Embedding formal and experiential public and patient involvement training in a structured PhD programme: process and impact evaluation.

BACKGROUND: Incorporating Public and Patient Involvement (PPI) into doctoral research is valued by PhD funders and scholars. Providing early career researchers with appropriate training to develop skills to conduct meaningful PPI involvement is important. The Health Research Board (HRB) Collaborative Doctoral Award in MultiMorbidity programme (CDA-MM) embedded formal PPI training in its structured education. The four participating PhD scholars established a PPI panel comprising people living with two or more chronic conditions, presenting an opportunity for experiential PPI training. This study aimed to evaluate the process and impact of embedding PPI training in a structured PhD programme. METHODS: This study was a longitudinal mixed-methods evaluation, conducted over 24 months (June 2020 to June 2022). A process evaluation provided an understanding of how PPI was embedded and explored the experiences of key stakeholders involved. An impact evaluation assessed the impact of embedding PPI training in the programme. Participants included PhD scholars, PPI contributors and PhD supervisors. The data collection and analysis was led by an independent researcher not aligned with the CDA-MM. Data collection methods included five focus groups, individual interviews (n = 6), an impact log, activity logs and group reflections. Qualitative data were analysed using thematic and content analysis and quantitative data analysed using descriptive statistics. RESULTS: Embedding formal and experiential PPI training in a structured PhD programme is feasible. Both approaches to training are fundamental to building PPI capacity. Involvement of an experienced and knowledgeable PPI lead throughout is perceived as critical. The PPI panel approach offered a good example of embedded consultation and worked well in a structured PhD programme, providing PhD scholars with ample opportunities for learning about PPI and its implementation. For PPI contributors, culture was the most important indicator of quality and was positively evaluated. Key roles for PhD supervisors were identified. Embedding formal and experiential PPI training impacted positively on many different aspects of individual PhD research projects and on PhD scholars as researchers. There were positive impacts for PPI contributors and PhD supervisors. CONCLUSIONS: Embedding formal and experiential PPI training in a structured PhD programme is a novel approach. The evaluation has identified a number of lessons that can inform future doctoral programmes seeking to embed formal and experiential PPI training.

Four PhD scholars participated in the CDA-MM. They received training and support from a PPI lead on how to conduct PPI in research. They established a PPI panel of people with two or more ongoing health conditions, to enable PhD scholars to get input from PPI contributors and learn how to do PPI well. An evaluation study was conducted to explore how the PhD scholars conducted PPI, how well it worked, the difference it made and to identify messages for PhD scholars wishing to involve PPI contributors. For the evaluation, the PPI contributors, PhD scholars and PhD supervisors were asked about their experiences and views. For many of the PPI contributors, being part of the CDA-MM PPI panel was their first experience of being involved in PPI. The ongoing support they received from PhD scholars was important. For them, relationships and the way that meetings are conducted matter for doing PPI well. They liked working in small groups and on concrete issues. They found the time they were expected to give was reasonable and within acceptable limits. They preferred in-person meetings. According to PPI contributors, when PPI is done well, it has benefits for the research, particularly ensuring that plain language is used and jargon avoided when researchers communicate with people with two or more ongoing health conditions. PhD scholars benefit from getting the patient perspective and learning how to communicate their research to patients. PPI contributors benefit in many different ways. Some PPI contributors argued that the PPI advisory panel worked so well in the CDA-MM that no changes were needed, whereas others would like to explore different ways of being involved in research.

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.

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.

A protocol for the evaluation of the process and impact of embedding formal and experiential Public and Patient Involvement training in a structured PhD programme.

BACKGROUND: Incorporating Public and Patient Involvement (PPI) into doctoral research is valued by PhD scholars. The importance of providing early career researchers with appropriate education and training to develop skills to conduct meaningful involvement has been articulated. The Collaborative Doctoral Award in MultiMorbidity (CDA-MM) PhD programme embedded formal PPI training as a postgraduate education component. Four PhD scholars taking part in the CDA-MM established a PPI panel comprising people, and carers of people, living with multimorbidity (≥2 chronic conditions), presenting an opportuning for experiential PPI training. The proposed study aims to evaluate the process and impact of formal and experiential PPI training during a PhD programme. DESIGN: Embedding PPI training in a PhD programme is a novel approach. This evaluation will include a process evaluation to provide an understanding of the workings of the PPI panel and explore the experiences of key stakeholders involved, and an impact evaluation to assess the impact of embedding PPI training in a PhD programme. This study is a longitudinal mixed-methods evaluation, conducted over 24 months. Participants include PhD scholars, PPI contributors and PhD supervisors. An independent researcher not aligned with the CDA-MM will lead the evaluation. Data collection methods include focus groups, individual interviews, an impact log and group reflections. Qualitative data will be analysed using thematic and content analysis and quantitative data will be analysed using descriptive statistics. DISCUSSION: This evaluation will report the learnings from embedding formal and experiential PPI training and education across a PhD programme.

Integrating clinical pharmacists within general practice: protocol for a pilot cluster randomised controlled trial.

INTRODUCTION: Managing patients with multiple conditions (multimorbidity) is a major challenge for healthcare systems internationally, particularly in older patients. Multimorbidity and subsequent polypharmacy increase treatment burden and the risk of potentially inappropriate prescribing, and both are complex to manage in primary care. Limited evidence suggests integration of pharmacists into general practice teams could improve medication management for patients with multimorbidity and polypharmacy. Building on findings from a non-randomised, uncontrolled General Practice Pharmacist (GPP) feasibility study conducted in Irish primary care, the aim of this study is to conduct a pilot cluster randomised controlled trial (cRCT) of the GPP study, to assess feasibility, intervention impact, costs and appropriateness of continuing to a definitive cRCT. METHODS AND ANALYSIS: This pilot cRCT will involve 8 general practitioner (GP) practices and 120 patients. Practices will identify and recruit patients aged ≥65 years, who are taking ≥10 regular medications. Practices will be allocated to intervention or control after baseline data collection. Intervention practices will have a pharmacist integrated within their service, working with GPs, patients and practice staff to optimise prescribing and other medication-related activities. Control practices will provide standard GP care. The primary feasibility outcomes will include recruitment rate, uptake of medication reviews and study retention. For the primary clinical outcome, the number of potentially inappropriate prescribing incidences per patient will be collected. Secondary outcomes will include medication-related outcomes, patient-reported outcome measures, and data pertaining to the role and impact of the pharmacist on prescribing. In addition, economic and process evaluations will be conducted. ETHICS AND DISSEMINATION: This trial has been approved by the Irish College of General Practitioners Research Ethics Committee and will be performed in accordance with the Declaration of Helsinki. The results will be reported in peer-reviewed journals and be presented at national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN Registry (https://doi.org/10.1186/ISRCTN18752158).

Effectiveness of link workers providing social prescribing on health outcomes and costs for adult patients in primary care and community settings. A protocol for a systematic review of the literature.

Introduction: The use of link workers for social prescribing and health and social care coordination is increasing, but there is insufficient data to demonstrate their effectiveness or for whom they work best. Multimorbidity is increasing in prevalence and affects those living in deprived areas ten years earlier than affluent areas. This systematic review aims to examine the evidence for the effectiveness and costs of link workers in improving health outcomes. We will also look for evidence for the use of link workers specifically for people living with multimorbidity and in deprived areas. Methods: Databases of published and grey literature will be searched for randomised and non-randomised controlled trials examining use of link workers based in primary care for community dwelling adults compared to usual care. Primary outcomes will be health related quality of life and mental health. Data on costs will be extracted. Studies will be selected for inclusion by title and abstract review by two reviewers. A Preferred Reporting Items for Systematic Reviews (PRISMA) flow diagram will document the selection process. A standardised form will be used to extract data. Data quality will be assessed using the Cochrane Risk of Bias tool for randomised controlled trials, a narrative synthesis will be completed and the GRADE assessment tool used to comment on evidence quality. A meta-analysis of effect size of primary outcomes and subgroup analysis for multimorbidity and social deprivation will be performed if there are sufficient comparable data. Conclusion: This systematic review will give an important overview of the evidence for the use of link workers providing social prescribing and health and social care coordination in primary care. This will help inform intervention development and guide policy makers on whether these interventions are cost effective and which groups stand to benefit most. Prospero registration: CRD42019134737 (04/07/2019).

The effectiveness of integrating clinical pharmacists within general practice to optimise prescribing and health outcomes in primary care patients with polypharmacy: A protocol for a systematic review.

Introduction: Coordinating prescribing for patients with polypharmacy is a challenge for general practitioners. Pharmacists may improve management and outcomes for patients with polypharmacy. This systematic review aims to examine the clinical and cost-effectiveness of pharmacist interventions to optimise prescribing and improve health outcomes in patients with polypharmacy in primary care settings.  Methods: The review will be reported using the PRISMA guidelines. A comprehensive search of 10 databases from inception to present, with no language restrictions will be conducted. Studies will be included where they evaluate the clinical or cost-effectiveness of a clinical pharmacist in primary care on potentially inappropriate prescriptions using validated indicators and number of medicines. Secondary outcomes will include health related quality of life measures, health service utilisation, clinical outcomes and data relating to cost effectiveness. Randomised controlled trials, non-randomised controlled trials, controlled before-after, interrupted-time-series and health economic studies will be eligible for inclusion.  Titles, abstracts and full texts will be screened for inclusion by two reviewers. Data will be extracted using a standard form. Risk of bias in all included studies will be assessed using the Effective Practice and Organisation of Care (EPOC) criteria. Economic studies will be assessed using the Consensus Health Economic Criteria (CHEC) list as per the Cochrane Handbook for critical appraisal of methodological quality. A narrative synthesis will be performed, and the certainty of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Where data support quantitative synthesis, a meta-analysis will be performed. Discussion: This systematic review will give an overview of the effectiveness of pharmacist interventions to improve prescribing and health outcomes in a vulnerable patient group. This will provide evidence to policy makers on strategies involving clinical pharmacists integrated within general practice, to address issues which arise in polypharmacy and multimorbidity.  PROSPERO Registration:  CRD42019139679 (28/08/19).

The vascular targeting agent combretastatin-A4 and a novel cis-Restricted {beta}-Lactam Analogue, CA-432, induce apoptosis in human chronic myeloid leukemia cells and ex vivo patient samples including those displaying multidrug resistance.

Combretastatin-A4 (CA-4) is a natural derivative of the African willow tree Combretum caffrum. CA-4 is one of the most potent antimitotic components of natural origin, but it is, however, intrinsically unstable. A novel series of CA-4 analogs incorporating a 3,4-diaryl-2-azetidinone (ß-lactam) ring were designed and synthesized with the objective to prevent cis -trans isomerization and improve the intrinsic stability without altering the biological activity of CA-4. Evaluation of selected ß-lactam CA-4 analogs demonstrated potent antitubulin, antiproliferative, and antimitotic effects in human leukemia cells. A lead ß-lactam analog, CA-432, displayed comparable antiproliferative activities with CA-4. CA-432 induced rapid apoptosis in HL-60 acute myeloid leukemia cells, which was accompanied by depolymerization of the microtubular network, poly(ADP-ribose) polymerase cleavage, caspase-3 activation, and Bcl-2 cleavage. A prolonged G(2)M cell cycle arrest accompanied by a sustained phosphorylation of mitotic spindle checkpoint protein, BubR1, and the antiapoptotic proteins Bcl-2 and Bcl-x(L) preceded apoptotic events in K562 chronic myeloid leukemia (CML) cells. Molecular docking studies in conjunction with comprehensive cell line data rule out CA-4 and ß-lactam derivatives as P-glycoprotein substrates. Furthermore, both CA-4 and CA-432 induced significantly more apoptosis compared with imatinib mesylate in ex vivo samples from patients with CML, including those positive for the T315I mutation displaying resistance to imatinib mesylate and dasatinib. In summary, synthetic intrinsically stable analogs of CA-4 that display significant clinical potential as antileukemic agents have been designed and synthesized.