ORCID Profile
0000-0002-0102-3453
Current Organisations
The Academy of Medical Sciences
,
Faculty of Public Health
,
University of Oxford
,
Royal College of General Practitioners
,
National Institute for Health Research
,
National Institute for Social Care and Health Research
,
Medical Research Council
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Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: European Respiratory Society (ERS)
Date: 04-2019
Publisher: Elsevier BV
Date: 08-2017
Publisher: John Wiley & Sons, Ltd
Date: 22-04-2003
Publisher: JMIR Publications Inc.
Date: 02-07-2020
DOI: 10.2196/19773
Abstract: Routinely recorded primary care data have been used for many years by sentinel networks for surveillance. More recently, real world data have been used for a wider range of research projects to support rapid, inexpensive clinical trials. Because the partial national lockdown in the United Kingdom due to the coronavirus disease (COVID-19) pandemic has resulted in decreasing community disease incidence, much larger numbers of general practices are needed to deliver effective COVID-19 surveillance and contribute to in-pandemic clinical trials. The aim of this protocol is to describe the rapid design and development of the Oxford Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID) and its first two platforms. The Surveillance Platform will provide extended primary care surveillance, while the Trials Platform is a streamlined clinical trials platform that will be integrated into routine primary care practice. We will apply the FAIR (Findable, Accessible, Interoperable, and Reusable) metadata principles to a new, integrated digital health hub that will extract routinely collected general practice electronic health data for use in clinical trials and provide enhanced communicable disease surveillance. The hub will be findable through membership in Health Data Research UK and European metadata repositories. Accessibility through an online application system will provide access to study-ready data sets or developed custom data sets. Interoperability will be facilitated by fixed linkage to other key sources such as Hospital Episodes Statistics and the Office of National Statistics using pseudonymized data. All semantic descriptors (ie, ontologies) and code used for analysis will be made available to accelerate analyses. We will also make data available using common data models, starting with the US Food and Drug Administration Sentinel and Observational Medical Outcomes Partnership approaches, to facilitate international studies. The Surveillance Platform will provide access to data for health protection and promotion work as authorized through agreements between Oxford, the Royal College of General Practitioners, and Public Health England. All studies using the Trials Platform will go through appropriate ethical and other regulatory approval processes. The hub will be a bottom-up, professionally led network that will provide benefits for member practices, our health service, and the population served. Data will only be used for SQUIRE (surveillance, quality improvement, research, and education) purposes. We have already received positive responses from practices, and the number of practices in the network has doubled to over 1150 since February 2020. COVID-19 surveillance has resulted in tripling of the number of virology sites to 293 (target 300), which has aided the collection of the largest ever weekly total of surveillance swabs in the United Kingdom as well as over 3000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology s les. Practices are recruiting to the PRINCIPLE (Platform Randomised trial of INterventions against COVID-19 In older PeopLE) trial, and these participants will be followed up through ORCHID. These initial outputs demonstrate the feasibility of ORCHID to provide an extended national digital health hub. ORCHID will provide equitable and innovative use of big data through a professionally led national primary care network and the application of FAIR principles. The secure data hub will host routinely collected general practice data linked to other key health care repositories for clinical trials and support enhanced in situ surveillance without always requiring large volume data extracts. ORCHID will support rapid data extraction, analysis, and dissemination with the aim of improving future research and development in general practice to positively impact patient care. DERR1-10.2196/19773
Publisher: JMIR Publications Inc.
Date: 19-02-2021
DOI: 10.2196/24341
Abstract: The Oxford–Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) and Public Health England (PHE) are commencing their 54th season of collaboration at a time when SARS-CoV-2 infections are likely to be cocirculating with the usual winter infections. The aim of this study is to conduct surveillance of influenza and other monitored respiratory conditions and to report on vaccine uptake and effectiveness using nationally representative surveillance data extracted from primary care computerized medical records systems. We also aim to have general practices collect virology and serology specimens and to participate in trials and other interventional research. The RCGP RSC network comprises over 1700 general practices in England and Wales. We will extract pseudonymized data twice weekly and are migrating to a system of daily extracts. First, we will collect pseudonymized, routine, coded clinical data for the surveillance of monitored and unexpected conditions data on vaccine exposure and adverse events of interest and data on approved research study outcomes. Second, we will provide dashboards to give general practices feedback about levels of care and data quality, as compared to other network practices. We will focus on collecting data on influenza-like illness, upper and lower respiratory tract infections, and suspected COVID-19. Third, approximately 300 practices will participate in the 2020-2021 virology and serology surveillance this will include responsive surveillance and long-term follow-up of previous SARS-CoV-2 infections. Fourth, member practices will be able to recruit volunteer patients to trials, including early interventions to improve COVID-19 outcomes and point-of-care testing. Lastly, the legal basis for our surveillance with PHE is Regulation 3 of the Health Service (Control of Patient Information) Regulations 2002 other studies require appropriate ethical approval. The RCGP RSC network has tripled in size there were previously 100 virology practices and 500 practices overall in the network and we now have 322 and 1724, respectively. The Oxford–RCGP Clinical Informatics Digital Hub (ORCHID) secure networks enable the daily analysis of the extended network currently, 1076 practices are uploaded. We are implementing a central swab distribution system for patients self-swabbing at home in addition to in-practice s ling. We have converted all our primary care coding to Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) coding. Throughout spring and summer 2020, the network has continued to collect specimens in preparation for the winter or for any second wave of COVID-19 cases. We have collected 5404 swabs and detected 623 cases of COVID-19 through extended virological s ling, and 19,341 s les have been collected for serology. This shows our preparedness for the winter season. The COVID-19 pandemic has been associated with a groundswell of general practices joining our network. It has also created a permissive environment in which we have developed the capacity and capability of the national primary care surveillance systems and our unique public health institute, the RCGP and University of Oxford collaboration.
Publisher: Wiley
Date: 18-01-2012
Publisher: Royal College of General Practitioners
Date: 26-07-2021
Abstract: The Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE) has provided in-pandemic evidence that azithromycin and doxycycline were not beneficial in the early primary care management of coronavirus 2019 disease (COVID-19). To explore the extent of in-pandemic azithromycin and doxycycline use, and the scope for trial findings impacting on practice. Crude rates of prescribing and respiratory tract infections (RTI) in 2020 were compared with 2019, using the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). Negative binomial models were used to compare azithromycin and doxycycline prescribing, lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), and influenza-like illness (ILI) in 2020 with 2019 reporting incident rate ratios (IRR) between years, and 95% confidence intervals (95% CI). Azithromycin prescriptions increased 7% in 2020 compared with 2019, whereas doxycycline decreased by 7%. Concurrently, LRTI and URTI incidence fell by over half (58.3% and 54.4%, respectively) while ILI rose slightly (6.4%). The overall percentage of RTI-prescribed azithromycin rose from 0.51% in 2019 to 0.72% in 2020 (risk difference 0.214% 95% CI = 0.211 to 0.217) doxycycline rose from 11.86% in 2019 to 15.79% in 2020 (risk difference 3.93% 95% CI = 3.73 to 4.14). The adjusted IRR showed azithromycin prescribing was 22% higher in 2020 (IRR = 1.22 95% CI = 1.19 to 1.26 P .0001). For every unit rise in confirmed COVID-19 there was an associated 3% rise in prescription (IRR = 1.03 95% CI = 1.02 to 1.03 P .0001) whereas these measures were static for doxycycline. PRINCIPLE demonstrates scope for improved antimicrobial stewardship during a pandemic.
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.PUHE.2019.07.005
Abstract: The public and patients are primary contributors and beneficiaries of pandemic-relevant clinical research. However, their views on research participation during a pandemic have not been systematically studied. We aimed to understand public views regarding participation in clinical research during a hypothetical influenza pandemic. This is an international cross-sectional survey. We surveyed the views of nationally representative s les of people in Belgium, Poland, Spain, Ireland, the United Kingdom, Canada, Australia and New Zealand, using a scenario-based instrument during the 2017 regional influenza season. Descriptive and regression analyses were conducted. Of the 6804 respondents, 5572 (81.8%) thought pandemic-relevant research was important, and 5089 (74.8%) thought 'special rules' should be applied to make this research feasible. The respondents indicated willingness to take part in lower risk (4715, 69.3%) and higher risk (3585, 52.7%) primary care and lower risk (4780, 70.3%) and higher risk (4113, 60.4%) intensive care unit (ICU) study scenarios. For primary care studies, most (3972, 58.4%) participants preferred standard enrolment procedures such as prospective written informed consent, but 2327 (34.2%) thought simplified procedures would be acceptable. For ICU studies, 2800 (41.2%) preferred deferred consent, and 2623 (38.6%) preferred prospective third-party consent. Greater knowledge about pandemics, trust in a health professional, trust in the government, therapeutic misconception and having had ICU experience as a patient or carer predicted increased willingness to participate in pandemic-relevant research. Our study indicates current public support for pandemic-relevant clinical research. Tailored information and initiatives to advance research literacy and maintain trust are required to support pandemic-relevant research participation and engagement.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2019
Publisher: JMIR Publications Inc.
Date: 30-04-2020
Abstract: outinely recorded primary care data have been used for many years by sentinel networks for surveillance. More recently, real world data have been used for a wider range of research projects to support rapid, inexpensive clinical trials. Because the partial national lockdown in the United Kingdom due to the coronavirus disease (COVID-19) pandemic has resulted in decreasing community disease incidence, much larger numbers of general practices are needed to deliver effective COVID-19 surveillance and contribute to in-pandemic clinical trials. he aim of this protocol is to describe the rapid design and development of the Oxford Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID) and its first two platforms. The Surveillance Platform will provide extended primary care surveillance, while the Trials Platform is a streamlined clinical trials platform that will be integrated into routine primary care practice. e will apply the FAIR (Findable, Accessible, Interoperable, and Reusable) metadata principles to a new, integrated digital health hub that will extract routinely collected general practice electronic health data for use in clinical trials and provide enhanced communicable disease surveillance. The hub will be findable through membership in Health Data Research UK and European metadata repositories. Accessibility through an online application system will provide access to study-ready data sets or developed custom data sets. Interoperability will be facilitated by fixed linkage to other key sources such as Hospital Episodes Statistics and the Office of National Statistics using pseudonymized data. All semantic descriptors (ie, ontologies) and code used for analysis will be made available to accelerate analyses. We will also make data available using common data models, starting with the US Food and Drug Administration Sentinel and Observational Medical Outcomes Partnership approaches, to facilitate international studies. The Surveillance Platform will provide access to data for health protection and promotion work as authorized through agreements between Oxford, the Royal College of General Practitioners, and Public Health England. All studies using the Trials Platform will go through appropriate ethical and other regulatory approval processes. he hub will be a bottom-up, professionally led network that will provide benefits for member practices, our health service, and the population served. Data will only be used for SQUIRE (surveillance, quality improvement, research, and education) purposes. We have already received positive responses from practices, and the number of practices in the network has doubled to over 1150 since February 2020. COVID-19 surveillance has resulted in tripling of the number of virology sites to 293 (target 300), which has aided the collection of the largest ever weekly total of surveillance swabs in the United Kingdom as well as over 3000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology s les. Practices are recruiting to the PRINCIPLE (Platform Randomised trial of INterventions against COVID-19 In older PeopLE) trial, and these participants will be followed up through ORCHID. These initial outputs demonstrate the feasibility of ORCHID to provide an extended national digital health hub. RCHID will provide equitable and innovative use of big data through a professionally led national primary care network and the application of FAIR principles. The secure data hub will host routinely collected general practice data linked to other key health care repositories for clinical trials and support enhanced in situ surveillance without always requiring large volume data extracts. ORCHID will support rapid data extraction, analysis, and dissemination with the aim of improving future research and development in general practice to positively impact patient care. ERR1-10.2196/19773
Publisher: Cold Spring Harbor Laboratory
Date: 04-02-2021
DOI: 10.1101/2021.02.02.21250902
Abstract: The Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE) trial has provided in-pandemic evidence of what does not work in the early primary care management of coronavirus-2019 disease (COVID-19). PRINCIPLE’s first finding was that azithromycin and doxycycline were not effective. To explore the extent to which azithromycin and doxycycline were being used in-pandemic, and the scope for trial findings impacting on practice. We compared crude rates of prescribing and respiratory tract infections (RTI) in 2020, the pandemic year, with 2019, using the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). We used a negative binomial model including age-band, gender, socioeconomic status, and NHS region to compare azithromycin and doxycycline lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), and influenza-like-illness (ILI) in 2020 with 2019 reporting incident rate ratios (IRR) between years and 95% confidence intervals (95%CI). Azithromycin prescriptions increased 7% in 2020 compared to 2019, whereas doxycycline decreased by 7%. Concurrently, LRTI and URTI incidence fell by over half (58.3% and 54.4% respectively) while ILI rose slightly (6.4%). The overall percentage of RTI prescribed azithromycin rose by 42.1% between 2019 and 2020, doxycycline increased by 33%. Our adjusted IRR showed azithromycin prescribing was 22% higher in 2020 (IRR=1.22, 95%CI:1.19-1.26, p .0001), for every unit rise in confirmed COVID there was an associated 3% rise in prescription (IRR=1.026, 95%CI 1.024-1.0285, p .0001) whereas these measures were static for doxycycline. PRINCIPLE trial flags scope for improvement in antimicrobial stewardship.
Publisher: Wiley
Date: 27-09-2017
DOI: 10.1111/HEX.12634
Publisher: American Association for the Advancement of Science (AAAS)
Date: 05-04-2019
Abstract: As antibiotic consumption grows, bacteria are becoming increasingly resistant to treatment. Antibiotic resistance undermines much of modern health care, which relies on access to effective antibiotics to prevent and treat infections associated with routine medical procedures. The resulting challenges have much in common with those posed by climate change, which economists have responded to with research that has informed and shaped public policy. Drawing on economic concepts such as externalities and the principal-agent relationship, we suggest how economics can help to solve the challenges arising from increasing resistance to antibiotics. We discuss solutions to the key economic issues, from incentivizing the development of effective new antibiotics to improving antibiotic stewardship through financial mechanisms and regulation.
Publisher: Springer Science and Business Media LLC
Date: 07-10-2021
Publisher: Elsevier BV
Date: 09-2021
Publisher: Public Library of Science (PLoS)
Date: 16-03-2022
DOI: 10.1371/JOURNAL.PONE.0264906
Abstract: To identify the experiences and concerns of health workers (HWs), and how they changed, throughout the first year of the COVID-19 pandemic in the UK. Longitudinal, qualitative study with HWs involved in patient management or delivery of care related to COVID-19 in general practice, emergency departments and hospitals. Participants were identified through snowballing. Semi-structured telephone or video interviews were conducted between February 2020 and February 2021, audio-recorded, summarised, and transcribed. Data were analysed longitudinally using framework and thematic analysis. We conducted 105 interviews with 14 participants and identified three phases corresponding with shifts in HWs’ experiences and concerns. (1) Emergency and mobilisation phase (late winter-spring 2020), with significant rapid shifts in responsibilities, required skills, and training, and challenges in patient care. (2) Consolidation and preparation phase (summer-autumn 2020), involving gradual return to usual care and responsibilities, sense of professional development and improvement in care, and focus on learning and preparing for future. (3) Exhaustion and survival phase (autumn 2020-winter 2021), entailing return of changes in responsibilities, focus on balancing COVID-19 and non-COVID care (until becoming overwhelmed with COVID-19 cases), and concerns about longer-term impacts of unceasing pressure on health services. Participants’ perceptions of COVID-19 risk and patient ublic attitudes changed throughout the year, and tiredness and weariness turned into exhaustion. Results showed a long-term impact of the COVID-19 pandemic on UK HWs’ experiences and concerns related to changes in their roles, provision of care, and personal wellbeing. Despite mobilisation in the emergency phase, and trying to learn from this, HWs’ experiences seemed to be similar or worse in the second wave partly due to many COVID-19 cases. The findings highlight the importance of supporting HWs and strengthening system-level resilience (e.g., with resources, processes) to enable them to respond to current and future demands and emergencies.
Publisher: Royal College of General Practitioners
Date: 08-2012
Publisher: Cold Spring Harbor Laboratory
Date: 08-02-2021
DOI: 10.1101/2021.02.04.21251134
Abstract: Multiple early hospital cohorts of coronavirus disease 2019 (COVID-19) showed that patients with chronic respiratory disease were significantly under-represented. We hypothesised that the widespread use of inhaled glucocorticoids was responsible for this finding and tested if inhaled glucorticoids would be an effective treatment for early COVID-19 illness. We conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalisation. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. 146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportion 0.131, p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever and proportion of participants with at least 1 day of fever was lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care. Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection. (Funded by Oxford NIHR Biomedical Research Centre and AstraZeneca ClinicalTrials.gov number, NCT04416399 ) The majority of interventions studied for the COVID-19 pandemic are focused on hospitalised patients. Widely available and broadly relevant interventions for mild COVID-19 are urgently needed. In this open label randomised controlled trial, inhaled budesonide, when given to adults with early COVID-19 illness, reduces the likelihood of requiring urgent care, emergency department consultation or hospitalisation. There was also a quicker resolution of fever, a known poor prognostic marker in COVID-19 and a faster self-reported and questionnaire reported symptom resolution. There were fewer participants with persistent COVID-19 symptoms at 14 and 28 days after budesonide therapy compared to usual care. The STOIC trial potentially provides the first easily accessible effective intervention in early COVID-19. By assessing health care resource utilisation, the study provides an exciting option to help with the worldwide pressure on health care systems due to the COVID-19 pandemic. Data from this study also suggests a potentially effective treatment to prevent the long term morbidity from persistent COVID-19 symptoms.
Publisher: Cold Spring Harbor Laboratory
Date: 12-04-2021
DOI: 10.1101/2021.04.10.21254672
Abstract: Inhaled budesonide has shown efficacy for treating COVID-19 in the community but has not yet been tested in effectiveness trials. We performed a multicenter, open-label, multi-arm, adaptive platform randomized controlled trial involving people aged ≥65 years, or ≥50 years with comorbidities, and unwell ≤14 days with suspected COVID-19 in the community (PRINCIPLE). Participants were randomized to usual care, usual care plus inhaled budesonide (800µg twice daily for 14 days), or usual care plus other interventions. The co-primary endpoints are time to first self-reported recovery, and hospitalization/death related to COVID-19, both measured over 28 days from randomisation and analysed using Bayesian models. The trial opened on April 2, 2020. Randomization to inhaled budesonide began on November 27, 2020 and was stopped on March 31, 2021 based on an interim analysis using data from March 4, 2021. Here, we report updated interim analysis data from March 25, 2021, at which point the trial had randomized 4663 participants with suspected COVID-19. Of these, 2617 (56.1%) tested SARS-CoV-2 positive and contributed data to this interim budesonide primary analysis 751 budesonide, 1028 usual care and 643 to other interventions. Time to first self-reported recovery was shorter in the budesonide group compared to usual care (hazard ratio 1.208 [95% BCI 1.076 – 1.356], probability of superiority 0.999, estimated benefit [95% BCI] of 3.011 [1.134 – 5.41] days). Among those in the interim budesonide primary analysis who had the opportunity to contribute data for 28 days follow up, there were 59/692 (8.5%) COVID-19 related hospitalizations/deaths in the budesonide group vs 100/968 (10.3%) in the usual care group (estimated percentage benefit, 2.1% [95% BCI −0.7% – 4.8%], probability of superiority 0.928). In this updated interim analysis, inhaled budesonide reduced time to recovery by a median of 3 days in people with COVID-19 with risk factors for adverse outcomes. Once 28 day follow up is complete for all participants randomized to budesonide, final analyses of time to recovery and hospitalization/death will be published. (Funded by the National Institute of Health Research/ United Kingdom Research Innovation [MC_PC_19079] PRINCIPLE ISRCTN number, ISRCTN86534580 .)
Publisher: Oxford University Press (OUP)
Date: 23-07-2020
Abstract: Targeted metagenomics using strand-specific libraries with target enrichment is a sensitive, generalized approach to pathogen sequencing and transcriptome profiling. Using this method, we recovered 13 (76%) complete human respiratory syncytial virus (RSV) genomes from 17 clinical respiratory s les, reconstructed the phylogeny of the infecting viruses, and detected differential gene expression between 2 RSV subgroups, specifically, a lower expression of the P gene and a higher expression of the M2 gene in RSV-A than in RSV-B. This methodology can help to relate viral genetics to clinical phenotype and facilitate ongoing population-level RSV surveillance and vaccine development. Clinical Trials Registration. NCT03627572 and NCT03756766.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: South Africa
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Christopher Butler.