Analysis of the use of antibiotics by AWaRe categories during the COVID-19 pandemic in hospitals across Scotland: a national population-based study.

OBJECTIVE: The Access, Watch and Reserve (AWaRe) list of antibiotics was developed by the WHO to support antibiotic stewardship programmes (ASP). The Access group incorporates first-line options, while Watch antibiotics have higher resistance potential or toxicity, and Reserve drugs should be used only for complex infections. ASP implementation has been challenged during the COVID-19 pandemic. There is a knowledge gap regarding in-hospital prescribing patterns of antibiotics nationally during the COVID-19 pandemic, and on the characteristics of hospitalised patients prescribed antibiotics during this time. We aimed to evaluate quality of antibiotic use according to AWaRe classification in Scottish hospitals, including assessing the impact of COVID-19 on trends. METHODS: Cross-sectional study of antibiotics prescribed to hospitalised patients from 1 January 2019 to 30 June 2022 in a selection of Scottish hospitals, covering approximately 60% (3.6 million people) of the Scottish population. Data were obtained from the Hospital Electronic Prescribing and Medicines Administration system. Prescribing trends were explored over time, by age and by sex. RESULTS: Overall, a total 1 353 003 prescriptions were identified. An increase in Access antibiotics was found from 55.3% (31 901/57 708) to 62.3% (106 449/170 995) over the study period, alongside a decrease in Watch antibiotics from 42.9% (24 772/57 708) to 35.4% (60 632/170 995). Reserve antibiotic use was limited throughout, with minor changes over time. Changes in prescribing were most pronounced in the older age group (>65 years): proportions of Access antibiotics increased from 56.4% (19 353/34 337) to 65.8% (64 387/97 815, p<0.05), while Watch antibiotics decreased from 41.9% (14 376/34 337) to 32.3% (31 568/97 815, p<0.05) between Q1 2019 and Q2 2022. Differences between males and females were insignificant. CONCLUSIONS: Findings showed encouraging trends in Access and Watch use among hospitalised patients, in line with Scottish national standards. There was no noteworthy effect of COVID-19 on prescribing trends despite reports indicating stewardship programmes being negatively impacted by the pandemic.

Involving Patients and Clinicians in the Design of Wireframes for Cancer Medicines Electronic Patient Reported Outcome Measures in Clinical Care: Mixed Methods Study.

BACKGROUND: Cancer treatment is a key component of health care systems, and the increasing number of cancer medicines is expanding the treatment landscape. However, evidence of the impact on patients has been focused more on chemotherapy toxicity and symptom control and less on the effect of cancer medicines more broadly on patients' lives. Evolving electronic patient-reported outcome measures (ePROMs) presents the opportunity to secure early engagement of patients and clinicians in shaping the collection of quality-of-life metrics and presenting these data to better support the patient-clinician decision-making process. OBJECTIVE: The aim of this study was to obtain initial feedback from patients and clinicians on the wireframes of a digital solution (patient app and clinician dashboard) for the collection and use of cancer medicines ePROMs. METHODS: We adopted a 2-stage, mixed methods approach. Stage 1 (March to June 2019) consisted of interviews and focus groups with cancer clinicians and patients with cancer to explore the face validity of the wireframes, informed by the technology acceptance model constructs (perceived ease of use, perceived usefulness, and behavioral intention to use). In stage 2 (October 2019 to February 2020), the revised wireframes were assessed through web-based, adapted technology acceptance model questionnaires. Qualitative data (stage 1) underwent a framework analysis, and descriptive statistics were performed on quantitative data (stage 2). Clinicians and patients with cancer were recruited from NHS Greater Glasgow & Clyde, the largest health board in Scotland. RESULTS: A total of 14 clinicians and 19 patients participated in a combination of stage 1 interviews and focus groups. Clinicians and patients indicated that the wireframes of a patient app and clinician dashboard for the collection of cancer medicines ePROMs would be easy to use and could focus discussions, and they would be receptive to using such tools in the future. In stage 1, clinicians raised the potential impact on workload, and both groups identified the need for adequate IT skills to use each technology. Changes to the wireframes were made, and in stage 2, clinicians (n=8) and patients (n=16) indicated it was "quite likely" that the technologies would be easy to use and they would be "quite likely" to use them in the future. Notably, clinicians indicated that they would use the dashboard to enable treatment decisions "with around half" of their patients. CONCLUSIONS: This study emphasizes the importance of consulting both patients and clinicians in the design of digital solutions. The wireframes were perceived positively by patients and clinicians who were willing to use such technologies if available in the future as part of routine care. However, challenges were raised, and some differences were identified between participant groups, which warrant further research.

Public health qualifications, motivation, and experience of pharmacy professionals: exploratory cross-sectional surveys of pharmacy and public health professionals.

BACKGROUND: Pharmacy professionals (pharmacists and pharmacy technicians; PPs) are recognised for delivering public health interventions (micro level). There is increased policy focus on population health management, but limited knowledge regarding the role of PPs within UK's public health meso and macro levels. This study aimed to explore UK PPs' public health qualifications, specialisations, and motivations and barriers to pursuing advanced public health practice. METHODS: In this cross-sectional study, we developed and piloted two surveys, and we disseminated them separately via email to UK pharmacy and public health networks and social media, between June 19, and Oct 26, 2021. PPs with an interest or experience in public or population health were invited to participate in the study. We asked PPs questions about public health qualifications, specialisations, motivations, and barriers, and we also asked PHPs for opinions regarding the value of specialist public health skills for PPs. Numerical data were summarised, and responses collated into themes. NHS Health Research Authority tool identified ethics approval not required; and the questionnaire included consent request. FINDINGS: 128 PPs (85% pharmacists) and 54 PHPs responded. Of the PPs who responded, 90 (70%) were female and 35 (27%) were male; 62 (48%) were White British, 19 (14%) were Asian or Asian British, 14 (12%) were Black or Black British. They worked in primary care (34%, n=43), secondary care (26%, n=33), Community Pharmacy (13%, n=16), and public health bodies (13%, n=16). Overall, 34 (27%) of 128 PPs (32 pharmacists; 2 pharmacy technicians) possessed public health qualifications (MPH, PhD). Motivations for these qualifications were ambition to work as PP in public health PP (31%; 17/55 respondents), public health as alternative career (29%; 16/55), general interest (27%; 15/55) recommended or required for current role (11%; 6/55). Themes of barriers included limited training opportunities and poor career pathways. For the PHP survey, 36 (67%) of 54 were female and 16 (30%) were male. They worked as Consultants or Directors (28%, n=15), Registrars (24%, n=13), Practitioners (15%, n=8). 45 (87%) of 52 PHP respondents agreed that specialist PPs in public health would be beneficial to public health; 13 (45%) of 29 respondents recommended a public health Master's degree, eight (27%) recommended experience or postgraduate modules in health economics and health inequalities, three (10%) recommended credentialing for PPs to specialise. INTERPRETATION: Findings suggest responding PPs are motivated to advance in public health practice, despite barriers. Collaboration with PHPs and development of communities of practice might address barriers identified and contribute to advanced public health practice for PPs, supporting the increased focus on population health management in the UK. Limitations include the exploratory nature of the study, and the fact that PPs responding to public health surveys might be more motivated to advance in public health practice than those not responding. FUNDING: NHS England and UK Health Security Agency.

Real-world effectiveness of systemic anticancer therapy for advanced melanoma in the west of Scotland from 2010 to 2018.

Aim: Assess the real-world effectiveness of systemic anticancer therapy in advanced (unresectable or metastatic) melanoma. Methods: This was a retrospective cohort study linking routine healthcare data with systemic anticancer therapy prescriptions for patients starting immunotherapy or targeted treatments between 1 November 2010 and 31 December 2017 in the west of Scotland. Results: Among 362 patients identified, median overall survival varied between 18.5 months (95% CI: 14.4-not estimable) for ipilimumab/nivolumab combination and 5.6 months (95% CI: 4.5-7.3) for dabrafenib, but there were differences in the characteristics of each regimen cohort. Raised lactate dehydrogenase levels and Eastern Cooperative Oncology Group performance status ≥2 negatively impacted overall survival. Conclusion: The patients had a shorter median overall survival than those in pivotal trials. This was expected, given that this real-world cohort included patients with poorer prognostic indicators, typically excluded from trials.

Evaluation of duration of antibiotic therapy across hospitals in Scotland including the impact of COVID-19 pandemic: a segmented interrupted time series analysis.

BACKGROUND: Little is known about the duration of antibiotic use in hospital settings. We evaluated the duration of hospital antibiotic therapy for four commonly prescribed antibiotics (amoxicillin, co-amoxiclav, doxycycline, and flucloxacillin) including the assessment of COVID-19 impact. METHODS: A repeated, cross-sectional study using the Hospital Electronic Prescribing and Medicines Administration system (January/2019-March/2022). Monthly median duration of therapy/duration categories was calculated, stratified by routes of administration, age, and sex. The impact of COVID-19 was assessed using segmented time-series analysis. RESULTS: There were significant variations in the median duration of therapy across routes of administration (P < 0.05), with the highest value among those antibiotic courses composed of both oral and IV antibiotics ('Both' group). Significantly higher proportions of prescriptions within the 'Both' group had a duration of >7 days compared to oral or IV. The duration of therapy differed significantly by age. Some small statistically significant changes in the level/trends of duration of therapy were observed in the post-COVID-19 period. CONCLUSIONS: No evidence for prolonged duration of therapy were observed, even during COVID-19 pandemic. The duration of IV therapy was relatively short, suggesting timely clinical review and consideration of IV to oral switch. Longer duration of therapy was observed among older patients.

The impact of the COVID-19 pandemic on cardiovascular disease prevention and management.

How the Coronavirus Disease 2019 (COVID-19) pandemic has affected prevention and management of cardiovascular disease (CVD) is not fully understood. In this study, we used medication data as a proxy for CVD management using routinely collected, de-identified, individual-level data comprising 1.32 billion records of community-dispensed CVD medications from England, Scotland and Wales between April 2018 and July 2021. Here we describe monthly counts of prevalent and incident medications dispensed, as well as percentage changes compared to the previous year, for several CVD-related indications, focusing on hypertension, hypercholesterolemia and diabetes. We observed a decline in the dispensing of antihypertensive medications between March 2020 and July 2021, with 491,306 fewer individuals initiating treatment than expected. This decline was predicted to result in 13,662 additional CVD events, including 2,281 cases of myocardial infarction and 3,474 cases of stroke, should individuals remain untreated over their lifecourse. Incident use of lipid-lowering medications decreased by 16,744 patients per month during the first half of 2021 as compared to 2019. By contrast, incident use of medications to treat type 2 diabetes mellitus, other than insulin, increased by approximately 623 patients per month for the same time period. In light of these results, methods to identify and treat individuals who have missed treatment for CVD risk factors and remain undiagnosed are urgently required to avoid large numbers of excess future CVD events, an indirect impact of the COVID-19 pandemic.

Identifying the important outcomes to measure for pharmacy-led, clinical services within primary care: A nominal group technique approach.

BACKGROUND: The introduction of clinical pharmacy services is part of a multi-disciplinary approach to reduce pressure on primary care. Ascertaining the impact of clinical pharmacists in general practice is vital to ensure intended benefits are achieved. However, this is complicated by poor quality evidence, multiple interventions, and a lack of agreement regarding outcome measures. OBJECTIVES: To develop an outcomes framework for clinical pharmacy services delivered in Scottish general practice using a consensus methodology. METHODS: A modified nominal group technique (NGT) was conducted using Microsoft Teams and Qualtrics. This involved a pre-NGT questionnaire, silent generation of ideas, round robin, discussions, ranking, and a final consensus exercise. A selective sampling strategy recruited experienced pharmacists from Scottish health regions. NGT ranking results were used to signify relative importance of the outcome areas. NGT discussions underwent inductive thematic analysis to explore key areas considered. RESULT: Overall, 13 (median: 24 years of experience) pharmacists participated, representing 11 of 14 Scottish regions. In total, 21 outcome areas, derived from the literature and a pre-NGT questionnaire, were considered during the NGT ranking exercise. Consensus identified five important outcome areas: Patient Experience, Medication Related Adverse Events, Cost-Effectiveness, Medication Optimisation, and Health Related Quality of Life. Thematic analysis highlighted the importance of the outcome framework's target audience, factors influencing the interpretation of outcomes, and the feasibility of the associated outcome measures. CONCLUSIONS: The five key outcome areas will facilitate evidence-based decisions regarding service delivery. Future work should develop a measurement plan, involving routinely collected sources of outcomes data. The feasibility of collecting outcomes in the real-world context should be considered, identifying measures which are easy to collect within existing data infrastructures. This paper describes a replicable method to gain consensus for a national approach to data collection from a strong theoretical basis using an online methodology.

Data Resource Profile: The Hospital Electronic Prescribing and Medicines Administration (HEPMA) National Data Collection in Scotland.

Introduction: To support both electronic prescribing and documentation of medicines administration in secondary care, hospitals in Scotland are currently implementing the Hospital Electronic Prescribing and Medicines Administration (HEPMA) software. Driven by the COVID-19 pandemic, agreements have been put in place to centrally collate data stemming from the operational HEPMA system. The aim was to develop a national data resource based on records created in secondary care, in line with pre-existing collections of data from primary care. Methods: HEPMA is a live clinical system and updated on a continuous basis. Data is automatically extracted from local systems at least weekly and, in most cases, on a nightly basis, and integrated into the national HEPMA dataset. Subsequently, the data are subject to quality checks including data consistency and completeness. Records contain a unique patient identified (Community Health Index number), enabling linkage to other routinely collected data including primary care prescriptions, hospital admission episodes, and death records. Results: The HEPMA data resource captures and compiles information on all medicines prescribed within the ward/hospital covered by the system; this includes medicine name, formulation, strength, dose, route, and frequency of administration, and dates and times of prescribing. In addition, the HEPMA dataset also captures information on medicines administration, including dates and time of administration. Data is available from January 2019 onwards and held by Public Health Scotland. Conclusion: The national HEPMA data resource supports cross-sectional/point-prevalence studies including drug utilisation studies, and also offers scope to conduct longitudinal studies, e.g., cohort and case-control studies. With the possibility to link to other relevant datasets, additional areas of interest may include health policy evaluations and health economics studies. Access to data is subject to approval; researchers need to contact the electronic Data Research and Innovation Service (eDRIS) in the first instance.

Assessing medication use patterns in patients hospitalised with COVID-19: a retrospective study.

OBJECTIVE: To describe patterns of medication use-that is, dexamethasone; remdesivir; and tocilizumab-in the management of patients hospitalised with COVID-19. DESIGN AND SETTING: Retrospective observational study, using routinely collected, linked electronic data from clinical practice in Scotland. Data on drug exposure in secondary care has been obtained from the Hospital Electronic Prescribing and Medicines Administration System. PARTICIPANTS: Patients being treated with the drugs of interest and hospitalised for COVID-19 between 1 March 2020 and 10 November 2021. OUTCOMES: Identification of patients subject to the treatments of interest; summary of patients' baseline characteristics; description of medication use patterns and treatment episodes. Analyses were descriptive in nature. RESULTS: Overall, 4063 patients matching the inclusion criteria were identified in Scotland, with a median (IQR) age of 64 years (52-76). Among all patients, 81.4% (n=3307) and 17.8% (n=725) were treated with one or two medicines, respectively; dexamethasone monotherapy accounted for the majority (n=3094, 76.2%) followed by dexamethasone in combination with tocilizumab (n=530, 13.0%). Treatment patterns were variable over time but roughly followed the waves of COVID-19 infections; however, the different drugs were used to varying degrees during the study period.The median (IQR) treatment duration differed by medicine: dexamethasone 5 days (2-9); remdesivir 5 days (2-5); and tocilizumab 1 day (1-1). The overall median (IQR) length of hospital stay among all patients included in the study cohort was 9 days (5-17); 24.7% of patients died in hospital. CONCLUSION: The use of adjuvant medicines in patients hospitalised with COVID-19 appears in line with evolving evidence and changing treatment guidelines. In-hospital electronic prescribing systems are a valuable source of information, providing detailed patient-level data on in-hospital drug use.

The impact of the COVID-19 pandemic on pharmacy personnel in primary care.

INTRODUCTION: The coronavirus (COVID-19) pandemic has impacted healthcare worldwide. It has altered service delivery and posed challenges to practitioners in relation to workload, well-being and support. Within primary care, changes in physicians' activities have been identified and innovative work solutions implemented. However, evidence is lacking regarding the impact of the pandemic on pharmacy personnel who work in primary care. AIM: To explore the impact of the pandemic on the working practice (including the type of services provided) and job satisfaction of pharmacists and pharmacy technicians within Scottish general practice. Due to the stressful nature of the pandemic, we hypothesise that job satisfaction will have been negatively affected. METHODS: An online questionnaire was distributed in May-July 2021, approximately 15 months since initial lockdown measures in the UK. The questionnaire was informed by previous literature and underwent expert review and piloting. Analysis involved descriptive statistics, non-parametric statistical tests and thematic analysis. RESULTS: 180 participants responded (approximated 16.1% response rate): 134 pharmacists (74.4%) and 46 technicians (25.6%). Responses indicated greater involvement with administrative tasks and a reduction in the provision of clinical services, which was negatively perceived by pharmacists. There was an increase in remote working, although most participants continued to have a physical presence within general practices. Face-to-face interactions with patients reduced, which was negatively perceived by participants, and telephone consults were considered efficient yet less effective. Professional development activities were challenged by increased workloads and reduced support available. Although workplace stress was apparent, there was no indication of widespread job dissatisfaction. CONCLUSION: The pandemic has impacted pharmacists and technicians, but it is unknown if changes will be permanent, and there is a need to understand which changes should continue. Future research should explore the impact of altered service delivery, including remote working, on patient care.

Feedback of Antibiotic Prescribing in Primary Care (FAPPC) trial: results of a real-world cluster randomized controlled trial in Scotland, UK.

OBJECTIVES: To evaluate the effect of general practice-level prescribing feedback on antibiotic prescribing in a real-world pragmatic cluster randomized controlled trial. METHODS: Three hundred and forty general practices in four territorial Health Boards in NHS Scotland were randomized in Quarter 1, 2016 to receive four quarterly antibiotic-prescribing feedback reports or not, from Quarter 2, 2016 to Quarter 1, 2017. Reports included different clinical topics, benchmarking against national and health board rates, and behavioural messaging with improvement actions. The primary outcome was total antibiotic prescribing rate. There were 16 secondary prescribing outcomes and 5 hospital admission outcomes (potential adverse effects of reduced prescribing). The main evaluation timepoint was 1 year after the final report (Quarter 1, 2018), with an additional evaluation in the quarter after the final report (Quarter 2, 2017). Routine administrative NHS data were used to generate the feedback reports and analyse the effects. RESULTS: Total antibiotic prescribing rates were lower at the main evaluation timepoint in both intervention (1.83 versus baseline 1.93 prescriptions/1000 patients/day) and control (1.90 versus baseline 1.98) practices, with no evidence of intervention effect [adjusted rate ratio (ARR) 0.98 (95% CI 0.94-1.02; P = 0.35)]. At the additional timepoint, adjusted total antibiotic prescribing rates were 1.67 and 1.73 prescriptions/1000 patients/day, with evidence of a small intervention effect, ARR 0.99 (0.98-1.00; P = 0.03). CONCLUSIONS: This well-designed, practice-level antibiotic-prescribing feedback had limited evidence of additional effects in the context of decreasing antibiotic prescribing and an established national stewardship programme.

A national, multicentre web-based point prevalence survey of antimicrobial use in community healthcare centres across South Africa and the implications.

OBJECTIVE: Up to 90% of antimicrobials globally are prescribed and dispensed in ambulatory care. However, there are considerable gaps regarding the extent and rationale for their use especially in low- and middle-income countries such as South Africa. Point prevalent surveys (PPS) are useful to determine current prescribing patterns, identify targets for quality improvement and evaluate the effectiveness of antimicrobial stewardship programmes (ASPs) within institutions. Consequently, the objective of this study was to undertake a PPS within community healthcare centers (CHCs) in South Africa given their importance to the public healthcare system. The findings will be used to provide guidance on future interventions to improve antimicrobial use in South Africa and wider. METHODS: A PPS of antimicrobial consumption was undertaken among patients attending 18 CHCs in South Africa. A web-based application was used to record the utilization data, with utilization assessed against World Health Organization (WHO) and South African guidelines. RESULTS: The overall prevalence of antimicrobial use amongst patients attending the CHCs was 21.5% (420 of 1958 patients). This included one or more antimicrobials per patient. The most frequently prescribed antimicrobials were amoxicillin (32.9%), isoniazide (11.3%) and a combination of rifampicin, isoniazid, pyrazinamide and ethambutol (Rifafour®) (10.5%), with the majority from the WHO Access list of antibiotics. There was high adherence to guidelines (93.4%). The most common indication for antibiotics were ear, nose and throat infections (22.8%), with no culture results recorded in patients' files. CONCLUSIONS: It's encouraging to see high adherence to South African guidelines when antimicrobials were prescribed, with the majority taken from the WHO Access list. However, there were concerns with appreciable prescribing of antimicrobials for upper respiratory tract infections that are essentially viral in origin, and a lack of microbiological testing. The establishment of ASPs can help address identified concerns through designing and implementing appropriate interventions.

Comparison of drug prescribing before and during the COVID-19 pandemic: A cross-national European study.

PURPOSE: The COVID-19 pandemic had an impact on health care, with disruption to routine clinical care. Our aim was to describe changes in prescription drugs dispensing in the primary and outpatient sectors during the first year of the pandemic across Europe. METHODS: We used routine administrative data on dispensed medicines in eight European countries (five whole countries, three represented by one region each) from January 2017 to March 2021 to compare the first year of the COVID-19 pandemic with the preceding 3 years. RESULTS: In the 10 therapeutic subgroups with the highest dispensed volumes across all countries/regions the relative changes between the COVID-19 period and the year before were mostly of a magnitude similar to changes between previous periods. However, for drugs for obstructive airway diseases the changes in the COVID-19 period were stronger in several countries/regions. In all countries/regions a decrease in dispensed DDDs of antibiotics for systemic use (from -39.4% in Romagna to -14.2% in Scotland) and nasal preparations (from -34.4% in Lithuania to -5.7% in Sweden) was observed. We observed a stockpiling effect in the total market in March 2020 in six countries/regions. In Czechia the observed increase was not significant and in Slovenia volumes increased only after the end of the first lockdown. We found an increase in average therapeutic quantity per pack dispensed, which, however, exceeded 5% only in Slovenia, Germany, and Czechia. CONCLUSIONS: The findings from this first European cross-national comparison show a substantial decrease in dispensed volumes of antibiotics for systemic use in all countries/regions. The results also indicate that the provision of medicines for common chronic conditions was mostly resilient to challenges faced during the pandemic. However, there were notable differences between the countries/regions for some therapeutic areas.

Survey to identify research priorities for primary care in Scotland during and following the COVID-19 pandemic.

OBJECTIVES: To identify research priorities for primary care in Scotland following the COVID-19 pandemic. DESIGN: Modified James Lind Alliance methodology; respondents completed an online survey to make research suggestions and rank research themes in order of priority. SETTING: Scotland primary care. PARTICIPANTS: Healthcare professionals in primary care in Scotland and members of primary care patient and public involvement groups. 512 respondents provided research suggestions; 8% (n=40) did not work in health or social care; of those who did work, 68.8% worked in primary care, 16.3% community care, 11.7% secondary care, 4.5% third sector, 4.2% university (respondents could select multiple options). Of those respondents who identified as healthcare professionals, 33% were in nursing and midwifery professions, 25% were in allied health professions (of whom 45% were occupational therapists and 35% were physiotherapists), 20% were in the medical profession and 10% were in the pharmacy profession. MAIN OUTCOMES: Suggestions for research for primary care made by respondents were categorised into themes and subthemes by researchers and ranked in order of priority by respondents. RESULTS: There were 1274 research suggestions which were categorised under 12 themes and 30 subthemes. The following five themes received the most suggestions for research: disease and illness (n=461 suggestions), access (n=202), workforce (n=164), multidisciplinary team (MDT; n=143) and integration (n=108). One hundred and three (20%) respondents to the survey participated in ranking the list of 12 themes in order of research priority. The five most highly ranked research priorities were disease and illness, health inequalities, access, workforce and MDTs. The disease and illness theme had the greatest number of suggestions for research and was scored the most highly in the ranking exercise. The subtheme ranked as the most important research priority in the disease and illness theme was 'mental health'. CONCLUSIONS: The themes and subthemes identified in this study should inform research funders so that the direction of primary healthcare is informed by evidence.

Impact of regulatory safety notices on valproate prescribing and pregnancy outcome among women of child-bearing potential in Scotland: a population-based cohort study.

OBJECTIVE: To examine the impact of Medicines and Healthcare products Regulatory Agency (MHRA) safety alerts on valproate prescribing among women aged 14-45 years in Scotland and examine trends in pregnancies exposed to valproate. DESIGN: Population-based cohort study. PARTICIPANTS: 21 983 women of all ages who received valproate between January 2011 and December 2019. METHODS: All valproate prescriptions issued to women in Scotland between January 2011 and December 2019 were identified and prevalence/incidence rates per 10 000 population derived. The impact of regulatory safety alerts on prescribing was analysed using Joinpoint models. Linked pregnancy records for January 2011 to September 2019 were identified and annual rates of pregnancy per 1000 valproate-treated women aged 14-45 years were calculated for each pregnancy outcome: live birth, stillbirth, miscarriage and termination. RESULTS: Annual prevalent and incident rates of valproate prescribing declined in women aged 14-45 years between 2011 and 2019 from 40.5 to 18.3 per 10 000 population (54.8% reduction) and 7.9 to 1.3 per 10 000 population (83.5% reduction), respectively. Statistically significant changes occurred around the times of the MHRA safety alerts. The number of valproate-exposed pregnancies conceived each year fell from 70 in 2011 to 20 in 2018, a 71.4% reduction, and the number of live births fell from 52 to 14, a 73.0% reduction. Expressed as a rate this was a 46.4% decrease from 15.3 to 8.2 per 1000 valproate-treated women aged 14-45 years in 2011 and 2018, respectively. Live birth was the most common pregnancy outcome. CONCLUSION: This study demonstrates, for the first time, the capabilities of national data sets to identify drug exposure and derive pregnancy outcome at scale across Scotland. Building on this as part of an evolving national/UK surveillance capability will continue efforts to minimise in-utero exposure to valproate; enabling ongoing surveillance to understand better long-term outcomes, and to inform better provision of health and wider support services.

Oral anticoagulants in patients with atrial fibrillation at low stroke risk: a multicentre observational study.

AIMS: There is currently no consensus on whether atrial fibrillation (AF) patients at low risk for stroke (one non-sex-related CHA2DS2-VASc point) should be treated with an oral anticoagulant. METHODS AND RESULTS: We conducted a multi-country cohort study in Sweden, Denmark, Norway, and Scotland. In total, 59 076 patients diagnosed with AF at low stroke risk were included. We assessed the rates of stroke or major bleeding during treatment with a non-vitamin K antagonist oral anticoagulant (NOAC), a vitamin K antagonist (VKA), or no treatment, using inverse probability of treatment weighted (IPTW) Cox regression. In untreated patients, the rate for ischaemic stroke was 0.70 per 100 person-years and the rate for a bleed was also 0.70 per 100 person-years. Comparing NOAC with no treatment, the stroke rate was lower [hazard ratio (HR) 0.72; 95% confidence interval (CI) 0.56-0.94], and the rate for intracranial haemorrhage (ICH) was not increased (HR 0.84; 95% CI 0.54-1.30). Comparing VKA with no treatment, the rate for stroke tended to be lower (HR 0.81; 95% CI 0.59-1.09), and the rate for ICH tended to be higher during VKA treatment (HR 1.37; 95% CI 0.88-2.14). Comparing NOAC with VKA treatment, the rate for stroke was similar (HR 0.92; 95% CI 0.70-1.22), but the rate for ICH was lower during NOAC treatment (HR 0.63; 95% CI 0.42-0.94). CONCLUSION: These observational data suggest that NOAC treatment may be associated with a positive net clinical benefit compared with no treatment or VKA treatment in patients at low stroke risk, a question that can be tested through a randomized controlled trial.

Opportunities and challenges when using record linkage of routinely collected electronic health care data to evaluate outcomes of systemic anti-cancer treatment in clinical practice.

The efficacy and safety of cancer medicines as reported from randomised clinical trials do not always translate into similar benefits in routine clinical practice; hence, post-marketing studies are a useful addition to the evidence base. With recent advances in digital infrastructure and the advent of electronically available health records, linkage of routinely collected data has emerged as a promising evaluation method for these studies. This paper discusses the opportunities and challenges when applying an electronic record linkage methodology with respect to systemic anti-cancer therapy by showcasing exemplar studies conducted over a three-year period in Scotland, and highlights some of the potential pitfalls spanning the entire breadth and depth of the research process. Our experiences as an interdisciplinary team indicate that there is scope to conduct large cohort studies to generate results from routine clinical practice within a reasonable time frame; however, close collaboration between researchers, data controllers and clinicians is required in order to obtain valid and meaningful results.

Drug prescriptions and dementia incidence: a medication-wide association study of 17000 dementia cases among half a million participants.

BACKGROUND: Previous studies have suggested that some medications may influence dementia risk. We conducted a hypothesis-generating medication-wide association study to investigate systematically the association between all prescription medications and incident dementia. METHODS: We used a population-based cohort within the Secure Anonymised Information Linkage (SAIL) databank, comprising routinely-collected primary care, hospital admissions and mortality data from Wales, UK. We included all participants born after 1910 and registered with a SAIL general practice at ≤60 years old. Follow-up was from each participant's 60th birthday to the earliest of dementia diagnosis, deregistration from a SAIL general practice, death or the end of 2018. We considered participants exposed to a medication if they received ≥1 prescription for any of 744 medications before or during follow-up. We adjusted for sex, smoking and socioeconomic status. The outcome was any all-cause dementia code in primary care, hospital or mortality data during follow-up. We used Cox regression to calculate hazard ratios and Bonferroni-corrected p values. RESULTS: Of 551 344 participants, 16 998 (3%) developed dementia (median follow-up was 17 years for people who developed dementia, 10 years for those without dementia). Of 744 medications, 221 (30%) were associated with dementia. Of these, 217 (98%) were associated with increased dementia incidence, many clustering around certain indications. Four medications (all vaccines) were associated with a lower dementia incidence. CONCLUSIONS: Almost a third of medications were associated with dementia. The clustering of many drugs around certain indications may provide insights into early manifestations of dementia. We encourage further investigation of hypotheses generated by these results.

Development of a primary care pharmacy outcomes framework: An umbrella literature review.

BACKGROUND: An aging population and rising multi-morbidity has shifted healthcare provision from secondary to primary care. Pharmacy-led services have been introduced to support this. The development of an outcomes framework for these services would facilitate conclusions to be drawn on their effectiveness. OBJECTIVES: To identify outcomes used to evaluate pharmacy-led medication therapy and disease management services within primary care settings to develop an outcomes framework for future studies. METHODS: An umbrella literature review was conducted. MEDLINE, EMBASE, The Cochrane Library and PsycINFO were searched in June 2020 to identify relevant articles. Eligible reviews were those including studies published from 2010 onwards which reported on the outcomes of pharmacy-led medication therapy and disease management services within primary care, excluding community pharmacy settings. Data were extracted and a content analysis, guided by the ECHO model, stratified the outcomes into four areas: economic, clinical, humanistic and service. RESULTS: Twenty-four reviews covering 52 unique studies were identified. Pharmacy-led services included: medication reviews (n=24, 46.2%), disease and therapy management (n=17, 32.7%), educational services (n=6, 11.5%), medicines reconciliation (n=3, 5.8%), and medication compliance support (n=1, 1.9%). Services were commonly targeted towards endocrine (n=23, 44.2%) or cardiovascular diseases (n=20, 38.5%). Outcomes most commonly explored were clinical (n=38, 73.1%) and service outcomes (n=37, 71.2%), followed by humanistic (n=23, 44.2%) and economic outcomes (n=13, 25.0%). Overall, 17 sub-categories of outcomes were identified; common sub-categories were: disease indicators [clinical]; medication use and healthcare utilisation [service]; adherence to medicines [humanistic]; and healthcare costs [economic]. CONCLUSIONS: The findings informed the development of an outcomes framework to guide the evaluation of medication therapy and disease management services, and facilitate international standardised outcome measures within primary care pharmacy to be developed. This could help offer vital evidence on the effectiveness of these services to ensure the pharmacy workforce is working optimally to support primary care.