Is palliative care a utopia for older patients with organ failure, dementia or frailty? A qualitative study through the prism of emergency department admission.

BACKGROUND: Nearly three out of four older people will use the emergency department (ED) during their last year of life. However, most of them do not benefit from palliative care. Providing palliative care is a real challenge for ED clinicians who are trained in acute, life-saving medicine. Our aim is to understand the ED's role in providing palliative care for this population. METHODS: We designed a qualitative study based on 1) interviews - conducted with older patients (≥ 75 years) with a palliative profile and their informal caregivers - and 2) focus groups - conducted with ED and primary care nurses and physicians. Palliative profiles were defined by the Supportive and Palliative Indicators tool (SPICT). Qualitative data was collected in French-speaking Belgium between July 2021 and July 2022. We used a constant inductive and comparative analysis. RESULTS: Five older patients with a palliative profile, four informal caregivers, 55 primary and ED caregivers participated in this study. A priori, the participants did not perceive any role for the ED in palliative care. In fact, there is widespread discomfort with caring for older patients and providing palliative care. This is explained by multiple areas of tensions. Palliative care is an approach fraught with pitfalls, i.e.: knowledge and know-how gaps, their implementation depends on patients'(co)morbidity profile and professional values, experiences and type of practice. In ED, there are constant tensions between emergency and palliative care requirements, i.e.: performance, clockwork and needs for standardised procedures versus relational care, time and diversity of palliative care projects. However, even though the ED's role in palliative care is not recognised at first sight, we highlighted four roles assumed by ED caregivers: 1) Investigator, 2) Objectifier, 3) Palliative care provider, and 4) Decision-maker on the intensity of care. A common perception among participants was that ED caregivers can assist in the early identification of patients with a palliative profile. CONCLUSIONS: Currently, there is widespread discomfort regarding ED caregivers caring for older patients and providing palliative care. Nonetheless, ED caregivers play four roles in palliative care for older patients. In the future, ED caregivers might also perform the role of early identifier.

Acute frailty services: results of a national day of care survey.

INTRODUCTION: Older people living with frailty are at high risk of emergency hospital admission and often have complex care needs which may not be adequately met by conventional models of acute care. This has driven the introduction of adaptations to acute care pathways designed to improve outcomes in this patient group. The identification of differences in the organisational approach to frailty may highlight opportunities for quality improvement. METHODS: The Society for Acute Medicine Benchmarking audit is a national service evaluation which uses a single day-of-care methodology to record patient and organisational level data. All acute hospitals in the United Kingdom are eligible to participate. Emergency admissions referred to acute medical services between 00:00 and 23:59 on Thursday 23rd June 2022 were recorded. Information on the structure and operational design of acute frailty services was collected. The use of a validated frailty assessment tool, clinical frailty scale within the first 24 h of admission, assessment by an acute frailty service and clinical outcomes were reported in patients aged 70 year and above. A mixed effect generalised linear model was used to determine factors associated same-day discharge without overnight stay in patients with frailty. RESULTS: A total of 152 hospitals participated. There was significant heterogeneity in the operational design and staffing model of acute frailty services. The presence of an acute frailty unit was reported in 57 (42.2%) hospitals. The use of validated frailty assessment tools was reported in 117 (90.0%) hospitals, of which 107 (91.5%) used the clinical frailty scale. Patient-level data were recorded for 3604 patients aged 70 years and above. At the patient level, 1626 (45.1%) were assessed using a validated tool during the admission process. Assessment by acute frailty services was associated with an increased likelihood of same-day discharge (adjusted OR 1.55, 95%CI 1.03- 2.39). CONCLUSION: There is significant variation in the provision of acute frailty services. Frailty-related policies and services are common at the organisational level but implemented inconsistently at the patient level. Older people with frailty or geriatric syndromes assessed by acute frailty services were more likely to be discharged without the need for overnight bed-based admission.

Frailty identification and management among Brazilian healthcare professionals: a survey.

BACKGROUND: National and international guidelines on frailty assessment and management recommend frailty screening in older people. This study aimed to determine how Brazilian healthcare professionals (HCPs) identify and manage frailty in practice. METHODS: An anonymous online survey on the assessment and management of frailty was circulated virtually through HCPs across Brazil. RESULTS: Most of the respondants used non-specific criteria such as gait speed (45%), handgrip strength (37.6%), and comprehensive geriatric assessment (33.2%). The use of frailty-specific criteria was lower than 50%. The most frequently used criteria were the Frailty Index (19.1%), Frailty Phenotype (13.2%), and FRAIL (12.5%). Only 43.5% felt confident, and 40% had a plan to manage frailty. In the multivariate-adjusted models, training was the most crucial factor associated with assessing frailty, confidence, and having a management plan (p < 0.001 for all). Those with fewer years of experience were more likely to evaluate frailty (p = 0.009). Being a doctor increased the chance of using a specific tool; the opposite was true for dietitians (p = 0.03). Those who assisted more older people had a higher likelihood of having a plan (p = 0.011). CONCLUSION: Frailty assessment was heterogeneous among healthcare professions groups, predominantly using non-specific criteria. Training contributed to frailty assessment, use of specific criteria, confidence, and having a management plan. This data informs the need for standardized screening criteria and management plans for frailty, in association with increasing training at the national level for all the HCPs who assist older people.

Fidelity, pragmatism and the "grey line" in between-exploring the delivery of a pragmatic physical activity randomised controlled trial-a secondary analysis.

BACKGROUND: Intervention fidelity in health services research has been poor with a reported lack of understanding about what constitutes pragmatic adaptation of interventions and what constitutes failure to maintain intervention fidelity. However, the challenges facing those delivering such interventions have not been thoroughly explored. The aims of this study were to critically explore the challenges in maintaining fidelity experienced by physiotherapy staff and support workers when delivering a complex intervention for older people living with frailty. METHODS: This study is a secondary analysis of data from a process evaluation of a large randomised controlled trial (RCT). The process evaluation employed qualitative methodologies with mixed methods including a variety of data collection methods, including participant observation, semi-structured interviews and documentary analysis. Thematic analysis was used to make sense of the data. RESULTS: Many therapy staff felt ongoing confusion about what was acceptable to adapt and what needed to follow the protocol exactly. We found that some therapy staff were able to embrace the challenges of pragmatically adapting interventions while maintaining intervention fidelity, others stuck rigidly to the protocol and failed to adapt interventions where it was necessary. CONCLUSION: It was clear that the understanding of fidelity and pragmatism was poor. While pragmatic trials are vital to replicate real world clinical practice, further guidance may need to be developed in order to guide the level of adaptation that is acceptable before fidelity is undermined.

Proactive care for frailty.

Many providers aspire to scale up proactive care that prevents escalation of health and care needs, delays onset of disability, and reduces demand for emergency department attendance or admission to hospital or care home. NHS England offers guidance on personalised and coordinated multi-professional support and interventions for people with moderate or severe frailty. This article reflects on the growing international evidence for an integrated proactive approach for older people with frailty and why investing in high-quality, joined-up care for older people across the whole system improves outcomes for people, reduces demand for services, increases system resilience, and delivers economic and societal benefits. Facing up to frailty requires creative whole system workforce planning and development that will be challenging to deliver in the current financial and recruitment context yet all the more worthwhile as scaling up proactive care has the potential to be a game changer.

DIALOR (DIgitAL cOaching for fRailty): protocol for a single-arm mixed-methods feasibility study of a digital health coaching intervention for older people with frailty in primary care.

BACKGROUND: Multidomain interventions in older adults offer the best opportunity to prevent, delay or reverse existing symptoms in the earlier stages of frailty and improve independence but can be costly, and difficult to deliver at scale. However, digital health interventions enable personalised care and empowerment through self-management of long-term conditions, used at any time and when combined with health coaching offer the potential to enhance well-being and facilitate the achievement of health-related goals. We aim to evaluate the feasibility and acceptability of a digital health platform for long-term disease management combined with health coaching for people living with mild-moderate frailty, targeting self-identified goals-activity, nutrition, mood, enhancing social engagement and well-being. METHODS AND ANALYSIS: This is a non-randomised feasibility, single-group, pretest/post-test study, using qualitative and quantitative methods. The digital health coaching intervention (DIALOR-DIgitAL cOaching for fRailty) has been developed for implementation to older adults, aged 65 years or older with mild to moderate frailty and diagnosis of one or more long-term health conditions in the community. Participants will receive 12 weeks of health coaching and have access to a mobile health platform for 6 months. The primary outcome measure is the acceptability and feasibility of DIALOR along with a range of secondary outcome measures (including frailty, functioning measures, quality of life, social engagement, diet quality and self-reported indicators) collected at baseline and at 6 months. The findings will inform whether a wider effectiveness trial is feasible and if so, how it should be designed. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Southeast Scotland Research Ethics Committee 02 (reference: 22/SS/0064). Research findings will be disseminated in a range of different ways to engage different audiences, including publishing in open-access peer-reviewed journals, conference presentations, social media, dissemination workshop with patients, carers, and healthcare professionals and on institution websites.

PReventing and Approaching Crises for frail community-dwelling patients Through Innovative Care (PRACTIC): protocol for an effectiveness cluster randomised controlled trial.

BACKGROUND: Demographic changes, with an increasing number and proportion of older people with multimorbidity and frailty, will put more pressure on home care services in municipalities. Frail multimorbid people receiving home care services are at high risk of developing crises, defined as critical challenges and symptoms, which demand immediate and new actions. The crises often result in adverse events, coercive measures, and acute institutionalisation. There is a lack of evidence-based interventions to prevent and resolve crises in community settings. METHODS: This is a participatory action research design (PAR) in a 6-month cluster randomised controlled trial (RCT). The trial will be conducted in 30 municipalities, including 150 frail community-dwelling participants receiving home care services judged by the services to be at risk of developing crisis. Each municipality (cluster) will be randomised to receive either the locally adapted TIME intervention (the intervention group) or care as usual (the control group). The Targeted Interdisciplinary Model for Evaluation and Treatment of Neuropsychiatric Symptoms (TIME) is a manual-based, multicomponent programme that includes a rigorous assessment of the crisis, one or more interdisciplinary case conferences, and the testing and evaluation of customised treatment measures. PAR in combination with an RCT will enhance adaptations of the intervention to the local context and needs. The primary outcome is as follows: difference in change between the intervention and control groups in individual goal achievement to resolve or reduce the challenges of the crises between baseline and 3 months using the PRACTIC Goal Setting Interview (PGSI). Among the secondary outcomes are the difference in change in the PGSI scale at 6 months and in neuropsychiatric symptoms (NPSs), quality of life, distress perceived by professional carers and next of kin, and institutionalisation at 3 and 6 months. DISCUSSION: Through customised interventions that involve patients, the next of kin, the social context, and health care services, crises may be prevented and resolved. The PReventing and Approaching Crises for frail community-dwelling patients Through Innovative Care (PRACTIC) study will enhance innovation for health professionals, management, and users in the development of new knowledge and a new adapted approach towards crises. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05651659. Registered 15.12.22.

Frailty evidence-practice gaps in acute care hospitals.

OBJECTIVES: Frailty is common in hospitalised older people. Clinical practice guidelines for the management of frailty provide recommendations for identification and management; however, adoption into practice in hospitals is limited. This study identified and quantified the evidence-practice gap between frailty guidelines and clinical practice in two hospitals using an audit tool. METHODS: A cross-sectional audit of medical records of frail older patients admitted to two hospitals was conducted. Data were collected using an audit tool based on the Asia Pacific Clinical Practice Guidelines for frailty management. Data were analysed using descriptive statistics and inter-rater reliability of the tool was assessed. RESULTS: Auditing of n = 70 electronic medical records showed that assessment of frailty in the acute setting did not regularly occur (17%). Few participants received guideline-recommended interventions. Physiotherapy treatment was limited, with 23% of participants receiving progressive resistance strength training. Gaps exist in provision of nutritional supplementation (26%) with limited recordings of weight during the admission for 10% of participants. Pharmacy review of medications was consistently documented on admission (84%) and discharge (93%). Vitamin D was prescribed for 57% of participants. Inter-rater reliability showed a high level of agreement using the audit tool. CONCLUSIONS: An audit tool was feasible to assess frailty evidence-practice gaps in the hospital setting. Further understanding of the contextual barriers is needed to inform implementation strategies (dedicated staffing, education and training and ongoing audit of practice cycles) for the uptake of frailty guidelines in hospital settings.

Outcomes of the LEAP feasibility trial-A low-threshold, exercise programme with protein supplementation to target frailty and poor physical functioning in people experiencing homelessness and addiction issues.

BACKGROUND: People experiencing homelessness are more likely to experience poor health with physical functioning deficits and frailty commonly reported. It is not well known how strategies to target physical functioning deficits and frailty work in practice in this group. The primary aim of this study was to explore the feasibility of an exercise intervention with protein supplementation to target physical functioning and frailty in people experiencing homelessness evaluated by recruitment and retention rates, adherence to the exercise sessions and protein supplement, adverse effects, programme feedback and characteristics of non-returners, sporadic and frequent attenders. The secondary aim was to evaluate changes in effectiveness outcomes of grip strength, muscle mass, lower extremity physical function, pain, frailty, and risk of malnutrition. METHOD: This prospective single-arm study evaluated the feasibility of a 16-week rolling, low-threshold, 'drop-in' once weekly exercise programme with protein supplementation. The main recruitment site was a day-service centre for people who are homeless. Feasibility was assessed by the recruitment and retention rates, adherence to the exercise sessions and protein supplement as well as adverse effects, programme feedback and evaluation of characteristics of non-returners, sporadic (≤50% of available sessions) and frequent attenders (≥50% of available sessions). Effectiveness outcomes included pain (Visual Analogue Scale), physical functioning and performance (hand-grip dynamometry, limb circumference, the Short Physical Performance Battery), frailty (SHARE-FI and Clinical Frailty Scale) and nutritional status (Mini Nutritional Assessment). RESULTS: Thirty-one participants were recruited mean (SD) age 45(16) years. There was a recruitment rate of a median (IQR) of 2(1-3) new participants per week. The retention rate was 45% (n = 14) to the main recruitment site. Adherence to the exercise sessions and nutritional intervention was 90% and 100% respectively. Three adverse events were recorded during 74 interventions over the 16-week programme. The acceptability of the programme was highlighted in participant feedback. Characteristics of frequent returners (≥50%) were older age, female, more stably housed and more stable in addiction. The programme did not induce any changes in effectiveness outcomes. CONCLUSION: The feasibility of this programme was demonstrated. Overall, the programme was well received with higher retention rates in older participants, females, those more stably housed and those stable in addiction. A higher powered, more intense programme is needed to demonstrate programme effectiveness.

How do primary care clinicians approach the management of frailty? A qualitative interview study.

BACKGROUND: Around 15% of adults aged over 65 live with moderate or severe frailty. Contractual requirements for management of frailty are minimal and neither incentivised nor reinforced. Previous research has shown frailty identification in primary care is ad hoc and opportunistic, but there has been little focus on the challenges of frailty management, particularly within the context of recent introduction of primary care networks and an expanding allied health professional workforce. AIM: Explore the views of primary care clinicians in England on the management of frailty. DESIGN AND SETTING: Semi-structured interviews were conducted with clinicians across England, including general practitioners (GPs), physician associates, nurse practitioners, paramedics and clinical pharmacists. Thematic analysis was facilitated through NVivo (Version 12). RESULTS: A total of 31 clinicians participated. Frailty management was viewed as complex and outside of clinical guidelines with medication optimisation highlighted as a key example. Senior clinicians, particularly experienced GPs, were more comfortable with managing risk. Relational care was important in prioritising patient wishes and autonomy, for instance to remain at home despite deteriorations in health. In settings where more formalised multidisciplinary frailty services had been established this was viewed as successful by clinicians involved. CONCLUSION: Primary care clinicians perceive frailty as best managed through trusted relationships with patients, and with support from experienced clinicians. New multidisciplinary working in primary care could enhance frailty services, but must keep continuity in mind. There is a lack of evidence or guidance for specific interventions or management approaches.

Clinical effectiveness and cost-effectiveness of a multicomponent frailty management program "Say No To Frailty" in Singapore: A cluster-randomized controlled trial protocol.

BACKGROUND: A 12-week multicomponent frailty management program - Say No To Frailty (SNTF) consisting of interactive talks and fitness exercises led by a trained program leader has shown feasibility and positive health outcomes in community-living older adults with frailty and pre-frailty in Singapore. This study aims to evaluate the clinical- and cost-effectiveness of SNTF on physical functions, self-confidence, community participation, quality of life and fall reduction in the local community setting. METHODS: This study will use the cluster-randomization method to randomly allocate 12 participating centres into three arms. Centres under two intervention arms will conduct the same SNTF program but led by a program leader with different training backgrounds (an Allied Health Professional (AHP) v.s. a non-AHP), whereas centres under the control arm will continue their usual care without an additional intervention. Eligible participants at each participating centre will be recruited via the convenience sampling method in the community setting. Primary outcome measure (frailty level) and secondary outcome measures (e.g., physical functions, self-confidence, community participation, quality of life) will be conducted by the blinded assessors at baseline, immediate, 3 months and 9 months post-intervention. Fall data will be collected during the one-year study period. Outcomes between and within groups will be compared and analysed using STATA to evaluate the clinical effectiveness. Program costs and relevant healthcare costs during the follow-up phase will be recorded for cost-effectiveness analysis. CONCLUSION: This study will provide significant insights into conducting SNTF for Singapore community-living older adults with frailty and pre-frailty on clinical- and cost-effectiveness. Australia New Zealand Clinical Trials Registry: ACTRN12621001673831.

Value of a multidisciplinary geriatric oncology committee on patient care in a community-based, academic cancer center.

INTRODUCTION: The heterogeneity in health and functional ability among older patients makes the management of cancer a unique challenge. The Geriatric Oncology Program at the University of Maryland Baltimore Washington Medical Center (BWMC) was created to optimize cancer management for older patients. This study aimed to assess the benefits of the implementation of such a program at a community-based academic cancer center. MATERIALS AND METHODS: We analyzed patients aged ≥80 years presenting to the Geriatric Oncology Program between 2017 and 2022. A multidisciplinary team of specialists collectively reviewed each patient using geriatric-specific domains and stratified each patient into one of three management groups- Group 1: those deemed fit to receive standard oncologic care (SOC); Group 2: those recommended to receive optimization services prior to reassessment for SOC; and Group 3: those deemed to be best suited for supportive care and/or hospice care. RESULTS: The study cohort consisted of 233 patients, of which 76 (32.6%) received SOC, 43 (18.5%) were optimized, and 114 (49.0%) received supportive care or hospice referral. Among the optimized patients, 69.8% were deemed fit for SOC upon re-evaluation following their respective optimization services. The Canadian Study of Health and Aging-Clinical Frailty Scale (CSHA-CFS) score was implemented in 2019 (n = 90). Patients receiving supportive/hospice care only had an average score of 5.8, while the averages for those in the optimization and SOC groups were 4.6 and 4.1, respectively (p ≤0.001). Patients receiving SOC had the longest average survival of 2.71 years compared to the optimization (2.30 years) and supportive care groups (0.93 years) (p ≤0.001). For all patients that underwent surgical interventions post-operatively, 23 patients (85%) were discharged home and four (15%) were discharged to a rehabilitation facility. DISCUSSION: The present study demonstrates the profound impact that the complexities in health status and frailty among older individuals can have during cancer management. The Geriatric Oncology Program at BWMC maximized treatment outcomes for older adults through the provision of SOC therapies and optimization services, while also minimizing unnecessary interventions on an individual patient-centric level.

Which Comprehensive Geriatric Assessment (CGA) instruments are currently used in Germany: a survey.

BACKGROUND: The Comprehensive Geriatric Assessment (CGA) records geriatric syndromes in a standardized manner, allowing individualized treatment tailored to the patient's needs and resources. Its use has shown a beneficial effect on the functional outcome and survival of geriatric patients. A recently published German S1 guideline for level 2 CGA provides recommendations for the use of a broad variety of different assessment instruments for each geriatric syndrome. However, the actual use of assessment instruments in routine geriatric clinical practice and its consistency with the guideline and the current state of literature has not been investigated to date. METHODS: An online survey was developed by an expert group of geriatricians and sent to all licenced geriatricians (n = 569) within Germany. The survey included the following geriatric syndromes: motor function and self-help capability, cognition, depression, pain, dysphagia and nutrition, social status and comorbidity, pressure ulcers, language and speech, delirium, and frailty. Respondents were asked to report which geriatric assessment instruments are used to assess the respective syndromes. RESULTS: A total of 122 clinicians participated in the survey (response rate: 21%); after data cleaning, 76 data sets remained for analysis. All participants regularly used assessment instruments in the following categories: motor function, self-help capability, cognition, depression, and pain. The most frequently used instruments in these categories were the Timed Up and Go (TUG), the Barthel Index (BI), the Mini Mental State Examination (MMSE), the Geriatric Depression Scale (GDS), and the Visual Analogue Scale (VAS). Limited or heterogenous assessments are used in the following categories: delirium, frailty and social status. CONCLUSIONS: Our results show that the assessment of motor function, self-help capability, cognition, depression, pain, and dysphagia and nutrition is consistent with the recommendations of the S1 guideline for level 2 CGA. Instruments recommended for more frequent use include the Short Physical Performance Battery (SPPB), the Montreal Cognitive Assessment (MoCA), and the WHO-5 (depression). There is a particular need for standardized assessment of delirium, frailty and social status. The harmonization of assessment instruments throughout geriatric departments shall enable more effective treatment and prevention of age-related diseases and syndromes.

Frailty as an Effect Modifier in Randomized Controlled Trials: A Systematic Review.

BACKGROUND: The effect of clinical interventions may vary by patients' frailty status. Understanding treatment effect heterogeneity by frailty could lead to frailty-guided treatment strategies and reduce overtreatment and undertreatment. This systematic review aimed to examine the effect modification by frailty in randomized controlled trials (RCTs) that evaluate pharmacological, non-pharmacological, and multicomponent interventions. METHODS: We searched PubMed, Web of Science, EMBASE, and ClinicalTrial.gov, from their inception to 8 December 2023. Two reviewers independently extracted trial data and examined the study quality with senior authors. RESULTS: Sixty-one RCTs that evaluated the interaction between frailty and treatment effects in older adults were included. Frailty was evaluated using different tools such as the deficit accumulation frailty index, frailty phenotype, and other methods. The effect of several pharmacological interventions (e.g., edoxaban, sacubitril/valsartan, prasugrel, and chemotherapy) varied according to the degree of frailty, whereas other treatments (e.g., antihypertensives, vaccinations, osteoporosis medications, and androgen medications) demonstrated consistent benefits across different frailty levels. Some non-pharmacological interventions had greater benefits in patients with higher (e.g., chair yoga, functional walking, physical rehabilitation, and higher dose exercise program) or lower (e.g., intensive lifestyle intervention, psychosocial intervention) levels of frailty, while others (e.g., resistance-type exercise training, moderate-intensive physical activity, walking and nutrition or walking) produced similar intervention effects. Specific combined interventions (e.g., hospital-based disease management programs) demonstrated inconsistent effects across different frailty levels. DISCUSSION: The efficacy of clinical interventions often varied by frailty levels, suggesting that frailty is an important factor to consider in recommending clinical interventions in older adults. REGISTRATION: PROSPERO registration number CRD42021283051.

Safety and efficacy of umbilical cord tissue-derived mesenchymal stem cells in the treatment of patients with aging frailty: a phase I/II randomized, double-blind, placebo-controlled study.

BACKGROUND: Mesenchymal stem cells (MSCs) hold a great promise for cell-based therapy in the field of regenerative medicine. In this study, we aimed to evaluate the safety and efficacy of intravenous infusion of human umbilical cord-derived MSCs (HUC-MSCs) in patients with aging frailty. METHODS: In this randomized, double-blind, placebo-controlled trial, participants diagnosed with aging frailty were randomly assigned to receive intravenous administrations of HUC-MSCs or placebo. All of serious adverse events and AEs were monitored to evaluate the safety of treatment during the 6-month follow-up. The primary efficacy endpoint was alteration of physical component scores (PCS) of SF-36 qualities of life at 6 months. The secondary outcomes including physical performance tests and pro-inflammatory cytokines, were also observed and compared at each follow-up visits. All evaluations were performed at 1 week, 1, 2, 3 and 6 months following the first intravenous infusion of HUC-MSCs. RESULTS: In the MSCs group, significant improvements in PCS of SF-36 were observed from first post-treatment visit and sustained throughout the follow-up period, with greater changes compared to the placebo group (p = 0.042). EQ-VAS scores of MSCs group improved significantly at 2 month (p = 0.023) and continued until the end of the 6-month visit (p = 0.002) in comparison to the placebo group. The timed up and go (TUG) physical performance test revealed significant group difference and showed continual enhancements over 6 months (p < 0.05). MSC transplantation improved the function of 4-m walking test (4MWT) compared with the placebo group with a decrease of 2.05 s at 6 months of follow-up (p = 0.21). The measurement of grip strength revealed group difference with MSCs group demonstrating better performance, particularly at 6 months (p = 0.002). Inflammatory cytokines (TNF-α, IL-17) exhibited declines in MSCs group at 6 months compared to the placebo group (p = 0.034 and 0.033, respectively). There was no difference of incidence of AEs between the two groups. CONCLUSION: Intravenous transplantation of HUC-MSCs is a safe and effective therapeutic approach on aging frailty. The positive outcomes observed in improving quality of life, physical performance, and reducing chronic inflammation, suggest that HUC-MSC therapy may be a promising potential treatment option for aging frailty. TRIAL REGISTRATION: Clinicaltrial.gov; NCT04314011; https://clinicaltrials.gov/ct2/show/NCT04314011 .

Long-term, patient-centered, frailty-based outcomes of older critical illness survivors from the emergency department: a post hoc analysis of the LIFE Study.

BACKGROUND: Evidence indicates frailty before intensive care unit (ICU) admission leads to poor outcomes. However, it is unclear whether quality of life (QOL) and activities of daily living (ADL) for survivors of critical illness admitted to the ICU via the emergency department remain consistent or deteriorate in the long-term compared to baseline. This study aimed to evaluate long-term QOL/ADL outcomes in these patients, categorized by the presence or absence of frailty according to Clinical Frailty Scale (CFS) score, as well as explore factors that influence these outcomes. METHODS: This was a post-hoc analysis of a prospective, multicenter, observational study conducted across Japan. It included survivors aged 65 years or older who were admitted to the ICU through the emergency department. Based on CFS scores, participants were categorized into either the not frail group or the frail group, using a threshold CFS score of < 4. Our primary outcome was patient-centered outcomes (QOL/ADL) measured by the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) and the Barthel Index six months post-ICU admission, comparing results from baseline. Secondary outcomes included exploration of factors associated with QOL/ADL six months post-ICU admission using multiple linear regression analyses. RESULTS: Of 514 candidates, 390 participants responded to the EQ-5D-5L questionnaire, while 237 responded to the Barthel Index. At six months post-admission, mean EQ-5D-5L values declined in both the not frail and frail groups (0.80 to 0.73, p = 0.003 and 0.58 to 0.50, p = 0.002, respectively); Barthel Index scores also declined in both groups (98 to 83, p < 0.001 and 79 to 61, p < 0.001, respectively). Multiple linear regression analysis revealed that baseline frailty (ß coefficient, -0.15; 95% CI, - 0.23 to - 0.07; p < 0.001) and pre-admission EQ-5D-5L scores (ß coefficient, 0.14; 95% CI, 0.02 to 0.26; p = 0.016) affected EQ-5D-5L scores at six months. Similarly, baseline frailty (ß coefficient, -12.3; 95% CI, - 23.9 to - 0.80; p = 0.036) and Barthel Index scores (ß coefficient, 0.54; 95% CI, 0.30 to 0.79; p < 0.001) influenced the Barthel Index score at six months. CONCLUSIONS: Regardless of frailty, older ICU survivors from the emergency department were more likely to experience reduced QOL and ADL six months after ICU admission compared to baseline.

Age- and sex-specific associations of frailty with mortality and healthcare utilization in community-dwelling adults from ontario, Canada.

BACKGROUND: Understanding how health trajectories are related to the likelihood of adverse outcomes and healthcare utilization is key to planning effective strategies for improving health span and the delivery of care to older adults. Frailty measures are useful tools for risk stratification in community-based and primary care settings, although their effectiveness in adults younger than 60 is not well described. METHODS: We performed a 10-year retrospective analysis of secondary data from the Ontario Health Study, which included 161,149 adults aged ≥ 18. Outcomes including all-cause mortality and hospital admissions were obtained through linkage to ICES administrative databases with a median follow-up of 7.1-years. Frailty was characterized using a 30-item frailty index. RESULTS: Frailty increased linearly with age and was higher for women at all ages. A 0.1-increase in frailty was significantly associated with mortality (HR = 1.47), the total number of outpatient (IRR = 1.35) and inpatient (IRR = 1.60) admissions over time, and length of stay (IRR = 1.12). However, with exception to length of stay, these estimates differed depending on age and sex. The hazard of death associated with frailty was greater at younger ages, particularly in women. Associations with admissions also decreased with age, similarly between sexes for outpatient visits and more so in men for inpatient. CONCLUSIONS: These findings suggest that frailty is an important health construct for both younger and older adults. Hence targeted interventions to reduce the impact of frailty before the age of 60 would likely have important economic and social implications in both the short- and long-term.

Effect of Lactobacillus plantarum BFS1243 on a female frailty model induced by fecal microbiota transplantation in germ-free mice.

Frailty, a complex geriatric syndrome, significantly impedes the goal of achieving 'healthy aging'. Increasing evidence suggests a connection between gut microbiota, systemic inflammation, and disease. However, it remains to be determined whether interventions targeting the intestinal flora can effectively ameliorate frailty. Our research involved fecal microbiota transplantation (FMT) experiments on germ-free (GF) mice, dividing these mice into three groups: a group receiving transplants from healthy elderly individuals (HF group), a group of frailty patients (FF group), and the FF group supplemented with Lactobacillus plantarum BFS1243 (FFL group). Our findings indicated a significant shift in the gut microbiota of the FF group, in contrast to the HF group, characterized by decreased Akkermansia and increased Enterocloster, Parabacteroides, and Eisenbergiella. Concurrently, there was a reduction in amino acids and SCFAs, with BFS1243 partially mitigating these changes. The FF group exhibited an upregulation of inflammatory markers, including PGE2, CRP, and TNF-α, and a downregulation of irisin, all of which were moderated by BFS1243 treatment. Furthermore, BFS1243 improved intestinal barrier integrity and physical endurance in the FF mice. Correlation analysis revealed a negative association between SCFA-producing species and metabolites like lysine and butyric acid with pro-inflammatory factors. In conclusion, our study conclusively demonstrated that alterations in the gut microbiota of elderly individuals can lead to physical frailty, likely due to detrimental effects on the intestinal barrier and a pro-inflammatory state. These findings underscore the potential of gut microbiome modulation as a clinical strategy for treating frailty.