Showing papers on "Randomized controlled trial published in 2010"

CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials.

Abstract: The CONSORT (Consolidated Standards of Reporting Trials) statement is used worldwide to improve the reporting of randomized, controlled trials. Schulz and colleagues describe the latest version, CONSORT 2010, which updates the reporting guideline based on new methodological evidence and accumulating experience.

A Systematic Review and Meta-analysis

Abstract: Methods: We conducted a systematic review of studies published from January 1, 1950, through November 31, 2008, using PubMed, EMBASE, Web of Knowledge, CINAHL, and all Evidence-Based Medicine Reviews. Randomized clinical trials and prospective studies of RRTs that reported data on changes in the primary outcome of hospital mortality or the secondary outcome of cardiopulmonary arrest cases were included.

Randomized, Controlled Trial of an Intervention for Toddlers With Autism: The Early Start Denver Model

Abstract: OBJECTIVE: To conduct a randomized, controlled trial to evaluate the efficacy of the Early Start Denver Model (ESDM), a comprehensive developmental behavioral intervention, for improving outcomes of toddlers diagnosed with autism spectrum disorder (ASD). METHODS: Forty-eight children diagnosed with ASD between 18 and 30 months of age were randomly assigned to 1 of 2 groups: (1) ESDM intervention, which is based on developmental and applied behavioral analytic principles and delivered by trained therapists and parents for 2 years; or (2) referral to community providers for intervention commonly available in the community. RESULTS: Compared with children who received community-intervention, children who received ESDM showed significant improvements in IQ, adaptive behavior, and autism diagnosis. Two years after entering intervention, the ESDM group on average improved 17.6 standard score points (1 SD: 15 points) compared with 7.0 points in the comparison group relative to baseline scores. The ESDM group maintained its rate of growth in adaptive behavior compared with a normative sample of typically developing children. In contrast, over the 2-year span, the comparison group showed greater delays in adaptive behavior. Children who received ESDM also were more likely to experience a change in diagnosis from autism to pervasive developmental disorder, not otherwise specified, than the comparison group. CONCLUSIONS: This is the first randomized, controlled trial to demonstrate the efficacy of a comprehensive developmental behavioral intervention for toddlers with ASD for improving cognitive and adaptive behavior and reducing severity of ASD diagnosis. Results of this study underscore the importance of early detection of and intervention in autism.

The impact of advance care planning on end of life care in elderly patients: randomised controlled trial

Abstract: Objective To investigate the impact of advance care planning on end of life care in elderly patients. Design Prospective randomised controlled trial. Setting Single centre study in a university hospital in Melbourne, Australia. Participants 309 legally competent medical inpatients aged 80 or more and followed for six months or until death. Interventions Participants were randomised to receive usual care or usual care plus facilitated advance care planning. Advance care planning aimed to assist patients to reflect on their goals, values, and beliefs; to consider future medical treatment preferences; to appoint a surrogate; and to document their wishes. Main outcome measures The primary outcome was whether a patient’s end of life wishes were known and respected. Other outcomes included patient and family satisfaction with hospital stay and levels of stress, anxiety, and depression in relatives of patients who died. Results 154 of the 309 patients were randomised to advance care planning, 125 (81%) received advance care planning, and 108 (84%) expressed wishes or appointed a surrogate, or both. Of the 56 patients who died by six months, end of life wishes were much more likely to be known and followed in the intervention group (25/29, 86%) compared with the control group (8/27, 30%; P Conclusions Advance care planning improves end of life care and patient and family satisfaction and reduces stress, anxiety, and depression in surviving relatives. Trial registration Australian New Zealand clinical trials registry ACTRN12608000539336.

Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis

Abstract: OBJECTIVE: To systematically review the literature and, where appropriate, meta-analyse studies investigating subsequent antibiotic resistance in individuals prescribed antibiotics in primary care. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Observational and experimental studies identified through Medline, Embase, and Cochrane searches. Review methods Electronic searches using MeSH terms and text words identified 4373 papers. Two independent reviewers assessed quality of eligible studies and extracted data. Meta-analyses were conducted for studies presenting similar outcomes. RESULTS: The review included 24 studies; 22 involved patients with symptomatic infection and two involved healthy volunteers; 19 were observational studies (of which two were prospective) and five were randomised trials. In five studies of urinary tract bacteria (14 348 participants), the pooled odds ratio (OR) for resistance was 2.5 (95% confidence interval 2.1 to 2.9) within 2 months of antibiotic treatment and 1.33 (1.2 to 1.5) within 12 months. In seven studies of respiratory tract bacteria (2605 participants), pooled ORs were 2.4 (1.4 to 3.9) and 2.4 (1.3 to 4.5) for the same periods, respectively. Studies reporting the quantity of antibiotic prescribed found that longer duration and multiple courses were associated with higher rates of resistance. Studies comparing the potential for different antibiotics to induce resistance showed no consistent effects. Only one prospective study reported changes in resistance over a long period; pooled ORs fell from 12.2 (6.8 to 22.1) at 1 week to 6.1 (2.8 to 13.4) at 1 month, 3.6 (2.2 to 6.0) at 2 months, and 2.2 (1.3 to 3.6) at 6 months. CONCLUSIONS: Individuals prescribed an antibiotic in primary care for a respiratory or urinary infection develop bacterial resistance to that antibiotic. The effect is greatest in the month immediately after treatment but may persist for up to 12 months. This effect not only increases the population carriage of organisms resistant to first line antibiotics, but also creates the conditions for increased use of second line antibiotics in the community.

EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision

Abstract: Background and objectives: This second European Federation of Neurological Societies Task Force aimed at updating the existing evidence about the pharmacological treatment of neuropathic pain since 2005. Methods: Studies were identified using the Cochrane Database and Medline. Trials were classified according to the aetiological condition. All class I and II randomized controlled trials (RCTs) were assessed; lower class studies were considered only in conditions that had no top-level studies. Treatments administered using repeated or single administrations were considered, provided they are feasible in an outpatient setting. Results: Most large RCTs included patients with diabetic polyneuropathies and post-herpetic neuralgia, while an increasing number of smaller studies explored other conditions. Drugs generally have similar efficacy in various conditions, except in trigeminal neuralgia, chronic radiculopathy and HIV neuropathy, with level A evidence in support of tricyclic antidepressants (TCA), pregabalin, gabapentin, tramadol and opioids (in various conditions), duloxetine, venlafaxine, topical lidocaine and capsaicin patches (in restricted conditions). Combination therapy appears useful for TCA-gabapentin and gabapentin-opioids (level A). Conclusions: There are still too few large-scale comparative studies. For future trials, we recommend to assess comorbidities, quality of life, symptoms and signs with standardized tools and attempt to better define responder profiles to specific drug treatments.

Meta-Analysis of Concomitant Versus Sequential Radiochemotherapy in Locally Advanced Non–Small-Cell Lung Cancer

Abstract: Purpose The previous individual patient data meta-analyses of chemotherapy in locally advanced non–small-cell lung cancer (NSCLC) showed that adding sequential or concomitant chemotherapy to radiotherapy improved survival. The NSCLC Collaborative Group performed a meta-analysis of randomized trials directly comparing concomitant versus sequential radiochemotherapy. Methods Systematic searches for trials were undertaken, followed by central collection, checking, and reanalysis of updated individual patient data. Results from trials were combined using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival; secondary outcomes were progression-free survival, cumulative incidences of locoregional and distant progression, and acute toxicity. Results Of seven eligible trials, data from six trials were received (1,205 patients, 92% of all randomly assigned patients). Median follow-up was 6 years. There was a significant benefit of concomitant radiochemother...

Randomized Controlled Trial

Abstract: OBJECTIVE: To determine if medical students’ attendance at specialized prenatal clinics for Southwest Native American women would impact their awareness of and comfort in discussing traditional and unique values during pregnancy. STUDY DESIGN: In this unblinded, randomized trial, all 154 third-year students rotating consecutively on our obstetrics-gynecology clerkship consented to enrolling in this study. Participants were randomly assigned either to attend a highrisk prenatal clinic (rural or urban locations) for Native American women or to not attend (control group). Each anonymously answered a 20-question survey at the beginning and end of the clerkship about their comfort level and their awareness of patients’ beliefs. A mixed model ANOVA was used to compare differences in scores between the groups while accounting for cluster effects in the study design. RESULTS: Regardless of whether the clinic was rural or urban, students became much more comfortable than controls in talking with Native American women about their pregnancy (p < 0.005). This applied especially to discussions about patients’ spiritual beliefs, taboos that may affect pregnancy, participation in tribal ceremonies and belief in traditional medicine. As compared with the control group, students assigned to either clinic became more aware of how spirituality played an integral role in pregnancy (p < 0.05). CONCLUSION: Attendance at these specialized prenatal clinics enhanced medical students’ comfort in talking with pregnant Native American women about the integrative roles of spiritual beliefs, tribal ceremonies and complementary medicine in their pregnancy outcome. (J Reprod Med 2009;54:603–608)

EFNS guidelines on the pharmacological treatment of neuropathic pain: 2009 revision

Abstract: Background and objectives: This second European Federation of Neurological Societies Task Force aimed at updating the existing evidence about the pharmacological treatment of neuropathic pain since 2005. Methods: Studies were identified using the Cochrane Database and Medline. Trials were classified according to the aetiological condition. All class I and II randomized controlled trials (RCTs) were assessed; lower class studies were considered only in conditions that had no top-level studies. Treatments administered using repeated or single administrations were considered, provided they are feasible in an outpatient setting. Results: Most large RCTs included patients with diabetic polyneuropathies and postherpetic neuralgia, while an increasing number of smaller studies explored other conditions. Drugs generally have similar e!cacy in various conditions, except in trigeminal neuralgia, chronic radiculopathy and HIV neuropathy, with level A evidence in support of tricyclic antidepressants (TCA), pregabalin, gabapentin, tramadol and opioids (in various conditions), duloxetine, venlafaxine, topical lidocaine and capsaicin patches (in restricted conditions). Combination therapy appears useful for TCAgabapentin and gabapentin-opioids (level A). Conclusions: There are still too few large-scale comparative studies. For future trials, we recommend to assess comorbidities, quality of life, symptoms and signs with standardized tools and attempt to better define responder profiles to specific drug treatments.

Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial

Abstract: Summary Background Sentinel-lymph-node (SLN) surgery was designed to minimise the side-effects of lymph-node surgery but still offer outcomes equivalent to axillary-lymph-node dissection (ALND). The aims of National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-32 were to establish whether SLN resection in patients with breast cancer achieves the same survival and regional control as ALND, but with fewer side-effects. Methods NSABP B-32 was a randomised controlled phase 3 trial done at 80 centres in Canada and the USA between May 1, 1999, and Feb 29, 2004. Women with invasive breast cancer were randomly assigned to either SLN resection plus ALND (group 1) or to SLN resection alone with ALND only if the SLNs were positive (group 2). Random assignment was done at the NSABP Biostatistical Center (Pittsburgh, PA, USA) with a biased coin minimisation approach in an allocation ratio of 1:1. Stratification variables were age at entry (≤49 years, ≥50 years), clinical tumour size (≤2·0 cm, 2·1–4·0 cm, ≥4·1 cm), and surgical plan (lumpectomy, mastectomy). SLN resection was done with a blue dye and radioactive tracer. Outcome analyses were done in patients who were assessed as having pathologically negative sentinel nodes and for whom follow-up data were available. The primary endpoint was overall survival. Analyses were done on an intention-to-treat basis. All deaths, irrespective of cause, were included. The mean time on study for the SLN-negative patients with follow-up information was 95·6 months (range 70·1–126·7). This study is registered with ClinicalTrials.gov, number NCT00003830. Findings 5611 women were randomly assigned to the treatment groups, 3989 had pathologically negative SLN. 309 deaths were reported in the 3986 SLN-negative patients with follow-up information: 140 of 1975 patients in group 1 and 169 of 2011 in group 2. Log-rank comparison of overall survival in groups 1 and 2 yielded an unadjusted hazard ratio (HR) of 1·20 (95% CI 0·96–1·50; p=0·12). 8-year Kaplan-Meier estimates for overall survival were 91·8% (95% CI 90·4–93·3) in group 1 and 90·3% (88·8–91·8) in group 2. Treatment comparisons for disease-free survival yielded an unadjusted HR of 1·05 (95% CI 0·90–1·22; p=0·54). 8-year Kaplan-Meier estimates for disease-free survival were 82·4% (80·5–84·4) in group 1 and 81·5% (79·6–83·4) in group 2. There were eight regional-node recurrences as first events in group 1 and 14 in group 2 (p=0·22). Patients are continuing follow-up for longer-term assessment of survival and regional control. The most common adverse events were allergic reactions, mostly related to the administration of the blue dye. Interpretation Overall survival, disease-free survival, and regional control were statistically equivalent between groups. When the SLN is negative, SLN surgery alone with no further ALND is an appropriate, safe, and effective therapy for breast cancer patients with clinically negative lymph nodes. Funding US Public Health Service, National Cancer Institute, and Department of Health and Human Services.

Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials.

Abstract: Objectives—Although the effects of exercise on neurocognition have been the subject of several previous reviews and meta-analyses, they have been hampered by methodological shortcomings and are now outdated as a result of the recent publication of several large-scale randomized controlled trials (RCTs). Methods—We conducted a systematic literature review of RCTs examining the association between aerobic exercise training on neurocognitive performance conducted between January, 1966 and July, 2009. Suitable studies were selected for inclusion according to the following criteria: randomized treatment allocation, mean age ≥ 18 years of age, duration of treatment > 1 month, incorporated aerobic exercise components, exercise training was supervised, the presence of a nonaerobic-exercise control group, and sufficient information to derive effect size (ES) data. Results—Twenty-nine studies met inclusion criteria and were included in our analyses, representing data from 2,049 participants and 234 effect sizes. Individuals randomly assigned to receive aerobic exercise training demonstrated modest improvements in attention and processing speed (g = .158 [95% CI: .055 to .260], P = .003), executive function (g = .123 [95% CI: .021 to . 225], P = .018), and memory (g = .128 [95% CI: .015 - .241], P = .026). Conclusions—Aerobic exercise training is associated with modest improvements in attention and processing speed, executive function, and memory, although the effects of exercise on working memory are less consistent. Rigorous RCTs are needed with larger samples, appropriate controls, and longer follow-up periods.

Robot-Assisted Therapy for Long-Term Upper-Limb Impairment after Stroke

Abstract: Background Effective rehabilitative therapies are needed for patients with long-term deficits after stroke. Methods In this multicenter, randomized, controlled trial involving 127 patients with moderate-to-severe upper-limb impairment 6 months or more after a stroke, we randomly assigned 49 patients to receive intensive robot-assisted therapy, 50 to receive intensive comparison therapy, and 28 to receive usual care. Therapy consisted of 36 1-hour sessions over a period of 12 weeks. The primary outcome was a change in motor function, as measured on the Fugl-Meyer Assessment of Sensorimotor Recovery after Stroke, at 12 weeks. Secondary outcomes were scores on the Wolf Motor Function Test and the Stroke Impact Scale. Secondary analyses assessed the treatment effect at 36 weeks. Results At 12 weeks, the mean Fugl-Meyer score for patients receiving robot-assisted therapy was better than that for patients receiving usual care (difference, 2.17 points; 95% confidence interval [CI], −0.23 to 4.58) and worse than ...

Computer Therapy for the Anxiety and Depressive Disorders Is Effective, Acceptable and Practical Health Care: A Meta-Analysis

Abstract: Background: Depression and anxiety disorders are common and treatable with cognitive behavior therapy (CBT), but access to this therapy is limited. Objective: Review evidence that computerized CBT for the anxiety and depressive disorders is acceptable to patients and effective in the short and longer term. Method: Systematic reviews and data bases were searched for randomized controlled trials of computerized cognitive behavior therapy versus a treatment or control condition in people who met diagnostic criteria for major depression, panic disorder, social phobia or generalized anxiety disorder. Number randomized, superiority of treatment versus control (Hedges g) on primary outcome measure, risk of bias, length of follow up, patient adherence and satisfaction were extracted. Principal Findings: 22 studies of comparisons with a control group were identified. The mean effect size superiority was 0.88 (NNT 2.13), and the benefit was evident across all four disorders. Improvement from computerized CBT was maintained for a median of 26 weeks follow-up. Acceptability, as indicated by adherence and satisfaction, was good. Research probity was good and bias risk low. Effect sizes were non-significantly higher in comparisons with waitlist than with active treatment control conditions. Five studies comparing computerized CBT with traditional face-to-face CBT were identified, and both modes of treatment appeared equally beneficial. Conclusions: Computerized CBT for anxiety and depressive disorders, especially via the internet, has the capacity to provide effective acceptable and practical health care for those who might otherwise remain untreated.

Effects on Coronary Heart Disease of Increasing Polyunsaturated Fat in Place of Saturated Fat: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract: Background: Reduced saturated fat (SFA) consumption is recommended to reduce coronary heart disease (CHD), but there is an absence of strong supporting evidence from randomized controlled trials (RCTs) of clinical CHD events and few guidelines focus on any specific replacement nutrient. Additionally, some public health groups recommend lowering or limiting polyunsaturated fat (PUFA) consumption, a major potential replacement for SFA. Methods and Findings: We systematically investigated and quantified the effects of increased PUFA consumption, as a replacement for SFA, on CHD endpoints in RCTs. RCTs were identified by systematic searches of multiple online databases through June 2009, grey literature sources, hand-searching related articles and citations, and direct contacts with experts to identify potentially unpublished trials. Studies were included if they randomized participants to increased PUFA for at least 1 year without major concomitant interventions, had an appropriate control group, and reported incidence of CHD (myocardial infarction and/or cardiac death). Inclusions/exclusions were adjudicated and data were extracted independently and in duplicate by two investigators and included population characteristics, control and intervention diets, follow-up duration, types of events, risk ratios, and SEs. Pooled effects were calculated using inverse-variance-weighted random effects meta-analysis. From 346 identified abstracts, eight trials met inclusion criteria, totaling 13,614 participants with 1,042 CHD events. Average weighted PUFA consumption was 14.9% energy (range 8.0%–20.7%) in intervention groups versus 5.0% energy (range 4.0%–6.4%) in controls. The overall pooled risk reduction was 19% (RR=0.81, 95% confidence interval [CI] 0.70–0.95, p=0.008), corresponding to 10% reduced CHD risk (RR=0.90, 95% CI=0.83–0.97) for each 5% energy of increased PUFA, without evidence for statistical heterogeneity (Q-statistic p=0.13; I 2 =37%). Meta-regression identified study duration as an independent determinant of risk reduction (p=0.017), with studies of longer duration showing greater benefits. Conclusions: These findings provide evidence that consuming PUFA in place of SFA reduces CHD events in RCTs. This suggests that rather than trying to lower PUFA consumption, a shift toward greater population PUFA consumption in place of SFA would significantly reduce rates of CHD. Please see later in the article for the Editors’ Summary.

Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: A randomized controlled trial

Abstract: Context Antiarrhythmic drugs are commonly used for prevention of recurrent atrial fibrillation (AF) despite inconsistent efficacy and frequent adverse effects. Catheter ablation has been proposed as an alternative treatment for paroxysmal AF. Objective To determine the efficacy of catheter ablation compared with antiarrhythmic drug therapy (ADT) in treating symptomatic paroxysmal AF. Design, Setting, and Participants A prospective, multicenter, randomized (2:1), unblinded, Bayesian-designed study conducted at 19 hospitals of 167 patients who did not respond to at least 1 antiarrhythmic drug and who experienced at least 3 AF episodes within 6 months before randomization. Enrollment occurred between October 25, 2004, and October 11, 2007, with the last follow-up on January 19, 2009. Intervention Catheter ablation (n = 106) or ADT (n = 61), with assessment for effectiveness in a comparable 9-month follow-up period. Main Outcome Measures Time to protocol-defined treatment failure. The proportion of patients who experienced major treatment-related adverse events within 30 days of catheter ablation or ADT was also reported. Results At the end of the 9-month effectiveness evaluation period, 66% of patients in the catheter ablation group remained free from protocol-defined treatment failure compared with 16% of patients treated with ADT. The hazard ratio of catheter ablation to ADT was 0.30 (95% confidence interval, 0.19-0.47; P Conclusion Among patients with paroxysmal AF who had not responded to at least 1 antiarrhythmic drug, the use of catheter ablation compared with ADT resulted in a longer time to treatment failure during the 9-month follow-up period. Trial Registration clinicaltrials.gov Identifier: NCT00116428

Effects of aerobic exercise on mild cognitive impairment: a controlled trial.

Abstract: Objectives To examine the effects of aerobic exercise on cognition and other biomarkers associated with Alzheimer disease pathology for older adults with mild cognitive impairment, and assess the role of sex as a predictor of response. Design Six-month, randomized, controlled, clinical trial. Setting Veterans Affairs Puget Sound Health Care System clinical research unit. Participants Thirty-three adults (17 women) with amnestic mild cognitive impairment ranging in age from 55 to 85 years (mean age, 70 years). Intervention Participants were randomized either to a high-intensity aerobic exercise or stretching control group. The aerobic group exercised under the supervision of a fitness trainer at 75% to 85% of heart rate reserve for 45 to 60 min/d, 4 d/wk for 6 months. The control group carried out supervised stretching activities according to the same schedule but maintained their heart rate at or below 50% of their heart rate reserve. Before and after the study, glucometabolic and treadmill tests were performed and fat distribution was assessed using dual-energy x-ray absorptiometry. At baseline, month 3, and month 6, blood was collected for assay and cognitive tests were administered. Main Outcome Measures Performance measures on Symbol-Digit Modalities, Verbal Fluency, Stroop, Trails B, Task Switching, Story Recall, and List Learning. Fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulinlike growth factor-I, and β-amyloids 40 and 42. Results Six months of high-intensity aerobic exercise had sex-specific effects on cognition, glucose metabolism, and hypothalamic-pituitary-adrenal axis and trophic activity despite comparable gains in cardiorespiratory fitness and body fat reduction. For women, aerobic exercise improved performance on multiple tests of executive function, increased glucose disposal during the metabolic clamp, and reduced fasting plasma levels of insulin, cortisol, and brain-derived neurotrophic factor. For men, aerobic exercise increased plasma levels of insulinlike growth factor I and had a favorable effect only on Trails B performance. Conclusions This study provides support, using rigorous controlled methodology, for a potent nonpharmacologic intervention that improves executive control processes for older women at high risk of cognitive decline. Moreover, our results suggest that a sex bias in cognitive response may relate to sex-based differences in glucometabolic and hypothalamic-pituitary-adrenal axis responses to aerobic exercise.

Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis

Abstract: Objective To investigate whether calcium supplements increase the risk of cardiovascular events. Design Patient level and trial level meta-analyses. Data sources Medline, Embase, and Cochrane Central Register of Controlled Trials (1966-March 2010), reference lists of meta-analyses of calcium supplements, and two clinical trial registries. Initial searches were carried out in November 2007, with electronic database searches repeated in March 2010. Study selection Eligible studies were randomised, placebo controlled trials of calcium supplements (≥500 mg/day), with 100 or more participants of mean age more than 40 years and study duration more than one year. The lead authors of eligible trials supplied data. Cardiovascular outcomes were obtained from self reports, hospital admissions, and death certificates. Results 15 trials were eligible for inclusion, five with patient level data (8151 participants, median follow-up 3.6 years, interquartile range 2.7-4.3 years) and 11 with trial level data (11 921 participants, mean duration 4.0 years). In the five studies contributing patient level data, 143 people allocated to calcium had a myocardial infarction compared with 111 allocated to placebo (hazard ratio 1.31, 95% confidence interval 1.02 to 1.67, P=0.035). Non-significant increases occurred in the incidence of stroke (1.20, 0.96 to 1.50, P=0.11), the composite end point of myocardial infarction, stroke, or sudden death (1.18, 1.00 to 1.39, P=0.057), and death (1.09, 0.96 to 1.23, P=0.18). The meta-analysis of trial level data showed similar results: 296 people had a myocardial infarction (166 allocated to calcium, 130 to placebo), with an increased incidence of myocardial infarction in those allocated to calcium (pooled relative risk 1.27, 95% confidence interval 1.01 to 1.59, P=0.038). Conclusions Calcium supplements (without coadministered vitamin D) are associated with an increased risk of myocardial infarction. As calcium supplements are widely used these modest increases in risk of cardiovascular disease might translate into a large burden of disease in the population. A reassessment of the role of calcium supplements in the management of osteoporosis is warranted.

[CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials (Chinese version)]

Abstract: Overwhelming evidence shows the quality of reporting of randomised controlled trials (RCTs) is not optimal. Without transparent reporting, readers cannot judge the reliability and validity of trial findings nor extract information for systematic reviews. Recent methodological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which are considered the gold standard for evaluating interventions because of their ability to minimise or avoid bias. A group of scientists and editors developed the CONSORT (Consolidated Standards of Reporting Trials) statement to improve the quality of reporting of RCTs. It was first published in 1996 and updated in 2001. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have endorsed the CONSORT statement. The statement facilitates critical appraisal and interpretation of RCTs. During the 2001 CONSORT revision, it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports. A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement. After an expert meeting in January 2007, the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement. This update improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition, such as selective outcome reporting bias. This explanatory and elaboration document intended to enhance the use, understanding, and dissemination of the CONSORT statement-has also been extensively revised. It presents the meaning and rationale for each new and updated checklist item providing examples of good reporting and, where possible, references to relevant empirical studies. Several examples of flow diagrams are included. The CONSORT 2010 Statement, this revised explanatory and elaboration document, and the associated website (www. consort-statement. org) should be helpful resources to improve reporting of randomised trials.

Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy: A Randomized Clinical Trial

Abstract: Context Goal-directed resuscitation for severe sepsis and septic shock has been reported to reduce mortality when applied in the emergency department. Objective To test the hypothesis of noninferiority between lactate clearance and central venous oxygen saturation (ScvO 2 ) as goals of early sepsis resuscitation. Design, Setting, and Patients Multicenter randomized, noninferiority trial involving patients with severe sepsis and evidence of hypoperfusion or septic shock who were admitted to the emergency department from January 2007 to January 2009 at 1 of 3 participating US urban hospitals. Interventions We randomly assigned patients to 1 of 2 resuscitation protocols. The ScvO 2 group was resuscitated to normalize central venous pressure, mean arterial pressure, and ScvO 2 of at least 70%; and the lactate clearance group was resuscitated to normalize central venous pressure, mean arterial pressure, and lactate clearance of at least 10%. The study protocol was continued until all goals were achieved or for up to 6 hours. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment. Main Outcome Measure The primary outcome was absolute in-hospital mortality rate; the noninferiority threshold was set at Δ equal to −10%. Results Of the 300 patients enrolled, 150 were assigned to each group and patients were well matched by demographic, comorbidities, and physiological features. There were no differences in treatments administered during the initial 72 hours of hospitalization. Thirty-four patients (23%) in the ScvO 2 group died while in the hospital (95% confidence interval [CI], 17%-30%) compared with 25 (17%; 95% CI, 11%-24%) in the lactate clearance group. This observed difference between mortality rates did not reach the predefined −10% threshold (intent-to-treat analysis: 95% CI for the 6% difference, −3% to 15%). There were no differences in treatment-related adverse events between the groups. Conclusion Among patients with septic shock who were treated to normalize central venous and mean arterial pressure, additional management to normalize lactate clearance compared with management to normalize ScvO 2 did not result in significantly different in-hospital mortality. Trial Registration clinicaltrials.gov Identifier: NCT00372502

Seventy-Five Trials and Eleven Systematic Reviews a Day: How Will We Ever Keep Up?

Abstract: When Archie Cochrane reproached the medical profession for not having critical summaries of all randomised controlled trials, about 14 reports of trials were being published per day. There are now 75 trials, and 11 systematic reviews of trials, per day and a plateau in growth has not yet been reached. Although trials, reviews, and health technology assessments have undoubtedly had major impacts, the staple of medical literature synthesis remains the non-systematic narrative review. Only a small minority of trial reports are being analysed in up-to-date systematic reviews. Given the constraints, Archie Cochrane's vision will not be achieved without some serious changes in course. To meet the needs of patients, clinicians, and policymakers, unnecessary trials need to be reduced, and systematic reviews need to be prioritised. Streamlining and innovation in methods of systematic reviewing are necessary to enable valid answers to be found for most patient questions. Finally, clinicians and patients require open access to these important resources.

Transfusion Requirements After Cardiac Surgery: the TRACS Randomized Controlled Trial

Abstract: Context Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding optimal blood transfusion practice in patients undergoing cardiac surgery is lacking. Objective To define whether a restrictive perioperative red blood cell transfusion strategy is as safe as a liberal strategy in patients undergoing elective cardiac surgery. Design, Setting, and Patients The Transfusion Requirements After Cardiac Surgery (TRACS) study, a prospective, randomized, controlled clinical noninferiority trial conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral center in Brazil. Consecutive adult patients (n = 502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention-to-treat. Intervention Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit ≥30%) or to a restrictive strategy (hematocrit ≥24%). Main Outcome Measure Composite end point of 30-day all-cause mortality and severe morbidity (cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The noninferiority margin was predefined at −8% (ie, 8% minimal clinically important increase in occurrence of the composite end point). Results Hemoglobin concentrations were maintained at a mean of 10.5 g/dL (95% confidence interval [CI], 10.4-10.6) in the liberal-strategy group and 9.1 g/dL (95% CI, 9.0-9.2) in the restrictive-strategy group (P Conclusion Among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in noninferior rates of the combined outcome of 30-day all-cause mortality and severe morbidity. Trial Registration clinicaltrials.gov Identifier: NCT01021631

Long-chain ω-3 fatty acids for indicated prevention of psychotic disorders: A randomized, placebo-controlled trial

Abstract: Context: The use of antipsychotic medication for the prevention of psychotic disorders is controversial. Longchain-3 (omega-3) polyunsaturated fatty acids (PUFAs) may be beneficial in a range of psychiatric conditions, including schizophrenia. Given that-3 PUFAs are generally beneficial to health and without clinically relevant adverse effects, their preventive use in psychosis merits investigation. Objective: To determine whether -3 PUFAs reduce the rate of progression to first-episode psychotic disorder in adolescents and young adults aged 13 to 25 years with subthreshold psychosis. Design: Randomized, d ouble-blind, p lacebocontrolled trial conducted between 2004 and 2007. Setting: Psychosis detection unit of a large public hospital in Vienna, Austria. Participants: Eighty-one individuals at ultra-high risk of psychotic disorder. Interventions: A 12-week intervention period of 1.2g/d -3 PUFA or placebo was followed by a 40-week monitoring period; the total study period was 12 months. Main Outcome Measures: The primary outcome measure was transition to psychotic disorder. Secondary outcomes included symptomatic and functional changes. The ratio of -6 to -3 fatty acids in erythrocytes was used to index pretreatment vs posttreatment fatty acid composition. Results: Seventy-six of 81 participants (93.8%) completed the intervention. By study’s end (12 months), 2 of 41 individuals (4.9%) in the -3 group and 11 of 40 (27.5%) in the placebo group had transitioned to psychotic disorder (P = .007). The difference between the groups in the cumulative risk of progression to fullthreshold psychosis was 22.6% (95% confidence interval, 4.8-40.4). -3 Polyunsaturated fatty acids also significantly reduced positive symptoms (P=.01), negative symptoms (P=.02), and general symptoms (P=.01) and improved functioning (P = .002) compared with placebo. The incidence of adverse effects did not differ between the treatment groups. Conclusions: Long-chain-3 PUFAs reduce the risk of progression to psychotic disorder and may offer a safe and efficacious strategy for indicated prevention in young people with subthreshold psychotic states. Trial Registration: clinicaltrials.gov Identifier: NCT00396643