Meta-analysis of clinical trials with low molecular weight heparins in orthopedic surgery

Peer Reviewe

Study-based registers of randomized controlled trials: starting a systematic review with data extraction or meta-analysis

Introduction: Despite years of use of study-based registers for storing reports of randomized controlled trials (RCTs), the methodology used in developing such registers/databases has not been documented. Such registers are integral to the process of scientific reviewing. We document and discuss methodological aspects of the development and use of study-based registers. Although the content is focused on the study-based register of randomized/controlled clinical trials, this work applies to developers of databases of all sorts of studies related to the human, animals, cells, genes, and molecules. Methods: We describe necessity, rationale, and steps for the development, utilization and maintenance of study-based registers as well as the challenges and gains for the organizations supporting systematic reviews of the published and unpublished literature. Conclusion: The ultimate goal of having a study-based register is to facilitate efficient production of systematic reviews providing rapid, yet accurate, evidence for the decision-makers. We argue that moving towards study-based registers is an inevitable welcome direction and that infrastructures are ready for such movement

Venous Thromboembolism in Korean Patients Undergoing Major Orthopedic Surgery: A Prospective Observational Study using Computed Tomographic (CT) Pulmonary Angiography and Indirect CT Venography

In patients undergoing major orthopedic surgery, data of deep venous thrombosis (DVT) and pulmonary embolism (PE) are lacking as studied by computed tomographic (CT) pulmonary angiography and indirect CT venography (CTPA-CTV). A prospective observational study was performed for 363 Korean patients undergoing major orthopedic surgery to determine the incidence of venous thromboembolism (VTE), especially proximal DVT and PE. The incidence of VTE was 16.3% (n=59). Of them, 8 patients (2.2%) were symptomatic. The rate of VTE was the highest in patients who underwent total knee replacement (40.4%), followed by hip fracture surgery (16.4%), and total hip replacement (8.7%; P<0.001). The incidence of PE was 6.6% (n=24). Of them, 4 patients (1.1%) were symptomatic. Forty-one patients (11.3%) were in the proximal DVT or PE group. Based on multivariate analysis, total knee replacement and age ≥65 yr were significant risk factors for proximal DVT or PE in patients undergoing major orthopedic surgery (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.1-5.1; P=0.025; and OR, 2.1; 95% CI, 1.0-4.4; P=0.046, respectively). Taken together, the overall incidence of PE was 6.6% and rate of symptomatic PE rate was 1.1%. Knee joint replacement and age ≥65 yr were significant risk factors for proximal DVT or PE

Pooling, meta-analysis, and the evaluation of drug safety

BACKGROUND: The "integrated safety report" of the drug registration files submitted to health authorities usually summarizes the rates of adverse events observed for a new drug, placebo or active control drugs by pooling the safety data across the trials. Pooling consists of adding the numbers of events observed in a given treatment group across the trials and dividing the results by the total number of patients included in this group. Because it considers treatment groups rather than studies, pooling ignores validity of the comparisons and is subject to a particular kind of bias, termed "Simpson's paradox." In contrast, meta-analysis and other stratified analyses are less susceptible to bias. METHODS: We use a hypothetical, but not atypical, application to demonstrate that the results of a meta-analysis can differ greatly from those obtained by pooling the same data. In our hypothetical model, a new drug is compared to 1) a placebo in 4 relatively small trials in patients at high risk for a certain adverse event and 2) an active reference drug in 2 larger trials of patients at low risk for this event. RESULTS: Using meta-analysis, the relative risk of experiencing the adverse event with the new drug was 1.78 (95% confidence interval [1.02; 3.12]) compared to placebo and 2.20 [0.76; 6.32] compared to active control. By pooling the data, the results were, respectively, 1.00 [0.59; 1.70] and 5.20 [2.07; 13.08]. CONCLUSIONS: Because these findings could mislead health authorities and doctors, regulatory agencies should require meta-analyses or stratified analyses of safety data in drug registration files

GEO-PRICING: UMA ANÁLISE JURÍDICA DAS RELAÇÕES DE CONSUMO NO E-COMMERCE E DA SEGREGAÇÃO ECONÔMICO-SOCIAL NA ERA DA PÓS-MODERNIDADE.

Analisou-se a prática do geo-pricing nas relações de consumo quanto à ocorrência de vantagens oriundas da geolocalização dos consumidores. Estabeleceu-se como problemática que referida prática eventualmente promoveria uma segregação econômico-social desses e-consumidores. Utilizou-se como referencial teórico Zymunt Bauman e o desenvolvimento deu-se meio de pesquisa bibliográfica nacional, estrangeira e análise doutrinária. Utilizou-se o método dedutivo com o fito de responder à problemática lançada, propondo-se que, por meio da intervenção do estado na economia, haverá uma mudança de paradigma de todos os envolvidos no e-commerce, tornando-o uma modalidade de comércio mais segura e transparente ao consumidor.

Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients

The efficacy and safety of prolonging prophylaxis for venous thromboembolism in medically ill patients beyond hospital discharge remain uncertain. We hypothesized that extended prophylaxis with apixaban would be safe and more effective than short-term prophylaxis with enoxaparin. METHODS: In this double-blind, double-dummy, placebo-controlled trial, we randomly assigned acutely ill patients who had congestive heart failure or respiratory failure or other medical disorders and at least one additional risk factor for venous thromboembolism and who were hospitalized with an expected stay of at least 3 days to receive apixaban, administered orally at a dose of 2.5 mg twice daily for 30 days, or enoxaparin, administered subcutaneously at a dose of 40 mg once daily for 6 to 14 days. The primary efficacy outcome was the 30-day composite of death related to venous thromboembolism, pulmonary embolism, symptomatic deep-vein thrombosis, or asymptomatic proximal-leg deep-vein thrombosis, as detected with the use of systematic bilateral compression ultrasonography on day 30. The primary safety outcome was bleeding. All efficacy and safety outcomes were independently adjudicated. RESULTS: A total of 6528 subjects underwent randomization, 4495 of whom could be evaluated for the primary efficacy outcome - 2211 in the apixaban group and 2284 in the enoxaparin group. Among the patients who could be evaluated, 2.71% in the apixaban group (60 patients) and 3.06% in the enoxaparin group (70 patients) met the criteria for the primary efficacy outcome (relative risk with apixaban, 0.87; 95% confidence interval [CI], 0.62 to 1.23; P = 0.44). By day 30, major bleeding had occurred in 0.47% of the patients in the apixaban group (15 of 3184 patients) and in 0.19% of the patients in the enoxaparin group (6 of 3217 patients) (relative risk, 2.58; 95% CI, 1.02 to 7.24; P = 0.04). CONCLUSIONS: In medically ill patients, an extended course of thromboprophylaxis with apixaban was not superior to a shorter course with enoxaparin. Apixaban was associated with significantly more major bleeding events than was enoxaparinSupported by Bristol-Myers Squibb and Pfize