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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.
Association between oral anticoagulants and COVID-19-related outcomes: a population-based cohort study
Background Early evidence has shown that anticoagulant reduces the risk of thrombotic events in those infected with COVID-19. However, evidence of the role of routinely prescribed oral anticoagulants (OACs) in COVID-19 outcomes is limited. Aim To investigate the association between OACs and COVID-19 outcomes in those with atrial fibrillation and a CHA2DS2-VASc score of 2. Design and setting On behalf of NHS England, a population-based cohort study was conducted. Method The study used primary care data and pseudonymously-linked SARS-CoV-2 antigen testing data, hospital admissions, and death records from England. Cox regression was used to estimate hazard ratios (HRs) for COVID-19 outcomes comparing people with current OAC use versus non-use, accounting for age, sex, comorbidities, other medications, deprivation, and general practice. Results Of 71 103 people with atrial fibrillation and a CHA2DS2-VASc score of 2, there were 52 832 current OAC users and 18 271 non-users. No difference in risk of being tested for SARS-CoV-2 was associated with current use (adjusted HR [aHR] 0.99, 95% confidence interval [CI] = 0.95 to 1.04) versus non-use. A lower risk of testing positive for SARS-CoV-2 (aHR 0.77, 95% CI = 0.63 to 0.95) and a marginally lower risk of COVID-19- related death (aHR, 0.74, 95% CI = 0.53 to 1.04) were associated with current use versus non-use. Conclusion Among those at low baseline stroke risk, people receiving OACs had a lower risk of testing positive for SARS-CoV-2 and severe COVID-19 outcomes than non-users; this might be explained by a causal effect of OACs in preventing severe COVID-19 outcomes or unmeasured confounding, including more cautious behaviours leading to reduced infection risk.
Patient Characteristics Associated with Repeat Antibiotic Prescribing Pre- and during the COVID-19 Pandemic: A Retrospective Nationwide Cohort Study of >19 Million Primary Care Records Using the OpenSAFELY Platform
COVID-19 pandemic-related pressures on primary care may have driven the inappropriate continuation of antibiotic prescriptions. Yet, prescribing modality (repeat/non-repeat) has not previously been investigated in a pandemic context. With the approval of NHS England, we conducted a retrospective cohort study of >19 million English primary care patient records using the OpenSAFELY-TPP analytics platform. We analysed repeat/non-repeat prescribing frequency in monthly patient cohorts between January 2020 and 2022. In-depth analysis was conducted on January 2020 (“pre-pandemic”) and January 2021 (“pandemic”) cohorts (with a particular focus on repeat prescribing). Per-patient prescribing and clinical conditions were determined by searching primary care records using clinical codelists. Prescriptions in a 6-month lookback period were used to delineate repeat prescribing (≥3 prescriptions) and non-repeat prescribing (1–2 prescriptions). Associations between demographics (e.g., age, sex, ethnicity) and prescribing were explored using unadjusted risk ratios. The frequency of clinical conditions among prescribed patients was examined. Antibiotic prescribing declined from May 2020; non-repeat prescribing declined more strongly than repeat prescribing (maximum declines −26% vs. −11%, respectively). Older patients were at a higher risk of prescribing (especially repeat prescribing). Comorbidities were more common among repeat- vs. non-repeat-prescribed patients. In the pandemic cohort, the most common clinical conditions linked to repeat prescribing were COPD comorbidity and urinary tract infection. Our findings inform the ongoing development of stewardship interventions in England, targeting patient groups wherein there is a high prevalence of repeat prescribing.
Trends in inequalities in avoidable hospitalisations across the COVID-19 pandemic: A cohort study of 23.5 million people in England
Objective To determine whether periods of disruption were associated with increased 'avoidable' hospital admissions and wider social inequalities in England. Design Observational repeated cross-sectional study. Setting England (January 2019 to March 2022). Participants With the approval of NHS England we used individual-level electronic health records from OpenSAFELY, which covered ∼40% of general practices in England (mean monthly population size 23.5 million people). Primary and secondary outcome measures We estimated crude and directly age-standardised rates for potentially preventable unplanned hospital admissions: ambulatory care sensitive conditions and urgent emergency sensitive conditions. We considered how trends in these outcomes varied by three measures of social and spatial inequality: neighbourhood socioeconomic deprivation, ethnicity and geographical region. Results There were large declines in avoidable hospitalisations during the first national lockdown (March to May 2020). Trends increased post-lockdown but never reached 2019 levels. The exception to these trends was for vaccine-preventable ambulatory care sensitive admissions which remained low throughout 2020-2021. While trends were consistent by each measure of inequality, absolute levels of inequalities narrowed across levels of neighbourhood socioeconomic deprivation, Asian ethnicity (compared with white ethnicity) and geographical region (especially in northern regions). Conclusions We found no evidence that periods of healthcare disruption from the COVID-19 pandemic resulted in more avoidable hospitalisations. Falling avoidable hospital admissions has coincided with declining inequalities most strongly by level of deprivation, but also for Asian ethnic groups and northern regions of England.
Evaluation of policies and practices to support safe and appropriate analgesic and sedative prescribing: The CDRx (controlled drug prescribing) protocol
Medications provide many therapeutic benefits; however, these must be balanced against the potential for patient harm. Two high-risk medications are benzodiazepine receptor agonists or BZRAs (including benzodiazepines and Z-drugs hypnotics) and opioid analgesics, which carry a risk of dependence, misuse, and abuse. Use of these medications has been growing internationally, along with associated morbidity and mortality. These medications are often classified as ‘controlled drugs’ and subject to legal restrictions in order to balance therapeutic benefits and risks of misuse. The aim of this project is to evaluate prescribing of analgesic and sedative drugs, in particular opioid and BZRA medications, to characterise time trends, the impact of policy changes, and regional and GP practice variation. This will be addressed across three workpackages, primarily using data on prescriptions dispensed to individuals eligible for the General Medical Services scheme in Ireland, held by the HSE Primary Care Reimbursement Service, along with other national and international data collections. Workpackage 1 will derive volume and patterns of utilisation indicators of controlled drugs and related medications and describe time trends in primary care in Ireland between 2014 and 2021 in two repeated cross-sectional studies. Workpackage 2 will consist of two interrupted time series studies on the impact of recent policy changes on prescribing. Workpackage 3 is a cohort study of GP practices, which will aim to quantify and explain regional and GP practice-level variation in analgesic and sedative prescribing, and, in relation to policy changes. This research will provide data-driven insights to inform policy-makers’ decisions and clinical practice to optimise regulation and use of these medications for the benefit of patients and society.
OpenSAFELY: Measuring BMI in 22 million patients in England
Background: Body mass index (BMI) has been identified as a risk factor for clinical outcomes in patients with COVID-19. Studies identifying this risk have used electronic health record (EHR) platforms in which clinical conditions must be properly identified. We set out to define and evaluate various methods of deriving BMI measurements in OpenSAFELY-TPP, an EHR platform that has been used in many studies relating to the COVID-19 pandemic. Methods With the approval of NHS England, we use routine clinical data from >22 million patients in England to define four derivations of BMI. We compare the number of patients with each type of BMI measurement and the number of measurements themselves. We also examine the plausibility of each derivation by looking at the distribution of measurements and counting values out of the expected range. To evaluate how frequently the BMI derivations are recorded, we track the number of new measurements recorded over time and the average time between updates in patients with multiple measurements. Results Primary constraints in creating the optimal BMI derivation is coverage, accuracy, and computational complexity. BMI derivations calculated from height and weight contain a few extreme outliers that affect aggregated statistics. SNOMED-recorded BMI records are more accurate on average and offer better coverage across the population. The canonical OpenSAFELY definition – which uses calculated BMI as a first instance and SNOMED-recorded BMI if missing – offers the best coverage, but contains the same extreme outliers found in calculated BMI and is the most computationally expensive of all methods. Conclusions Across all derivations, some cleaning should be performed to drop implausible outliers. Using calculated BMI on its own does not offer the best coverage or accuracy. In choosing between SNOMED-recorded BMI and the current OpenSAFELY implementation, users should decide whether they would like to maximise computational efficiency or coverage.
OpenSAFELY: Do adults prescribed non-steroidal anti-inflammatory drugs have an increased risk of death from COVID-19?
Importance There has been speculation that non-steroidal anti-inflammatory drugs (NSAIDs) may negatively affect coronavirus disease 2019 (COVID-19) outcomes, yet clinical evidence is limited. Objective To assess the association between NSAID use and deaths from COVID-19 using OpenSAFELY, a secure analytical platform. Design Two cohort studies (1 st March-14 th June 2020). Setting Working on behalf of NHS England, we used routine clinical data from >17 million patients in England linked to death data from the Office for National Statistics. Participants Study 1: General population (people with an NSAID prescription in the last three years). Study 2: people with rheumatoid arthritis/osteoarthritis. Exposures Current NSAID prescription within the 4 months before 1 st March 2020. Main Outcome and Measure We used Cox regression to estimate hazard ratios (HRs) for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, adjusting for age, sex, comorbidities and other medications. Results In Study 1, we included 535,519 current NSAID users and 1,924,095 non-users in the general population. The crude HR for current use was 1.25 (95% CI, 1.07–1.46), versus non-use. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR, 0.95, 95% CI, 0.80–1.13) in the fully adjusted model. In Study 2, we included 1,711,052 people with rheumatoid arthritis/osteoarthritis, of whom 175,631 (10%) were current NSAID users. The crude HR for current use was 0.43 (95% CI, 0.36–0.52), versus non-use. In the fully adjusted model, we observed a lower risk of COVID-19 related death (HR, 0.78, 95% CI, 0.65–0.94) associated with current use of NSAID versus non-use. Conclusion and Relevance We found no evidence of a harmful effect of NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about therapeutic use of NSAIDs.
Private prescribing of controlled opioids in England, 2014-2021: a retrospective observational study
BACKGROUND: Trends in NHS opioid prescribing have been well published, yet trends in private prescribing of opioids have not been widely established. AIM: To assess trends and geographical variation in controlled opioids prescribed by private prescribers in England. DESIGN AND SETTING: This was a retrospective observational study in English primary health care. METHOD: Data on Schedule 2 and 3 controlled opioids ('controlled opioids') were obtained from the NHS Business Services Authority (BSA) using Freedom of Information (FOI) requests between 1 January 2014 and 30 November 2021. Absolute counts and rates of the number of items dispensed per cumulative number of registered private prescribers were calculated and stratified over time, by opioid type, and geographical region. RESULTS: This study found that 128 341 items of controlled opioids were prescribed by private prescribers in England between January 2014 and November 2021, which decreased by 50% from 23 339 items (4.09 items/prescriber) in 2014 to 11 573 items (1.49 items/prescriber) in 2020. Methadone (36%, n = 46 660) was the most common controlled opioid prescribed privately, followed by morphine (18%, n = 22 543), buprenorphine (16%, n = 20 521), and oxycodone (12%, n = 15 319). Prescriptions were highest in London (74%, n = 94 438), followed by the South-East of England (7%, n = 9237). A proportion of items (n = 462; 0.36%) were prescribed by 'unidentified doctors' where the prescription is not readily attributable to an individual prescriber by the BSA. CONCLUSION: Controlled opioids prescribed by private prescribers in England decreased and were primarily prescribed in London. To ensure patient safety, the monitoring and surveillance of controlled opioids dispensed privately should continue and items linked to 'unidentified doctors' should be addressed further.
Impact Of Electronic Health Record Interface Design On Unsafe Prescribing Of Ciclosporin, Tacrolimus and Diltiazem: A Cohort Study In English NHS Primary Care
Background In England, national safety guidance recommends that ciclosporin, tacrolimus and diltiazem are prescribed by brand name due to their narrow therapeutic windows and, in the case of tacrolimus, to reduce the chance of organ transplantation rejection. Various small studies have shown that changes to electronic health records (EHR) interface can affect prescribing choices. Objectives Our objectives were to assess variation by EHR system in breaches of safety guidance around prescribing of ciclosporin, tacrolimus and diltiazem; and to conduct user-interface research into the causes of such breaches. Methods We carried out a retrospective cohort study using prescribing data in English primary care. Participants were English general practices and their respective electronic health records. The main outcome measures were (1) variation in ratio of breaching / adherent prescribing all practices (2) description of observations of EHR usage. Results A total of 2,575,411 prescriptions were issued in 2018 for ciclosporin, tacrolimus and diltiazem (over 60mg); of these, 316,119 prescriptions breached NHS guidance (12.3%). Breaches were most common amongst users of the EMIS EHR (in 23.2% of ciclosporin & tacrolimus prescriptions, and 22.7% of diltiazem prescriptions); but breaches were observed in all EHRs. Conclusion Design: choices in EHR strongly influence safe prescribing of ciclosporin, tacrolimus and diltiazem; and breaches are prevalent in general practices in England. We recommend that all EHR vendors review their systems to increase safe prescribing of these medicines in line with national guidance. Almost all clinical practice is now mediated through an EHR system: further quantitative research into the effect of EHR design on clinical practice is long overdue.
Rates of serious clinical outcomes in survivors of hospitalisation with COVID-19 in England: a descriptive cohort study within the OpenSAFELY platform
Background: Patients surviving hospitalisation for COVID-19 are thought to be at high risk of cardiometabolic and pulmonary complications, but quantification of that risk is limited. We aimed to describe the overall burden of these complications in people after discharge from hospital with COVID-19. Methods: Working on behalf of NHS England, we used linked primary care records, death certificate and hospital data from the OpenSAFELY platform. We constructed three cohorts: patients discharged following hospitalisation with COVID-19, patients discharged following pre-pandemic hospitalisation with pneumonia, and a frequency-matched cohort from the general population in 2019. We studied seven outcomes: deep vein thrombosis (DVT), pulmonary embolism (PE), ischaemic stroke, myocardial infarction (MI), heart failure, AKI and new type 2 diabetes mellitus (T2DM) diagnosis. Absolute rates were measured in each cohort and Fine and Gray models were used to estimate age/sex adjusted subdistribution hazard ratios comparing outcome risk between discharged COVID-19 patients and the two comparator cohorts. Results: Amongst the population of 77,347 patients discharged following hospitalisation with COVID-19, rates for the majority of outcomes peaked in the first month post-discharge, then declined over the following four months. Patients in the COVID-19 population had markedly higher risk of all outcomes compared to matched controls from the 2019 general population. Across the whole study period, the risk of outcomes was more similar when comparing patients discharged with COVID-19 to those discharged with pneumonia in 2019, although COVID-19 patients had higher risk of T2DM (15.2 versus 37.2 [rate per 1,000-person-years for COVID-19 versus pneumonia, respectively]; SHR, 1.46 [95% CI: 1.31 - 1.63]). Conclusions: Risk of cardiometabolic and pulmonary adverse outcomes is markedly raised following discharge from hospitalisation with COVID-19 compared to the general population. However, excess risks were similar to those seen following discharge post-pneumonia. Overall, this suggests a large additional burden on healthcare resources.
Clinical coding of long COVID in English primary care: a federated analysis of 58 million patient records in situ using OpenSAFELY
This OpenSAFELY report is a routine update of our peer-review paper published in the British Journal of General Practice on the Clinical coding of long COVID in English primary care: a federated analysis of 58 million patient records in situ using OpenSAFELY. It is a routine update of the analysis described in the paper. The data requires careful interpretation and there are a number of caveats. Please read the full detail about our methods and discussionis and the full analytical methods on this routine report are available on GitHub. OpenSAFELY is a new secure analytics platform for electronic patient records built on behalf of NHS England to deliver urgent academic and operational research during the pandemic. You can read more about OpenSAFELY on our website.
Impact of Electronic Health Record Interface Design on Unsafe Prescribing of Ciclosporin, Tacrolimus, and Diltiazem: Cohort Study in English National Health Service Primary Care
Background: In England, national safety guidance recommends that ciclosporin, tacrolimus, and diltiazem are prescribed by brand name due to their narrow therapeutic windows and, in the case of tacrolimus, to reduce the chance of organ transplantation rejection. Various small studies have shown that changes to electronic health record (EHR) system interfaces can affect prescribing choices. Objective: Our objectives were to assess variation by EHR systems in breach of safety guidance around prescribing of ciclosporin, tacrolimus, and diltiazem, and to conduct user-interface research into the causes of such breaches. Methods: We carried out a retrospective cohort study using prescribing data in English primary care. Participants were English general practices and their respective EHR systems. The main outcome measures were (1) the variation in ratio of safety breaches to adherent prescribing in all practices and (2) the description of observations of EHR system usage. Results: A total of 2,575,411 prescriptions were issued in 2018 for ciclosporin, tacrolimus, and diltiazem (over 60 mg); of these, 316,119 prescriptions breached NHS guidance (12.27%). Breaches were most common among users of the EMIS EHR system (breaches in 18.81% of ciclosporin and tacrolimus prescriptions and in 17.99% of diltiazem prescriptions), but breaches were observed in all EHR systems. Conclusions: Design choices in EHR systems strongly influence safe prescribing of ciclosporin, tacrolimus, and diltiazem, and breaches are prevalent in general practices in England. We recommend that all EHR vendors review their systems to increase safe prescribing of these medicines in line with national guidance. Almost all clinical practice is now mediated through an EHR system; further quantitative research into the effect of EHR system design on clinical practice is long overdue.
Factors associated with COVID-19-related death using OpenSAFELY
Coronavirus disease 2019 (COVID-19) has rapidly affected mortality worldwide1. There is unprecedented urgency to understand who is most at risk of severe outcomes, and this requires new approaches for the timely analysis of large datasets. Working on behalf of NHS England, we created OpenSAFELY—a secure health analytics platform that covers 40% of all patients in England and holds patient data within the existing data centre of a major vendor of primary care electronic health records. Here we used OpenSAFELY to examine factors associated with COVID-19-related death. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19-related deaths. COVID-19-related death was associated with: being male (hazard ratio (HR) 1.59 (95% confidence interval 1.53–1.65)); greater age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared with people of white ethnicity, Black and South Asian people were at higher risk, even after adjustment for other factors (HR 1.48 (1.29–1.69) and 1.45 (1.32–1.58), respectively). We have quantified a range of clinical factors associated with COVID-19-related death in one of the largest cohort studies on this topic so far. More patient records are rapidly being added to OpenSAFELY, we will update and extend our results regularly.
Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records
The frequency of, and risk factors for, long COVID are unclear among community-based individuals with a history of COVID-19. To elucidate the burden and possible causes of long COVID in the community, we coordinated analyses of survey data from 6907 individuals with self-reported COVID-19 from 10 UK longitudinal study (LS) samples and 1.1 million individuals with COVID-19 diagnostic codes in electronic healthcare records (EHR) collected by spring 2021. Proportions of presumed COVID-19 cases in LS reporting any symptoms for 12+ weeks ranged from 7.8% and 17% (with 1.2 to 4.8% reporting debilitating symptoms). Increasing age, female sex, white ethnicity, poor pre-pandemic general and mental health, overweight/obesity, and asthma were associated with prolonged symptoms in both LS and EHR data, but findings for other factors, such as cardio-metabolic parameters, were inconclusive.
Projected spending for brand-name drugs in English primary care given US prices: a cross-sectional study
Objectives: To estimate additional spending if NHS England paid the same prices as US Medicare Part D for the 50 single-source brand-name drugs with the highest expenditure in English primary care in 2018. Design: Retrospective analysis of 2018 drug prescribing and spending in the NHS England prescribing data and the Medicare Part D Drug Spending Dashboard and Data. We examined the 50 costliest drugs in English primary care available as brand-name-only in the US and England. We performed cost projections of NHS England spending with US Medicare Part D prices. We estimated average 2018 US rebates as 1 minus the quotient of net divided by gross Medicare Part D spending. Setting: England and US Participants: NHS England and US Medicare systems Main outcome measures: Total spending, prescriptions and claims in NHS England and Medicare Part D. All spending and cost measures were reported in 2018 British pounds. Results: NHS England spent £1.39 billion on drugs in the cohort. All drugs were more expensive under US Medicare Part D than NHS England. The US–England price ratios ranged from 1.3 to 9.9 (mean ratio 4.8). Accounting for prescribing volume, if NHS England had paid US Medicare Part D prices after adjusting for estimated US rebates, it would have spent 4.6 times as much in 2018 on drugs in the cohort (£6.42 billion). Conclusions: Spending by NHS England would be substantially higher if it paid US Medicare Part D prices. This could result in decreased access to medicines and other health services.
Hydroxychloroquine for prevention of COVID-19 mortality: a population-based cohort study
Background Hydroxychloroquine has been shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, but early clinical studies found no benefit treating patients with coronavirus disease 2019 (COVID-19). We set out to evaluate the effectiveness of hydroxychloroquine for prevention, as opposed to treatment, of COVID-19 mortality. Methods We pre-specified and conducted an observational, population-based cohort study using national primary care data and linked death registrations in the OpenSAFELY platform, representing 40% of the general population in England. We used Cox regression to estimate the association between ongoing routine hydroxychloroquine use prior to the COVID-19 outbreak in England and risk of COVID-19 mortality among people with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Model adjustment was informed by a directed acyclic graph. Results Of 194,637 patients with RA or SLE, 30,569 (15.7%) received ≥ 2 prescriptions of hydroxychloroquine in the six months prior to 1 March 2020. Between 1 March 2020 and 13 July 2020, there were 547 COVID-19 deaths, 70 among hydroxychloroquine users. Estimated standardised cumulative COVID-19 mortality was 0.23% (95% CI 0.18–0.29) among users and 0.22% (95% CI 0.20–0.25) among non-users; an absolute difference of 0.008% (95% CI –0.051-0.066). After accounting for age, sex, ethnicity, use of other immunuosuppressives, and geographic region, no association with COVID-19 mortality was observed (HR 1.03, 95% CI 0.80–1.33). We found no evidence of interactions with age or other immunosuppressives. Quantitative bias analyses indicated observed associations were robust to missing information regarding additional biologic treatments for rheumatological disease. We observed similar associations with the negative control outcome of non-COVID-19 mortality. Conclusion We found no evidence of a difference in COVID-19 mortality among patients who received hydroxychloroquine for treatment of rheumatological disease prior to the COVID-19 outbreak in England. Research in context Evidence before this study Published trials and observational studies to date have shown no evidence of benefit of hydroxychloroquine as a treatment for hospitalised patients who already have COVID-19. A separate question remains: whether routine ongoing use of hydroxychloroquine in people without COVID-19 protects against new infections or severe outcomes. We searched MEDLINE/PubMed for pharmacoepidemiological studies evaluating hydroxychloroquine for prevention of severe COVID-19 outcomes. The keywords “hydroxychloroquine AND (COVID OR coronavirus OR SARS-CoV-2) AND (prophyl* OR prevent*) AND (rate OR hazard OR odds OR risk)” were used and results were filtered to articles from the last year with abstracts available. 109 papers were identified for screening; none investigated pre-exposure prophylactic use of hydroxychloroquine for prevention of severe COVID-19 outcomes. Clinical trials of prophylactic use of hydroxychloroquine are ongoing; however, the largest trial does not expect to meet recruitment targets due to “…unjustified extrapolation and exaggerated safety concerns together with intense politicisation and negative publicity.” In the absence of reported clinical trials, evidence can be generated from real-world data to support the need for randomised clinical trials. Added value of this study In this cohort study representing 40% of the population of England, we investigated whether routine use of hydroxychloroquine prior to the COVID-19 outbreak prevented COVID-19 mortality. Using robust pharmacoepidemiological methods, we found no evidence to support a substantial benefit of hydroxychloroquine in preventing COVID-19 mortality. At the same time, we have shown no significant harm, and this generates the equipoise to justify continuing randomised trials. We have demonstrated in this study that it is feasible to address specific hypotheses about medicines in a rapid and transparent manner to inform interim clinical decision making and support the need for large-scale, randomised trial data. Implications of all the available evidence This is the first study to investigate the ongoing routine use of hydroxychloroquine and risk of COVID-19 mortality in a general population. While we found no evidence of any protective benefit, due to the observational nature of the study, residual confounding remains a possibility. Completion of trials for prevention of severe outcomes is warranted, but prior to the completion of these, we found no evidence to support the use of hydroxychloroquine for prevention of COVID-19 mortality.
Trends and variation in unsafe prescribing of methotrexate: A cohort study in English NHS primary care
Background Prescribing high doses of methotrexate increases the potentially fatal risk of toxicity. To minimise risk, it is recommended that only 2.5 mg tablets are used. Aim To describe trends in GP prescribing of methotrexate over time; the harm associated with methotrexate errors at a national level; ascertain variation between practices and clinical commissioning groups (CCGs) in their implementation of the safety guidance; and map current variations at CCG and practice level. Design and setting A retrospective cohort study of English GP prescribing data (August 2010-April 2018), and data acquired via freedom of information (FOI) requests. Method The main outcome measures were: variation in ratio of non-adherent/adherent prescribing, geographically and over time, between practices and CCGs; and description of responses to FOI requests. Results Of 7349 practices in England, 1689 prescribed both 2.5 mg and 10 mg tablets to individual patients in 2017, breaching national guidance. In April 2018, 697 practices (≥90th percentile) prescribed >14.3% of all methotrexate as 10 mg tablets, likewise breaching national guidance. The 66 practices at ≥99th percentile gave >52.4% of all prescribed methotrexate in the form of 10 mg tablets. The prescribing of 10 mg tablets fell during the study period, with 10 mg tablets as a proportion of all prescribed methotrexate tablets falling from 9.1% to 3.4%. Twenty-one deaths caused by methotrexate poisoning were reported from 1993-2017 in England and Wales. Conclusion The prevalence of unsafe methotrexate prescribing has reduced but remains common, with substantial variation between practices and CCGs. The authors recommend investment in better strategies around implementation. As 21 deaths that occurred from 1993-2017 in England and Wales were attributed to methotrexate poisoning, the coroners' reports for these deaths should be reviewed to identify recurring themes.
Recording of “COVID-19 vaccine declined” among vaccination priority groups: a cohort study on 57.9 million NHS patients’ primary care records in situ using OpenSAFELY
Background All patients in England within vaccine priority groups were offered a COVID-19 vaccine by mid-April 2021. Clinical record systems contain codes to denote when such an offer has been declined by a patient (although these can in some cases be entered for a variety of other reasons including vaccination delay, or other administrative issues). We set out to describe the patterns of usage of codes for COVID-19 vaccines being declined. Methods With the approval of NHS England and using the full pseudonymised primary care records for 57.9 million NHS patients, we identified all patients in key vaccine priority groups: aged over 50, or over 16 and at increased risk from COVID-19 (Clinically Extremely Vulnerable [CEV] or otherwise “at risk”). We describe the proportion of patients recorded as declining a COVID-19 vaccination for each priority group, and by other clinical and demographic factors; whether patients recorded as “declined” subsequently went on to receive a vaccination; and the distribution of code usage across GP practices. Results Of 24.5 million patients in priority groups as of May 25th 2021, 89.2% had received a vaccine, 8.8% had neither a vaccination nor a decline recorded, and 663,033 (2.7%) had a decline code recorded. Of patients with a recorded decline, 125,587 (18.9%) were subsequently vaccinated. Subsequent vaccination was slightly more common in the South Asian population than other ethnicities (e.g. 32.3% vs 22.8%, over 65s). The proportion of declining-unvaccinated patients varied strongly with ethnicity (Black 15.3%, South Asian 5.6%, White 1.5% in over 80s); and was higher in patients from more deprived areas. COVID-19 vaccine decline codes were present in almost all practices (98.8%), but with wide variation between practices in rates of usage. Among all priority groups, declining-unvaccinated status was most common in CEV (3.3%). Conclusions Clinical codes indicative of COVID-19 vaccinations being declined are widely used in English general practice. They are substantially more common among Black and South Asian patients, and patients from more deprived areas. There is a need for more detailed survey and/or qualitative research with patients and clinicians to determine the most common reasons for these recorded declines.
Gout incidence and management during the COVID-19 pandemic in England, UK: a nationwide observational study using OpenSAFELY
Background: Gout is the most prevalent inflammatory arthritis, yet one of the worst managed. Our objective was to assess how the COVID-19 pandemic impacted incidence and quality of care for people with gout in England, UK. Methods: With the approval of National Health Service England, we did a population-level cohort study using primary care and hospital electronic health record data for 17·9 million adults registered with general practices using TPP health record software, via the OpenSAFELY platform. The study period was from March 1, 2015, to Feb 28, 2023. Individuals aged 18–110 years were defined as having incident gout if they were assigned index diagnostic codes for gout, were registered with TPP practices in England for at least 12 months before diagnosis, did not receive prescriptions for urate-lowering therapy more than 30 days before diagnosis, and had not been admitted to hospital or attended an emergency department for gout flares more than 30 days before diagnosis. Outcomes assessed were incidence and prevalence of people with recorded gout diagnoses, incidence of gout hospitalisations, initiation of urate-lowering therapy, and attainment of serum urate targets (≤360 μmol/L). Findings: From a reference population of 17 865 145 adults, 246 695 individuals were diagnosed with incident gout. The mean age of individuals with incident gout was 61·3 years (SD 16·2). 66 265 (26·9%) of 246 695 individuals were female, 180 430 (73·1%) were male, and 189 035 (90·9%) of 208 050 individuals with available ethnicity data were White. Incident gout diagnoses decreased by 30·9% in the year beginning March, 2020, compared with the preceding year (1·23 diagnoses vs 1·78 diagnoses per 1000 adults). Gout prevalence was 3·07% in 2015–16, and 3·21% in 2022–23. Gout hospitalisations decreased by 30·1% in the year commencing March, 2020, compared with the preceding year (9·6 admissions vs 13·7 admissions per 100 000 adults). Of 228 095 people with incident gout and available follow-up, 66 560 (29·2%) were prescribed urate-lowering therapy within 6 months. Of 65 305 individuals who initiated urate-lowering therapy with available follow-up, 16 790 (25·7%) attained a serum urate concentration of 360 μmol/L or less within 6 months of urate-lowering therapy initiation. In interrupted time-series analyses, urate-lowering therapy prescribing improved modestly during the pandemic, compared with pre-pandemic, whereas urate target attainment was similar. Interpretation: Using gout as an exemplar disease, we showed the complexity of how health care was impacted during the COVID-19 pandemic. We observed a reduction in gout diagnoses but no effect on treatment metrics. We showed how country-wide, routinely collected data can be used to map disease epidemiology and monitor care quality. Funding: None.