Impacts of ambient air quality on acute asthma hospital admissions during the COVID-19 pandemic in Oxford City, UK: a time-series study.

OBJECTIVES: The study aims to investigate the short-term associations between exposure to ambient air pollution (nitrogen dioxide (NO2), particulate matter pollution-particles with diameter<2.5 µm (PM2.5) and PM10) and incidence of asthma hospital admissions among adults, in Oxford, UK. DESIGN: Retrospective time-series study. SETTING: Oxford City (postcode areas OX1-OX4), UK. PARTICIPANTS: Adult population living within the postcode areas OX1-OX4 in Oxford, UK from 1 January 2015 to 31 December 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: Hourly NO2, PM2.5 and PM10 concentrations and meteorological data for the period 1 January 2015 to 31 December 2020 were analysed and used as exposures. We used Poisson linear regression analysis to identify independent associations between air pollutant concentrations and asthma admissions rate among the adult study population, using both single (NO2, PM2.5, PM10) and multipollutant (NO2 and PM2.5, NO2 and PM10) models, where they adjustment for temperature and relative humidity. RESULTS: The overall 5-year average asthma admissions rate was 78 per 100 000 population during the study period. The annual average rate decreased to 46 per 100 000 population during 2020 (incidence rate ratio 0.58, 95% CI 0.42 to 0.81, p<0.001) compared to the prepandemic years (2015-2019). In single-pollutant analysis, we observed a significantly increased risk of asthma admission associated with each 1 µg/m3 increase in monthly concentrations of NO2 4% (95% CI 1.009% to 1.072%), PM2.5 3% (95% CI 1.006% to 1.052%) and PM10 1.8% (95% CI 0.999% to 1.038%). However, in the multipollutant regression model, the effect of each individual pollutant was attenuated. CONCLUSIONS: Ambient NO2 and PM2.5 air pollution exposure increased the risk of asthma admissions in this urban setting. Improvements in air quality during COVID-19 lockdown periods may have contributed to a substantially reduced acute asthma disease burden. Large-scale measures to improve air quality have potential to protect vulnerable people living with chronic asthma in urban areas.

The impact of COVID-19 public health restrictions on particulate matter pollution measured by a validated low-cost sensor network in Oxford, UK.

Emergency responses to the COVID-19 pandemic led to major changes in travel behaviours and economic activities with arising impacts upon urban air quality. To date, these air quality changes associated with lockdown measures have typically been assessed using limited city-level regulatory monitoring data, however, low-cost air quality sensors provide capabilities to assess changes across multiple locations at higher spatial-temporal resolution, thereby generating insights relevant for future air quality interventions. The aim of this study was to utilise high-spatial resolution air quality information utilising data arising from a validated (using a random forest field calibration) network of 15 low-cost air quality sensors within Oxford, UK to monitor the impacts of multiple COVID-19 public heath restrictions upon particulate matter concentrations (PM10, PM2.5) from January 2020 to September 2021. Measurements of PM10 and PM2.5 particle size fractions both within and between site locations are compared to a pre-pandemic related public health restrictions baseline. While average peak concentrations of PM10 and PM2.5 were reduced by 9-10 µg/m3 below typical peak levels experienced in recent years, mean daily PM10 and PM2.5 concentrations were only ∼1 µg/m3 lower and there was marked temporal (as restrictions were added and removed) and spatial variability (across the 15-sensor network) in these observations. Across the 15-sensor network we observed a small local impact from traffic related emission sources upon particle concentrations near traffic-oriented sensors with higher average and peak concentrations as well as greater dynamic range, compared to more intermediate and background orientated sensor locations. The greater dynamic range in concentrations is indicative of exposure to more variable emission sources, such as road transport emissions. Our findings highlight the great potential for low-cost sensor technology to identify highly localised changes in pollutant concentrations as a consequence of changes in behaviour (in this case influenced by COVID-19 restrictions), generating insights into non-traffic contributions to PM emissions in this setting. It is evident that additional non-traffic related measures would be required in Oxford to reduce the PM10 and PM2.5 levels to within WHO health-based guidelines and to achieve compliance with PM2.5 targets developed under the Environment Act 2021.

What factors influence the introduction of a national undergraduate general practice curriculum in the UK?

A national undergraduate curriculum for General Practice might address current concerns regarding intellectual challenge and recruitment through articulating disciplinary knowledge and providing teaching guidance. However, there is ambivalence regarding this idea and the reasons appear incompletely understood. Aims: To better understand ambivalence towards a GP curriculum and to assess the acceptability of a new approach to national curriculum design. Methods: Questionnaire informed by Kotter's model of change, distributed to Heads of Teaching (HOTs) at each UK medical school, regarding the acceptability of both conventional and new approaches to the design of national curriculum guidelines.  Qualitative and quantitative data collection with grounded theory-informed analysis of qualitative data. Results: Support for a conventional, detailed curriculum of clinical conditions is weak but there is strong support for a curriculum outlining general disciplinary principles. Identification with general practice as an independent academic discipline is important in predicting support or otherwise for any type of national curriculum. Conclusion: The identity of GP as an independent academic discipline emerges as a key issue.  Further research on designing and implementing curricula that use principles rather than detailed outcomes is needed.

Pharmacological inhibition of porcupine induces regression of experimental skin fibrosis by targeting Wnt signalling.

OBJECTIVES: Wnt signalling has been implicated in activating a fibrogenic programme in fibroblasts in systemic sclerosis (SSc). Porcupine is an O-acyltransferase required for secretion of Wnt proteins in mammals. Here, we aimed to evaluate the antifibrotic effects of pharmacological inhibition of porcupine in preclinical models of SSc. METHODS: The porcupine inhibitor GNF6231 was evaluated in the mouse models of bleomycin-induced skin fibrosis, in tight-skin-1 mice, in murine sclerodermatous chronic-graft-versus-host disease (cGvHD) and in fibrosis induced by a constitutively active transforming growth factor-ß-receptor I. RESULTS: Treatment with pharmacologically relevant and well-tolerated doses of GNF6231 inhibited the activation of Wnt signalling in fibrotic murine skin. GNF6231 ameliorated skin fibrosis in all four models. Treatment with GNF6231 also reduced pulmonary fibrosis associated with murine cGvHD. Most importantly, GNF6231 prevented progression of fibrosis and showed evidence of reversal of established fibrosis. CONCLUSIONS: These data suggest that targeting the Wnt pathway through inhibition of porcupine provides a potential therapeutic approach to fibrosis in SSc. This is of particular interest, as a close analogue of GNF6231 has already demonstrated robust pathway inhibition in humans and could be available for clinical trials.

Identifying Glucokinase Monogenic Diabetes in a Multiethnic Gestational Diabetes Mellitus Cohort: New Pregnancy Screening Criteria and Utility of HbA1c.

OBJECTIVE: Glucokinase monogenic diabetes (GCK-maturity-onset diabetes of the young [MODY]) should be differentiated from gestational diabetes mellitus (GDM) because management differs. New pregnancy-specific screening criteria (NSC) have been proposed to identify women who warrant GCK genetic testing. We tested NSC and HbA1c in a multiethnic GDM cohort and examined projected referrals for GCK testing. RESEARCH DESIGN AND METHODS: Using a GDM database, 63 of 776 women had a postpartum oral glucose tolerance test suggestive of GCK-MODY. Of these 63 women, 31 agreed to undergo GCK testing. NSC accuracy and HbA1c were examined. Projected referrals were calculated by applying the NSC to a larger GDM database (n = 4,415). RESULTS: Four of 31 women were confirmed as having GCK-MODY (prevalence ∼0.5-1/100 with GDM). The NSC identified all Anglo-Celtic women but did not identify one Indian woman. The NSC will refer 6.1% of GDM cases for GCK testing, with more Asian/Indian women referred despite lower disease prevalence. Antepartum HbA1c was not higher in those with GCK-MODY. CONCLUSIONS: The NSC performed well in Anglo-Celtic women. Ethnic-specific criteria should be explored.

The EPAS1 gene influences the aerobic-anaerobic contribution in elite endurance athletes.

EPAS1 is a gene involved in complex oxygen sensing. It is expressed in microvascular endothelial cells, lung epithelial cells, cardiac myocytes and the brain. An association study was undertaken comparing elite endurance athletes classified into two groups according to a power-time model of performance intensity: power-time-maximum (PT-MAX; N=242, event duration 50 s to 10 min) and power-time-steady state (PT-SS; N=151, event duration ~2-10 h), with normal controls (N=444) using 12 SNPs across EPAS1. Ordinal regression analysis of allele frequencies revealed significant differences at SNPs 2 and 3 (P=0.01). Haplotype analysis revealed the presence of haplotypes involving SNPs 2-5 that significantly differentiated (P<0.05) the groups based on an ordinal ranking using the power-time classification. These same haplotypes differentiated the PT-MAX group in which a significant decrease in a haplotype (F: G-C-C-G; OR=0.57, P=0.02, 95% CI 0.36-0.92) and increase in a second haplotype (G: A-T-G-G; OR=1.75, P=0.03, 95% CI 1.05-2.91) was observed compared to controls. The PT-SS group was differentiated from the PT-MAX group by a third haplotype (H: A-T-G-A; OR=0.46, P=0.04, 95% CI 0.22-0.96). Since EPAS1 has a role as a sensor capable of integrating cardiovascular function, energetic demand, muscle activity and oxygen availability into physiological adaptation, we propose that DNA variants in EPAS1 influence the relative contribution of aerobic and anaerobic metabolism and hence the maximum sustainable metabolic power for a given event duration.