RESUMEN
BackgroundHealthcare across all sectors, in the UK and globally, was negatively affected by the COVID-19 pandemic. We investigated the effect of the COVID-19 pandemic on the quantity of healthcare services delivered to people with pancreatic cancer. MethodsWith the approval of NHS England, and drawing from a nationally representative OpenSAFELY-TPP dataset of 24 million patients (over 40% of the English population), we undertook a cohort study of people diagnosed with pancreatic cancer. We queried electronic healthcare records for information on the provision of healthcare services across the pancreatic cancer pathway. To estimate the effect of the COVID-19 pandemic, we predicted the rates of healthcare services if the pandemic had not happened. We used generalised linear models (GLM) and the pre-pandemic data from January 2015 to February 2020 to predict rates in March 2020 to September 2022. The 95% confidence intervals of the predicted values were used to estimate the significance of the difference between the predicted and observed rates. ResultsThe rate of pancreatic cancer and diabetes diagnoses in the cohort was not affected by the pandemic. There were 24,500 people diagnosed with pancreatic cancer from January 2015 to September 2022. The mean age at diagnosis was 72 ({+/-}11 SD), 48% of people were female, 95% were of White ethnicity and 39% were diagnosed with diabetes. We found a reduction in surgical resections by nearly 25% during the pandemic. In addition, 20%, 10% and 5% fewer people received BMI, HbA1c and liver function tests respectively before they were diagnosed with pancreatic cancer. There was no impact of the pandemic on the number of people making contact with primary care, but the number of contacts increased on average by 1 to 2 per person amongst those who made contact. Abdominal scans decreased by 7% and reporting of jaundice decreased by 20%, but recovered within six months into the pandemic. Emergency department visits, hospital admissions and deaths were not affected. ConclusionsThe pandemic affected healthcare in England across the pancreatic cancer pathway. Positive lessons could be learnt from services that recovered quickly. The reductions in healthcare experienced by people with cancer have the potential to lead to worse outcomes. Current efforts should focus on addressing the unmet needs of people with cancer.
RESUMEN
BackgroundPatients on kidney replacement therapy (KRT; dialysis and kidney transplantation) are at the highest risk of severe outcomes from COVID-19. Due to limited inclusion of patients on KRT in clinical trials, information is limited on the effectiveness of sotrovimab (a neutralising monoclonal antibody). We sought to address this by comparing its effectiveness against molnupiravir (an antiviral) in preventing severe COVID-19 outcomes in non-hospitalised adults with symptomatic COVID-19. MethodsWith the approval of NHS England we used routine clinical data from 24 million patients in England linked to the UK Renal Registry (UKRR) to identify patients on KRT, and data on antiviral treatments, COVID-19 test results, hospitalisation events and death from the OpenSAFELY-TPP data resource. Cox proportional hazards models (stratified for region) were used to estimate hazard ratios of sotrovimab vs. molnupiravir with regards to COVID-19 related hospitalisation or deaths in the subsequent 28 days (as the primary outcome). Further analyses were conducted using propensity score weighting (adjusted for region) and to investigate robustness of results with regards to different time periods, missing data, and adjustment variables. We also conducted a complementary analysis using data from patients in the Scottish Renal Registry (SRR) treated with sotrovimab or molnupiravir, following similar analytical approaches. ResultsAmong the 2367 renal patients treated with sotrovimab (n=1852) or molnupiravir (n=515) between December 16, 2021 and August 1, 2022 in England, 38 cases (1.6%) of COVID-19 related hospitalisations/deaths were observed during the 28 days of follow-up after treatment initiation, with 21 (1.1%) in the sotrovimab group and 17 (3.3%) in the molnupiravir group. In multiple-adjusted analysis sotrovimab was associated with substantially lower risk of 28-day COVID-19 related hospitalisation/death than treatment with molnupiravir (hazard ratio, HR=0.35, 95% CI: 0.17 to 0.71; P=0.004), with results remaining robust in sensitivity analyses. In the SRR cohort, there were 19 cases (1.9%) of COVID-19 related hospitalisations/deaths during the 28 days of follow-up after treatment initiation of sotrovimab (n=723) or molnupiravir (n=270). In multiple-adjusted analysis, sotrovimab showed a trend toward lower risk of 28-day COVID-19 related hospitalisation/death than treatment with molnupiravir (HR=0.39, 95% CI: 0.13 to 1.21; P=0.106). In both datasets, sotrovimab had no evidence of association with other hospitalisation/death compared with molnupiravir (HRs ranging from 0.73-1.29; P>0.05). ConclusionsIn routine care of non-hospitalised patients with COVID-19 on kidney replacement therapy, those who received sotrovimab had substantially lower risk of severe COVID-19 outcomes than those receiving molnupiravir.
RESUMEN
BackgroundKidney disease is a key risk factor for COVID-19-related mortality and suboptimal vaccine response. Optimising vaccination strategies is essential to reduce the disease burden in this vulnerable population. MethodsWith the approval of NHS England, we performed a retrospective cohort study to estimate the comparative effectiveness of schedules involving AZD1222 (AZ; ChAdOx1-S) and BNT162b2 (BNT) among people with kidney disease. Using linked primary care and UK Renal Registry records in the OpenSAFELY-TPP platform, we identified adults with stage 3- 5 chronic kidney disease, dialysis recipients, and kidney transplant recipients. We used Cox proportional hazards models to compare COVID-19-related outcomes and non-COVID-19 death after two-dose (AZ-AZ vs BNT-BNT) and three-dose (AZ-AZ-BNT vs BNT-BNT- BNT) schedules. FindingsAfter two doses, incidence during the Delta wave was higher in AZ-AZ (n=257,580) than BNT-BNT recipients (n=169,205; adjusted hazard ratios [95% CIs] 1{middle dot}43 [1{middle dot}37-1{middle dot}50], 1{middle dot}59 [1{middle dot}43-1{middle dot}77], 1{middle dot}44 [1{middle dot}12-1{middle dot}85], and 1{middle dot}09 [1{middle dot}02-1{middle dot}17] for SARS-CoV-2 infection, COVID-19-related hospitalisation, COVID-19-related death, and non-COVID-19 death, respectively). Findings were consistent across disease subgroups, including dialysis and transplant recipients. After three doses, there was little evidence of differences between AZ- AZ-BNT (n=220,330) and BNT-BNT-BNT recipients (n=157,065) for any outcome during a period of Omicron dominance. InterpretationAmong individuals with moderate-to-severe kidney disease, two doses of BNT conferred stronger protection than AZ against SARS-CoV-2 infection and severe disease. A subsequent BNT dose levelled the playing field, emphasising the value of heterologous RNA doses in vulnerable populations. FundingNational Core Studies, Wellcome Trust, MRC, and Health Data Research UK. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched Medline for studies published between 1st December 2020 and 7th September 2022 using the following term: "(coronavir* or covid* or sars*) and (vaccin* or immunis* or immuniz*) and (kidney or dialysis or h?emodialysis or transplant or renal) and (efficacy or effectiveness)". We identified studies reporting on the effectiveness of various COVID-19 vaccines in individuals with chronic kidney disease (CKD) or end-stage renal disease. Several studies have reported no clear differences in effectiveness against outcomes of varying severity after two doses of BNT162b2 or AZD1222 compared to unvaccinated controls, which is contrary to the significantly higher antibody levels observed after BNT162b2 in immunogenicity studies. One study also showed that a third dose of RNA vaccine restored some protection against the Omicron variant among BNT162b2- and AZD1222-primed individuals, with no clear differences between these groups. This finding is consistent with immunogenicity data suggesting that a third dose of BNT162b2 may reduce the gap in antibody levels observed after two of AZD1222 versus BNT162b2. Notably, we found few studies directly comparing effectiveness in BNT162b2 versus AZD1222 recipients, which reduces biases associated with comparison to a small and potentially unrepresentative group of unvaccinated controls. We also found no studies exploring COVID-19 vaccine effectiveness in kidney disease groups of varying severity (CKD, dialysis, and kidney transplant). Added value of this studyThis is the largest study to compare the effectiveness of two- and three-dose regimens involving AZD1222 and BNT162b2 among people with moderate-to-severe kidney disease. We compared effectiveness after two and three doses in 426,780 and 377,395 individuals, respectively, and harnessed unique data linkages between primary care records and UK Renal Registry data to identify people with CKD and end-stage renal disease (including dialysis and kidney transplant recipients) with high accuracy. During the Delta wave of infection, we observed a higher risk of COVID-19-related outcomes of varying severity after two doses of AZD1222 versus BNT162b2, with consistent findings in CKD, dialysis, and transplant subgroups. After a third dose of BNT162b2, AZD1222- and BNT162b2-primed individuals had similar rates of COVID-19-related outcomes during a period of Omicron dominance. Implications of all the available evidence A growing body of immunogenicity and effectiveness data - including the present study - suggest that two doses of BNT162b2 confers stronger protection than AZD1222 among people with moderate-to-severe kidney disease. However, a third dose of BNT162b2 appears to compensate for this immunity deficit, providing equivalent protection in BNT162b2- and AZD1222-primed individuals. Achieving high coverage with additional RNA vaccine doses (whether homologous or heterologous) has the capacity to reduce the burden of disease in this vulnerable population.
RESUMEN
ObjectivesTo quantify in absolute and relative terms how population-level COVID-19 death rates have changed in demographic and clinical subgroups. DesignRetrospective cohort study on behalf of NHS England. SettingLinked 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). ParticipantsIn total, 18.7, 18.8, and 18.7 million adults were included for waves 1, 2, and 3 respectively. Main outcome measuresCOVID-19-related mortality based on linked death registry records. ResultsThe crude absolute COVID-19-related death rate per 1,000 person-years decreased from 4.48 in wave 1 (95%CI 4.41;4.55), to 2.70 in wave 2 (95%CI 2.67;2.73), to 0.64 in wave 3 (95%CI 0.63;0.66). 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). ConclusionsCOVID-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.
RESUMEN
BackgroundSince its inception in March 2020, data from the OpenSAFELY-TPP electronic health record platform has been used for more than 50 studies relating to the global COVID-19 emergency. OpenSAFELY-TPP data is derived from practices in England using SystmOne software, and has been used for the majority of these studies. We set out to investigate the representativeness of OpenSAFELY-TPP data by comparing it to national population estimates. MethodsWith the approval of NHS England, we describe the age, sex, Index of Multiple Deprivation and ethnicity of the OpenSAFELY-TPP population compared to national estimates from the Office for National Statistics. The five leading causes of death occurring between the 1st January 2020 and the 31st December 2020 were also compared to deaths registered in England during the same period. ResultsDespite regional variations, TPP is largely representative of the general population of England in terms of IMD (all within 1.1 percentage points), age, sex (within 0.1 percentage points), ethnicity and causes of death. The proportion of the five leading causes of death is broadly similar to those reported by ONS (all within 1 percentage point). ConclusionsData made available via OpenSAFELY-TPP is broadly representative of the English population. SummaryUsers of OpenSAFELY must consider the issues of representativeness, generalisability and external validity associated with using TPP data for health research. Although the coverage of TPP practices varies regionally across England, TPP registered patients are generally representative of the English population as a whole in terms of key demographic characteristics. Key messagesO_LIThere is regional variability across England in terms of key population characteristics C_LIO_LIUsers of OpenSAFELY should carefully consider the issues of representativeness, generalisability and external validity associated with using TPP data for health research. C_LIO_LITPP registered patients are a representative sub-sample of the English population as a whole in terms of age, sex, IMD and ethnicity. C_LIO_LIThe proportions of the five leading causes of death in TPP in 2020 are broadly similar to those reported by ONS. C_LI
RESUMEN
BackgroundKidney disease is a significant risk factor for COVID-19-related mortality. Achieving high COVID-19 vaccine coverage among people with kidney disease is therefore a public health priority. MethodsWith the approval of NHS England, we performed a retrospective cohort study using the OpenSAFELY-TPP platform. Individual-level routine clinical data from 24 million people in England were included. A cohort of individuals with stage 3-5 chronic kidney disease (CKD) or receiving renal replacement therapy (RRT) at the start of the COVID-19 vaccine roll-out was identified based on evidence of reduced estimated glomerular filtration rate or inclusion in the UK Renal Registry. Individual-level factors associated with vaccine uptake were explored via Cox proportional hazards models. Results948,845 people with stage 3-5 CKD or receiving RRT were included. Cumulative vaccine coverage as of 11th May 2022 was 97.5%, 97.0%, and 93.5% for doses 1, 2, and 3, respectively, and 61.1% among individuals with one or more indications for receipt of a fourth dose. Delayed 3-dose vaccine uptake was associated with non-White ethnicity, social deprivation, and severe mental illness - associations that were consistent across CKD stages and in RRT recipients. Similar associations were observed for 4-dose uptake, which was also delayed among care home residents. ConclusionAlthough high primary and booster dose coverage has been achieved among people with kidney disease in England, key disparities in vaccine uptake remain across demographic groups. Identifying how to address these disparities remains a priority to reduce the risk of severe disease in this vulnerable patient group.
RESUMEN
BackgroundLong COVID is a term to describe new or persistent symptoms at least four weeks after onset of acute COVID-19. Clinical codes to describe this phenomenon were released in November 2020 in the UK, but it is not known how these codes have been used in practice. MethodsWorking on behalf of NHS England, we used OpenSAFELY data encompassing 96% of the English population. We measured the proportion of people with a recorded code for long COVID, overall and by demographic factors, electronic health record software system, and week. We also measured variation in recording amongst practices. ResultsLong COVID was recorded for 23,273 people. Coding was unevenly distributed amongst practices, with 26.7% of practices having not used the codes at all. Regional variation was high, ranging between 20.3 per 100,000 people for East of England (95% confidence interval 19.3-21.4) and 55.6 in London (95% CI 54.1-57.1). The rate was higher amongst women (52.1, 95% CI 51.3-52.9) compared to men (28.1, 95% CI 27.5-28.7), and higher amongst practices using EMIS software (53.7, 95% CI 52.9-54.4) compared to TPP software (20.9, 95% CI 20.3-21.4). ConclusionsLong COVID coding in primary care is low compared with early reports of long COVID prevalence. This may reflect under-coding, sub-optimal communication of clinical terms, under-diagnosis, a true low prevalence of long COVID diagnosed by clinicians, or a combination of factors. We recommend increased awareness of diagnostic codes, to facilitate research and planning of services; and surveys of clinicians experiences, to complement ongoing patient surveys.
RESUMEN
BackgroundEarly descriptions of the coronavirus outbreak showed a lower prevalence of asthma and COPD than was expected for people diagnosed with COVID-19, leading to speculation that inhaled corticosteroids (ICS) may protect against infection with SARS-CoV-2, and development of serious sequelae. We evaluated the association between ICS and COVID-19 related death using linked electronic health records in the UK. MethodsWe conducted cohort studies on two groups of people (COPD and asthma) using the OpenSAFELY platform to analyse data from primary care practices linked to national death registrations. People receiving an ICS were compared to those receiving alternative respiratory medications. Our primary outcome was COVID-19 related death. FindingsWe identified 148,588 people with COPD and 817,973 people with asthma receiving relevant respiratory medications in the four months prior to 01 March 2020. People with COPD receiving ICS were at a greater risk of COVID-19 related death compared to those receiving a long-acting beta agonist (LABA) and a long-acting muscarinic antagonist (LAMA) (adjusted HR = 1.38, 95% CI = 1.08 - 1.75). People with asthma receiving high dose ICS were at an increased risk of death compared to those receiving a short-acting beta agonist (SABA) only (adjusted HR = 1.52, 95%CI = 1.08 - 2.14); the adjusted HR for those receiving low-medium dose ICS was 1.10 (95% CI = 0.82 - 1.49). Quantitative bias analyses indicated that an unmeasured confounder of only moderate strength of association with exposure and outcome could explain the observed associations in both populations. InterpretationThese results do not support a major role of ICS in protecting against COVID-19 related deaths. Observed increased risks of COVID-19 related death among people with COPD and asthma receiving ICS can be plausibly explained by unmeasured confounding due to disease severity. FundingThis work was supported by the Medical Research Council MR/V015737/1.
RESUMEN
BackgroundEstablishing 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. Data sourcesPrimary 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. Population17,425,445 adults. Time period1st Feb 2020 to 25th April 2020. Primary outcomeDeath in hospital among people with confirmed COVID-19. MethodsCohort 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. ResultsThere 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). ConclusionsWe 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.
