or OL (6MW tests, Borg dyspnea scores, and WHO FC assessments third-party blind) bosentan (n = 60). The primary end point was change in 6MW distance from baseline to week 18. Secondary end points included change in WHO FC, time to clinical worsening, and change in Borg dyspnea score.\n At week 18, patients treated with sitaxsentan 100 mg had an increased 6MW distance compared with the placebo group (31.4 m, p = 0.03), and an improved WHO FC (p = 0.04). The placebo-subtracted treatment effect for sitaxsentan 50 mg was 24.2 m (p = 0.07) and for OL bosentan, 29.5 m (p = 0.05). The incidence of elevated hepatic transaminases (>3x the upper limit of normal) was 6% for placebo, 5% for sitaxsentan 50 mg, 3% for sitaxsentan 100 mg, and 11% for bosentan.\n Treatment with the selective ET(A) receptor antagonist sitaxsentan, orally once daily at a dose of 100 mg, improves exercise capacity and WHO FC in PAH patients, with a low incidence of hepatic toxicity.", "Endothelin 1, a powerful endogenous vasoconstrictor and mitogen, might be a cause of pulmonary hypertension. We describe the efficacy and safety of bosentan, a dual endothelin-receptor antagonist that can be taken orally, in patients with severe pulmonary hypertension.\n In this double-blind, placebo-controlled study, 32 patients with pulmonary hypertension (primary or associated with scleroderma) were randomly assigned to bosentan (62.5mg taken twice daily for 4 weeks then 125 mg twice daily) or placebo for a minimum of 12 weeks. The primary endpoint was change in exercise capacity. Secondary endpoints included changes in cardiopulmonary haemodynamics, Borg dyspnoea index, WHO functional class, and withdrawal due to clinical worsening. Analysis was by intention to treat.\n In patients given bosentan, the distance walked in 6 min improved by 70 m at 12 weeks compared with baseline, whereas it worsened by 6 m in those on placebo (difference 76 m [95% CI 12-139], p=0.021). The improvement was maintained for at least 20 weeks. The cardiac index was 1.0 L min(-1) m(-2) (95% CI 0.6-1.4, p<0.0001) greater in patients given bosentan than in those given placebo. Pulmonary vascular resistance decreased by 223 dyn s cm(-)(5) with bosentan, but increased by 191 dyn s cm(-5) with placebo (difference -415 [-608 to -221], p=0.0002). Patients given bosentan had a reduced Borg dyspnoea index and an improved WHO functional class. All three withdrawals from clinical worsening were in the placebo group (p=0.033). The number and nature of adverse events did not differ between the two groups.\n Bosentan increases exercise capacity and improves haemodynamics in patients with pulmonary hypertension, suggesting that endothelin has an important role in pulmonary hypertension.", "The purpose of this study was to investigate the effects of bosentan (125 or 250 mg twice daily) on echocardiographic and Doppler variables in 85 patients with World Health Organization class III or IV pulmonary arterial hypertension (PAH).\n Bosentan, an orally active dual endothelin-receptor antagonist, improves symptoms, exercise capacity, and hemodynamics in patients with PAH.\n Patients had primary pulmonary hypertension (84%) or PAH associated with connective tissue disease. Of these, 29 patients received placebo and 56 received bosentan (1:2 randomization). Six-minute walk tests and echocardiograms were performed at baseline and after 16 weeks of treatment.\n Baseline characteristics were similar in the placebo and bosentan groups, and echocardiographic and Doppler findings were consistent with marked abnormalities of right ventricular (RV) and left ventricular (LV) structure and function that were due to PAH. The treatment effect on 6-min walking distance was 37 m in favor of bosentan (p = 0.036). Treatment effects of bosentan compared with placebo on other parameters were as follows: Doppler-derived cardiac index = +0.4 l/min/m(2) (p = 0.007), LV early diastolic filling velocity = +10.5 cm/s (p = 0.003), LV end-diastolic area = +4.2 cm(2) (p = 0.003), LV systolic eccentricity index = -0.12 (p = 0.047), RV end-systolic area = -2.3 cm(2) (p = 0.057), RV:LV diastolic areas ratio = -0.64 (p = 0.007), Doppler RV index = -0.06 (p = 0.03), and percentage of patients with an improvement in pericardial effusion score = 17% (p = 0.05).\n Bosentan improves RV systolic function and LV early diastolic filling and leads to a decrease in RV dilation and an increase in LV size in patients with PAH.", "The efficacy and safety of combining bosentan, an orally active dual endothelin receptor antagonist and epoprostenol, a continuously infused prostaglandin, in the treatment of pulmonary arterial hypertension (PAH) was investigated. In this double-blind, placebo-controlled prospective study, 33 patients with PAH started epoprostenol treatment (2 ng.kg(-1)min(-1) starting dose, up to 14+/-2 ng.kg(-1)min(-1) at week 16) and were randomised for 16 weeks in a 2:1 ratio to bosentan (62.5 mg b.i.d for 4 weeks then 125 mg b.i.d) or placebo. Haemodynamics, exercise capacity and functional class improved in both groups at week 16. In the combination treatment group, there was a trend for a greater (although nonsignificant) improvement in all measured haemodynamic parameters. There were four withdrawals in the bosentan/epoprostenol group (two deaths due to cardiopulmonary failure, one clinical worsening, and one adverse event) and one withdrawal in the placebo/epoprostenol group (adverse event). This study showed a trend but no statistical significance towards haemodynamics or clinical improvement due to the combination of bosentan and epoprostenol therapy in patients with pulmonary arterial hypertension. Several cases of early and late major complications were reported. Additional information is needed to evaluate the risk/benefit ratio of combined bosentan-epoprostenol therapy in pulmonary arterial hypertension.", "Eisenmenger syndrome is characterized by the development of pulmonary arterial hypertension with consequent intracardiac right-to-left shunt and hypoxemia in patients with preexisting congenital heart disease. Because Eisenmenger syndrome is associated with increased endothelin expression, patients may benefit from endothelin receptor antagonism. Theoretically, interventions that have some effect on the systemic vascular bed could worsen the shunt and increase hypoxemia.\n The Bosentan Randomized Trial of Endothelin Antagonist Therapy-5 (BREATHE-5) was a 16-week, multicenter, randomized, double-blind, placebo-controlled study evaluating the effect of bosentan, a dual endothelin receptor antagonist, on systemic pulse oximetry (primary safety end point) and pulmonary vascular resistance (primary efficacy end point) in patients with World Health Organization functional class III Eisenmenger syndrome. Hemodynamics were assessed by right- and left-heart catheterization. Secondary end points included exercise capacity assessed by 6-minute walk distance, additional hemodynamic parameters, functional capacity, and safety. Fifty-four patients were randomized 2:1 to bosentan (n=37) or placebo (n=17) for 16 weeks. The placebo-corrected effect on systemic pulse oximetry was 1.0% (95% confidence interval, -0.7 to 2.8), demonstrating that bosentan did not worsen oxygen saturation. Compared with placebo, bosentan reduced pulmonary vascular resistance index (-472.0 dyne.s.cm(-5); P=0.0383). The mean pulmonary arterial pressure decreased (-5.5 mm Hg; P=0.0363), and the exercise capacity increased (53.1 m; P=0.0079). Four patients discontinued as a result of adverse events, 2 (5%) in the bosentan group and 2 (12%) in the placebo group.\n In this first placebo-controlled trial in patients with Eisenmenger syndrome, bosentan was well tolerated and improved exercise capacity and hemodynamics without compromising peripheral oxygen saturation.", "Ambrisentan is a propanoic acid-based, A-selective endothelin receptor antagonist for the once-daily treatment of pulmonary arterial hypertension.\n Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Study 1 and 2 (ARIES-1 and ARIES-2) were concurrent, double-blind, placebo-controlled studies that randomized 202 and 192 patients with pulmonary arterial hypertension, respectively, to placebo or ambrisentan (ARIES-1, 5 or 10 mg; ARIES-2, 2.5 or 5 mg) orally once daily for 12 weeks. The primary end point for each study was change in 6-minute walk distance from baseline to week 12. Clinical worsening, World Health Organization functional class, Short Form-36 Health Survey score, Borg dyspnea score, and B-type natriuretic peptide plasma concentrations also were assessed. In addition, a long-term extension study was performed. The 6-minute walk distance increased in all ambrisentan groups; mean placebo-corrected treatment effects were 31 m (P=0.008) and 51 m (P<0.001) in ARIES-1 for 5 and 10 mg ambrisentan, respectively, and 32 m (P=0.022) and 59 m (P<0.001) in ARIES-2 for 2.5 and 5 mg ambrisentan, respectively. Improvements in time to clinical worsening (ARIES-2), World Health Organization functional class (ARIES-1), Short Form-36 score (ARIES-2), Borg dyspnea score (both studies), and B-type natriuretic peptide (both studies) were observed. No patient treated with ambrisentan developed aminotransferase concentrations >3 times the upper limit of normal. In 280 patients completing 48 weeks of treatment with ambrisentan monotherapy, the improvement from baseline in 6-minute walk at 48 weeks was 39 m.\n Ambrisentan improves exercise capacity in patients with pulmonary arterial hypertension. Improvements were observed for several secondary end points in each of the studies, although statistical significance was more variable. Ambrisentan is well tolerated and is associated with a low risk of aminotransferase abnormalities.", "Treatments for pulmonary arterial hypertension have been mainly studied in patients with advanced disease (WHO functional class [FC] III and IV). This study was designed to assess the effect of the dual endothelin receptor antagonist bosentan in patients with WHO FC II pulmonary arterial hypertension.\n Patients with WHO FC II pulmonary arterial hypertension aged 12 years or over with 6-min walk distance of less than 80% of the normal predicted value or less than 500 m associated with a Borg dyspnoea index of 2 or greater were enrolled in this double-blind, placebo-controlled, multicentre trial. 185 patients were randomly assigned to receive bosentan (n=93) or placebo (n=92) for the 6-month double-blind treatment period via a centralised integrated voice recognition system. Primary endpoints were pulmonary vascular resistance at month 6 expressed as percentage of baseline and change from baseline to month 6 in 6-min walk distance. Analyses of the primary endpoints were done with all randomised patients who had a valid baseline assessment and an assessment or an imputed value for month 6. This trial was registered with ClinicalTrials.gov, number NCT00091715.\n Analyses were done with 168 patients (80 in the bosentan group, 88 in the placebo group) for pulmonary vascular resistance and with 177 (86 and 91) for 6-min walking distance. At month 6, geometric mean pulmonary vascular resistance was 83.2% (95% CI 73.8-93.7) of the baseline value in the bosentan group and 107.5% (97.6-118.4) of the baseline value in the placebo group (treatment effect -22.6%, 95% CI -33.5 to -10.0; p<0.0001). Mean 6-min walk distance increased from baseline in the bosentan group (11.2 m, 95% CI -4.6 to 27.0) and decreased in the placebo group (-7.9 m, -24.3 to 8.5), with a mean treatment effect of 19.1 m (95% CI 3.6-41.8; p=0.0758). 12 (13%) patients in the bosentan group and eight (9%) in the placebo group reported serious adverse events, the most common of which were syncope in the bosentan group and right ventricular failure in the placebo group.\n Bosentan treatment could be beneficial for patients with WHO FC II pulmonary arterial hypertension.", "Endothelin-1 is a potent vasoconstrictor and smooth-muscle mitogen. In a preliminary study, the orally administered dual endothelin-receptor antagonist bosentan improved exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary arterial hypertension. The present trial investigated the effect of bosentan on exercise capacity in a larger number of patients and compared two doses.\n In this double-blind, placebo-controlled study, we randomly assigned 213 patients with pulmonary arterial hypertension (primary or associated with connective-tissue disease) to receive placebo or to receive 62.5 mg of bosentan twice daily for 4 weeks followed by either of two doses of bosentan (125 or 250 mg twice daily) for a minimum of 12 weeks. The primary end point was the degree of change in exercise capacity. Secondary end points included the change in the Borg dyspnea index, the change in the World Health Organization (WHO) functional class, and the time to clinical worsening.\n At week 16, patients treated with bosentan had an improved six-minute walking distance; the mean difference between the placebo group and the combined bosentan groups was 44 m (95 percent confidence interval, 21 to 67; P<0.001). Bosentan also improved the Borg dyspnea index and WHO functional class and increased the time to clinical worsening.\n The endothelin-receptor antagonist bosentan is beneficial in patients with pulmonary arterial hypertension and is well tolerated at a dose of 125 mg twice daily. Endothelin-receptor antagonism with oral bosentan is an effective approach to therapy for pulmonary arterial hypertension.", "Doppler-defined pulmonary hypertension (PH) in sickle cell disease (SCD) is associated with 40% mortality at 40 months. To assess the effect of bosentan in SCD-PH, two randomized, double-blind, placebo-controlled, 16-week studies were initiated. Safety concerns are particularly relevant in SCD due to comorbid conditions. ASSET-1 and -2 enrolled patients with pulmonary arterial hypertension (PAH) and pulmonary venous hypertension (PH), respectively. Haemodynamics and 6-min walk distance (6MWD) were obtained at baseline and week 16. The studies were terminated due to slow site initiation and patient enrolment (n = 26). Bosentan appeared to be well tolerated. Although sample sizes were limited, in ASSET-1 at baseline, 6MWD correlated with cardiac output (CO; P = 0.006) with non-significant inverse correlations between 6MWD and pulmonary vascular resistance (PVR; P = 0.07) and between 6MWD and right atrial pressure (P = 0.08). In ASSET-2 at baseline, there was a non-significant correlation between 6MWD and CO (P = 0.06). Due to limited sample sizes, efficacy endpoints were not analysed. However, in both studies, non-significant increases in CO were observed with bosentan compared to placebo. Similarly, non-significant decreases in PVR were observed with bosentan. Limited data in SCD-PH suggest that a low 6MWD predicts a low CO. Standard-dose bosentan appears to be well tolerated. Further investigation is warranted. Clinicaltrials.gov registration numbers NCT00310830, NCT00313196, NCT00360087.", "Phosphodiesterase type 5 (PDE5) inhibition has been proposed for the treatment for pulmonary arterial hypertension (PAH).\n This study compared adding sildenafil, a PDE5 inhibitor, to conventional treatment with the current practice of adding bosentan, an endothelin receptor antagonist.\n Twenty-six patients with PAH, idiopathic or associated with connective tissue disease, World Health Organization (WHO) functional class III, were randomized in a double-blind fashion to receive sildenafil (50 mg twice daily for 4 weeks, then 50 mg three times daily) or bosentan (62.5 mg twice daily for 4 weeks, then 125 mg twice daily) over 16 weeks.\n Changes in right ventricular (RV) mass (using cardiovascular magnetic resonance), 6-minute walk distance, cardiac function, brain natriuretic peptide, and Borg dyspnea index.\n When analyzed by intention to treat, there were no significant differences between the two treatment groups. One patient on sildenafil died suddenly. Patients on sildenafil who completed the protocol showed significant changes from baseline, namely, reductions in RV mass (-8.8 g; 95% confidence interval [CI], -2, -16; n = 13, p = 0.015) and plasma brain natriuretic peptide levels (-19.4 fmol x ml(-1); 95% CI, -5, -34; p = 0.014) and improvements in 6-minute walk distance (114 m; 95% CI, 67, 160; p = 0.0002), cardiac index (0.3 L x min(-1) x m(-2); 95% CI, 0.1, 0.4; p = 0.008), and systolic left ventricular eccentricity index (-0.2; 95% CI, -0.02, -0.37; p = 0.031). Bosentan improved 6-minute walk distance (59 m; 95% CI, 29, 89; n = 12, p = 0.001) and cardiac index (0.3; 95% CI, 0.1, 0.4; p = 0.008).\n Sildenafil added to conventional treatment reduces RV mass and improves cardiac function and exercise capacity in patients with PAH, WHO functional class III. Safety monitoring is important until more experience is obtained." ]

[ "7773582", "9195083", "8769617", "10615231", "9462438", "1437036", "3879598", "8295245", "8168557", "11866717" ]

[ "Comparison of fluconazole with oral polyenes in the prevention of fungal infections in neutropenic patients. A prospective, randomized, single-center study.", "Oropharyngeal candidiasis in patients with AIDS: randomized comparison of fluconazole versus nystatin oral suspensions.", "Randomized trial of fluconazole versus nystatin for the prophylaxis of Candida infection following liver transplantation.", "A double-blind comparison of fluconazole and nystatin in the prevention of candidiasis in patients with leukaemia. Antifungal Prophylaxis Study Group.", "Fluconazole versus nystatin in the prevention of candida infections in children and adolescents undergoing remission induction or consolidation chemotherapy for cancer.", "Efficacy of chlorhexidine and nystatin rinses in prevention of oral complications in leukemia and bone marrow transplantation.", "Nystatin prophylaxis of fungal colonization and infection in granulocytopenic patients: correlation of colonization and clinical outcome.", "Routine prophylactic antifungal agents (clotrimazole, ketoconazole, and nystatin) in nontransplant/nonburned critically ill surgical and trauma patients.", "Controlled study of fluconazole in the prevention of fungal infections in neutropenic patients with haematological malignancies and bone marrow transplant recipients.", "Antifungal Prophylaxis in Severely Neutropenic Patients: How Much Fluconazole is Necessary?" ]

[ "The goal of this prospective randomized single-center study was the comparison of safety and efficacy of high-dose oral/intravenous fluconazole (400 mg daily) (group A) with oral nystatin plus miconazole inhalations (group B) in the prevention of fungal infections on a hemato-oncological isolation Ward. Of 157 patients admitted to the isolation ward during the study period only 90 (57%) were eligible for randomization; 22 (14%) had a fungal infection at admission. Of the 90 randomized patients, 89 were evaluable, 43 in group A and 46 in group B. The age, sex, diagnosis, planned therapy and risk factors for fungal infections at admission as well as the duration of neutropenia were in the same proportions in both groups. Oral thrush and mucocutaneous candidiasis were prevented in all patients of both groups, and 29 patients (32%: 17 in group A, 12 in group B) were discharged after successful prophylaxis (NS). Empiric amphotericin B was given according to predetermined criteria to 45 patients (51%: 23 group A, 22 group B; NS). Fluconazole significantly delayed the time before the start of intravenous amphotericin B. It was begun after a median of 10 days (0-45 days, range) of neutropenia below 0.5 x 10(9) granulocytes/l in group A and 7.5 days (0-26, range) in group B (P < 0.05). The duration of successful prophylaxis was significantly longer in group A (26 days median) than in group B (21 days, median) (P < 0.05). Systematic fungal infection was documented in 3 patients (1 group A, 2 group B; NS).", "A total of 167 human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis were randomly assigned to receive 14 days of therapy with liquid suspension fluconazole (100 mg once daily) or liquid nystatin (500,000 U four times daily). At day 14, 87% of the fluconazole-treated patients were clinically cured, as opposed to 52% in the nystatin-treated group (P < .001). Fluconazole eradicated Candida organisms from the oral flora in 60%, vs. a 6% eradication rate with nystatin (P < .001). The fluconazole group had fewer relapses noted on day 28 (18%, vs. 44% in the nystatin group; P < .001). This relapse difference no longer existed by day 42. Fluconazole oral suspension as a systemic therapy was more effective than liquid nystatin as a topical therapy in the treatment of oral candidiasis in HIV-infected patients and provided a longer disease-free interval before relapse.", "A prospective, randomized, multicenter study addressed the safety and efficacy of fluconazole therapy in 143 liver transplant patients. Seventy-six patients received daily oral fluconazole (100 mg), and 67 received nystatin (4 X 10(6) U) during the first 28 days after transplantation. Candida colonization occurred in 25% and 53% of patients in the fluconazole and nystatin groups, respectively (P = .04), and 13% and 34% of patients in the respective groups had Candida infections (P = .022). Of these patients, 10.5% in the fluconazole group and 25.3% in the nystatin group had superficial candidal infections (P = .024). Invasive candidiasis developed in 2 patients in the fluconazole group (2.6%) and 6 in the nystatin group (9.0%) (P = .12). There was no increased hepatotoxicity, cyclosporine interaction, or emergence of clinically relevant resistant Candida strains attributable to fluconazole. Thus, oral fluconazole (100 mg) is safe and reduces Candida colonization and infection after liver transplantation.", "In this multicentre, randomised, double-blind study, the safety and efficacy of oral fluconazole (200 micrograms/day) and nystatin suspension (6,000,000 IU/day) for the prevention of fungal infections were compared in patients with leukaemia undergoing remission induction chemotherapy. Antifungal prophylaxis was initiated at the time chemotherapy was started and continued throughout the hospital stay or the period of neutropenia to a maximum of 42 days. Prophylaxis was successful (no evidence of fungal infection or fever of unknown origin unresponsive to antibiotics) in 38 of 56 (68%) fluconazole-treated and 25 of 53 (47%) nystatin-treated patients (P = 0.03). 2 patients (4%) in the fluconazole group and 6 (11%) patients in the nystatin group developed systemic fungal infections (P = 0.15). The overall frequency of adverse events was similar among fluconazole-treated (29%) and nystatin-treated (32%); most events in both treatment groups involved the gastrointestinal tract. These results indicated fluconazole was more effective than nystatin in preventing Candida infections in patients with leukaemia; fluconazole was well tolerated.", "An open, prospective, randomized pilot study was performed to assess the efficacy and safety of oral fluconazole 3 mg/kg once daily compared with oral nystatin 50,000 units/kg/day in four divided doses in preventing candida infections in 50 children undergoing remission induction or consolidation therapy for cancer. In 21 of 25 fluconazole-treated and 20 of 25 nystatin-treated patients the overall outcome of prophylaxis was clearly successful. Mild and transient oropharyngeal candidosis was observed in two and three patients in the fluconazole and nystatin groups respectively. One patient randomized to fluconazole and two patients randomized to nystatin required empirical treatment with amphotericin B and one patient assigned to fluconazole developed tissue-proven candida colitis. Initially non-colonized patients remained yeast-free throughout treatment with no differences between the two study arms. Initially colonized patients stayed colonized throughout treatment although at the end of the study, more patients randomized to nystatin were still harbouring yeasts (P = 0.05). Almost exclusively, Candida albicans (95%) was isolated. A change in species was observed in one patient in each arm of the study. Candida krusei or Candida glabrata were not encountered. Transient elevations of hepatic transaminases were more common in the fluconazole group, although not statistically significant (28% vs 12%, P = 0.15). Reversible grade I gastrointestinal and skin symptoms were observed in four patients randomized to fluconazole (16 vs 0%, P < 0.05). Fluconazole was as safe and effective as nystatin in controlling yeast colonization and in preventing superficial and invasive candida infections and the empirical use of amphotericin B in children and adolescents undergoing intensive chemotherapy for cancer.", "The goal of reducing oral complications during chemotherapy and bone marrow transplantation has received attention at several centers. The current randomized study of 86 adults with leukemia treated with chemotherapy or bone marrow transplantation assessed the potential role of chlorhexidine, nystatin, and saline solution rinses to reduce the findings of oral mucositis, gingivitis, and oral infection. The results of this study did not show a reduction in mucositis with the use of these rinses. However, potential bacterial and fungal pathogens were identified less frequently in the patients using chlorhexidine rinse.", "Nystatin, one million units every four hours, was prospectively studied as a prophylactic antifungal agent in 164 neutropenic patients who were not initially colonized by fungi: 104 received nystatin and 60 served as controls. Fungal colonization occurred in 68/104 (65%) nystatin recipients and in 43/60 (71%) controls. However, nystatin significantly reduced multiple body site colonization and persistent oropharyngeal colonization. Despite these alterations in colonization profile, 16/104 (15%) nystatin recipients developed disseminated fungal infections, as compared to 5/60 (8%) control patients (0.5 greater than p greater than 0.1, N.S). Differences in the clinical course of colonized and non-colonized patients were observed. Eighteen of 111 (16%) colonized patients had afebrile clinical courses as compared to 16/53 (30%) non-colonized patients (p less than 0.05). Twenty-nine of 93 (31%) febrile episodes in colonized patients failed to respond to empiric antibiotic therapy as compared to 3/37 (8%) episodes in non-colonized patients (p less than 0.01). Disseminated fungal infections were diagnosed in 19/111 (17%) of colonized patients, as compared to 1/53 (2%) non-colonized patients (p less than 0.02). We conclude that colonized patients are more likely to develop febrile clinical courses, to fail to respond to empiric antibiotic therapy, and to develop disseminated fungal infection. Nystatin altered colonization patterns but did not prevent disseminated fungal infection.", "A prospective, randomized study was conducted to determine if prophylactic antifungal agents prevented yeast colonization (YC) or yeast sepsis (YS), or if they diminished mortality in 292 critically ill adult (nontransplant/nonburned) surgical and trauma patients admitted to the SICU for 48 hours or longer. Patients were randomized to receive (group I) no therapy, (group II) clotrimazole 10 mg three times a day, (group III) ketoconazole 200 mg per day, or (group IV) nystatin 2 million units every 6 hours. For comparison patients were stratified by the criteria of Slotman and Burchard into high risk (> or = 3 risk factors) and low risk (< 3 risk factors). Fifty patients (17%) had yeast colonization, nine (3.1%) had yeast sepsis, and 41 (14%) died. Stepwise logistic regression analysis of yeast colonization and sepsis using the variables APACHE II scores > 10, need for ventilator support > 48 hours, and 14 risk factors (Slotman and Burchard) showed that treatment with three or more antibiotics, APACHE II > 10, and ventilatory support > 48 hours were the only three variables that were significant predictors of yeast colonization and sepsis. There was no significant difference between the four groups with regard to YC (23%, 18%, 12%, and 15%, respectively), YS (3%, 1%, 2%, and 7%, respectively), or mortality (15%, 14%, 6%, and 20%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)", "The efficacy and safety of oral fluconazole versus a polyene regimen in preventing mycoses in neutropenic patients was compared. Patients with haematological malignancy or bone marrow transplantation received as antifungal prophylaxis either fluconazole 200 mg daily or a regimen consisting of clotrimazole trouches 10 mg twice daily with mycostatin, 500,000 I.U. four times daily, benadryl and cepacol mouthwash. Ninety patients at risk for fungus infection were evaluable. Four of 42 patients (9.5%; confidence interval 2%-23%) on fluconazole and 17 of 48 patients (35.4%; confidence interval 22%-52%) (p < 0.01) on the clotrimazole regimen developed a clinically significant fungal infection, including 3 (7.1%) and 11 (22.9%) patients respectively who had severe fungal infection, mainly pulmonary aspergillosis. Death directly due to a fungal infection within 100 days of the start of prophylaxis occurred in 2 of 42 patients (4.8%) and 9 of 48 patients (18.8%) respectively (p < 0.06). Kaplan-Meier analysis showed that the chance of survival on fluconazole was statistically greater than for the clotrimazole regimen (p < 0.04). A decrease of candidal colonisation of the gastrointestinal and genitourinary tracts occurred only in patients receiving fluconazole. No significant toxicity occurred. A 200 mg daily dose of fluconazole given to these patients thus appears to be well tolerated and to provide a protective effect against the development of fungal infection and death from severe fungal disease.", "OBJECTIVES: To evaluate the efficacy of low dose fluconazole treatment for the prevention of yeast colonization and infection in severely neutropenic patients. METHODS: An open randomized trial, comparing fluconazole (100 mg per day) with nystatin (800,000 IU per day), in a University Hospital setting. RESULTS: Antifungal prophylaxis was given during the period of neutropenia, defined as less than 500 polymorphonuclear cells (PMN)/mm3). Thirty-six patients were randomly assigned to fluconazole and 33 to nystatin treatment groups. New oropharyngeal colonizations were significantly reduced by fluconazole (P=0.005), and oropharyngeal infections occurred less frequently in the fluconazole group (3% versus 16%, P=0.07). Stool colonization was identical between both groups. Systemic fungal infections were rare; one fluconazole patient had pulmonary aspergillosis and one nystatin patient developped Candida pseudotropicalis fungemia. Empiric amphotericin B was given with the same frequency in both groups. No side effects were associated with fluconazole. However, the administration of nystatin became impossible for three patients because of vomiting and lack of compliance. CONCLUSIONS: Fluconazole (100 mg per day) is more effective than nystatin for the prevention of oropharyngeal yeast colonization. Comparison with results in the literature suggests that a 100-mg dose of fluconazole has similar effects to 200 or 400 mg per day." ]

[ "19229549", "17176279", "9659650", "19215547", "20482535", "10076146", "21336835", "19538418" ]

[ "Utilization of carbetocin for prevention of postpartum hemorrhage after cesarean section: a randomized clinical trial.", "A randomised trial of carbetocin versus syntometrine in the management of the third stage of labour.", "Double-blind, randomized comparison of the effect of carbetocin and oxytocin on intraoperative blood loss and uterine tone of patients undergoing cesarean section.", "Carbetocin versus syntometrine in prevention of post-partum hemorrhage following vaginal delivery.", "Carbetocin versus oxytocin for the prevention of postpartum haemorrhage following caesarean section: the results of a double-blind randomised trial.", "Double-blind comparison of carbetocin versus oxytocin in prevention of uterine atony after cesarean section.", "Carbetocin versus syntometrine in the management of third stage of labor following vaginal delivery.", "Carbetocin versus syntometrine for the third stage of labour following vaginal delivery--a double-blind randomised controlled trial." ]

[ "A randomized study involving pregnant women was conducted to compare the effectiveness of a single intravenous (IV) injection of carbetocin with that of a standard 2-h oxytocin IV infusion with respect to intraoperative blood loss in the prevention of uterine atony after cesarean section (CS). The two treatments also were compared for safety and ability to maintain adequate uterine tone and to reduce the incidence and severity of postpartum hemorrhage (PPH) in women at risk for this condition.\n Between 1 September 2007 and 5 January 2008, we enrolled 104 patients with at least one risk factor for PPH undergoing CS in a randomized, controlled clinical trial. We compared the effect of a single 100 microg IV dose of carbetocin with that of a standard 2-h ten international units (IU) IV infusion of oxytocin. The primary outcome was the proportion of patients requiring additional oxytocic intervention for uterine atony. Fiftytwo women received 100 microg carbetocin IV immediately after placental delivery, while 52 women received 10 IU oxytocin IV infusion. Complete blood count was collected at entry and 24 h postpartum. All outcome measures, including the need for additional uterotonic agents or uterine massage, and blood loss, were analyzed using chi-square, Fisher exact, and Student's t tests.\n A single 100 microg IV injection of carbetocin was as effective as a continuous 2-h infusion of oxytocin in controlling intraoperative blood loss after placental delivery. Mean blood loss after carbetocin administration was 30 ml less than after oxytocin administration (P = 0.5). The percentage of patients with blood loss < or =500 ml was greater with carbetocin (81 vs. 55%; P = 0.05). Carbetocin enhanced early postpartum uterine involution. The fundus was below the umbilicus in more patients who received carbetocin at 0, 2, 6, and 24 h on the ward (P < 0.05). The main additional uterotonic agent used was a further administration of oxytocin (20 IU in physiological solution 500 ml at an infusion rate of 200 ml/h). In the carbetocin group, 20 of the 52 women (38.4%) required at least one uterine massage compared to 30 of the 52 women (57.7%) in the oxytocin group (P < 0.01). Overall, uterotonic intervention was clinically indicated in two of the women (3.8%) receiving carbetocin compared to five of the women (9.6%) given an IV oxytocin infusion (P < 0.01). The odds ratio of treatment failure requiring oxytocic intervention was 1.83 (95% confidence interval, CI, 0.9-2.6) times higher in the oxytocin group compared with the carbetocin group.\n Carbetocin makes possible to obtain, with a single IV injection, results equivalent to those of oxytocin on the maintenance of uterine tonicity and the limitation of blood losses, in the peri- and in the post-operative period, during a delivery by CS. It has in addition a comparable tolerance. Even in our series adverse events are practically of the same type and similar frequency in both study groups. Thus, the effectiveness of carbetocin consists, thanks to its long half-life, on an unique injection, whereas oxytocin requires repeated injections or a perfusion of several hours, with a variability of the administered doses.", "Syntometrine is an effective uterotonic agent used in preventing primary postpartum haemorrhage but has adverse effects including nausea, vomiting, hypertension and coronary artery spasm. Carbetocin is a newly developed long-acting oxytocin analogue that might be used as an uterotonic agent. We compare the efficacy and safety of intramuscular (IM) carbetocin with IM syntometrine in preventing primary postpartum haemorrhage.\n Prospective, double-blinded, randomised controlled trial.\n Delivery suite of a university-based obstetrics unit.\n Women with singleton pregnancy achieving vaginal delivery after and throughout 34 weeks.\n Three hundred and twenty-nine eligible women were randomised to receive either a single dose of 100 microgram IM carbetocin or 1 ml IM syntometrine (a mixture of 5 iu oxytocin and 0.5 mg ergometrine) at the end of second stage of labour.\n Difference in haemoglobin drop measured 2 days after delivery between the two groups.\n There was no difference in the drop of haemoglobin concentration within the first 48 hours between the two groups. The incidence of additional oxytocic injections, postpartum haemorrhage (blood loss > or = 500 ml) and retained placenta were also similar. The use of carbetocin was associated with significant lower incidence of nausea (relative risk [RR] 0.18, 95% confidence interval [CI] 0.04-0.78), vomiting (RR 0.1, 95% CI 0.01-0.74), hypertension 30 minutes (0 versus 8 cases, P < 0.01) and 60 minutes (0 versus 6 cases, P < 0.05) after delivery but a higher incidence of maternal tachycardia (RR 1.68, 95% CI 1.03-3.57).\n IM carbetocin is as effective as IM syntometrine in preventing primary postpartum haemorrhage after vaginal delivery. It is less likely to induce hypertension and has a low incidence of adverse effect. It should be considered as a good alternative to conventional uterotonic agents used in managing the third stage of labour.", "A double-blind randomized study involving pregnant women undergoing cesarean section was conducted to compare the effectiveness of a single 100 micrograms intravenous injection of the long-acting oxytocin analog, carbetocin, with that of a standard infusion of oxytocin with respect to intraoperative blood loss. The two treatments also were compared for safety and ability to maintain adequate uterine tone.\n The study drug was administered to 57 women during elective cesarean section after placental delivery; blood was collected until abdominal closure. Intraoperative blood loss was calculated with a sensitive colorimetric method. Position, tone of the fundus, and vital signs were assessed up to 24 hours after the operation. The need for additional uterotonic agents was recorded.\n A single 100 micrograms intravenous injection of carbetocin was as effective as a continuous 16 hour infusion of oxytocin in controlling intraoperative blood loss after placental delivery. Mean blood loss after carbetocin administration was 29 ml less than after oxytocin administration (p = 0.3). Subset analysis deleting two patients who received oxytocic intervention in the operating room and one extreme outlier revealed a mean blood loss of 41 ml less in the carbetocin group (p = 0.14) with lower variances (p = 0.02). The percentage of patients with blood loss of 200 ml or less was greater with carbetocin (79% vs 53%; p = 0.041). Carbetocin enhanced early postpartum uterine involution. The fundus was below the umbilicus in more patients who received carbetocin at 0, 2, 3, and 24 hours on the ward (p < 0.05). There were no significant differences in uterine tone or type or amount of lochia. Additional oxytocin was used to treat three patients for postpartum hemorrhage or persistent uterine atony. All interventions were in the oxytocin group. Vital signs and hematologic values were comparable in each group, confirming similar safety profiles.\n A single 100 micrograms intravenous injection of carbetocin is as effective and more reliable than a standard continuous infusion of oxytocin in maintaining adequate uterine tone and preventing excessive intraoperative blood loss during cesarean section after delivery of the placenta. Patients receiving carbetocin required less intervention. Carbetocin was well tolerated.", "To compare the efficacy of a single dose of 100 microg intramuscular carbetocin to a single dose of intramuscular syntometrine (0.5 mg ergometrine and 5IU oxytocin), in preventing post-partum hemorrhage (PPH) in high risk patients following vaginal delivery.\n A prospective, randomized controlled study was conducted in a tertiary hospital where 120 pregnant women with risk factors for PPH who delivered vaginally were randomized into two groups: the study group where 100 microg intramuscular carbetocin was administered and the control group, who received intramuscular syntometrine. Outcome measures compared included changes in vital signs, amount of intrapartum blood loss, uterine fundal position, addition of another oxytocic agent, side-effects of the drugs, amount of lochia and hemoglobin drop after 24 hours post-partum. Incidence of PPH or other adverse events were also compared.\n There were no significant differences in terms of requirement for additional oxytocic agents, time interval to well contracted uterus, blood transfusion requirements, adverse effects or complications. There was a significantly lower mean estimated blood loss in the carbetocin group compared to the syntometrine group (244 +/- 114 mL vs 343 +/- 143 mL, 95% CI 52-146 mL). There was also a significantly reduced drop in hemoglobin in the carbetocin group compared to the syntometrine group (0.3 +/- 0.2 g/dL vs 0.4 +/- 0.2 g/dL, 95% CI 0.1-0.2 g/dL).\n Intramuscular carbetocin may be more effective than intramuscular syntometrine in reducing post-partum blood loss and the drop in hemoglobin level.", "To compare the effectiveness of carbetocin and oxytocin when they are administered after caesarean section for prevention of postpartum haemorrhage (PPH).\n Double-blind randomised single centre study (1:1 ratio).\n Teaching hospital in Bristol, UK with 6000 deliveries per annum.\n Women at term undergoing elective or emergency caesarean section under regional anaesthesia, excluding women with placenta praevia, multiple gestation and placental abruption.\n Women were randomised to receive either carbetocin 100 microg or oxytocin 5 IU intravenously after the delivery of the baby. Perioperative care was otherwise normal and use of additional oxytocics was at the discretion of the operating obstetrician. Analysis was by intention to treat.\n The proportion of women in each arm of the trial that needed additional pharmacological oxytocic interventions.\n Significantly more women needed additional oxytocics in the oxytocin group (45.5% versus 33.5%, Relative risk 0.74, 95% CI 0.57-0.95). The majority of women had oxytocin infusions. There were no significant differences in the secondary outcomes, including major PPH, blood transfusions and fall in haemoglobin.\n Carbetocin is associated with a reduced use of additional oxytocics. It is unclear whether this may reduce rates of PPH and blood transfusions.", "The goal of this study was to compare carbetocin, a long-acting oxytocin analog, with oxytocin in the prevention of uterine atony after cesarean section. Study Design: We enrolled 694 patients undergoing elective cesarean section in a Canadian multicenter, double-blind, randomized clinical trial. We compared the effect of a single 100 microg dose of carbetocin with that of a standard 8-hour infusion of oxytocin. The primary outcome was the proportion of patients requiring additional oxytocic intervention for uterine atony. A variable sample size, sequential design was used.\n The overall oxytocic intervention rate was 7.4%. The odds of treatment failure requiring oxytocic intervention was 2.03 (95% confidence interval 1.1 to 2.8) times higher in the oxytocin group compared with the carbetocin group, respectively, 32 of 318 (10.1%) versus 15 of 317 (4.7%), P <.05.\n Carbetocin, a new drug for the prevention of uterine atony, appears to be more effective than a continuous infusion of oxytocin and has a similar safety profile.", "To assess and compare the efficacy and safety of a single intramuscular dose of carbetocin to a single intramuscular dose of syntometrine in managing the third stage of labor following vaginal delivery among women with low risk factors for postpartum hemorrhage.\n Prospective double-blind randomized controlled study.\n The study included 240 healthy women with viable normal singleton pregnancies achieving normal vaginal delivery at or beyond 37 weeks' gestation during the period from May 2009 to December 2009 at TAIBA Hospital in Kuwait. Women were randomized to receive either a single dose of carbetocin or syntometrine intramuscularly following the delivery of the anterior shoulder of the baby. Outcome measures compared included postpartum hemorrhage requiring additional uterotonic therapy, incidence of postpartum hemorrhage, amount of intrapartum blood loss as well as adverse effects profile.\n There was a statistically highly significant difference in the estimated mean blood loss between the carbetocin and syntometrine groups, with a blood loss of 81.5 ml higher in the syntometrine group. The mean drop of hemoglobin concentration 24 h after delivery was 0.8 g/dl in carbetocin group and 1.1 g/dl in syntometrine group, and the difference was statistically highly significant. Women in the carbetocin group were less likely to experience nausea and vomiting.\n Single dose of intramuscular carbetocin 100 μg may be more effective as compared to a single intramuscular dose of syntometrine in reducing postpartum blood loss with a smaller drop in hemoglobin levels and less adverse effects.", "Prevention of postpartum haemorrhage is essential in the pursuit of improved health care for women. However, limited literature is available for comparing the use of oxytocin agonist carbetocin with syntometrine in women undergoing vaginal deliveries. We aimed to compare intramuscular carbetocin with intramuscular syntometrine for the routine prevention of postpartum haemorrhage in women who deliver vaginally.\n Prospective double-blind randomised controlled trial.\n Tertiary referral centre.\n Pregnant women with no contraindication for vaginal delivery recruited from January 2005 to April 2008.\n Participants were randomised to receive either syntometrine or carbetocin during the third stage of labour.\n Primary outcome measure was postpartum haemorrhage requiring additional uterotonics. Secondary outcome measures were the incidence of postpartum haemorrhage (> or =500 ml), severe postpartum haemorrhage (> or =1000 ml) and adverse effects profile.\n Women in the carbetocin group (13.5%) and in the syntometrine group (16.8%) had postpartum haemorrhage requiring additional uterotonics (P = 0.384). 1.6% of women in each group had postpartum haemorrhage (P = 1.0) and the estimated blood loss during the third stage of labour was similar between the two groups (P = 0.294). Women who had syntometrine were four times more likely to experience nausea (RR = 4.2; 95% CI 2.2-7.8) and vomiting (RR = 4.3; 95% CI 1.9-9.5) compared with women who had carbetocin. Tremor, sweating, retching and uterine pain were also more likely in the syntometrine group compared with the carbetocin group (P < 0.05).\n Carbetocin has an efficacy similar to syntometrine for prevention of postpartum haemorrhage, but is associated with less adverse effects." ]

[ "2296269", "2048857", "2721145", "15719207", "11844004", "9102069", "3083912", "13679324", "8489642", "8479356", "1995760", "1984536", "2564506", "3171037", "8177244", "8598504", "9801019", "7862179" ]

[ "Thiazide diuretic agents and the incidence of hip fracture.", "Diuretic drug use and the risk for hip fracture.", "Drugs affecting postural stability and other risk factors in the hip fracture epidemic--case-control study.", "Reduced fracture risk in users of thiazide diuretics.", "Zolpidem use and hip fractures in older people.", "A prospective study of thiazide use and fractures in women.", "Role of drugs in fractures of the femoral neck.", "Thiazide diuretics and the risk for hip fracture.", "Effects of thiazide diuretic therapy on bone mass, fractures, and falls. The Study of Osteoporotic Fractures Research Group.", "Psychotropics, thiazide diuretics and hip fractures in the elderly.", "Drugs and femoral neck fracture: a case-control study.", "Thiazide diuretics and the risk of hip fracture. Results from the Framingham Study.", "Long-term use of thiazide diuretics and risk of hip fracture.", "Do drugs affect the risk of hip fracture in elderly women?", "Risk factors for hip fracture in black women. The Northeast Hip Fracture Study Group.", "Current use of thiazide diuretics and prevention of femur fractures.", "Cognitive impairment, drug use, and the risk of hip fracture in persons over 75 years old: a community-based prospective study.", "Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group." ]

[ "Thiazide diuretic agents lower the urinary excretion of calcium. Their use has been associated with increased bone density, but their role in preventing hip fracture has not been established. We prospectively studied the effect of thiazide diuretic agents on the incidence of hip fracture among 9518 men and women 65 years of age or older residing in three communities. At base line, 24 to 30 percent of the subjects were thiazide users. In the subsequent four years, 242 subjects had hip fractures. The incidence rates of hip fracture were lower among thiazide users than nonusers in each community; the Mantel-Haenszel relative risk of hip fracture, adjusted for community and age, was 0.63 (95 percent confidence interval, 0.46 to 0.86). The protective effect of the use of thiazides was independent of sex, age, impaired mobility, body-mass index, and current and former smoking status; the multivariate adjusted relative risk of hip fracture was 0.68 (95 percent confidence interval, 0.49 to 0.94). Furthermore, the protective effect was specific to thiazide diuretic agents, since there was no association between the use of antihypertensive medications other than thiazides and the risk of hip fracture. These prospective data suggest that in older men and women the use of thiazide diuretic agents is associated with a reduction of approximately one third in the risk of hip fracture.", "To test the hypothesis that use of thiazide diuretics prevents hip fracture and to study the risk for hip fracture associated with furosemide use.\n A case-control study.\n Hospitals owned by a health maintenance organization in Washington.\n Elderly patients (n = 462) hospitalized because of a hip fracture between 1977 and 1983 and an equal number of age- and sex-matched population-based control patients.\n Use of thiazide diuretics and furosemide was ascertained from medical records and computerized pharmacy records. The relative risk for hip fracture associated with diuretic use was calculated and adjusted for the potentially confounding effects of nursing home residence; previous hospitalizations; a history of stroke, alcoholism, or the organic brain syndrome; body weight; leg paralysis; and use of phenobarbital, corticosteroids, or other diuretics. Current and former users of diuretics were analyzed separately.\n The adjusted risk for hip fracture was 1.6 (95% CI, 1.0 to 2.5) for current thiazide users. The adjusted risk for hip fracture for current furosemide use was 3.9 (CI, 1.5 to 10.4).\n According to this study, use of thiazide diuretics did not protect against hip fracture and cannot be recommended for fracture prevention. Current furosemide use was also associated with hip fracture.", "A parallel rise in hip fracture incidence and the rate of prescription of drugs affecting postural stability have been investigated by a case-control study. Other risk factors were also considered. One hundred and seventy-three cases and 134 hospital emergency surgical controls were interviewed and briefly examined, and drug data were corroborated by letter to general practitioners. The analysis revealed no significant difference between consumption of benzodiazepines in cases and controls, major tranquillizers, diuretics or other anti-hypertensives. However, they differed significantly in their average body weight and incidence of stroke. It is suggested that hip fractures on the whole occur in a particularly frail group of elderly people and that the increased fracture incidence over the last 20 years results from the survival of a more frail or less active group than hitherto.", "Thiazide diuretics (TD) reduce renal calcium excretion and may increase bone mineral density. A reduced fracture risk has been reported in some but not all studies. The aim of this study was to assess fracture risk in users of TD. The study design was nationwide population-based pharmacoepidemiological case-control study with fracture in year 2000 as outcome and use of TD during the previous 5 years as the exposure variable. Individual use of TD was derived from the Danish National Pharmacological Database and related to fracture data from the National Hospital Discharge Register. These data were combined with information on use of other drugs, social status, working status, income, educational status, contacts with general practitioners and practicing specialists, and comorbidity. A total of 64,699 patients (age = 40 years) who sustained a fracture during the year 2000 were compared to 194,111 age- and gender-matched controls. After adjustment for potential confounders, current use of TD was associated with a 10% (95% confidence interval [CI], 7% to 12%) reduced risk of any fracture and a 17% (95% CI 11% to 23%) reduced risk of forearm fractures. In former TD users, the risk reduction was slightly less pronounced. Similar results were found in men and women, and in subjects younger or > or = 65 years of age. Dose-effect analysis revealed a decreased risk of any fracture and fractures at the forearm and hip with an increased number of redeemed defined daily dosages (DDDs) of TD. Therefore, use of more than 2000 DDD was associated with a 19% (95% CI 10% to 27%) decreased hip fracture risk. We conclude that use of TD is associated with a significantly reduced fracture risk.", "The widespread use of sedative-hypnotics in older populations makes it imperative to identify hazardous regimens that should be avoided and safer regimens that may be used preferentially by older people. Although benzodiazepines have been shown to increase fall and fracture risk, zolpidem, a nonbenzodiazepine hypnotic, has been advocated as a safer alternative.\n Case-control study of hip fracture cases and controls in 1994.\n All subjects were age 65 and older and enrolled in Medicare, and in Medicaid or the Pharmaceutical Assistance to the Aged and Disabled program of New Jersey.\n Cases (n=1,222) were patients who underwent surgical repair of a hip fracture. They were frequency-matched to four controls (n=4,888) based on age and gender.\n Use of sedative-hypnotics and other medications was assessed in the 180 days before the index event. We assessed other covariates, including demographic, clinical, and healthcare utilization variables in the prior 180 days.\n Zolpidem use was associated with a significant increased risk of hip fracture (adjusted odds ratio (AOR) 1.95; 95% confidence interval (CI)=1.09-3.51). Other psychotropic medication classes with significantly increased risks included benzodiazepines (AOR 1.46; 95% CI=1.21-1.76), antipsychotic medications (AOR 1.61; 95% CI=1.29-2.01), and antidepressants (AOR 1.46; 95% CI=1.22-1.75). In subanalyses, preferential use of zolpidem by subjects at greater risk of hip fracture did not appear to explain the apparent risk of hip fracture with zolpidem use.\n Use of zolpidem by older people was associated with nearly twice the risk of hip fracture, even after controlling for possible demographic and clinical confounders. Rather than being a safer alternative, zolpidem may be associated with risks that are as great as those seen with conventional benzodiazepines in older patients.", "Thiazide diuretics reduce urinary calcium and may inhibit bone resorption, and hence may help to attenuate age-related bone loss and to lower the risk of osteoporotic fracture. We followed 83728 women, who were 36-61 years of age at baseline in 1982, for 10 years with biennial mailed questionnaires on which they reported incident fractures, use of thiazide diuretics, and other medical behavioral information. From descriptions of fracture sites and circumstances, 251 hip (proximal femur) and 1594 forearm (distal radius) fractures were identified as low or moderate trauma events. After controlling for age, body mass index, menopausal status, postmenopausal hormone use, cigarette smoking and dietary factors, we observed a statistically significant 22% reduction in the risk of forearm fractures among current thiazide users compared with women who reported no thiazide use. Risk appeared to decline with longer duration of use, reaching a 37% reduction in risk among women who had been using thiazides for 8 or more years. For hip fractures, thiazide use was protective among the postmenopausal women (relative risk = 0.69, 95% confidence interval 0.48-0.99). We conclude that the potential benefit of thiazide diuretics for osteoporosis should be considered when prescribing antihypertensive treatment.", "To investigate the role of drugs in the rising incidence of fractures of the femoral neck in the elderly a case-control study inquiring about the use of prescribed drugs was carried out. The drug histories of 102 patients with femoral neck fractures were obtained from general practice records and compared with those of 204 controls matched for age and sex from the same practices. At the time of fracture 41 patients with fractures and 126 controls were receiving at least one prescription (relative risk of fracture of the femoral neck in patients taking drugs = 0.42, p = 0.0006). For all types of prescribed drugs except antibiotics the risk of fracture of the femoral neck was less in patients taking drugs than in those not doing so, and this was true at all times in the year before fracture. Six patients with fractures were receiving thiazide diuretics compared with 37 controls (relative risk 0.28, p = 0.004). These results indicate that, contrary to popular belief, drugs that sedate or that impair postural control are not important factors in fractures of the femoral neck. The results are consistent with the hypothesis that the hypocalciuria induced by thiazides protects against fracture, but the degree of protection is not significantly greater than that associated with other drugs.", "Since most hip fractures are related to osteoporosis, treating accelerated bone loss can be an important strategy to prevent hip fractures. Thiazides have been associated with reduced age-related bone loss by decreasing urinary calcium excretion.\n To examine the association between dose and duration of thiazide diuretic use and the risk for hip fracture and to study the consequences of discontinuing use.\n Prospective population-based cohort study.\n The Rotterdam Study.\n 7891 individuals 55 years of age and older.\n Hip fractures were reported by the general practitioners and verified by trained research assistants. Details of all dispensed drugs were available on a day-to-day basis. Exposure to thiazides was divided into 7 mutually exclusive categories: never use, current use for 1 to 42 days, current use for 43 to 365 days, current use for more than 365 days, discontinuation of use since 1 to 60 days, discontinuation of use since 61 to 120 days, and discontinuation of use since more than 120 days.\n 281 hip fractures occurred. Relative to nonuse, current use of thiazides for more than 365 days was statistically significantly associated with a lower risk for hip fracture (hazard ratio, 0.46 [95% CI, 0.21 to 0.96]). There was no clear dose dependency. This lower risk disappeared approximately 4 months after thiazide use was discontinued.\n Thiazide diuretics protect against hip fracture, but this protective effect disappears within 4 months after use is discontinued.", "To determine the relation between the use of thiazide diuretics and bone mass, fractures, and falls in older women.\n Cross-sectional study of thiazide diuretics, bone mass, and prevalent vertebral deformities; cohort analysis of thiazide diuretics and nonspinal fractures and falls.\n Four clinical centers located in Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela Valley, Pennsylvania.\n A total of 9704 ambulatory, nonblack women who were 65 years or older.\n Information on thiazide use, demographic data, medical history, and anthropometric measurements were obtained by questionnaire, interview, and examination. Appendicular bone mass was measured by single-photon absorptiometry. Incident falls and fractures were ascertained every 4 months.\n Women using thiazide diuretics for more than 10 years had significantly higher bone mass than women who had never used thiazide diuretics (for example, 0.381 g/cm2 compared with 0.355 g/cm2 for the distal radius [P < 0.001]). Current users of thiazide diuretics had an incidence of falls (relative risk, 1.06; 95% CI, 0.90 to 1.25) that was similar to that of those who had never used these drugs. After adjusting for age, body weight, functional status, total calcium intake, duration of estrogen replacement therapy, and self-reported health status, we found that current users of thiazide diuretics who had taken these drugs for more than 10 years had a risk for nonspinal (relative risk, 0.99; CI, 0.81 to 1.20) and osteoporotic (relative risk, 0.98; CI, 0.79 to 1.22) fractures that was similar to that of women who had never used thiazides; however, thiazide users did have a lower risk for fractures of the hip (relative risk, 0.63; CI, 0.34 to 1.16) and wrist (relative risk, 0.66; CI, 0.40 to 1.08), neither of which was significant.\n Thiazide diuretics have no effect on a women's risk for falling or for experiencing nonspinal fractures. The trend toward a lower risk for hip and wrist fractures is consistent with findings in previous cohort studies but may reflect selection factors for the use of thiazide diuretics. A randomized trial is needed to determine the effect ot thiazide diuretics on the incidence of fractures.", "To determine whether psychotropic medications increase, and thiazide diuretics decrease, the risk of hip fractures in elderly Australians.\n Population-based case-control study.\n The population aged 65 years and over living in a defined area in western Sydney, Australia, during 1990-1991. Cases (n = 209) were recruited from hospitals and controls (n = 207) were selected by an area probability sampling method, with additional sampling from nursing homes. Response rates were 96% for cases and 84% for controls.\n Data were collected directly from subjects by questionnaire; a proxy respondent was required for 27% of subjects. In addition to medication use, information was also collected on potential confounders: alcohol consumption, body mass index, cognitive status, dairy product consumption, health status, physical activity, smoking history and type of residence.\n The use of temazepam, a short-acting benzodiazepine, was associated with an increase in the risk of hip fracture--odds ratio, adjusted for age, gender and residence is 3.78; 95% confidence interval (CI), 1.60-8.92. After adjusting for multiple potential confounders by logistic regression, the odds ratio for temazepam use was 3.52. There was a non-significant (P > 0.05) increase in hip fracture risk associated with the use of antidepressants and antipsychotics. Thiazide diuretics were not associated with a risk of hip fracture--the multivariate-adjusted odds ratio was 0.98 (95% CI, 0.49-1.99).\n Temazepam may increase the risk of hip fracture in elderly people. The effect of thiazide diuretics on fracture risk should be assessed in a large randomised trial.", "Two hundred consecutive patients with femoral neck fractures (FNF) and 200 controls matched by age, sex, nursing home residency and number of admissions within the last 2 years, were interviewed about recent drug use. The matching criteria were chosen to achieve case and control groups that were comparable with regard to overall physical disability. Thus a preliminary study had shown FNF to be strongly associated with nursing home residency and to be correlated with the number of recent hospital admissions. FNF was found to be negatively associated with use of coronary drugs (OR = 0.27; 95% CI = 0.11-0.70) and positively associated with drug use in general (OR = 2.00; 95% CI = 1.04-3.05). The OR for the various classes of psychotropic drugs was consistently greater than 1., although this was not statistically significant. An inherent problem in interpreting such findings is that underlying disease may predispose the subject to both FNF and drug use, thus creating a non-causal relationship.", "Thiazide diuretics may preserve bone mass and prevent elderly women's osteopenic fractures, but studies have not distinguished between thiazide preparations or examined former users. We performed a case-control study looking at thiazide use and subsequent hip fracture in postmenopausal female members of the Framingham Study cohort. Cases who had experienced a first hip fracture (n = 176) were compared with age-matched controls (n = 672). Results showed a modest protective effect of any recent thiazide use (not significant). However, recent pure thiazide users experienced significant protection against fracture (adjusted odds ratio, 0.31; 95% confidence interval, 0.11 to 0.88), whereas recent users of combination drugs containing thiazides experienced no protection (adjusted odds ratio, 1.16; 95% confidence interval, 0.44 to 3.05). Combination drugs generally contained only 25 mg of hydrochlorothiazide, suggesting that the small amount of thiazide was insufficient to preserve bone mass. Former thiazide users were not protected against fracture. In sum, recent pure thiazide use in women protects against hip fracture.", "To assess whether long-term thiazide use is associated with a decreased risk of hip fracture, a nested case-control study was done in the Canadian province of Saskatchewan between 1984 and 1985 among residents who were 65 years of age or older and who were not receiving other drugs thought to affect bone mass. There were 905 hip fractures identified from hospital discharge records and 5137 population controls matched for age, sex, and calendar year. Drug use was ascertained from computerised pharmacy records. Risk of hip fracture decreased significantly with increasing duration of current thiazide use: relative risk (95% confidence interval) of 1.2 (0.9-1.5) for less than 2 years use, 0.8 (0.7-1.0) for use of 2-5 years, and 0.5 (0.3-0.7) for 6 or more years. In contrast, there was no such trend for use of other antihypertensive-diuretic drugs (relative risk 0.9 [0.6-1.3] for use of 6 or more years). This protective effect was not altered by age, sex, nursing home residence, previous hospital admission, or use of other antihypertensive-diuretic drugs or psychotropic drugs. Medical record review for a sample of 235 cases suggested this finding was not due to confounding by body mass, ambulatory status, functional status, or dementia. These results support the hypothesis that thiazides protect against osteoporosis in elderly people.", "The drugs prescribed for 280 women with hip fractures (mean age 83 years) were compared with those prescribed for 145 women controls (mean age 81 years) as recorded in a family practice age-sex register. Thirty-three percent of the fracture patients were taking diuretics compared with 24% of the controls (.10 greater than P greater than .05). Forty-six percent of these diuretics taken by the fracture group (compared with 40% taken by the controls) were either loop or potassium sparing diuretics in combination with another diuretic. Twenty-five percent of the controls (compared with 9% of the fracture patients) were taking nonsteroidal anti-inflammatory drugs (NSAIDs) (P less than .001). The greater use of NSAIDs by control subjects may be due to the small overlap between osteoporosis and osteoarthritis. No significant differences were found for digoxin, anti-hypertensive drugs, and those taking no drugs. Thirty percent of fracture patients were taking sedatives and hypnotics compared with 28% of controls. Within this category, 54% of the fracture patients and 80% controls were receiving drugs (mainly benzodiazepines) with half-lives longer than 24 hours. Thus, this population did not confirm a previously identified association between long-acting sedatives and the risk of fracture. As only 3.5% of fracture patients and 2.1% controls were receiving phenothiazines, a role for these drugs in hip fracture cannot be ruled out. In summary, hip fracture patients were slightly more likely to be taking diuretics and somewhat less likely to be taking NSAIDs than controls but there were no differences with respect to other drugs.", "Although more than 1 percent of black women 80 years of age or older have hip fractures each year, little is known about risk factors for hip fracture in these women.\n We carried out a case-control study involving 144 black women admitted with a first hip fracture to 1 of 30 hospitals in New York and Philadelphia. The control were 218 black women living in the community who were matched to the case patients according to age and ZIP Code or telephone exchange and 181 hospitalized black women matched according to age and hospital. Information was obtained through personal interviews and was studied by multivariable logistic-regression analysis.\n When the case patients were compared with the control subjects from the community, the women in the lowest quintile for body-mass index had a markedly increased risk of hip fracture as compared with the women in the highest quintile (odds ratio, 13.5; 95 percent confidence interval, 4.2 to 43.3). Postmenopausal estrogen therapy for one year or more was protective for women under 75 years of age (odds ratio, 0.1; 95 percent confidence interval, < 0.1 to 0.5). Factors associated with an increased risk of hip fracture included a history of stroke (odds ratio, 3.1; 95 percent confidence interval, 1.2 to 8.1), use of aids in walking (odds ratio, 5.6; 95 percent confidence interval, 2.7 to 11.5), and consumption of seven or more alcoholic drinks per week (odds ratio, 4.6; 95 percent confidence interval, 1.5 to 14.1). The results were similar when the case patients were compared with the hospitalized control subjects.\n Among black women thinness, previous stroke, use of aids in walking, and alcohol consumption are associated with an increased risk of hip fracture. Postmenopausal estrogen therapy protects against hip fracture in women under 75 years of age.", "A case control study of a defined population from The Netherlands was performed to evaluate the risk of femur fractures associated with the use of thiazide diuretics. Included were 386 patients hospitalized for femur fractures between 1986 and 1990 who were residents and 45 years of age and older. Per case, one age-, sex-, pharmacy-, and general practitioner-matched control was chosen from the general population. Drug use was ascertained from computerized pharmacy records. The adjusted odds ratio of current use of thiazide diuretics was 0.5 (95% confidence interval, 0.3-0.9). The protective effect of thiazide diuretics was greatest for use of 1 year or longer at relatively high doses of thiazides (odds ratio, 0.3; 95% confidence interval, 0.1-0.9). We also found that patients who discontinued thiazide use longer than 2 months were not protected against femur fractures. These results support the hypothesis that use of thiazide diuretics protects against femur fractures.", "The authors examined the effects of cognitive function, as assessed by the Mini-Mental State Examination, and drug use on the incidence of hip fracture in a community-based Swedish population of 1,608 subjects who were aged > or = 75 years on October 1, 1987, and who had not had a hip fracture. During the 7,123.8 person-year follow-up, 134 first hip fractures were identified. The Cox proportional hazards model was used to estimate the relative risk of developing hip fracture, taking into account several potential confounders. Compared with those without cognitive impairment, subjects with mild impairment (Mini-Mental State Examination scores 18-23) had a relative risk of 2.04 (95% confidence interval (CI) 1.29-3.24), and subjects with moderate-severe impairment (Mini-Mental State Examination score < 18) had a relative risk of 2.09 (95% CI 1.17-3.72). Subjects using opioid analgesics (97% took propoxyphene) had a relative risk of 2.01 (95% CI 1.19-3.40). Taking potassium supplements (99% took potassium chloride) was related to a reduced risk of hip fracture (relative risk = 0.55, 95% CI 0.31-0.98), while diuretics did not have an independent impact. In summary, the results show that cognitive impairment and use of propoxyphene are associated with increased risk of hip fracture. The observed protection of potassium chloride merits further attention. The limitation of the study was that the assessment of drug use was made only at baseline.", "Many risk factors for hip fractures have been suggested but have not been evaluated in a comprehensive prospective study.\n We assessed potential risk factors, including bone mass, in 9516 white women 65 years of age or older who had had no previous hip fracture. We then followed these women at 4-month intervals for an average of 4.1 years to determine the frequency of hip fracture. All reports of hip fractures were validated by review of x-ray films.\n During the follow-up period, 192 women had first hip fractures not due to motor vehicle accidents. In multivariable age-adjusted analyses, a maternal history of hip fracture doubled the risk of hip fracture (relative risk, 2.0; 95 percent confidence interval, 1.4 to 2.9), and the increase in risk remained significant after adjustment for bone density. Women who had gained weight since the age of 25 had a lower risk. The risk was higher among women who had previous fractures of any type after the age of 50, were tall at the age of 25, rated their own health as fair or poor, had previous hyperthyroidism, had been treated with long-acting benzodiazepines or anticonvulsant drugs, ingested greater amounts of caffeine, or spent four hours a day or less on their feet. Examination findings associated with an increased risk included the inability to rise from a chair without using one's arms, poor depth perception, poor contrast sensitivity, and tachycardia at rest. Low calcaneal bone density was also an independent risk factor. The incidence of hip fracture ranged from 1.1 (95 percent confidence interval, 0.5 to 1.6) per 1,000 woman-years among women with no more than two risk factors and normal calcaneal bone density for their age to 27 (95 percent confidence interval, 20 to 34) per 1,000 woman-years among those with five or more risk factors and bone density in the lowest third for their age.\n Women with multiple risk factors and low bone density have an especially high risk of hip fracture. Maintaining body weight, walking for exercise, avoiding long-acting benzodiazepines, minimizing caffeine intake, and treating impaired visual function are among the steps that may decrease the risk." ]

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[ "Comparison of two triphasic oral contraceptives containing either gestodene or norethindrone: a randomized, controlled trial.", "Efficacy and tolerability of a monophasic oral contraceptive containing ethinylestradiol and drospirenone.", "Triphasic Randomized Clinical Trial: comparative frequency of intermenstrual bleeding.", "Cycle control on low-dose oral contraceptives: a comparative trial.", "Clinical comparison of monophasic oral contraceptive preparations of gestodene/ethinyl estradiol and desogestrel/ethinyl estradiol. Latin American Oral Contraceptive Study Group.", "Initial selection of oral contraceptives.", "A comparison of the cycle control, safety, and efficacy profile of a 21-day regimen of ethinylestradiol 20mug and drospirenone 3mg with a 21-day regimen of ethinylestradiol 20mug and desogestrel 150mug.", "A comparison of the cycle control and tolerability of two ultra low-dose oral contraceptives containing 20 micrograms ethinylestradiol and either 150 micrograms desogestrel or 75 micrograms gestodene.", "Efficacy and safety of the combined oral contraceptive ethinylestradiol/drospirenone (Yasmin) in healthy Chinese women: a randomized, open-label, controlled, multicentre trial.", "Multicenter randomized comparative trial of two low-dose triphasic combined oral contraceptives containing desogestrel or norethindrone.", "An open-label randomized comparative study of oral contraceptives between medications containing 3 mg drospirenone/30 microg ethinylestradiol and 150 microg levonogestrel/30 microg ethinylestradiol in Thai women.", "A triphasic oral contraceptive pill, CTR-05: clinical efficacy and safety.", "A comparative analysis of three different dose combinations of oral contraceptives.", "Comparative study on the acceptability of two modern monophasic oral contraceptive preparations: 30 microgram ethinyl estradiol combined with 150 microgram desogestrel or 75 microgram gestodene.", "Multicenter, comparative study of cycle control, efficacy and tolerability of two low-dose oral contraceptives containing 20 microg ethinylestradiol/100 microg levonorgestrel and 20 microg ethinylestradiol/500 microg norethisterone.", "Comparison of efficacy, cycle control, and tolerability of two low-dose oral contraceptives in a multicenter clinical study.", "Effects of oral contraceptives containing ethinylestradiol with either drospirenone or levonorgestrel on various parameters associated with well-being in healthy women: a randomized, single-blind, parallel-group, multicentre study.", "Efficacy and acceptability of two monophasic oral contraceptives containing ethinylestradiol and either desogestrel or gestodene.", "A comparative study of two low-dose combined oral contraceptives: results from a multicenter trial.", "A comparative investigation of contraceptive reliability, cycle control and tolerance of two monophasic oral contraceptives containing either drospirenone or desogestrel.", "Bleeding pattern with drospirenone 3 mg+ethinyl estradiol 20 mcg 24/4 combined oral contraceptive compared with desogestrel 150 mcg+ethinyl estradiol 20 mcg 21/7 combined oral contraceptive.", "Effect of oral contraceptive containing ethinyl estradiol combined with drospirenone vs. desogestrel on clinical and biochemical parameters in patients with polycystic ovary syndrome.", "A comparative study of monophasic oral contraceptives containing either drospirenone 3 mg or levonorgestrel 150 microg on premenstrual symptoms.", "A double-blind comparison of the efficacy and acceptability of Femodene and Microgynon-30.", "Cycle control, quality of life and acne with two low-dose oral contraceptives containing 20 microg ethinylestradiol." ]

[ "Two triphasic oral contraceptives containing either gestodene or norethindrone as the progestogenic compound combined with ethinyl estradiol were compared in a randomized clinical trial to assess their contraceptive reliability, clinical tolerance and cycle control. Both preparations were effective in preventing pregnancy. The gestodene preparation proved significantly superior regarding cycle control and general tolerance.", "To assess the contraceptive reliability, cycle control and tolerability of a new monophasic oral contraceptive containing 30 g ethinylestradiol plus 3 mg drospirenone (Yasmin, Schering AG, Berlin, Germany), it was compared with an established oral contraceptive containing 30 g ethinylestradiol plus 150 g desogestrel (Marvelon, NV Organon, Oss, The Netherlands).\n A randomized, open-label, 13-cycle study was performed at 80 European centers. Contraceptive reliability, cycle control, blood pressure, body weight, the incidence of adverse events and skin condition were assessed during 13 cycles of oral contraceptive use, and at follow-up. Subjects recorded body weight on three consecutive days pretreatment and weekly thereafter.\n Of 2069 women who started the study and received the trial preparations in a ratio of 4:1 (ethinylestradiol/drospirenone, n = 1657; ethinylestradiol/desogestrel, n = 412), 1615 completed the 13 cycles plus follow-up, providing data for over 23,000 evaluable cycles. Eleven pregnancies occurred during treatment, only one of which (in the ethinylestradiol/drospirenone group) could not be ascribed to user failure or interaction with other factors. Both preparations provided effective contraception and cycle control. Pre-existing acne and seborrhea were improved and blood pressure was essentially unchanged. The two treatments differed in their effect on body weight, the difference being statistically significant. In the ethinylestradiol/drospirenone group, there was a distinct decrease over the whole treatment phase, while a subtle and less distinct decrease was documented in the ethinylestradiol/desogestrel group.\n The combination of 30 g ethinylestradiol/3 mg drospirenone provides effective oral contraception, excellent cycle control, good tolerability and a level of weight loss that may have a significant beneficial effect on compliance in women with a tendency to weight gain due to water retention.", "Oral contraceptives have the highest theoretic efficacy of all reversible forms of contraception, yet in practice they have an actual failure rate equivalent to that of some barrier methods. The efficacy of oral contraceptives depends primarily on patient compliance. So-called \"nuisance\" side effects, such as intermenstrual bleeding (breakthrough bleeding or spotting), play a major role in their discontinuation. The Triphasic Randomized Clinical Trial compared the incidence of these side effects in three groups of subjects taking NET (A) (Ortho-Novum 7/7/7), LNG (Tri-Levlen), or NET (B) (Tri-Norinyl). Subjects taking NET (A) had the highest incidence of intermenstrual bleeding (63%) followed by NET (B) (44%) and LNG (33%). Only the difference between NET (A) and LNG attained statistical significance (p less than 0.030). Control subjects had no breakthrough bleeding and a 4% incidence of spotting. Further research is warranted to establish the cause of the disparity in the incidence of intermenstrual bleeding among patient groups assigned to the three oral triphasic contraceptives.", "Cycle control was studied comparing the monophasic oral contraceptive Loestrin with three low-dose phasic preparations (Triphasil, Ortho 10/11 and Ortho 7/7/7) in 391 women of whom 300 completed 6 cycles. Loestrin subjects had a rate of occurrence (31% of cycles) for intermenstrual bleeding (IMB) comparable to the rates for subjects on the phasic preparations (36%, 37% and 37%, respectively). Triphasil subjects had lower rates than the Ortho 10/11 and Ortho 7/7/7 subjects (p less than 0.01) in cycle one when all subjects were analyzed and in pre-study users when continuing menstrual flow (CMF) episodes were not included as IMB. IMB was a cause for dropping out of the study in 7% of subjects who were evenly distributed between groups. There were no differences between groups for BTB when perceived by subjects as a side effect. Spotting was perceived as a side effect more often with Ortho 10/11 and Ortho 7/7/7 use than with Triphasil (p less than 0.01). Loestrin, Ortho 10/11 and Ortho 7/7/7 subjects were more likely to report amenorrhea (p less than 0.001) and less likely to report leg cramps (p less than 0.01) compared to those on Triphasil. Triphasil subjects were less likely to report acne than subjects on Ortho 7/7/7 (p less than 0.01).", "The efficacy, cycle control, subjective complaints, and safety of monophasic preparations of the oral contraceptives containing gestodene 75 mcg plus ethinyl estradiol 30 mcg versus desogestrel 150 mcg plus ethinyl estradiol 30 mcg were compared in a 6-cycle, open-label, parallel, randomized, multicenter phase IV clinical study in Latin America. Of a total of 176 women in each group, 163 in the gestodene group and 160 in the desogestrel group completed 6 cycles, providing data for 1,015 and 1,006 cycles, respectively. Subject compliance was excellent; pills were missed during only 6.9% of the cycles in each group. No woman became pregnant during the study. Gestodene group exhibited significantly better cycle control as evidenced by the lower incidence of breakthrough bleeding and spotting. Spotting in some cycles was reported by 11.9% of women taking the gestodene-combination compared with 21% of women taking the desogestrel-combination. Based on number of women, 86.4% of the gestodene group reported all cycles were normal (no BTB) compared with 76.7% of the desogestrel group. Also, the women in the gestodene group reported a significantly lower incidence of nuisance side effects during treatment cycles. No amenorrhea was observed for either group. There were no clinically significant differences between groups with respect to body weight, blood pressure, or laboratory evaluations. Seven women withdrew from the gestodene group and 8 women withdrew from the desogestrel group because of adverse reactions. The results of this study indicate that, although both OCs provided effective contraception, in comparison to the desogestrel-combination, the gestodene-containing OC is associated with better cycle control, less bleeding, and fewer subjective complaints.", "A prospective, randomized trial compared client experiences with three popular oral contraceptives--Triphasil, Ortho-Novum 7/7/7 and Ortho-Novum 1/35. After one year, no significant relationship was found between the contraceptive prescribed and either breakthrough bleeding or satisfaction with the medication. The monophasic formulation, Ortho-Novum 1/35, was associated with amenorrhea more often.", "To compare the cycle control, efficacy, and safety of a new low-dose combined oral contraceptive containing ethinylestradiol 20mug and drospirenone 3mg with an established formulation containing ethinylestradiol 20mug and desogestrel 150mug.\n This was a randomized, open-label, parallel-group, multicenter study of healthy women (aged 18-35 years) over seven treatment cycles. Both combined oral contraceptives were administered once daily for 21 consecutive days followed by a 7-day hormone-free interval.\n A total of 445 women were randomized to treatment; of these, 441 (ethinylestradiol 20mug/drospirenone 3mg, n = 220; ethinylestradiol 20mug/desogestrel 150mug, n = 221) went on to receive study medication. There was a trend towards reduced intracyclic bleeding with continued treatment in both treatment groups, consistent with clinical experience. Intracyclic bleeding was highest during the first treatment cycle in both treatment groups, but was generally much lower in subsequent cycles. More than 90% of women in each of the groups experienced withdrawal bleeding during the study. The duration of withdrawal bleeding remained fairly constant throughout the study. The maximum intensity was mainly bleeding, rather than spotting. Overall, cycle control, efficacy, and safety profiles were comparable between both groups. Adverse events were generally of mild-to-moderate intensity and were those typical of hormonal contraceptive use.\n In conclusion, both ethinylestradiol 20mug/drospirenone 3mg and ethinylestradiol 20mug/desogestrel 150mug are effective and well tolerated contraceptives that provide good cycle control.", "To compare the cycle control and tolerability of two oral contraceptives containing 20 micrograms ethinylestradiol and either 150 micrograms desogestrel or 75 micrograms gestodene.\n A randomized, multicenter study was conducted in which 1016 healthy adult women received the desogestrel (n = 509) or the gestodene (n = 507) preparation for six treatment cycles.\n No significant differences in bleeding patterns were detected between the two treatments. The incidence and duration of irregular bleeding decreased markedly, and to a similar extent, during each treatment. The occurrence of irregular bleeding per cycle decreased from 24.6 to 9.4% in the desogestrel group and from 19.7 to 8.6% in the gestodene group. Its duration fell from 1.1 to 0.2 days and from 0.9 to 0.3 days, respectively. There was a consistently low incidence of amenorrhea (1.0-2.8%). There were no significant differences between treatments for the incidence, intensity or emergence of dysmenorrhea. During both treatments, the incidence of premenstrual syndrome and complaints such as breast tenderness, nausea and headache dropped markedly.\n Ultra low-dose oral contraceptives containing desogestrel or gestodene offer equivalent, good cycle control and improvements in dysmenorrhea and premenstrual syndrome and have similar, excellent tolerability profiles.", "To evaluate and compare the contraceptive efficacy, bleeding pattern, side effects and other positive effects of a combined oral contraceptive (COC) containing drospirenone (DRSP) [Yasmin] with those of a COC containing desogestrel (DSG) in healthy Chinese women. This was a randomized, open-label, controlled, multicentre study of 768 healthy Chinese women requiring contraception. The subjects were randomized to ethinylestradiol (EE) 30 microg/DRSP 3 mg (n = 573) or EE 30 microg/ DSG 150 microg (n = 195), at a ratio of 3 : 1. Each individual was treated for 13 cycles. Further visits were required at cycle 4, cycle 7, cycle 10 and cycle 13 of treatment. Weight, height and body mass index were evaluated at each visit. The Menstrual Distress Questionnaire (MDQ) was administered at baseline, visit 3 (cycle 7) and visit 5 (after cycle 13). Baseline characteristics were similar between the two groups (p > 0.05). The Pearl Index (method failure) for EE/DRSP was 0.208 per 100 women-years, which was lower than that for EE/DSG (0.601 per 100 women-years). There were no significant differences between the treatment groups with regard to bleeding patterns. According to the MDQ subscale, improvements in water retention and increases in appetite during the intermenstrual period and in water retention and general well-being during the menstrual period in the EE/DRSP group (-0.297, -0.057, 0.033 and 0.150, respectively) were significantly improved compared with the EE/DSG group (-0.108, 0.023, 0.231 and -0.023, respectively) [all p < 0.05]. Other values that improved in both groups, particularly improvement in breast pain and tenderness and skin condition, were more evident in the EE/DRSP group (18.0%, 89/494; 12.6%, 62/494) than in the EE/DSG group (11.3%, 19/168; 5.4%, 9/168). Mean weight increased in the EE/DSG group (0.57 kg) while there was a significant decrease in mean weight (-0.28 kg) in the EE/DRSP group (p < 0.01). Both EE/DRSP and EE/DSG have good contraceptive efficacy and a comparable bleeding pattern. EE/DRSP had a more favourable effect on weight and premenstrual symptoms than EE/DSG.", "To compare a new triphasic oral contraceptive (OC) containing desogestrel and ethinyl estradiol (DSG/EE) with triphasic norethindrone/ethinyl estradiol (NE/EE) regarding effects on clinical efficacy, cycle control, and safety indices.\n In an open-label, comparative multicenter study, 407 subjects were randomized to a triphasic preparation containing DSG/EE and 405 subjects to a triphasic preparation containing NE/EE. The women were observed during six cycles of OC use.\n The contraceptive efficacy of the triphasic DSG/EE OC was at least comparable to that of triphasic NE/EE. No pregnancies were reported with DSG/EE, whereas there were two pregnancies with NE/EE, both user failures. Cycle control with triphasic DSG/EE was statistically superior to that with triphasic NE/EE. Acceptability was excellent with both preparations as measured by the low discontinuation rates (particularly for adverse menstrual experiences). No thromboembolic or other serious drug-related adverse experiences were reported. The incidence of other drug-related adverse experiences was generally low and decreased with time in both groups. No adverse effects were seen in terms of blood pressure, body weight, laboratory indices, cervical cytology, and breast nodularity.\n Triphasic DSG/EE is an effective and safe OC with excellent acceptability and cycle control superior to that of triphasic NE/EE.", "This study was conducted to compare the cycle control, efficacy and adverse events of a new low-dose oral contraceptive pill regimen containing 3 mg drospirenone (DRSP)/30 microg ethinylestradiol (EE), with a widely prescribed 150 microg levonogestrel (LNG)/30 microg EE. The results of this comparative trial demonstrated that the two preparations had no statistically significant difference in terms of cycle control, efficacy and adverse events. The occurrence of spotting and breakthrough bleeding was low and was not different between the two regimens. There was neither amenorrhea nor pregnancies reported in either group. The most common adverse events in both groups were nausea, headache and breast tenderness. Also statistically significant changes were found in body weight and blood pressure in both groups at the end of the study. In conclusion, the 3 mg DRSP/30 microg EE regimen provides good cycle control with reliable contraceptive efficacy and a low incidence of adverse events equal to the 150 microg LNG/30 microg EE preparation. Compared with the 150 microg LNG/30 microg EE preparation, the 3 mg DRSP/30 microg EE preparation demonstrated a more favorable effect on body weight and blood pressure, with the mean body weight and mean blood pressure remaining lower than baseline mean. The new formulation may be especially beneficial for women susceptible to body weight gain and rise in blood pressure.", "The primary objective of this study was to compare the safety, contraceptive efficacy, and menstrual cycle patterns in women using triphasic oral contraceptive pills, namely CTR-05, containing 50/100/150 micrograms desogestrel and 35/30/30 micrograms ethinylestradiol, and Orthonovum777 containing 500/750/1000 micrograms norethindrone and 35/35/35 micrograms ethinylestradiol.\n Forty-six female volunteers, satisfying the selection criteria, were evaluated for six cycles, in an open-label, randomized study. Volunteers using CTR-05 were studied for 13 additional cycles for efficacy and safety.\n No serious adverse effects were observed in either group. The incidences of other drug-related adverse effects, such as headache and nausea, were transient in both groups. CTR-05 did not lower levels of high density lipoprotein (HDL) cholesterol. This may be attributed to the lower androgenicity of its progestin component, desogestrel. No pregnancies were reported in either group. Clinical and laboratory parameters remained within normal limits in both groups. In the CTR-05 group, the lower dose of ethinylestradiol did not affect the safety, efficacy and acceptability of the product.\n Desogestrel, with little estrogenic activity and only minimal androgenic activity, leads to lipoprotein changes, resulting in a favorable cardiovascular profile, as well as minimal androgen-related effects, such as hirsutism and acne.", "Three different low-dose formulations of oral contraceptives were compared to determine the most suitable preparation for Filipino women as reflected in the first year continuation rates, incidence of side effects and failure rates. A total of 1,800 subjects were enrolled in the study from 18 health centers in six provinces in two regions of the Philippines, covering a total of 18,282 women-months of use. Sociodemographic characteristics were comparable. The monophasic levonorgestrel group showed the best performance followed by the triphasic preparation. The norethindrone group consistently showed higher drop-out rates, which may be due to the relatively higher incidence of side effects. For all three preparations, bleeding irregularities were low. There were no major side effects and no pregnancy was reported in one year of use. Noted was a distinct regional and provincial difference in recruitment and follow-up performance, possibly due to clinic, client or program factors.", "Cycle control and tolerability of two monophasic oral contraceptive pills containing 30 microg ethinyl estradiol (EE) with either 150 microg desogestrel (DSG) or 75 microg gestodene (GSD) were compared in women starting oral contraception. A minimum of 200 healthy women at risk for pregnancy were to be treated for a total of 6 cycles per patient in a prospective, randomized open parallel-group multicenter trial. Two hundred and forty-one subjects were randomized, 115 to DSG/EE and 126 to GSD/EE. Compliance to the study preparation was high (around 95%) in both groups and no pregnancies occurred during the study. Cycle control was excellent; there were no differences between the two groups with regard to incidence of spotting and breakthrough bleeding or duration and intensity of withdrawal bleeding. Side-effects were mild and in general comparable in the two groups. Both at baseline and during treatment, a higher proportion of women taking GSD/EE complained about breast tenderness. This resulted in more early withdrawals because of breast tenderness in the GSD/EE group. It was concluded that monophasic DSG/EE and GSD/EE are equally effective, have similar cycle control and both are generally well tolerated.", "A comparison of cycle control, efficacy and tolerability of two oral contraceptive preparations containing 20 microg ethinylestradiol combined with either 100 microg levonorgestrel (EE/LNG 20/100) or 500 microg norethisterone (EE/NET 20/500) was conducted. These results were compared to a standard reference preparation, containing 30 microg ethinylestradiol combined with 150 microg levonorgestrel (EE/LNG 30/150). Efficacy data from 8,544 treatment cycles were obtained from 767 women. Good cycle control and effective contraception was achieved with the two LNG preparations, however, the cycle control results were less favorable with EE/NET 20/500. The cumulative incidence of women with at least one episode of intermenstrual bleeding from cycles 2 to 7 (primary target variable) was 43.9% for EE/LNG 20/100, 72.7% for EE/NET 20/500, and 15.7% for the standard EE/LNG 30/150. The difference between the 2 20 microg of EE preparations, which favored EE/LNG 20/100, was statistically significant (p = 0.001). The overall spotting rates (cycles 1-13) were 9.3% for EE/LNG 20/100, 21.7% for EE/NET 20/500, and 3.3% for the standard EE/LNG 30/150. Amenorrhea was reported in 7.1% (EE/LNG 20/100), 20.6% (EE/NET 20/500), and 0.9% (standard EE/LNG 30/150), respectively. Intermenstrual bleeding episodes were shorter with EE/LNG 20/100 and EE/LNG 30/150 of the 13 treatment cycles. The study Pearl indices were 0.9 for EE/LNG 20/100, 1.9 for EE/NET 20/500, and 0.0 for EE/LNG 30/150. All three treatments were well tolerated. However, tolerability was somewhat less favorable with EE/NET 20/500. A total of 160 women prematurely discontinued the study for various reasons (EE/LNG 20/100: 7%; EE/NET 20/500: 18%; EE/LNG 30/150: 4%). The overall adverse event incidence rate during the trial was low in all groups. Blood pressure remained largely unaffected. Thirteen serious adverse events were recorded for all treatment groups, all but one were assessed as not related to the treatments. There were no remarkable treatment related differences in mean body weight throughout the study and the laboratory values were largely unaffected in all three treatments groups.", "This study compares the contraceptive reliability, cycle control, and tolerability of two oral contraceptive preparations containing 20 micrograms of ethinyl estradiol combined with either 75 micrograms of gestodene (EE/GSD) or 150 micrograms of desogestrel (EE/DSG). Women received the trial preparations daily for 21 days, followed by a 7-day pill-free interval. Contraceptive efficacy, cycle control, and tolerability were evaluated over a period of 12 cycles. Efficacy data of 14,700 treatment cycles (EE/GSD: 7299; EE/DSG: 7401) were obtained from 1476 women (EE/GSD, n = 740; EE/DSG, n = 736). Both preparations provided effective contraception and good cycle control with a similarly low incidence of both spotting and breakthrough bleeding. The spotting rates in both treatment groups decreased from 35.1% (EE/GSD) and 37.5% (EE/DSG) in the first treatment cycle to approximately 10% in the fourth treatment cycle. The spotting incidence as percent of the total number of cycles was 12.7% for EE/GSD and 14.3% for EE/DSG. The breakthrough bleeding incidence was 5.2% of all cycles for EE/GSD and 6.0% of all cycles for EE/DSG. For 84.7% of the cycles in the gestodene group and for 82.5% of the cycles in the desogestrel group, neither spotting nor breakthrough bleeding were recorded. Overall, the spotting and breakthrough bleeding incidence tended to be lower with EE/GSD than with EE/DSG. However, the difference was not statistically significant. Amenorrhea was recorded in 2.7% of the cycles with EE/GSD and in 2.9% with EE/DSG. Both preparations were well tolerated and showed a similar pattern of adverse events. More than 83% of the women in both groups either did not gain weight or lost more than 2 kg. Both preparations had a beneficial effect on dysmenorrhea. Both regimens provided reliable contraception and good cycle control. The incidence of adverse events was relatively low and both preparations were well tolerated.", "The combined oral contraceptive Yasmin (drospirenone 3 mg plus ethinylestradiol 30 microg [DRSP 3 mg/EE 30 microg]) has been shown to be a well tolerated and effective combination that provides high contraceptive reliability and good cycle control. Furthermore, DRSP 3 mg/EE 30 microg has been shown to have a positive effect on premenstrual symptoms and well-being/health-related quality of life, and to improve the skin condition of women with acne. To date, however, there have been relatively few studies that have compared the effects of DRSP 3 mg/EE 30 microg on the general well-being of women with those of other oral contraceptives.\n To compare the impact of DRSP 3 mg/EE 30 microg with that of levonorgestrel 150 microg/EE 30 microg (LNG 150 microg/EE 30 microg; Microgynon 30) on various parameters associated with well-being in healthy female subjects.\n This was a randomized, single-blind, parallel-group, multicentre study conducted using 21/7-day regimens of DRSP 3 mg/EE 30 microg and LNG 150 microg/EE 30 microg over seven cycles. Efficacy parameters included: changes in Menstrual Distress Questionnaire (MDQ) normative T scores; the proportion of subjects with acne; and menstrual symptoms. Cycle control and subjective well-being parameters were also assessed.\n Treatment with DRSP 3 mg/EE 30 microg had similar beneficial effects on symptoms of water retention and impaired concentration to LNG 150 microg/EE 30 microg, but was significantly better in alleviating negative affect symptoms during the menstrual phase (median difference in MDQ T score -3; p = 0.027; Wilcoxon rank sum test). The proportion of subjects with acne decreased from approximately 55% to approximately 45% in the DRSP 3 mg/EE 30 microg group, but remained static at approximately 60% in the LNG 150 microg/EE 30 microg group. Somatic and psychological symptoms occurred at the greatest intensity and for most subjects during the menstrual phase of the cycle in both groups.\n Both drugs had similar cycle control parameters with a tendency towards reduced bleeding with continued use. More subjects in the DRSP 3 mg/EE 30 microg group reported improved physical well-being (60% vs 46%; p = 0.035; chi-squared [chi2] test). Emotional well-being was reported improved in 61% and 51% of DRSP 3 mg/EE 30 microg and LNG 150 microg/EE 30 microg users, respectively (p = 0.1190; chi2 test). Adverse events were typical of oral contraceptive use and did not give rise to any safety concerns. Both products had similar beneficial effects on symptoms of water retention and impaired concentration, but DRSP 3 mg/EE 30 microg was significantly better in alleviating negative affect symptoms during the menstrual phase. The proportion of subjects with acne decreased in the DRSP 3 mg/EE 30 microg group but not in the LNG 150 microg/EE 30 microg group. More subjects in the DRSP 3 mg/EE 30 microg group reported improved physical well-being compared with the LNG 150 microg/EE 30 microg group.", "To assess the contraceptive efficacy, cycle control and acceptability of two monophasic oral contraceptives containing either 30 micrograms ethinylestradiol plus 150 micrograms desogestrel or 30 micrograms ethinylestradiol plus 75 micrograms gestodene.\n In a randomized, open-label, six-cycle, group-comparative, multicenter study performed in Brazil, pregnancies, cycle-control parameters, incidence of side-effects and the presence and severity of acne vulgaris were assessed, and blood pressure and body weight were measured at pretreatment and after one, three and six cycles of oral contraceptive use.\n Of the 595 women enrolled, 274 (86.7%) in the desogestrel/ethinylestradiol group and 227 (81.4%) in the gestodene/ethinylestradiol group completed the six cycles, providing data for 1753 and 1487 treatment cycles, respectively. Two pregnancies occurred, one of which (in the desogestrel/ethinylestradiol group) was attributed to user failure, whilst the other (in the gestodene/ethinylestradiol group) was thought to result from method failure. Cycle control was observed to be excellent; the incidences of irregular bleeding and minor side-effects were low in both groups and decreased after an initial increase in the first cycle. Pre-existing acne improved in both groups, whereas blood pressure and body weight remained essentially unchanged.\n Both desogestrel/ethinylestradiol and gestodene/ethinylestradiol provide effective oral contraception with comparable cycle control and acceptability.", "A comparative multicenter clinical trial of two low-dose combined oral contraceptives (OCs) was conducted in Malaysia, Egypt, Thailand, and Mexico. Efficacy, safety and acceptability were investigated in women taking either a norgestrel-based (NG) OC or a norethindrone acetate-based (NA) OC. This paper includes analysis of 892 women, all of whom were at least 42 days but within 26 weeks postpartum and randomly allocated to one of the above OCs. Follow-up visits were scheduled at 1, 4, 8 and 12 months after admission. Baseline sociodemographic characteristics were similar for both groups, as well as compliance. There were nine unintended pregnancies reported; eight of these occurring in the NA group. Adverse experiences were minor with headaches and dizziness being the most common complaints; frequency of reports was similar in both groups. The group taking the NG-based OC had significantly (p < .05) fewer menstrual-related complaints. Discontinuations due to menstrual problems were significantly more common among NA users (primarily amenorrhea). Discontinuations in the NG group were primarily for other personal reasons, e.g. unable to return to the clinic. There was also a significant difference between the two groups for the 11-month gross cumulative life table discontinuation rates due to menstrual problems (p < .01); the NA group had the higher rate.", "To assess the contraceptive reliability, cycle control and tolerance of a new monophasic oral contraceptive (Yasmin) containing 30 microg ethinylestradiol and 3 mg drospirenone and compare it with a preparation containing an equal dose of ethinylestradiol combined with 150 microg desogestrel (Marvelon).\n A multicenter, open-label, randomized study was carried out in 26 European centers. Contraceptive efficacy, cycle control and tolerance (including body weight, blood pressure and heart rate) were assessed over 26 cycles, plus a 3-month follow-up period.\n Of 900 women who were randomized, 887 started treatment and 627 completed the 26 cycles plus follow-up (310 in the ethinylestradiol/drospirenone group and 317 in the ethinylestradiol/desogestrel group). Both study preparations were found to be effective with regard to contraceptive reliability and cycle control was good. There were six pregnancies (three in each group), but none were considered to have been the result of method failures. The subjective and objective tolerances were good in both groups. A statistically significant difference was found in body weight changes between the two groups. While there was an increase in mean body weight in the ethinylestradiol/desogestrel group from cycle 5 onward, the mean body weight per cycle in the ethinylestradiol/drospirenone group was slightly below the baseline value throughout the study. The incidence ofpremenstrual symptoms was higher in the ethinylestradiol/drospirenone group than in the ethinylestradiol/desogestrel group during the 6 months prior to the study, but lower during treatment. The rates ofdysmenorrhea were identical under both treatments but the symptoms were more often mild and less often severe in the ethinylestradiol/drospirenone group.\n The combination of 30 microg ethinylestradiol combined with 3 mg drospirenone provides effective oral contraception and good cycle control, and is well tolerated. Ethinylestradiol/drospirenone had a more favorable effect on body weight than ethinylestradiol/desogestrel, with the mean body weight remaining lower than baseline for the majority of the women.", "The study was conducted to compare cycle control, bleeding pattern and efficacy of two low-dose combined oral contraceptives.\n Four hundred fifty-three women were randomized to receive a 24/4 regimen of drospirenone 3 mg/ethinyl estradiol 20 mcg (drsp 3 mg/EE 20 mcg; n=230) or a 21/7 regimen of desogestrel 150 mcg/EE 20 mcg (DSG 150 mcg/EE 20 mcg; n=223), and recorded bleeding daily over 7 treatment cycles.\n The duration [mean 4.7 (SD 1.5)-5.2 (SD 2.2) days in the drsp 3 mg/EE 20 mcg 24/4 group and 5.1 (SD 1.5)-5.4 (SD 2.1) days in the DSG 150 mcg/ EE 20 mcg group] and maximum intensity (\"normal bleeding\" for >50% of all subjects) of scheduled bleeding in Cycles 1-6 was comparable between treatment groups. The incidence of unscheduled bleeding during Cycles 2-6 was also similar between the two groups (drsp 3 mg/EE 20 mcg, 8.8-17.3%; DSG 150 mcg/ EE 20 mcg, 9.4-16.3%).\n Drsp 3 mg/EE 20 mcg 24/4 achieved an acceptable bleeding profile with reliable cycle control, comparable with an established formulation.", "A prospective randomized trial was conducted to compare efficacy of a drospirenone-containing combined oral contraceptives (COC) with desogestrel-containing COC in women with polycystic ovary-syndrome (PCOS) not desirous of child-bearing.\n Sixty women were randomized into study group [ethinylestradiol (EE) 30 mcg+drospirenone 3 mg] and control group (EE 30 mcg+desogestrel 150 mcg), treated for 6 months and followed up at 1 month, 3 months, 6 months, during treatment and 3 and 6 months post-treatment. Acne and hirsutism scoring, bodyweight, body mass index (BMI), blood pressure (BP), ultrasound parameters, lipid profile, glycemic profile and hormonal profile were compared.\n Cycles were regular in both groups during treatment. Effect of regular cycles persisted in 44.83% (13/30) vs. 17.24% (5/30) in study vs. control group at 6 months post-treatment with 33.3% decreased hirsutism score in the study group (versus no change in control group) even at 6 months after stopping treatment. With treatment, BMI fell by 0.52 kg/m(2) in the study group; systolic and diastolic BP fell in the study group while it rose in the control group. Low-density lipoprotein significantly decreased and high-density lipoprotein was elevated in the study group (p<.05). The study group showed a significant fall in fasting/postprandial blood sugar and insulin and total testosterone against a rise in the control group.\n In women with PCOS, a drospirenone containing COC has better outcome in terms of persistent regular cycles, antiandrogenic effect, fall in BMI and BP, better lipid profile, favorable glycemic and hormonal profile than desogestrel-containing COC.\n Copyright 2010 Elsevier Inc. All rights reserved.", "This open-label randomized study compared the effects of two combined oral contraceptives (OCs) containing 3 mg drospirenone (DRSP)/30 microg ethinyl estradiol (EE) with 150 microg levonorgestrel (LNG)/30 microg EE on the prevalence and changes from baseline of premenstrual symptoms after six cycles. The symptoms were measured using the Women's Health Assessment Questionnaire. Subjects receiving DRSP/EE had fewer prevalence of premenstrual symptoms than those receiving LNG/EE after six cycles. A significantly lower score of negative affect category in the premenstrual phase was demonstrated in those receiving DRSP/EE more than LNG/EE. The DRSP/EE group showed a greater improvement of mean scores from baseline in the premenstrual phase compared with those who received LNG/EE on negative affect as seen in the items on anxiety, irritability, feeling sad or blue and weight gain in the category of water retention. In conclusion, OCs containing DRSP have beneficial effects in reducing the prevalence of premenstrual symptoms especially the symptoms of negative affect and weight gain, particularly when compared to LNG/EE. Hence, it should be recommended for women who are susceptible to these adverse symptoms.", "The efficacy, cycle-control and tolerance of Microgynon-30, a widely prescribed levonorgestrel containing oral contraceptive, and Femodene, a new oral-contraceptive containing gestodene, were compared in a randomised, double-blind study involving 456 healthy women over a 6 month period. 229 women were allocated to receive Femodene and 227 received Microgynon-30. No differences between the groups in terms of obstetric and gynaecological history, previous contraceptive history, smoking habits, blood-pressure or body weight at admission were observed. No pregnancies were reported in either group, despite tablet-taking errors recorded in 6.3% of the Femodene group and 7.6% of the Microgynon-30 group. Both oral contraceptives were compared in terms of cycle length, intensity of the withdrawal bleed and side effects. Cycle-control was similar in the two groups. However, significantly fewer subjects reported breakthrough bleeding (with or without spotting) in the Femodene group (18% of patients) compared with the Microgynon-30 group (26% of patients). The incidence of absent withdrawal bleeds was 1% or less in both groups and no significant effects on body weight or blood pressure were observed.", "Poor cycle control and tolerability can be reasons for irregular pill intake. This study compared the tolerability of two low-dose oral contraceptives and their effect on cycle control.\n In this open, group-comparative, randomized multicenter trial in Germany and the Netherlands, women received either 20 microg ethinylestradiol plus 150 microg desogestrel (20EE/DSG; n = 500) or 20 microg ethinylestradiol plus 100 microg levonorgestrel (20EE/LNG; n = 498) for six treatment cycles. Cycle control, dysmenorrhea and premenstrual syndrome (PMS) were assessed using diary cards. Tolerability was assessed using the self-administered questionnaires Psychological General Well-Being Index (PGWBI) and the Profile of Mood States (POMS). Acne was assessed by objective (acne counts) and subjective (no, moderate, mild, severe) acne scoring of the facial area at baseline and treatment cycles 1, 3 and 6.\n A total of 404 (78.1%) and 384 (75.3%) women in the 20EE/DSG and 20EE/LNG groups, respectively, completed the trial. The occurrence rate of irregular bleeding and spotting was statistically significantly higher with 20EE/LNG than with 20EE/DSG (0.18 vs. 0.13; p < 0.05). The mean number of bleeding-spotting days per cycle was statistically significantly higher with 20EE/LNG than with 20EE/DSG (0.63 vs. 0.48; p < 0.05). Early withdrawal bleeding was more frequent with 20EE/LNG (0.15 vs. 0.08; p < 0.005), whereas continued withdrawal bleeding was more frequent with 20EE/DSG (0.32 vs. 0.45; p < 0.001); absence of withdrawal bleeding was comparable (0.06 vs. 0.04, respectively). Thirteen subjects in the 20EE/LNG group and three in the 20EE/DSG group discontinued due to unacceptable bleeding (p < 0.05). Dysmenorrhea and PMS decreased comparably in both groups. There were no differences between groups for the mean total scores of PGWBI or POMS at all time-points. Fewer acne lesions were counted with 20EE/DSG vs. 20EE/LNG after six cycles (p < 0.05). The subjective acne scores supported this finding.\n 20EE/DSG provided better cycle control than 20EE/LNG with less treatment discontinuation due to unacceptable bleeding. There were no apparent differences between the two groups regarding tolerability and quality of life. There was less acne with 20EE/DSG.\n Copyright 2004 Elsevier Inc." ]

[ "10213986", "1951162", "20777111", "8116059", "9345118", "2194128", "8610656" ]

[ "[The efficacy of oral vitamin A supplementation for measles and respiratory syncytial virus (RSV) infection].", "Vitamin A supplementation reduces measles morbidity in young African children: a randomized, placebo-controlled, double-blind trial.", "INTENSIVE VITAMIN THERAPY IN MEASLES.", "Effect of vitamin A on diarrhoeal and respiratory complications of measles.", "Measles incidence, case fatality, and delayed mortality in children with or without vitamin A supplementation in rural Ghana.", "A randomized, controlled trial of vitamin A in children with severe measles.", "Efficacy of a single oral dose of 200,000 IU of oil-soluble vitamin A in measles-associated morbidity." ]

[ "Recently, the efficacy of oral vitamin A supplementation for measles and respiratory syncytial (RSV) infection has been evaluated in developing countries. However, in developed countries where vitamin A deficiency is little worth consideration, few studies have been conducted on the effect of vitamin A supplementation. The effect of oral vitamin A (100,000 IU) supplementation was evaluated in 105 children with measles (age 5 months to 4 years) and in 96 children with RSV infection (ages a month to 2.5 years) in Fukushima, Japan. Comparisons were made of clinical signs, duration of hospitalization and complications between treated groups and non-treated groups. Treated group (measles n = 47, RSV n = 54) and non-treated groups (measles n = 58, RSV n = 42) had similar baseline characteristics. Patients with measles given a vitamin A supplementation had a shorter duration of cough (7.2 +/- 1.6 vs 9.2 +/- 1.8 days, p < 0.05) and patients with severe RSV infection given a vitamin A supplementation had a shorter duration of retraction (3.6 +/- 1.4 vs 5.3 +/- 0.8 days, p < 0.05) and wheezing (4.4 +/- 1.7 vs 6.3 +/- 1.5 days, p < 0.05). Toxicities, including excess vomiting and bulging fontanel were not observed. Our findings may suggest the efficacy of oral vitamin A supplementation for measles and severe RSV infection, in children who have no malnutrition.", "The effects of vitamin A supplementation on measles morbidity are unclear. Sixty hospitalized children aged 4-24 mo with complicated measles received a World Health Organization--(WHO) recommended dose of vitamin A or placebo. The two groups were comparable in known covariants of measles severity: weight-for-age percentiles, overcrowding, rash, total lymphocytes, and serum concentrations of zinc, albumin, prealbumin, retinol-binding protein, and vitamins A and E. Ninety percent of the patients had hyporetinemia. Integrated morbidity scores, determined by severity of condition (eg, diarrhoea, herpes, and respiratory-tract infection) were assigned on day 8 and 6 wk and 6 mo; these were reduced by 82%, 61%, and 85%, respectively, in the supplemented group, which was mainly due to reduced respiratory-tract infection. There was one death in the placebo group. At 6 wk weight gain was significant in the supplemented group. Despite the selected sample, attention to multiple covariates enhances the validity of the data obtained and supports the current WHO recommendations for vitamin A supplementation during measles.", "nan", "A randomized placebo-controlled trial of high dose vitamin A in acute measles was performed in Nairobi, Kenya to determine if it reduced the incidence or severity of diarrhoeal and respiratory complications. On enrollment laryngotracheobronchitis (LTB) pneumonia, diarrhoea and otitis media were each found in 45-80% of children in the treatment and placebo groups. While 4 of 119 cases of LTB in the placebo group progressed to grade III (loud stridor, markedly diminished air entry, chest indrawing, cyanosis), none of 116 in the vitamin A group did. Episodes of diarrhoea, but not pneumonia, resolved faster and were less severe in the vitamin A group. There were no differences in the incidences of pneumonia, LTB or diarrhoea during hospitalization, but children treated with vitamin A had a lower rate of developing otitis media. The overall case fatality rate was 2.7% and did not differ by group. These findings, along with those from three other trials in Africa, suggest that high dose vitamin A reduces the severity of complications during measles.", "Data on measles incidence, acute case fatality, and delayed mortality were collected on 25,443 children aged 0-95 months during the course of a community-based, double-blind, placebo-controlled, randomized trial of vitamin A supplementation in rural, northern Ghana between 1989 and 1991. Measles vaccine coverage in these children was 48%. The overall estimated measles incidence rate was 24.3 per 1,000 child-years, and acute case fatality was 15.7%. There was not significantly increased mortality in survivors of the acute phase of measles compared with controls (rate ratio = 1.22, 95% confidence interval (CI) 0.65-2.30). Reported incidence rates and case fatality were higher in families with low paternal education, in the dry season, and in unvaccinated children, and case fatality was higher in malnourished children. There was no sex difference in incidence, but acute case fatality was somewhat higher in girls than boys (adjusted odds ratio = 1.3, 95% CI 0.9-2.1). Measles incidence was lower in vitamin A-supplemented groups (23.6 per 1,000 child-years) than in placebo groups (28.9 per 1,000 child-years), but this difference was not statistically significant (p = 0.33). Among 946 measles cases in clusters randomized to receive vitamin A or placebo, there was no marked difference in acute measles case fatality between vitamin A-supplemented and placebo groups (15.4% vs. 14.5%, respectively). The biologic effects of vitamin A supplemented on the subsequent clinical manifestations and severity of measles need further elucidation.", "Measles kills about 2 million children annually, and there is no specific therapy for the disease. It has been suggested that vitamin A may be of benefit in the treatment of measles.\n We conducted a randomized, double-blind trial involving 189 children who were hospitalized at a regional center in South Africa because of measles complicated by pneumonia, diarrhea, or croup. The children (median age, 10 months) were assigned to receive either vitamin A (total dose, 400,000 IU of retinyl palmitate, given orally; n = 92) or placebo (n = 97), beginning within five days of the onset of the rash. At base line, the characteristics of the two groups were similar.\n Although clinically apparent vitamin A deficiency is rare in this population, the children's serum retinol levels were markedly depressed (mean [+/- SEM], 0.405 +/- 0.021 mumols per liter [11.6 +/- 0.6 micrograms per deciliter]), and 92 percent of them had hyporetinemia (serum retinol level less than 0.7 mumols per liter [20 micrograms per deciliter]). Serum concentrations of retinol-binding protein (mean, 30.1 +/- 2.0 mg per liter) and albumin (mean, 33.4 +/- 0.5 g per liter) were also low. As compared with the placebo group, the children who received vitamin A recovered more rapidly from pneumonia (mean, 6.3 vs. 12.4 days, respectively; P less than 0.001) and diarrhea (mean, 5.6 vs. 8.5 days; P less than 0.001), had less croup (13 vs. 27 cases; P = 0.03), and spent fewer days in the hospital (mean, 10.6 vs. 14.8 days; P = 0.01). Of the 12 children who died, 10 were among those given placebo (P = 0.05). For the group treated with vitamin A, the risk of death or a major complication during the hospital stay was half that of the control group (relative risk, 0.51; 95 percent confidence interval, 0.35 to 0.74).\n Treatment with vitamin A reduces morbidity and mortality in measles, and all children with severe measles should be given vitamin A supplements, whether or not they are thought to have a nutritional deficiency.", "The authors assessed the efficacy of the World Health Organization (WHO) recommendation of 200,000 IU of vitamin A in oil to treat acute non-xerophthalmic measles patients. Acute measles patients who did not require hospitalization were enrolled in a randomized, double-masked, clinical trial of vitamin A (n=90) versus placebo (n=110) carried out in Ndola, Zambia, in 1991. Measles-associated morbidity was defined by the presence of signs and symptoms of acute respiratory infection. Daily evaluations for the first 3 days were followed by weekly visits for a month at urban health centers. Baseline demographic, clinical, and biochemical characteristics were similar in both groups. Cross-sectional analysis of morbidity status, by group, at each weekly evaluation showed no significant differences until week 4, when more placebo-treated patients had cough or pneumonia (p=0.005). However, longitudinal analysis, which looked at changes among individuals and controlled for initial health status, showed more equivocal results. The odds ratio for the development of pneumonia in patients with measles cough in vitamin A-treated subjects was 0.73 (95% confidence interval (Cl) 0.30-1.80). The odds ratio for the development of measles-associated cough or pneumonia in asymptomatic measles patients was 0.52 (95% Cl 0.24-1.13), in favor of vitamin A, but the odds ratio for failing to improve from pneumonia in vitamin A-treated subjects was 1.23 (95% Cl 0.68-2.3), a result in favor of placebo. These results suggest that the evidence for the efficacy of one dose of vitamin A in oil to prevent measles complications is not as strong as that previously shown for two 200,000 IU doses of water-miscible vitamin A, and that the WHO recommendation may need to be reexamined." ]

[ "19286847", "20370912", "15751090", "16339094", "19141576", "18975369" ]

[ "Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout.", "The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial.", "Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: a twenty-eight-day, multicenter, phase II, randomized, double-blind, placebo-controlled, dose-response clinical trial examining safety and efficacy in patients with gout.", "Febuxostat compared with allopurinol in patients with hyperuricemia and gout.", "Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study.", "Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial." ]

[ "To determine longterm urate-lowering efficacy and clinical benefits and safety of therapy with febuxostat or allopurinol in subjects with gout.\n Subjects (n=1086) in this open-label extension study were assigned to fixed-dose daily urate-lowering treatment (ULT) with febuxostat (80 mg or 120 mg) or allopurinol (300 mg). ULT reassignment was permitted during months 1 to 6 to achieve serum urate (SUA) concentrations between 3.0 and <6.0 mg/dl. Flares requiring treatment, tophus size, safety, and SUA levels were monitored during up to 40 months of ULT maintenance.\n After 1 month initial treatment, >80% of subjects receiving either febuxostat dose, but only 46% of subjects receiving allopurinol, achieved SUA<6.0 mg/dl. After ULT reassignment, >80% of all remaining subjects maintained the primary efficacy endpoint of SUA<6.0 mg/dl at each visit. More subjects initially randomized to allopurinol required ULT reassignment to achieve SUA<6.0 mg/dl compared with subjects receiving febuxostat. Maintenance of SUA<6.0 mg/dl resulted in progressive reduction to nearly 0 in proportion of subjects requiring gout flare treatment. Baseline tophus resolution was achieved by 46%, 36%, and 29% of subjects maintained on febuxostat 80 mg, febuxostat 120 mg, and allopurinol, respectively. Overall adverse event rates (including cardiovascular adverse event rates), adjusted for 10-fold greater febuxostat than allopurinol exposure, did not differ significantly among treatment groups.\n Durable maintenance of goal range SUA level with either dose of febuxostat or in smaller numbers of subjects with allopurinol resulted in near elimination of gout flares and improved tophus status over time. Registered as NCT00175019.", "The purpose of this study was to compare urate-lowering (UL) efficacy and safety of daily febuxostat and allopurinol in subjects with gout and serum urate (sUA) > or = 8.0 mg/dL in a six-month trial.\n Subjects (n = 2,269) were randomized to febuxostat 40 mg or 80 mg, or allopurinol 300 mg (200 mg in moderate renal impairment). Endpoints included the proportion of all subjects with sUA <6.0 mg/dL and the proportion of subjects with mild/moderate renal impairment and sUA <6.0 mg/dL. Safety assessments included blinded adjudication of each cardiovascular (CV) adverse event (AE) and death.\n Comorbidities included: renal impairment (65%); obesity (64%); hyperlipidemia (42%); and hypertension (53%). In febuxostat 40 mg, febuxostat 80 mg, and allopurinol groups, primary endpoint was achieved in 45%, 67%, and 42%, respectively. Febuxostat 40 mg UL was statistically non-inferior to allopurinol, but febuxostat 80 mg was superior to both (P < 0.001). Achievement of target sUA in subjects with renal impairment was also superior with febuxostat 80 mg (72%; P < 0.001) compared with febuxostat 40 mg (50%) or allopurinol (42%), but febuxostat 40 mg showed greater efficacy than allopurinol (P = 0.021). Rates of AEs did not differ across treatment groups. Adjudicated (APTC) CV event rates were 0.0% for febuxostat 40 mg and 0.4% for both febuxostat 80 mg and allopurinol. One death occurred in each febuxostat group and three in the allopurinol group.\n Urate-lowering efficacy of febuxostat 80 mg exceeded that of febuxostat 40 mg and allopurinol (300/200 mg), which were comparable. In subjects with mild/moderate renal impairment, both febuxostat doses were more efficacious than allopurinol and equally safe. At the doses tested, safety of febuxostat and allopurinol was comparable.\n NCT00430248.", "Gout affects approximately 1-2% of the American population. Current options for treating hyperuricemia in chronic gout are limited. The purpose of this study was to assess the safety and efficacy of febuxostat, a nonpurine selective inhibitor of xanthine oxidase, in establishing normal serum urate (sUA) concentrations in gout patients with hyperuricemia (>or=8.0 mg/dl).\n We conducted a phase II, randomized, double-blind, placebo-controlled trial in 153 patients (ages 23-80 years). Subjects received febuxostat (40 mg, 80 mg, 120 mg) or placebo once daily for 28 days and colchicine prophylaxis for 14 days prior to and 14 days after randomization. The primary end point was the proportion of subjects with sUA levels <6.0 mg/dl on day 28.\n Greater proportions of febuxostat-treated patients than placebo-treated patients achieved an sUA level <6.0 mg/dl at each visit (P < 0.001 for each comparison). The targeted sUA level was attained on day 28 in 0% of those taking placebo and in 56% of those taking 40 mg, 76% taking 80 mg, and 94% taking 120 mg of febuxostat. The mean sUA reduction from baseline to day 28 was 2% in the placebo group and 37% in the 40-mg, 44% in the 80-mg, and 59% in the 120-mg febuxostat groups. Gout flares occurred with similar frequency in the placebo (37%) and 40-mg febuxostat (35%) groups and with increased frequency in the higher dosage febuxostat groups (43% taking 80 mg; 55% taking 120 mg). During colchicine prophylaxis, gout flares occurred less frequently (8-13%). Incidences of treatment-related adverse events were similar in the febuxostat and placebo groups.\n Treatment with febuxostat resulted in a significant reduction of sUA levels at all dosages. Febuxostat therapy was safe and well tolerated.", "Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia and gout.\n We randomly assigned 762 patients with gout and with serum urate concentrations of at least 8.0 mg per deciliter (480 micromol per liter) to receive either febuxostat (80 mg or 120 mg) or allopurinol (300 mg) once daily for 52 weeks; 760 received the study drug. Prophylaxis against gout flares with naproxen or colchicine was provided during weeks 1 through 8. The primary end point was a serum urate concentration of less than 6.0 mg per deciliter (360 micromol per liter) at the last three monthly measurements. The secondary end points included reduction in the incidence of gout flares and in tophus area.\n The primary end point was reached in 53 percent of patients receiving 80 mg of febuxostat, 62 percent of those receiving 120 mg of febuxostat, and 21 percent of those receiving allopurinol (P<0.001 for the comparison of each febuxostat group with the allopurinol group). Although the incidence of gout flares diminished with continued treatment, the overall incidence during weeks 9 through 52 was similar in all groups: 64 percent of patients receiving 80 mg of febuxostat, 70 percent of those receiving 120 mg of febuxostat, and 64 percent of those receiving allopurinol (P=0.99 for 80 mg of febuxostat vs. allopurinol; P=0.23 for 120 mg of febuxostat vs. allopurinol). The median reduction in tophus area was 83 percent in patients receiving 80 mg of febuxostat and 66 percent in those receiving 120 mg of febuxostat, as compared with 50 percent in those receiving allopurinol (P=0.08 for 80 mg of febuxostat vs. allopurinol; P=0.16 for 120 mg of febuxostat vs. allopurinol). More patients in the high-dose febuxostat group than in the allopurinol group (P=0.003) or the low-dose febuxostat group discontinued the study. Four of the 507 patients in the two febuxostat groups (0.8 percent) and none of the 253 patients in the allopurinol group died; all deaths were from causes that the investigators (while still blinded to treatment) judged to be unrelated to the study drugs (P=0.31 for the comparison between the combined febuxostat groups and the allopurinol group).\n Febuxostat, at a daily dose of 80 mg or 120 mg, was more effective than allopurinol at the commonly used fixed daily dose of 300 mg in lowering serum urate. Similar reductions in gout flares and tophus area occurred in all treatment groups.\n Copyright 2005 Massachusetts Medical Society.", "This 5-yr study assessed urate-lowering and clinical efficacy and safety of long-term febuxostat therapy in subjects with gout. The primary efficacy end-point was reduction to and maintenance of serum urate (sUA) levels < 6.0 mg/dl.\n Subjects who completed a previous 28-day study were entered into an open-label extension study and initially received febuxostat 80 mg daily. Between Weeks 4 and 24, dosing could be adjusted to febuxostat 40 or 120 mg. All subjects received gout flare prophylaxis during the first 4 weeks. Gout flares were recorded and treated throughout the study, and sUA, baseline tophi and safety were monitored.\n Among 116 subjects initially enrolled, dose adjustments were made for 44 (38%) subjects. As a result, 8 subjects received febuxostat 40 mg, 79 received 80 mg, and 29 received 120 mg daily maintenance dose. At 5 yrs, 93% (54/58) of the remaining subjects had sUA < 6.0 mg/dl. Fifty-eight subjects (50%) discontinued prematurely; 38 did so in the first year. Thirteen subjects withdrew due to an adverse event. Sustained reduction of sUA was associated with nearly complete elimination of gout flares. In 26 subjects with a tophus at baseline, resolution was achieved in 69% (18/26) by last visit on study drug at any point during the study (Final Visit). There were no deaths reported during the study.\n Long-term treatment with febuxostat resulted in durable maintenance of sUA < 6.0 mg/dl for most subjects. There was nearly complete abolition of gout flares in patients completing the study. Baseline tophi resolved in a majority of subjects.", "To compare the urate-lowering efficacy and safety of febuxostat, allopurinol, and placebo in a large group of subjects with hyperuricemia and gout, including persons with impaired renal function.\n Subjects (n = 1,072) with hyperuricemia (serum urate level > or = 8.0 mg/dl) and gout with normal or impaired (serum creatinine level >1.5 to < or = 2.0 mg/dl) renal function were randomized to receive once-daily febuxostat (80 mg, 120 mg, or 240 mg), allopurinol (300 or 100 mg, based on renal function), or placebo for 28 weeks.\n Significantly (P < or = 0.05) higher percentages of subjects treated with febuxostat 80 mg (48%), 120 mg (65%), and 240 mg (69%) attained the primary end point of last 3 monthly serum urate levels <6.0 mg/dl compared with allopurinol (22%) and placebo (0%). A significantly (P < 0.05) higher percentage of subjects with impaired renal function treated with febuxostat 80 mg (4 [44%] of 9), 120 mg (5 [45%] of 11), and 240 mg (3 [60%] of 5) achieved the primary end point compared with those treated with 100 mg of allopurinol (0 [0%] of 10). Proportions of subjects experiencing any adverse event or serious adverse event were similar across groups, although diarrhea and dizziness were more frequent in the febuxostat 240 mg group. The primary reasons for withdrawal were similar across groups except for gout flares, which were more frequent with febuxostat than with allopurinol.\n At all doses studied, febuxostat more effectively lowered and maintained serum urate levels <6.0 mg/dl than did allopurinol (300 or 100 mg) or placebo in subjects with hyperuricemia and gout, including those with mild to moderately impaired renal function." ]

[ "15148494", "11850709", "11313239", "11960266", "12774056", "14561987" ]

[ "An evaluation of the donor experience in the canadian multicenter randomized trial of bone marrow versus peripheral blood allografting.", "Healthy sibling donor anxiety and pain during bone marrow or peripheral blood stem cell harvesting for allogeneic transplantation: results of a randomised study.", "Experiences of donors enrolled in a randomized study of allogeneic bone marrow or peripheral blood stem cell transplantation.", "Donation of stem cells from blood or bone marrow: results of a randomised study of safety and complaints.", "Impact of stem cell donation modality on normal donor quality of life: a prospective randomized study.", "Differences between graft product and donor side effects following bone marrow or stem cell donation." ]

[ "We compared the donation of bone marrow (BM) versus recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells (PBPC) in HLA-matched sibling donors. Donors randomized to donate BM or PBPC completed questionnaires (Profile of Mood States [POMS] and Short-Form 36 Health Survey) assessing peridonation health-related quality of life (QoL), donation experience, and acceptability of donation before and 1 week and 4 weeks after donation. Between January 1996 and March 1999, 184 patients and their donors were randomized. Predonation and postdonation data were available on 52 (56%) and 35 (38%) of the BM and PBPC donors, respectively. The median donor age was 45 years, and 44% were female. The median time (range) to return to full activity for the BM and PBPC donors was 4 days (1-21 days) and 2 days (0-21 days), respectively (P = .01). One week after donation, BM donors reported more fatigue and less energy than the PBPC donors. BM donors' POMS total mood disturbance scores were worse 1 week after versus before donation, whereas the PBPC donors' scores did not change. POMS subscores indicated more fatigue and less energy in the BM versus PBPC donors. Anxiety improved in both groups, but more in PBPC donors. Four weeks after donation, the Short-Form 36 Health Survey indicated persistent moderate negative effects on QoL with BM donation versus small effects with PBPC donation. BM donation was associated with more physical morbidity and negative effects on QoL up to 1 month after donation than was PBPC donation. Despite this, most donors would donate again. Further work is needed to decrease donor anxiety and symptoms. If both BM and PBPC donation are feasible, then the graft source should be dictated by the predicted patient outcome as determined from the results of randomized trials.\n Copyright 2004 American Society for Blood and Marrow Transplantation", "This study reports the first comparison of healthy donor subjective well-being during two alternative procedures of hematopoietic stem cells harvesting for allogeneic transplantation. Among the 105 donors included between September 1996 and October 1998 in the SFGM French randomised trial aiming to compare allogeneic bone marrow (BM) transplantation and blood cell (BC) transplantation, 64 donors (33 in BC and 31 in BM groups) were relevant for the analysis. They had received a set of self-administered questionnaires to complete during the collection process, aiming to measure anxiety (assessed using the Spielberger's State-Trait Anxiety Inventory) and pain induced by the procedure (evaluated using a visual analogical scale). Results showed that no harvest procedure is free from pain even if none was more painful than the other. Levels of anxiety before the collection procedure were high in both groups and significantly so for BC donors. Although BC collection induces at least similar levels of pain and anxiety as does BM collection, they were of a different kind, and the short-term impact of G-CSF stimulation on the well-being of BC donors has to be taken into account in improving quality of care in the allogeneic setting.", "The experiences of 69 (38 marrow and 31 peripheral blood stem cell [PBSC]) donors participating in a randomized trial comparing allogeneic bone marrow with PBSC transplantation were studied. Marrow was collected by means of standard harvest techniques and general or regional anesthesia. PBSC donors were treated with 5 to 7 days of filgrastim at a dose of 16 microg/kg/d and underwent 1 to 3 days of apheresis to obtain 5 x 10(6) CD34(+) cells per kilogram recipient weight. Donors completed questionnaires describing their health experiences before, during, and then weekly after donation until return to baseline status. Both marrow and PBSC donors reported minimal fluctuation in symptoms measuring emotional status. In contrast, both groups of donors reported deterioration in physical status starting with administration of filgrastim (PBSC donors) or after the marrow collection procedure. The symptom burden reported was similar, with pain a prominent symptom for both groups. Equivalent mean levels of maximal pain, average pain, and pain duration through the day were reported, although toxicity peaks occurred at different time points during the harvest procedures. All PBSC donors but only 79% of marrow donors reported good physical status by 14 days after the harvest procedures. These data demonstrate similar levels of physical discomfort for hematopoietic stem cell donors regardless of the collection procedure used, but a quicker resolution of symptoms for PBSC donors.", "Biological consequences and physical complaints were compared for donors randomly assigned either to blood stem cell (BSC) or bone marrow (BM) donation. In the period 1994-1999, 61 consecutive donors were included. The BSC donors were given G-CSF 10 microg/kg s.c., daily during 5 days before the first leukapheresis. Nineteen donors had one leukapheresis, 10 required two and one donor needed three leukaphereses in order to reach the target cell number of 2 x 10(6) CD34(+) cells/kg bw of the recipient. A median platelet nadir of 102 x 10(9)/l was reached shortly after the last leukapheresis. Three weeks post harvest, 17 of 30 BSC donors had a mild leukopenia. Six had a leukopenia lasting more than a year before returning to normal values. Both groups were monitored prospectively through a standardised questionnaire completed by the donors. BSC donation was significantly less burdensome than BM donation and was preferred by the donors. The short-term risks of BSC mobilisation and harvest seem negligible. The potential long-term effects of G-CSF are unresolved and the donors must be followed closely.", "As part of a previously reported trial comparing granulocyte-colony stimulating factor (G-CSF) stimulated bone marrow and peripheral blood stem cells (PBSCs) in allogeneic stem cell transplantation, we included a questionnaire to compare donor morbidity and long-term complications between the two donation procedures. Bone marrow donation was associated with significantly more donors experiencing localized pain at the donation site compared to PBSC collection. However, this was not associated with any increased delay in returning to normal activity. Although a minority of bone marrow donors suffered chronic pain at the donation site, no serious long-term side effects relating to G-CSF stimulated stem cell donation were identified.", "We report graft product stem cell yields and donor safety results of a randomized multicenter study comparing allogeneic peripheral blood stem cell (PBSC) PBSC transplantation with BM transplantation. Matched HLA-identical sibling donors (n=329) were randomized to filgrastim-mobilized PBSC or bone marrow (BM) donation groups. Median yields per kg recipient weight of CD34(+) cells, T cells, and natural killer (NK) cells, respectively, were approximately two-fold, eight-fold, and greater than eight-fold in the PBSC group than in the BM group (CD34(+) cells, 5.8 x 10(6)/kg vs 2.7 x 10(6)/kg; T cells, 300.1 x 10(6)/kg vs 35.7 x 10(6)/kg; NK cells, 28.2 x 10(6)/kg vs 3.6 x 10(6)/kg; P<0.001 for each). In connection with the cell collection procedures, PBSC donors spent a shorter median time in hospital than BM donors (0 vs 2 days; median difference -2 days, 95% CI -2 to 2) and had fewer median days of restricted activity (2 vs 6 days; median difference -3 days, 95% CI -4 to 2). Overall, 65% of PBSC donors and 57% of BM donors reported at least one adverse event (AE), most of which were transient, mild-moderate in severity, and without clinical sequelae. PBSC donors experienced predominantly filgrastim-related AEs, while BM donors experienced predominantly harvest-related AEs." ]

[ "8151587", "17414533", "8182625", "2242059", "10606360", "2919941", "1747136", "12375317", "15903023", "19783714", "8777850", "3823910", "17102944", "8215627", "7788170" ]

[ "Incidence, prevalence and possible risk factors for pneumonitis in patients with rheumatoid arthritis receiving methotrexate.", "Risk factors associated with the cumulative survival of low-dose methotrexate in 273 Japanese patients with rheumatoid arthritis.", "Effect of etodolac on methotrexate pharmacokinetics in patients with rheumatoid arthritis.", "Aspirin, hydroxychloroquine, and hepatic enzyme abnormalities with methotrexate in rheumatoid arthritis.", "Celecoxib, a specific COX-2 inhibitor, has no significant effect on methotrexate pharmacokinetics in patients with rheumatoid arthritis.", "Toxicity of methotrexate compared with azathioprine in the treatment of rheumatoid arthritis. A case-control study of 131 patients.", "Aspirin alters methotrexate disposition in rheumatoid arthritis patients.", "Longitudinal measurement of methotrexate liver concentrations does not correlate with liver damage, clinical efficacy, or toxicity during a 3.5 year double blind study in rheumatoid arthritis.", "Urinary excretion of alpha-GST and albumin in rheumatoid arthritis patients treated with methotrexate or other DMARDs alone or in combination with NSAIDs.", "Examination of the effect of increasing doses of etoricoxib on oral methotrexate pharmacokinetics in patients with rheumatoid arthritis.", "Thrombocytopenia in patients with rheumatoid arthritis on long-term treatment with low dose methotrexate.", "Pulmonary disease during the treatment of rheumatoid arthritis with low dose pulse methotrexate.", "Durability of treatment with methotrexate in Venezuelan patients with rheumatoid arthritis.", "Renal effects of aspirin and low dose methotrexate in rheumatoid arthritis.", "Total and free methotrexate pharmacokinetics, with and without piroxicam, in rheumatoid arthritis patients." ]

[ "Methotrexate (MTX) is being used increasingly to treat rheumatoid arthritis (RA). Pneumonitis is a serious side effect of MTX therapy (P-MTX). Our aim was to determine in patients with RA the incidence and prevalence of P-MTX in Western Australia and identify risk factors for the development of this adverse reaction.\n Patients with P-MTX were identified by (a) direct communication with rheumatologists in Western Australia, (b) use of a computerized clinical database, (c) questionnaire inquiry of all other rheumatologists in Australia. Possible risk factors for P-MTX were examined using age/sex matched case controls selected from the computerized clinical database.\n Ten definite and 3 probable cases of P-MTX were identified. Local incidence of P-MTX was 1/35.4 patient years MTX treatment; if definite and probable cases are included (1/49.6 patient years MTX treatment for definite cases alone). Twelve patients with P-MTX were compared with 24 age/sex matched controls. A shorter duration of MTX treatment and a higher incidence of preexisting lung disease were observed in P-MTX cases but these differences were not statistically significant. No difference was observed between the P-MTX and control patients with respect to rheumatoid factor, duration of RA, use of tobacco, dose of MTX, serum creatinine, creatinine clearance or concurrent treatment with aspirin, nonsteroidal antirheumatic drugs or prednisolone.\n Our results indicate that in hospital clinic patients with RA pneumonitis is a common adverse reaction. They suggest that hypersensitivity is probably responsible for most cases of pneumonitis associated with MTX, but preexisting lung disease may confer increased risk.", "Methotrexate (MTX) has become the most commonly prescribed disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). In the Western countries, the MTX dosage is safely increased to a maximum of 25 mg/wk until a significant response is observed. On the contrary, in Japan, MTX has been approved only as a second-line agent, and the approved maximum MTX dosage is only 8 mg/wk. This suboptimal dosage may affect MTX survival in Japanese RA patients.\n To study risk factors associated with the cumulative survival of MTX in Japanese RA patients.\n Data on 273 patients (male 44, female 229) with RA treated with MTX between January 1, 2000 and September 30, 2004 in our center were studied.\n Two hundred seventy-three patients were followed for 437 person-years of MTX exposure. Mean MTX dosage was 5.5 +/- 1.9 mg/wk. The cumulative MTX survival probability after 5 years was 61.9%. Univariate Cox regression analysis showed a significant correlation between MTX survival probability and use of fewer previous DMARDs, higher dose of MTX, inclusion of folate supplementation, and shorter disease duration. In the multivariate Cox regression model, use of fewer previous DMARDs remained significantly related to MTX survival. Reasons for discontinuation included adverse effects in 34 patients (12.5%) and inefficacy in 6 patients (2.2%).\n Cumulative survival was the same or slightly better than those in reports from Western countries, with less withdrawals reported due to adverse events or inefficacy. Whether these results are due to different MTX needs in Japanese or to acceptance of less clinical efficacy will require further studies. The use of fewer previous DMARDs was associated with longer MTX survival.", "To determine if the pharmacokinetics of methotrexate (MTX) is modified by the coadministration of etodolac.\n MTX (10 mg) was administered intramuscularly in the absence and presence of steady state levels of etodolac in 19 patients with rheumatoid arthritis. MTX levels were assayed by fluorescence polarization immunoassay. Concentrations of 7-hydroxymethotrexate (7-OH-MTX) were assayed by a reverse phase high performance liquid chromatography method. The unbound fraction was determined by ultrafiltration.\n When etodolac was coadministered with MTX, the highest observed concentration decreased and the mean residence time increased to become statistically significant. However, these differences are not of great clinical importance especially given that the area under the curve and clearances were unchanged. There were no significant differences in binding protein and 7-OH-MTX concentrations between MTX with and without etodolac administration.\n The pharmacokinetics of MTX is slightly modified by coadministration of etodolac. Moreover, no clinical toxicity was observed.", "Levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in patients with rheumatoid arthritis from 5 centers involved in the Arthritis, Rheumatism, and Aging Medical Information System were correlated with the use of specific antirheumatic medications. Elevated levels of SGOT and SGPT were most frequent in patients taking salicylates and methotrexate (MTX) and least frequent in patients taking hydroxychloroquine. The combination of MTX and salicylates greatly increased the frequency of abnormal liver enzyme values. In contrast, the addition of hydroxychloroquine to a regimen of either MTX or aspirin essentially eliminated the SGOT and SGPT abnormalities. Results from all 5 centers were consistent and remained so after adjustment for age, sex, and disease duration. Knowledge of these important drug interactions may permit continuation of MTX therapy in patients in whom the drug might otherwise be discontinued.", "To determine the effects of celecoxib, a specific inhibitor of cyclooxygenase 2 (COX-2) on the renal clearance and plasma pharmacokinetic profile of stable methotrexate (MTX) doses in patients with rheumatoid arthritis (RA).\n Fourteen adult female patients with RA taking a stable weekly dose of MTX (5 to 15 mg/wk) for a minimum of 3 months were randomized to receive concomitantly either celecoxib (200 mg BID) or placebo for a period of 7 days in a single blind, 2 period crossover study of MTX pharmacokinetics and renal clearance.\n The plasma pharmacokinetic profile of MTX did not change significantly when celecoxib or a placebo was coadministered. The mean renal clearance of MTX alone, 7.98+/-2.18 l/h, was virtually unchanged by coadministration of celecoxib (7.94+/-1.61 l/h) or placebo (7.97+/-1.19 l/h).\n Celecoxib has no significant effect on the pharmacokinetics or renal clearance of MTX in patients with RA, although these results should be confirmed in prospective studies of elderly and renally impaired patients.", "One hundred thirty-one patients with rheumatoid arthritis treated with either azathioprine sodium (n = 37, 102.7 +/- 32.9 mg/d) or methotrexate sodium (n = 94, 8.4 +/- 3.0 mg/wk) were followed up for 38 +/- 23.3 months to determine the nature, frequency, and potential predictors of \"major\" toxic reactions. Thirty-one methotrexate-treated patients (33%) and 11 patients (30%) receiving azathioprine experienced a major toxic reaction during the study period. With the case-control method, no predictors of major toxic reactions secondary to azathioprine therapy were found. Sex, drug dosage, response to prior slow-acting antirheumatic drug therapy, concurrent use of salicylates, and age did not predict major toxic reactions secondary to methotrexate treatment, but the methotrexate-treated patients who experienced a major toxic reaction had a significantly greater mean level of blood urea nitrogen at the time of their reaction compared with the control group. Life-table analysis suggested toxic reactions posed a greater risk of treatment termination in methotrexate-treated patients compared with the lack or loss of efficacy. This trend was not apparent in the azathioprine group. The majority of patients in each treatment group (79 for methotrexate and 29 for azathioprine) experienced one or more \"minor\" toxic reactions during the follow-up period.", "Intravenous methotrexate (MTX) (10 mg), either alone or with oral aspirin (ASA) (3,900 mg/day), was administered to 15 patients with rheumatoid arthritis. Systemic and renal clearance of MTX were lower, and the unbound fraction of MTX was higher when patients were also receiving ASA than when taking MTX alone. No acute hematologic, renal, or hepatic toxicity was observed with either treatment. The findings of this study therefore indicate that concomitant aspirin therapy acutely alters the clearance of low-dose MTX in patients with rheumatoid arthritis.", "In patients with rheumatoid arthritis (RA), we examined whether methotrexate (MTX) and MTX polyglutamate accumulation in the liver correlated with clinical efficacy or clinical/laboratory toxicity. We also began preliminary examination of a new histologic index of liver histology (the Iowa Score) relative to the Roenigk grading system.\n Forty patients with RA participated in a prospective, double blind, 3.5 year study of MTX treatment. Liver biopsies, liver MTX and MTX polyglutamate concentrations, laboratory tests, evaluation of disease activity, and evaluation of adverse events were done prospectively at baseline and at 1, 2, and 3.5 years. Biopsies were examined using the Roenigk grading system and an additional histological scoring system. Radiochemical ligand binding assays and HPLC methods were used to measure MTX and MTX polyglutamates. Statistical analysis included ANOVA, linear regression, and logistic regression modeling.\n No significant changes in the mean values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, albumin, or hemoglobin occurred. A significant percentage of patients had at least one abnormal alkaline phosphatase, AST, or ALT (25 to 52%), although most abnormalities were small and transient. Histological abnormalities did not progress using either the Roenigk or the Iowa score. The last abnormal AST, the number of abnormal AST and ALT, and female sex correlated with histological liver abnormalities (r2 = 0.41) using a new preliminary histologic scoring system (the Iowa Score). Amount of alcohol use correlated with fatty change, and the MTX dose at biopsy was associated with liver histological abnormalities (p = 0.03 and 0.049, respectively). Total liver MTX concentrations were stable from Year 1 to Year 3.5 and the percentage of higher order polyglutamates was relatively high (38 to 56%) relative to monoglutamates. No correlation of these concentrations with clinical response or toxicity, histology, or liver function tests could be documented.\n This analysis describes the accumulation and stabilization of MTX concentrations in the liver and examined correlations between MTX liver concentrations, patient demographics, liver histology, concomitant medications, and disease activity. No such correlations were found, decreasing the likelihood that MTX concentrations in serum would be useful measures to predict significant hepatotoxicity.", "To evaluate the effect of methotrexate (MTX) and other disease-modifying anti-rheumatic drugs (DMARDs) alone or in combination with non-steroidal anti-inflammatory drugs (NSAIDs) on the urinary excretion of alpha-glutathione S-transferase (alpha-GST) and albumin in rheumatoid arthritis (RA) patients.\n Nineteen RA patients starting treatment with MTX were followed for 1 year with measurements of urinary alpha-GST, urinary albumin, and urinary and plasma creatinine at the start of treatment, and after 16, 28, and 52 weeks. A larger group of RA patients (n = 72) undergoing long-term treatment with different DMARDs was compared with 79 healthy controls regarding urinary alpha-GST and albumin. alpha-GST was quantified by an enzyme immunoassay. Urine albumin was measured turbidimetrically.\n The urine-alpha-GST/urine-creatinine ratio and the urine-albumin/urine-creatinine ratio did not change during 52 weeks of treatment with MTX. The long-term DMARD-treated RA patients and the healthy controls were comparable with regard to the urine-alpha-GST/urine-creatinine ratio and the urine-albumin/urine-creatinine ratio. All patients had preserved renal function as assessed by plasma creatinine, and none had proteinuria using urine dipstick methods.\n DMARD-treated RA patients with normal serum creatinine had no detectable renal injuries assessed by the urinary excretions of alpha-GST and albumin.", "The authors designed 2 randomized controlled studies to examine the effects of etoricoxib 60 to 120 mg daily on methotrexate pharmacokinetics in 50 rheumatoid arthritis (RA) patients on stable doses of methotrexate (7.5-20 mg). Patients received oral methotrexate at baseline and on days 7 and 14. In study 1, patients received etoricoxib 60 mg (days 1-7) and then 120 mg (days 8-14); in study 2, patients received etoricoxib 90 mg (days 1-7) and then 120 mg (days 8-14). For study 1, the AUC(0-infinity) geometric mean ratio (GMR) (90% confidence interval [CI]) for day 7 versus baseline was 1.01 (0.91, 1.12) for etoricoxib 60 mg; the area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) GMR (90% CI) for day 14 was 1.28 (1.15, 1.42) for etoricoxib 120 mg. For study 2, the AUC(0-infinity) GMR (90% CI) for day 7 versus baseline was 1.07 (1.01, 1.13) for etoricoxib 90 mg; the AUC(0-infinity) GMR (90% CI) for day 14 was 1.05 (0.99, 1.11) for etoricoxib 120 mg. In summary, etoricoxib 60 and 90 mg had no effect on methotrexate plasma concentrations. Although no effect on methotrexate pharmacokinetics was observed with etoricoxib 120 mg in study 2, GMR AUC(0-infinity) fell outside the prespecified bounds in study 1. Standard monitoring of methotrexate-related toxicity should be continued when etoricoxib and methotrexate are administered concurrently, especially with doses >90 mg etoricoxib.", "We reviewed the records of 315 patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX) and evaluated the conditions contributing to thrombocytopenia. Thirteen out of 315 patients with RA presented with low platelet counts (< or = 100.000/mm3). The age of these patients (51 +/- 12.6 years) did not correlate with thrombocytopenia (r = 0.211, p > 0.05). Thrombocytopenia resulted from coadministration of MTX and NSAID or multiple drug interactions. We observed a significant (r = 0.48, p < 0.05) increase of discontinuation of NSAID's but not of MTX therapy (r = 0.42, p > 0.05) with a mounting weekly dosage of MTX (12.5 +/- 5 mg orally). There was a significant correlation between this weekly dosage of MTX coadministered on the same day with NSAID and thrombocytopenia (r = 0.6, p < 0.05). In most cases (9/13) MTX was not or just temporarily withdrawn. Three of the remaining patients had multiple drug interactions. Reintroduction of low dose MTX treatment in patients having had thrombocytopenia could be performed safely, if thrombocytopenia occurred as a result of concomitant application of MTX and NSAID and no other multiple drug interactions. Preferably, MTX and NSAID should be given to these risk patients on separate days or intervals considering half time clearance of NSAIDs. This procedure has avoided the reoccurrence of thrombocytopenia and controlled further drug interactions of NSAIDs and MTX in our patients.", "Methotrexate therapy has been effective in the treatment of RA with short term experience suggesting little serious adverse reactions. Our review of 168 patients receiving methotrexate has identified nine patients with probable or possible methotrexate-induced pulmonary toxicity, giving a prevalence of 5% and an incidence of 3.9 per 100 patients per year. No clinical or laboratory features showed an association that could potentially predict the development of pulmonary disease. All patients experienced complete recovery with supportive care and/or corticosteroid therapy. Clinical monitoring for this complication is warranted in all patients receiving long term methotrexate therapy for RA.", "A multicenter, national, retrospective, and cross-sectional study of 219 hospital-based Venezuelan patients with rheumatoid arthritis (RA) was aimed to evaluate the probability of continuity of treatment with oral methotrexate (MTX). Treatment survival decreased from 92% at 12 months to 42% at 180 months, as assessed by life table analysis and the Kaplan-Meier method. Forty-seven patients stopped treatment and adverse effects (29.7%) and lack of continuous access to medication (19.1%) were the most common causes for withdrawal. MTX survival was decreased in the group with combined MTX plus leflunomide therapy, as shown by the log-rank test. Venezuelan patients with RA have a probability of continuing treatment with oral MTX comparable to non-Hispanic patient populations. However, concomitant use of leflunomide may increase the risk of interruption of MTX treatment in this RA population.", "The aim of this investigation was to study the glomerular and tubular effects of low doses (15 mg) of methotrexate in patients with rheumatoid arthritis with and without combined treatment with aspirin (2 g single dose).\n Renal function was measured by the plasma clearance of EDTA labelled with chromium-51 (51Cr-EDTA) and mercaptoacetyltriglycine labelled with technetium-99m (99mTc-MAG-3).\n Clearance of 51Cr-EDTA was reduced from 98 (6) to 87 (5) ml/min (mean (SEM)) for patients receiving methotrexate only and further reduced to 76 (5) ml/min for patients receiving methotrexate and aspirin. This effect was reversible as 51Cr-EDTA increased to 85 (6) ml/min during continued treatment with methotrexate alone. Clearance of 99mTc-MAG-3 also decreased from 366 (18) to 315 (17) ml/min in patients receiving methotrexate alone and further to 295 (17) ml/min during treatment with aspirin and methotrexate. Continued treatment with methotrexate alone resulted in a further decrease in the 99mTc-MAG-3 clearance to 253 (17) ml/min.\n The study shows that treatment with low doses of methotrexate particularly when combined with aspirin affects glomerular and tubular function. These effects may be of clinical importance and renal function should therefore be monitored with more sensitive methods than serum creatinine as this may not reflect these changes.", "The pharmacokinetic profile of total and free methotrexate (MTX) and the effect of piroxicam on MTX pharmacokinetics was studied in 20 rheumatoid arthritis patients receiving a stable dosage of MTX (10 mg/week). Plasma protein binding ranged from 25 to 55%. To describe the variations with time of the unbound fractions a mathematical characterization relationship between the total and free MTX was used. Total and free MTX were correlated with the sigmoid maximum effect model. The slope factor (gamma) was proportional to the number of binding sites. The free fraction for a given patient can be evaluated from this relationship. Total clearance of MTX was not statistically different with piroxicam (8.0 l/h for total MTX, 13.7 l/h for free MTX) vs without piroxicam. Likewise, there were no significant difference in tmax, area under the plasma concentration vs time curve, distribution and elimination half-lives, mean resonance time, and volumes of distribution. Although the highest observed total MTX concentration was significantly lower with piroxicam, there were no significant pharmacokinetic interactions between low-dose MTX and piroxicam." ]

[ "12445222", "15016259", "9151611", "18031439" ]

[ "Two-part implants inserted in a one-stage or a two-stage procedure. A prospective comparative study.", "Submerged or non-submerged healing of endosseous implants to be used in the rehabilitation of partially dentate patients.", "Comparison of soft tissue healing and osseointegration of IMZ implants placed in one-stage and two-stage techniques: a pilot study.", "A prospective multicenter study using two different surgical approaches in the mandible with turned Brånemark implants: conventional loading using fixed prostheses." ]

[ "The aim of this study was to evaluate the feasibility of using a two-part implant system in a one-stage procedure and to monitor the microflora in the peri-implant area in relation to clinical and radiographic outcome.\n After randomisation, 40 edentulous patients (Cawood & Howell class V-VI) received two IMZ implants in the anterior mandible inserted by either a one-stage (n = 20) or a two-stage (n = 20) surgical procedure for overdenture treatment. A standardised clinical and radiographic evaluation was performed after denture insertion as well as 6 and 12 months thereafter. Twelve months after loading, peri-implant samples were collected and analysed for the presence of putative periodontal pathogens using culture technique.\n No striking differences were found between the two groups with regard to the clinical parameters during the evaluation period. The mean bone loss in the first year of functioning was 0.6 mm in both groups. With regard to the gingiva score, plaque score, bleeding score or bone loss between T0 and T12, no associations were found with the presence of the cultured microorganisms. An association was present between pockets >or= 4 mm and the presence of Peptostreptococcus micros in the two-stage group.\n The short-term results indicate that two-part implants inserted in a one-stage procedure may be as predictable as inserted in the common two-stage procedure. The peri-implant sulcus can and does harbour potential periodontal pathogens without significant signs of tissue breakdown.", "To evaluate bone-level alterations that occurred at implants of the Astra Tech(R) System that were placed in the load carrying, posterior parts of the dentition using either a submerged (two-stage) or a non-submerged (one-stage) installation protocol.\n Eighty-four patients that required 115 fixed partial dentures (FPDs or cases) entered the prospective study. All subjects were assigned one patient and > or =one case numbers. For the randomization of cases, a custom-made program based on balanced random permuted blocks was utilized. The cases were assigned to two treatment groups, namely one-stage installation procedure, non-submerged technique (group A) and two-stage installation procedure, submerged technique (group B). Several subjects contributed with cases to both groups A and B. Periodontal, endodontal and open caries lesions were treated prior to implant installation. All patients received careful oral hygiene instruction and training in self-performed plaque control measures. The surgical technique used for fixture installation followed the outline described in the manual for the Astra Tech System. The FPDs were placed 3 months (mandible) and 6 months (maxilla) following implant installation. Immediately following FPD placement, a baseline examination was performed that included assessment of plaque, soft-tissue inflammation and bone level. Clinicians who were otherwise not involved in the study performed the radiographic measurements. Clinical and radiographical examinations were repeated once a year after the baseline examination.\n The primary outcome variable was the change in the bone level at the implants from the time of placement of the bridge (FPD) to the 1- and 2-year reexaminations. Fisher's permutation test was used to test if differences existed between groups A and B, and between patients (men/women, smokers/non-smokers, age), sites (maxilla/mandible) and implants (length, diameter). Pitman's test was used to study correlations between bone shape and quality data and different radiographic bone-level data.\n It was demonstrated that tissue healing following implant installation appeared to be independent of the surgical protocol, i.e. whether the marginal portions of the implants during surgery were fully or only partly submerged under the ridge mucosa. Thus, (i) in both treatment groups the number of implants that failed to osseointegrate (early failures) was small (<2%); (ii) at the end of the recommended periods of bone healing prior to loading, - in both groups, maxilla=6 months and mandible=3 months - the level of the marginal bone was close to the coronal rim of the fixture; group A: 1.54+/-0.92 mm, group B: 1.31+/-0.77 mm. The current study also demonstrated that irrespective of surgical protocol (two-stage, one-stage), implants supporting the FPDs exhibited only small amount of radiographic bone loss during the first year of function (group A: 0.02+/-038 mm, group B: 0.17+/-0.64 mm). Moreover, during the second year of function, the amount of additional bone loss that occurred in the two treatment groups was close to zero.\n Periimplant bone-level change during function seemed to be unrelated to whether initial soft- and hard-tissue healing following implant installation had occurred under submerged or non-submerged conditions.", "The osseointegration of endosseous dental implants is well documented. Implants have proven to be a viable treatment option for the replacement of missing teeth. The surgical phase of implant dentistry for most implant systems involves two stages--the placement of the implant and its subsequent uncovering. The IMZ (Interpore International) implant system is classically a two-stage system. No significant differences were demonstrated in osseointegration and soft tissue healing for IMZ implants placed in one-stage and two-stage procedures in this pilot study.", "The use of a submerged implant system in a nonsubmerged surgical procedure has been reported to have promising results. At the time this study was initiated, no prospective, comparative studies with randomization between submerged and nonsubmerged surgical techniques had been published.\n To evaluate the submerged and nonsubmerged surgical techniques when treating mandibular edentulism using a submerged implant system, with regard to implant survival and complications.\n A total of 77 patients were included and treated at nine clinics in Sweden and Norway. In total, 404 Brånemark System implants (standard and MkII implants) were inserted in the edentulous mandible; 198 implants according to the nonsubmerged protocol and 206 implants according to the traditional submerged procedure. The follow-up period was up to 36 months after prosthesis insertion.\n In the nonsubmerged group, 17 implants out of 198 implants (8.6%) were lost and in the submerged group, 5 out of 206 implants (2.4%) were lost. All implant failures occurred before the delivery of the final prosthesis. No major complications were reported during the implant surgery. However, at the clinical check-up postoperatively and at the abutment connection surgery, 6 patients in the nonsubmerged group complained of pain at the implant sites, whereas there were no complaints of pain in the submerged group.\n The results of this study suggest that a turned Brånemark implant designed for a submerged implant placement procedure can be used in a nonsubmerged procedure and may be as predictable as the conventional submerged approach." ]

[ "10890136", "4449526", "22944" ]

[ "A blinded, controlled trial of an ultrasound device as mosquito repellent.", "[Unfavorable results of testing model sound generators designed for repelling mosquitoes].", "Trials with an electronic mosquito-repelling device in West Africa." ]

[ "Ultrasound emitting devices are used to repel mosquitoes. We tested the repelling properties of a commercially available ultrasound device in a domestic setting in Gabon. Devices emitting three different block frequencies ranging from 3 to 11 kHz were tested in a paired, cross-over blinded and placebo controlled trial during eighteen nights in nine pairs of houses. A total of 7485 mosquitoes (10% Anopheles, 62% Culex, 27% Mansonia and 1% Aedes) were caught, 23 per house per night. There was no significant difference in landing rate between the houses with ultrasound device and the houses with placebo for any species of mosquito. Thus the ultrasound device used was not effective against mosquitoes in this strictly controlled trial.", "nan", "nan" ]

[ "11172189", "20154071", "10556125" ]

[ "Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure.", "Helmet continuous positive airway pressure vs oxygen therapy to improve oxygenation in community-acquired pneumonia: a randomized, controlled trial.", "Acute respiratory failure in patients with severe community-acquired pneumonia. A prospective randomized evaluation of noninvasive ventilation." ]

[ "Avoiding intubation is a major goal in the management of respiratory failure, particularly in immunosuppressed patients. Nevertheless, there are only limited data on the efficacy of noninvasive ventilation in these high-risk patients.\n We conducted a prospective, randomized trial of intermittent noninvasive ventilation, as compared with standard treatment with supplemental oxygen and no ventilatory support, in 52 immunosuppressed patients with pulmonary infiltrates, fever, and an early stage of hypoxemic acute respiratory failure. Periods of noninvasive ventilation delivered through a face mask were alternated every three hours with periods of spontaneous breathing with supplemental oxygen. The ventilation periods lasted at least 45 minutes. Decisions to intubate were made according to standard, predetermined criteria.\n The base-line characteristics of the two groups were similar; each group of 26 patients included 15 patients with hematologic cancer and neutropenia. Fewer patients in the noninvasive-ventilation group than in the standard-treatment group required endotracheal intubation (12 vs. 20, P=0.03), had serious complications (13 vs. 21, P=0.02), died in the intensive care unit (10 vs. 18, P=0.03), or died in the hospital (13 vs. 21, P=0.02).\n In selected immunosuppressed patients with pneumonitis and acute respiratory failure, early initiation of noninvasive ventilation is associated with significant reductions in the rates of endotracheal intubation and serious complications and an improved likelihood of survival to hospital discharge.", "Our objective was to evaluate the efficacy of noninvasive continuous positive airway pressure (CPAP) delivered by helmet in improving oxygenation in comparison with oxygen therapy in community-acquired pneumonia (CAP).\n This was a multicenter, randomized, controlled trial enrolling patients with CAP admitted to an ED with moderate hypoxemic acute respiratory failure (ARF) (Pa(O(2))/Fi(O(2)) ratio > or = 210 and < or = 285). Patients were randomized to helmet CPAP or standard oxygen therapy (control group). The primary end point was the time to reach a Pa(O(2))/Fi(O(2)) ratio > 315. After reaching this value, patients randomized to CPAP were switched to oxygen, and the proportion of subjects who could maintain a Pa(O(2))/Fi(O(2)) ratio > 315 at 1 h was recorded.\n Forty-seven patients were recruited: 20 randomized to CPAP and 27 to controls. Patients randomized to CPAP reached the end point in a median of 1.5 h, whereas controls reached the end point in 48 h (P < .001). The proportion of patients who reached the primary end point was 95% (19/20) among the CPAP group and 30% (8/27) among controls (P < .001). One hour after reaching the primary end point, 2/14 patients in the CPAP group maintained a Pa(O(2))/Fi(O(2)) value > 315.\n CPAP delivered by helmet rapidly improves oxygenation in patients with CAP suffering from a moderate hypoxemic ARF. This trial represents a proof-of-concept evaluation of the potential usefulness of CPAP in patients with CAP.", "In uncontrolled studies, noninvasive positive pressure ventilation (NPPV) was found useful in avoiding endotracheal intubation in patients with acute respiratory failure (ARF) caused by severe community-acquired pneumonia (CAP). We conducted a prospective, randomized study comparing standard treatment plus NPPV delivered through a face mask to standard treatment alone in patients with severe CAP and ARF. Patients fitting the American Thoracic Society criteria for severe CAP were included in presence of ARF (refractory hypoxemia and/or hypercapnia with acidosis). Exclusion criteria were: severe hemodynamic instability, requirement for emergent cardiopulmonary resuscitation, home mechanical ventilation or oxygen long-term supplementation, concomitant severe disease with a low expectation of life, inability to expectorate or contraindications to the use of the mask. Fifty-six consecutive patients (28 in each arm) were enrolled, and the two groups were similar at study entry. The use of NPPV was well tolerated, safe, and associated with a significant reduction in respiratory rate, need for endotracheal intubation (21% versus 50%; p = 0.03), and duration of intensive care unit (ICU) stay (1.8 +/- 0.7 d versus 6 +/- 1.8 d; p = 0.04). The two groups had a similar intensity of nursing care workload, time interval from study entry to endotracheal intubation, duration of hospitalization, and hospital mortality. Among patients with chronic obstructive pulmonary disease (COPD), those randomized to NPPV had a lower intensity of nursing care workload (p = 0.04) and improved 2-mo survival (88.9% versus 37.5%; p = 0.05). We conclude that in selected patients with ARF caused by severe CAP, NPPV was associated with a significant reduction in the rate of endotracheal intubation and duration of ICU stay. A 2-mo survival advantage was seen in patients with COPD." ]

[ "8000747", "2087335", "2135016" ]

[ "The analgesic effect of acupuncture in chronic tennis elbow pain.", "Laser treatment applied to acupuncture points in lateral humeral epicondylalgia. A double-blind study.", "Acupuncture treatment in epicondylalgia: a comparative study of two acupuncture techniques." ]

[ "The immediate analgesic effect of a single non-segmental acupuncture stimulation treatment on chronic tennis elbow pain was studied in a placebo-controlled single-blind trial completed by 48 patients. Before and after treatment, all patients were examined physically by an unbiased independent examiner. Eleven-point box scales were used [13] for pain measurement. Patients in the verum group were treated at non-segmental distal points (homolateral leg) for elbow pain following Chinese acupuncture rules, whereas patients in the placebo group were treated with placebo acupuncture avoiding penetration of the skin with an acupuncture needle. Overall reduction in the pain score was 55.8% (S = 2.95) in the verum group and 15% (S = 2.77) in the placebo group. After one treatment 19 out of 24 patients in the verum group (79.2%) reported pain relief of at least 50% (placebo group: six patients out of 24). The average duration of analgesia after one treatment was 20.2 h in the verum group (S = 21.54) and 1.4 h (S = 3.50) in the placebo group. The results are statistically significant (P < 0.01); they show that non-segmental verum acupuncture has an intrinsic analgesic effect in the clinical treatment of tennis elbow pain which exceeds that of placebo acupuncture.", "Forty-nine patients suffering from lateral humeral epicondylalgia were enrolled in a double-blind study to observe the effects of Ga-As laser applied to acupuncture points. The Mid 1500 IRRADIA laser machine was used, wavelength: 904 nm, mean power output: 12 mW, peak value: 8.3 W; frequency: 70 Hz (pulse train). Localization of points: LI 10, 11, 12, Lu 5 and SJ 5. Each point was treated for 30 sec resulting in a dose of treatment of 0.36 J/point. The patients were treated 2-3 times weekly with 10 treatments in all. Follow-ups were done after 3 months and 1 year. No significant differences were observed between the laser and the placebo group in relation to the subjective or objective outcome after 10 treatments or at the follow-ups.", "The purpose of this study was to compare the pain-alleviating effect of classical acupuncture with superficial needle insertion in 82 patients suffering from lateral epicondylalgia. Sessions were 20 min long, two to three times weekly with 10 treatments in all. Five acupuncture points were treated: LI 10, 11, 12, Lu 5, and SJ 5. After 10 treatments significant differences were observed between the groups favoring the classical acupuncture technique in relation to subjective and objective outcome. No such differences could be observed at the follow-ups after 3 months and 1 year. This study showed that classical \"deep\" acupuncture is superior to superficial needle insertion in the short-term symptomatic treatment of lateral epicondylalgia, but not at 3- and 12-month follow-up." ]

[ "3883815", "11561930", "2963048", "15232326", "15243735", "8912401", "10695642", "2201223", "8942464" ]

[ "The pharmacological treatment of delusional depression.", "A double-blind randomized comparison of nortriptyline plus perphenazine versus nortriptyline plus placebo in the treatment of psychotic depression in late life.", "Placebo response rates in psychotic and nonpsychotic depression.", "A double-blind, randomized study of olanzapine and olanzapine/fluoxetine combination for major depression with psychotic features.", "A double-blind randomized study comparing imipramine with fluvoxamine in depressed inpatients.", "A double-blind, fixed blood-level study comparing mirtazapine with imipramine in depressed in-patients.", "Venlafaxine versus fluvoxamine in the treatment of delusional depression: a pilot double-blind controlled study.", "Amoxapine versus amitriptyline combined with perphenazine in the treatment of psychotic depression.", "Double-blind controlled trial of sertraline versus paroxetine in the treatment of delusional depression." ]

[ "The authors investigated the pharmacological treatment of delusional depression by assigning patients on a random double-blind basis to amitriptyline alone, perphenazine alone, or a combination of the two. Fourteen (78%) of the 18 patients assigned to amitriptyline plus perphenazine were responders, compared with seven (41%) of 17 patients treated with amitriptyline alone and three (19%) of the 16 patients treated with perphenazine alone. The combination of amitriptyline and perphenazine was clearly superior (p less than .01).", "To conduct the first randomized study comparing the efficacy of an antidepressant alone versus an antidepressant plus a neuroleptic in the treatment of late-life psychotic depression.\n The efficacy of nortriptyline plus placebo versus nortriptyline plus perphenazine was compared in 36 patients aged 50 years or older presenting with a major depressive episode with psychotic features (DSM-III-R criteria). Patients were started openly on nortriptyline treatment titrated to therapeutic levels. They were then randomly assigned under double-blind conditions to addition of perphenazine or placebo. Outcomes were compared in the 2 treatment groups using measures including the Hamilton Rating Scale for Depression (HAM-D) and the Brief Psychiatric Rating Scale (BPRS); side effects were assessed with the Geriatric Movement Disorder Assessment.\n Both treatments were well tolerated. Of the 36 randomly assigned patients, 2 (1 in each group) dropped out due to treatment-related adverse effects. Four additional patients dropped out for administrative reasons. Thirty patients received nortriptyline for at least 4 weeks combined with either perphenazine (N = 14) or placebo (N = 16) for at least 2 weeks (median = 9 weeks). There was no significant difference between the completers in the 2 treatment groups when comparing their scores on the HAM-D, the BPRS, its psychoticism subscale, or any side effects measure. Rates of response (defined as resolution of both depression and psychosis) did not differ significantly in the 2 groups (nortriptyline-plus-perphenazine group, 50% vs. nortriptyline-plus-placebo group, 44%).\n When treating older patients with psychotic depression, the addition of a moderate dose of a traditional neuroleptic to a tricyclic antidepressant was well tolerated but did not improve efficacy. This finding supports existing data suggesting that the pathophysiology (and thus the required treatment) of psychotic depression may be different early and late in life.", "The authors reanalyzed data from two earlier studies that used double-blind placebo-controlled formats to study the efficacy of amitriptyline. Using a 14-day drug-free 'wash-out' period, they found that the placebo response rates were 0% for psychotic depressives and 13.3% for nonpsychotic depressives. Amitriptyline was significantly superior to placebo for both psychotic (P less than or equal to 0.05) and nonpsychotic (P less than or equal to 0.05) depressed patients.", "The purpose of this study was to compare the efficacy and safety of olanzapine (OLZ) monotherapy and an olanzapine/fluoxetine combination (OFC) with placebo (PLA) for unipolar major depression with psychotic features. Under a single protocol, two 8-week, double-blind trials were conducted at 27 sites. Patients (n = 124 trial 1, n = 125 trial 2) were randomized to 1 of 3 treatment groups: OLZ (5 to 20 mg/d), PLA, or OFC (olanzapine 5 to 20 mg/d + fluoxetine 20 to 80 mg/d). The primary outcome measure was the 24-item Hamilton Depression Rating Scale total score. For trial 1, endpoint improvement for the OLZ group (-14.9) was not significantly different from the PLA or OFC groups. The OFC group had significantly greater endpoint improvement (-20.9) than the PLA group (-10.4, P = 0.001); this significant difference was present within 7 days of therapy and maintained at every subsequent visit. The OFC group also had significantly higher response rate (63.6%) than the PLA (28.0%, P = 0.004) or OLZ (34.9%, P = 0.027) groups. For trial 2, there were no significant differences among treatment groups on the 24-item Hamilton Depression Rating Scale total scores or response rates. The combination exhibited a comparable safety profile with OLZ monotherapy and no significant increases in extrapyramidal symptoms compared with placebo. Patients with major depression with psychotic features treated with OLZ monotherapy did not demonstrate significant depressive symptom improvement compared with placebo in either trial; however, an olanzapine/fluoxetine combination was associated with significant improvement compared with placebo in one trial and was well tolerated.\n Copyright 2004 Lippincott Williams and Wilkins", "To compare the efficacy of imipramine and fluvoxamine in inpatients from two centers suffering from a depressive disorder according to DSM IV criteria.\n The study included 141 patients with a depressive disorder according to DSM IV criteria. After a drug-free and placebo run-in period of 1 week, patients were randomized to imipramine or fluvoxamine; doses of both drugs were adjusted to a predefined target blood level. Efficacy was evaluated 4 weeks after attaining predefined adequate plasma level.\n The mean age of the study group (47 males, 94 females) was 51.8 (range 19-65) years. Of these 141 patients, 56 had episode duration longer than 1 year, 48 had mood congruent psychotic features, and 138 patients received medication. Seven patients did not complete the medication trial. The total number of patients using concurrent medication was 12/138 (8.6%). On the primary outcome criteria patients on imipramine improved significantly better on the change of illness severity score of the CGI (chi2 exact trend test=4.089, df=1, P=-0.048). There was no significant difference in 50% or more reduction on the HRSD, the other primary outcome criterion. On the secondary outcome criteria the mean reduction of the HRSD scores was significantly larger in the imipramine group than in the fluvoxamine group (mean difference=3.1, standard error (SE)=1.4, t=2.15, df=136, P=0.033). There was no significant difference in the number of patients with an HRSD < or =7 at the final evaluation.\n In depressed inpatients imipramine is more efficacious than fluvoxamine. Both drugs were well tolerated by all patients.", "Antidepressant effects of mirtazapine and imipramine were compared in a randomized, double blind, fixed blood-levels study with in-patients in a single centre. Patients with a DSM-III-R diagnosis of major depression and a Hamilton (17-item) score of > or = 18 were selected. After a drug-free and a placebo-washout period of 7 days in total, 107 patients still fulfilling the HRSD criterion of > or = 18, started on active treatment. The dose was adjusted to a predefined fixed blood level to avoid suboptimal dosing of imipramine. Concomitant psychotropic medication was administered only in a few cases because of intolerable anxiety or intolerable psychotic symptoms. Eight patients dropped out and two were excluded from analyses because of non-compliance; 97 completed the study. According to the main response criterion (50% or more reduction on the HRSD score) 11/51 (21.6%) patients responded on mirtazapine and 23/46 (50%) on imipramine after 4 weeks' treatment on the predefined blood level. Such a dramatic difference in efficacy between antidepressants has not often been reported before. The selection of (severely ill) in-patients, including those with suicidal or psychotic features, may have significance in this respect. Optimization of treatment with the reference drug imipramine through blood level control, exclusion of non-compliance for both drugs, exclusion of most concomitant medication and a low drop-out rate may also have contributed. It is concluded that imipramine is superior to mirtazapine in the patient population studied.", "Previous studies have reported the efficacy of selective serotonin reuptake inhibitors as monotherapy in the treatment of delusional depression. The clinical efficacy of venlafaxine, a serotonin-norepinephrine reuptake blocker, has been demonstrated in the treatment of patients with moderate-to-severe depression, but, to date, no evidence is available about its use in depressed patients with psychotic features.\n Under double-blind conditions, 28 hospitalized patients who met DSM-IV criteria for major depression, severe with psychotic features, were randomly assigned to receive fluvoxamine or venlafaxine, 300 mg/day, for 6 weeks. Severity was evaluated using the Hamilton Rating Scale for Depression (HAM-D) and the Dimensions of Delusional Experience Rating Scale (DDERS) administered at baseline and every week thereafter. Side effects were also recorded. Clinical response was defined as a reduction of the scores in the 21-item HAM-D to 8 or below and in the DDERS to 0.\n At study completion, the response rates were 78.6% (N = 11) and 58.3% (N = 7) for fluvoxamine and venlafaxine, respectively. No significant difference was found between drugs (Fisher exact test, p = .40). Analysis of covariance on HAM-D scores did not reveal a significantly different decrease of depressive symptomatology between the 2 treatment groups (p = .14). Treatment response appeared to be unrelated to the demographic and clinical characteristics recorded. The overall safety profile of both fluvoxamine and venlafaxine was favorable.\n The results of this pilot double-blind trial show that fluvoxamine is useful in the treatment of delusional depression and suggest that venlafaxine may also be an effective compound in the treatment of this disorder. The latter finding, although promising, warrants further replication in a larger sample of patients.", "In a double-blind study lasting for 4 weeks, the authors compared the effectiveness of amoxapine, an antidepressant with potential antipsychotic properties, with a combination of amitriptyline plus perphenazine in the treatment of 38 patients who had the diagnosis of major depression with psychotic features (psychotic or delusional depression). Patients in each group showed similar improvement in depression and psychosis. There was a tendency for the patients treated with amitriptyline plus perphenazine to have higher global response rates. However, the patients given amoxapine had significantly fewer extrapyramidal side effects.", "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." ]

[ "9761043" ]

[ "A multicenter trial on the efficacy of using tirilazad mesylate in cases of head injury." ]

[ "The authors prospectively studied the efficacy of tirilazad mesylate, a novel aminosteroid, in humans with head injuries.\n A cohort of 1120 head-injured patients received at least one dose of study medication (tirilazad or placebo). Eighty-five percent (957) of the patients had suffered a severe head injury (Glasgow Coma Scale [GCS] score 4-8) and 15% (163) had sustained a moderate head injury (GCS score 9-12). Six-month outcomes for the tirilazad- and placebo-treated groups for the Glasgow Outcome Scale categories of both good recovery and death showed no significant difference (good recovery in the tirilazad-treated group was 39% compared with the placebo group in which it was 42% [p=0.461]; death in the tirilazad-treated group occurred in 26% of patients compared with the placebo group, in which it occurred in 25% [p=0.750]). Subgroup analysis suggested that tirilazad mesylate may be effective in reducing mortality rates in males suffering from severe head injury with accompanying traumatic subarachnoid hemorrhage (death in the tirilazad-treated group occurred in 34% of patients; in the placebo group it occurred in 43% [p=0.026]). No significant differences in frequency or types of serious adverse events were shown between the treatment and placebo groups.\n Striking problems with imbalance concerning basic prognostic variables were observed in spite of the large population studied. These imbalances concerned pretreatment hypotension, pretreatment hypoxia, and the incidence of epidural hematomas. In future trials of pharmacological therapy for severe head injury, serious consideration must be given to alternative randomization strategies. Given the heterogeneous nature of head injury and the identification of populations that do relatively well with standard therapy, target populations with a higher risk for mortality and morbidity may be more suitable for clinical trials of such agents." ]

[ "17157112", "17933414", "17277036", "17130197", "18248490", "17223217", "15562200", "17373638", "17593236", "17485570", "17130196", "18034842", "17509069", "17300595", "17001471", "16823726", "16219012", "17259484", "17300593", "17387446", "17300592", "17156104" ]

[ "Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.", "Efficacy and safety of sitagliptin monotherapy in Japanese patients with type 2 diabetes.", "Effects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metformin.", "Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone.", "Efficacy and tolerability of vildagliptin in drug-naïve patients with type 2 diabetes and mild hyperglycaemia*.", "Efficacy and tolerability of vildagliptin monotherapy in drug-naïve patients with type 2 diabetes.", "Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes.", "Vildagliptin in drug-naïve patients with type 2 diabetes: a 24-week, double-blind, randomized, placebo-controlled, multiple-dose study.", "Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin.", "Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes.", "Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes.", "Efficacy and tolerability of vildagliptin vs. pioglitazone when added to metformin: a 24-week, randomized, double-blind study.", "Comparison between vildagliptin and metformin to sustain reductions in HbA(1c) over 1 year in drug-naïve patients with Type 2 diabetes.", "Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial.", "Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus.", "Twelve-week monotherapy with the DPP-4 inhibitor vildagliptin improves glycemic control in subjects with type 2 diabetes.", "Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response.", "Comparison of vildagliptin and rosiglitazone monotherapy in patients with type 2 diabetes: a 24-week, double-blind, randomized trial.", "Efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component monotherapy in patients with type 2 diabetes.", "Addition of vildagliptin to insulin improves glycaemic control in type 2 diabetes.", "Vildagliptin in combination with pioglitazone improves glycaemic control in patients with type 2 diabetes failing thiazolidinedione monotherapy: a randomized, placebo-controlled study.", "Efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy over 12 weeks in patients with type 2 diabetes." ]

[ "The efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy were assessed in patients with type 2 diabetes and inadequate glycemic control (glycosylated hemoglobin [HbA(1c)] > or =7% and < or =10%) while receiving a stable dose of pioglitazone.\n This was a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel group study in patients aged > or =18 years (ClinicalTrials. gov NCT00086502). At screening, all patients began a diet/exercise program that continued throughout the study period. Patients taking antihyperglycemic therapy other than pioglitazone underwent a washout of this therapy and entered an 8- to 14-week open-label pioglitazone dose-titration/stabilization period. Patients with an HbA(1c) > or =7% and < or =10% at the end of this period entered a 2-week, single-blind, placebo run-in period (total duration of run-in period, up to 21 weeks). Patients who had been receiving pioglitazone monotherapy (30 or 45 mg/d) and had an HbA(1c) > or =7% and < or =10% entered the 2-week, single-blind, placebo run-in period directly. Thus, at the time of randomization, all patients were receiving ongoing pioglitazone (30 or 45 mg/d). Patients were randomized in a 1:1 ratio to receive sitagliptin 100 mg once daily or placebo for 24 weeks. The primary efficacy end point was the change from baseline in HbA(1c) at week 24. Secondary efficacy end points included the change from baseline in fasting plasma glucose (FPG), insulin, and proinsulin; the Homeostasis Model Assessment beta-cell function and insulin-resistance indexes; the proinsulin/ insulin ratio; the Quantitative Insulin Sensitivity Check Index; the percent changes from baseline in selected lipid parameters; the proportion of patients meeting the American Diabetes Association HbA(1c), goal of <7.0%; the proportion of patients requiring metformin rescue therapy; and the time to the initiation of rescue therapy.\n One hundred seventy-five patients were randomized to receive sitagliptin, and 178 were randomized to receive placebo. The mean (SD) baseline HbAlc value was 8.1% (0.8) in the sitagliptin group and 8.0% (0.8) in the placebo group. After 24 weeks, sitagliptin added to pioglitazone therapy was associated with significant reductions compared with placebo in HbA(1c) (between-treatment difference in least squares [LS] mean change from baseline. -0.70 %; 95 % CI, -0.85 to -0.54; P < 0.001) and FPG (-17.7 mg/dL; 95% CI, -24.3 to -11.0; P < 0.001). Mean HbA(1c) values at end point were 7.2% (0.9) and 7.8% (1.1) in the respective treatment groups, and the proportions of patients reaching a target HbA(1c) of <7.0% were 45.4% and 23.0% (P < 0.001). Significant reductions in fasting serum proinsulin levels and the proinsulin/insulin ratio were seen with sitagliptin treatment compared with placebo (both, P < 0.01). Sitagliptin was generally well tolerated, with no increased risk of hypoglycemia compared with placebo (2 vs 0 patients, respectively).", "Efficacy and tolerability of sitagliptin, a dipeptidyl peptidase-4 inhibitor, were assessed in Japanese patients with type 2 diabetes. In a multicenter, double-blind, randomized, placebo-controlled trial in Japan, 151 patients with inadequate glycemic control [HbA(1c) > or =6.5% to <10%, fasting plasma glucose (FPG) > or =126 to < or =240 mg/dL] were randomized to once-daily sitagliptin 100mg or placebo for 12 weeks. After 12 weeks, the least squares (LS) mean change from baseline HbA(1c) was -0.65% (95% CI: -0.80, -0.50) with sitagliptin versus 0.41% (0.26, 0.56) with placebo [between-group difference=-1.05% (-1.27, -0.84); p<0.001]. LS mean change from baseline FPG was -22.5mg/dL (95% CI: -28.0, -17.0) with sitagliptin versus 9.4 mg/dL (3.9, 14.9) with placebo [between-group difference=-31.9 mg/dL (95% CI: -39.7,-24.1); p<0.001]. More patients achieved HbA(1c) <7% or <6.5% with sitagliptin than with placebo (p<0.001). Following a meal tolerance test, 2-h postprandial glucose was significantly reduced with sitagliptin relative to placebo. Clinical and laboratory adverse experiences were similar between treatments, with no reported hypoglycemia adverse events with sitagliptin. Body weight was unchanged relative to baseline in the sitagliptin group (-0.1 kg), but significantly (p<0.01) different relative to the placebo group (-0.7 kg). In this study, once-daily sitagliptin 100mg for 12 weeks improved fasting and postprandial glycemic control and was generally well tolerated in Japanese patients with type 2 diabetes.", "We sought to evaluate the efficacy and safety of vildagliptin, a new dipeptidyl peptidase-4 inhibitor, added to metformin during 24 weeks of treatment in patients with type 2 diabetes.\n This was a double-blind, randomized, multicenter, parallel group study of a 24-week treatment with 50 mg vildagliptin daily (n = 177), 100 mg vildagliptin daily (n = 185), or placebo (n = 182) in patients continuing a stable metformin dose regimen (> or =1,500 mg/day) but achieving inadequate glycemic control (A1C 7.5-11%).\n The between-treatment difference (vildagliptin-placebo) in adjusted mean change (AMDelta) +/- SE in A1C from baseline to end point was -0.7 +/- 0.1% (P < 0.001) and -1.1 +/- 0.1% (P < 0.001) in patients receiving 50 or 100 mg vildagliptin daily, respectively. The between-treatment difference in the AMDelta fasting plasma glucose (FPG) was -0.8 +/- 0.3 mmol/l (P = 0.003) and -1.7 +/- 0.3 mmol/l (P < 0.001) in patients receiving 50 or 100 mg vildagliptin daily, respectively. Adverse events (AEs) were reported by 63.3, 65.0, and 63.5% of patients receiving 50 mg vildagliptin daily, 100 mg vildagliptin daily, or placebo, respectively. Gastrointestinal AEs were reported by 9.6 (P = 0.022 vs. placebo), 14.8, and 18.2% of patients receiving 50 mg vildagliptin daily, 100 mg vildagliptin daily, or placebo, respectively. One patient in each treatment group experienced one mild hypoglycemic event.\n Vildagliptin is well tolerated and produces clinically meaningful, dose-related decreases in A1C and FPG as add-on therapy in patients with type 2 diabetes inadequately controlled by metformin.", "The efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, added to ongoing metformin therapy, were assessed in patients with type 2 diabetes who had inadequate glycemic control (HbA(1c) [A1C] >or=7 and <or=10%) with metformin alone.\n After a screening diet/exercise run-in period, a metformin dose titration/stabilization period, and a 2-week, single-blind, placebo run-in period, 701 patients, aged 19-78 years, with mild to moderate hyperglycemia (mean A1C 8.0%) receiving ongoing metformin (>or=1,500 mg/day) were randomly assigned to receive the addition of placebo or sitagliptin 100 mg once-daily in a 1:2 ratio for 24 weeks. Patients exceeding specific glycemic limits were provided rescue therapy (pioglitazone) until the end of the study. The efficacy analyses were based on an all-patients-treated population using an ANCOVA and excluded data obtained after glycemic rescue.\n At week 24, sitagliptin treatment led to significant reductions compared with placebo in A1C (-0.65%), fasting plasma glucose, and 2-h postmeal glucose. Fasting insulin, fasting C-peptide, fasting proinsulin-to-insulin ratio, postmeal insulin and C-peptide areas under the curve (AUCs), postmeal insulin AUC-to-glucose AUC ratio, homeostasis model assessment of beta-cell function, and quantitative insulin sensitivity check index were significantly improved with sitagliptin relative to placebo. A significantly greater proportion of patients achieved an A1C <7% with sitagliptin (47.0%) than with placebo (18.3%). There was no increased risk of hypoglycemia or gastrointestinal adverse experiences with sitagliptin compared with placebo. Body weight decreased similarly with sitagliptin and placebo.\n Sitagliptin 100 mg once-daily added to ongoing metformin therapy was efficacious and well tolerated in patients with type 2 diabetes who had inadequate glycemic control with metformin alone.", "This study was conducted to assess efficacy and tolerability of vildagliptin in drug-naïve patients with type 2 diabetes and mild hyperglycaemia.\n Multicentre, double-blind, randomized, placebo-controlled, parallel-group study of 52-week treatment with vildagliptin (50 mg q.d.) in 306 drug-naïve patients with type 2 diabetes (A1C = 6.2-7.5%). A1C, fasting plasma glucose (FPG) and measures of prandial glucose control and beta-cell function determined during standard meal tests were assessed.\n Baseline A1C and FPG averaged 6.7% and 7.1 mmol/l, respectively, in patients randomized to vildagliptin (n = 156) and 6.8% and 7.2 mmol/l in those randomized to placebo (n = 150). A1C decreased modestly in vildagliptin-treated patients (Delta = -0.2 +/- 0.1%) and increased in patients receiving placebo (Delta = 0.1 +/- 0.1%). The between-group difference (vildagliptin - placebo) in adjusted mean change (AM Delta) in A1C was -0.3 +/- 0.1% (p < 0.001). FPG increased in patients receiving placebo (Delta = 0.5 +/- 0.1 mmol/l) and to a significantly lesser extent in vildagliptin-treated patients (between-group difference in AM Delta FPG = -0.4 +/- 0.2 mmol/l, p = 0.032). Relative to placebo, 2-h postprandial glucose (PPG) decreased (-0.9 +/- 0.4 mmol/l, p = 0.012), and insulin secretory rate (ISR) relative to glucose [ISR area under the curve (AUC)(0-2) (h)/glucose AUC(0-2) (h)] increased (+5.0 +/- 1.2 pmol/min/m(2)/mM, p < 0.001). Mean body weight decreased by 0.5 +/- 0.3 kg in vildagliptin-treated patients and by 0.2 +/- 0.3 kg in patients receiving placebo. The side-effect profile of vildagliptin was similar to that of placebo, and one hypoglycaemic episode occurred in one patient receiving placebo.\n In drug-naïve patients with mild hyperglycaemia, relative to placebo, 52-week treatment with vildagliptin 50 mg q.d. significantly decreases A1C, FPG and PPG and improves beta-cell function without weight gain or hypoglycaemia.", "This 24-week, double-blind, randomized, multicenter, placebo-controlled, parallel-group study performed in 354 drug-naïve patients with type 2 diabetes (T2DM) assessed efficacy and tolerability of vildagliptin (50mg qd, 50mg bid, or 100mg qd). The primary assessment was change from baseline to endpoint in hemoglobin A1c (A1C), comparing vildagliptin to placebo by ANCOVA. Baseline A1C averaged 8.4% and the between-treatment difference (vildagliptin-placebo) in adjusted mean change (AMDelta) in A1C was -0.5+/-0.2% (P=0.011), -0.7+/-0.2% (P<0.001), and -0.9+/-0.2% (P<0.001) in patients receiving vildagliptin 50 mg qd, 50 mg bid, or 100 mg qd, respectively. Baseline FPG averaged 10.5 mmol/L; the between-treatment difference in AMDelta FPG was -0.6+/-0.4 mmol/L in patients receiving vildagliptin 50mg qd and -1.3+/-0.4 mmol/L (P=0.001) in both groups receiving 100mg daily. Relative to baseline, body weight did not change significantly in any of the three vildagliptin groups and decreased by 1.4+/-0.4 kg in the placebo group. Adverse events (AEs) occurred with similar frequency in each group: 55.8%, 59.3%, 59.3%, and 57.6% of patients receiving vildagliptin 50 mg qd, 50 mg bid, 100 mg qd, or placebo, respectively, experienced an AE. No confirmed hypoglycemia was reported. Conclusion: Vildagliptin is effective and well-tolerated in drug-naïve patients with T2DM and 100 mg vildagliptin provides similar clinical benefit whether given as single or in divided doses.", "To assess the 12- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 versus placebo in patients with type 2 diabetes continuing metformin treatment.\n We conducted a 12-week, randomized, double-blind, placebo-controlled trial in 107 patients with type 2 diabetes with a 40-week extension in those completing the core study and agreeing, together with the investigator, to extend treatment to 1 year. Placebo (n=51) or LAF237 (50 mg once daily, n=56) was added to ongoing metformin treatment (1,500-3,000 mg/day). HbA1c and fasting plasma glucose (FPG) were measured periodically, and standardized meal tests were performed at baseline, week 12, and week 52.\n In patients randomized to LAF237, baseline HbA1c averaged 7.7 +/- 0.1% and decreased at week 12 (Delta=-0.6 +/- 0.1%), whereas HbA1c did not change from a baseline of 7.9 +/- 0.1% in patients given placebo (between-group difference in DeltaHbA1c=-0.7 +/- 0.1%, P <0.0001). Mean prandial glucose and FPG were significantly reduced in patients receiving LAF237 versus placebo by 2.2 +/- 0.4 mmol/l (P <0.0001) and 1.2 +/- 0.4 mmol/l (P=0.0057), respectively, but plasma insulin levels were not affected. At end point of the extension, the between-group differences in change in mean prandial glucose, insulin, and FPG were -2.4 +/- 0.6 mmol/l (P=0.0001), 40 +/- 16 pmol/l (P=0.0153), and -1.1 +/- 0.5 mmol/l (P=0.0312), respectively. HbA1c did not change from week 12 to week 52 in LAF237-treated patients (n=42) but increased in participants given placebo (n=29). The between-group difference in DeltaHbA1c after 1 year was -1.1 +/- 0.2% (P <0.0001).\n Data from this study demonstrate that LAF237 effectively prevents deterioration of glycemic control when added to metformin monotherapy in type 2 diabetes.", "This 24-week double-blind, randomized, multicenter, placebo-controlled, parallel-group study was performed in 632 drug-naïve patients with type 2 diabetes to assess efficacy and tolerability of vildagliptin (50 mg qd, 50 mg bid, or 100 mg qd). HbA1c decreased modestly in patients receiving placebo (Delta=-0.3+/-0.1%) and to a significantly greater extent in patients receiving vildagliptin 50 mg qd (Delta=-0.8+/-0 .1%), 50 mg bid (Delta=-0.8+/-0.1%), or 100 mg qd (Delta=-0.9+/-0.1%, p<0.01 for all groups VS. placebo) from an average baseline of 8.4%. In patients diagnosed >or=3 months before enrollment, HbA1c increased with placebo (Delta=+0.2+/-0.2%) and between-treatment differences (vildagliptin-placebo) were -0.8+/-0.2% (p<0.001), -0.7+/-0.2% (p=0.003), and -0.9+/-0.2% (p<0.001) with vildagliptin 50 mg qd, 50 mg bid, and 100 mg qd, respectively. There was no apparent dose-response in the overall population; however, in patients with high baseline HbA1c, there were greater reductions with either 100 mg dose regimen (Delta=-1.3+/-0.2% and -1.4+/-0.2%) compared to 50 mg qd (Delta=-0.8+/-0.1%). Body weight decreased modestly in all groups (by 0.3 to 1.8 kg). The incidence of adverse events was similar across all groups and <or=1.2% of patients in any treatment group reported mild hypoglycemia. In conclusion, vildagliptin monotherapy decreases HbA1c in drug-naïve patients without weight gain and is well tolerated with minimal hypoglycemia.", "To assess the efficacy and safety of a 24-week treatment with sitagliptin, a highly selective once-daily oral dipeptidyl peptidase-4 (DPP-4) inhibitor, in patients with type 2 diabetes who had inadequate glycaemic control [glycosylated haemoglobin (HbA(1c)) >or=7.5% and <or=10.5%] while on glimepiride alone or in combination with metformin.\n After a screening, diet/exercise run-in and drug wash-off period, a glimepiride +/- metformin dose titration/stabilization period and a 2-week, single-blind placebo run-in, 441 patients (of ages 18-75 years) were randomized to receive the addition of sitagliptin 100 mg once daily or placebo in a 1 : 1 ratio for 24 weeks. Of these patients, 212 were on glimepiride (>or=4 mg/day) monotherapy and 229 were on glimepiride (>or=4 mg/day) plus metformin (>or=1,500 mg/day) combination therapy. Patients exceeding pre-specified glycaemic thresholds during the double-blind treatment period were provided open-label rescue therapy (pioglitazone) until study end. The primary efficacy analysis evaluated the change in HbA(1c) from baseline to Week 24. Secondary efficacy endpoints included fasting plasma glucose (FPG), 2-h post-meal glucose and lipid measurements.\n Mean baseline HbA(1c) was 8.34% in the sitagliptin and placebo groups. After 24 weeks, sitagliptin reduced HbA(1c) by 0.74% (p < 0.001) relative to placebo. In the subset of patients on glimepiride plus metformin, sitagliptin reduced HbA(1c) by 0.89% relative to placebo, compared with a reduction of 0.57% in the subset of patients on glimepiride alone. The addition of sitagliptin reduced FPG by 20.1 mg/dl (p < 0.001) and increased homeostasis model assessment-beta, a marker of beta-cell function, by 12% (p < 0.05) relative to placebo. In patients who underwent a meal tolerance test (n = 134), sitagliptin decreased 2-h post-prandial glucose (PPG) by 36.1 mg/dl (p < 0.001) relative to placebo. The addition of sitagliptin was generally well tolerated, although there was a higher incidence of overall (60 vs. 47%) and drug-related adverse experiences (AEs) (15 vs. 7%) in the sitagliptin group than in the placebo group. This was largely because of a higher incidence of hypoglycaemia AEs (12 vs. 2%, respectively) in the sitagliptin group compared with the placebo group. Body weight modestly increased with sitagliptin relative to placebo (+0.8 vs. -0.4 kg; p < 0.001).\n Sitagliptin 100 mg once daily significantly improved glycaemic control and beta-cell function in patients with type 2 diabetes who had inadequate glycaemic control with glimepiride or glimepiride plus metformin therapy. The addition of sitagliptin was generally well tolerated, with a modest increase in hypoglycaemia and body weight, consistent with glimepiride therapy and the observed degree of glycaemic improvement.", "To assess the efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes and inadequate glycemic control on diet and exercise.\n In a 24-week, randomized, double-blind, placebo-controlled, parallel-group study, 1,091 patients with type 2 diabetes and A1C 7.5-11% were randomized to one of six daily treatments: sitagliptin 100 mg/metformin 1,000 mg (S100/M1000 group), sitagliptin 100 mg/metformin 2,000 mg (S100/M2000 group), metformin 1,000 mg (M1000 group), metformin 2,000 mg (M2000 group) (all as divided doses administered twice daily [b.i.d.]), sitagliptin 100 mg q.d. (S100 group), or placebo. Patients who had an A1C >11% or a fasting glucose value >280 mg/dl after the run-in period were not eligible to be randomized; these patients could participate in an open-label substudy and were treated with S100/M2000 for 24 weeks.\n The mean baseline A1C was 8.8% in the randomized patients. The placebo-subtracted A1C change from baseline was -2.07% (S100/M2000), -1.57% (S100/M1000), -1.30% (M2000), -0.99% (M1000), and -0.83% (S100) (P < 0.001 for comparisons versus placebo and for coadministration versus respective monotherapies). The proportion of patients achieving an A1C <7% and <6.5% was 66 and 44%, respectively, in the S100/M2000 group (P < 0.001 vs. S100 or M2000). For the open-label cohort (n = 117; baseline A1C 11.2%) treated with S100/M2000, the within-group mean A1C change from baseline was -2.9%. The incidence of hypoglycemia was low (0.5-2.2%) across active treatment groups and not significantly different from that in the placebo group (0.6%). The incidence of gastrointestinal adverse experiences was similar for coadministration therapies compared with their respective metformin monotherapy.\n The initial combination of sitagliptin and metformin provided substantial and additive glycemic improvement and was generally well tolerated in patients with type 2 diabetes.", "To examine the efficacy and safety of once-daily oral sitagliptin as monotherapy in patients with type 2 diabetes.\n In a randomized, double-blind, placebo-controlled study, 741 patients (baseline HbA(1c) [A1C] 8.0%) were randomized to sitagliptin 100 or 200 mg or placebo for 24 weeks.\n Sitagliptin 100 and 200 mg produced significant (P < 0.001) placebo-subtracted reductions in A1C (-0.79 and -0.94%, respectively) and fasting plasma glucose (-1.0 mmol/l [-17.1 mg/dl] and -1.2 mmol/l [-21.3 mg/dl], respectively). Patients with baseline A1C >or=9% had greater reductions in placebo-subtracted A1C with sitagliptin 100 and 200 mg (-1.52 and -1.50%, respectively) than those with baseline A1C <8% (-0.57 and -0.65%) or >or=8 to <9.0% (-0.80 and -1.13%, respectively). In a meal tolerance test, sitagliptin 100 and 200 mg significantly decreased 2-h postprandial glucose (PPG) (placebo-subtracted PPG -2.6 mmol/l [-46.7 mg/dl] and -3.0 mmol/l [-54.1 mg/dl], respectively). Results for the above key efficacy parameters were not significantly different between sitagliptin doses. Homeostasis model assessment of beta-cell function and proinsulin-to-insulin ratio improved with sitagliptin. The incidence of hypoglycemia was similar, and overall gastrointestinal adverse experiences were slightly higher with sitagliptin. No meaningful body weight changes from baseline were observed with sitagliptin 100 (-0.2 kg) or 200 mg (-0.1 kg). The body weight change with placebo (-1.1 kg) was significantly (P < 0.01) different from that observed with sitagliptin.\n In this 24-week study, once-daily sitagliptin monotherapy improved glycemic control in the fasting and postprandial states, improved measures of beta-cell function, and was well tolerated in patients with type 2 diabetes.", "The aim of this study was to compare the efficacy and tolerability of vildagliptin vs. pioglitazone as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy.\n This 24-week, multicentre, double-blind, randomized, active-controlled study compared vildagliptin (100 mg daily, given as equally divided doses, n = 295) and pioglitazone (30 mg daily, given as a single q.d. dose, n = 281) in patients with inadequate glycaemic control (A1C 7.5-11%) while receiving a stable metformin dose (> or =1500 mg daily). The adjusted mean changes from baseline to study endpoint (AMDelta) in A1C, fasting plasma glucose (FPG), fasting lipids and body weight were compared by analysis of covariance.\n When added to a stable dose of metformin (mean dose at baseline >2000 mg/day), both vildagliptin and pioglitazone decreased A1C (AMDelta = -0.9 +/- 0.1% and -1.0 +/- 0.1%, respectively) from identical baseline values (8.4 +/- 0.1%). The between-group difference in AMDelta A1C was 0.1 +/- 0.1%, and non-inferiority of vildagliptin to pioglitazone was established at both 0.4 and 0.3% margins for upper limit of the 95% confidence intervals. Pioglitazone decreased FPG (AMDelta = -2.1 +/- 0.1 mmol/l) to a greater extent than vildagliptin (AMDelta = -1.4 +/- 0.1 mmol/l), but only pioglitazone increased body weight (AMDelta = +1.9 +/- 0.2 kg: between-group difference = -1.6 +/- 0.3 kg, p < 0.001). Adverse events (AEs) were reported by 60% of vildagliptin-treated patients and by 56.4% of pioglitazone-treated patients; serious AEs were reported by 2.0 and 4.6% of patients receiving vildagliptin and pioglitazone respectively. Mild hypoglycaemia was reported by one patient (0.3%) in the vildagliptin group and by no patients receiving pioglitazone.\n When added to metformin, the efficacy of vildagliptin is non-inferior to that of pioglitazone. The treatments were similarly well tolerated, but only pioglitazone increased body weight.", "To evaluate the ability of vildagliptin and metformin to sustain reductions in HbA(1c) over a 1-year treatment period in drug-naïve patients with Type 2 diabetes (Type 2 DM).\n Double-blind, randomized, multicentre, active-controlled, parallel-group study of 52-week treatment with vildagliptin (100 mg daily, n = 526) or metformin (titrated to 2000 mg daily, n = 254) in drug-naïve patients (baseline HbA(1c) = 7.5-11.0%). HbA(1c) was measured periodically over 1 year.\n Vildagliptin and metformin each rapidly decreased HbA(1c) from an equal baseline of 8.7%. Most of the HbA(1c) reduction was attained by week 12, and the efficacy was sustained throughout 1-year treatment with both agents. At the study end, significant HbA(1c) reductions from baseline were seen with both vildagliptin (-1.0 +/- 0.1%, P < 0.001) and metformin (-1.4 +/- 0.1%, P < 0.001); however, statistical non-inferiority of 50 mg vildagliptin twice daily to 1000 mg metformin twice daily was not established. Body weight did not change during the 1-year treatment with vildagliptin (0.3 +/- 0.2 kg, P = 0.17) and decreased in metformin-treated patients (-1.9 +/- 0.3 kg, P < 0.001). The proportion of patients experiencing an adverse event was 70.1 vs. 75.4% in patients receiving vildagliptin and metformin, respectively. The proportion of patients experiencing a gastrointestinal adverse event was twofold higher in the metformin group, driven by a 3-4-fold greater incidence of diarrhoea, nausea and abdominal pain. The incidence of hypoglycaemia was similarly low in both groups (< 1%).\n A clinically meaningful decrease in HbA(1c) that was sustained throughout a 1-year treatment in drug-naïve patients with Type 2 DM was seen with both metformin and vildagliptin monotherapy.", "To compare the efficacy and safety of sitagliptin vs. glipizide in patients with type 2 diabetes and inadequate glycaemic control [haemoglobin A(1c) (HbA(1c)) > or = 6.5 and < or = 10%] on metformin monotherapy.\n After a metformin dose titration/stabilization period (> or = 1500 mg/day), 1172 patients were randomized to the addition of sitagliptin 100 mg q.d. (N = 588) or glipizide 5 mg/day (uptitrated to a potential maximum 20 mg/day) (N = 584) for 52 weeks. The primary analysis assessed whether sitagliptin was non-inferior to glipizide regarding HbA(1c) changes from baseline at Week 52 using a per-protocol approach.\n From a mean baseline of 7.5%, HbA(1c) changes from baseline were -0.67% at Week 52 in both groups, confirming non-inferiority. The proportions achieving an HbA(1c) < 7% were 63% (sitagliptin) and 59% (glipizide). Fasting plasma glucose changes from baseline were -0.56 mmol/l (-10.0 mg/dl) and -0.42 mmol/l (-7.5 mg/dl) for sitagliptin and glipizide, respectively. The proportion of patients experiencing hypoglycaemia episodes was significantly (p < 0.001) higher with glipizide (32%) than with sitagliptin (5%), with 657 events in glipizide-treated patients compared with 50 events in sitagliptin-treated patients. Sitagliptin led to weight loss (change from baseline =-1.5 kg) compared with weight gain (+1.1 kg) with glipizide [between-treatment difference (95% confidence interval) =-2.5 kg (-3.1, -2.0); p < 0.001].\n In this study, the addition of sitagliptin compared with glipizide provided similar HbA(1c)-lowering efficacy over 52 weeks in patients on ongoing metformin therapy. Sitagliptin was generally well tolerated, with a lower risk of hypoglycaemia relative to glipizide and with weight loss compared with weight gain with glipizide.", "The aim of this study was to assess the efficacy and safety of sitagliptin (MK-0431) as monotherapy in patients with type 2 diabetes mellitus and inadequate glycaemic control (HbA(1c) > or =7% and < or =10%) on exercise and diet.\n A total of 521 patients aged 27-76 years with a mean baseline HbA(1c) of 8.1% were randomised in a 1:2:2 ratio to treatment with placebo, sitagliptin 100 mg once daily, or sitagliptin 200 mg once daily, for 18 weeks. The efficacy analysis was based on an all-patients-treated population using an analysis of covariance, excluding data obtained after glycaemic rescue.\n After 18 weeks, HbA(1c) was significantly reduced with sitagliptin 100 mg and 200 mg compared with placebo (placebo-subtracted HbA(1c) reduction: -0.60% and -0.48%, respectively). Sitagliptin also significantly decreased fasting plasma glucose relative to placebo. Patients with higher baseline HbA(1c) (> or =9%) experienced greater placebo-subtracted HbA(1c) reductions with sitagliptin (-1.20% for 100 mg and -1.04% for 200 mg) than those with HbA(1c) <8% (-0.44% and -0.33%, respectively) or > or =8% to 8.9% (-0.61% and -0.39%, respectively). Homeostasis model assessment beta cell function index and fasting proinsulin:insulin ratio, markers of insulin secretion and beta cell function, were significantly improved with sitagliptin. The incidence of hypoglycaemia and gastrointestinal adverse experiences was not significantly different between sitagliptin and placebo. Sitagliptin had a neutral effect on body weight.\n Sitagliptin significantly improved glycaemic control and was well tolerated in patients with type 2 diabetes mellitus who had inadequate glycaemic control on exercise and diet.", "Inhibition of dipeptidyl peptidase-4 enhances the activity of incretin hormones, improving glycemic control in subjects with type 2 diabetes. This twelve-week randomized, double-masked, placebo-controlled study assessed the efficacy and tolerability of the specific and potent oral dipeptidyl peptidase-4 inhibitor, vildagliptin (25 mg, bid, n=70) VS. placebo (bid, n=28) in previously diet-treated subjects with type 2 diabetes. Standardized meal tests were performed at baseline and endpoint. The between-group difference in adjusted mean change in HbA1c from baseline to endpoint was - 0.6 +/- 0.2 % (p=0.0012) for the whole cohort (baseline 8.0 %) and -1.2 % for subjects with baseline HbA1c 8.0 - 9.5 %. Fasting glucose and mean prandial glucose were reduced by 1.1 +/- 0.4 (p=0.0043) and 1.9 +/- 0.5 mmol/l (p <0.0001), respectively. The between-group differences in corrected insulin response at peak glucose and mean prandial C-peptide were + 0.06 +/- 0.02 (p=0.0258) and + 0.10 +/- 0.03 nmol/l (p=0.0031), respectively. Vildagliptin had no effect on fasting lipid levels or body weight. The incidence of adverse events was similar in subjects receiving placebo (71.4 %) and vildagliptin (55.7 %).\n monotherapy with vildagliptin is well tolerated and improves glycemic control in diet-treated subjects with type 2 diabetes. Concomitant improvements in beta-cell function were also observed. Subjects with higher baseline HbA1c levels showed greater response.", "A novel treatment option for diabetic patients is the enhancement of incretin hormone activity by inhibition of the enzyme dipeptidyl peptidase-4 (DPP-4). This study was designed to establish a dose of the DPP-4-inhibitor vildagliptin (LAF237) that was effective in reducing HbA1c levels and was safe and well tolerated in patients with type 2 diabetes.\n The study of 279 patients with type 2 diabetes consisted of a 4-week run-in phase where patients received placebo and a 12-week active treatment phase where they received one of the following dosages of vildagliptin: 25 mg twice daily, 25, 50 or 100 mg once daily (qd), or placebo.\n There was a statistically significant reduction in HbA1c levels in the vildagliptin 50 mg qd (p=0.003) and 100 mg qd groups (p=0.004) compared with the placebo group. The mean 4-h postprandial glucose level was significantly reduced from placebo in the vildagliptin 50 mg qd group (p = 0.012) and mean 4-h postprandial insulin was significantly increased from baseline vs. placebo in the vildagliptin 100 mg qd group (p=0.022). The assessment of beta-cell function (HOMA-B) was significantly increased in the vildagliptin 100 mg qd treatment group (p=0.007). The incidence of adverse events was similar in all treatment groups including placebo.\n Vildagliptin, at 50 and 100 mg qd, was effective in reducing HbA1c levels compared with placebo in patients with type 2 diabetes. Vildagliptin at dosages up to 100 mg qd appeared safe and well tolerated.", "To compare the efficacy and tolerability of vildagliptin and rosiglitazone during a 24-week treatment in drug-naïve patients with type 2 diabetes.\n This was a double-blind, randomized, active-controlled, parallel-group, multicenter study of 24-week treatment with vildagliptin (100 mg daily, given as equally divided doses; n = 519) or rosiglitazone (8 mg daily, given as a once-daily dose; n = 267).\n Monotherapy with vildagliptin and rosiglitazone decreased A1C (baseline = 8.7%) to a similar extent during the 24-week treatment, with most of the A1C reduction achieved by weeks 12 and 16, respectively. At end point, vildagliptin was as effective as rosiglitazone, improving A1C by -1.1 +/- 0.1% (P < 0.001) and -1.3 +/- 0.1% (P < 0.001), respectively, meeting the statistical criterion for noninferiority (upper-limit 95% CI for between-treatment difference < or =0.4%). Fasting plasma glucose decreased more with rosiglitazone (-2.3 mmol/l) than with vildagliptin (-1.3 mmol/l). Body weight did not change in vildagliptin-treated patients (-0.3 +/- 0.2 kg) but increased in rosiglitazone-treated patients (+1.6 +/- 0.3 kg, P < 0.001 vs. vildagliptin). Relative to rosiglitazone, vildagliptin significantly decreased triglycerides, total cholesterol, and LDL, non-HDL, and total-to-HDL cholesterol (-9 to -16%, all P < or = 0.01) but produced a smaller increase in HDL cholesterol (+4 vs. +9%, P = 0.003). The proportion of patients experiencing an adverse event was 61.4 vs. 64.0% in patients receiving vildagliptin and rosiglitazone, respectively. Only one mild hypoglycemic episode was experienced by one patient in each treatment group, while the incidence of edema was greater with rosiglitazone (4.1%) than vildagliptin (2.1%).\n Vildagliptin is an effective and well-tolerated treatment option in patients with type 2 diabetes, demonstrating similar glycemic reductions as rosiglitazone but without weight gain.", "The aim of this study was to compare efficacy and tolerability of initial combination therapy with vildagliptin/pioglitazone to component monotherapy.\n This 24-week, multicentre, randomized, double-blind, active-controlled study assessed the effects of the dipeptidyl peptidase-4 inhibitor vildagliptin (100 mg q.d.), pioglitazone (30 mg q.d.) and vildagliptin combined with pioglitazone (100/30 mg q.d. or 50/15 mg q.d.) in 607 drug-naive patients with type 2 diabetes (T2DM). The primary outcome measure was change from baseline in HbA(1c) in patients receiving initial combination therapy compared with pioglitazone monotherapy.\n After 24-week treatment, adjusted mean changes in HbA(1c) from baseline (approximately 8.7%) in patients receiving pioglitazone monotherapy, 50/15 mg combination, 100/30 mg combination and vildagliptin monotherapy were -1.4 +/- 0.1%, -1.7 +/- 0.1%, -1.9 +/- 0.1% and -1.1 +/- 0.1% respectively. Both low-dose and high-dose combinations were significantly more efficacious than pioglitazone alone (p = 0.039 and p < 0.001 respectively). Adjusted mean changes in fasting plasma glucose were -1.9 +/- 0.2, -2.4 +/- 0.2, -2.8 +/- 0.2 and -1.3 +/- 0.2 mmol/l respectively, and both combination groups were significantly more effective than pioglitazone monotherapy (p = 0.022 and p < 0.001 respectively). The overall incidence of adverse events ranged from 45.8% in the low-dose combination to 51.6% in the pioglitazone monotherapy group. The incidence of peripheral oedema was highest in patients receiving pioglitazone monotherapy (9.3%) and lowest in those receiving low-dose combination (3.5%). One mild hypoglycaemic event was reported by one patient receiving high-dose combination and one patient receiving vildagliptin monotherapy.\n First-line treatment with vildagliptin/pioglitazone combination in patients with T2DM provides better glycaemic control than either monotherapy component yet has minimal risk of hypoglycaemia and a tolerability profile comparable with component monotherapy.", "Type 2 diabetes is difficult to manage in patients with a long history of disease requiring insulin therapy. Moreover, addition of most currently available oral antidiabetic agents increases the risk of hypoglycaemia. Vildagliptin is a dipeptidyl peptidase-IV inhibitor, which improves glycaemic control by increasing pancreatic beta cell responsiveness to glucose and suppressing inappropriate glucagon secretion. This study assessed the efficacy and tolerability of vildagliptin added to insulin therapy in patients with type 2 diabetes.\n This was a multicentre, 24-week, double-blind, randomised, placebo-controlled, parallel-group study in patients with type 2 diabetes that was inadequately controlled (HbA(1c) = 7.5-11%) by insulin. Patients received vildagliptin (n = 144; 50 mg twice daily) or placebo (n = 152) while continuing insulin therapy.\n Baseline HbA(1c) averaged 8.4 +/- 0.1% in both groups. The adjusted mean change from baseline to endpoint (AMDelta) in HbA(1c) was -0.5 +/- 0.1% and -0.2 +/- 0.1% in patients receiving vildagliptin or placebo, respectively, with a significant between-treatment difference (p = 0.01). In patients aged >/=65 years, the AMDelta HbA(1c) was -0.7 +/- 0.1% in the vildagliptin group vs -0.1 +/- 0.1% in the placebo group (p < 0.001). The incidence of adverse events was similar in the vildagliptin (81.3%) and placebo (82.9%) groups. However, hypoglycaemic events were less common (p < 0.001) and less severe (p < 0.05) in patients receiving vildagliptin than in those receiving placebo.\n Vildagliptin decreases HbA(1c) in patients whose type 2 diabetes is poorly controlled with high doses of insulin. Addition of vildagliptin to insulin therapy is also associated with reduced confirmed and severe hypoglycaemia. ClinicalTrials.gov ID no.: NCT 00099931.", "The purpose of this study was to assess the efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor vildagliptin in combination with the thiazolidinedione (TZD) pioglitazone in patients with type 2 diabetes (T2DM).\n This was a 24-week, multicentre, double-blind, randomized, parallel-group study comparing the effects of vildagliptin (50 or 100 mg daily) with placebo as an add-on therapy to pioglitazone (45 mg daily) in 463 patients with T2DM inadequately controlled by prior TZD monotherapy. Between-treatment comparisons of efficacy parameters were made by analysis of covariance model.\n The adjusted mean change (AM Delta) in haemoglobin A(1c) from baseline to endpoint was -0.8 +/- 0.1% (p = 0.001 vs. placebo) and -1.0 +/- 0.1% (p < 0.001 vs. placebo), respectively, in patients receiving vildagliptin 50 or 100 mg daily. Relative to baseline, vildagliptin added to pioglitazone also reduced fasting plasma glucose (FPG) (AM Delta FPG =-0.8 +/- 0.2 mmol/l and -1.1 +/- 0.2 mmol/l; not significant (NS) vs. placebo) and postprandial glucose (PPG) [AM Delta PPG =-1.9 +/- 0.6 mmol/l and -2.6 +/- 0.6 mmol/l (p = 0.008 vs. placebo)] for 50 and 100 mg daily respectively. Relative to placebo, both doses of vildagliptin significantly increased the insulin secretory rate/glucose by more than threefold. The overall incidence of adverse events (AEs) was 55.5, 50.0 and 48.7% in patients receiving vildagliptin 50 mg, 100 mg daily or placebo respectively. Serious AEs were experienced by 6.8, 1.3 and 5.7% of patients receiving vildagliptin 50 mg, 100 mg daily or placebo respectively. Mild hypoglycaemia was reported by 0, 0.6 and 1.9% of patients, respectively, receiving vildagliptin 50 mg, 100 mg daily or placebo.\n Vildagliptin is effective and well tolerated when added to a maximum dose of pioglitazone, without increasing the risk of hypoglycaemia.", "The aim of this study was to assess the efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes who have inadequate glycaemic control on diet and exercise. In a randomised, double-blind, placebo- and active-controlled study, 743 patients with type 2 diabetes and a mean baseline HbA(1c) of 7.9% were randomised to receive one of six treatments for 12 weeks: placebo, sitagliptin 5, 12.5, 25 or 50 mg b.i.d., or glipizide 5 mg/day (electively titrated up to 20 mg/day). At week 12, treatment with sitagliptin at all doses tested led to a significant (p < 0.001) reduction in HbA(1c) relative to placebo, with the largest reductions occurring in the 50-mg b.i.d. group. The placebo-subtracted differences in HbA(1c) for the sitagliptin dose groups ranged from -0.38% to -0.77% in a dose-dependent manner, and -1.00% in the glipizide group. Sitagliptin also produced significant reductions in fasting plasma glucose and mean daily glucose across the dose range studied. Sitagliptin treatment was well tolerated and resulted in no significant weight change relative to placebo. There was a modest weight gain observed with glipizide treatment relative to placebo. Hypoglycaemia adverse experiences were reported with the highest incidence in the glipizide group (17%) compared with the placebo (2%) or sitagliptin groups (0-4%, not dose-dependent). In summary, in this study sitagliptin improved glycaemic control, with 50 mg b.i.d. being the most effective dose, and was generally well-tolerated in patients with type 2 diabetes." ]

[ "9389394", "11109037", "6096982", "10024861" ]

[ "Cutaneous closure after cardiac operations: a controlled, randomized, prospective comparison of intradermal versus staple closures.", "Clips versus suture technique: is there a difference?", "Comparative study of leg wound skin closure in coronary artery bypass graft operations.", "Reduction of leg wound infections following coronary artery bypass surgery." ]

[ "To determine the difference in wound complication and infection rates between suture and staple closure techniques applied to clean incisions in coronary bypass patients.\n The true incidence of postoperative wound complications, and their correlation with closure techniques, has been obscured by study designs incorporating small numbers, retrospective short follow-up, uncontrolled host factors, and narrowly defined complications.\n Sternal and leg wounds were studied prospectively, each patient serving as his or her own control. Two hundred forty-two patients with sternal and saphenous vein harvest wounds had half of each wound closed with staples and the other half with intradermal sutures (484 sternal and 516 leg segments). Wound complications were defined as drainage, erythema, separation, necrosis, seroma, or infection. Infections were identified in the subset having purulent drainage, antibiotic therapy, or debridement. Wounds were examined at discharge, at 1 week after discharge, and at 3 to 4 weeks after operation. Patient preferences for closure type were assessed 3 to 4 weeks after operation.\n Neither leg nor sternal wounds had a statistically significant difference in infection rate according to closure method (leg sutured = 9.3% vs. leg stapled = 8.9%; p = 0.99, and sternal sutured = 0.4% vs. sternal stapled = 2.5%; p = 0.128). There was, however, a greater complication rate in stapled segments (leg stapled = 46.9% vs. leg sutured = 32.6%; p = 0.001, and sternal stapled = 14.9% vs. sternal sutured = 3.7%; p = 0.00005). Sutures were favored over staples among patients who expressed a preference (sternal = 75.6%, leg = 74.6%).\n With the host factors controlled by pairing staples and sutures in each patient, we demonstrated a similar incidence of infection but a significantly lower incidence of total wound complications with intradermal suture closure than with staple closure.", "Coronary artery bypass grafting (CABG) is one of the most common procedures performed today, and wound complications are a major source of morbidity and cost.\n To determine whether there is any difference in wound outcome (including cost in a Canadian context) between a subcuticular suture technique and skin stapling technique for closure of sternal and leg incisions in CABG patients.\n One hundred and sixty-two patients undergoing CABG were prospectively, randomly placed to have their sternal and leg incisions closed with either a subcuticular suture technique or with a skin clip. Data were obtained through chart review, in-hospital assessments and follow-up visits. Nonblinded assessments were made regarding wound leakage, inflammation, infection, necrosis, swelling, dehiscence and cosmesis. Each of the parameters was graded on a scale from 1 to 4. The cost was evaluated in Canadian dollars.\n There were trends toward increased rates of in-hospital sternal (P=0.09) and leg (P=0.17) incision inflammation when the wounds were closed with skin clips. There was a significantly greater (P=0.05) rate of sternal wound infection with clips, as well as a tendency (P=0.15) toward a greater rate of mediastinitis at follow-up assessment. Cosmetic outcome was similar for both groups. The cost incurred was significantly greater when skin clips were used for closure. There was a greater than threefold difference, which translates to a greater than $10,000 difference over one year.\n Closure with a subcuticular technique achieves better outcomes than the use of skin clips. When factoring in the increased cost incurred by using clips, as well as other intangible factors such as surgical skill acquisition, subcuticular suture closure appears to be a favourable method of wound closure in CABG patients compared with the use of skin stapling techniques.", "A prospective randomised study of four different methods of leg wound skin closure after removal of the long saphenous vein was carried out in 113 patients undergoing coronary artery bypass grafting. These methods were: (1) continuous nylon vertical mattress suture (27 patients); (2) continuous subcuticular absorbable (Dexon) suture (29 patients); (3) metal skin staples (Autosuture) (27 patients); and (4) adhesive sutureless skin closure (\"Op-site\") (30 patients). All wounds were examined by two independent observers at five, 10, and 45 days after operation. At five days, inflammation, extent of oedema, discharge, and infection were assessed. At 10 days attention was paid to the state of wound healing and at 45 days to the final cosmetic appearance. The use of continuous subcuticular suture resulted in significantly less discharge than did the use of metal staples, nylon vertical mattress suture, or Op-site. The incidence of established wound infection was 4.5% overall, with no infection in the wounds closed with Dexon. Assessment of the healing process showed subcuticular Dexon to be more effective than metal staples or vertical mattress nylon suture. The final cosmetic result showed continuous subcuticular suture to be superior to nylon vertical mattress suture and skin staples but as effective as Op-site sutureless skin closure.", "To reduce the rate of infection at the saphenous vein harvest site after coronary artery bypass surgery, to identify predictors of infection and to determine the best method for leg wound closure.\n A randomized clinical trial was undertaken to determine the best technique for reducing the postoperative leg wound infection rate. Patients were allocated to one of four leg wound closure methods: staples, close immediately; staples, close after protamine administration; subcuticular sutures, close immediately; and subcuticular sutures, close after protamine. Risk factors evaluated were age, sex, diabetes, obesity, peripheral vascular disease, reoperation, time in surgery, wound length, wound depth, time that the wound was open, wound quality and harvest site.\n The Walter C Mackenzie Health Sciences Centre, University of Alberta, Edmonton, Alberta.\n All consenting patients undergoing elective coronary artery bypass surgery involving saphenous vein harvesting were considered for the study. Exclusion criteria were insertion of a drain, insertion of an intra-aortic balloon pump in the index limb and inability to complete follow-up at the authors' centre. Eighty patients were initially enrolled, with 77 completing the study.\n Patients underwent standard saphenous vein harvesting followed by wound closure as indicated by the study group.\n The major infection rate was reduced from 13% to 3% (P = 0.02). Each closure method was equally effective, and wound depth was the only factor related to infection.\n Leg wound infections continue to be a major source of morbidity after coronary bypass surgery." ]

[ "15209959", "1466940", "4398815", "9265991", "17561929", "17941284" ]

[ "Safety and efficacy of oral fexofenadine in children with seasonal allergic rhinitis--a pooled analysis of three studies.", "A multicentre randomized placebo-controlled double-blind study on the efficacy of Ketotifen in infants with chronic cough or wheeze.", "[Palliative treatment of estival rhinitis in children. A double blind combined study of an antiamine, pimethixen, and an antihistamine, Paradryl].", "Cetirizine treatment of allergic cough in children with pollen allergy.", "Safety of levocetirizine treatment in young atopic children: An 18-month study.", "Safety and tolerability of fexofenadine for the treatment of allergic rhinitis in children 2 to 5 years old." ]

[ "Allergic rhinitis is one of the most common clinical conditions in children; however, data regarding the safety of antihistamines in children with seasonal allergic rhinitis are limiting. To evaluate the safety and efficacy of fexofenadine in children with seasonal allergic rhinitis, data were pooled from three, double-blind, randomized, placebo-controlled, parallel-group, 2-week trials in children (6-11 year) with seasonal allergic rhinitis. All studies assessed fexofenadine HCl 30 mg b.i.d.; two studies included fexofenadine HCl at 15 and 60 mg b.i.d. Patients (and investigators) reported any adverse events during the trial. Physical examinations, including measurements of vital signs and laboratory tests, were performed. Efficacy assessments (total symptom score and individual symptom scores) were evaluated. Exposure to fexofenadine HCl 30 mg b.i.d. and to any fexofenadine dose exceeded 10,000 and 17,000 patient days, respectively. Incidences of adverse events, and discontinuations because of adverse events, were low and similar across treatment groups. In the placebo group, 24.4% of subjects reported adverse events compared with 24.1% for fexofenadine HCl 30 mg b.i.d., and 28.4% for all fexofenadine-treated groups. The most common adverse event overall was headache (4.3% placebo; 5.8% fexofenadine HCl 30 mg b.i.d.; and 7.2% any fexofenadine doses). Treatment-related adverse events were similar across treatment groups with no sedative effects. Fexofenadine HCl 30 mg b.i.d. was significantly superior to placebo in reducing the total symptom score and all individual seasonal allergic rhinitis symptoms, including nasal congestion (p < 0.05). Fexofenadine, at doses of up to 60 mg b.i.d., is safe and non-sedating, and fexofenadine HCl 30 mg b.i.d. effectively reduces all seasonal allergic rhinitis symptoms in children aged 6-11 years.\n Copyright 2004 Blackwell Munksgaard", "The efficacy of Ketotifen was examined in the treatment of 113 infants between 6 and 36 months of age presenting with a history of cough and/or wheeze in a multicentre randomized placebo-controlled double-blind study. A 4 week no-medication baseline phase preceded the 16 week treatment phase in which infants took 2.5 mL twice daily of either placebo or Ketotifen (0.5 mg) syrup; this was followed by a 4 week wash-out phase. Diary card evaluation was performed by the parent or guardian for the duration of the study and recorded wheeze and cough twice daily as well as medication used. The percentage of symptom-free days decreased significantly in both groups (P < 0.005) with placebo-treated infants experiencing significantly more symptom-free days compared with the Ketotifen group (P < 0.01), although this difference was never more than 10% in any 4 week treatment period. Symptom severity scores and use of beta-agonist medication were also less in the placebo-treated infants but did not reach statistical significance. This study was unable to show a therapeutic advantage of Ketotifen over placebo in this group of infants with chronic cough and/or wheeze and the apparent statistical advantage of placebo is not a clinically relevant finding.", "nan", "Cetirizine, an antihistamine widely used in the treatment of allergic rhinoconjunctivitis, also has antiallergic activity. The present study aimed to evaluate cetirizine as a treatment for children with allergic cough due to pollen allergy. This was a parallel-group, double-blind, placebo-controlled, randomized study. Twenty children with pollinosis were enrolled: they were subdivided into two groups receiving a 1-month treatment during the pollen season. The following variables were monitored: 1) clinical symptoms and respiratory data (spirometry and PEF) evaluated at baseline and at the end of the study by allergists and by a daily diary card, and 2) pollen count. This study shows that cetirizine treatment reduces cough intensity (P < 0.05) and frequency (P < 0.01). In conclusion, cetirizine does clinically improve cough due to pollen allergy.", "There are more than 40 H(1)-antihistamines available worldwide. Most of these medications have never been optimally studied in prospective, randomized, double-masked, placebo-controlled trials in children. The aim was to perform a long-term study of levocetirizine safety in young atopic children. In the randomized, double-masked Early Prevention of Asthma in Atopic Children Study, 510 atopic children who were age 12-24 months at entry received either levocetirizine 0.125 mg/kg or placebo twice daily for 18 months. Safety was assessed by: reporting of adverse events, numbers of children discontinuing the study because of adverse events, height and body mass measurements, assessment of developmental milestones, and hematology and biochemistry tests. The population evaluated for safety consisted of 255 children given levocetirizine and 255 children given placebo. The treatment groups were similar demographically, and with regard to number of children with: one or more adverse events (levocetirizine, 96.9%; placebo, 95.7%); serious adverse events (levocetirizine, 12.2%; placebo, 14.5%); medication-attributed adverse events (levocetirizine, 5.1%; placebo, 6.3%); and adverse events that led to permanent discontinuation of study medication (levocetirizine, 2.0%; placebo, 1.2%). The most frequent adverse events related to: upper respiratory tract infections, transient gastroenteritis symptoms, or exacerbations of allergic diseases. There were no significant differences between the treatment groups in height, mass, attainment of developmental milestones, and hematology and biochemistry tests. The long-term safety of levocetirizine has been confirmed in young atopic children.", "The safety of fexofenadine has been examined extensively in adults and school-age children. However, the safety of fexofenadine in children younger than 6 years has not been reported to date.\n To compare the safety and tolerability of twice-daily fexofenadine hydrochloride, 30 mg, and placebo in preschool children aged 2 to 5 years with allergic rhinitis.\n This was a multicenter, double-blind, randomized, placebo-controlled, parallel-group study, conducted between February 29, 2000, and June 14, 2001. Participants were randomized to either fexofenadine hydrochloride, 30 mg, or placebo twice daily for a 2-week period. To facilitate dosing, capsule content was mixed with applesauce (approximately 10 mL). Safety assessments depended on date of entry into the study because of an amendment to the protocol. Before the amendment, assessments included physical examination, vital signs reporting (oral temperature, heart rate, and respiratory rate), and adverse event (AE) reporting. After the amendment, safety assessments included laboratory testing (blood chemistry and hematology profiles), physical examination, 12-lead electrocardiography, and vital signs (oral temperature, blood pressure, heart rate, and respiratory rate) and AE reporting.\n Treatment-emergent AEs were observed in 116 of 231 participants receiving placebo and 111 of 222 receiving fexofenadine. These AEs were possibly related to study medication in 19 (8.2%) and 21 (9.5%) of the participants receiving placebo and fexofenadine, respectively, and most frequently involved the digestive system. No clinically relevant differences in laboratory measures, vital signs, and physical examinations were observed.\n The findings show that fexofenadine hydrochloride, 30 mg, is well tolerated and has a good safety profile in children aged 2 to 5 years with allergic rhinitis." ]

[ "10322887", "8732151", "8880292", "14626197", "8721940", "11194229", "11922229", "2201413", "9812648", "11789185", "12575375", "11477815", "8593925", "9812643", "11477863", "11789183", "10322847" ]

[ "[Effect of sanhuang jiangtang recipe on insulin peripheral resistance in type II diabetics].", "[Effect of bushenhuoxue tablet on serum lipid peroxide, blood lipid and blood sugar in type II diabetics].", "Randomized placebo-controlled, single blind trial of holy basil leaves in patients with noninsulin-dependent diabetes mellitus.", "[Effect of Astragalus injection on insulin resistance in auxiliary treating patients with diabetes mellitus type 2].", "Ginseng therapy in non-insulin-dependent diabetic patients.", "Efficacy of Tibetan medicine as an adjunct in the treatment of type 2 diabetes.", "A randomized placebo controlled trial of Inolter (herbal product) in the treatment of type 2 diabetes.", "Clinical trial of Myrcia uniflora and Bauhinia forficata leaf extracts in normal and diabetic patients.", "[Clinical study of glibenclamide in combination with kelening treatment in non-insulin dependent diabetes mellitus].", "[Clinical study in treating type 2 diabetes mellitus according to liver in TCM].", "[Effect of qidan tongmai tablet on glucose and lipid metabolism in patients with diabetes mellitus type 2].", "[Effects of Chinese herbs xianzhen tablet on the deformability of erythrocyte in non-insulin-dependent diabetes mellitus patients with deficiency of both qi and yin and deficiency of kidney with blood stasis].", "Randomized study of glibenclamide versus traditional Chinese treatment in type 2 diabetic patients. Chinese-French Scientific Committee for the Study of Diabetes.", "[Effect of xianzhen tablet on Na(+)-K(+)-ATPase, Ca(2+)-Mg(2+)-ATPase, of red blood cell membrane in patients with non-insulin dependent diabetes mellitus].", "[Treatment of diabetes mellitus by integrated traditional Chinese and western medicine].", "[Effect of yiqi yangyin huoxue recipe on endothelin and nitric oxide of type 2 diabetic patients with deficiency of both Qi-Yin and blood stasis syndrome].", "[Effect of jiangtangkang on blood glucose, sensitivity of insulin and blood viscosity in non-insulin dependent diabetes mellitus]." ]

[ "To observe the effect of Sanhuang Jiangtang recipe (SHJT) on insulin peripheral resistance in type II diabetics.\n Ninety-five patients with type II diabetics were randomly divided into two groups. Fifty-three cases of SHJT group were given orally decoction and tablets of SHJT for 4-6 months. The efficacy was compared with that of 42 cases treated with Glipizide as the control. Before and after treatment standard steamed bread meal test was performed to measure the insulin peripheral sensitivity, insulin release to glucose and insulin sensitivity index.\n (1) The total effective rates of improving insulin peripheral resistance and reducing blood sugar in SHJT group were 79.2% and 80.1%, which was equivalent to levels in the control group, but SHJT recipe was more effective in relieving symptoms of Qi deficiency and signs of blood stasis. (2) In SHJT group, the insulin peripheral sensitivity and insulin sensitivity index were significantly increased (P < 0.05 and P < 0.01), meanwhile the fasting blood sugar and blood sugar area were reduced (P < 0.05), but the change of insulin release to glucose was blunted. (3) The lowering of blood sugar in SHJT group was significantly negative correlated with the changing of degree of insulin peripheral sensitivity and index of insulin sensitivity (P < 0.01 and P < 0.05), but not with that of insulin area.\n It suggested that the treatment of SHJT recipe might decrease insulin peripheral resistance (partial reversal) by means of reducing hyperinsulinemia and improving insulin sensitivity.", "Sixty-eight patients suffering from diabetes mellitus (DM) type II with Kidney Deficiency and blood stasis were enrolled and divided randomly into treatment group (34 cases) and placebo group (34 healthy subjects). The amount of serum lipid peroxide (LPO), blood lipid and blood sugar was determined. The results showed that the serum LPO in treatment group was higher than that in placebo group. The serum LPO increased significantly in DM patients with vascular disease or with uncontrolled blood sugar. The serum LPO was positively correlated with triglyceride (TG). After using Bushenhuoxue Tablet (BSHX) serum LPO lowered, blood sugar decreased and high density lipoprotein-cholesterol (HDL-C)increased in treatment group, but in placebo group these three parameters were not changed significantly. These results indicated that LPO reaction in type II DM patients increased. The higher the blood sugar and TG or complicated with vascular disease, the LPO reaction enhanced markedly. BSHX tablets have the function of reducing the serum LPO and blood sugar, clearing cholesterol. Therefore, this tablet will have a good prospect in the prevention and treatment for DM patients complicated with vascular disease.", "Experimental studies on albino rats reported that leaf extract of Ocimum sanctum and Ocimum album (holy basil) had hypoglycemic effect. To explore further evidence we studied the effects of treatment with holy basil leaves on fasting and postprandial blood glucose and serum cholesterol levels in humans through randomized, placebo-controlled, crossover single blind trial. Results indicated a significant decrease in fasting and postprandial blood glucose levels during treatment with holy basil leaves compared to during treatment with placebo leaves. Fasting blood glucose fell by 21.0 mg/dl, confidence interval of difference -31.4 - (-)11.2 (p < 0.001), and postprandial blood glucose fell by 15.8 mg/dl, confidence interval -27.0 - (-)5.6 (p < 0.02). The lower values of glucose represented reductions of 17.6% and 7.3% in the levels of fasting and postprandial blood glucose, respectively. Urine glucose levels showed similar trend. Mean total cholesterol levels showed mild reduction during basil treatment period. The findings from this study suggest that basil leaves may be prescribed as adjunct to dietary therapy and drug treatment in mild to moderate NIDDM.", "nan", "To investigate the effect of ginseng on newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients.\n In this double-blind placebo-controlled study, 36 NIDDM patients were treated for 8 weeks with ginseng (100 or 200 mg) or placebo. Efficacy was evaluated with psychophysical tests and measurements of glucose balance, serum lipids, aminoterminalpropeptide (PIIINP) concentration, and body weight.\n Ginseng therapy elevated mood, improved psychophysical performance, and reduced fasting blood glucose (FBG) and body weight. The 200-mg dose of ginseng improved glycated hemoglobin, serum PIIINP, and physical activity. Placebo reduced body weight and altered the serum lipid profile but did not alter FBG.\n Ginseng may be a useful therapeutic adjunct in the management of NIDDM.", "nan", "To evaluate the safety and effectiveness of Inolter in achieving glycemic control and changes in lipid profile of newly diagnosed type 2 diabetics.\n Study design: A randomized, placebo-controlled double blind. Sixty newly diagnosed patients of type-2 diabetes were randomized. Of these, 30 were put on Inolter monotherapy and 30 patients on placebo. Efficacy of Inolter was determined by observing glycemic control by estimating glycosylated haemoglobin (HbA1c) and fasting blood sugar (FBS), alteration of lipid profile by serum cholesterol, LDL, VLDL, HDL and triglycerides.\n Student's unpaired 't' test.\n Patients compliance was satisfactory and no adverse effects were observed. Better hypoglycemic effect was observed with Inolter both respect to fasting blood sugar (mean 65.4 +/- 63.72 mg/dl) compared to placebo (mean 26.45 +/- 38.3 mg/dl) (p < 0.001). The mean change, with Inolter, in serum cholesterol (21.33 +/- 26.05 mg/dl), serum triglyceride (30.36 +/- 32.62 mg/dl), VLDL (8.85 +/- 3.25 mg/dl), LDL (10.00 +/- 4.48 mg/dl) and HDL (-2.33 +/- 5.66 mg/dl) was also significantly different (p < 0.001) from those given placebo, where it was 15.7 +/- 20.14 mg/dl, 8.70 +/- 13.24, 0.10 +/- 4.10 mg/dl, -0.70 +/- 4.58 mg/dl and 0.65 +/- 0.00 mg/dl, respectively.\n Inolter appears to be an useful adjunctive therapy to exercise and diet control in newly diagnosed type 2 diabetes mellitus.", "1. Myrcia uniflora and Bauhinia forficata were compared with placebo for their hypoglycemic effect in randomized cross-over double-blind studies in 2 groups of normal subjects (10 subjects each) and 2 groups of Type II diabetic patients (18 in the M. uniflora group and 16 in the B. forficata group). The protocol with each plant lasted 56 days. 2. After the ingestion of infusions of 3 g leaves/day of M. uniflora and B. forficata leaves, no acute or chronic effects on plasma glucose levels or glycated hemoglobin were found in either group. However, plasma insulin levels in the diabetic group were lower after M. uniflora than after placebo. 3. Among other clinical parameters tested, a statistically significant difference was found only in the alkaline phosphatase level after placebo compared with that after M. uniflora in the normal group. 4. There were no differences in any clinical parameters after the use of placebo or of B. forficata. 5. We conclude that infusions prepared from the leaves of M. uniflora or B. forficata have no hypoglycemic effect on normal subjects or Type II diabetic patients.", "To asses the efficacy of combination therapy of glibenclamide and Kelening in treating the non-insulin dependent diabetes mellitus (NIDDM).\n Sixty-five patients with NIDDM were randomly divided into two groups. One group was treated with both glibenclamide and Kelening, the other with glibenclamide alone.\n After treatment for 12 weeks, the levels of fasting blood glucose (FBG), postprandial blood glucose (PBG) and HBAIC were reduced significantly in glibenclamide-Kelening group. In both groups, the degree dropped of the levels of FBG were almost the same, but the levels of PBG and HBAIC in glibenclamide-Kelening group were reduced more significantly than those in glibenclamide group, and the incidence of hyperinsulinemia had dropped considerably.\n Glibenclamide in combination with Kelening in the treatment of NIDDM is more effective and less toxic, and the combination may reduce the dosage of glibenclamide in NIDDM.", "To explore the clinical effect of Danzhi Xiaoyao powder (DZXY) in treating type 2 diabetes mellitus (DM) according to Liver in TCM.\n Fifty-one type 2 DM patients were randomly divided into the treated group and the control group, 31 patients of the treated group were treated with conventional and DZXY therapy, while 20 patients in the control were treated with conventional therapy alone. Before and after treatment for 3 months, the levels of fasting blood glucose (FBG), fasting insulin, glycosylated hemoglobin (HbA1c), blood cholesterol (CH) and triglycerides (TG) were examined in all the patients.\n By the end of 3 months, the effect in treating type 2 DM in the treated group was better than that in the control group (P < 0.05). Compared with those before treatment in each group and those of the control, the levels of FBG, fasting insulin, HbA1c after DZXY treatment were reduced (P < 0.05), but levels of CH and TG in all groups had no significant difference.\n DZXY could soothe the Liver to relieve depression, which is effective in treating type 2 DM and could improve the symptoms of DM patients.", "To study the effect of Qidan Tongmai tablet (QDTMT) on glucose and lipid metabolism in patients with diabetes mellitus (DM) type 2.\n Patients of DM, with or without hyperlipidemia complication (HLC) were divided into 4 groups, Group A (33 cases without HLC) and B (33 cases with HLC) were treated by QDTMT, Group C (31 cases without HLC) and D (31 cases with HLC) were not treated by QDTMT. The treatment was carried out on the previous basic hypoglycemic treatment with a therapeutic course of 2 months.\n The levels of fasting glucose, 2 hrs postprandial blood glucose and glycosylated hemoglobin, as well as the levels of total cholesterol and triglyceride lowered, and the high density lipoprotein increased in Group A and B after treatment, as compared with those before treatment, the difference was significant (P < 0.01). While in Group C and D, the above-mentioned indexes were not changed significantly (P > 0.05). No apparent side-effect was found in the QDTMT treatment period.\n Besides regulating abnormal blood lipid, QDTMT has also a hypoglycemic effect in certain degree in patients with DM type 2.", "To explore the effects of Xianzhen Tablet (XZT) on the hemorheology of type 2 diabetes (NIDDM) on the basis of previous studies in XZT, that have indicated its ability to deplete fasting blood glucose, to reduce the injury of free radical to the body, to improve the Na(+)-K(+)-ATPase in the erythrocyte membrane of NIDDM.\n Erythrocyte deformability and aggregation were studied with Ektacytometer in a total of 60 type 2 diabetes who were randomly divided into two groups. One was ZXT treated group, another was placebo group.\n (1) The erythrocyte deformability of type 2 diabetes was lower than that in normal subjects (P < 0.001), but the erythrocyte aggregation increased abnormally than that of health people (P < 0.001). The correlation test indicated there were negative correlation with plasma fibronogen and positive correlation with blood cholesterol (P < 0.05). (2) The erythrocyte deformability in the ZXT treated group with 30 patients improved after 8 weeks treatment (P < 0.01), with the decreased fasting blood glucose and plasma fibrinogen (P < 0.05). Compared with placebo group, there was significant statistical difference (P < 0.01).\n XZT could improve the erythrocyte deformability in the type 2 diabetes.", "The purpose of this study was to evaluate the efficacy of a traditional Chinese treatment (TCT) based on three plants in association with a sulfonylurea, glibenclamide (2.5 mg X 3/d). A 2 X 2 factorial design was adopted for this multicentre randomized double-blind trial involving 4 groups [A = placebo (P) TCT + P glibenclamide; B = P TCT + verum glibenclamide; C = verum TCT + P glibenclamide; D = verum TCT + verum glibenclamide]. Patients included were type 2 diabetic outpatients, 40-70 years of age, treated by diet alone or oral anti-diabetic drugs. Endpoint criteria evaluated were HbA1, blood glucose and plasma insulin (at fasting, and 1 and 2 h after a test meal). At each visit, a clinical examination was performed, and a questionnaire on side effects and associated symptoms was completed. The dose was reduced by half in the case of hypoglycaemia. The 216 patients were recruited in 5 centres [Shanghai (1) = 48, Shanghai (2) = 40, Beijing = 40, Canton = 42, Chengdu = 46 and randomized into treatment groups A, B, C, D (56, 56, 50 and 54 respectively). Eleven patients were withdrawn for administrative reasons. In patients treated with glibenclamide, a significant increase in weight and insulinaemia was observed, together with a significant decrease in blood glucose values; in those receiving TCT, blood glucose values were significantly decreased only 2 h after the test meal. A synergistic effect on blood glucose was observed when both treatments were given. Hypoglycaemia occurred in 19 patients (all in the two verum glibenclamide groups). This first multicentre controlled trial showed that the 3 Chinese plants tested were well-tolerated and effective in Type 2 diabetes as indicated by a significant synergistic effect in association with a sulfonylurea.", "To assess the effect of Xianzhen tablet in treating non-insulin dependent diabetes mellitus (NIDDM).\n Seventy-two cases of NIDDM patients with deficiency of both Qi and Yin, deficiency of the Kidney and blood stasis were selected, and the effects of treatment on Na(+)-K(+)-ATPase, Ca(2+)-Mg(2+)-ATPase, whole blood viscosity, blood sugar and clinical symptoms were observed.\n After treatment, the treated group showed increased activities that were statistically significant of Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase (P < 0.01, P < 0.02). The whole blood viscosity and symptoms showed improvement to an extent and the total effective rate of blood sugar lowering were as follows: fasting blood glucose (FBG) 77.8%, 2hr. postprandial plasma blood glucose (2hr. postprandial PBG)69.4%. Whereas, the placebo group showed no marked improvement in either whole blood viscosity or symptoms and the total effective rate of blood sugar lowering were FBG 41.7%, 2hr. postprandial PBG 38.9%.\n Xianzhen tablet is effective in improving the activities of Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase, as well as the whole blood viscosity, blood sugar lowering and in improving clinical symptoms, it could treat effectively NIDDM patients with deficiency of both Qi and Yin, deficiency of the Kidney and blood stasis.", "nan", "To study the effect of Yiqi Yangyin Huoxue recipe (YQYYHX) in treating type 2 diabetes mellitus (DM) patients with deficiency of both Qi-Yin (DQY) and blood stasis Syndrome.\n Forty-one type 2 DM patients compared with those in the control group were observed.\n After treatment, the endothelin (ET) level of the treated group reduced significantly, and the total effective rate of blood sugar lowering were as follows: Fasting blood glucose (FBG) 87.80%, 2 hours postprandial plasma blood glucose (PBG) 90.24%.\n YQYYHX is effective in improving the patient's vascular endothelia cell functions by reducing the plasma ET level, clinical symptoms and blood sugar lowering.", "To study the hypoglycemic effect of Jiangtangkang (JTK), a Chrysanthemum product and its influence on sensitivity of insulin in non-insulin dependant diabetes mellitus (NIDDM).\n Newly discovered (71 cases) and poorly controlled (117 cases) NIDDM were divided to JTK, 8 g each time, 3 times per day, and the control (Glibenclazide in newly discovered, no treatment in poorly controlled) group respectively.\n After 2 months of treatment, the fasting blood glucose (FBG), postprandial blood glucose (PBG), glucosylated hemoglobin (GHb) improved remarkably and insulin of plasma remained unchanged in JTK group, their blood viscosity and triglyceride decreased after 6-month reatment, the FBG, PBG lowered in the control group while their viscosity and lipids were unaffected. Insulin tolerance test on newly discovered NIDDMs showed an increased sensitivity to insulin, their serum chromium elevated, and the urinary albumin in poorly controlled persons lowered significantly.\n JTK might improve the sensitivity to insulin and decrease the blood viscosity in NIDDM." ]

[ "12727703", "10665159", "8770436", "15866560", "14992983", "16168151", "12830564", "14565892", "9659862", "9735577", "15101068", "12204928" ]

[ "Self-help for bulimia nervosa: a randomized controlled trial.", "Guided and unguided self-help for binge eating.", "Sequential treatment for bulimia nervosa incorporating a self-care manual.", "Cognitive behavioral therapy guided self-help and orlistat for the treatment of binge eating disorder: a randomized, double-blind, placebo-controlled trial.", "Treatment of bulimia nervosa in a primary care setting.", "Guided self-help for bulimia nervosa in primary care: a randomized controlled trial.", "Specialist treatment versus self-help for bulimia nervosa: a randomised controlled trial in general practice.", "Pure and guided self-help for full and sub-threshold bulimia nervosa and binge eating disorder.", "Guided self-change for bulimia nervosa incorporating use of a self-care manual.", "Cognitive-behavioral self-help for binge eating disorder: a controlled effectiveness study.", "Guided self-help versus cognitive-behavioral group therapy in the treatment of bulimia nervosa.", "Self-help for bulimic disorders: a randomised controlled trial comparing minimal guidance with face-to-face or telephone guidance." ]

[ "The authors examined the effectiveness of unguided self-help as a first step in the treatment of bulimia nervosa.\n A total of 85 women with bulimia nervosa who were on a waiting list for treatment at a hospital-based clinic participated. The patients were randomly assigned to receive one of two self-help manuals or to a waiting list control condition for 8 weeks. One of the self-help manuals addressed the specific symptoms of bulimia nervosa (cognitive behavior self-help), while the other focused on self-assertion skills (nonspecific self-help).\n Twenty patients (23.5%) dropped out of the study. The data were analyzed with intention-to-treat analysis. Although the group-by-time interaction for binge eating and purging was not statistically significant, simple effects showed that there was a significant reduction in symptom frequency in both self-help conditions at posttreatment but not in the waiting list condition. There were no statistically significant changes in levels of dietary restraint, eating concerns, concerns about shape and weight, or general psychopathology. A greater proportion of patients in the cognitive behavior self-help (53.6%) and nonspecific self-help (50.0%) conditions reported at least a 50% reduction in binge eating or purging at posttreatment, compared with the waiting list condition (31.0%). A lower baseline knowledge about eating disorders, more problems with intimacy, and higher compulsivity scores predicted a better response.\n The findings suggest that a subgroup of patients with bulimia nervosa may benefit from unguided self-help as a first step in their treatment. Cognitive behavior self-help and nonspecific self-help had equivalent effects.", "This study compared the relative short- and longer-term efficacy of therapist-guided and unguided use of a cognitive behavioral self-help manual for binge eating [Fairburn, C. G. (1995). Overcome binge eating. New York: The Guilford Press.] Forty women (82.5% with binge eating disorder) were randomized to one of the two treatment levels. Results indicate that both conditions represent viable means of treating binge eating. Overall, patients improved their eating behavior, eliminated any inappropriate compensatory behaviors, reduced their shape concern, weight concern, and other symptoms of eating-related psychopathology, and improved their general psychological functioning. The guided self-help condition was notably superior in reducing the occurrence of binge eating and its associated symptomatology, as well as lowering interpersonal sensitivity. A high degree of general psychopathology was a negative prognostic indicator. The implications for a stepped-care approach to treating binge eating are discussed.", "The aim of this study was to evaluate the effectiveness of a stepped care approach to the treatment of bulimia nervosa: a self-care manual followed, if necessary, by a course of attenuated cognitive behavioural treatment (CBT) in comparison with standard CBT.\n One hundred and ten patients, presenting at a tertiary referral centre with ICD-10 bulimia nervosa or atypical bulimia nervosa, were randomly assigned to one of two treatment conditions; a) a sequential treatment group: 8 weeks with a self-care manual followed by up to eight sessions of CBT (if still symptomatic) or b) 16 sessions of CBT.\n Bulimic symptoms improved significantly in both groups with no significant differences between the two groups on any of the measures at the end of treatment or at 18 months follow-up. At end of treatment 30% (95% CI: 18-46%) of the sequential group and 30% (95% CI: 17-47%) of the standard treatment group were free from all bulimic symptoms. Sixteen of those in the sequential group improved significantly with self-care and did not require additional treatment. The median number of sessions taken by the sequential group was three (95% CI: 0-6). At 18 months follow-up 40% (95% CI: 23-59%) of the sequential group and 41% (95% CI: 25-59%) of the CBT group were symptom free. Conclusions: A sequential approach to the treatment of bulimia may be as effective as standard CBT and can considerably reduce the amount of therapist contact required.", "Cognitive behavioral therapy (CBT) has efficacy for binge eating disorder (BED) but not obesity. No controlled studies have tested whether adding obesity medication to CBT facilitates weight loss. We performed a randomized, placebo-controlled study of orlistat administered with guided self-help CBT (CBTgsh).\n Fifty obese BED patients were randomly assigned to 12-week treatments of either orlistat plus CBTgsh (120 mg three times a day [t.i.d.]) or placebo plus CBTgsh and were followed in double-blind fashion for 3 months after treatment.\n Seventy-eight percent of patients completed treatments without differential dropout between orlistat+CBTgsh and placebo+CBTgsh. Intent-to-treat remission rates (zero binges for past 28 days on Eating Disorder Examination Interview) were significantly higher for orlistat+CBTgsh than placebo+CBTgsh (64% versus 36%) at posttreatment but not at 3-month follow-up (52% in both). Intent-to-treat rates for achieving 5% weight loss were significantly higher for orlistat+CBTgsh than placebo+CBTgsh at posttreatment (36% versus 8%) and 3-month follow-up (32% versus 8%). Significant and comparable improvements in eating disorder psychopathology and psychological distress occurred in both treatments.\n The addition of orlistat to CBTgsh was associated with greater weight loss than the addition of placebo to CBTgsh. Clinical improvements were generally maintained at 3-month follow-up after treatment discontinuation.", "The authors' goal was to determine whether treatments known to be effective for bulimia nervosa in specialized treatment centers can be used successfully in primary health care settings. They examined the benefits of two treatments for bulimia: 1) fluoxetine, an antidepressant medication, and 2) guided self-help, an adaptation of cognitive behavior therapy.\n Ninety-one female patients in two primary care settings were randomly assigned to receive fluoxetine alone, placebo alone, fluoxetine plus guided self-help, or placebo and guided self-help.\n The majority of the patients did not complete the treatment trial; many patients found the treatment program too demanding, but others indicated it was not sufficiently intensive. Patients assigned to fluoxetine attended more physician visits, exhibited a greater reduction in binge eating and vomiting, and had a greater improvement in psychological symptoms than those assigned to placebo. There was no evidence of benefit from guided self-help.\n The treatment of patients with bulimia nervosa in a primary care setting is hampered by a high dropout rate. Guided self-help, a psychological treatment based on cognitive behavior therapy, appears ineffective, but treatment with fluoxetine is associated with better retention and substantial symptomatic improvement.", "To increase access to cognitive behavioural therapy for bulimia nervosa new delivery modes are being examined. Guided Self-Help (GSH) in primary care is potentially valuable in this respect. This research aimed to compare outcomes following GSH delivered by general practitioners (GPs) in the normal course of their practice to a delayed treatment control (DTC) condition, and to examine the maintenance of treatment gains at 3 and 6 months following completion of GSH.\n Participants were 109 women with full syndrome or sub-threshold bulimia nervosa, randomly allocated to GSH ( n = 54) and DTC ( n = 55). The GSH group received direction and support from a GP over a 17-week period while working through the manual in Bulimia Nervosa and Binge-Eating: A Guide to Recovery by P. J. Cooper (1995). GSH and DTC groups were assessed pre-treatment and 1 week following the 17-week intervention or waiting interval. The GSH group was reassessed at 3- and 6-month follow-up.\n Intention-to-treat analyses at end of treatment revealed significant improvements in bulimic and psychological symptoms in GSH compared with DTC, reduction in mean frequency of binge-eating episodes by 60% in GSH and 6% in DTC, and remission from all binge-eating and compensatory behaviours in 28% of the GSH and 11% of the DTC sample. Treatment gains were maintained at 3- and 6-month follow-up.\n Outcomes in GSH compare favourably with those of specialist-delivered psychological treatments. These findings are considered in light of the nature of the therapy offered and the primary care context.", "Little is known about general practice management of patients with eating disorders.\n To compare the effectiveness of a general practice-based, self-help approach to the treatment of bulimia nervosa with that of specialist outpatient treatment.\n A prospective, parallel group, randomised controlled trial.\n General practices and specialist eating disorder clinics in London.\n Patients were recruited from general practitioner (GP) referrals to specialist eating disorder clinics. Thirty-four patients were randomised to receive the self-help intervention in general practice and thirty-four were randomised to the clinic intervention. Patients randomised to the self-help arm of the trial worked through a manual based on cognitive behaviour principles, while keeping in contact with their GPs. Those randomised to receive specialist treatment were managed in the specialist clinic to which they had been referred. The main outcome measure was the Bulimic Investigatory Test Edinburgh score, assessed at baseline and at six and nine months. Secondary measures were eating pathology, depression, and social adjustment.\n A total of 74% and 80% of patients were followed up at six and nine months respectively. An intention-to-treat analysis revealed that, while bulimic symptoms declined in both groups over time, there was no significant difference in outcome between the two groups.\n The findings lend support to the idea that patients with bulimia nervosa can be treated in general practice and that this approach warrants further investigation.", "The study compared the efficacy of self-help without and with guidance (referred to as 'pure' and 'guided' self-help), using a cognitive behavioral self-help manual (Fairburn, 1995) for binge eating.\n A sample of 31 participants with bulimia nervosa, subthreshold bulimia nervosa and binge-eating disorder were assigned randomly to one of the self-help levels for 16 weeks, after four weeks of baseline observations.\n The results indicated that both forms of self-help treatments had a modestly positive and sustained effect on the participants' eating problems. Intention-to-treat analyses showed that participants reduced their mean number of objective bulimic episodes and purging behaviour by 33% and 17% over the course of the treatment. The corresponding reduction levels for the treatment completers (N = 18) were 58% and 61%, respectively. Furthermore, there were no significant differences between the pure and guided self-help groups in terms of outcome, reflecting the probable insignificance of guidance for the broader group of individuals with binge-eating problems. At follow-up, no further significant improvement or deterioration was observed in the ensuing six months compared with the post-treatment data.\n Given the heterogeneity of the diagnostic groups in the present study, resulting in high external validity, and the conservative nature of the analyses, self-help is discussed as a viable means of initial treatment for binge eating.", "The aim of this study was to evaluate the effectiveness of guided self-change for bulimia nervosa.\n Sixty-two patients with DSM-III-R-defined bulimia nervosa were randomly assigned to 1) use of a self-care manual plus eight fortnightly sessions of cognitive behavior therapy (guided self-change) or 2) 16 sessions of weekly cognitive behavior therapy.\n At the end of treatment and at follow-up an average of 43 weeks after the end of therapy, substantial improvements had been achieved in both groups on the main outcome measures: eating disorder symptoms according to experts' ratings (Eating Disorder Examination subscores on overeating, vomiting, dietary restraint, and shape and weight concerns), self-reports (Bulimic Investigatory Test Edinburgh), and a 5-point severity scale. Also, improvement was seen on the subsidiary outcome measures: the Beck Depression Inventory, the Self-Concept Questionnaire, and knowledge of nutrition, weight, and shape. At follow-up, 71% of the cognitive behavior therapy group had not binged or vomited during the week preceding. In the guided self-change group, 70% had not binged and 61% had not vomited during the week before follow-up.\n Guided self-change incorporating use of a self-care manual offers an approach that can be as effective as standard cognitive behavior therapy in the long term and can considerably reduce the amount of therapist contact required.", "The aim of this study was to evaluate the effectiveness of 2 methods of administering a cognitive-behavioral self-help program for binge eating disorder. The study was designed to reproduce many of the conditions that apply in settings in which self-help interventions are most relevant. Seventy-two women with binge eating disorder were randomly assigned to 1 of 3 conditions for 12 weeks: pure self-help (PSH), guided self-help (GSH), or a waiting list (WL) control condition (followed by PSH or GSH). They were then followed up for 6 months. Both PSH and GSH had a substantial and sustained impact with almost half the participants ceasing to binge eat. There was little change in the WL condition. Cognitive-behavioral self-help may be of value both as an initial treatment for binge eating disorder and as a form of secondary prevention.", "The aim of the current study was to evaluate whether guided self-help was effective in the short and long term in the treatment of bulimia nervosa.\n Eighty-one patients with bulimia nervosa were randomly assigned to either a self-help manual with a maximum of 18 short weekly visits (guided self-help) or to 18 weekly 1.5-h sessions of cognitive-behavioral group therapy (CBT). The primary outcome variables were monthly frequencies of self-reported binge eating and vomiting episodes. Secondary outcome variables were eating disorder-related psychopathology (assessed with the Eating Disorders Inventory [EDI]) and depression (assessed by the Beck Depression Inventory [BDI]). Patients were followed up 1 year after the end of treatment.\n A mixed-effects linear regression analysis indicated that subjects in both treatment conditions showed a significant decrease over time in binge eating and vomiting frequencies, in the scores of the EDI subscales, and in the BDI. Both treatment modalities led to a sustained improvement at follow-up. A separate analysis of the completer sample showed significantly higher remission rates in the self-help condition (74%) compared with the CBT condition (44%) at follow-up.\n Guided self-help incorporating the use of a self-help manual offers an approach that can be effective in the short and long-term treatment of bulimia nervosa.\n Copyright 2004 by Wiley Periodicals, Inc. Int J Eat Disord 35: 522-537, 2004.", "There is great potential demand for treatment of bulimia nervosa and binge eating disorder. Skilled therapists are in short supply. Self-help and guided self-help based upon books have shown some promise as an economical alternative to full therapy in some cases.\n To investigate the efficacy and effectiveness of self-help with and without guidance in a specialist secondary service.\n A randomised controlled trial comparing three forms of self-help over 4 months with a waiting-list comparison group and measurement of service consumption over the subsequent 8 months.\n Self-help delivered with four sessions of face-to-face guidance led to improved outcome over 4 months. There is also some evidence to support the use of telephone guidance. A minority of participants achieved lasting remission of their disorder in relation to self-help, but there was no significant difference in final outcome between the groups after they had progressed through the stepped care programme. Patients initially offered guided self-help had a lower long-term drop-out rate.\n Guided self-help is a worthwhile initial response to bulimia nervosa and binge eating disorder. It is a treatment that could be delivered in primary care and in other non-specialist settings." ]

[ "18723909", "12165579", "11585480", "16846587", "20227053", "17272618", "12196868", "16765760", "19101390" ]

[ "Single versus multiple courses of antenatal betamethasone and neonatal outcome: a randomized controlled trial.", "The effect of a single remote course versus weekly courses of antenatal corticosteroids on functional residual capacity in preterm infants: a randomized trial.", "Single vs weekly courses of antenatal corticosteroids for women at risk of preterm delivery: A randomized controlled trial.", "Single versus weekly courses of antenatal corticosteroids: evaluation of safety and efficacy.", "Respiratory compliance in preterm infants after a single rescue course of antenatal steroids: a randomized controlled trial.", "Randomized trial of a single repeat dose of prenatal betamethasone treatment in imminent preterm birth.", "Multiple versus single courses of antenatal corticosteroids for preterm birth: a pilot study.", "Neonatal respiratory distress syndrome after repeat exposure to antenatal corticosteroids: a randomised controlled trial.", "Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial." ]

[ "This study compared the beneficial and adverse neonatal effects of a single versus repeated courses of antenatal betamethasone.\n Tertiary care hospital\n Open labeled, randomized controlled trial.\n Pregnant women (26-33 weeks) at risk of preterm delivery, who received one course of antenatal betamethasone and remained undelivered for 7 days. Those with uncertain gestation, major malformations and frank chorioamnionitis were excluded.\n Subjects were randomized to receive weekly antenatal betamethasone until 34 weeks or no further betamethasone.\n Primary: incidence of severe respiratory distress syndrome (RDS). Secondary: incidence of non-severe RDS and other neonatal morbidity; birth weight, length and occipito-frontal circumference (OFC); and, development and growth at 6 mo corrected age.\n 38 subjects were allocated to each group. Severe RDS was similar in multiple and single course groups (7% vs. 3% respectively, P=0.34), as was incidence of other morbidity. Composite outcome of RDS and or death within 28 days tended to be less in multiple course group (P=0.07). Birth anthropometry was similar in the 2 groups. At 6 mo corrected age (n=44), weight and length were significantly lower in multiple course group (p=0.003 and P=0.007, respectively), whereas OFC was not different (P=0.1). There were no differences vis a vis neurodevelopmental outcomes.\n A single course of antenatal betamethasone was as efficacious as multiple courses, with respect to prevention of neonatal morbidity. Multiple antenatal betamethasone courses have long-term adverse effects on infant weight and length growth, but not on OFC and neurodevelopment.", "There are no randomized data on the effect of repeat courses of corticosteroids during pregnancy on newborn pulmonary function. Our objective was to compare the effect of a single remote course of antenatal steroids (AS) with weekly courses of AS on functional residual capacity (FRC) and respiratory compliance in preterm infants.\n Pregnant women 25 to 33 weeks' gestation, who remained undelivered 1 week after their first course of antenatal corticosteroids (two 12-mg doses of betamethasone) were randomized to weekly courses of corticosteroids versus weekly placebo until delivery or 34 weeks' gestation. FRC was measured with the nitrogen washout technique and respiratory compliance with the single breath occlusion technique within 48 hours of life.\n Thirty-seven infants (mean gestational age at delivery approximately 32.5 weeks) were studied. Maternal and infant demographics were similar. There was no significant difference in FRC (28.5 vs 27.5 mL/kg) or respiratory compliance between the infants who received a single remote course of antenatal corticosteroids and those who received weekly courses of corticosteroids until delivery. There was no significant difference in admission head circumference or birth weights between the groups.\n Our results demonstrate that weekly repetitive courses of AS do not significantly increase FRC or respiratory compliance in preterm infants when compared with a single remote course of steroids given at a mean gestational age of 29 weeks.", "The practice of administering weekly courses of antenatal corticosteroids to pregnant women at risk of preterm delivery is widespread, but no randomized trial has established the efficacy or safety of this practice.\n To evaluate the efficacy of weekly administration of antenatal corticosteroids compared with a single course in reducing the incidence of neonatal morbidity and to evaluate potential complications of weekly treatment.\n Randomized, double-blind, placebo-controlled intention-to-treat trial conducted in 13 academic centers in the United States from February 1996 through April 2000.\n A total of 502 pregnant women between 24 and 32 completed weeks' gestation who were at high risk of preterm delivery.\n All patients received a complete single course of antenatal corticosteroids (either betamethasone, 12 mg intramuscularly repeated once in 24 hours for 2 doses, or dexamethasone, 6 mg intramuscularly repeated every 12 hours for 4 doses). Participants who had not delivered 1 week after receipt of the single course were randomly assigned to receive either betamethasone, 12 mg intramuscularly repeated once in 24 hours for 2 doses every week until 34 weeks' gestation or delivery, whichever came first (n = 256), or a similarly administered placebo (n = 246).\n Composite neonatal morbidity (including severe respiratory distress syndrome, bronchopulmonary dysplasia, severe intraventricular hemorrhage, periventricular leukomalacia, proven sepsis, necrotizing enterocolitis, or perinatal death).\n Composite morbidity occurred in 22.5% of the weekly-course group vs 28.0% of the single-course group (unadjusted relative risk, 0.80; 95% confidence interval, 0.59-1.10). Neither group assignment nor the number of treatment courses was associated with a reduction in composite morbidity.\n Weekly courses of antenatal corticosteroids did not reduce composite neonatal morbidity compared with a single course of treatment. Weekly courses of antenatal corticosteroids should not be routinely prescribed for women at risk of preterm delivery.", "The purpose of this study was to determine if weekly corticosteroids improve neonatal outcome without undue harm.\n Women 23 to 32 weeks receiving 1 course of corticosteroids 7 to 10 days prior were randomized to weekly betamethasone or placebo.\n The study was terminated by the independent data and safety monitoring committee with 495 of the anticipated 2400 patients enrolled. There was no significant reduction in the composite primary morbidity outcome (8.0% vs 9.1%, P = .67). Repeated courses significantly reduced neonatal surfactant administration (P = .02), mechanical ventilation (P = .004), CPAP (P = .05), pneumothoraces (P = .03). There was no significant difference in mean birth weight or head circumference. The repeat group had a reduction in multiples of the birth weight median by gestational age (0.88 vs 0.91) (P = .01) and more neonates weighing less than the 10th percentile (23.7 vs 15.3%, P = .02). Significant weight reductions occurred for the group receiving > or = 4 courses.\n Repeat antenatal corticosteroids significantly reduce specific neonatal morbidities but do not improve composite neonatal outcome. This is accompanied by reduction in birth weight and increase in small for gestational age infants.", "To compare respiratory compliance and functional residual capacity in infants randomized to a rescue course of antenatal steroids vs placebo.\n Randomized, double-blinded trial. Pregnant women > or =14 days after initial antenatal steroids were randomized to rescue antenatal steroids or placebo. The primary outcomes were measurements of respiratory compliance and functional residual capacity. This study is registered with clinicaltrials.gov (NCT00669383).\n Forty-four mothers (56 infants) received rescue antenatal steroids and 41 mothers (57 infants) received placebo. There was no significant difference in birthweight, or head circumference. Infants in the rescue group had an increased respiratory compliance (1.21 vs 1.01 mL/cm H(2)O/kg; adjusted 95% confidence interval, 0.01-0.49; P = .0433) compared with placebo. 13% in the rescue vs 29% in the placebo group required > or =30% oxygen (P < .05). Patients delivered at < or =34 weeks had greater pulmonary benefits.\n Infants randomized to rescue antenatal steroids have a significantly increased respiratory compliance compared with placebo.\n Copyright 2010 Mosby, Inc. All rights reserved.", "A single dose of prenatal betamethasone treatment decreases neonatal morbidity rates when administered within 7 days before preterm delivery. A single repeat dose or booster dose of betamethasone before delivery has been proposed to be effective, but its efficacy has not been subjected to a randomized, blinded trial.\n Women with imminent delivery before 34.0 gestational weeks were eligible if they remained without delivery for >7 days after a single course of betamethasone. After stratification, a single repeat dose of betamethasone (12 mg) or placebo was administered. The primary outcome was survival without respiratory distress syndrome or severe intraventricular hemorrhage (grade 3 or 4).\n A total of 249 mothers had been enrolled by the time the study was discontinued. All of the 159 infants in the betamethasone group and 167 in the placebo group were born before 36 weeks of gestation. The intact survival rate was unaffected and was lower than anticipated, because the gestational age-adjusted incidence of respiratory distress syndrome was higher than the population incidence. The requirement for surfactant therapy in respiratory distress syndrome was increased in the betamethasone group. According to posthoc analysis of the data for 206 infants who were delivered within 1 to 24 hours, the betamethasone booster tended to increase the risk of respiratory distress syndrome and to decrease intact survival rates.\n According to this study, a single booster dose of betamethasone just before preterm birth may perturb respiratory adaptation. These results caution against uncontrolled use of a repeat dose of glucocorticoid in high-risk pregnancies.", "(1) To determine the feasibility of a multicentre, randomized, double-masked, placebo-controlled trial to investigate the effects of multiple courses of antenatal corticosteroids (ACS), more than 7 days following the initial course of ACS therapy, on perinatal or neonatal mortality or neonatal morbidity. (2) To determine the risk of complications that would require discontinuation of ACS therapy. (3) To determine if multiple courses of ACS have an effect on the concentrations of plasma cortisol and adrenocorticotropin hormone (ACTH) in cord blood and in maternal blood immediately following delivery, compared to a single course of ACS.\n Women at 24 to 30 weeks' gestation, at continued increased risk of preterm birth 7 or more days following a single course of ACS, were randomized to receive weekly courses of betamethasone or placebo until 33 weeks' gestation or delivery.\n Women were recruited at two hospitals in Toronto from 01 September 1999 to 31 August 2000. Of the 78 women who were approached and were eligible for the study, 12 (15%) were recruited and 66 (85%) refused to participate. Of the 66 refusals, 38 (58%) did not feel their physicians were supportive of the study, 10 (15%) did not want to be randomized, and 4 (6%) had other personal reasons for refusing to enter the trial. Fourteen women (21%) had physicians who did not allow them to join the study. The lack of physician support was due to concerns related to the potential adverse effects of multiple courses of ACS. There were no complications requiring discontinuation of ACS. Plasma cortisol and ACTH concentrations in cord and maternal blood taken after delivery were not significantly different between ACS and placebo groups.\n A multicentre randomized controlled trial is required to determine the benefits and risks of multiple versus a single course of ACS. If the study protocols are supported by physicians and their patients, a multicentre randomized controlled trial is feasible.", "The efficacy and safety of repeat doses of prenatal corticosteroids remains uncertain. Our aim was to establish whether repeat prenatal corticosteroids given to women at risk of preterm birth can reduce neonatal morbidity without harm.\n In this hospital-based study, 982 women who remained at risk of preterm birth at less than 32 weeks' gestation, 7 or more days after receiving a first course of prenatal corticosteroids, were randomly assigned to receive a repeat intramuscular dose of either 11.4 mg betamethasone (as Celestone Chronodose), or saline placebo. This was repeated every week the woman remained undelivered, at less than 32 weeks' gestation, and at risk of preterm birth. Primary outcomes were occurrence and severity of neonatal respiratory distress syndrome, use and duration of oxygen and mechanical ventilation, and weight, length, and head circumference at birth and hospital discharge. Statistical analyses were on an intention to treat basis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN48656428.\n Fewer babies exposed to repeat corticosteroids had respiratory distress syndrome (33%vs 41%; relative risk 0.82, 95% CI 0.71-0.95, p=0.01) and fewer had severe lung disease (12%vs 20%; relative risk 0.60, 95% CI 0.46-0.79, p=0.0003) than those in the placebo group. In keeping with these benefits, babies exposed to repeat corticosteroids needed less oxygen therapy (p=0.03), and shorter duration of mechanical ventilation (p=0.01). Mean weight, length, and head circumference at birth and hospital discharge did not differ between treatment groups. Z-scores for weight (p=0.04) and head circumference (p=0.03) at birth were lower in the babies who received repeat corticosteroids although at the time of hospital discharge Z-scores did not differ between treatment groups (p=0.29 for weight, p=0.48 for head circumference).\n Exposure to repeat doses of antenatal corticosteroids reduces neonatal morbidity. Pending long-term outcome results, the short-term benefits for the babies in our study support the use of repeat doses of corticosteroids in women who remain at risk of very preterm birth 7 or more days after an initial course.", "One course of antenatal corticosteroids reduces the risk of respiratory distress syndrome and neonatal death. Weekly doses given to women who remain undelivered after a single course may have benefits (less respiratory morbidity) or cause harm (reduced growth in utero). We aimed to find out whether multiple courses of antenatal corticosteroids would reduce neonatal morbidity and mortality without adversely affecting fetal growth.\n 1858 women at 25-32 weeks' gestation who remained undelivered 14-21 days after an initial course of antenatal corticosteroids and continued to be at high risk of preterm birth were randomly assigned to multiple courses of antenatal corticosteroids (n=937) or placebo (n=921), every 14 days until week 33 or delivery, whichever came first. The primary outcome was a composite of perinatal or neonatal mortality, severe respiratory distress syndrome, intraventricular haemorrhage (grade III or IV), periventricular leucomalacia, bronchopulmonary dysplasia, or necrotising enterocolitis. Analysis was by intention to treat. All patients and caregivers were unaware of the treatment given. This trial is registered as number ISRCTN2654148.\n Infants exposed to multiple courses of antenatal corticosteroids had similar morbidity and mortality to those exposed to placebo (150 [12.9%] vs 143 [12.5%]). Those receiving multiple doses of corticosteroids also weighed less at birth than those exposed to placebo (2216 g vs 2330 g, p=0.0026), were shorter (44.5 cm vs 45.4 cm, p<0.001), and had a smaller head circumference (31.1 cm vs 31.7 cm, p<0.001).\n Multiple courses of antenatal corticosteroids, every 14 days, do not improve preterm-birth outcomes, and are associated with a decreased weight, length, and head circumference at birth. Therefore, this treatment schedule is not recommended.\n Canadian Institutes of Health Research." ]

[ "8975955", "2844044", "6284457", "6272072", "346140", "4593226" ]

[ "Effect of fiber supplements on internal bleeding hemorrhoids.", "Maintenance bran therapy for prevention of symptoms after rubber band ligation of third-degree haemorrhoids.", "High-fiber diet reduces bleeding and pain in patients with hemorrhoids: a double-blind trial of Vi-Siblin.", "Fybogel in haemorrhoid treatment.", "The use of bulk evacuant in patients with haemorrhoids.", "Evaluation of a bulk-forming evacuant in the management of haemorrhoids." ]

[ "The aim of this study is to assess prospectively the effect of fiber additions on internal bleeding hemorrhoids.\n Fifty patients with bleeding internal hemorrhoids are studied and randomized in two groups. Patients in the study group were treated with a commercially available preparation of Plantago Ovata and those in the control group were treated with a placebo. Endoscopy was performed on every patient before and after treatment to establish: a) the degree of hemorrhoidal prolapse, b) the number of congested hemorrhoidal cushions and c) contact bleeding hemorrhoids.\n During the 15 days of treatment, the average number of bleeding episodes was 4.8 +/- 3.8 for the study group versus 6.4 +/- 3 for the control group (n.s.). During the following 15 days, it decreased to 3.1 +/- 2.7 in the study group versus 5.5 +/- 3.2 (p < 0.05) in the control group and in the last 10 days of treatment a further reduction to 1.1 +/- 1.4 was found in the study group versus 5.5 +/- 2.9 (p < 0.001). The number of congested hemorrhoidal cushions diminished from 2.6 +/- 1 to 1.6 +/- 2.2 after fiber treatment (p < 0.01) and no differences were found in the control group. In the fiber group, hemorrhoids bled on contact in 5 out of 22 patients before treatment and in none after treatment; no differences were found in the control group. No modification of the degree of prolapse was observed after treatment.\n Addition of dietary fiber may improve internal bleeding hemorrhoids although with no immediate effect. Fiber addition should be ensured in patients who refuse invasive treatment, waiting for a more defined form of treatment, or with contraindications.", "Proctoscopically diagnosed third-degree haemorrhoids were treated with rubber band ligation (RBL) in 92 patients, who were randomly assigned to management with or without twice-daily intake of unprocessed bran for 18 months. RBL was performed maximally five times at 2-week intervals. Patients who were symptom-free 10 weeks after first banding were considered cured and were enrolled in a follow-up study. The two treatment groups did not differ in regard to clinical or proctoscopic characteristics. The number of RBL required for cure was lower in the bran-treated group (p less than 0.01). The intergroup difference in cure rate 10 weeks after the first treatment was not significant (85% v. 91%). During the follow-up period symptoms recurred in 45% of the RBL group, but in only 15% of the RBL + bran group (p less than 0.01). A high-fiber diet thus increased the long-term cure rate among patients with third-degree haemorrhoids initially cured by RBL.", "nan", "nan", "Fifty-three patients with symptomatic haemorrhoids have been studied in a double-blind cross-over trial of a bulk forming agent (ispaghula husk) against a placebo. Although only 11 per cent of patients ocmplained of constipation, a significant benefit in symptoms and improved bowel habit was demonstrated.", "nan" ]

[ "15829777", "11986538", "16480553", "10078796", "16472039" ]

[ "Effect of the self-monitoring approach on exercise maintenance during cardiac rehabilitation: a randomized, controlled trial.", "Staying on course: the effects of an adherence facilitation intervention on home exercise participation.", "Action plans and coping plans for physical exercise: A longitudinal intervention study in cardiac rehabilitation.", "Follow-up care in general practice of patients with myocardial infarction or angina pectoris: initial results of the SHIP trial. Southampton Heart Integrated Care Project.", "Effects of a CHANGE intervention to increase exercise maintenance following cardiac events." ]

[ "To evaluate the effect of the self-monitoring approach (SMA) on self-efficacy for physical activity (SEPA), exercise maintenance, and objective physical activity level over a 6-mo period after a supervised 6-mo cardiac rehabilitation (CR) program.\n We conducted a randomized, controlled trial with 45 myocardial infarction patients (38 men, seven women; mean age, 64.2 yrs) recruited after completion of an acute-phase, exercise-based CR program. Patients were randomly assigned to an SMA group (n = 24) or control group (n = 21). Along with CR, the subjects in the SMA group self-monitored their weight and physical activity for 6 mos. The SMA used in this study was based on Bandura's self-efficacy theory and was designed to enhance confidence for exercise maintenance. The control group participated in CR only. All patients were evaluated with the SEPA assessment tool. Exercise maintenance, SEPA scores, and objective physical activity (average steps per week) as a caloric expenditure were assessed at baseline and during a 6-mo period after the supervised CR program.\n Mean period from myocardial infarction onset did not differ significantly between the SMA and control groups (12.1 +/- 1.3 vs. 12.2 +/- 1.2 mos, P = 0.692). All patients maintained their exercise routine in the SMA group. Mean SEPA score (90.5 vs. 72.7 points, P < 0.001) and mean objective physical activity (10,458.7 vs. 6922.5 steps/wk, P < 0.001) at 12 mos after myocardial infarction onset were significantly higher in the SMA than control group. SEPA showed significant positive correlation with objective physical activity (r = 0.642, P < 0.001).\n SMA during supervised CR may effectively increase exercise maintenance, SEPA, and objective physical activity at 12 mos after myocardial infarction onset.", "The purpose of this investigation was to test the effectiveness of an adherence facilitation intervention consisting of goal setting, graphic feedback, and provider guidance to support adherence to home exercise in a sample of patients with heart failure who had completed a supervised exercise program. The sample consisted of 13 patients with an ejection fraction of 40% or less who were randomly assigned to either the exercise only group (n=6) or the exercise with adherence facilitation group (n=7). The format of the intervention was graphic depiction of each patient's exercise goals in comparison to each patient's exercise participation. Graphs were mailed at 3-week intervals for 12 weeks. Results indicate that patients who received the intervention demonstrated higher exercise adherence and greater confidence in continuing to exercise in the future. The adherence facilitation intervention may be helpful to heart failure patients in adapting to a program of home exercise. (c)2002 CHF, Inc.", "The aim of the present study was to test two brief planning interventions designed to encourage cardiac patients to engage in regular physical exercise following discharge from rehabilitation. The interventions comprised action plans on (a) when, where, and how to act, and (b) coping plans on how to deal with anticipated barriers.\n An experimental longitudinal trial was conducted to test two interventions that either focused on action planning alone, or on a combination of action planning and coping planning. A total of 211 participants completed assessments at baseline and 2 months after discharge. Participants were randomly assigned to either one of the intervention groups or a standard-care control group.\n Participants in the combined planning group did significantly more physical exercise 2 months post-discharge than those in the other groups.\n The theoretical distinction between action planning and coping planning as introduced in the present study has proven useful in explaining changes in health-related behaviour. The combined planning intervention can be applied in the context of cardiac rehabilitation programmes.", "We aimed to assess the effectiveness of a nurse-led programme to ensure that follow-up care is provided in general practice after hospital diagnosis of myocardial infarction (MI) or angina pectoris.\n We conducted a randomized controlled trial with stratified random allocation of practices to intervention and control groups within all 67 practices in Southampton and South-West Hampshire, England. The subjects were 422 adult patients with a MI and 175 patients with a new diagnosis of angina recruited during hospital admission or chest pain clinic attendance between April 1995 and September 1996. Intervention involved a programme of secondary preventive care led by specialist liaison nurses in which we sought to improve communication between hospital and general practice and to encourage general practice nurses to provide structured follow-up. The main outcome measures were: extent of general practice follow-up; attendance for cardiac rehabilitation; medication prescribed at hospital discharge; self-reported smoking, diet and exercise; and symptoms of chest pain and shortness of breath. Follow-ups of 90.1 % of subjects at 1 month and 80.6% at 4 months were carried out.\n Median attendance for nurse follow-up in the 4 months following diagnosis was 3 (IQR 2-5) in intervention practices and 0 (IQR 0-1) in control practices; the median number of visits to a doctor was the same in both groups. At hospital discharge, levels of prescribing of preventive medication were low in both intervention and control groups: aspirin 77 versus 74% (P = 0.32), cholesterol lowering agents 9 versus 10% (P = 0.8). Conversely, 1 month after diagnosis, the vast majority of patients in both groups reported healthy lifestyles: 90 versus 84% reported eating healthy food (P = 0.53); 73 versus 67% taking regular exercise (P = 0.13); 89 versus 92% not smoking (P = 0.77). Take up of cardiac rehabilitation was 37% in the intervention group and 22% in the control group (P = 0.001); the median number of sessions attended was also higher (5 versus 3 out of 6).\n The intervention of a liaison nurse is effective in ensuring that general practice nurses follow-up patients after hospital discharge. It does not alter the number of follow-up visits made by the patient to the doctor. Levels of prescribing and reported changes in behaviour at hospital discharge indicate that the main tasks facing practice nurses during follow-up are to help patients to sustain changes in behaviour, to encourage doctors to prescribe appropriate medication and to encourage patients to adhere to medication while returning to an active life. These are very different tasks to those traditionally undertaken by practice nurses in relation to primary prevention, where the emphasis has been on identifying risk and motivating change. Assessment of the effectiveness of practice nurses in undertaking these new tasks requires a longer follow-up.", "Despite participation in a cardiac rehabilitation program, there is a downward trajectory of exercise participation during the year following a cardiac event.\n The purpose of this study was to test the effectiveness of CHANGE (Change Habits by Applying New Goals and Experiences), a lifestyle modification program designed to increase exercise maintenance in the year following a cardiac rehabilitation program. The CHANGE intervention consists of 5 small-group cognitive-behavioral change counseling sessions in which participants are taught self-efficacy enhancement, problem-solving skills, and relapse prevention strategies to address exercise maintenance problems.\n Participants (N = 250) were randomly assigned to the CHANGE intervention (supplemental to usual care) or a usual-care-only group. Exercise was measured using portable wristwatch heart rate monitors worn during exercise for 1 year. Cox proportional hazards regression was used to determine differences in exercise over the study year between the study groups.\n Participants in the usual-care group were 76% more likely than those in the CHANGE group to stop exercising during the year following a cardiac rehabilitation program (hazard ratio = 1.76, 95% confidence interval = 1.08-2.86, p = .02) when adjusting for the significant covariates race, gender, comorbidity, muscle and joint pain, and baseline motivation. Most participants, however, had less than recommended levels of exercise amount and intensity.\n Counseling interventions that use contemporary behavior change strategies, such as the CHANGE intervention, can reduce the number of individuals who do not exercise following cardiac events." ]

[ "7710536", "8362228" ]

[ "Children with persistent cough--outcome with treatment and role of Moraxella catarrhalis?", "Erythromycin treatment is beneficial for longstanding Moraxella catarrhalis associated cough in children." ]

[ "52 children with severe cough persisting for more than 10 days were randomized to treatment with amoxycillin/clavulanic acid or placebo in a prospective double-blinded study. Clinically suspected cases of pertussis were excluded, yet 12 (23%) of the children had laboratory verified pertussis infection. The nasopharyngeal colonization showed a predominance of Moraxella catarrhalis which was isolated in 37 (71%) children. Streptococcus pneumoniae and Haemophilus influenzae were isolated in 11 (20%) and 16 (30%) children, respectively. The antibiotic-treated group had a significantly better recovery in both the pediatrician's estimation (p = 0.02) and the independent parental judgement (p = 0.002). These findings are consistent with the view that Moraxella catarrhalis could be directly involved in the pathogenesis of persistent cough in children.", "The benefits of antibiotic treatment and a nasopharyngeal culture in children with longstanding cough were analysed in a prospective randomized open study. Clinically suspected pertussis was excluded. Of 40 children given erythromycin for 7 days, 35 (88%) recovered in one week, compared with 17/47 (36%) untreated (p < 0.0001). Erythromycin eliminated Moraxella catarrhalis from the nasopharynx in 21/31 children (68%), compared with spontaneous disappearance in 7/35 (20%) untreated controls (p < 0.001). Purulent bronchitis or otitis media occurred in 2 children (5%) in the treatment group and in 21 (45%) in the control group (p < 0.01). To evaluate the clinical role of isolated pathogens, the 47 untreated subjects were studied. Seven of 35 children harbouring M. catarrhalis recovered, compared with 8/12 in whom this bacterium was absent (p < 0.01). No correlation was found between the isolation of Haemophilus influenzae or Streptococcus pneumoniae and the clinical outcome. Children with persistent cough > 10 days may benefit from erythromycin treatment. M. catarrhalis in the nasopharynx indicates prolonged symptoms and increased risk of bacterial complications." ]

[ "9846090", "17074548", "17652452", "4612152" ]

[ "[Prophylactic use of prostaglandin synthesis inhibitors in connection with IUD insertion].", "Pain from copper intrauterine device insertion: randomized trial of prophylactic ibuprofen.", "Cervical priming with sublingual misoprostol prior to insertion of an intrauterine device in nulliparous women: a randomized controlled trial.", "Pain relief with naproxen following insertion of an intrauterine device." ]

[ "In a double-blind, randomized, placebo-controlled study conducted at a contraception clinic, 55 women (three nulliparous) were given either ibuprofen 600 mg or placebo 1-4 hours prior to insertion of IUD, 4-6 hours after insertion of IUD and the following morning. Pain was assessed by ten point Numerical Rating Scales during insertion, in the first 4-6 hours and in the following three days. No benefit of ibuprofen was demonstrated at insertion or at any other time during the first three days. The patients were further randomized to type of IUD: TCu-380A and Nova T (R.). No difference in pain scores was evaluated between these.", "This study was undertaken to determine whether 400 mg of prophylactic ibuprofen can alleviate pain from insertion of an intrauterine device (IUD) and to measure level of pain with improved techniques.\n We conducted a randomized, double-blind, placebo-controlled trial of 2019 first-time IUD users: 1008 women received placebo and 1011 women received 400 mg of ibuprofen. Participants took the single tablet at least 45 minutes before IUD insertion. Immediately after insertion, participants recorded level of pain by using a 10-cm visual analog scale, with the value of 10 meaning \"worst imaginable pain.\"\n Median level of pain was 1.0 for both ibuprofen and placebo participants; rank test statistics confirmed no difference. Some subgroups of women experienced higher pain (eg, nulliparous women), but ibuprofen still had no important impact on level of pain.\n Even among first-time users, pain from IUD insertion is generally low. Prophylactic ibuprofen as used in this protocol does not reduce IUD insertion pain.", "The copper intrauterine device (IUD) is a highly effective and safe contraceptive method, also in nulliparous women. However, insertion of an IUD through a narrow cervix may be technically difficult. Misoprostol has been shown to be effective for cervical priming in non-pregnant women prior to hysteroscopy.\n Eighty nulliparous women requesting an IUD were randomly allocated to receive sublingually 400 microg misoprostol and 100 mg diclofenac (misoprostol group) or 100 mg diclofenac alone (control group) 1 h prior to IUD insertion. Cervical dilatation was measured prior to insertion using Hegar pins. Ease of insertion was judged by the investigator. Pain, bleeding and side effects were recorded at insertion and until follow-up performed one month later.\n Following treatment with misoprostol, insertion was significantly easier than in the control group [P = 0.039, difference 19.36%, confidence interval (CI) -0.013, 39.99]. Pain estimated on a visual analogue scale (1-10) showed no evidence of a difference between the groups. The overall distribution of side effects did not differ. However, shivering was more common in the misoprostol group (P = 0.0084, difference 23.27%, CI 6.64, 39.90).\n Misoprostol facilitates insertion of an IUD, and reduces the number of difficult and failed attempts of insertions in women with a narrow cervical canal. The optimal regimen of misoprostol remains to be defined.", "nan" ]

[ "8748919", "15521874", "15567883", "17362946" ]

[ "The use of fibrin sealant in in vitro fertilization and embryo transfer.", "Bed rest versus free mobilisation following embryo transfer: a prospective randomised study.", "Minimizing embryo expulsion after embryo transfer: a randomized controlled study.", "Bed rest after embryo transfer: a randomized controlled trial." ]

[ "To evaluate the role of fibrin sealant for embryo transfer (ET) and the effect of patient mobilization after ET on pregnancy rates.\n A prospective, randomized, controlled study.\n Two hundred eleven patients who were admitted to the IVF Unit over a period of 6 months participated in the study. Patients who had three or more embryos were randomly divided into two groups: group 1 (study group), in which ET was performed using fibrin sealant, and group 2, who served as the controls. Ovulation induction was carried out using the long GnRH-a suppression protocol.\n Comparison of the results regarding the implantation and pregnancy rates and ectopic pregnancy rate revealed a nonsignificant difference between the two groups. However, analysis of the results according to the patients' age revealed a significant increase in pregnancy (P < .05) and implantation (P < .01) rate in elderly patients (aged 39-42) using fibrin sealant for ET as compared with controls. Furthermore, we found that bed rest has no advantage over patient mobilization after ET.\n The use of fibrin sealant for ET is advantageous in elderly women, but has no apparent effect on the success rate or ectopic pregnancy rate in younger patients. Immediate mobilization does not jeopardize the results of IVF-ET.", "To evaluate the efficacy of two clinical methods of post-embryo transfer protocols in patients undergoing in vitro fertilisation.\n Prospective, randomised clinical trial.\n Hospital-based clinic for reproductive medicine.\n Women under 40 years of age who were undergoing in vitro fertilisation with GnRH pituitary down-regulation and controlled ovarian hyperstimulation.\n Patients were randomised to rest for either 1 or 24 hours after embryo transfer.\n Clinical pregnancy per cycle rate (the percentage of cycles started that demonstrated a live fetus on ultrasound examination performed at six or seven weeks of gestation).\n The clinical pregnancy rates were 21.5% for the 1-hour and 18.2% for the 24-hour post-embryo transfer groups. The implantation rate per embryo was significantly higher in the 1-hour group (14.4%) than in the 24-hour group (9%).\n One-hour and 24-hour rest post-embryo transfer result in comparable rates of clinical pregnancy. However, 24-hour rest results in reduced implantation rate per embryo.", "The aim of this work was to modify the embryo transfer technique to prevent expulsion of the embryos by exerting gentle mechanical pressure on the cervix using the vaginal speculum.\n A total of 639 infertile patients undergoing ICSI were prospectively randomized into two groups using sealed dark envelopes. In the study group (n=325) the screw of the vaginal speculum was loosened in order to exert a gentle pressure on the portiovaginalis of the cervix before ejecting the embryos, and was maintained for 7 min afterwards. In the control group (n=314) no pressure was applied on the cervix during embryo transfer and the vaginal speculum was removed after transferring the embryos.\n The clinical pregnancy rate was significantly higher in the study group than in the control group [207/325 (67%) versus 150/314 (47.8%); odds ratio (OR) 1.39; 95% confidence interval (CI) 1.11-1.74]. The implantation rate was also significantly higher in the study group [304/913 (33.3%) versus 198/920 (21.5%); OR 1.54; 95% CI 1.26-1.89].\n Applying gentle mechanical pressure on the portiovaginalis of the cervix using the vaginal speculum during and after transferring the embryos significantly improved clinical pregnancy and implantation rates.", "To determine whether bed rest after embryo transfer leads to improved pregnancy rates (PR).\n Randomized controlled trial.\n University reproductive health clinic.\n Women undergoing IVF.\n Patients undergoing 164 cycles of IVF were randomized to 30 minutes of bed rest after embryo transfer or immediate discharge from the clinic.\n Clinical PR defined by visualized fetal heart beat and ongoing PR defined by viable intrauterine gestation beyond 11 weeks.\n The clinical and ongoing PR for both groups were 50% and 46.3%, respectively, with no statistically significant difference between the two groups.\n Thirty minutes of bed rest after embryo transfer does not improve PR." ]

[ "9932855", "9517521", "10636971", "2007745", "15209619", "2032513", "9252925" ]

[ "Cisapride in management of chronic pediatric constipation.", "The symptomatic effect of cisapride in patients with irritable bowel syndrome and constipation.", "Cisapride for the treatment of constipation in children: A double-blind study.", "\"Prokinetic\" treatment of constipation-predominant irritable bowel syndrome: a placebo-controlled study of cisapride.", "Cisapride treatment of constipation-predominant irritable bowel syndrome is not superior to placebo.", "Effect of cisapride on chronic idiopathic constipation in children.", "Use of cisapride in treatment of idiopathic constipation in children." ]

[ "This study was conducted to explore the use of cisapride in the treatment of chronic idiopathic constipation in children.\n Seventy-nine children were screened. Seventy-three of them met the selection criteria that included clinical, laboratory, radiologic, and histopathologic investigations. These patients entered a week-long phase I of disimpaction using lactulose. Four of them were noncompliant and thus were excluded from the next phase. In phase II sixty-nine patients were assigned to two treatment groups: 0.3 mg/kg cisapride four times a day versus matching placebo for 8 weeks in a double-blind study. The two groups that completed phase II were similar in age and duration of symptoms, confirmed by statistical analysis. Stool frequency was assessed weekly, beginning at the end of the disimpaction phase and continuing for 9 weeks. Total gastrointestinal transit time was measured twice, on completion of phase I and 9 weeks later. Transit time is the time required for a carmine marker taken orally after overnight fast to appear in the stool.\n There was a significant difference between stool frequency per week before and after cisapride treatment, stool frequency per week at the end of phase II with cisapride versus placebo, and total gastrointestinal transit time before and after treatment with cisapride (p < 0.05 for all values). No such difference was demonstrated when comparing stool frequency per week or total gastrointestinal transit time before and after placebo (p > 0.05 for both).\n Cisapride may have a role in the management of chronic idiopathic constipation in children.", "Cisapride improves symptoms in patients with idiopathic constipation. This trial compares the effect of cisapride with that of placebo in patients with irritable bowel syndrome (IBS) and constipation.\n Seventy patients were randomized to 12 weeks' treatment with 5 mg cisapride three times daily or placebo in a double-blind trial. The dose could be doubled after 4 weeks in patients without satisfactory improvement. The patients scored their symptoms on a 100-mm visual analogue scale (VAS) (0 = best, 100 = worst), and the investigators evaluated the symptomatic effect.\n The dose was doubled in 17 and 23 patients in the cisapride and placebo groups, respectively, after 4 weeks. The patients' mean VAS score for global evaluation of IBS symptoms in the cisapride and placebo groups was 73 and 71 mm, respectively, at the start of treatment and 47 and 41 mm at the end. The difference between cisapride and placebo at the end was 6 mm in favour of placebo (95% confidence interval (CI), -6, 18) (NS). The investigators evaluated the effect as good or excellent in 39.2% and 58.8% in the cisapride and placebo groups, respectively. The difference in favour of placebo was 19.5% (95% CI, -5, 44) (NS). Nor were any statistically significant differences seen between cisapride and placebo in the other effect factors.\n The trial seems to exclude a clinically significant effect of 15-30 mg cisapride daily in patients with IBS and constipation during a 12-week treatment period.", "To determine whether cisapride is effective in the treatment of children with constipation.\n Double-blind, placebo-controlled study in which children with chronic constipation were randomly assigned to treatment with cisapride or placebo for 12 weeks.\n Forty children were enrolled, and 36 completed the therapy. Treatment successes occurred in 13 of 17 (76%) subjects in the cisapride group and 8 of 19 (37%) subjects in the placebo group (P <.03). The odds ratio for response after cisapride administration was 8.2 times higher (95% CI 1.3 to 49.4). During cisapride therapy, there was a significant improvement in number of spontaneous bowel movements per week (from 0.9 +/- 0.1 to 4.1 +/- 1.1), and there was a significant decrease in number of fecal soiling episodes per day (1.8 +/- 0.5 to 0.08 +/- 0.4), percent with encopresis (82% vs 23%), number of laxative doses per week (from 10.3 +/- 2.6 to 0.8 +/- 0.6), percent using laxatives (77% to 24%), and total gastrointestinal transit time (from 115.0 +/- 3.7 hours to 77.0 +/- 11.1 hours). With placebo, there were no significant changes in the number of spontaneous bowel movements (from 1.0 +/- 0.8 to 2.2 +/- 0.6), percent with encopresis (74% vs 47%), or total gastrointestinal transit time (from 112.5 +/- 4.9 hours to 95.4 +/- 9.8 hours); but there was a significant decrease in number of fecal soiling episodes per day (from 1.3 +/- 0.4 to 0.4 +/- 0.2) and number of laxative doses used per week (from 11.5 +/- 2.9 to 2.05 +/- 0.7). The final number of spontaneous bowel movements, fecal soiling episodes, laxatives used, or percent patients with encopresis was not different when patients receiving cisapride were compared with those receiving placebo.\n Cisapride was effective in the treatment of children with constipation.", "The effects of prokinetic treatment with cisapride in patients with constipation-predominant irritable bowel syndrome (IBS) were evaluated in a randomized, double-blind, placebo-controlled study. Sixty-nine IBS patients were assigned to a 12-week treatment with either 5 mg cisapride or placebo t.i.d.; this dosage could be changed if necessary. The mean weekly number of days on which a stool was passed in the cisapride and placebo group increased to 5.3 and 4.4 (p less than 0.05) during weeks 8-12 of treatment, and the number of days with stools of normal consistency increased to 3.5 and 1.9 (p less than 0.05), respectively. At week 12, the reduction in severity and frequency scores for abdominal pain was significantly greater (p less than or equal to 0.05) in the cisapride group (60 and 61%) than in the placebo group (40 and 32%), as it was for abdominal distension (p less than 0.05). Cisapride tended to be better than placebo in diminishing flatulence. In 71% versus 39% of the patients the overall rating for the response to treatment was good or excellent at week 12. Cisapride was well tolerated. These results suggest that the drug will be useful for the management of constipation-predominant IBS.", "Previous studies with cisapride reported conflicting results in patients with constipation-predominant irritable bowel syndrome (IBS). To gain further evidence, this randomized double-blind study was carried out.\n Eighty-two symptomatic outpatients were randomized to receive either 5 mg oral cisapride or placebo three times daily for a period of 12 weeks. In patients without satisfactory improvement after 4 weeks, the dose was doubled. Symptom evaluation used visual analog scales (VAS) and the investigators' global assessment.\n After 4 weeks, in 18 (45%) cisapride and 24 (57%) placebo patients the dose was doubled because of insufficient improvement of symptoms. The mean VAS score for patients' global rating of IBS symptoms at baseline was 67.5 mm for cisapride versus 70.7 mm for placebo, and improved to 38.4 mm versus 44.5 mm after 12 weeks of treatment. Investigators rated the overall effect of therapy as good or excellent in 70% of the cisapride and 50% of the placebo group. Neither these nor further efficacy parameter differences reached statistical significance.\n These results indicate that the effect of 15-30 mg cisapride daily on symptoms of constipation-predominant IBS is not significantly superior to placebo. During the 12 week treatment of this trial cisapride proved to be safe and tolerable.", "The efficacy of cisapride, a new prokinetic drug, as a treatment for chronic functional constipation of childhood was studied in 20 constipated children. Each subject had a stool frequency less than 4/week and/or total gastrointestinal transit time greater than 33 hr and was randomly assigned to double-blind treatment with either cisapride (N = 10) or placebo (N = 10) for 12 weeks. Stool habits, total gastrointestinal transit time, and anorectal motility were evaluated in all children before and at the end of the treatment period. Cisapride significantly increased stool frequency from 1.2 +/- 0.6 to 5.1 +/- 1.9 stools/week (mean +/- SD; P less than 0.05), whereas the lesser effect of placebo was not significant (1.2 +/- 0.8 to 2.8 +/- 0.8 stools/week; P = 0.4). Both treatments significantly (P less than 0.05) decreased laxative or suppository use. Total gastrointestinal transit time was decreased by cisapride (90.8 +/- 9.2 hr to 57.2 +/- 20.2 hr; P less than 0.05) but was not affected by placebo. Anorectal manometry showed that cisapride, but not placebo, significantly decreased the rectoanal inhibitory reflex threshold and the conscious rectal sensitivity threshold. It is concluded that cisapride improves gastrointestinal motility and bowel habits in children with chronic idiopathic constipation and may be useful in the management of some children with this disorder.", "nan" ]