Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study.

OBJECTIVE: To investigate risks of multiple adverse outcomes associated with use of antipsychotics in people with dementia. DESIGN: Population based matched cohort study. SETTING: Linked primary care, hospital and mortality data from Clinical Practice Research Datalink (CPRD), England. POPULATION: Adults (≥50 years) with a diagnosis of dementia between 1 January 1998 and 31 May 2018 (n=173 910, 63.0% women). Each new antipsychotic user (n=35 339, 62.5% women) was matched with up to 15 non-users using incidence density sampling. MAIN OUTCOME MEASURES: The main outcomes were stroke, venous thromboembolism, myocardial infarction, heart failure, ventricular arrhythmia, fracture, pneumonia, and acute kidney injury, stratified by periods of antipsychotic use, with absolute risks calculated using cumulative incidence in antipsychotic users versus matched comparators. An unrelated (negative control) outcome of appendicitis and cholecystitis combined was also investigated to detect potential unmeasured confounding. RESULTS: Compared with non-use, any antipsychotic use was associated with increased risks of all outcomes, except ventricular arrhythmia. Current use (90 days after a prescription) was associated with elevated risks of pneumonia (hazard ratio 2.19, 95% confidence interval (CI) 2.10 to 2.28), acute kidney injury (1.72, 1.61 to 1.84), venous thromboembolism (1.62, 1.46 to 1.80), stroke (1.61, 1.52 to 1.71), fracture (1.43, 1.35 to 1.52), myocardial infarction (1.28, 1.15 to 1.42), and heart failure (1.27, 1.18 to 1.37). No increased risks were observed for the negative control outcome (appendicitis and cholecystitis). In the 90 days after drug initiation, the cumulative incidence of pneumonia among antipsychotic users was 4.48% (4.26% to 4.71%) versus 1.49% (1.45% to 1.53%) in the matched cohort of non-users (difference 2.99%, 95% CI 2.77% to 3.22%). CONCLUSIONS: Antipsychotic use compared with non-use in adults with dementia was associated with increased risks of stroke, venous thromboembolism, myocardial infarction, heart failure, fracture, pneumonia, and acute kidney injury, but not ventricular arrhythmia. The range of adverse outcomes was wider than previously highlighted in regulatory alerts, with the highest risks soon after initiation of treatment.

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.

The impact of ageing on adults with cerebral palsy: the results of a national online survey.

BACKGROUND: Cerebral palsy (CP) is one of the most common neurological disorders in children and results in lifelong physical impairments. Adults with CP have approximately the same life expectancy as their non-disabled peers, so helping them to stay healthy throughout the life course will have long-term cost benefits via reductions in hospital admissions, long-term care, and unemployment rates. AIM: To explore how adults with CP experience ageing. DESIGN & SETTING: National online survey given to adults with CP in the UK. METHOD: The participants were adults with CP. Items for the online survey were taken from existing self-report measures, with additional items developed for the survey. Several domains of functioning were assessed including mobility, dexterity, fatigue, pain, speech, mental health, swallowing and health maintenance/self-care as well as healthcare usage. Data were analysed using χ2 to examine the relationships between the demographic variables and the survey responses. RESULTS: The survey was completed by 395 participants, of whom 74.2% were female and approximately 59.3% aged <45 years. Responders reported having problems with mobility, pain, and fatigue with older participants reporting higher levels of pain and more mobility problems, although the correlations were fairly small. Healthcare usage was surprisingly low. CONCLUSION: The study found that age was associated with a decline in mobility and a higher level of pain, although the relationships were weak. It is possible that the low healthcare usage among the responders is owing to services not being available to respond to their needs.

Evaluating the UK's first national prescribing assessment for GPs in training using an online survey.

BACKGROUND: GP trainees may not have experienced a systematic and comprehensive education in safe prescribing. Therefore, a self-assessment prescribing review was developed. AIM: To determine whether the assessment was feasible, had face validity, and did not disadvantage particular groups of participants. DESIGN & SETTING: An online survey that evaluates the opinions of GPs in training of a prescribing assessment in the UK. All full-time UK trainees who started their final year of GP training in August 2019 undertook the prescribing assessment along with their trainers, after which they completed an online anonymous feedback questionnaire. METHOD: The questionnaire completed by trainees sought their opinions of the assessment, and collected ethnicity and disability data. The trainer questionnaire was similar but did not include any demographic information. RESULTS: The questionnaire was completed by 1741 trainees and 1576 trainers. There was no evidence that ethnic group and disability were related to aspects of the review. Most of the trainees (76.4%, n = 1330) and trainers (82.0%, n = 1293) agreed or strongly agreed that the prescribing review was helpful for assessing and learning about the trainee's prescribing. However, most participants (63.2%, n = 1092) took >4 hours to review their prescriptions. A majority of trainees (90.2%, n = 1571) reported that completing the assessment had resulted in a change in their prescribing practice. CONCLUSION: The majority of trainers and trainees reported that the prescribing assessment was helpful. The study was not able to assess whether there had been an actual change in practice that resulted in an error reduction.

Frequency and impact of medication reviews for people aged 65 years or above in UK primary care: an observational study using electronic health records.

BACKGROUND: Medication reviews in primary care provide an opportunity to review and discuss the safety and appropriateness of a person's medicines. However, there is limited evidence about access to and the impact of routine medication reviews for older adults in the general population, particularly in the UK. We aimed to quantify the proportion of people aged 65 years and over with a medication review recorded in 2019 and describe changes in the numbers and types of medicines prescribed following a review. METHODS: We used anonymised primary care electronic health records from the UK's Clinical Practice Research Datalink (CPRD GOLD) to define a population of people aged 65 years or over in 2019. We counted people with a medication review record in 2019 and used Cox regression to estimate associations between demographic characteristics, diagnoses, and prescribed medicines and having a medication review. We used linear regression to compare the number of medicines prescribed as repeat prescriptions in the three months before and after a medication review. Specifically, we compared the 'prescription count' - the maximum number of different medicines with overlapping prescriptions people had in each period. RESULTS: Of 591,726 people prescribed one or more medicines at baseline, 305,526 (51.6%) had a recorded medication review in 2019. Living in a care home (hazard ratio 1.51, 95% confidence interval 1.40-1.62), medication review in the previous year (1.83, 1.69-1.98), and baseline prescription count (e.g. 5-9 vs 1 medicine 1.41, 1.37-1.46) were strongly associated with having a medication review in 2019. Overall, the prescription count tended to increase after a review (mean change 0.13 medicines, 95% CI 0.12-0.14). CONCLUSIONS: Although medication reviews were commonly recorded for people aged 65 years or over, there was little change overall in the numbers and types of medicines prescribed following a review. This study did not examine whether the prescriptions were appropriate or other metrics, such as dose or medicine changes within the same class. However, by examining the impact of medication reviews before the introduction of structured medication review requirements in England in 2020, it provides a useful benchmark which these new reviews can be compared with.

Changes in medication safety indicators in England throughout the covid-19 pandemic using OpenSAFELY: population based, retrospective cohort study of 57 million patients using federated analytics.

Objective: To implement complex, PINCER (pharmacist led information technology intervention) prescribing indicators, on a national scale with general practice data to describe the impact of the covid-19 pandemic on safe prescribing. Design: Population based, retrospective cohort study using federated analytics. Setting: Electronic general practice health record data from 56.8 million NHS patients by use of the OpenSAFELY platform, with the approval of the National Health Service (NHS) England. Participants: NHS patients (aged 18-120 years) who were alive and registered at a general practice that used TPP or EMIS computer systems and were recorded as at risk of at least one potentially hazardous PINCER indicator. Main outcome measure: Between 1 September 2019 and 1 September 2021, monthly trends and between practice variation for compliance with 13 PINCER indicators, as calculated on the first of every month, were reported. Prescriptions that do not adhere to these indicators are potentially hazardous and can cause gastrointestinal bleeds; are cautioned against in specific conditions (specifically heart failure, asthma, and chronic renal failure); or require blood test monitoring. The percentage for each indicator is formed of a numerator of patients deemed to be at risk of a potentially hazardous prescribing event and the denominator is of patients for which assessment of the indicator is clinically meaningful. Higher indicator percentages represent potentially poorer performance on medication safety. Results: The PINCER indicators were successfully implemented across general practice data for 56.8 million patient records from 6367 practices in OpenSAFELY. Hazardous prescribing remained largely unchanged during the covid-19 pandemic, with no evidence of increases in indicators of harm as captured by the PINCER indicators. The percentage of patients at risk of potentially hazardous prescribing, as defined by each PINCER indicator, at mean quarter 1 (Q1) 2020 (representing before the pandemic) ranged from 1.11% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 36.20% (amiodarone and no thyroid function test), while Q1 2021 (representing after the pandemic) percentages ranged from 0.75% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 39.23% (amiodarone and no thyroid function test). Transient delays occurred in blood test monitoring for some medications, particularly angiotensin-converting enzyme inhibitors (where blood monitoring worsened from a mean of 5.16% in Q1 2020 to 12.14% in Q1 2021, and began to recover in June 2021). All indicators substantially recovered by September 2021. We identified 1 813 058 patients (3.1%) at risk of at least one potentially hazardous prescribing event. Conclusion: NHS data from general practices can be analysed at national scale to generate insights into service delivery. Potentially hazardous prescribing was largely unaffected by the covid-19 pandemic in primary care health records in England.

Patient safety in prisons: a multi-method analysis of reported incidents in England.

OBJECTIVES: Prisoners use healthcare services three times more frequently than the general population with poorer health outcomes. Their distinct healthcare needs often pose challenges to safe healthcare provision. This study aimed to characterise patient safety incidents reported in prisons to guide practice improvement and identify health policy priorities.Design: We carried out an exploratory multi-method analysis of anonymised safety incidents from prisons. SETTING: Safety incidents had been reported to the National Reporting and Learning System by prisons in England between April 2018 and March 2019. PARTICIPANTS: Reports were reviewed to identify any unintended or unexpected incident(s) which could have, or did, lead to harm for prisoners receiving healthcare. MAIN OUTCOME MEASURES: Free-text descriptions were examined to identify the type and nature of safety incidents, their outcomes and harm severity. Analysis was contextualised with subject experts through structured workshops to explain relationships between the most common incidents and contributory factors. RESULTS: Of 4112 reports, the most frequently observed incidents were medication-related (n = 1167, 33%), specifically whilst administering medications (n = 626, 54%). Next, were access-related (n = 559,15%), inclusive of delays in patients accessing healthcare professionals (n = 236, 42%) and managing medical appointments (n = 171, 31%). The workshops contextualised incidents involving contributing factors (n = 1529, 28%) into three key themes, namely healthcare access, continuity of care and the balance between prison and healthcare priorities. CONCLUSIONS: This study highlights the importance of improving medication safety and access to healthcare services for prisoners. We recommend staffing level reviews to ensure healthcare appointments are attended, and to review procedures for handling missed appointments, communication during patient transfers and medication prescribing.

Risk of Venous Thromboembolism With Gout Flares.

OBJECTIVE: Previous studies demonstrated that the risk of venous thromboembolism (VTE) is increased in patients with gout, but not whether there was a temporal association between gout flare and VTE. This study was undertaken to evaluate potential temporal associations between gout flare and VTE. METHODS: Data were obtained from electronic primary-care records from the UK's Clinical Practice Research Datalink, which links data from hospitalization and mortality registers. Using self-controlled case series analysis adjusted for season and age, we evaluated the temporal association between gout flare and VTE. The 90 days after primary-care consultation or hospitalization for gout flare was designated the exposed period. This was divided into three 30-day intervals. The baseline period was up to 2 years before the start of and up to 2 years after the end of the exposed period. The association between gout flare and VTE was measured using adjusted incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs). RESULTS: In total, 314 patients met the inclusion criteria (age ≥18 years, incident gout, no presence of VTE or use of a primary-care anticoagulant prescription before the start of the pre-exposure period). Among the 314 patients, VTE incidence was significantly higher in the exposed period than in the baseline period (adjusted IRR 1.83, 95% CI 1.30-2.59). The adjusted IRR of VTE during the first 30 days after gout flare was 2.31 (95% CI 1.39-3.82) relative to the baseline period. No increase in the adjusted IRRs was observed in days 31-60 (adjusted IRR 1.49, 95% CI 0.79-2.81) and days 61-90 (adjusted IRR 1.67, 95% CI 0.91-3.06) relative to baseline. Results were consistent across sensitivity analyses. CONCLUSION: Among patients with gout, there was a transient increase in the rate of VTE within 30 days after primary-care consultation or hospitalization for gout flare.

A systems approach to the safety and efficiency of prescribing at the primary-secondary care interface.

The interface between primary and secondary care represents a highly complex and heterogeneous system that continues to pose risks to the safety and quality of care. Many issues relate to prescribing activities, and suboptimal information sharing between stakeholders can lead to avoidable harm events and system inefficiencies that increase workload. The framework of a systems approach is used to structure four key interface issues: medicines reconciliation, prescribing at secondary care outpatient appointments, shared records, and quality of communication. We outline opportunities for improved safety and efficiency, and identify key barriers that need to be addressed. Significant further development is required for the measures discussed. We recommend the use of a systems approach to methodologically support this process, particularly due to the inherent system-wide understanding of problems that it generates. We argue such understanding is essential to ensure that risks and workload are not shifted around a system, without overall gain.

Scaling-up a pharmacist-led information technology intervention (PINCER) to reduce hazardous prescribing in general practices: Multiple interrupted time series study.

BACKGROUND: We previously reported on a randomised trial demonstrating the effectiveness and cost-effectiveness of a pharmacist-led information technology intervention (PINCER). We sought to investigate whether PINCER was effective in reducing hazardous prescribing when rolled out at scale in UK general practices. METHODS AND FINDINGS: We used a multiple interrupted time series design whereby successive groups of general practices received the PINCER intervention between September 2015 and April 2017. We used 11 prescribing safety indicators to identify potentially hazardous prescribing and collected data over a maximum of 16 quarterly time periods. The primary outcome was a composite of all the indicators; a composite for indicators associated with gastrointestinal (GI) bleeding was also reported, along with 11 individual indicators of hazardous prescribing. Data were analysed using logistic mixed models for the quarterly event numbers with the appropriate denominator, and calendar time included as a covariate. PINCER was implemented in 370 (94.1%) of 393 general practices covering a population of almost 3 million patients in the East Midlands region of England; data were successfully extracted from 343 (92.7%) of these practices. For the primary composite outcome, the PINCER intervention was associated with a decrease in the rate of hazardous prescribing of 16.7% (adjusted odds ratio (aOR) 0.83, 95% confidence interval (CI) 0.80 to 0.86) at 6 months and 15.3% (aOR 0.85, 95% CI 0.80 to 0.90) at 12 months postintervention. The unadjusted rate of hazardous prescribing reduced from 26.4% (22,503 patients in the numerator/853,631 patients in the denominator) to 20.1% (11,901 patients in the numerator/591,364 patients in the denominator) at 6 months and 19.1% (3,868 patients in the numerator/201,992 patients in the denominator). The greatest reduction in hazardous prescribing associated with the intervention was observed for the indicators associated with GI bleeding; for the GI composite indicator, there was a decrease of 23.9% at both 6 months (aOR 0.76, 95% CI 0.73 to 0.80) and 12 months (aOR 0.76, 95% CI 0.70 to 0.82) postintervention. The unadjusted rate of hazardous prescribing reduced from 31.4 (16,185 patients in the numerator/515,879 patients in the denominator) to 21.2% (7,607 patients in the numerator/358,349 patients in the denominator) at 6 months and 19.5% (2,369 patients in the numerator/121,534 patients in the denominator). We adjusted for calendar time and practice, but since this was an observational study, the findings may have been influenced by unknown confounding factors or behavioural changes unrelated to the PINCER intervention. Data were also not collected for all practices at 6 months and 12 months postintervention. CONCLUSIONS: The PINCER intervention, when rolled out at scale in routine clinical practice, was associated with a reduction in hazardous prescribing by 17% and 15% at 6 and 12 months postintervention. The greatest reductions in hazardous prescribing were for indicators associated with risk of GI bleeding. These findings support the wider national rollout of PINCER in England.

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.

Association Between Gout Flare and Subsequent Cardiovascular Events Among Patients With Gout.

Importance: Gout is associated with cardiovascular diseases. The temporal association between gout flares and cardiovascular events has not been investigated. Objective: To investigate whether there is a transient increase in risk of cardiovascular events after a recent gout flare. Design, Setting, and Participants: A retrospective observational study was conducted using electronic health records from the Clinical Practice Research Datalink in England between January 1, 1997, and December 31, 2020. A multivariable nested case-control study was performed among 62 574 patients with gout, and a self-controlled case series, adjusted for season and age, was performed among 1421 patients with gout flare and cardiovascular event. Exposures: Gout flares were ascertained using hospitalization, primary care outpatient, and prescription records. Main Outcomes and Measures: The primary outcome was a cardiovascular event, defined as an acute myocardial infarction or stroke. Association with recent prior gout flares was measured using adjusted odds ratios (ORs) with 95% CIs in a nested case-control study and adjusted incidence rate ratios (IRRs) with 95% CIs in a self-controlled case series. Results: Among patients with a new diagnosis of gout (mean age, 76.5 years; 69.3% men, 30.7% women), 10 475 patients with subsequent cardiovascular events were matched with 52 099 patients without cardiovascular events. Patients with cardiovascular events, compared with those who did not have cardiovascular events, had significantly higher odds of gout flare within the prior 0 to 60 days (204/10 475 [2.0%] vs 743/52 099 [1.4%]; adjusted OR, 1.93 [95% CI, 1.57-2.38]) and within the prior 61 to 120 days (170/10 475 [1.6%] vs 628/52 099 [1.2%]; adjusted OR, 1.57 [95% CI, 1.26-1.96]). There was no significant difference in the odds of gout flare within the prior 121 to 180 days (148/10 475 [1.4%] vs 662/52 099 [1.3%]; adjusted OR, 1.06 [95% CI, 0.84-1.34]). In the self-controlled case series (N = 1421), cardiovascular event rates per 1000 person-days were 2.49 (95% CI, 2.16-2.82) within days 0 to 60; 2.16 (95% CI, 1.85-2.47) within days 61 to 120; and 1.70 (95% CI, 1.42-1.98) within days 121 to 180 after a gout flare, compared with cardiovascular event rates of 1.32 (95% CI, 1.23-1.41) per 1000 person-days within the 150 days before or the 181 to 540 days after the gout flare. Compared with 150 days before or the 181 to 540 days after a gout flare, incidence rate differences for cardiovascular events were 1.17 (95% CI, 0.83-1.52) per 1000 person-days, and adjusted IRRs were 1.89 (95% CI, 1.54-2.30) within days 0 to 60; 0.84 (95% CI, 0.52-1.17) per 1000 person-days and 1.64 (95% CI, 1.45-1.86) within days 61 to 120; and 0.38 (95% CI, 0.09-0.67) per 1000 person-days and 1.29 (95% CI, 1.02-1.64) within days 121 to 180 after a gout flare. Conclusions and Relevance: Among individuals with gout, those who experienced a cardiovascular event, compared with those who did not experience such an event, had significantly higher odds of a recent gout flare in the preceding days. These findings suggest gout flares are associated with a transient increase in cardiovascular events following the flare.

The frequency and nature of prescribing problems by GPs-in-training (REVISiT): a retrospective review.

BACKGROUND: Prescribing errors can cause significant morbidity and occur in about 5% of prescriptions in English general practices. AIM: To describe the frequency and nature of prescribing problems in a cohort of GPs-in-training to determine whether they need additional prescribing support. DESIGN & SETTING: A primary care pharmacist undertook a retrospective review of prescriptions issued between 9 October 2014 and 11 March 2015 by 10 GPs in their final year of training from 10 practices in England. METHOD: Pre-existing standards and expert panel discussion were used to classify the appropriateness of prescribing. Data were imported into Stata (version 13) to perform descriptive analysis. An individualised report highlighting prescribing errors, suboptimal prescribing, and areas of good practice identified during the review was shared with the GPs-in-training and their trainers. This report was used to guide discussions during the GP-in-training's feedback session. RESULTS: A total of 1028 prescription items were reviewed from 643 consultations performed by 10 GPs-in-training. There were 92 prescribing errors (8.9%) and 360 episodes of suboptimal prescribing (35.0%). The most common types of error concerned medication dosages (n = 30, 32.6% of errors). CONCLUSION: Personalised review of prescribing revealed an error rate higher than recorded in a previous similar study mainly comprising GPs who had completed postgraduate training, and a substantially higher rate of suboptimal prescribing. A larger intervention study is now required to evaluate the effectiveness of receiving a personalised review of prescribing, and to assess its impact on patient safety.

Development of 2 Short Patient-Report Questionnaires of Patient Safety in Primary Care.

OBJECTIVES: The Patient Reported Experiences and Outcomes of Safety in Primary Care (PREOS-PC) is a valid and reliable instrument (61 items across 5 domains) of patients' perceptions of safety. Stakeholder feedback has supported shorter versions for improving choice and facilitating uptake of routine patient-centered evaluation. We sought to develop 2 shorter versions of PREOS-PC: one including the shortest possible scales that met established measurement performance standards and a screening version including a single item per domain. METHODS: A total of 1244 patients from 45 general practices across England completed PREOS-PC questionnaires. All scale items in PREOS-PC underwent Item Response Theory analysis, applying standard criteria for the item reduction. Cognitive debriefing from 10 patient interviews allowed for the assessment of the instruments' readability. The instruments' psychometrics properties were reassessed in a validation sample of 1557 patients in 21 English general practices. RESULTS: "PREOS-PC Compact" includes 25 items and 2 open-ended questions across the 5 domains, 44% of the length of the original instrument. "PREOS-PC Screen" consists of 6 items: the best-performing single items for 2 domains, 1 item modified from original items for each of the remaining 3 domains, and 1 open-ended question. The evaluation of the instruments confirmed they were acceptable to patients and met standards for readability; construct, convergent, and divergent validity; and reliability. CONCLUSIONS: PREOS-PC Compact meets high-performance standards while reducing patient burden for routine monitoring of patient safety in primary care. PREOS-PC Screen is a concise tool apt for incorporation into audits and to target more in-depth review as needed.

Recruitment to a large scale randomised controlled clinical trial in primary care: the Helicobacter Eradication Aspirin Trial (HEAT).

BACKGROUND: The Helicobacter Eradication Aspirin Trial (HEAT) is a multicentre, double blind, randomised controlled trial investigating whether Helicobacter (H.) pylori eradication reduces hospitalisation for peptic ulcer bleeding. Recruited participants were aged 60 and over and taking aspirin (≤325 mg daily) for at least four months prior to consent. Based on results of a pilot study, a sample size calculation predicted 6600 H. pylori-positive randomised participants would be required, from 33,000 volunteers, recruited from 170,000 invited patients. Methodology was therefore designed for recruitment of large numbers of patients from primary care using a novel electronic search tool, automated mail-out and electronic follow-up. Recruitment started in 2012 and completed in 2017. METHODS: All participants were recruited from GP practices, with assistance from the UK Clinical Research Network (UKCRN). H. pylori-positive participants were randomised to one week of eradication treatment or placebo. Recruitment was managed using a bespoke web-based database that communicated directly with a programmed search tool downloaded at participating practices. The primary endpoint is hospitalisation due to peptic ulcer bleeding. The trial will end when 87 adjudicated events have occurred, identified from searches of GP databases, review of secondary care admission data and mortality data, and reported events from randomised participants and GPs. RESULTS: HEAT has recruited participants from 1208 GP practices across the UK. Of the 188,875 invitation letters sent, 38,771 returned expressions of interest. Of these, 30,166 patients were consented to the trial, of whom 5355 H. pylori-positive participants (17.8% of those consented) were randomised. Mean age at consent was 73.1 ± 6.9 (SD) years and 72.2% of participants were male. Of the randomised (H. pylori-positive) participants, 531 have died (as of 17 Sep 2020); none of the deaths was due to trial treatment. CONCLUSION: The HEAT trial methodology has demonstrated that recruitment of large numbers of patients from primary care is attainable, with the assistance of the UKCRN, and could be applied to other clinical outcomes studies. TRIAL REGISTRATION: ClinicalTrials.gov ; registration number NCT01506986 . Registered on 10 Jan 2012.

Strategies supporting sustainable prescribing safety improvement interventions in English primary care: a qualitative study.

BACKGROUND: While the use of prescribing safety indicators (PSI) can reduce potentially hazardous prescribing, there is a need to identify actionable strategies for the successful implementation and sustainable delivery of PSI-based interventions in general practice. AIM: To identify strategies for the successful implementation and sustainable use of PSI-based interventions in routine primary care. DESIGN & SETTING: Qualitative study in primary care settings across England. METHOD: Anchoring on a complex pharmacist-led IT-based intervention (PINCER) and clinical decision support (CDS) for prescribing and medicines management, a qualitative study was conducted using sequential, multiple methods. The methods comprised documentary analysis, semi-structured interviews, and online workshops to identify challenges and possible solutions to the longer-term sustainability of PINCER and CDS. Thematic analysis was used for the documentary analysis and stakeholder workshops, while template analysis was used for the semi-structured interviews. Findings across the three methods were synthesised using the RE-AIM (reach, efficacy, adoption, implementation, and maintenance) framework. RESULTS: Forty-eight documents were analysed, and 27 interviews and two workshops involving 20 participants were undertaken. Five main issues were identified, which aligned with the adoption and maintenance dimensions of RE-AIM: fitting into current context (adoption); engaging hearts and minds (maintenance); building resilience (maintenance); achieving engagement with secondary care (maintenance); and emphasising complementarity (maintenance). CONCLUSION: Extending ownership of prescribing safety beyond primary care-based pharmacists, and achieving greater alignment between general practice and hospital prescribing safety initiatives, is fundamental to achieve sustained impact of PSI-based interventions in primary care.