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Frailty represents a state of susceptibility to stressors and constitutes a dynamic process. Untreated, this state can progress to disability. Hence, timely detection of alterations in patients' frailty status is imperative to institute prompt clinical interventions and impede frailty progression. With this aim, the FACET (Frailty Care and Well Function) technological ecosystem was developed to provide clinically gathered data from the home to a medical team for early intervention. The aim of this study was to assess whether the FACET technological ecosystem prevents frailty progression and improves frailty status, according to the frailty phenotype criteria and Frailty Trait Scale-5 items (FTS-5) at 3 and 6 months of follow-up. This randomized clinical trial involved 90 older adults aged ≥70 years meeting 2 or more Fried frailty phenotype criteria, having 4 or more comorbidities, and having supervision at home. This study was conducted between August 2018 and June 2019 at the geriatrics outpatient clinics in Getafe University Hospital and Albacete University Hospital. Participants were randomized into a control group receiving standard treatment and the intervention group receiving standard treatment along with the FACET home monitoring system. The system monitored functional tests at home (gait speed, chair stand test, frailty status, and weight). Outcomes were assessed using multivariate linear regression models for continuous response and multivariate logistic models for dichotomous response. P values less than .05 were considered statistically significant. The mean age of the participants was 82.33 years, with 28% (25/90) being males. Participants allocated to the intervention group showed a 74% reduction in the risk of deterioration in the FTS-5 score (P=.04) and 92% lower likelihood of worsening by 1 point according to Fried frailty phenotype criteria compared to the control group (P=.02) at 6 months of follow-up. Frailty status, when assessed through FTS-5, improved in the intervention group at 3 months (P=.004) and 6 months (P=.047), while when the frailty phenotype criteria were used, benefits were shown at 3 months of follow-up (P=.03) but not at 6 months. The FACET technological ecosystem helps in the early identification of changes in the functional status of prefrail and frail older adults, facilitating prompt clinical interventions, thereby improving health outcomes in terms of frailty and functional status and potentially preventing disability and dependency. ClinicalTrials.gov NCT03707145; https://clinicaltrials.gov/study/NCT03707145.

Sarcopenia, the age-dependent loss of muscle mass and function, is a common condition among older adults, and is associated with several adverse health outcomes. Owing to the impact of sarcopenia on quality of life, disability and mortality, a greater awareness is necessary in order to correctly identify the condition both in community and geriatric settings. Research on sarcopenia prevention and treatment is developing quickly, but many questions are still unanswered. The core of the sarcopenia condition involves quantitative and qualitative losses of skeletal muscle. These two dimensions should therefore be considered when designing and testing preventive and therapeutic interventions. The recently released operationalization of sarcopenia by the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project allows for the framing of an objective, standardized, and clinically relevant condition, which should facilitate its translation into the clinical arena as well as its adoption by public health and regulatory agencies. Such a conceptualization might eventually encourage key stakeholders to combine their efforts in approaching the sarcopenia condition. Bearing these considerations in mind, the “Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies” project has operationalized a specific condition, named physical frailty and sarcopenia (PF&S), characterized by the combination of low physical performance (based on the Short Physical Performance Battery) and low muscle mass (according to the FNIH cut-points). A randomized controlled trial will be conducted to evaluate the efficacy of a multi-component intervention for preventing mobility disability and other adverse health outcomes in older adults with PF&S.

Sarcopenia a recognised geriatric syndrome. This study aims to evaluate the prevalence of possible sarcopenia, sarcopenia and severe sarcopenia among older Chinese adults and to identify any associated factors for possible sarcopenia according to the updated diagnostic criteria of the Asian Working Group for Sarcopenia 2019 (AWGS 2019). We used data from the China Health and Retirement Longitudinal Study (CHARLS). The main outcome of this study was possible sarcopenia. Handgrip strength was measured via a dynamometer. The muscle mass was estimated by anthropometric measures. Physical performance was measured by 5-time chair stand test and gait speed test. A multivariate logistic regression model with stepwise method was employed to identify factors associated with possible sarcopenia. A total of 6172 participants aged 60–94 years were included. The prevalence of possible sarcopenia, sarcopenia and severe sarcopenia was 38.5%, 18.6%, and 8.0%, respectively. Age, rural area, falls, higher C-reactive protein (CRP), and chronic diseases (including hypertension, chronic lung diseases, heart disease, psychiatric disease and arthritis) were associated with a higher risk of possible sarcopenia. Conversely, alcohol consumption, higher gait speed and high levels of hemoglobin were associated with decreased risk of possible sarcopenia. However, the associations between possible sarcopenia with alcohol consumption, heart disease, psychiatric disease and hemoglobin were not significant after Bonferroni correction. Our study reported a relatively high prevalence of sarcopenia among older Chinese population, and identified a range of factors associated with sarcopenia. We also found rural elders are more vulnerable to sarcopenia than urban elders. Additionally, we discovered systemic inflammation might be one of the contributing factors between sarcopenia and related comorbidities. We believe the findings of this study would help to identify individuals at high risk of sarcopenia early and therefore implement the prevention and treatment strategies to reduce the disease burden in China.

Elderly patients (aged ≥65 years) with acute myeloid leukaemia have poor outcomes and no effective standard-of-care therapy exists. Treatment with hypomethylating agents such as azacitidine and decitabine is common, but responses are modest and typically short-lived. The oral anti-apoptotic B-cell lymphoma 2 protein inhibitor, venetoclax, has shown promising single-agent activity in patients with relapsed or refractory acute myeloid leukaemia and preclinical data suggested synergy between hypomethylating agents and venetoclax, which led to this combination phase 1b study. Previously untreated patients aged 65 years and over with acute myeloid leukaemia who were ineligible for standard induction therapy were enrolled into this non-randomised, open-label, phase 1b study. Patients were required to have an Eastern Cooperative Oncology Group performance status of 0–2 and either intermediate-risk or poor-risk cytogenetics. Patients were enrolled into one of three groups for the dose-escalation phase of this study: group A (venetoclax and intravenous decitabine 20 mg/m2 [days 1–5 of each 28-day cycle]), group B (venetoclax and subcutaneous or intravenous azacitidine 75 mg/m2 [days 1–7 of each 28-day cycle]), and group C (a venetoclax and decitabine substudy with the oral CYP3A inhibitor posaconazole, 300 mg twice on cycle 1, day 21, and 300 mg once daily from cycle 1, days 22–28, to assess its effect on venetoclax pharmacokinetics). Dose escalation followed a standard 3 + 3 design with at least three evaluable patients enrolled per cohort; daily target doses of venetoclax for groups A and B were 400 mg (cohort 1), 800 mg (cohorts 2 and 3), and 1200 mg (cohort 4), and 400 mg for group C. The primary endpoints were the safety and pharmacokinetics of venetoclax plus decitabine or azacitidine, and to determine the maximum tolerated dose and recommended phase 2 dose. Secondary endpoints included the preliminary anti-leukaemic activity of venetoclax with decitabine or azacitidine through the analysis of overall response, duration of response, and overall survival. We analysed safety, pharmacokinetics, and anti-leukaemic activity in all patients who received one or more venetoclax doses. The expansion phase of the study is ongoing but is closed to accrual. This trial is registered with ClinicalTrials.gov, number NCT02203773. 57 patients were enrolled in the study. 23 patients in group A and 22 patients in group B were enrolled between Nov 19, 2014, and Dec 15, 2015, and 12 patients in group C were enrolled between June 14, 2015, and Jan 16, 2016. As of data cutoff on June 15, 2016, the most common grade 3–4 treatment-emergent adverse events were thrombocytopenia (27 [47%] of 57 patients; nine in group A, 13 in group B, and five in group C), febrile neutropenia (24 [42%] of 57; 11 in group A, ten in group B, and three in group C), and neutropenia (23 [40%] of 57; 12 in group A, eight in group B, and three in group C). The most common serious treatment-emergent adverse event in groups A and B was febrile neutropenia (seven [30%] of 23 patients vs seven [32%] of 22), whereas in group C it was lung infection (four [33%] of 12 patients). 49 (86%) of 57 patients had treatment-related adverse events; the most common in groups A and B included nausea (12 [52%] patients vs seven [32%] patients), fatigue (six [26%] patients vs seven [32%]), and decreased neutrophil count (six [26%] patients vs six [27%]), whereas in group C the most common were nausea (seven [58%] of 12 patients), leucopenia (six [50%]), vomiting (five [42%]), and decreased platelet count (five [42%]). The maximum tolerated dose was not reached. The recommended phase 2 dose was 400 mg once a day or 800 mg with an interrupted dosing schedule (safety expansion). In total, four (7%) of 57 patients had died within 30 days of the first venetoclax dose caused by sepsis (group B), bacteraemia (group A), lung infection (group C), and respiratory failure (group A). Tumour lysis syndrome was not observed. Decitabine and azacitidine did not substantially affect venetoclax exposures. Overall, 35 (61%; 95% CI 47·6–74·0) of 57 patients achieved complete remission or complete remission with incomplete marrow recovery. In groups A and B, 27 (60%; 95% CI 44·3–74·3) of 45 patients had complete remission or complete remission with incomplete marrow recovery. Venetoclax plus hypomethylating agent therapy seems to be a novel, well-tolerated regimen with promising activity in this underserved patient population. Evaluation of expansion cohorts is ongoing at 400 mg and 800 mg doses using both hypomethylating agent combinations. AbbVie and Genentech.

Using machine learning techniques, we developed a brief questionnaire to aid neurologists and neuropsychologists in the screening of mild cognitive impairment (MCI) and dementia. With the reduction of the survey size as a goal of this research, feature selection based on information gain was performed to rank the contribution of the 45 items corresponding to patient responses to the specified questions. The most important items were used to build the optimal screening model based on the accuracy, practicality, and interpretability. The diagnostic accuracy for discriminating normal cognition (NC), MCI, very mild dementia (VMD) and dementia was validated in the test group. The screening model (NMD-12) was constructed with the 12 items that were ranked the highest in feature selection. The receiver-operator characteristic (ROC) analysis showed that the area under the curve (AUC) in the test group was 0.94 for discriminating NC vs. MCI, 0.88 for MCI vs. VMD, 0.97 for MCI vs. dementia, and 0.96 for VMD vs. dementia, respectively. The NMD-12 model has been developed and validated in this study. It provides healthcare professionals with a simple and practical screening tool which accurately differentiates NC, MCI, VMD, and dementia.

Background Multimorbidity and frailty are often associated and Comprehensive Geriatric Assessment (CGA) is considered the gold standard of care for these patients. Aims This study aimed to evaluate the effect of outpatient Comprehensive Geriatric Assessment (CGA) on frailty in community-dwelling older people with multimorbidity and high health care utilization. Methods The Ambulatory Geriatric Assessment—Frailty Intervention Trial (AGe-FIT) was a randomized controlled trial (intervention group, n  = 208, control group n  = 174) with a follow-up period of 24 months. Frailty was a secondary outcome. Inclusion criteria were: age ≥ 75 years, ≥ 3 current diagnoses per ICD-10, and ≥ 3 inpatient admissions during 12 months prior to study inclusion. The intervention group received CGA-based care and tailored interventions by a multidisciplinary team in an Ambulatory Geriatric Unit, in addition to usual care. The control group received usual care. Frailty was measured with the Cardiovascular Health Study (CHS) criteria. At 24 months, frail and deceased participants were combined in the analysis. Results Ninety percent of the population were frail or pre-frail at baseline. After 24 months, there was a significant smaller proportion of frail and deceased ( p  = 0.002) and a significant higher proportion of pre-frail patients in the intervention group ( p  = 0.004). Mortality was high, 18% in the intervention group and 26% in the control group. Conclusion Outpatient CGA may delay the progression of frailty and may contribute to the improvement of frail patients in older persons with multimorbidity.

BackgroundOlder adults receiving cancer therapy have heightened risk for treatment-related toxicity. Geriatric assessment (GA) can identify impairments, which may contribute to vulnerability and adverse outcomes. GA management interventions can address these impairments and have the potential to improve outcomes when implemented.MethodsWe conducted a randomized pilot study comparing GA with management interventions versus usual care in patients with stage III/IV solid tumor malignancies (N = 71). In all patients, a trained coordinator conducted and scored a baseline GA with pre-determined cutoffs for impairment. For patients randomized to the intervention arm, an algorithm was used to identify GA management recommendations based upon identified impairments. Recommendations were relayed to the primary oncologist for implementation. GA was repeated at 3 months. The primary outcome was grade 3–5 chemotherapy toxicity. Secondary outcomes included feasibility, hospitalizations, dose reductions, dose delays, and early treatment discontinuation.ResultsThe mean participant age was 76 (70–89). The total number of GA management recommendations relayed was 409, of which 35.4% were implemented by the primary oncologist. Incidence of grade 3–5 chemotherapy toxicity did not differ between the two groups. Prevalence of hospitalization, dose reductions, dose delays, and early treatment discontinuation also did not differ between the two groups.ConclusionsAn algorithm can be used to guide GA management recommendations in older adults with cancer. However, reliance upon the primary oncologist for execution resulted in a low prevalence of implementation. Future work should aim to understand barriers to implementation and explore alternate models of implementing geriatric-focused care for older adults with cancer.

Background The capacity of Short-Physical Performance Battery (SPPB) test to discriminate between fallers and non-fallers is controversial, and has never been compared with fall risk assessment-specific tools, such as Performance-Oriented Mobility Assessment (POMA). Aim To verify the association of SPPB and POMA scores with falls in older outpatients. Methods 451 older subjects (150 males, mean age 82.1 ± 6.8) evaluated in a geriatric outpatient clinic for suspected frailty were enrolled in this cross-sectional study. Self-reported history of falls and medication history were carefully assessed. Each participant underwent comprehensive geriatric assessment, including SPPB, POMA, Geriatric Depression Scale (GDS), mini-mental state examination (MMSE) and mini-nutritional assessment-short form (MNA-SF). Multivariate logistic regression and receiver-operating characteristic (ROC) analyses were performed to determine the factors associated with the status of faller. Results 245 (54.3%) subjects were identified as fallers. They were older and had lower SPPB and POMA test scores than non-fallers. At ROC analysis, SPPB (AUC 0.676, 95% CI 0.627–0.728, p  < 0.001) and POMA (AUC 0.677, 95% CI 0.627–0.726, p  < 0.001) scores were both associated with falls. At multivariate logistic regression models, SPPB total score (OR 0.83, 95% CI 0.76–0.92, p  < 0.001), POMA total score (OR 0.94, 95% CI 0.91–0.98, p  = 0.002) and SPPB balance score alteration (OR 2.88, 95% CI 1.42–5.85, p  = 0.004), but not POMA balance subscale score alteration, were independently associated with recorded falls, as also GDS, MMSE and MNA-SF scores. Conclusions SPPB total score was independently associated with reported falls in older outpatients, resulting non-inferior to POMA scale. The use of SPPB for fall risk assessment should be implemented.

Background Longer length of hospital stay (LOS) negatively affects the organizational efficiency of public health systems and both clinical and functional aspects of older patients. Data on the effects of transitional care programs based on multicomponent interventions to reduce LOS of older patients are scarce and controversial. Aims The PRO‐HOME study aimed to assess the efficacy in reducing LOS of a transitional care program involving a multicomponent intervention inside a technologically monitored in‐hospital discharge facility. Methods This is a Randomized Clinical Trial on 60 patients (≥65 years), deemed stable and dischargeable from the Acute Geriatrics Unit, equally assigned to the Control Group (CG) or Intervention Group (IG). The latter underwent a multicomponent intervention including lifestyle educational program, cognitive and physical training. At baseline, multidimensional frailty according to the Multidimensional Prognostic Index (MPI), and Health‐Related Quality of Life (HRQOL) were assessed in both groups, along with physical capacities for the IG. Enrolled subjects were evaluated after 6 months of follow‐up to assess multidimensional frailty, HRQOL, and re‐hospitalization, institutionalization, and death rates. Results The IG showed a significant 2‐day reduction in LOS (median days IG = 2 (2–3) vs. CG = 4 (3–6); p  < 0.001) and an improvement in multidimensional frailty at 6 months compared to CG (median score IG = 0.25(0.25–0.36) vs. CG = 0.38(0.31–0.45); p  = 0.040). No differences were found between the two groups in HRQOL, and re‐hospitalization, institutionalization, and death rates. Discussion Multidimensional frailty is a reversible condition that can be improved by reduced LOS. Conclusions The PRO‐HOME transitional care program reduces LOS and multidimensional frailty in hospitalized older patients. Trial registration : ClinicalTrials.gov n. NCT06227923 (retrospectively registered on 29/01/2024).

Background Delirium affects > 15% of hospitalised patients but is grossly underdetected, contributing to poor care. The 4 ‘A’s Test (4AT, www.the4AT.com ) is a short delirium assessment tool designed for routine use without special training. The primary objective was to assess the accuracy of the 4AT for delirium detection. The secondary objective was to compare the 4AT with another commonly used delirium assessment tool, the Confusion Assessment Method (CAM). Methods This was a prospective diagnostic test accuracy study set in emergency departments or acute medical wards involving acute medical patients aged ≥ 70. All those without acutely life-threatening illness or coma were eligible. Patients underwent (1) reference standard delirium assessment based on DSM-IV criteria and (2) were randomised to either the index test (4AT, scores 0–12; prespecified score of > 3 considered positive) or the comparator (CAM; scored positive or negative), in a random order, using computer-generated pseudo-random numbers, stratified by study site, with block allocation. Reference standard and 4AT or CAM assessments were performed by pairs of independent raters blinded to the results of the other assessment. Results Eight hundred forty-three individuals were randomised: 21 withdrew, 3 lost contact, 32 indeterminate diagnosis, 2 missing outcome, and 785 were included in the analysis. Mean age was 81.4 (SD 6.4) years. 12.1% (95/785) had delirium by reference standard assessment, 14.3% (56/392) by 4AT, and 4.7% (18/384) by CAM. The 4AT had an area under the receiver operating characteristic curve of 0.90 (95% CI 0.84–0.96). The 4AT had a sensitivity of 76% (95% CI 61–87%) and a specificity of 94% (95% CI 92–97%). The CAM had a sensitivity of 40% (95% CI 26–57%) and a specificity of 100% (95% CI 98–100%). Conclusions The 4AT is a short, pragmatic tool which can help improving detection rates of delirium in routine clinical care. Trial registration International standard randomised controlled trial number (ISRCTN) 53388093 . Date applied 30/05/2014; date assigned 02/06/2014.