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.

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.

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.

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.

Evaluation of a pharmacist-led actionable audit and feedback intervention for improving medication safety in UK primary care: An interrupted time series analysis.

BACKGROUND: We evaluated the impact of the pharmacist-led Safety Medication dASHboard (SMASH) intervention on medication safety in primary care. METHODS AND FINDINGS: SMASH comprised (1) training of clinical pharmacists to deliver the intervention; (2) a web-based dashboard providing actionable, patient-level feedback; and (3) pharmacists reviewing individual at-risk patients, and initiating remedial actions or advising general practitioners on doing so. It was implemented in 43 general practices covering a population of 235,595 people in Salford (Greater Manchester), UK. All practices started receiving the intervention between 18 April 2016 and 26 September 2017. We used an interrupted time series analysis of rates (prevalence) of potentially hazardous prescribing and inadequate blood-test monitoring, comparing observed rates post-intervention to extrapolations from a 24-month pre-intervention trend. The number of people registered to participating practices and having 1 or more risk factors for being exposed to hazardous prescribing or inadequate blood-test monitoring at the start of the intervention was 47,413 (males: 23,073 [48.7%]; mean age: 60 years [standard deviation: 21]). At baseline, 95% of practices had rates of potentially hazardous prescribing (composite of 10 indicators) between 0.88% and 6.19%. The prevalence of potentially hazardous prescribing reduced by 27.9% (95% CI 20.3% to 36.8%, p < 0.001) at 24 weeks and by 40.7% (95% CI 29.1% to 54.2%, p < 0.001) at 12 months after introduction of SMASH. The rate of inadequate blood-test monitoring (composite of 2 indicators) reduced by 22.0% (95% CI 0.2% to 50.7%, p = 0.046) at 24 weeks; the change at 12 months (23.5%) was no longer significant (95% CI -4.5% to 61.6%, p = 0.127). After 12 months, 95% of practices had rates of potentially hazardous prescribing between 0.74% and 3.02%. Study limitations include the fact that practices were not randomised, and therefore unmeasured confounding may have influenced our findings. CONCLUSIONS: The SMASH intervention was associated with reduced rates of potentially hazardous prescribing and inadequate blood-test monitoring in general practices. This reduction was sustained over 12 months after the start of the intervention for prescribing but not for monitoring of medication. There was a marked reduction in the variation in rates of hazardous prescribing between practices.

Understanding the utilisation of a novel interactive electronic medication safety dashboard in general practice: a mixed methods study.

BACKGROUND: Improving medication safety is a major concern in primary care settings worldwide. The Salford Medication safety dASHboard (SMASH) intervention provided general practices in Salford (Greater Manchester, UK) with feedback on their safe prescribing and monitoring of medications through an online dashboard, and input from practice-based trained clinical pharmacists. In this study we explored how staff working in general practices used the SMASH dashboard to improve medication safety, through interactions with the dashboard to identify potential medication safety hazards and their workflow to resolve identified hazards. METHODS: We used a mixed-methods study design involving quantitative data from dashboard user interaction logs from 43 general practices during the first year of receiving the SMASH intervention, and qualitative data from semi-structured interviews with 22 pharmacists and physicians from 18 practices in Salford. RESULTS: Practices interacted with the dashboard a median of 12.0 (interquartile range, 5.0-15.2) times per month during the first quarter of use to identify and resolve potential medication safety hazards, typically starting with the most prevalent hazards or those they perceived to be most serious. Having observed a potential hazard, pharmacists and practice staff worked together to resolve that in a sequence of steps (1) verifying the dashboard information, (2) reviewing the patient's clinical records, and (3) deciding potential changes to the patient's medicines. Over time, dashboard use transitioned towards regular but less frequent (median of 5.5 [3.5-7.9] times per month) checks to identify and resolve new cases. The frequency of dashboard use was higher in practices with a larger number of at-risk patients. In 24 (56%) practices only pharmacists used the dashboard; in 12 (28%) use by other practice staff increased as pharmacist use declined after the initial intervention period; and in 7 (16%) there was mixed use by both pharmacists and practice staff over time. CONCLUSIONS: An online medication safety dashboard enabled pharmacists to identify patients at risk of potentially hazardous prescribing. They subsequently worked with GPs to resolve risks on a case-by-case basis, but there were marked variations in processes between some practices. Workload diminished over time as it shifted towards resolving new cases of hazardous prescribing.

Developing a measure of polypharmacy appropriateness in primary care: systematic review and expert consensus study.

BACKGROUND: Polypharmacy is an increasing challenge for primary care. Although sometimes clinically justified, polypharmacy can be inappropriate, leading to undesirable outcomes. Optimising care for polypharmacy necessitates effective targeting and monitoring of interventions. This requires a valid, reliable measure of polypharmacy, relevant for all patients, that considers clinical appropriateness and generic prescribing issues applicable across all medications. Whilst there are several existing measures of potentially inappropriate prescribing, these are not specifically designed with polypharmacy in mind, can require extensive clinical input to complete, and often cover a limited number of drugs. The aim of this study was to identify what experts consider to be the key elements of a measure of prescribing appropriateness in the context of polypharmacy. METHODS: Firstly, we conducted a systematic review to identify generic (not drug specific) prescribing indicators relevant to polypharmacy appropriateness. Indicators were subject to content analysis to enable categorisation. Secondly, we convened a panel of 10 clinical experts to review the identified indicators and assess their relative clinical importance. For each indicator category, a brief evidence summary was developed, based on relevant clinical and indicator literature, clinical guidance, and opinions obtained from a separate patient discussion panel. A two-stage RAND/UCLA Appropriateness Method was used to reach consensus amongst the panel on a core set of indicators of polypharmacy appropriateness. RESULTS: We identified 20,879 papers for title/abstract screening, obtaining 273 full papers. We extracted 189 generic indicators, and presented 160 to the panel grouped into 18 classifications (e.g. adherence, dosage, clinical efficacy). After two stages, during which the panel introduced 18 additional indicators, there was consensus that 134 indicators were of clinical importance. Following the application of decision rules and further panel consultation, 12 indicators were placed into the final selection. Panel members particularly valued indicators concerned with adverse drug reactions, contraindications, drug-drug interactions, and the conduct of medication reviews. CONCLUSIONS: We have identified a set of 12 indicators of clinical importance considered relevant to polypharmacy appropriateness. Use of these indicators in clinical practice and informatics systems is dependent on their operationalisation and their utility (e.g. risk stratification, targeting and monitoring polypharmacy interventions) requires subsequent evaluation. TRIAL REGISTRATION: Registration number: PROSPERO ( CRD42016049176 ).

Mindful organizing in patients' contributions to primary care medication safety.

BACKGROUND: There is a need to ensure that the risks associated with medication usage in primary health care are controlled. To maintain an understanding of the risks, health-care organizations may engage in a process known as "mindful organizing." While this is typically conceived of as involving organizational members, it may in the health-care context also include patients. Our study aimed to examine ways in which patients might contribute to mindful organizing with respect to primary care medication safety. METHOD: Qualitative focus groups and interviews were carried out with 126 members of the public in North West England and the East Midlands. Participants were taking medicines for a long-term health condition, were taking several medicines, had previously encountered problems with their medication or were caring for another person in any of these categories. Participants described their experiences of dealing with medication-related concerns. The transcripts were analysed using a thematic method. RESULTS: We identified 4 themes to explain patient behaviour associated with mindful organizing: knowledge about clinical or system issues; artefacts that facilitate control of medication risks; communication with health-care professionals; and the relationship between patients and the health-care system (in particular, mutual trust). CONCLUSIONS: Mindful organizing is potentially useful for framing patient involvement in safety, although there are some conceptual and practical issues to be addressed before it can be fully exploited in this setting. We have identified factors that influence (and are strengthened by) patients' engagement in mindful organizing, and as such would be a useful focus of efforts to support patient involvement.

Professional, structural and organisational interventions in primary care for reducing medication errors.

BACKGROUND: Medication-related adverse events in primary care represent an important cause of hospital admissions and mortality. Adverse events could result from people experiencing adverse drug reactions (not usually preventable) or could be due to medication errors (usually preventable). OBJECTIVES: To determine the effectiveness of professional, organisational and structural interventions compared to standard care to reduce preventable medication errors by primary healthcare professionals that lead to hospital admissions, emergency department visits, and mortality in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, three other databases, and two trial registries on 4 October 2016, together with reference checking, citation searching and contact with study authors to identify additional studies. We also searched several sources of grey literature. SELECTION CRITERIA: We included randomised trials in which healthcare professionals provided community-based medical services. We also included interventions in outpatient clinics attached to a hospital where people are seen by healthcare professionals but are not admitted to hospital. We only included interventions that aimed to reduce medication errors leading to hospital admissions, emergency department visits, or mortality. We included all participants, irrespective of age, who were prescribed medication by a primary healthcare professional. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data. Each of the outcomes (hospital admissions, emergency department visits, and mortality), are reported in natural units (i.e. number of participants with an event per total number of participants at follow-up). We presented all outcomes as risk ratios (RRs) with 95% confidence intervals (CIs). We used the GRADE tool to assess the certainty of evidence. MAIN RESULTS: We included 30 studies (169,969 participants) in the review addressing various interventions to prevent medication errors; four studies addressed professional interventions (8266 participants) and 26 studies described organisational interventions (161,703 participants). We did not find any studies addressing structural interventions. Professional interventions included the use of health information technology to identify people at risk of medication problems, computer-generated care suggested and actioned by a physician, electronic notification systems about dose changes, drug interventions and follow-up, and educational interventions on drug use aimed at physicians to improve drug prescriptions. Organisational interventions included medication reviews by pharmacists, nurses or physicians, clinician-led clinics, and home visits by clinicians.There is a great deal of diversity in types of professionals involved and where the studies occurred. However, most (61%) of the interventions were conducted by pharmacists or a combination of pharmacists and medical doctors. The studies took place in many different countries; 65% took place in either the USA or the UK. They all ranged from three months to 4.7 years of follow-up, they all took place in primary care settings such as general practice, outpatients' clinics, patients' homes and aged-care facilities. The participants in the studies were adults taking medications and the interventions were undertaken by healthcare professionals including pharmacists, nurses or physicians. There was also evidence of potential bias in some studies, with only 18 studies reporting adequate concealment of allocation and only 12 studies reporting appropriate protection from contamination, both of which may have influenced the overall effect estimate and the overall pooled estimate. Professional interventionsProfessional interventions probably make little or no difference to the number of hospital admissions (risk ratio (RR) 1.24, 95% confidence interval (CI) 0.79 to 1.96; 2 studies, 3889 participants; moderate-certainty evidence). Professional interventions make little or no difference to the number of participants admitted to hospital (adjusted RR 0.99, 95% CI 0.92 to 1.06; 1 study, 3661 participants; high-certainty evidence). Professional interventions may make little or no difference to the number of emergency department visits (adjusted RR 0.71, 95% CI 0.50 to 1.02; 2 studies, 1067 participants; low-certainty evidence). Professional interventions probably make little or no difference to mortality in the study population (adjusted RR 0.98, 95% CI 0.82 to 1.17; 1 study, 3538 participants; moderate-certainty evidence). Organisational interventionsOverall, it is uncertain whether organisational interventions reduce the number of hospital admissions (adjusted RR 0.85, 95% CI 0.71 to 1.03; 11 studies, 6203 participants; very low-certainty evidence). Overall, organisational interventions may make little difference to the total number of people admitted to hospital in favour of the intervention group compared with the control group (adjusted RR 0.92, 95% CI 0.86 to 0.99; 13 studies, 152,237 participants; low-certainty evidence. Overall, it is uncertain whether organisational interventions reduce the number of emergency department visits in favour of the intervention group compared with the control group (adjusted RR 0.75, 95% CI 0.49 to 1.15; 5 studies, 1819 participants; very low-certainty evidence. Overall, it is uncertain whether organisational interventions reduce mortality in favour of the intervention group (adjusted RR 0.94, 95% CI 0.85 to 1.03; 12 studies, 154,962 participants; very low-certainty evidence. AUTHORS' CONCLUSIONS: Based on moderate- and low-certainty evidence, interventions in primary care for reducing preventable medication errors probably make little or no difference to the number of people admitted to hospital or the number of hospitalisations, emergency department visits, or mortality. The variation in heterogeneity in the pooled estimates means that our results should be treated cautiously as the interventions may not have worked consistently across all studies due to differences in how the interventions were provided, background practice, and culture or delivery of the interventions. Larger studies addressing both professional and organisational interventions are needed before evidence-based recommendations can be made. We did not identify any structural interventions and only four studies used professional interventions, and so more work needs to be done with these types of interventions. There is a need for high-quality studies describing the interventions in more detail and testing patient-related outcomes.

Assessing the impact of the introduction of an electronic hospital discharge system on the completeness and timeliness of discharge communication: a before and after study.

BACKGROUND: Hospital discharge summaries are a key communication tool ensuring continuity of care between primary and secondary care. Incomplete or untimely communication of information increases risk of hospital readmission and associated complications. The aim of this study was to evaluate whether the introduction of a new electronic discharge system (NewEDS) was associated with improvements in the completeness and timeliness of discharge information, in Nottingham University Hospitals NHS Trust, England. METHODS: A before and after longitudinal study design was used. Data were collected using the gold standard auditing tool from the Royal College of Physicians (RCP). This tool contains a checklist of 57 items grouped into seven categories, 28 of which are classified as mandatory by RCP. Percentage completeness (out of the 28 mandatory items) was considered to be the primary outcome measure. Data from 773 patients discharged directly from the acute medical unit over eight-week long time periods (four before and four after the change to the NewEDS) from August 2010 to May 2012 were extracted and evaluated. Results were summarised by effect size on completeness before and after changeover to NewEDS respectively. The primary outcome variable was represented with percentage of completeness score and a non-parametric technique was used to compare pre-NewEDS and post-NewEDS scores. RESULTS: The changeover to the NewEDS resulted in an increased completeness of discharge summaries from 60.7% to 75.0% (p < 0.001) and the proportion of summaries created under 24 h from discharge increased significantly from 78.0% to 93.0% (p < 0.001). Furthermore, five of the seven grouped checklist categories also showed significant improvements in levels of completeness (p < 0.001), although there were reduced levels of completeness for three items (p < 0.001). CONCLUSION: The introduction of a NewEDS was associated with a significant improvement in the completeness and timeliness of hospital discharge communication.

Understanding the implementation and adoption of a technological intervention to improve medication safety in primary care: a realist evaluation.

BACKGROUND: Monitoring for potentially hazardous prescribing is increasingly important to improve medication safety. Healthcare information technology can be used to achieve this aim, for example by providing access to prescribing data through surveillance of patients' electronic health records. The aim of our study was to examine the implementation and adoption of an electronic medicines optimisation system that was intended to facilitate clinical audit in primary care by identifying patients at risk of an adverse drug event. We adopted a sociotechnical approach that focuses on how complex social, organisational and institutional factors may impact upon the use of technology within work settings. METHODS: We undertook a qualitative realist evaluation of the use of an electronic medicines optimisation system in one Clinical Commissioning Group in England. Five semi-structured interviews, four focus groups and one observation were conducted with a range of stakeholders. Consistent with a realist evaluation methodology, the analysis focused on exploring the links between context, mechanism and outcome to explain the ways the intervention might work, for whom and in what circumstances. RESULTS: Using the electronic medicines optimisation system could lead to a number of improved patient safety outcomes including pre-emptively reviewing patients at risk of adverse drug events. The effective use of the system depended upon engagement with the system, the flow of information between different health professionals centrally placed at the Clinical Commissioning Group and those locally placed at individual general practices, and upon variably adapting work practices to facilitate the use of the system. The use of the system was undermined by perceptions of ownership, lack of access, and lack of knowledge and awareness. CONCLUSIONS: The use of an electronic medicines optimisation system may improve medication safety in primary care settings by identifying those patients at risk of an adverse drug event. To fully realise the potential benefits for medication safety there needs to be better utilisation across primary care and with a wider range of stakeholders. Engaging with all potential stakeholders and users prior to implementation of such systems might allay perceptions that the system is owned centrally and increase knowledge of the potential benefits.

Measuring Patient Safety in Primary Care: The Development and Validation of the "Patient Reported Experiences and Outcomes of Safety in Primary Care" (PREOS-PC).

PURPOSE: We set out to develop and validate a patient-reported instrument for measuring experiences and outcomes related to patient safety in primary care. METHOD: The instrument was developed in a multistage process supported by an international expert panel and informed by a systematic review of instruments, a meta-synthesis of qualitative studies, 4 patient focus groups, 18 cognitive interviews, and a pilot study. The trial version of Patient Reported Experiences and Outcomes of Safety in Primary Care (PREOS-PC) covered 5 domains and 11 scales: practice activation (1 scale); patient activation (1 scale); experiences of patient safety events (1 scale); harm (6 scales); and general perceptions of patient safety (2 scales). The questionnaire was posted to 6,736 patients in 45 practices across England. We used "gold standard" psychometric methods to evaluate its acceptability, reliability, structural and construct validity, and ability to discriminate among practices. RESULTS: 1,244 completed questionnaires (18.5%) were returned. Median item-specific response rate was 91.3% (interquartile range 28.0%). No major ceiling or floor effects were observed. All 6 multi-item scales showed high internal consistency (Cronbach's α 0.75-0.96). Factor analysis, correlation between scales, and known group analyses generally supported structural and construct validity. The scales demonstrated a heterogeneous ability to discriminate between practices. The final version of PREOS-PC consisted of 5 domains, 8 scales, and 58 items. CONCLUSIONS: PREOS-PC is a new multi-dimensional patient safety instrument for primary care developed with experts and patients. Initial testing shows its potential for use in primary care, and future developments will further address its use in actual clinical practice.

Assessing the safety features of electronic patient medication record systems used in community pharmacies in England.

AIMS: To evaluate the ability of electronic patient medication record (ePMR) systems used in community pharmacies in England to detect and alert users about clinical hazards, errors and other safety problems. METHODS: Between September 2012 and November 2012, direct on-site observational data about the performance of ePMR systems were collected from nine sites. Twenty-eight scenarios were developed by consensus agreement between a general practitioner and two community pharmacists. Each scenario was entered into the ePMR system, and the results obtained from the assessment of six unique systems in nine sites, in terms of the presence or absence of an alert, were recorded onto a prespecified form. RESULTS: None of the systems produced the correct responses for all of the 28 scenarios tested. Only two systems provided an alert to penicillin sensitivity. No dose or frequency check was observed when processing a prescription for methotrexate. One system did not warn about nonsuitability of aspirin prescribed to a child of 14 years of age. In another system, it was not possible to record a patient's pregnancy status. None of the six systems provided any warning for diclofenac overdose, high initiation dose of morphine sulfate or significant dose increase. Only one of the systems did not produce any spurious alerts. CONCLUSIONS: The performance of the ePMR systems tested was variable and suboptimal. The findings suggest the need for minimum specifications and standards for ePMR systems to ensure consistency of performance.

Is polypharmacy always hazardous? A retrospective cohort analysis using linked electronic health records from primary and secondary care.

AIMS: Prescribing multiple medications is associated with various adverse outcomes, and polypharmacy is commonly considered suggestive of poor prescribing. Polypharmacy might thus be associated with unplanned hospitalization. We sought to test this assumption. METHODS: Scottish primary care data for 180 815 adults with long-term clinical conditions and numbers of regular medications were linked to national hospital admissions data for the following year. Using logistic regression (age, gender and deprivation adjusted), we modelled the association of prescribing with unplanned admission for patients with different numbers of long-term conditions. RESULTS: Admissions were more common in patients on multiple medications, but admission risk varied with the number of conditions. For patients with one condition, the odds ratio for unplanned admission for four to six medications was 1.25 (95% confidence interval 1.11-1.42) vs. one to three medications, and 3.42 (95% confidence interval 2.72-4.28) for ≥10 medications vs. one to three medications. However, this effect was greatly reduced for patients with multiple conditions; amongst patients with six or more conditions, those on four to six medications were no more likely to have unplanned admissions than those taking one to three medications (odds ratio 1.00; 95% confidence interval 0.88-1.14), and those taking ≥10 medications had a modestly increased risk of admission (odds ratio 1.50; 95% confidence interval 1.31-1.71). CONCLUSIONS: Unplanned hospitalization is strongly associated with the number of regular medications. However, the effect is reduced in patients with multiple conditions, in whom only the most extreme levels of polypharmacy are associated with increased admissions. Assumptions that polypharmacy is always hazardous and represents poor care should be tempered by clinical assessment of the conditions for which those drugs are being prescribed.

Tools for measuring patient safety in primary care settings using the RAND/UCLA appropriateness method.

BACKGROUND: The majority of patient contacts occur in general practice but general practice patient safety has been poorly described and under-researched to date compared to hospital settings. Our objective was to produce a set of patient safety tools and indicators that can be used in general practices in any healthcare setting and develop a 'toolkit' of feasible patient safety measures for general practices in England. METHODS: A RAND/UCLA Appropriateness Method exercise was conducted with a panel of international experts in general practice patient safety. Statements were developed from an extensive systematic literature review of patient safety in general practice. We used standard RAND/UCLA Appropriateness Method rating methods to identify necessary items for assessing patient safety in general practice, framed in terms of the Structure-Process-Outcome taxonomy. Items were included in the toolkit if they received an overall panel median score of ≥ 7 with agreement (no more than two panel members rating the statement outside a 3-point distribution around the median). RESULTS: Of 205 identified statements, the panel rated 101 as necessary for assessing the safety of general practices. Of these 101 statements, 73 covered structures or organisational issues, 22 addressed processes and 6 focused on outcomes. CONCLUSIONS: We developed and tested tools that can lead to interventions to improve safety outcomes in general practice. This paper reports the first attempt to systematically develop a patient safety toolkit for general practice, which has the potential to improve safety, cost effectiveness and patient experience, in any healthcare system.

Meeting user needs in national healthcare systems: lessons from early adopter community pharmacists using the electronic prescriptions service.

BACKGROUND: The Electronic Prescription Service release Two (EPS2) is a new national healthcare information and communication technology in England that aims to deliver effective prescription writing, dispensing and reimbursement service to benefit patients. The aim of the study was to explore initial user experiences of Community Pharmacists (CPs) using EPS2. METHODS: We conducted nonparticipant observations and interviews in eight EPS2 early adopter community pharmacies classified as 'first-of-type' in midlands and northern regions in England. We interviewed eight pharmacists and two dispensers in addition to 56 hours recorded nonparticipant observations as field notes. Line-by-line coding and thematic analysis was conducted on the interview transcripts and field notes. RESULTS: CPs faced two types of challenge. The first was to do with missing electronic prescriptions. This was sometimes very disrupting to work practice, but pharmacists considered it a temporary issue resolvable with minor modifications to the system and user familiarity. The second was to do with long term design-specific issues. Pharmacists could only overcome these by using the system in ways not intended by the developers. Some felt that these issues would not exist had 'real' users been involved in the initial development. The issues were: 1) printing out electronic prescriptions (tokens) to dispense from for safe dispensing practices and to free up monitors for other uses, 2) logging all dispensing activities with one user's Smartcard for convenience and use all human resources in the pharmacy, and, 3) problematic interface causing issues with endorsing prescriptions and claiming reimbursements. CONCLUSIONS: We question if these unintended uses and barriers would have occurred had a more rigorous user-centric principles been applied at the earlier stages of design and implementation of EPS. We conclude that, since modification can occur at the evaluation stage, there is still scope for some of these barriers to be corrected to address the needs, and enhance the experiences, of CPs using the service, and make recommendations on how current challenges could be resolved.

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.