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People with severe mental illness (SMI) have a shorter life expectancy than the rest of the population. Multimorbidity and poorer physical health contribute to this health inequality. Cardiometabolic multimorbidity confers a significant mortality risk in this population. Multimorbidity is not restricted to older people and people with SMI present with multimorbidity earlier in life. Despite this, most screening, prevention and treatment strategies target older people. People under 40 years with SMI are underserved by current guidelines for cardiovascular risk assessment and reduction. Research is needed to develop and implement interventions to reduce cardiometabolic risk in this population.

Conventional medicines optimisation interventions in people with multimorbidity and polypharmacy are complex and yet limited; a more holistic and integrated approach to healthcare delivery is required. Pharmacogenetics has potential as a component of medicines optimisation. Studies involving multi-medicine pharmacogenetics in adults with multimorbidity or polypharmacy, reporting on outcomes derived from relevant core outcome sets, were included in this systematic review. Narrative synthesis was undertaken to summarise the data; meta-analysis was inappropriate due to study heterogeneity. Fifteen studies of diverse design and variable quality were included. A small, randomised study involving pharmacist-led medicines optimisation, including pharmacogenetics, suggests this approach could have significant benefits for patients and health systems. However, due to study design heterogeneity and the quality of the included studies, it is difficult to draw generalisable conclusions. Further pragmatic, robust pharmacogenetics studies in diverse, real-world patient populations, are required to establish the benefit of multi-medicine pharmacogenetic screening on patient outcomes.

Background For older populations with multimorbidity, polypharmacy (use of multiple medications) is a standard practice. PolyPrime is a theory-based intervention developed to improve appropriate polypharmacy in older people in primary care. This pilot study aims to assess the feasibility of the PolyPrime intervention in primary care in Northern Ireland (NI) and the Republic of Ireland (ROI). Methods This external pilot cluster randomised controlled trial (cRCT) aimed to recruit 12 general practitioner (GP) practices (six in NI; six in the ROI counties that border NI) and ten older patients receiving polypharmacy (≥ 4 medications) per GP practice (n = 120). Practices allocated to the intervention arm watched an online video and scheduled medication reviews with patients on two occasions. We assessed the feasibility of collecting GP record (medication appropriateness, health service use) and patient self-reported data [health-related quality of life (HRQoL), health service use)] at baseline, 6 and 9 months. HRQoL was measured using the EuroQol-5 dimension-5 level questionnaire (EQ-5D-5L) and medication-related burden quality-of-life (MRB-QoL) tool. An embedded process evaluation and health economics analysis were also undertaken. Pre-specified progression criteria were used to determine whether to proceed to a definitive cRCT. Results Twelve GP practices were recruited and randomised. Three GP practices withdrew from the study due to COVID-related factors. Sixty-eight patients were recruited, with 47 (69.1%) being retained until the end of the study. GP record data were available for 47 patients for medication appropriateness analysis at 9 months. EQ-5D-5L and MRB-QoL data were available for 46 and 41 patients, respectively, at 9 months. GP record and patient self-reported health service use data were available for 47 patients at 9 months. Health service use was comparable in terms of overall cost estimated from GP record versus patient self-reported data. The intervention was successfully delivered as intended; it was acceptable to GPs, practice staff, and patients; and potential mechanisms of action have been identified. All five progression criteria were met (two ‘Go’, three ‘Amend’). Conclusion Despite challenges faced during the COVID-19 pandemic, this study has demonstrated that it may be feasible to conduct an intervention to improve appropriate polypharmacy in older people in primary care across two healthcare jurisdictions. Trial registration ISRCTN, ISRCTN41009897. Registered 19 November 2019. Clinicaltrials.gov, NCT04181879. Registered 02 December 2019.

Background Metabolic syndrome is a cluster of factors that increase the risk of cardiovascular disease and include: diabetes and prediabetes, abdominal obesity, elevated triglycerides, low high-density lipoprotein cholesterol and high blood-pressure. However, the role of the pharmacist in the metabolic syndrome has not yet been fully explored. Aim of the review This systematic review aimed to critically appraise, synthesise, and present the available evidence on pharmacists’ input to the screening, prevention and management of metabolic syndrome. Method The final protocol was based on the “Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P)”. Studies published in English from January 2008 to March 2020 reporting any pharmacist activities in the screening, prevention or management of metabolic syndrome were included. Databases searched were Medline, Cumulative Index to Nursing and Allied Health Literature, International Pharmaceutical Abstracts, Cochrane and Google Scholar. Studies were assessed for quality by two researchers, data extracted and findings synthesised using a narrative approach. Results Of the 39,430 titles reviewed, ten studies were included (four were randomised controlled trials). Most studies focused on pharmacist input to metabolic syndrome screening and management. Screening largely involved communicating metabolic parameters to physicians. Management of metabolic syndrome described pharmacists collaborating with members of the multidisciplinary team. A positive impact was reported in all studies, including achieving metabolic syndrome parameter goals, reverting to a non-metabolic syndrome status and, improved medication adherence. The populations studied were paediatrics with risk factors, adults with comorbidities and psychiatric patients. Integration of the pharmacist within the multidisciplinary team, an easy referral process and accessibility of service were potential facilitators. Inadequate funding was the key barrier. Conclusion The studies describing pharmacist input in metabolic syndrome provide limited evidence of positive outcomes from screening and management as part of collaborative practice. Further work is required to provide more robust evidence of effectiveness and cost-effectiveness while considering key barriers.

Background To improve the effectiveness of interventions targeting non-adherence in older adults, a systematic approach to intervention design is required. The content of complex interventions and design decisions are often poorly described in published reports which makes it difficult to explore why they are ineffective. This intervention development study reports on the design of a community pharmacy-based adherence intervention using 11 Behaviour Change Techniques (BCTs) which were identified from previous qualitative research with older patients using the Theoretical Domains Framework. Methods Using a group consensus approach, a five-step design process was employed. This focused on decisions regarding: (1) the overall delivery format, (2) formats for delivering each BCT; (3) methods for tailoring BCTs to individual patients; (4) intervention structure; and (5) materials to support intervention delivery. The APEASE (Affordability; Practicability; Effectiveness/cost-effectiveness; Acceptability; Side effects/safety; Equity) criteria guided the selection of BCT delivery formats. Results Formats for delivering the 11 BCTs were agreed upon, for example, a paper medicines diary was selected to deliver the BCT ‘Self-monitoring of behaviour’. To help tailor the intervention, BCTs were categorised into ‘Core’ and ‘Optional’ BCTs. For example, ‘Feedback on behaviour’ and ‘Action planning’ were selected as ‘Core’ BCTs (delivered to all patients), whereas ‘Prompts and cues’ and ‘Health consequences’ were selected as ‘Optional’ BCTs. A paper-based adherence assessment tool was designed to guide intervention tailoring by mapping from identified adherence problems to BCTs. The intervention was designed for delivery over three appointments in the pharmacy including an adherence assessment at Appointment 1 and BCT delivery at Appointments 2 and 3. Conclusions This paper details key decision-making processes involved in moving from a list of BCTs through to a complex intervention package which aims to improve older patients’ medication adherence. A novel approach to tailoring the content of a complex adherence intervention using ‘Core’ and ‘Optional’ BCT categories is also presented. The intervention is now ready for testing in a feasibility study with community pharmacists and patients to refine the content. It is hoped that this detailed report of the intervention content/design process will allow others to better interpret the future findings of this work.

Summary Background & aims Oral nutritional supplements (ONS) are commonly used to treat malnutrition. Many patients are prescribed ONS without assessment of nutritional status. This conflicts with prescribing guidelines and has considerable cost implications. This scoping review aimed to provide an overview of interventions to improve appropriate ONS prescribing in primary care. Methods A systematic scoping review was undertaken. PubMed, EMBASE and CINAHL were searched from inception to September 2018. Studies meeting inclusion criteria had to: evaluate interventions targeting ONS prescribing in primary care; use a comparative evaluation; be published in English. Two reviewers independently screened abstracts and extracted data relating to study design, intervention characteristics, outcome assessments and key findings. Extracted data were collated using figures, tables and accompanying descriptive summaries. Results 10 studies met inclusion criteria. All studies involved uncontrolled before-and-after designs. Interventions ranged from dietitian-led reviews of patients prescribed ONS to transfer of ONS prescribing privileges from general practitioners to dietitians. Post-intervention results showed improvements in ONS prescribing based on study-specific assessments of prescribing appropriateness and absolute reductions in prescribing, as well as potential cost-savings. Conclusions This review provides a detailed overview of interventions aimed at improving appropriate ONS prescribing in primary care. Interventions evaluated to date most commonly involved dietitians. However, use of controlled experimental design was lacking. Lack of consistency in defining appropriate ONS prescribing and assessment outcomes was apparent. Future research should attend to rigour during intervention development, evaluation and reporting in order to generate findings which could inform relevant policy and practice.

Background The life expectancy of people with severe mental illness (SMI) is shorter than those without SMI, with multimorbidity and poorer physical health contributing to health inequality. Screening tools could potentially assist the optimisation of medicines to protect the physical health of people with SMI. The aim of our research was to design and validate a medicines optimisation tool (OPTIMISE) to help clinicians to optimise physical health in people with SMI. Methods A review of existing published guidelines, PubMed and Medline was carried out. Literature was examined for medicines optimisation recommendations and also for reference to the management of physical illness in people with mental illness. Potential indicators were grouped according to physiological system. A multidisciplinary team with expertise in mental health and the development of screening tools agreed that 83 indicators should be included in the first draft of OPTIMISE. The Delphi consensus technique was used to develop and validate the contents. A 17-member multidisciplinary panel of experts from the UK and Ireland completed 2 rounds of Delphi consensus, rating their level of agreement to 83 prescribing indicators using a 5-point Likert scale. Indicators were accepted for inclusion in the OPTIMISE tool after achieving a median score of 1 or 2, where 1 indicated strongly agree and 2 indicated agree, and 75th centile value of ≤ 2. Interrater reliability was assessed among 4 clinicians across 20 datasets and the chance corrected level of agreement (kappa) was calculated. The kappa statistic was interpreted as poor if 0.2 or less, fair if 0.21–0.4, moderate if 0.41–0.6, substantial if 0.61–0.8, and good if 0.81–1.0. Results Consensus was achieved after 2 rounds of Delphi for 62 prescribing indicators where 53 indicators were accepted after round 1 and a further 9 indicators were accepted after round 2. Interrater reliability of OPTIMISE between physicians and pharmacists indicated a substantial level of agreement with a kappa statistic of 0.75. Conclusions OPTIMISE is a 62 indicator medicines optimisation tool designed to assist decision making in those treating adults with SMI. It was developed using a Delphi consensus methodology and interrater reliability is substantial. OPTIMISE has the potential to improve medicines optimisation by ensuring preventative medicines are considered when clinically indicated. Further research involving the implementation of OPTIMISE is required to demonstrate its true benefit. Trial registration This article does not report the results of a health care intervention on human participants.

Introduction Existing interventions to reduce long‐term benzodiazepine receptor agonist (BZRA) use lack theoretical underpinning and detailed descriptions. This creates difficulties in understanding how interventions work and how to replicate them in practice. The Theoretical Domains Framework (TDF) can be used to identify behaviour change determinants to target during intervention development. Objective To explore barriers and facilitators to discontinuing BZRA use from the perspective of both current and previous long‐term BZRA users. Design/Setting and Participants Semistructured TDF‐based interviews were conducted with community‐based individuals with current or previous experience of long‐term BZRA use. Data were recorded, transcribed and analysed using the framework method. Results Twenty‐eight individuals were interviewed. Despite commonalities in perceived barriers/facilitators to discontinuing BZRA use within individual TDF domains, individual participants had different experiences of identified determinants of BZRA discontinuation. For example, both similarities and differences existed within and between each participant group in terms of knowledge of the appropriate duration of BZRA use (‘Knowledge’ domain) and experience of withdrawal symptoms (‘Reinforcement’ domain). Compared to previous users, current users typically anticipated more barriers to discontinuing BZRA use and fewer positive consequences of discontinuation. Conclusion This study reports on barriers and facilitators to discontinuing BZRA use from the perspectives of current and previous long‐term users. The findings highlight the challenging nature of BZRA discontinuation and a multitude of barriers that impact participants’ behaviour regarding BZRA use. Future work will involve developing a theory‐based intervention to support BZRA discontinuation in primary care. Patient Contribution The study included patients as participants.

AIMS: Guidelines support the role of B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT-proBNP) for risk stratification of patients in programmes to prevent heart failure (HF). Although biologically formed in a 1:1 ratio, the ratio of NT-proBNP to BNP exhibits wide inter-individual variability. A report on an Asian population suggests that molar NT-proBNP/BNP ratio is associated with incident HF. This study aims to determine whether routine, simultaneous evaluation of both BNP and NT-proBNP is warranted in a European, Caucasian population.METHODS AND RESULTS: We determined BNP and NT-proBNP levels for 782 Stage A/B HF patients in the STOP-HF programme. The clinical, echocardiographic, and biochemical associates of molar NT-proBNP/BNP ratio were analysed. The primary endpoint was the adjusted association of baseline molar NT-proBNP/BNP ratio with new-onset HF and/or progression of left ventricular dysfunction (LVD). We estimated the C-statistic, integrated discrimination improvement, and the category-free net reclassification improvement metric for the addition of molar NT-proBNP/BNP ratio to adjusted models. The median age was 66.6 years [interquartile range (IQR) 59.5-73.1], 371 (47.4%) were female, and median molar NT-proBNP/BNP ratio was 1.91 (IQR 1.37-2.93). Estimated glomerular filtration rate, systolic blood pressure, left ventricular mass index, and heart rate were associated with NT-proBNP/BNP ratio in a linear regression model (all P < 0.05). Over a median follow-up period of 5 years (IQR 3.4-6.8), 247 (31.5%) patients developed HF or progression of LVD. Log-transformed NT-proBNP/BNP ratio is inversely associated with HF and LVD risk when adjusted for age, gender, diabetes, hypertension, vascular disease, obesity, heart rate, number of years of follow-up, estimated glomerular filtration rate, and baseline NT-proBNP (odds ratio 0.71, 95% confidence interval 0.55-0.91; P = 0.008). However, molar NT-proBNP/BNP ratio did not increase the C-statistic (Δ -0.01) and net reclassification improvement (0.0035) for prediction of HF and LVD compared with NT-proBNP or BNP alone. Substitution of NT-proBNP for BNP in the multivariable model eliminated the association with HF and LVD risk.CONCLUSIONS: This study characterized, for the first time in a Caucasian Stage A/B HF population, the relationship between NT-proBNP/BNP ratio and biological factors and demonstrated an inverse relationship with the future development of HF and LVD. However, this study does not support routine simultaneous BNP and NT-proBNP measurement in HF prevention programmes amongst European, Caucasian patients.

BackgroundIntolerance to oral iron is thought to result in poor adherence and persistence of nutritional deficit amongst women of childbearing age, however few studies have evaluated oral iron intolerance, iron deficiency and anaemia in this setting. Iron-whey protein microspheres (IWP) could help.MethodsWe documented self-reported oral iron gastrointestinal intolerance, ferritin and haemoglobin levels in a screening study of women of childbearing age. Following a washout period of 16 days, we randomised 59 of these women with iron deficiency, stratified according to the presence of anaemia, to three doses of IWP: (14mg daily, 25mg daily and 50mg daily). We excluded those with established gastrointestinal disease, potential allergy to whey protein and severe anaemia. The primary endpoint was persistence and adherence (>80% based on pill-counts). Secondary endpoints included changes in self-reported oral iron gastrointestinal intolerance, gastro-intestinal symptom rating scale (GSRS), serum iron, serum ferritin, transferrin saturation and haemoglobin levels.ResultsA total of 128 (62.7%) of the participants had low iron stores (ferritin < 30 µg/L), 65 (31.9%) had moderate to severe iron deficiency (ferritin ConclusionsLow iron, iron deficiency and anaemia are common in women of childbearing age with a history of intolerance to oral iron. Patients with low iron (ferritin < 30 µg/L) and moderate to severe iron deficiency (ferritin

Background Adhering to multiple medications as prescribed is challenging for older patients (aged ≥ 65 years) and a difficult behaviour to improve. Previous interventions designed to address this have been largely complex in nature but have shown limited effectiveness and have rarely used theory in their design. It has been recognised that theory (‘a systematic way of understanding events or situations’) can guide intervention development and help researchers better understand how complex adherence interventions work. This pilot study aims to test a novel community pharmacy-based intervention that has been systematically developed using the Theoretical Domains Framework (12-domain version) of behaviour change. Methods As part of a non-randomised pilot study, pharmacists in 12 community pharmacies across Northern Ireland (n = 6) and London, England (n = 6), will be trained to deliver the intervention to older patients who are prescribed ≥ 4 regular medicines and are non-adherent (self-reported). Ten patients will be recruited per pharmacy (n = 120) and offered up to four tailored one-to-one sessions, in the pharmacy or via telephone depending on their adherence, over a 3–4-month period. Guided by an electronic application (app) on iPads, the intervention content will be tailored to each patient’s underlying reasons for non-adherence and mapped to the most appropriate solutions using established behaviour change techniques. This study will assess the feasibility of collecting data on the primary outcome of medication adherence (self-report and dispensing data) and secondary outcomes (health-related quality of life and unplanned hospitalisations). An embedded process evaluation will assess training fidelity for pharmacy staff, intervention fidelity, acceptability to patients and pharmacists and the intervention’s mechanism of action. Process evaluation data will include audio-recordings of training workshops, intervention sessions, feedback interviews and patient surveys. Analysis will be largely descriptive. Discussion Using pre-defined progression criteria, the findings from this pilot study will guide the decision whether to proceed to a cluster randomised controlled trial to test the effectiveness of the S-MAP intervention in comparison to usual care in community pharmacies. The study will also explore how the intervention components may work to bring about change in older patients’ adherence behaviour and guide further refinement of the intervention and study procedures. Trial registration This study is registered at ISRCTN: 10.1186/ISRCTN73831533

Background Older patients prescribed multiple medications commonly experience difficulties with adherence. High-quality evidence on interventions targeting older patients is lacking. Theory is rarely used to tailor adherence solutions. This study aimed to pilot test a novel intervention, developed using the Theoretical Domains Framework, which guides community pharmacists in identifying adherence barriers and delivering tailored solutions (behaviour change techniques). Key study procedures (e.g. recruitment, data collection) for a future randomised controlled trial (cRCT) were also assessed. Methods Using purposive sampling, this non-randomised pilot study aimed to recruit 12 community pharmacies (six in Northern Ireland; six in London, England). Pharmacists were trained to deliver the intervention to non-adherent older patients (maximum 10 per pharmacy; target n = 60-120) aged ≥ 65 years (reduced to 50 years due to recruitment challenges) and prescribed ≥ 4 regular medicines. The intervention, guided by an iPad web-application, was delivered over 3-4 face-to-face or telephone sessions, tailored to specific barriers to adherence. We assessed the feasibility of collecting adherence data (primary outcome: self-report and dispensing records), health-related quality of life (HRQOL) and unplanned hospitalisations (secondary outcomes) at baseline and 6-months. The final decision on progressing to a cRCT, using pre-defined ‘stop-amend-go’ criteria, is presented. Results Fifteen pharmacists from 12 pharmacies were recruited and trained. One pharmacy subsequently dropped out. Sixty patients were recruited (meeting the ‘Amend’ progression criteria), with 56 receiving the intervention. Adherence barriers were identified for 55 patients (98%) and a wide range of behaviour change solutions delivered (median: 5 per patient). Self-report and dispensing adherence data were available for 37 (61.7%) and 44 (73.3%) patients, respectively. HRQOL data were available for 35 (58.3%) patients. GP-reported and self-reported hospitalisations data were available for 47 (78.3%) and 23 (38.3%) patients, respectively. All progression concepts were met (nine ‘Go’ and three ‘Amend’ criteria). Conclusion This study demonstrates the feasibility of key study procedures (e.g. pharmacy recruitment) and delivery of a tailored adherence intervention in community pharmacies. However, modifications are required to enhance issues identified with patient recruitment, retention and missing data. A future definitive cRCT will explore the effectiveness of the intervention. Trial registration ISRCTN, ISRCTN73831533, Registered 12 January 2018.

Additional file 1. SPIRIT 2013 Checklist.

Additional file 2. SPIRIT figure.

Objectives: To critically appraise, synthesise, and present the available evidence on pharmacists' input to the screening, prevention and management of metabolic syndrome (MetS). Design: Systematic review. Methods: The protocol was developed based on the 'Preferred Reporting Items for Systematic review and Meta-Analysis Protocols'. Studies published in English from January 2008 to December 2018 reporting any pharmacist activities in the screening, prevention or management of MetS were included. The search was conducted in Medline, Cumulative Index to Nursing and Allied Health Literature, International Pharmaceutical Abstracts and Cochrane. Studies were assessed for quality by two researchers, data extracted and ndings synthesized using a narrative approach. Results: Nine studies were included in the review, with four being randomised controlled trials. Most studies focused on pharmacist input to MetS screening and management. Screening largely involved communicating metabolic parameters to physicians. Studies involving the management of MetS described pharmacists collaborating with physicians and other health professionals. The positive impact was reported in all studies. These included achieving MetS parameter goals, reverting to a non-MetS status, improved medication adherence and self-reported improved lifestyle modification. The populations studied were paediatrics with risk factors and adults with comorbidities and psychiatric patients. Integration within the multidisciplinary team, an easy referral process and accessibility service were potential facilitators and inadequate funding the key barrier. Conclusion: The limited number of studies describing pharmacist input in MetS provides some evidence of positive outcomes from screening and management as part of collaborative practice. Further work is required to provide more robust evidence of effectiveness and cost-effectiveness while considering key barriers

Objective:Identify facilitators and barriers to successful medicines management for people with dementia (PwD) in primary care from the perspectives of community‐dwelling PwD and carers.Methods:Semi‐structured interviews conducted with PwD and carers in Northern Ireland. The 14‐domain Theoretical Domains Framework guided data collection and analysis. Interviews explored participants’ experiences and perceptions of medicines management. PwD also completed the Beliefs about Medicines Questionnaire indicating their level of agreement with statements about medicines. Qualitative data were analysed using the framework method and content analysis. Quantitative data were analysed descriptively.Results:Eighteen PwD and 15 carers were interviewed. PwD believed they were competent with medicines management (‘Beliefs about capabilities’). Most PwD reported having strategies to prompt them to take their medicines (‘Memory, attention and decision processes’). Carers played an important role in supporting PwD with medicines management (‘Social influences’) and monitoring adherence (‘Behavioural regulation’) and anticipated having to take on a greater role as patients’ cognitive impairment worsened (‘Beliefs about consequences’). Participants highlighted assistance provided by community pharmacies with medicines acquisition and delivery (‘Environmental context and resources’) and placed great trust in primary healthcare professionals (‘Social influences’). PwD had positive attitudes towards medication and believed strongly in the necessity of their medicines.Conclusions:This is the first study to use a theoretical approach to explore medicines management for community‐dwelling PwD. The findings provide new insights into the critical role of carers in facilitating optimal medicines management and will inform future intervention development, in which carers’ needs assessment and involvement will be key.

Background The use of multiple medications (polypharmacy) is a concern in older people (≥65 years) and is associated with negative health outcomes. For older populations with multimorbidity, polypharmacy is the reality and the key challenge is ensuring appropriate polypharmacy (as opposed to inappropriate polypharmacy). This external pilot cluster randomised controlled trial (cRCT) aims to further test a theory-based intervention to improve appropriate polypharmacy in older people in primary care in two jurisdictions, Northern Ireland (NI) and the Republic of Ireland (ROI). Methods Twelve GP practices across NI (n=6) and the six counties in the ROI that border NI will be randomised to either the intervention or usual care group. Members of the research team have developed an intervention to improve appropriate polypharmacy in older people in primary care using the Theoretical Domains Framework of behaviour change. The intervention consists of two components: (1) an online video which demonstrates how a GP may prescribe appropriate polypharmacy during a consultation with an older patient and (2) a patient recall process, whereby patients are invited to scheduled medication review consultations with GPs. Ten older patients receiving polypharmacy (≥4 medications) will be recruited per GP practice (n=120). GP practices allocated to the intervention arm will be asked to watch the online video and schedule medication reviews with patients on two occasions; an initial and a 6-month follow-up appointment. GP practices allocated to the control arm will continue to provide usual care to patients. The study will assess the feasibility of recruitment, retention and study procedures including collecting data on medication appropriateness (from GP records), quality of life and health service use (i.e. hospitalisations). An embedded process evaluation will assess intervention fidelity (i.e. was the intervention delivered as intended), acceptability of the intervention and potential mechanisms of action. Discussion This pilot cRCT will provide evidence of the feasibility of a range of study parameters such as recruitment and retention, data collection procedures and the acceptability of the intervention. Pre-specified progression criteria will also be used to determine whether or not to proceed to a definitive cRCT. Trial registration ISRCTN, ISRCTN41009897. Registered 19 November 2019. ClinicalTrials.gov, NCT04181879. Registered 02 December 2019.

Background Hypertension and/or myocardial infarction are common causes of heart failure in Type 2 diabetes. Progression to heart failure is usually preceded by ventricular dysfunction, linked to matrix metalloproteinase (MMP) mediated extracellular matrix changes. We hypothesise that the minor allele of genetic variant rs3918242 in the promoter region of the MMP-9 gene is associated with hypertension and/or myocardial infarction, with resultant progression of dysfunctional cardiac remodelling in patients with diabetes without symptomatic heart failure. Methods We genotyped 498 diabetes patients participating in the St Vincent’s Screening TO Prevent Heart Failure (STOP-HF) follow-up programme for the rs3918242 single nucleotide polymorphism and investigated associations with the co-primary endpoints hypertension and/or myocardial infarction using a dominant model. We also evaluated resulting cardiometabolic phenotype and progression of ventricular dysfunction and cardiac structural abnormalities over a median follow-up period of 3.5 years. Results The CT/TT genotype comprised 28.1% of the cohort and was associated with a twofold higher risk of myocardial infarction (17.9% vs 8.4%), a reduction in ejection fraction and greater left ventricular systolic dysfunction progression [adjusted OR = 2.56 (1.09, 6.01), p = 0.026] over a median follow-up of 3.5 years [IQR 2.6, 4.9 years]. Conversely, rs3918242 was not associated with hypertension, blood pressure, pulse pressure or left ventricular mass index at baseline or over follow up. Conclusions Diabetes patients with the minor T allele of rs3918242 in the STOP-HF follow up programme have greater risk of myocardial infarction, lower ejection fraction and greater progression of left ventricular systolic abnormalities, a precursor to heart failure. These data may support further work on MMP-9 as a biomarker of ventricular dysfunction and the investigation of MMP-9 inhibitors for heart failure prevention in diabetes, particularly in the post-infarction setting. ClinicalTrials.gov Identifier: NCT00921960

Background Community pharmacists have an important role to play in providing medication adherence support (MAS) to older patients. However, research has shown that pharmacists rarely ask patients about adherence and offer limited solutions. The Theoretical Domains Framework (TDF) can guide the selection of behaviour change techniques (BCTs), to enhance behaviours such as MAS provision. Objectives This study aimed to: (1) explore barriers/facilitators influencing community pharmacists’ provision of MAS to older patients prescribed multiple medications; (2) Identify theoretical domains to target for behaviour change; (3) Select BCTs to deliver to pharmacists to enhance MAS provision. Method As part of a two-phase study, semi-structured interviews and a cross-sectional survey were conducted. In Phase 1, community pharmacists in Northern Ireland (NI) were recruited using purposive/snowball sampling. TDF-based interviews were audio-recorded, transcribed and analysed by two independent researchers using the framework method/content analysis. In Phase 2, a TDF-based postal survey was mailed to all community pharmacies in NI (n = 521) and analysed using descriptive statistics. Triangulated findings informed selection of target TDF domains and BCTs to deliver to enhance MAS provision. Results Fifteen pharmacists were interviewed for Phase 1. Barriers and facilitators included inadequate remuneration, time and knowledge of solutions and professional confidence. In Phase 2, 143 (27.4%) survey responses were received. Potential barriers included inadequate training in motivational techniques and difficulties with decision-making. Based on triangulated findings, seven domains (e.g. skills, motivation/goals) were identified as targets and mapped across to 18 BCTs (e.g. behavioural practice/rehearsal, prompts/cues). Conclusions This mixed methods study provides unique perspectives on the wide range of barriers/facilitators that are perceived to influence the provision of MAS by community pharmacists. The 18 BCTs identified to target each of the seven key target domains identified in this study will be tested in a future pilot study of a patient-targeted intervention.

Background: The prescribing of medications with anticholinergic and/or sedative properties is considered potentially inappropriate in older people (due to their side-effect profile), and the Drug Burden Index (DBI) is an evidence-based tool which measures exposure to these medications. Life and Living in Advanced Age: a Cohort Study in New Zealand (LiLACS NZ) is an ongoing longitudinal study investigating the determinants of healthy ageing. Using data from LiLACS NZ, this study aimed to determine whether a higher DBI was associated with poorer outcomes (hospitalisation, falls, mortality and cognitive function and functional status) over 36 months follow-up. Methods: LiLACS NZ consists of two cohorts: Māori (the indigenous population of New Zealand) aged ≥ 80 years and non-Māori aged 85 years at the time of enrolment. Data relating to regularly prescribed medications at baseline, 12 months and 24 months were used in this study. Medications with anticholinergic and/or sedative properties (i.e. medications with a DBI > 0) were identified using the Monthly Index of Medical Specialities (MIMS) medication formulary, New Zealand. DBI was calculated for everyone enrolled at each time point. The association between DBI at baseline and outcomes was evaluated throughout a series of 12-month follow-ups using negative binomial (hospitalisations and falls), Cox (mortality) and linear (cognitive function and functional status) regression analyses (significance p < 0.05). Regression models were adjusted for age, gender, general practitioner (GP) visits, socioeconomic deprivation, number of medicines prescribed and one of the following: prior hospitalisation, history of falls, baseline cognitive function [Modified Mini-Mental State Examination (3MS)] or baseline functional status [Nottingham Extended Activities of Daily Living (NEADL)]. Results: Full demographic data were obtained for 671, 510 and 403 individuals at baseline, 12 months and 24 months, respectively. Overall, 31%, 30% and 34% of individuals were prescribed a medication with a DBI > 0 at baseline, 12 months and 24 months, respectively. At baseline and 12 months, non-Māori had a greater mean DBI (0.28 ± 0.5 and 0.27 ± 0.5, respectively) compared to Māori (0.16 ± 0.3 and 0.18 ± 0.5, respectively). At baseline, the most commonly prescribed medicines with a DBI > 0 were zopiclone, doxazosin, amitriptyline and codeine. In Māori, a higher DBI was significantly associated with a greater risk of mortality: at 36 months follow-up, adjusted hazard ratio [95% confidence interval (CI)] 1.89 (1.11–3.20), p = 0.02. In non-Māori, a higher DBI was significantly associated with a greater risk of mortality [at 12 months follow-up, adjusted hazard ratio (95% CIs) 2.26 (1.09–4.70), p = 0.03] and impaired cognitive function [at 24 months follow-up, adjusted mean difference in 3MS score (95% CIs) 0.89 (− 3.89 to − 0.41), p = 0.02). Conclusions: Using data from LiLACS NZ, a higher DBI was significantly associated with a greater risk of mortality (in Māori and non-Māori) and impaired cognitive function (in non-Māori). This highlights the importance of employing strategies to manage the prescribing of medications with a DBI > 0 in older adults.

Additional file 1: Table S1. Assumptions used in the application of STOPP criteria to LiLACS NZ data. Table S2. Assumptions used in the application of START to LiLACS NZ data. Table S3. Potentially inappropriate medicines (PIMs) identified by STOPP, for all individuals enrolled in LiLACS NZ at 12-months and 24-months. Table S4. Potential prescribing omissions (PPOs) identified by START, for all individuals enrolled in LiLACS NZ at 12-months and 24-months. Table S5. The prevalence of Potentially inappropriate medicines (PIMs) within each physiological system, identified by STOPP, for all individuals enrolled in LiLACS NZ at 12-months and 24-months. Table S6. The prevalence of Potential prescribing omissions (PPOs) within each physiological system, identified by START, for all individuals enrolled in LiLACS NZ at 12-months and 24-months.

Additional file 3. Community pharmacist interview topic guide. TDF-based topic guide used during community pharmacist that was used to explore theoretical domains as barriers and facilitators to medicines management for PwD in primary care.

Additional file 6. Draft intervention outlines. Description of draft interventions to improve medicines management for PwD in primary care. (DOCX 24 kb)

Additional file 5. BCT mapping. Mapping of behaviour change techniques (BCTs) to key domains for inclusion in an intervention to improve medicines management for PwD in primary care

Irrespective of the field of research, the underpinning methodologies used are critical in generating high-quality data and evidence. Most importantly, the method selected should answer the research question that has been posed. It is important to accept that no single method will answer all research questions, and in the field of health services and pharmacy practice research, there may be a number of questions that will form part of an overarching programme or project. In such circumstances, more than one method will be required to answer all the research questions within a single programme or project, an approach known as mixed methods.

Additional file 2. GP interview topic guide. TDF-based topic guide used during GP interviews that was used to explore theoretical domains as barriers and facilitators to medicines management for PwD in primary care.

Background Prescribing for older people is complex, and many studies have highlighted that appropriate prescribing in this cohort is not always achieved. However, the long-term effect of inappropriate prescribing on outcomes such as hospitalisation and mortality has not been demonstrated. The aim of this study was to determine the level of potentially inappropriate prescribing (PIP) for participants of the Life and Living in Advanced Age: A Cohort Study in New Zealand (LiLACS NZ) study at baseline and examine the association between PIP and hospitalisation and mortality at 12-months follow-up. Methods PIP was determined using STOPP/START. STOPP identified potentially inappropriate medicines (PIMs) prescribed, START identified potential prescribing omissions (PPOs). STOPP/START were applied to all LiLACS NZ study participants, a longitudinal study of ageing, which includes 421 Māori aged 80–90 years and 516 non-Māori aged 85 years. Participants’ details (e.g. age, sex, living arrangements, socioeconomic status, physical functioning, medical conditions) were gathered by trained interviewers. Some participants completed a core questionnaire only, which did not include medications details. Medical conditions were established from a combination of self-report, review of hospital discharge and general practitioner records. Binary logistic regression, controlled for multiple potential confounders, was conducted to determine if either PIMs or PPOs were associated with hospital admissions and mortality (p Results Full data were obtained for 267 Māori and 404 non-Māori. The mean age for Māori was 82.3(±2.6) years, and 84.6(±0.53) years for non-Māori. 247 potentially inappropriate medicines were identified, affecting 24.3% Māori and 28.0% non-Māori. PIMs were not associated with 12-month mortality or hospitalisation for either cohort (p > 0.05; adjusted models). 590 potential prescribing omissions were identified, affecting 58.1% Māori and 49.0% non-Māori. PPOs were associated with hospitalisation (p = 0.001 for Māori), but were not associated with risk of mortality (p > 0.05) for either cohort within the 12-month follow-up (adjusted models). Conclusion PPOs were more common than PIMs and were associated with an increased risk of hospitalisation for Māori. This study highlights the importance of carefully considering all indicated medicines when deciding what to prescribe. Further follow-up is necessary to determine the long-term effects of PIP on mortality and hospitalisation.

Background Polypharmacy is associated with an increased risk of adverse drug events, inappropriate prescribing and medication errors. People with bronchiectasis have frequent pulmonary exacerbations that require antibiotic therapy. Objective This study aimed to measure polypharmacy and medication regimen complexity in bronchiectasis patients and to explore associations between these factors and oral and intravenous (IV) antibiotic use for suspected pulmonary exacerbations. Setting Patients were sampled from the Regional Bronchiectasis Clinic at the Belfast Health and Social Care Trust, Northern Ireland. Method Data on medicines were collected from patients’ records and used to measure polypharmacy using three thresholds (≥ 4, ≥ 10, and ≥ 15 medicines’). Medication regimen complexity was calculated using the medication regimen complexity index (MRCI). Data analysis investigated differences in outcomes across polypharmacy thresholds and correlations with MRCI. Main outcome measure Primary outcomes were prescriptions for oral antibiotics and IV antibiotics, in the past 6 months and 2 years, respectively. Results Over three-quarters of the sample (N = 95) were prescribed ≥ 4 medicines (n = 74; 77.9%), 31 patients were prescribed ≥ 10 medicines (33.0%), and 12 patients (12.8%) were prescribed ≥ 15 medicines. The median MRCI was 26. Patients prescribed ≥ 10 medicines were over three times more likely to have had an IV antibiotic in the past 2 years (adjusted odd ratio 3.44, 95% confidence intervals 1.15–10.31). Conclusion There were significant differences in all outcomes across the ‘≥ 10 medicines’ threshold. MRCI was positively correlated with oral and IV antibiotic usage. These findings also suggest a possible link between polypharmacy and medicines regimen complexity, and poorer outcomes. Electronic supplementary material The online version of this article (10.1007/s11096-018-0681-1) contains supplementary material, which is available to authorized users.

Aims The aim of this study was to examine prescribing trends for benzodiazepines and Z-drugs to General Medical Services (GMS) patients in Ireland. Methods A repeated cross-sectional analysis of the national pharmacy claims database was conducted for GMS patients aged ≥16 years from 2005 to 2015. Prescribing rates per 1000 eligible GMS population were calculated with 95% confidence intervals (CIs). Negative binomial regression was used to determine longitudinal trends and compare prescribing rates across years, gender and age groups. Duration of supply and rates of concomitant benzodiazepine and Z-drug prescribing were determined. Age (16-44, 45-64, ≥65 years) and gender trends were investigated. Results Benzodiazepine prescribing rates decreased significantly from 225.92/1000 population (95% CI 224.94-226.89) in 2005 to 166.07/1000 population (95% CI 165.38-166.75) in 2015 (P 90 days). The proportion of those receiving >1 benzodiazepine and/or Z-drug concomitantly increased from 11.9% in 2005 to 15.3% in 2015. Benzodiazepine and Z-drug prescribing rates were highest for older women (≥65 years) throughout the study period. Conclusions Benzodiazepine prescribing to the GMS population in Ireland decreased significantly from 2005 to 2015, and was coupled with significant increases in Z-drug prescribing. The study shows that benzodiazepine and Z-drug prescribing is common in this population, with high proportions of individuals receiving long-term prescriptions. Targeted interventions are needed to reduce potentially inappropriate long-term prescribing and use of these medications in Ireland.

Background multi-morbidity is associated with poor outcomes and increased healthcare utilisation. We aim to identify multi-morbidity patterns and associations with potentially inappropriate prescribing (PIP), subsequent hospitalisation and mortality in octogenarians. Methods life and Living in Advanced Age; a Cohort Study in New Zealand (LiLACS NZ) examined health outcomes of 421 Māori (indigenous to New Zealand), aged 80-90 and 516 non-Māori, aged 85 years in 2010. Presence of 14 chronic conditions was ascertained from self-report, general practice and hospitalisation records and physical assessments. Agglomerative hierarchical cluster analysis identified clusters of participants with co-existing conditions. Multivariate regression models examined the associations between clusters and PIP, 48-month hospitalisations and mortality. Results six clusters were identified for Māori and non-Māori, respectively. The associations between clusters and outcomes differed between Māori and non-Māori. In Māori, those in the complex multi-morbidity cluster had the highest prevalence of inappropriately prescribed medications and in cluster 'diabetes' (20% of sample) had higher risk of hospitalisation and mortality at 48-month follow-up. In non-Māori, those in the 'depression-arthritis' (17% of the sample) cluster had both highest prevalence of inappropriate medications and risk of hospitalisation and mortality. Conclusions in octogenarians, hospitalisation and mortality are better predicted by profiles of clusters of conditions rather than the presence or absence of a specific condition. Further research is required to determine if the cluster approach can be used to target patients to optimise resource allocation and improve outcomes.

Background Potentially inappropriate prescribing (PIP) is associated with negative health outcomes, including hospitalisation and mortality. Life and Living in Advanced Age: a Cohort Study in New Zealand (LiLACS NZ) is a longitudinal study of Māori (the indigenous population of New Zealand) and non-Māori octogenarians. Health disparities between indigenous and non-indigenous populations are prevalent internationally and engagement of indigenous populations in health research is necessary to understand and address these disparities. Using LiLACS NZ data, this study reports the association of PIP with hospitalisations and mortality prospectively over 36-months follow-up. Methods PIP, from pharmacist applied criteria, was reported as potentially inappropriate medicines (PIMs) and potential prescribing omissions (PPOs). The association between PIP and hospitalisations (all-cause, cardiovascular disease-specific and ambulatory-sensitive) and mortality was determined throughout a series of 12-month follow-ups using binary logistic (hospitalisations) and Cox (mortality) regression analysis, reported as odds ratios (ORs) and hazard ratios (HRs), respectively, and the corresponding confidence intervals (CIs). Results Full demographic data were obtained for 267 Māori and 404 non-Māori at baseline, 178 Māori and 332 non-Māori at 12-months, and 122 Māori and 281 non-Māori at 24-months. The prevalence of any PIP (i.e. ≥1 PIM and/or PPO) was 66, 75 and 72% for Māori at baseline, 12-months and 24-months, respectively. In non-Māori, the prevalence of any PIP was 62, 71 and 73% at baseline, 12-months and 24-months, respectively. At each time-point, there were more PPOs than PIMs; at baseline Māori were exposed to a significantly greater proportion of PPOs compared to non-Māori (p = 0.02). In Māori: PPOs were associated with a 1.5-fold increase in hospitalisations and mortality. In non-Māori, PIMs were associated with a double risk of mortality. Conclusions PIP was associated with an increased risk of hospitalisation and mortality in this cohort. Omissions appear more important for Māori in predicting hospitalisations, and PIMs were more important in non-Māori in predicting mortality. These results suggest understanding prescribing outcomes across and between population groups is needed and emphasises prescribing quality assessment is useful.

Background Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. Early intervention for those with high cardiovascular risk is crucial in improving patient outcomes. Traditional prevention strategies for CVD have focused on conventional risk factors, such as overweight, dyslipidaemia, diabetes, and hypertension, which may reflect the potential for cardiovascular insult. Natriuretic peptides (NPs), including B-type natriuretic peptide (BNP) and N-terminal pro B-type natriuretic peptide (NT-proBNP), are well-established biomarkers for the detection and diagnostic evaluation of heart failure. They are of interest for CVD prevention because they are secreted by the heart as a protective response to cardiovascular stress, strain, and damage. Therefore, measuring NP levels in patients without heart failure may be valuable for risk stratification, to identify those at highest risk of CVD who would benefit most from intensive risk reduction measures. Objectives To assess the effects of natriuretic peptide (NP)-guided treatment for people with cardiovascular risk factors and without heart failure. Search methods Searches of the following bibliographic databases were conducted up to 9 July 2019: CENTRAL, MEDLINE, Embase, and Web of Science. Three clinical trial registries were also searched in July 2019. Selection criteria We included randomised controlled trials enrolling adults with one or more cardiovascular risk factors and without heart failure, which compared NP-based screening and subsequent NP-guided treatment versus standard care in all settings (i.e. community, hospital). Data collection and analysis Two review authors independently screened titles and abstracts and selected studies for inclusion, extracted data, and evaluated risk of bias. Risk ratios (RRs) were calculated for dichotomous data, and mean differences (MDs) with 95% confidence intervals (CIs) were calculated for continuous data. We contacted trial authors to obtain missing data and to verify crucial study characteristics. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, two review authors independently assessed the quality of the evidence and GRADE profiler (GRADEPRO) was used to import data from Review Manager to create a 'Summary of findings' table. Main results We included two randomised controlled trials (three reports) with 1674 participants, with mean age between 64.1 and 67.8 years. Follow-up ranged from 2 years to mean 4.3 years.For primary outcome measures, effect estimates from a single study showed uncertainty for the effect of NP-guided treatment on cardiovascular mortality in patients with cardiovascular risk factors and without heart failure (RR 0.33, 95% CI 0.04 to 3.17; 1 study; 300 participants; low-quality evidence). Pooled analysis demonstrated that in comparison to standard care, NP-guided treatment probably reduces the risk of cardiovascular hospitalisation (RR 0.52, 95% CI 0.40 to 0.68; 2 studies; 1674 participants; moderate-quality evidence). This corresponds to a risk of 163 per 1000 in the control group and 85 (95% CI 65 to 111) per 1000 in the NP-guided treatment group.When secondary outcome measures were evaluated, evidence from a pooled analysis showed uncertainty for the effect of NP-guided treatment on all-cause mortality (RR 0.90, 95% CI 0.60 to 1.35; 2 studies; 1354 participants; low-quality evidence). Pooled analysis indicates that NP-guided treatment probably reduces the risk of all-cause hospitalisation (RR 0.83, 95% CI 0.75 to 0.92; 2 studies; 1354 participants; moderate-quality evidence). This corresponds to a risk of 601 per 1000 in the control group and 499 (95% CI 457 to 553) per 1000 in the NP-guided treatment group. The effect estimate from a single study indicates that NP-guided treatment reduced the risk of ventricular dysfunction (RR 0.61, 95% CI 0.41 to 0.91; 1374 participants; high-quality evidence). The risk in this study's control group was 87 per 1000, compared with 53 (95% CI 36 to 79) per 1000 with NP-guided treatment. Results from the same study show that NP-guided treatment does not affect change in NP level at the end of follow-up, relative to standard care (MD -4.06 pg/mL, 95% CI -15.07 to 6.95; 1 study; 1374 participants; moderate-quality evidence). Authors' conclusions This review shows that NP-guided treatment is likely to reduce ventricular dysfunction and cardiovascular and all-cause hospitalisation for patients who have cardiovascular risk factors and who do not have heart failure. Effects on mortality and natriuretic peptide levels are less certain. Neither of the included studies were powered to evaluate mortality. Available evidence shows uncertainty regarding the effects of NP-guided treatment on both cardiovascular mortality and all-cause mortality; very low event numbers resulted in a high degree of imprecision in these effect estimates. Evidence also shows that NP-guided treatment may not affect NP level at the end of follow-up.As both trials included in our review were pragmatic studies, non-blinding of patients and practices may have biased results towards a finding of equivalence. Further studies with more adequately powered sample sizes and longer duration of follow-up are required to evaluate the effect of NP-guided treatment on mortality. As two trials are ongoing, one of which is a large multi-centre trial, it is hoped that future iterations of this review will benefit from larger sample sizes across a wider geographical area.

The life expectancy of people with severe mental illness (SMI) is considerably shorter than those without SMI. Multimorbidity and poorer physical health outcomes contribute significantly to this health inequality. Psychotropic medicines, including antipsychotics, antidepressants, mood stabilisers and anxiolytic medicines, are the mainstay of treatment for SMI, and overall improve life expectancy and quality of life. Optimising medicines is required to ensure adequate control of symptoms while avoiding complications and negative physical health outcomes. Screening tools would offer an opportunity to assist clinicians in decision making and optimising medicines for people with SMI, who are particularly vulnerable to medication-related problems and poorer physical health.