Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci.

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants).

Proximal HbA1C Level and First Hypoglycemia Hospitalization in Adults With Incident Type 2 Diabetes.

Context: Hemoglobin A1C (HbA1C) is an important predictor of severe hypoglycemia.

Objective: To determine the association of proximal HbA1C level with first hypoglycemia hospitalization (HH) in adults with incident type 2 diabetes (T2D).

Design, Setting, And Participants: A nested case-control study was designed using linked data from the Clinical Practice Research Datalink and Hospital Episode Statistics in England in 1997 to 2014.

Survival after cardiac resynchronization therapy: results from 50 084 implantations.

Aims: Randomized controlled trials have shown that cardiac resynchronization therapy (CRT) prolongs survival in patients with heart failure. No studies have explored survival after CRT in relation to individuals in the general population (relative survival, RS). We sought to determine observed and RS after CRT in a nationwide cohort undergoing CRT.

Association of pre-eclampsia risk with maternal levels of folate, homocysteine and vitamin B12 in Colombia: A case-control study.

Background: Maternal serum concentrations of folate, homocysteine, and vitamin B12 have been associated with pre-eclampsia. Nevertheless, reported studies involve limited number of cases to reliably assess the nature of these associations. Our aim was to examine the relation of these three biomarkers with pre-eclampsia risk in a large Colombian population.

The temporal pattern of immune and inflammatory proteins prior to a recurrent coronary event in post-acute coronary syndrome patients.

Purpose: We assessed the temporal pattern of 29 immune and inflammatory proteins in post-acute coronary syndrome (ACS) patients, prior to the development of recurrent ACS.

Methods: High-frequency blood sampling was performed in 844 patients admitted for ACS during one-year follow-up. We conducted a case-control study on the 45 patients who experienced reACS (cases) and two matched event-free patients (controls) per case.

The use of capture-recapture methods to provide better estimates of the burden of norovirus outbreaks from seafood in England, 2004-2011.

Norovirus (NoV) is the greatest cause of infectious intestinal disease in the UK. The burden associated with foodborne outbreaks is underestimated in part because data are dispersed across different organisations. Each looks at outbreaks through a different lens.

Sequence variants associating with urinary biomarkers.

Urine dipstick tests are widely used in routine medical care to diagnose kidney and urinary tract and metabolic diseases. Several environmental factors are known to affect the test results, whereas the effects of genetic diversity are largely unknown. We tested 32.

Outcomes of midfoot and hindfoot fractures in multitrauma patients.

Introduction: Multitrauma patients suffering hindfoot fractures, including calcaneal and talar fractures, often result in poor outcomes. However, less is known about the outcomes following midfoot fracture in the mutitrauma population. This study aims to describe the epidemiology of midfoot fractures in multitrauma patients and to compare the outcomes of midfoot and hindfoot fractures in this population.

Dilated Cardiomyopathy Due to BLC2-Associated Athanogene 3 (BAG3) Mutations.

Background: The BAG3 (BLC2-associated athanogene 3) gene codes for an antiapoptotic protein located on the sarcomere Z-disc. Mutations in BAG3 are associated with dilated cardiomyopathy (DCM), but only a small number of cases have been reported to date, and the natural history of BAG3 cardiomyopathy is poorly understood.

Objectives: This study sought to describe the phenotype and prognosis of BAG3 mutations in a large multicenter DCM cohort.

Comparative safety and effectiveness of direct oral anticoagulants in patients with atrial fibrillation in clinical practice in Scotland.

Aims: The aim of this study was to compare the clinical effectiveness and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) in routine clinical practice.

Methods: This retrospective cohort study used linked administrative data. The study population (n = 14 577) included patients with a diagnosis of AF (confirmed in hospital) who initiated DOAC treatment in Scotland between August 2011 and December 2015.

Genome-wide associations for benign prostatic hyperplasia reveal a genetic correlation with serum levels of PSA.

Benign prostatic hyperplasia and associated lower urinary tract symptoms (BPH/LUTS) are common conditions affecting the majority of elderly males. Here we report the results of a genome-wide association study of symptomatic BPH/LUTS in 20,621 patients and 280,541 controls of European ancestry, from Iceland and the UK. We discovered 23 genome-wide significant variants, located at 14 loci.

Study investigating the generalisability of a COPD trial based in primary care (Salford Lung Study) and the presence of a Hawthorne effect.

Introduction: Traditional phase IIIb randomised trials may not reflect routine clinical practice. The Salford Lung Study in chronic obstructive pulmonary disease (SLS COPD) allowed broad inclusion criteria and followed patients in routine practice. We assessed whether SLS COPD approximated the England COPD population and evidence for a Hawthorne effect.

Body mass index trajectories across adulthood and smoking in relation to prostate cancer risks: the NIH-AARP Diet and Health Study.

Background: Previously we showed that adulthood body mass index (BMI) trajectories that result in obesity were associated with elevated risks of fatal prostate cancer (PCA). To further explore this relationship, we conducted a study within the NIH-AARP Diet and Health Study.

Methods: Among 153 730 eligible men enrolled in the NIH-AARP cohort from 1995 to 1996 (median follow-up = 15.

Self-Reported Sleep Duration and Quality and Cardiovascular Disease and Mortality: A Dose-Response Meta-Analysis.

Background There is growing evidence that sleep duration and quality may be associated with cardiovascular harm and mortality. Methods and Results We conducted a systematic review, meta-analysis, and spline analysis of prospective cohort studies that evaluate the association between sleep duration and quality and cardiovascular outcomes. We searched MEDLINE and EMBASE for these studies and extracted data from identified studies.

Essential components in natriuretic peptide-guided management of heart failure: an intervention synthesis.

Aim: To identify the key components of natriuretic peptide (NP)-guided treatment interventions which reduced hospitalisation in patients with heart failure (HF).

Methods And Results: We extracted detailed information on the components of interventions from studies of NP-guided treatment of HF identified in a previous systematic review. We used meta-regression techniques to assess univariate associations between components and the strength of the reduction in HF hospitalisations and all-cause mortality.

Prevalence and risk factors of community-associated methicillin-resistant carriage in Asia-Pacific region from 2000 to 2016: a systematic review and meta-analysis.

Objective: Community-associated methicillin-resistant (CA-MRSA) is an emerging global public health threat. In response to a highlighted strategic priority of the World Health Organization Global Action Plan on Antimicrobial Resistance, to "strengthen the knowledge and evidence base through surveillance and research", we synthesized published articles to estimate CA-MRSA carriage prevalence in the Asia-Pacific region.

Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO CRD:42017067399).

Comparative anti-fracture effectiveness of different oral anti-osteoporosis therapies based on "real-world" data: a meta-analysis of propensity-matched cohort findings from the UK Clinical Practice Research Database and the Catalan SIDIAP Database.

Purpose: This paper aims to compare the clinical effectiveness of oral anti-osteoporosis drugs based on the observed risk of fracture while on treatment in primary care actual practice.

Materials And Methods: We investigated two primary care records databases covering UK National Health Service (Clinical Practice Research Datalink, CPRD) and Catalan healthcare (Information System for Research in Primary Care, SIDIAP) patients during 1995-2014 and 2006-2014, respectivey. Treatment-naive incident users of anti-osteoporosis drugs were included and followed until treatment cessation, switching, death, transfer out, or study completion.

Seasonal fluctuation of lung function in cystic fibrosis: A national register-based study in two northern European populations.

Background: Many risk factors for lung disease in cystic fibrosis (CF) display a seasonal pattern yet it is unclear whether this is reflected in seasonal fluctuations in lung function.

Methods: We conducted a longitudinal study using CF registries in Denmark and the UK. 471 individuals with a median of 104 FEV measurements per person and 7586 individuals with a median of nine FEV measures per person were included from Denmark and the UK respectively.

The influence of residential and workday population mobility on exposure to air pollution in the UK.

Traditional approaches of quantifying population-level exposure to air pollution assume that concentrations of air pollutants at the residential address of the study population are representative for overall exposure. This introduces potential bias in the quantification of human health effects. Our study combines new UK Census data comprising information on workday population densities, with high spatio-temporal resolution air pollution concentration fields from the WRF-EMEP4UK atmospheric chemistry transport model, to derive more realistic estimates of population exposure to NO, PM and O.

Paramedics' perceptions of the care they provide to people who self-harm: A qualitative study using evolved grounded theory methodology.

Background: Self-harm (SH) accounts for over 5% of the workload of emergency ambulance services, and therefore Paramedics are often the first health professional in contact with people who SH. The authors of this paper have reported elsewhere the significant gaps in our understandings which exist surrounding this early care interaction, and some of the challenges paramedics and opportunities in paramedic care for people who SH. This study aimed to explore paramedics' perceptions of caring for those who SH using Evolved Grounded Theory Methodology.

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder.

Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree ( ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder.

New approaches to pharmacosurveillance for monitoring prescription frequency, diversity, and co-prescription in a large sentinel network of companion animal veterinary practices in the United Kingdom, 2014-2016.

Pharmaceutical agents (PAs) are commonly prescribed in companion animal practice in the United Kingdom. However, little is known about PA prescription on a population-level, particularly with respect to PAs authorised for human use alone prescribed via the veterinary cascade; this raises important questions regarding the efficacy and safety of PAs prescribed to companion animals. This study explored new approaches for describing PA prescription, diversity and co-prescription in dogs, cats and rabbits utilising electronic health records (EHRs) from a sentinel network of 457 companion animal-treating veterinary sites throughout the UK over a 2-year period (2014-2016).