Impact of changing medical workforce demographics in renal medicine over 7 years: Analysis of GMC national trainee survey data.

Increasing numbers of doctors in training are taking career breaks, with burnout cited as a potential cause. This study analysed General Medical Council (GMC) national training survey data (renal medicine) to understand the impacts of changing workforce demographics on trainee outcomes and wellbeing. Increasing proportions of female, Black, Asian and minority ethnic (BAME), and international medical graduates are entering the workforce.

Efficacy of iGlarLixi in adults with type 2 diabetes inadequately controlled (glycated haemoglobin ≥8%, ≥64 mmol/mol) on two oral antidiabetes drugs: Post hoc analysis of the LixiLan-O randomized trial.

Aims: To assess the efficacy and safety of iGlarLixi (the titratable fixed-ratio combination of insulin glargine 100 U/mL [iGlar] plus lixisenatide [Lixi]), in adults with type 2 diabetes (T2D) with glycated haemoglobin (HbA1c) levels ≥8% (≥64 mmol/mol).

Materials And Methods: The LixiLan-O study (NCT02058147) compared iGlarLixi with iGlar or Lixi in adults with T2D inadequately controlled on metformin ± a second oral antidiabetes drug (OAD). This exploratory analysis evaluated the LixiLan-O subgroup of participants with baseline HbA1c levels of ≥8% (≥64 mmol/mol) who were receiving metformin plus a second OAD at screening.

Early invasive versus non-invasive assessment in patients with suspected non-ST-elevation acute coronary syndrome.

Non-ST-elevation acute coronary syndrome (NSTE-ACS) comprises a broad spectrum of disease ranging from unstable angina to myocardial infarction. International guidelines recommend a routine invasive strategy for managing patients with NSTE-ACS at high to very high-risk, supported by evidence of improved composite ischaemic outcomes as compared with a selective invasive strategy. However, accurate diagnosis of NSTE-ACS in the acute setting is challenging due to the spectrum of non-coronary disease that can manifest with similar symptoms.

Antihypertensives and Statin Therapy for Primary Stroke Prevention: A Secondary Analysis of the HOPE-3 Trial.

Background And Purpose: The HOPE-3 trial (Heart Outcomes Prevention Evaluation–3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups.

Methods: Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.

The new UK SARS-CoV-2 variant and lockdown - causes and consequences.

The new variant of concern (VOC), B.1.1.

Multi-omics links IL-6 trans-signalling with neutrophil extracellular trap formation and infection in COPD.

Background: Interleukin (IL)-6 trans-signalling (IL-6TS) is emerging as a pathogenic mechanism in chronic respiratory diseases; however, the drivers of IL-6TS in the airways and the phenotypic characteristic of patients with increased IL-6TS pathway activation remain poorly understood.

Objective: Our aim was to identify and characterise COPD patients with increased airway IL-6TS and to elucidate the biological drivers of IL-6TS pathway activation.

Methods: We used an IL-6TS-specific sputum biomarker profile (soluble IL-6 receptor (sIL-6R), IL-6, IL-1β, IL-8, macrophage inflammatory protein-1β) to stratify sputum data from patients with COPD (n=74; Biomarkers to Target Antibiotic and Systemic Corticosteroid Therapy in COPD Exacerbation (BEAT-COPD)) by hierarchical clustering.

Non-adherence to heart failure medications predicts clinical outcomes: assessment in a single spot urine sample by liquid chromatography-tandem mass spectrometry (results of a prospective multicentre study).

Aims: Liquid chromatography-mass spectrometry (LC-MS/MS) is an objective new technique to assess non-adherence to medications. We used this method to study the prevalence, predictors and outcomes of non-adherence in patients with heart failure with reduced left ventricular ejection fraction (HFrEF).

Methods And Results: This study included 1296 patients with HFrEF from BIOSTAT-CHF, a study that aimed to optimise guideline-recommended therapies.

Joint associations of accelero-meter measured physical activity and sedentary time with all-cause mortality: a harmonised meta-analysis in more than 44 000 middle-aged and older individuals.

Objectives: To examine the joint associations of accelerometer-measured physical activity and sedentary time with all-cause mortality.

Methods: We conducted a harmonised meta-analysis including nine prospective cohort studies from four countries. 44 370 men and women were followed for 4.

Device-measured physical activity and its association with physical function in adults with type 2 diabetes mellitus.

Aim: To quantify how differences in metrics characterizing physical activity and sedentary behaviour in type 2 diabetes are associated with physical function.

Methods: This analysis included participants' data from the Chronotype of Patients with Type 2 Diabetes and Effect on Glycaemic Control (CODEC) cross-sectional study. Data were stratified into two groups according to their short physical performance battery (SPPB) score (impaired physical function = SPPB < 10 and normal physical function = SPPB ≥ 10).

Co-producing Progression Criteria for Feasibility Studies: A Partnership between Patient Contributors, Clinicians and Researchers.

There is a lack of guidance for developing progression criteria (PC) within feasibility studies. We describe a process for co-producing PC for an ongoing feasibility study. Patient contributors, clinicians and researchers participated in discussions facilitated using the modified Nominal Group Technique (NGT).

Five-Year Outcomes after PCI or CABG for Left Main Coronary Disease.

Background: Long-term outcomes after percutaneous coronary intervention (PCI) with contemporary drug-eluting stents, as compared with coronary-artery bypass grafting (CABG), in patients with left main coronary artery disease are not clearly established.

Methods: We randomly assigned 1905 patients with left main coronary artery disease of low or intermediate anatomical complexity (according to assessment at the participating centers) to undergo either PCI with fluoropolymer-based cobalt-chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). The primary outcome was a composite of death, stroke, or myocardial infarction.

Sputum microbiomic clustering in asthma and chronic obstructive pulmonary disease reveals a Haemophilus-predominant subgroup.

Background: Airway ecology is altered in asthma and chronic obstructive pulmonary disease (COPD). Anti-microbial interventions might have benefit in subgroups of airway disease. Differences in sputum microbial profiles at acute exacerbation of airways disease are reflected by the γProteobacteria:Firmicutes (γP:F) ratio.

Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality: systematic review and harmonised meta-analysis.

Objective: To examine the dose-response associations between accelerometer assessed total physical activity, different intensities of physical activity, and sedentary time and all cause mortality.

Design: Systematic review and harmonised meta-analysis.

Data Sources: PubMed, PsycINFO, Embase, Web of Science, Sport Discus from inception to 31 July 2018.

Severe exacerbations in moderate-to-severe asthmatics are associated with increased pro-inflammatory and type 1 mediators in sputum and serum.

Background: Asthma is a heterogeneous disease and understanding this heterogeneity will enable the realisation of precision medicine. We sought to compare the sputum and serum inflammatory profiles in moderate-to-severe asthma during stable disease and exacerbation events.

Methods: We recruited 102 adults and 34 children with asthma.

Glycaemic benefit of iGlarLixi in insulin-naive type 2 diabetes patients with high HbA1c or those with inadequate glycaemic control on two oral antihyperglycaemic drugs in the LixiLan-O randomized trial.

In this post hoc analysis of the randomized controlled LixiLan-O trial in insulin-naive patients with type 2 diabetes mellitus (T2DM) not controlled with metformin, with or without a second oral antihyperglycaemic drug (OAD), the efficacy and safety of the fixed-ratio combination, iGlarLixi (insulin glargine 100 U [iGlar] and lixisenatide [Lixi]), compared to its individual components was assessed in two patient subgroups: group 1) baseline HbA1c ≥9% (n = 134); group 2) inadequate control (HbA1c ≥7.0% and ≤9.0%) despite administration of two OADs at screening (n = 725).

T2 Biologics for Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity and mortality worldwide. In contrast to other chronic diseases, COPD is increasing in prevalence and is projected to be the third leading cause of death and disability worldwide by 2030. Recent advances in understanding the underlying pathophysiology of COPD has led to the development of novel targeted therapies (biologics and small molecules) that address the underlying pathophysiology of the disease.

Differences in objectively measured physical activity and sedentary behaviour between white Europeans and south Asians recruited from primary care: cross-sectional analysis of the PROPELS trial.

Background: Self-reported data have consistently shown South Asians (SAs) to be less physically active than White Europeans (WEs) in developed countries, however objective data is lacking. Differences in sedentary time have not been elucidated in this population. This study aimed to quantify differences in objectively measured physical activity and sedentary behaviour between WEs and SAs recruited from primary care and to investigate differences in demographic and lifestyle correlates of these behaviours.

Biological exacerbation clusters demonstrate asthma and chronic obstructive pulmonary disease overlap with distinct mediator and microbiome profiles.

Background: Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous.

Objective: We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations.

Methods: Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center.

CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial.

Background: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint.

Effects of intradialytic cycling exercise on exercise capacity, quality of life, physical function and cardiovascular measures in adult haemodialysis patients: a systematic review and meta-analysis.

Background: Intradialytic cycling (IDC), delivered during haemodialysis (HD), has the potential to improve many health issues. This systematic review and meta-analysis examine the evidence on the effects of IDC on exercise capacity, quality of life (QoL), physical function and cardiovascular health.

Methods: Twenty-four databases were searched alongside Internet and hand searching, and consultation with experts.

Fevipiprant in the treatment of asthma.

Asthma is common and in many, particularly those with more severe disease, there remains a substantial unmet need. Success with biologics targeting eosinophilic inflammation underscore the value of treating inflammation in asthma beyond corticosteroids. Fevipiprant (QAW039) is an oral treatment for asthma.