ORCID Profile
0000-0002-5127-4728
Current Organisation
University of Oxford
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Publisher: Elsevier BV
Date: 07-2022
Publisher: Cold Spring Harbor Laboratory
Date: 02-08-2022
DOI: 10.1101/2022.07.30.22278161
Abstract: To quantify in absolute and relative terms how population-level COVID-19 death rates have changed in demographic and clinical subgroups. Retrospective cohort study on behalf of NHS England. Linked primary care and death registry data from the OpenSAFELY-TPP platform, covering the first three pandemic waves in England (wave 1: March 23 to May 30, 2020 wave 2: September 7, 2020 to April 24, 2021 and wave 3, delta: May 28 to December 14, 2021). In total, 18.7, 18.8, and 18.7 million adults were included for waves 1, 2, and 3 respectively. COVID-19-related mortality based on linked death registry records. The crude absolute COVID-19-related death rate per 1,000 person-years decreased from 4.48 in wave 1 (95%CI 4.41 .55), to 2.70 in wave 2 (95%CI 2.67 .73), to 0.64 in wave 3 (95%CI 0.63 .66). The absolute death rate decreased by 90% between waves 1 and 3 in patients aged 80+, but by only 20% in patients aged 18-39. This higher proportional reduction in age- and sex-standardised death rates was also seen for other groups, such as neurological disease, learning disability and severe mental illness. Conversely, standardised death rates in transplant recipients stayed constant across successive waves at 10 per 1,000 person-years. There was also only a small decrease in death rates between waves in people with kidney disease, haematological malignancies or conditions associated with immunosuppression. Consequently, the relative hazard of COVID-19-related death decreased over time for some variables (e.g. age), remained similar for some (e.g. sex, ethnicity), and increased for others (e.g. transplant). COVID-19 death rates decreased over the first three pandemic waves. An especially large decrease was seen in older age groups and people with neurological disease, learning disability or severe mental illness. Some demographic inequalities in death rates persisted over time. Groups more likely to experience impaired vaccine effectiveness did not see the same benefit in COVID-19 mortality reduction.
Publisher: BMJ
Date: 20-07-2022
Abstract: To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and the ChAdOx1 (Oxford-AstraZeneca) covid-19 vaccines against infection and covid-19 disease in health and social care workers. Cohort study, emulating a comparative effectiveness trial, on behalf of NHS England. Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 Alpha variant was dominant. 317 341 health and social care workers vaccinated between 4 January and 28 February 2021, registered with a general practice using the TPP SystmOne clinical information system in England, and not clinically extremely vulnerable. Vaccination with either BNT162b2 or ChAdOx1 administered as part of the national covid-19 vaccine roll-out. Recorded SARS-CoV-2 positive test, or covid-19 related attendance at an accident and emergency (A& E) department or hospital admission occurring within 20 weeks of receipt of the first vaccine dose. Over the duration of 118 771 person-years of follow-up there were 6962 positive SARS-CoV-2 tests, 282 covid-19 related A& E attendances, and 166 covid-19 related hospital admissions. The cumulative incidence of each outcome was similar for both vaccines during the first 20 weeks after vaccination. The cumulative incidence of recorded SARS-CoV-2 infection 20 weeks after first-dose vaccination with BNT162b2 was 21.7 per 1000 people (95% confidence interval 20.9 to 22.4) and with ChAdOx1 was 23.7 (21.8 to 25.6), representing a difference of 2.04 per 1000 people (0.04 to 4.04). The difference in the cumulative incidence per 1000 people of covid-19 related A& E attendance at 20 weeks was 0.06 per 1000 people (95% CI −0.31 to 0.43). For covid-19 related hospital admission, this difference was 0.11 per 1000 people (−0.22 to 0.44). In this cohort of healthcare workers where we would not anticipate vaccine type to be related to health status, we found no substantial differences in the incidence of SARS-CoV-2 infection or covid-19 disease up to 20 weeks after vaccination. Incidence dropped sharply at 3-4 weeks after vaccination, and there were few covid-19 related hospital attendance and admission events after this period. This is in line with expected onset of vaccine induced immunity and suggests strong protection against Alpha variant covid-19 disease for both vaccines in this relatively young and healthy population of healthcare workers.
Publisher: Cold Spring Harbor Laboratory
Date: 05-01-2023
DOI: 10.1101/2023.01.04.22283762
Abstract: Quantifying the waning effectiveness of second COVID-19 vaccination beyond six months and against the omicron variant is important for scheduling subsequent doses. With the approval of NHS England, we estimated effectiveness up to one year after second dose, but found that bias in such estimates may be substantial.
Publisher: F1000 Research Ltd
Date: 27-04-2021
DOI: 10.12688/WELLCOMEOPENRES.16737.1
Abstract: Background: Care home residents have been severely affected by the COVID-19 pandemic. Electronic Health Records (EHR) hold significant potential for studying the healthcare needs of this vulnerable population however, identifying care home residents in EHR is not straightforward. We describe and compare three different methods for identifying care home residents in the newly created OpenSAFELY-TPP data analytics platform. Methods: Working on behalf of NHS England, we identified in iduals aged 65 years or older potentially living in a care home on the 1st of February 2020 using (1) a complex address linkage, in which cleaned GP registered addresses were matched to old age care home addresses using data from the Care and Quality Commission (CQC) (2) coded events in the EHR (3) household identifiers, age and household size to identify households with more than 3 in iduals aged 65 years or older as potential care home residents. Raw addresses were not available to the investigators. Results: Of 4,437,286 in iduals aged 65 years or older, 2.27% were identified as potential care home residents using the complex address linkage, 1.96% using coded events, 3.13% using household size and age and 3.74% using either of these methods. 53,210 in iduals (32.0% of all potential care home residents) were classified as care home residents using all three methods. Address linkage had the largest overlap with the other methods 93.3% of in iduals identified as care home residents using the address linkage were also identified as such using either coded events or household age and size. Conclusion: We have described the partial overlap between three methods for identifying care home residents in EHR, and provide detailed instructions for how to implement these in OpenSAFELY-TPP to support research into the impact of the COVID-19 pandemic on care home residents.
Publisher: Cold Spring Harbor Laboratory
Date: 31-07-2023
DOI: 10.1101/2023.07.31.23293419
Abstract: The COVID-19 pandemic caused significant disruption to routine activity in primary care. Medication reviews are an important primary care activity to ensure safety and appropriateness of ongoing prescribing and a disruption could have significant negative implications for patient care. Using routinely collected data, our aim was to i) describe the SNOMED CT codes used to report medication review activity ii) report the impact of COVID-19 on the volume and variation of medication reviews. With the approval of NHS England, we conducted a cohort study of 20 million adult patient records in general practice, in-situ using the OpenSAFELY platform. For each month between April 2019 - March 2022, we report the percentage of patients with a medication review coded monthly and in the previous 12 months. These measures were broken down by regional, clinical and demographic subgroups and amongst those prescribed high risk medications. In April 2019, 32.3% of patients had a medication review coded in the previous 12 months. During the first COVID-19 lockdown, monthly activity substantially decreased (−21.1% April 2020), but the rate of patients with a medication review coded in the previous 12 months was not substantially impacted according to our classification (−10.5% March 2021). There was regional and ethnic variation (March 2022 - London 21.9% vs North West 33.6% Chinese 16.8% vs British 33.0%). Following the introduction of “structured medication reviews”, the rate of structured medication review in the last 12 months reached 2.9% by March 2022, with higher percentages in high risk groups (March 2022 - care home residents 34.1%, 90+ years 13.1%, high risk medications 10.2%). The most used SNOMED CT medication review code across the study period was Medication review done - 314530002 (59.5%). We have reported a substantial reduction in the monthly rate of medication reviews during the pandemic but rates recovered by the end of the study period.
Publisher: F1000 Research Ltd
Date: 10-07-2023
DOI: 10.12688/WELLCOMEOPENRES.19424.1
Abstract: Background: Living with children has been associated with greater risks of SARS-CoV-2 infection, COVID-19 hospitalisation, and COVID-19 death. We examined how these associations varied during 2021–22 and according to the COVID-19 vaccination status of adults. Methods : We carried out a population-based cohort study, with the approval of NHS England. Primary care data and pseudonymously-linked hospital and death records from England, between 20 th December 2020 and 21 st February 2022, were used for adults (≥18 years) registered at a general practice on 20 th December 2020. Adjusted hazard ratios (HRs) for SARS-CoV-2 infection, COVID-19 hospitalisation, or COVID-19 death, by presence of children in the household were calculated. Results: The cohort included 9,417,278 adults aged ≤65 years and 2,866,602 adults aged years. Adults aged ≤65 years living with children of any age ( versus no children) had greater risks of SARS-CoV-2 infection and COVID-19 hospitalisation (but not COVID-19 death), both when schools were open and closed ( e.g. HR=1.50, 95% CI:1.49-1.51, for SARS-CoV-2 infection in the ‘Omicron dominant’ period, when schools were open, in adults living with children aged 0–11 years only). These associations also existed for adults aged years, and there was some evidence that adults living with children also had greater risks of COVID-19 death. Vaccinated adults living with children had greater risks of SARS-CoV-2 infection, but lower risks of COVID-19 hospitalisation and death, than unvaccinated adults not living with children. Conclusions : In an era of widespread adult vaccination, adults living with children remained at increased risk of SARS-CoV-2 infection and COVID-19 hospitalisation.
Publisher: Wiley
Date: 05-2015
DOI: 10.1111/JEBM.12155
Abstract: Testing Treatments is a book written to help everyone understand why testing treatments is so important, why treatment tests have to be fair, and how everyone can help to promote better research for better health care. The book proved to be very popular and its second edition has already been translated into a dozen languages, with more translations in the pipeline. The texts of the original English and all the translations are feely downloadable from Testing Treatments interactive at www.testingtreatments.org. The editors of all the different language websites have established an TTi Editorial Alliance, to share experiences and provide each other with mutual support. The TTi Editorial Alliance seeks to promote a world in which health professionals, patients and the public use reliable research to inform their health decisions. Its missions are (i) To promote a global network, involving members of the public in partnership with professionals, to communicate and discuss basic principles and general knowledge about testing treatments (ii) to help the public increase critical thinking and skills in accessing, apprehending, appraising and using research evidence and (iii) to help patients and the public to participate more actively in health research.
Publisher: Cold Spring Harbor Laboratory
Date: 03-2021
DOI: 10.1101/2021.02.25.21252433
Abstract: To compare approaches for obtaining relative and absolute estimates of risk of 28-day COVID-19 mortality for adults in the general population of England in the context of changing levels of circulating infection. Three designs were compared. (A) case-cohort which does not explicitly account for the time-changing prevalence of COVID-19 infection, (B) 28-day landmarking, a series of sequential overlapping sub-studies incorporating time-updating proxy measures of the prevalence of infection, and (C) daily landmarking. Regression models were fitted to predict 28-day COVID-19 mortality. Working on behalf of NHS England, we used clinical data from adult patients from all regions of England held in the TPP SystmOne electronic health record system, linked to Office for National Statistics (ONS) mortality data, using the OpenSAFELY platform. Eligible participants were adults aged 18 or over, registered at a general practice using TPP software on 1 st March 2020 with recorded sex, postcode and ethnicity. 11,972,947 in iduals were included, and 7,999 participants experienced a COVID-19 related death. The study period lasted 100 days, ending 8 th June 2020. A range of demographic characteristics and comorbidities were used as potential predictors. Local infection prevalence was estimated with three proxies: modelled based on local prevalence and other key factors rate of A& E COVID-19 related attendances and rate of suspected COVID-19 cases in primary care. COVID-19 related death. All models discriminated well between patients who did and did not experience COVID-19 related death, with C-statistics ranging from 0.92-0.94. Accurate estimates of absolute risk required data on local infection prevalence, with modelled estimates providing the best performance. Reliable estimates of absolute risk need to incorporate changing local prevalence of infection. Simple models can provide very good discrimination and may simplify implementation of risk prediction tools in practice.
Publisher: Cold Spring Harbor Laboratory
Date: 06-06-2022
DOI: 10.1101/2022.06.06.22276026
Abstract: The UK COVID-19 vaccination programme delivered its first “booster” doses in September 2021, initially in groups at high risk of severe disease then across the adult population. The BNT162b2 Pfizer-BioNTech vaccine was used initially, with Moderna mRNA-1273 subsequently also used. We used the OpenSAFELY-TPP database, covering 40% of English primary care practices and linked to national coronavirus surveillance, hospital episodes, and death registry data, to estimate the effectiveness of boosting with BNT162b2 compared with no boosting in eligible adults who had received two primary course vaccine doses between 16 September and 16 December 2021 when the Delta variant of SARS-CoV-2 was dominant. Follow up was for up to 10 weeks. Each booster recipient was matched with an unboosted control on factors relating to booster priority status and prior immunisation. Additional factors were adjusted for in Cox models estimating hazard ratios (HRs). Outcomes were positive SARS-CoV-2 test, COVID-19 hospitalisation, COVID-19 death and non-COVID-9 death. Booster vaccine effectiveness was defined as 1−HR. Among 4,352,417 BNT162b2 booster recipients matched with unboosted controls, estimated effectiveness of a booster dose compared with two doses only was 50.7% (95% CI 50.1-51.3) for positive SARS-CoV-2 test, 80.1% (78.3-81.8) for COVID-19 hospitalisation, 88.5% (85.0-91.1) for COVID-19 death, and 80.3% (79.0-81.5) for non-COVID-19 death. Estimated effectiveness was similar among those who had received a BNT162b2 or ChAdOx1-S two-dose primary vaccination course, but effectiveness against severe COVID-19 was slightly lower in those classified as clinically extremely vulnerable (76.3% (73.1-79.1) for COVID-19 hospitalisation, and 85.1% (79.6-89.1) for COVID-19 death). Estimated effectiveness against each outcome was lower in those aged 18-65 years than in those aged 65 and over. Our findings are consistent with strong protection of BNT162b2 boosting against positive SARS-CoV-2 test, COVID-19 hospitalisation, and COVID-19 death.
Publisher: Cold Spring Harbor Laboratory
Date: 08-09-2023
Publisher: Oxford University Press (OUP)
Date: 13-08-2022
DOI: 10.1093/IJE/DYAC158
Abstract: Ethnic differences in the risk of severe COVID-19 may be linked to household composition. We quantified the association between household composition and risk of severe COVID-19 by ethnicity for older in iduals. With the approval of NHS England, we analysed ethnic differences in the association between household composition and severe COVID-19 in people aged 67 or over in England. We defined households by number of age-based generations living together, and used multivariable Cox regression stratified by location and wave of the pandemic and accounted for age, sex, comorbidities, smoking, obesity, housing density and deprivation. We included 2 692 223 people over 67 years in Wave 1 (1 February 2020–31 August 2020) and 2 731 427 in Wave 2 (1 September 2020–31 January 2021). Multigenerational living was associated with increased risk of severe COVID-19 for White and South Asian older people in both waves [e.g. Wave 2, 67+ living with three other generations vs 67+-year-olds only: White hazard ratio (HR) 1.61 95% CI 1.38–1.87, South Asian HR 1.76 95% CI 1.48–2.10], with a trend for increased risks of severe COVID-19 with increasing generations in Wave 2. There was also an increased risk of severe COVID-19 in Wave 1 associated with living alone for White (HR 1.35 95% CI 1.30–1.41), South Asian (HR 1.47 95% CI 1.18–1.84) and Other (HR 1.72 95% CI 0.99–2.97) ethnicities, an effect that persisted for White older people in Wave 2. Both multigenerational living and living alone were associated with severe COVID-19 in older adults. Older South Asian people are over-represented within multigenerational households in England, especially in the most deprived settings, whereas a substantial proportion of White older people live alone. The number of generations in a household, number of occupants, ethnicity and deprivation status are important considerations in the continued roll-out of COVID-19 vaccination and targeting of interventions for future pandemics.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Cold Spring Harbor Laboratory
Date: 08-11-2021
DOI: 10.1101/2021.11.08.21265380
Abstract: While the vaccines against COVID-19 are considered to be highly effective, COVID-19 vaccine breakthrough is likely and a small number of people will still fall ill, be hospitalised, or die from COVID-19, despite being fully vaccinated. With the continued increase in numbers of positive SARS-CoV-2 tests, describing the characters of in iduals who have experienced a COVID-19 vaccine breakthrough could be hugely important in helping to determine who may be at greatest risk. With the approval of NHS England we conducted a retrospective cohort study using routine clinical data from the OpenSAFELY TPP database of fully vaccinated in iduals, linked to secondary care and death registry data, and described the characteristics of those experiencing a COVID-19 vaccine breakthrough. As of 01 st November 2021, a total of 15,436,455 in iduals were identified as being fully vaccinated against COVID-19, with a median follow-up time of 149 days (IQR: 107-179). From within this population, a total of 577245 ( %) in iduals reported a positive SARS-CoV-2 test. For every 1000 years of patient follow-up time, the corresponding incidence rate was 98.02 (95% CI 97.9-98.15). There were 16,120 COVID-19-related hospital admissions, 1,100 COVID-19 critical care admission patients and 3,925 COVID-19-related deaths corresponding incidence rates of 2.72 (95% C 2.7-2.74), 0.19 (95% C 0.18-0.19) and 0.66 (95% C 0.65-0.67), respectively. When broken down by the initial priority group, higher rates of hospitalisation and death were seen in those in care homes and those over 80 years of age. Comorbidities with the highest rates of breakthrough COVID-19 included chronic kidney disease, dialysis, transplant, haematological malignancy, and immunocompromised. The majority of COVID-19 vaccine breakthrough cases in England were mild with relatively few fully vaccinated in iduals being hospitalised or dying as a result. However, some concerning differences in rates of breakthrough cases were identified in several clinical and demographic groups. While it is important to note that these findings are simply descriptive and cannot be used to answer why certain groups have higher rates of COVID-19 breakthrough than others, the emergence of the Omicron variant of COVID-19 coupled with the continued increase in numbers of positive SARS-CoV-2 tests are concerning. As numbers of fully vaccinated in iduals increases and follow-up time lengthens, so too will the number of COVID-19 breakthrough cases. Additional analyses, aimed at identifying in iduals at higher risk, are therefore required.
Publisher: BMJ
Date: 30-07-2018
DOI: 10.1136/BMJ.K3229
Publisher: Cold Spring Harbor Laboratory
Date: 05-08-2023
DOI: 10.1101/2023.07.28.23293269
Abstract: Fit notes (“sick notes”) are issued by general practitioners (GPs) when a person can’t work for health reasons and is an indication of the public health and economic burden for people recovering from COVID-19. With NHS England approval, we used routine clinical data from million patients to compare fit note incidence in people 18-64 years with and without evidence of COVID-19 in 2020, 2021 and 2022. We fit Cox regression models to estimate adjusted hazard ratios, overall and by time post-diagnosis and within demographic subgroups. We identified 365,421, 1,206,555 and 1,321,313 people with evidence of COVID-19 in 2020, 2021 and 2022. The fit note rate was 4.88 per 100 person-months (95%CI 4.83-4.93) in 2020, 2.66 (95%CI 2.64-2.67) in 2021, and 1.73 (95%CI 1.72-1.73) in 2022. Compared with the age, sex and region matched general population, the hazard ratio (HR) adjusted for demographics and clinical characteristics over the follow-up period was 4.07 (95%CI 4.02-4.12) in 2020 decreasing to 1.57 (95%CI 1.56-1.58) in 2022. The HR was highest in the first 30 days post-diagnosis in all years. Despite likely underestimation of the fit note rate, we identified a considerable increase among people with COVID-19, even in an era when most people are vaccinated. Most fit notes are associated with the acute phase of the disease, but the increased risk several months post-diagnosis provides further evidence of the long-term impact. We searched Pubmed from 1 March 2020 to 30 June 2023 using the following search terms: (“COVID-19” OR “SARS-CoV-2” OR “coronavirus”) AND (“United Kingdom” OR “England” OR “Britain” OR “Scotland” OR “Wales”) AND (“fit note” OR “sick note” OR “sick leave” OR “sickness absence”). We also searched the reference list of relevant articles. We included both peer-reviewed research studies and grey literature that quantified receipt of fit notes or sick leave during the COVID-19 pandemic. We found two peer-reviewed studies and one briefing by an independent think tank. A study of 959,356 National Health Service (NHS) employees in England quantified receipt of non-COVID-19 related fit notes during the first wave of the pandemic. They found that the overall fit note rate was lower in 2020 compared with 2019. However, increases in the number of people receiving fit notes were observed for respiratory, infectious disease, and mental health conditions. The second study of 15,931 domiciliary care workers in Wales between Mar 2020 and Nov 2021 found that 15% had been issued a fit note over the study period. Fit notes were more common among women, people ≥45 years, and those with comorbidities. The briefing found that the percentage of sickness absence days taken by NHS employees was higher in 2022 (5.6%) compared with 2019 (4.3%), with a particular increase in absences due to mental health and infectious diseases. In 2022, 18% of sickness absence days were attributable to COVID-19. This study is the first to quantify changes in fit note rate since the start of the COVID-19 pandemic among people with a reported SARS-CoV-2 infection and how this compares with the general population in the UK. We found that people with evidence of SARS-CoV-2 infection had a higher fit note rate than the general population, even after adjusting for demographics and clinical characteristics. While this increased risk was greatest in 2020 (hazard ratio [HR] = 4.07, 95%CI 4.02-4.12), it continued to a lesser extent even into 2022 (HR = 1.57, 95%CI 1.56-1.58). The fit note rate was greatest in the first 30 days post-diagnosis, suggesting that most sick leave is associated with the acute phase. In subgroup analyses, the groups with the greatest relative increased risk changed over the years. People aged 18-24 years had a larger relative increased risk of fit notes (as measured by HR) in 2022 than 2021, when compared with the general population in each year. Additionally, while in 2020 and 2021 the HR increased along with lessening deprivation, this effect dissipated in 2022. In contrast, people hospitalised with COVID-19 were less likely to be issued a fit note than the pneumonia cohort, suggesting the long-term effects may be similar to comparable severe respiratory infections cases resulting in hospitalisation. While we have likely underestimated the fit note rate due to overcounting of people in the workforce and misclassification of COVID-19 status, we still identified a substantial increased risk of receiving a fit note in people with COVID-19 compared with the general population over all years, even after adjusting for demographics and a wide range of clinical characteristics. The increased risk persisted into 2022, in an era where most people are vaccinated and the severity of COVID-19 illness is lessened. Given the high infection rates still occurring, these findings provide evidence for a substantial impact of COVID-19 on productivity and further evidence of the long-term impacts of COVID-19.
Publisher: Springer Science and Business Media LLC
Date: 08-07-2020
Publisher: Cold Spring Harbor Laboratory
Date: 07-05-2020
DOI: 10.1101/2020.05.06.20092999
Abstract: Establishing who is at risk from a novel rapidly arising cause of death, and why, requires a new approach to epidemiological research with very large datasets and timely data. Working on behalf of NHS England we therefore set out to deliver a secure and pseudonymised analytics platform inside the data centre of a major primary care electronic health records vendor establishing coverage across detailed primary care records for a substantial proportion of all patients in England. The following results are preliminary. Primary care electronic health records managed by the electronic health record vendor TPP, pseudonymously linked to patient-level data from the COVID-19 Patient Notification System (CPNS) for death of hospital inpatients with confirmed COVID-19, using the new OpenSAFELY platform. 17,425,445 adults. 1st Feb 2020 to 25th April 2020. Death in hospital among people with confirmed COVID-19. Cohort study analysed by Cox-regression to generate hazard ratios: age and sex adjusted, and multiply adjusted for co-variates selected prospectively on the basis of clinical interest and prior findings. There were 5683 deaths attributed to COVID-19. In summary after full adjustment, death from COVID-19 was strongly associated with: being male (hazard ratio 1.99, 95%CI 1.88-2.10) older age and deprivation (both with a strong gradient) uncontrolled diabetes (HR 2.36 95% CI 2.18-2.56) severe asthma (HR 1.25 CI 1.08-1.44) and various other prior medical conditions. Compared to people with ethnicity recorded as white, black people were at higher risk of death, with only partial attenuation in hazard ratios from the fully adjusted model (age-sex adjusted HR 2.17 95% CI 1.84-2.57 fully adjusted HR 1.71 95% CI 1.44-2.02) with similar findings for Asian people (age-sex adjusted HR 1.95 95% CI 1.73-2.18 fully adjusted HR 1.62 95% CI 1.431.82). We have quantified a range of clinical risk factors for death from COVID-19, some of which were not previously well characterised, in the largest cohort study conducted by any country to date. People from Asian and black groups are at markedly increased risk of in-hospital death from COVID-19, and contrary to some prior speculation this is only partially attributable to pre-existing clinical risk factors or deprivation further research into the drivers of this association is therefore urgently required. Deprivation is also a major risk factor with, again, little of the excess risk explained by co-morbidity or other risk factors. The findings for clinical risk factors are concordant with policies in the UK for protecting those at highest risk. Our OpenSAFELY platform is rapidly adding further NHS patients’ records we will update and extend these results regularly.
Publisher: BMJ
Date: 22-06-2017
DOI: 10.1136/BMJ.J2782
Publisher: BMJ
Date: 06-06-2014
DOI: 10.1136/BMJ.G3768
Publisher: F1000 Research Ltd
Date: 29-04-2022
DOI: 10.12688/WELLCOMEOPENRES.17735.1
Abstract: 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.
Publisher: National Institute for Health and Care Research
Date: 03-2021
DOI: 10.3310/HTA25160
Abstract: Uncertainty persists about whether or not statins cause symptomatic muscle adverse effects (e.g. pain, stiffness and weakness) in the absence of severe myositis. To establish the effect of statins on all muscle symptoms, and the effect of statins on muscle symptoms that are perceived to be statin related. A series of 200 double-blinded N-of-1 trials. Participants were recruited from 50 general practices in England and Wales. Patients who were considering discontinuing statin use and those who had discontinued statin use in the last 3 years because of perceived muscle symptoms. Participants were randomised to a sequence of six 2-month treatment periods during which they received 20 mg of atorvastatin daily or a matched placebo. The primary outcome was self-reported muscle symptoms rated using a visual analogue scale on the last week of each treatment period. Secondary outcomes included the participant’s belief about the cause of their muscle symptoms, the site of muscle symptoms, how the muscle symptoms affected the participant, any other symptoms they experienced, adherence to medication, the participant’s decision about statin treatment following the trial, and whether or not they found their own trial result helpful. A total of 151 out of 200 (75.5%) randomised participants provided one or more visual analogue scale measurements in a placebo period and one or more measurements in a statin period, and were included in the primary analysis. There was no evidence of a difference in muscle symptom scores between statin and placebo periods (mean difference statin minus placebo –0.11, 95% confidence interval –0.36 to 0.14 p = 0.398). Withdrawals, adherence and missing data were similar during the statin periods and the placebo periods. Among people who previously reported severe muscle symptoms while taking statins, this series of randomised N-of-1 trials found no overall effect of statins on muscle symptoms compared with the placebo. The slight difference in withdrawals due to muscle symptoms suggests that statins may contribute to symptoms in a small number of patients. The results are generalisable to patients who are considering discontinuing or have already discontinued statins because of muscle symptoms, and who are willing to re-challenge or participate in their own N-of-1 trial. We recommend that additional statins and doses are explored using N-of-1 trials. More broadly, N-of-1 trials present a useful tool for exploring transient symptoms with other medications. This study used 20-mg doses of atorvastatin only. Furthermore, a dropout rate of 43% was observed, but this was accounted for in the power calculations. Current Controlled Trials ISRCTN30952488 and EudraCT 2016-000141-31. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 25, No. 16. See the NIHR Journals Library website for further project information.
Publisher: Cold Spring Harbor Laboratory
Date: 14-08-2020
DOI: 10.1101/2020.08.12.20171405
Abstract: 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. To assess the association between NSAID use and deaths from COVID-19 using OpenSAFELY, a secure analytical platform. Two cohort studies (1 st March-14 th June 2020). Working on behalf of NHS England, we used routine clinical data from million patients in England linked to death data from the Office for National Statistics. Study 1: General population (people with an NSAID prescription in the last three years). Study 2: people with rheumatoid arthritis/osteoarthritis. Current NSAID prescription within the 4 months before 1 st March 2020. 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. 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. 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.
Publisher: Cold Spring Harbor Laboratory
Date: 10-09-2021
DOI: 10.1101/2021.09.03.21262888
Abstract: It is unclear if people with immune-mediated inflammatory diseases (IMIDs) (joint, bowel and skin) and on immune modifying therapy have increased risk of serious COVID-19 outcomes. With the approval of NHS England we conducted a cohort study, using OpenSAFELY, analysingroutinely-collected primary care data linked to hospital admission, death and previously unavailable hospital prescription data. We used Cox regression (adjusting for confounders) to estimate hazard ratios (HR) comparing risk of COVID-19-death, death/critical care admission, and hospitalisation (March to September 2020) in: 1) people with IMIDs compared to the general population and 2) people with IMIDs on targeted immune modifying drugs (e.g., biologics) compared to standard systemic treatment (e.g., methotrexate). We identified 17,672,065 adults of 1,163,438 (7%) with IMIDs, 19,119 people received targeted immune modifying drugs, and 200,813 received standard systemics. We saw evidence of increased COVID-19-death (HR 1.23, 95%CI 1.20, 1.27), and COVID-19 hospitalisation (HR 1.32, 95%CI 1.29, 1.35) in in iduals with IMIDs overall compared to in iduals without IMIDs of the same age, sex, deprivation and smoking status. We saw no evidence of increased COVID-19 deaths with targeted compared to standard systemic treatments (HR 1.03, 95%CI 0.80, 1.33). There was no evidence of increased COVID-19-related death in those prescribed TNF inhibitors, IL-12/23, IL7, IL-6 or JAK inhibitors compared to standard systemics. Rituximab was associated with increased COVID-19 death (HR 1.68, 95%CI 1.11, 2.56) however, this finding may relate to confounding. COVID-19 death and hospitalisation was higher in people with IMIDs. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune modifying drugs for IMIDs compared to standard systemics. We searched PubMed on May 19 th , 2021, using the terms “COVID-19”, “SARS-CoV-2” and “rheumatoid arthritis”, “psoriatic arthritis” “ankylosing spondylitis”, “Crohn’s disease” “ulcerative colitis” “hidradenitis suppurativa” and “psoriasis”, to identify primary research articles examining severe COVID-19 outcome risk in in iduals with immune-mediated inflammatory diseases (IMIDs) and those on immune modifying therapy. The studies identified (including matched cohort studies and studies in disease-specific registries) were limited by small s le sizes and number of outcomes. Most studies did not show a signal of increased adverse COVID-19 outcomes in those on targeted therapies, with the exception of rituximab. Additionally, disease-specific registries are subject to selection bias and lack denominator populations. In our large population-based study of 17 million in iduals, including 1 million people with IMIDs and just under 200,000 receiving immune modifying medications, we saw evidence that people with IMIDs had an increased risk of COVID-19-related death compared to the general population after adjusting for potential confounders (age, sex, deprivation, smoking status) (HR 1.23, 95%CI 1.20, 1.27). We saw differences by IMID type, with COVID-19-related death being increased by the most in people with inflammatory joint disease (HR 1.47, 95%CI 1.40, 1.54). We also saw some evidence that those with IMIDs were more likely, compared to the general population, to have COVID-19-related critical care admission/death (HR 1.24, 95%CI 1.21, 1.28) and hospitalisation (HR 1.32, 95%CI 1.29, 1.35). Compared to people with IMIDs taking standard systemics, we saw no evidence of differences in severe COVID-19-related outcomes with TNF inhibitors, IL-17 inhibitors, IL-12/23 inhibitors, IL-6 inhibitors and JAK inhibitors. However, there was some evidence that rituximab was associated with an increased risk of COVID-19-related death (HR 1.68, 95%CI 1.11, 2.56) and death/critical care admission (HR 1.92, 95%CI 1.31, 2.81). We also saw evidence of an increase in COVID-19-related hospital admissions in people prescribed rituximab (HR 1.59, 95%CI 1.16, 2.18) or JAK inhibition (HR 1.81, 95%CI 1.09, 3.01) compared to those on standard systemics, although this could be related to worse underlying health rather than the drugs themselves, and numbers of events were small. This is the first study to our knowledge to use high-cost drug data on medicines supplied by hospitals at a national scale in England (to identify targeted therapies). The availability of these data fills an important gap in the medication record of those with more specialist conditions treated by hospitals creating an important opportunity to generate insights to these conditions and these medications Our study offers insights into future risk mitigation strategies and SARS-CoV-2 vaccination priorities for in iduals with IMIDs, as it highlights that those with IMIDs and those taking rituximab may be at risk of severe COVID-19 outcomes. Critically, our study does not show a link between most targeted immune modifying medications compared to standard systemics and severe COVID-19 outcomes. However, the increased risk of adverse COVID-19 outcomes that we saw in people with IMIDs and those treated with rituximab merits further study.
Publisher: Cold Spring Harbor Laboratory
Date: 08-07-2021
DOI: 10.1101/2021.07.07.21253295
Abstract: Residents in care homes have been severely impacted by the COVID-19 pandemic. We describe trends in risk of mortality among care home residents compared to residents in private homes in England. On behalf of NHS England, we used OpenSAFELY-TPP, an analytics platform running across the linked electronic health records of approximately a third of the English population, to calculate monthly age-standardised risks of death due to all causes and COVID-19 among adults aged =65 years between 1/2/2019 and 31/03/2021. Care home residents were identified using linkage to the Care and Quality Commission. We included 4,329,078 people aged 65 years or older on the 1st of February 2019, 2.2% of whom were classified as residing in a care or nursing home. Age-standardised mortality risks were approximately 10 times higher among care home residents compared to non-residents in February 2019 residents (CMF = 10.59, 95%CI = 9.51, 11.81 among women, CMF = 10.82, 95%CI = 9.89, 11.84 among men). This increased to more than 17 times in April 2020 (CMF = 17.52, 95%CI = 16.38, 18.74 among women, CMF = 18.12, 95%CI = 17.17 – 19.12 among men) before returning to pre-pandemic levels in June 2020. CMFs did not increase during the second wave, despite a rise in the absolute age-standardised COVID-19 mortality risks. The first COVID-19 wave had a disproportionate impact on care home residents in England compared to older private home residents. A degree of immunity, improved protective measures or changes in the underlying frailty of the populations may explain the lack of an increase in the relative mortality risks during the second wave. The care home population should be prioritised for measures aimed at controlling the spread of COVID-19. Medical Research Council MR/V015737/1
Publisher: Cold Spring Harbor Laboratory
Date: 23-09-2020
DOI: 10.1101/2020.09.22.20198754
Abstract: COVID-19 has had a disproportionate impact on ethnic minority populations, both in the UK and internationally. To date, much of the evidence has been derived from studies within single healthcare settings, mainly those hospitalised with COVID-19. Working on behalf of NHS England, the aim of this study was to identify ethnic differences in the risk of COVID-19 infection, hospitalisation and mortality using a large general population cohort in England. We conducted an observational cohort study using linked primary care records of 17.5 million adults between 1 February 2020 and 3 August 2020. Exposure was self-reported ethnicity collapsed into the 5 and 16 ethnicity categories of the English Census. Multivariable Cox proportional hazards regression was used to identify ethnic differences in the risk of being tested and testing positive for SARS-CoV-2 infection, COVID-19 related intensive care unit (ICU) admission, and COVID-19 mortality, adjusted for socio-demographic factors, clinical co-morbidities, geographic region, care home residency, and household size. A total of 17,510,002 adults were included in the study 63% white (n=11,030,673), 6% south Asian (n=1,034,337), 2% black (n=344,889), 2% other (n=324,730), 1% mixed (n=172,551), and 26% unknown (n=4,602,822). After adjusting for measured explanatory factors, south Asian, black, and mixed groups were marginally more likely to be tested (south Asian HR 1.08, 95%CI 1.07-1.09 black HR 1.08 95%CI 1.06-1.09, mixed HR 1.03, 95%CI 1.01-1.05), and substantially more likely to test positive for SARS-CoV-2 compared with white adults (south Asian HR 2.02. 95% CI 1.97-2.07 black HR 1.68, 95%CI 1.61-1.76 mixed HR 1.46, 95%CI 1.36-1.56). The risk of being admitted to ICU for COVID-19 was substantially increased in all ethnic minority groups compared with white adults (south Asian HR 2.22, 95%CI 1.96-2.52 black HR 3.07, 95%CI 2.61-3.61 mixed HR 2.86, 95%CI 2.19-3.75, other HR 2.86, 95%CI 2.31-3.63). Risk of COVID-19 mortality was increased by 25-56% in ethnic minority groups compared with white adults (south Asian HR 1.27, 95%CI 1.17-1.38 black HR 1.55, 95%CI 1.38-1.75 mixed HR 1.40, 95%CI 1.12-1.76 other HR 1.25, 95%CI 1.05-1.49). We observed heterogeneity of associations after disaggregation into detailed ethnic groupings Indian and African groups were at higher risk of all outcomes Pakistani, Bangladeshi and Caribbean groups were less or equally likely to be tested for SARS-CoV-2, but at higher risk of all other outcomes, Chinese groups were less likely to be tested for and test positive for SARS-CoV-2, more likely to be admitted to ICU, and equally likely to die from COVID-19. We found evidence of substantial ethnic inequalities in the risk of testing positive for SARS-CoV-2, ICU admission, and mortality, which persisted after accounting for explanatory factors, including household size. It is likely that some of this excess risk is related to factors not captured in clinical records such as occupation, experiences of structural discrimination, or inequitable access to health and social services. Prioritizing linkage between health, social care, and employment data and engaging with ethnic minority communities to better understand their lived experiences is essential for generating evidence to prevent further widening of inequalities in a timely and actionable manner.
Publisher: Cold Spring Harbor Laboratory
Date: 16-05-2023
DOI: 10.1101/2023.05.12.23289914
Abstract: The effectiveness of COVID-19 monoclonal antibody and antiviral therapies against severe COVID-19 outcomes is unclear. Initial benefit was shown in unvaccinated patients and before the Omicron variant emerged. We used the OpenSAFELY platform to emulate target trials to estimate the effectiveness of sotrovimab or molnupiravir, versus no treatment. With the approval of NHS England, we derived population-based cohorts of non-hospitalised high-risk in iduals in England testing positive for SARS-CoV-2 during periods of dominance of the BA.1 (16/12/2021-10/02/2022) and BA.2 (11/02/2022-21/05/2022) Omicron sublineages. We used the clone-censor-weight approach to estimate the effect of treatment with sotrovimab or molnupiravir initiated within 5 days after positive test versus no treatment. Hazard ratios (HR) for COVID-19 hospitalisation or death within 28 days were estimated using weighted Cox models. Of the 35,856 [BA.1 period] and 39,192 [BA.2 period] patients, 1,830 [BA.1] and 1,242 [BA.2] were treated with molnupiravir and 2,244 [BA.1] and 4,164 [BA.2] with sotrovimab. The estimated HRs for molnupiravir versus untreated were 1.00 (95%CI: 0.81 .22) [BA.1] and 1.22 (0.96 .56) [BA.2] corresponding HRs for sotrovimab versus untreated were 0.76 (0.66 .89) [BA.1] and 0.92 (0.79 .06) [BA.2]. Compared with no treatment, sotrovimab was associated with reduced risk of adverse outcomes after COVID-19 in the BA.1 period, but there was weaker evidence of benefit in the BA2 period. Molnupiravir was not associated with reduced risk in either period. UKRI, Wellcome Trust, MRC, NIHR and HDRUK.
Publisher: Cold Spring Harbor Laboratory
Date: 04-12-2020
DOI: 10.1101/2020.12.03.20243535
Abstract: Early in the COVID-19 pandemic the NHS recommended that appropriate patients anticoagulated with warfarin should be switched to direct acting oral anticoagulants (DOACs), requiring less frequent blood testing. Subsequently, a national safety alert was issued regarding patients being inappropriately co-prescribed two anticoagulants following a medication change, and associated monitoring. To describe which people were switched from warfarin to DOACs identify potentially unsafe co-prescribing of anticoagulants and assess whether abnormal clotting results have become more frequent during the pandemic. Working on behalf of NHS England we conducted a population cohort based study using routine clinical data from million adults in England. 20,000 of 164,000 warfarin patients (12.2%) switched to DOACs between March and May 2020, most commonly to edoxaban and apixaban. Factors associated with switching included: older age, recent renal function test, higher number of recent INR tests recorded, atrial fibrillation diagnosis and care home residency. There was a sharp rise in co-prescribing of warfarin and DOACs from typically 50-100 per month to 246 in April 2020, 0.06% of all people receiving a DOAC or warfarin. INR testing fell by 14% to 506.8 patients tested per 1000 warfarin patients each month. We observed a very small increase in elevated INRs (n=470) during April compared with January (n=420). Increased switching of anticoagulants from warfarin to DOACs was observed at the outset of the COVID-19 pandemic in England following national guidance. There was a small but substantial number of people co-prescribed warfarin and DOACs during this period. Despite a national safety alert on the issue, a widespread rise in elevated INR test results was not found. Primary care has responded rapidly to changes in patient care during the COVID-19 pandemic.
Publisher: OpenSAFELY
Date: 2021
Abstract: 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.
Publisher: BMJ
Date: 20-07-2022
Abstract: To estimate waning of covid-19 vaccine effectiveness over six months after second dose. Cohort study, approved by NHS England. Linked primary care, hospital, and covid-19 records within the OpenSAFELY-TPP database. Adults without previous SARS-CoV-2 infection were eligible, excluding care home residents and healthcare professionals. People who had received two doses of BNT162b2 or ChAdOx1 (administered during the national vaccine rollout) were compared with unvaccinated people during six consecutive comparison periods, each of four weeks. Adjusted hazard ratios for covid-19 related hospital admission, covid-19 related death, positive SARS-CoV-2 test, and non-covid-19 related death comparing vaccinated with unvaccinated people. Waning vaccine effectiveness was quantified as ratios of adjusted hazard ratios per four week period, separately for subgroups aged ≥65 years, 18-64 years and clinically vulnerable, 40-64 years, and 18-39 years. 1 951 866 and 3 219 349 eligible adults received two doses of BNT162b2 and ChAdOx1, respectively, and 2 422 980 remained unvaccinated. Waning of vaccine effectiveness was estimated to be similar across outcomes and vaccine brands. In the ≥65 years subgroup, ratios of adjusted hazard ratios for covid-19 related hospital admission, covid-19 related death, and positive SARS-CoV-2 test ranged from 1.19 (95% confidence interval 1.14 to 1.24) to 1.34 (1.09 to 1.64) per four weeks. Despite waning vaccine effectiveness, rates of covid-19 related hospital admission and death were substantially lower among vaccinated than unvaccinated adults up to 26 weeks after the second dose, with estimated vaccine effectiveness ≥80% for BNT162b2, and ≥75% for ChAdOx1. By weeks 23-26, rates of positive SARS-CoV-2 test in vaccinated people were similar to or higher than in unvaccinated people (adjusted hazard ratios up to 1.72 (1.11 to 2.68) for BNT162b2 and 1.86 (1.79 to 1.93) for ChAdOx1). The rate at which estimated vaccine effectiveness waned was consistent for covid-19 related hospital admission, covid-19 related death, and positive SARS-CoV-2 test and was similar across subgroups defined by age and clinical vulnerability. If sustained to outcomes of infection with the omicron variant and to booster vaccination, these findings will facilitate scheduling of booster vaccination.
Publisher: Cold Spring Harbor Laboratory
Date: 07-06-2023
DOI: 10.1101/2023.06.06.23290826
Abstract: The COVID-19 pandemic created unprecedented pressure on healthcare services. This study aimed to investigate if disease-modifying anti-rheumatic drug (DMARD) safety monitoring was affected during the COVID-19 pandemic. A population-based cohort study was conducted with the approval of NHS England, using the OpenSAFELY platform to access electronic health record data from 24·2 million patients registered at general practices using TPP’s SystmOne software. Patients were included for further analysis if prescribed azathioprine, leflunomide, or methotrexate between November 2019 and July 2022. Outcomes were assessed as monthly trends and variation between various sociodemographic and clinical groups for adherence with standard safety monitoring recommendations. An acute increase in the rate of missed monitoring occurred across the study population (+12·4 percentage points) when lockdown measures were implemented in March 2020. This increase was more pronounced for some patient groups (70-79 year-olds: +13·7 percentage points females: +12·8 percentage points), regions (North West: +17·0 percentage points), medications (Leflunomide: +20·7 percentage points), and monitoring tests (Blood Pressure: +24·5 percentage points). Missed monitoring rates decreased substantially for all groups by July 2022. Substantial and consistent differences were observed in overall missed monitoring rates between several groups throughout the study. DMARD monitoring rates temporarily deteriorated during the COVID-19 pandemic. Deterioration coincided with the onset of lockdown measures, with monitoring rates recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between medications, tests, regions, and patient groups, highlight opportunities to tackle potential inequalities in the provision or uptake of monitoring services. Further research should aim to evaluate the causes of the differences identified between groups. None. Disease-modifying anti-rheumatic drugs (DMARDs) are immunosuppressive and/or immunomodulatory drugs, which carry risks of serious adverse effects such as gastrointestinal, renal, hepatic, and pulmonary toxicity myelosuppression and increased susceptibility to infection. To mitigate these safety risks, national safety guidance recommends that patients taking these drugs receive regular monitoring. We searched PubMed, Web of Science and Scopus for studies published between database inception and July 28th, 2022, using the terms ([covid-19] AND [monitoring OR shared care OR dmard OR outcome factors] AND [primary care]), with no language restrictions. Studies that investigated the effect of the COVID-19 pandemic on healthcare services were identified. One key study in England showed disruption to various monitoring services in primary care had occurred during the pandemic. Another English study highlighted a disproportionate impact of the COVID-19 pandemic on health outcomes in certain groups. Prior to this study knowledge of how high-risk drugs, such as DMARDs, were affected by the COVID-19 pandemic was limited. This study reports the impact of COVID-19 on the safety monitoring of DMARDs. Moreover, it reports variation in DMARD monitoring rates between demographic, clinical and regional subgroups, which has not yet been described. This is enabled through use of the OpenSAFELY platform, which provides secure access to pseudonymised primary care patient records in England for the purposes of analysing the COVID-19 pandemic impact. DMARD monitoring rates transiently deteriorated during the COVID-19 pandemic, consistent with previous research on other monitoring tests. Deterioration coincided with the onset of lockdown measures, with performance recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between demographic, clinical and regional subgroups highlight opportunities to identify and tackle potential inequalities in the provision or uptake of monitoring services. Further research should aim to evaluate the causes of the differences identified between groups, and establish the clinical relevance of missed monitoring. Several studies have demonstrated the capability of the OpenSAFELY platform as a secure and efficient approach for analysing NHS primary care data at scale, generating meaningful insights on service delivery.
Publisher: Springer Science and Business Media LLC
Date: 24-02-2022
DOI: 10.1186/S41512-022-00120-2
Abstract: Obtaining accurate estimates of the risk of COVID-19-related death in the general population is challenging in the context of changing levels of circulating infection. We propose a modelling approach to predict 28-day COVID-19-related death which explicitly accounts for COVID-19 infection prevalence using a series of sub-studies from new landmark times incorporating time-updating proxy measures of COVID-19 infection prevalence. This was compared with an approach ignoring infection prevalence. The target population was adults registered at a general practice in England in March 2020. The outcome was 28-day COVID-19-related death. Predictors included demographic characteristics and comorbidities. Three proxies of local infection prevalence were used: model-based estimates, rate of COVID-19-related attendances in emergency care, and rate of suspected COVID-19 cases in primary care. We used data within the TPP SystmOne electronic health record system linked to Office for National Statistics mortality data, using the OpenSAFELY platform, working on behalf of NHS England. Prediction models were developed in case-cohort s les with a 100-day follow-up. Validation was undertaken in 28-day cohorts from the target population. We considered predictive performance (discrimination and calibration) in geographical and temporal subsets of data not used in developing the risk prediction models. Simple models were contrasted to models including a full range of predictors. Prediction models were developed on 11,972,947 in iduals, of whom 7999 experienced COVID-19-related death. All models discriminated well between in iduals who did and did not experience the outcome, including simple models adjusting only for basic demographics and number of comorbidities: C-statistics 0.92–0.94. However, absolute risk estimates were substantially miscalibrated when infection prevalence was not explicitly modelled. Our proposed models allow absolute risk estimation in the context of changing infection prevalence but predictive performance is sensitive to the proxy for infection prevalence. Simple models can provide excellent discrimination and may simplify implementation of risk prediction tools.
Publisher: Cold Spring Harbor Laboratory
Date: 30-07-2022
DOI: 10.1101/2022.07.29.22278186
Abstract: The COVID-19 booster vaccination programme in England used both BNT162b2 and mRNA-1273 vaccines. Direct comparisons of the effectiveness against severe COVID-19 of these two vaccines for boosting have not been made in trials or observational data. On behalf of NHS England, we used the OpenSAFELY-TPP database to match adult recipients of each vaccine type on date of vaccination, primary vaccine course, age, and other characteristics. Recipients were eligible if boosted between 29 October 2021 and 31 January 2022, and followed up for 12 weeks. Outcomes were positive SARS-CoV-2 test, COVID-19 hospitalisation, and COVID-19 death. We estimated the cumulative incidence of each outcome, and quantified comparative effectiveness using risk differences (RD) and hazard ratios (HRs). 1,528,431 people were matched in each group, contributing a total 23,150,504 person-weeks of follow-up. The 12-week risks per 1,000 people of positive SARS-CoV-2 test were 103.2 (95%CI 102.4 to 104.0) for BNT162b2 and 96.0 (95.2 to 96.8) for mRNA-1273: the HR comparing mRNA-1273 with BNT162b2 was 0.92 (95%CI 0.91 to 0.92). For COVID-19 hospitalisations the 12-week risks per 1,000 were 0.65 (95%CI 0.56 to 0.75) and 0.44 (0.36 to 0.54): HR 0.67 (95%CI 0.58 to 0.78). COVID-19 deaths were rare: the 12-week risks per 1,000 were 0.03 (95%CI 0.02 to 0.06) and 0.01 (0.01 to 0.02): HR 1.23 (95%CI 0.59 to 2.56). Comparative effectiveness was generally similar within subgroups defined by the primary course vaccine brand, age, prior SARS-CoV-2 infection and clinical vulnerability. Booster vaccination with mRNA-1273 COVID-19 vaccine was more effective than BNT162b2 in preventing SARS-CoV-2 infection and COVID-19 hospitalisation during the first 12 weeks after vaccination, during a period of Delta followed by Omicron variant dominance.
Publisher: Cold Spring Harbor Laboratory
Date: 09-09-2020
DOI: 10.1101/2020.09.04.20187781
Abstract: 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. 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. 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. 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. 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. 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. 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.
Publisher: American College of Physicians
Date: 05-2023
DOI: 10.7326/M21-4269
Publisher: BMJ
Date: 24-02-2021
DOI: 10.1136/BMJ.N135
Abstract: To establish the effect of statins on muscle symptoms in people who had previously reported muscle symptoms when taking statins. Series of randomised, placebo controlled n-of-1 trials. Primary care across 50 sites in the United Kingdom, December 2016 to April 2018. 200 participants who had recently stopped or were considering stopping treatment with statins because of muscle symptoms. Participants were randomised to a sequence of six double blinded treatment periods (two months each) of atorvastatin 20 mg daily or placebo. At the end of each treatment period, participants rated their muscle symptoms on a visual analogue scale (0-10). The primary analysis compared symptom scores in the statin and placebo periods. 151 participants provided symptoms scores for at least one statin period and one placebo period and were included in the primary analysis. Overall, no difference in muscle symptom scores was found between the statin and placebo periods (mean difference statin minus placebo −0.11, 95% confidence interval −0.36 to 0.14 P=0.40)). Withdrawals because of intolerable muscle symptoms were 18 participants (9%) during a statin period and 13 (7%) during a placebo period. Two thirds of those completing the trial reported restarting long term treatment with statins. No overall effect of atorvastatin 20 mg on muscle symptoms compared with placebo was found in participants who had previously reported severe muscle symptoms when taking statins. Most people completing the trial intended to restart treatment with statins. N-of-1 trials can assess drug effects at the group level and guide in idual treatment. ISRCTN30952488 , EUDRACT 2016-000141-31, NCT02781064 .
Publisher: European Centre for Disease Control and Prevention (ECDC)
Date: 18-08-2022
DOI: 10.2807/1560-7917.ES.2022.27.33.2100885
Abstract: Priority patients in England were offered COVID-19 vaccination by mid-April 2021. Codes in clinical record systems can denote the vaccine being declined. We describe records of COVID-19 vaccines being declined, according to clinical and demographic factors. With the approval of NHS England, we conducted a retrospective cohort study between 8 December 2020 and 25 May 2021 with primary care records for 57.9 million patients using OpenSAFELY, a secure health analytics platform. COVID-19 vaccination priority patients were those aged ≥ 50 years or ≥ 16 years clinically extremely vulnerable (CEV) or ’at risk’. We describe the proportion recorded as declining vaccination for each group and stratified by clinical and demographic subgroups, subsequent vaccination and distribution of clinical code usage across general practices. Of 24.5 million priority patients, 663,033 (2.7%) had a decline recorded, while 2,155,076 (8.8%) had neither a vaccine nor decline recorded. Those recorded as declining, who were subsequently vaccinated (n = 125,587 18.9%) were overrepresented in the South Asian population (32.3% vs 22.8% for other ethnicities aged ≥ 65 years). The proportion of declining unvaccinated patients was highest in CEV (3.3%), varied strongly with ethnicity (black 15.3%, South Asian 5.6%, white 1.5% for ≥ 80 years) and correlated positively with increasing deprivation. Clinical codes indicative of COVID-19 vaccinations being declined are commonly used in England, but substantially more common among black and South Asian people, and in more deprived areas. Qualitative research is needed to determine typical reasons for recorded declines, including to what extent they reflect patients actively declining.
Publisher: Cold Spring Harbor Laboratory
Date: 18-10-2021
DOI: 10.1101/2021.10.13.21264937
Abstract: To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and the ChAdOx1 (Oxford-AstraZeneca) COVID-19 vaccines against infection and COVID-19 disease in health and social care workers. Cohort study, emulating a comparative effectiveness trial. Linked primary care, hospital, and COVID-19 surveillance records available within the OpenSAFELY-TPP research platform. 317,341 health and social care workers vaccinated between 4 January and 28 February 2021, registered with a GP practice using the TPP SystmOne clinical information system in England, and not clinically extremely vulnerable. Vaccination with either BNT162b2 or ChAdOx1 administered as part of the national COVID-19 vaccine roll-out. Recorded SARS-CoV-2 positive test, or COVID-19 related Accident and Emergency attendance or hospital admission occurring within 20 weeks of vaccination. The cumulative incidence of each outcome was similar for both vaccines during the first 20 weeks post-vaccination. The cumulative incidence of recorded SARS-CoV-2 infection 6 weeks after vaccination with BNT162b2 was 19.2 per 1000 people (95%CI 18.6 to 19.7) and with ChAdOx1 was 18.9 (95%CI 17.6 to 20.3), representing a difference of -0.24 per 1000 people (95%CI -1.71 to 1.22). The difference in the cumulative incidence per 1000 people of COVID-19 accident and emergency attendance at 6 weeks was 0.01 per 1000 people (95%CI -0.27 to 0.28). For COVID-19 hospital admission, this difference was 0.03 per 1000 people (95%CI -0.22 to 0.27). In this cohort of healthcare workers where we would not anticipate vaccine type to be related to health status, we found no substantial differences in the incidence of SARS-CoV-2 infection or COVID-19 disease up to 20 weeks after vaccination. Incidence dropped sharply after 3-4 weeks and there were very few COVID-19 hospital attendance and admission events after this period. This is in line with expected onset of vaccine-induced immunity, and suggests strong protection against COVID-19 disease for both vaccines.
Publisher: F1000 Research Ltd
Date: 22-12-2021
DOI: 10.12688/WELLCOMEOPENRES.17360.1
Abstract: Background: At the outset of the COVID-19 pandemic, there was no routine comprehensive hospital medicines data from the UK available to researchers. These records can be important for many analyses including the effect of certain medicines on the risk of severe COVID-19 outcomes. With the approval of NHS England, we set out to obtain data on one specific group of medicines, “high-cost drugs” (HCD) which are typically specialist medicines for the management of long-term conditions, prescribed by hospitals to patients. Additionally, we aimed to make these data available to all approved researchers in OpenSAFELY-TPP. This report is intended to support all studies carried out in OpenSAFELY-TPP, and those elsewhere, working with this dataset or similar data. Methods: Working with the North East Commissioning Support Unit and NHS Digital, we arranged for collation of a single national HCD dataset to help inform responses to the COVID-19 pandemic. The dataset was developed from payment submissions from hospitals to commissioners. Results: In the financial year (FY) 2018/19 there were 2.8 million submissions for 1.1 million unique patient IDs recorded in the HCD. The average number of submissions per patient over the year was 2.6. In FY 2019/20 there were 4.0 million submissions for 1.3 million unique patient IDs. The average number of submissions per patient over the year was 3.1. Of the 21 variables in the dataset, three are now available for analysis in OpenSafely-TPP: Financial year and month of drug being dispensed drug name and a description of the drug dispensed. Conclusions: We have described the process for sourcing a national HCD dataset, making these data available for COVID-19-related analysis through OpenSAFELY-TPP and provided information on the variables included in the dataset, data coverage and an initial descriptive analysis.
Publisher: F1000 Research Ltd
Date: 15-10-2020
DOI: 10.12688/WELLCOMEOPENRES.16353.1
Abstract: On March 11th 2020, the World Health Organization characterised COVID-19 as a pandemic. Responses to containing the spread of the virus have relied heavily on policies involving restricting contact between people. Evolving policies regarding shielding and in idual choices about restricting social contact will rely heavily on perceived risk of poor outcomes from COVID-19. In order to make informed decisions, both in idual and collective, good predictive models are required. For outcomes related to an infectious disease, the performance of any risk prediction model will depend heavily on the underlying prevalence of infection in the population of interest. Incorporating measures of how this changes over time may result in important improvements in prediction model performance. This protocol reports details of a planned study to explore the extent to which incorporating time-varying measures of infection burden over time improves the quality of risk prediction models for COVID-19 death in a large population of adult patients in England. To achieve this aim, we will compare the performance of different modelling approaches to risk prediction, including static cohort approaches typically used in chronic disease settings and landmarking approaches incorporating time-varying measures of infection prevalence and policy change, using COVID-19 related deaths data linked to longitudinal primary care electronic health records data within the OpenSAFELY secure analytics platform.
Publisher: Wiley
Date: 25-09-2021
DOI: 10.1002/PDS.5360
Publisher: Cold Spring Harbor Laboratory
Date: 23-03-2022
DOI: 10.1101/2022.03.23.22272804
Abstract: The rate at which COVID-19 vaccine effectiveness wanes over time is crucial for vaccination policies, but is incompletely understood with conflicting results from different studies. This cohort study, using the OpenSAFELY-TPP database and approved by NHS England, included in iduals without prior SARS-CoV-2 infection assigned to vaccines priority groups 2-12 defined by the UK Joint Committee on Vaccination and Immunisation. We compared in iduals who had received two doses of BNT162b2 or ChAdOx1 with unvaccinated in iduals during six 4-week comparison periods, separately for subgroups aged 65+ years 16-64 years and clinically vulnerable 40-64 years and 18-39 years. We used Cox regression, stratified by first dose eligibility and geographical region and controlled for calendar time, to estimate adjusted hazard ratios (aHRs) comparing vaccinated with unvaccinated in iduals, and quantified waning vaccine effectiveness as ratios of aHRs per-4-week period. The outcomes were COVID-19 hospitalisation, COVID-19 death, positive SARS-CoV-2 test, and non-COVID-19 death. The BNT162b2, ChAdOx1 and unvaccinated groups comprised 1,773,970, 2,961,011 and 2,433,988 in iduals, respectively. Waning of vaccine effectiveness was similar across outcomes and vaccine brands: e.g. in the 65+ years subgroup ratios of aHRs versus unvaccinated for COVID-19 hospitalisation, COVID-19 death and positive SARS-CoV-2 test ranged from 1.23 (95% CI 1.15-1.32) to 1.27 (1.20-1.34) for BNT162b2 and 1.16 (0.98-1.37) to 1.20 (1.14-1.27) for ChAdOx1. Despite waning, rates of COVID-19 hospitalisation and COVID-19 death were substantially lower among vaccinated in iduals compared to unvaccinated in iduals up to 26 weeks after second dose, with estimated aHRs .20 ( % vaccine effectiveness) for BNT162b2, and .26 ( %) for ChAdOx1. By weeks 23-26, rates of SARS-CoV-2 infection in fully vaccinated in iduals were similar to or higher than those in unvaccinated in iduals: aHRs ranged from 0.85 (0.78-0.92) to 1.53 (1.07-2.18) for BNT162b2, and 1.21 (1.13-1.30) to 1.99 (1.94-2.05) for ChAdOx1. The rate at which estimated vaccine effectiveness waned was strikingly consistent for COVID-19 hospitalisation, COVID-19 death and positive SARS-CoV-2 test, and similar across subgroups defined by age and clinical vulnerability. If sustained to outcomes of infection with the Omicron variant and to booster vaccination, these findings will facilitate scheduling of booster vaccination doses.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Ben Goldacre.