Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials

BACKGROUND: Multivitamins are the most commonly used supplement in the developed world. Recent epidemiologic findings suggest that multivitamin use increases the risk of mortality. OBJECTIVE: We aimed to determine whether multivitamin-multimineral treatment, used for primary or secondary prevention, increases the risk of mortality in independently living adults. DESIGN: We performed a meta-analysis of randomized controlled trials. Multiple electronic databases were systematically searched from March to October 2012. Randomized controlled primary or secondary prevention trials were considered for inclusion. Eligible trials investigated daily multivitamin-multimineral supplementation for ≥1 y. Cohorts described as institutionalized or as having terminal illness (tertiary prevention) were excluded. The number of deaths and the sample size of each study arm were extracted independently by 2 researchers. Twenty-one articles were included in the analysis, which generated a total pooled sample of 91,074 people and 8794 deaths. These trials were pooled in a meta-analysis, and the outcomes were expressed as RRs and 95% CIs. RESULTS: The average age of the pooled sample was 62 y, and the average duration of supplementation was 43 mo. Across all studies, no effect of multivitamin-multimineral treatment on all-cause mortality (RR: 0.98; 95% CI: 0.94, 1.02) was observed. There was a trend for a reduced risk of all-cause mortality across primary prevention trials (RR: 0.94; 95% CI: 0.89, 1.00). Multivitamin-multimineral treatment had no effect on mortality due to vascular causes (RR: 1.01; 95% CI: 0.93, 1.09) or cancer (RR: 0.96; 95% CI: 0.88, 1.04). No statistical evidence of heterogeneity or publication bias was observed. CONCLUSION: Multivitamin-multimineral treatment has no effect on mortality risk.

Adding a new anticoagulant or antiplatelet agent for patient receiving aspirin after an acute coronary syndrome? - Results from a pairwise and network meta-analysis of randomized-controlled trials

 Objectives: To synthesize the efficacy and safety outcomes from randomized-controlled trials (RCTs) regarding new oral anticoagulant, protease-activated receptor-1 (PAR-1) antagonist, and warfarin adjunctive to aspirin for patients after acute coronary syndrome (ACS) via pair-wise and network meta-analyses.
Methods: A comprehensive literature search was performed in Embase, Medline, Cochrane Library Web of Knowledge, and Scopus. The pair-wise meta-analysis was undertaken respectively to each agent/treatment category via Revmen 5.1. In order to estimate the relative efficacy of each agent/treatment category whilst preserving the randomized comparisons within each trial, a Bayesian network meta-analysis was conducted in WinBUGS using both fixed- and random-effects model. Covariate analysis was performed to explore the effects of length of follow-up and age of subject on the final results.
Results: In total, 23 RCTs were included in the meta-analysis. As shown by the results (OR,95%CI) for the pair-wise meta-analysis, new oral anticoagulants (0.85, [0.78, 0.93] and 3.04, [2.21, 4.19]), PAR-1 antagonists (0.80, [0.52, 1.22] and 1.55, [1.25, 1.93]) and warfarin (0.87, [0.74, 1.02] and 1.77, [1.46, 2.14]) might be able to provide better outcome in the incidences of major adverse events (MAE) but with higher bleeding risk comparing to aspirin treatment alone. Based on the model fit assessment, the random-effects model was adopted. The network meta-analysis (treatment effect comparing to aspirin lone) identified ximelagatran (-0.3044, [-0.8601, 0.2502]), dabigatran (-0.2144, [-0.8666, 0.4525]), rivoroxaban (-0.2179, [-0.5986, 0.1628]) and vorapaxar (-0.2272, [-0.81, 0.1664]) produced better improvements in MAE incidences whereas vorapaxar (0.3764, [-0.4444, 1.124]), warfarin (0.663, [0.3375, 1.037]), ximelagatran (0.7509, [-0.4164, 2.002]) and apixaban (0.8594, [-0.0049, 1.7]) produced less major bleeding events. The indirect comparisons among drug category (difference in incidence comparing to aspirin lone) showed new oral anticoagulants (-0.1974, [-0.284, -0.111]) and PAR-1 antagonists (-0.1239, [-0.215, -0.033]) to besuperior to warfarin (-0.1004, [-0.166, -0.035]) in the occurrences of MAE whereas PAR-1 antagonists (0.4292, [0.2123, 0.6476]) afforded better outcomes in major bleeding events against warfarin (0.5742, [0.3889, 0.7619]) and new oral anticoagulants (1.169, [0.8667, 1.485]).
Conclusion: Based on the study results, we cannot recommend the routine administration of new oral anticoagulant as add-on treatment for patients after ACS. However, for ACS patients comorbid with atrial fibrillation, new oral anticoagulant might be superior to warfarin in both efficacy and safety outcomes.

Ximelagatran versus warfarin for prophylaxis of venous thromboembolism in major orthopedic surgery: systematic review of randomized controlled trials

INTRODUÇÃO: O ximelagatrano foi recentemente estudada para profilaxia do tromboembolismo venoso (TEV). OBJETIVO: Avaliar se o ximelagatrano comparado com a varfarina melhora a profilaxia do TEV em pacientes submetidos à cirurgia ortopédica do joelho. FONTE DE DADOS: Estudos randomizados identificados por pesquisa eletrônica na literatura médica, até 2006, cujos dados foram compilados no programa Review Manager, versão 4.2.5. RESULTADOS: Foram incluídos três estudos randomizados bem conduzidos envolvendo 4.914 participantes. Foram definidos dois sub-grupos com dosagens diferentes de ximelagatrano (24 mg and 36 mg, duas vezes ao dia). O tratamento com ximelagatrano mostrou freqüência significantemente menor de TEV que o tratamento com varfarina, mas somente na dosagem de 36-mg [risco relativo, RR 0.72 ([intervalo de confiança, IC, 95% 0.64, 0.81), p < 0.00001]. A freqüência de TEV no sub-grupo de 24-mg foi similar a da varfarina [RR 0.86 (IC 95% 0.73, 1.01), p = 0.06]. Para TEV maior, embolia pulmonar, sangramento e sangramento maior não houve diferença entre varfarina e a ximelagatrano. Ao final do tratamento, a elevação da alanino-aminotransferase (ALT) foi menos freqüente no sub-grupo de 24 mg de ximelagatrano que no grupo da varfarina [RR 0.33 (IC 95% 0.12, 0.91) p = 0.03], mas no período de acompanhamento essa elevação foi maior com 36 mg de ximelagatrano [RR 6.97 (IC 95% 1.26, 38.50) p = 0.03]. CONCLUSÃO: O ximelagatrano foi mais efetivo que a varfarina quando usado em dosagens maiores (36 mg, 2 vezes ao dia), mas às expensas de aumento de enzimas hepáticas no período de acompanhamento.

Cabergoline versus bromocriptine in the treatment of hyperprolactinemia: a systematic review of randomized controlled trials and meta-analysis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of motor intervention in elderly patients with dementia: An analysis of randomized controlled trials

The objective of this study was to analyze randomized controlled trials published in the last decades involving motor intervention as a treatment for dementia, based on Physiotherapy Evidence Database (PEDro) criteria. A database search was performed using the following keywords: randomized controlled trial, dementia, physiotherapy, physical therapy, occupational therapy, physical education, motor approach, exercise, and physical activity. Ten trials were found: 4 related to physiotherapy, 3 to occupational therapy, 1 to physical education, and 2 to interdisciplinary motor intervention. The efficacy of motor intervention was confirmed in the following variables: psychosocial function, physical health and function, affective status, and caregiver's distress (P < .05). Results related to mobility were not significant (P > .05). Behavior, cognitive performance, activities of daily living, and risk of falls were not similar among the articles. From a total score of 10 points, with excellence characterized as the highest punctuation, the articles were classified between 3 and 7 by PEDro. Motor intervention was shown to be an alternative for minimizing physical and mental decline. PEDro has been confirmed as a very reliable tool to analyze studies and as an evaluation criteria, both qualitative and quantitative, allowing the establishment of motor intervention strategies for the treatment of patients with dementia. © 2007 Lippincott Williams & Wilkins, Inc.

Systematic review of randomized controlled trials of new anticoagulants for venous thromboembolism prophylaxis in major orthopedic surgeries, compared with enoxaparin

Background: In the past 10 years, new anticoagulants (NACs) have been studied for venous thromboembolism (VTE) prophylaxis. Objective: To evaluate the risk/benefit profile of NACs versus enoxaparin for VTE prophylaxis in major orthopedic surgery. Methods: A systematic review of double-blind randomized phase III studies was performed. The search strategy was run from 2000 to 2011 in the main medical electronic databases in any language. Independent extraction of articles was performed by 2 authors using predefined data fields, including study quality indicators. Results: Fifteen published clinical trials evaluating fondaparinux, rivaroxaban, dabigatran, and apixaban were included. Primary efficacy (any deep vein thrombosis [DVT], nonfatal pulmonary embolism, or all-cause mortality) favored fondaparinux (relative risk [RR] 0.50; 95% CI, 0.39, 0.63) and rivaroxaban (RR, 0.50; 95% CI, 0.34, 0.73) over enoxaparin, although significant heterogeneity was observed in both series. The primary efficacy of dabigatran at 220 mg, apixaban, and bemiparin were similar, with RRs of 1.02 (95% CI, 0.86, 1.20), 0.63 (95% CI, 0.39, 1.01), and 0.87 (95% CI, 0.65, 1.17), respectively. The primary efficacy of dabigatran at 150 mg (RR, 1.20; 95% CI, 1.03, 1.41), was inferior to enoxaparin. The incidence of proximal DVT favored apixaban (RR, 0.45; 95% CI, 0.27, 0.75) only. Rivaroxaban (RR, 0.45; 95% CI, 0.27, 0,77) and apixaban (RR, 0.38; 95% CI, 0.16, 0.90) produced significantly lower frequencies of symptomatic DVT. The incidence of major VTE favored rivaroxaban (RR, 0.44; 95% CI, 0.25, 0.81), only. Bleeding risk was similar for all NACs, except fondaparinux (RR, 1.27; 95% CI, 1.04, 1.55), which exhibited a significantly higher any-bleeding risk compared with enoxaparin, and apixaban (RR, 0.88; 95% CI, 0.79, 0.99), which was associated with a reduced risk of any bleeding. Alanine amino transferase was significantly lower with 220 mg of dabigatran, (RR, 0.67; 95% CI, 0.79, 0.99) than with enoxaparin. Conclusions: NACs can be considered alternatives to conventional thromboprophylaxis regimens in patients undergoing elective major orthopedic surgery, depending on clinical characteristics and cost-effectiveness. The knowledge of some differences concerning efficacy or safety profile, pointed out in this systematic review, along with the respective limitations, may be useful in clinical practice. © 2013 Elsevier Inc. All rights reserved.

Efficacy of brief alcohol screening intervention for college students (BASICS): a meta-analysis of randomized controlled trials

Background: Many studies reported that brief interventions are effective in reducing excessive drinking. This study aimed to assess the efficacy of a protocol of brief intervention for college students (BASICS), delivered face-to-face, to reduce risky alcohol consumption and negative consequences. Methods: A systematic review with meta-analysis was performed by searching for randomized controlled trials (RCTs) in Medline, PsycInfo, Web of Science and Cochrane Library databases. A quality assessment of RCTs was made by using a validated scale. Combined mean effect sizes, using meta-analysis random-effects models, were calculated. Results: 18 studies were included in the review. The sample sizes ranged from 54 to 1275 (median = 212). All studies presented a good evaluation of methodological quality and four were found to have excellent quality. After approximately 12 months of follow-up, students receiving BASICS showed a significant reduction in alcohol consumption (difference between means = -1.50 drinks per week, 95% CI: -3.24 to -0.29) and alcohol-related problems (difference between means = -0.87, 95% CI: -1.58 to -0.20) compared to controls. Conclusions: Overall, BASICS lowered both alcohol consumption and negative consequences in college students. Gender and peer factors seem to play an important role as moderators of behavior change in college drinking. Characteristics of BASICS procedure have been evaluated as more favorable and acceptable by students in comparison with others interventions or control conditions. Considerations for future researches were discussed.

Sonothrombolysis for acute ischemic stroke: a systematic review of randomized controlled trials

Object. Sonothrombolysis has recently been considered an emerging modality for the treatment of stroke. The purpose of the present paper was to review randomized clinical studies concerning the effects of sonothrombolysis associated with tissue plasminogen activator (tPA) on acute ischemic stroke. Methods. Systematic searches for literature published between January 1996 and July 2011 were performed for studies regarding sonothrombolysis combined with tPA for acute ischemic stroke. Only randomized controlled trials were included. Data extraction was based on ultrasound variables, patient characteristics, and outcome variables (rate of intracranial hemorrhages and arterial recanalization). Results. Four trials were included in this study; 2 trials evaluated the effect of transcranial Doppler (TCD) ultrasonography on sonothrombolysis, and 2 addressed transcranial color-coded duplex (TCCD) ultrasonography. The frequency of ultrasound waves varied from 1.8 to 2 MHz. The duration of thrombus exposure to ultrasound energy ranged from 60 to 120 minutes. Sample sizes were small, recanalization was evaluated at different time points (60 and 120 minutes), and inclusion criteria were heterogeneous. Sonothrombolysis combined with tPA did not lead to an increase in symptomatic intracranial hemorrhagic complications. Two studies demonstrated that patients treated with ultrasound combined with tPA had statistically significant higher rates of recanalization than patients treated with tPA alone. Conclusions. Despite the heterogeneity and the limitations of the reviewed studies, there is evidence that sonothrombolysis associated with tPA is a safe procedure and results in an increased rate of recanalization in the setting of acute ischemic stroke when wave frequencies and energy intensities of diagnostic ultrasound systems are used. (http://thejns.org/doi/abs/10.3171/2011.10.FOCUS11251)

Radiation therapy for Graves' ophthalmopathy: a systematic review and meta-analysis of randomized controlled trials

PURPOSE: To evaluate the efficacy of radiotherapy (RT) with total dose of 20 Gy (RT 20 Gy) in the treatment of Graves' ophthalmopathy. METHODS: A systematic review and meta-analysis of randomized controlled trials was performed comparing RT 20 Gy with or without glucocorticoid to clinical treatments for Graves' ophthalmopathy. The MEDLINE, EMBASE, Cochrane Library databases and recent relevant journals were searched. Relevant reports were reviewed by two reviewers. Response to radiotherapy was defined as clinical success according to each trial. We also evaluated the quality of life and whether RT to produce fewer side effects than other treatments. RESULTS: A total of 8 randomized controlled trials (439 patients) were identified. In the subgroup analysis, the overall response to treatment rates was better for: RT 20 Gy plus glucocorticoid vs glucocorticoids alone, OR=17.5 (CI95% 1.85-250, p=0.04), RT 20 Gy vs sham RT, OR= 3.15 (CI95%1.59-6.23, p=0.003) and RT 20Gy plus intravenous glucocorticoid vs RT 20Gy plus oral glucocorticoid, OR=4.15(CI95% 1.34-12.87, p=0.01). There were no differences between RT 20 Gy versus other fractionations and RT 20 Gy versus glucocorticoid alone. RT 20 Gy with or without glucocorticoids showed an improvement in diplopia grade, visual acuity, optic neuropathy, lid width, proptosis and ocular motility. No difference was seen for costs, intraocular pressure and quality of life. CONCLUSION: Our data have shown that RT 20 Gy should be offered as a valid therapeutic option to patients with moderate to severe ophthalmopathy. The effectiveness of orbital radiotherapy can be increased by the synergistic interaction with glucocorticoids. Moreover, RT 20 Gy is useful to improve a lot of ocular symptoms, excluding intraocular pressure, without any difference in quality of life and costs.

Efficacy of experimental treatments compared with standard treatments in non-inferiority trials: a meta-analysis of randomized controlled trials

Background There is concern that non-inferiority trials might be deliberately designed to conceal that a new treatment is less effective than a standard treatment. In order to test this hypothesis we performed a meta-analysis of non-inferiority trials to assess the average effect of experimental treatments compared with standard treatments. Methods One hundred and seventy non-inferiority treatment trials published in 121 core clinical journals were included. The trials were identified through a search of PubMed (1991 to 20 February 2009). Combined relative risk (RR) from meta-analysis comparing experimental with standard treatments was the main outcome measure. Results The 170 trials contributed a total of 175 independent comparisons of experimental with standard treatments. The combined RR for all 175 comparisons was 0.994 [95% confidence interval (CI) 0.978–1.010] using a random-effects model and 1.002 (95% CI 0.996–1.008) using a fixed-effects model. Of the 175 comparisons, experimental treatment was considered to be non-inferior in 130 (74%). The combined RR for these 130 comparisons was 0.995 (95% CI 0.983–1.006) and the point estimate favoured the experimental treatment in 58% (n = 76) and standard treatment in 42% (n = 54). The median non-inferiority margin (RR) pre-specified by trialists was 1.31 [inter-quartile range (IQR) 1.18–1.59]. Conclusion In this meta-analysis of non-inferiority trials the average RR comparing experimental with standard treatments was close to 1. The experimental treatments that gain a verdict of non-inferiority in published trials do not appear to be systematically less effective than the standard treatments. Importantly, publication bias and bias in the design and reporting of the studies cannot be ruled out and may have skewed the study results in favour of the experimental treatments. Further studies are required to examine the importance of such bias.

Does land-based exercise reduce pain and disability associated with hip osteoarthritis? A meta-analysis of randomized controlled trials

Objective To determine if clinical guidelines recommending therapeutic exercise for people with hip osteoarthritis (OA) are supported by rigorous scientific evidence. Methods A meta-analysis of randomized controlled trials (RCTs) recruiting people with hip OA and comparing some form of land-based exercise program (as opposed to exercises conducted in the water) with a non-exercise group in terms of hip pain and/or self-reported physical function. Results Thirty-two RCTs were identified, but only five met the inclusion criteria. Only one of the five included RCTs restricted recruitment to people with hip OA, the other four RCTs also recruiting participants with knee OA. The five included studies provided data on 204 and 187 hip OA participants for pain and physical function, respectively. Combining the results of the five included RCTs using a fixed-effects model demonstrated a small treatment effect for pain (standardized mean difference (SMD) −0.38; 95% confidence interval (CI) −0.67 to −0.09). No significant benefit in terms of improved self-reported physical function was detected (SMD −0.02; 95% CI −0.31 to 0.28). Conclusion Currently there is only silver level evidence (one small RCT) supporting the benefit of land-based therapeutic exercise for people with symptomatic hip OA in terms of reduced pain and improved physical function. The limited number and small sample size of the included RCTs restricts the confidence that can be attributed to these results.

Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials

Long-term sedation with midazolam or propofol in intensive care units (ICUs) has serious adverse effects. Dexmedetomidine, an α(2)-agonist available for ICU sedation, may reduce the duration of mechanical ventilation and enhance patient comfort.