Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease: the ALL-HEART RCT and economic evaluation.

Background: Allopurinol is a xanthine oxidase inhibitor that lowers serum uric acid and is used to prevent acute gout flares in patients with gout. Observational and small interventional studies have suggested beneficial cardiovascular effects of allopurinol. Objective: To determine whether allopurinol improves major cardiovascular outcomes in patients with ischaemic heart disease. Design: Prospective, randomised, open-label, blinded endpoint multicentre clinical trial. Setting: Four hundred and twenty-four UK primary care practices. Participants: Aged 60 years and over with ischaemic heart disease but no gout. Interventions: Participants were randomised (1 : 1) using a central web-based randomisation system to receive allopurinol up to 600 mg daily that was added to usual care or to continue usual care. Main outcome measures: The primary outcome was the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes were non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, all-cause mortality, hospitalisation for heart failure, hospitalisation for acute coronary syndrome, coronary revascularisation, hospitalisation for acute coronary syndrome or coronary revascularisation, all cardiovascular hospitalisations, quality of life and cost-effectiveness. The hazard ratio (allopurinol vs. usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis. Results: From 7 February 2014 to 2 October 2017, 5937 participants were enrolled and randomised to the allopurinol arm (n = 2979) or the usual care arm (n = 2958). A total of 5721 randomised participants (2853 allopurinol; 2868 usual care) were included in the modified intention-to-treat analysis population (mean age 72.0 years; 75.5% male). There was no difference between the allopurinol and usual care arms in the primary endpoint, 314 (11.0%) participants in the allopurinol arm (2.47 events per 100 patient-years) and 325 (11.3%) in the usual care arm (2.37 events per 100 patient-years), hazard ratio 1.04 (95% confidence interval 0.89 to 1.21); p = 0.65. Two hundred and eighty-eight (10.1%) participants in the allopurinol arm and 303 (10.6%) participants in the usual care arm died, hazard ratio 1.02 (95% confidence interval 0.87 to 1.20); p = 0.77. The pre-specified health economic analysis plan was to perform a 'within trial' cost-utility analysis if there was no statistically significant difference in the primary endpoint, so NHS costs and quality-adjusted life-years were estimated over a 5-year period. The difference in costs between treatment arms was +£115 higher for allopurinol (95% confidence interval £17 to £210) with no difference in quality-adjusted life-years (95% confidence interval -0.061 to +0.060). We conclude that there is no evidence that allopurinol used in line with the study protocol is cost-effective. Limitations: The results may not be generalisable to younger populations, other ethnic groups or patients with more acute ischaemic heart disease. One thousand six hundred and thirty-seven participants (57.4%) in the allopurinol arm withdrew from randomised treatment, but an on-treatment analysis gave similar results to the main analysis. Conclusions: The ALL-HEART study showed that treatment with allopurinol 600 mg daily did not improve cardiovascular outcomes compared to usual care in patients with ischaemic heart disease. We conclude that allopurinol should not be recommended for the secondary prevention of cardiovascular events in patients with ischaemic heart disease but no gout. Future work: The effects of allopurinol on cardiovascular outcomes in patients with ischaemic heart disease and co-existing hyperuricaemia or clinical gout could be explored in future studies. Trial registration: This trial is registered as EU Clinical Trials Register (EudraCT 2013-003559-39) and ISRCTN (ISRCTN 32017426). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/36/41) and is published in full in Health Technology Assessment; Vol. 28, No. 18. See the NIHR Funding and Awards website for further award information.

The purpose of the ALL-HEART study was to determine whether giving allopurinol to people with ischaemic heart disease (also commonly known as coronary heart disease) would reduce their risk of having a heart attack, stroke or of dying from cardiovascular disease. Allopurinol is a medication usually given to patients with gout to prevent acute gout flares. It is not currently used to treat ischaemic heart disease. We randomly allocated people aged over 60 years with ischaemic heart disease to take up to 600 mg of allopurinol daily (in addition to their usual care) or to continue with their usual care. We then monitored participants for several years and recorded any major health events such as heart attacks, strokes and deaths. We obtained most of the follow-up data from centrally held electronic hospital admissions and death records, making the study easier for participants and more cost-efficient. We asked participants in both groups to complete questionnaires to assess their quality of life during the study. We also collected data to determine whether there was any economic benefit to the NHS of using allopurinol in patients with ischaemic heart disease. There was no difference in the risk of heart attacks, strokes or death from cardiovascular disease between the participants given allopurinol and those in the group continuing their usual care. We also found no difference in the risks of other cardiovascular events, deaths from any cause or quality-of-life measurements between the allopurinol and usual care groups. The results of the ALL-HEART study suggest that we should not recommend that allopurinol be given to people with ischaemic heart disease to prevent further cardiovascular events or deaths.

Comparison of the effectiveness of exclusively facilitated clinical teaching as an alternative to traditional practice-based primary care placements.

INTRODUCTION: COVID-19 presented major challenges to undergraduate GP placement capacity and there was an increased reliance on clinical training using facilitated simulation. The authors present a novel comparison of the effectiveness and cost-effectiveness of delivering a one-week primary care course using entirely GP-facilitated clinical teaching outside the GP setting against traditional practice-based GP clinical education. METHODS: A one-week GP placement was redeveloped from a traditional teaching model (TT-M) to an exclusively facilitated teaching model (FT-M) delivered outside the GP practice setting, using principles of blended learning, flipped classroom methods, e-learning and simulation. Both teaching models, delivered in different locations during 2022 to pre-clinical students, were evaluated using student feedback surveys for attainment of learning outcomes and course satisfaction. RESULTS: The students reported their consultation skills and clinical knowledge (amalgamated mean score 4.36 for FT-M versus 4.63 for TT-M; P = 0.05), as well as preparation for the clinical phases (mean scores 4.35 for FT-M versus 4.41 for TT-M; P = 0.68), were well developed and similar for both courses. Students reported similar enjoyment across both teaching models (FT-M mean score 4.31 versus 4.41 for TT-M; P = 0.49). The costs for delivering teaching per 4-h session for 100 students were £1,379 and £5,551 for FT-M and TT-M, respectively. CONCLUSION: Delivery of a one-week primary care attachment to third year medical students using an FT-M was similarly effective and more cost effective than delivering it by a TT-M. FT-M potentially offers an important adjunct to clinical learning and resilience to capacity challenges for GP placements.

The educational value of situational judgement tests (SJTs) when used during undergraduate medical training: A systematic review and narrative synthesis.

INTRODUCTION: Situational judgement tests (SJTs) are a recognised assessment method for admission into medical school, selection into postgraduate training programs, and postgraduate competency assessment. More recently, however, SJTs have been used during undergraduate medical training (UMT). This systematic review identifies, describes, and appraises the evidence for SJTs in UMT to determine educational associations and outcomes. METHODS: MEDLINE, EMBASE, ERIC, PsycINFO, SCOPUS, Web of Science, and grey literature were searched for original research studies evaluating SJTs implemented within UMT to 1 November 2022. Studies reporting evaluation outcomes were included. Narrative data syntheses were undertaken. Risk of Bias was appraised using the Quality in Prognosis Studies tool. RESULTS: 24 studies were included. National database-derived SJTs (n = 14) assessed against professionalism, postgraduate attainment, construct of medical degree, medical school admissions scores, personality attributes, and declaration of disability. In-house derived SJTs (n = 10) assessed against professionalism, clinical skills, and personality attributes. Most evidence evaluated and reported inverse SJT associations with professionalism and were moderate risk of bias. CONCLUSION: SJTs may have utility for developing professional behaviours in medical students. However, further research testing SJT robustness, standard setting methodologies, and prospectively evaluating SJTs against objective outcome measures within the context of UMT is warranted.

Allopurinol versus usual care in UK patients with ischaemic heart disease (ALL-HEART): a multicentre, prospective, randomised, open-label, blinded-endpoint trial.

BACKGROUND: Allopurinol is a urate-lowering therapy used to treat patients with gout. Previous studies have shown that allopurinol has positive effects on several cardiovascular parameters. The ALL-HEART study aimed to determine whether allopurinol therapy improves major cardiovascular outcomes in patients with ischaemic heart disease. METHODS: ALL-HEART was a multicentre, prospective, randomised, open-label, blinded-endpoint trial done in 18 regional centres in England and Scotland, with patients recruited from 424 primary care practices. Eligible patients were aged 60 years or older, with ischaemic heart disease but no history of gout. Participants were randomly assigned (1:1), using a central web-based randomisation system accessed via a web-based application or an interactive voice response system, to receive oral allopurinol up-titrated to a dose of 600 mg daily (300 mg daily in participants with moderate renal impairment at baseline) or to continue usual care. The primary outcome was the composite cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death. The hazard ratio (allopurinol vs usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis (excluding randomly assigned patients later found to have met one of the exclusion criteria). The safety analysis population included all patients in the modified intention-to-treat usual care group and those who took at least one dose of randomised medication in the allopurinol group. This study is registered with the EU Clinical Trials Register, EudraCT 2013-003559-39, and ISRCTN, ISRCTN32017426. FINDINGS: Between Feb 7, 2014, and Oct 2, 2017, 5937 participants were enrolled and then randomly assigned to receive allopurinol or usual care. After exclusion of 216 patients after randomisation, 5721 participants (mean age 72·0 years [SD 6·8], 4321 [75·5%] males, and 5676 [99·2%] white) were included in the modified intention-to-treat population, with 2853 in the allopurinol group and 2868 in the usual care group. Mean follow-up time in the study was 4·8 years (1·5). There was no evidence of a difference between the randomised treatment groups in the rates of the primary endpoint. 314 (11·0%) participants in the allopurinol group (2·47 events per 100 patient-years) and 325 (11·3%) in the usual care group (2·37 events per 100 patient-years) had a primary endpoint (hazard ratio [HR] 1·04 [95% CI 0·89-1·21], p=0·65). 288 (10·1%) participants in the allopurinol group and 303 (10·6%) participants in the usual care group died from any cause (HR 1·02 [95% CI 0·87-1·20], p=0·77). INTERPRETATION: In this large, randomised clinical trial in patients aged 60 years or older with ischaemic heart disease but no history of gout, there was no difference in the primary outcome of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death between participants randomised to allopurinol therapy and those randomised to usual care. FUNDING: UK National Institute for Health and Care Research.

Virtual teaching of undergraduate primary care small groups during Covid-19.

The impact of the COVID-19 pandemic required Higher Educational Institutions to redesign and implement new ways of delivering core-learning outcomes for medical students. Much of this change resulted in a transition to virtual teaching across medical schools. Medical education in primary care is often delivered as part of GP-facilitated small group teaching and with this came unique challenges for the transition to online education.Transition to virtual small group teaching utilised blended learning and flipped classroom methodologies alongside the use of virtual teaching platforms. This quality improvement project describes the educational approaches used when transitioning medical education, and compares student experience from receiving small group teaching using face-to-face and virtual teaching methods before and during the COVID-19 pandemic, respectively. Analysis of student feedback found an ongoing delivery of high-quality primary care education using virtual small group teaching, and that there was no attrition in student experience when compared to face-to-face teaching delivered before COVID-19 for the same learning outcomes.These findings are reassuring and suggest that the transition to virtual small group teaching, using methods such as flipped classrooms and blended learning, enables continued and sustained delivery of high-quality education and student experiences in primary care.

The association between Situational Judgement Test (SJT) scores and professionalism concerns in undergraduate medical education.

Introduction: Situational judgement tests (SJTs) are widely used in selecting medical students and doctors. Emerging evidence suggests SJTs are capable of testing an individual's ability to respond to role-relevant professionalism scenarios, however, evidence is lacking for their use in identifying students with concerning professional behaviours.This study aimed to determine the association between medical student professionalism-based SJT scores and recorded professionalism concerns during training.Methods: A cross-sectional study was conducted utilising SJT scores from second-year medical students and occurrences of student professionalism concerns. Concerns were reviewed and mapped to General Medical Council standards. Multivariate logistic regression was used to determine associations between SJT scores and professionalism concerns.Results: 247 students were included in the study. For every point increase in SJT score, students were 10% less likely to have multiple professionalism concerns [OR (95% CI) 0.90 (0.83-0.97); p = .007].Students scoring below 1 and 2 standard deviations from the mean score were 4 and 11-times more likely to have multiple concerns [OR (95% CI) 4.52 (1.12-18.25); p = .034] and [OR (95% CI) 11.45 (1.72-76.15); p = .012].Conclusion: Lower SJT scores were significantly associated with an increased risk of professionalism concerns. These findings support the potential for SJT exams to identify medical students that may require closer supervision and remediation during undergraduate education.

Screening for Atrial Fibrillation--A Cross-Sectional Survey of Healthcare Professionals in Primary Care.

INTRODUCTION: Screening for atrial fibrillation (AF) in primary care has been recommended; however, the views of healthcare professionals (HCPs) are not known. This study aimed to determine the opinions of HCP about the feasibility of implementing screening within a primary care setting. METHODS: A cross-sectional mixed methods census survey of 418 HCPs from 59 inner-city practices (Nottingham, UK) was conducted between October-December 2014. Postal and web-surveys ascertained data on existing methods, knowledge, skills, attitudes, barriers and facilitators to AF screening using Likert scale and open-ended questions. Responses, categorized according to HCP group, were summarized using proportions, adjusting for clustering by practice, with 95% C.Is and free-text responses using thematic analysis. RESULTS: At least one General Practitioner (GP) responded from 48 (81%) practices. There were 212/418 (51%) respondents; 118/229 GPs, 67/129 nurses [50 practice nurses; 17 Nurse Practitioners (NPs)], 27/60 healthcare assistants (HCAs). 39/48 (81%) practices had an ECG machine and diagnosed AF in-house. Non-GP HCPs reported having less knowledge about ECG interpretation, diagnosing and treating AF than GPs. A greater proportion of non-GP HCPs reported they would benefit from ECG training specifically for AF diagnosis than GPs [proportion (95% CI) GPs: 11.9% (6.8-20.0); HCAs: 37.0% (21.7-55.5); nurses: 44.0% (30.0-59.0); NPs 41.2% (21.9-63.7)]. Barriers included time, workload and capacity to undertake screening activities, although training to diagnose and manage AF was a required facilitator. CONCLUSION: Inner-city general practices were found to have adequate access to resources for AF screening. There is enthusiasm by non-GP HCPs to up-skill in the diagnosis and management of AF and they may have a role in future AF screening. However, organisational barriers, such as lack of time, staff and capacity, should be overcome for AF screening to be feasibly implemented within primary care.

Accuracy of methods for detecting an irregular pulse and suspected atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: Pulse palpation has been recommended as the first step of screening to detect atrial fibrillation. We aimed to determine and compare the accuracy of different methods for detecting pulse irregularities caused by atrial fibrillation. METHODS: We systematically searched MEDLINE, EMBASE, CINAHL and LILACS until 16 March 2015. Two reviewers identified eligible studies, extracted data and appraised quality using the QUADAS-2 instrument. Meta-analysis, using the bivariate hierarchical random effects method, determined average operating points for sensitivities, specificities, positive and negative likelihood ratios (PLR, NLR); we constructed summary receiver operating characteristic plots. RESULTS: Twenty-one studies investigated 39 interventions (n = 15,129 pulse assessments) for detecting atrial fibrillation. Compared to 12-lead electrocardiography (ECG) diagnosed atrial fibrillation, blood pressure monitors (BPMs; seven interventions) and non-12-lead ECGs (20 interventions) had the greatest accuracy for detecting pulse irregularities attributable to atrial fibrillation (BPM: sensitivity 0.98 (95% confidence interval (CI) 0.92-1.00), specificity 0.92 (95% CI 0.88-0.95), PLR 12.1 (95% CI 8.2-17.8) and NLR 0.02 (95% CI 0.00-0.09); non-12-lead ECG: sensitivity 0.91 (95% CI 0.86-0.94), specificity 0.95 (95% CI 0.92-0.97), PLR 20.1 (95% CI 12-33.7), NLR 0.09 (95% CI 0.06-0.14)). There were similar findings for smartphone applications (six interventions) although these studies were small in size. The sensitivity and specificity of pulse palpation (six interventions) were 0.92 (95% CI 0.85-0.96) and 0.82 (95% CI 0.76-0.88), respectively (PLR 5.2 (95% CI 3.8-7.2), NLR 0.1 (95% CI 0.05-0.18)). CONCLUSIONS: BPMs and non-12-lead ECG were most accurate for detecting pulse irregularities caused by atrial fibrillation; other technologies may therefore be pragmatic alternatives to pulse palpation for the first step of atrial fibrillation screening.

Do cravings predict smoking cessation in smokers calling a national quit line: secondary analyses from a randomised trial for the utility of 'urges to smoke' measures.

BACKGROUND: Single-item urges to smoke measures have been contemplated as important measures of nicotine dependence This study aimed to prospectively determine the relationships between measures of craving to smoke and smoking cessation, and compare their ability to predict cessation with the Heaviness of Smoking Index, an established measure of nicotine dependence. METHODS: We conducted a secondary analysis of data from the randomised controlled PORTSSS trial. Measures of nicotine dependence, ascertained before making a quit attempt, were the HSI, frequency of urges to smoke (FUTS) and strength of urges to smoke (SUTS). Self-reported abstinence at six months after quitting was the primary outcome measure. Multivariate logistic regression and Receiver Operating Characteristic (ROC) analysis were used to assess associations and abilities of the nicotine dependence measures to predict smoking cessation. RESULTS: Of 2,535 participants, 53.5% were female; the median (Interquartile range) age was 38 (28-50) years. Both FUTS and HSI were inversely associated with abstinence six months after quitting; for each point increase in HSI score, participants were 16% less likely to have stopped smoking (OR 0.84, 95% C.I 0.78-0.89, p < 0.0001). Compared to participants with the lowest possible FUTS scores, those with greater scores had generally lower odds of cessation (p across frequency of urges categories=0.0026). SUTS was not associated with smoking cessation. ROC analysis suggested the HSI and FUTS had similar predictive validity for cessation. CONCLUSIONS: Higher FUTS and HSI scores were inversely associated with successful smoking cessation six months after quit attempts began and both had similar validity for predicting cessation.

Accuracy of methods for diagnosing atrial fibrillation using 12-lead ECG: A systematic review and meta-analysis.

BACKGROUND: Screening for atrial fibrillation (AF) using 12-lead-electrocardiograms (ECGs) has been recommended; however, the best method for interpreting ECGs to diagnose AF is not known. We compared accuracy of methods for diagnosing AF from ECGs. METHODS: We searched MEDLINE, EMBASE, CINAHL and LILACS until March 24, 2014. Two reviewers identified eligible studies, extracted data and appraised quality using the QUADAS-2 instrument. Meta-analysis, using the bivariate hierarchical random effects method, determined average operating points for sensitivities, specificities, positive and negative likelihood ratios (PLR, NLR) and enabled construction of Summary Receiver Operating Characteristic (SROC) plots. RESULTS: 10 studies investigated 16 methods for interpreting ECGs (n=55,376 participant ECGs). The sensitivity and specificity of automated software (8 studies; 9 methods) were 0.89 (95% C.I. 0.82-0.93) and 0.99 (95% C.I. 0.99-0.99), respectively; PLR 96.6 (95% C.I. 64.2-145.6); NLR 0.11 (95% C.I. 0.07-0.18). Indirect comparisons with software found healthcare professionals (5 studies; 7 methods) had similar sensitivity for diagnosing AF but lower specificity [sensitivity 0.92 (95% C.I. 0.81-0.97), specificity 0.93 (95% C.I. 0.76-0.98), PLR 13.9 (95% C.I. 3.5-55.3), NLR 0.09 (95% C.I. 0.03-0.22)]. Sub-group analyses of primary care professionals found greater specificity for GPs than nurses [GPs: sensitivity 0.91 (95% C.I. 0.68-1.00); specificity 0.96 (95% C.I. 0.89-1.00). Nurses: sensitivity 0.88 (95% C.I. 0.63-1.00); specificity 0.85 (95% C.I. 0.83-0.87)]. CONCLUSIONS: Automated ECG-interpreting software most accurately excluded AF, although its ability to diagnose this was similar to all healthcare professionals. Within primary care, the specificity of AF diagnosis from ECG was greater for GPs than nurses.

The impact of the Quality and Outcomes Framework (QOF) on the recording of smoking targets in primary care medical records: cross-sectional analyses from The Health Improvement Network (THIN) database.

BACKGROUND: Smoking is a UK public health threat but GPs can be effective in helping patients to quit; consequently, the Quality and Outcomes Framework (QOF) incentivises the recording of smoking status and delivery of cessation advice in patients' medical records. This study investigates the association between smoking-related QOF targets and such recording, and the factors which influence these clinical activities. METHODS: For 2000 to 2008, using medical records in The Health Improvement Network (THIN) database, the annual proportions of i) patients who had a record of smoking status made in the previous 27 months and ii) current smokers recorded as receiving cessation advice in the previous 15 months were calculated. Then, for all patients at selected points before and after the QOF's implementation, data on gender, age, Townsend score, and smoking-related morbidity were extracted. Multivariate logistic regression was used to investigate individual-level characteristics associated with the recording of smoking status and cessation advice. RESULTS: Rapid increases in recording smoking status and advice occurred around the QOF's introduction in April 2004. Subsequently, compliance to targets has been sustained, although rates of increase have slowed. By 2008 64.5% of patients aged 15+ had smoking status documented in the previous 27 months and 50.5% of current smokers had cessation advice recorded in the last 15 months. Adjusted odds ratios show that, both before and after the introduction of the QOF, those with chronic medical conditions, greater social deprivation and women were more likely to have a recent recording of smoking status or cessation advice. Since the QOF's introduction, the strongest characteristic associated with recording activities was the presence of co-morbidity. An example of this was patients with COPD, who in 2008, were 15.38 (95% CI 13.70-17.27) times and 11.72 (95% CI 10.41-13.21) times more likely to have a record of smoking status and cessation advice, respectively. CONCLUSIONS: Rates of recording smoking status and cessation advice plateaued after large increases during the QOF's introduction; however, recording remains most strongly associated with the presence of chronic disease as specified by the QOF, and suggests that incentivised targets have a direct effect on clinical behaviour.

Kounis syndrome presenting as ST-segment elevation myocardial infarction following a hymenoptera (bee) sting.

We described a patient presenting with acute myocardial infarction after sustaining a hymenoptera (bee) sting. Cardiac catheterisation confirmed significant intra-coronary thrombosis in the left anterior descending artery with minimal underlying plaque disease. A unifying diagnosis of Kounis syndrome secondary to hymenoptera envenomation was made. This is followed by a brief review of the pathophysiology of acute myocardial infarction in the context of Kounis syndrome.

Anticoagulation in atrial fibrillation: the trials and tribulations of keeping within therapeutic range.

Atrial fibrillation (AF) is a growing epidemic in the developed world that has attracted much attention due to the associated risk of stroke and thromboembolism. This article discusses the application of oral anticoagulation (OAC) therapy with vitamin K antagonists (VKA) in order to reduce these risks. The article provides an overview of OAC management and highlights the need for greater efforts to increase time within therapeutic range.