Missing Data in Randomized Clinical Trials for Weight Loss: Scope of the Problem, State of the Field, and Performance of Statistical Methods

BACKGROUND: Dropouts and missing data are nearly-ubiquitous in obesity randomized controlled trails, threatening validity and generalizability of conclusions. Herein, we meta-analytically evaluate the extent of missing data, the frequency with which various analytic methods are employed to accommodate dropouts, and the performance of multiple statistical methods. METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed and Cochrane databases (2000-2006) for articles published in English and manually searched bibliographic references. Articles of pharmaceutical randomized controlled trials with weight loss or weight gain prevention as major endpoints were included. Two authors independently reviewed each publication for inclusion. 121 articles met the inclusion criteria. Two authors independently extracted treatment, sample size, drop-out rates, study duration, and statistical method used to handle missing data from all articles and resolved disagreements by consensus. In the meta-analysis, drop-out rates were substantial with the survival (non-dropout) rates being approximated by an exponential decay curve (e(-lambdat)) where lambda was estimated to be .0088 (95% bootstrap confidence interval: .0076 to .0100) and t represents time in weeks. The estimated drop-out rate at 1 year was 37%. Most studies used last observation carried forward as the primary analytic method to handle missing data. We also obtained 12 raw obesity randomized controlled trial datasets for empirical analyses. Analyses of raw randomized controlled trial data suggested that both mixed models and multiple imputation performed well, but that multiple imputation may be more robust when missing data are extensive. CONCLUSION/SIGNIFICANCE: Our analysis offers an equation for predictions of dropout rates useful for future study planning. Our raw data analyses suggests that multiple imputation is better than other methods for handling missing data in obesity randomized controlled trials, followed closely by mixed models. We suggest these methods supplant last observation carried forward as the primary method of analysis

A Theoretical Model of Ultrasonic Examination of Smooth Flat Cracks

As the Introductory Paper to this Conference explains,1 the CEGB and other high technology organisations are very interested in quantitative NDE for the guidance it gives in the design of inspections and for the support it offers in Safety Submissions to the Regulatory Authorities. An important part of this work is the theoretical modelling and prediction of defect detectability and signal behaviour. This present paper complements the Introductory Paper by describing the technical content of a model we have developed at the CEGB NDT Applications Centre

Cardiovascular Risk Associated with Interactions among Polymorphisms in Genes from the Renin-Angiotensin, Bradykinin, and Fibrinolytic Systems

Vascular fibrinolytic balance is maintained primarily by interplay of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1). Previous research has shown that polymorphisms in genes from the renin-angiotensin (RA), bradykinin, and fibrinolytic systems affect plasma concentrations of both t-PA and PAI-1 through a set of gene-gene interactions. In the present study, we extend this finding by exploring the effects of polymorphisms in genes from these systems on incident cardiovascular disease, explicitly examining two-way interactions in a large population-based study

Design of a prospective cohort study to assess ethnic inequalities in patient safety in hospital care using mixed methods

<p>Abstract</p> <p>Background</p> <p>While US studies show a higher risk of adverse events (AEs) for ethnic minorities in hospital care, in Europe ethnic inequalities in patient safety have never been analysed. Based on existing literature and exploratory research, our research group developed a conceptual model and empirical study to increase our understanding of the role ethnicity plays in patient safety. Our study is designed to (1) assess the risk of AEs for hospitalised patients of non-Western ethnic origin in comparison to ethnic Dutch patients; (2) analyse what patient-related determinants affect the risk of AEs; (3) explore the mechanisms of patient-provider interactions that may increase the risk of AEs; and (4) explore possible strategies to prevent inequalities in patient safety.</p> <p>Methods</p> <p>We are conducting a prospective mixed methods cohort study in four Dutch hospitals, which began in 2010 and is running until 2013. 2000 patients (1000 ethnic Dutch and 1000 of non-Western ethnic origin, ranging in age from 45-75 years) are included. Survey data are collected to capture patients’ explanatory variables (e.g., Dutch language proficiency, health literacy, socio-economic status (SES)-indicators, and religion) during hospital admission. After discharge, a two-stage medical record review using a standardized instrument is conducted by experienced reviewers to determine the incidence of AEs. Data will be analysed using multilevel multivariable logistic regression. Qualitative interviews with providers and patients will provide insight into the mechanisms of AEs and potential prevention strategies.</p> <p>Conclusion</p> <p>This study uses a robust study plan to quantify the risk difference of AEs between ethnic minority and Dutch patients in hospital care. In addition we are developing an in-depth description of the mechanisms of excess risk for some groups compared to others, while identifying opportunities for more equitable distributions of patient safety for all.</p

Multiple Colonization with S. pneumoniae before and after Introduction of the Seven-Valent Conjugated Pneumococcal Polysaccharide Vaccine

Simultaneous carriage of more than one strain of Streptococcus pneumoniae promotes horizontal gene transfer events and may lead to capsule switch and acquisition of antibiotic resistance. We studied the epidemiology of cocolonization with S. pneumoniae before and after introduction of the seven-valent conjugated pneumococcal vaccine (PCV7)

Design considerations of high RAP-content asphalt produced at reduced temperatures

In many countries recycling of reclaimed asphalt pavement (RAP) for road surface layers is limited to a maximum of 10–30%. This is due to technical limitation of common asphalt plant but also to specifications that are still restrictive when it comes to increasing RAP in surface courses. The mistrust in this practice is mainly related to uncertainty in performance of these mixes as well as to existing fundamental issues with the mix design, especially when production temperatures are lowered. This paper analyses some of the factors affecting the design of warm asphalt mixtures for surface course layers containing 50% RAP, and suggests a framework to justify the common assumption of full blending by optimising production conditions. A control hot mix asphalt which was manufactured with 49 dmm penetration binder and asphalt mixtures containing 50% RAP produced at temperatures between 95 and 135 °C and at different mixing times were investigated in terms of volumetric properties, indirect tensile stiffness modulus, and indirect tensile strength. The high-content RAP mixtures were produced within the warm mix region by using only a very soft binder as a rejuvenator, which reduces production costs. Statistical analysis was deployed, and different models were developed to estimate degree of blending between RAP binder and rejuvenator binder, and to predict the equivalent penetration of the blend without binder extraction and recovery. The analysis results showed that the selected performance indicators correlate significantly with mixing time and temperature, and provide evidence that only in certain circumstances and if the production conditions are accurately controlled, the practical full blending approach is acceptable

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV