Loss of Trem2 in microglia leads to widespread disruption of cell coexpression networks in mouse brain.

Rare heterozygous coding variants in the triggering receptor expressed in myeloid cells 2 (TREM2) gene, conferring increased risk of developing late-onset Alzheimer's disease, have been identified. We examined the transcriptional consequences of the loss of Trem2 in mouse brain to better understand its role in disease using differential expression and coexpression network analysis of Trem2 knockout and wild-type mice. We generated RNA-Seq data from cortex and hippocampus sampled at 4 and 8 months.

The economic burden of stroke care in England, Wales and Northern Ireland: Using a national stroke register to estimate and report patient-level health economic outcomes in stroke.

Introduction: Stroke registries are used in many settings to measure stroke treatment and outcomes, but rarely include data on health economic outcomes. We aimed to extend the Sentinel Stroke National Audit Programme registry of England, Wales and Northern Ireland to derive and report patient-level estimates of the cost of stroke care.

Methods: An individual patient simulation model was built to estimate health and social care costs at one and five years after stroke, and the cost-benefits of thrombolysis and early supported discharge.

Use of Whole-Genome Sequencing in the Investigation of a Nosocomial Influenza Virus Outbreak.

Traditional epidemiological investigation of nosocomial transmission of influenza involves the identification of patients who have the same influenza virus type and who have overlapped in time and place. This method may misidentify transmission where it has not occurred or miss transmission when it has. We used influenza virus whole-genome sequencing (WGS) to investigate an outbreak of influenza A virus infection in a hematology/oncology ward and identified 2 separate introductions, one of which resulted in 5 additional infections and 79 bed-days lost.

Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2016: A Systematic Analysis for the Global Burden of Disease Study.

Importance: The increasing burden due to cancer and other noncommunicable diseases poses a threat to human development, which has resulted in global political commitments reflected in the Sustainable Development Goals as well as the World Health Organization (WHO) Global Action Plan on Non-Communicable Diseases. To determine if these commitments have resulted in improved cancer control, quantitative assessments of the cancer burden are required.

Objective: To assess the burden for 29 cancer groups over time to provide a framework for policy discussion, resource allocation, and research focus.

Evaluation of Semantic Web Technologies for Storing Computable Definitions of Electronic Health Records Phenotyping Algorithms.

Electronic Health Records are electronic data generated during or as a byproduct of routine patient care. Structured, semi-structured and unstructured EHR offer researchers unprecedented phenotypic breadth and depth and have the potential to accelerate the development of precision medicine approaches at scale. A main EHR use-case is defining phenotyping algorithms that identify disease status, onset and severity.

From lipid locus to drug target through human genomics.

In the last decade, over 175 genetic loci have robustly been associated to levels of major circulating blood lipids. Most loci are specific to one or two lipids, whereas some (SUGP1, ZPR1, TRIB1, HERPUD1, and FADS1) are associated to all. While exposing the polygenic architecture of circulating lipids and the underpinnings of dyslipidaemia, these genome-wide association studies (GWAS) have provided further evidence of the critical role that lipids play in coronary heart disease (CHD) risk, as indicated by the 2.

Identification of new risk factors for rolandic epilepsy: CNV at Xp22.31 and alterations at cholinergic synapses.

Background: Rolandic epilepsy (RE) is the most common genetic childhood epilepsy, consisting of focal, nocturnal seizures and frequent neurodevelopmental impairments in speech, language, literacy and attention. A complex genetic aetiology is presumed in most, with monogenic mutations in accounting for >5% of cases.

Objective: To identify rare, causal CNV in patients with RE.

Vitamin D status and the risk of type 2 diabetes: The Melbourne Collaborative Cohort Study.

Aims: Inverse associations between vitamin D status and risk of type 2 diabetes observed in epidemiological studies could be biased by confounding and reverse causality. We investigated the prospective association between vitamin D status and type 2 diabetes and the possible role of reverse causality.

Methods: We conducted a case-cohort study within the Melbourne Collaborative Cohort Study (MCCS), including a random sample of 628 participants who developed diabetes and a sex-stratified random sample of the cohort (n = 1884).

Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval.

Background: Electrical conduction from the cardiac sinoatrial node to the ventricles is critical for normal heart function. Genome-wide association studies have identified more than a dozen common genetic loci that are associated with PR interval. However, it is unclear whether rare and low-frequency variants also contribute to PR interval heritability.

Child mortality in England compared with Sweden: a birth cohort study.

Background: Child mortality is almost twice as high in England compared with Sweden. We aimed to establish the extent to which adverse birth characteristics and socioeconomic factors explain this difference.

Methods: We developed nationally representative cohorts of singleton livebirths between Jan 1, 2003, and Dec 31, 2012, using the Hospital Episode Statistics in England, and the Swedish Medical Birth Register in Sweden, with longitudinal follow-up from linked hospital admissions and mortality records.

Feasibility and implementation of CYP2C19 genotyping in patients using antiplatelet therapy.

Aim: A tailored antiplatelet strategy based on CYP2C19 genotype may reduce atherothrombotic and bleeding events. We describe our experience with CYP2C19 genotyping, using on-site TaqMan or Spartan genotyping or shipment to a central laboratory.

Methodology: Data from two ongoing projects were used: Popular Risk Score project (non-urgent percutaneous coronary intervention patients) and the Popular Genetics study (ST-segment elevation myocardial infarction patients).

Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies.

Background: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease.

Methods: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank).

Integrative Bioinformatics Approaches for Identification of Drug Targets in Hypertension.

High blood pressure or hypertension is an established risk factor for a myriad of cardiovascular diseases. Genome-wide association studies have successfully found over nine hundred loci that contribute to blood pressure. However, the mechanisms through which these loci contribute to disease are still relatively undetermined as less than 10% of hypertension-associated variants are located in coding regions.

Hip fracture incidence and mortality in chronic kidney disease: the GLOMMS-II record linkage cohort study.

Background: Individuals on renal replacement therapy (RRT) have increased fracture risk, but risk in less advanced chronic kidney disease (CKD) is unclear.

Objective: To investigate CKD associations with hip fracture incidence and mortality.

Design: Record linkage cohort study Grampian Laboratory Outcomes Mortality and Morbidity Study II.

Usefulness of a clinical risk score to predict the response to cardiac resynchronization therapy.

Background: Almost 1/3 of heart failure patients fail to respond to cardiac resynchronization therapy (CRT). A simple clinical score to predict who these patients are at the moment of referral or at time of implant may be of importance for early optimization of their management.

Methods: Observational study.

A Blood Test for Alzheimer's Disease: Progress, Challenges, and Recommendations.

Ever since the discovery of APOEɛ4 around 25 years ago, researchers have been excited about the potential of a blood test for Alzheimer's disease (AD). Since then researchers have looked for genetic, protein, metabolite, and/or gene expression markers of AD and related phenotypes. However, no blood test for AD is yet being used in the clinical setting.

Personalized survival predictions via Trees of Predictors: An application to cardiac transplantation.

Background: Risk prediction is crucial in many areas of medical practice, such as cardiac transplantation, but existing clinical risk-scoring methods have suboptimal performance. We develop a novel risk prediction algorithm and test its performance on the database of all patients who were registered for cardiac transplantation in the United States during 1985-2015.

Methods And Findings: We develop a new, interpretable, methodology (ToPs: Trees of Predictors) built on the principle that specific predictive (survival) models should be used for specific clusters within the patient population.

Systematic review of outcome measures following chemoradiotherapy for the treatment of anal cancer (CORMAC).

Aim: Six Phase III randomized trials have determined the effectiveness of chemoradiotherapy as primary treatment for anal squamous cell carcinoma (ASCC), but outcomes reported in these trials varied widely, hindering evidence synthesis. To improve reporting in all future trials, we aim to develop a core outcomes set (COS). As the first stage of COS development, we undertook a systematic review to summarize the outcomes reported in studies evaluating chemoradiotherapy for ASCC.

Chemotherapy-Related Cardiac Dysfunction: A Systematic Review of Genetic Variants Modulating Individual Risk.

Chemotherapy-related cardiac dysfunction is a significant side effect of anticancer treatment. Risk stratification is based on clinical- and treatment-related risk factors that do not adequately explain individual susceptibility. The addition of genetic variants may improve risk assessment.

Socioeconomic disparities in first stroke incidence, quality of care, and survival: a nationwide registry-based cohort study of 44 million adults in England.

Background: We aimed to estimate socioeconomic disparities in the incidence of hospitalisation for first-ever stroke, quality of care, and post-stroke survival for the adult population of England.

Methods: In this cohort study, we obtained data collected by a nationwide register on patients aged 18 years or older hospitalised for first-ever acute ischaemic stroke or primary intracerebral haemorrhage in England from July 1, 2013, to March 31, 2016. We classified socioeconomic status at the level of Lower Super Output Areas using the Index of Multiple Deprivation, a neighbourhood measure of deprivation.

Correction to: Risk of Adverse Outcomes for Older People with Dementia Prescribed Antipsychotic Medication: A Population Based e-Cohort Study.

This article was originally published under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0), but has now been made available under a Creative Commons Attribution 4.

Feasibility of real-time capture of routine clinical data in the electronic health record: a hospital-based, observational service-evaluation study.

Objectives: The electronic health record (EHR) is underused in the hospital setting. The aim of this service evaluation study was to respond to National Health Service (NHS) Digital's ambition for a paperless NHS by capturing routinely collected cardiac outpatient data in the EHR to populate summary patient reports and provide a resource for audit and research.

Design: A PowerForm template was developed within the Cerner EHR, for real-time entry of routine clinical data by clinicians attending a cardiac outpatient clinic.