An exploratory randomised trial investigating feasibility, potential impact and cost effectiveness of link workers for people living with multimorbidity attending general practices in deprived urban communities.

BACKGROUND: Social prescribing link workers are non-health or social care professionals who connect people with psychosocial needs to non-clinical community supports. They are being implemented widely, but there is limited evidence for appropriate target populations or cost effectiveness. This study aimed to explore the feasibility, potential impact on health outcomes and cost effectiveness of practice-based link workers for people with multimorbidity living in deprived urban communities. METHODS: A pragmatic exploratory randomised trial with wait-list usual care control and blinding at analysis was conducted during the COVID 19 pandemic (July 2020 to January 2021). Participants had two or more ongoing health conditions, attended a general practitioner (GP) serving a deprived urban community who felt they may benefit from a one-month practice-based social prescribing link worker intervention.. Feasibility measures were recruitment and retention of participants, practices and link workers, and completion of outcome data. Primary outcomes at one month were health-related quality of life (EQ-5D-5L) and mental health (HADS). Potential cost effectiveness from the health service perspective was evaluated using quality adjusted life years (QALYs), based on conversion of the EQ-5D-5L and ICECAP-A capability index to utility scoring. RESULTS: From a target of 600, 251 patients were recruited across 13 general practices. Randomisation to intervention (n = 123) and control (n = 117) was after baseline data collection. Participant retention at one month was 80%. All practices and link workers (n = 10) were retained for the trial period. Data completion for primary outcomes was 75%. There were no significant differences identified using mixed effects regression analysis in EQ-5D-5L (MD 0.01, 95% CI -0.07 to 0.09) or HADS (MD 0.05, 95% CI -0.63 to 0.73), and no cost effectiveness advantages. A sensitivity analysis that considered link workers operating at full capacity in a non-pandemic setting, indicated the probability of effectiveness at the €45,000 ICER threshold value for Ireland was 0.787 using the ICECAP-A capability index. CONCLUSIONS: While the trial under-recruited participants mainly due to COVID-19 restrictions, it demonstrates that robust evaluations and cost utility analyses are possible. Further evaluations are required to establish cost effectiveness and should consider using the ICE-CAP-A wellbeing measure for cost utility analysis. REGISTRATION: This trial is registered on ISRCTN. TITLE: Use of link workers to provide social prescribing and health and social care coordination for people with complex multimorbidity in socially deprived areas. TRIAL ID: ISRCTN10287737. Date registered 10/12/2019. Link: https://www.isrctn.com/ISRCTN10287737.

Healthcare fragmentation, multimorbidity, potentially inappropriate medication, and mortality: a Danish nationwide cohort study.

BACKGROUND: Patients with multimorbidity are frequent users of healthcare, but fragmented care may lead to suboptimal treatment. Yet, this has never been examined across healthcare sectors on a national scale. We aimed to quantify care fragmentation using various measures and to analyze the associations with patient outcomes. METHODS: We conducted a register-based nationwide cohort study with 4.7 million Danish adult citizens. All healthcare contacts to primary care and hospitals during 2018 were recorded. Clinical fragmentation indicators included number of healthcare contacts, involved providers, provider transitions, and hospital trajectories. Formal fragmentation indices assessed care concentration, dispersion, and contact sequence. The patient outcomes were potentially inappropriate medication and all-cause mortality adjusted for demographics, socioeconomic factors, and morbidity level. RESULTS: The number of involved healthcare providers, provider transitions, and hospital trajectories rose with increasing morbidity levels. Patients with 3 versus 6 conditions had a mean of 4.0 versus 6.9 involved providers and 6.6 versus 13.7 provider transitions. The proportion of contacts to the patient's own general practice remained stable across morbidity levels. High levels of care fragmentation were associated with higher rates of potentially inappropriate medication and increased mortality on all fragmentation measures after adjusting for demographic characteristics, socioeconomic factors, and morbidity. The strongest associations with potentially inappropriate medication and mortality were found for ≥ 20 contacts versus none (incidence rate ratio 2.83, 95% CI 2.77-2.90) and ≥ 20 hospital trajectories versus none (hazard ratio 10.8, 95% CI 9.48-12.4), respectively. Having less than 25% of contacts with your usual provider was associated with an incidence rate ratio of potentially inappropriate medication of 1.49 (95% CI 1.40-1.58) and a mortality hazard ratio of 2.59 (95% CI 2.36-2.84) compared with full continuity. For the associations between fragmentation measures and patient outcomes, there were no clear interactions with number of conditions. CONCLUSIONS: Several clinical indicators of care fragmentation were associated with morbidity level. Care fragmentation was associated with higher rates of potentially inappropriate medication and increased mortality even when adjusting for the most important confounders. Frequent contact to the usual provider, fewer transitions, and better coordination were associated with better patient outcomes regardless of morbidity level.

The effectiveness and cost of integrating pharmacists within general practice to optimize prescribing and health outcomes in primary care patients with polypharmacy: a systematic review.

BACKGROUND: Polypharmacy and associated potentially inappropriate prescribing (PIP) place a considerable burden on patients and represent a challenge for general practitioners (GPs). Integration of pharmacists within general practice (herein 'pharmacist integration') may improve medications management and patient outcomes. This systematic review assessed the effectiveness and costs of pharmacist integration. METHODS: A systematic search of ten databases from inception to January 2021 was conducted. Studies that evaluated the effectiveness or cost of pharmacist integration were included. Eligible interventions were those that targeted medications optimization compared to usual GP care without pharmacist integration (herein 'usual care'). Primary outcomes were PIP (as measured by PIP screening tools) and number of prescribed medications. Secondary outcomes included health-related quality of life, health service utilization, clinical outcomes, and costs. Randomised controlled trials (RCTs), non-RCTs, interrupted-time-series, controlled before-after trials and health-economic studies were included. Screening and risk of bias using Cochrane EPOC criteria were conducted by two reviewers independently. A narrative synthesis and meta-analysis of outcomes where possible, were conducted; the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: In total, 23 studies (28 full text articles) met the inclusion criteria. In ten of 11 studies, pharmacist integration probably reduced PIP in comparison to usual care (moderate certainty evidence). A meta-analysis of number of medications in seven studies reported a mean difference of -0.80 [-1.17, -0.43], which indicated pharmacist integration probably reduced number of medicines (moderate certainty evidence). It was uncertain whether pharmacist integration improved health-related quality of life because the certainty of evidence was very low. Twelve health-economic studies were included; three investigated cost effectiveness. The outcome measured differed across studies limiting comparisons and making it difficult to make conclusions on cost effectiveness. CONCLUSIONS: Pharmacist integration probably reduced PIP and number of medications however, there was no clear effect on other patient outcomes; and while interventions in a small number of studies appeared to be cost-effective, further robust, well-designed cluster RCTs with economic evaluations are required to determine cost-effectiveness of pharmacist integration. TRIAL REGISTRATION: CRD42019139679.

What is the impact of multimorbidity on out-of-pocket healthcare expenditure among community-dwelling older adults in Ireland? A cross-sectional study.

OBJECTIVES: Individuals with multimorbidity use more health services and take more medicines. This can lead to high out-of-pocket (OOP) healthcare expenditure. This study, therefore, aimed to assess the association between multimorbidity (two or more chronic conditions) and OOP healthcare expenditure in a nationally representative sample of adults aged 50 years or over. DESIGN: Cross-sectional analysis of data collected in 2016 from wave 4 of The Irish Longitudinal Study on Ageing.SettingIreland.ParticipantsCommunity-dwelling adults aged 50 years and over.MethodA generalised linear model with log-link and gamma distributed errors was fitted to assess the association between multimorbidity and OOP healthcare expenditure (including general practitioner, emergency department, outpatients, specialist consultations, hospital admissions, home care and prescription drugs). RESULTS: Overall, 3453 (58.5%) participants had multimorbidity. Among those with any OOP healthcare expenditure, individuals with multimorbidity spent more on average per annum (€806.8 for two conditions, €885.8 for three or more conditions), than individuals with no conditions (€580.3). Pharmacy-dispensed medicine expenditure was the largest component of expenditure. People with multimorbidity on average spent more of their equivalised household income on healthcare (7.1% for two conditions, 9.7% for three or more conditions), than people with no conditions (5.0%). A strong positive association was found between number of conditions and OOP healthcare expenditure (p<0.001) and between having private health insurance and OOP healthcare expenditure (p<0.001). A strong negative association was found between eligibility for free primary/hospital care and heavily subsidised medicines and OOP healthcare expenditure (p<0.001). CONCLUSIONS: This study suggests that having multimorbidity in Ireland increases OOP healthcare expenditure, which is problematic for those with more conditions who have lower incomes. This highlights the need for this financial burden to be considered when designing healthcare/funding systems to address multimorbidity, so that access to essential healthcare can be maximised for those with greatest need.

Effect of social prescribing link workers on health outcomes and costs for adults in primary care and community settings: a systematic review.

OBJECTIVES: To establish the evidence base for the effects on health outcomes and costs of social prescribing link workers (non-health or social care professionals who connect people to community resources) for people in community settings focusing on people experiencing multimorbidity and social deprivation. DESIGN: Systematic review and narrative synthesis using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. DATA SOURCES: Cochrane Database, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, EU Clinical Trials Register, CINAHL, Embase, Global Health, PubMed/MEDLINE, PsycInfo, LILACS, Web of Science and grey literature were searched up to 31 July 2021. A forward citation search was completed on 9 June 2022. ELIGIBILITY CRITERIA: Controlled trials meeting the Cochrane Effectiveness of Practice and Organisation of Care (EPOC) guidance on eligible study designs assessing the effect of social prescribing link workers for adults in community settings on any outcomes. No language restrictions were applied. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data, evaluated study quality using the Cochrane EPOC risk of bias tool and judged certainty of the evidence. Results were synthesised narratively. RESULTS: Eight studies (n=6500 participants), with five randomised controlled trials at low risk of bias and three controlled before-after studies at high risk of bias, were included. Four included participants experiencing multimorbidity and social deprivation. Four (n=2186) reported no impact on health-related quality of life (HRQoL). Four (n=1924) reported mental health outcomes with three reporting no impact. Two US studies found improved ratings of high-quality care and reduced hospitalisations for people with multimorbidity experiencing deprivation. No cost-effectiveness analyses were identified. The certainty of the evidence was low or very low. CONCLUSIONS: There is an absence of evidence for social prescribing link workers. Policymakers should note this and support evaluation of current programmes before mainstreaming. PROSPERO REGISTRATION NUMBER: CRD42019134737.

Another Step Toward Hepatitis C Elimination: An Economic Evaluation of an Irish National Birth Cohort Testing Program.

OBJECTIVES: We aimed to evaluate the cost-effectiveness of offering once-off birth cohort testing for hepatitis C virus (HCV) to people in Ireland born between 1965 and 1985, the cohort with the highest reported prevalence of undiagnosed chronic HCV infection. METHODS: Systematic and opportunistic HCV birth cohort testing programs, implemented over a 4-year timeframe, were compared with the current practice of population risk-based testing only in a closed-cohort decision tree and Markov model hybrid over a lifetime time horizon. Outcomes were expressed in quality-adjusted life-years (QALYs). Costs were presented from the health system's perspective in 2020 euro (€). Uncertainty was assessed via deterministic, probabilistic, scenario, and threshold analyses. RESULTS: In the base case, systematic testing yielded the largest cost and health benefits, followed by opportunistic testing and risk-based testing. Compared with risk-based testing, the incremental cost-effectiveness ratio for opportunistic testing was €14 586 (95% confidence interval €4185-€33 527) per QALY gained. Compared with opportunistic testing, the incremental cost-effectiveness ratio for systematic testing was €16 827 (95% confidence interval €5106-€38 843) per QALY gained. These findings were robust across a range of sensitivity analyses. CONCLUSIONS: Both systematic and opportunistic birth cohort testing would be considered an efficient use of resources, but systematic testing was the optimal strategy at willingness-to-pay threshold values typically used in Ireland. Although cost-effective, any decision to introduce birth cohort testing for HCV (in Ireland or elsewhere) must be balanced with considerations regarding the feasibility and budget impact of implementing a national testing program given high initial costs and resource use.

Variation of prescription drug prices in community pharmacies: A national cross-sectional study.

Background; There is evidence of significant variation of prescription drug prices in community pharmacies in several countries. Prescription drugs are a major source of expenditure for patients. High prices can lead to cost-related non-adherence and adverse health outcomes. Objective; This study's aim was to establish the variation and availability of prescription drug prices in community pharmacies in Ireland. Methods; Using a cross-sectional design, prices were sought in community pharmacies using phone, email and website enquiries. A purposive sample of 12 prescription drugs was included. The prescription drugs were selected from the top 100 medications by dispensing frequency in 2017 on Ireland's main state drug scheme. For each pharmacy, the price was checked for three drugs only. Researchers sought to contact 1,500 pharmacies by phone and 320 by email, as well as consult the website of 370 pharmacies. Results; In total, 1,529 pharmacies responded to queries, 1,362 by telephone and 167 by email. Overall, 88.5% (N = 1,353) of pharmacies who answered queries, provided prices. For each drug, the average price quoted to researchers was higher than the price paid by the state for patients who can access subsidised medicines. The ratio of 90th to 10th percentile prices ranged from 1.3 to 2.0 for the twelve drugs. A Welch's t-test found that for nine of the 12 drugs, the price was significantly higher (p < .05) for chain pharmacies compared to independent pharmacies. Conclusions; Evidence was found of significant price variation in community pharmacies. There was also evidence that some community pharmacies were not following regulatory guidance on drug pricing transparency. Policy measures such as mandated price transparency, or fixed prescription drug prices could help address these price issues.

The MultimorbiditY COllaborative Medication Review And DEcision Making (MyComrade) study: a protocol for a cross-border pilot cluster randomised controlled trial.

BACKGROUND: While international guidelines recommend medication reviews as part of the management of multimorbidity, evidence on how to implement reviews in practice in primary care is lacking. The MultimorbiditY Collaborative Medication Review And Decision Making (MyComrade) intervention is an evidence-based, theoretically informed novel intervention which aims to support the conduct of medication reviews for patients with multimorbidity in primary care. Our aim in this pilot study is to evaluate the feasibility of a trial of the intervention with unique modifications accounting for contextual variations in two neighbouring health systems (Republic of Ireland (ROI) and Northern Ireland (NI)). METHODS: A pilot cluster randomised controlled trial will be conducted, using a mixed-methods process evaluation to investigate the feasibility of a trial of the MyComrade intervention based on pre-defined progression criteria. A total of 16 practices will be recruited (eight in ROI; eight in NI), and four practices in each jurisdiction will be randomly allocated to intervention or control. Twenty people living with multimorbidity and prescribed ≥ 10 repeat medications will be recruited from each practice prior to practice randomisation. In intervention practices, the MyComrade intervention will be delivered by pairs of general practitioners (GPs) in ROI, and a GP and practice-based pharmacist (PBP) in NI. The GPs/GP and PBP will schedule the time to review the medications together using a checklist. Usual care will proceed in practices in the control arm. Data will be collected via electronic health records and postal questionnaires at recruitment and 4 and 8 months after randomisation. Qualitative interviews to assess the feasibility and acceptability of the intervention and explore experiences related to multimorbidity management will be conducted with a purposive sample of GPs, PBPs, practice administration staff and patients in intervention and control practices. The feasibility of conducting a health economic evaluation as part of a future definitive trial will be assessed. DISCUSSION: The findings of this pilot study will assess the feasibility of a trial of the MyComrade intervention in two different health systems. Evaluation of the progression criteria will guide the decision to progress to a definitive trial and inform trial design. The findings will also contribute to the growing evidence-base related to intervention development and feasibility studies. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN80017020 . Date of confirmation is 4/11/2019.

Effectiveness of rapid antigen testing for screening of asymptomatic individuals to limit the transmission of SARS-CoV-2: A rapid review.

Rapid antigen detection tests (RADTs) offer advantages over gold-standard reverse transcription polymerase chain reaction (RT-PCR) tests in that they are cheaper and provide faster results, thus enabling prompt isolation of positive SARS-CoV-2 cases and quarantine of close contacts. The aim of this study was to collate and synthesise empirical evidence on the effectiveness of rapid antigen testing for the screening (including serial testing) and surveillance of asymptomatic individuals to limit the transmission of SARS-CoV-2. A rapid review was undertaken in MEDLINE (EBSCO), EMBASE (OVID), Cochrane Library, Europe PMC and Google Scholar up until 19 July 2021, supplemented by a grey literature search. Of the identified 1222 records, 19 reports referring to 16 studies were included. Eight included studies examined the effectiveness of RADTs for population-level screening, four for pre-event screening and four for serial testing (schools, a prison, a university sports programme and in care homes). Overall, there is uncertainty regarding the effectiveness of rapid antigen testing for the screening of asymptomatic individuals to limit the transmission of SARS-CoV-2. This uncertainty is due to the inconsistent results, the relatively low number of studies identified, the predominantly observational and/or uncontrolled nature of the study designs used, and concerns regarding methodological quality. Given this uncertainty, more real-world research evidence in relevant settings, which is of good quality and timely, as well as economic evaluation, is required to inform public policy on the widespread use of RADTs in asymptomatic individuals.

Cost-effectiveness of an occupational therapy-led self-management support programme for multimorbidity in primary care.

BACKGROUND: Multimorbidity is a major public health concern. Complex interventions, incorporating individualized care plans, may be appropriate for patients with multimorbidity given their individualized and variable needs. There is a dearth of evidence on the cost-effectiveness of complex multimorbidity interventions. OBJECTIVE: This study examines the cost-effectiveness of a 6-week occupational therapy-led self-management support programme (OPTIMAL) for adults with multimorbidity. METHODS: Economic evaluation, from a healthcare perspective, was conducted alongside a randomized controlled trial of 149 adults with multimorbidity. Intervention was the OPTIMAL programme with a comparison of usual primary care. Incremental costs, quality-adjusted life years (QALYs) gained, and expected cost-effectiveness were estimated at 6 months and uncertainty was explored using cost-effectiveness acceptability curves. RESULTS: The intervention was associated with a mean improvement in QALYs gained of 0.031 per patient (P-value: 0.063; 95% confidence intervals [CIs]: -0.002 to 0.063) and a mean reduction in total costs of €2,548 (P-value: 0.114; 95% CIs: -5,606 to 509) per patient. At cost-effectiveness threshold values of €20,000 and €45,000 per QALY, the probability of the intervention being cost-effective was estimated to be 0.951 and 0.958, respectively. The results remained consistent across all subgroups examined. CONCLUSIONS: This study adds to the limited evidence base on the cost-effectiveness of complex interventions for multimorbidity, and highlights the potential for the OPTIMAL programme to be cost-effective. Further studies are warranted to explore the clinical and cost-effectiveness of complex interventions for the multimorbidity patient population, and for subgroups within it. TRIAL REGISTRATION: Trial number: ISRCTN67235963.

Population-Based Testing for Undiagnosed Hepatitis C: A Systematic Review of Economic Evaluations.

BACKGROUND AND OBJECTIVES: Recognising the significant public health threat posed by hepatitis C, international targets have been established by the World Health Organization with the aim of eradicating the hepatitis C virus (HCV) by 2030. With the availability of safe and effective therapies, the greatest challenge to achieving elimination is the identification and treatment of those currently undiagnosed. This systematic review aimed to identify and appraise the international literature on the cost-effectiveness of birth cohort, universal, and age-based general population testing for identifying people with undiagnosed chronic HCV infection. METHODS: A comprehensive literature search was undertaken in Medline, Embase and grey literature sources to identify studies published between 1 January 2000 and 17 July 2020. Retrieved citations were independently reviewed by two reviewers according to pre-defined eligibility criteria. Data extraction and critical appraisal were completed in duplicate. Study quality, relevance and credibility were assessed using the Consensus for Health Economic Criteria and the ISPOR questionnaires. All costs were reported in 2019 Irish Euro following adjustment for inflation and purchasing power parity. Willingness-to-pay (WTP) thresholds of €20,000 and €45,000 were adopted as reference points for interpreting cost-effectiveness in the narrative synthesis. The systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. RESULTS: Overall, 4622 citations were retrieved in the literature search. Of these, 27 studies met the inclusion criteria. Six (22%) of the 27 studies were rated as low quality, 17 (63%) were moderate quality and four (15%) were high quality. Compared with no testing or risk-based testing: 14 of 16 (88%) cost-utility analyses found that birth cohort testing was cost effective, eight of nine (89%) analyses found that universal testing was cost effective, and eight of eight (100%) analyses found that age-based general population testing was cost effective. Cost effectiveness was influenced by disease prevalence and progression, testing and treatment uptake, treatment eligibility of those identified by testing, the cost of treatment and the proportion of those treated that achieve sustained virological response. CONCLUSION: Overall, the international evidence supports the potential cost effectiveness of birth cohort, universal, and age-based general population testing, but is caveated by study generalisability, specifically the transferability of findings from one jurisdiction to another, and institutional variations in healthcare delivery systems and budgetary constraints. The cost effectiveness of each approach will vary according to population- and health system-specific characteristics such as epidemiological context, testing coverage, linkage to care and capacity to treat. Given issues regarding the transferability of economic evaluations (for example, model inputs and assumptions) and the significant resources required to implement these interventions, jurisdiction-specific economic evaluations and budget impact analyses will likely be required to inform investment and implementation decisions. REGISTRATION: PROSPERO, CRD42019127159. Registered 29 April 2019.

GPs' perceptions of their relationship with the pharmaceutical industry: a qualitative study.

BACKGROUND: The pharmaceutical industry invests heavily in promoting medications to physicians. This promotion may influence physicians' prescribing behaviour and lead to inappropriately increased prescribing rates. AIM: To understand GPs' experience of interacting with the pharmaceutical industry, and explore their views and perceptions of the impact of this interaction in general practice in Ireland. DESIGN & SETTING: A qualitative design was used, and GPs practicing in Ireland were eligible. METHOD: A combination of purposive and snowball sampling techniques was applied and semi-structured interviews were conducted. Thematic analysis was used to develop themes from the data. RESULTS: Twenty-one GPs and one GP trainee participated. Five themes were developed: 1) GP and pharmaceutical industry interface; 2) the industry's methods of influence; 3) the uncomfortable relationship between GPs and industry; 4) GPs' perceptions of being unconsciously influenced; and 5) GPs' lack of knowledge of relevant regulations.Participants interacted with pharmaceutical representatives in their surgery and through continuing professional development (CPD). Reported methods of influence included biased information and the offer of gifts. Most participants felt their prescribing was unconsciously influenced. A minority felt that they were only influenced in a way that improved their prescribing. CONCLUSION: The study shows that there can be a lack of clarity among GPs about relevant regulations and about the potential impact on prescribing of interactions with the pharmaceutical industry. Education of trainees and GPs has the potential to address this. Restrictions on interactions with the pharmaceutical industry may also play a role, although alternative CPD funding sources would need to be established.

Effect of the OPTIMAL programme on self-management of multimorbidity in primary care: a randomised controlled trial.

BACKGROUND: Effective primary care interventions for multimorbidity are needed. AIM: To evaluate the effectiveness of a group-based, 6-week, occupational therapy-led self-management support programme (OPTIMAL) for patients with multimorbidity. DESIGN AND SETTING: A pragmatic parallel randomised controlled trial across eight primary care teams in Eastern Ireland with 149 patients with multimorbidity, from November 2015 to December 2018. Intervention was OPTIMAL with a usual care comparison. METHOD: Primary outcomes were health-related quality of life (EQ-5D-3L) and frequency of activity participation (Frenchay Activities Index [FAI]). Secondary outcomes included independence in activities of daily living, occupational performance and satisfaction, anxiety and depression, self-efficacy, and healthcare utilisation. Complete case linear regression analyses were conducted. Age (<65/≥65 years) and the number of chronic conditions (<4/≥4) were explored further. RESULTS: A total of 124 (83.2%) and 121 (81.2%) participants had complete data at immediate and 6-month post-intervention follow-up, respectively. Intervention participants had significant improvement in EQ-VAS (visual analogue scale) at immediate follow-up (adjusted mean difference [aMD] = 7.86; 95% confidence interval [CI] = 0.92 to 14.80) but no difference in index score (aMD = 0.04; 95% CI = -0.06 to 0.13) or FAI (aMD = 1.22; 95% CI = -0.84 to 3.29). At 6-month follow-up there were no differences in primary outcomes and mixed results for secondary outcomes. Pre-planned subgroup analyses suggested participants aged <65 years were more likely to benefit. CONCLUSION: OPTIMAL was found to be ineffective in improving health-related quality of life or activity participation at 6-month follow-up. Existing multimorbidity interventions tend to focus on older adults; preplanned subgroup analyses results in the present study suggest that future research should target younger adults (<65 years) with multimorbidity.

Link workers providing social prescribing and health and social care coordination for people with multimorbidity in socially deprived areas (the LinkMM trial): protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Link workers are non-health or social care professionals based in primary care who support people to develop and achieve a personalised set of health and social goals by engaging with community resources. Link workers have been piloted in areas of deprivation, but there remains insufficient evidence to support their effectiveness. Multimorbidity is increasing in prevalence, but there are limited evidence-based interventions. This paper presents the protocol for a randomised controlled trial (RCT) that will test the effectiveness of link workers based in general practices in deprived areas in improving health outcomes for people with multimorbidity. METHODS AND ANALYSIS: The protocol presents the proposed pragmatic RCT, involving 10 general practitioner (GP) practices and 600 patients. Eligible participants will be community dwelling adults with multimorbidity (≥two chronic conditions) identified as being suitable for referral to a practice-based link worker. Following baseline data collection, the patients will be randomised into intervention group that will meet the link worker over a1-month period, or a 'wait list' control that will receive usual GP care. Primary outcomes are health-related quality of life as assessed by EQ-5D-5L and mental health assessed by Hospital Anxiety and Depression Scale. Secondary outcomes are based on the core outcome set for multimorbidity. Data will be collected at baseline and on intervention completion at 1 month using questionnaires self-completed by participants and GP records. Parallel process and economic analyses will be conducted to explore participants' experiences and examine cost-effectiveness of the link worker intervention. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Irish College of General Practitioners Ethics Committee. The findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN10287737;Pre-results.

A micro costing analysis of the development of a primary care intervention to improve the uptake of diabetic retinopathy screening.

BACKGROUND: The application of economic analysis within implementation science is still developing and the cost of intervention development, which differs markedly from the costs of initial implementation and maintenance, is often overlooked. Our aim was to retrospectively cost the development of a multifaceted intervention in primary care to improve attendance at diabetic retinopathy screening. METHODS: A retrospective micro costing of developing the intervention from the research funder perspective was conducted. It was based on a systematic intervention development process involving analysis of existing audit data and interviews with patients and healthcare professionals (HCPs), conducting consensus meetings with patients and HCPs, and using these data together with a rapid review of the effectiveness of interventions, to inform the final intervention. Both direct (non-personnel, e.g. travel, stationary, room hire) and indirect (personnel) costs were included. Data sources included researcher time logs, payroll data, salary scales, an online financial management system, invoices and purchase orders. Personnel involved in the intervention development were consulted to determine the activities they conducted and the duration of their involvement. Sensitivity and scenario analyses were conducted to estimate uncertainty around parameters and scope. RESULTS: The total cost of intervention development (July 2014-January 2019) was €40,485 of which 78% were indirect (personnel) costs (€31,451). In total, personnel contributed 1368 h to intervention development. Highest cost activities were the patient interviews, and consensus process, contributing 23% and 34% of the total cost. Varying estimated time spent on intervention development activities by + 10% increased total intervention development cost by 6% to €42,982. CONCLUSIONS: Our results highlight that intervention development requires a significant amount of human capital input, combining research experience, patient and public experience, and expert knowledge in relevant fields. The time committed to intervention development is critical but has a significant opportunity cost. With limited resources for research on developing and implementing interventions, capturing intervention development costs and incorporating them as part of assessment of cost-effective interventions, could inform research priority and resource allocation decisions.

Interventions for improving outcomes in patients with multimorbidity in primary care and community settings.

BACKGROUND: Many people with chronic disease have more than one chronic condition, which is referred to as multimorbidity. The term comorbidity is also used but this is now taken to mean that there is a defined index condition with other linked conditions, for example diabetes and cardiovascular disease. It is also used when there are combinations of defined conditions that commonly co-exist, for example diabetes and depression. While this is not a new phenomenon, there is greater recognition of its impact and the importance of improving outcomes for individuals affected. Research in the area to date has focused mainly on descriptive epidemiology and impact assessment. There has been limited exploration of the effectiveness of interventions to improve outcomes for people with multimorbidity. OBJECTIVES: To determine the effectiveness of health-service or patient-oriented interventions designed to improve outcomes in people with multimorbidity in primary care and community settings. Multimorbidity was defined as two or more chronic conditions in the same individual. SEARCH METHODS: We searched MEDLINE, EMBASE, CINAHL and seven other databases to 28 September 2015. We also searched grey literature and consulted experts in the field for completed or ongoing studies. SELECTION CRITERIA: Two review authors independently screened and selected studies for inclusion. We considered randomised controlled trials (RCTs), non-randomised clinical trials (NRCTs), controlled before-after studies (CBAs), and interrupted time series analyses (ITS) evaluating interventions to improve outcomes for people with multimorbidity in primary care and community settings. Multimorbidity was defined as two or more chronic conditions in the same individual. This includes studies where participants can have combinations of any condition or have combinations of pre-specified common conditions (comorbidity), for example, hypertension and cardiovascular disease. The comparison was usual care as delivered in that setting. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included studies, evaluated study quality, and judged the certainty of the evidence using the GRADE approach. We conducted a meta-analysis of the results where possible and carried out a narrative synthesis for the remainder of the results. We present the results in a 'Summary of findings' table and tabular format to show effect sizes across all outcome types. MAIN RESULTS: We identified 17 RCTs examining a range of complex interventions for people with multimorbidity. Nine studies focused on defined comorbid conditions with an emphasis on depression, diabetes and cardiovascular disease. The remaining studies focused on multimorbidity, generally in older people. In 11 studies, the predominant intervention element was a change to the organisation of care delivery, usually through case management or enhanced multidisciplinary team work. In six studies, the interventions were predominantly patient-oriented, for example, educational or self-management support-type interventions delivered directly to participants. Overall our confidence in the results regarding the effectiveness of interventions ranged from low to high certainty. There was little or no difference in clinical outcomes (based on moderate certainty evidence). Mental health outcomes improved (based on high certainty evidence) and there were modest reductions in mean depression scores for the comorbidity studies that targeted participants with depression (standardized mean difference (SMD) -0.41, 95% confidence interval (CI) -0.63 to -0.2). There was probably a small improvement in patient-reported outcomes (moderate certainty evidence). The intervention may make little or no difference to health service use (low certainty evidence), may slightly improve medication adherence (low certainty evidence), probably slightly improves patient-related health behaviours (moderate certainty evidence), and probably improves provider behaviour in terms of prescribing behaviour and quality of care (moderate certainty evidence). Cost data were limited. AUTHORS' CONCLUSIONS: This review identifies the emerging evidence to support policy for the management of people with multimorbidity and common comorbidities in primary care and community settings. There are remaining uncertainties about the effectiveness of interventions for people with multimorbidity in general due to the relatively small number of RCTs conducted in this area to date, with mixed findings overall. It is possible that the findings may change with the inclusion of large ongoing well-organised trials in future updates. The results suggest an improvement in health outcomes if interventions can be targeted at risk factors such as depression in people with co-morbidity.

Protocol for a mixed methods process evaluation of the LinkMM randomised controlled trial "Use of link workers to provide social prescribing and health and social care coordination for people with complex multimorbidity in socially deprived areas".

Background  Multimorbidity, defined as two or more chronic conditions is increasing in prevalence and is associated with increased health care use, fragmented care and poorer health outcomes. Link workers are non-health or social care professionals who support people to connect with resources in their community to improve their well-being, a process commonly referred to as social prescribing. The use of link workers in primary care may be an effective intervention in helping those with long-term conditions manage their illness and improve health and well-being, but the evidence base in limited. The LinkMM study is a randomised controlled trial of the effectiveness of link workers based in primary care, providing social prescribing and health and social care coordination for people with multimorbidity. The aim of the LinkMM process evaluation is to investigate the implementation of the link worker intervention, mechanisms of impact and influence of the specific context on these, as per the Medical Research Council framework, using quantitative and qualitative methods. Methods  Quantitative data will be gathered from a number of sources including researcher logbooks, participant baseline questionnaires, client management database, and will be analysed using descriptive statistics. Semi structured interviews with participants will investigate their experiences of the intervention. Interviews with link workers, practices and community stakeholders will explore how the intervention was implemented and barriers and facilitators to this. Thematic analysis of interview transcripts will be conducted. Discussion  The process evaluation of the LinkMM trial will provide important information allowing a more in-depth understanding of how the intervention worked and lessons for future wider scale implementation.

The experience of financial burden for people with multimorbidity: A systematic review of qualitative research.

BACKGROUND: Multimorbidity prevalence is increasing globally. People with multimorbidity have higher health care costs, which can create a financial burden. OBJECTIVE: To synthesize qualitative research exploring experience of financial burden for people with multimorbidity. SEARCH STRATEGY: Six databases were searched in May 2019. A grey literature search and backward and forward citation checking were also conducted. INCLUSION CRITERIA: Studies were included if they used a qualitative design, conducted primary data collection, included references to financial burden and had at least one community-dwelling adult participant with two or more chronic conditions. DATA EXTRACTION AND SYNTHESIS: Screening and critical appraisal were conducted by two reviewers independently. One reviewer extracted data from the results section; this was checked by a second reviewer. GRADE-CERQual was used to summarize the certainty of the evidence. Data were analysed using thematic synthesis. MAIN RESULTS: Forty-six studies from six continents were included. Four themes were generated: the high costs people with multimorbidity experience, the coping strategies they use to manage these costs, and the negative effect of both these on their well-being. Health insurance and government supports determine the manageability and level of costs experienced. DISCUSSION: Financial burden has a negative effect on people with multimorbidity. Continuity of care and an awareness of the impact of financial burden of multimorbidity amongst policymakers and health care providers may partially address the issue. PATIENT OR PUBLIC CONTRIBUTION: Results were presented to a panel of people with multimorbidity to check whether the language and themes 'resonated' with their experiences.

Evaluation of the General Practice Pharmacist (GPP) intervention to optimise prescribing in Irish primary care: a non-randomised pilot study.

OBJECTIVE: Limited evidence suggests integration of pharmacists into the general practice team could improve medicines management for patients, particularly those with multimorbidity and polypharmacy. This study aimed to develop and assess the feasibility of an intervention involving pharmacists, working within general practices, to optimise prescribing in Ireland. DESIGN: Non-randomised pilot study. SETTING: Primary care in Ireland. PARTICIPANTS: Four general practices, purposively sampled and recruited to reflect a range of practice sizes and demographic profiles. INTERVENTION: A pharmacist joined the practice team for 6 months (10 hours/week) and undertook medication reviews (face to face or chart based) for adult patients, provided prescribing advice, supported clinical audits and facilitated practice-based education. OUTCOME MEASURES: Anonymised practice-level medication (eg, medication changes) and cost data were collected. Patient-reported outcome measure (PROM) data were collected on a subset of older adults (aged ≥65 years) with polypharmacy using patient questionnaires, before and 6 weeks after medication review by the pharmacist. RESULTS: Across four practices, 786 patients were identified as having 1521 prescribing issues by the pharmacists. Issues relating to deprescribing medications were addressed most often by the prescriber (59.8%), compared with cost-related issues (5.8%). Medication changes made during the study equated to approximately €57 000 in cost savings assuming they persisted for 12 months. Ninety-six patients aged ≥65 years with polypharmacy were recruited from the four practices for PROM data collection and 64 (66.7%) were followed up. There were no changes in patients' treatment burden or attitudes to deprescribing following medication review, and there were conflicting changes in patients' self-reported quality of life. CONCLUSIONS: This non-randomised pilot study demonstrated that an intervention involving pharmacists, working within general practices is feasible to implement and has potential to improve prescribing quality. This study provides rationale to conduct a randomised controlled trial to evaluate the clinical and cost-effectiveness of this intervention.

Quality, scope and reporting standards of randomised controlled trials in Irish Health Research: an observational study.

BACKGROUND: Despite efforts to improve the accuracy and transparency of the design, conduct, and reporting of randomised controlled trials (RCTs), deficiencies remain. Such deficiencies contribute to significant, avoidable waste of health research investment and impede reproducibility. This study aimed to synthesise and critically analyse changes over time in the conduct and reporting of internationally published evidence on patient and/or population health-oriented RCTs conducted in one country. METHODS: This observational study drew on systematic review methods. We searched six databases for published RCTs (database inception to December 2018) where ≥ 80% of participants were recruited in the Republic of Ireland. RCTs of interventions targeted at patients, providers and/or policy makers intended to improve health, healthcare or health research were included. For each study, screening, data extraction and methodological quality appraisal were conducted by one member of the author team. RESULTS: From 17,560 titles and abstracts, 752 unique RCTs were published in 745 papers between 1968 and 2018, with a steady year-on-year increase since 1968. The number of participants was in the range of 2-8628. The majority were parallel design (86%) and classified as treatment evaluation. Of the 418 RCTs published since the introduction of mandatory clinical trial registration by the International Committee of Medical Journal Editors in 2005, 32% (n = 134) provided a trial registration number. This increased to 47% when taking studies published between 2013 and 2018 (n = 232). Since the 1996 publication of the CONSORT statement, 16% of included RCTs made specific reference to a standardised reporting guideline and this increased to 31% for more recent studies published between 2013 and 2018. Overall, 7% (n = 53) of studies referred to a published study protocol, increasing to 20% for studies published between 2013 and 2018. CONCLUSION: Evidence from this single-country study of RCTs published in the international literature suggests that both the number overall, the number registered and the number referencing reporting guidelines have increased steadily over time. Despite widespread endorsement of reporting standards, reporting of RCTs remains suboptimal in domains such as compliance with the CONSORT statement and prospective trial registration. Researchers, funders and journal editors, nationally and internationally, should continue to focus on improving reporting and examining avoidable waste of health research investment.