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

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Linked electronic health records for research on a nationwide cohort of more than 54 million people in England: data resource

Abstract: Objective: To describe a novel England-wide electronic health record (EHR) resource enabling whole population research on covid-19 and cardiovascular disease while ensuring data security and privacy and maintaining public trust. Design: Data resource comprising linked person level records from national healthcare settings for the English population, accessible within NHS Digital’s new trusted research environment. Setting: EHRs from primary care, hospital episodes, death registry, covid-19 laboratory test results, and community dispensing data, with further enrichment planned from specialist intensive care, cardiovascular, and covid-19 vaccination data. Participants: 54.4 million people alive on 1 January 2020 and registered with an NHS general practitioner in England. Main measures of interest: Confirmed and suspected covid-19 diagnoses, exemplar cardiovascular conditions (incident stroke or transient ischaemic attack and incident myocardial infarction) and all cause mortality between 1 January and 31 October 2020. Results: The linked cohort includes more than 96% of the English population. By combining person level data across national healthcare settings, data on age, sex, and ethnicity are complete for around 95% of the population. Among 53.3 million people with no previous diagnosis of stroke or transient ischaemic attack, 98 721 had a first ever incident stroke or transient ischaemic attack between 1 January and 31 October 2020, of which 30% were recorded only in primary care and 4% only in death registry records. Among 53.2 million people with no previous diagnosis of myocardial infarction, 62 966 had an incident myocardial infarction during follow-up, of which 8% were recorded only in primary care and 12% only in death registry records. A total of 959 470 people had a confirmed or suspected covid-19 diagnosis (714 162 in primary care data, 126 349 in hospital admission records, 776 503 in covid-19 laboratory test data, and 50 504 in death registry records). Although 58% of these were recorded in both primary care and covid-19 laboratory test data, 15% and 18%, respectively, were recorded in only one. Conclusions: This population-wide resource shows the importance of linking person level data across health settings to maximise completeness of key characteristics and to ascertain cardiovascular events and covid-19 diagnoses. Although this resource was initially established to support research on covid-19 and cardiovascular disease to benefit clinical care and public health and to inform healthcare policy, it can broaden further to enable a wide range of research

Linked electronic health records for research on a nationwide cohort of more than 54 million people in England: data resource

Abstract: Objective: To describe a novel England-wide electronic health record (EHR) resource enabling whole population research on covid-19 and cardiovascular disease while ensuring data security and privacy and maintaining public trust. Design: Data resource comprising linked person level records from national healthcare settings for the English population, accessible within NHS Digital’s new trusted research environment. Setting: EHRs from primary care, hospital episodes, death registry, covid-19 laboratory test results, and community dispensing data, with further enrichment planned from specialist intensive care, cardiovascular, and covid-19 vaccination data. Participants: 54.4 million people alive on 1 January 2020 and registered with an NHS general practitioner in England. Main measures of interest: Confirmed and suspected covid-19 diagnoses, exemplar cardiovascular conditions (incident stroke or transient ischaemic attack and incident myocardial infarction) and all cause mortality between 1 January and 31 October 2020. Results: The linked cohort includes more than 96% of the English population. By combining person level data across national healthcare settings, data on age, sex, and ethnicity are complete for around 95% of the population. Among 53.3 million people with no previous diagnosis of stroke or transient ischaemic attack, 98 721 had a first ever incident stroke or transient ischaemic attack between 1 January and 31 October 2020, of which 30% were recorded only in primary care and 4% only in death registry records. Among 53.2 million people with no previous diagnosis of myocardial infarction, 62 966 had an incident myocardial infarction during follow-up, of which 8% were recorded only in primary care and 12% only in death registry records. A total of 959 470 people had a confirmed or suspected covid-19 diagnosis (714 162 in primary care data, 126 349 in hospital admission records, 776 503 in covid-19 laboratory test data, and 50 504 in death registry records). Although 58% of these were recorded in both primary care and covid-19 laboratory test data, 15% and 18%, respectively, were recorded in only one. Conclusions: This population-wide resource shows the importance of linking person level data across health settings to maximise completeness of key characteristics and to ascertain cardiovascular events and covid-19 diagnoses. Although this resource was initially established to support research on covid-19 and cardiovascular disease to benefit clinical care and public health and to inform healthcare policy, it can broaden further to enable a wide range of research

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

New host for the parasitoid Pachycrepoideus vindemmiae (Rondani) (Hymenoptera: Pteromalidae) in Brazil Novo hospedeiro para o parasitóide Pachycrepoideus vindemmiae (Rondani) (Hymenoptera: Pteromalidae) no Brasil

<abstract language="por">Relatou-se um novo hospedeiro para o parasitóide Pachycrepoideus vindemmiae (Rondani) (Hymenoptera: Pteromalidae) em fezes bovinas no Brasil. As pupas foram obtidas pelo método de flutuação. Elas foram colocadas, individualmente, em cápsulas de gelatina e mantidas até a emergência das moscas e/ou parasitóides. A porcentagem total de parasitismo foi de 12,5%. Este trabalho registra a primeira ocorrência de P. vindemmiae em pupas de Cyrtoneurina pararescita Couri (Diptera: Muscidae) no Brasil

Aerobic exercise during chemotherapy infusion for cancer treatment : a novel randomised crossover safety and feasibility trial

Purpose: Exercise is a powerful adjunct therapy for patients diagnosed with cancer which can alleviate treatment side-effects and improve a range of outcomes including fatigue and health-related quality of life. Recently, preclinical evidence has suggested that if exercise is performed during chemotherapy infusion, there is enhanced perfusion that may improve drug delivery and attenuate the hypoxic microenvironment. This study aimed to determine the safety and feasibility of delivering an aerobic exercise intervention to cancer patients during chemotherapy infusion. Methods: A randomised crossover trial was conducted for adults (18–60) undergoing chemotherapy treatment with non-vesicant agents for cancer. In randomised order, during two consecutive chemotherapy infusions, participants either received usual care or performed 20 min of supervised low-intensity cycling. Results: Sixty-five percent of patients approached agreed to participate, and exercise was safely delivered with neither adverse events nor interference to treatment reported for all participants with a mixed cancer diagnosis (N = 10, 90% female, 51.2 ± 7.4 years). There were no significant differences between exercise and usual care in participant-reported difficulty or comfort levels, but exercise significantly reduced boredom (p = 0.01). No significant differences were detected in the symptoms experienced following either intervention. Conclusions: Exercise during chemotherapy infusion appears to be safe and feasible. Further research is required with a larger sample size to evaluate the impact on tumour perfusion, symptom experience, and opportunity for physical activity increase

Effect of a 16-week Bikram yoga program on perceived stress, self-efficacy and health-related quality of life in stressed and sedentary adults:A randomised controlled trial

Objectives: The purpose of this study was to investigate the effect of 16 weeks of Bikram yoga on perceivedstress, self-efficacy and health related quality of life (HRQoL) in sedentary, stressed adults.Design: 16 week, parallel-arm, randomised controlled trial with flexible dosing.Methods: Physically inactive, stressed adults (37.2 +/- 10.8 years) were randomised to Bikram yoga (threeto five classes per week) or control (no treatment) group for 16 weeks. Outcome measures, collectedvia self-report, included perceived stress, general self-efficacy, and HRQoL. Outcomes were assessed atbaseline, midpoint and completion.Results: Individuals were randomised to the experimental (n = 29) or control group (n = 34). Averageattendance in the experimental group was 27 +/- 18 classes. Repeated measure analyses of variance(intention-to-treat) demonstrated significantly improved perceived stress (p = 0.003, partial n2= 0.109),general self-efficacy (p = 0.034, partial n2= 0.056), and the general health (p = 0.034, partial n2= 0.058)and energy/fatigue (p = 0.019, partial n2= 0.066) domains of HRQoL in the experimental group versusthe control group. Attendance was significantly associated with reductions in perceived stress, and anincrease in several domains of HRQoL.Conclusions: 16 weeks of Bikram yoga significantly improved perceived stress, general self-efficacy andHRQoL in sedentary, stressed adults. Future research should consider ways to optimise adherence, andshould investigate effects of Bikram yoga intervention in other populations at risk for stress-relatedillness.Trial registration

Piloting the effect of aerobic exercise during chemotherapy infusion in patients with cancer

Exercise in cancer patients is safe and can improve a range of outcomes including cancer-related fatigue, physical functioning and quality of life. Preclinical trials suggest an acute exercise bout during chemotherapy infusion may improve the treatment efficiency. It would also present an additional opportunity for supervised exercise. However, there are currently no published human trials of such an intervention. PURPOSE: To determine the safety and feasibility of delivering an aerobic exercise intervention to cancer patients during chemotherapy infusion. METHODS: A randomised crossover trial has commenced with eligible patients receiving either usual care or performing 20 minutes of low intensity cycling during infusion. Data collection includes patient uptake, physiological exercise response, perceived exertion, patient experience and a daily symptom diary for 1 week subsequent. RESULTS: Exercise has been safely delivered with neither adverse events nor interference to usual care reported for all subjects (N=3, Female, 52 ± 8 yrs). 60% of patients approached agreed to participate, and all reported that the exercise was no less comfortable, no more difficult, and less boring than usual care. Heart rate rose to the target 30%-40%HRR within 5-8 minutes and was steady during exercise, recovering to within 10 beats of resting rates in 4.7 ± 4.6 min. On average, systolic blood pressure rose 15% during exercise, with a maximum reading of 153mmHg, and full recovery to resting levels within 15 minutes. Oxygen saturation remained above 95% at all times. Rated perceived exertion during exercise ranged from 9-13 on the Borg scale. Reported daily symptom data was similar after both exercise and usual care. CONCLUSIONS: Exercise during chemotherapy infusion may be a safe and feasible addition to chemotherapy. Larger data collection is required to evaluate drug delivery efficiency, symptom reduction and opportunity for physical activity increase

Predictors of and barriers to adherence in a 16-week randomised controlled trial of Bikram yoga in stressed and sedentary adults

Background Bikram yoga may enhance health outcomes in healthy adults and those at risk for chronic disease, however, challenges remain in achieving optimal adherence to this practice. This study investigated factors influencing adherence to a 16-week Bikram yoga intervention in stressed and sedentary adults. Methods Experimental group participants (n = 29) were instructed to attend 3–5 Bikram yoga classes weekly for 16 weeks. Baseline demographics, behaviours and health measures were investigated as predictors of adherence. Barriers were assessed via documentation of adverse events, and exit survey responses. Results Participants (38.2 ± 10.1 years) were predominantly overweight-obese (83%), female (79%), and attended 27 ± 18 classes. Higher adherence was associated with older age (p = 0.094), less pain (p = 0.011), fewer physical limitations (p = 0.011), poorer blood lipid profile, and higher heart rate variability (HRV; total power, (p = 0.097)). In multi-variable analysis, three variables: age (β = 0.492, p = 0.006), HRV (β = 0.413, p = 0.021) and pain (β = 0.329, p = 0.048) remained predictors of adherence. Difficulty committing to the trial, lack of enjoyment and adverse events were barriers to adherence. Conclusions These findings should be considered in the development of future Bikram yoga trials to facilitate higher levels of adherence, which may enhance health outcomes and inform community practice. Future trials should investigate and address additional barriers and facilitators of Bikram yoga practice