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 .

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.

"It's a stressful, trying time for the caretaker": an interpretive description qualitative study of postoperative transitions in care for older adults with frailty from the perspectives of informal caregivers.

BACKGROUND: Older adults with frailty have surgery at a high rate. Informal caregivers often support the postoperative transition in care. Despite the growing need for family and caregiver support for this population, little is known about the experience of providing informal care to older adults with frailty during the postoperative transition in care. The purpose of this study was to explore what is important during a postoperative transition in care for older adults with frailty from the perspective of informal caregivers. METHODS: This was a qualitative study using an interpretive description methodology. Seven informal caregivers to older adults [aged ≥ 65 years with frailty (Clinical Frailty Scale score ≥ 4) who had an inpatient elective surgery] participated in a telephone-based, semi-structured interview. Audio files were transcribed and analyzed using reflexive thematic analysis. RESULTS: Four themes were constructed: (1) being informed about what to expect after surgery; (2) accessible communication with care providers; (3) homecare resources are needed for the patient; and (4) a support network for the caregivers. Theme 4 included two sub-themes: (a) respite and emotional support and (b) occupational support. CONCLUSIONS: Transitions in care present challenges for informal caregivers of older adults with frailty, who play an important role in successful transitions. Future postoperative transitional care programs should consider making targeted information, accessible communication, and support networks available for caregivers as part of facilitating successful transitions in care.

Geriatric screening and frailty intervention in older patients with cancer.

Frailty in older patients with cancer increases the risk of treatment related toxicity, mortality, physical decline, and quality of life. This review summarises various screening tools. Screening tools identifying frailty serve multiple purposes, providing awareness of health issues impacting oncologic treatment and prognosis and facilitating the delivery of a Comprehensive Geriatric Assessment (CGA). CGA is an overall health assessment and treatment targeting frailty. Providing CGA to older patients with cancer reduces the risk of toxicity and functional decline, increases treatment completion, and prevents loss of quality of life.

Impact of FRAilty screening and Geriatric assessment and INtervention in older patients with epithelial Ovarian Cancer: A multicenter randomized clinical trial protocol (FRAGINOC).

INTRODUCTION: Radical surgery combined with chemotherapy is the only potential curative treatment of patients with advanced epithelial ovarian cancer (EOC). However, 43% of older Danish patients with EOC are not referred to surgery due to frailty, age, or fear of complications. Comprehensive geriatric assessment (CGA) has demonstrated ability to reduce frailty in older patients, but there is a knowledge gap regarding its effect before or during treatment in older adults with EOC. This protocol presents a randomized controlled trial (RCT), which evaluates the effect of CGA-based interventions including individualized physical exercise therapy in older adults with EOC during neoadjuvant chemotherapy (NACT). MATERIALS AND METHODS: This RCT will include patients aged ≥70 years with primary EOC referred to NACT. Patients will be randomized 1:1 to intervention or standard of care, along with neoadjuvant antineoplastic treatment. Stratification for performance status and center of inclusion will be performed. In the intervention arm, a geriatrician will perform CGA and corresponding geriatric interventions and patients will undergo an individualized home-based exercise program managed by a physiotherapist. All patients will be evaluated with Geriatric-8, modified Geriatric-8, clinical frailty scale, and physical tests at randomization. Predictive values (positive/negative) will be evaluated for CGA detected impairments. The primary endpoint is the proportion of patients referred to interval debulking surgery (IDS). Secondary endpoints include the proportion who complete oncological treatment, improvements in physical tests, quality of life measured by European Organization for Research and Treatment of Cancer-Quality of Life questionnaires at inclusion, after three cycles of chemotherapy, and at end of chemotherapy treatment. Furthermore, the association between results of geriatric screening tests, CGA, and physical tests with complication rate and progression free survival will be examined. The primary outcome will be analyzed with logistic regression in the intention-to-treat population. Power calculations reveal the need to enroll 216 patients. DISCUSSION: The present study examines whether CGA-based interventions including individualized physical exercise can increase the referral rate for potential curative IDS in older patients with EOC. If successful, this will result in more patients undergoing surgery and completing chemotherapy, preventing complications, and ultimately improving quality of life and survival. The study setup may establish the basis for direct clinical implementation if proven effective.

Physical Interventions Restore Physical Frailty and the Expression of CXCL-10 and IL-1ß Inflammatory Biomarkers in Old Individuals and Mice.

BACKGROUND: Frailty is a geriatric syndrome associated with negative health outcomes that represents a dynamic condition with a potential of reversibility after physical exercise interventions. Typically, inflammatory and senescence markers are increased in frail individuals. However, the impact that physical exercise exerts on inflammatory and senescence biomarkers remains unknown. We assessed the effect of physical intervention in old individuals and mice and determined the expression of inflammatory and senescence markers. METHODS: Twelve elderly individuals were enrolled from a primary care setting to a 3-month intervention. Frailty was measured by SPPB and the expression of biomarkers by cytokine array and RT-qPCR. In addition, 12 aged C57BL/6 mice completed an intervention, and inflammation and senescence markers were studied. RESULTS: The physical intervention improved the SPPB score, reducing frail and pre-frail individuals. This was correlated with a reduction in several pro-inflammatory biomarkers such as IL-6, CXCL-1, CXCL-10, IL-1ß, IL-7, GM-CSF as well as p16INK4a and p21CIP1 senescence markers. Otherwise, the levels of anti-inflammatory biomarker IL-4 were significantly increased. Moreover, the physical intervention in mice also improved their functional capacity and restored the expression of inflammatory (Il-1ß, Cxcl-10, Il-6, and Cxcl-1) and senescence (p21Cip1) markers. Additionally, PLSDA and ROC curve analysis revealed CXCL-10 and IL-1ß to be the biomarkers of functional improvement in both cohorts. CONCLUSIONS: Our results showed that a physical intervention improves physical frailty, and reverses inflammation and senescence biomarkers comprising CXCL-10 and IL-1ß.

An overview of multimorbidity and polypharmacy in older people living with HIV.

The availability of effective antiretroviral therapy (ART) has revolutionized the care of people living with HIV (PLHIV). As a result, PLHIV now have a life expectancy comparable with that of the general population. PLHIV are increasingly confronted with age-related comorbidities and geriatric syndromes, including frailty and polypharmacy, which occur at a higher prevalence and set in at an earlier age compared with their uninfected counterparts. The underlying pathophysiology for multimorbidity and polypharmacy are multifactorial, multidimensional and complex. Therefore, regular review and optimization of risk factors to maintain physical function, social and psychological health is of utmost importance. With an ever-growing population of older PLHIV, there is a pressing need to provide holistic care to address these emerging issues. Accelerated aging observed in PLHIV suggests that early involvement of a multidisciplinary team, including geriatricians, and implementation of integrated models of care can potentially improve the care of older PLHIV, who are at increased risk of frailty and complex multimorbidity. This article reviews the current global situation, discusses the challenges involved and suggests approaches to deliver comprehensive care for older PLHIV. Geriatr Gerontol Int 2024; 24: 49-59.

Effectiveness of a randomized intervention by a geriatric team in frail hospital inpatients in non-geriatric settings: FRAILCLINIC project.

BACKGROUND: Little research has been undertaken on the benefits of frailty management within different hospital settings. The objective of this study is to provide evidence on the viability and effectiveness of frailty management in non-geriatric hospital settings on mortality and functional decline after discharge. METHODS: Data from the FRAILCLINIC (NCT02643069) study were used. FRAILCLINIC is a randomized controlled trial developed in non-geriatric hospital inpatient settings (emergency room, cardiology and surgery) from Spain (2), Italy (2) and the United Kingdom (1). Inpatients must met frailty criteria (according to the Frailty Phenotype and/or FRAIL scale), ≥75 years old. The control group (CG) received usual care. The intervention group (IG) received comprehensive geriatric assessment (CGA) and a coordinated intervention consisting in recommendations to the treating physician about polypharmacy, delirium, falls, nutrition and physical exercise plus a discharge plan. The main outcomes included functional decline (worsening ≥5 points in Barthel Index) and mortality at 3 months. We used multivariate logistic regression models adjusted by age, gender and the Charlson index. Intention-to-treat (ITT) and per-protocol (PP) analyses were used. RESULTS: Eight hundred twenty one participants (IG: 416; mean age 83.00 ± 4.91; 51.44% women; CG: 405; mean age 82.46 ± 6.03; 52.35% women) were included. In the IG, 77.16% of the participants followed the geriatric team's recommendations as implemented by the treating physicians. The intervention showed a benefit on functional decline and mortality [OR: 0.67(0.47-0.96), P-value 0.027 and 0.29(0.14-0.57), P-value < 0.001, respectively) when fully followed by the treating physician. A trend to benefit (close to statistical significance) in functional decline and mortality were also observed when any of the recommendations were not followed [OR (95% CI): 0.72 (0.51-1.01), P-value: 0.055; and 0.64 (0.37-1.10), P-value: 0.105, respectively]. CONCLUSIONS: An individualized intervention in frail in-patients reduces the risk of functional deterioration and mortality at 3 months of follow-up when a care management plan is designed and followed.

"I can't imagine having to do it on your own": a qualitative study on postoperative transitions in care from the perspectives of older adults with frailty.

BACKGROUND: Adults aged 65 and older have surgery more often than younger people and often live with frailty. The postoperative transition in care from hospital to home after surgey is a challenging time for older adults with frailty as they often experience negative outcomes. Improving postoperative transitions in care for older adults with frailty is a priority. However, little knowledge from the perspective of older adults with frailty is available to support meaningful improvements in postoperative transitions in care. OBJECTIVE: To explore what is important to older adults with frailty during a postoperative transition in care. METHODS: This qualitative study used an interpretive description methodology. Twelve adults aged ≥ 65 years with frailty (Clinical Frailty Scale score ≥ 4) who had an inpatient elective surgery and could speak in English participated in a telephone-based, semi-structured interview. Audio files were transcribed and analyzed using thematic analysis. RESULTS: Five themes were constructed: 1) valuing going home after surgery; 2) feeling empowered through knowledge and resources; 3) focusing on medical and functional recovery; 4) informal caregivers and family members play multiple integral roles; and 5) feeling supported by healthcare providers through continuity of care. Each theme had 3 sub-themes. CONCLUSION: Future programs should focus on supporting patients to return home by empowering patients with resources and clear communication, ensuring continuity of care, creating access to homecare and virtual support, focusing on functional and medical recovery, and recognizing the invaluable role of informal caregivers.

Attitudes of healthcare professionals in treatment decision-making for older adults with cancer: a scoping review protocol.

INTRODUCTION: The number of older adults with cancer is increasing worldwide. These patients' unique care needs, arising from comorbidity, polypharmacy and frailty, often necessitate healthcare professionals (HCPs) to rely on their own attitudes and assumptions to a greater extent when making decisions due to limited evidence. Differences in patient and HCP attitudes can impact treatment decisions and patient outcomes. There is limited research, however, on HCP attitudes in treatment decision-making for older adults with cancer. This scoping review aims to explore the attitudes of HCPs in treatment decision-making for older adults with cancer. METHODS AND ANALYSIS: The electronic databases PubMed, Elsevier Embase, Medline (from Embase) and EBSCO CINAHL Complete will be searched on 4 July 2023 to identify eligible studies based on the developed inclusion and exclusion criteria. No restrictions on study period, geography or language will be applied. Screening and data extraction will be completed independently by teams of two reviewers, with conflicts resolved by a third reviewer. The review findings will be presented as tables and in a narrative summary.This scoping review follows the framework of Arksey and O'Malley with the Levac extension. Data extraction and analysis will be performed to identify patterns and gaps in the literature to provide an overview of the attitudes of HCPs in treatment decision-making for older adults with cancer. ETHICS AND DISSEMINATION: No ethical approval is needed. The findings will be published in a peer-reviewed journal and presented at conferences, providing insights to improve treatment decision-making for older adults with cancer and guide future interventions for HCPs in geriatric oncology. TRIAL REGISTRATION NUMBER: Registered on Open Science Framework at https://doi.org/10.17605/OSF.IO/T7FD3.

The Impact of Frailty on Palliative Care Receipt, Emergency Room Visits and Hospital Deaths in Cancer Patients: A Registry-Based Study.

BACKGROUND: Eastern Cooperative Oncology Group (ECOG) performance status is used in decision-making to identify fragile patients, despite the development of new and possibly more reliable measures. This study aimed to examine the impact of frailty on end-of-life healthcare utilization in deceased cancer patients. METHOD: Hospital Frailty Risk Scores (HFRS) were calculated based on 109 weighted International Classification of Diseases 10th revision (ICD-10) diagnoses, and HFRS was related to (a) receipt of specialized palliative care, (b) unplanned emergency room (ER) visits during the last month of life, and (c) acute hospital deaths. RESULTS: A total of 20,431 deceased cancer patients in ordinary accommodations were studied (nursing home residents were excluded). Frailty, as defined by the HFRS, was more common in men than in women (42% vs. 38%, p < 0.001) and in people residing in less affluent residential areas (42% vs. 39%, p < 0.001). Patients with frailty were older (74.1 years vs. 70.4 years, p < 0.001). They received specialized palliative care (SPC) less often (76% vs. 81%, p < 0.001) but had more unplanned ER visits (50% vs. 35%, p < 0.001), and died more often in acute hospital settings (22% vs. 15%, p < 0.001). In multiple logistic regression models, the odds ratio (OR) was higher for frail people concerning ER visits (OR 1.81 (1.71-1.92), p < 0.001) and hospital deaths (OR 1.66 (1.51-1.81), p < 0.001), also in adjusted models, when controlled for age, sex, socioeconomic status at the area level, and for receipt of SPC. CONCLUSION: Frailty, as measured by the HFRS, significantly affects end-of-life cancer patients and should be considered in oncologic decision-making.

Fecal microbiota transplantation for recurrent Clostridioides difficile infection in frail and very old patients.

BACKGROUND: Older age is a well-known risk factor for recurrent and severe Clostridioides difficile infection (CDI). Fecal microbiota transplantation (FMT) is widely recognized as an effective and safe therapeutic option for the treatment of recurrent CDI (rCDI). However, the efficacy and safety of FMT for rCDI in very old patients are uncertain. This study evaluated the efficacy and safety of FMT in a group of very old subjects with rCDI, and the reliability of overall comorbidity and frailty assessment for identifying patients at higher risk of worse clinical outcomes. METHODS: This is a retrospective single-center study including patients ≥85 years undergoing FMT for rCDI between 2014 and 2022. Primary outcomes included efficacy of FMT, defined as cure of CDI at 8 week-follow-up, and safety evaluation. At baseline, comorbidity was measured with the Charlson Comorbidity Index (CCI). Frailty was measured with the Clinical Frailty Scale (CFS). RESULTS: Overall, 43 patients with a median age of 88 years underwent FMT by colonoscopy in the study period. The rate of first FMT success was 77%. Five of the 10 patients who failed the first FMT infusion were cured after repeat FMT, with an overall efficacy of 88%. In patients with successful treatment, the CFS was significantly lower compared to those who failed the FMT or underwent repeat FMT (p < 0.01 for both). Mild adverse events occurred in 11 patients (25%). One death, not related to FMT or rCDI, occurred within 7 days from the first procedure. CONCLUSIONS: FMT is effective and safe in very old patients. Frailty and high comorbidity do not limit use of FMT in these patients. Frailty assessment has potential to better identify patients at higher risk of worse outcomes or for repeat treatment with FMT.

Symptom Management in the Older Adult: 2023 Update.

In the older adult with a serious illness, the goal of palliative medicine and symptom management is to optimize quality of life. Frailty has become an overarching finding in many older adults with serious illness. Symptom management options need to be considered in the lens of increasing frailty along an illness trajectory. Here, the authors emphasize literature updates and best practices for the most common symptoms experienced by the older adult with a serious illness.

Developing the evidence and associated service models to support older adults living with frailty to manage their pain and to reduce its impact on their lives: protocol for a mixed-method, co-design study (The POPPY Study).

INTRODUCTION: The Pain in Older People with Frailty Study is a mixed-method, co-design study, which aims to develop the content, implementation strategies, service and professional guidance to support older adults with frailty to manage their pain. METHODS AND ANALYSIS: The study has four phases: Phase 1, research evidence and information synthesis from randomised controlled trials of multicomponent pain management programmes and psychological therapies for community-dwelling older adults. Phase 2, qualitative interviews with 30 community-dwelling older adults (≥75 years) living with frailty and persistent pain, including dyadic interviews with a spouse or unpaid carer. Phase 3, qualitative interviews with healthcare professionals (HCPs) working within various pain service types; 5-8 HCPs per service and up to 12 services including primary care, secondary care, tertiary centres and services with voluntary sector input. Phase 4, co-design workshops with older adults, HCPs and commissioners. Inclusion criteria (Phase 2): community-dwelling older adults (≥75 years) living with frailty and persistent pain. Exclusion criteria (Phase 2): care home residents, a dementia or cancer diagnosis. Cancer survivors, ≥5 years cancer free, and not undergoing active cancer treatment can participate. Analysis for Phase 1 will use narrative synthesis, Phase 2 will use grounded theory analysis and Phase 3 will use thematic analysis. Oversight is provided from a patient and public involvement group and an independent steering committee. ETHICS AND DISSEMINATION: The protocol was approved by Leeds-East Research Ethics Committee on 28 April 2022 (22/YH/0080). Consent is sought if an individual is willing to participate (Phases 2-4) and has capacity. Findings will be disseminated at conferences, in newsletters and journals and to local authorities and charities.

Circulating inflammatory biomarker responses in intervention trials in frail and sarcopenic older adults: A systematic review and meta-analysis.

Consistent with the inflammaging concept, cross-sectional associations have been established between inflammatory biomarkers, frailty and sarcopenia. Less certain is the value of inflammatory markers in monitoring potential anti-inflammatory effects of therapeutic interventions targeted at frailty and sarcopenia. The aims of this systematic review and meta-analysis are to determine if there is a measurable change in inflammatory or immune biomarkers in interventions that improve frailty or sarcopenia and 2. To determine if there are specific inflammatory biomarkers with greater sensitivity to change. In total, 3051 articles were scanned with 16, primarily exercise and nutrition interventions, included in the systematic review and 11 in the meta-analysis. At least one of C reactive protein (CRP), interleukin-6 (IL-6) or tumour necrosis factor alpha (TNF-α) was reduced in 10 of the 16 review studies but only 3/13 studies reported reductions in multiple markers. CRP, IL-6 and TNF-α were individually sensitive to change in 5/11, 3/12 and 5/12 studies respectively. In meta-analyses, there was a positive effect favouring intervention conditions for CRP (SMD = -0.28, p = 0.05) and IL-6 (SMD = -0.28, p = 0.05) but not TNF- α (SMD = -0.12, p = 0.48). There were specific issues with the quality of these studies which were not designed with an inflammatory marker as the primary outcome. In conclusion, interventions that improve frailty and sarcopenia can also reduce CRP, IL-6 and TNF-α but the literature lacks consistency. We are unable to conclude any one marker as being superior to others.

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Hype or Hope for Skeletal Muscle Anti-Frailty.

Steadily rising population ageing is a global demographic trend due to the advancement of new treatments and technologies in the medical field. This trend also indicates an increasing prevalence of age-associated diseases, such as loss of muscle mass (sarcopenia), which tends to afflict the older population. The deterioration in muscle function can cause severe disability and seriously affects a patient's quality of life. Currently, there is no treatment to prevent and reverse age-related skeletal muscle ageing frailty. Existing interventions mainly slow down and control the signs and symptoms. Mesenchymal stem cell-derived extracellular vesicle (MSC-EV) therapy is a promising approach to attenuate age-related skeletal muscle ageing frailty. However, more studies, especially large-scale randomised clinical trials need to be done in order to determine the adequacy of MSC-EV therapy in treating age-related skeletal muscle ageing frailty. This review compiles the present knowledge of the causes and changes regarding skeletal muscle ageing frailty and the potential of MSC-EV transplantation as a regenerative therapy for age-related skeletal muscle ageing frailty and its clinical trials.

EHRA expert consensus document on the management of arrhythmias in frailty syndrome, endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA).

There is an increasing proportion of the general population surviving to old age with significant chronic disease, multi-morbidity, and disability. The prevalence of pre-frail state and frailty syndrome increases exponentially with advancing age and is associated with greater morbidity, disability, hospitalization, institutionalization, mortality, and health care resource use. Frailty represents a global problem, making early identification, evaluation, and treatment to prevent the cascade of events leading from functional decline to disability and death, one of the challenges of geriatric and general medicine. Cardiac arrhythmias are common in advancing age, chronic illness, and frailty and include a broad spectrum of rhythm and conduction abnormalities. However, no systematic studies or recommendations on the management of arrhythmias are available specifically for the elderly and frail population, and the uptake of many effective antiarrhythmic therapies in these patients remains the slowest. This European Heart Rhythm Association (EHRA) consensus document focuses on the biology of frailty, common comorbidities, and methods of assessing frailty, in respect to a specific issue of arrhythmias and conduction disease, provide evidence base advice on the management of arrhythmias in patients with frailty syndrome, and identifies knowledge gaps and directions for future research.

Personalised Assessment and Rapid Intervention in Frail Patients With Lung Cancer: The Impact of an Outpatient Occupational Therapy Service.

INTRODUCTION: Lung cancer and its treatments cause or accelerate frailty, detrimentally affecting function and quality of life. Occupational therapists (OTs) provide global assessments and interventions, but services are often available for inpatients. The impact of holistic assessment and early intervention in the outpatient setting is unknown. MATERIALS AND METHODS: A tertiary cancer center in North East England piloted a Lung Cancer Outpatient OT Service for patients with thoracic malignancy and a Clinical Frailty Scale Score (CFS) ≥ 5. Service effectiveness was evaluated through calculation of admission avoidance, hospital length-of-stay reduction, completion/impact of advance care planning and patient/family feedback. Demographics, frailty level, required interventions, and onward referrals were recorded. RESULTS: A total of 153 patients (median age of 71 (range 46-90) received OT assessment and intervention. 48% were in the lowest socioeconomic quintile. Median CFS score was 5 (mildly frail (range: 4-7)) at initial assessment. Total of 918 interventions were delivered (median: 5, IQR: 3-7, Range 0-22). 48% of patients engaged in future planning (national average: 10%-15% P < .0001) and 78.5% achieved preferred place of death (national average 30%). An estimated 37 hospital admissions were avoided. In admitted patients, average inpatient stay when known to the service was 6.5 days less than other frail lung cancer patients in our unit (95% CI 4-9.1 days P < .0001). Higher CFS was associated with poor survival (P < .05). CONCLUSION: Outpatient OT services can avoid and shorten hospital admissions through advance care planning, management of functional disruption, onward referral to other allied health professionals and palliative care. A comprehensive multidisciplinary outpatient service may benefit patients further and should be the focus of future research.

Effects of non-pharmacological interventions on psychological outcomes among older people with frailty: A systematic review and meta-analysis.

BACKGROUND: Older people with frailty are more likely to experience negative psychological well-being, depressive symptoms, anxiety, and stress. Deterioration of psychological outcomes, in turn, further aggravates the frailty status among this vulnerable population. Considering the undesirable effects of polypharmacy on older people, the use of non-pharmacological intervention has attracted increasing attention. However, the effects of non-pharmacological interventions on psychological outcomes are not clear. AIMS: This review aims to systematically identify and synthesise evidence to examine the effectiveness of non-pharmacological interventions on psychological outcomes among older people with frailty. METHODS: Eight electronic databases, including PubMed, MEDLINE, EMBASE, CINAHL, APA PsycInfo, Cochrane Library, CNKI and WANFANG were searched from inception to 14 November 2022. Randomised controlled trials and clinical controlled trials of non-pharmacological interventions on psychological outcomes in older people with frailty were included. The quality of the included studies was assessed using The Cochrane Risk of Bias Tool v2. Meta-analysis was performed using the RevMan5.3. The certainty of the evidence was evaluated by GRADE approach. RESULTS: A total of 4726 articles were initially identified and screened for title and abstract. Eventually, 13 articles from 11 studies were included in this review. The results of the overall risk of bias indicated that four studies had low risk; five studies had some concerns, and two studies had high risk. Four types of intervention were identified, including physical exercise (n = 3), complementary and alternative medicine (music therapy = 1, acupressure = 1), case management (n = 5), and advance care planning (n = 1). The pooled analysis showed that group-based physical exercise had significant beneficial effects on depressive symptoms (SMD: -0.46, 95% CI: -0.81 to -0.10, p = .01; low certainty). There is no difference between the effects of case management and usual care on depressive symptoms (SMD: 0.02, 95% CI: -0.14 to 0.19, p = .79; high certainty). Narrative synthesis of evidence suggested the effects of complementary and alternative medicine on improving depressive symptoms and general mental status. CONCLUSIONS: Psychological outcomes in older people with frailty are understudied. Group-based physical exercise could be a strategy to reduce depressive symptoms among older people with frailty. There is limited evidence showing the effects of complementary and alternative medicine on improving psychological outcomes. More rigorous trials are needed to examine the effects of non-pharmacological interventions on psychological outcomes among older people with frailty. REGISTRATION: (PROSPERO): CRD42022303370.