Genomic Risk Prediction of Coronary Artery Disease in 480,000 Adults: Implications for Primary Prevention.

Background: Coronary artery disease (CAD) has substantial heritability and a polygenic architecture. However, the potential of genomic risk scores to help predict CAD outcomes has not been evaluated comprehensively, because available studies have involved limited genomic scope and limited sample sizes.

Objectives: This study sought to construct a genomic risk score for CAD and to estimate its potential as a screening tool for primary prevention.

Mitigating bias in observational vaccine effectiveness studies using simulated comparator populations: Application to rotavirus vaccination in the UK.

Background: Measuring vaccine effectiveness (VE) relies on the use of observational study designs. However, achieving robust estimates of direct and indirect VE is frequently compromised by bias, particularly when using syndromic diagnoses of low-specificity.

Methods: In order to mitigate confounding between the measured outcome and vaccine uptake, we developed a method to balance comparator populations using individual-level propensity scoring derived from the vaccine-exposed population, and applied it to the unexposed comparator population.

Causes and characteristics of injury in paediatric major trauma and trends over time.

Objective: To investigate causes, characteristics and temporal trends of paediatric major trauma.

Design: A retrospective review of paediatric major trauma (<16 years of age) was conducted using data from the population-based Victorian State Trauma Registry from 2006 to 2016. Temporal trends in population-based incidence rates were evaluated using Poisson regression.

Epidemiology of work-related burn injuries presenting to burn centres in Australia and New Zealand.

Background: Burn injuries to workers can have a devastating impact, however knowledge of the epidemiology of work-related burn injuries in Australia and New Zealand is limited.

Purpose: To describe epidemiological characteristics of work-related burn injuries in Australia and New Zealand, and to compare these with non-work-related burns.

Methods: Adult burn injury data, 2009-2016, were extracted from the Burns Registry of Australia and New Zealand.

Coding variants in and increase risk of atrial fibrillation.

Most sequence variants identified hitherto in genome-wide association studies (GWAS) of atrial fibrillation are common, non-coding variants associated with risk through unknown mechanisms. We performed a meta-analysis of GWAS of atrial fibrillation among 29,502 cases and 767,760 controls from Iceland and the UK Biobank with follow-up in samples from Norway and the US, focusing on low-frequency coding and splice variants aiming to identify causal genes. We observe associations with one missense (OR = 1.

Major trauma in older persons.

Background: Globally, populations are ageing, creating challenges for trauma system design. Despite this, little is known about causes of injury and long-term outcomes in older injured patients. This study aims to describe temporal trends in the incidence, causes and functional outcomes of major trauma in older adults.

A case study in distributed team science in research using electronic health records.

Introduction: Due to various regulatory barriers, it is increasingly difficult to move pseudonymised routine health data across platforms and among jurisdictions. To tackle this challenge, we summarized five approaches considered to support a scientific research project focused on the risk of the new non-vitamin K Target Specific Oral Anticoagulants (TSOACs) and collaborated between the Farr institute in Wales and Scotland.

Approach: In Wales, routinely collected health records held in the Secure Anonymous Information Linkage (SAIL) Databank were used to identify the study cohort.

Dynamic Prediction of Survival in Cystic Fibrosis: A Landmarking Analysis Using UK Patient Registry Data.

Background: Cystic fibrosis (CF) is an inherited, chronic, progressive condition affecting around 10,000 individuals in the United Kingdom and over 70,000 worldwide. Survival in CF has improved considerably over recent decades, and it is important to provide up-to-date information on patient prognosis.

Methods: The UK Cystic Fibrosis Registry is a secure centralized database, which collects annual data on almost all CF patients in the United Kingdom.

The limitations of using simple definitions of glucocorticoid exposure to predict fracture risk: A cohort study.

Purpose: To evaluate the effects of different definitions of glucocorticoid (GC) exposure on the magnitude and pattern of fracture risk using the same dataset.

Methods: Data from patients with rheumatoid arthritis (RA) were extracted from the Clinical Practice Research Datalink, a primary care database with electronic health records in the United Kingdom. Patients exposed to oral GCs were matched to up to two unexposed patients by age, gender and location.

Guideline-indicated treatments and diagnostics, GRACE risk score, and survival for non-ST elevation myocardial infarction.

Aims: To investigate whether improved survival from non-ST-elevation myocardial infarction (NSTEMI), according to GRACE risk score, was associated with guideline-indicated treatments and diagnostics, and persisted after hospital discharge.

Methods And Results: National cohort study (n = 389 507 patients, n = 232 hospitals, MINAP registry), 2003-2013. The primary outcome was adjusted all-cause survival estimated using flexible parametric survival modelling with time-varying covariates.

Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits.

Uterine leiomyomas are common benign tumors of the myometrium. We performed a meta-analysis of two genome-wide association studies of leiomyoma in European women (16,595 cases and 523,330 controls), uncovering 21 variants at 16 loci that associate with the disease. Five variants were previously reported to confer risk of various malignant or benign tumors (rs78378222 in TP53, rs10069690 in TERT, rs1800057 and rs1801516 in ATM, and rs7907606 at OBFC1) and four signals are located at established risk loci for hormone-related traits (endometriosis and breast cancer) at 1q36.

Variable cardiac myosin binding protein-C expression in the myofilaments due to MYBPC3 mutations in hypertrophic cardiomyopathy.

Background: Mutations in MYBPC3 are the most common cause of hypertrophic cardiomyopathy (HCM). These mutations produce dysfunctional protein that is quickly degraded and not incorporated in the myofilaments. Most patients are heterozygous and allelic expression differs between cells.

Modelling inherited cardiac disease using human induced pluripotent stem cell-derived cardiomyocytes: progress, pitfalls, and potential.

In the past few years, the use of specific cell types derived from induced pluripotent stem cells (iPSCs) has developed into a powerful approach to investigate the cellular pathophysiology of numerous diseases. Despite advances in therapy, heart disease continues to be one of the leading causes of death in the developed world. A major difficulty in unravelling the underlying cellular processes of heart disease is the extremely limited availability of viable human cardiac cells reflecting the pathological phenotype of the disease at various stages.

Machine learning models in electronic health records can outperform conventional survival models for predicting patient mortality in coronary artery disease.

Prognostic modelling is important in clinical practice and epidemiology for patient management and research. Electronic health records (EHR) provide large quantities of data for such models, but conventional epidemiological approaches require significant researcher time to implement. Expert selection of variables, fine-tuning of variable transformations and interactions, and imputing missing values are time-consuming and could bias subsequent analysis, particularly given that missingness in EHR is both high, and may carry meaning.

A population-based study of treated mental health and persistent pain conditions after transport injury.

Background: Persistent pain and mental health conditions often co-occur after injury, cause enormous disability, reduce social and economic participation, and increase long-term healthcare costs. This study aimed to characterise the incidence, profile and healthcare cost implications for people who have a treated mental health condition, persistent pain, or both conditions, after compensable transport injury.

Methods: The study comprised a population cohort of people who sustained a transport injury (n = 74,217) between 2008 to 2013 and had an accepted claim in the no-fault transport compensation system in Victoria, Australia.

Cardio-oncology: an overview on outpatient management and future developments.

Recent advances in the early detection and treatment of cancer have led to increasing numbers of cancer survivors worldwide. Nonetheless, despite major improvements in the outcome of these patients, long-term side effects of radio- and chemotherapy affect both patient survival and quality of life, independent of the oncological prognosis. Chemotherapy-related cardiac dysfunction is one of the most notorious short-term side effects of anticancer treatment, occurring in ~10% of patients.

Predictors of return to work in survivors of critical illness.

Purpose: To determine predictors of inability to return to work due to health six-months after intensive care admission; and compare functional recovery between patients who had not returned to work and employed patients.

Methods: Participants were working adults admitted to ICU who received >24 h of mechanical ventilation. Outcomes included inability to return to work due to health at six-months post-ICU admission, disability, health status, anxiety, depression and post-traumatic stress.

Perinatal risks in female cancer survivors: A population-based analysis.

Background/objectives: Advances in cancer management have resulted in improved survival rates, particularly in children and young adults. However, treatment may adversely affect reproductive outcomes among female cancer survivors. The objective of this study was to investigate their risk of adverse perinatal outcomes compared to the general population.

Assessing life-space mobility for a more holistic view on wellbeing in geriatric research and clinical practice.

Life-space mobility (LSM) is a holistic measure of resilience to physical decline and social isolation in later life. To promote its use as an outcome in geriatric studies and in clinical practice, this review paper explains the concept of LSM; outlines available questionnaires for LSM assessment, provides an overview of associations between LSM and other outcomes, and discusses emerging methods to measure LSM using wearable sensors. Based on performed activity around a central geographical anchor, LSM aims to quantify the observed contraction of daily activities associated with ageing.