Adjusting trial results for biases in meta-analysis: combining data-based evidence on bias with detailed trial assessment.

Flaws in the conduct of randomized trials can lead to biased estimation of the intervention effect. Methods for adjustment of within-trial biases in meta-analysis include the use of empirical evidence from an external collection of meta-analyses, and the use of expert opinion informed by the assessment of detailed trial information. Our aim is to present methods to combine these two approaches to gain the advantages of both. We make use of the risk of bias information that is routinely available in Cochrane reviews, by obtaining empirical distributions for the bias associated with particular bias profiles (combinations of risk of bias judgements). We propose three methods: a formal combination of empirical evidence and opinion in a Bayesian analysis; asking experts to give an opinion on bias informed by both summary trial information and a bias distribution from the empirical evidence, either numerically or by selecting areas of the empirical distribution. The methods are demonstrated through application to two example binary outcome meta-analyses. Bias distributions based on opinion informed by trial information alone were most dispersed on average, and those based on opinions obtained by selecting areas of the empirical distribution were narrowest. Although the three methods for combining empirical evidence with opinion vary in ease and speed of implementation, they yielded similar results in the two examples.

Computationally efficient methods for fitting mixed models to electronic health records data.

Motivated by two case studies using primary care records from the Clinical Practice Research Datalink, we describe statistical methods that facilitate the analysis of tall data, with very large numbers of observations. Our focus is on investigating the association between patient characteristics and an outcome of interest, while allowing for variation among general practices. We explore ways to fit mixed-effects models to tall data, including predictors of interest and confounding factors as covariates, and including random intercepts to allow for heterogeneity in outcome among practices. We introduce (1) weighted regression and (2) meta-analysis of estimated regression coefficients from each practice. Both methods reduce the size of the dataset, thus decreasing the time required for statistical analysis. We compare the methods to an existing subsampling approach. All methods give similar point estimates, and weighted regression and meta-analysis give similar standard errors for point estimates to analysis of the entire dataset, but the subsampling method gives larger standard errors. Where all data are discrete, weighted regression is equivalent to fitting the mixed model to the entire dataset. In the presence of a continuous covariate, meta-analysis is useful. Both methods are easy to implement in standard statistical software.

Label-invariant models for the analysis of meta-epidemiological data.

Rich meta-epidemiological data sets have been collected to explore associations between intervention effect estimates and study-level characteristics. Welton et al proposed models for the analysis of meta-epidemiological data, but these models are restrictive because they force heterogeneity among studies with a particular characteristic to be at least as large as that among studies without the characteristic. In this paper we present alternative models that are invariant to the labels defining the 2 categories of studies. To exemplify the methods, we use a collection of meta-analyses in which the Cochrane Risk of Bias tool has been implemented. We first investigate the influence of small trial sample sizes (less than 100 participants), before investigating the influence of multiple methodological flaws (inadequate or unclear sequence generation, allocation concealment, and blinding). We fit both the Welton et al model and our proposed label-invariant model and compare the results. Estimates of mean bias associated with the trial characteristics and of between-trial variances are not very sensitive to the choice of model. Results from fitting a univariable model show that heterogeneity variance is, on average, 88% greater among trials with less than 100 participants. On the basis of a multivariable model, heterogeneity variance is, on average, 25% greater among trials with inadequate/unclear sequence generation, 51% greater among trials with inadequate/unclear blinding, and 23% lower among trials with inadequate/unclear allocation concealment, although the 95% intervals for these ratios are very wide. Our proposed label-invariant models for meta-epidemiological data analysis facilitate investigations of between-study heterogeneity attributable to certain study characteristics.

Is Achenbach's syndrome a surgical emergency? A systematic review.

AIM: The aim of this study is to establish the nature (urgent vs. non-urgent), demographics, presentation and management of Achenbach's syndrome and to formulate an algorithmic approach for their diagnosis and management. MATERIALS AND METHODS: A systematic review and met-aggregation of literature from 1944 to 2015 in English language in MedLine, Embase and Cochrane database were conducted. RESULTS: Achenbach's syndrome is a female-dominant disease with median age of 49.5 years (range 22-76) (age ≤60, n = 11/12, 91 %). It presents with unilateral volar discoloration of a finger (100 %). It is associated with pain (n = 7/12, 58. %), edema (n = 7/12, 58 %), and paresthesia (n = 3/12, 25 %). The median time to resolution of symptoms without any intervention was 4 days (range 2-14). CONCLUSION: AS is self-limiting and a non-urgent surgical condition. It can be differentiated from other pathologies by clinical spectrum, patient demographics and in doubtful circumstances (acute limb ischemia) by Doppler sonography. An algorithmic approach can avoid hospital admissions, partially unnecessary investigation and assist in patient assurance.

Blunt abdominal trauma and mesenteric avulsion: a systematic review.

PURPOSE: The aim of this study is to establish the biomechanics, presentation and diagnosis of mesenteric avulsions following blunt abdominal trauma and reach a consensus on their overall management. MATERIALS AND METHODS: A systematic review of literature in MedLine, Embase, Scopus and CINHAL in English language from 1951 to November 2014 was performed. A total of 20 reported cases were identified. Variables including patient's demographics, signs and symptoms, mechanism of injury, investigative modality, management, length of stay, follow-up and outcomes were reviewed and analyzed. RESULTS: The median age of the cohort was 28.5 years (range 10-58 years), with a male-to-female ratio of 3:1. The commonest mechanism of injury was road traffic accident due to seat belt restraint (n = 12, 60 %). The commonest presentation was diffuse abdominal tenderness (n = 10, 45 %) followed by ecchymosis/bruising (n = 9, 40 %). Computed tomography (CT) remained the investigative modality of choice (n = 9, 45 %). All cases had an emergency exploratory laparotomy (n = 18, 90 %) within the initial 24 h and the median length of stay was 19 days (range 4-90 days). The overall mortality was 15 % (n = 3). CONCLUSION: Mesenteric avulsion is rare and has a complex and vague presentation. Due to its potential mortality and morbidity, emergency physicians should keep a high index of suspicion in individuals with blunt abdominal trauma from any mechanism of injury.

Amyloidosis in Vanuatu.

Thirteen cases of amyloidosis are reported from Vanuatu between 1983 and 1985. There appears to be a high incidence of the disease similar to that found in Papua New Guinea. The role of malaria as an aetiological agent is discussed although most cases had a history of past or active tuberculosis. Most patients presented as either nephrotic syndrome or a syndrome of abdominal pain, diarrhoea, weight loss and proteinuria.

Effects of mitral valve surgery on static lung function and exercise performance.

Lung function at rest was assessed in 50 patients before and six months after mitral valve surgery. There were small increases in spirometric volumes (FEV1 and vital capacity) with decreases in total lung capacity and residual volume, but no change in carbon monoxide transfer factor or transfer coefficient (KCO). Progressive exercise tests performed before and after operation in 19 of the patients confirmed an improved exercise capacity after surgery. The patients with the greatest symptomatic improvement in breathlessness were also those who achieved the greatest increase in maximum work load and the greatest decrease in ventilation for a given oxygen consumption. Depression of the ST segment of the electrocardiogram and frequent ventricular ectopic beats on exercise remained common after surgery and may have been due to digoxin treatment.

Relation between severity of mitral valve disease and results of routine lung function tests in non-smokers.

The effects of mitral valve disease on lung function have been studied in 26 non-smoking patients by relating values for lung volumes and carbon monoxide transfer factor (TLCO) to various indices of cardiac function measured at catheterisation. In general, more severe mitral disease was associated with greater abnormalities of lung function. Reductions of the one-second forced expiratory volume, vital capacity, TLCO and transfer coefficient, and increase in residual volume were all significantly related to the severity of mitral valve disease. In addition, the cardiothoracic ratio, measured radiographically, showed an inverse correlation with both vital capacity and total lung capacity. Although some of the consequences of mitral valve disease on lung function resemble those of primary airway disease, useful distinguishing points are the relative normality of the forced expiratory ratio and the absence of an increase in total lung capacity.