Kidney-Metabolic Factors Associated with Cognitive Impairment in Chronic Kidney Disease: A Pilot Study.

INTRODUCTION: The associations of kidney-metabolic biomarkers with cognitive impairment (CI) beyond the estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2) and albuminuria levels are not well understood. In exploratory analysis, our objective was to determine the extent that three kidney-metabolic factors, previously proposed as mechanisms of CI and commonly abnormal in chronic kidney disease (CKD), were associated with prevalent CI in CKD participants, adjusted for kidney function measures. METHODS: The study cohort included community-dwelling individuals aged ≥45 years with CKD (eGFR <60), not requiring dialysis, recruited from four health systems. We examined the serum biomarkers bicarbonate (CO2), TNFαR1, and cholesterol as primary exposures. A structured neuropsychological battery conducted by trained staff measured global and domain-specific cognitive performance. Logistic regression analyses estimated the cross-sectional associations between kidney-metabolic measures and global and cognitive domain-specific moderate/severe (Mod/Sev) CI, adjusted for the eGFR, urinary albumin-creatinine ratio (UACR, mg/g), demographics, comorbid conditions, and other kidney-metabolic biomarkers commonly abnormal in CKD. RESULTS: Among 436 CKD participants with mean age 70 years, 16% were Black, the mean eGFR was 34, and the median [IQR] UACR was 49 [0.0, 378] mg/g. In adjusted models, increased TNFαR1 was associated with global Mod/Sev CI (odds ratio [95% confidence interval] = 1.40 [1.02, 1.93]; p = 0.04); low bicarbonate (CO2 <20 mEq/L) with Mod/Sev memory impairment (3.04 [1.09, 8.47]; p = 0.03), and each 10-mg/dL lower cholesterol was associated with Mod/Sev executive function/processing speed impairment (1.12 [1.02, 1.23]; p = 0.02). However, after adjustment for multiple comparisons, these associations were no longer significant nor were any other kidney-metabolic factors significant for any CI classification. CONCLUSION: In exploratory analyses in a CKD population, three kidney-metabolic factors were associated with CI, but after adjustment for multiple comparisons, were no longer significant. Future studies in larger CKD populations are needed to assess these potential risk factors for CI.

Antibiotic Timing in Previable Prelabor Rupture of Membranes Less Than 24 Weeks of Gestation.

OBJECTIVE: This study aimed to compare neonatal and maternal outcomes between immediate and delayed prophylactic antibiotic administration after previable prelabor premature rupture of membranes (PROM) less than 24 weeks of gestation. STUDY DESIGN: Retrospective cohort study of singleton pregnancies with PROM between 160/7 and 236/7 weeks of gestational age conducted at a single tertiary care referral center between June 2011 and December 2015. Patients with multiple gestations, fetal anomalies, those who elected augmentation, or with a contradiction to expectant management, such as suspected intra-amniotic infection or stillbirth, were excluded from the study. We compared pregnancy characteristics, maternal complications, and neonatal outcomes between women who received a course of antibiotics within 24 hours of PROM and women who received antibiotics after 24 hours of PROM. The primary outcome was neonatal survival to hospital discharge. Secondary outcomes included gestational age at delivery, time from PROM to delivery, neonatal birth weight, days in the neonatal intensive care unit (NICU), composite adverse neonatal outcomes, and maternal morbidity. RESULTS: Ninety-four women met inclusion criteria, 57 (61%) received antibiotics within 24 hours of PROM and 37 (39%) received antibiotics 24 hours after PROM. Baseline maternal characteristics were similar in both groups. The mean gestational age at PROM was similar between groups at 20.8 ± 2.3 weeks in the immediate antibiotics group and 20.6 ± 2.1 weeks in the delayed antibiotics group (p = 0.48). Compared with delayed antibiotic administration, immediate antibiotic administration was not associated with a significant difference in latency time from PROM to delivery, rate of stillbirth, days in an ICU, or adverse neonatal outcomes. Maternal outcomes also did not differ significantly between groups. Neonatal birth weight was lower in the immediate antibiotics group (p = 0.012). CONCLUSION: Our data suggest that there is no maternal or neonatal benefit to immediate administration of latency antibiotics compared with delayed administration. KEY POINTS: · Adverse neonatal outcomes did not differ based on timing of latency antibiotics for previable PROM.. · Maternal outcomes did not differ based on timing of latency antibiotics for previable PROM.. · Neonatal birth weight was lower in infants that received immediate antibiotics after previable PROM..

Identifying High-Risk Individuals for Chronic Kidney Disease: Results of the CHERISH Community Demonstration Project.

BACKGROUND: Most people with chronic kidney disease (CKD) are not aware of their condition. OBJECTIVES: To assess screening criteria in identifying a population with or at high risk for CKD and to determine their level of control of CKD risk factors. METHOD: CKD Health Evaluation Risk Information Sharing (CHERISH), a demonstration project of the Centers for Disease Control and Prevention, hosted screenings at 2 community locations in each of 4 states. People with diabetes, hypertension, or aged ≥50 years were eligible to participate. In addition to CKD, screening included testing and measures of hemoglobin A1C, blood pressure, and lipids. -Results: In this targeted population, among 894 people screened, CKD prevalence was 34%. Of participants with diabetes, 61% had A1C < 7%; of those with hypertension, 23% had blood pressure < 130/80 mm Hg; and of those with high cholesterol, 22% had low-density lipoprotein < 100 mg/dL. CONCLUSIONS: Using targeted selection criteria and simple clinical measures, CHERISH successfully identified a population with a high CKD prevalence and with poor control of CKD risk factors. CHERISH may prove helpful to state and local programs in implementing CKD detection programs in their communities.

The Brain in Kidney Disease (BRINK) Cohort Study: Design and Baseline Cognitive Function.

BACKGROUND: The Brain in Kidney Disease (BRINK) Study aims to identify mechanisms that contribute to increased risk for cognitive impairment in patients with chronic kidney disease (CKD). We describe the rationale, design, and methods of the study and report baseline recruitment and cognitive function results. STUDY DESIGN: Longitudinal observational cohort study of the epidemiology of cognitive impairment in CKD. The primary aim is to characterize the association between (1) baseline and incident stroke, white matter disease, estimated glomerular filtration rate (eGFR), inflammation, microalbuminuria, and dialysis initiation and (2) cognitive decline over 3 years in a CKD cohort with a mean eGFR<45 mL/min/1.73 m(2). SETTING & PARTICIPANTS: Community-dwelling participants 45 years or older recruited from 4 health systems into 2 groups: reduced eGFR, defined as eGFR<60 mL/min/1.73 m(2) (non-dialysis dependent), and control, defined as eGFR≥60 mL/min/1.73 m(2). PREDICTOR: eGFR group. OUTCOMES: Performance on cognitive function tests and structural brain magnetic resonance imaging. MEASUREMENTS: Sequential cognitive and physical function testing, serum and urine biomarker measurement, and brain magnetic resonance images over 3 years. RESULTS: Of 554 participants, mean age was 69.3 years; 333, 88, and 133 had eGFRs<45 (non-dialysis dependent, nontransplantation), 45 to <60, and ≥60 (controls) mL/min/1.73 m(2), respectively. Mean eGFR in reduced-eGFR participants was 34.3 mL/min/1.73 m(2). Baseline cognitive performance was significantly associated with eGFR in all domains except language. Participants with eGFRs<30 mL/min/1.73 m(2) performed significantly worse than those with eGFRs≥30 mL/min/1.73 m(2) on tests of memory, processing speed, and executive function. Participants with reduced eGFRs overall scored worst on the Immediate Brief Visual-Spatial Memory Test-Revised. LIMITATIONS: Healthy cohort bias, competing risk for death versus cognitive decline. CONCLUSIONS: Cognitive function was significantly worse in participants with eGFRs<30 mL/min/1.73 m(2). Future BRINK analyses will measure risk factors for cognitive decline using the longitudinal data.

Cognitive impairment in peritoneal dialysis patients.

BACKGROUND: The prevalence of moderate to severe cognitive impairment in hemodialysis patients is more than double the prevalence in the general population. This study describes cognitive impairment occurrence in a peritoneal dialysis cohort compared with a cohort without chronic kidney disease (CKD). STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 51 English-speaking peritoneal dialysis patients from 2 urban dialysis units compared with 338 hemodialysis patients from 16 urban dialysis units and 101 voluntary controls without CKD from urban general medicine clinics. PREDICTOR: 45-minute battery of 9 validated neuropsychological tests (cognitive domains memory, executive function, and language). OUTCOMES: Mild, moderate, or severe cognitive impairment, classified according to a previously designed algorithm. RESULTS: Of the peritoneal dialysis cohort, 33.3% had no or mild, 35.3% had moderate, and 31.4% had severe cognitive impairment; corresponding values were 60.4%, 26.7%, and 12.9% of the non-CKD cohort and 26.6%, 36.4%, and 37.0% of the hemodialysis cohort. A logistic regression model including age, sex, race, education, hemoglobin level, diabetes, and stroke showed that only nonwhite race (P = 0.002) and low education (P = 0.002) were associated with moderate to severe cognitive impairment in the peritoneal dialysis cohort. Compared with hemodialysis patients, more peritoneal dialysis patients had moderate to severe memory impairment (58% vs 51%), but fewer had impaired executive function (one-third vs one-half). Peritoneal dialysis was associated with a more than 2.5-fold increased risk of moderate to severe global cognitive impairment compared with no CKD (OR, 2.58; 95% CI, 1.02-6.53), as was hemodialysis (OR, 3.16; 95% CI, 1.91-5.24), in an adjusted logistic regression model. LIMITATIONS: Small sample size, participation rate somewhat low. CONCLUSIONS: Similar to hemodialysis patients, two-thirds of peritoneal dialysis patients had moderate to severe cognitive impairment, enough to interfere with safely self-administering dialysis and adhering to complex medication regimens. These patients could benefit from cognitive assessment before and periodically after dialysis therapy initiation.

Prevalence and Risk of Severe Cognitive Impairment in Advanced Chronic Kidney Disease.

Background: Our primary goal is to describe the prevalence, severity, and risk of cognitive impairment (CI) by estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2) in a cohort enriched for advanced chronic kidney disease (CKD; eGFR < 45), adjusting for albuminuria, as measured by urine albumin-to-creatinine ratio (UACR, in mg/g). As both eGFR and albuminuria are associated with CI risk in CKD, we also seek to determine the extent that eGFR remains a useful biomarker for risk of CI in those with CKD and concomitant albuminuria. Methods: Chi-square tests measured the prevalence of severe CI and mild cognitive impairment (MCI) by eGFR level. Logistic regression models and generalized linear models measured risk of CI by eGFR, adjusted for UACR. Results: Participants were 574 adults with a mean age of 69; 433 with CKD (eGFR < 60, nondialysis) and 141 controls (eGFR ≥ 60). Forty-eight percent of participants with CKD had severe CI or MCI. The prevalence of severe CI was highest (25%) in those with eGFR < 30. eGFR < 30 was only associated with severe CI in those without albuminuria (UACR < 30; OR = 3.3; p = .02) and was not associated with MCI in similar models. Conclusions: One quarter of those with eGFR < 30 had severe CI. eGFR < 30 was associated with over threefold increased odds of severe CI in those with UACR < 30, but not with UACR > 30, suggesting that eGFR < 30 is a valid biomarker for increased risk of severe CI in those without concomitant albuminuria.

Acute variation in cognitive function in hemodialysis patients: a cohort study with repeated measures.

BACKGROUND: Although cognitive function in hemodialysis patients is believed to be best 24 hours after the dialysis session, the extent of variation during the dialysis cycle is unknown. STUDY DESIGN: Cohort study with repeated measures. SETTING & PARTICIPANTS: Hemodialysis centers; patients aged 55 years or older. PREDICTOR: Time of assessment related to the dialysis session. Time 1 (T1) occurred approximately 1 hour before the dialysis session; T2, 1 hour into the session; T3, 1 hour after; and T4, the next day. OUTCOMES: Measures of cognitive function using a 45-minute cognitive battery. An average composite score was calculated to measure global cognitive function, equal to the average of subjects' standardized scores on all tests given at each test time. Times were classified as best and worst according to composite scores. MEASUREMENTS: Testing was conducted on average over 2 dialysis sessions to avoid test fatigue. The cognitive battery included tests of verbal fluency, immediate and delayed verbal and visual memory, and executive function, administered at 4 times. RESULTS: In the 28 subjects who completed testing at 3 or 4 testing times, mean age was 66.7 +/- 9.5 years and mean dialysis vintage was 44.7 +/- 33.3 months. Using a general linear model for correlated data, the composite score was significantly lower (poorer) during dialysis (T2) than shortly before the session (T1) or on the next day (T4; P < 0.001 for both). LIMITATIONS: Relatively small sample size, testing delays, results may not be generalizable. CONCLUSION: Global cognitive function varies significantly during the dialysis cycle, being worst during dialysis and best shortly before the session or on the day after. Clinician visits may be most effective at these times.

Driving after use of alcohol and marijuana in college students.

Driving after use of marijuana is almost as common as driving after use of alcohol in youth (P. M. O'Malley & L. D. Johnston, 2003). The authors compared college students' attitudes, normative beliefs and perceived negative consequences of driving after use of either alcohol or marijuana and tested these cognitive factors as risk factors for substance-related driving. Results indicated that youth perceived driving after marijuana use as more acceptable to peers and the negative consequences as less likely than driving after alcohol use, even after controlling for substance use. Results of zero-inflated Poisson regression analyses indicated that lower perceived dangerousness and greater perceived peer acceptance were associated with increased engagement in, and frequency of, driving after use of either substance. Lower perceived likelihood of negative consequences was associated with increased frequency for those who engage in substance-related driving. These results provide a basis for comparing how youth perceive driving after use of alcohol and marijuana, as well as similarities in the risk factors for driving after use of these substances.

"I'm not trying to be cured, so there's not much he can do for me": hospice patients' constructions of hospice's holistic care approach in a biomedical culture.

The hospice philosophy was founded on a mission to provide comprehensive and holistic services to individuals at the end of life. Hospice interdisciplinary teams work together to offer therapies such as spiritual services, comfort care, and massage therapy to meet patients' physical, psychological, emotional, and spiritual needs. Although the hospice philosophy is guided toward patient-centered care, limited research has examined how patients understand holistic care services. Through a social constructionist lens and qualitative interviews, we examined hospice patients' understandings of holistic care and argue that these perceptions of care are constructed through the biomedical model of medicine.

Expecting innovation: psychoactive drug primes and the generation of creative solutions.

Many individuals expect that alcohol and drug consumption will enhance creativity. The present studies tested whether substance related primes would influence creative performance for individuals who possessed creativity-related substance expectancies. Participants (n = 566) were briefly exposed to stimuli related to psychoactive substances (alcohol, for Study 1, Sample 1, and Study 2; and marijuana, for Study 1, Sample 2) or neutral stimuli. Participants in Study 1 then completed a creative problem-solving task, while participants in Study 2 completed a divergent thinking task or a task unrelated to creative problem solving. The results of Study 1 revealed that exposure to the experimental stimuli enhanced performance on the creative problem-solving task for those who expected the corresponding substance would trigger creative functioning. In a conceptual replication, Study 2 showed that participants exposed to alcohol cues performed better on a divergent thinking task if they expected alcohol to enhance creativity. It is important to note that this same interaction did not influence performance on measures unrelated to creative problem solving, suggesting that the activation of creativity-related expectancies influenced creative performance, specifically. These findings highlight the importance of assessing expectancies when examining pharmacological effects of alcohol and marijuana. Future directions and implications for substance-related interventions are discussed.

The comprehensive dialysis study (CDS): a USRDS special study.

BACKGROUND AND OBJECTIVES: The Comprehensive Dialysis Study (CDS) aimed to understand factors contributing to physical, functional, and nutritional health status among patients starting dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A phone interview survey was conducted with patients from a geographically stratified national random sample of dialysis units, and quarterly serum samples were obtained for patients at a preidentified subset of units. The phone survey collected standardized measures of physical activity, employment and disability status, perceived health and well-being, and dietary intake. Serum samples were obtained to measure prealbumin, albumin, creatinine, normalized protein catabolic rate, and C-reactive protein. To comply with restrictions required under the Health Insurance Portability and Accountability Act (HIPAA), dialysis unit personnel could not participate in any research-related activities. RESULTS: Overall participation rate was 18.5%. One thousand six hundred forty-six patients affiliated with 295 dialysis units completed the phone survey; 361 patients affiliated with 68 dialysis units also completed a dietary intake survey, with 269 providing serum samples. Despite challenges in the design and implementation of CDS, the population was diverse and results should be generalizable. CONCLUSIONS: Constraints within the dialysis industry and HIPAA requirements render the assembly of nationally representative cohorts extremely difficult. Nevertheless, the CDS represents the largest cohort of incident dialysis patients containing detailed information on self-reported physical activity and dietary intake and is one of few cohorts simultaneously measuring laboratory proxies of nutrition and inflammatory status. Data from CDS can be used to inform the design of interventions addressing several conditions that affect longevity and health status in ESRD.