Interventions to improve the appropriate use of polypharmacy for older people.

BACKGROUND: Inappropriate polypharmacy is a particular concern in older people and is associated with negative health outcomes. Choosing the best interventions to improve appropriate polypharmacy is a priority, so that many medicines may be used to achieve better clinical outcomes for patients. This is the third update of this Cochrane Review. OBJECTIVES: To assess the effects of interventions, alone or in combination, in improving the appropriate use of polypharmacy and reducing medication-related problems in older people. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL and two trials registers up until 13 January 2021, together with handsearching of reference lists to identify additional studies. We ran updated searches in February 2023 and have added potentially eligible studies to 'Characteristics of studies awaiting classification'. SELECTION CRITERIA: For this update, we included randomised trials only. Eligible studies described interventions affecting prescribing aimed at improving appropriate polypharmacy (four or more medicines) in people aged 65 years and older, which used a validated tool to assess prescribing appropriateness. These tools can be classified as either implicit tools (judgement-based/based on expert professional judgement) or explicit tools (criterion-based, comprising lists of drugs to be avoided in older people). DATA COLLECTION AND ANALYSIS: Four review authors independently reviewed abstracts of eligible studies, and two authors extracted data and assessed the risk of bias of the included studies. We pooled study-specific estimates, and used a random-effects model to yield summary estimates of effect and 95% confidence intervals (CIs). We assessed the overall certainty of evidence for each outcome using the GRADE approach. MAIN RESULTS: We identified 38 studies, which includes an additional 10 in this update. The included studies consisted of 24 randomised trials and 14 cluster-randomised trials. Thirty-six studies examined complex, multi-faceted interventions of pharmaceutical care (i.e. the responsible provision of medicines to improve patients' outcomes), in a variety of settings. Interventions were delivered by healthcare professionals such as general physicians, pharmacists, nurses and geriatricians, and most were conducted in high-income countries. Assessments using the Cochrane risk of bias tool found that there was a high and/or unclear risk of bias across a number of domains. Based on the GRADE approach, the overall certainty of evidence for each pooled outcome ranged from low to very low. It is uncertain whether pharmaceutical care improves medication appropriateness (as measured by an implicit tool) (mean difference (MD) -5.66, 95% confidence interval (CI) -9.26 to -2.06; I2 = 97%; 8 studies, 947 participants; very low-certainty evidence). It is uncertain whether pharmaceutical care reduces the number of potentially inappropriate medications (PIMs) (standardised mean difference (SMD) -0.19, 95% CI -0.34 to -0.05; I2 = 67%; 9 studies, 2404 participants; very low-certainty evidence). It is uncertain whether pharmaceutical care reduces the proportion of patients with one or more PIM (risk ratio (RR) 0.81, 95% CI 0.68 to 0.98; I2 = 84%; 13 studies, 4534 participants; very low-certainty evidence). Pharmaceutical care may slightly reduce the number of potential prescribing omissions (PPOs) (SMD -0.48, 95% CI -1.05 to 0.09; I2 = 92%; 3 studies, 691 participants; low-certainty evidence), however it must be noted that this effect estimate is based on only three studies, which had serious limitations in terms of risk of bias. Likewise, it is uncertain whether pharmaceutical care reduces the proportion of patients with one or more PPO (RR 0.50, 95% CI 0.27 to 0.91; I2 = 95%; 7 studies, 2765 participants; very low-certainty evidence). Pharmaceutical care may make little or no difference to hospital admissions (data not pooled; 14 studies, 4797 participants; low-certainty evidence). Pharmaceutical care may make little or no difference to quality of life (data not pooled; 16 studies, 7458 participants; low-certainty evidence). Medication-related problems were reported in 10 studies (6740 participants) using different terms (e.g. adverse drug reactions, drug-drug interactions). No consistent intervention effect on medication-related problems was noted across studies. This also applied to studies examining adherence to medication (nine studies, 3848 participants). AUTHORS' CONCLUSIONS: It is unclear whether interventions to improve appropriate polypharmacy resulted in clinically significant improvement. Since the last update of this review in 2018, there appears to have been an increase in the number of studies seeking to address potential prescribing omissions and more interventions being delivered by multidisciplinary teams.

Pharmacogenetic interventions to improve outcomes in patients with multimorbidity or prescribed polypharmacy: a systematic review.

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.

The development and validation of a medicines optimisation tool to protect the physical health of people with severe mental illness (OPTIMISE).

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.

'I just thought that it was such an impossible thing': A qualitative study of barriers and facilitators to discontinuing long-term use of benzodiazepine receptor agonists using the Theoretical Domains Framework.

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.

Supporting safe and gradual reduction of long-term benzodiazepine receptor agonist use: Development of the SAFEGUARDING-BZRAs toolkit using a codesign approach.

INTRODUCTION: Long-term benzodiazepine receptor agonist (BZRA) use persists in healthcare settings worldwide and poses risks of patient harm. OBJECTIVE: This study aimed to develop an intervention to support discontinuation of long-term BZRA use among willing individuals. METHODS: The intervention development process aligned with the UK Medical Research Council's complex intervention framework. This involved a previous systematic review of brief interventions targeting long-term BZRA use in primary care and qualitative interviews based on the Theoretical Domains Framework that explored barriers and facilitators to discontinuing long-term BZRA use. A codesign approach was used involving an active partnership between experts by experience, researchers and clinicians. Intervention content was specified in terms of behaviour change techniques (BCTs). RESULTS: The SAFEGUARDING-BZRAs (Supporting sAFE and GradUAl ReDuctIon of loNG-term BenZodiazepine Receptor Agonist uSe) toolkit comprises 24 BCTs and includes recommendations targeted at primary care-based clinicians for operationalizing each BCT to support individuals with BZRA discontinuation. CONCLUSION: The SAFEGUARDING-BZRAs toolkit has been developed using a systematic and theory-based approach that addresses identified limitations of previous research. Further research is needed to assess its usability and acceptability by service users and clinicians, as well as its potential to effectively support safe and gradual reduction of long-term BZRA use. PATIENT OR PUBLIC CONTRIBUTION: The qualitative interview phase included patients as participants. The codesign process included 'experts by experience' with either current or previous experience of long-term BZRA use as collaborators.

'I just take them because I know the people that give them to me': A theory-informed interview study of community-dwelling people with dementia and carers' perspectives of medicines management.

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.

Investigation of association of genetic variant rs3918242 of matrix metalloproteinase-9 with hypertension, myocardial infarction and progression of ventricular dysfunction in Irish Caucasian patients with diabetes: a report from the STOP-HF follow-up programme.

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.

Does potentially inappropriate prescribing predict an increased risk of admission to hospital and mortality? A longitudinal study of the 'oldest old'.

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 Maori (the indigenous population of New Zealand) and non-Maori 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 Maori and 404 non-Maori at baseline, 178 Maori and 332 non-Maori at 12-months, and 122 Maori and 281 non-Maori at 24-months. The prevalence of any PIP (i.e. ≥1 PIM and/or PPO) was 66, 75 and 72% for Maori at baseline, 12-months and 24-months, respectively. In non-Maori, 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 Maori were exposed to a significantly greater proportion of PPOs compared to non-Maori (p = 0.02). In Maori: PPOs were associated with a 1.5-fold increase in hospitalisations and mortality. In non-Maori, 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 Maori in predicting hospitalisations, and PIMs were more important in non-Maori in predicting mortality. These results suggest understanding prescribing outcomes across and between population groups is needed and emphasises prescribing quality assessment is useful.

Views and experiences of decision-makers on organisational safety culture and medication errors.

BACKGROUND: In 2017, the World Health Organization published "Medication Without Harm, WHO Global Patient Safety Challenge," to reduce patient harm caused by unsafe medication use practices. While the five objectives emphasise the need to create a framework for action, engaging key stakeholders and others, most published research has focused on the perspectives of health professionals. The aim was to explore the views and experiences of decision-makers in Qatar on organisational safety culture, medication errors and error reporting. METHOD: Qualitative, semi-structured interviews were conducted with healthcare decision-makers (policy-makers, professional leaders and managers, lead educators and trainers) in Qatar. Participants were recruited via purposive and snowball sampling, continued to the point of data saturation. The interview schedule focused on: error causation and error prevention; engendering a safety culture; and initiatives to encourage error reporting. Interviews were digitally recorded, transcribed and independently analysed by two researchers using the Framework Approach. RESULTS: From the 21 interviews conducted, key themes were the need to: promote trust within the organisation through articulating a fair blame culture; eliminate management, professional and cultural hierarchies; focus on team building, open communication and feedback; promote professional development; and scale-up successful initiatives. There was recognition that the current medication error reporting processes and systems were suboptimal, with suggested enhancements in themes of promoting a fair blame culture and open communication. CONCLUSION: These positive and negative aspects of organisational culture can inform the development of theory-based interventions to promote patient safety. Central to these will be the further development and sustainment of a "fair" blame culture in Qatar and beyond.

Improving medicines management for people with dementia in primary care: a qualitative study of healthcare professionals to develop a theory-informed intervention.

BACKGROUND: People with dementia (PwD) face unique challenges with medicines management, yet little is known about these challenges from the perspectives of primary healthcare professionals, particularly general practitioners (GPs) and community pharmacists. Few medicines management interventions have been developed which are aimed at community-dwelling PwD. This study sought to develop an intervention to improve medicines management for PwD in primary care using a theory-informed approach. METHODS: Semi-structured interviews were conducted with GPs (n = 15) and community pharmacists (n = 15) to explore participants' views and experiences of medicines management for PwD, and their perceptions of barriers and facilitators to successful medicines management for PwD. The 14-domain Theoretical Domains Framework was the underpinning theoretical guide, allowing key theoretical domains to be identified and mapped to behaviour change techniques (BCTs) which are considered the 'active ingredients' of an intervention. Draft interventions were developed to operationalise selected BCTs and were presented to GPs and community pharmacists during task groups. Final selection of an intervention for feasibility testing was guided by feedback provided during these task groups and through application of the APEASE (Affordability, Practicability, Effectiveness/cost-effectiveness, Acceptability, Side-effects/safety, Equity) criteria. RESULTS: Participants expressed a number of concerns about medicines management for PwD, particularly monitoring adherence to medication regimens and conducting medication review. Two draft interventions comprising selected BCTs ('Modelling or demonstration of behaviour'; 'Salience of consequences'; 'Health consequences'; 'Social and environmental consequences'; 'Action planning'; Social support or encouragement', 'Self-monitoring of behaviour') were developed, each targeting GPs and community pharmacists. Following the task groups and discussions within the research team, the community pharmacy-based intervention was selected for future feasibility testing. The intervention will target community pharmacists to conduct a medication review (incorporating an adherence check) with a PwD, delivered as an online video demonstrating key behaviours. The video will include feedback emphasising positive outcomes of performing the behaviours. Action planning and a quick reference guide will be used as complementary intervention components. CONCLUSIONS: A community pharmacist-based intervention has been developed targeting medicines management for PwD in primary care using a systematic, theory-informed approach. Future work will determine the usability and acceptability of implementing this intervention in clinical practice.

The development of a Core Outcome Set for medicines management interventions for people with dementia in primary care.

BACKGROUND: people with dementia (PWD), and their carers, face challenges with medicines management activities. As interventions to support medicines management for PWD are developed, consideration must be given to the outcomes chosen to measure their effectiveness. A Core Outcome Set (COS) is a minimum set of outcomes to be measured in all trials in a particular clinical area, which seeks to reduce heterogeneity of outcome reporting across trials. OBJECTIVE: to develop a COS for trials assessing the effectiveness of medicines management interventions for PWD in primary care. METHODS: a comprehensive list of outcomes was compiled through a systematic review and semi-structured interviews with PWD (n = 18), their carers (n = 15), community pharmacists (n = 15) and general practitioners (n = 15). These outcomes were rated by a Delphi panel (n = 52) on a nine-point Likert scale from 1 (limited importance) to 9 (critical) during three sequential rounds of questionnaire distribution. The Delphi panel comprised participants with expertise in dementia and medicines management, including academics and healthcare professionals. An outcome was eligible for inclusion in the COS if ≥70% of participants rated it critical and <15% of participants rated it of limited importance. RESULTS: twenty-nine outcomes identified from the systematic review and stakeholder interviews were presented to the Delphi panel. Consensus was reached on 21 outcomes, of which the 7 most highly rated were recommended for inclusion in the COS. CONCLUSION: this study used robust methodology to develop a COS for medicines management interventions for PWD. Future work should identify the most appropriate tools to measure these outcomes.

Natriuretic peptide-guided treatment for the prevention of cardiovascular events in patients without heart failure.

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.

Quality of prescribing predicts hospitalisation in octogenarians: life and living in advanced age: a cohort study in New Zealand (LiLACS NZ).

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 Maori aged 80-90 years and 516 non-Maori 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 < 0.05 was considered significant). RESULTS: Full data were obtained for 267 Maori and 404 non-Maori. The mean age for Maori was 82.3(±2.6) years, and 84.6(±0.53) years for non-Maori. 247 potentially inappropriate medicines were identified, affecting 24.3% Maori and 28.0% non-Maori. 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% Maori and 49.0% non-Maori. PPOs were associated with hospitalisation (p = 0.001 for Maori), 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 Maori. 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.

Development of a core outcome set for trials investigating the long-term management of bronchiectasis.

Heterogeneity in outcomes measured in trials limits accurate comparison of bronchiectasis studies. A core outcome set (COS) is an agreed, standardized set of outcomes that should be measured in trials for specific clinical areas. A COS for bronchiectasis could encourage consistency in future studies. An overview of systematic reviews and qualitative study on outcome selection in bronchiectasis informed an initial list of outcomes. A Delphi panel ( n = 86) rated the importance of each outcome from 1 to 9 in 3 sequential questionnaires, as a means to achieve consensus: 1-3 = 'of limited importance'; 4-6 = 'important, but not critical'; and 7-9 = 'critical'. Outcomes rated 'critical' by ≥70% of the panel were added to the COS. Eighty-two participants responded to the first questionnaire. Attrition between each questionnaire was 5%. After 3 rounds of questioning, 18 outcomes exceeded the threshold for consensus and were included in the COS. This study has achieved consensus on 18 outcomes that should be measured in trials of interventions for bronchiectasis. Selection of the highest ranked outcomes may represent a pragmatic means for comparison. Further research is required to condense the number of outcomes selected and to determine its relevance to interventions.

Benzodiazepine and Z-drug prescribing in Ireland: analysis of national prescribing trends from 2005 to 2015.

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 < 0.0001). Z-drug prescribing rates increased significantly from 95.36/1000 population (95% CI 94.73-96.00) in 2005 to 109.11/1000 population (95% CI 108.56-109.67) in 2015 (P = 0.048). Approximately one-third of individuals dispensed either benzodiazepines or Z-drugs were receiving long-term prescriptions (>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.

Patterns of multi-morbidity and prediction of hospitalisation and all-cause mortality in advanced age.

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 Maori (indigenous to New Zealand), aged 80-90 and 516 non-Maori, 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 Maori and non-Maori, respectively. The associations between clusters and outcomes differed between Maori and non-Maori. In Maori, 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-Maori, 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.

Interventions to improve the appropriate use of polypharmacy for older people.

BACKGROUND: Inappropriate polypharmacy is a particular concern in older people and is associated with negative health outcomes. Choosing the best interventions to improve appropriate polypharmacy is a priority, hence interest in appropriate polypharmacy, where many medicines may be used to achieve better clinical outcomes for patients, is growing. This is the second update of this Cochrane Review. OBJECTIVES: To determine which interventions, alone or in combination, are effective in improving the appropriate use of polypharmacy and reducing medication-related problems in older people. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL and two trials registers up until 7 February 2018, together with handsearching of reference lists to identify additional studies. SELECTION CRITERIA: We included randomised trials, non-randomised trials, controlled before-after studies, and interrupted time series. Eligible studies described interventions affecting prescribing aimed at improving appropriate polypharmacy in people aged 65 years and older, prescribed polypharmacy (four or more medicines), which used a validated tool to assess prescribing appropriateness. These tools can be classified as either implicit tools (judgement-based/based on expert professional judgement) or explicit tools (criterion-based, comprising lists of drugs to be avoided in older people). DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed abstracts of eligible studies, extracted data and assessed risk of bias of included studies. We pooled study-specific estimates, and used a random-effects model to yield summary estimates of effect and 95% confidence intervals (CIs). We assessed the overall certainty of evidence for each outcome using the GRADE approach. MAIN RESULTS: We identified 32 studies, 20 from this update. Included studies consisted of 18 randomised trials, 10 cluster randomised trials (one of which was a stepped-wedge design), two non-randomised trials and two controlled before-after studies. One intervention consisted of computerised decision support (CDS); and 31 were complex, multi-faceted pharmaceutical-care based approaches (i.e. the responsible provision of medicines to improve patient's outcomes), one of which incorporated a CDS component as part of their multi-faceted intervention. Interventions were provided in a variety of settings. Interventions were delivered by healthcare professionals such as general physicians, pharmacists and geriatricians, and all were conducted in high-income countries. Assessments using the Cochrane 'Risk of bias' tool, found that there was a high and/or unclear risk of bias across a number of domains. Based on the GRADE approach, the overall certainty of evidence for each pooled outcome ranged from low to very low.It is uncertain whether pharmaceutical care improves medication appropriateness (as measured by an implicit tool), mean difference (MD) -4.76, 95% CI -9.20 to -0.33; 5 studies, N = 517; very low-certainty evidence). It is uncertain whether pharmaceutical care reduces the number of potentially inappropriate medications (PIMs), (standardised mean difference (SMD) -0.22, 95% CI -0.38 to -0.05; 7 studies; N = 1832; very low-certainty evidence). It is uncertain whether pharmaceutical care reduces the proportion of patients with one or more PIMs, (risk ratio (RR) 0.79, 95% CI 0.61 to 1.02; 11 studies; N = 3079; very low-certainty evidence). Pharmaceutical care may slightly reduce the number of potential prescribing omissions (PPOs) (SMD -0.81, 95% CI -0.98 to -0.64; 2 studies; N = 569; low-certainty evidence), however it must be noted that this effect estimate is based on only two studies, which had serious limitations in terms of risk bias. Likewise, it is uncertain whether pharmaceutical care reduces the proportion of patients with one or more PPOs (RR 0.40, 95% CI 0.18 to 0.85; 5 studies; N = 1310; very low-certainty evidence). Pharmaceutical care may make little or no difference in hospital admissions (data not pooled; 12 studies; N = 4052; low-certainty evidence). Pharmaceutical care may make little or no difference in quality of life (data not pooled; 12 studies; N = 3211; low-certainty evidence). Medication-related problems were reported in eight studies (N = 10,087) using different terms (e.g. adverse drug reactions, drug-drug interactions). No consistent intervention effect on medication-related problems was noted across studies. AUTHORS' CONCLUSIONS: It is unclear whether interventions to improve appropriate polypharmacy, such as reviews of patients' prescriptions, resulted in clinically significant improvement; however, they may be slightly beneficial in terms of reducing potential prescribing omissions (PPOs); but this effect estimate is based on only two studies, which had serious limitations in terms of risk bias.

Improving adherence to multiple medications in older people in primary care: Selecting intervention components to address patient-reported barriers and facilitators.

BACKGROUND: Medication adherence is vital to ensuring optimal patient outcomes, particularly amongst multimorbid older people prescribed multiple medications. Interventions targeting adherence often lack a theoretical underpinning and this may impact on effectiveness. The theoretical domains framework (TDF) of behaviour can aid intervention development by systematically identifying key determinants of medication adherence. OBJECTIVES: This study aimed to (i) identify determinants (barriers, facilitators) of adherence to multiple medications from older people's perspectives; (ii) identify key domains to target for behaviour change; and (iii) map key domains to intervention components [behaviour change techniques (BCTs)] that could be delivered in an intervention by community pharmacists. METHOD: Focus groups were conducted with older people (>65 years) receiving ≥4 medications. Questions explored the 12 domains of the TDF (eg "Knowledge," "Emotion"). Data were analysed using the framework method and content analysis. Identification of key domains and mapping to intervention components (BCTs) followed established methods. RESULTS: Seven focus groups were convened (50 participants). A wide range of determinants were identified as barriers (eg forgetfulness, prioritization of medications) and facilitators (eg social support, personalized routines) of adherence to multiple medications. Eight domains were identified as key targets for behaviour change (eg "Social influences," "Memory, attention and decision processes," "Motivation and goals") and mapped to 11 intervention components (BCTs) to include in an intervention [eg "Social support or encouragement (general)," "Self-monitoring of the behaviour," "Goal-setting (behaviour)"]. CONCLUSION: This study used a theoretical underpinning to identify potential intervention components (BCTs). Future work will incorporate the selected BCTs into an intervention that will undergo feasibility testing in community pharmacies.

Potentially inappropriate prescribing in two populations with differing socio-economic profiles: a cross-sectional database study using the PROMPT criteria.

PURPOSE: The purpose of this study is to establish the prevalence of potentially inappropriate prescribing (PIP) in middle-aged adults (45-64 years) in two populations with differing socio-economic profiles, and to investigate factors associated with PIP, using the PROMPT (PRescribing Optimally in Middle-aged People's Treatments) criteria. METHODS: A retrospective cross-sectional study was conducted using 2012 data from the Enhanced Prescribing Database (EPD), covering the full population in Northern Ireland and the Health Services Executive Primary Care Reimbursement Service (HSE-PCRS) database, covering the most socio-economically deprived third of the population in this age group in the Republic of Ireland. The prevalence for each PROMPT criterion and overall prevalence of PIP were calculated. Logistic regression was used to investigate the association between PIP and gender, age group and polypharmacy. RESULTS: This study included 441,925 patients from the EPD and 309,748 patients from the HSE-PCRS database. Polypharmacy was common in both datasets (46.7 % in the HSE-PCRS and 20.3 % in the EPD). The prevalence of PIP was 42.9 % (95%CI 42.7, 43.1) in the HSE-PCRS and 21.1 % (95%CI 21.0, 21.2) in the EPD. Age group, female gender and polypharmacy were significantly associated with PIP in both populations (p < 0.05) and polypharmacy had the strongest association. CONCLUSIONS: PIP is common amongst middle-aged people with the risk of PIP increasing with polypharmacy. Differences in the prevalence of polypharmacy and PIP between the two populations may relate to heterogeneity in healthcare services and different socio-economic profiles, with higher rates of multimorbidity and associated polypharmacy in more deprived groups.