Uptake of systematic reviews and meta-analyses based on individual participant data in clinical practice guidelines: descriptive study.

To establish the extent to which systematic reviews and meta-analyses of individual participant data (IPD) are being used to inform the recommendations included in published clinical guidelines

Splash control of drop impacts with geometric targets

Drop impacts on solid and liquid surfaces exhibit complex dynamics due to the competition of inertial, viscous, and capillary forces. After impact, a liquid lamella develops and expands radially, and under certain conditions, the outer rim breaks up into an irregular arrangement of filaments and secondary droplets. We show experimentally that the lamella expansion and subsequent break up of the outer rim can be controlled by length scales that are of comparable dimension to the impacting drop diameter. Under identical impact parameters, ie. fluid properties and impact velocity, we observe unique splashing dynamics by varying the target cross-sectional geometry. These behaviors include: (i) geometrically-shaped lamellae and (ii) a transition in splashing stability, from regular to irregular splashing. We propose that regular splashes are controlled by the azimuthal perturbations imposed by the target cross-sectional geometry and that irregular splashes are governed by the fastest-growing unstable Plateau-Rayleigh mode

No benefits of statins for sudden cardiac death prevention in patients with heart failure and reduced ejection fraction: A meta-analysis of randomized controlled trials.

Statins showed mixed results in heart failure (HF) patients. The benefits in major HF outcomes, including all-cause mortality and sudden cardiac death (SCD), have always been discordant across systematic reviews and meta-analyses. We intended to systematically identify and appraise the available evidence that evaluated the effectiveness of statins in clinical outcomes for HF patients. Systematic review and meta-analysis. We searched, until April 28, 2016: Medline, Embase, ISI Web of Science and EBM reviews (Cochrane DSR, ACP journal club, DARE, CCTR, CMR, HTA, and NHSEED), checked clinicaltrials.gov for ongoing trials and manually searched references of included studies. We identified 24 randomized clinical trials that evaluated the efficacy of statins for HF patients. All randomized clinical trials were assessed for risk of bias and pooled together in a meta-analysis. Pre-specified outcomes were sudden cardiac death, all-cause mortality, and hospitalization for worsening heart failure. Statins did not reduce sudden cardiac death (SCD) events in HF patients [relative risk (RR) 0.92, 95% confidence interval (CI) 0.70 to 1.21], all-cause mortality [RR 0.88, 95% CI 0.75 to 1.02] but significantly reduced hospitalization for worsening heart failure (HWHF) although modestly [RR 0.79, 95% CI 0.66 to 0.94]. Nevertheless, estimated predictive intervals were insignificant in SCD, all-cause mortality and HWHF [RR, 0.54 to 1.63, 0.64 to 1.19, and 0.54 to 1.15], respectively. An important finding was the possible presence of publication bias, small-study effects and heterogeneity of the trials conducted in HF patients. Statins do not reduce sudden cardiac death, all-cause mortality, but may slightly decrease hospitalization for worsening heart failure in HF patients. The evaluation of the risk of biases suggested moderate quality of the published results. Until new evidence is available, this study supports the 2013 ACCF/AHA guidelines to not systematically prescribe statins in "only" HF patients, which should help avoid unnecessary polypharmacy

Large droplet impact on water layers

The impact of large droplets onto an otherwise undisturbed layer of water is considered. The work, which is motivated primarily with regard to aircraft icing, is to try and help understand the role of splashing on the formation of ice on a wing, in particular for large droplets where splash appears, to have a significant effect. Analytical and numerical approaches are used to investigate a single droplet impact onto a water layer. The flow for small times after impact is determined analytically, for both direct and oblique impacts. The impact is also examined numerically using the volume of fluid (VOF) method. At small times there are promising comparisons between the numerical results, the analytical solution and experimental work capturing the ejector sheet. At larger times there is qualitative agreement with experiments and related simulations. Various cases are considered, varying the droplet size to layer depth ratio, including surface roughness, droplet distortion and air effects. The amount of fluid splashed by such an impact is examined and is found to increase with droplet size and to be significantly influenced by surface roughness. The makeup of the splash is also considered, tracking the incoming fluid, and the splash is found to consist mostly of fluid originating in the layer

Multiple imputation for IPD meta-analysis: allowing for heterogeneity and studies with missing covariates.

Recently, multiple imputation has been proposed as a tool for individual patient data meta-analysis with sporadically missing observations, and it has been suggested that within-study imputation is usually preferable. However, such within study imputation cannot handle variables that are completely missing within studies. Further, if some of the contributing studies are relatively small, it may be appropriate to share information across studies when imputing. In this paper, we develop and evaluate a joint modelling approach to multiple imputation of individual patient data in meta-analysis, with an across-study probability distribution for the study specific covariance matrices. This retains the flexibility to allow for between-study heterogeneity when imputing while allowing (i) sharing information on the covariance matrix across studies when this is appropriate, and (ii) imputing variables that are wholly missing from studies. Simulation results show both equivalent performance to the within-study imputation approach where this is valid, and good results in more general, practically relevant, scenarios with studies of very different sizes, non-negligible between-study heterogeneity and wholly missing variables. We illustrate our approach using data from an individual patient data meta-analysis of hypertension trials. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd

Multifluid flows with weak and strong discontinuous interfaces using an elemental enriched space

In a previous paper, the authors presented an elemental enriched space to be used in a finite-element framework (EFEM) capable of reproducing kinks and jumps in an unknown function using a fixed mesh in which the jumps and kinks do not coincide with the interelement boundaries. In this previous publication, only scalar transport problems were solved (thermal problems). In the present work, these ideas are generalized to vectorial unknowns, in particular, the incompressible Navier-Stokes equations for multifluid flows presenting internal moving interfaces. The advantage of the EFEM compared with global enrichment is the significant reduction in computing time when the internal interface is moving. In the EFEM, the matrix to be solved at each time step has not only the same amount of degrees of freedom (DOFs) but also the same connectivity between the DOFs. This frozen matrix graph enormously improves the efficiency of the solver. Another characteristic of the elemental enriched space presented here is that it allows a linear variation of the jump, thus improving the convergence rate, compared with other enriched spaces that have a constant variation of the jump. Furthermore, the implementation in any existing finite-element code is extremely easy with the version presented here because the new shape functions are based on the usual finite-element method shape functions for triangles or tetrahedrals, and once the internal DOFs are statically condensed, the resulting elements have exactly the same number of unknowns as the nonenriched finite elements.Peer ReviewedPreprin

Are concomitant treatments confounding factors in randomized controlled trials on intensive blood-glucose control in type 2 diabetes? a systematic review

International audienceBackgroundOpen-label, randomized controlled trials (RCTs) are subject to observer bias. If patient management is conducted without blinding, a difference between groups may be explained by other factors than study treatment. One factor may come from taking concomitant treatments with an efficacy on the studied outcomes. In type 2 diabetes, some antihypertensive or lipid-lowering drugs are effective against diabetic complications. We wanted to determine if these concomitant treatments were correctly reported in articles of RCTs on type 2 diabetes and if they might have influenced the outcome.MethodsWe performed a systematic review using Medline, Embase, and the Cochrane Library (from January 1950 to July 2010). Open-label RCTs assessing the effectiveness of intensive blood-glucose control in type 2 diabetes were included. We chose five therapeutic classes with proven efficacy against diabetes complications: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor antagonists (AIIRAs), fibrates, statins, and aspirin. Differences between concomitant treatments were considered statistically significant when p ResultsA total of eight open-label RCTs were included, but only three (37.5%) of them published concomitant treatments. In two studies (ACCORD and ADVANCE), a statistically significant difference was observed between the two groups for aspirin (p = 0.02) and ACEIs (p = 0.02).ConclusionsFew concomitant treatments were published in this sample of open-label RCTs. We cannot completely eliminate an observer bias for these studies. This bias probably influenced the results to an extent that has yet to be determined

Effectiveness of enhanced diabetes care to patients of South Asian ethnicity : the United Kingdom Asian Diabetes Study (UKADS) : a cluster randomised controlled trial

Background: Delivering high quality and evidence based healthcare to deprived sectors of the community is a major goal for society. We investigated the effectiveness of a culturally sensitive enhanced care package in UK general practice in improving cardiovascular risk factors in South Asian patients with type 2 diabetes. Methods: 21 inner city practices were randomised to intervention (enhanced practice nurse time, link worker and diabetes specialist nurse support) (n=868) or control (standard care) (n=618) groups. Prescribing algorithms with clearly defined targets were provided for all practices. Main outcome measures comprised changes in blood pressure, total cholesterol and glycaemic control (HbA1c) after 2 years. Findings: At baseline, groups were similar with respect to age, sex and cardiovascular risk factors. Comparing treatment groups, after adjustment for confounders, and clustering, differences in diastolic blood pressure (1.91mmHg, P=0.0001) and mean arterial pressure (1.36mmHg, P=0.0180) were significant. There were no significant differences between groups for total cholesterol or HbA1c. Economic analysis indicates the nurse-led intervention was not cost-effective. Across the whole study population systolic blood pressure, diastolic blood pressure and cholesterol decreased significantly by 4.9mmHg, 3.8mmHg and 0.45mmol/L respectively, but there was no change in HbA1c. Interpretation: Additional, although limited, benefits were observed from our culturally enhanced care package over and above the secular changes achieved in the UK in recent years. Stricter targets in general practice and further measures to motivate patients are needed to maximise healthcare outcomes in South Asian patients with diabetes