Structured medication reviews for adults with multimorbidity and polypharmacy in primary care: a systematic review protocol.

INTRODUCTION: Polypharmacy is common among individuals with multimorbidity, often leading to inappropriate medication use and is associated with an increased risk of frailty, hospitalisation and mortality. Structured medication reviews (SMRs) have emerged as a promising method for optimising medication use. However, research examining their efficacy is limited. This review aims to evaluate the impact of SMRs on improving outcomes for adults with multimorbidity and polypharmacy in primary care settings. Additionally, this review seeks to identify prevailing patterns and trends in the mode of delivery of SMRs. METHODS AND ANALYSIS: A systematic review will be conducted using Ovid MEDLINE, Ovid EMBASE, Web of Science and CINAHL (1997-present). Primary outcomes will include medication-related measures such as dose, frequency and dosage form. Secondary outcomes under investigation will include physical, mental, functional and health service outcomes, as reported. Two independent reviewers will conduct the screening and data extraction, resolving disagreements through discussion. Once eligible studies are identified, the extracted data will be summarised in tabular format. The risk of bias in the articles will be assessed using either the Cochrane Risk of Bias 2 tool or the Newcastle-Ottawa scale, depending on the design of the studies retrieved. Subgroup analysis will be performed using demographic variables and modes of delivery where the data supports. If appropriate, a meta-analysis of the data extracted will be conducted to determine the impact of the SMRs on reported outcomes. If a meta-analysis is not possible due to heterogeneity, a narrative synthesis approach will be adopted. ETHICS AND DISSEMINATION: This proposed review is exempt from ethical approval as it aims to collate and summarise peer-reviewed, published evidence. This protocol and the subsequent review will be disseminated in peer-reviewed journals, conferences and patient-led lay summaries. PROSPERO REGISTRATION NUMBER: CRD42023454965.

Medication management in Minority, Asian and Black ethnic older people in the United Kingdom: A mixed-studies systematic review.

WHAT IS NEW AND OBJECTIVES: Older people from ethnic minorities experience the intersectionality of age and ethnicity in relation to complex medication management and polypharmacy. Minority ethnic groups in the United Kingdom are at risk of poor medication management because factors such as cultural beliefs, language barriers, lack of knowledge of how the healthcare system works may affect their ability to safely manage their medications. The aim of this systematic review was to review the literature focussing on medication management in the older population amongst ethnic minority communities in United Kingdom. METHODS: The review was conducted and reported according to methods in the Cochrane Handbook and in the PRISMA 2020 statement using databases such as EMBASE, ASSIA, MEDLINE, PsychINFO and others. Studies conducted in the United Kingdom on individuals over 60 years of age and from a minority ethnic background were included. A thematic analysis was used to synthesize the results. RESULTS AND DISCUSSION: Nine studies (eight from initial searches, one from a search update in 2021) met the inclusion criteria. Three main themes were identified: misbeliefs around medications, poor health literacy, communication and education as possible intervention to improve medication management. Misbeliefs around long-term illnesses exert a negative impact on medication management. Poor health literacy around medications influences patients' adherence to treatments. Poor communication is perceived as barrier to successful medication management. Despite extensive searching, the team identified a limited number of studies and a lack of intersectional studies focussing on minority ethnic groups and the older population. WHAT IS NEW AND CONCLUSION: Our findings suggest tailored education as a possible intervention to improve medication management amongst these minority groups. Future research should look at recruiting participants from specific ethnic groups and from rural as well as urban areas to explore how medication management operates in different areas of the United Kingdom.

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.

Benzodiazepines for catatonia in people with schizophrenia or other serious mental illnesses.

BACKGROUND: Catatonia is a debilitating disorder of movement and volition associated with schizophrenia and some other mental illnesses. People with catatonia are more likely to require hospitalisation and highly supervised care than those without the disorder. They also have an increased risk of secondary complications such as pneumonia, malnutrition and dehydration. The mainstay of treatment has been drug therapies and electroconvulsive therapy. OBJECTIVES: To compare the effects of benzodiazepines with other drugs, placebo or electroconvulsive therapy for catatonia in people with schizophrenia or other similar serious mental illnesses (SMIs). SEARCH METHODS: We updated our previous search (28 February 2007) by searching the Cochrane Schizophrenia Group's Study-Based Register of Trials (9 November 2016; 6 February 2019). This register is compiled by systematic searches of major resources (including CENTRAL, MEDLINE, Embase, AMED, BIOSIS, CINAHL, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings, with no language, date, document type, or publication status limitations for inclusion of records into the register. We also manually searched reference lists from studies selected by the search. SELECTION CRITERIA: All controlled clinical trials that randomised people who have schizophrenia or other similar SMI and experiencing catatonia to receive benzodiazepines or another relevant treatment. We included studies that met our inclusion criteria and reported usable data. We excluded those not meeting our inclusion criteria or those not reporting usable data. We contacted authors when we required further information; and if we received no response, we put those studies aside as 'awaiting assessment'. DATA COLLECTION AND ANALYSIS: Review authors extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis using a fixed-effect model. We completed a 'Risk of bias' assessment for the included study and generated a 'Summary of findings' table using GRADE. MAIN RESULTS: The searches found 130 citations, from which we could identify 22 possibly relevant studies. From these, we could only include one study. This study had a relatively small sample size of 17 participants who received lorazepam or oxazepam and were drug free for one week before the trial started. The only usable data reported by this study were clinically important change in symptoms of catatonia measured as 50% improvement on the Visual Analogue Scale (VAS). There was no difference in the numbers of participants showing a clinically important change in their catatonic symptoms (RR 0.95, 95% CI 0.42 to 2.16; participants = 17; studies = 1; very low quality evidence).No data were reported for other important outcomes of hospital stay, clinically important change in satisfaction with care, global state, adverse effects or general functioningWe did find a few studies meeting our inclusion criteria but they reported no usable data. We had to exclude these. Although poorly reported, these studies do illustrate that relevant studies have been undertaken - they are not impossible to design and conduct. AUTHORS' CONCLUSIONS: Analysis of the results from this review, which was a head-to-head comparison of two benzodiazepine monotherapies, does not show a clear difference in effect. No data were available for benzodiazepines compared to placebo or standard care. The lack of usable data and very low quality of data available makes it impossible to draw firm conclusions and further studies with a high-quality methodology and reporting are required in order to determine more definitively the outcomes associated with benzodiazepine use in the clinical management of catatonia in persons with schizophrenia and other SMI.

Characterisation of aggregates of cyclodextrin-drug complexes using Taylor Dispersion Analysis.

There is a need to understand the nature of aggregation of cyclodextrins (CDs) with guest molecules in increasingly complex formulation systems. To this end an innovative application of Taylor dispersion analysis (TDA) and comparison with dynamic light scattering (DLS) have been carried out to probe the nature of ICT01-2588 (ICT-2588), a novel tumor-targeted vascular disrupting agent, in solvents including a potential buffered formulation containing 10% hydroxypropyl-ß-cyclodextrin. The two hydrodynamic sizing techniques give measurement responses are that fundamentally different for aggregated solutions containing the target molecule, and the benefits of using TDA in conjunction with DLS are that systems are characterised through measurement of both mass- and z-average hydrodynamic radii. Whereas DLS measurements primarily resolve the large aggregates of ICT01-2588 in its formulation medium, methodology for TDA is described to determine the size and notably to quantify the proportion of monomers in the presence of large aggregates, and at the same time measure the formulation viscosity. Interestingly TDA and DLS have also distinguished between aggregate profiles formed using HP-ß-CD samples from different suppliers. The approach is expected to be widely applicable to this important class of drug formulations where drug solubility is enhanced by cyclodextrin and other excipients.