Poor Nutritional Status Is Associated with Death in a Population of Dialyzed Older Persons.

BACKGROUND: Older patients in hemodialysis have high prevalence of malnutrition that is often associated with rapid weight loss till cachexia. OBJECTIVES: We aimed to investigate whether in older patients undergoing hemodialysis the association between poor nutritional status and mortality may be independent of comorbidities and other risk factors. DESIGN: Retrospective longitudinal study. SETTING: Unit of Nephrology, Dialysis and Kidney Transplantation of the Policlinic Hospital of Milan, Milan, Italy. PARTICIPANTS: A total of 107 prevalent patients undergoing hemodialysis for at least three months. MEASUREMENTS: Sociodemographic, clinical, and biological data were recorded. Unintentional weight loss (UWL) was defined as loss of body weight > 5% in 3 months or > 10% in 6 months. We computed a 21-item Frailty Index that included clinical conditions associated with malnutrition and mortality in this population. Unadjusted and adjusted Cox proportional hazard models were performed to test the association of UWL, albumin and transferrin levels with death. Survival analyses based on Kaplan-Meier estimates were performed. RESULTS: Patients' age was 79 (±7.7) years; 38 (35%) were women. Thirty-one patients (29%) died during follow-up. Eighteen (16.8%) patients experienced UWL during the follow-up period. UWL was positively associated with death in the unadjusted model and even after the progressive inclusion of potential confounders. Low albumin levels were positively associated with death only in the unadjusted and partially adjusted models while low transferrin levels were not associated with death in none of the models. Mortality was significantly higher in those patients experiencing both UWL and albumin levels below 3.5 mg/dL. CONCLUSIONS: In older patients undergoing chronic hemodialysis UWL is associated with mortality independently of comorbidities and other risk factors. Patients presenting both UWL and low albumin levels were those experiencing the worst outcomes in terms of mortality.

The Impact of Delirium on Recovery in Geriatric Rehabilitation after Acute Infection.

OBJECTIVES: Delirium is common during acute infection in older patients and is associated with functional decline. Geriatric rehabilitation (GR) can help older patients to return to their premorbid functional level. It is unknown whether delirium affects GR outcomes in patients with acute infection. We evaluated whether delirium affects trajectories of activities of daily living (ADL) and quality of life (QoL) recovery in GR after COVID-19 infection. DESIGN: This study was part of the EU-COGER study, a multicenter cohort study conducted between October 2020 and October 2021. SETTING AND PARTICIPANTS: Participants were recruited after COVID-19 infection from 59 GR centers in 10 European countries. METHODS: Data were collected at GR admission, discharge, and at the 6-week and 6-month follow-ups. Trajectories of ADL [using the Barthel index (BI)] and QoL [using the EuroQol-5 Dimensions-5 Level (EQ-5D-5L)] recovery were examined using linear mixed models. RESULTS: Of the 723 patients included (mean age 75.5 ± 9.9 years; 52.4% male), 28.9% had delirium before or during GR admission. Participants with delirium recovered in ADL at approximately the same rate as those without (linear slope effect = -0.13, SE 0.16, P = .427) up to an estimated BI score of 16.1 at 6 months. Similarly, participants with delirium recovered in QoL at approximately the same rate as those without (linear slope effect = -0.017, SE 0.015, P = .248), up to an estimated EQ-5D-5L score of 0.8 at 6 months. CONCLUSIONS AND IMPLICATIONS: Presence of delirium during the acute phase of infection or subsequent GR did not influence the recovery trajectory of ADL functioning and QoL.

Social Vulnerability, Frailty and Self-Perceived Health: Findings from The Irish Longitudinal Study on Ageing (TILDA).

BACKGROUND: Social vulnerability interacts with frailty and influences individuals' health status. Although frailty and social vulnerability are highly predictive of adverse outcomes, their relationship with self-perceived health(SPH) has been less investigated. METHODS: Data are from the Irish Longitudinal Study on Ageing(TILDA), a population-based longitudinal study of ageing. We included 4,222 participants aged ≥50 years (age 61.4±8.5 years;women 56%) from Wave 1 (2009-2011) followed over three longitudinal waves (2012,2014-2015,2016). Participants responded to single questions with five response options to rate their 1)physical health, 2)mental health, and 3)health compared to peers. 30-item Frailty (FI) and Social Vulnerability (SVI) indices were calculated using standardised methods. Multivariable regression analyses were performed to establish the association between FI and SVI cross-sectionally and longitudinally over 6 years. RESULTS: Cross-sectionally, SVI (mean:0.40±0.08; range:0.14-0.81) and FI (mean: 0.13±0.08; range:0.10-0.58) were modestly correlated (r=0.256), and independently associated with poor physical health (SVI: OR 1.43, 95%CI 1.15-1.78; FI: OR 3.16, 95%CI 2.54-3.93), poor mental health (SVI: OR 1.65, 95%CI 1.17-2.35; FI: OR 3.64, 95%CI 2.53-5.24), and poor health compared to peers (SVI: OR 1.41,95%CI 1.06-1.89; FI: OR 3.86, 95%CI 2.9-5.14). Longitudinally, FI and SVI were independently and positively associated with poor physical health (SVI: ß 1.08, 95%CI 0.76-1.39; FI: ß 1.97, 95%CI 1.58-2.36), poor mental health (SVI: ß 1.18, 95%CI 0.86-1.5; FI: ß 1.58, 95%CI 1.2-1.97), and poor overall health compared to peers (SVI: ß 0.78, 95%CI 0.89-1.33; FI: ß 1.74, 95%CI 0.47-1.1). CONCLUSIONS: In a large cohort of community-dwelling older adults, frailty and social vulnerability were associated with poor SPH and with risk of SPH decline over six years.

Relationship among Age, Education and Frailty in Older Persons.

Preliminary data suggest that frailty tend to increase with age and is associated with fewer years of formal education. However, it is still unclear whether age and education synergistically act in the definition of frailty. Aim of the study is to evaluate the interaction between age and education in defining frailty in community-dwelling older persons. We considered 911 community-dwelling older adults (mean age 79.5 years) who underwent a comprehensive geriatric assessment. Our results showed that education and age interact in the definition of frailty following an exponential-type relationship. Whereas age is a non-modifiable risk factor, much can be done to address the social component of frailty here represented by education. The reported interaction suggests that social interventions might be particularly effective at an older age, paving the way for multidisciplinary interventions beyond the clinical field.

IDH mutations in G2-3 conventional central bone chondrosarcoma: a mono institutional experience.

BACKGROUND: Heterozygous isocitrate dehydrogenase (IDH) mutations occur in about half of conventional central bone chondrosarcomas (CCBC). Aim of this study was to assess the frequency and prognostic impact of IDH mutations in high grade CCBC patients. METHODS: 64 patients with G2 and G3 CCBC were included. DNA extraction, PCR amplification of IDH1/2 exon 4s, and sequencing analysis with Sanger were performed. RESULTS: IDH mutations were detected in 24/54 patients (44%): IDH1 in 18, IDH2 in 4, and both IDH1/2 in 2 patients. The frequency of mutations was 37% in G2 vs. 69% in G3 (p = 0.039), and 100% in three Ollier disease associated chondrosarcoma. 5-year overall survival (OS) at 124 months (range 1-166) was 51%, with no significant difference based on the IDH mutational status: 61% in IDHmut vs. 44% in IDH wild type (IDHwt). The 5-year relapse free survival (RFS) was 33% (95% CI:10-57) for IDHmut vs. 57% (95%CI: 30-77) for IDHwt. Progression free survival (PFS) was 25% (95%CI:1-65) IDHmut vs. 16% (95%CI: 0.7-52) IDHwt. 55% (5/9) of IDHmut G2 became higher grade at the recurrence, as compared with 25% (3/12) of G2 IDHwt. CONCLUSIONS: This study shows a higher frequency of IDH mutations in G3 CCBC as compared with G2. No significant differences in OS, RFS, and PFS by mutational status were detected. After relapse, a higher rate of G3 for IDH mutated CCBC was observed.

The Number of Medications Is Associated with Fractures in a Population of Dialyzed Older Patients with Frailty.

Older persons with chronic kidney disease (CKD) undergoing hemodialysis represent a growing portion of patients characterized by high vulnerability but still marginally studied. This study aimed at exploring the relationship between the number of prescriptions and fractures in older patients with CKD undergoing hemodialysis. A 24-item Frailty Index (FI) based on sociodemographic, clinical and biological data was computed. Unadjusted and adjusted logistic regression models were performed to test the association of prescribed medications with history of fractures. A total of 107 older patients undergoing hemodialysis (38 [35.5%] women, mean age 79.1 standard deviation, SD=7.7) were included in the study. Mean number of prescribed medications was 9.9 (SD=3.9) and was significantly associated with fractures (OR 1.18, 95% CI 1.06-1.32, p=0.003), even after adjustment for potential confounders (OR 1.16, 95% CI 1.03-1.30, p=0.016). If these results will be confirmed, interventions based on deprescribing will become essential in older persons undergoing hemodialysis.

Assessment and Management of Appetite Loss in Older Adults: An ICFSR Task Force Report.

The Appetite loss in older people is an important unmet clinical need in geriatrics. The International Conference on Frailty and Sarcopenia Research (ICFSR) organized a Task Force on April 20th 2022, in Boston, to discuss issues related to appetite loss in older people, in particular, the assessment tools currently available, its evaluation in the primary care setting, and considerations about its management. There is a high heterogeneity in terms of the etiology of appetite loss in older people and a gold standard assessment tool for evaluating this condition is still absent. Although this may render difficult the management of poor appetite in clinical practice, validated assessment tools are currently available to facilitate early identification of appetite loss and support care decisions. As research on biomarkers of appetite loss progresses, assessment tools will soon be used jointly with biomarkers for more accurate diagnosis and prognosis. In addition, efforts to foster the development of drugs with a favorable risk/benefit ratio to combat poor appetite should be strengthened.

Resilience: Biological Basis and Clinical Significance - A Perspective Report from the International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force.

The Resilience is a construct receiving growing attention from the scientific community in geriatrics and gerontology. Older adults show extremely heterogeneous (and often unpredictable) responses to stressors. Such heterogeneity can (at least partly) be explained by differences in resilience (i.e., the capacity of the organism to cope with stressors). The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met in Boston (MA,USA) on April 20, 2022 to discuss the biological and clinical significance of resilience in older adults. The identification of persons with low resilience and the prompt intervention in this at-risk population may be critical to develop and implement preventive strategies against adverse events. Unfortunately, to date, it is still challenging to capture resilience, especially due to its dynamic nature encompassing biological, clinical, subjective, and socioeconomic factors. Opportunities to dynamically measure resilience were discussed during the ICFSR Task Force meeting, emphasizing potential biomarkers and areas of intervention. This article reports the results of the meeting and may serve to support future actions in the field.

Frailty and Persistent Pain in Oncological Patients Undergoing Rehabilitation.

OBJECTIVES: Pain is one of the most common symptoms among oncological patients and has a strong negative impact on quality of life. The aim of this study is to assess if frailty and polypharmacy are associated with persistent pain in oncological patients undergoing rehabilitation. DESIGN: Observational, prospective, longitudinal study. SETTING AND PARTICIPANTS: Data are from oncological patients admitted to the Oncological Rehabilitation Unit. METHODS: Presence of pain, its intensity and characteristics were evaluated at the admission and after 7 days. A Frailty Index (FI) was computed from Comprehensive Geriatric Assessment (CGA) data. RESULTS: Among the 45 consecutively recruited patients (mean age 72 years, woman 44%), pain was present in 20 (44%) patients at the admission and 9 (20%) after 7 days of stay. Forty-one patients (92%) were taking more than 5 drugs at the admission (mean 9 drugs). The FI was normally distributed and descriptive statistics define our population as frail (mean 0.44; range 0.23-0.64). The FI was significantly associated with the presence of pain (OR 2.66; 95%CI 1.13-6.27, p=0.03) and its intensity after 7 days from the admission (ß 4.24 95% CI 1.28 - 7.19, p=0.006), even after adjustment for potential confounders. CONCLUSIONS AND IMPLICATIONS: Investigating frailty in cancer patients to implement multidisciplinary strategies could play an important role in improving persistent pain.

Appetite Loss and Anorexia of Aging in Clinical Care: An ICFSR Task Force Report.

Appetite loss/anorexia of aging is a highly prevalent and burdensome geriatric syndrome that strongly impairs the quality of life of older adults. Loss of appetite is associated with several clinical conditions, including comorbidities and other geriatric syndromes, such as frailty. Despite its importance, appetite loss has been under-evaluated and, consequently, under-diagnosed and under-treated in routine clinical care. The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met virtually on September 27th 2021 to debate issues related to appetite loss/anorexia of aging. In particular, topics related to the implementation and management of appetite loss in at-risk older adult populations, energy balance during aging, and the design of future clinical trials on this topic were discussed. Future actions in this field should focus on the systematic assessment of appetite in the care pathway of older people, such as the Integrated Care for Older People (ICOPE) program recommended by the World Health Organization. Moreover, clinical care should move from the assessment to the treatment of appetite loss/anorexia. Researchers continue to pursue their efforts to find out effective pharmacologic and non-pharmacologic interventions with a favorable risk/benefit ratio.

Challenges in the Development of Drugs for Sarcopenia and Frailty - Report from the International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force.

Sarcopenia and frailty represent two burdensome conditions, contributing to a broad spectrum of adverse outcomes. The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met virtually in September 2021 to discuss the challenges in the development of drugs for sarcopenia and frailty. Lifestyle interventions are the current mainstay of treatment options in the prevention and management of both conditions. However, pharmacological agents are needed for people who do not respond to lifestyle modifications, for those who are unable to adhere, or for whom such interventions are inaccessible/unfeasible. Preliminary results of ongoing trials were presented and discussed. Several pharmacological candidates are currently under clinical evaluation with promising early results, but none have been approved for either frailty or sarcopenia. The COVID-19 pandemic has reshaped how clinical trials are conducted, in particular by enhancing the usefulness of remote technologies and assessments/interventions.

Frailty in Caregivers and Its Relationship with Psychological Stress and Resilience: A Cross-SectionalStudy Based on the Deficit Accumulation Model.

BACKGROUND: Studies increasingly suggest that chronic exposure to psychological stress can lead to health deterioration and accelerated ageing, thus possibly contributing to the development of frailty. Recent approaches based on the deficit accumulation model measure frailty on a continuous grading through the "Frailty Index" (FI), i.e. a macroscopic indicator of biological senescence and functional status. OBJECTIVES: The study aimed at testing the relationship of FI with caregiving, psychological stress, and psychological resilience. DESIGN: Cross-sectional study, with case-control and correlational analyses. PARTICIPANTS: Caregivers of patients with dementia (n=64), i.e. individuals a priori considered to be exposed to prolonged psychosocial stressors, and matched controls (n=64) were enrolled. MEASUREMENTS: The two groups were compared using a 38-item FI condensing biological, clinical, and functional assessments. Within caregivers, the association of FI with Perceived Stress Scale (PSS) and Brief Resilience Scale (BRS) was tested. RESULTS: Caregivers had higher FI than controls (F=8.308, p=0.005). FI was associated directly with PSS (r=0.660, p<0.001) and inversely with BRS (r=-0.637, p<0.001). Findings remained significant after adjusting for certain confounding variables, after excluding from the FI the conditions directly related to psychological stress, and when the analyses were performed separately among participants older and younger than 65 years. CONCLUSIONS: The results provide insight on the relationship of frailty with caregiving, psychological stress, and resilience, with potential implications for the clinical management of individuals exposed to chronic emotional strain.

Frailty Is Associated with Impaired Diabetic Foot Ulcer Healing and All-Cause Re-Hospitalization.

BACKGROUND: Diabetic Foot Ulcers (DFUs) are a common and feared complication of type 1 and type 2 diabetes. People with DFUs often present a significant clinical complexity due to multimorbidity, frailty, polypharmacy, and disabling conditions. Frailty, defined using the accumulation of health deficits model, has shown to predict worsening health status, hospitalizations, and death in older persons. There are no clinical studies, to date, that have examined the prevalence and effect of frailty on DFUs outcomes. The aim of our study was to explore the impact of frailty on DFUs healing and re-hospitalization in a cohort of patients hospitalized with DFUs. DESIGN: prospective cohort study. SETTING AND PARTICIPANTS: The frailty status of 76 consecutive hospitalized patients with DFUs was assessed by using the Frailty Index (FI). MEASUREMENTS: The primary outcome was the non-healing of the DFU. Secondary outcome was re-hospitalization events (for any cause) within 6 months from hospital discharge. Frailty was defined as FI>0.25. RESULTS: Out of 76 patients (median age 65 years, range 31-84), 56 (74%) were frail. At six months, 81.5% of frail patients had non-healing of the DFU compared to 55% in non-frail patients (p=0.02). The rate of of re-hospitalization was also higher in frail compared to non-frail (90.3% vs 54%, respectively; p=0.01) patients. In multivariable analyses, frailty was significantly associated with a more than fivefold increased risk of DFU non-healing [odds ratio 5.54 (95% confidence interval 1.28-23.91), p=0.02]. Similarly, re-hospitalization was also significantly higher in frail patients compared to the non-frail ones. CONCLUSIONS: In hospitalized patients with DFUs, frailty was highly prevalent. Frailty emerged as an independent risk factor for DFU non-healing and re-hospitalization events. Patients with DFUs require a comprehensive assessment of their frailty status which would enable personalization of their management and interventions.

Molecular phylogenetics, speciation, and long distance dispersal in tardigrade evolution: A case study of the genus Milnesium.

Microorganisms (sensu lato, i.e., including micrometazoans) are thought to have cosmopolitan geographic distributions due to their theoretically unlimited dispersal capabilities, a consequence of their tiny size, population dynamics, and resistant forms. However, several molecular studies of microorganisms have identified biogeographic patterns indicating cryptic speciation and/or weak species definitions. Using a multi-locus approach with the genus Milnesium (Tardigrada), we aimed to determine the genetic structure of populations worldwide and the effects of long distance dispersal (LDD) on genetic connectivity and relationships across the six continents. Our results on this micrometazoan's genetic structure and LDD at global and micro-local scales indicate contrasting patterns not easily explained by a unique or simple phenomenon. Overall, we report three key findings: (i) confirmation of long distance dispersal for tardigrades, (ii) populations with globally-shared or endemic micro-local haplotypes, and (iii) a supported genetic structure instead of the homogeneous genetic distribution hypothesized for microorganisms with LDD capabilities. Moreover, incongruences between our morphological and molecular results suggest that species delimitation within the genus Milnesium could be problematic due to homoplasy. Duality found for Milnesium populations at the global scale, namely, a molecular phylogenetic structure mixed with widely distributed haplotypes (but without any apparent biogeographic structure), is similar to patterns observed for some unicellular, prokaryotic and eukaryotic, microorganisms. Factors influencing these patterns are discussed within an evolutionary framework.

Impact of Age, Frailty, and Dementia on Prescribing for Type 2 Diabetes at Hospital Discharge 2012-2016.

BACKGROUND: The risks of intensive blood glucose lowering may outweigh the benefits in vulnerable older people. OBJECTIVES: Our primary aim was to determine whether age, frailty, or dementia predict discharge treatment types for patients with type 2 diabetes (T2D) and related complications. Secondly, we aimed to determine the association between prior hypoglycemia and discharge treatment types. DESIGN, SETTING AND PARTICIPANTS: We conducted a cohort study involving 3,067 patients aged 65-99 years with T2D and related complications, discharged from Melbourne's Eastern Health Hospital Network between 2012 and 2016. MEASUREMENTS: Multinomial logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CI) for the association between age, frailty, dementia and hypoglycemia, and being prescribed insulin-only, non-insulin glucose-lowering drugs (GLDs) or combined insulin and non-insulin GLDs compared to no GLD. International Classification of Diseases-10 codes were used to identify dementia status and prior hypoglycemia; frailty was quantified using the Hospital Frailty Risk Score. RESULTS: Insulin-only, non-insulin GLDs, combined insulin and non-insulin GLDs, and no GLDs were prescribed to 19%, 39%, 20%, and 23% of patients, respectively. Patients >80 years were less likely than patients aged 65-80 to be prescribed any of the GLD therapies, (eg. non-insulin GLDs [OR 0.67; 95%CI 0.55-0.82]), compared to no GLD. Similarly, high vs. low frailty scores were associated with not being prescribed any of the three GLD therapies, (eg. non-insulin GLDs [OR 0.63; 95%CI 0.45-0.87]). However, dementia was not associated with discharge prescribing of GLD therapies. Patients with a hypoglycemia-related admission were more likely than those not hospitalized with hypoglycemia to receive insulin-only (OR 4.28; 95%CI 2.89-6.31). CONCLUSIONS: Clinicians consider age and frailty when tailoring diabetes treatment regimens for patients discharged from hospital with T2D and related complications. There is scope to optimize prescribing for patients with dementia and for those admitted with hypoglycemia.