Acute black tea consumption improves cutaneous vascular function in healthy middle-aged humans.

BACKGROUND & AIMS: Dietary flavonoids, such as those present in black tea, are associated with reduced risk of cardiovascular disease (CVD), possibly through improving nitric oxide (NO) mediated vascular function. The aim of this study was to examine the effect of acute black tea ingestion on cutaneous microvascular function. METHODS: Twenty healthy participants (58 ± 5 y, 9 men) attended two experimental trials (tea, placebo), 7-days apart in a randomised, controlled, double-blind, cross-over design. Participants ingested a single dose of 200 ml black tea or placebo, followed by assessment of forearm cutaneous perfusion using laser-Doppler flowmetry (LDF) using three distinct heating protocols, enabling us to distinguish between axon- and endothelium-dependent vasodilation: 1. rapid 42°C, 2. rapid 39°C and 3. gradual 42°C. On the contralateral arm, full-field laser perfusion imaging (FLPI) was used to assess forearm perfusion during gradual 42°C. Data were presented as cutaneous vascular conductance (CVC; flux/mean arterial pressure, MAP) and CVC expressed as a percentage of maximal CVC (%CVCmax). RESULTS: Rapid local heating to 39°C or 42°C demonstrated no effect of tea for flux, CVC or %CVCmax (all P > 0.05). Gradual local heating to 42 °C, however, produced a higher skin blood flow following black tea ingestion for absolute CVC (P = 0.04) when measured by LDF, and higher absolute flux (P < 0.001) and CVC (P < 0.001) measured with FLPI. No effect of tea was found for %CVCmax when assessed by either LDF or FLPI. CONCLUSIONS: Acute tea ingestion enhanced cutaneous vascular responses to gradual local heating to 42 °C in healthy, middle-aged participants, possibly through a mechanism related to activation of endothelium-derived chemical mediators, such as NO. These improvements may contribute to the cardiovascular health benefits of regular tea ingestion

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A family of process-based models to simulate landscape use by multiple taxa

Context: Land-use change is a key driver of biodiversity loss. Models that accurately predict how biodiversity might be affected by land-use changes are urgently needed, to help avoid further negative impacts and inform landscape-scale restoration projects. To be effective, such models must balance model realism with computational tractability and must represent the different habitat and connectivity requirements of multiple species. Objectives: We explored the extent to which process-based modelling might fulfil this role, examining feasibility for different taxa and potential for informing real-world decision-making. Methods: We developed a family of process-based models (*4pop) that simulate landscape use by birds, bats, reptiles and amphibians, derived from the well-established poll4pop model (designed to simulate bee populations). Given landcover data, the models predict spatially-explicit relative abundance by simulating optimal home-range foraging, reproduction, dispersal of offspring and mortality. The models were co-developed by researchers, conservation NGOs and volunteer surveyors, parameterised using literature data and expert opinion, and validated against observational datasets collected across Great Britain. Results: The models were able to simulate habitat specialists, generalists, and species requiring access to multiple habitats for different types of resources (e.g. breeding vs foraging). We identified model refinements required for some taxa and considerations for modelling further species/groups. Conclusions: We suggest process-based models that integrate multiple forms of knowledge can assist biodiversity-inclusive decision-making by predicting habitat use throughout the year, expanding the range of species that can be modelled, and enabling decision-makers to better account for landscape context and habitat configuration effects on population persistence

Pregnancy and neonatal outcomes of COVID-19: The PAN-COVID study

Objective To assess perinatal outcomes for pregnancies affected by suspected or confirmed SARS-CoV-2 infection. Methods Prospective, web-based registry. Pregnant women were invited to participate if they had suspected or confirmed SARS-CoV-2 infection between 1st January 2020 and 31st March 2021 to assess the impact of infection on maternal and perinatal outcomes including miscarriage, stillbirth, fetal growth restriction, pre-term birth and transmission to the infant. Results Between April 2020 and March 2021, the study recruited 8239 participants who had suspected or confirmed SARs-CoV-2 infection episodes in pregnancy between January 2020 and March 2021. Maternal death affected 14/8197 (0.2%) participants, 176/8187 (2.2%) of participants required ventilatory support. Pre-eclampsia affected 389/8189 (4.8%) participants, eclampsia was reported in 40/ 8024 (0.5%) of all participants. Stillbirth affected 35/8187 (0.4 %) participants. In participants delivering within 2 weeks of delivery 21/2686 (0.8 %) were affected by stillbirth compared with 8/4596 (0.2 %) delivering ≥ 2 weeks after infection (95 % CI 0.3–1.0). SGA affected 744/7696 (9.3 %) of livebirths, FGR affected 360/8175 (4.4 %) of all pregnancies. Pre-term birth occurred in 922/8066 (11.5%), the majority of these were indicated pre-term births, 220/7987 (2.8%) participants experienced spontaneous pre-term births. Early neonatal deaths affected 11/8050 livebirths. Of all neonates, 80/7993 (1.0%) tested positive for SARS-CoV-2. Conclusions Infection was associated with indicated pre-term birth, most commonly for fetal compromise. The overall proportions of women affected by SGA and FGR were not higher than expected, however there was the proportion affected by stillbirth in participants delivering within 2 weeks of infection was significantly higher than those delivering ≥ 2 weeks after infection. We suggest that clinicians’ threshold for delivery should be low if there are concerns with fetal movements or fetal heart rate monitoring in the time around infection

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

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

Effect of empagliflozin on left ventricular volumes in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF)

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on cardiac structure and function in HFrEF are uncertain. Methods: We designed a multicenter randomized, double-blind, placebo-controlled trial to investigate the cardiac effects of empagliflozin in patients in NYHA functional class II to IV with a left ventricular (LV) ejection fraction ≤40% and type 2 diabetes or prediabetes. Patients were randomized 1:1 to empagliflozin 10 milligrams once daily or placebo, stratified by age (&lt;65 and ≥65 years) and glycemic status (diabetes or prediabetes). The co-primary outcomes were change from baseline to 36 weeks in LV end-systolic volume indexed to body surface area (LVESVi) and LV global longitudinal strain (LV GLS) measured using cardiovascular magnetic resonance (CMR). Secondary efficacy outcomes included other CMR measures (LVEDVi, LVEF), diuretic intensification, symptoms (Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS)), 6-minute walk distance (6MWD), B-lines on lung ultrasound and biomarkers (including NT-proBNP). Results: From April 2018 to August 2019, 105 patients were randomized: 77 (73.3%) male, mean age 68.7 [SD 11.1] years, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LVEF 32.5% [9.8%], and 81 (77.1%) NYHA II and 24 (22.9%) NYHA III. Patients received standard treatment for HFrEF. Compared with placebo, empagliflozin reduced LVESVi by 6.0 (-10.8 to -1.2) ml/m2 (p=0.015). There was no difference in LV GLS. Empagliflozin reduced LVEDVi by 8.2 (-13.7 to -2.6) ml/m2 (p=0.0042) and reduced NT-proBNP by 28 (2 to 47) %, p=0.038. There were no between-group differences in other CMR measures, KCCQ-TSS, 6MWD or B-lines. Conclusions: The SGLT2 inhibitor empagliflozin reduced LV volumes in patients with HFrEF and type 2 diabetes or prediabetes. Favorable reverse LV remodeling may be a mechanism by which SGLT2 inhibitors reduce HF hospitalization and mortality in HFrEF. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT03485092

A family of process-based models to simulate landscape use by multiple taxa

Acknowledgements: We would like to thank all the volunteer surveyors who contributed data to the BTO/RSPB/JNCC Breeding Bird Survey and those who contributed data to the Field Survey within the BCT’s National Bat Monitoring Programme, without whom validation of the bird and bat models would not have been possible. We would also like to thank all the volunteer surveyors of Surrey Amphibian and Reptile Group, who kindly contributed their common lizard sightings and enabled validation of the reptile model. Finally, we would like to thank the regional ARGs and all the Toad Patrol volunteers, supported by Froglife, who took the time to fill in the toad habitat use questionnaire, so enabling validation of the amphibian model. EG acknowledges funding from a Research Programme Fellowship provided by the Natural Environment Research Council through UK Research and Innovation’s Landscape Decisions Programme (NE/V007831/1).Context: Land-use change is a key driver of biodiversity loss. Models that accurately predict how biodiversity might be affected by land-use changes are urgently needed, to help avoid further negative impacts and inform landscape-scale restoration projects. To be effective, such models must balance model realism with computational tractability and must represent the different habitat and connectivity requirements of multiple species. Objectives: We explored the extent to which process-based modelling might fulfil this role, examining feasibility for different taxa and potential for informing real-world decision-making. Methods: We developed a family of process-based models (*4pop) that simulate landscape use by birds, bats, reptiles and amphibians, derived from the well-established poll4pop model (designed to simulate bee populations). Given landcover data, the models predict spatially-explicit relative abundance by simulating optimal home-range foraging, reproduction, dispersal of offspring and mortality. The models were co-developed by researchers, conservation NGOs and volunteer surveyors, parameterised using literature data and expert opinion, and validated against observational datasets collected across Great Britain. Results: The models were able to simulate habitat specialists, generalists, and species requiring access to multiple habitats for different types of resources (e.g. breeding vs foraging). We identified model refinements required for some taxa and considerations for modelling further species/groups. Conclusions: We suggest process-based models that integrate multiple forms of knowledge can assist biodiversity-inclusive decision-making by predicting habitat use throughout the year, expanding the range of species that can be modelled, and enabling decision-makers to better account for landscape context and habitat configuration effects on population persistence