Stakeholder perceptions of and attitudes towards problematic polypharmacy and prescribing cascades: a qualitative study.

INTRODUCTION: Problematic polypharmacy is the prescribing of five or more medications potentially inappropriately. Unintentional prescribing cascades represent an under-researched aspect of problematic polypharmacy and occur when an adverse drug reaction (ADR) is misinterpreted as a new symptom resulting in the initiation of a new medication. The aim of this study was to elicit key stakeholders' perceptions of and attitudes towards problematic polypharmacy, with a focus on prescribing cascades. METHODS: qualitative one-to-one semi-structured interviews were conducted with predefined key stakeholder groups. Inductive thematic analysis was employed. RESULTS: Thirty-one stakeholders were interviewed: six patients, two carers, seven general practitioners, eight pharmacists, four hospital doctors, two professional organisation representatives and two policymakers. Three main themes were identified: (i) ADRs and prescribing cascades-a necessary evil. Healthcare professionals (HCPs) expressed concern that experiencing an ADR would negatively impact patients' confidence in their doctor. However, patients viewed ADRs pragmatically as an unpredictable risk. (ii) Balancing the risk/benefit tipping point. The complexity of prescribing decisions in the context of polypharmacy made balancing this tipping point challenging. Consequently, HCPs avoided medication changes. (iii) The minefield of medication reconciliation. Stakeholders, including patients and carers, viewed medication reconciliation as a perilous activity due to systemic communication deficits. CONCLUSION: Stakeholders believed that at a certain depth of polypharmacy, the risk that a new symptom is being caused by an existing medication becomes incalculable. Therefore, in the absence of harm, medication changes were avoided. However, medication reconciliation post hospital discharge compelled prescribing decisions and was seen as a high-risk activity by stakeholders.

Potentially Inappropriate Prescribing and Potential Prescribing Omissions and Their Association with Adverse Drug Reaction-Related Hospital Admissions.

BACKGROUND: This study aimed to determine the prevalence of potentially inappropriate prescribing (PIP) and potential prescribing omissions (PPOs) and their association with ADR-related hospital admissions in patients aged ≥ 65 years admitted acutely to the hospital. METHODS: Information on medications and morbidities was extracted from the Adverse Drug Reactions in an Ageing Population (ADAPT) cohort (N = 798: N = 361 ADR-related admissions; 437 non-ADR-related admissions). PIP and PPOs were assessed using Beers Criteria 2019 and STOPP/START version 2. Multivariable logistic regression (adjusted odds ratios (aOR), 95%CI) was used to examine the association between PIP, PPOs and ADR-related admissions, adjusting for covariates (age, gender, comorbidity, polypharmacy). RESULTS: In total, 715 (90%; 95% CI 87-92%) patients had ≥1 Beers Criteria, 555 (70%; 95% CI 66-73%) had ≥ 1 STOPP criteria and 666 patients (83%; 95% CI 81-86%) had ≥ 1 START criteria. Being prescribed at least one Beers (aOR = 1.66, 95% CI = 1.00-2.77), or meeting STOPP (aOR = 1.07, 95% CI = 0.79-1.45) or START (aOR = 0.72; 95%CI = 0.50-1.06) criteria or the number of PIP/PPO criteria met was not significantly associated with ADR-related admissions. Patients prescribed certain drug classes (e.g., antiplatelet agents, diuretics) per individual PIP criteria were more likely to have an ADR-related admission. CONCLUSION: There was a high prevalence of PIP and PPOs in this cohort but no association with ADR-related admissions.

Association between patient attitudes towards deprescribing and subsequent prescription changes.

Deprescribing is an essential component of safe prescribing, especially for people with higher levels of polypharmacy. Identifying individuals prepared to consider medicine changes may facilitate deprescribing-orientated reviews. We aimed to explore the relationship between revised patients' attitudes towards deprescribing (rPATD) scores and medication changes in older people prescribed ≥15 medicines. A secondary analysis of rPATD scores and prescription data from a cluster randomised controlled trial of a GP-delivered, deprescribing-orientated medication review was conducted. The association between number of medicines stopped, started and changed and baseline rPATD scores was assessed using Poisson regression, adjusting for patient age, gender, study group allocation, baseline number of medicines and effects of clustering. Participants (n = 404) had a mean age of 76.4 years and were prescribed a mean of 17.1 medicines at baseline. Willingness to stop a medicine was associated with higher rates of both deprescribing (IRR: 1.40; 95% CI: 1.06-1.84) and initiating medicines (IRR: 1.43; 95% CI: 1.09-1.88). Satisfaction with current medicines was associated with a lower rate of deprescribing (IRR: 0.69; 95% CI: 0.57-0.85). The rPATD questionnaire could be used as part of a deprescribing intervention to identify participants who may be prepared to engage in deprescribing, enabling more efficient use of clinician time during complex consultations.

Adverse drug reactions and associated patient characteristics in older community-dwelling adults: a 6-year prospective cohort study.

BACKGROUND: To date, research on adverse drug reactions (ADRs) has focused on secondary care, and there is a paucity of studies that have prospectively examined ADRs affecting older adults in general practice. AIM: To examine the cumulative incidence and severity of ADRs and associated patient characteristics in a sample of community-dwelling older adults. DESIGN AND SETTING: Prospective cohort study of older adults (aged ≥70 years, N = 592) recruited from 15 general practices in the Republic of Ireland. METHOD: Manual review of the participant's general practice electronic medical record, linked to the national dispensed prescription medicine database, and a detailed, self-reported patient postal questionnaire. The primary outcomes were ADR occurrence and severity over a 6-year period (2010-2016). Unadjusted and adjusted logistic regression models examined potential associations between patient characteristics and ADR occurrence. RESULTS: A total of 211 ADRs were recorded for 159 participants, resulting in a cumulative incidence of 26.9% over 6 years. The majority of ADRs detected were mild (89.1%), with the remainder classified as moderate (10.9%). Eight moderate ADRs, representing 34.8% of moderate ADRs and 3.8% of all ADRs, required an emergency hospital admission. ADRs were independently associated with female sex (adjusted odds ratio [OR] 1.83, 95% confidence interval [CI] = 1.17 to 2.85; P = 0.008), polypharmacy (5-9 drug classes) (adjusted OR 1.81, 95% CI = 1.17 to 2.82; P = 0.008), and major polypharmacy (≥10 drug classes) (adjusted OR = 3.33, 95% CI = 1.62 to 6.85; P = 0.001). CONCLUSION: This prospective cohort study of ADRs in general practice shows that over one-quarter of older adults experienced an ADR over a 6-year period. Polypharmacy is independently associated with ADR risk in general practice and older adults on ≥10 drug classes should be prioritised for regular medication review.

Medication changes and potentially inappropriate prescribing in older patients with significant polypharmacy.

BACKGROUND: Number of medicines and medicines appropriateness are often used as outcome measures to evaluate the effectiveness of deprescribing interventions. AIM: The aim of this study was to evaluate changes in prescribing, potentially inappropriate prescriptions (PIP) and prescribing of low-value medicines in older people with multimorbidity and significant polypharmacy. METHOD: This study was a retrospective secondary analysis of prescription data from a cluster randomised controlled trial involving 404 participants aged ≥ 65 years and prescribed ≥ 15 repeat medicines from 51 different general practices. For this study, repeat medications at baseline and follow-up (~ 1 year later) were assigned Anatomical Therapeutic Classification (ATC) codes. Outcomes were the most commonly prescribed and potentially inappropriately prescribed drug groups, the most frequently discontinued or initiated drug groups and the number of changes per person between baseline and follow-up. RESULTS: There were 7051 medicines prescribed to 404 participants at baseline. There was a median of 17 medicines (IQR 15-19) at baseline and 16 (IQR 14-19) at follow-up. PIP represented 17.1% of prescriptions at baseline and 15.7% (n = 6777) at follow-up. There were reductions in the prescription of most drug groups with the largest reduction in antiplatelet prescriptions. Considering medication discontinuations, initiations and switches, there was a median of five medication changes per person (range 0-30, IQR 3-9) by follow-up. There were 95 low-value prescriptions at baseline reducing to 78 at follow-up. CONCLUSION: The number of medication changes per person was not reflected by summarising medication count at two time points, highlighting the complexity of prescribing for patients with polypharmacy. Frequent medication changes has potentially important implications for patients in terms of adherence and medication safety. TRIAL REGISTRY: The SPPiRE trial was registered prospectively on the ISRCTN registry (ISRCTN12752680).

Effective maNagement of depression among patients witH cANCEr (ENHANCE): a protocol for a hybrid systematic review and network meta-analysis of randomised controlled trials of interventions for depressive symptoms.

BACKGROUND: Depression is common among patients with cancer and is associated with lower treatment participation, lower satisfaction with care, poorer quality of life, greater symptom burden and higher healthcare costs. Various types of interventions (e.g. pharmacological, psychotherapy) are used for the treatment of depression. However, evidence for these among patients with cancer is limited. Furthermore, the relative effectiveness and acceptability of different approaches are unknown because a direct comparison between all available treatments has not been carried out. We will address this by conducting a network meta-analysis (NMA) of interventions for depression among people with cancer using a hybrid overview of reviews and systematic review methodology. METHODS: We will search for and extract data from systematic reviews of randomised controlled trials (RCTs) of depression interventions for patients with cancer from inception, before performing a supplemental search for more recent RCTs. We will include RCTs comparing pharmacological, psychotherapy, exercise, combination therapy, collaborative care or complementary and alternative medicine interventions with pill placebo, no treatment, waitlist, treatment as usual or minimal treatment control groups, or directly in head-to-head trials, among adults who currently have cancer or have a history of any cancer and elevated depressive symptoms (scores above a cut-off on validated scales or meeting diagnostic criteria). Our primary outcomes will be change in depressive symptoms (standardised mean difference) and intervention acceptability (% who withdrew). Our secondary outcomes will be 6-month change in depressive symptoms, health-related quality of life, adverse events and mortality. We will independently screen for eligibility, extract data and assess risk of bias using the RoB 2 tool. We will use frequentist random-effects multivariate NMA in Stata, rankograms and surface under the cumulative ranking curves to synthesise evidence and obtain a ranking of intervention groups. We will explore heterogeneity and inconsistency using local and global measures and evaluate the credibility of results using the Confidence in NEtwork Meta-Analysis (CINeMA) framework. DISCUSSION: Our findings will provide the best available evidence for managing depression among patients with cancer. Such information will help to inform clinical guidelines, evidence-based treatment decisions and future research by identifying gaps in the current literature. SYSTEMATIC REVIEW REGISTRATION: Submitted to PROSPERO (record number: 290145), awaiting registration.

Patient and general practitioner experiences of implementing a medication review intervention in older people with multimorbidity: Process evaluation of the SPPiRE trial.

INTRODUCTION: The SPPiRE cluster randomized controlled trial found that a general practitioner (GP)-delivered medication review that incorporated screening for potentially inappropriate prescriptions (PIP), a brown bag review and a patient priority assessment, resulted in a significant but small reduction in the number of medicines and no significant reduction in PIP. This process evaluation aims to explore the experiences of GPs and patients and the potential for system-wide implementation. METHODS: The trial included 51 general practices and 404 participants with multimorbidity aged ≥65 years, prescribed ≥15 medicines. The process evaluation used mixed methods and ran parallel to the trial. Quantitative data was collected from the SPPiRE intervention website and analysed descriptively. Qualitative data on medication changes were collected from intervention GPs (18/26) and a purposive sample of intervention patients (27/208) via semi-structured telephone interviews. All interviews were transcribed verbatim and analysed using a thematic analysis. Qualitative and quantitative data were integrated using a triangulation protocol. RESULTS: The analysis generated two themes, intervention implementation and mechanisms of action, and both were underpinned by the theme of context. Intervention delivery varied among practices and 45 patients (28%) had no review, primarily due to insufficient GP time. 80% of reviewed patients had ≥1 PIP identified, 59% had ≥1 problem identified during the brown bag review and 79% had ≥1 priority recorded. The brown bag review resulted in the most deprescription of medications. GPs and patients responded positively to the intervention but most GPs did not engage with the patient priority-setting process. GPs identified a lack of integration into practice software and resources as barriers to future implementation. CONCLUSION: The SPPiRE intervention had a small effect in reducing the number of medicines and this was primarily mediated through the brown bag review. The context of resource shortages and deep-seated views around medical decision-making influenced intervention implementation. PATIENT OR PUBLIC CONTRIBUTION: Qualitative data on the implementation of the medication review and their wider views on their medicines was collected from older people with multimorbidity through semi-structured telephone interviews. CLINICAL TRIAL REGISTRATION: The SPPiRE trial was registered prospectively on the ISRCTN registry (ISRCTN12752680).

Optimising a person-centred approach to stopping medicines in older people with multimorbidity and polypharmacy using the DExTruS framework: a realist review.

BACKGROUND: Tackling problematic polypharmacy requires tailoring the use of medicines to individual circumstances and may involve the process of deprescribing. Deprescribing can cause anxiety and concern for clinicians and patients. Tailoring medication decisions often entails beyond protocol decision-making, a complex process involving emotional and cognitive work for healthcare professionals and patients. We undertook realist review to highlight and understand the interactions between different factors involved in deprescribing and to develop a final programme theory that identifies and explains components of good practice that support a person-centred approach to deprescribing in older patients with multimorbidity and polypharmacy. METHODS: The realist approach involves identifying underlying causal mechanisms and exploring how, and under what conditions they work. We conducted a search of electronic databases which were supplemented by citation checking and consultation with stakeholders to identify other key documents. The review followed the key steps outlined by Pawson et al. and followed the RAMESES standards for realist syntheses. RESULTS: We included 119 included documents from which data were extracted to produce context-mechanism-outcome configurations (CMOCs) and a final programme theory. Our programme theory recognises that deprescribing is a complex intervention influenced by a multitude of factors. The components of our final programme theory include the following: a supportive infrastructure that provides clear guidance around professional responsibilities and that enables multidisciplinary working and continuity of care, consistent access to high-quality relevant patient contextual data, the need to support the creation of a shared explanation and understanding of the meaning and purpose of medicines and a trial and learn approach that provides space for monitoring and continuity. These components may support the development of trust which may be key to managing the uncertainty and in turn optimise outcomes. These components are summarised in the novel DExTruS framework. CONCLUSION: Our findings recognise the complex interpretive practice and decision-making involved in medication management and identify key components needed to support best practice. Our findings have implications for how we design medication review consultations, professional training and for patient records/data management. Our review also highlights the role that trust plays both as a central element of tailored prescribing and a potential outcome of good practice in this area.

Deprescribing medicines in older people living with multimorbidity and polypharmacy: the TAILOR evidence synthesis.

BACKGROUND: Tackling problematic polypharmacy requires tailoring the use of medicines to individual needs and circumstances. This may involve stopping medicines (deprescribing) but patients and clinicians report uncertainty on how best to do this. The TAILOR medication synthesis sought to help understand how best to support deprescribing in older people living with multimorbidity and polypharmacy. OBJECTIVES: We identified two research questions: (1) what evidence exists to support the safe, effective and acceptable stopping of medication in this patient group, and (2) how, for whom and in what contexts can safe and effective tailoring of clinical decisions related to medication use work to produce desired outcomes? We thus described three objectives: (1) to undertake a robust scoping review of the literature on stopping medicines in this group to describe what is being done, where and for what effect; (2) to undertake a realist synthesis review to construct a programme theory that describes 'best practice' and helps explain the heterogeneity of deprescribing approaches; and (3) to translate findings into resources to support tailored prescribing in clinical practice. DATA SOURCES: Experienced information specialists conducted comprehensive searches in MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Web of Science, EMBASE, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials), Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports, Google (Google Inc., Mountain View, CA, USA) and Google Scholar (targeted searches). REVIEW METHODS: The scoping review followed the five steps described by the Joanna Briggs Institute methodology for conducting a scoping review. The realist review followed the methodological and publication standards for realist reviews described by the Realist And Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) group. Patient and public involvement partners ensured that our analysis retained a patient-centred focus. RESULTS: Our scoping review identified 9528 abstracts: 8847 were removed at screening and 662 were removed at full-text review. This left 20 studies (published between 2009 and 2020) that examined the effectiveness, safety and acceptability of deprescribing in adults (aged ≥ 50 years) with polypharmacy (five or more prescribed medications) and multimorbidity (two or more conditions). Our analysis revealed that deprescribing under research conditions mapped well to expert guidance on the steps needed for good clinical practice. Our findings offer evidence-informed support to clinicians regarding the safety, clinician acceptability and potential effectiveness of clinical decision-making that demonstrates a structured approach to deprescribing decisions. Our realist review identified 2602 studies with 119 included in the final analysis. The analysis outlined 34 context-mechanism-outcome configurations describing the knowledge work of tailored prescribing under eight headings related to organisational, health-care professional and patient factors, and interventions to improve deprescribing. We conclude that robust tailored deprescribing requires attention to providing an enabling infrastructure, access to data, tailored explanations and trust. LIMITATIONS: Strict application of our definition of multimorbidity during the scoping review may have had an impact on the relevance of the review to clinical practice. The realist review was limited by the data (evidence) available. CONCLUSIONS: Our combined reviews recognise deprescribing as a complex intervention and provide support for the safety of structured approaches to deprescribing, but also highlight the need to integrate patient-centred and contextual factors into best practice models. FUTURE WORK: The TAILOR study has informed new funded research tackling deprescribing in sleep management, and professional education. Further research is being developed to implement tailored prescribing into routine primary care practice. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018107544 and PROSPERO CRD42018104176. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 32. See the NIHR Journals Library website for further project information.

Many patients take multiple medicines, every day, on a long-term basis. Some feel overloaded by their medicines. However, both doctors and patients have told us that they feel anxious about knowing when and how to safely stop medicines. TAILOR aimed to help by providing the information that doctors and patients need to make individual (tailored) decisions about whether or not to stop (deprescribe) medicines. We had two research questions and so used a different research method to answer each. Both methods involved us first finding all the published research looking at deprescribing for older people living with long-term conditions and using five or more medicines a day. Our first (scoping) review produced a map of what we know about deprescribing: how it is done and if it is safe. We found evidence that structured deprescribing can be safe and acceptable to clinicians, but specific effects were very varied and patient views were often not reported. Our team's patient partners continuously reminded us that medicines mean more to individuals than just a medical effect (e.g. a 'tablet for my blood pressure'), meaning that our research needed to describe good person-centred deprescribing. Our second (realist) review focused on this by looking at if and how tailored deprescribing decisions happen. Our results showed that health-care services need to give clinicians the permission and resources they need to work with patients to develop a joint understanding of the value of medicines, to guide decisions about using/changing medicines, and so to build and maintain trust. Our findings remind us that decisions about medicines are personal. We need to remember that any changes in medicines affect not just an individual's disease, but also their understanding of their health and health care. Our work makes recommendations on how future practice and research can be more person centred. We are now working with patients and health-care professionals to share our findings with a wide audience.

GP-delivered medication review of polypharmacy, deprescribing, and patient priorities in older people with multimorbidity in Irish primary care (SPPiRE Study): A cluster randomised controlled trial.

BACKGROUND: There is a rising prevalence of multimorbidity, particularly in older patients, and a need for evidence-based medicines management interventions for this population. The Supporting Prescribing in Older Adults with Multimorbidity in Irish Primary Care (SPPiRE) trial aimed to investigate the effect of a general practitioner (GP)-delivered, individualised medication review in reducing polypharmacy and potentially inappropriate prescriptions (PIPs) in community-dwelling older patients with multimorbidity in primary care. METHODS AND FINDINGS: We conducted a cluster randomised controlled trial (RCT) set in 51 GP practices throughout the Republic of Ireland. A total of 404 patients, aged ≥65 years with complex multimorbidity, defined as being prescribed ≥15 regular medicines, were recruited from April 2017 and followed up until October 2020. Furthermore, 26 intervention GP practices received access to the SPPiRE website where they completed an educational module and used a template for an individualised patient medication review that identified PIP, opportunities for deprescribing, and patient priorities for care. A total of 25 control GP practices delivered usual care. An independent blinded pharmacist assessed primary outcome measures that were the number of medicines and the proportion of patients with any PIP (from a predefined list of 34 indicators based predominantly on the STOPP/START version 2 criteria). We performed an intention-to-treat analysis using multilevel modelling. Recruited participants had substantial disease and treatment burden at baseline with a mean of 17.37 (standard deviation [SD] 3.50) medicines. At 6-month follow-up, both intervention and control groups had reductions in the numbers of medicines with a small but significantly greater reduction in the intervention group (incidence rate ratio [IRR] 0.95, 95% confidence interval [CI]: 0.899 to 0.999, p = 0.045). There was no significant effect on the odds of having at least 1 PIP in the intervention versus control group (odds ratio [OR] 0.39, 95% CI: 0.140 to 1.064, p = 0.066). Adverse events recorded included mortality, emergency department (ED) presentations, and adverse drug withdrawal events (ADWEs), and there was no evidence of harm. Less than 2% of drug withdrawals in the intervention group led to a reported ADWE. Due to the inability to electronically extract data, primary outcomes were measured at just 2 time points, and this is the main limitation of this work. CONCLUSIONS: The SPPiRE intervention resulted in a small but significant reduction in the number of medicines but no evidence of a clear effect on PIP. This reduction in significant polypharmacy may have more of an impact at a population rather than individual patient level. TRIAL REGISTRATION: ISRCTN Registry ISRCTN12752680.

Contexts and mechanisms relevant to General Practitioner (GP) based interventions to reduce adverse drug events (ADE) in community dwelling older adults: a rapid realist review.

Background: Older adults in Ireland are at increased risk of adverse drug events (ADE) due, in part, to increasing rates of polypharmacy. Interventions to reduce ADE in community dwelling older adults (CDOA) have had limited success, therefore, new approaches are required.A realist review uses a different lens to examine why and how interventions were supposed to work rather than if, they worked. A rapid realist review (RRR) is a more focused and accelerated version.The aim of this RRR is to identify and examine the contexts and mechanisms that play a role in the outcomes relevant to reducing ADE in CDOA in the GP setting that could inform the development of interventions in Ireland. Methods: Six candidate theories (CT) were developed, based on knowledge of the field and recent literature, in relation to how interventions are expected to work. These formed the search strategy. Eighty full texts from 633 abstracts were reviewed, of which 27 were included. Snowballing added a further five articles, relevant policy documents increased the total number to 45. Data were extracted relevant to the theories under iteratively developed sub-themes using NVivo software. Results: Of the six theories, three theories, relating to GP engagement in interventions, relevance of health policy documents for older adults, and shared decision-making, provided data to guide future interventions to reduce ADEs for CDOA in an Irish setting. There was insufficient data for two theories, a third was rejected as existing barriers in the Irish setting made it impractical to use. Conclusions: To improve the success of Irish GP based interventions to reduce ADEs for CDOA, interventions must be relevant and easily applied in practice, supported by national policy and be adequately resourced. Future research is required to test our theories within a newly developed intervention.

Prescribing cascades in community-dwelling adults: protocol for a systematic review.

Introduction: Internationally, health systems face the challenge of managing a growing ageing population living with multimorbidity and polypharmacy. Potentially inappropriate prescribing is common among patients with polypharmacy, increasing the risk for adverse drug reactions (ADRs). Several prescribing indicator sets exist to improve prescribing and reduce potentially inappropriate prescribing, but do not address prescribing cascades. Prescribing cascades occur when a medication is prescribed to treat an ADR to another prescribed medication, whether intentionally or unintentionally, and constitute an important area to consider when characterising problematic polypharmacy. This is a protocol for a systematic review examining prescribing cascades in community-dwelling adults. Methods: The review will be reported adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A systematic search of Medline (Ovid), EMBASE, PsycINFO, CINAHL and the Cochrane Library will be conducted from inception to March 2021, using a predetermined strategy. Grey literature will be searched using Open Grey, MedNar, Dart Europe, and the Turning Research Into Practice (TRIP) databases. No restrictions will be placed on language or publication year. Inclusion criteria are: population - community-dwelling adults (≥18 years), including those in residential or nursing homes; risk - prescription medication with the potential to cause side effects; outcomes - initiation of a new medicine to 'treat' or reduce the risk of experiencing an ADR. Prospective and retrospective cohort studies, case control and case series studies will be included. Two reviewers will independently screen titles and abstracts; studies meeting inclusion criteria will undergo independent full-text screening by two reviewers.  A narrative synthesis will be conducted. Study quality will be independently assessed using the relevant Joanna Briggs Institute Critical Appraisal Checklist. Discussion: This systematic review will identify examples of prescribing cascades for community-dwelling adults and contribute to developing an evidence base regarding such cascades. Registration: PROSPERO [ CRD42021243163, 31/03/2021].

The evolution of an evidence based intervention designed to improve prescribing and reduce polypharmacy in older people with multimorbidity and significant polypharmacy in primary care (SPPiRE).

INTRODUCTION: By the time an intervention is ready for evaluation in a definitive RCT the context of the evidence base may have evolved. To avoid research waste, it is imperative that intervention design and evaluation is an adaptive process incorporating emerging evidence and novel concepts. The aim of this study is to describe changes that were made to an evidence based intervention at the protocol stage of the definitive RCT to incorporate emerging evidence. METHODS: The original evidence based intervention, a GP delivered web guided medication review, was modified in a five step process:Identification of core components of the original intervention.Literature review.Modification of the intervention.Pilot study.Final refinements. A framework, developed in public health research, was utilised to describe the modification process. RESULTS: The population under investigation changed from older people with a potentially inappropriate prescription (PIP) to older people with significant polypharmacy, a proxy marker for complex multimorbidity. An assessment of treatment priorities and brown bag medication review, with a focus on deprescribing were incorporated into the original intervention. The number of repeat medicines was added as a primary outcome measure as were additional secondary patient reported outcome measures to assess treatment burden and attitudes towards deprescribing. CONCLUSIONS: A framework was used to systematically describe how and why the original intervention was modified, allowing the new intervention to build upon an effective and robustly developed intervention but also to be relevant in the context of the current evidence base.

Identifying Adherence Patterns Across Multiple Medications and Their Association With Health Outcomes in Older Community-Dwelling Adults With Multimorbidity.

OBJECTIVES: To classify older people with multimorbidity according to their adherence patterns and to examine the association between medication adherence and health outcomes. METHODS: This is a secondary analysis of a cohort study. Community-dwelling adults aged ≥70 years were recruited from 15 general practices in Ireland in 2010 (wave 1) and followed up 2 years later (wave 2). Participants had ≥2 RxRisk-V multimorbidity conditions at wave 1 and had ≥2 dispensations of RxRisk-V medications (wave 1-wave 2). Average adherence across RxRisk-V conditions was estimated based on continuous multiple-interval measure of medication availability (CMA7 function in AdhereR). Group-based trajectory models were used to group participants' adherence patterns for RxRisk-V medications. Multilevel regression was used to examine the association between adherence and (1) EuroQol 5-dimension (EQ-5D) utility (linear) and (2) vulnerability, using the Vulnerable Elders Survey (≥3 defined as vulnerable; logistic) at wave 2, controlling for potential confounders. RESULTS: Average adherence (CMA7) was 77% across 501 participants. Group-based trajectory models identified 5 adherence groups: (1) initial low adherers, gradual increase; (2) high adherers, sharp decline; (3) steady adherers, gradual decline; (4) consistent high adherers; and (5) consistent nonadherers. Higher average adherence was associated with a significant increase in EQ-5D utility (adjusted ß = 0.11, robust standard error 0.04). Group 5 was associated with significantly increased vulnerability compared to group 4 (adjusted odds ratio = 1.88; 95% confidence interval 1.01-3.50). CONCLUSION: Increased average adherence was associated with higher EQ-5D utility. Adherence grouping did not significantly impact utility. Suboptimal adherence to multiple medications in older adults with multimorbidity was associated with vulnerability.

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.

Predicting poorer health outcomes in older community-dwelling patients with multimorbidity: prospective cohort study assessing the accuracy of different multimorbidity definitions.

PURPOSE: Multimorbidity is commonly defined and measured using condition counts. The UK National Institute for Health Care Excellence Guidelines for Multimorbidity suggest that a medication-orientated approach could be used to identify those in need of a multimorbidity approach to management. OBJECTIVES: To compare the accuracy of medication-based and diagnosis-based multimorbidity measures at higher cut-points to identify older community-dwelling patients who are at risk of poorer health outcomes. DESIGN: A secondary analysis of a prospective cohort study with a 2-year follow-up (2010-2012). SETTING: 15 general practices in Ireland. PARTICIPANTS: 904 older community-dwelling patients. EXPOSURE: Baseline multimorbidity measurements based on both medication classes count (MCC) and chronic disease count (CDC). OUTCOMES: Mortality, self-reported health related quality of life, mental health and physical functioning at follow-up. ANALYSIS: Sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) adjusting for clustering by practice for each outcome using both definitions. RESULTS: Of the 904 baseline participants, 53 died during follow-up and 673 patients completed the follow-up questionnaire. At baseline, 223 patients had 3 or more chronic conditions and 89 patients were prescribed 10 or more medication classes. Sensitivity was low for both MCC and CDC measures for all outcomes. For specificity, MCC was better for all outcomes with estimates varying from 88.8% (95% CI 85.2% to 91.6%) for physical functioning to 90.9% (95% CI 86.2% to 94.1%) for self-reported health-related quality of life. There were no differences between MCC and CDC in terms of PPV and NPV for any outcomes. CONCLUSIONS: Neither measure demonstrated high sensitivity. However, MCC using a definition of 10 or more regular medication classes to define multimorbidity had higher specificity for predicting poorer health outcomes. While having limitations, this definition could be used for proactive identification of patients who may benefit from targeted clinical care.

Examining the association of body mass index and the depth of epidural space, radiation dose exposure and fluoroscopic screening time during transforaminal nerve block injection: a retrospective cohort study.

OBJECTIVE: The primary objective of this study was to examine the association between body mass index (BMI) and the depth of tissue overlying the epidural space. Secondary objectives examined the association between BMI and (1) radiation dose exposure and (2) fluoroscopic screening time during transforaminal nerve block (TFNB) injections. METHODOLOGY: This is a retrospective cohort study including patients aged ≥ 16 years who underwent unilateral single-level TFNB in a single centre over a 28-month period, by a single spinal orthopaedic surgeon. Demographic data, BMI (kg/m2), fluoroscopic screening time (seconds) and radiation dose exposure (centi-gray per square centimetre squared (cGy-cm2)) were recorded. Exposure of interest: BMI. PRIMARY OUTCOME: depth of epidural space. SECONDARY OUTCOMES: (1) radiation dose exposure, (2) fluoroscopic screening time. Descriptive statistics for study participants' demographics are presented. Spearman's rank (r) coefficient and linear regression analysis was performed examining the association between BMI and the outcome measures. RESULTS: A total of 362 patients met inclusion criteria; n = 45 patients were excluded due to incomplete data, final analysis included 317 patients. Mean age was 62.6 years (IQR 53-74). Male:female ratio was 37.9% (n = 120):62.1%(n = 197). Mean BMI was 26.9 kg/m2 (IQR 24.4-28.9 kg/m2). Following adjustment for age, gender and spinal comorbidities there is a statistically significant association between BMI and the depth of tissue overlying the epidural space (adjusted coefficient 2.41, (95% CI (2.14, 2.68), p < 0.001)). We also found a significant association between BMI and both secondary outcomes, radiation dose exposure (adjusted coefficient 1.45, (95% CI (0.84, 2.06), p < 0.001)) and fluoroscopic screening time (adjusted coefficient 0.11, (95% CI (0.02, 0.20), p = 0.02)). CONCLUSION: This study has demonstrated a significant association between increasing BMI and increased depth of the epidural space. Furthermore, significant associations between increasing BMI, radiation dose exposure and fluoroscopy screening time have been identified. BMI may represent a modifiable risk factor with a view to decreasing patient exposure to medical ionised radiation.

Measuring medication adherence in older community-dwelling patients with multimorbidity.

PURPOSE: Older people with several chronic conditions require multiple drugs from different classes to be adequately treated. This study aims to: (i) measure medication adherence across multiple conditions and therapeutic drug groups in older community-dwelling patients, and (ii) examine the effect of multimorbidity on adherence. METHODS: This is a retrospective cohort study of medication adherence in 855 community-dwelling patients aged ≥ 70 years from 15 practices in Ireland using the Health Service Executive Primary Care Reimbursement Service (HSE-PCRS) pharmacy claims database. Multimorbidity was measured using the RxRisk-V and by the number of different drug classes. The RxRisk-V algorithm classifies prescription drug fills into 45 chronic disease classes for older populations based on the WHO Anatomical Therapeutic Chemical classification system. Adherence to medications was assessed by: (i) calculating the average medication possession ratio (MPR) per patient and (ii) an MPR< 80%. RESULTS: The overall median MPR for the cohort was 0.83 (IQR 0.69, 0.91). The conditions with the highest MPRs were hypothyroidism (mean MPR = 0.88, SD = 0.20) and type 2 diabetes (mean MPR = 0.83, SD = 0.19), followed by heart disease. On average, 20-40% of patients were non-adherent (MPR < 80%) across all conditions. There was an inverted U-shaped relationship between the mean MPR and number of morbidities and drug classes. Adherence varied per patients' morbidity burden, with higher adherence for certain combinations of chronic conditions. CONCLUSION: In total, 31% of older patients with multimorbidity were non-adherent to their medication but adherence levels varied across treatment categories and chronic conditions.

Supporting prescribing in older people with multimorbidity and significant polypharmacy in primary care (SPPiRE): a cluster randomised controlled trial protocol and pilot.

BACKGROUND: Multimorbidity, defined as the presence of at least two chronic conditions, becomes increasingly common in older people and is associated with poorer health outcomes and significant polypharmacy. The National Institute for Clinical Excellence (NICE) recently published a multimorbidity guideline that advises providing an individualised medication review for all people prescribed 15 or more repeat medicines. This study incorporates this guideline and aims to assess the effectiveness of a complex intervention designed to support general practitioners (GPs) to reduce potentially inappropriate prescribing and consider deprescribing in older people with multimorbidity and significant polypharmacy in Irish primary care. METHODS: This study is a cluster randomised controlled trial, involving 30 general practices and 450 patients throughout Ireland. Practices will be eligible to participate if they have at least 300 patients aged 65 years and over on their patient panel and if they use either one of the two predominant practice management software systems in use in Ireland. Using a software patient finder tool, practices will identify and recruit patients aged 65 years and over, who are prescribed at least 15 repeat medicines. Once baseline data collection is complete, practices will be randomised using minimisation by an independent third party to either intervention or control. Given the nature of the intervention, it is not possible to blind participants or study personnel. GPs in intervention practices will receive login details to a website where they will access training videos and a template for conducting an individualised structured medication review, which they will undertake with each of their included patients. Control practices will deliver usual care over the 6-month study period. Primary outcome measures pertain to the individual patient level and are the proportion of patients with any PIP and the number of repeat medicines. DISCUSSION: Disease-specific approaches in multimorbidity may be inappropriate and result in fragmented and poorly co-ordinated care. This pragmatic study is evaluating a complex intervention that is relevant across multiple conditions and addresses potential concerns around medicines safety in this vulnerable group of patients. The potential for system-wide implementation will be explored with a parallel mixed methods process evaluation. TRIAL REGISTRATION: ISRCTN: 12752680 , Registered 20 October 2016.