Permanent URI for this collection

Research ouputs from RD&E staff


Recent Submissions

Now showing 1 - 5 of 116
  • Item
    Omicron BA.1-containing mRNA-1273 boosters compared with the original COVID-19 vaccine in the UK: a randomised, observer-blind, active-controlled trial
    (Elsevier, 2023-09-01) Lee, I. T.; Cosgrove, C. A.; Moore, P.; Bethune, C.; Nally, R.; Bula, M.; Kalra, P. A.; Clark, R.; Dargan, P. I.; Boffito, M.; Sheridan, R.; Moran, E.; Darton, T. C.; Burns, F.; Saralaya, D.; Duncan, C. J. A.; Lillie, P. J.; San Francisco Ramos, A.; Galiza, E. P.; Heath, P. T.; Girard, B.; Parker, C.; Rust, D.; Mehta, S.; de Windt, E.; Sutherland, A.; Tomassini, J. E.; Dutko, F. J.; Chalkias, S.; Deng, W.; Chen, X.; Feng, J.; Tracy, L.; Zhou, H.; Miller, J. M.; Das, R.
    BACKGROUND: The omicron BA.1 bivalent booster is used globally. Previous open-label studies of the omicron BA.1 (Moderna mRNA-1273.214) booster showed superior neutralising antibody responses against omicron BA.1 and other variants compared with the original mRNA-1273 booster. We aimed to compare the safety and immunogenicity of omicron BA.1 monovalent and bivalent boosters with the original mRNA-1273 vaccine in a large, randomised controlled trial. METHODS: In this large, randomised, observer-blind, active-controlled, phase 3 trial in the UK (28 hospital and vaccination clinic sites), individuals aged 16 years or older who had previously received two injections of any authorised or approved COVID-19 vaccine, with or without an mRNA vaccine booster (third dose), were randomly allocated (1:1) using interactive response technology to receive 50 μg omicron BA.1 monovalent or bivalent vaccines or 50 μg mRNA-1273 administered as boosters via deltoid intramuscular injection. The primary outcomes were safety and immunogenicity at day 29, including prespecified non-inferiority and superiority of booster immune responses, based on the neutralising antibody geometric mean concentration (GMC) ratios of the monovalent and bivalent boosters compared with mRNA-1273. Safety was assessed in all participants who received first or second boosters, and primary immunogenicity outcomes were assessed in all participants who received the planned booster dose, had pre-booster and day 29 antibody data, had no major protocol deviations, and who were SARS-CoV-2-negative. The study is registered with EudraCT (2022-000063-51) and (NCT05249829) and is ongoing. FINDINGS: Between Feb 16 and March 24, 2022, 724 participants were randomly allocated to receive omicron BA.1 monovalent (n=366) or mRNA-1273 (n=357), and between April 2 and June 17, 2022, 2824 participants were randomly allocated to receive omicron BA.1 bivalent (n=1418) or mRNA-1273 (n=1395) vaccines as second boosters. Median durations (months) between the most recent COVID-19 vaccine and study boosters were similar for omicron BA.1 monovalent (4·0 months [IQR 3·6-4·7]) and mRNA-1273 (4·1 [3·5-4·7]), and for the omicron BA.1 bivalent (5·5 [4·8-6·2]) and mRNA-1273 (5·4 [4·8-6·2]) boosters. The omicron BA.1 monovalent and bivalent boosters elicited superior neutralising GMCs against the omicron BA.1 variant compared with mRNA-1273, with GMC ratios of 1·68 (99% CI 1·45-1·95) and 1·53 (1·41-1·67) at day 29 post-booster doses in participants without previous SARS-CoV-2 infection. Both boosters induced non-inferior ancestral SARS-CoV-2 (Asp614Gly) immune responses with GMCs that were similar for the bivalent (2987·2 [95% CI 2814·9-3169·9]) versus mRNA-1273 (2911·3 [2750·9-3081·0]) and lower for the monovalent (2699·7 [2431·3-2997·7] vs 3020·6 [2776·5-3286·2]) boosters, with respective GMC ratios of 1·05 (99% CI 0·96-1·15) and 0·82 (95% CI 0·74-0·91). Results were comparable regardless of previous SARS-CoV-2 infection status. Incidences of solicited adverse reactions with the omicron BA.1 monovalent (335 [91·3%] of 367 participants) and omicron BA.1 bivalent (1285 [90·4%] of 1421 participants) boosters were similar to those observed previously for mRNA-1273, with no new safety concerns identified and no occurrences of fatal adverse events. INTERPRETATION: Omicron-containing booster vaccines generated superior immunogenicity against omicron BA.1 and comparable immunogenicity against the original strain with no new safety concerns. It remains important to continuously monitor the immune responses and real-world vaccine effectiveness as divergent SARS-CoV-2 variants emerge. FUNDING: Moderna.
  • Item
    OpenSAFELY NHS Service Restoration Observatory 2: changes in primary care clinical activity in England during the COVID-19 pandemic
    (Royal College of General Practitioners, 2023-05-01) Curtis, H. J.; MacKenna, B.; Wiedemann, M.; Fisher, L.; Croker, R.; Morton, C. E.; Inglesby, P.; Walker, A. J.; Morley, J.; Mehrkar, A.; Bacon, S. C.; Hickman, G.; Evans, D.; Ward, T.; Davy, S.; Hulme, W. J.; Macdonald, O.; Conibere, R.; Lewis, T.; Myers, M.; Wanninayake, S.; Collison, K.; Drury, C.; Samuel, M.; Sood, H.; Cipriani, A.; Fazel, S.; Sharma, M.; Baqir, W.; Bates, C.; Parry, J.; Goldacre, B.
    BACKGROUND: The COVID-19 pandemic has disrupted healthcare activity across a broad range of clinical services. The NHS stopped non-urgent work in March 2020, later recommending services be restored to near-normal levels before winter where possible. AIM: To describe changes in the volume and variation of coded clinical activity in general practice across six clinical areas: cardiovascular disease, diabetes, mental health, female and reproductive health, screening and related procedures, and processes related to medication. DESIGN AND SETTING: With the approval of NHS England, a cohort study was conducted of 23.8 million patient records in general practice, in situ using OpenSAFELY. METHOD: Common primary care activities were analysed using Clinical Terms Version 3 codes and keyword searches from January 2019 to December 2020, presenting median and deciles of code usage across practices per month. RESULTS: Substantial and widespread changes in clinical activity in primary care were identified since the onset of the COVID-19 pandemic, with generally good recovery by December 2020. A few exceptions showed poor recovery and warrant further investigation, such as mental health (for example, for 'Depression interim review' the median occurrences across practices in December 2020 was down by 41.6% compared with December 2019). CONCLUSION: Granular NHS general practice data at population-scale can be used to monitor disruptions to healthcare services and guide the development of mitigation strategies. The authors are now developing real-time monitoring dashboards for the key measures identified in this study, as well as further studies using primary care data to monitor and mitigate the indirect health impacts of COVID-19 on the NHS.
  • Item
    Differential impact of COVID-19 on mental health and burnout
    (Oxford University Press, 2023-04-01) Maniero, C.; Ng, S. M.; Collett, G.; Godec, T.; Siddiqui, I.; Antoniou, S.; Kumar, A.; Janmohamed, A.; Nair, S.; Kotecha, A.; Khan, R.; Khanji, M. Y.; Kapil, V.; Gupta, J.; Gupta, A. K.
    BACKGROUND: There may be differential impact of the COVID-19 pandemic on mental health and burnout rates of healthcare professionals (HCPs) performing different roles. AIMS: To examine mental health and burnout rates, and possible drivers for any disparities between professional roles. METHODS: In this cohort study, online surveys were distributed to HCPs in July-September 2020 (baseline) and re-sent 4 months later (follow-up; December 2020) assessing for probable major depressive disorder (MDD), generalized anxiety disorder (GAD), insomnia, mental well-being and burnout (emotional exhaustion and depersonalization). Separate logistic regression models (at both phases) compared the risk of outcomes between roles: healthcare assistants (HCAs), nurses and midwives (nurses), allied health professionals (AHPs) and doctors (reference group). Separate linear regression models were also developed relating the change in scores to professional role. RESULTS: At baseline (n = 1537), nurses had a 1.9-fold and 2.5-fold increased risk of MDD and insomnia, respectively. AHPs had a 1.7-fold and 1.4-fold increased risk of MDD and emotional exhaustion, respectively. At follow-up (n = 736), the disproportionate risk between doctors and others worsened: nurses and HCAs were at 3.7-fold and 3.6-fold increased risk of insomnia, respectively. Nurses also had a significantly increased risk of MDD, GAD, poor mental well-being and burnout. Nurses also had significantly worsened anxiety, mental well-being and burnout scores over time, relative to doctors. CONCLUSIONS: Nurses and AHPs had excess risk of adverse mental health and burnout during the pandemic, and this difference worsened over time (in nurses especially). Our findings support adoption of targeted strategies accounting for different HCP roles.
  • Item
    Eleven key measures for monitoring general practice clinical activity during COVID-19: A retrospective cohort study using 48 million adults' primary care records in England through OpenSAFELY
    (eLife Sciences Publications Ltd., 2023-07-01) Fisher, L.; Curtis, H. J.; Croker, R.; Wiedemann, M.; Speed, V.; Wood, C.; Brown, A.; Hopcroft, L. E. M.; Higgins, R.; Massey, J.; Inglesby, P.; Morton, C. E.; Walker, A. J.; Morley, J.; Mehrkar, A.; Bacon, S.; Hickman, G.; Macdonald, O.; Lewis, T.; Wood, M.; Myers, M.; Samuel, M.; Conibere, R.; Baqir, W.; Sood, H.; Drury, C.; Collison, K.; Bates, C.; Evans, D.; Dillingham, I.; Ward, T.; Davy, S.; Smith, R. M.; Hulme, W.; Green, A.; Parry, J.; Hester, F.; Harper, S.; Cockburn, J.; O'Hanlon, S.; Eavis, A.; Jarvis, R.; Avramov, D.; Griffiths, P.; Fowles, A.; Parkes, N.; MacKenna, B.; Goldacre, B.
    BACKGROUND: The COVID-19 pandemic has had a significant impact on delivery of NHS care. We have developed the OpenSAFELY Service Restoration Observatory (SRO) to develop key measures of primary care activity and describe the trends in these measures throughout the COVID-19 pandemic. METHODS: With the approval of NHS England, we developed an open source software framework for data management and analysis to describe trends and variation in clinical activity across primary care electronic health record (EHR) data on 48 million adults.We developed SNOMED-CT codelists for key measures of primary care clinical activity such as blood pressure monitoring and asthma reviews, selected by an expert clinical advisory group and conducted a population cohort-based study to describe trends and variation in these measures January 2019-December 2021, and pragmatically classified their level of recovery one year into the pandemic using the percentage change in the median practice level rate. RESULTS: We produced 11 measures reflective of clinical activity in general practice. A substantial drop in activity was observed in all measures at the outset of the COVID-19 pandemic. By April 2021, the median rate had recovered to within 15% of the median rate in April 2019 in six measures. The remaining measures showed a sustained drop, ranging from a 18.5% reduction in medication reviews to a 42.0% reduction in blood pressure monitoring. Three measures continued to show a sustained drop by December 2021. CONCLUSIONS: The COVID-19 pandemic was associated with a substantial change in primary care activity across the measures we developed, with recovery in most measures. We delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. We will continue to expand the set of key measures to be routinely monitored using our publicly available NHS OpenSAFELY SRO dashboards with near real-time data. FUNDING: This research used data assets made available as part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058).The OpenSAFELY Platform is supported by grants from the Wellcome Trust (222097/Z/20/Z); MRC (MR/V015757/1, MC_PC-20059, MR/W016729/1); NIHR (NIHR135559, COV-LT2-0073), and Health Data Research UK (HDRUK2021.000, 2021.0157).
  • Item
    Impact of the COVID-19 Pandemic on Outcomes for Patients with Lung Cancer Receiving Curative-intent Radiotherapy in the UK
    (Elsevier, 2023-07-01) Fornacon-Wood, I.; Banfill, K.; Ahmad, S.; Britten, A.; Carson, C.; Dorey, N.; Hatton, M.; Hiley, C.; Thippu Jayaprakash, K.; Jegannathen, A.; Kidd, A. C.; Koh, P.; Panakis, N.; Peedell, C.; Peters, A.; Pope, A.; Powell, C.; Stilwell, C.; Thomas, B.; Toy, E.; Wicks, K.; Wood, V.; Yahya, S.; Price, G.; Faivre-Finn, C.
    AIMS: Previous work found that during the first wave of the COVID-19 pandemic, 34% of patients with lung cancer treated with curative-intent radiotherapy in the UK had a change to their centre's usual standard of care treatment (Banfill et al. Clin Oncol 2022;34:19-27). We present the impact of these changes on patient outcomes. MATERIALS AND METHODS: The COVID-RT Lung database was a prospective multicentre UK cohort study including patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between April and October 2020. Data were collected on patient demographics, radiotherapy and systemic treatments, toxicity, relapse and death. Multivariable Cox and logistic regression were used to assess the impact of having a change to radiotherapy on survival, distant relapse and grade ≥3 acute toxicity. The impact of omitting chemotherapy on survival and relapse was assessed using multivariable Cox regression. RESULTS: Patient and follow-up forms were available for 1280 patients. Seven hundred and sixty-five (59.8%) patients were aged over 70 years and 603 (47.1%) were female. The median follow-up was 213 days (119, 376). Patients with stage I-II non-small cell lung cancer (NSCLC) who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.859) or death (P = 0.884); however, they did have increased odds of grade ≥3 acute toxicity (P = 0.0348). Patients with stage III NSCLC who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.216) or death (P = 0.789); however, they did have increased odds of grade ≥3 acute toxicity (P < 0.001). Patients with stage III NSCLC who had their chemotherapy omitted had no significant increase in distant relapse (P = 0.0827) or death (P = 0.0661). CONCLUSION: This study suggests that changes to radiotherapy and chemotherapy made in response to the COVID-19 pandemic did not significantly affect distant relapse or survival. Changes to radiotherapy, namely increased hypofractionation, led to increased odds of grade ≥3 acute toxicity. These results are important, as hypofractionated treatments can help to reduce hospital attendances in the context of potential future emergency situations.