Carlos O Weiss

Association between inflammatory-related disease burden and frailty: Results from the Women's Health and Aging Studies (WHAS) I and II

Frailty is associated with a pro-inflammatory state, which has been characterized by elevated levels of systemic inflammatory biomarkers, but has not been related to the number of co-existing chronic diseases associated with inflammation. We sought to determine the extent to which a higher number of inflammatory-related diseases is associated with frailty and to identify the most common disease patterns associated with being frail in older adults. We performed binomial regression analyses to assess whether a higher count of inflammatory-related diseases increases the probability of frailty using data from the WHAS I and II, companion cohorts composed of 70-79-year-old community-dwelling older women in Baltimore, Maryland (n=620). An increase of one inflammatory-related disease was associated log-linearly with frailty (Prevalence Ratio (PR)=2.28, 95% Confidence Interval (CI)=1.81-2.87). After adjusting for age, race, education, and smoking status, the probability of frailty remained significant (PR=1.97, 95%CI=1.52-2.55). In the frail population, chronic kidney disease (CKD) and depressive symptoms (Prevalence=22.9%, 95%CI=14.2-34.8%); CVD and depressive symptoms (21.7%, 95%CI=13.2-33.5%); CKD and anemia (18.7%, 95%CI=11.1-29.7%); cardiovascular disease (CVD), CKD, and pulmonary disease (10.7%, 95%CI=5.2-21.0%); CKD, anemia, and depressive symptoms (8.7%, 95%CI=3.9-18.2%); and CVD, anemia, pulmonary disease, and depressive symptoms (5.0%, 95%CI=1.6-14.4%) were among the most frequent disease combinations. Their prevalence percentages were significantly higher in the frail versus non-frail women. A higher inflammatory-related disease count, perhaps reflecting a greater pro-inflammatory burden, increases the likelihood of frailty. Shared mechanisms among specific disease combinations may further contribute to this risk.

Transitions Among Disability Levels or Death in African American and White Older Women

BACKGROUNDnThis study examined the racial differences in probabilities of transitioning across three disability levels of walking (1/2) mile in a community-dwelling population of older women.nnnMETHODSnThe sample comprised 436 community-dwelling older women who were among the two-third least disabled women in Baltimore, Maryland. The levels of disability status of walking (1/2) mile included high functioning defined as reporting no difficulty, preclinical disability defined as reports of task modification but no reported difficulty, and disability defined as reported difficulty. First-order Markov transition models were specified to determine whether race influences the types of individual-level transitions between difficulty levels of walking (1/2) mile.nnnRESULTSnAmong high-functioning women, African Americans were more likely to be disabled at the next round than their White counterparts. African American women who began with preclinical disability were more likely to die before the next round. After adjusting for age, education, and perceived income inadequacy, African American women tended to have an increased risk of becoming disabled if preclinically disabled than White women.nnnCONCLUSIONSnPrevention through identification of individuals at an early phase of decline appears to be key to addressing racial disparities in physical disability even in later life.

Thyroid autoantibodies are associated with a reduced prevalence of frailty in community-dwelling older women.

CONTEXTnThe contribution of autoimmunity to the multisystem dysregulation that characterizes the frailty syndrome in older adults is unknown.nnnOBJECTIVEnThe aim of the study was to investigate the relationship between thyroid antibodies and frailty in older women.nnnDESIGN, SETTING, AND PARTICIPANTSnWe conducted a cross-sectional study nested within the Womens Health and Aging Studies I and II. Thyroglobulin antibodies (TgAbs), thyroid peroxidase antibodies (TPOAbs), and antinuclear antibodies were measured in the baseline sera of 641 community-dwelling older women.nnnMAIN OUTCOME MEASUREnFrailty was defined using a validated five-component measure.nnnRESULTSnThe prevalence of prefrailty and frailty was lower in TgAb-positive than negative older women (37.1 vs. 47.8% and 6.7 vs.11.9%, respectively; P = 0.01 and 0.03). The prevalence of prefrailty, but not frailty, was lower in TPOAb-positive than negative women (38.9 vs. 48.0% and 10.1 vs. 11.3%; P = 0.04 and 0.34). After adjustment for covariates including serum thyroid stimulation hormone concentration and thyroid medication usage in multinomial regression models, TgAb-positive older women had lower odds of prefrailty and frailty compared with TgAb-negative women (odds ratio 0.57 and 0.30; 95% confidence interval 0.34-0.98 and 0.10-0.85, respectively). Similarly, TPOAb-positive older women had lower odds of frailty compared with TPOAb-negative women (odds ratio 0.44; 95% confidence interval 0.20-0.96). These trends were not observed with antinuclear antibodies.nnnCONCLUSIONnIndependent of thyroid function status, community-dwelling older women who are seropositive for TgAbs and TPOAbs are less likely to be frail than seronegative women.

Where do we go from here? A small scale observation of transfer results from chronic to skilled ventilator facilities ☆

PURPOSEnSkilled nursing facility ventilator units (SNF) are a recent attempt to reduce the costs of an increasing number of patients who are in acute intensive care units and are not able to be liberated from ventilators. Transfers of such patients from long-term care chronic vent units (LTCVs) to SNFs in Maryland began in 2006. The safety of these transfers needs to be assessed.nnnMETHODSnWe retrospectively followed up all patients designated as eligible by their insurance for transfer from our LTCV units to SNF from July 1, 2008 through June 30, 2010 looking only at survival. Those patients who refused transfer and appealed and remained in our LTCV were compared to those who were transferred to SNF ventilator units. The analysis was by Kaplan-Meier statistics.nnnRESULTSnThere was an increased mortality (P=.025) of those transferred to SNF ventilator facilities as compared to those remaining in the LTCV.nnnCONCLUSIONnWe recognize that bias may occur in patients choosing to remain in our LTCV compared to those accepting transfers, the magnitude of the difference in mortality indicates the need for more comprehensive well designed analysis investigating the outcome of all transfers occurring to and from LTCVs.

CROSS-DESIGN SYNTHESIS FOR EXTENDING THE APPLICABILITY OF TRIAL EVIDENCE WHEN TREATMENT EFFECT IS HETEROGENEOUS-I. METHODOLOGY

ABSTRACT Randomized controlled trials (RCTs) provide reliable evidence for approval of new treatments, informing clinical practice , and coverage decisions. The participants in RCTs are often not a representative sample of the larger at-risk population. Hence, it is argued that the average treatment effect from the trial is not generalizable to the larger at-risk population. An essential premise of this argument is that there is significant heterogeneity in the treatment effect (HTE). We present a new method to extrapolate the treatment effect from a trial to a target group that is inadequately represented in the trial, when HTE is present. Our method integrates trial and observational data (cross-design synthesis). The target group is assumed to be well-represented in the observational database such that the observational study essentially acts as an “evidentiary bridge” that allows evidence to be transported from the trial sample to the target population. An essential component of the methodology is the estimation of calibration adjustments for unmeasured confounding in the observational sample. The estimate of treatment effect, adjusted for unmeasured confounding, is projected onto the target sample using a weighted G-computation approach. We present simulation studies to demonstrate the methodology for estimating the marginal treatment effect in a target sample that differs from the trial sample to varying degrees. In a companion article, we demonstrate and validate the methodology in a clinical application.