Predictors of transitions in frailty severity and mortality among people aging with HIV.

BACKGROUND: People aging with HIV show variable health trajectories. Our objective was to identify longitudinal predictors of frailty severity and mortality among a group aging with HIV. METHODS: Exploratory analyses employing a multistate transition model, with data from the prospective Modena HIV Metabolic Clinic Cohort Study, based in Northern Italy, begun in 2004. Participants were followed over four years from their first available visit. We included all 963 participants (mean age 46.8±7.1; 29% female; 89% undetectable HIV viral load; median current CD4 count 549, IQR 405–720; nadir CD4 count 180, 81–280) with four-year data. Frailty was quantified using a 31-item frailty index. Outcomes were frailty index score or mortality at four-year follow-up. Candidate predictor variables were baseline frailty index score, demographic (age, sex), HIV-disease related (undetectable HIV viral load, current CD4+ T-cell count, nadir CD4 count, duration of HIV infection, and duration of antiretroviral therapy [ARV] exposure), and behavioral factors (smoking, injection drug use (IDU), and hepatitis C virus co-infection). RESULTS: Four-year mortality was 3.0% (n = 29). In multivariable analyses, independent predictors of frailty index at follow-up were baseline frailty index (RR 1.06, 95% CI 1.05–1.07), female sex (RR 0.93, 95% CI 0.87–0.98), nadir CD4 cell count (RR 0.96, 95% CI 0.93–0.99), duration of HIV infection (RR 1.06, 95% CI 1.01–1.12), duration of ARV exposure (RR 1.08, 95% CI 1.02–1.14), and smoking pack-years (1.03, 1.01–1.05). Independent predictors of mortality were baseline frailty index (OR 1.19, 1.02–1.38), current CD4 count (0.34, 0.20–0.60), and IDU (2.89, 1.30–6.42). CONCLUSIONS: Demographic, HIV-disease related, and social and behavioral factors appear to confer risk for changes in frailty severity and mortality among people aging with HIV

Moving Towards Common Data Elements and Core Outcome Measures in Frailty Research

With aging populations around the world, frailty is becoming more prevalent increasing the need for health systems and social systems to deliver optimal evidence based care. However, in spite of the growing number of frailty publications, high-quality evidence for decision making is often lacking. Inadequate descriptions of the populations enrolled including frailty severity and frailty conceptualization, lack of use of validated frailty assessment tools, utilization of different frailty instruments between studies, and variation in reported outcomes impairs the ability to interpret, generalize and implement the research findings. The utilization of common data elements (CDEs) and core outcome measures (COMs) in clinical trials is increasingly being adopted to address such concerns. To catalyze the development and use of CDEs and COMs for future frailty studies, the Canadian Frailty Network (http://www.cfn-nce.ca; CFN), a not-for-profit pan-Canadian nationally-funded research network, convened an international group of experts to examine the issue and plan the path forward. The meeting was structured to allow for an examination of current frailty evidence, ability to learn from other COMs and CDEs initiatives, discussions about specific considerations for frailty COMs and CDEs and finally the identification of the necessary steps for a COMs and CDEs consensus initiative going forward. It was agreed at the onset of the meeting that a statement based on the meeting would be published and herein we report the statement

Mapping the multicausality of Alzheimer's disease through group model building.

Alzheimer's disease (AD) is a complex, multicausal disorder involving several spatiotemporal scales and scientific domains. While many studies focus on specific parts of this system, the complexity of AD is rarely studied as a whole. In this work, we apply systems thinking to map out known causal mechanisms and risk factors ranging from intracellular to psychosocial scales in sporadic AD. We report on the first systemic causal loop diagram (CLD) for AD, which is the result of an interdisciplinary group model building (GMB) process. The GMB was based on the input of experts from multiple domains and all proposed mechanisms were supported by scientific literature. The CLD elucidates interaction and feedback mechanisms that contribute to cognitive decline from midlife onward as described by the experts. As an immediate outcome, we observed several non-trivial reinforcing feedback loops involving factors at multiple spatial scales, which are rarely considered within the same theoretical framework. We also observed high centrality for modifiable risk factors such as social relationships and physical activity, which suggests they may be promising leverage points for interventions. This illustrates how a CLD from an interdisciplinary GMB process may lead to novel insights into complex disorders. Furthermore, the CLD is the first step in the development of a computational model for simulating the effects of risk factors on AD

Number of Cardiometabolic disorders is associated with degree of frailty among people aging with HIV.

Inflammatory cardiometabolic disorders become more common and can accumulate with age. Frailty also worsens with age and is associated with pro-inflammatory states. We sought to assess the burden of cardiometabolic disorders in a large ongoing HIV-positive cohort study, the relationship between cardiometaolic disorders and frailty, and whether they independently contribute to mortality

Correlates of frailty phenotype and frailty index and their associations with clinical outcomes

Frailty is a predictor of adverse health outcomes and can be measured across the life course, including among people living with HIV. The purpose of this study was to examine two commonly used measures of frailty - the frailty index (FI) and frailty phenotype - to assess common characteristics and to describe associations with multimorbidity, falls, and disability in people aging with HIV

Genetic predisposition and modifiable risks for late-life dementia

Dementia is a syndrome of cognitive and functional impairment. Although age remains the primary risk factor, several other diverse risks have been linked with dementia, including genetic factors, such as the presence of the APOE4 allele, and lifestyle factors including smoking and exercise. With ever-aging populations, interventions that offer some prospect of dementia prevention are being scrutinized. A critical issue is how the genetic and lifestyle factors interact; that is, whether the genetic risk for dementia can be modified by a healthful lifestyle. In this issue, Licher et al.1 have found that modifiable lifestyle risk factors were able to decrease dementia risk only in people with low genetic risk. This finding is in contrast to those from previous studies showing that lifestyle is able to mitigate the effects of genetic risk on the development of dementia

Comprehensive Geriatric Assessment

The CGA is a multidisciplinary diagnostic and treatment process that identifies medical, psychosocial, and functional capabilities of older adults in order to develop a coordinated plan to maximize overall health with aging. At present, no standard criteria are available to readily identify patients who are likely to benefit from the CGA. Specific criteria used by CGA programs to evaluate patients include age, medical comorbidities, psychosocial problems, previous or predicted high healthcare utilization, change in living situation, and specific geriatric conditions. Evidence coming from RCTs and large systematic reviews and meta-analyses suggests that the healthcare setting may influence the effectiveness of CGA programs. Home CGA programs as well as the CGA performed in hospital have been shown to be consistently beneficial for several health outcomes. The effectiveness of CGA programs may be modified also by particular settings or specific clinical conditions, with tailored CGA programs in older frail patients evaluated for preoperative assessment, admitted or discharged from emergency departments and orthogeriatric units or with cognitive impairment and dementia. The CGA, capable to effectively exploring multiple domains in older age, is indeed the multidimensional and multidisciplinary tool of choice to determine the clinical profile, the pathological risk and the residual skills, as well as the shortand long-term prognosis, i.e., the Multidimensional Prognostic Index (MPI), to facilitate the clinical decision making on the personalized care plan of older subjects