General practitioners' risk literacy and real-world prescribing of potentially hazardous drugs: a cross-sectional study.
BACKGROUND: Overuse of medical care is a pervasive problem. Studies using hypothetical scenarios suggest that physicians' risk literacy influences medical decisions; real-world correlations, however, are lacking. We sought to determine the association between physicians' risk literacy and their real-world prescriptions of potentially hazardous drugs, accounting for conflicts of interest and perceptions of benefit-harm ratios in low-value prescribing scenarios. SETTING AND SAMPLE: Cross-sectional study-conducted online between June and October 2023 via field panels of Sermo (Hamburg, Germany)-with a convenience sample of 304 English general practitioners (GPs). METHODS: GPs' survey responses on their treatment-related risk literacy, conflicts of interest and perceptions of the benefit-harm ratio in low-value prescribing scenarios were matched to their UK National Health Service records of prescribing volumes for antibiotics, opioids, gabapentin and benzodiazepines and analysed for differences. RESULTS: 204 GPs (67.1%) worked in practices with ≥6 practising GPs and 226 (76.0%) reported 10-39 years of experience. Compared with GPs demonstrating low risk literacy, GPs with high literacy prescribed fewer opioids (mean (M): 60.60 vs 43.88 prescribed volumes/1000 patients/6 months, p=0.016), less gabapentin (M: 23.84 vs 18.34 prescribed volumes/1000 patients/6 months, p=0.023), and fewer benzodiazepines (M: 17.23 vs 13.58 prescribed volumes/1000 patients/6 months, p=0.037), but comparable volumes of antibiotics (M: 48.84 vs 40.61 prescribed volumes/1000 patients/6 months, p=0.076). High-risk literacy was associated with lower conflicts of interest (ϕ = 0.12, p=0.031) and higher perception of harms outweighing benefits in low-value prescribing scenarios (p=0.007). Conflicts of interest and benefit-harm perceptions were not independently associated with prescribing behaviour (all ps >0.05). CONCLUSIONS AND RELEVANCE: The observed association between GPs with higher risk literacy and the prescription of fewer hazardous drugs suggests the importance of risk literacy in enhancing patient safety and quality of care.
Randomised controlled trial of population screening for atrial fibrillation in people aged 70 years and over to reduce stroke: protocol for the SAFER trial.
INTRODUCTION: There is a lack of evidence that the benefits of screening for atrial fibrillation (AF) outweigh the harms. Following the completion of the Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) pilot trial, the aim of the main SAFER trial is to establish whether population screening for AF reduces incidence of stroke risk. METHODS AND ANALYSIS: Approximately 82 000 people aged 70 years and over and not on oral anticoagulation are being recruited from general practices in England. Patients on the palliative care register or residents in a nursing home are excluded. Eligible people are identified using electronic patient records from general practices and sent an invitation and consent form to participate by post. Consenting participants are randomised at a ratio of 2:1 (control:intervention) with clustering by household. Those randomised to the intervention arm are sent an information leaflet inviting them to participate in screening, which involves use of a handheld single-lead ECG four times a day for 3 weeks. ECG traces identified by an algorithm as possible AF are reviewed by cardiologists. Participants with AF are seen by a general practitioner for consideration of anticoagulation. The primary outcome is stroke. Major secondary outcomes are: death, major bleeding and cardiovascular events. Follow-up will be via electronic health records for an average of 4 years. The primary analysis will be by intention-to-treat using time-to-event modelling. Results from this trial will be combined with follow-up data from the cluster-randomised pilot trial by fixed-effects meta-analysis. ETHICS AND DISSEMINATION: The London-Central National Health Service Research Ethics Committee (19/LO/1597) provided ethical approval. Dissemination will include public-friendly summaries, reports and engagement with the UK National Screening Committee. TRIAL REGISTRATION NUMBER: ISRCTN72104369.
Intravenous immunoglobulin treatment for encephalitis in children aged 6 months to 16 years: the IgNiTE RCT
Background There are data suggesting that intravenous immunoglobulin treatment has some benefit for certain forms of encephalitis but robust evidence from large randomised controlled trials in children with all-cause encephalitis is lacking. Objective To evaluate whether intravenous immunoglobulin treatment improves neurological outcomes in childhood encephalitis when given early in the illness. Design Phase 3b, investigator-initiated, randomised, double-blind, placebo-controlled trial of intravenous immunoglobulin for the treatment of encephalitis in children. Setting Twenty-one NHS Hospitals in the UK. Participants Children aged 6 months to 16 years with a diagnosis of acute or sub-acute encephalitis. Intervention Two doses (1 g/kg/dose) of either intravenous immunoglobulin or matching placebo, given 24–36 hours apart, in addition to standard treatment. Main outcome measure Participants were followed up for 12 months (+/– 4 weeks) after randomisation. The primary outcome measure was a ‘good recovery’ defined as a score of ≤ 2 on the Paediatric Glasgow Outcome Score Extended at 12 months after randomisation. Secondary outcomes The secondary outcomes were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and intravenous immunoglobulin safety data. Results We planned to recruit 308 children over a 42-month period. After enrolment of 18 participants (8 male; 44%) over 21 months (from December 2015 to September 2017), funding was withdrawn due to slow recruitment and the study was terminated. Ten participants were randomised to the intravenous immunoglobulin group, and eight to the placebo group, and all 18 participants were included in the analysis. At 12 months after randomisation, 9 participants [50%; intravenous immunoglobulin n = 5 (50%), placebo n = 4 (50%)] made good recovery and 5 participants [28%; intravenous immunoglobulin n = 3 (30%), placebo n = 2 (25%)] made a poor recovery. Three participants in the placebo group (43%) experienced a total of 10 serious adverse events compared with none in the intravenous immunoglobulin group but none of the adverse events were judged to be related to the study treatment. No deaths occurred during the study period. Conclusion ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE) was halted prematurely due to slow recruitment. Given the small sample size, the study was underpowered to evaluate the effect of intravenous immunoglobulin when compared with placebo in childhood encephalitis. The study findings, albeit from a small sample size, support existing evidence that encephalitis results in poor neurological outcomes for many children. Lessons learned from the ImmunoglobuliN in the Treatment of Encephalitis trial would be valuable for the success of future trials set up to address the efficacy of early treatment with intravenous immunoglobulin in all-cause encephalitis in children. Study limitations and future work The study was underpowered to evaluate the efficacy of intravenous immunoglobulin in the treatment of childhood encephalitis due to the small sample size achieved. Future trials should seek to address this important question. Trial registration This trial is registered as Clinical Trials.gov (NCT02308982) and ISRCTN15791925. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/212/15) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 6. See the NIHR Funding and Awards website for further award information.
Changes in the rate of cardiometabolic and pulmonary events during the COVID-19 pandemic
Background There has been extensive speculation about the relationship between COVID-19 and various cardiometabolic and pulmonary conditions. This a complex question: COVID-19 may cause a cardiometabolic or respiratory event; admission for a clinical event may result in hospital-acquired SARS-CoV-2 infection; both may contribute to a patient surpassing the threshold for presenting to services; and the presence of a pandemic may change whether patients present to services at all. To inform analysis of these questions, we set out to describe the overall rate of various key clinical events over time, and their relationship with COVID-19. Methods Working on behalf of NHS England, we used data from the OpenSAFELY platform containing data from approximately 40% of the population of England. We selected the whole adult population of 17m patients and within this identified two further mutually exclusive groups: patients who tested positive for SARS-CoV-2 in the community; and patients hospitalised with COVID-19. We report counts of death, DVT, PE, ischaemic stroke, MI, heart failure, AKI and diabetic ketoacidosis in each month between February 2019 and October 2020 within each of: the general population, community SARS-CoV-2 cases, and hospitalised patients with COVID-19. Outcome events were defined using hospitalisations, GP records and cause of death data. Results For all outcomes except death there was a lower count of events in April 2020 compared to April 2019. For most outcomes the minimum count of events was in April 2020, where the decrease compared to April 2019 in events ranged from 5.9% (PE) to 40.0% (heart failure). Despite hospitalised COVID-19 patients making up just 0.14% of the population in April 2020, these patients accounted for an extremely high proportion of cardiometabolic and respiratory events in that month (range of proportions 10.3% (DVT) to 33.5% (AKI)). Interpretation We observed a substantial drop in the incidence of cardiometabolic and pulmonary events in the non-COVID-19 general population, but high occurrence of COVID-19 among patients with these events. Shortcomings in routine NHS secondary care data, especially around the timing and order of events, make causal interpretations challenging. We caution that the intermediate findings reported here should be used to inform the design and interpretation of any studies using a general population comparator to evaluate the relationship between COVID-19 and other clinical events.
Potentially inappropriate prescribing of DOACs to people with mechanical heart valves: a federated analysis of 57.9 million patients’ primary care records in situ using OpenSAFELY
National guidance was issued during the COVID-19 pandemic to switch patients on warfarin to direct oral anticoagulants (DOACs) where appropriate as these require less frequent blood testing. DOACs are not recommended for patients with mechanical heart valves. We conducted a retrospective cohort study of DOAC prescribing in people with a record of a mechanical heart valve between September 2019 and May 2021, and describe the characteristics of this population. We identified 15,457 individuals with a mechanical heart valve recorded in their records, of whom 1058 (6.8%) had been prescribed a DOAC during the study period. 767 individuals with a record of a mechanical heart valve were currently prescribed a DOAC as of May 31st 2021. This is suggestive of inappropriate prescribing of DOACs in individuals with mechanical heart valves. Direct alerts have been issued to clinicians through their EHR software informing the issue. We show that the OpenSAFELY platform can be used for rapid audit and feedback to mitigate the indirect health impacts of COVID-19 on the NHS. We will monitor changes in prescribing for this risk group over the following months.
Evaluating the efficacy and mechanisms of a ketogenic diet as adjunctive treatment for people with treatment-resistant depression: A protocol for a randomised controlled trial
Background: One-third of people with depression do not respond to antidepressants, and, after two adequate courses of antidepressants, are classified as having treatment-resistant depression (TRD). Some case reports suggest that ketogenic diets (KDs) may improve some mental illnesses, and preclinical data indicate that KDs can influence brain reward signalling, anhedonia, cortisol, and gut microbiome which are associated with depression. To date, no trials have examined the clinical effect of a KD on TRD. Methods: This is a proof-of-concept randomised controlled trial to investigate the efficacy of a six-week programme of weekly dietitian counselling plus provision of KD meals, compared with an intervention involving similar dietetic contact time and promoting a healthy diet with increased vegetable consumption and reduction in saturated fat, plus food vouchers to purchase healthier items. At 12 weeks we will assess whether participants have continued to follow the assigned diet. The primary outcome is the difference between groups in the change in Patient Health Questionnaire-9 (PHQ-9) score from baseline to 6 weeks. PHQ-9 will be measured at weeks 2, 4, 6 and 12. The secondary outcomes are the differences between groups in the change in remission of depression, change in anxiety score, functioning ability, quality of life, cognitive performance, reward sensitivity, and anhedonia from baseline to 6 and 12 weeks. We will also assess whether changes in reward sensitivity, anhedonia, cortisol awakening response and gut microbiome may explain any changes in depression severity. Discussion: This study will test whether a ketogenic diet is an effective intervention to reduce the severity of depression, anxiety and improve quality of life and functioning ability for people with treatment-resistant depression.
Rates of serious clinical outcomes in survivors of hospitalisation with COVID-19: a descriptive cohort study within the OpenSAFELY platform
Background Patients with COVID-19 are thought to be at higher risk of cardiometabolic and pulmonary complications, but quantification of that risk is limited. We aimed to describe the overall burden of these complications in survivors of severe COVID-19. Methods Working on behalf of NHS England, we used linked primary care records, death certificate and hospital data from the OpenSAFELY platform. We constructed three cohorts: patients discharged following hospitalisation with COVID-19, patients discharged following hospitalisation with pneumonia in 2019, and a frequency-matched cohort from the general population in 2019. We studied eight cardiometabolic and pulmonary outcomes. Absolute rates were measured in each cohort and Cox regression models were fitted to estimate age/sex adjusted hazard ratios comparing outcome rates between discharged COVID-19 patients and the two comparator cohorts. Results Amongst the population of 31,716 patients discharged following hospitalisation with COVID-19, rates for majority of outcomes peaked in the first month post-discharge, then declined over the following four months. Patients in the COVID-19 population had markedly increased risk of all outcomes compared to matched controls from the 2019 general population, especially for pulmonary embolism (HR 12.86; 95% CI: 11.23 - 14.74). Outcome rates were more similar when comparing patients discharged with COVID-19 to those discharged with pneumonia in 2019, although COVID-19 patients had increased risk of type 2 diabetes (HR 1.23; 95% CI: 1.05 - 1.44). Interpretation Cardiometabolic and pulmonary adverse outcomes are markedly raised following hospitalisation for COVID-19 compared to the general population. However, the excess risks were more comparable to those seen following hospitalisation with pneumonia. Identifying patients at particularly high risk of outcomes would inform targeted preventive measures. Funding Wellcome, Royal Society, National Institute for Health Research, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, UK Research and Innovation, Health and Safety Executive.
Predicting COVID-19 related death using the OpenSAFELY platform
Objectives To compare approaches for obtaining relative and absolute estimates of risk of 28-day COVID-19 mortality for adults in the general population of England in the context of changing levels of circulating infection. Design Three designs were compared. (A) case-cohort which does not explicitly account for the time-changing prevalence of COVID-19 infection, (B) 28-day landmarking, a series of sequential overlapping sub-studies incorporating time-updating proxy measures of the prevalence of infection, and (C) daily landmarking. Regression models were fitted to predict 28-day COVID-19 mortality. Setting Working on behalf of NHS England, we used clinical data from adult patients from all regions of England held in the TPP SystmOne electronic health record system, linked to Office for National Statistics (ONS) mortality data, using the OpenSAFELY platform. Participants Eligible participants were adults aged 18 or over, registered at a general practice using TPP software on 1 st March 2020 with recorded sex, postcode and ethnicity. 11,972,947 individuals were included, and 7,999 participants experienced a COVID-19 related death. The study period lasted 100 days, ending 8 th June 2020. Predictors A range of demographic characteristics and comorbidities were used as potential predictors. Local infection prevalence was estimated with three proxies: modelled based on local prevalence and other key factors; rate of A&E COVID-19 related attendances; and rate of suspected COVID-19 cases in primary care. Main outcome measures COVID-19 related death. Results All models discriminated well between patients who did and did not experience COVID-19 related death, with C-statistics ranging from 0.92-0.94. Accurate estimates of absolute risk required data on local infection prevalence, with modelled estimates providing the best performance. Conclusions Reliable estimates of absolute risk need to incorporate changing local prevalence of infection. Simple models can provide very good discrimination and may simplify implementation of risk prediction tools in practice.