Bayesian hierarchical approaches for multiple outcomes in routinely collected healthcare data

Background: Routinely collected healthcare data provides a rich environment for the investigation of drug performance in the general population, while also offering the possibility of assessing rare outcomes. The statistical analysis of this data poses a number of challenges. The data may be biased and lack the structure and balance provided by the drugs’ clinical trials. Outcomes are often modelled individually with an associated lack of control for multiple comparisons, as well as a difficulty in assessing multiple risks. Methods: Bayesian models provide methods for analysing multiple clinical outcomes, using relationships between outcomes and handling the types of multiple comparison issues which may occur when using multiple single-variate approaches. Lack of balance within the data may be catered for by dividing the population into clusters with similar characteristics, allowing within cluster inferences to be made. A Bayesian hierarchical model for multiple outcomes is proposed and applied to data from a safety and effectiveness study of direct oral anticoagulants (DOACs) in Scotland 2009 – 2015. Results: The Bayesian modelling results were comparable to the results from the original safety and effectiveness study, with the additional benefit of balancing patient clusters and controlling for relationships in the data. Conclusion: Bayesian hierarchical models are a suitable approach for modelling routinely collected healthcare data. There is the possibility of moving to an integrated Bayesian approach, with the inclusion of treatment relationships; uncertainty regarding cluster membership; and treatment allocation in the model, eventually leading to more reliable treatment decisions

Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against Invasive Pneumococcal Disease incidence in European adults aged 65 years and above : results of SpIDnet/I-MOVE+ multicentre study (2012-2016)

Background and Aims: We measured the effectiveness of 23-valent pneumococcal polysaccharidic vaccine(PPV23) against invasive pneumococcal disease (IPD) in 65+ year-olds, pooling surveillance data from seven European sites. PPV23 vaccination is recommended in all sites (8-69% uptake) and PCV13 in high risk groups in two sites (<5%uptake). Methods: We compared the vaccination status of IPD cases caused byPPV23 serotypes (cases) to that of nonPPV23 IPD (controls) notified between2012 and 2016. We defined PPV23 vaccination as at least one dose. PPV23 pooled effectiveness was calculated as (1 –odds ratio of vaccination)*100, adjusted for site, age, sex, underlying conditions and year. We stratified PPV23effectiveness by time since last dose of vaccine: <2, 2-4, 5-9 and 10+years. Results: We included 2011 cases and 878 controls. Compared to controls,cases were younger (p=0.001), less likely to have an underlying condition(p=0.025), more likely to be admitted for intensive care (p=0.038) and to have pneumonia (p=0.005). PPV23 effectiveness was 24% (95%CI: 4; 41) against PPV23-serotypes.By serotype, PPV23 effectiveness ranged between -2% (95%CI: -48; 30) against serotype 3 (n=687) and 55% (95%CI: 15; 76) against serotype 9N IPD (n=540). By years since vaccination, PPV23 effectiveness was 43% (95%CI: 3-66) and 15%(95%CI: -25; 43) for <2 years and 10+ years, respectively. Conclusion: Our findings suggest a low PPV23 effectiveness against IPD caused by PPV23serotypes in the elderly, varying by serotype, and higher in the first two years after vaccination. Despite low effectiveness, PPV23 in the elderly may prevent at least 25% of cases among vaccinated

CTF Challenge: Result summary

Image formation in bright field electron microscopy can be described with the help of the contrast transfer function (CTF). In this work the authors describe the "CTF Estimation Challenge", called by the Madrid Instruct Image Processing Center (I2PC) in collaboration with the National Center for Macromolecular Imaging (NCMI) at Houston. Correcting for the effects of the CTF requires accurate knowledge of the CTF parameters, but these have often been difficult to determine. In this challenge, researchers have had the opportunity to test their ability in estimating some of the key parameters of the electron microscope CTF on a large micrograph data set produced by well-known laboratories on a wide set of experimental conditions. This work presents the first analysis of the results of the CTF Estimation Challenge, including an assessment of the performance of the different software packages under different conditions, so as to identify those areas of research where further developments would be desirable in order to achieve high-resolution structural information. (C) 2015 Elsevier Inc. All rights reserved

CryoEM Maps and Associated Data Submitted to the 2015/2016 EMDataBank Map Challenge

Files and metadata associated with the EMDataBank/Unified Data Resource for 3DEM 2015/2016 Map Challenge hosted at challenges.emdatabank.org are deposited. All members of the Scientific Community--at all levels of experience--were invited to participate as Challengers, and/or as Assessors. Seven benchmark raw image datasets were selected for the challenge. Six are selected from recently described single particle structure determinations with image data collected as multi-frame movies; one is based on simulated (in silico) images. All of the raw image datasets are archived at pdbe.org/empiar. 27 Challengers created 66 single particle reconstructions from the targets, and then uploaded their results with associated details. 15 of the reconstructions were calculated using the SDSC Gordon supercomputer. This map challenge was one of two community-wide challenges sponsored by EMDataBank in 2015/2016 to critically evaluate 3DEM methods that are coming into use, with the ultimate goal of developing validation criteria associated with every 3DEM map and map-derived model

NSC230304

This report describes the outcomes of the Data Management Challenges in 3D Electron Microscopy workshop. Key topics discussed include data models, validation and raw-data archiving. The meeting participants agreed that the EMDataBank should take the lead in addressing these issues, and concrete action points were agreed upon that will have a substantial impact on the accessibility of three-dimensional EM data in biology and medicine