Showing papers on "Randomized controlled trial published in 2005"

Effect of treatment of gestational diabetes mellitus on pregnancy outcomes

Abstract: Background We conducted a randomized clinical trial to determine whether treatment of women with gestational diabetes mellitus reduced the risk of perinatal complications. Methods We randomly assig...

Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial.

Abstract: Background Observational studies suggest that male circumcision may provide protection against HIV-1 infection. A randomized, controlled intervention trial was conducted in a general population of South Africa to test this hypothesis. Methods and Findings A total of 3,274 uncircumcised men, aged 18–24 y, were randomized to a control or an intervention group with follow-up visits at months 3, 12, and 21. Male circumcision was offered to the intervention group immediately after randomization and to the control group at the end of the follow-up. The grouped censored data were analyzed in intention-to-treat, univariate and multivariate, analyses, using piecewise exponential, proportional hazards models. Rate ratios (RR) of HIV incidence were determined with 95% CI. Protection against HIV infection was calculated as 1 � RR. The trial was stopped at the interim analysis, and the mean (interquartile range) follow-up was 18.1 mo (13.0–21.0) when the data were analyzed. There were 20 HIV infections (incidence rate ¼0.85 per 100 person-years) in the intervention group and 49 (2.1 per 100 person-years) in the control group, corresponding to an RR of 0.40 (95% CI: 0.24%–0.68%; p , 0.001). This RR corresponds to a protection of 60% (95% CI: 32%–76%). When controlling for behavioural factors, including sexual behaviour that increased slightly in the intervention group, condom use, and health-seeking behaviour, the protection was of 61% (95% CI: 34%– 77%).

Computerized Training of Working Memory in Children With ADHD - A Randomized, Controlled Trial

Abstract: Computerized Training of Working Memory in Children With ADHD - A Randomized, Controlled Trial

Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials.

Abstract: ContextAtypical antipsychotic medications are widely used to treat delusions, aggression, and agitation in people with Alzheimer disease and other dementia; however, concerns have arisen about the increased risk for cerebrovascular adverse events, rapid cognitive decline, and mortality with their use.ObjectiveTo assess the evidence for increased mortality from atypical antipsychotic drug treatment for people with dementia.Data SourcesMEDLINE (1966 to April 2005), the Cochrane Controlled Trials Register (2005, Issue 1), meetings presentations (1997-2004), and information from the sponsors were searched using the terms for atypical antipsychotic drugs (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone), dementia, Alzheimer disease, and clinical trial.Study SelectionPublished and unpublished randomized placebo-controlled, parallel-group clinical trials of atypical antipsychotic drugs marketed in the United States to treat patients with Alzheimer disease or dementia were selected by consensus of the authors.Data ExtractionTrials, baseline characteristics, outcomes, all-cause dropouts, and deaths were extracted by one reviewer; treatment exposure was obtained or estimated. Data were checked by a second reviewer.Data SynthesisFifteen trials (9 unpublished), generally 10 to 12 weeks in duration, including 16 contrasts of atypical antipsychotic drugs with placebo met criteria (aripiprazole [n = 3], olanzapine [n = 5], quetiapine [n = 3], risperidone [n = 5]). A total of 3353 patients were randomized to study drug and 1757 were randomized to placebo. Outcomes were assessed using standard methods (with random- or fixed-effects models) to calculate odds ratios (ORs) and risk differences based on patients randomized and relative risks based on total exposure to treatment. There were no differences in dropouts. Death occurred more often among patients randomized to drugs (118 [3.5%] vs 40 [2.3%]. The OR by meta-analysis was 1.54; 95% confidence interval [CI], 1.06-2.23; P = .02; and risk difference was 0.01; 95% CI, 0.004-0.02; P = .01). Sensitivity analyses did not show evidence for differential risks for individual drugs, severity, sample selection, or diagnosis.ConclusionsAtypical antipsychotic drugs may be associated with a small increased risk for death compared with placebo. This risk should be considered within the context of medical need for the drugs, efficacy evidence, medical comorbidity, and the efficacy and safety of alternatives. Individual patient analyses modeling survival and causes of death are needed.

Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial.

Abstract: Objective. Several treatment strategies have proven value in the amelioration of rheumatoid arthritis (RA), but the optimal strategy for preventing long-term joint damage and functional decline is unclear. We undertook this study to compare clinical and radiographic outcomes of 4 different treatment strategies, with intense monitoring in all patients. Methods. In a multicenter, randomized clinical trial, 508 patients were allocated to 1 of 4 treatment strategies: sequential disease-modifying antirheumatic drug monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with tapered high-dose prednisone (group 3), and initial combination therapy with the tumor necrosis factor antagonist infliximab (group 4). Treatment adjustments were made every 3 months in an effort to obtain low disease activity (a Disease Activity Score in 44 joints of <2.4). Results. Initial combination therapy including either prednisone (group 3) or infliximab (group 4) resulted in earlier functional improvement than did sequential monotherapy (group 1) and step-up combination therapy (group 2), with mean scores at 3 months on the Dutch version of the Health Assessment Questionnaire (D-HAQ) of 1.0 in groups 1 and 2 and 0.6 in groups 3 and 4 (P < 0.001). After 1 year, mean D-HAQ scores were 0.7 in groups 1 and 2 and 0.5 in groups 3 and 4( P 0.009). The median increases in total Sharp/Van der Heijde radiographic joint score were 2.0, 2.5, 1.0, and 0.5 in groups 1–4, respectively (P < 0.001). There were no significant differences in the number of adverse events and withdrawals between the groups. Conclusion. In patients with early RA, initial combination therapy including either prednisone or infliximab resulted in earlier functional improvement and less radiographic damage after 1 year than did sequential monotherapy or step-up combination therapy.

Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial.

Abstract: Context Experimental and epidemiological data suggest that vitamin E supplementation may prevent cancer and cardiovascular events. Clinical trials have generally failed to confirm benefits, possibly due to their relatively short duration. Objective To evaluate whether long-term supplementation with vitamin E decreases the risk of cancer, cancer death, and major cardiovascular events. Design, setting, and patients A randomized, double-blind, placebo-controlled international trial (the initial Heart Outcomes Prevention Evaluation [HOPE] trial conducted between December 21, 1993, and April 15, 1999) of patients at least 55 years old with vascular disease or diabetes mellitus was extended (HOPE-The Ongoing Outcomes [HOPE-TOO]) between April 16, 1999, and May 26, 2003. Of the initial 267 HOPE centers that had enrolled 9541 patients, 174 centers participated in the HOPE-TOO trial. Of 7030 patients enrolled at these centers, 916 were deceased at the beginning of the extension, 1382 refused participation, 3994 continued to take the study intervention, and 738 agreed to passive follow-up. Median duration of follow-up was 7.0 years. Intervention Daily dose of natural source vitamin E (400 IU) or matching placebo. Main outcome measures Primary outcomes included cancer incidence, cancer deaths, and major cardiovascular events (myocardial infarction, stroke, and cardiovascular death). Secondary outcomes included heart failure, unstable angina, and revascularizations. Results Among all HOPE patients, there were no significant differences in the primary analysis: for cancer incidence, there were 552 patients (11.6%) in the vitamin E group vs 586 (12.3%) in the placebo group (relative risk [RR], 0.94; 95% confidence interval [CI], 0.84-1.06; P = .30); for cancer deaths, 156 (3.3%) vs 178 (3.7%), respectively (RR, 0.88; 95% CI, 0.71-1.09; P = .24); and for major cardiovascular events, 1022 (21.5%) vs 985 (20.6%), respectively (RR, 1.04; 95% CI, 0.96-1.14; P = .34). Patients in the vitamin E group had a higher risk of heart failure (RR, 1.13; 95% CI, 1.01-1.26; P = .03) and hospitalization for heart failure (RR, 1.21; 95% CI, 1.00-1.47; P = .045). Similarly, among patients enrolled at the centers participating in the HOPE-TOO trial, there were no differences in cancer incidence, cancer deaths, and major cardiovascular events, but higher rates of heart failure and hospitalizations for heart failure. Conclusion In patients with vascular disease or diabetes mellitus, long-term vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure.

The effects of a smoking cessation intervention on 14.5-year mortality: a randomized clinical trial.

Abstract: Background Randomized clinical trials have not yet demonstrated the mortality benefit of smoking cessation. Objective To assess the long-term effect on mortality of a randomly applied smoking cessation program. Design The Lung Health Study was a randomized clinical trial of smoking cessation. Special intervention participants received the smoking intervention program and were compared with usual care participants. Vital status was followed up to 14.5 years. Setting 10 clinical centers in the United States and Canada. Patients 5887 middle-aged volunteers with asymptomatic airway obstruction. Measurements All-cause mortality and mortality due to cardiovascular disease, lung cancer, and other respiratory disease. Intervention The intervention was a 10-week smoking cessation program that included a strong physician message and 12 group sessions using behavior modification and nicotine gum, plus either ipratropium or a placebo inhaler. Results At 5 years, 21.7% of special intervention participants had stopped smoking since study entry compared with 5.4% of usual care participants. After up to 14.5 years of follow-up, 731 patients died: 33% of lung cancer, 22% of cardiovascular disease, 7.8% of respiratory disease other than cancer, and 2.3% of unknown causes. All-cause mortality was significantly lower in the special intervention group than in the usual care group (8.83 per 1000 person-years vs. 10.38 per 1000 person-years; P = 0.03). The hazard ratio for mortality in the usual care group compared with the special intervention group was 1.18 (95% CI, 1.02 to 1.37). Differences in death rates for both lung cancer and cardiovascular disease were greater when death rates were analyzed by smoking habit. Limitations Results apply only to individuals with airway obstruction. Conclusion Smoking cessation intervention programs can have a substantial effect on subsequent mortality, even when successful in a minority of participants.

Outcome criteria in smoking cessation trials: proposal for a common standard

Abstract: Smoking cessation treatment is now integrated into many health-care systems and a major research effort is under way to improve current success rates. Until now results from randomized clinical trials have been reported in many different ways, leading to problems of interpretation. We propose six standard criteria comprising the 'Russell Standard' (RS). These criteria are applicable to trials of cessation aids where participants have a defined target quit date and there is face-to-face contact with researchers or clinic staff, as follows. (1) Follow-up for 6 months (RS6) or 12 months (RS12) from the target quit date or the end of a predefined 'grace period'; (2) self-report of smoking abstinence over the whole follow-up period allowing up to five cigarettes in total; (3) biochemical verification of abstinence at least at the 6-month or 12-month follow-up point; (4) use of an 'intention-to-treat' approach in which data from all randomized smokers are included in the analysis unless they have died or moved to an untraceable address (participants who are included in the analysis are counted as smokers if their smoking status at the final follow-up cannot be determined); (5) following-up 'protocol violators' and using their true smoking status in the analysis; and (6) collecting follow-up data blind to smokers' allocation to trial group. We believe that these criteria provide the best compromise between practicability and surrogacy for long-term cessation and will enable meaningful comparison between studies. There may be good reasons why other outcome criteria would also be reported, and studies that involve interventions with special groups or where there is no designated target quit date or face to face contact would need to adapt these criteria accordingly.

Treatment of complicated grief: a randomized controlled trial

Abstract: ContextComplicated grief is a debilitating disorder associated with important negative health consequences, but the results of existing treatments for it have been disappointing.ObjectiveTo compare the efficacy of a novel approach, complicated grief treatment, with a standard psychotherapy (interpersonal psychotherapy).DesignTwo-cell, prospective, randomized controlled clinical trial, stratified by manner of death of loved one and treatment site.SettingA university-based psychiatric research clinic as well as a satellite clinic in a low-income African American community between April 2001 and April 2004.ParticipantsA total of 83 women and 12 men aged 18 to 85 years recruited through professional referral, self-referral, and media announcements who met criteria for complicated grief.InterventionsParticipants were randomly assigned to receive interpersonal psychotherapy (n = 46) or complicated grief treatment (n = 49); both were administered in 16 sessions during an average interval of 19 weeks per participant.Main Outcome MeasureTreatment response, defined either as independent evaluator-rated Clinical Global Improvement score of 1 or 2 or as time to a 20-point or better improvement in the self-reported Inventory of Complicated Grief.ResultsBoth treatments produced improvement in complicated grief symptoms. The response rate was greater for complicated grief treatment (51%) than for interpersonal psychotherapy (28%; P = .02) and time to response was faster for complicated grief treatment (P = .02). The number needed to treat was 4.3.ConclusionComplicated grief treatment is an improved treatment over interpersonal psychotherapy, showing higher response rates and faster time to response.

The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial.

Abstract: At the beginning of the Diabetes Prevention Program, half of the participants had the metabolic syndrome. Both the lifestyle intervention and metformin therapy reduced the incidence of the syndrome...

Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence.

Abstract: ContextNeuropsychiatric symptoms of dementia are common and associated with poor outcomes for patients and caregivers. Although nonpharmacological interventions should be the first line of treatment, a wide variety of pharmacological agents are used in the management of neuropsychiatric symptoms; therefore, concise, current, evidence-based recommendations are needed.ObjectiveTo evaluate the efficacy of pharmacological agents used in the treatment of neuropsychiatric symptoms of dementia.Evidence AcquisitionA systematic review of English-language articles published from 1966 to July 2004 using MEDLINE, the Cochrane Database of Systematic Reviews, and a manual search of bibliographies was conducted. Inclusion criteria were double-blind, placebo-controlled, randomized controlled trials (RCTs) or meta-analyses of any drug therapy for patients with dementia that included neuropsychiatric outcomes. Trials reporting only depression outcomes were excluded. Data on the inclusion criteria, patients, methods, results, and quality of each study were independently abstracted. Twenty-nine articles met inclusion criteria.Evidence SynthesisFor typical antipsychotics, 2 meta-analyses and 2 RCTs were included. Generally, no difference among specific agents was found, efficacy was small at best, and adverse effects were common. Six RCTs with atypical antipsychotics were included; results showed modest, statistically significant efficacy of olanzapine and risperidone, with minimal adverse effects at lower doses. Atypical antipsychotics are associated with an increased risk of stroke. There have been no RCTs designed to directly compare the efficacy of typical and atypical antipsychotics. Five trials of antidepressants were included; results showed no efficacy for treating neuropsychiatric symptoms other than depression, with the exception of 1 study of citalopram. For mood stabilizers, 3 RCTs investigating valproate showed no efficacy. Two small RCTs of carbamazepine had conflicting results. Two meta-analyses and 6 RCTs of cholinesterase inhibitors generally showed small, although statistically significant, efficacy. Two RCTs of memantine also had conflicting results for treatment of neuropsychiatric symptoms.ConclusionsPharmacological therapies are not particularly effective for management of neuropsychiatric symptoms of dementia. Of the agents reviewed, the atypical antipsychotics risperidone and olanzapine currently have the best evidence for efficacy. However, the effects are modest and further complicated by an increased risk of stroke. Additional trials of cholinesterase inhibitors enrolling patients with high levels of neuropsychiatric symptoms may be warranted.

Randomized Trial of Prolonged Exposure for Posttraumatic Stress Disorder with and without Cognitive Restructuring: Outcome at Academic and Community Clinics.

Abstract: Female assault survivors (N=171) with chronic posttraumatic stress disorder (PTSD) were randomly assigned to prolonged exposure (PE) alone, PE plus cognitive restructuring (PE/CR), or wait-list (WL). Treatment, which consisted of 9-12 sessions, was conducted at an academic treatment center or at a community clinic for rape survivors. Evaluations were conducted before and after therapy and at 3-, 6-, and 12-month follow-ups. Both treatments reduced PTSD and depression in intent-to-treat and completer samples compared with the WL condition; social functioning improved in the completer sample. The addition of CR did not enhance treatment outcome. No site differences were found: Treatment in the hands of counselors with minimal cognitive- behavioral therapy (CBT) experience was as efficacious as that of CBT experts. Treatment gains were maintained at follow-up, although a minority of patients received additional treatment.

Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis

Abstract: Idiopathic pulmonary fibrosis (IPF) is a fatal disorder without an effective therapy to date. In a double-blind, randomized, placebo-controlled trial, 107 patients were prospectively evaluated for efficacy of a novel compound, pirfenidone. The difference in the change in the lowest oxygen saturation by pulse oximetry (SpO2) during a 6-minute exercise test, the primary endpoint, from baseline to 6 months was not significant between the two groups (p = 0.0722). In a prespecified subset of patients who maintained a SpO2 greater than 80% during a 6-minute exercise test at baseline, the lowest SpO2 improved during a 6-minute exercise test in the pirfenidone group at 6 and 9 months (p = 0.0069 and 0.0305, respectively). Positive treatment effect was demonstrated in secondary endpoints: (1) change in VC measurements at 9 months (p = 0.0366) and (2) episodes of acute exacerbation of IPF occurring exclusively in the placebo group during the 9 months (p = 0.0031). Significant adverse events were associated with pir...

Exercise therapy for treatment of non-specific low back pain.

Abstract: Background Exercise therapy is widely used as an intervention in low-back pain. Objectives To evaluate the effectiveness of exercise therapy in adult non-specific acute, subacute and chronic low-back pain versus no treatment and other conservative treatments. Search methods The Cochrane Central Register of Controlled Trials (Issue 3, 2004), MEDLINE, EMBASE, PsychInfo, CINAHL databases to October 2004; citation searches and bibliographic reviews of previous systematic reviews. Selection criteria Randomized controlled trials evaluating exercise therapy for adult non-specific low-back pain and measuring pain, function, return-to-work/absenteeism, and/or global improvement outcomes. Data collection and analysis Two reviewers independently selected studies and extracted data on study characteristics, quality, and outcomes at short, intermediate, and long-term follow-up. Main results Sixty-one randomized controlled trials (6390 participants) met inclusion criteria: acute (11), subacute (6) and chronic (43) low-back pain (1 unclear). Evidence was found of effectiveness in chronic populations relative to comparisons at all follow-up periods; pooled mean improvement was 7.3 points (95% CI, 3.7 to 10.9) for pain (out of 100), 2.5 points (1.0 to 3.9) for function (out of 100) at earliest follow-up. In studies investigating patients (i.e. presenting to healthcare providers) mean improvement was 13.3 points (5.5 to 21.1) for pain, 6.9 (2.2 to 11.7) for function, representing significantly greater improvement over studies where participants included those recruited from a general population (e.g. with advertisements). There is some evidence of effectiveness of graded-activity exercise program in subacute low-back pain in occupational settings, though the evidence for other types of exercise therapy in other populations is inconsistent. There was evidence of equal effectiveness relative to comparisons in acute populations [pain: 0.03 points (95% CI, -1.3 to 1.4)]. Limitations: This review largely reflects limitations of the literature, including low quality studies with heterogeneous outcome measures, inconsistent and poor reporting, and possibility of publication bias. Authors' conclusions Exercise therapy appears to be slightly effective at decreasing pain and improving function in adults with chronic low-back pain, particularly in healthcare populations. In subacute low-back pain there is some evidence that a graded activity program improves absenteeism outcomes, though evidence for other types of exercise is unclear. In acute low-back pain, exercise therapy is as effective as either no treatment or other conservative treatments.

Cognitive therapy for the prevention of suicide attempts: a randomized controlled trial.

Abstract: ContextSuicide attempts constitute a major risk factor for completed suicide, yet few interventions specifically designed to prevent suicide attempts have been evaluated.ObjectiveTo determine the effectiveness of a 10-session cognitive therapy intervention designed to prevent repeat suicide attempts in adults who recently attempted suicide.Design, Setting, and ParticipantsRandomized controlled trial of adults (N = 120) who attempted suicide and were evaluated at a hospital emergency department within 48 hours of the attempt. Potential participants (N = 350) were consecutively recruited from October 1999 to September 2002; 66 refused to participate and 164 were ineligible. Participants were followed up for 18 months.InterventionCognitive therapy or enhanced usual care with tracking and referral services.Main Outcome MeasuresIncidence of repeat suicide attempts and number of days until a repeat suicide attempt. Suicide ideation (dichotomized), hopelessness, and depression severity at 1, 3, 6, 12, and 18 months.ResultsFrom baseline to the 18-month assessment, 13 participants (24.1%) in the cognitive therapy group and 23 participants (41.6%) in the usual care group made at least 1 subsequent suicide attempt (asymptotic z score, 1.97; P = .049). Using the Kaplan-Meier method, the estimated 18-month reattempt-free probability in the cognitive therapy group was 0.76 (95% confidence interval [CI], 0.62-0.85) and in the usual care group was 0.58 (95% CI, 0.44-0.70). Participants in the cognitive therapy group had a significantly lower reattempt rate (Wald χ21 = 3.9; P = .049) and were 50% less likely to reattempt suicide than participants in the usual care group (hazard ratio, 0.51; 95% CI, 0.26-0.997). The severity of self-reported depression was significantly lower for the cognitive therapy group than for the usual care group at 6 months (P= .02), 12 months (P = .009), and 18 months (P = .046). The cognitive therapy group reported significantly less hopelessness than the usual care group at 6 months (P = .045). There were no significant differences between groups based on rates of suicide ideation at any assessment point.ConclusionCognitive therapy was effective in preventing suicide attempts for adults who recently attempted suicide.

Spinal cord stimulation versus repeated lumbosacral spine surgery for chronic pain: a randomized, controlled trial.

Abstract: OBJECTIVE Persistent or recurrent radicular pain after lumbosacral spine surgery is often associated with nerve root compression and is treated by repeated operation or, as a last resort, by spinal cord stimulation (SCS). We conducted a prospective, randomized, controlled trial to test our hypothesis that SCS is more likely than reoperation to result in a successful outcome by standard measures of pain relief and treatment outcome, including subsequent use of health care resources. METHODS For an average of 3 years postoperatively, disinterested third-party interviewers followed 50 patients selected for reoperation by standard criteria and randomized to SCS or reoperation. If the results of the randomized treatment were unsatisfactory, patients could cross over to the alternative. Success was based on self-reported pain relief and patient satisfaction. Crossover to the alternative procedure was an outcome measure. Use of analgesics, activities of daily living, and work status were self-reported. RESULTS Among 45 patients (90%) available for follow-up, SCS was more successful than reoperation (9 of 19 patients versus 3 of 26 patients, P <0.01). Patients initially randomized to SCS were significantly less likely to cross over than were those randomized to reoperation (5 of 24 patients versus 14 of 26 patients, P=0.02). Patients randomized to reoperation required increased opiate analgesics significantly more often than those randomized to SCS (P <0.025). Other measures of activities of daily living and work status did not differ significantly. CONCLUSION SCS is more effective than reoperation as a treatment for persistent radicular pain after lumbosacral spine surgery, and in the great majority of patients, it obviates the need for reoperation.

Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT).

Abstract: Objective The signs and symptoms of ankylosing spondylitis (AS) respond inadequately to nonsteroidal antiinflammatory drugs, corticosteroids, and disease-modifying antirheumatic drugs in quite a number of patients. Tumor necrosis factor inhibitors have demonstrated success in reducing AS disease activity in a limited number of clinical trials. The objective of this multicenter, randomized, placebo-controlled study was to evaluate the efficacy and safety of infliximab in patients with AS. Methods Patients were randomly assigned to receive infusions of placebo or 5 mg/kg infliximab at weeks 0, 2, 6, 12, and 18. Efficacy was assessed using the ASsessment in Ankylosing Spondylitis (ASAS) International Working Group criteria, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), night pain, patient's global assessment, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath Ankylosing Spondylitis Metrology Index (BASMI), chest expansion, the Mander enthesis index, the total swollen joint index, the C-reactive protein level, and the Short Form 36 (SF-36) health survey questionnaire. The primary end point in this study was the proportion of patients with a 20% improvement response according to the ASAS International Working Group criteria (ASAS20 responders) at week 24. Results Of the 357 patients screened, 201 were assigned to receive 5 mg/kg infliximab and 78 were assigned to receive placebo. After 24 weeks, 61.2% of patients in the infliximab group were ASAS20 responders compared with 19.2% of patients in the placebo group (P < 0.001). Clinical benefit was observed in patients receiving infliximab as early as week 2 and was maintained over the 24-week study period. Patients receiving infliximab also showed significant improvements in the BASDAI, BASFI, BASMI, chest expansion, and physical component summary score of the SF-36. Adverse events were reported by 82.2% of patients receiving infliximab and by 72.0% of patients receiving placebo; however, most adverse events in both treatment groups were mild or moderate in severity. Conclusion Infliximab was well tolerated and effective in a large cohort of patients with AS during a 24-week study period.

Randomized trials stopped early for benefit: a systematic review

Abstract: ContextRandomized clinical trials (RCTs) that stop earlier than planned because of apparent benefit often receive great attention and affect clinical practice. Their prevalence, the magnitude and plausibility of their treatment effects, and the extent to which they report information about how investigators decided to stop early are, however, unknown.ObjectiveTo evaluate the epidemiology and reporting quality of RCTs involving interventions stopped early for benefit.Data SourcesSystematic review up to November 2004 of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify RCTs stopped early for benefit.Study SelectionRandomized clinical trials of any intervention reported as having stopped early because of results favoring the intervention. There were no exclusion criteria.Data ExtractionTwelve reviewers working independently and in duplicate abstracted data on content area and type of intervention tested, reporting of funding, type of end point driving study termination, treatment effect, length of follow-up, estimated sample size and total sample studied, role of a data and safety monitoring board in stopping the study, number of interim analyses planned and conducted, and existence and type of monitoring methods, statistical boundaries, and adjustment procedures for interim analyses and early stopping.Data SynthesisOf 143 RCTs stopped early for benefit, the majority (92) were published in 5 high-impact medical journals. Typically, these were industry-funded drug trials in cardiology, cancer, and human immunodeficiency virus/AIDS. The proportion of all RCTs published in high-impact journals that were stopped early for benefit increased from 0.5% in 1990-1994 to 1.2% in 2000-2004 (P<.001 for trend). On average, RCTs recruited 63% (SD, 25%) of the planned sample and stopped after a median of 13 (interquartile range [IQR], 3-25) months of follow-up, 1 interim analysis, and when a median of 66 (IQR, 23-195) patients had experienced the end point driving study termination (event). The median risk ratio among truncated RCTs was 0.53 (IQR, 0.28-0.66). One hundred thirty-five (94%) of the 143 RCTs did not report at least 1 of the following: the planned sample size (n = 28), the interim analysis after which the trial was stopped (n = 45), whether a stopping rule informed the decision (n = 48), or an adjusted analysis accounting for interim monitoring and truncation (n = 129). Trials with fewer events yielded greater treatment effects (odds ratio, 28; 95% confidence interval, 11-73).ConclusionsRCTs stopped early for benefit are becoming more common, often fail to adequately report relevant information about the decision to stop early, and show implausibly large treatment effects, particularly when the number of events is small. These findings suggest clinicians should view the results of such trials with skepticism.

Impact of the Pulmonary Artery Catheter in Critically Ill Patients: Meta-analysis of Randomized Clinical Trials

Abstract: Context Randomized clinical trials (RCTs) evaluating the pulmonary artery catheter (PAC) have been limited by small sample size. Some nonrandomized studies suggest that PAC use is associated with increased morbidity and mortality. Objective To estimate the impact of the PAC device in critically ill patients. Data Sources MEDLINE (1985-2005), the Cochrane Controlled Trials Registry (19882005), the National Institutes of Health ClinicalTrials.gov database, and the US Food and Drug Administration Web site for RCTs in which patients were randomly assigned to PAC or no PAC were searched. Results from the ESCAPE trial of patients with severe heart failure were also included. Search terms included pulmonary artery catheter, right heart catheter, catheter, and Swan-Ganz. Study Selection Eligible studies included patients who were undergoing surgery, in the intensive care unit (ICU), admitted with advanced heart failure, or diagnosed with acute respiratory distress syndrome and/or sepsis; and studies that reported death and the number of days hospitalized or the number of days in the ICU as outcome measures. Data Extraction Information on eligibility criteria, baseline characteristics, interventions, outcomes, and methodological quality was extracted by 2 reviewers. Disagreements were resolved by consensus. Data Synthesis In 13 RCTs, 5051 patients were randomized. Hemodynamic goals and treatment strategies varied among trials. A random-effects model was used to estimate the odds ratios (ORs) for death, number of days hospitalized, and use of inotropes and intravenous vasodilators. The combined OR for mortality was 1.04 (95% confidence interval [CI], 0.90-1.20; P=.59). The difference in the mean number of days hospitalized for PAC minus the mean for no PAC was 0.11 (95% CI, �0.51 to 0.74; P=.73). Use of the PAC was associated with a higher use of inotropes (OR, 1.58; 95% CI, 1.19-2.12; P=.002) and intravenous vasodilators (OR, 2.35; 95% CI, 1.75-3.15; P.001). Conclusions In critically ill patients, use of the PAC neither increased overall mortality or days in hospital nor conferred benefit. Despite almost 20 years of RCTs, a clear strategy leading to improved survival with the PAC has not been devised. The neutrality of the PAC for clinical outcomes may result from the absence of effective evidence-based treatments to use in combination with PAC information across the spectrum of critically ill patients.

Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials

Abstract: Background. We performed a meta-analysis of randomized clinical trials to determine the risks of adverse events associated with testosterone replacement in older men. Methods. The MEDLINE database was searched from 1966 to April 2004, using testosterone as the indexing term; limits included human, male, � 45 years old, and randomized controlled trial. Of the 417 studies thus identified, 19 met the inclusion criteria: testosterone replacement for at least 90 days, men � 45 years old with low or low-normal testosterone level, randomized controlled trial, and medically stable men. Odds ratios (ORs) were pooled using a random effects model, assuming heterogeneous results across studies, and were weighted for sample size. Results. In the 19 studies that met eligibility criteria, 651 men were treated with testosterone and 433 with placebo. The combined rate of all prostate events was significantly greater in testosterone-treated men than in placebo-treated men (OR ¼1.78, 95% confidence interval [CI], 1.07‐2.95). Rates of prostate cancer, prostate-specific antigen (PSA) .4 ng/ml, and prostate biopsies were numerically higher in the testosterone group than in the placebo group, although differences between the groups were not individually statistically significant. Testosterone-treated men were nearly four times as likely to have hematocrit .50% as placebo-treated men (OR ¼3.69, 95% CI, 1.82‐7.51). The frequency of cardiovascular events, sleep apnea or death was not significantly different between the two groups. Conclusions. Testosterone replacement in older men was associated with a significantly higher risk of detection of prostate events and of hematocrit .50% than was placebo; hematocrit increase was the most frequent adverse event associated with testosterone replacement. These data reaffirm the need to monitor hematocrit, PSA, and digital examination of the prostate during testosterone replacement in older men.

Prevention of relapse following cognitive therapy vs medications in moderate to severe depression.

Abstract: Background Antidepressant medication prevents the return of depressive symptoms, but only as long as treatment is continued. Objectives To determine whether cognitive therapy (CT) has an enduring effect and to compare this effect against the effect produced by continued antidepressant medication. Design Patients who responded to CT in a randomized controlled trial were withdrawn from treatment and compared during a 12-month period with medication responders who had been randomly assigned to either continuation medication or placebo withdrawal. Patients who survived the continuation phase without relapse were withdrawn from all treatment and observed across a subsequent 12-month naturalistic follow-up. Setting Outpatient clinics at the University of Pennsylvania and Vanderbilt University. Patients A total of 104 patients responded to treatment (57.8% of those initially assigned) and were enrolled in the subsequent continuation phase; patients were initially selected to represent those with moderate to severe depression. Interventions Patients withdrawn from CT were allowed no more than 3 booster sessions during continuation; patients assigned to continuation medication were kept at full dosage levels. Main Outcome Measures Relapse was defined as a return, for at least 2 weeks, of symptoms sufficient to meet the criteria for major depression or Hamilton Depression Rating Scale scores of 14 or higher during the continuation phase. Recurrence was defined in a comparable fashion during the subsequent naturalistic follow-up. Results Patients withdrawn from CT were significantly less likely to relapse during continuation than patients withdrawn from medications (30.8% vs 76.2%; P = .004), and no more likely to relapse than patients who kept taking continuation medication (30.8% vs 47.2%; P = .20). There were also indications that the effect of CT extends to the prevention of recurrence. Conclusions Cognitive therapy has an enduring effect that extends beyond the end of treatment. It seems to be as effective as keeping patients on medication.