Towards an understanding of the burdens of medication management affecting older people: the MEMORABLE realist synthesis

Background More older people are living in the community with multiple diagnoses and medications. Managing multiple medications produces issues of unrivalled complexity for those involved. Despite increasing literature on the subject, gaps remain in understanding how, why and for whom complex medication management works, and therefore how best to improve practice and outcomes. MEMORABLE, MEdication Management in Older people: Realist Approaches Based on Literature and Evaluation, aimed to address these gaps. Methods MEMORABLE used realism to understand causal paths within medication management. Informed by RAMESES (Realist And Meta-narrative Evidence Synthesis: and Evolving Standards) guidelines, MEMORABLE involved three overlapping work packages: 1) Realist Review of the literature (24 articles on medication management exploring causality); 2) Realist Evaluation (50 realist-informed interviews with older people, family carers and health and care practitioners, explaining their experiences); and 3) data synthesis and theorising from 1) and 2). Results Medication management was viewed from the perspective of ‘implementation’ and structured into five stages: identifying a problem (Stage 1), getting a diagnosis and/or medications (Stage 2), starting, changing or stopping medications (Stage 3), continuing to take medications (Stage 4), and reviewing/reconciling medications (Stage 5). Three individual stages (1, 3 and 4) are conducted by the older person sometimes with family carer support when they balance routines, coping and risk. Stages 2 and 5 are interpersonal where the older person works with a practitioner-prescriber-reviewer, perhaps with carer involvement. Applying Normalisation Process Theory, four steps were identified within each stage: 1) sense making: information, clarification; 2) action: shared-decision-making; 3) reflection/monitoring; and 4) enduring relationships, based on collaboration and mutual trust. In a detailed analysis of Stage 5: Reviewing/reconciling medications, adopting the lens of ‘burden’, MEMORABLE identified five burdens amenable to mitigation: ambiguity, concealment, unfamiliarity, fragmentation and exclusion. Two initial improvement propositions were identified for further research: a risk screening tool and individualised information. Conclusions Older people and family carers often find medication management challenging and burdensome particularly for complex regimens. Practitioners need to be aware of this potential challenge, and work with older people and their carers to minimise the burden associated with medication management. Trial registration PROSPERO 2016:CRD42016043506

Medication management in older people: the MEMORABLE realist synthesis

Background The number and proportion of older people in the UK are increasing, as are multimorbidity (potentially reducing quality of life) and polypharmacy (increasing the risk of adverse drug events). Together, these complex factors are challenging for older people, informal carers, and health and care practitioners. Objectives MEMORABLE (MEdication Management in Older people: Realist Approaches Based on Literature and Evaluation) aimed to understand how medication management works and propose improvements. Design A realist approach informed three work packages, combining a realist review of secondary data with a realist evaluation of primary interview data, in a theory-driven, causal analysis. Setting The setting was in the community. Participants Older people, informal carers, and health and care practitioners. Interventions Studies relating to medication management and to reviewing and reconciling medications; and realist-informed interviews. Main outcome measures Not applicable. Data sources MEDLINE, CINAHL (Cumulative Index of Nursing and Allied Health Literature) and EMBASE were searched (all searched from January 2009 to July 2017; searched on 1 August 2017). Supplementary articles were identified by the Research Team. Data were also obtained through interviews. Review methods Searches of electronic databases were supplemented by citation-tracking for explanatory contributions, as well as accessing topic-relevant grey literature. Following RAMESES (Realist And Meta-narrative Evidence Syntheses: Evolving Standards) guidelines, articles were screened and iteratively analysed with interview data, to generate theory-informed (normalisation process theory) explanations. Results Developing a framework to explain medication management as a complex intervention across five stages: identifying problem (Stage 1), starting, changing or stopping medications (Stage 3) and continuing to take medications (Stage 4), where older people, sometimes with informal carers, make individual decisions and follow routines that fit medication management into their day-to-day lives, engendering a sense of control. In getting diagnosis and/or medications (Stage 2) and reviewing/reconciling medications (Stage 5), older people and practitioners share decision-making in time-limited contacts: involving four steps – sense-making, relationships, action and reflection/monitoring (normalisation process theory); and conceptualising burden – through a detailed analysis of Stage 5, generating a theoretical framework and identifying five burden types amendable to mitigation: ambiguity, concealment, unfamiliarity, fragmentation and exclusion. Proposing interventions: risk identification – a simple way of identifying older people and informal carers who are not coping, at risk and who need appropriate help and support; and individualised information – a short, personalised record and reference point, co-produced and shared by older people, informal carers and practitioners that addresses the experience of living with multimorbidities and polypharmacy. Limitations Few studies directly address the complexity of medication management as a process and how it works. Limitations included, having identified the overall complexity, the need to focus the analysis on reviewing/reconciling medications (Stage 5), the exclusion of non-English-language literature, the focus on non-institutionalised populations and the broad definition of older people. Conclusions MEMORABLE explored the complexity of medication management. It highlighted the way interpersonal stages in the medication management process, notably reviewing/reconciling medications, contribute to the mitigation of burdens that are often hidden. Future work Co-produced studies to scope and trial the two proposed interventions; studies to extend the detailed understanding of medication management, linked to burden mitigation; and a study to clarify the medication management outcomes wanted by older people, informal carers and practitioners. Study registration This study is registered as PROSPERO CRD42016043506

Rapid realist review of the role of community pharmacy in the public health response to COVID-19

INTRODUCTION: Community pharmacists and their teams have remained accessible to the public providing essential services despite immense pressures during the COVID-19 pandemic. They have successfully expanded the influenza vaccination programme and are now supporting the delivery of the COVID-19 vaccination roll-out. AIM: This rapid realist review aims to understand how community pharmacy can most effectively deliver essential and advanced services, with a focus on vaccination, during the pandemic and in the future. METHOD: An embryonic programme theory was generated using four diverse and complementary documents along with the expertise of the project team. Academic databases, preprint services and grey literature were searched and screened for documents meeting our inclusion criteria. The data were extracted from 103 documents to develop and refine a programme theory using a realist logic of analysis. Our analysis generated 13 context-mechanism-outcome configurations explaining when, why and how community pharmacy can support public health vaccination campaigns, maintain essential services during pandemics and capitalise on opportunities for expanded, sustainable public health service roles. The views of stakeholders including pharmacy users, pharmacists, pharmacy teams and other healthcare professionals were sought throughout to refine the 13 explanatory configurations. RESULTS: The 13 context-mechanism-outcome configurations are organised according to decision makers, community pharmacy teams and community pharmacy users as key actors. Review findings include: supporting a clear role for community pharmacies in public health; clarifying pharmacists' legal and professional liabilities; involving pharmacy teams in service specification design; providing suitable guidance, adequate compensation and resources; and leveraging accessible, convenient locations of community pharmacy. DISCUSSION: Community pharmacy has been able to offer key services during the pandemic. Decision makers must endorse, articulate and support a clear public health role for community pharmacy. We provide key recommendations for decision makers to optimise such a role during these unprecedented times and in the future

Barriers to Exercise in Younger and Older Non-Exercising Adult Women: A Cross Sectional Study in London, United Kingdom

A survey of 100 women in the south of London, United Kingdom (UK) compared exercise barrier intensities between non-exercising younger (20–27 years) and older (28–35 years) adult women; and examined childcare duties as perceived barriers to exercise. Perceived barriers to exercise were examined using an Exercise Benefits/Barriers Scale (EBBS) comprising four subscales (exercise milieu; time expenditure; physical exertion; family discouragement). Participants’ number of children was also noted. Non-exercising older women reported significantly higher total exercise barriers, as well as across three barrier subscales: exercise milieu, time expenditure, and family discouragement. For both age groups, significant correlation existed between number of children and women’s total exercise barrier scores. Number of children explained ≈25% and ≈30% of the variance of younger and older women’s total barrier scores respectively. For both women groups, the strongest correlation between exercise barrier and number of children was for the time expenditure subscale. Broad grouping of 20–35 year old non-exercising women does not reflect a homogenous sample. Age categories employing narrower age brackets are recommended. Issues surrounding family responsibilities e.g. childcare duties may be shared between these groups and require further research and policy attention

Internet-based medical education: a realist review of what works, for whom and in what circumstances

http://creativecommons.org/licenses/by/2.0

Challenges, solutions and research priorities for sustainable rangelands

Australia’s rangeland communities, industries, and environment are under increasing pressures from anthropogenic activities and global changes more broadly. We conducted a horizon scan to identify and prioritise key challenges facing Australian rangelands and their communities, and outline possible avenues to address these challenges, with a particular focus on research priorities. We surveyed participants of the Australian Rangeland Society 20th Biennial Conference, held in Canberra in September 2019, before the conference and in interactive workshops during the conference, in order to identify key challenges, potential solutions, and research priorities. The feedback was broadly grouped into six themes associated with supporting local communities, managing natural capital, climate variability and change, traditional knowledge, governance, and research and development. Each theme had several sub-themes and potential solutions to ensure positive, long-term outcomes for the rangelands. The survey responses made it clear that supporting ‘resilient and sustainable rangelands that provide cultural, societal, environmental and economic outcomes simultaneously’ is of great value to stakeholders. The synthesis of survey responses combined with expert knowledge highlighted that sustaining local communities in the long term will require that the inherent social, cultural and natural capital of rangelands are managed sustainably, particularly in light of current and projected variability in climate. Establishment of guidelines and approaches to address these challenges will benefit from: (i) an increased recognition of the value and contributions of traditional knowledge and practices; (ii) development of better governance that is guided by and benefits local stakeholders; and (iii) more funding to conduct and implement strong research and development activities, with research focused on addressing critical knowledge gaps as identified by the local stakeholders. This requires strong governance with legislation and policies that work for the rangelands. We provide a framework that indicates the key knowledge gaps and how innovations may be implemented and scaled out, up and deep to achieve the resilience of Australia’s rangelands. The same principles could be adapted to address challenges in rangelands on other continents, with similar beneficial outcomes

A mixed-methods feasibility study of a new digital health support package for people after stroke : The Recovery-focused Community support to Avoid readmissions and improve Participation after Stroke (ReCAPS) intervention

Background Evidence for digital health programmes to support people living with stroke is growing. We assessed the feasibility of a protocol and procedures for the Recovery-focused Community support to Avoid readmissions and improve Participation after Stroke (ReCAPS) trial. Methods We conducted a mixed-method feasibility study. Participants with acute stroke were recruited from three hospitals (Melbourne, Australia). Eligibility: Adults with stroke discharged from hospital to home within 10 days, modified Rankin Score 0–4 and prior use of Short Message System (SMS)/email. While in hospital, recruited participants contributed to structured person-centred goal setting and completed baseline surveys including self-management skills and health-related quality of life. Participants were randomised 7–14 days after discharge via REDCap® (1:1 allocation). Following randomisation, the intervention group received a 12-week programme of personalised electronic support messages (average 66 messages sent by SMS or email) aligned with their goals. The control group received six electronic administrative messages. Feasibility outcomes included the following: number of patients screened and recruited, study retainment, completion of outcome measures and acceptability of the ReCAPS intervention and trial procedures (e.g. participant satisfaction survey, clinician interviews). Protocol fidelity outcomes included number of goals developed (and quality), electronic messages delivered, stop messages received and engagement with messages. We undertook inductive thematic analysis of interview/open-text survey data and descriptive analysis of closed survey questions. Results Between November 2018 and October 2019, 312 patients were screened; 37/105 (35%) eligible patients provided consent (mean age 61 years; 32% female); 33 were randomised (17 to intervention). Overall, 29 (88%) participants completed the12-week outcome assessments with 12 (41%) completed assessments in the allocated timeframe and 16 also completing the satisfaction survey (intervention=10). Overall, trial participants felt that the study was worthwhile and most would recommend it to others. Six clinicians participated in one of three focus group interviews; while they reported that the trial and the process of goal setting were acceptable, they raised concerns regarding the additional time required to personalise goals. Conclusion The study protocol and procedures were feasible with acceptable retention of participants. Consent and goal personalisation procedures should be centralised for the phase III trial to reduce the burden on hospital clinicians. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12618001468213 (date 31/08/2018); Universal Trial Number: U1111-1206-723

A scoping study of interventions to increase the uptake of physical activity (PA) amongst individuals with mild-to-moderate depression (MMD)

Background - Depression is the largest contributor to disease burden globally. The evidence favouring physical activity as a treatment for mild-to-moderate depression is extensive and relatively uncontested. It is unclear, however, how to increase an uptake of physical activity amongst individuals experiencing mild-to-moderate depression. This leaves professionals with no guidance on how to help people experiencing mild-to-moderate depression to take up physical activity. The purpose of this study was to scope the evidence on interventions to increase the uptake of physical activity amongst individuals experiencing mild-to-moderate depression, and to develop a model of the mechanisms by which they are hypothesised to work. Methods - A scoping study was designed to include a review of primary studies, grey literature and six consultation exercises; two with individuals with experience of depression, two pre-project consultations with physical activity, mental health and literature review experts, one with public health experts, and one with community engagement experts. Results - Ten papers met the inclusion criteria and were included in the review. Consultation exercises provided insights into the mechanisms of an uptake of physical activity amongst individuals experiencing mild-to-moderate depression; evidence concerning those mechanisms is (a) fragmented in terms of design and purpose; (b) of varied quality; (c) rarely explicit about the mechanisms through which the interventions are thought to work. Physical, environmental and social factors that may represent mediating variables in the uptake of physical activity amongst people experiencing mild-to-moderate depression are largely absent from studies. Conclusions - An explanatory model was developed. This represents mild-to-moderate depression as interfering with (a) the motivation to take part in physical activity and (b) the volition that it is required to take part in physical activity. Therefore, both motivational and volitional elements are important in any intervention to increase physical activity in people with mild-to-moderate depression. Furthermore, mild-to-moderate depression-specific factors need to be tackled in any physical activity initiative, via psychological treatments such as Cognitive Behavioural Therapy. We argu

Targeting breast cancer stem cells

The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self‐renewing CSC population that is also capable of differentiating into non‐self‐renewing cell populations that constitute the bulk of the tumor. Although, the CSC hypothesis does not directly address the cell of origin of cancer, it is postulated that tissue‐resident stem or progenitor cells are the most common targets of transformation. Clinically, CSCs are predicted to mediate tumor recurrence after chemo‐ and radiation‐therapy due to the relative inability of these modalities to effectively target CSCs. If this is the case, then CSC must be efficiently targeted to achieve a true cure. Similarities between normal and malignant stem cells, at the levels of cell‐surface proteins, molecular pathways, cell cycle quiescence, and microRNA signaling present challenges in developing CSC‐specific therapeutics. Approaches to targeting CSCs include the development of agents targeting known stem cell regulatory pathways as well as unbiased high‐throughput siRNA or small molecule screening. Based on studies of pathways present in normal stem cells, recent work has identified potential “Achilles heals” of CSC, whereas unbiased screening provides opportunities to identify new pathways utilized by CSC as well as develop potential therapeutic agents. Here, we review both approaches and their potential to effectively target breast CSC.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135704/1/mol2201045404.pd

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation