Effectiveness of mRNA COVID-19 Vaccines as First Booster Doses in England: An Observational Study in OpenSAFELY-TPP.

Background: The UK delivered its first "booster" COVID-19 vaccine doses in September 2021, initially to individuals at high risk of severe disease, then to all adults. The BNT162b2 Pfizer-BioNTech vaccine was used initially, then also Moderna mRNA-1273.

Methods: With the approval of the National Health Service England, we used routine clinical data to estimate the effectiveness of boosting with BNT162b2 or mRNA-1273 compared with no boosting in eligible adults who had received two primary course vaccine doses.

Comparative effectiveness of BNT162b2 versus mRNA-1273 covid-19 vaccine boosting in England: matched cohort study in OpenSAFELY-TPP.

Objective: To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and mRNA-1273 (Moderna) covid-19 vaccines during the booster programme in England.

Design: Matched cohort study, emulating a comparative effectiveness trial.

Setting: Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 delta and omicron variants were dominant.

To Adjust or Not to Adjust? When a "Confounder" Is Only Measured After Exposure.

Advice regarding the analysis of observational studies of exposure effects usually is against adjustment for factors that occur after the exposure, as they may be caused by the exposure (or mediate the effect of exposure on outcome), so potentially leading to collider stratification bias. However, such factors could also be caused by unmeasured confounding factors, in which case adjusting for them will also remove some of the bias due to confounding. We derive expressions for collider stratification bias when conditioning and confounding bias when not conditioning on the mediator, in the presence of unmeasured confounding (assuming that all associations are linear and there are no interactions).

The role of combinatorial health technologies in supporting older people with long-term conditions: Responsibilisation or co-management of healthcare?

Neoliberalism, austerity and health responsibilisation are increasingly informing policies and practices designed to encourage older patients to take responsibility for the management of their own healthcare. Combined with an ageing population, novel ways to address the increasing healthcare needs of older people have become a priority, with the emergence in recent years of new models of integrated care enhanced by combinatorial health technologies (CHTs). This paper presents qualitative findings from the evaluation of one programme, the Lancashire and Cumbria Innovation Alliance (LCIA) Test Bed, a programme funded by NHS England and conducted in England between 2016 and 2018.

Collider bias undermines our understanding of COVID-19 disease risk and severity.

Numerous observational studies have attempted to identify risk factors for infection with SARS-CoV-2 and COVID-19 disease outcomes. Studies have used datasets sampled from patients admitted to hospital, people tested for active infection, or people who volunteered to participate. Here, we highlight the challenge of interpreting observational evidence from such non-representative samples.

Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis.

Background: Circulating lipoprotein lipids cause coronary heart disease (CHD). However, the precise way in which one or more lipoprotein lipid-related entities account for this relationship remains unclear. Using genetic instruments for lipoprotein lipid traits implemented through multivariable Mendelian randomisation (MR), we sought to compare their causal roles in the aetiology of CHD.

How effective and cost-effective are innovative combinatorial technologies and practices for supporting older people with long-term conditions to remain well in the community? An evaluation protocol for an NHS Test Bed in North West England.

Introduction: The Lancashire and Cumbria Innovation Alliance (LCIA) Test Bed is a partnership between the National Health Service in England, industry (led by Philips) and Lancaster University. Through the implementation of a combination of innovative health technologies and practices, it aims to determine the most effective and cost-effective ways of supporting frail older people with long-term conditions to remain well in the community. Among the Test Bed's objectives are to improve patient activation and the ability of older people to self-care at home, reduce healthcare system utilisation, and deliver increased workforce productivity.

Reading comprehension difficulties in children with rolandic epilepsy.

Aim: Difficulties in reading comprehension can arise from either word reading or listening comprehension difficulties, or a combination of the two. We sought to determine whether children with rolandic epilepsy had poor reading comprehension relative to typically developing comparison children, and whether such difficulties were associated with word reading and/or general language comprehension difficulties.

Method: In this cross-sectional study, children with rolandic epilepsy (n=25; 16 males, 9 females; mean age 9y 1mo, SD 1y 7mo) and a comparison group (n=39; 25 males, 14 females; mean age 9y 1mo, SD 1y 3mo) completed assessments of reading comprehension, listening comprehension, word/non-word reading, speech articulation, and Non-verbal IQ.

Correcting the Standard Errors of 2-Stage Residual Inclusion Estimators for Mendelian Randomization Studies.

Mendelian randomization studies use genotypes as instrumental variables to test for and estimate the causal effects of modifiable risk factors on outcomes. Two-stage residual inclusion (TSRI) estimators have been used when researchers are willing to make parametric assumptions. However, researchers are currently reporting uncorrected or heteroscedasticity-robust standard errors for these estimates.

Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis.

Background: The implications of different adiposity measures on cardiovascular disease etiology remain unclear. In this article, we quantify and contrast causal associations of central adiposity (waist-to-hip ratio adjusted for body mass index [WHRadjBMI]) and general adiposity (body mass index [BMI]) with cardiometabolic disease.

Methods: Ninety-seven independent single-nucleotide polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics; combined total 66 842 cases), stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants) consortia.

Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight.

Importance: Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain.

Objective: To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight.

Harnessing publicly available genetic data to prioritize lipid modifying therapeutic targets for prevention of coronary heart disease based on dysglycemic risk.

Therapeutic interventions that lower LDL-cholesterol effectively reduce the risk of coronary artery disease (CAD). However, statins, the most widely prescribed LDL-cholesterol lowering drugs, increase diabetes risk. We used genome-wide association study (GWAS) data in the public domain to investigate the relationship of LDL-C and diabetes and identify loci encoding potential drug targets for LDL-cholesterol modification without causing dysglycemia.

Effect of smoking on physical and cognitive capability in later life: a multicohort study using observational and genetic approaches.

Objectives: The observed associations between smoking and functional measures at older ages are vulnerable to bias and confounding. Mendelian randomisation (MR) uses genotype as an instrumental variable to estimate unconfounded causal associations. We conducted a meta-analysis of the observational associations and implemented an MR approach using the smoking-related single nucleotide polymorphism rs16969968 to explore their causal nature.

Improving health outcomes for young people with long term conditions: The role of digital communication in current and future patient-clinician communication for NHS providers of specialist clinical services for young people - LYNC study protocol.

Background: Young people living with long term conditions are vulnerable to health service disengagement. This endangers their long term health. Studies report requests for digital forms of communication - email, text, social media - with their health care team.

Using genetics to test the causal relationship of total adiposity and periodontitis: Mendelian randomization analyses in the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium.

Background: The observational relationship between obesity and periodontitis is widely known, yet causal evidence is lacking. Our objective was to investigate causal associations between periodontitis and body mass index (BMI).

Methods: We performed Mendelian randomization analyses with BMI-associated loci combined in a genetic risk score (GRS) as the instrument for BMI.

Adult height, coronary heart disease and stroke: a multi-locus Mendelian randomization meta-analysis.

Background: We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis.

Methods: We developed an allele score based on 69 single nucleotide polymorphisms (SNPs) associated with adult height, identified by the IBCCardioChip, and used it for IV analysis against cardiovascular risk factors and events in 21 studies and 60 028 participants. IV analysis on CHD was supplemented by summary data from 180 height-SNPs from the GIANT consortium and their corresponding CHD estimates derived from CARDIoGRAMplusC4D.

A Mendelian Randomization Study of Circulating Uric Acid and Type 2 Diabetes.

We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric acid-associated loci. We used data of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, comprising 24,265 individuals of European ancestry from eight European countries.

Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study.

Background: Observational studies have reported associations between body mass index (BMI) and asthma, but confounding and reverse causality remain plausible explanations. We aim to investigate evidence for a causal effect of BMI on asthma using a Mendelian randomization approach.

Methods And Findings: We used Mendelian randomization to investigate causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ y in the Avon Longitudinal Study of Parents and Children (ALSPAC).

Lack of identification in semiparametric instrumental variable models with binary outcomes.

A parameter in a statistical model is identified if its value can be uniquely determined from the distribution of the observable data. We consider the context of an instrumental variable analysis with a binary outcome for estimating a causal risk ratio. The semiparametric generalized method of moments and structural mean model frameworks use estimating equations for parameter estimation.

Alcohol consumption and cognitive performance: a Mendelian randomization study.

Aims: To use Mendelian randomization to assess whether alcohol intake was causally associated with cognitive function.

Design: Mendelian randomization using a genetic variant related to alcohol intake (ADH1B rs1229984) was used to obtain unbiased estimates of the association between alcohol intake and cognitive performance.

Setting: Europe.

Genetic variants at chromosome 9p21 and risk of first versus subsequent coronary heart disease events: a systematic review and meta-analysis.

Objectives: The purpose of this analysis was to compare the association between variants at the chromosome 9p21 locus (Ch9p21) and risk of first versus subsequent coronary heart disease (CHD) events through systematic review and meta-analysis.

Background: Ch9p21 is a recognized risk factor for a first CHD event. However, its association with risk of subsequent events in patients with established CHD is less clear.

Mendelian randomization of blood lipids for coronary heart disease.

Aims: To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization.

Methods And Results: We developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores.