Real-world severe COVID-19 outcomes associated with use of antivirals and neutralising monoclonal antibodies in Scotland.

We sought to investigate the incidence of severe COVID-19 outcomes after treatment with antivirals and neutralising monoclonal antibodies, and estimate the comparative effectiveness of treatments in community-based individuals. We conducted a retrospective cohort study investigating clinical outcomes of hospitalisation, intensive care unit admission and death, in those treated with antivirals and monoclonal antibodies for COVID-19 in Scotland between December 2021 and September 2022. We compared the effect of various treatments on the risk of severe COVID-19 outcomes, stratified by most prevalent sub-lineage at that time, and controlling for comorbidities and other patient characteristics. We identified 14,365 individuals treated for COVID-19 during our study period, some of whom were treated for multiple infections. The incidence of severe COVID-19 outcomes (inpatient admission or death) in community-treated patients (81% of all treatment episodes) was 1.2% (n = 137/11894, 95% CI 1.0-1.4), compared to 32.8% in those treated in hospital for acute COVID-19 (re-admissions or death; n = 40/122, 95% CI 25.1-41.5). For community-treated patients, there was a lower risk of severe outcomes (inpatient admission or death) in younger patients, and in those who had received three or more COVID-19 vaccinations. During the period in which BA.2 was the most prevalent sub-lineage in the UK, sotrovimab was associated with a reduced treatment effect compared to nirmaltrelvir + ritonavir. However, since BA.5 has been the most prevalent sub-lineage in the UK, both sotrovimab and nirmaltrelvir + ritonavir were associated with similarly lower incidence of severe outcomes than molnupiravir. Around 1% of those treated for COVID-19 with antivirals or neutralising monoclonal antibodies required hospital admission. During the period in which BA.5 was the prevalent sub-lineages in the UK, molnupiravir was associated with the highest incidence of severe outcomes in community-treated patients.

Patterns of initial and first-intensifying antidiabetic drug utilization among patients with type 2 diabetes mellitus in Scotland, 2010-2020: A retrospective population-based cohort study.

AIM: To evaluate the utilization and prescribing patterns of antidiabetic drugs (ADDs) for patients with type 2 diabetes mellitus (T2DM) at treatment initiation and first intensification. METHODS: A retrospective cohort study was performed using linked routinely collected data of patients with T2DM who received ADDs between January 2010 and December 2020 in Scotland. The prescribing patterns were quantified using frequency/percentages, absolute/relative change, and trend tests. RESULTS: Overall, 145 909 new ADD users were identified, with approximately 91% (N = 132 382) of patients receiving a single ADD at first treatment initiation. Metformin was the most often prescribed monotherapy (N = 118 737, 89.69%). A total of 50 731 patients (39.40%) who were started on metformin (N = 46 730/118 737, 39.36%) or sulphonylurea (SU; N = 4001/10 029, 39.89%) monotherapy had their treatment intensified with one or more additional ADD. Most initial-metformin (45 963/46 730; 98.36%) and initial-SU users (3894/4001; 97.33%) who added further drugs were intensified with single ADDs. SUs (22 197/45 963; 48.29%) were the most common first-intensifying monotherapy after initial metformin use, but these were replaced by sodium-glucose cotransporter-2 (SGLT2) inhibitors in 2019 (SGLT2 inhibitors: 2039/6065, 33.62% vs. SUs: 1924/6065, 31.72%). Metformin was the most frequently added monotherapy to initial SU use (2924/3894, 75.09%). Although the majority of patients received a single ADD, the use of combination therapy significantly increased over time. Nevertheless, there was a significant increasing trend towards prescribing the newer ADD classes (SGLT2 inhibitors, dipeptidyl peptidase-4 inhibitors) as monotherapy or in combination compared with the older ones (SUs, insulin, thiazolidinediones) at both drug initiation and first intensification. CONCLUSIONS: An overall increasing trend in prescribing the newer ADD classes compared to older ADDs was observed. However, metformin remained the most commonly prescribed first-line ADD, while SGLT2 inhibitors replaced SUs as the most common add-on therapy to initial metformin use in 2019.

Risk of winter hospitalisation and death from acute respiratory infections in Scotland: national retrospective cohort study.

OBJECTIVES: We undertook a national analysis to characterise and identify risk factors for acute respiratory infections (ARIs) resulting in hospitalisation during the winter period in Scotland. DESIGN: A population-based retrospective cohort analysis. SETTING: Scotland. PARTICIPANTS: The study involved 5.4 million residents in Scotland. MAIN OUTCOME MEASURES: Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the association between risk factors and ARI hospitalisation. RESULTS: Between 1 September 2022 and 31 January 2023, there were 22,284 (10.9% of 203,549 with any emergency hospitalisation) ARI hospitalisations (1759 in children and 20,525 in adults) in Scotland. Compared with the reference group of children aged 6-17 years, the risk of ARI hospitalisation was higher in children aged 3-5 years (aHR = 4.55; 95% CI: 4.11-5.04). Compared with those aged 25-29 years, the risk of ARI hospitalisation was highest among the oldest adults aged ≥80 years (aHR = 7.86; 95% CI: 7.06-8.76). Adults from more deprived areas (most deprived vs. least deprived, aHR = 1.64; 95% CI: 1.57-1.72), with existing health conditions (≥5 vs. 0 health conditions, aHR = 4.84; 95% CI: 4.53-5.18) or with history of all-cause emergency admissions (≥6 vs. 0 previous emergency admissions, aHR = 7.53; 95% CI: 5.48-10.35) were at a higher risk of ARI hospitalisations. The risk increased by the number of existing health conditions and previous emergency admission. Similar associations were seen in children. CONCLUSIONS: Younger children, older adults, those from more deprived backgrounds and individuals with greater numbers of pre-existing conditions and previous emergency admission were at increased risk for winter hospitalisations for ARI.

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.

Meta-analysis of factors associated with antidiabetic drug prescribing for type 2 diabetes mellitus.

BACKGROUND: There is a lack of consensus on prescribing alternatives to initial metformin therapy and intensification therapy for type 2 diabetes mellitus (T2DM) management. This review aimed to identify/quantify factors associated with prescribing of specific antidiabetic drug classes for T2DM. METHODS: Five databases (Medline/PubMed, Embase, Scopus, Web of Science) were searched using the synonyms of each concept (patients with T2DM, antidiabetic drugs and factors influencing prescribing) in both free text and Medical Subject Heading (MeSH) forms. Quantitative observational studies evaluating factors associated with antidiabetic prescribing of metformin, sulfonylurea, thiazolidinedione, Dipeptidyl-peptidase 4 inhibitors (DPP4-I), sodium glucose transporter 2 inhibitors (SGLT2-I), Glucagon-Like peptide receptor agonist (GLP1-RA) and insulin in outpatient settings and published from January 2009 to January 2021 were included. Quality assessment was performed using a Newcastle-Ottawa scale. The validation was done for 20% of identified studies. The pooled estimate was measured using a three-level random-effect meta-analysis model based on odds ratio [95% confidence interval]. Age, sex, body mass index (BMI), glycaemic control (HbA1c) and kidney-related problems were quantified. RESULTS: Of 2331 identified studies, 40 met the selection criteria. Of which, 36 and 31 studies included sex and age, respectively, while 20 studies examined baseline BMI, HbA1c and kidney-related problems. The majority of studies (77.5%, 31/40) were rated as good and despite that the overall heterogeneity for each studied factor was more than 75%, it is mostly related to within-study variance. Older age was significantly associated with higher sulfonylurea prescription (1.51 [1.29-1.76]), yet lower prescribing of metformin (0.70 [0.60-0.82]), SGLT2-I (0.57 [0.42-0.79]) and GLP1-RA (0.52 [0.40-0.69]); while higher baseline BMI showed opposite significant results (sulfonylurea: 0.76 [0.62-0.93], metformin: 1.22 [1.08-1.37], SGLT2-I: 1.88 [1.33-2.68], and GLP1-RA: 2.35 [1.54-3.59]). Both higher baseline HbA1c and having kidney-related problems were significantly associated with lower metformin prescription (0.74 [0.57-0.97], 0.39 [0.25-0.61]), but more insulin prescriptions (2.41 [1.87-3.10], 1.52 [1.10-2.10]). Also, DPP4-I prescriptions were higher for patients with kidney-related problems (1.37 [1.06-1.79]) yet lower among patients with higher HbA1c (0.82 [0.68-0.99]). Sex was significantly associated with GLP1-RA and thiazolidinedione prescribing (F:M; 1.38 [1.19-1.60] and 0.91 [0.84-0.98]). CONCLUSION: Several factors were identified as potential determinants of antidiabetic drug prescribing. The magnitude and significance of each factor differed by antidiabetic class. Patient's age and baseline BMI had the most significant association with the choice of four out of the seven studied antidiabetic drugs followed by the baseline HbA1c and kidney-related problems which had an impact on three studied antidiabetic drugs, whereas sex had the least impact on prescribing decision as it was associated with GLP1-RA and thiazolidinedione only.

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.

An umbrella review and meta-analysis of renin-angiotensin system drugs use and COVID-19 outcomes.

BACKGROUND: Despite the availability of extensive literature on the effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin-receptor blockers (ARBs) on COVID-19 outcomes, the evidence is still controversial. We aimed to provide a comprehensive assessment of the effect of ACEIs/ARBs on COVID-19-related outcomes by summarising the currently available evidence. METHODS: An umbrella review was conducted using Medline (OVID), Embase, Scopus, Cochrane library and medRxiv from inception to 1 February 2021. Systematic reviews with meta-analysis that evaluated the effect of ACEIs/ARBs on COVID-19-related clinical outcomes were eligible. Studies' quality was appraised using the AMSTAR 2 Critical Appraisal Tool. Data were analysed using the random-effects modelling including several subgroup analyses. Heterogenicity was assessed using I2 statistic. The study protocol was registered in PROSPERO (CRD42021233398) and reported using PRISMA guidelines. RESULTS: Overall, 47 reviews were eligible for inclusion. Out of the nine COVID-19 outcomes evaluated, there was significant associations between ACEIs/ARBs use and each of death (OR = 0.80, 95%CI = 0.75-0.86; I2  = 51.9%), death/ICU admission as composite outcome (OR = 0.86, 95%CI = 0.80-0.92; I2  = 43.9%), severe COVID-19 (OR = 0.86, 95%CI = 0.78-0.95; I2  = 68%) and hospitalisation (OR = 1.23, 95%CI = 1.04-1.46; I2  = 76.4%). The significant reduction in death/ICU admission, however, was higher among studies which presented adjusted measure of effects (OR = 0.63, 95%CI = 0.47-0.84) and were of moderate quality (OR = 0.74, 95%CI = 0.63-0.85). CONCLUSIONS: Collective evidence from observational studies indicate a good quality evidence on the significant association between ACEIs/ARBs use and reduction in death and death/ICU admission, but poor-quality evidence on both reducing severe COVID-19 and increasing hospitalisation. Our findings further support the current recommendations of not discontinuing ACEIs/ARBs therapy in patients with COVID-19.

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.

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.

Healthcare Costs for Metastatic Castration-Resistant Prostate Cancer Patients Treated with Abiraterone or Enzalutamide.

OBJECTIVE: The aim was to assess the real-world healthcare resource use and direct medical costs for metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone or enzalutamide, in whom chemotherapy is not yet indicated (pre-chemotherapy) or who had previously received docetaxel-based chemotherapy (post-chemotherapy), before commencing these medicines. METHODS: A retrospective cost analysis of mCRPC patients who commenced abiraterone or enzalutamide between 2012 and 2015 was conducted. Routinely collected datasets from the largest health board in Scotland and the UK, Greater Glasgow and Clyde, were linked. They contained information on patient demographics, diagnosis, outpatient consultations, hospital admissions, treatments (abiraterone and enzalutamide), and supportive medicines. Unit costs were obtained from the Scottish Health Service Costs, Personal Social Services Research Unit, and British National Formulary. Generalised linear model-based regression was used to estimate total mean direct costs, and two-part models were used to estimate separate cost components. All models were adjusted for propensity score and key variables. Sensitivity analysis was conducted to explore the impact of hypothetical patient access scheme discounts. RESULTS: Estimated total mean direct medical costs of treating mCRPC patients were similar, albeit with wide and overlapping confidence intervals. Across both treatments, patients who received abiraterone or enzalutamide in a pre-chemotherapy setting incurred the highest total mean direct medical costs. However, post-chemotherapy patients were associated with higher outpatient clinic visits, inpatient hospital admissions, and supportive medicines. Regarding relative contribution to the total mean direct medical cost, the treatment costs were the main contributor, followed by inpatient admissions, outpatient clinic visits, and supportive medicines. CONCLUSION: The total mean direct medical costs were similar for abiraterone and enzalutamide patients. The costs were not driven by the choice of treatment regimen, but treatment setting (pre-chemotherapy or post-chemotherapy indications) and related healthcare resource utilisation. Future studies should focus on economic evaluations, such as cost-effectiveness analyses, using real-world data.

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.

Retrospective cohort study to evaluate medication use in patients hospitalised with COVID-19 in Scotland: protocol for a national observational study.

INTRODUCTION: COVID-19 has caused millions of hospitalisations and deaths globally. A range of vaccines have been developed and are being deployed at scale in the UK to prevent SARS-CoV-2 infection, which have reduced risk of infection and severe COVID-19 outcomes. Those with COVID-19 are now being treated with several repurposed drugs based on evidence emerging from recent clinical trials. However, there is currently limited real-world data available related to the use of these drugs in routine clinical practice. The purpose of this study is to address the prevailing knowledge gaps regarding the use of dexamethasone, remdesivir and tocilizumab by conducting an exploratory drug utilisation study, aimed at providing in-depth descriptions of patients receiving these drugs as well as the treatment patterns observed in Scotland. METHODS AND ANALYSIS: Retrospective cohort study, comprising adult patients admitted to hospital with confirmed or suspected COVID-19 across five Scottish Health Boards using data from in-hospital ePrescribing linked to the Early Estimation of Vaccine and Anti-Viral Effectiveness (EAVE II) COVID-19 surveillance platform. The primary outcome will be exposure to the medicines of interest (dexamethasone, remdesivir, tocilizumab), either alone or in combination; exposure will be described in terms of drug(s) of choice; prescribed and administered dose; treatment duration; and any changes in treatment, for example, dose escalation and/or switching to an alternative drug. Analyses will primarily be descriptive in nature. ETHICS AND DISSEMINATION: Ethical and information governance approvals have been obtained by the National Research Ethics Service Committee, South East Scotland 02 and the Public Benefit and Privacy Panel for Health and Social Care, respectively. Findings from this study will be presented at academic and clinical conferences, and to the funders and other interested parties as appropriate; study findings will also be published in peer-reviewed journals. Publications will be available on the EAVE II website (https://www.ed.ac.uk/usher/eave-ii/key-outputs/our-publications), alongside lay summaries and infographics aimed at the general public. Press releases will also be considered, if appropriate.

Implementation of pharmacist-led services in primary care: A mixed-methods exploration of pharmacists' perceptions of a national educational resource package.

BACKGROUND: To help alleviate the global pressure on primary care, there has been an increase in the number of clinical pharmacists within primary care. Educational resources are necessary to support this workforce and their development within this role. An educational resource package was developed in Scotland to support the General Practice Clinical Pharmacists (GPCPs), containing a hard copy Competency and Capability Framework (CCF), an online platform (TURAS) and both clinical and educational supervisors in 2016. OBJECTIVE: To examine the implementation of a competency-based educational resource package through the exploration of pharmacists' perceptions of its adoption, acceptability, appropriateness, and feasibility. METHODS: Participants were GPCPs who had been part of a national training event between 2016 and 2018. The participants were given the opportunity to complete an online questionnaire or a semi-structured telephone interview. Both data collection tools were based on Proctor's model of implementation outcomes: adoption, acceptability, appropriateness and feasibility. Areas covered included GPCPs' perceptions and level of adoption of the educational resource package developed to support them in their role. RESULTS: Of a potential 164 participants, 52 (31.7%) completed the questionnaire and 12 (7.3%) completed the interview. GPCPs indicated widespread adoption and were accepting of the resources; however, it was suggested that its value was undermined, as it was not associated with a qualification. The appropriateness and feasibility of the resources depended on GPCPs' individual situation (including current role, previous job experience, time available, support received from peers and supervisors, and perceptions of resources available). CONCLUSIONS: The suitability of the CCF was evidenced by participants' adoption and acceptance of the resource, indicating the necessity of a competence-based framework to support the GPCPs' role. However, its suitability was hindered in terms of varied perceptions of appropriateness and feasibility. Despite the limited sample size, the results indicate that the value of these resources should be promoted across primary care; nevertheless further facilitation is required to allow GPCPs to fully engage with the resources.

Implementation of pharmacist-led services in primary care: A mixed-methods exploration of pharmacists’ perceptions of a national educational resource package

Background: To help alleviate the global pressure on primary care, there has been an increase in the number of clinical pharmacists within primary care. Educational resources are necessary to support this workforce and their development within this role. An educational resource package was developed in Scotland to support the General Practice Clinical Pharmacists (GPCPs), containing a hard copy Competency and Capability Framework (CCF), an online platform (TURAS) and both clinical and educational supervisors in 2016. Objective: To examine the implementation of a competency-based educational resource package through the exploration of pharmacists’ perceptions of its adoption, acceptability, appropriateness, and feasibility. Methods: Participants were GPCPs who had been part of a national training event between 2016 and 2018. The participants were given the opportunity to complete an online questionnaire or a semi-structured telephone interview. Both data collection tools were based on Proctor’s model of implementation outcomes: adoption, acceptability, appropriateness and feasibility. Areas covered included GPCPs’ perceptions and level of adoption of the educational resource package developed to support them in their role. Results: Of a potential 164 participants, 52 (31.7%) completed the questionnaire and 12 (7.3%) completed the interview. GPCPs indicated widespread adoption and were accepting of the resources; however, it was suggested that its value was undermined, as it was not associated with a qualification. The appropriateness and feasibility of the resources depended on GPCPs’ individual situation (including current role, previous job experience, time available, support received from peers and supervisors, and perceptions of resources available) (AU)