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We lead multidisciplinary applied research and training to rethink the way health care is delivered in general practice and across the community.
Continued versus discontinued cannabis use in patients with psychosis: A systematic review and meta-analysis
Background: Although the link between cannabis use and development of psychosis is well established, less is known about the effect of continued versus discontinued cannabis use after the onset of psychosis. We aimed to summarise available evidence focusing on the relationship between continued and discontinued cannabis use after onset of psychosis and its relapse. Methods: In this systematic review and meta-analysis, we searched MEDLINE for articles published in any language from the database inception date up until April 21, 2015 that included a sample of patients with a pre-existing psychotic disorder with a follow-up duration of at least 6 months. We used a combination of search terms for describing cannabis, the outcome of interest (relapse of psychosis), and the study population. We excluded studies if continued cannabis use or discontinued cannabis use could not be established. We compared relapse outcomes between those who continued (CC) or discontinued (DC) cannabis use or were non-users (NC). We used summary data (individual patient data were not sought out) to estimate Cohen's d, which was entered into random effects models (REM) to compare CC with NC, CC with DC, and DC with NC. Meta-regression and sensitivity analyses were used to address the issue of heterogeneity. Findings: Of 1903 citations identified, 24 studies (16 565 participants) met the inclusion criteria. Independent of the stage of illness, continued cannabis users had a greater increase in relapse of psychosis than did both non-users (dCC-NC=0·36, 95% CI 0·22-0·50, p<0·0001) and discontinued users (dCC-DC=0·28, 0·12-0·44, p=0·0005), as well as longer hospital admissions than non-users (dCC-NC=0·36, 0·13 to 0·58, p=0·02). By contrast, cannabis discontinuation was not associated with relapse (dDC-NC=0·02, -0·12 to 0·15; p=0·82). Meta-regression suggested greater effects of continued cannabis use than discontinued use on relapse (dCC-NC=0·36 vs dDC-NC=0·02, p=0·04), positive symptoms (dCC-NC=0·15 vs dDC-NC=-0·30, p=0·05) and level of functioning (dCC-NC=0·04 vs dDC-NC=-0·49, p=0·008) but not on negative symptoms (dCC-NC=-0·09 vs dDC-NC=-0·31, p=0·41). Interpretation: Continued cannabis use after onset of psychosis predicts adverse outcome, including higher relapse rates, longer hospital admissions, and more severe positive symptoms than for individuals who discontinue cannabis use and those who are non-users. These findings point to reductions in cannabis use as a crucial interventional target to improve outcome in patients with psychosis.
Educational interventions delivered to prescribing advisers to influence primary care prescribing: a very low-cost pragmatic randomised trial using routine data from OpenPrescribing.net
BACKGROUND: NHS England issued commissioning guidance on 18 low-priority treatments which should not be routinely prescribed in primary care. We aimed to monitor the impact of an educational intervention delivered to regional prescribing advisors by senior pharmacists from NHS England on the primary care spend on low-priority items. METHODS: An opportunistic randomised, controlled parallel-group trial. Participants (clinical commissioning groups, CCGs) were randomised to intervention or control in a 1:1 ratio. The intervention group were invited to participate. The intervention was a one-off educational session. Our primary outcomes concerned the total prescribing of low-priority items in primary care. Secondary outcomes concerned the prescribing of specific low-priority items. We also measured the impact on information-seeking behaviour. RESULTS: 40 CCGs were randomised, 20 allocated to intervention, with 11 receiving the intervention. There was no significant impact on any prescribing outcomes. There was some possible evidence of increased engagement with data, in the form of CCG email alert sign-ups (p = 0.077). No harms were detected. CONCLUSIONS: A one-off intervention delivered to CCGs by NHS England did not significantly influence low-priority prescribing. This trial demonstrates how routine interventions planned to improve uptake or adherence to healthcare guidance can be delivered as low-cost randomised trials and how to robustly assess their effectiveness. TRIAL REGISTRATION: ISRCTN31218900, October 01 2018.
The reliability of replications: a study in computational reproductions.
This study investigates researcher variability in computational reproduction, an activity for which it is least expected. Eighty-five independent teams attempted numerical replication of results from an original study of policy preferences and immigration. Reproduction teams were randomly grouped into a 'transparent group' receiving original study and code or 'opaque group' receiving only a method and results description and no code. The transparent group mostly verified original results (95.7% same sign and p-value cutoff), while the opaque group had less success (89.3%). Second-decimal place exact numerical reproductions were less common (76.9 and 48.1%). Qualitative investigation of the workflows revealed many causes of error, including mistakes and procedural variations. When curating mistakes, we still find that only the transparent group was reliably successful. Our findings imply a need for transparency, but also more. Institutional checks and less subjective difficulty for researchers 'doing reproduction' would help, implying a need for better training. We also urge increased awareness of complexity in the research process and in 'push button' replications.
Clinical diagnosis of SARS-CoV-2 infection: An observational study of respiratory tract infection in primary care in the early phase of the pandemic
Background: Early in the COVID-19 pandemic, GPs had to distinguish SARS-CoV-2 from other aetiologies in patients presenting with respiratory tract infection (RTI) symptoms on clinical grounds and adapt management accordingly. Objectives: To test the diagnostic accuracy of GPs’ clinical diagnosis of a SARS-CoV-2 infection in a period when COVID-19 was a new disease. To describe GPs’ management of patients presenting with RTI for whom no confirmed diagnosis was available. To investigate associations between patient and clinical features with a SARS-CoV-2 infection. Methods: In April 2020–March 2021, 876 patients (9 countries) were recruited when they contacted their GP with symptoms of an RTI of unknown aetiology. A swab was taken at baseline for later analysis. Aetiology (PCR), diagnostic accuracy of GPs’ clinical SARS-CoV-2 diagnosis, and patient management were explored. Factors related to SARS-CoV-2 infection were determined by logistic regression modelling. Results: GPs suspected SARS-CoV-2 in 53% of patients whereas 27% of patients tested positive for SARS-CoV-2. True-positive patients (23%) were more intensively managed for follow-up, antiviral prescribing and advice than true-negatives (42%). False negatives (5%) were under-advised, particularly for social distancing and isolation. Older age (OR: 1.02 (1.01–1.03)), male sex (OR: 1.68 (1.16–2.41)), loss of taste/smell (OR: 5.8 (3.7–9)), fever (OR: 1.9 (1.3–2.8)), muscle aches (OR: 2.1 (1.5–3)), and a known risk factor for COVID-19 (travel, health care worker, contact with proven case; OR: 2.7 (1.8–4)) were predictive of SARS-CoV-2 infection. Absence of loss of taste/smell, fever, muscle aches and a known risk factor for COVID-19 correctly excluded SARS-CoV-2 in 92.3% of patients, whereas presence of 3, or 4 of these variables correctly classified SARS-CoV-2 in 57.7% and 87.1%. Conclusion: Correct clinical diagnosis of SARS-CoV-2 infection, without POC-testing available, appeared to be complicated.
De-labelling erroneous penicillin allergy records in general practice: healthcare professionals' experiences.
BACKGROUND: Penicillin allergy (PenA) prevalence is approximately 6%, but fewer than 10% of these people are expected to be truly allergic. Consequently, a significant proportion of the population are prescribed alternative antibiotics with potential increased risk of acquiring multi-drug resistant bacteria and worse health outcomes. The ALABAMA trial aimed to determine if a penicillin allergy assessment pathway (PAAP) initiated in primary care, is effective in de-labelling erroneous records, improving antibiotic prescribing and patient outcomes. AIM: To investigate healthcare professionals' experiences of the ALABAMA trial. DESIGN & SETTING: Qualitative study using semi-structured interviews in general practice in England. METHOD: Semi-structured interviews were conducted with healthcare professionals (including general practitioners, research nurses, pharmacists) who delivered the trial. Interviews explored their views about de-labelling incorrect PenA records, their role(s) in the trial, and, where relevant, their experience of prescribing following de-labelling. RESULTS: Healthcare professionals (n=18) believed many patients were incorrectly labelled PenA and were aware of the individual and public health risks this posed. However, GPs explained labels were rarely challenged in general practice because the perceived risks to patients and their professionalism were too great. The PAAP intervention, alongside the 'protocolisation' within the ALABAMA trial, was successful at mitigating these risks. Consequently, the trial was well-accepted and commended by healthcare professionals. CONCLUSIONS: GPs welcomed and accepted the PAAP as a means of correcting erroneous PenA records. There is great potential for PAAP to be supported in primary care if testing becomes more accessible.
Point-of-care testing reduces antibiotic prescribing in acute exacerbations of chronic obstructive pulmonary disease: a systematic review and meta-analysis.
BACKGROUND: Challenges in identifying the causes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have led to overuse of antibiotics. The advantages of point-of-care testing (POCT) may help to identify pathogens and use antibiotics more appropriately. METHODS: We conducted a systematic review to evaluate the effect of POCT to guide antibiotic prescriptions for AECOPD. Adhering to a protocol (CRD42024555847), we searched eligible studies. The outcomes included antibiotic-related and clinical outcomes. We evaluated the risk of bias and performed meta-analyses with subgroup based on the type and testing timing of POCT. RESULTS: A total of 18 studies evaluating 4,346 AECOPD patients were included. Overall, POCT significantly reduced the number of AECOPD patients given antibiotic prescriptions by 16% (p < 0.001). Additionally, antibiotic treatment was reduced by 1.19 days (p = 0.04). There was no detrimental impact on clinical outcomes, such as the length of hospital stay (p = 0.19). Our results proved robust to sensitivity analyses. CONCLUSIONS: We offered reasonable evidence for using POCT to reduce antibiotic exposure for AECOPD without adversely affecting clinical outcomes. As diagnostic techniques become increasingly important in combating antimicrobial resistance, the use of POCT should be encouraged.
In what context and by which mechanisms can creative arts interventions improve wellbeing in older people? A realist review protocol
Background: In recent years, there has been growing interest at national and international policy level in the potential of creative arts to support individual and community wellbeing. Creative arts encompass a wide range of activities, including performing arts, visual arts, design and craft, literature, culture and digital and electronic arts. Participation in creative arts has been linked to lower mental distress, increased social connection, improved quality of life, personal growth and empowerment. Despite this, it remains unclear exactly how participation in creative arts interventions can improve wellbeing in older individuals. This realist review aims to synthesize evidence on how elements of creative arts interventions improve wellbeing amongst older people, in particular when, how, for whom and to what extent they work. Methods and analysis This review will follow the RAMESES (Realist And Meta-narrative Evidence Syntheses: Evolving Standards) quality standards and Pawson’s five iterative stages to locate existing theories, search for evidence, select literature, extract data, and draw conclusions. It will be guided by stakeholder engagement with policymakers, practitioners, commissioners, and people with lived experience. A realist approach will be used to analyse data and develop causal explanations, in the form of context-mechanism-outcome-configurations (CMOCs), which explain how creative arts interventions impact wellbeing in older people. The CMOCs will be organised into one or more programme theories. Our refined programme theory will then be used to develop guidance for service providers of creative arts who want to use their services to improve wellbeing of older people. Ethics and dissemination This research will comply with the UK Policy Framework for Health and Social Care Research. Dissemination will be guided by our stakeholder group, building on links with policymakers, commissioners, providers, and the public. A final stakeholder event focused on knowledge mobilisation will aid development of recommendations. PROSPERO registration CRD42024580770.
Effectiveness of behavioural interventions with motivational interviewing on physical activity outcomes in adults: Systematic review and meta-analysis
Objective: To evaluate the effectiveness of behavioural interventions that include motivational interviewing on physical activity outcomes in adults. Design: Systematic review and meta-analysis. Study selection: A search of seven databases for randomised controlled trials published from inception to 1 March 2023 comparing a behavioural intervention including motivational interviewing with a comparator without motivational interviewing on physical activity outcomes in adults. Outcomes of interest were differences in change in quantitative measures of total physical activity, moderate to vigorous physical activity (MVPA), and sedentary time. Data extraction and synthesis: Two reviewers extracted data and assessed risk of bias. Population characteristics, intervention components, comparison groups, and outcomes of studies were summarised. For overall main effects, random effects meta-analyses were used to report standardised mean differences (SMDs) and 95% confidence intervals (CIs). Differential effects based on duration of follow-up, comparator type, intervention duration, and disease or health condition of participants were also examined. Results: 129 papers reporting 97 randomised controlled trials totalling 27 811 participants and 105 comparisons were included. Interventions including motivational interviewing were superior to comparators for increases in total physical activity (SMD 0.45, 95% CI 0.33 to 0.65, equivalent to 1323 extra steps/day; low certainty evidence) and MVPA (0.45, 0.19 to 0.71, equivalent to 95 extra min/week; very low certainty evidence) and for reductions in sedentary time (-0.58, -1.03 to -0.14, equivalent to -51 min/day; very low certainty evidence). Evidence for a difference in any outcome compared with comparators of similar intensity was lacking. The magnitude of effect diminished over time, and evidence of an effect of motivational interviewing beyond one year was lacking. Most interventions involved patients with a specific health condition, and evidence of an effect of motivational interviewing to increase MVPA or decrease sedentary time was lacking in general population samples. Conclusions: Certainty of the evidence using motivational interviewing as part of complex behavioural interventions for promoting total physical activity in adults was low, and for MVPA and sedentary time was very low. The totality of evidence suggests that although interventions with motivational interviewing increase physical activity and decrease sedentary behaviour, no difference was found in studies where the effect of motivational interviewing could be isolated. Effectiveness waned over time, with no evidence of a benefit of motivational interviewing to increase physical activity beyond one year.
COVID-19 vaccine effectiveness against hospitalisation and death of people in clinical risk groups during the Delta variant period: English primary care network cohort study
Background: COVID-19 vaccines have been shown to be highly effective against hospitalisation and death following COVID-19 infection. COVID-19 vaccine effectiveness estimates against severe endpoints among individuals with clinical conditions that place them at increased risk of critical disease are limited. Methods: We used English primary care medical record data from the Oxford-Royal College of General Practitioners Research and Surveillance Centre sentinel network (N > 18 million). Data were linked to the National Immunisation Management Service database, Second Generation Surveillance System for virology test data, Hospital Episode Statistics, and death registry data. We estimated adjusted vaccine effectiveness (aVE) against COVID-19 infection followed by hospitalisation and death among individuals in specific clinical risk groups using a cohort design during the delta-dominant period. We also report mortality statistics and results from our antibody surveillance in this population. Findings: aVE against severe endpoints was high, 14–69d following a third dose aVE was 96.4% (95.1%–97.4%) and 97.9% (97.2%–98.4%) for clinically vulnerable people given a Vaxzevria and Comirnaty primary course respectively. Lower aVE was observed in the immunosuppressed group: 88.6% (79.1%–93.8%) and 91.9% (85.9%–95.4%) for Vaxzevria and Comirnaty respectively. Antibody levels were significantly lower among the immunosuppressed group than those not in this risk group across all vaccination types and doses. The standardised case fatality rate within 28 days of a positive test was 3.9/1000 in people not in risk groups, compared to 12.8/1000 in clinical risk groups. Waning aVE with time since 2nd dose was also demonstrated, for example, Comirnaty aVE against hospitalisation reduced from 96.0% (95.1–96.7%) 14–69days post-dose 2–82.9% (81.4–84.2%) 182days+ post-dose 2. Interpretation: In all clinical risk groups high levels of vaccine effectiveness against severe endpoints were seen. Reduced vaccine effectiveness was noted among the immunosuppressed group.
Postpandemic Sentinel Surveillance of Respiratory Diseases in the Context of the World Health Organization Mosaic Framework: Protocol for a Development and Evaluation Study Involving the English Primary Care Network 2023-2024
Background: Prepandemic sentinel surveillance focused on improved management of winter pressures, with influenza-like illness (ILI) being the key clinical indicator. The World Health Organization (WHO) global standards for influenza surveillance include monitoring acute respiratory infection (ARI) and ILI. The WHO’s mosaic framework recommends that the surveillance strategies of countries include the virological monitoring of respiratory viruses with pandemic potential such as influenza. The Oxford-Royal College of General Practitioner Research and Surveillance Centre (RSC) in collaboration with the UK Health Security Agency (UKHSA) has provided sentinel surveillance since 1967, including virology since 1993. Objective: We aim to describe the RSC’s plans for sentinel surveillance in the 2023-2024 season and evaluate these plans against the WHO mosaic framework. Methods: Our approach, which includes patient and public involvement, contributes to surveillance objectives across all 3 domains of the mosaic framework. We will generate an ARI phenotype to enable reporting of this indicator in addition to ILI. These data will support UKHSA’s sentinel surveillance, including vaccine effectiveness and burden of disease studies. The panel of virology tests analyzed in UKHSA’s reference laboratory will remain unchanged, with additional plans for point-of-care testing, pneumococcus testing, and asymptomatic screening. Our sampling framework for serological surveillance will provide greater representativeness and more samples from younger people. We will create a biomedical resource that enables linkage between clinical data held in the RSC and virology data, including sequencing data, held by the UKHSA. We describe the governance framework for the RSC. Results: We are co-designing our communication about data sharing and sampling, contextualized by the mosaic framework, with national and general practice patient and public involvement groups. We present our ARI digital phenotype and the key data RSC network members are requested to include in computerized medical records. We will share data with the UKHSA to report vaccine effectiveness for COVID-19 and influenza, assess the disease burden of respiratory syncytial virus, and perform syndromic surveillance. Virological surveillance will include COVID-19, influenza, respiratory syncytial virus, and other common respiratory viruses. We plan to pilot point-of-care testing for group A streptococcus, urine tests for pneumococcus, and asymptomatic testing. We will integrate test requests and results with the laboratory-computerized medical record system. A biomedical resource will enable research linking clinical data to virology data. The legal basis for the RSC’s pseudonymized data extract is The Health Service (Control of Patient Information) Regulations 2002, and all nonsurveillance uses require research ethics approval. Conclusions: The RSC extended its surveillance activities to meet more but not all of the mosaic framework’s objectives. We have introduced an ARI indicator. We seek to expand our surveillance scope and could do more around transmissibility and the benefits and risks of nonvaccine therapies.