Management of antipsychotics in primary care: Insights from healthcare professionals and policy makers in the United Kingdom.

INTRODUCTION: Antipsychotic medication is increasingly prescribed to patients with serious mental illness. Patients with serious mental illness often have cardiovascular and metabolic comorbidities, and antipsychotics independently increase the risk of cardiometabolic disease. Despite this, many patients prescribed antipsychotics are discharged to primary care without planned psychiatric review. We explore perceptions of healthcare professionals and managers/directors of policy regarding reasons for increasing prevalence and management of antipsychotics in primary care. METHODS: Qualitative study using semi-structured interviews with 11 general practitioners (GPs), 8 psychiatrists, and 11 managers/directors of policy in the United Kingdom. Data was analysed using thematic analysis. RESULTS: Respondents reported competency gaps that impaired ability to manage patients prescribed antipsychotic medications, arising from inadequate postgraduate training and professional development. GPs lacked confidence to manage antipsychotic medications alone; psychiatrists lacked skills to address cardiometabolic risks and did not perceive this as their role. Communication barriers, lack of integrated care records, limited psychology provision, lowered expectation towards patients with serious mental illness by professionals, and pressure to discharge from hospital resulted in patients in primary care becoming 'trapped' on antipsychotics, inhibiting opportunities to deprescribe. Organisational and contractual barriers between services exacerbate this risk, with socioeconomic deprivation and lack of access to non-pharmacological interventions driving overprescribing. Professionals voiced fears of censure if a catastrophic event occurred after stopping an antipsychotic. Facilitators to overcome these barriers were suggested. CONCLUSIONS: People prescribed antipsychotics experience a fragmented health system and suboptimal care. Several interventions could be taken to improve care for this population, but inadequate availability of non-pharmacological interventions and socioeconomic factors increasing mental distress need policy change to improve outcomes. The role of professionals' fear of medicolegal or regulatory censure inhibiting antipsychotic deprescribing was a new finding in this study.

An observational analysis of frailty in combination with loneliness or social isolation and their association with socioeconomic deprivation, hospitalisation and mortality among UK Biobank participants.

Frailty, social isolation, and loneliness have individually been associated with adverse health outcomes. This study examines how frailty in combination with loneliness or social isolation is associated with socioeconomic deprivation and with all-cause mortality and hospitalisation rate in a middle-aged and older population. Baseline data from 461,047 UK Biobank participants (aged 37-73) were used to assess frailty (frailty phenotype), social isolation, and loneliness. Weibull models assessed the association between frailty in combination with loneliness or social isolation and all-cause mortality adjusted for age/sex/smoking/alcohol/socioeconomic-status and number of long-term conditions. Negative binomial regression models assessed hospitalisation rate. Frailty prevalence was 3.38%, loneliness 4.75% and social isolation 9.04%. Frailty was present across all ages and increased with age. Loneliness and social isolation were more common in younger participants compared to older. Co-occurrence of frailty and loneliness or social isolation was most common in participants with high socioeconomic deprivation. Frailty was associated with increased mortality and hospitalisation regardless of social isolation/loneliness. Hazard ratios for mortality were 2.47 (2.27-2.69) with social isolation and 2.17 (2.05-2.29) without social isolation, 2.14 (1.92-2.38) with loneliness and 2.16 (2.05-2.27) without loneliness. Loneliness and social isolation were associated with mortality and hospitalisation in robust participants, but this was attenuated in the context of frailty. Frailty and loneliness/social isolation affect individuals across a wide age spectrum and disproportionately co-occur in areas of high deprivation. All were associated with adverse outcomes, but the association between loneliness and social isolation and adverse outcomes was attenuated in the context of frailty. Future interventions should target people living with frailty or loneliness/social isolation, regardless of age.

Epidemiology of multimorbidity in low-income countries of sub-Saharan Africa: Findings from four population cohorts.

We investigated prevalence and demographic characteristics of adults living with multimorbidity (≥2 long-term conditions) in three low-income countries of sub-Saharan Africa, using secondary population-level data from four cohorts; Malawi (urban & rural), The Gambia (rural) and Uganda (rural). Information on; measured hypertension, diabetes and obesity was available in all cohorts; measured hypercholesterolaemia and HIV and self-reported asthma was available in two cohorts and clinically diagnosed epilepsy in one cohort. Analyses included calculation of age standardised multimorbidity prevalence and the cross-sectional associations of multimorbidity and demographic/lifestyle factors using regression modelling. Median participant age was 29 (Inter quartile range-IQR 22-38), 34 (IQR25-48), 32 (IQR 22-53) and 37 (IQR 26-51) in urban Malawi, rural Malawi, The Gambia, and Uganda, respectively. Age standardised multimorbidity prevalence was higher in urban and rural Malawi (22.5%;95% Confidence intervals-CI 21.6-23.4%) and 11.7%; 95%CI 11.1-12.3, respectively) than in The Gambia (2.9%; 95%CI 2.5-3.4%) and Uganda (8.2%; 95%CI 7.5-9%) cohorts. In multivariate models, females were at greater risk of multimorbidity than males in Malawi (Incidence rate ratio-IRR 1.97, 95% CI 1.79-2.16 urban and IRR 2.10; 95%CI 1.86-2.37 rural) and Uganda (IRR- 1.60, 95% CI 1.32-1.95), with no evidence of difference between the sexes in The Gambia (IRR 1.16, 95% CI 0.86-1.55). There was strong evidence of greater multimorbidity risk with increasing age in all populations (p-value <0.001). Higher educational attainment was associated with increased multimorbidity risk in Malawi (IRR 1.78; 95% CI 1.60-1.98 urban and IRR 2.37; 95% CI 1.74-3.23 rural) and Uganda (IRR 2.40, 95% CI 1.76-3.26), but not in The Gambia (IRR 1.48; 95% CI 0.56-3.87). Further research is needed to study multimorbidity epidemiology in sub-Saharan Africa with an emphasis on robust population-level data collection for a wide variety of long-term conditions and ensuring proportionate representation from men and women, and urban and rural areas.

Multimorbidity and Blood Pressure Control in Patients Attending Primary Care in Canada.

BACKGROUND: There has been conflicting evidence on the association between multimorbidity and blood pressure (BP) control. This study aimed to investigate this associations in people with hypertension attending primary care in Canada, and to assess whether individual long-term conditions are associated with BP control. METHODS: This was a cross-sectional study in people with hypertension attending primary care in Toronto between January 1, 2017 and December 31, 2019. Uncontrolled BP was defined as systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. A list of 11 a priori selected chronic conditions was used to define multimorbidity. Multimorbidity was defined as having ≥1 long-term condition in addition to hypertension. Logistic regression models were used to estimate the association between multimorbidity (or individual long-term conditions) with uncontrolled BP. RESULTS: A total of 67 385 patients with hypertension were included. They had a mean age of 70, 53.1% were female, 80.6% had multimorbidity, and 35.7% had uncontrolled BP. Patients with multimorbidity had lower odds of uncontrolled BP than those without multimorbidity (adjusted OR = 0.72, 95% CI 0.68-0.76). Among the long-term conditions, diabetes (aOR = 0.73, 95%CI 0.70-0.77), heart failure (aOR = 0.81, 95%CI 0.73-0.91), ischemic heart disease (aOR = 0.74, 95%CI 0.69-0.79), schizophrenia (aOR = 0.79, 95%CI 0.65-0.97), depression/anxiety (aOR = 0.91, 95%CI 0.86-0.95), dementia (aOR = 0.87, 95%CI 0.80-0.95), and osteoarthritis (aOR = 0.89, 95%CI 0.85-0.93) were associated with a lower likelihood of uncontrolled BP. CONCLUSION: We found that multimorbidity was associated with better BP control. Several conditions were associated with better control, including diabetes, heart failure, ischemic heart disease, schizophrenia, depression/anxiety, dementia, and osteoarthritis.

Factors associated with COVID-19 vaccine uptake among people with type 2 diabetes in Kenya and Tanzania: a mixed-methods study.

BACKGROUND: People with type 2 diabetes (T2D) are at increased risk of poor outcomes from COVID-19. Vaccination can improve outcomes, but vaccine hesitancy remains a major challenge. We examined factors influencing COVID-19 vaccine uptake among people with T2D in two sub-Saharan Africa countries that adopted different national approaches to combat COVID-19, Kenya and Tanzania. METHODS: A mixed-methods study was conducted in February-March 2022, involving a survey of 1000 adults with T2D (500 Kenya; 500 Tanzania) and 51 in-depth interviews (21 Kenya; 30 Tanzania). Determinants of COVID-19 vaccine uptake were identified using a multivariate logistic regression model, while thematic content analysis explored barriers and facilitators. RESULTS: COVID-19 vaccine uptake was lower in Tanzania (26%) than in Kenya (75%), which may reflect an initial political hesitancy about vaccines in Tanzania. People with college/university education were four times more likely to be vaccinated than those with no education (Kenya AOR=4.25 (95% CI 1.00 to 18.03), Tanzania AOR=4.07 (1.03 to 16.12)); and people with health insurance were almost twice as likely to be vaccinated than those without health insurance (Kenya AOR=1.70 (1.07 to 2.70), Tanzania AOR=1.81 (1.04 to 3.13)). Vaccine uptake was higher in older people in Kenya, and among those with more comorbidities and higher socioeconomic status in Tanzania. Interviewees reported that wanting protection from severe illness promoted vaccine uptake, while conflicting information, misinformation and fear of side-effects limited uptake. CONCLUSION: COVID-19 vaccine uptake among people with T2D was suboptimal, particularly in Tanzania, where initial political hesitancy had a negative impact. Policy-makers must develop strategies to reduce fear and misconceptions, especially among those who are less educated, uninsured and younger.

Social connection and mortality in UK Biobank: a prospective cohort analysis.

BACKGROUND: Components of social connection are associated with mortality, but research examining their independent and combined effects in the same dataset is lacking. This study aimed to examine the independent and combined associations between functional and structural components of social connection and mortality. METHODS: Analysis of 458,146 participants with full data from the UK Biobank cohort linked to mortality registers. Social connection was assessed using two functional (frequency of ability to confide in someone close and often feeling lonely) and three structural (frequency of friends/family visits, weekly group activities, and living alone) component measures. Cox proportional hazard models were used to examine the associations with all-cause and cardiovascular disease (CVD) mortality. RESULTS: Over a median of 12.6 years (IQR 11.9-13.3) follow-up, 33,135 (7.2%) participants died, including 5112 (1.1%) CVD deaths. All social connection measures were independently associated with both outcomes. Friends/family visit frequencies < monthly were associated with a higher risk of mortality indicating a threshold effect. There were interactions between living alone and friends/family visits and between living alone and weekly group activity. For example, compared with daily friends/family visits-not living alone, there was higher all-cause mortality for daily visits-living alone (HR 1.19 [95% CI 1.12-1.26]), for never having visits-not living alone (1.33 [1.22-1.46]), and for never having visits-living alone (1.77 [1.61-1.95]). Never having friends/family visits whilst living alone potentially counteracted benefits from other components as mortality risks were highest for those reporting both never having visits and living alone regardless of weekly group activity or functional components. When all measures were combined into overall functional and structural components, there was an interaction between components: compared with participants defined as not isolated by both components, those considered isolated by both components had higher CVD mortality (HR 1.63 [1.51-1.76]) than each component alone (functional isolation 1.17 [1.06-1.29]; structural isolation 1.27 [1.18-1.36]). CONCLUSIONS: This work suggests (1) a potential threshold effect for friends/family visits, (2) that those who live alone with additional concurrent markers of structural isolation may represent a high-risk population, (3) that beneficial associations for some types of social connection might not be felt when other types of social connection are absent, and (4) considering both functional and structural components of social connection may help to identify the most isolated in society.

Correlations between comorbidities in trials and the community: An individual-level participant data meta-analysis.

Background: People with comorbidities are under-represented in randomised controlled trials, and it is unknown whether patterns of comorbidity are similar in trials and the community. Methods: Individual-level participant data were obtained for 83 clinical trials (54,688 participants) for 16 index conditions from two trial repositories: Yale University Open Data Access (YODA) and the Centre for Global Clinical Research Data (Vivli). Community data (860,177 individuals) were extracted from the Secure Anonymised Information Linkage (SAIL) databank for the same index conditions. Comorbidities were defined using concomitant medications. For each index condition, we estimated correlations between comorbidities separately in trials and community data. For the six commonest comorbidities we estimated all pairwise correlations using Bayesian multivariate probit models, conditioning on age and sex. Correlation estimates from trials with the same index condition were combined into a single estimate. We then compared the trial and community estimates for each index condition. Results: Despite a higher prevalence of comorbidities in the community than in trials, the correlations between comorbidities were mostly similar in both settings. On comparing correlations between the community and trials, 21% of correlations were stronger in the community, 10% were stronger in the trials and 68% were similar in both. In the community, 5% of correlations were negative, 21% were null, 56% were weakly positive and 18% were strongly positive. Equivalent results for the trials were 11%, 33%, 45% and 10% respectively. Conclusions: Comorbidity correlations are generally similar in both the trials and community, providing some evidence for the reporting of comorbidity-specific findings from clinical trials.

Personalised lung cancer risk stratification and lung cancer screening: do general practice electronic medical records have a role?

BACKGROUND: In the United Kingdom (UK), cancer screening invitations are based on general practice (GP) registrations. We hypothesize that GP electronic medical records (EMR) can be utilised to calculate a lung cancer risk score with good accuracy/clinical utility. METHODS: The development cohort was Secure Anonymised Information Linkage-SAIL (2.3 million GP EMR) and the validation cohort was UK Biobank-UKB (N = 211,597 with GP-EMR availability). Fast backward method was applied for variable selection and area under the curve (AUC) evaluated discrimination. RESULTS: Age 55-75 were included (SAIL: N = 574,196; UKB: N = 137,918). Six-year lung cancer incidence was 1.1% (6430) in SAIL and 0.48% (656) in UKB. The final model included 17/56 variables in SAIL for the EMR-derived score: age, sex, socioeconomic status, smoking status, family history, body mass index (BMI), BMI:smoking interaction, alcohol misuse, chronic obstructive pulmonary disease, coronary heart disease, dementia, hypertension, painful condition, stroke, peripheral vascular disease and history of previous cancer and previous pneumonia. The GP-EMR-derived score had AUC of 80.4% in SAIL and 74.4% in UKB and outperformed ever-smoked criteria (currently the first step in UK lung cancer screening pilots). DISCUSSION: A GP-EMR-derived score may have a role in UK lung cancer screening by accurately targeting high-risk individuals without requiring patient contact.

EXPERTS II - How are patient and caregiver participation in health and social care shaped by experienced burden of treatment and social inequalities? Protocol for a qualitative synthesis.

Background: The workload health and social care service users and caregivers take on, and their capacity to do this work is important. It may play a key part in shaping the implementation of innovations in health service delivery and organisation; the utilisation and satisfaction with services; and the outcomes of care. Previous research has often focused on experiences of a narrow range of long-term conditions, and on factors that shape adherence to self-care regimes. Aims: With the aim of deriving policy and practice implications for service redesign, this evidence synthesis will extend our understanding of service user and caregiver workload and capacity by comparing how they are revealed in qualitative studies of lived experience of three kinds of illness trajectories: long-term conditions associated with significant disability (Parkinson's disease, schizophrenia); serious relapsing remitting disease (Inflammatory Bowel Disease, bipolar disorder); and rapidly progressing acute disease (brain cancer, early onset dementia). Methods: We will review and synthesise qualitative studies of lived experience of participation in health and social care that are shaped by interactions between experienced treatment burdens, social inequalities and illness trajectories. The review will involve:   1.  Construction of a theory-informed coding manual; systematic search of bibliographic databases to identify, screen and quality assess full-text papers.   2.  Analysis of papers using manual coding techniques, and text mining software; construction of taxonomies of service user and caregiver work and capacity.   3.  Designing a model of core components and identifying common factors across conditions, trajectories, and contexts.   4.  Work with practitioners, and a Patient and Public Involvement (PPI) group, to explore the validity of the models produced; to develop workload reduction strategies; and to consider person-centred service design. Dissemination: We will promote workload reduction models to support service users and caregivers and produce policy briefs and peer-reviewed publications for practitioners, policy-makers, and researchers.

Our experiences of illness are often complex. We may have to work hard too. We may need to monitor and record symptoms: take up different diets and physical activity; use different drugs and medical devices; develop expertise in using websites and information technology; coordinate input from health and care services; sometimes we have to work out how to pay for the services we need. How we get through this work is affected by our capacity to do it, and that is shaped by personal and wider resources, we can draw on. All of this is also affected by the services that are available to us, and by the ways our chances in life are shaped by income, ethnicity, education, gender, and age. The kinds of illnesses we have and how they progress, mean that these factors change over time. We call these changes trajectories. To better understand service user work and capacity, we will review published studies that tell us about people's everyday experiences of living with illnesses. We focus on three rarely studied trajectories. These are long-term conditions associated with significant disability; serious relapsing remitting disease; and rapidly progressing acute disease. We will first use existing research to build a framework in which we can describe and understand relevant aspects of the published studies. We will use this framework to extract relevant information from the studies. This will enable us to make a model of common features of service user work and capacity across different conditions, their trajectories, service organisation and delivery, and patterns of social and economic disadvantage. Finally, we will work with groups of service users and caregivers, and with health and social care professionals to apply the model to the development of strategies to reduce workload and improve service design for people with complex health problems.

A conceptual framework for characterising lifecourse determinants of multiple long-term condition multimorbidity.

Objective: Social, biological and environmental factors in early-life, defined as the period from preconception until age 18, play a role in shaping the risk of multiple long-term condition multimorbidity. However, there is a need to conceptualise these early-life factors, how they relate to each other, and provide conceptual framing for future research on aetiology and modelling prevention scenarios of multimorbidity. We develop a conceptual framework to characterise the population-level domains of early-life determinants of future multimorbidity. Method: This work was conducted as part of the Multidisciplinary Ecosystem to study Lifecourse Determinants and Prevention of Early-onset Burdensome Multimorbidity (MELD-B) study. The conceptualisation of multimorbidity lifecourse determinant domains was shaped by a review of existing research evidence and policy, and co-produced with public involvement via two workshops. Results: Early-life risk factors incorporate personal, social, economic, behavioural and environmental factors, and the key domains discussed in research evidence, policy, and with public contributors included adverse childhood experiences, socioeconomics, the social and physical environment, and education. Policy recommendations more often focused on individual-level factors as opposed to the wider determinants of health discussed within the research evidence. Some domains highlighted through our co-production process with public contributors, such as religion and spirituality, health screening and check-ups, and diet, were not adequately considered within the research evidence or policy. Conclusions: This co-produced conceptualisation can inform research directions using primary and secondary data to investigate the early-life characteristics of population groups at risk of future multimorbidity, as well as policy directions to target public health prevention scenarios of early-onset multimorbidity.

Ubuntu as a mediator in coping with multimorbidity treatment burden in a disadvantaged rural and urban setting in South Africa.

BACKGROUND: People living with multimorbidity in economically precarious circumstances in low- and middle-income countries (LMICs) experience a high workload trying to meet self-management demands. However, in countries such as South Africa, the availability of social networks and support structures may improve patient capacity, especially when networks are governed by cultural patterns linked to the Pan-African philosophy of Ubuntu, which promotes solidarity through humanness and human dignity. We explore the mediating role Ubuntu plays in people's ability to self-manage HIV/NCD multimorbidity in underprivileged settings in urban and rural South Africa. METHODS: We conducted semi-structured interviews with 30 patients living with HIV/NCD multimorbidity between February-April 2022. Patients attended public health clinics in Gugulethu, Cape Town and Bulungula, Eastern Cape. We analysed interviews using framework analysis, using the Cumulative Complexity Model (CuCoM) and Burden of Treatment Theory (BoTT) as frameworks through which to conceptualise the data. RESULTS: Despite facing economic hardship, people with multimorbidity in South Africa were able to cope with their workload. They actively used and mobilized family relations and external networks that supported them financially, practically, and emotionally, allowing them to better self-manage their chronic conditions. Embedded in their everyday life, patients, often unconsciously, embraced Ubuntu and its core values, including togetherness, solidarity, and receiving Imbeko (respect) from health workers. This enabled participants to share their treatment workload and increase self-management capacity. CONCLUSION: Ubuntu is an important mediator for people living with multimorbidity in South Africa, as it allows them to navigate their treatment workload and increase their social capital and structural resilience, which is key to self-management capacity. Incorporating Ubuntu and linked African support theories into current treatment burden models will enable better understandings of patients' collective support and can inform the development of context-specific social health interventions that fit the needs of people living with chronic conditions in African settings.

Multidisciplinary ecosystem to study lifecourse determinants and prevention of early-onset burdensome multimorbidity (MELD-B) - protocol for a research collaboration.

Background: Most people living with multiple long-term condition multimorbidity (MLTC-M) are under 65 (defined as 'early onset'). Earlier and greater accrual of long-term conditions (LTCs) may be influenced by the timing and nature of exposure to key risk factors, wider determinants or other LTCs at different life stages. We have established a research collaboration titled 'MELD-B' to understand how wider determinants, sentinel conditions (the first LTC in the lifecourse) and LTC accrual sequence affect risk of early-onset, burdensome MLTC-M, and to inform prevention interventions. Aim: Our aim is to identify critical periods in the lifecourse for prevention of early-onset, burdensome MLTC-M, identified through the analysis of birth cohorts and electronic health records, including artificial intelligence (AI)-enhanced analyses. Design: We will develop deeper understanding of 'burdensomeness' and 'complexity' through a qualitative evidence synthesis and a consensus study. Using safe data environments for analyses across large, representative routine healthcare datasets and birth cohorts, we will apply AI methods to identify early-onset, burdensome MLTC-M clusters and sentinel conditions, develop semi-supervised learning to match individuals across datasets, identify determinants of burdensome clusters, and model trajectories of LTC and burden accrual. We will characterise early-life (under 18 years) risk factors for early-onset, burdensome MLTC-M and sentinel conditions. Finally, using AI and causal inference modelling, we will model potential 'preventable moments', defined as time periods in the life course where there is an opportunity for intervention on risk factors and early determinants to prevent the development of MLTC-M. Patient and public involvement is integrated throughout.

Development and piloting of a primary school-based salt reduction programme: Formative work and a process evaluation in rural and urban Malawi.

Excess salt intake is a major modifiable risk factor for cardiovascular disease. Promoting salt reduction as part of routine school-health programming may be a pragmatic way to address this risk factor early in the life course but has not been tested in sub-Saharan Africa (SSA). Here we describe the formative work with stakeholders and process evaluation of pilot work to develop a school-based salt reduction programme for children aged 11-14 years, in preparation for a cluster-randomised trial in rural/urban Malawi. Collection of observational data and documentary evidence (meeting minutes/field notes) from the earliest key stakeholder engagement with Malawi Ministries of Health, Education, Local Government and Rural Development and Malawi Institute of Education, and non-governmental stakeholders; and a series of semi-structured interviews and focus groups (with head teachers (n = 2); teachers (n = 4); parents (n = 30); and learners (n = 40)). Data was analysed thematically and conceptualised through a Normalization Process Theory lens. Formative work illustrated a range of administrative, technical, and practical issues faced during development of the programme; including allocation of stakeholder roles and responsibilities, harmonisation with pre-existing strategies and competing priorities, resources required for programme development, and design of effective teaching materials. While participants were positive about the programme, the process evaluation identified features to be refined including perceived challenges to participation, recommended adaptations to the content and delivery of lessons, and concerns related to quantity/quality of learning resources provided. This study demonstrates the importance of comprehensive, sustained, and participatory stakeholder engagement in the development of a novel school health programme in SSA; and highlights the factors that were critical to successfully achieving this. We also demonstrate the value of detailed process evaluation in informing development of the programme to ensure that it was feasible and relevant to the context prior to evaluation through a cluster-randomised trial.

Adaptation and content validation of a patient-reported measure of treatment burden for use in stroke survivors: the patient experience with treatment and self-management in stroke (PETS-stroke) measure.

PURPOSE: Stroke survivors often live with significant treatment burden yet our ability to examine this is limited by a lack of validated measurement instruments. We aimed to adapt the 60-item, 12-domain Patient Experience with Treatment and Self-Management (PETS) (version 2.0, English) patient-reported measure to create a stroke-specific measure (PETS-stroke) and to conduct content validity testing with stroke survivors. MATERIALS AND METHODS: Step 1 - Adaptation of PETS to create PETS-stroke: a conceptual model of treatment burden in stroke was utilised to amend, remove or add items. Step 2 - Content validation: Fifteen stroke survivors in Scotland were recruited through stroke groups and primary care. Three rounds of five cognitive interviews were audio recorded and transcribed. Framework analysis was used to explore importance/relevance/clarity of PETS-stroke content. COSMIN reporting guidelines were followed. RESULTS: The adapted PETS-stroke had 34 items, spanning 13 domains; 10 items unchanged from PETS, 6 new and 18 amended. Interviews (n = 15) resulted in further changes to 19 items, including: instructions; wording; item location; answer options; and recall period. CONCLUSIONS: PETS-stroke has content that is relevant, meaningful and comprehensible to stroke survivors. Content validity and reliability testing are now required. The validated tool will aid testing of tailored interventions to lessen treatment burden.IMPLICATIONS FOR REHABILITATIONTreatment burden is reported by stroke survivors but no stroke-specific measure of treatment burden exists.We adapted an existing measure of treatment burden for use in multimorbid patients (PETS) to create a stroke specific version (PETS-stroke).The items in PETS-stroke are relevant and meaningful to people with stroke.Further testing will examine construct validity, reliability, and useability.This measure will be useful in future RCTs to measure treatment burden and to identify stroke patients who are at high risk of treatment burden.

Understanding the impacts of the COVID-19 pandemic on the care experiences of people with mental-physical multimorbidity: protocol for a mixed methods study.

BACKGROUND: Primary care and other health services have been disrupted during the COVID-19 pandemic, yet the consequences of these service disruptions on patients' care experiences remain largely unstudied. People with mental-physical multimorbidity are vulnerable to the effects of the pandemic, and to sudden service disruptions. It is thus essential to better understand how their care experiences have been impacted by the current pandemic. This study aims to improve understanding of the care experiences of people with mental-physical multimorbidity during the pandemic and identify strategies to enhance these experiences. METHODS: We will conduct a mixed-methods study with multi-phase approach involving four distinct phases. Phase 1 will be a qualitative descriptive study in which we interview individuals with mental-physical multimorbidity and health professionals in order to explore the impacts of the pandemic on care experiences, as well as their perspectives on how care can be improved. The results of this phase will inform the design of study phases 2 and 3. Phase 2 will involve journey mapping exercises with a sub-group of participants with mental-physical multimorbidity to visually map out their care interactions and experiences over time and the critical moments that shaped their experiences. Phase 3 will involve an online, cross-sectional survey of care experiences administered to a larger group of people with mental disorders and/or chronic physical conditions. In phase 4, deliberative dialogues will be held with key partners to discuss and plan strategies for improving the delivery of care to people with mental-physical multimorbidity. Pre-dialogue workshops will enable us to synthesize an prepare the results from the previous three study phases. DISCUSSION: Our study results will generate much needed evidence of the positive and negative impacts of the COVID-19 pandemic on the care experiences of people with mental-physical multimorbidity and shed light on strategies that could improve care quality and experiences.

Treatment burden for people experiencing homelessness with a recent non-fatal overdose: a questionnaire study.

BACKGROUND: People experiencing homelessness (PEH) who have problem drug use have complex medical and social needs, with barriers to accessing services and treatments. Their treatment burden (workload of self-management and impact on wellbeing) remains unexplored. AIM: To investigate treatment burden in PEH with a recent non-fatal overdose using a validated questionnaire, the Patient Experience with Treatment and Self-management (PETS). DESIGN AND SETTING: The PETS questionnaire was collected as part of a pilot randomised control trial (RCT) undertaken in Glasgow, Scotland; the main outcome is whether this pilot RCT should progress to a definitive RCT. METHOD: An adapted 52-item, 12-domain PETS questionnaire was used to measure treatment burden. Greater treatment burden was indicated by higher PETS scores. RESULTS: Of 128 participants, 123 completed PETS; mean age was 42.1 (standard deviation [SD] 8.4) years, 71.5% were male, and 99.2% were of White ethnicity. Most (91.2%) had >5 chronic conditions, with an average of 8.5 conditions. Mean PETS scores were highest in domains focusing on the impact of self-management on wellbeing: physical and mental exhaustion (mean 79.5, SD 3.3) and role and social activity limitations (mean 64.0, SD 3.5) Scores were higher than those observed in studies of patients who are not homeless. CONCLUSION: In a socially marginalised patient group at high risk of drug overdose, the PETS showed a very high level of treatment burden and highlights the profound impact of self-management work on wellbeing and daily activities. Treatment burden is an important person-centred outcome to help compare the effectiveness of interventions in PEH and merits inclusion in future trials as an outcome measure.

Frailty in randomised controlled trials for dementia or mild cognitive impairment measured via the frailty index: prevalence and prediction of serious adverse events and attrition.

BACKGROUND: Frailty and dementia have a bidirectional relationship. However, frailty is rarely reported in clinical trials for dementia and mild cognitive impairment (MCI) which limits assessment of trial applicability. This study aimed to use a frailty index (FI)-a cumulative deficit model of frailty-to measure frailty using individual participant data (IPD) from clinical trials for MCI and dementia. Moreover, the study aimed to quantify the prevalence of frailty and its association with serious adverse events (SAEs) and trial attrition. METHODS: We analysed IPD from dementia (n = 1) and MCI (n = 2) trials. An FI comprising physical deficits was created for each trial using baseline IPD. Poisson and logistic regression were used to examine associations with SAEs and attrition, respectively. Estimates were pooled in random effects meta-analysis. Analyses were repeated using an FI incorporating cognitive as well as physical deficits, and results compared. RESULTS: Frailty could be estimated in all trial participants. The mean physical FI was 0.14 (SD 0.06) and 0.14 (SD 0.06) in the MCI trials and 0.24 (SD 0.08) in the dementia trial. Frailty prevalence (FI > 0.24) was 6.9%/7.6% in MCI trials and 48.6% in the dementia trial. After including cognitive deficits, the prevalence was similar in MCI (6.1% and 6.7%) but higher in dementia (75.4%). The 99th percentile of FI (0.31 and 0.30 in MCI, 0.44 in dementia) was lower than in most general population studies. Frailty was associated with SAEs: physical FI IRR = 1.60 [1.40, 1.82]; physical/cognitive FI IRR = 1.64 [1.42, 1.88]. In a meta-analysis of all three trials, the estimated association between frailty and trial attrition included the null (physical FI OR = 1.17 [0.92, 1.48]; physical/cognitive FI OR = 1.16 [0.92, 1.46]), although higher frailty index values were associated with attrition in the dementia trial. CONCLUSION: Measuring frailty from baseline IPD in dementia and MCI trials is feasible. Those living with more severe frailty may be under-represented. Frailty is associated with SAEs. Including only physical deficits may underestimate frailty in dementia. Frailty can and should be measured in future and existing trials for dementia and MCI, and efforts should be made to facilitate inclusion of people living with frailty.

Treatment effect modification due to comorbidity: Individual participant data meta-analyses of 120 randomised controlled trials.

BACKGROUND: People with comorbidities are underrepresented in clinical trials. Empirical estimates of treatment effect modification by comorbidity are lacking, leading to uncertainty in treatment recommendations. We aimed to produce estimates of treatment effect modification by comorbidity using individual participant data (IPD). METHODS AND FINDINGS: We obtained IPD for 120 industry-sponsored phase 3/4 trials across 22 index conditions (n = 128,331). Trials had to be registered between 1990 and 2017 and have recruited ≥300 people. Included trials were multicentre and international. For each index condition, we analysed the outcome most frequently reported in the included trials. We performed a two-stage IPD meta-analysis to estimate modification of treatment effect by comorbidity. First, for each trial, we modelled the interaction between comorbidity and treatment arm adjusted for age and sex. Second, for each treatment within each index condition, we meta-analysed the comorbidity-treatment interaction terms from each trial. We estimated the effect of comorbidity measured in 3 ways: (i) the number of comorbidities (in addition to the index condition); (ii) presence or absence of the 6 commonest comorbid diseases for each index condition; and (iii) using continuous markers of underlying conditions (e.g., estimated glomerular filtration rate (eGFR)). Treatment effects were modelled on the usual scale for the type of outcome (absolute scale for numerical outcomes, relative scale for binary outcomes). Mean age in the trials ranged from 37.1 (allergic rhinitis trials) to 73.0 (dementia trials) and percentage of male participants range from 4.4% (osteoporosis trials) to 100% (benign prostatic hypertrophy trials). The percentage of participants with 3 or more comorbidities ranged from 2.3% (allergic rhinitis trials) to 57% (systemic lupus erythematosus trials). We found no evidence of modification of treatment efficacy by comorbidity, for any of the 3 measures of comorbidity. This was the case for 20 conditions for which the outcome variable was continuous (e.g., change in glycosylated haemoglobin in diabetes) and for 3 conditions in which the outcomes were discrete events (e.g., number of headaches in migraine). Although all were null, estimates of treatment effect modification were more precise in some cases (e.g., sodium-glucose co-transporter-2 (SGLT2) inhibitors for type 2 diabetes-interaction term for comorbidity count 0.004, 95% CI -0.01 to 0.02) while for others credible intervals were wide (e.g., corticosteroids for asthma-interaction term -0.22, 95% CI -1.07 to 0.54). The main limitation is that these trials were not designed or powered to assess variation in treatment effect by comorbidity, and relatively few trial participants had >3 comorbidities. CONCLUSIONS: Assessments of treatment effect modification rarely consider comorbidity. Our findings demonstrate that for trials included in this analysis, there was no empirical evidence of treatment effect modification by comorbidity. The standard assumption used in evidence syntheses is that efficacy is constant across subgroups, although this is often criticised. Our findings suggest that for modest levels of comorbidities, this assumption is reasonable. Thus, trial efficacy findings can be combined with data on natural history and competing risks to assess the likely overall benefit of treatments in the context of comorbidity.

Baseline characteristics of people experiencing homelessness with a recent drug overdose in the PHOENIx pilot randomised controlled trial.

BACKGROUND: Drug-related deaths in Scotland are the highest in Europe. Half of all deaths in people experiencing homelessness are drug related, yet we know little about the unmet health needs of people experiencing homelessness with recent non-fatal overdose, limiting a tailored practice and policy response to a public health crisis. METHODS: People experiencing homelessness with at least one non-fatal street drug overdose in the previous 6 months were recruited from 20 venues in Glasgow, Scotland, and randomised into PHOENIx plus usual care, or usual care. PHOENIx is a collaborative assertive outreach intervention by independent prescriber NHS Pharmacists and third sector homelessness workers, offering repeated integrated, holistic physical, mental and addictions health and social care support including prescribing. We describe comprehensive baseline characteristics of randomised participants. RESULTS: One hundred and twenty-eight participants had a mean age of 42 years (SD 8.4); 71% male, homelessness for a median of 24 years (IQR 12-30). One hundred and eighteen (92%) lived in large, congregate city centre temporary accommodation. A quarter (25%) were not registered with a General Practitioner. Participants had overdosed a mean of 3.2 (SD 3.2) times in the preceding 6 months, using a median of 3 (IQR 2-4) non-prescription drugs concurrently: 112 (87.5%) street valium (benzodiazepine-type new psychoactive substances); 77 (60%) heroin; and 76 (59%) cocaine. Half (50%) were injecting, 50% into their groins. 90% were receiving care from Alcohol and Drug Recovery Services (ADRS), and in addition to using street drugs, 90% received opioid substitution therapy (OST), 10% diazepam for street valium use and one participant received heroin-assisted treatment. Participants had a mean of 2.2 (SD 1.3) mental health problems and 5.4 (SD 2.5) physical health problems; 50% received treatment for physical or mental health problems. Ninety-one per cent had at least one mental health problem; 66% had no specialist mental health support. Participants were frail (70%) or pre-frail (28%), with maximal levels of psychological distress, 44% received one or no daily meal, and 58% had previously attempted suicide. CONCLUSIONS: People at high risk of drug-related death continue to overdose repeatedly despite receiving OST. High levels of frailty, multimorbidity, unsuitable accommodation and unmet mental and physical health care needs require a reorientation of services informed by evidence of effectiveness and cost-effectiveness. Trial registration UK Clinical Trials Registry identifier: ISRCTN 10585019.

The impact of persistent precarity on patients' capacity to manage their treatment burden: A comparative qualitative study between urban and rural patients with multimorbidity in South Africa.

Background: People living with multimorbidity in low-and middle-income countries (LMICs) experience a high workload trying to meet the demands of self-management. In an unequal society like South Africa, many people face continuous economic uncertainty, which can impact on their capacity to manage their illnesses and lead to poor health outcomes. Using precariousness - the real and perceived impact of uncertainty - as a lens, this paper aims to identify, characterise, and understand the workload and capacity associated with self-management amongst people with multimorbidity living in precarious circumstances in urban and rural South Africa. Methods: We conducted qualitative semi-structured interviews with 30 patients with HIV and co-morbidities between February and April 2021. Patients were attending public clinics in Cape Town (Western Cape) and Bulungula (Eastern Cape). Interviews were transcribed and data analysed using qualitative framework analysis. Burden of Treatment Theory (BoTT) and the Cumulative Complexity Model (CuCoM) were used as theoretical lenses through which to conceptualise the data. Results: People with multimorbidity in rural and urban South Africa experienced multi-faceted precariousness, including financial and housing insecurity, dangerous living circumstances and exposure to violence. Women felt unsafe in their communities and sometimes their homes, whilst men struggled with substance use and a lack of social support. Older patients relied on small income grants often shared with others, whilst younger patients struggled to find stable employment and combine self-management with family responsibilities. Precariousness impacted access to health services and information and peoples' ability to buy healthy foods and out-of-pocket medication, thus increasing their treatment burden and reducing their capacity. Conclusion: This study highlights that precariousness reduces the capacity and increases treatment burden for patients with multimorbidity in low-income settings in South Africa. Precariousness is both accumulative and cyclic, as financial insecurity impacts every aspect of peoples' daily lives. Findings emphasise that current models examining treatment burden need to be adapted to accommodate patients' experiences in low-income settings and address cumulative precariousness. Understanding treatment burden and capacity for patients in LMICs is a crucial first step to redesign health systems which aim to improve self-management and offer comprehensive person-centred care.