Physical activity for people with dementia: A scoping study

Background: This scoping study aimed to identify how physical activity may benefit people with dementia; how and/or if current service provide these benefits; and what support they need to do so. Methods: Methods included an evidence review using literature; mapping current service provision through a survey; and in-depth interviews with a sample of service providers. Results: The 26 studies included in the review indicated the potential effectiveness of physical activity for people with dementia, including improvements in cognition and mood, behaviour and physical condition. Mechanisms of action and the link with outcomes were poorly defined and implemented. The mapping survey and related interviews showed that service providers were delivering a range of services broadly consistent with the scientific evidence. They tended to take a holistic view of possible benefits, and focused on enjoyment and well-being, more than specific cognitive, physical and behavioural outcomes highlighted in literature. Service providers needed more evidence based information and resources to develop services and realise their potential. Conclusion: Despite potential benefits demonstrated in literature and practice, there is a need for further research to optimise interventions and to consider some neglected issues including delivery at home and in communities; impacts for carers; physical activities through ADLs; and individual needs. Studies are needed which take a more holistic approach to the effects of physical activity, and outcomes should be broader and include mental health and wellbeing

Population genomics of cardiometabolic traits: design of the University College London-London School of Hygiene and Tropical Medicine-Edinburgh-Bristol (UCLEB) Consortium.

Substantial advances have been made in identifying common genetic variants influencing cardiometabolic traits and disease outcomes through genome wide association studies. Nevertheless, gaps in knowledge remain and new questions have arisen regarding the population relevance, mechanisms, and applications for healthcare. Using a new high-resolution custom single nucleotide polymorphism (SNP) array (Metabochip) incorporating dense coverage of genomic regions linked to cardiometabolic disease, the University College-London School-Edinburgh-Bristol (UCLEB) consortium of highly-phenotyped population-based prospective studies, aims to: (1) fine map functionally relevant SNPs; (2) precisely estimate individual absolute and population attributable risks based on individual SNPs and their combination; (3) investigate mechanisms leading to altered risk factor profiles and CVD events; and (4) use Mendelian randomisation to undertake studies of the causal role in CVD of a range of cardiovascular biomarkers to inform public health policy and help develop new preventative therapies

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Mind the gap:difference between Framingham heart age and real age increases with age in HIV-positive individuals-a clinical cohort study

OBJECTIVES: To measure the excess risk of cardiovascular disease (CVD) in HIV-positive individuals by comparing ‘heart age’ with real age and to estimate associations of patients’ characteristics with heart age deviation (heart age–real age). DESIGN: Clinical Cohort Study. SETTING: Bristol HIV clinic, Brecon Unit at Southmead Hospital, Bristol, UK. PARTICIPANTS: 749 HIV-positive adults who attended for care between 2008 and 2011. Median age was 42 years (IQR 35–49), 67% were male and 82% were treated with antiretroviral therapy. MAIN OUTCOME MEASURES: We calculated the Framingham 10-year risk of CVD and traced back to ‘heart age’, the age of an individual with the same score but ideal risk factor values. We estimated the relationship between heart age deviation and real age using fractional polynomial regression. We estimated crude and mutually adjusted associations of sex, age, CD4 count, viral load/treatment status and period of starting antiretroviral therapy with heart age deviation. RESULTS: The average heart age for a male aged 45 years was 48 years for a non-smoker and 60 years for a smoker. Heart age deviation increased with real age and at younger ages was smaller for females than males, although this reversed after 48 years. Compared to patients with CD4 count <500 cells/mm(3), heart age deviation was 2.4 (95% CI 0.7 to 4.0) and 4.3 (2.3 to 6.3) years higher for those with CD4 500–749 cells/mm(3) and ≥750 cells/mm(3), respectively. CONCLUSIONS: In HIV-positive individuals, the difference between heart age and real age increased with age and CD4 count and was very dependent on smoking status. Heart age could be a useful tool to communicate CVD risk to patients and the benefits of stopping smoking