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Ranin Soliman, DPhil Student in EBHC, describes her experiences of the qualitative research methods module.
Critical components of 'Early Intervention in Psychosis': National retrospective cohort study
Background Psychotic disorders are severe mental health conditions frequently associated with long-term disability, reduced quality of life and premature mortality. Early Intervention in Psychosis (EIP) services aim to provide timely, comprehensive packages of care for people with psychotic disorders. However, it is not clear which components of EIP services contribute most to the improved outcomes they achieve. Aims We aimed to identify associations between specific components of EIP care and clinically significant outcomes for individuals treated for early psychosis in England. Method This national retrospective cohort study of 14 874 EIP individuals examined associations between 12 components of EIP care and outcomes over a 3-year follow-up period, by linking data from the National Clinical Audit of Psychosis (NCAP) to routine health outcome data held by NHS England. The primary outcome was time to relapse, defined as psychiatric inpatient admission or referral to a crisis resolution (home treatment) team. Secondary outcomes included duration of admissions, detention under the Mental Health Act, emergency department and general hospital attendances and mortality. We conducted multilevel regression analyses incorporating demographic and service-level covariates. Results Smaller care coordinator case-loads and the use of clozapine for eligible people were associated with reduced relapse risk. Physical health interventions were associated with reductions in mortality risk. Other components, such as cognitive-behavioural therapy for psychosis (CBTp), showed associations with improvements in secondary outcomes. Conclusions Smaller case-loads should be prioritised and protected in EIP service design and delivery. Initiatives to improve the uptake of clozapine should be integrated into EIP care. Other components, such as CBTp and physical health interventions, may have specific benefits for those eligible. These findings highlight impactful components of care and should guide resource allocation to optimise EIP service delivery.
Making it Personal - play script
Making it Personal is an innovative public and community engagement with research project at the University of Oxford. Theatre offers a unique platform to “set the scene” on an emotional and personal level, highlighting how individuals process risk and medical information—often in ways that differ significantly from clinical perspectives. Making it Personal utilises theatre to engage the public with genetics research (the iPREGCARE study) and to spark conversations around how a couple might receive and process a de novo (new) genetic diagnosis in their child and approach the question could it happen again? This play script was developed over several months (January – April 2025) by Dr Alison Kay and Dr Minna Jeffery and a co-production panel of genetics practitioners and people with lived experience of genetic diagnosis. A staged reading took place on 17 May 2025 at the MOLT Theatre, St Anne’s College. The recording of the staged reading is available to view on the YouTube channel of the Centre for Personalised Medicine, Oxford.
A Remotely Delivered GLP-1RA–Supported Specialist Weight Management Program in Adults Living With Obesity: Retrospective Service Evaluation
Background: Limited access to specialist weight management services restricts the implementation of novel pharmacotherapies for obesity such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the UK National Health Service (NHS). Second Nature, a commercial digital health company, offers a remotely delivered program combining a GLP-1RA medication (semaglutide) with digital behavioral support, potentially providing a scalable solution. However, evidence for long-term effectiveness in this real-world context is limited. Objective: This study aimed to evaluate the 12-month effectiveness, feasibility, acceptability, and potential cost-effectiveness of the remotely delivered, semaglutide-supported weight management program by Second Nature. Methods: This retrospective service evaluation analyzed data from participants who initiated the program between September and December 2023. The primary outcome was weight change at 12 months among participants with available data (completers). Secondary outcomes included retention, program engagement (measured by views of the Home screen in the app), behavioral changes, side effects, participant experience (qualitative analysis), and a comparative cost analysis against an NHS specialist weight management service. An “active subscription” was defined as maintaining a paid subscription for the full 12-month period. Descriptive statistics and paired 2-tailed t tests evaluated outcomes. Results: Data from 341 participants were included at baseline (282/341, 82.7% women; mean age 49, SD 11.1 years; mean baseline BMI 37.9, SD 6.9 kg/m2). At 12 months, 39.6% (135/206) maintained an active subscription, while 60.4% (206/341) became inactive. Weight data at 12 months were available for 179 participants (52.5% of the baseline cohort; 100% of active and 19.4% of inactive participants). Among completers who maintained an active subscription, the mean weight loss was 20.0 kg (SD 8.7 kg; P
Effect of a 2-week interruption in methotrexate treatment versus continued treatment on COVID-19 booster vaccine immunity in adults with inflammatory conditions (VROOM study): a randomised, open label, superiority trial
This article consists of a citation of a published article describing research funded by the Efficacy and Mechanism Evaluation programme under project number NIHR134607, and is provided as as part of the complete record of research outputs for this project. The original publication is available at: https://doi.org/10.1016/S2213-2600(22)00186-2 Background Immunosuppressive treatments inhibit vaccine-induced immunity against SARS-CoV-2. We evaluated whether a 2-week interruption of methotrexate treatment immediately after the COVID-19 vaccine booster improved antibody responses against the S1 receptor-binding domain (S1-RBD) of the SARS-CoV-2 spike protein compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. Methods We did an open-label, prospective, two-arm, parallel-group, multicentre, randomised, controlled, superiority trial in 26 hospitals in the UK. We recruited adults from rheumatology and dermatology clinics who had been diagnosed with an immune-mediated inflammatory disease (eg, rheumatoid arthritis, psoriasis with or without arthritis, axial spondyloarthritis, atopic dermatitis, polymyalgia rheumatica, and systemic lupus erythematosus) and who were taking low-dose weekly methotrexate (≤25 mg per week) for at least 3 months. Participants also had to have received two primary vaccine doses from the UK COVID-19 vaccination programme. We randomly assigned the participants (1:1), using a centralised validated computer randomisation program, to suspend methotrexate treatment for 2 weeks immediately after their COVID-19 booster (suspend methotrexate group) or to continue treatment as usual (continue methotrexate group). Participants, investigators, clinical research staff, and data analysts were unmasked, while researchers doing the laboratory analyses were masked to group assignment. The primary outcome was S1-RBD antibody titres 4 weeks after receiving the COVID-19 booster vaccine dose, assessed in the intention-to-treat population. This trial is registered with ISRCT, ISRCTN11442263; following the pre-planned interim analysis, recruitment was stopped early. Findings Between Sept 30, 2021 and March 3, 2022, we recruited 340 participants, of whom 254 were included in the interim analysis and had been randomly assigned to one of the two groups: 127 in the continue methotrexate group and 127 in the suspend methotrexate group. Their mean age was 59·1 years, 155 (61%) were female, 130 (51%) had rheumatoid arthritis, and 86 (34%) had psoriasis with or without arthritis. After 4 weeks, the geometric mean S1-RBD antibody titre was 22 750 U/mL (95% CI 19 314-26 796) in the suspend methotrexate group and 10 798 U/mL (8970-12 997) in the continue methotrexate group, with a geometric mean ratio (GMR) of 2·19 (95% CI 1·57-3·04; p<0·0001; mixed-effects model). The increased antibody response in the suspend methotrexate group was consistent across methotrexate dose, administration route, type of immune-mediated inflammatory disease, age, primary vaccination platform, and history of SARS-CoV-2 infection. There were no intervention-related serious adverse events. Interpretation A 2-week interruption of methotrexate treatment for people with immune-mediated inflammatory diseases resulted in enhanced boosting of antibody responses after COVID-19 vaccination. This intervention is simple, low-cost, and easy to implement, and could potentially translate to increased vaccine efficacy and duration of protection for susceptible groups. Funding National Institute for Health and Care Research. Funding This publication was funded by the Efficacy and Mechanism Evaluation programme as a part of award number NIHR134607. This article reports on one component of the research award Vaccine Response On/Off Methotrexate (VROOM): does temporarily suspending methotrexate treatment for two weeks enhance COVID-19 vaccine response? A randomised controlled trial. For more information about this research please view the award page [https://fundingawards.nihr.ac.uk/award/NIHR134607] DOI https://doi.org/10.1016/S2213-2600(22)00186-2
The Use of Online Consultation Systems or Remote Consulting in England Characterized Through the Primary Care Health Records of 53 Million People in the OpenSAFELY Platform: Retrospective Cohort Study
BACKGROUND: The National Health Service (NHS) Long Term Plan, published in 2019, committed to ensuring that every patient in England has the right to digital-first primary care by 2023-2024. The COVID-19 pandemic and infection prevention and control measures accelerated work by the NHS to enable and stimulate the use of online consultation (OC) systems across all practices for improved access to primary care. OBJECTIVE: We aimed to explore general practice coding activity associated with the use of OC systems in terms of trends, COVID-19 effect, variation, and quality. METHODS: With the approval of NHS England, the OpenSAFELY platform was used to query and analyze the in situ electronic health records of suppliers The Phoenix Partnership (TPP) and Egton Medical Information Systems, covering >53 million patients in >6400 practices, mainly in 2019-2020. Systematized Medical Nomenclature for Medicine-Clinical Terminology (SNOMED-CT) codes relevant to OC systems and written OCs were identified including eConsultation. Events were described by volumes and population rates, practice coverage, and trends before and after the COVID-19 pandemic. Variation was characterized among practices, by sociodemographics, and by clinical history of long-term conditions. RESULTS: Overall, 3,550,762 relevant coding events were found in practices using TPP, with the code eConsultation detected in 84.56% (2157/2551) of practices. Activity related to digital forms of interaction increased rapidly from March 2020, the onset of the pandemic; namely, in the second half of 2020, >9 monthly eConsultation coding events per 1000 registered population were registered compared to <1 a year prior. However, we found large variations among regions and practices: December 2020 saw the median practice have 0.9 coded instances per 1000 population compared to at least 36 for the highest decile of practices. On sociodemographics, the TPP cohort with OC instances, when compared (univariate analysis) to the cohort with general practitioner consultations, was more predominantly female (661,235/1,087,919, 60.78% vs 9,172,833/17,166,765, 53.43%), aged 18 to 40 years (349,162/1,080,589, 32.31% vs 4,295,711/17,000,942, 25.27%), White (730,389/1,087,919, 67.14% vs 10,887,858/17,166,765, 63.42%), and less deprived (167,889/1,068,887, 15.71% vs 3,376,403/16,867,074, 20.02%). Looking at the eConsultation code through multivariate analysis, it was more commonly recorded among patients with a history of asthma (adjusted odds ratio [aOR] 1.131, 95% CI 1.124-1.137), depression (aOR 1.144, 95% CI 1.138-1.151), or atrial fibrillation (aOR 1.119, 95% CI 1.099-1.139) when compared to other patients with general practitioner consultations, adjusted for long-term conditions, age, and gender. CONCLUSIONS: We successfully queried general practice coding activity relevant to the use of OC systems, showing increased adoption and key areas of variation during the pandemic at both sociodemographic and clinical levels. The work can be expanded to support monitoring of coding quality and underlying activity. This study suggests that large-scale impact evaluation studies can be implemented within the OpenSAFELY platform, namely looking at patient outcomes.
Routine testing for group B streptococcus in pregnancy: protocol for a UK cluster randomised trial (GBS3)
Introduction It is unclear whether routine testing of women for group B streptococcus (GBS) colonisation either in late pregnancy or during labour reduces early-onset neonatal sepsis, compared with a risk factor-based strategy. Methods and analysis Cluster randomised trial. Sites and participants 320 000 women from up to 80 hospital maternity units. Strategies Sites will be randomised 1:1 to a routine testing strategy or the risk factor-based strategy, using a web-based minimisation algorithm. A second-level randomisation allocates routine testing sites to either antenatal enriched culture medium testing or intrapartum rapid testing. Intrapartum antibiotic prophylaxis will be offered if a test is positive for GBS, or if a maternal risk factor for early-onset GBS infection in her baby is identified before or during labour. Economic and acceptability evaluations will be embedded within the trial design. Outcomes The primary outcome is all-cause early (<7 days of birth) neonatal sepsis, defined as either a positive blood/cerebrospinal fluid culture, early neonatal death from infection or a negative/unknown culture status with ≥3 agreed clinical signs or symptoms, who receive intravenous antibiotics ≥5 days. All women giving birth ≥24 weeks' gestation, regardless of mode of birth, and all her babies will be included in the dataset. Cost-effectiveness will be expressed in terms of incremental cost per case of early neonatal sepsis avoided and incremental cost per quality-adjusted life-year associated with each strategy. Ethics and dissemination The trial received a favourable opinion from Derby Research Ethics Committee on 16 September 2019 (19/EM/0253). The allocated testing strategy will be adopted as standard clinical practice by the site. Women in the routine testing sites will give verbal consent for the test. The trial will use routinely collected data retrieved from National Health Service databases, supplemented with limited participant-level collection of process outcomes. Individual written consent will not be sought. The trial results, and parallel economic, qualitative, implementation and methodological results, will be published in the journal Health Technology Assessment.
The impact of inter-infection time on antimicrobial resistance profiles in women with multiple urinary tract infections over time.
BACKGROUND: Urinary tract infection (UTI) treatment in primary care is increasingly complicated by antimicrobial resistance (AMR), and antimicrobial susceptibility profiles are rarely available to prescribers at the point of prescription. Susceptibility profiles from previous urine culture results could inform prescribing, but little is known about associations between previous and current susceptibilities and the impact of time between infections (inter-infection time) on these associations. METHODS: We analysed routinely collected healthcare records of women ≥16 years in Oxfordshire, UK, who had two or more culture-positive urine specimens consistent with a UTI between 2013 and 2019. We used generalized additive logistic models to estimate associations between resistance to each of eight commonly prescribed antibiotics at first UTI and at second UTI, and their interaction with inter-infection time, adjusted for age and calendar year. RESULTS: In 10 216 women, significant associations were observed between AMR at first and second UTIs. For all antibiotics, these were largest for short inter-infection times. Pivmecillinam resistance at first UTI (OR: 41.70; 95% CI: 27.70-62.80), followed by fosfomycin (OR: 19.90; CI: 13.66-28.92) and ciprofloxacin resistance (OR: 19.65; 95% CI: 16.30-23.75), were strongly associated with resistance to the same antibiotic at the second UTI for inter-infection times ≤3 months. Lower magnitude associations were observed for other antibiotics. For UTIs caused by Escherichia coli only, these associations were generally larger. CONCLUSIONS: In a cohort of women experiencing UTIs, AMR at the first UTI and inter-infection time were key determinants of AMR in the second UTI. This information could inform empirical antimicrobial treatment to limit treatment failure in women with recurrent UTI.
Risk of death by suicide following self-harm presentations to healthcare: development and validation of a multivariable clinical prediction rule (OxSATS)
BACKGROUND: Assessment of suicide risk in individuals who have self-harmed is common in emergency departments, but is often based on tools developed for other purposes. OBJECTIVE: We developed and validated a predictive model for suicide following self-harm. METHODS: We used data from Swedish population-based registers. A cohort of 53 172 individuals aged 10+ years, with healthcare episodes of self-harm, was split into development (37 523 individuals, of whom 391 died from suicide within 12 months) and validation (15 649 individuals, 178 suicides within 12 months) samples. We fitted a multivariable accelerated failure time model for the association between risk factors and time to suicide. The final model contains 11 factors: age, sex, and variables related to substance misuse, mental health and treatment, and history of self-harm. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis guidelines were followed for the design and reporting of this work. FINDINGS: An 11-item risk model to predict suicide was developed using sociodemographic and clinical risk factors, and showed good discrimination (c-index 0.77, 95% CI 0.75 to 0.78) and calibration in external validation. For risk of suicide within 12 months, using a 1% cut-off, sensitivity was 82% (75% to 87%) and specificity was 54% (53% to 55%). A web-based risk calculator is available (Oxford Suicide Assessment Tool for Self-harm or OxSATS). CONCLUSIONS: OxSATS accurately predicts 12-month risk of suicide. Further validations and linkage to effective interventions are required to examine clinical utility. CLINICAL IMPLICATIONS: Using a clinical prediction score may assist clinical decision-making and resource allocation.
Risk of repeat self-harm among individuals presenting to healthcare services: development and validation of a clinical risk assessment model (OxSET)
Background A self-harm episode is a major risk factor for repeat self-harm. Existing tools to assess and predict repeat self-harm have major methodological limitations, and few are externally validated. Objective To develop and validate a risk assessment model of repeat self-harm up to 6 months after an episode of non-fatal self-harm that resulted in an emergency visit to hospital or specialised care. Methods Using Swedish national registers, we identified 53 172 people aged≥10 years who self-harmed during 2008–2012. We allocated 37 523 individuals to development (2820 or 7.5% repeat self-harm incidents within 6 months) and 15 649 to geographic validation (1373 repeat episodes) samples, based on region of residence. In a temporal validation of people who self-harmed during 2018–2019, we identified 25 036 individuals (2886 repeat episodes). We fitted a multivariable accelerated failure time model to predict risk of repeat self-harm. Findings In the external validations (n=40 685), rates of repeat self-harm were 8.8%–11.5% over 6 months. The final model retained 17 factors. Calibration and discrimination were similar in both validation samples, with observed-to-expected ratio=1.15 (95% CI=1.09 to 1.21) and c-statistic=0.72 (95% CI=0.70 to 0.73) in the geographical validation. At 6 months and a 10% risk cutoff, sensitivity was 51.5% (95% CI=48.8% to 54.2%) and specificity was 80.7% (95% CI=80.1% to 81.4%) in geographic validation; corresponding values were 56.9% (95% CI=55.1% to 58.7%) and 76.0% (95% CI=75.5% to 76.6%) in temporal validation. Discrimination was slightly worse at the 1-month prediction horizon (c-statistics of 0.66–0.68). Conclusions Using mostly routinely collected data, simple risk assessment models and tools can provide acceptable levels of accuracy for repeat of self-harm. Clinical implications This risk model (OXford SElf-harm repeat tool) may assist clinical decision-making.
Epidemiology and microbiology of recurrent UTI in women in the community in Oxfordshire, UK
Background: Recurrent urinary tract infection (rUTI) contributes to significant morbidity and antibiotic usage. Objectives: To characterize the age of women experiencing rUTI, the microbiology of rUTIs, and the risk of further rUTIs in Oxfordshire, UK. Patients and methods: We retrospectively analysed de-identified linked microbiology and hospital admissions data (Infections in Oxfordshire Research Database), between 2008 and 2019, including positive urine cultures from women aged ≥16 years in community settings. We defined rUTI as ≥2 positive urine cultures within 6 months or ≥3 within 12 months. Results: Of 201 927 women with urine culture performed, 84 809 (42%) had ≥1 positive culture, and 15 617 (18%) of these experienced ≥1 rUTI over a median (IQR) follow-up of 6 (3-9) years. Women with rUTI were 17.0 (95% CI: 16.3-17.7) years older on average. rUTI was commonest (6204; 40%) in those aged 70-89 years. Post-rUTI, the risk of further UTI within 6 months was 29.4% (95% CI: 28.7-30.2). Escherichia coli was detected in 65% of positive cultures. Among rUTIs where the index UTI was E. coli associated, the second UTI was also E. coli associated in 81% of cases. Conclusions: rUTIs represent a substantial healthcare burden, particularly in women >60 years. One-third of women experiencing rUTI have a further microbiologically confirmed UTI within 6 months.
UMBRELLA protocol: systematic reviews of multivariable biomarker prognostic models developed to predict clinical outcomes in patients with heart failure.
BACKGROUND: Heart failure (HF) is a chronic and common condition with a rising prevalence, especially in the elderly. Morbidity and mortality rates in people with HF are similar to those with common forms of cancer. Clinical guidelines highlight the need for more detailed prognostic information to optimise treatment and care planning for people with HF. Besides proven prognostic biomarkers and numerous newly developed prognostic models for HF clinical outcomes, no risk stratification models have been adequately established. Through a number of linked systematic reviews, we aim to assess the quality of the existing models with biomarkers in HF and summarise the evidence they present. METHODS: We will search MEDLINE, EMBASE, Web of Science Core Collection, and the prognostic studies database maintained by the Cochrane Prognosis Methods Group combining sensitive published search filters, with no language restriction, from 1990 onwards. Independent pairs of reviewers will screen and extract data. Eligible studies will be those developing, validating, or updating any prognostic model with biomarkers for clinical outcomes in adults with any type of HF. Data will be extracted using a piloted form that combines published good practice guidelines for critical appraisal, data extraction, and risk of bias assessment of prediction modelling studies. Missing information on predictive performance measures will be sought by contacting authors or estimated from available information when possible. If sufficient high quality and homogeneous data are available, we will meta-analyse the predictive performance of identified models. Sources of between-study heterogeneity will be explored through meta-regression using pre-defined study-level covariates. Results will be reported narratively if study quality is deemed to be low or if the between-study heterogeneity is high. Sensitivity analyses for risk of bias impact will be performed. DISCUSSION: This project aims to appraise and summarise the methodological conduct and predictive performance of existing clinically homogeneous HF prognostic models in separate systematic reviews.Registration: PROSPERO registration number CRD42019086990.
Detection of post-traumatic stress disorder using learned time-frequency representations from pupillometry
Post-traumatic stress disorder is a major public health concern with a lifetime prevalence rate of 6.1-9.2% in North America. PTSD is known to alter the autonomic nervous system leading to chronic sympathetic arousal including heightened anxiety and hypervigilance. Pupillometry offers a quick and accessible measure of autonomic nervous system imbalances characteristic of PTSD. This study investigates the utility of pupillometry as a biomarker to detect PTSD in a sample of 39 adults with (n = 22) and without (n = 17) PTSD. Participants viewed a 25-minute computer protocol consisting of 5-minute rest phase, 10-minute negative emotionally valent images, and 10-minute guided meditation. We relied on a time-frequency analysis to represent the pupillary responses of two different groups (PTSD-affected individuals and healthy-control subjects). These data were then employed with a CNN network to learn a prediction model. Individuals with PTSD demonstrated increased pupil dilation across the entire protocol. The final outcome revealed an accuracy of 81.09% which indicates the feasibility of using this approach to detecting participants with PTSD in an automated way. Findings from this research have important implications for clinical mental health assessment, diagnostics and treatment.
Utilising primary care electronic health records to deliver the ALABAMA randomised controlled trial of penicillin allergy assessment
Background: Use of electronic health records (EHR) to provide real-world data for research is established, but using EHR to deliver randomised controlled trials (RCTs) more efficiently is less developed. The Allergy AntiBiotics And Microbial resistAnce (ALABAMA) RCT evaluated a penicillin allergy assessment pathway versus usual clinical care in a UK primary care setting. The aim of this paper is to describe how EHRs were used to facilitate efficient delivery of a large-scale randomised trial of a complex intervention embracing efficient participant identification, supporting minimising GP workload, providing accurate post-intervention EHR updates of allergy status, and facilitating participant follow up and outcome data collection. The generalisability of the EHR approach and health economic implications of EHR in clinical trials will be reported in the main ALABAMA trial cost-effectiveness analysis. Methods: A descriptive account of the adaptation of functionality within SystmOne used to deliver/facilitate multiple trial processes from participant identification to outcome data collection. Results: An ALABAMA organisation group within SystmOne was established which allowed sharing of trial functions/materials developed centrally by the research team. The ‘ALABAMA unit’ within SystmOne was also created and provided a secure efficient environment to access participants’ EHR data. Processes of referring consented participants, allocating them to a trial arm, and assigning specific functions to the intervention arm were developed by adapting tools such as templates, reports, and protocols which were already available in SystmOne as well as pathways to facilitate allergy de-labelling processes and data retrieval for trial outcome analysis. Conclusions: ALABAMA is one of the first RCTs to utilise SystmOne EHR functionality and data across the RCT delivery, demonstrating feasibility and applicability to other primary care RCTs. Trial registration: ClinicalTrials.gov: NCT04108637, registered 05/03/2019. ISRCTN: ISRCTN20579216.
Overcoming challenges in the economic evaluation of interventions to optimise antibiotic use
Bacteria are becoming increasingly resistant to antibiotics, reducing our ability to treat infections and threatening to undermine modern health care. Optimising antibiotic use is a key element in tackling the problem. Traditional economic evaluation methods do not capture many of the benefits from improved antibiotic use and the potential impact on resistance. Not capturing these benefits is a major obstacle to optimising antibiotic use, as it fails to incentivise the development and use of interventions to optimise the use of antibiotics and preserve their effectiveness (stewardship interventions). Estimates of the benefits of improving antibiotic use involve considerable uncertainty as they depend on the evolution of resistance and associated health outcomes and costs. Here we discuss how economic evaluation methods might be adapted, in the face of such uncertainties. We propose a threshold-based approach that estimates the minimum resistance-related costs that would need to be averted by an intervention to make it cost-effective. If it is probable that without the intervention costs will exceed the threshold then the intervention should be deemed cost-effective.