Early rehospitalization (<30 days) after discharge from kidney transplantation (KT) is associated with poor outcomes. We explored summary metrics of pre-transplant health status that may improve the ...identification of KT recipients at risk for early rehospitalization and mortality after transplant.
We performed a retrospective cohort study of 8,870 adult (≥ 18 years) patients on hemodialysis who received KT between 2000 and 2010 at United States transplant centers. We linked Medicare data to United Network for Organ Sharing data and data from a national dialysis provider to examine pre-KT (1) Elixhauser Comorbidity Index, (2) physical function (PF) measured by the Short Form 36 Health Survey, and (3) the number of hospitalizations during the 12 months before KT as potential predictors of early rehospitalization after KT. We also explored whether these metrics are confounders of the known association between early rehospitalization and post-transplant mortality.
The median age was 52 years (interquartile range IQR 41, 60) and 63% were male. 29% were rehospitalized in <30 days, and 20% died during a median follow-up time of five years (IQR 3.6-6.5). In a multivariable logistic model, kidney recipients with more pre-KT Elixhauser comorbidities (adjusted odds ratio aOR 1.09 per comorbidity, 95% Confidence Interval CI 1.07-1.11), the poorest pre-KT PF (aOR 1.24, 95% CI 1.08-1.43), or >1 pre-KT hospitalizations (aOR 1.32, 95% CI 1.17-1.49) were more likely to be rehospitalized. All three health status metrics and early rehospitalization were independently associated with post-KT mortality in a multivariable Cox model (adjusted hazard ratio for rehospitalization: 1.41, 95% CI 1.28-1.56).
Pre-transplant metrics of health status, measured by dialysis providers or administrative data, are independently associated with early rehospitalization and mortality risk after KT. Transplant providers may consider utilizing metrics of pre-KT global health status as early signals of vulnerability when transitioning care after KT.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
With the onset of prevention trials for individuals at high risk for Alzheimer disease, there is increasing need for accurate risk prediction to inform study design and enrollment, but available risk ...estimates are limited. We developed risk estimates for the incidence of mild cognitive impairment (MCI) or dementia among cognitively unimpaired individuals by APOE-e4 dose for the genetic disclosure process of the Alzheimer's Prevention Initiative Generation Study, a prevention trial in cognitively unimpaired APOE-e4/e4 homozygote individuals.
We included cognitively unimpaired individuals aged 60-75 y, consistent with Generation Study eligibility criteria, from the National Alzheimer's Coordinating Center (NACC) (n = 5,073, 158 APOE-e4/e4), the Rotterdam Study (n = 6,399, 156 APOE-e4/e4), the Framingham Heart Study (n = 4,078, 67 APOE-e4/e4), and the Sacramento Area Latino Study on Aging (SALSA) (n = 1,294, 11 APOE-e4/e4). We computed stratified cumulative incidence curves by age (60-64, 65-69, 70-75 y) and APOE-e4 dose, adjusting for the competing risk of mortality, and determined risk of MCI and/or dementia by genotype and baseline age. We also used subdistribution hazard regression to model relative hazard based on age, APOE genotype, sex, education, family history of dementia, vascular risk, subjective memory concerns, and baseline cognitive performance. The four cohorts varied considerably in age, education, ethnicity/race, and APOE-e4 allele frequency. Overall, cumulative incidence was uniformly higher in NACC than in the population-based cohorts. Among APOE-e4/e4 individuals, 5-y cumulative incidence was as follows: in the 60-64-y age stratum, it ranged from 0% to 5.88% in the three population-based cohorts versus 23.06% in NACC; in the 65-69-y age stratum, from 9.42% to 10.39% versus 34.62%; and in the 70-75-y age stratum, from 18.64% to 33.33% versus 38.34%. Five-year incidence of dementia was negligible except for APOE-e4/e4 individuals and those over 70 y. Lifetime incidence (to age 80-85 y) of MCI or dementia for the APOE-e4/e4 individuals in the long-term Framingham and Rotterdam cohorts was 34.69%-38.45% at age 60-64 y, 30.76%-40.26% at 65-69 y, and 33.3%-35.17% at 70-75 y. Confidence limits for these estimates are often wide, particularly for APOE-e4/e4 individuals and for the dementia outcome at 5 y. In regression models, APOE-e4 dose and age both consistently increased risk, as did lower education, subjective memory concerns, poorer baseline cognitive performance, and family history of dementia. We discuss several limitations of the study, including the small numbers of APOE-e4/e4 individuals, missing data and differential dropout, limited ethnic and racial diversity, and differences in definitions of exposure and outcome variables.
Estimates of the absolute risk of MCI or dementia, particularly over short time intervals, are sensitive to sampling and a variety of methodological factors. Nonetheless, such estimates were fairly consistent across the population-based cohorts, and lower than those from a convenience cohort and those estimated in prior studies-with implications for informed consent and design for clinical trials targeting high-risk individuals.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although the federal government funds research to improve the lives of critically ill adults and of the people who care for them, recent investigations show that it does not provide investigators ...with guidelines for ensuring that such research is on firm ethical grounds, especially in the case of cognitively impaired subjects.
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Federal regulations for the protection of research participants, known as “the common rule,” require that research involving “vulnerable” subjects include “additional safeguards” (45 CFR 46.111) and that the investigator obtain informed consent from a “legally authorized representative” (45 CFR 46.116).
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But the rule does not describe safeguards in . . .
Abstract Widespread adoption of digital health tools has the potential to improve health and health care for individuals and their communities, but realizing this potential requires anticipating and ...addressing numerous ethical and regulatory challenges. Here, we help digital health tool developers identify ethical and regulatory considerations – and opportunities to advance desirable outcomes – by organizing them within a general product-development lifecycle that spans generation of ideas to commercialization of a product.
We performed semistructured interviews with 30 family members of patients with advanced dementia to identify the factors that facilitate or hinder advance planning by persons with dementia. All ...interviews were analyzed using qualitative data analysis techniques. The majority (77%) of family members reported that their relative had some form of written advance directive, and at least half reported previous discussions about health care preferences (57%), living situation or placement issues (50%), and finances or estate planning (60%) with the patient. Family members reported some themes that prompted planning and others that were barriers to planning. Events that most often triggered planning were medical, living situation, or financial issues associated with a friend or family member of the patient (57%). Barriers to planning included both passive and active avoidance. The most common form of passive avoidance was not realizing the importance of planning until it was too late to have the discussion (63%). The most common form of active avoidance was avoiding the discussion (53%). These data suggest potentially remediable strategies to address barriers to advance planning discussions.
Objective
Frontotemporal lobar degeneration (FTLD) is characterized by impairments in social, behavioral, and/or language function, but postmortem studies indicate that multiple neuropathological ...entities lead to FTLD. This study assessed whether specific clinical features predict the underlying pathology.
Methods
A clinicopathological correlation was performed on 90 consecutive patients with a pathological diagnosis of frontotemporal dementia and was compared with an additional 24 cases accrued during the same time period with a clinical diagnosis of FTLD, but with pathology not typically associated with frontotemporal dementia.
Results
Postmortem examination showed multiple pathologies including tauopathies (46%), FTLD with ubiquitin‐positive inclusions (29%), and Alzheimer's disease (17%). The pathological groups manifested some distinct demographic, clinical, and neuropsychological features, although these attributes showed only a statistical association with the underlying pathology. FTLD with ubiquitin‐positive inclusions was more likely to present with both social and language dysfunction, and motor neuron disease was more likely to emerge in these patients. Tauopathies were more commonly associated with an extrapyramidal disorder. Alzheimer's disease was associated with relatively greater deficits in memory and executive function.
Interpretation
Clinical and neuropsychological features contribute to delineating the spectrum of pathology underlying a patient diagnosed with FTLD, but biomarkers are needed that, together with the clinical phenotype, can predict the underlying neuropathology. Ann Neurol 2006;59:952‐962
Background: Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD) research typically requires participants to enroll with a “study partner” (SP). Little is known about what predicts ...who steps into the SP role or whether the SP’s relationship to the participant affects their reports of disease severity.Methods: Health and Retirement Study data (HRS), collected prior to the Aging, Demographics and Memory Study (ADAMS), was used to identify sociocultural factors that predict who serves as a SP in ADAMS. SP-reported outcomes were compared between three types of participant-SP relationships: spousal, adult child, and other.Results: Spouses (35%) and adult children (39%) were similarly likely to serve as SPs. Factors predicting who served differed. In multivariable analyses, adult children rated participants less impaired than spouses on measures of memory, judgment, and organizational abilities (p < .05). Conclusions: The participant-SP relationship has independent effects on the SP’s reports of the severity of cognitive impairments.
Cognitive impairment (CI) in older adults is frequently accompanied by difficulty performing complex everyday activities (e.g., managing finances). However, it is unclear if and how older adults with ...CI modify their activities (i.e., Do individuals continue, monitor, seek help with, change their approach to, or stop different activities?). In the current study, we examined if older adults with CI are concerned about their ability to carry out complex activities, if and how they modify activities based on their concern, and the factors associated with activity modification. We hypothesized that older adults with CI will more frequently be concerned about, and modify, everyday activities than cognitively healthy (HE) older adults, and that higher awareness of memory loss in the CI group would relate to more frequent modification. The sample included 81 older adults (51 HEs; mean age 70.02 (7.34) and 30 CI; mean age 75.97 (8.12)). Compared to HEs, the CI group reported having more concern about, F(3,77) = 5.50, p = 0.02, and modifying a greater number of activities, F(3,77) = 5.02, p = 0.03. Medication management (30%) and completing taxes (33.3%) were among the most frequently modified activities for the CI and HE groups, respectively. In the CI group, higher memory awareness was associated with more concern (r = .53, p = .005) and activity modification (r = 0.55, p = .003). Findings provide novel information about how cognitively diverse older adults navigate complex activities in daily life. We propose a preliminary theoretical model by which self-awareness may influence navigation of everyday activities in the context of CI.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In an effort to intervene earlier in Alzheimer's disease (AD), clinical trials are testing promising candidate therapies in preclinical disease. Preclinical AD trial participants are cognitively ...normal, functionally independent, and autonomous decision-makers. Yet, like AD dementia trials, preclinical trials require dual enrollment of a participant and a knowledgeable informant, or study partner.
The requirement of dyadic enrollment is a barrier to recruitment and may present unique ethical challenges. Despite these limitations, the requirement should continue. Study partners may be essential to ensure participant safety and wellbeing, including overcoming distress related to biomarker disclosure and minimizing risk for catastrophic reactions and suicide. The requirement may maximize participant retention and ensure data integrity, including that study partners are the source of data that will ultimately instruct whether a new treatment has a clinical benefit and meaningful impact on the population health burden associated with AD. Finally, study partners are needed to ensure the scientific and clinical value of trials.
Preclinical AD will represent a new model of care, in which persons with no symptoms are informed of probable cognitive decline and eventual dementia. The rationale for early diagnosis in symptomatic AD is equally applicable in preclinical AD-to minimize risk, maximize quality of life, and ensure optimal planning and communication. Family members and other sources of support will likely be essential to the goals of this new model of care for preclinical AD patients and trials must instruct this clinical practice.
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