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We lead multidisciplinary applied research and training to rethink the way health care is delivered in general practice and across the community.
Eleven key measures for monitoring general practice clinical activity during COVID-19: A retrospective cohort study using 48 million adults’ primary care records in England through OpenSAFELY
Background: The COVID-19 pandemic has had a significant impact on delivery of NHS care. We have developed the OpenSAFELY Service Restoration Observatory (SRO) to develop key measures of primary care activity and describe the trends in these measures throughout the COVID-19 pandemic. Methods: With the approval of NHS England, we developed an open source software framework for data management and analysis to describe trends and variation in clinical activity across primary care electronic health record (EHR) data on 48 million adults. We developed SNOMED-CT codelists for key measures of primary care clinical activity such as blood pressure monitoring and asthma reviews, selected by an expert clinical advisory group and conducted a population cohort-based study to describe trends and variation in these measures January 2019-December 2021, and pragmatically classified their level of recovery one year into the pandemic using the percentage change in the median practice level rate. Results: We produced 11 measures reflective of clinical activity in general practice. A substantial drop in activity was observed in all measures at the outset of the COVID-19 pandemic. By April 2021, the median rate had recovered to within 15% of the median rate in April 2019 in six measures. The remaining measures showed a sustained drop, ranging from a 18.5% reduction in medication reviews to a 42.0% reduction in blood pressure monitoring. Three measures continued to show a sustained drop by December 2021. Conclusions: The COVID-19 pandemic was associated with a substantial change in primary care activity across the measures we developed, with recovery in most measures. We delivered an open source software framework to describe trends and variation in clinical activity across an unprec-edented scale of primary care data. We will continue to expand the set of key measures to be routinely monitored using our publicly available NHS OpenSAFELY SRO dashboards with near real-time data. Funding: This research used data assets made available as part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058).The OpenSAFELY Platform is supported by grants from the Wellcome Trust (222097/Z/20/Z); MRC (MR/V015757/1, MC_PC-20059, MR/W016729/1); NIHR (NIHR135559, COV-LT2-0073), and Health Data Research UK (HDRUK2021.000, 2021.0157).
Trends and variation in prescribing of suboptimal statin treatment regimes: a cohort study in English primary care
Objectives We set out to describe trends and variation in statin prescribing in England that breaches 2014 national guidance on “high-intensity” statins. We identify factors associated with breaching; and assess the feasibility of rapid prescribing behaviour change. Design, Setting and Participants Retrospective cohort study in NHS primary care in England, including all 8,142 standard general practices from August 2010 to March 2019. Main Outcome Measures We categorised statins as high or low/medium-intensity based on two different thresholds, and calculated the proportion prescribed below these thresholds across all practices. We plotted trends and geographical variation, carried out mixed effects logistic regression to identify practice characteristics associated with breaching guidance, and used indicator saturation to identify practices exhibiting sudden changes in prescribing. Results We included all 8,142 practices across the study period. The proportion of statin prescriptions below the recommended 40% LDL-lowering threshold decreased gradually since 2012 from 80% to 45%; the proportion below a pragmatic 37% threshold decreased from 30% to 18%. The 2014 guidance had minimal impact on these trends. We found wide variation between practices (interdecile ranges 20% to 85% and 10% to 30% respectively in 2018). Mixed effects logistic regression did not identify practice characteristics strongly associated with breaching guidance. Indicator saturation identified several practices exhibiting sudden changes in prescribing towards greater guideline compliance. Conclusions Breaches of English guidance on choice of statin remain common, with substantial variation between GP practices. Some practices and regions have implemented rapid change, indicating the feasibility of rapid prescribing behaviour change. We discuss the potential for a national strategic approach, using data and evidence to optimise care, including targeted education alongside audit and feedback to outliers through services such as OpenPrescribing. Summary What is already known on this topic English national guidance recommends the use of a high-intensity statin, capable of reducing LDL (low-density lipoprotein) cholesterol by 40% or more. Adherence at the time of guideline release was low, but has not been documented since. What this study adds Adherence is improving, but breaches of national guidance remain common, with 45% of prescriptions below the recommended strength, and there is very substantial variation between practices. Some practices have exhibited rapid positive change in prescribing, which indicates that better adherence could readily be achieved. We have produced a live data tool allowing anyone to explore any practice’s current statin prescribing behaviour.
Identifying Patterns of Clinical Interest in Clinicians’ Treatment Preferences: Hypothesis-free Data Science Approach to Prioritizing Prescribing Outliers for Clinical Review
Background: Data analysis is used to identify signals suggestive of variation in treatment choice or clinical outcome. Analyses to date have generally focused on a hypothesis-driven approach. Objective: This study aimed to develop a hypothesis-free approach to identify unusual prescribing behavior in primary care data. We aimed to apply this methodology to a national data set in a cross-sectional study to identify chemicals with significant variation in use across Clinical Commissioning Groups (CCGs) for further clinical review, thereby demonstrating proof of concept for prioritization approaches. Methods: Here we report a new data-driven approach to identify unusual prescribing behaviour in primary care data. This approach first applies a set of filtering steps to identify chemicals with prescribing rate distributions likely to contain outliers, then applies two ranking approaches to identify the most extreme outliers amongst those candidates. This methodology has been applied to three months of national prescribing data (June-August 2017). Results: Our methodology provides rankings for all chemicals by administrative region. We provide illustrative results for 2 antipsychotic drugs of particular clinical interest: promazine hydrochloride and pericyazine, which rank highly by outlier metrics. Specifically, our method identifies that, while promazine hydrochloride and pericyazine are barely used by most clinicians (with national prescribing rates of 11.1 and 6.2 per 1000 antipsychotic prescriptions, respectively), they make up a substantial proportion of antipsychotic prescribing in 2 small geographic regions in England during the study period (with maximum regional prescribing rates of 298.7 and 241.1 per 1000 antipsychotic prescriptions, respectively). Conclusions: Our hypothesis-free approach is able to identify candidates for audit and review in clinical practice. To illustrate this, we provide 2 examples of 2 very unusual antipsychotics used disproportionately in 2 small geographic areas of England.
During the COVID-19 pandemic 20 000 prostate cancer diagnoses were missed in England
Objectives: To investigate the effect of the COVID-19 pandemic on prostate cancer incidence, prevalence, and mortality in England. Patients and Methods: With the approval of NHS England and using the OpenSAFELY-TPP dataset of 24 million patients, we undertook a cohort study of men diagnosed with prostate cancer. We visualised monthly rates in prostate cancer incidence, prevalence, and mortality per 100 000 adult men from January 2015 to July 2023. To assess the effect of the pandemic, we used generalised linear models and the pre-pandemic data to predict the expected rates from March 2020 as if the pandemic had not occurred. The 95% confidence intervals (CIs) of the predicted values were used to estimate the significance of the difference between the predicted and observed rates. Results: In 2020, there was a drop in recorded incidence by 4772 (31%) cases (15 550 vs 20 322; 95% CI 19 241–21 403). In 2021, the incidence started to recover, and the drop was 3148 cases (18%, 17 950 vs 21 098; 95% CI 19 740–22 456). By 2022, the incidence returned to the levels that would be expected. During the pandemic, the age at diagnosis shifted towards older men. In 2020, the average age was 71.6 (95% CI 71.5–71.8) years, in 2021 it was 71.8 (95% CI 71.7–72.0) years as compared to 71.3 (95% CI 71.1–71.4) years in 2019. Conclusions: Given that our dataset represents 40% of the population, we estimate that proportionally the pandemic led to 20 000 missed prostate cancer diagnoses in England alone. The increase in incidence recorded in 2023 was not enough to account for the missed cases. The prevalence of prostate cancer remained lower throughout the pandemic than expected. As the recovery efforts continue, healthcare should focus on finding the men who were affected. The research should focus on investigating the potential harms to men diagnosed at older age.
Interpreting pathology test result values with comparators () in Electronic Health Records research: an OpenSAFELY short data report.
BackgroundNumeric results of pathology tests are sometimes returned as a range rather than a precise value, e.g. "<10". In health data research, test result values above or below clinical threshold values are often used to categorise patients into groups; however comparators ( etc) are typically stored separately to the numeric values and often ignored, but may influence interpretation.MethodsWith the approval of NHS England we used routine clinical data from 24 million patients in OpenSAFELY to identify pathology tests with comparators commonly attached to result values. For each test we report: the proportion returned with comparators present, split by comparator type and geographic region; the specific numeric result values returned with comparators, and the associated reference limits.ResultsWe identified 11 common test codes where at least one in four results had comparators. Three codes related to glomerular filtration rate (GFR) tests/calculations, with 31-45% of results returned with "≥" comparators. At least 90% of tests with numeric values 60 and 90 represented ranges (≥60 and ≥90 respectively) rather than exact values. The other tests - four blood tests (Nucleated red blood cell count, Plasma C reactive protein, Tissue transglutaminase immunoglobulin A, and Rheumatoid factor), two urine tests (albumin/microalbumin) and two faecal tests (calprotectin and quantitative faecal immunochemical test) - were returned with "≤" comparators (29-86%).ConclusionsComparators appear commonly in certain pathology tests in electronic health records. For most common affected tests, we expect there to be minimal implications for researchers for most use-cases. However, care should be taken around whether results falling exactly on clinical threshold values should be considered "normal" or "abnormal". Results from GFR tests/calculations cannot reliably distinguish between mild kidney disease (60-<90) versus healthy kidney function (90+). More broadly, health data researchers using numeric test result values should consider the impact of comparators.
First dose COVID-19 vaccine coverage amongst adolescents and children in England: an analysis of 3.21 million patients' primary care records in situ using OpenSAFELY
Background: The coronavirus disease 2019 (COVID-19) vaccination programme in England was extended to include all adolescents and children by April 2022. The aim of this paper is to describe trends and variation in vaccine coverage in different clinical and demographic groups amongst adolescents and children in England by August 2022. Methods: With the approval of NHS England, a cohort study was conducted of 3.21 million children and adolescents’ records in general practice in England, in situ and within the infrastructure of the electronic health record software vendor TPP using OpenSAFELY. Vaccine coverage across various demographic (sex, deprivation index and ethnicity) and clinical (risk status) populations is described. Results: Coverage is higher amongst adolescents than it is amongst children, with 53.5% adolescents and 10.8% children having received their first dose of the COVID-19 vaccine. Within those groups, coverage varies by ethnicity, deprivation index and risk status; there is no evidence of variation by sex. Conclusion: First dose COVID-19 vaccine coverage is shown to vary amongst various demographic and clinical groups of children and adolescents.
Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England, 16 November to 5 February
The SARS-CoV-2 B.1.1.7 variant of concern (VOC) is increasing in prevalence across Europe. Accurate estimation of disease severity associated with this VOC is critical for pandemic planning. We found increased risk of death for VOC compared with non-VOC cases in England (hazard ratio: 1.67; 95% confidence interval: 1.34-2.09; p<0.0001). Absolute risk of death by 28 days increased with age and comorbidities. This VOC has potential to spread faster with higher mortality than the pandemic to date The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern B.1.1.7 (VOC) was first identified in Kent, United Kingdom (UK) in autumn 2020. Early analysis suggests it is more transmissible than previously circulating forms (non-VOC) [1]. It is now the dominant strain throughout the UK and is increasing in prevalence across Europe [2]. Early reports of increased mortality have not included data on individuals' comorbidities, and this information is needed to facilitate pandemic planning. Certain PCR assays for SARS-CoV-2 do not amplify one of the spike protein gene targets in this VOC. Spike gene target failure (SGTF) is therefore a proxy for VOC identification, with greater than 95% sensitivity for VOC diagnosis during the period from 16 November to 11 January [3]. Working on behalf of NHS England, we estimate the risk of death following confirmation of SARS-CoV-2 infection in England, comparing infection with VOC to non-VOC, after accounting for demographic factors and comorbidities. The code and configuration of our analysis is available online (github.com/opensafely/ sgtf-cfr-research).
A National Audit of Pancreatic Enzyme Prescribing in Pancreatic Cancer from 2015 to 2023 in England Using OpenSAFELY-TPP
Objectives: Cancer treatments were variably disrupted during the coronavirus disease 2019 (COVID-19) pandemic. UK guidelines recommend pancreatic enzyme replacement therapy (PERT) to all people with unresectable pancreatic cancer. The aim was to investigate the impact of the COVID-19 pandemic on PERT prescribing to people with unresectable pancreatic cancer and to investigate the national and regional rates from January 2015 to January 2023. Data Sources: With the approval of NHS England, we conducted this study using 24 million electronic health records of people within the OpenSAFELY-TPP research platform. There were 22,860 people diagnosed with pancreatic cancer in the study cohort. We visualized the trends over time and modeled the effect of the COVID-19 pandemic with the interrupted time-series analysis. Conclusion: In contrast to many other treatments, prescribing of PERT was not affected during the pandemic. Overall, since 2015, the rates increased steadily over time by 1% every year. The national rates ranged from 41% in 2015 to 48% in early 2023. There was substantial regional variation, with the highest rates of 50% to 60% in West Midlands. Implications for Nursing Practice: In pancreatic cancer, if PERT is prescribed, it is usually initiated in hospitals by clinical nurse specialists and continued after discharge by primary care practitioners. At just under 50% in early 2023, the rates were still below the recommended 100% standard. More research is needed to understand barriers to prescribing of PERT and geographic variation to improve quality of care. Prior work relied on manual audits. With OpenSAFELY, we developed an automated audit that allows for regular updates (https://doi.org/10.53764/rpt.a0b1b51c7a).
Impact of first UK COVID-19 lockdown on hospital admissions: Interrupted time series study of 32 million people
Background: Uncontrolled infection and lockdown measures introduced in response have resulted in an unprecedented challenge for health systems internationally. Whether such unprecedented impact was due to lockdown itself and recedes when such measures are lifted is unclear. We assessed the short- and medium-term impacts of the first lockdown measures on hospital care for tracer non-COVID-19 conditions in England, Scotland and Wales across diseases, sexes, and socioeconomic and ethnic groups. Methods: We used OpenSAFELY (for England), EAVEII (Scotland), and SAIL Databank (Wales) to extract weekly hospital admission rates for cancer, cardiovascular and respiratory conditions (excluding COVID-19) from the pre-pandemic period until 25/10/2020 and conducted a controlled interrupted time series analysis. We undertook stratified analyses and assessed admission rates over seven months during which lockdown restrictions were gradually lifted. Findings: Our combined dataset included 32 million people who contributed over 74 million person-years. Admission rates for all three conditions fell by 34.2% (Confidence Interval (CI): -43.0, -25.3) in England, 20.9% (CI: -27.8, -14.1) in Scotland, and 24.7% (CI: -36.7, -12.7) in Wales, with falls across every stratum considered. In all three nations, cancer-related admissions fell the most while respiratory-related admissions fell the least (e.g., rates fell by 40.5% (CI: -47.4, -33.6), 21.9% (CI: -35.4, -8.4), and 19.0% (CI: -30.6, -7.4) in England for cancer, cardiovascular-related, and respiratory-related admissions respectively). Unscheduled admissions rates fell more in the most than the least deprived quintile across all three nations. Some ethnic minority groups experienced greater falls in admissions (e.g., in England, unscheduled admissions fell by 9.5% (CI: -20.2, 1.2) for Whites, but 44.3% (CI: -71.0, -17.6), 34.6% (CI: -63.8, -5.3), and 25.6% (CI: -45.0, -6.3) for Mixed, Other and Black ethnic groups respectively). Despite easing of restrictions, the overall admission rates remained lower in England, Scotland, and Wales by 20.8%, 21.6%, and 22.0%, respectively when compared to the same period (August-September) during the pre-pandemic years. This corresponds to a reduction of 26.2, 23.8 and 30.2 admissions per 100,000 people in England, Scotland, and Wales respectively. Interpretation: Hospital care for non-COVID diseases fell substantially across England, Scotland, and Wales during the first lockdown, with reductions persisting for at least six months. The most deprived and minority ethnic groups were impacted more severely. Funding: This work was funded by the Medical Research Council as part of the Lifelong Health and Wellbeing study as part of National Core Studies (MC_PC_20030). SVK acknowledges funding from the Medical Research Council (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE – The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. BG has received research funding from the NHS National Institute for Health Research (NIHR), the Wellcome Trust, Health Data Research UK, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme.
Risks of covid-19 hospital admission and death for people with learning disability: Population based cohort study using the OpenSAFELY platform
Objective To assess the association between learning disability and risk of hospital admission and death from covid-19 in England among adults and children. Design Population based cohort study on behalf of NHS England using the OpenSAFELY platform. Setting Patient level data were obtained for more than 17 million people registered with a general practice in England that uses TPP software. Electronic health records were linked with death data from the Office for National Statistics and hospital admission data from NHS Secondary Uses Service. Participants Adults (aged 16-105 years) and children (<16 years) from two cohorts: wave 1 (registered with a TPP practice as of 1 March 2020 and followed until 31 August 2020); and wave 2 (registered 1 September 2020 and followed until 8 February 2021). The main exposure group consisted of people on a general practice learning disability register; a subgroup was defined as those having profound or severe learning disability. People with Down's syndrome and cerebral palsy were identified (whether or not they were on the learning disability register). Main outcome measure Covid-19 related hospital admission and covid-19 related death. Non-covid-19 deaths were also explored. Results For wave 1, 14 312 023 adults aged ≥16 years were included, and 90 307 (0.63%) were on the learning disability register. Among adults on the register, 538 (0.6%) had a covid-19 related hospital admission; there were 222 (0.25%) covid-19 related deaths and 602 (0.7%) non-covid deaths. Among adults not on the register, 29 781 (0.2%) had a covid-19 related hospital admission; there were 13 737 (0.1%) covid-19 related deaths and 69 837 (0.5%) non-covid deaths. Wave 1 hazard ratios for adults on the learning disability register (adjusted for age, sex, ethnicity, and geographical location) were 5.3 (95% confidence interval 4.9 to 5.8) for covid-19 related hospital admission and 8.2 (7.2 to 9.4) for covid-19 related death. Wave 2 produced similar estimates. Associations were stronger among those classified as having severe to profound learning disability, and among those in residential care. For both waves, Down's syndrome and cerebral palsy were associated with increased hazards for both events; Down's syndrome to a greater extent. Hazard ratios for non-covid deaths followed similar patterns with weaker associations. Similar patterns of increased relative risk were seen for children, but covid-19 related deaths and hospital admissions were rare, reflecting low event rates among children. Conclusions People with learning disability have markedly increased risks of hospital admission and death from covid-19, over and above the risks observed for non-covid causes of death. Prompt access to covid-19 testing and healthcare is warranted for this vulnerable group, and prioritisation for covid-19 vaccination and other targeted preventive measures should be considered.
Impact of the COVID-19 pandemic on antipsychotic prescribing in individuals with autism, dementia, learning disability, serious mental illness or living in a care home: A federated analysis of 59 million patients' primary care records in situ using OpenSAFELY
Background The COVID-19 pandemic affected how care was delivered to vulnerable patients, such as those with dementia or learning disability. Objective To explore whether this affected antipsychotic prescribing in at-risk populations. Methods With the approval of NHS England, we completed a retrospective cohort study, using the OpenSAFELY platform to explore primary care data of 59 million patients. We identified patients in five at-risk groups: autism, dementia, learning disability, serious mental illness and care home residents. We calculated the monthly prevalence of antipsychotic prescribing in these groups, as well as the incidence of new prescriptions in each month. Findings The average monthly rate of antipsychotic prescribing increased in dementia from 82.75 patients prescribed an antipsychotic per 1000 patients (95% CI 82.30 to 83.19) in January-March 2019 to 90.1 (95% CI 89.68 to 90.60) in October-December 2021 and from 154.61 (95% CI 153.79 to 155.43) to 166.95 (95% CI 166.23 to 167.67) in care homes. There were notable spikes in the rate of new prescriptions issued to patients with dementia and in care homes. In learning disability and autism groups, the rate of prescribing per 1000 decreased from 122.97 (95% CI 122.29 to 123.66) to 119.29 (95% CI 118.68 to 119.91) and from 54.91 (95% CI 54.52 to 55.29) to 51.04 (95% CI 50.74 to 51.35), respectively. Conclusion and implications We observed a spike in antipsychotic prescribing in the dementia and care home groups, which correlated with lockdowns and was likely due to prescribing of antipsychotics for palliative care. We observed gradual increases in antipsychotic use in dementia and care home patients and decreases in their use in patients with learning disability or autism.
The impact of the COVID-19 pandemic on the treatment of common infections in primary care and the change to antibiotic prescribing in England
Background: There is concern that the COVID-19 pandemic altered the management of common infections in primary care. This study aimed to evaluate infection-coded consultation rates and antibiotic use during the pandemic and how any change may have affected clinical outcomes. Methods: With the approval of NHS England, a retrospective cohort study using the OpenSAFELY platform analysed routinely collected electronic health data from GP practices in England between January 2019 and December 2021. Infection coded consultations and antibiotic prescriptions were used estimate multiple measures over calendar months, including age-sex adjusted prescribing rates, prescribing by infection and antibiotic type, infection consultation rates, coding quality and rate of same-day antibiotic prescribing for COVID-19 infections. Interrupted time series (ITS) estimated the effect of COVID-19 pandemic on infection-coded consultation rates. The impact of the pandemic on non- COVID-19 infection-related hospitalisations was also estimated. Results: Records from 24 million patients were included. The rate of infection-related consultations fell for all infections (mean reduction of 39% in 2020 compared to 2019 mean rate), except for UTI which remained stable. Modelling infection-related consultation rates highlighted this with an incidence rate ratio of 0.44 (95% CI 0.36–0.53) for incident consultations and 0.43 (95% CI 0.33–0.54) for prevalent consultations. Lower respiratory tract infections (LRTI) saw the largest reduction of 0.11 (95% CI 0.07–0.17). Antibiotic prescribing rates fell with a mean reduction of 118.4 items per 1000 patients in 2020, returning to pre-pandemic rates by summer 2021. Prescribing for LRTI decreased 20% and URTI increased 15.9%. Over 60% of antibiotics were issued without an associated same-day infection code, which increased during the pandemic. Infection-related hospitalisations reduced (by 62%), with the largest reduction observed for pneumonia infections (72.9%). Same-day antibiotic prescribing for COVID-19 infection increased from 1 to 10.5% between the second and third national lockdowns and rose again during 2022. Conclusions: Changes to consultations and hospital admissions may be driven by reduced transmission of non-COVID-19 infections due to reduced social mixing and lockdowns. Inconsistencies in coding practice emphasises the need for improvement to inform new antibiotic stewardship policies and prevent resistance to novel infections.
Trends and variation in unsafe prescribing of methotrexate: a cohort study in English NHS primary care
Objective To describe trends and geographical variation in methotrexate prescribing that breaches national safety recommendations; deaths from methotrexate poisoning; and associated litigation. Methods A retrospective cohort study of English NHS primary care prescribing data, complemented by information obtained through Freedom of Information (FOI) requests. The main outcome measures were: (1) variation in ratio of breaching / adherent prescribing, geographically and over time, between General Practices and Clinical Commissioning Groups; (2) description of responses to FOI requests. Results Out of 7349 NHS General Practices in England, 1689 practices prescribed both 2.5mg and 10mg tablets to individual patients in 2017, breaching national guidance. In April 2018, 697 practices (at the 90th centile and above) prescribed at least 14.3% of all methotrexate as 10mg tablets, breaching national guidance. The 66 practices at the 99th percentile and above gave at least 52.4% of all prescribed methotrexate in the form of 10 mg tablets. The prescribing of 10mg tablets has fallen over 7 years, with 10mg tablets as a proportion of all methotrexate tablets falling from 9.1% to 3.4%. 21 deaths caused by methotrexate poisoning have been reported from 1993-2017. Conclusions The prevalence of unsafe methotrexate prescribing has reduced but it remains common, with substantial variation between organisations. We recommend the NHS invests in better strategies around implementation of safety recommendations. 21 deaths have been attributed to methotrexate poisoning but with no further details easily available: the full coroners reports for these deaths should be reviewed to identify recurring themes.
Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe covid-19 outcomes in patients in the community: Observational cohort study with the OpenSAFELY platform
Objective: To compare the effectiveness of sotrovimab (a neutralising monoclonal antibody) with molnupiravir (an antiviral) in preventing severe outcomes of covid-19 in adult patients infected with SARS-CoV-2 in the community and at high risk of severe outcomes from covid-19. Design: Observational cohort study with the OpenSAFELY platform. Setting: With the approval of NHS England, a real world cohort study was conducted with the OpenSAFELY-TPP platform (a secure, transparent, open source software platform for analysis of NHS electronic health records), and patient level electronic health record data were obtained from 24 million people registered with a general practice in England that uses TPP software. The primary care data were securely linked with data on SARS-CoV-2 infection and treatments, hospital admission, and death, over a period when both drug treatments were frequently prescribed in community settings. Participants: Adult patients with covid-19 in the community at high risk of severe outcomes from covid-19, treated with sotrovimab or molnupiravir from 16 December 2021. Interventions: Sotrovimab or molnupiravir given in the community by covid-19 medicine delivery units. Main outcome measures: Admission to hospital with covid-19 (ie, with covid-19 as the primary diagnosis) or death from covid-19 (ie, with covid-19 as the underlying or contributing cause of death) within 28 days of the start of treatment. Results: Between 16 December 2021 and 10 February 2022, 3331 and 2689 patients were treated with sotrovimab and molnupiravir, respectively, with no substantial differences in baseline characteristics. Mean age of all 6020 patients was 52 (standard deviation 16) years; 59% were women, 89% were white, and 88% had received three or more covid-19 vaccinations. Within 28 days of the start of treatment, 87 (1.4%) patients were admitted to hospital or died of infection from SARS-CoV-2 (32 treated with sotrovimab and 55 with molnupiravir). Cox proportional hazards models stratified by area showed that after adjusting for demographic information, high risk cohort categories, vaccination status, calendar time, body mass index, and other comorbidities, treatment with sotrovimab was associated with a substantially lower risk than treatment with molnupiravir (hazard ratio 0.54, 95% confidence interval 0.33 to 0.88, P=0.01). Consistent results were found from propensity score weighted Cox models (0.50, 0.31 to 0.81, P=0.005) and when restricted to people who were fully vaccinated (0.53, 0.31 to 0.90, P=0.02). No substantial effect modifications by other characteristics were detected (all P values for interaction >0.10). The findings were similar in an exploratory analysis of patients treated between 16 February and 1 May 2022 when omicron BA.2 was the predominant variant in England. Conclusions: In routine care of adult patients in England with covid-19 in the community, at high risk of severe outcomes from covid-19, those who received sotrovimab were at lower risk of severe outcomes of covid-19 than those treated with molnupiravir.
Safety of direct-acting oral anticoagulant (DOAC) prescribing: OpenSAFELY-TPP analysis of 20.5 million adults' electronic health records.
BACKGROUND: During the COVID-19 pandemic many patients were switched from warfarin to DOACs which require the creatinine clearance calculated to ensure the correct dose is prescribed to avoid bleeding or reduced efficacy. AIM: To identify the study population proportion prescribed a DOAC. Of these, the proportion with recorded: weight, estimated Glomerular Filtration Rate (eGFR), creatinine, creatinine clearance (CrCl) and atrial fibrillation (AF). To analyse the proportion of patients with recorded AF and CrCl prescribed a recommended DOAC dose. DESIGN & SETTING: A retrospective cohort study of 20.5 million adult NHS patients' electronic health records (EHRs) in England in the OpenSAFELY-TPP platform (January 2018 to February 2023). METHOD: Patients on DOACs were analysed for age, sex, recorded weight, eGFR, creatinine, CrCl and AF. Prescribed DOAC doses in patients with recorded AF were compared to recommended doses for recorded CrCl and determined as either recommended, underdose or overdose. RESULTS: In February 2023, weight, eGFR, creatinine, CrCl, AF and, AF and CrCl were recorded in 72.8%; 92.4%; 94.3%; 73.5%; 73.9% of study population respectively. Both AF and CrCl were recorded for 56.7% of patients. Of these, 86.2% received the recommended and 13.8% non-recommended DOAC doses. CONCLUSIONS: CrCl is not recorded for a substantial number of patients on DOACs. We recommend that national organisations tasked with safety, collectively update guidance on the appropriate weight to use in the Cockcroft-Gault equation, clarify that CrCl is not equivalent to eGFR and work with GP clinical system suppliers to standardise the calculation of CrCl in the EHR.
Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: An OpenSAFELY cohort analysis based on two cohorts
To assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform. We conducted two cohort studies from 1 March to 14 June 2020. Working on behalf of National Health Service England, we used routine clinical data in England linked to death data. In study 1, we identified people with an NSAID prescription in the last 3 years from the general population. In study 2, we identified people with rheumatoid arthritis/osteoarthritis. We defined exposure as current NSAID prescription within the 4 months before 1 March 2020. We used Cox regression to estimate HRs for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, accounting for age, sex, comorbidities, other medications and geographical region. In study 1, we included 536 423 current NSAID users and 1 927 284 non-users in the general population. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR 0.96, 95% CI 0.80 to 1.14) in the multivariable-adjusted model. In study 2, we included 1 708 781 people with rheumatoid arthritis/osteoarthritis, of whom 175 495 (10%) were current NSAID users. In the multivariable-adjusted model, we observed a lower risk of COVID-19 related death (HR 0.78, 95% CI 0.64 to 0.94) associated with current use of NSAID versus non-use. We found no evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about the routine therapeutic use of NSAIDs.