Refined selection of individuals for preventive cardiovascular disease treatment with a transformer-based risk model.

Background: Although statistical models have been commonly used to identify patients at risk of cardiovascular disease for preventive therapy, these models tend to over-recommend therapy. Moreover, in populations with pre-existing diseases, the current approach is to indiscriminately treat all, as modelling in this context is currently inadequate. This study aimed to develop and validate the Transformer-based Risk assessment survival (TRisk) model, a novel deep learning model, for predicting 10-year risk of cardiovascular disease in both the primary prevention population and individuals with diabetes.

Blood Pressure Lowering and Risk of Cancer: Individual Participant-Level Data Meta-Analysis and Mendelian Randomization Studies.

Background: Pharmacologic blood pressure (BP) lowering is typically a lifelong treatment, and both clinicians and patients may have concerns about the long-term use of antihypertensive agents and the risk for cancer. However, evidence from randomized controlled trials (RCTs) regarding the effect of long-term pharmacologic BP lowering on the risk for new-onset cancer is limited, with most knowledge derived from observational studies.

Objectives: The aim of this study was to assess whether long-term BP lowering affects the risk for new-onset cancer, cause-specific cancer death, and selected site-specific cancers.

Blood pressure management in type 2 diabetes: a review of recent evidence.

The frequent concurrence of elevated blood pressure (BP) and type 2 diabetes markedly elevates the risk of cardiovascular disease and mortality. In this review, we discuss the evidence supporting the role of BP-lowering therapies in preventing cardiovascular events in people with type 2 diabetes and the most appropriate BP treatment target in these individuals. We outline possible reasons for the heterogeneous effect of BP lowering in patients with and without diabetes and consider several pathophysiological mechanisms that could potentially explain such differences.

Efficacy of decentralised home-based antihypertensive treatment in older adults with multimorbidity and polypharmacy (ATEMPT): an open-label randomised controlled pilot trial.

Background: Older patients with multimorbidity and polypharmacy have been under-represented in clinical trials. We aimed to assess the effect of different intensities of antihypertensive treatment on changes in blood pressure, major safety outcomes, and patient-reported outcomes in this population.

Methods: ATEMPT was a decentralised, two-armed, parallel-group, open-label randomised controlled pilot trial conducted in the Thames Valley area, South East England.

The effect of immunomodulatory drugs on aortic stenosis: a Mendelian randomisation analysis.

There are currently no approved pharmacological treatment options for aortic stenosis (AS), and there are limited identified drug targets for this chronic condition. It remains unclear whether inflammation plays a role in AS pathogenesis and whether immunomodulation could become a therapeutic target. We evaluated the potentially causal association between inflammation and AS by investigating the genetically proxied effects of tocilizumab (IL6 receptor, IL6R, inhibitor), canakinumab (IL1β inhibitor) and colchicine (β-tubulin inhibitor) through a Mendelian randomisation (MR) approach.

Sodium-based paracetamol: impact on blood pressure, cardiovascular events, and all-cause mortality.

Background And Aims: Effervescent formulations of paracetamol containing sodium bicarbonate have been reported to associate with increased blood pressure and a higher risk of cardiovascular diseases and all-cause mortality. Given the major implications of these findings, the reported associations were re-examined.

Methods: Using linked electronic health records data, a cohort of 475 442 UK individuals with at least one prescription of paracetamol, aged between 60 and 90 years, was identified.

Stratification of diabetes in the context of comorbidities, using representation learning and topological data analysis.

Diabetes is a heterogenous, multimorbid disorder with a large variation in manifestations, trajectories, and outcomes. The aim of this study is to validate a novel machine learning method for the phenotyping of diabetes in the context of comorbidities. Data from 9967 multimorbid patients with a new diagnosis of diabetes were extracted from Clinical Practice Research Datalink.

Systolic blood pressure, chronic obstructive pulmonary disease and cardiovascular risk.

Objective: In individuals with complex underlying health problems, the association between systolic blood pressure (SBP) and cardiovascular disease is less well recognised. The association between SBP and risk of cardiovascular events in patients with chronic obstructive pulmonary disease (COPD) was investigated.

Methods And Analysis: In this cohort study, 39 602 individuals with a diagnosis of COPD aged 55-90 years between 1990 and 2009 were identified from validated electronic health records (EHR) in the UK.

High-Frequency Rheological and Piezo-Voltage Waveform Characterization of Inkjet-Printed Polymer-Based Dopant-Source Inks.

This work focuses on developing an understanding of the rheological properties of polymer-based dopant-source inks at the timescales relevant to inkjet printing and their corresponding roles in determining the production of defect-free droplets. Ink-specific optimization of printing processes for phosphorus and boron dopant-source inks with different compositions is demonstrated. Rheological flow curves measured by a piezo axial vibrator (PAV) were used to study the changes in complex viscosity (*) and in the elastic (G') and viscous (G″) components of the shear modulus (G*) with respect to changes in frequency (from f = 1 kHz to f = 10 kHz) to obtain an insight into the high-frequency behaviour of inks, as well as the effects of temperature (25 °C and 45 °C) and the natural aging time of the inks.

Systolic Blood Pressure and Cardiovascular Risk in Patients With Diabetes: A Prospective Cohort Study.

Background: Whether the association between systolic blood pressure (SBP) and risk of cardiovascular disease is monotonic or whether there is a nadir of optimal blood pressure remains controversial. We investigated the association between SBP and cardiovascular events in patients with diabetes across the full spectrum of SBP.

Methods: A cohort of 49 000 individuals with diabetes aged 50 to 90 years between 1990 and 2005 was identified from linked electronic health records in the United Kingdom.

Blood pressure and risk of venous thromboembolism: a cohort analysis of 5.5 million UK adults and Mendelian randomization studies.

Aims: Evidence for the effect of elevated blood pressure (BP) on the risk of venous thromboembolism (VTE) has been conflicting. We sought to assess the association between systolic BP and the risk of VTE.

Methods And Results: Three complementary studies comprising an observational cohort analysis, a one-sample and two-sample Mendelian randomization were conducted using data from 5 588 280 patients registered in the Clinical Practice Research Datalink (CPRD) dataset and 432 173 UK Biobank participants with valid genetic data.

The association of dietary insulin load and index with the risk of cancer and cancer mortality: a systematic review and meta-analysis.

Purpose: Insulin levels play an important role in cancer development. However, the link between an insulinogenic diet and cancer is still unclear. Therefore, we performed a systematic review with meta-analysis to investigate the association between dietary insulin index (II) and load (IL) with cancer risk and mortality.

Investigating the association of environmental exposures and all-cause mortality in the UK Biobank using sparse principal component analysis.

Multicollinearity refers to the presence of collinearity between multiple variables and renders the results of statistical inference erroneous (Type II error). This is particularly important in environmental health research where multicollinearity can hinder inference. To address this, correlated variables are often excluded from the analysis, limiting the discovery of new associations.

How Much Lowering of Blood Pressure Is Required to Prevent Cardiovascular Disease in Patients With and Without Previous Cardiovascular Disease?

Purpose Of Review: To review the recent large-scale randomised evidence on pharmacologic reduction in blood pressure for the primary and secondary prevention of cardiovascular disease.

Recent Findings: Based on findings of the meta-analysis of individual participant-level data from 48 randomised clinical trials and involving 344,716 participants with mean age of 65 years, the relative reduction in the risk of developing major cardiovascular events was proportional to the magnitude of achieved reduction in blood pressure. For each 5-mmHg reduction in systolic blood pressure, the risk of developing cardiovascular events fell by 10% (hazard ratio [HR] (95% confidence interval [CI], 0.

ABCG2, SCN1A and CYP3A5 genes polymorphism and drug-resistant epilepsy in children: A case-control study.

Purpose: Drug Resistant -Epilepsy is still a major challenge in pharmacotherapy of epilepsy. Pharmacogenetic pathways are one of the most important elements that can help clinicians determine medication response and provide more efficient drug therapy, especially in cases of drug resistance. Genetic alterations in drug target and transporter proteins, in part, could explain the development of drug-resistant epilepsy.

The Blood Pressure Lowering Treatment Trialists' Collaboration: methodological clarifications of recent reports.

Epidemiological evidence has consistently shown that people with higher systolic or diastolic blood pressure are at greater risk of cardiovascular diseases. However, there has been limited randomized evidence to determine the role of blood pressure level at treatment initiation in the reduction of cardiovascular diseases risk. The extent to which other characteristics of individuals, such as prior disease history, age or sex, should be taken into account has also been controversial.

Antihypertensive drug effects on long-term blood pressure: an individual-level data meta-analysis of randomised clinical trials.

Objective: Evidence from randomised trials of pharmacological treatments on long-term blood pressure (BP) reduction is limited. We investigated the antihypertensive drug effects on BP over time and across different participant characteristics.

Methods: We conducted an individual patient-level data meta-analysis of 52 large-scale randomised clinical trials in the Blood Pressure Lowering Treatment Trialists' Collaboration using mixed models to examine treatment effects on BP over 4 years of mean follow-up.

Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis.

Background: Blood pressure lowering is an established strategy for preventing microvascular and macrovascular complications of diabetes, but its role in the prevention of diabetes itself is unclear. We aimed to examine this question using individual participant data from major randomised controlled trials.

Methods: We performed a one-stage individual participant data meta-analysis, in which data were pooled to investigate the effect of blood pressure lowering per se on the risk of new-onset type 2 diabetes.