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Background/Aims The impact of the pandemic on the incidence and management of inflammatory arthritis (IA) is not understood. Routinely-captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how IA was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for IA in England, and replicate key metrics from the National Early Inflammatory Arthritis Audit. Methods With the approval of NHS England, we used primary care and hospital data for 17 million adults registered with general practices using TPP health record software, to explore the following outcomes between 1 April 2019 and 31 March 2022: 1) incidence of IA diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, undifferentiated IA) recorded in primary care; 2) time to first rheumatology assessment; 3) time to first prescription of a conventional synthetic DMARD (csDMARD) in primary care, and choice of first csDMARD. Results From 17,683,500 adults (representing 40% of the English population), there were 31,280 incident IA diagnoses recorded between April 2019 and March 2022. New IA diagnoses decreased by 39.7% in the early months of the pandemic. Overall, a 20.3% decrease in IA diagnoses was seen in the year commencing April 2020, relative to the preceding year (5.1 vs. 6.4 diagnoses per 10,000 adults, respectively). Further decreases coincided with rising COVID-19 numbers, before returning to pre-pandemic levels by the end of the study period. No rebound increase in IA incidence was observed as of April 2022. The median time from referral to first rheumatology assessment was shorter during the pandemic (18 days; IQR 8-35 days) than before (21 days; 9-41 days). The proportion of patients prescribed csDMARDs in primary care was comparable to before the pandemic; however, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine. Conclusion IA diagnoses decreased markedly during the early phase of the pandemic; however, the impact on rheumatology assessment times and DMARD prescribing was less marked than might have been anticipated. This study demonstrates the feasibility of using routinely-captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection. Disclosure M.D. Russell: Honoraria; Lilly, Menarini, Biogen. Other; Lilly, Pfizer, Janssen, UCB. J.B. Galloway: Honoraria; Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi, UCB. C.D. Andrews: None. B. MacKenna: None. B. Goldacre: Grants/research support; Laura and John Arnold Foundation, NIHR, Mohn-Westlake Foundation, Wellcome Trust, Good Thinking Foundation, Health Data Research UK, Health Foundation, World Health Organisation, UKRI, Asthma UK, British Lung Foundation, and National Core Studies programme. A. Mehrkar: Other; Former employee and interim CMO of NHS Digital, and RCGP representative on GP Data Professional Advisory Group to NHS Digital. H.J. Curtis: None. B. Butler-Cole: None. T. O'Dwyer: None. S. Qureshi: Grants/research support; BMS. J.M. Ledingham: Other; Clinical director for NEIAA, Secretary for The Federation of Joint Royal Colleges of Physicians SCE Board, and trustee of the BSR. A. Mahto: Honoraria; Abbvie, Galapagos. Other; Lilly. A.I. Rutherford: Other; Lilly. M.A. Adas: None. E. Alveyn: None. S. Norton: None. A.P. Cope: Consultancies; BMS, Abbvie, GSK/Galvini. Member of speakers’ bureau; BMS, Abbvie. Grants/research support; BMS. Other; Executive committee of the EULAR research centre. K. Bechman: Grants/research support; Versus Arthritis and Pfizer Global Medical Grants.

The impact of the COVID-19 pandemic on the incidence and management of inflammatory arthritis is not understood. Routinely captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how care for patients with inflammatory arthritis was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for inflammatory arthritis in England and to replicate key metrics from the National Early Inflammatory Arthritis Audit.In this population-level cohort study, we used primary care and hospital data for 17·7 million adults registered with general practices using TPP health record software, to explore the following outcomes between April 1, 2019, and March 31, 2022: (1) incidence of inflammatory arthritis diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and undifferentiated inflammatory arthritis) recorded in primary care; (2) time to first rheumatology assessment; (3) time to first prescription of a disease-modifying antirheumatic drug (DMARD) in primary care; and (4) choice of first DMARD.Among 17 683 500 adults, there were 31 280 incident inflammatory arthritis diagnoses recorded between April 1, 2019, and March 31, 2022. The mean age of diagnosed patients was 55·4 years (SD 16·6), 18 615 (59·5%) were female, 12 665 (40·5%) were male, and 22 925 (88·3%) of 25 960 with available ethnicity data were White. New inflammatory arthritis diagnoses decreased by 20·3% in the year commencing April, 2020, relative to the preceding year (5·1Inflammatory arthritis diagnoses decreased markedly during the early phase of the pandemic. The impact on rheumatology assessment times and DMARD prescribing in primary care was less marked than might have been anticipated. This study demonstrates the feasibility of using routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection.None.

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 messagesThere is regional variability across England in terms of key population characteristicsUsers of OpenSAFELY should carefully consider the issues of representativeness, generalisability and external validity associated with using TPP data for health research.TPP registered patients are a representative sub-sample of the English population as a whole in terms of age, sex, IMD and ethnicity.The proportions of the five leading causes of death in TPP in 2020 are broadly similar to those reported by ONS.

Objective To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and mRNA-1273 (Moderna) covid-19 vaccines during the booster programme in England. Design Matched cohort study, emulating a comparative effectiveness trial. Setting Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 delta and omicron variants were dominant. Participants 3 237 918 adults who received a booster dose of either vaccine between 29 October 2021 and 25 February 2022 as part of the national booster programme in England and who received a primary course of BNT162b2 or ChAdOx1. Intervention Vaccination with either BNT162b2 or mRNA-1273 as a booster vaccine dose. Main outcome measures Recorded SARS-CoV-2 positive test, covid-19 related hospital admission, covid-19 related death, and non-covid-19 related death at 20 weeks after receipt of the booster dose. Results 1 618 959 people were matched in each vaccine group, contributing a total 64 546 391 person weeks of follow-up. The 20 week risks per 1000 for a positive SARS-CoV-2 test were 164.2 (95% confidence interval 163.3 to 165.1) for BNT162b2 and 159.9 (159.0 to 160.8) for mRNA-1273; the hazard ratio comparing mRNA-1273 with BNT162b2 was 0.95 (95% confidence interval 0.95 to 0.96). The 20 week risks per 1000 for hospital admission with covid-19 were 0.75 (0.71 to 0.79) for BNT162b2 and 0.65 (0.61 to 0.69) for mRNA-1273; the hazard ratio was 0.89 (0.82 to 0.95). Covid-19 related deaths were rare: the 20 week risks per 1000 were 0.028 (0.021 to 0.037) for BNT162b2 and 0.024 (0.018 to 0.033) for mRNA-1273; hazard ratio 0.83 (0.58 to 1.19). Comparative effectiveness was generally similar within subgroups defined by the primary course vaccine brand, age, previous SARS-CoV-2 infection, and clinical vulnerability. Relative benefit was similar when vaccines were compared separately in the delta and omicron variant eras. Conclusions This matched observational study of adults estimated a modest benefit of booster vaccination with mRNA-1273 compared with BNT162b2 in preventing positive SARS-CoV-2 tests and hospital admission with covid-19 20 weeks after vaccination, during a period of delta followed by omicron variant dominance.

Publisher Copyright: © 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged

Background: The coronavirus disease 2019 (COVID-19) vaccination programme in England was extended to include all adolescents and children by April 2022. The aim of this paper is to describe trends and variation in vaccine coverage in different clinical and demographic groups amongst adolescents and children in England. Methods: With the approval of NHS England, a cohort study was conducted of 3.21 million children and adolescents’ records in general practice in England, in situ and within the infrastructure of the electronic health record software vendor TPP using OpenSAFELY. Vaccine coverage across various demographic (sex, deprivation index and ethnicity) and clinical (risk status) populations is described. Results: Coverage is higher amongst adolescents than it is amongst children, with 53.5% adolescents and 10.8% children having received their first dose of the COVID-19 vaccine. Within those groups, coverage varies by ethnicity, deprivation index and risk status; there is no evidence of variation by sex. Conclusion: First dose COVID-19 vaccine coverage is shown to vary amongst various demographic and clinical groups of children and adolescents.

ObjectiveTo ascertain patient eligibility status and describe coverage of antiviral drugs and neutralising monoclonal antibodies (nMAB) as treatment for covid-19 in community settings in England.DesignRetrospective, descriptive cohort study, approved by NHS England.SettingRoutine clinical data from 23.4 million people linked to data on covid-19 infection and treatment, within the OpenSAFELY-TPP database.ParticipantsOutpatients with covid-19 at high risk of severe outcomes.InterventionsNirmatrelvir/ritonavir (paxlovid), sotrovimab, molnupiravir, casirivimab/imdevimab, or remdesivir, used in the community by covid-19 medicine delivery units.Results93 870 outpatients with covid-19 were identified between 11 December 2021 and 28 April 2022 to be at high risk of severe outcomes and therefore potentially eligible for antiviral or nMAB treatment (or both). Of these patients, 19 040 (20%) received treatment (sotrovimab, 9660 (51%); molnupiravir, 4620 (24%); paxlovid, 4680 (25%); casirivimab/imdevimab, 50 (ConclusionsUsing the OpenSAFELY platform, we were able to identify patients with covid-19 at high risk of severe outcomes who were potentially eligible to receive treatment and assess the coverage of these new treatments among these patients. In the context of a rapid deployment of a new service, the NHS analytical code used to determine eligibility could have been over-inclusive and some of the eligibility criteria not fully captured in healthcare data. However targeted activity might be needed to resolve apparent lower treatment coverage observed among certain groups, in particular (at present): different NHS regions, ethnic groups, people aged ≥80 years, those living in socioeconomically deprived areas, and care home residents.

Colm D Andrews,1,2 Aislin A Sheldon,3 Holly Bridge,3 Susan M Downes,2,4 Robert E MacLaren,2,4 Jasleen K Jolly2– 5 1Nuffield Department of Population Health, University of Oxford, Oxford, UK; 2Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; 3Oxford Centre for Functional MRI of the Brain (FMRIB), Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, UK; 4Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 5Vision and Eye Research Institute, Anglia Ruskin University, Cambridge, UKCorrespondence: Jasleen K Jolly, Vision and Eye Research Institute, School of Medicine, Anglia Ruskin University, Young Street, Cambridge, CB1 2LZ, UK, Email jasleen.jolly@aru.ac.ukPurpose: We aimed to assess the performance of the modified-Esterman test (mET) as a rapid suprathreshold binocular quantification tool for the assessment of peripheral visual fields. The mET consists of an even spread of test points across the visual field.Materials and Methods: The mET was implemented on the Octopus 0900 perimeter using the Open Perimetry Interface (OPI) and consisted of 160 points. Patients with choroideremia, a rod-cone dystrophy, Stargardt disease, a cone-rod dystrophy, and healthy volunteers underwent both the mET and the standard Esterman tests twice. Disease severity (mild/moderate/severe) was graded on both tests independently. Voronoi tessellation was utilised to compare the tests.Results: The Voronoi visualisation was able to demonstrate that the mET was able to provide more information about the disease state at all stages of diseases. This was confirmed by the agreement statistic, which showed that the mET detected 27% more points of visual field loss compared to the Esterman test, being most useful in patients with rod-cone dystrophies.Conclusion: The mET provides a speedy quantitative measure of the peripheral visual field loss, which can be used in clinical trials to monitor longitudinal assessment of peripheral visual function. The mET provides a more even coverage across the visual field compared to the Esterman test points, making it more suitable for this purpose. This is a key part of safety monitoring in retinal clinical trials. The mET can easily be implemented on commercially available perimeters that allow Open Perimetry.Keywords: visual field, functional testing, screening, Stargardt disease, choroideremia

Background/Aim To report the efficacy and tolerability of antitumour necrosis factor-alpha therapy (TNF inhibitors [TNFi]) in the management of non-infectious ocular inflammation, including uveitis and scleritis, in adult patients over an 8-year period.Materials and methods This is a prospective cohort study of infliximab and adalimumab in the treatment of non-infectious ocular inflammatory disease. 43 of 85 adult patients on TNFi (34 infliximab, 9 adalimumab) for ≥1 year with non-infectious uveitis or scleritis were followed from 2006 to 2014. Clinical assessments, medication, adverse events and history of steroid rescues were collected at 6 monthly intervals. General quality of life (Short Form Health Survey (SF-36)) and visual quality of life (Vision-related quality of life Core Measure (VCM1)) were assessed annually. Outcome measures included rate of sustained remission, rate of relapse, systemic corticosteroid reduction, adverse events, and VCM1 and SF-36 scores.Results The median time on infliximab was 3.2 years (IQR 4.3) and on adalimumab was 2.4 years (IQR 1.8). Sustained remission was induced in 39 patients (91%) (0.5 per patient year) after a median of 1.2 years on a TNFi. 22 (51%) experienced one relapse, and 5 (12%) had two relapses. 23 (54%) had at least one adverse event; serious adverse events necessitating hospitalisation or cessation of medication occurred in four (9%) patients. 10 patients (23%) switched from the initiation of TNFi, at 1.7 years after starting, to another TNFi or another class of biologic therapy.Conclusion TNFi treatment is associated with long-term drug-induced remission of ocular inflammation, visual stability and corticosteroid reduction. Adverse events were common and no new safety signals occurred. Relapse of inflammation occurs in half of the treated population.This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.