Hasil untuk "Geriatrics"

Shuhao Que, Dieuwke van Dartel, Ilse Heeringa et al.

Physical activity during hip fracture rehabilitation is essential for mitigating long-term functional decline in geriatric patients. However, it is rarely quantified in clinical practice. Existing continuous monitoring systems with commercially available wearable activity trackers are typically developed in middle-aged adults and therefore perform unreliably in older adults with slower and more variable gait patterns. This study aimed to develop a robust human activity recognition (HAR) system to improve continuous physical activity recognition in the context of hip fracture rehabilitation. 24 healthy older adults aged over 80 years were included to perform activities of daily living (walking, standing, sitting, lying down, and postural transfers) under simulated free-living conditions for 75 minutes while wearing two accelerometers positioned on the lower back and anterior upper thigh. Model robustness was evaluated using leave-one-subject-out cross-validation. The synthetic data demonstrated potential to improve generalization across participants. The resulting feature intervention model (FIM), aided by synthetic data guidance, achieved reliable activity recognition with mean F1-scores of 0.896 for walking, 0.927 for standing, 0.997 for sitting, 0.937 for lying down, and 0.816 for postural transfers. Compared with a control condition model without synthetic data, the FIM significantly improved the postural transfer detection, i.e., an activity class of high clinical relevance that is often overlooked in existing HAR literature. In conclusion, these preliminary results demonstrate the feasibility of robust activity recognition in older adults. Further validation in hip fracture patient populations is required to assess the clinical utility of the proposed monitoring system.

Jie Shi, Hong Lei, Yu Zhang et al.

ABSTRACT Respiratory syncytial virus (RSV) ranks as the second leading cause of infant death globally and a significant contributor to morbidity and mortality among adults over 60 years old. The development of effective RSV vaccines and immunoprophylaxis remains a key focus. In our research, we formulated a protein‐based vaccine known as MF59/preF, which combines the RSV pre‐fusion (preF) antigen with an MF59‐like oil‐in‐water adjuvant. Intramuscular (IM) or intranasal (IN) immunization of the MF59‐adjuvanted preF protein vaccine elicited robust immune responses and neutralizing antibodies against both RSV A2 and RSV B strains, with the IM showing a particularly pronounced effect. Notably, IN immunization with MF59/preF demonstrated superior mucosal immunity, characterized by elevated levels of IgA antibodies and an increased frequency of tissue‐resident memory T (TRM) cells locally. More importantly, the combined IM and IN delivery of the MF59/preF vaccine synergistically enhanced antigen‐specific humoral and cellular immune responses at both systemic and mucosal sites. Our study highlights the crucial impact of the route of administration and adjuvanted‐protein subunit vaccines on triggering strong humoral and cellular immunity in mice.

Patricio Arrué, Kaveh Laksari, Nancy Sweitzer et al.

Background: Aortic stenosis (AS) is the most common acquired valvar disease and is associated with increased risk for frailty. Frailty as a geriatric syndrome is associated with muscle weakness and a compromised autonomic nervous system (ANS) performance in older adults. The purpose of the current work was to assess differences in both motor and ANS performance, and interaction between them, as symptoms of frailty in community dwelling older adults with and without AS. Results: Eighty-six participants were recruited, including 30 with (age=72$\pm$11, 10 non-frail and 20 pre-frail/frail) and 56 without AS (age=80$\pm$8, 12 non-frail and 44 pre-frail/frail). There was a significant difference in UEF motor score between older adults with and without AS (p<0.01, mean values of 0.57$\pm$0.25 and 0.48$\pm$0.23, respectively). Differences in UEF motor score was also observed between the frailty groups (p=0.02, mean values of 0.55$\pm$0.24 and 0.40$\pm$0.20 for pre-frail/frail and non-frail, respectively). CCM parameters showed significant differences between the frailty groups (p=0.02, mean CCM of 0.69$\pm$0.05 for non-frail and 0.54$\pm$0.03 for pre-frail/frail), but not between the AS groups (p>0.70). No significant interaction was observed between frailty and AS condition (p>0.08). Conclusion: Current findings suggest that ANS measures may be highly associated with frailty regardless of AS condition. Combining motor and HR dynamics parameters in a multimodal model may provide a promising tool for frailty assessment

Alessandro Gasparini, Michael J. Crowther, Emiel O. Hoogendijk et al.

Stepped wedge cluster-randomized trial (CRTs) designs randomize clusters of individuals to intervention sequences, ensuring that every cluster eventually transitions from a control period to receive the intervention under study by the end of the study period. The analysis of stepped wedge CRTs is usually more complex than parallel-arm CRTs due to more complex intra-cluster correlation structures. A further challenge in the analysis of closed-cohort stepped wedge CRTs, which follow groups of individuals enrolled in each period longitudinally, is the occurrence of dropout. This is particularly problematic in studies of individuals at high risk for mortality, which causes non-ignorable missing outcomes. If not appropriately addressed, missing outcomes from death will erode statistical power, at best, and bias treatment effect estimates, at worst. Joint longitudinal-survival models can accommodate informative dropout and missingness patterns in longitudinal studies. Specifically, within the joint longitudinal-survival modeling framework, one directly models the dropout process via a time-to-event submodel together with the longitudinal outcome of interest. The two submodels are then linked using a variety of possible association structures. This work extends linear mixed-effects models by jointly modeling the dropout process to accommodate informative missing outcome data in closed-cohort stepped wedge CRTs. We focus on constant intervention and general time-on-treatment effect parametrizations for the longitudinal submodel and study the performance of the proposed methodology using Monte Carlo simulation under several data-generating scenarios. We illustrate the methodology in practice by reanalyzing data from the 'Frail Older Adults: Care in Transition' (ACT) trial, a stepped wedge CRT of a multifaceted geriatric care model versus usual care in 35 primary care practices in the Netherlands.

Zhiwei Zhang, MD, Xiaoting Li, MD, Jiawei Zhuang, MD et al.

Summary: Recent evidence demonstrates that low engraftment rates limit the efficacy of human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) for cardiac repair after myocardial infarction. In this study, we attempted to overcome this limitation by enhancing the proliferative capacity of transplanted hiPSC-CMs. We found that miR-590-3p overexpression increased the proliferative capacity of hiPSC-CMs. miR-590-3p overexpression increased the number of engrafted cells and had a higher efficacy for myocardial repair than control cells. Moreover, we confirmed the safety of using miR-590-3p-overexpressing hiPSC-CMs in pig hearts. These results indicated that miR-590-3p overexpression stimulated hiPSC-CM cell cycle re-entry to induce cell proliferation and increased the therapeutic efficacy in MI.

Athagran Nakham, Christine Bond, Moira Cruickshank et al.

<b>Background:</b> Anticholinergic burden (ACB) from medications has been associated with adverse outcomes in older adults. <b>Aim:</b> The aim was to conduct a non-randomized feasibility study of an intervention to reduce the anticholinergic burden in older patients (REGENERATE) to inform a subsequent definitive trial. <b>Methods:</b> The development and evaluation of an ACB reduction intervention was guided by the Medical Research Council framework. Findings from preliminary studies, two systematic reviews, and two qualitative studies informed the design of a mixed-method feasibility study. The study was conducted in one UK primary care site. The clinical pharmacist identified and invited potentially eligible patients, reviewed their medications, and made recommendations to reduce the ACB as needed. Patients completed surveys at baseline and 6 and 12 weeks post-intervention. A purposive sample of patients and healthcare professionals was interviewed. <b>Results:</b> There was a response of 16/20; 14/16 attended the pharmacist-led consultation and completed the baseline questionnaire, and 13/14 completed both follow-up questionnaires. The sustainability of deprescribing was confirmed. The results suggest the potential of the intervention to reduce side effects from medications and improve quality of life (EQ-5D-5L). The interviews showed patients were happy with the study processes and the medication changes and were satisfied with the pharmacist’s consultation. <b>Conclusions:</b> This feasibility study demonstrated that a deprescribing/reducing ACB intervention in older adults is feasible in a primary care setting and may benefit patients. Well-designed RCTs and cost-effectiveness studies should be undertaken to confirm the benefits of ACB deprescribing in primary care settings.

Elisa Salsano, Oriana Rossi, Cecilia Rispoli et al.

The proportion of older adults using medical cannabis is rising. Most of the cannabinoid research has focused on a healthy, younger population free from frailty and major comorbidity. In this case report, we describe an 82-year-old woman who was autonomous in basic and instrumental activities of daily living and who came to our geriatric department for marked weight loss over the past 2 months (about 10 kg) and anemia. After appropriate clinical and endoscopic checks, it was concluded that the weight loss was induced by the initiation of therapy with oral cannabis for the control of rheumatic pain.

Aaron T. Seaman, Julia H. Rowland, Samantha J. Werts et al.

Introduction: Cancer rates increase with age, and older cancer survivors have unique medical care needs, making assessment of health status and identification of appropriate supportive resources key to delivery of optimal cancer care. Comprehensive geriatric assessments (CGAs) help determine an older person’s functional capabilities as cancer care providers plan treatment and follow-up care. Despite its proven utility, research on implementation of CGA is lacking.Methods: Guided by a qualitative description approach and through interviews with primary care providers and oncologists, our goal was to better understand barriers and facilitators of CGA use and identify training and support needs for implementation. Participants were identified through Cancer Prevention and Control Research Network partner listservs and a national cancer and aging organization. Potential interviewees, contacted via email, were provided with a description of the study purpose. Eight semi-structured interviews were conducted via Zoom, recorded, and transcribed verbatim by a professional transcription service. The interview guide explored providers’ knowledge and use of CGAs. For codebook development, three representative transcripts were independently reviewed and coded by four team members. The interpretive process involved reflecting, transcribing, coding, and searching for and identifying themes.Results: Providers shared that, while it would be ideal to administer CGAs with all new patients, they were not always able to do this. Instead, they used brief screening tools or portions of CGAs, or both. There was variability in how CGA domains were assessed; however, all considered CGAs useful and they communicated with patients about their benefits. Identified facilitators of implementation included having clinic champions, an interdisciplinary care team to assist with implementation and referrals for intervention, and institutional resources and buy-in. Barriers noted included limited staff capacity and competing demands on time, provider inexperience, and misaligned institutional priorities.Discussion: Findings can guide solutions for improving the broader and more systematic use of CGAs in the care of older cancer patients. Uptake of processes like CGA to better identify those at risk of poor outcomes and intervening early to modify treatments are critical to maximize the health of the growing population of older cancer survivors living through and beyond their disease.

John Mirams

I am 88 years old—a widower and retired businessman living in West Sussex [...]

Lintao Zhang, Lihong Wang, Minhui Yu et al.

Late-life depression (LLD) is a highly prevalent mood disorder occurring in older adults and is frequently accompanied by cognitive impairment (CI). Studies have shown that LLD may increase the risk of Alzheimer's disease (AD). However, the heterogeneity of presentation of geriatric depression suggests that multiple biological mechanisms may underlie it. Current biological research on LLD progression incorporates machine learning that combines neuroimaging data with clinical observations. There are few studies on incident cognitive diagnostic outcomes in LLD based on structural MRI (sMRI). In this paper, we describe the development of a hybrid representation learning (HRL) framework for predicting cognitive diagnosis over 5 years based on T1-weighted sMRI data. Specifically, we first extract prediction-oriented MRI features via a deep neural network, and then integrate them with handcrafted MRI features via a Transformer encoder for cognitive diagnosis prediction. Two tasks are investigated in this work, including (1) identifying cognitively normal subjects with LLD and never-depressed older healthy subjects, and (2) identifying LLD subjects who developed CI (or even AD) and those who stayed cognitively normal over five years. To the best of our knowledge, this is among the first attempts to study the complex heterogeneous progression of LLD based on task-oriented and handcrafted MRI features. We validate the proposed HRL on 294 subjects with T1-weighted MRIs from two clinically harmonized studies. Experimental results suggest that the HRL outperforms several classical machine learning and state-of-the-art deep learning methods in LLD identification and prediction tasks.

Xiaxia Man, Xiaolin Yang, Zhentong Wei et al.

Abstract Background CXCL1 belongs to a member of the ELR + CXC chemokine subgroups that also known as GRO-alpha. It has been recognized that several types of human cancers constitutively express CXCL1, which may serve as a crucial mediator involved in cancer development and metastasis via an autocrine and/or paracrine fashion. However, the expression pattern and clinical significance of CXCL1 in human uterine cervix cancer (UCC), as well as its roles and mechanisms in UCC tumor biology remains entirely unclear. Methods The expression and clinical significance of CXCL1 in UCC tissues was explored using immunohistochemistry and bioinformatics analyses. The expression and effects of CXCL1 in HeLa UCC cells were assessed using ELISA, CCK-8 and transwell assays. Western blotting experiments were performed to evaluate the potential mechanism of CXCL1 on malignant behaviors of HeLa UCC cells. Results The current study demonstrated that CXCL1 was expressed in HeLa UCC cells, PHM1-41 human immortalized cervical stromal cells, as well as cervical tissues, with UCC tissues having an evidently high level of CXCL1. This high level of CXCL1 in cancer tissues was notably related to poor clinical stages and worse survival probability, rather than tumor infiltration and patient age. In addition, CXCL1 expression was extremely correlated with CCL20, CXCL8 and CXCL3 cancer-associated chemokines expression. In vitro, the growth and migration abilities of HeLa cells were significantly enhanced in the presence of exogenous CXCL1. Gain-function assay revealed that CXCL1 overexpression significantly promoted growth and migration response in HeLa cells in both autocrine and paracrine manners. Finally, we found that CXCL1 overexpression in HeLa cells influenced the expression of ERK signal-related genes, and HeLa cell malignant behaviors derived from CXCL1 overexpression were further interrupted in the presence of the ERK1/2 blocker. Conclusion Our findings demonstrate the potential roles of CXCL1 as a promoter and a novel understanding of the functional relationship between CXCL1 and the ERK signaling pathway in UCC.

Mei Wang, Feizhen Wu, Zhongkai Gu

Saccharomyces cerevisiae is an important model organism and a typical fungal representative for studies of eukaryotes. The cell cycle of yeast can be analyzed by flow cytometry, and refining the cytometric resolution of the cell cycle with this technique is important. Such refinement is potentially influenced by multiple factors, including enzymatic treatment and variations in the culture media used, although this has been subject to only limited investigation. Here, we examined the effect of different enzymatic pre‐treatments and various media on cytometric resolution. We show that cytometric resolution is significantly altered by both enzymatic conditions and the media used. Culture media with different amino nitrogen concentrations potentially impact the protein content in the yeast cell wall, which may affect the permeability of the cell wall and alter cytometric resolution. The present study provides beneficial technical information about the influence of media and enzymes on the cytometric resolution of the yeast cell cycle and most likely other fungi, which should be considered in future research.

José Ernesto Picado Ovares

Resumen Objetivos Comparar los tipos de asistencia domiciliar geriátrica y paliativa para determinar cuál obtiene mejores resultados en los pacientes con demencia avanzada. Métodos El presente es un estudio de cohorte retrospectiva. Se incluyeron pacientes con demencia avanzada ingresados al programa de Atención Comunitaria Geriátrica de un hospital geriátrico público de Costa Rica en el periodo entre enero de 2018 y junio de 2019. Ellos se dividieron en dos grupos dependiendo del equipo especializado que realizó la atención domiciliaria y se analizaron sus características sociodemográficas y clínicas. Posteriormente, se analizaron los datos generados de los registros médicos sobre consultas de emergencia, hospitalización, lugar de defunción y costo de la visita generados por cada paciente entre junio de 2018 y diciembre de 2019. Se compararon 192 pacientes con demencia avanzada Global Dementia Scale 7 visitados por el equipo geriátricos especializado domiciliar con 19 de visitados por el equipo de cuidados paliativos especializado domiciliar del Hospital Geriátrico Nacional. Resultados Se analizaron 226 datos generados (192 por el programa de geriatría y 34 por el de paliativos). Los que recibían atención domiciliaria por un equipo paliativo tenían menos probabilidades de acudir a la sala de emergencias y morir en un centro de salud en comparación con aquellos que reciben atención domiciliaria por un equipo geriátrico, con un costo menor. Conclusiones El programa de cuidado paliativo especializado domiciliar reduce las consultas de emergencia, la muerte en el domicilio y los costos de atención en pacientes con demencia avanzada en comparación con el programa geriátrico.

A. Mark Clarfield, A. Mark Clarfield, Tzvi Dwolatzky et al.

The distribution of the SARS-CoV-2 virus has reached pandemic proportions. While COVID-19 can affect anyone, it is particularly hazardous for those with “co-morbidities.” Older age is an especially strong and independent risk factor for hospital and ICU admission, mechanical ventilation and death. Health systems must protect persons at any age while paying particular attention to those with risk factors. However, essential freedoms must be respected and social/psychological needs met for those shielded. The example of the older population in Israel may provide interesting public health lessons. Relatively speaking, Israel is a demographically young country, with only 11.5% of its population 65 years and older as compared with the OECD average of &gt;17%. As well, a lower proportion of older persons is in long-term institutions in Israel than in most other OECD countries. The initiation of a national program to protect older residents of nursing homes and more latterly, a successful vaccine program has resulted in relatively low rates of serious COVID-19 related disease and mortality in Israel. However, the global situation remains unstable and the older population remains at risk. The rollout of efficacious vaccines is in progress but it will probably take years to cover the world's population, especially those living in low- and middle-income countries. Every effort must be made not to leave these poorer countries behind. Marrying the principles of public health (care of the population) with those of geriatric medicine (care of the older individual) offers the best way forward.

Yi Liu, Juan Xiang, Gang Peng et al.

PDZ-binding kinase (PBK) is known to regulate tumor progression in some cancer types. However, its relationship to immune cell infiltration and prognosis in different cancers is unclear. This was investigated in the present study by analyzing data from TCGA, GEO, GETx, TIMER, CPTAC, GEPIA2, cBioPortal, GSCALite, PROGNOSCAN, PharmacoDB, STRING, and ENCORI databases. PBK was overexpressed in most tumors including adenocortical carcinoma (hazard ratio [HR] = 2.178, p &lt; 0.001), kidney renal clear cell carcinoma (KIRC; HR = 1.907, p &lt; 0.001), kidney renal papillary cell carcinoma (HR = 3.024, p &lt; 0.001), and lung adenocarcinoma (HR = 1.255, p &lt; 0.001), in which it was associated with poor overall survival and advanced pathologic stage. PBK methylation level was a prognostic marker in thyroid carcinoma (THCA). PBK expression was positively correlated with the levels of BIRC5, CCNB1, CDC20, CDK1, DLGAP5, MAD2L1, MELK, PLK1, TOP2A, and TTK in 32 tumor types; and with the levels of the transcription factors E2F1 and MYC, which regulate apoptosis, the cell cycle, cell proliferation and invasion, tumorigenesis, and metastasis. It was also negatively regulated by the microRNAs hsa-miR-101-5p, hsa-miR-145-5p, and hsa-miR-5694. PBK expression in KIRC, liver hepatocellular carcinoma, THCA, and thymoma was positively correlated with the infiltration of immune cells including B cells, CD4+T cells, CD8+ T cells, macrophages, monocytes, and neutrophils. The results of the functional enrichment analysis suggested that PBK and related genes contribute to tumor development via cell cycle regulation. We also identified 20 drugs that potentially inhibit PBK expression. Thus, PBK is associated with survival outcome in a variety of cancers and may promote tumor development and progression by increasing immune cell infiltration into the tumor microenvironment. These findings indicate that PBK is a potential therapeutic target and has prognostic value in cancer treatment.

Sean Clouston, Graciela Muniz Terrera

Marjan Abbasi, Sheny Khera, Julia Dabravolskaj et al.

(1) Background: Integrated models of primary care deliver the comprehensive and preventative approach needed to identify and manage frailty in older people. Seniors’ Community Hub (SCH) was developed to deliver person-centered, evidence-informed, coordinated, and integrated care services to older community dwelling adults living with frailty. This paper aims to describe the SCH model, and to present patient-oriented results of the pilot. (2) Methods: SCH was piloted in an academic clinic with six family physicians. Eligible patients were community dwelling, 65 years of age and older, and considered to be at risk of frailty (eFI > 0.12). Health professionals within the clinic received training in geriatrics and interprofessional teamwork to form the SCH team working with family physicians, patients and caregivers. The SCH intervention consisted of a team-based multi-domain assessment with person-centered care planning and follow-up. Patient-oriented outcomes (EQ-5D-5L and EQ-VAS) and 4-metre gait speed were measured at initial visit and 12 months later. (3) Results: 88 patients were enrolled in the pilot from April 2016–December 2018. No statistically significant differences in EQ-5D-5L/VAS or the 4-metre gait speed were detected in 38 patients completing the 12-month assessment. (4) Conclusions: Future larger scale studies of longer duration are needed to demonstrate impacts of integrated models of primary care on patient-oriented outcomes for older adults living with frailty.

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Qiaomei Li, Rachel Cummings, Yonatan Mintz

A key challenge for decision makers when incorporating black box machine learned models into practice is being able to understand the predictions provided by these models. One proposed set of methods is training surrogate explainer models which approximate the more complex model. Explainer methods are generally classified as either local or global, depending on what portion of the data space they are purported to explain. The improved coverage of global explainers usually comes at the expense of explainer fidelity. One way of trading off the advantages of both approaches is to aggregate several local explainers into a single explainer model with improved coverage. However, the problem of aggregating these local explainers is computationally challenging, and existing methods only use heuristics to form these aggregations. In this paper we propose a local explainer aggregation method which selects local explainers using non-convex optimization. In contrast to other heuristic methods, we use an integer optimization framework to combine local explainers into a near-global aggregate explainer. Our framework allows a decision-maker to directly tradeoff coverage and fidelity of the resulting aggregation through the parameters of the optimization problem. We also propose a novel local explainer algorithm based on information filtering. We evaluate our algorithmic framework on two healthcare datasets---the Parkinson's Progression Marker Initiative (PPMI) data set and a geriatric mobility dataset---which is motivated by the anticipated need for explainable precision medicine. Our method outperforms existing local explainer aggregation methods in terms of both fidelity and coverage of classification and improves on fidelity over existing global explainer methods, particularly in multi-class settings where state-of-the-art methods achieve 70% and ours achieves 90%.