Faculty Bibliography

BACKGROUND:Frailty increases early hospital readmission and mortality risk among kidney transplantation (KT) recipients. Although frailty represents a high-risk state for this population, the correlates of frailty, the patterns of the 5 frailty components, and the risk associated with these patterns are unclear. METHODS:Six hundred sixty-three KT recipients were enrolled in a cohort study of frailty in transplantation (12/2008-8/2015). Frailty, activities of daily living (ADL)/instrumental ADL (IADL) disability, Centers for Epidemiologic Studies Depression Scale depression, education, and health-related quality of life (HRQOL) were measured. We used multinomial regression to identify frailty correlates. We identified which patterns of the 5 components were associated with mortality using adjusted Cox proportional hazards models. RESULTS:Frailty prevalence was 19.5%. Older recipients (adjusted prevalence ratio [PR], 2.22; 95% confidence interval [CI], 1.21-4.07) were more likely to be frail. The only other factors that were independently associated with frailty were IADL disability (PR, 3.22; 95% CI, 1.72-6.06), depressive symptoms (PR, 11.31; 95% CI, 4.02-31.82), less than a high school education (PR, 3.10; 95% CI, 1.30-7.36), and low HRQOL (fair/poor: PR, 3.71; 95% CI, 1.48-9.31). The most common pattern was poor grip strength, low physical activity, and slowed walk speed (19.4%). Only 2 patterns of the 5 components emerged as having an association with post-KT mortality. KT recipients with exhaustion and slowed walking speed (hazards ratio = 2.43; 95% CI, 1.17-5.03) and poor grip strength, exhaustion, and slowed walking speed (hazard ratio, 2.61; 95% CI, 1.14-5.97) were at increased mortality risk. CONCLUSIONS:Age was the only conventional factor associated with frailty among KT recipients; however, factors rarely measured as part of clinical practice, namely, HRQOL, IADL disability, and depressive symptoms, were significant correlates of frailty. Redefining the frailty phenotype may be needed to improve risk stratification for KT recipients.

BACKGROUND:Clinical cognitive impairment and physical frailty often co-occur. However, it is unclear whether preclinical impairment or decline in cognitive domains are associated with onset of physical frailty. We tested this hypothesis and further hypothesized that preclinical impairment and decline in executive functioning are more strongly associated with frailty onset than memory or general cognitive performance. METHODS:We used 9 years of data from the Women's Health and Aging Study II (six visits) that longitudinally measured psychomotor speed and executive functioning using the Trail Making Test, parts A and B, respectively, and immediate and delayed word-list recall from the Hopkins Verbal Learning Test. We used Cox proportional hazards models to regress time to frailty on indicators for impairment on these cognitive tests and on rates of change of the tests. Models adjusted for depressive symptoms, age, years of education, and race. RESULTS:Of the 331 women initially free of dementia and frailty, 44 (13%) developed frailty. A binary indicator of impaired executive functioning (Trail Making Test, part B [TMT-B]) was most strongly associated with hazard, or risk, of frailty onset (hazard ratio [HR] = 3.3, 95% confidence interval [CI] = 1.4, 7.6) after adjustment for covariates and other tests. Adjusting for baseline cognitive performance, faster deterioration on TMT-B (HR = 0.6, 95% CI = 0.4, 1.0) was additionally associated with hazard of frailty onset. CONCLUSIONS:Findings inform the association of executive functioning with transitions to frailty, suggesting both impairments in and declines in executive functioning are associated with risk of frailty onset. It remains to be determined whether these associations are causal or whether shared aging related or other mechanisms are involved.

BACKGROUND: Frailty is associated with worse health-related quality of life (HRQOL) in older adults and worse clinical outcomes in adults of all ages with end stage renal disease (ESRD). It is unclear whether frail adults of all ages with ESRD are more likely to experience worse HRQOL. OBJECTIVE: The goal of this study was to identify factors associated with worsening HRQOL in this population. DESIGN, SETTING AND MEASUREMENTS: We studied 233 adults of all ages with ESRD enrolled (11/2009-11/2013) in a longitudinal cohort study. Frailty status was measured at enrollment and HRQOL was reported (Excellent, Very Good, Good, Fair or Poor) at the initial assessment and follow-up (median follow-up 9.4 months). We studied factors associated with Fair/Poor HRQOL at follow-up using logistic regression and factors associated with HRQOL change using multinomial regression. All models were adjusted for age, sex, race, education, BMI, diabetes status, history of a previous transplant, type of dialysis and time between assessments. RESULTS: Fair/Poor HRQOL was reported by 28% at initial assessment and 33% at follow-up. 47.2% of participants had stable HRQOL, 22.8% better HRQOL, and 30.0% worse HRQOL at follow-up (P<0.001). In adjusted models, only frailty was associated with Fair/Poor HRQOL at follow-up (OR: 2.79, 95% CI: 1.32-5.90) and worsening HRQOL at follow-up (RR: 2.91, 95%CI: 1.08-7.80). CONCLUSIONS: Frail adults of all ages with ESRD are more likely to experience fair/poor HRQOL and worsening HRQOL over time. Frailty represents a state of decreased physiologic reserve that impacts not only clinical outcomes but also the patient-centered outcome of HRQOL.

INTRODUCTION/BACKGROUND:Inflammatory diseases increase risk of venous thromboembolism (VTE). Whether gout, the most common rheumatologic inflammatory arthritis, or its cause, elevated serum uric acid (SUA), is associated with VTE incidence is unknown. MATERIALS AND METHODS/METHODS:The Atherosclerosis Risk in Communities Study measured SUA in 14126 participants aged 45-64, without a history of VTE or gout and not using anticoagulants/gout medications, and obtained information on incident gout between 1987 and 1998 from 10247. We followed them for VTE occurrence from 1987 to 2011. Hazard ratios (HRs) of VTE were estimated using Cox proportional hazards models. RESULTS:We documented 632 incident cases of VTE (236 unprovoked and 396 provoked). Age, sex, and race-adjusted HRs for total VTE were 1, 1.40, 1.43, 1.91, 1.71, and 3.25 (P for trend<0.001) across levels of SUA (range mg/dL: ≤4.9, 5.0-5.9, 6.0-6.9, 7.0-7.5, 7.6-8.7, and ≥8.8). After adjustment for other VTE risk factors, those in the highest level of SUA had HRs [95% confidence interval] of 2.13 (1.47-3.07) for total VTE, 2.07 (1.17-3.67) for unprovoked VTE and 2.16 (1.33-3.50) for provoked VTE. Those with incident gout had a nonsignificantly increased risk of total VTE [HR (95% CI): 1.33 (0.95-1.86)]. CONCLUSIONS:Elevated SUA was associated with an increased risk of VTE, suggesting that SUA might be a novel risk factor or marker for VTE. Further studies are needed to assess the association between gout and VTE.

BACKGROUND:Patients with end stage renal disease (ESRD), including stage 5 chronic kidney disease (CKD), hemodialysis (HD) and peritoneal dialysis (PD), are at high risk for stroke-related morbidity, mortality and bleeding. The overall risk/benefit balance of warfarin treatment among patients with ESRD and AF remains unclear. METHODS:We systematically reviewed the associations of warfarin use and stroke outcome, bleeding outcome or mortality in patients with ESRD and AF. We conducted a comprehensive literature search in Feb 2016 using key words related to ESRD, AF and warfarin in PubMed, Embase and Cochrane Library without language restriction. We searched for randomized trials and observational studies that compared the use of warfarin with no treatment, aspirin or direct oral anticoagulants (DOACs), and reported quantitative risk estimates on these outcomes. Paired reviewers screened articles, collected data and performed qualitative assessment using the Cochrane Risk of Bias Assessment Tool for Non-randomized Studies of Interventions. We conducted meta-analyses using the random-effects model with the DerSimonian - Laird estimator and the Knapp-Hartung methods as appropriate. RESULTS:We identified 2709 references and included 20 observational cohort studies that examined stroke outcome, bleeding outcome and mortality associated with warfarin use in 56,146 patients with ESRD and AF. The pooled estimates from meta-analysis for the stroke outcome suggested that warfarin use was not associated with all-cause stroke (HR = 0.92, 95 % CI 0.74-1.16) or any stroke (HR = 1.01, 95 % CI 0.81-1.26), or ischemic stroke (HR = 0.80, 95 % CI 0.58-1.11) among patients with ESRD and AF. In contrast, warfarin use was associated with significantly increased risk of all-cause bleeding (HR = 1.21, 95 % CI 1.01-1.44), but not associated with major bleeding (HR = 1.18, 95 % CI 0.82-1.69) or gastrointestinal bleeding (HR = 1.19, 95 % CI 0.81-1.76) or any bleeding (HR = 1.21, 95 % CI 0.99-1.48). There was insufficient evidence to evaluate the association between warfarin use and mortality in this population (pooled risk estimate not calculated due to high heterogeneity). Results on DOACs were inconclusive due to limited relevant studies. CONCLUSIONS:Given the absence of efficacy and an increased bleeding risk, these findings call into question the use of warfarin for AF treatment among patients with ESRD.

BACKGROUND:Dual-energy computed tomography (DECT) is a new diagnostic tool for gout, but its sensitivity has not been established. Our goal was to assess the sensitivity of DECT for the detection of monosodium urate (MSU) deposits in non-tophaceous and tophaceous gout, both at the level of the patient and that of the individual joint or lesion. METHODS:DECT was performed on 11 patients with crystal-proven non-tophaceous gout and 10 with tophaceous gout and included both the upper and lower extremities in 20/21 patients. DECT images were simultaneously acquired at 80 and 140 kV and then processed on a workstation with proprietary software using a two-material decomposition algorithm. MSU deposits were color coded as green by the software and fused onto grey-scale CT images. The number and location of these deposits was tallied independently by two DECT-trained radiologists blinded to the clinical characteristics of the patient. Sensitivity of DECT was defined as the proportion of patients with a confirmed diagnosis of gout which was correctly identified as such by the imaging technique. All patients provided informed consent to participate in this IRB-approved study. RESULTS:MSU deposits were detected by DECT in ≥1 joint area in 7/11 (64 %) patients with non-tophaceous gout, but were only detected in 3/12 (25 %) joints proven by aspiration to be affected with gout. Inclusion of the upper extremity joints in the scanning protocol did not improve sensitivity. All 10 patients with tophaceous gout had MSU deposits evident by DECT. The sensitivity of DECT for individual gouty erosions was assessed in 3 patients with extensive foot involvement. MSU deposits were detected by DECT within or immediately adjacent to 13/26 (50 %) erosions. CONCLUSIONS:A DECT protocol that includes all lower extremity joints has moderate sensitivity in non-tophaceous and high sensitivity in tophaceous gout. However, DECT has lower sensitivity when restricted to individual crystal-proven gouty joints in non-tophaceous disease or individual erosive lesions in tophaceous gout. The detection of MSU deposits by DECT relates to their size and density and the detection parameters of the DECT scanner and adjustment of the latter might improve sensitivity.