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The dominant paradigm in clinical medicine, public health and global health has been to split clinical practice, research, education, training and funding into communicable versus non-communicable diseases. This dichotomy was borne out of the context of colonialism and increasingly, not least during the recent COVID-19 pandemic, evidence suggests that a much closer relationship between these ‘disease siloes’ would be beneficial, from risk factors to therapeutics. In this lecture, the synergies between communicable and non-communicable diseases are explored in order to inform future policy and practice.

Cardiovascular disease is both a risk factor and potential outcome of the direct, indirect and long-term effects of COVID-19. A recent analysis in >150,000 survivors of COVID-19 demonstrates an increased 1-year risk of numerous cardiovascular diseases. Preventing and managing this new disease burden presents challenges to health systems and requires a learning health system approach.

ObjectiveTo assess medium-term organ impairment in symptomatic individuals following recovery from acute SARS-CoV-2 infection.DesignBaseline findings from a prospective, observational cohort study.SettingCommunity-based individuals from two UK centres between 1 April and 14 September 2020.ParticipantsIndividuals ≥18 years with persistent symptoms following recovery from acute SARS-CoV-2 infection and age-matched healthy controls.InterventionAssessment of symptoms by standardised questionnaires (EQ-5D-5L, Dyspnoea-12) and organ-specific metrics by biochemical assessment and quantitative MRI.Main outcome measuresSevere post-COVID-19 syndrome defined as ongoing respiratory symptoms and/or moderate functional impairment in activities of daily living; single-organ and multiorgan impairment (heart, lungs, kidneys, liver, pancreas, spleen) by consensus definitions at baseline investigation.Results201 individuals (mean age 45, range 21–71 years, 71% female, 88% white, 32% healthcare workers) completed the baseline assessment (median of 141 days following SARS-CoV-2 infection, IQR 110–162). The study population was at low risk of COVID-19 mortality (obesity 20%, hypertension 7%, type 2 diabetes 2%, heart disease 5%), with only 19% hospitalised with COVID-19. 42% of individuals had 10 or more symptoms and 60% had severe post-COVID-19 syndrome. Fatigue (98%), muscle aches (87%), breathlessness (88%) and headaches (83%) were most frequently reported. Mild organ impairment was present in the heart (26%), lungs (11%), kidneys (4%), liver (28%), pancreas (40%) and spleen (4%), with single-organ and multiorgan impairment in 70% and 29%, respectively. Hospitalisation was associated with older age (p=0.001), non-white ethnicity (p=0.016), increased liver volume (p<0.0001), pancreatic inflammation (p<0.01), and fat accumulation in the liver (p<0.05) and pancreas (p<0.01). Severe post-COVID-19 syndrome was associated with radiological evidence of cardiac damage (myocarditis) (p<0.05).ConclusionsIn individuals at low risk of COVID-19 mortality with ongoing symptoms, 70% have impairment in one or more organs 4 months after initial COVID-19 symptoms, with implications for healthcare and public health, which have assumed low risk in young people with no comorbidities.Trial registration numberNCT04369807; Pre-results.

Obesity and ethnicity are known risk factors for COVID-19 outcomes, but their combination has not been extensively examined. We investigate the association between body mass index (BMI) and COVID-19 mortality across different ethnic groups using linked national Census, electronic health records and mortality data for adults in England from the start of pandemic (January 2020) to December 2020. There were 30,067 (0.27%), 1,208 (0.29%), 1,831 (0.29%), 845 (0.18%) COVID-19 deaths in white, Black, South Asian and other ethnic minority groups, respectively. Here we show that BMI was more strongly associated with COVID-19 mortality in ethnic minority groups, resulting in an ethnic risk of COVID-19 mortality that was dependant on BMI. The estimated risk of COVID-19 mortality at a BMI of 40 kg/m 2 in white ethnicities was equivalent to the risk observed at a BMI of 30.1 kg/m 2 , 27.0 kg/m 2 , and 32.2 kg/m 2 in Black, South Asian and other ethnic minority groups, respectively. Obesity is a known risk factor for severe COVID-19 disease. Here, the authors use linked Census, electronic health records, and mortality data for 12.6 million adults in England and show that the association between COVID-19 mortality and body mass index is stronger in ethnic minority groups.

Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data. This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out. Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.

Even within countries, there are significant variations in baseline characteristics, particularly countries as large as India. [...]considerable variations are to be expected between countries and by HDI or GNI. Investigators must take these factors into account when designing, conducting and analysing trials to enable the proper interpretation of their trial findings. 9 Predefined subgroups with regards to geographical location, poverty and development are the gold standard. 14 As suggested by Rothwell, external validity should be part of (a) further research, (b) stricter requirements for trials submitted to pharmaceutical licensing authorities, (c) guidelines on the reporting of trials and systematic reviews and (d) primary reports of trials or systematic reviews in publications. 12 An analysis of poverty and development with respect to clinical trials must mention ethical considerations of multinational trials.

Ethnic minorities have experienced disproportionate COVID-19 mortality rates in the UK and many other countries. We compared the differences in the risk of COVID-19 related death between ethnic groups in the first and second waves the of COVID-19 pandemic in England. We also investigated whether the factors explaining differences in COVID-19 death between ethnic groups changed between the two waves. Using data from the Office for National Statistics Public Health Data Asset, a linked dataset combining the 2011 Census with primary care and hospital records and death registrations, we conducted an observational cohort study to examine differences in the risk of death involving COVID-19 between ethnic groups in the first wave (from 24th January 2020 until 31st August 2020) and the first part of the second wave (from 1st September to 28th December 2020). We estimated age-standardised mortality rates (ASMR) in the two waves stratified by ethnic groups and sex. We also estimated hazard ratios (HRs) for ethnic-minority groups compared with the White British population, adjusted for geographical factors, socio-demographic characteristics, and pre-pandemic health conditions. The study population included over 28.9 million individuals aged 30–100 years living in private households. In the first wave, all ethnic minority groups had a higher risk of COVID-19 related death compared to the White British population. In the second wave, the risk of COVID-19 death remained elevated for people from Pakistani (ASMR: 339.9 [95% CI: 303.7–376.2] and 166.8 [141.7–191.9] deaths per 100,000 population in men and women) and Bangladeshi (318.7 [247.4–390.1] and 127.1 [91.1–171.3] in men and women) background but not for people from Black ethnic groups. Adjustment for geographical factors explained a large proportion of the differences in COVID-19 mortality in the first wave but not in the second wave. Despite an attenuation of the elevated risk of COVID-19 mortality after adjusting for sociodemographic characteristics and health status, the risk was substantially higher in people from Bangladeshi and Pakistani background in both the first and the second waves. Between the first and second waves of the pandemic, the reduction in the difference in COVID-19 mortality between people from Black ethnic background and people from the White British group shows that ethnic inequalities in COVID-19 mortality can be addressed. The continued higher rate of mortality in people from Bangladeshi and Pakistani background is alarming and requires focused public health campaign and policy changes.

New Findings What is the topic of this review? The emerging condition of long COVID, its epidemiology, pathophysiological impacts on patients of different backgrounds, physiological mechanisms emerging as explanations of the condition, and treatment strategies being trialled. The review leads from a Physiological Society online conference on this topic. What advances does it highlight? Progress in understanding the pathophysiology and cellular mechanisms underlying Long COVID and potential therapeutic and management strategies. Long COVID, the prolonged illness and fatigue suffered by a small proportion of those infected with SARS‐CoV‐2, is placing an increasing burden on individuals and society. A Physiological Society virtual meeting in February 2022 brought clinicians and researchers together to discuss the current understanding of long COVID mechanisms, risk factors and recovery. This review highlights the themes arising from that meeting. It considers the nature of long COVID, exploring its links with other post‐viral illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome, and highlights how long COVID research can help us better support those suffering from all post‐viral syndromes. Long COVID research started particularly swiftly in populations routinely monitoring their physical performance – namely the military and elite athletes. The review highlights how the high degree of diagnosis, intervention and monitoring of success in these active populations can suggest management strategies for the wider population. We then consider how a key component of performance monitoring in active populations, cardiopulmonary exercise training, has revealed long COVID‐related changes in physiology – including alterations in peripheral muscle function, ventilatory inefficiency and autonomic dysfunction. The nature and impact of dysautonomia are further discussed in relation to postural orthostatic tachycardia syndrome, fatigue and treatment strategies that aim to combat sympathetic overactivation by stimulating the vagus nerve. We then interrogate the mechanisms that underlie long COVID symptoms, with a focus on impaired oxygen delivery due to micro‐clotting and disruption of cellular energy metabolism, before considering treatment strategies that indirectly or directly tackle these mechanisms. These include remote inspiratory muscle training and integrated care pathways that combine rehabilitation and drug interventions with research into long COVID healthcare access across different populations. Overall, this review showcases how physiological research reveals the changes that occur in long COVID and how different therapeutic strategies are being developed and tested to combat this condition.

BackgroundDespite simpler regimens than vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF), adherence (taking drugs as prescribed) and persistence (continuation of drugs) to direct oral anticoagulants are suboptimal, yet understudied in electronic health records (EHRs).ObjectiveWe investigated (1) time trends at individual and system levels, and (2) the risk factors for and associations between adherence and persistence.MethodsIn UK primary care EHR (The Health Information Network 2011–2016), we investigated adherence and persistence at 1 year for oral anticoagulants (OACs) in adults with incident AF. Baseline characteristics were analysed by OAC and adherence/persistence status. Risk factors for non-adherence and non-persistence were assessed using Cox and logistic regression. Patterns of adherence and persistence were analysed.ResultsAmong 36 652 individuals with incident AF, cardiovascular comorbidities (median CHA2DS2VASc[Congestive heart failure, Hypertension, Age≥75 years, Diabetes mellitus, Stroke, Vascular disease, Age 65-74 years, Sex category] 3) and polypharmacy (median number of drugs 6) were common. Adherence was 55.2% (95% CI 54.6 to 55.7), 51.2% (95% CI 50.6 to 51.8), 66.5% (95% CI 63.7 to 69.2), 63.1% (95% CI 61.8 to 64.4) and 64.7% (95% CI 63.2 to 66.1) for all OACs, VKA, dabigatran, rivaroxaban and apixaban. One-year persistence was 65.9% (95% CI 65.4 to 66.5), 63.4% (95% CI 62.8 to 64.0), 61.4% (95% CI 58.3 to 64.2), 72.3% (95% CI 70.9 to 73.7) and 78.7% (95% CI 77.1 to 80.1) for all OACs, VKA, dabigatran, rivaroxaban and apixaban. Risk of non-adherence and non-persistence increased over time at individual and system levels. Increasing comorbidity was associated with reduced risk of non-adherence and non-persistence across all OACs. Overall rates of ‘primary non-adherence’ (stopping after first prescription), ‘non-adherent non-persistence’ and ‘persistent adherence’ were 3.5%, 26.5% and 40.2%, differing across OACs.ConclusionsAdherence and persistence to OACs are low at 1 year with heterogeneity across drugs and over time at individual and system levels. Better understanding of contributory factors will inform interventions to improve adherence and persistence across OACs in individuals and populations.

Socio-economic hardships put children in an underprivileged position. This systematic review was conducted to identify factors linked to underachievement of disadvantaged pupils in school science and maths. What could be done as evidence-based practice to make the lives of these young people better? The protocol from preferred reporting items for systematic reviews and meta-analyses (PRISMA) was followed. Major electronic educational databases were searched. Papers meeting pre-defined selection criteria were identified. Studies included were mainly large-scale evaluations with a clearly defined comparator group and robust research design. All studies used a measure of disadvantage such as lower SES, language barrier, ethnic minority or temporary immigrant status and an outcome measure like attainment in standardised national tests. A majority of papers capable of answering the research question were correlational studies. The review reports findings from 771 studies published from 2005 to 2014 in English language. Thirty-four studies were synthesised. Results suggest major factors linking deprivation to underachievement can be thematically categorised into a lack of positive environment and support. Recommendations from the research reports are discussed.