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140 result(s) for "Witham, Miles D."
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Repurposing Drugs for Diabetes Mellitus as Potential Pharmacological Treatments for Sarcopenia – A Narrative Review
Sarcopenia, the age-related loss of muscle strength and mass or quality, is a common condition with major adverse consequences. Although the pathophysiology is incompletely understood, there are common mechanisms between sarcopenia and the phenomenon of accelerated ageing seen in diabetes mellitus. Drugs currently used to treat type 2 diabetes mellitus may have mechanisms of action that are relevant to the prevention and treatment of sarcopenia, for those with type 2 diabetes and those without diabetes. This review summarises shared pathophysiology between sarcopenia and diabetes mellitus, including the effects of advanced glycation end products, mitochondrial dysfunction, chronic inflammation and changes to the insulin signalling pathway. Cellular and animal models have generated intriguing, albeit mixed, evidence that supports possible beneficial effects on skeletal muscle function for some classes of drugs used to treat diabetes, including metformin and SGLT2 inhibitors. Most human observational and intervention evidence for the effects of these drugs has been derived from populations with type 2 diabetes mellitus, and there is a need for intervention studies for older people with, and at risk of, sarcopenia to further investigate the balance of benefit and risk in these target populations. Not all diabetes treatments will be safe to use in those without diabetes because of variable side effects across classes. However, some agents [including glucagon-like peptide (GLP)-1 receptor agonists and SGLT2 inhibitors] have already demonstrated benefits in populations without diabetes, and it is these agents, along with metformin, that hold out the most promise for further investigation in sarcopenia.
Developing a roadmap to improve trial delivery for under-served groups: results from a UK multi-stakeholder process
Background Participants in clinical research studies often do not reflect the populations for which healthcare interventions are needed or will be used. Enhancing representation of under-served groups in clinical research is important to ensure that research findings are widely applicable. We describe a multicomponent workstream project to improve representation of under-served groups in clinical trials. Methods The project comprised three main strands: (1) a targeted scoping review of literature to identify previous work characterising under-served groups and barriers to inclusion, (2) surveys of professional stakeholders and participant representative groups involved in research delivery to refine these initial findings and identify examples of innovation and good practice and (3) a series of workshops bringing together key stakeholders from funding, design, delivery and participant groups to reach consensus on definitions, barriers and a strategic roadmap for future work. The work was commissioned by the UK National Institute for Health Research Clinical Research Network. Output from these strands was integrated by a steering committee to generate a series of goals, workstream plans and a strategic roadmap for future development work in this area. Results ‘Under-served groups’ was identified and agreed by the stakeholder group as the preferred term. Three-quarters of stakeholders felt that a clear definition of under-served groups did not currently exist; definition was challenging and context-specific, but exemplar groups (e.g. those with language barriers or mental illness) were identified as under-served. Barriers to successful inclusion of under-served groups could be clustered into communication between research teams and participant groups; how trials are designed and delivered, differing agendas of research teams and participant groups; and lack of trust in the research process. Four key goals for future work were identified: building long-term relationships with under-served groups, developing training resources to improve design and delivery of trials for under-served groups, developing infrastructure and systems to support this work and working with funders, regulators and other stakeholders to remove barriers to inclusion. Conclusions The work of the INCLUDE group over the next 12 months will build on these findings by generating resources customised for different under-served groups to improve the representativeness of trial populations.
Nutrition and Frailty: Opportunities for Prevention and Treatment
Frailty is a syndrome of growing importance given the global ageing population. While frailty is a multifactorial process, poor nutritional status is considered a key contributor to its pathophysiology. As nutrition is a modifiable risk factor for frailty, strategies to prevent and treat frailty should consider dietary change. Observational evidence linking nutrition with frailty appears most robust for dietary quality: for example, dietary patterns such as the Mediterranean diet appear to be protective. In addition, research on specific foods, such as a higher consumption of fruit and vegetables and lower consumption of ultra-processed foods are consistent, with healthier profiles linked to lower frailty risk. Few dietary intervention studies have been conducted to date, although a growing number of trials that combine supplementation with exercise training suggest a multi-domain approach may be more effective. This review is based on an interdisciplinary workshop, held in November 2020, and synthesises current understanding of dietary influences on frailty, focusing on opportunities for prevention and treatment. Longer term prospective studies and well-designed trials are needed to determine the causal effects of nutrition on frailty risk and progression and how dietary change can be used to prevent and/or treat frailty in the future.
Developing the INCLUDE Ethnicity Framework—a tool to help trialists design trials that better reflect the communities they serve
Background Ensuring that a trial is designed so that its participants reflect those who might benefit from the results, or be spared harms, is key to the potential benefits of the trial reaching all they should. This paper describes the process, facilitated by Trial Forge, that was used between July 2019 and October 2020 to develop the INCLUDE Ethnicity Framework, part of the wider INCLUDE initiative from the National Institute for Health Research to improve inclusion of under-served groups in clinical research studies. Methods Development of the Framework was done in seven phases: (1) outline, (2) initial draft, (3) stakeholder meeting, (4) modify draft, (5) Stakeholder feedback, (6) applying the Framework and (7) packaging. Phases 2 and 3 were face-to-face meetings. Consultation with stakeholders was iterative, especially phases 4 to 6. Movement to the next phase was done once all or most stakeholders were comfortable with the results of the current phase. When there was a version of the Framework that could be considered final, the Framework was applied to six trials to create a set of examples (phase 6). Finally, the Framework, guidance and examples were packaged ready for dissemination (phase 7). Results A total of 40 people from stakeholder groups including patient and public partners, clinicians, funders, academics working with various ethnic groups, trial managers and methodologists contributed to the seven phases of development. The Framework comprises two parts. The first part is a list of four key questions: Who should my trial apply to? Are the groups identified likely to respond in different ways? Will my study intervention make it harder for some groups to engage? Will the way I have designed the study make it harder for some groups to engage? The second part is a set of worksheets to help trial teams address these questions. The Framework can be used for any stage of trial, for a healthcare intervention in any disease area. The Framework was launched on 1st October 2020 and is available open access at the Trial Forge website: https://www.trialforge.org/trial-forge-centre/include/ . Conclusion Thinking about the number of people in our trials is not enough: we need to start thinking more carefully about who our participants are.
Perceptions of Hospital Care Quality According to People Living With Multiple Long‐Term Conditions: A Scoping Review
Background Delivering high‐quality hospital care for people with multiple long‐term conditions (MLTC), defined as the co‐existence of two or more chronic health conditions, is important. However, evidence on care quality from the perspective of people living with MLTC has not been synthesised. The aim of this scoping review was to identify studies investigating how people living with MLTC perceive hospital care quality and to summarise key concepts and gaps in the evidence base. Methods Systematic searches of five databases to identify all eligible studies published up until March 2024 were undertaken and supplemented by citation tracking. Peer‐reviewed articles featuring people with MLTC's perceptions of the quality of ‘usual’ care in hospitals were eligible for inclusion. All records were screened independently by two reviewers. Results Of the 3178 titles and s screened, 17 papers were eligible for inclusion (9 qualitative, 7 quantitative and 1 mixed‐methods). Studies highlighted an unmet desire for holistic interdisciplinary care (n = 4), prioritisation of inpatients' acute conditions over long‐term conditions (n = 2), barriers to patient engagement (n = 3) and insufficient discharge planning (n = 3). Conclusion Existing studies that have investigated how people living with MLTC perceive the quality of their hospital care are diverse. However, all included studies point to ways in which hospital care for people with MLTC could be improved. The review highlights a need for studies including people of a wider range of ages, mixed‐methods studies and studies that focus on under‐researched elements of care quality, such as safety and preventative care. Patient or Public Contribution There have been regular opportunities for engagement with the ADMISSION research collaborative's Patient Advisory Group (PAG), a group of patients and carers with lived experience of multiple long‐term conditions, who meet every 4 months. At these meetings, hospital care quality (and patients' perception thereof) has been a recurring theme, which encouraged the conceptualisation of this review. The PAG had no further direct involvement in the conduct of this review.
Causes and correlates of 30 day and 180 day readmission following discharge from a Medicine for the Elderly Rehabilitation unit
Background Recently hospitalized patients experience a period of generalized risk of adverse health events. This study examined reasons for, and predictors of, readmission to acute care facilities within 30 and 180 days of discharge from an inpatient rehabilitation unit for older people. Methods Routinely collected, linked clinical data on admissions to a single inpatient rehabilitation facility over a 13-year period were analysed. Data were available regarding demographics, comorbid disease, admission and discharge Barthel scores, length of hospital stay, and number of medications on discharge. Discharge diagnoses for the index admission and readmissions were available from hospital episode statistics. Univariate and multivariate Cox regression analyses were performed to identify baseline factors that predicted 30 and 180-day readmission. Results A total of 3984 patients were included in the analysis. The cohort had a mean age of 84.1 years (SD 7.4), and 39.7% were male. Overall, 5.6% ( n  = 222) and 23.2% ( n  = 926) of the patients were readmitted within 30 days and 180 days of discharge respectively. For patients readmitted to hospital, 26.6% and 21.1% of patients were readmitted with the same condition as their initial admission at 30 days and 180 respectively. For patients readmitted within 30 days, 13.5% ( n  = 30) were readmitted with the same condition with the most common diagnoses associated with readmission being chest infection, falls/immobility and stroke. For patients readmitted within 180 days, 12.4% ( n  = 115) of patients were readmitted with the same condition as the index condition with the most common diagnoses associated with readmission being falls/immobility, cancer and chest infections. In multivariable Cox regression analyses, older age, male sex, length of stay and heart failure predicted 30 or 180-day readmission. In addition, discharge from hospital to patients own home predicted 30-day readmission, whereas diagnoses of cancer, previous myocardial infarction or chronic obstructive pulmonary disease predicted 180-day readmission. Conclusion Most readmissions of older people after discharge from inpatient rehabilitation occurred for different reasons to the original hospital admission. Patterns of predictors for early and late readmission differed, suggesting the need for different mitigation strategies.
Trial Forge Guidance 3: randomised trials and how to recruit and retain individuals from ethnic minority groups—practical guidance to support better practice
Randomised trials, especially those intended to directly inform clinical practice and policy, should be designed to reflect all those who could benefit from the intervention under test should it prove effective. This does not always happen. The UK National Institute for Health and Care Research (NIHR) INCLUDE project identified many groups in the UK that are under-served by trials, including ethnic minorities. This guidance document presents four key recommendations for designing and running trials that include the ethnic groups needed by the trial. These are (1) ensure eligibility criteria and recruitment pathway do not limit participation in ways you do not intend, (2) ensure your trial materials are developed with inclusion in mind, (3) ensure staff are culturally competent and (4) build trusting partnerships with community organisations that work with ethnic minority groups. Each recommendation comes with best practice advice, public contributor testimonials, examples of the inclusion problem tackled by the recommendation, or strategies to mitigate the problem, as well as a collection of resources to support implementation of the recommendations. We encourage trial teams to follow the recommendations and, where possible, evaluate the strategies they use to implement them. Finally, while our primary audience is those designing, running and reporting trials, we hope funders, grant reviewers and approvals agencies may also find our guidance useful.
Sarcopenia and sarcopenic obesity among community-dwelling Peruvian adults: A cross-sectional study
Sarcopenia and sarcopenic obesity (SO) have emerged as significant contributors to negative health outcomes in the past decade. We aimed to estimate the prevalence of probable sarcopenia, sarcopenia, and SO in a community-dwelling population of 1151 adults aged ≥55 years in Lima, Peru. This cross-sectional study was conducted between 2018 and 2020. Sarcopenia was defined as the presence of low muscle strength (LMS) and low muscle mass (LMM) according to European (EWGSOP2), US (FNIH) and Asian (AWGS2) guidelines. We measured muscle strength by maximum handgrip strength and muscle mass using bioelectrical impedance analyzer. SO was defined as a body mass index ≥ 30 kg/m2 and sarcopenia. The study participants had a mean age of 66.2 years (SD 7.1), age range between 60 to 92 years old, of which 621 (53.9%) were men. Among the sample, 41.7% were classified as obese (BMI ≥30.0 kg/m²). The prevalence of probable sarcopenia was estimated to be 22.7% (95%CI: 20.3-25.1) using the EWGSOP2 criteria and 27.8% (95%CI: 25.2-30.4) using the AWGS2 criteria. Sarcopenia prevalence, assessed using skeletal muscle index (SMI), was 5.7% (95%CI: 4.4-7.1) according to EWGSOP2 and 8.3% (95%CI: 6.7-9.9) using AWGS2 criteria. The prevalence of sarcopenia based on the FNIH criteria was 18.1% (95%CI: 15.8-20.3). The prevalence of SO, considering different sarcopenia definitions, ranged from 0.8% (95%CI: 0.3-1.3) to 5.0% (95%CI: 3.8-6.3). Our findings reveal substantial variation in the prevalence of sarcopenia and SO, underscoring the necessity for context-specific cut-off values. Although the prevalence of SO was relatively low, this result may be underestimated. Furthermore, the consistently high proportion of probable sarcopenia and sarcopenia point to a substantial public health burden.
Experiences of hospital care for people with multiple long-term conditions: a scoping review of qualitative research
Background Multiple long-term conditions—the co-existence of two or more chronic health conditions in an individual—present an increasing challenge to populations and healthcare systems worldwide. This challenge is keenly felt in hospital settings where care is oriented around specialist provision for single conditions. The aim of this scoping review was to identify and summarise published qualitative research on the experiences of hospital care for people living with multiple long-term conditions, their informal caregivers and healthcare professionals. Methods We undertook a scoping review, following established guidelines, of primary qualitative research on experiences of hospital care for people living with multiple long-term conditions published in peer-reviewed journals between Jan 2010 and June 2022. We conducted systematic electronic searches of MEDLINE, CINAHL, PsycInfo, Proquest Social Science Premium, Web of Science, Scopus and Embase, supplemented by citation tracking. Studies were selected for inclusion by two reviewers using an independent screening process. Data extraction included study populations, study design, findings and author conclusions. We took a narrative approach to reporting the findings. Results Of 8002 titles and abstracts screened, 54 papers reporting findings from 41 studies conducted in 14 countries were identified as eligible for inclusion. The perspectives of people living with multiple long-term conditions (21 studies), informal caregivers ( n  = 13) and healthcare professionals ( n  = 27) were represented, with 15 studies reporting experiences of more than one group. Findings included poor service integration and lack of person-centred care, limited confidence of healthcare professionals to treat conditions outside of their specialty, and time pressures leading to hurried care transitions. Few studies explored inequities in experiences of hospital care. Conclusions Qualitative research evidence on the experiences of hospital care for multiple long-term conditions illuminates a tension between the desire to provide and receive person-centred care and time pressures inherent within a target-driven system focussed on increasing specialisation, reduced inpatient provision and accelerated journeys through the care system. A move towards more integrated models of care may enable the needs of people living with multiple long-term conditions to be better met. Future research should address how social circumstances shape experiences of care.
Attitudes and barriers to resistance exercise training for older adults living with multiple long-term conditions, frailty, and a recent deterioration in health: qualitative findings from the Lifestyle in Later Life – Older People’s Medicine (LiLL-OPM) study
Background Many older adults live with the combination of multiple long-term conditions (MLTC) and frailty and are at increased risk of a deterioration in health requiring interaction with healthcare services. Low skeletal muscle strength is observed in individuals living with MLTC and is central to physical frailty. Resistance exercise (RE) is the best available treatment for improving muscle strength, but little is known about the attitudes and barriers to RE in this group of older adults. This study therefore aimed to explore the knowledge of and attitudes towards RE, as well as the barriers and enabling factors, in older adults living with MLTC, frailty and a recent deterioration in health. Methods Fourteen participants aged 69–92 years (10 women) from the Lifestyle in Later Life – Older People’s Medicine (LiLL-OPM) study were recruited from an Older People’s Medicine Day Unit in Newcastle, UK. Participants were invited to take part in a semi-structured interview exploring their knowledge and attitudes as well as barriers and enabling factors to RE. Data were analysed using thematic analysis. Results The analysis generated three themes (1) a lack of awareness and understanding of RE, (2) a self-perceived inability to perform RE; physical and psychological barriers and (3) willingness to perform RE under expert guidance. There was a general lack of awareness and understanding of RE, with most participants having never heard of the term and being unaware of its potential benefits. When RE was described, participants stated that they would be willing to try RE, but it was apparent that an individualised approach underpinned by expert guidance would be required to support engagement. Conclusions Older adults living with MLTC, frailty and a recent deterioration in health lack awareness and understanding of RE. Despite a range of barriers, this group appear willing to engage in RE if they are appropriately supported. There is a need to co-design and deliver effective strategies, including education, to raise awareness and understanding of RE, as well as promote engagement in RE, in this group of older adults.