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.

The prevalence of polypharmacy in older Europeans: A multi-national database study of general practitioner prescribing.

AIMS: The aims of this study were to measure the prevalence of polypharmacy and describe the prescribing of selected medications known for overuse in older people with polypharmacy in primary care. METHODS: This was a multinational retrospective cohort study across six countries: Belgium, France, Germany, Italy, Spain and the UK. We used anonymized longitudinal patient-level information from general practice databases hosted by IQVIA. Patients ≥65 years were included. Polypharmacy was defined as having 5-9 and ≥10 distinct drug classes (ATC Level 3) prescribed during a 6-month period. Selected medications were: opioids, antipsychotics, proton pump inhibitors (PPI), benzodiazepines (ATC Level 5). We included country experts on the healthcare context to interpret findings. RESULTS: Age and gender distribution was similar across the six countries (mean age 75-76 years; 54-56% female). The prevalence of polypharmacy of 5-9 drugs was 22.8% (UK) to 58.3% (Germany); ≥10 drugs from 11.3% (UK) to 28.5% (Germany). In the polypharmacy population prescribed ≥5 drugs, opioid prescribing ranged from 11.5% (France) to 27.5% (Spain). Prescribing of PPI was highest with almost half of patients receiving a PPI, 42.3% (Germany) to 65.5% (Spain). Benzodiazepine prescribing showed a marked variation between countries, 2.7% (UK) to 34.9% (Spain). The healthcare context information explained possible underreporting for selected medications. CONCLUSIONS: We have found a high prevalence of polypharmacy with more than half of the older population being prescribed ≥5 drugs in four of the six countries. Whilst polypharmacy may be appropriate in many patients, worryingly high usage of PPIs and benzodiazepines supports current efforts to improve polypharmacy management across Europe.

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.

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.

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.

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.

What matters to patients and clinicians when discussing the impact of cancer medicines on health-related quality of life? Consensus-based mixed methods approach in prostate cancer.

OBJECTIVE: To identify what matters to clinicians and patients when discussing cancer medicines' impact on health-related quality of life (HRQoL). METHODS: A framework of HRQoL domain/domain elements was developed, informed by analysis of published patient reported outcome measures (PROMs), applicable to prostate cancer. Using mixed methods (eDelphi, Nominal Group Technique and questionnaire), prostate cancer clinicians and patients attending prostate cancer clinics and support groups were asked which domains/domain elements would be important to them when discussing the impact prostate cancer medicines have on their HRQoL. RESULTS: Twenty-one clinicians and 71 patients participated from the West of Scotland. Clinicians and patients identified 53/62 domain elements across seven domains as important, of which 32 (60%) were common to both groups. Clinicians placed more importance than patients on Mood & Emotion; in contrast, patients placed importance on a broader range of Symptoms & Side Effects, being informed about their care, and having effective healthcare professional collaboration. CONCLUSION: This study provides insight into the similarities and differences between what clinicians and patients think is important when discussing the impact of cancer medicines on HRQoL. Future research should involve exploring the potential for consistency of medicines PROMs across different cancer types to support patient-clinician communication and drive improvements in care.

What are the competency requirements for clinical pharmacist verification of systemic anti-cancer therapy (SACT) prescribed within a clinical trial? A consensus study.

BACKGROUND: Since 2005 it has been a legal requirement in Scotland to have a suitably trained pharmacist verify SACT prescriptions. Published information for verification of SACT does not currently cover SACT prescribed within a clinical trial and the additional knowledge this requires. This poses the question of how pharmacists are deemed suitably trained to competently verify SACT prescribed within a clinical trial to ensure patient safety and service efficiency. AIM: To determine and gain consensus on the competency requirements for clinical pharmacist verification of SACT prescribed within a clinical trial. METHOD: A two stage process was adopted. Firstly, a Nominal Group Technique (NGT) was conducted with a multi-disciplinary expert panel (n = 7) from National Health Service (NHS) Lothian, part of the South East Scotland Cancer Network (SCAN). Secondly, a national survey was distributed to expert cancer care pharmacists with experience in clinical trial verification across NHS Scotland (n = 86). RESULTS: Of the 28 competencies proposed, 100% achieved consensus and were deemed important by the expert panel during the NGT. From the national survey, 26 (92.9%) of the competencies achieved national agreement and were considered transferable across Scotland. The final national competencies were split into four categories: general trial background (n = 13); calculations, laboratory results and toxicity assessments (n = 7); administration details (n = 3); prescription and patient details (n = 3). Based on the themes identified during the NGT the final national competencies were further split into two suggested complexity levels; Level 1 (core) and Level 2 (advanced). CONCLUSION: The competency requirements for clinical pharmacist verification of SACT prescribed within a clinical trial were defined for national use across Scotland. The competencies were split into four categories and two complexity levels. Further work will be required to identify training requirements, develop a training programme to support these and to determine how these competencies should be assessed. In addition, further work could be undertaken to develop a United Kingdom wide competency framework based on the results of this study.

Impact of EU regulatory label changes for diclofenac in people with cardiovascular disease in four countries: Interrupted time series regression analysis.

OBJECTIVE: Due to cardiovascular safety concerns, the European Medicines Agency (EMA) recommended new contraindications and changes to product information for diclofenac across Europe in 2013. This study aims to measure their impact among targeted populations. METHOD: Quarterly interrupted time series regression (ITS) analyses of diclofenac initiation among cohorts with contraindications (congestive cardiac failure [CHF], ischaemic heart disease [IHD], peripheral arterial disease [PAD], cerebrovascular disease [CVD]) and cautions (hypertension, hyperlipidaemia, diabetes) from Denmark, the Netherlands, England and Scotland. RESULTS: The regulatory action was associated with significant immediate absolute reductions in diclofenac initiation in all countries for IHD (Denmark -0.08%, 95%CI -0.13, -0.03; England -0.09%, 95%CI -0.13 to -0.06%; the Netherlands -1.84%, 95%CI -2.51 to -1.17%; Scotland -0.34%, 95%CI -0.38 to -0.30%), PAD and hyperlipidaemia, the Netherlands, England and Scotland for hypertension and diabetes, and England and Scotland for CHF and CVD. Post-intervention there was a significant negative trend in diclofenac initiation in the Netherlands for IHD (-0.12%, 95%CI -0.19 to -0.04), PAD (-0.13%, 95%CI -0.22 to -0.05), hypertension, hyperlipidaemia and diabetes, and in Scotland for CHF (-0.01%, 95%CI -0.02 to -0.007%), IHD (-0.017, 95%CI -0.02, -0.01%), PAD and hypertension. In England, diclofenac initiation rates fell less steeply. In Denmark changes were more strongly associated with the earlier EMA 2012 regulatory action. CONCLUSION: Although significant reductions in diclofenac initiation occurred, patients with contraindications continued to be prescribed diclofenac, the extent of which varied by country and target condition. Understanding reasons for such variation may help to guide the design or dissemination of future safety warnings.

Persistence and adherence to non-vitamin K antagonist oral anticoagulant treatment in patients with atrial fibrillation across five Western European countries.

AIMS: To assess persistence and adherence to non-vitamin K antagonist oral anticoagulant (NOAC) treatment in patients with atrial fibrillation (AF) in five Western European healthcare settings. METHODS AND RESULTS: We conducted a multi-country observational cohort study, including 559 445 AF patients initiating NOAC therapy from Stockholm (Sweden), Denmark, Scotland, Norway, and Germany between 2011 and 2018. Patients were followed from their first prescription until they switched to a vitamin K antagonist, emigrated, died, or the end of follow-up. We measured persistence and adherence over time and defined adequate adherence as medication possession rate ≥90% among persistent patients only. RESULTS: Overall, persistence declined to 82% after 1 year and to 63% after 5 years. When including restarters of NOAC treatment, 85% of the patients were treated with NOACs after 5 years. The proportion of patients with adequate adherence remained above 80% throughout follow-up. Persistence and adherence were similar between countries and was higher in patients starting treatment in later years. Both first year persistence and adherence were lower with dabigatran (persistence: 77%, adherence: 65%) compared with apixaban (86% and 75%) and rivaroxaban (83% and 75%) and were statistically lower after adjusting for patient characteristics. Adherence and persistence with dabigatran remained lower throughout follow-up. CONCLUSION: Persistence and adherence were high among NOAC users in five Western European healthcare settings and increased in later years. Dabigatran use was associated with slightly lower persistence and adherence compared with apixaban and rivaroxaban.

Impact of EMA regulatory label changes on hydroxyzine initiation, discontinuation and switching to other medicines in Denmark, Scotland, England and the Netherlands: An interrupted time series regression analysis.

BACKGROUND: Hydroxyzine is indicated for the management of anxiety, skin and sleep disorders. In 2015, the European Medicines Agency (EMA) concluded that hydroxyzine was pro-arrhythmogenic and changes to the product information were implemented in Europe. This study aimed to evaluate their impact in Denmark, Scotland, England and the Netherlands. METHOD: Quarterly time series analyses measuring hydroxyzine initiation, discontinuation, and switching to other antihistamines, benzodiazepines and antidepressants in Denmark, England, Scotland and the Netherlands from 2009 to 2018. Data were analysed using interrupted time series regression. RESULTS: Hydroxyzine initiation in quarter one 2010 in Denmark, Scotland, England and the Netherlands per 100 000 was: 23.5, 91.5, 35.9 and 34.4 respectively. Regulatory action was associated with a significant: immediate fall in hydroxyzine initiation per 100 000 in England (-12.05, 95%CI -18.47 to -5.63) and Scotland (-19.01, 95%CI -26.99 to -11.02); change to a negative trend in hydroxyzine initiation per 100 000/quarter in England (-1.72, 95%CI -2.69 to -0.75) and Scotland (-2.38, 95%CI -3.32 to -1.44). Regulatory action was associated with a significant: immediate rise in hydroxyzine discontinuation per 100 000 in England (3850, 95%CI 440-7240). No consistent changes were observed in the Netherlands or Denmark. Regulatory action was associated with no switching to other antihistamines, benzodiazepines or antidepressants following hydroxyzine discontinuation in any country. CONCLUSION: The 2015 EMA regulatory action was associated with heterogeneous impact with reductions in hydroxyzine initiation varying by country. There was limited impact on discontinuation with no strong evidence suggesting unintended consequences of major switching to other antihistamines, benzodiazepines or antidepressants.

Development and evaluation of a national gentamicin and vancomycin quality improvement programme.

BACKGROUND: Scottish Antimicrobial Prescribing Group (SAPG) recommendations to reduce broad-spectrum antimicrobial use led to an increase in gentamicin and vancomycin prescribing. In 2009, SAPG introduced national guidance to standardize dosage regimens, reduce calculation errors and improve the monitoring of these antibiotics. Studies conducted in 2010 and 2011 identified limitations in guideline implementation. OBJECTIVES: To develop, implement and assess the long-term impact of quality improvement (QI) resources to support gentamicin and vancomycin prescribing, administration and monitoring. METHODS: New resources, comprising revised guidelines, online and mobile app dose calculators, educational material and specialized prescribing and monitoring charts were developed in collaboration with antimicrobial specialists and implemented throughout Scotland during 2013-16. An online survey in 2017 evaluated the use of these resources and a before (2011) and after (2018) point prevalence study assessed their impact. RESULTS: All 12 boards who responded to the survey (80%) were using the guidance, electronic calculators and gentamicin prescription chart; 8 used a vancomycin chart. The percentage of patients who received the recommended gentamicin dose increased from 44% to 89% (OR 10.99, 95% CI = 6.37-18.95) between 2011 and 2018. For vancomycin, the correct loading dose increased from 50% to 85% (OR = 5.69, CI = 2.76-11.71) and the correct maintenance dose from 55% to 90% (OR = 7.17, CI = 3.01-17.07). CONCLUSIONS: This study demonstrated improvements in the national prescribing of gentamicin and vancomycin through the development and coordinated implementation of a range of QI resources and engagement with local and national multidisciplinary teams.

A Bayesian hierarchical approach for multiple outcomes in routinely collected healthcare data.

Clinical trials are the standard approach for evaluating new treatments, but may lack the power to assess rare outcomes. Trial results are also necessarily restricted to the population considered in the study. The availability of routinely collected healthcare data provides a source of information on the performance of treatments beyond that offered by clinical trials, but the analysis of this type of data presents a number of challenges. Hierarchical methods, which take advantage of known relationships between clinical outcomes, while accounting for bias, may be a suitable statistical approach for the analysis of this data. A study of direct oral anticoagulants in Scotland is discussed and used to motivate a modeling approach. A Bayesian hierarchical model, which allows a stratification of the population into clusters with similar characteristics, is proposed and applied to the direct oral anticoagulant study data. A simulation study is used to assess its performance in terms of outcome detection and error rates.

Improving prescribing through big data approaches-Ten years of the Scottish Prescribing Information System.

Medicines are a major component of modern healthcare delivery, both in resource consumption and as drivers of innovation. The ever-increasing application of digitalisation within day-to-day living and as part of our healthcare systems-with the resultant data generation-presents the opportunity to better define the populations exposed to medicines, and their benefits and harm in real world settings. This article outlines the development of the Scottish National Prescribing Information System (PIS) and describes how this capability is being used to support the safe and effective use of medicines, both nationally and internationally. Since 2009, PIS has included e-prescribed/e-dispensed and reimbursed medicines data, now totalling 976 million prescriptions, with codified structured data on dose instructions. A literature review, covering the period from January 2009 to March 2019, identified 40 full publications using PIS, the first occurring in 2014. The majority involved pharmacoepidemiology/drug-use studies (50%) in cancer and cardiovascular disease. Measuring the value and impact of PIS was extended beyond publication quantification by illustrating the translation of PIS outputs into the learning health system at scale. The developing Scottish capabilities add breadth and depth to the wider evolving international environment, and offer the potential to contribute collegiately to the global effort on medicine safety and effectiveness, including support for the World Health Organisation Global Patient Safety Challenge: Medication Without Harm.

Real-world evaluation of the impact of statin intensity on adherence and persistence to therapy: A Scottish population-based study.

AIM: To assess associations between statin intensity and adherence, persistence and discontinuation of statin therapy in Scotland. METHOD: Retrospective cohort study, using linked electronic health records covering a period from January 2009 to December 2016. The study cohort included adult patients (≥18 years) newly initiating statins within Greater Glasgow and Clyde, Scotland. Study outcomes comprised adherence, discontinuation and persistence to treatment, stratified by three exposure groups (high, moderate and low intensity). Discontinuation and persistence were calculated using the refill-gap and anniversary methods, respectively. Proportion of days covered (PDC) was used as a proxy for adherence. Kaplan-Meier survival curves and Cox proportional hazard models were used to evaluate discontinuation, and associations between adherence/persistence and statin intensity were assessed using logistic regression. RESULTS: A total of 73 716 patients with a mean age of 61.4 ± 12.6 years were included; the majority (88.3%) received moderate intensity statins. Discontinuation rates differed between intensity levels, with high-intensity patients less likely to discontinue treatment compared to those on moderate intensity (prior cardiovascular disease [CVD]: HR 0.43 [95% CI 0.34-0.55]; no prior CVD: 0.80 [0.74-0.86]). Persistence declined over time, and high-intensity patients had the highest persistence rates. Overall, 52.6% of patients were adherent to treatment (PDC ≥ 80%), but adherence was considerably higher among high-intensity patients (63.7%). CONCLUSION: High-intensity statins were associated with better persistence and adherence to treatment, but overall long-term persistence and adherence remain a challenge, particularly among patients without prior CVD. This needs addressing.

Use of record linkage to evaluate treatment outcomes and trial eligibility in a real-world metastatic prostate cancer population in Scotland.

PURPOSE: New treatments are introduced into standard care based on clinical trial results. However, it is not clear if these benefits are reflected in the broader population. This study analysed the clinical outcomes of patients with metastatic castration-resistant prostate cancer, treated with abiraterone and enzalutamide, within the Scottish National Health Service. METHODS: Retrospective cohort study using record linkage of routinely collected healthcare data (study period: February 2012 to February 2017). Overall survival (OS) was analysed using Kaplan-Meier methods and Cox Proportional Hazard models; a subgroup analysis comprised potentially trial-eligible patients. RESULTS: Overall, 271 patients were included and 73.8% died during the study period. Median OS was poorer than in the pivotal trials, regardless of medication and indication: 10.8 months (95% confidence interval [CI] 8.6-15.1) and 20.9 months (95% CI 14.9-29.0) for abiraterone, and 12.6 months (95% CI 10.5-18.2) and 16.0 months (95% CI 9.8-not reached) for enzalutamide, post and pre chemotherapy, respectively. Only 46% of patients were potentially "trial eligible" and in this subgroup OS improved. Factors influencing survival included baseline performance status, and baseline prostate-specific antigen, alkaline phosphatase, and albumin levels. CONCLUSIONS: Poorer prognostic features of non-trial eligible patients impact real-world outcomes of cancer medicines. Electronic record linkage of routinely collected healthcare data offers an opportunity to report outcomes on cancer medicines at scale and describe population demographics. The availability of such observational data to supplement clinical trial results enables patients and clinicians to make more informed treatment decisions, and policymakers to contextualise trial findings.

Impact of EMA regulatory label changes on systemic diclofenac initiation, discontinuation, and switching to other pain medicines in Scotland, England, Denmark, and The Netherlands.

PURPOSE: In June 2013 a European Medicines Agency referral procedure concluded that diclofenac was associated with an elevated risk of acute cardiovascular events and contraindications, warnings, and changes to the product information were implemented across the European Union. This study measured the impact of the regulatory action on the prescribing of systemic diclofenac in Denmark, The Netherlands, England, and Scotland. METHODS: Quarterly time series analyses measuring diclofenac prescription initiation, discontinuation and switching to other systemic nonsteroidal anti-inflammatory (NSAIDs), topical NSAIDs, paracetamol, opioids, and other chronic pain medication in those who discontinued diclofenac. Absolute effects were estimated using interrupted time series regression. RESULTS: Overall, diclofenac prescription initiations fell during the observation periods of all countries. Compared with Denmark where there appeared to be a more limited effect, the regulatory action was associated with significant immediate reductions in diclofenac initiation in The Netherlands (-0.42%, 95% CI, -0.66% to -0.18%), England (-0.09%, 95% CI, -0.11% to -0.08%), and Scotland (-0.67%, 95% CI, -0.79% to -0.55%); and falling trends in diclofenac initiation in the Netherlands (-0.03%, 95% CI, -0.06% to -0.01% per quarter) and Scotland (-0.04%, 95% CI, -0.05% to -0.02% per quarter). There was no significant impact on diclofenac discontinuation in any country. The regulatory action was associated with modest differences in switching to other pain medicines following diclofenac discontinuation. CONCLUSIONS: The regulatory action was associated with significant reductions in overall diclofenac initiation which varied by country and type of exposure. There was no impact on discontinuation and variable impact on switching.

A cross-sectional survey of the pharmacy workforce in general practice in Scotland.

BACKGROUND: In Scotland, there has been significant investment in pharmacy teams in general medical practices over recent years, aligned to current government policy. OBJECTIVES: To characterize the national pharmacy workforce including activities undertaken, perceived competence and confidence, as well as perception of integration of the intervention. METHODS: A cross-sectional survey of all pharmacists and pharmacy technicians in general practices. Survey items were demographics, activities undertaken and experiences. The NoMAD tool (Improving the Normalization of Complex Interventions) was included as a measure of perspectives of implementation. Post-piloting, a questionnaire link was sent to all pharmacists (n = 471) and pharmacy technicians (n = 112). A total NoMAD score was obtained by assigning 1 (strongly disagree) to 5 (strongly agree) to each item. RESULTS: Responses were received from 393 (83.4%) pharmacists and 101 (91.8%) pharmacy technicians. Three quarters of pharmacists (74.6%) and pharmacy technicians (73.3%) had been qualified for over 10 years. Two-thirds of pharmacists (68.4%) were independent prescribers, with three quarters (72.3%) currently prescribing. Respondents worked in a median of two practices and were providing a range of activities including medication/polypharmacy reviews, medicines reconciliation, prescribing efficiencies and training. Respondents reported high levels of competence and confidence (median 8, scale 0-10 highest). Median NoMAD total score (scale 20-100 highest, Cronbach's alpha 0.89) was 80 for pharmacists and 75 for pharmacy technicians, P ≤ 0.001. CONCLUSIONS: The general practice pharmacy workforce in Scotland is experienced, well-qualified and integrated within general practices, delivering a range of activities. These findings have implications for workforce planning and future education and training.

Comparative safety and effectiveness of direct oral anticoagulants in patients with atrial fibrillation in clinical practice in Scotland.

AIMS: The aim of this study was to compare the clinical effectiveness and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) in routine clinical practice. METHODS: This retrospective cohort study used linked administrative data. The study population (n = 14 577) included patients with a diagnosis of AF (confirmed in hospital) who initiated DOAC treatment in Scotland between August 2011 and December 2015. Multivariate Cox proportional hazard models were used to estimate hazard ratios of thromboembolic events, mortality and bleeding events. RESULTS: No differences between the DOACs were observed with regard to the risk of stroke, systemic embolism or cardiovascular death. In contrast, the risk of myocardial infarction was higher among patients prescribed apixaban in comparison to those on rivaroxaban (HR 1.67, 95% CI 1.02-2.71), and all-cause mortality was higher among rivaroxaban patients in contrast to both apixaban (1.22 [1.01-1.47]) and dabigatran (1.55 [1.16-2.05]) patients; rivaroxaban patients also had a higher risk of pulmonary embolism than apixaban patients (5.27 [1.79-15.53]). The risk of other major bleeds was higher among rivaroxaban patients compared to apixaban (1.50 [1.10-2.03]) and dabigatran (1.58 [1.01-2.48]) patients; the risks of gastrointestinal bleeds and overall bleeding were higher among rivaroxaban patients than among apixaban patients (1.48 [1.01-2.16] and 1.52 [1.21-1.92], respectively). CONCLUSIONS: All DOACs were similarly effective in preventing strokes and systemic embolisms, while patients being treated with rivaroxaban exhibited the highest bleeding risks. Observed differences in the risks of all-cause mortality, myocardial infarction and pulmonary embolism warrant further research.