Andrew Law

Frailty as a Novel Predictor of Mortality and Hospitalization in Individuals of All Ages Undergoing Hemodialysis

To quantify the prevalence of frailty in adults of all ages undergoing chronic hemodialysis, its relationship to comorbidity and disability, and its association with adverse outcomes of mortality and hospitalization.

Frailty and falls among adult patients undergoing chronic hemodialysis: a prospective cohort study

BackgroundPatients undergoing hemodialysis are at high risk of falls, with subsequent complications including fractures, loss of independence, hospitalization, and institutionalization. Factors associated with falls are poorly understood in this population. We hypothesized that insights derived from studies of the elderly might apply to adults of all ages undergoing hemodialysis; we focused on frailty, a phenotype of physiological decline strongly associated with falls in the elderly.MethodsIn this prospective, longitudinal study of 95 patients undergoing hemodialysis (1/2009-3/2010), the association of frailty with future falls was explored using adjusted Poisson regression. Frailty was classified using the criteria established by Fried et al., as a combination of five components: shrinking, weakness, exhaustion, low activity, and slowed walking speed.ResultsOver a median 6.7-month period of longitudinal follow-up, 28.3% of study participants (25.9% of those under 65, 29.3% of those 65 and older) experienced a fall. After adjusting for age, sex, race, comorbidity, disability, number of medications, marital status, and education, frailty independently predicted a 3.09-fold (95% CI: 1.38-6.90, P=0.006) higher number of falls. This relationship between frailty and falls did not differ for younger and older adults (P=0.57).ConclusionsFrailty, a validated construct in the elderly, was a strong and independent predictor of falls in adults undergoing hemodialysis, regardless of age. Our results may aid in identifying frail hemodialysis patients who could be targeted for multidimensional fall prevention strategies.

Age and Sex Disparities in Discussions About Kidney Transplantation in Adults Undergoing Dialysis

To explore whether disparities in age and sex in access to kidney transplantation (KT) originate at the time of prereferral discussions about KT.

Patient- and Provider-Reported Information about Transplantation and Subsequent Waitlisting

Because informed consent requires discussion of alternative treatments, proper consent for dialysis should incorporate discussion about other renal replacement options including kidney transplantation (KT). Accordingly, dialysis providers are required to indicate KT provision of information (KTPI) on CMS Form-2728; however, provider-reported KTPI does not necessarily imply adequate provision of information. Furthermore, the effect of KTPI on pursuit of KT remains unclear. We compared provider-reported KTPI (Form-2728) with patient-reported KTPI (in-person survey of whether a nephrologist or dialysis staff had discussed KT) in a prospective ancillary study of 388 hemodialysis initiates. KTPI was reported by both patient and provider for 56.2% of participants, by provider only for 27.8%, by patient only for 8.3%, and by neither for 7.7%. Among participants with provider-reported KTPI, older age was associated with lack of patient-reported KTPI. Linkage with the Scientific Registry for Transplant Recipients showed that 20.9% of participants were subsequently listed for KT. Patient-reported KTPI was independently associated with a 2.95-fold (95% confidence interval [95% CI], 1.54 to 5.66; P=0.001) higher likelihood of KT listing, whereas provider-reported KTPI was not associated with listing (hazard ratio, 1.18; 95% CI, 0.60 to 2.32; P=0.62). Our findings suggest that patient perception of KTPI is more important for KT listing than provider-reported KTPI. Patient-reported and provider-reported KTPI should be collected for quality assessment in dialysis centers because factors associated with discordance between these metrics might inform interventions to improve this process.

Racial Differences in Gout Incidence in a Population-Based Cohort: Atherosclerosis Risk in Communities Study

We examined racial differences in gout incidence among black and white participants in a longitudinal, population-based cohort and tested whether racial differences were explained by higher levels of serum urate. The Atherosclerosis Risk in Communities Study is a prospective, US population-based cohort study of middle-aged adults enrolled between 1987 and 1989 with ongoing annual follow-up through 2012. We estimated the adjusted hazard ratios and 95% confidence intervals of incident gout by race among 11,963 men and women using adjusted Cox proportional hazards models. The cohort was 23.6% black. The incidence rate of gout was 8.4 per 10,000 person-years (15.5/10,000 person-years for black men, 12.0/10,000 person-years for black women, 9.4/10,000 person-years for white men, and 5.0/10,000 person-years for white women; P < 0.001). Black participants had an increased risk of incident gout (for women, adjusted hazard ratio (HR) = 1.69, 95% confidence interval (CI): 1.29, 2.22; for men, adjusted HR = 1.92, 95% CI: 1.44, 2.56). Upon further adjustment for uric acid levels, there was modest attenuation of the association of race with incident gout (for women, adjusted HR = 1.62, 95% CI: 1.24, 2.22; for men, adjusted HR = 1.49, 95% CI: 1.11, 2.00) compared with white participants. In this US population-based cohort, black women and black men were at increased risk of developing gout during middle and older ages compared with whites, which appears, particularly in men, to be partly related to higher urate levels in middle-aged blacks.

Frailty, mycophenolate reduction, and graft loss in kidney transplant recipients.

Background Mycophenolate mofetil (MMF) side effects often prompt dose reduction or discontinuation, and this MMF dose reduction (MDR) can lead to rejection and possibly graft loss. Unfortunately, little is known about what factors might cause or contribute to MDR. Frailty, a measure of physiologic reserve, is emerging as an important, novel domain of risk in kidney transplantation recipients. We hypothesized that frailty, an inflammatory phenotype, might be associated with MDR. Methods We measured frailty (shrinking, weakness, exhaustion, low physical activity, and slowed walking speed), other patient and donor characteristics, longitudinal MMF doses, and graft loss in 525 kidney transplantation recipients. Time-to-MDR was quantified using an adjusted Cox proportional hazards model. Results By 2 years after transplantation, 54% of frail recipients and 45% of nonfrail recipients experienced MDR; by 4 years, incidence was 67% and 51%. Frail recipients were 1.29 times (95% confidence interval [95% CI], 1.01–1.66; P = 0.04) more likely to experience MDR, as were deceased donor recipients (adjusted hazard ratio [aHR], 1.92; 95% CI, 1.44–2.54, P < 0.001) and older adults (age ≥ 65 vs <65; aHR, 1.47; 95% CI, 1.10–1.96, P = 0.01). Mycophenolate mofetil dose reduction was independently associated with a substantially increased risk of death-censored graft loss (aHR, 5.24; 95% CI, 1.97–13.98, P = 0.001). Conclusion A better understanding of risk factors for MMF intolerance might help in planning alternate strategies to maintain adequate immunosuppression and prolong allograft survival.

Standards should be applied in the prevention and handling of missing data for patient-centered outcomes research: a systematic review and expert consensus

OBJECTIVESnTo recommend methodological standards in the prevention and handling of missing data for primary patient-centered outcomes research (PCOR).nnnSTUDY DESIGN AND SETTINGnWe searched National Library of Medicine Bookshelf and Catalog as well as regulatory agencies and organizations Web sites in January 2012 for guidance documents that had formal recommendations regarding missing data. We extracted the characteristics of included guidance documents and recommendations. Using a two-round modified Delphi survey, a multidisciplinary panel proposed mandatory standards on the prevention and handling of missing data for PCOR.nnnRESULTSnWe identified 1,790 records and assessed 30 as having relevant recommendations. We proposed 10 standards as mandatory, covering three domains. First, the single best approach is to prospectively prevent missing data occurrence. Second, use of valid statistical methods that properly reflect multiple sources of uncertainty is critical when analyzing missing data. Third, transparent and thorough reporting of missing data allows readers to judge the validity of the findings.nnnCONCLUSIONnWe urge researchers to adopt rigorous methodology and promote good science by applying best practices to the prevention and handling of missing data. Developing guidance on the prevention and handling of missing data for observational studies and studies that use existing records is a priority for future research.

Review ArticleStandards should be applied in the prevention and handling of missing data for patient-centered outcomes research: a systematic review and expert consensus

OBJECTIVESnTo recommend methodological standards in the prevention and handling of missing data for primary patient-centered outcomes research (PCOR).nnnSTUDY DESIGN AND SETTINGnWe searched National Library of Medicine Bookshelf and Catalog as well as regulatory agencies and organizations Web sites in January 2012 for guidance documents that had formal recommendations regarding missing data. We extracted the characteristics of included guidance documents and recommendations. Using a two-round modified Delphi survey, a multidisciplinary panel proposed mandatory standards on the prevention and handling of missing data for PCOR.nnnRESULTSnWe identified 1,790 records and assessed 30 as having relevant recommendations. We proposed 10 standards as mandatory, covering three domains. First, the single best approach is to prospectively prevent missing data occurrence. Second, use of valid statistical methods that properly reflect multiple sources of uncertainty is critical when analyzing missing data. Third, transparent and thorough reporting of missing data allows readers to judge the validity of the findings.nnnCONCLUSIONnWe urge researchers to adopt rigorous methodology and promote good science by applying best practices to the prevention and handling of missing data. Developing guidance on the prevention and handling of missing data for observational studies and studies that use existing records is a priority for future research.

Perceived frailty and measured frailty among adults undergoing hemodialysis: a cross-sectional analysis.

BackgroundFrailty, a validated measure of physiologic reserve, predicts adverse health outcomes among adults with end-stage renal disease. Frailty typically is not measured clinically; instead, a surrogate—perceived frailty—is used to inform clinical decision-making. Because correlations between perceived and measured frailty remain unknown, the aim of this study was to assess their relationship.Methods146 adults undergoing hemodialysis were recruited from a single dialysis center in Baltimore, Maryland. Patient characteristics associated with perceived (reported by nephrologists, nurse practitioners (NPs), or patients) or measured frailty (using the Fried criteria) were identified using ordered logistic regression. The relationship between perceived and measured frailty was assessed using percent agreement, kappa statistic, Pearson’s correlation coefficient, and prevalence of misclassification of frailty. Patient characteristics associated with misclassification were determined using Fisher’s exact tests, t-tests, or median tests.ResultsOlder age (adjusted OR [aOR]u2009=u20091.36, 95%CI:1.11-1.68, Pu2009=u20090.003 per 5-years older) and comorbidity (aORu2009=u20091.49, 95%CI:1.27-1.75, Pu2009<u20090.001 per additional comorbidity) were associated with greater likelihood of nephrologist-perceived frailty. Being non-African American was associated with greater likelihood of NP- (aORu2009=u20095.51, 95%CI:3.21-9.48, Pu2009=u20090.003) and patient- (aORu2009=u20094.20, 95%CI:1.61-10.9, Pu2009=u20090.003) perceived frailty. Percent agreement between perceived and measured frailty was poor (nephrologist, NP, and patient: 64.1%, 67.0%, and 55.5%). Among non-frail participants, 34.4%, 30.0%, and 31.6% were perceived as frail by a nephrologist, NP, or themselves. Older adults (Pu2009<u20090.001) were more likely to be misclassified as frail by a nephrologist; women (Pu2009=u20090.04) and non-African Americans (Pu2009=u20090.02) were more likely to be misclassified by an NP. Neither age, sex, nor race was associated with patient misclassification.ConclusionsPerceived frailty is an inadequate proxy for measured frailty among patients undergoing hemodialysis.

Health-Related and Psychosocial Concerns about Transplantation among Patients Initiating Dialysis

BACKGROUND AND OBJECTIVESnDisparities in kidney transplantation remain; one mechanism for disparities in access to transplantation (ATT) may be patient-perceived concerns about pursuing transplantation. This study sought to characterize prevalence of patient-perceived concerns, explore interrelationships between concerns, determine patient characteristics associated with concerns, and assess the effect of concerns on ATT.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnPrevalences of 12 patient-perceived concerns about pursuing transplantation were determined among 348 adults who recently initiated dialysis, recruited from 26 free-standing dialysis centers around Baltimore, Maryland (January 2009-March 2012). Using variable reduction techniques, concerns were clustered into two categories (health-related and psychosocial) and quantified with scale scores. Associations between patient characteristics and concerns were estimated using modified Poisson regression. Associations between concerns and ATT were estimated using Cox models.nnnRESULTSnThe most frequently cited patient-perceived concerns were that participants felt they were doing fine on dialysis (68.4%) and felt uncomfortable asking someone to donate a kidney (29.9%). Older age was independently associated with having high health-related (adjusted relative risk, 1.35 [95% confidence interval, 1.20 to 1.51], for every 5 years older for those ≥ 60 years) or psychosocial (1.15 [1.00 to 1.31], for every 5 years older for those aged ≥ 60 years) concerns, as was being a woman (1.72 [1.21 to 2.43] and 1.55 [1.09 to 2.20]), having less education (1.59 [1.08 to 2.35] and 1.77 [1.17 to 2.68], comparing postsecondary education to grade school or less), and having more comorbidities (1.18 [1.08 to 1.30] and 1.18 [1.07 to 1.29], per one comorbidity increase). Having never seen a nephrologist before dialysis initiation was associated with high psychosocial concerns (1.48 [1.01 to 2.18]). Those with high health-related (0.37 [0.16 to 0.87]) or psychosocial (0.47 [0.23 to 0.95]) concerns were less likely to achieve ATT (median follow-up time 2.2 years; interquartile range, 1.6-3.2).nnnCONCLUSIONSnPatient-perceived concerns about pursuing kidney transplantation are highly prevalent, particularly among older adults and women. Reducing these concerns may help decrease disparities in ATT.