Surveillance of CKD epidemiology in the US - a joint analysis of NHANES and KEEP.

Chronic Kidney Disease (CKD), is highly prevalent in the United States. Epidemiological systems for surveillance of CKD rely on data that are based solely on the NHANES survey, which does not include many patients with the most severe and less frequent forms of CKD. We investigated the feasibility of estimating CKD prevalence from the large-scale community disease detection Kidney Early Evaluation and Program (KEEP, n = 127,149). We adopted methodologies from the field of web surveys to address the self-selection bias inherent in KEEP. Primary outcomes studied were CKD Stage 3-5 (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2, and CKD Stage 4-5 (eGFR <30 mL/min/1.73 m2). The unweighted prevalence of Stage 4-5 CKD was higher in KEEP (1.00%, 95%CI: 0.94-1.05%) than in NHANES (0.51%, 95% CI: 0.43-0.59%). Application of a selection model that used  variables related to demographics, recruitment and socio-economic factors resulted in estimates similar to NHANES (0.55%, 95% CI: 0.50-0.60%). Weighted prevalence of Stages 3-5 CKD in KEEP was 6.45% (95% CI: 5.70-7.28%) compared to 6.73% (95% CI: 6.30-7.19%) for NHANES. Application of methodologies that address the self-selection bias in the KEEP program may allow the use of this large, geographically diverse dataset for CKD surveillance.

Risk Factors for Hospitalization of Home Hospice Enrollees Development and Validation of a Predictive Tool.

BACKGROUND: Over 10% of hospice patients experience at least 1 care transition 6 months prior to death. Transitions at the end of life, particularly from hospice to hospital, result in burdensome and fragmented care for patients and families. Little is known about factors that predict hospitalization in this population. OBJECTIVES: To develop and validate a model predictive of hospitalization after enrollment into home hospice using prehospice admission risk factors. DESIGN: Retrospective cohort study using Medicare fee-for-service claims. PARTICIPANTS: Patients enrolled into the Medicare hospice benefit were ≥18 years old in 2012. OUTCOME MEASURED: Hospitalization within 2 days from a hospice discharge. RESULTS: We developed a predictive model using 61 947 hospice enrollments, of which 3347 (5.4%) underwent a hospitalization. Seven variables were associated with hospitalization: age 18 to 55 years old (adjusted odds ratio [95% confidence interval]: 2.94 [2.41-3.59]), black race (2.13 [1.93-2.34]), east region (1.97 [1.73-2.24]), a noncancer diagnosis (1.32 [1.21-1.45]), 4 or more chronic conditions (8.11 [7.19-9.14]), 2 or more prior hospice enrollments (1.75 [1.35-2.26]), and enrollment in a not-for-profit hospice (2.01 [1.86-2.18]). A risk scoring tool ranging from 0 to 29 was developed, and a cutoff score of 18 identified hospitalized patients with a positive predictive value of 22%. CONCLUSIONS: Reasons for hospitalization among home hospice patients are complex. Patients who are younger, belong to a minority group, and have a greater number of chronic conditions are at increased odds of hospitalization. Our newly developed predictive tool identifies patients at risk for hospitalization and can serve as a benchmark for future model development.

Cancer risk with alemtuzumab following kidney transplantation.

Alemtuzumab has been employed for induction therapy in kidney transplantation with low rates of acute rejection and excellent graft and patient survival. Antibody induction therapy has been linked to increased vulnerability to cancer. Data regarding malignancy rates with alemtuzumab are limited. We studied 1350 kidney transplant recipients (between 2001 and 2009) at the University of Pittsburgh Starzl Transplant Institute, for post-transplant de novo and recurrent malignancy, excluding non-melanoma skin cancer, among patients receiving alemtuzumab, thymoglobulin, and no induction therapies. Of the 1350 patients, 1002 (74.2%) received alemtuzumab, 205 (15.2%) received thymoglobulin, and 122 (9%) received no induction therapy. After excluding cancers occurring within 60 d post-transplantation, 43 (3.25%) malignancies were observed during a median follow-up time of 4.0 yr. The incidence of malignancy was 5.4% (1.09 per 100 patient-years [PY]) with thymoglobulin, 2.8% (0.74 per 100 PY) with alemtuzumab, and 3.3% (0.66 per 100 PY) with no induction (across all groups; p = 0.2342, thymoglobulin vs. alemtuzumab; p = 0.008). Thus, with the exception of non-melanoma skin cancer which we did not evaluate, alemtuzumab induction was not associated with increased cancer incidence post-kidney transplantation when compared to no induction therapy and was associated with lower cancer incidence when compared to thymoglobulin.

A national survey of independent living donor advocates: the need for practice guidelines.

In 2000, representatives of the transplant community convened for a meeting on living donation in an effort to provide recommendations to promote the welfare of living donors. One key recommendation included in the consensus statement was that all transplant centers which have performed living donor surgeries have an independent living donor advocate (ILDA) "whose only focus is on the best interest of the donor." The aims of this study were to begin to understand the sociodemographic characteristics, selection and training, and clinical practices of ILDAs. All US transplant centers performing living donor surgeries were contacted to identify the ILDA at their center. One hundred and twenty ILDAs completed an anonymous survey. Results indicated considerable variability with regard to the sociodemographic characteristics of ILDAs, how the ILDA was selected and trained, and the ILDAs' clinical practices, particularly ethical challenges encountered by ILDAs. The variability observed may result in differential selection of donors and could have a potential negative impact on the lives of both donors and transplant candidates. The variability in the background, training, and practice of ILDAs suggests the need for strategies, such as practice guidelines, to standardize the interaction between ILDAs and living donors.

The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial.

Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea), a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome.

Two hundred living donor kidney transplantations under alemtuzumab induction and tacrolimus monotherapy: 3-year follow-up.

Alemtuzumab has been used in off-label studies of solid organ transplantation. We extend our report of the first 200 consecutive living donor solitary kidney transplantations under alemtuzumab pretreatment with tacrolimus monotherapy and subsequent spaced weaning to 3 years of follow-up. We focused especially on the causes of recipient death and graft loss, and the characteristics of rejection. The actuarial 1-, 2- and 3-year patient and graft survivals were 99.0% and 98.0%, 96.4% and 90.8% and 93.3% and 86.3%, respectively. The cumulative incidence of acute cellular rejection (ACR) at the following months was 2%

Sleep disorders in end-stage renal disease: 'Markers of inadequate dialysis'?

Excessive daytime sleepiness and sleep disorders, including sleep apnea syndrome, restless legs syndrome, and periodic limb movement disorder, occur with increased frequency in patients with end-stage renal disease (ESRD). The detection and management of sleep disorders in ESRD patients is often challenging but may have significant clinical benefits. Some of the poor quality of life in ESRD may be attributed to the presence of concomitant sleep disorders, yet the classical symptoms of sleep disorders (poor concentration, daytime sleepiness, and insomnia) are often ascribed to the uremic syndrome itself. Conventional risk factors and screening tools used in the diagnosis of sleep disorders seem to have limited applicability in dialysis patients implicating the unique pathophysiology of sleep disorders in ESRD. Emerging evidence suggests that sleep apnea may contribute to the augmented cardiovascular event rates and to the accelerated development of atherosclerosis in ESRD. Whether treatment of sleep disorders in ESRD patients can affect the high morbidity and mortality of ESRD patients has yet to be elucidated. To date, conventional renal replacement therapies do not appear to have a significant impact on the treatment of sleep disorders in ESRD. The promising therapeutic effects of optimal uremia control in the forms of nocturnal hemodialysis and renal transplantation on sleep disorders require further mechanistic and clinical studies.

Living donor renal transplantation using alemtuzumab induction and tacrolimus monotherapy.

Alemtuzumab was used as an induction agent in 205 renal transplant recipients undergoing 207 living donor renal transplants. All donor kidneys were recovered laparoscopically. Postoperatively, patients were treated with tacrolimus monotherapy, and immunosuppression was weaned when possible. Forty-seven recipients of living donor renal transplants prior to the induction era who received conventional triple drug immunosuppression without antibody induction served as historic controls. The mean follow-up was 493 days in the alemtuzumab group and 2101 days in the historic control group. Actuarial 1-year patient and graft survival were 98.6% and 98.1% in the alemtuzumab group, compared to 93.6% and 91.5% in the control group, respectively. The incidence of acute cellular rejection (ACR) at 1 year was 6.8% in the alemtuzumab group and 17.0% (p < 0.05) in the historic control group. Most (81.3%) episodes of ACR in the alemtuzumab group were Banff 1 (a or b) and were sensitive to steroid pulses for the treatment of rejection. There was no cytomegalovirus disease or infection. The incidence of delayed graft function was 0%, and the incidence of posttransplant insulin-dependent diabetes mellitus was 0.5%. This study represents the largest series to date of live donor renal transplant recipients undergoing alemtuzumab induction, and confirms the short-term safety and efficacy of this approach.

Steroid-free tacrolimus monotherapy after pretransplantation thymoglobulin or Campath and laparoscopy in living donor renal transplantation.

Living donor renal transplantation was performed under a regimen of recipient pretreatment and low-dose postoperative immunosuppression with subsequent weaning. From October 9, 2002, to December 31, 2004, 196 consecutive, unselected laparoscopic live donor nephrectomies resulting in 196 living donor renal transplantations were performed. Recipients were pretreated with rabbit antithymocyte globulin (thymoglobulin; 24 patients or [12%]) or Campath 1H (alemtuzumab; 166 patients [85%]), or were not in protocol (6 patients [3%]), and were given postoperative steroid-free low-dose tacrolimus immunosuppressive monotherapy with subsequent weaning. There was no donor mortality. Major and minor donor morbidities were 2.6% and 4.2%, respectively. Laparoscopic live donor nephrectomy recipient outcomes with a mean follow-up of 401 days included (1) recipient and graft survival of 99.0% and 97.4%, respectively; (2) no ureteral stenosis; (3) 0.5% delayed graft function, from recurrent focal segmental glomerulosclinosis; and (4) no vascular thrombosis. The incidence of acute rejection at 30, 90, and 401 days was 1.5%, 3.8%, and 11.2% (all 196 recipients), 0%, 25%, and 29.2% (thymoglobulin recipients), and 1.8%, 3.9%, and 8.4% (Campath 1H recipients), respectively. Sixty-six patients (33.7%) are receiving spaced-dose immunosuppressive monotherapy. The mean creatinine concentration in all recipients was 1.5 +/- 1.1 mg/dL. There were no instances of cytomegalovirus tissue invasive disease or posttransplantation lymphoproliferative disease. The incidence of new-onset posttransplantation insulin-dependent diabetes was 0.5%. At current follow-up, the use of Campath 1H rather than thymoglobulin for pretreatment seems to have significantly improved the efficacy of our regimen.

Sleep quality and clinical correlates in patients on maintenance dialysis.

BACKGROUND: Sleep quality is a subject of increasing interest to clinicians caring for dialysis patients. Self-assessed sleep disturbances have been associated with quality of life outcomes. The goal of this study was to identify clinical and laboratory parameters that are independently associated with overall sleep quality among prevalent dialysis patients. METHODS: The Epworth Sleepiness Scale (ESS) and the Sleep Problems Index (SPI), a questionnaire derived from the Medical Outcomes Study, were administered to 71 dialysis patients and 68 subjects without known kidney disease (control group). The ESS and the SPI sleep item responses between the 2 groups were compared. The sleep items from the SPI were also aggregated into a sleep quality score. Multivariate linear regression analyses of sleep quality scores were used to identify clinical factors that were independently associated with poor sleep. RESULTS: The ESS score was not significantly different between the 2 groups. However, the responses to the SPI sleep items demonstrated significantly impaired subjective sleep quality in dialysis patients compared with control subjects. In addition, overall sleep quality, as measured by the aggregated sleep score, was lower in dialysis patients compared with the control group (41 vs. 47, p < 0.001). In multivariate analyses, factors that were independently associated with poor sleep quality in dialysis patients were male gender (p = 0.006), history of coronary artery disease (p = 0.003), and high phosphate level (p = 0.05). CONCLUSION: This study demonstrates that global sleep quality of dialysis patients is substantially impaired. Poor sleep quality was associated with male gender, coronary artery disease and high serum phosphate level, a modifiable factor. Future studies are needed to examine the relationship of serum phosphate level to sleep quality in dialysis patients.

Discrete targeting signals direct Pmp47 to oleate-induced peroxisomes in Saccharomyces cerevisiae.

Pmp47 is a peroxisomal membrane protein consisting of six transmembrane domains (TMDs). We previously showed that the second matrix loop containing a basic cluster of amino acids is important for peroxisomal targeting, and similar basic targeting motifs have been found in other peroxisomal membrane proteins. However, this basic cluster by itself targets to peroxisomes very poorly. We have developed a sensitive quantitative localization assay based on the targeting of Pmp47-GFP fusion proteins to identify the important elements of the basic cluster and to search for other targeting information on Pmp47. Our data suggest that side-chain structure and position as well as charge are important for targeting by the basic cluster. Analysis of other regions of Pmp47 indicates that all TMDs except TMD2 can be eliminated or substituted without significant loss of targeting. TMD2 plus an adjacent cytoplasmic-oriented sequence is crucial for targeting. Cytoplasmic-oriented sequences from two other peroxisomal membrane proteins, ScPex15p and ScPmp22, could partially substitute for the analogous sequence in Pmp47. Targeting with high fidelity to oleate-induced peroxisomes required the following elements: the cytoplasmic-oriented sequence and TMD2, a short matrix loop containing a basic cluster, and a membrane-anchoring TMD.

Comparison of the effects of zaleplon, zolpidem, and triazolam on memory, learning, and psychomotor performance.

Twenty-four healthy male and female subjects, who participated in this randomized, double-blind, crossover study, received single nighttime doses of zaleplon 10 mg (therapeutic dose), zaleplon 20 mg, zolpidem 10 mg (therapeutic dose), zolpidem 20 mg, triazolam 0.25 mg (positive control), and placebo. Subjective behavioral ratings and psychomotor tests were completed before and 1.25 and 8.25 hours after administration of the study drug. The Immediate and Delayed Word Recall tests and the Digit Span Test were used to assess memory. The Digit-Symbol Substitution Test, Paired Associates Learning Test, and Divided Attention Test were used to assess other cognitive skills. Zaleplon 10 mg did not produce any significant changes in memory or learning compared with placebo. All other active treatments, including zolpidem 10 mg, caused psychomotor impairment at the 1.25-hour test battery. Zolpidem 20 mg (twice the therapeutic dose) produced more psychomotor impairment at the 1.25-hour assessment than did any of the other active treatments, including zaleplon 20 mg. At the 8.25-hour time point, test scores for subjects who received zaleplon 10 mg and 20 mg did not differ from the test scores for those who received placebo. However, cognitive impairment persisted up to the 8.25-hour observation for subjects who were administered triazolam 0.25 mg and zolpidem 20 mg. Adverse events associated with the use of zaleplon were transient and mild-to-moderate in severity. Overall, this study shows that zaleplon is a safe hypnotic that does not affect memory, learning, or psychomotor skills associated with vigilance.

A comparison of the residual effects of zaleplon and zolpidem following administration 5 to 2 h before awakening.

AIMS: To compare the duration of the residual hypnotic and sedative effects of zaleplon with those of zolpidem and placebo following nocturnal administration at various times before morning awakening. METHODS: Zaleplon 10 mg, zolpidem 10 mg, or placebo was administered double-blind to 36 healthy subjects under standardized conditions in a six-period, incomplete-block, crossover study. Subjects were gently awakened and given medication at predetermined times 5, 4, 3, or 2 h before morning awakening, which occurred 8 h after bedtime. When the subjects awoke in the morning, a battery of subjective and objective assessments of residual effects of hypnotics was administered. RESULTS: No residual effects were demonstrated after zaleplon 10 mg, when administered as little as 2 h before waking, on either subjective or objective assessments, whereas zolpidem 10 mg showed significant residual effects on DSST and memory (immediate and delayed free recall) after administration up to 5 h before waking and choice reaction time, critical flicker fusion threshold and Sternberg memory scanning after administration up to 4 h before waking. Residual effects of zolpidem were apparent in all objective and subjective measurements when the drug was administered later in the night. CONCLUSIONS: The present results demonstrate that zaleplon at the dose of 10 mg is free of residual hypnotic or sedative effects when administered nocturnally as little as 2 h before waking in normal subjects. In contrast, residual effects of zolpidem are still apparent on objective assessments up to 5 h after nocturnal administration, longer than has been reported from studies involving daytime administration.

Pharmacokinetic and pharmacodynamic evaluation of the potential drug interaction between venlafaxine and ethanol.

Venlafaxine is a new antidepressant with a unique mode of action. Because many patients taking antidepressant therapy may self-medicate with ethanol, this study was undertaken to assess the possible pharmacokinetic and pharmacodynamic interactions between venlafaxine and ethanol. This randomized, double-blind, placebo-controlled, two-period crossover study was conducted with 16 healthy men. Multiple doses of venlafaxine (50 mg every 8 hours) or placebo were administered for 7 days. On days 5 and 7 a single dose of 0.5 g/kg of ethanol or a placebo solution was administered in a randomized fashion. Pharmacokinetic data indicated that ethanol administration did not affect the disposition of venlafaxine or O-desmethylvenlafaxine. Similarly, venlafaxine administration did not affect the pharmacokinetic disposition of ethanol. Ethanol produced its expected effects on the eight psychometric tests administered. Venlafaxine produced small effects on the results of the Digit Symbol Substitution Test, the Divided Attention Reaction Time, and the Profile of Mood States. No pharmacodynamic interaction was detected between venlafaxine and ethanol.

Disorder of excessive daytime somnolence: a case series of 1,000 patients.

Symptoms of excessive daytime somnolence range from mild to severe. In mild cases, there may be minimal interference with normal daytime function. The hypersomnia can be disabling. When severe the patient finds it difficult to remain awake at times when physically inactive. Excessive daytime somnolence is the chief complaint of the majority of our adult patients. In this paper, we present the findings for 1,000 consecutive patients (755 males and 245 females) who were seen at the Humana Hospital Audubon Sleep Disorders Center. Patients ranged in age from 15 to 83. All patients had a sleep history, medical history and physical, psychological evaluation, polysomnographic evaluation, and other laboratory tests as indicated. Obstructive sleep apnea syndrome was the most prevalent diagnosis for males (84.2%) and females (59.6%). It accounted for over three-fourths of all diagnoses. Hypersomnia secondary to a psychiatric disorder was the next most frequent diagnosis overall (6.1%). A psychiatric disorder was second for females and third for males. Narcolepsy was diagnosed for 5.8% of all patients. This was the second most prevalent diagnosis for males and third for females. Eighteen males (47.4% of all males with a diagnosis of narcolepsy) and 9 females (45.0%) had cataplexy. Nocturnal myoclonus was the primary diagnosis in 2.5% of all patients with excessive daytime somnolence. An additional 49 patients with sleep apnea syndrome and 18 patients with narcolepsy also had periodic leg movements during sleep. A diagnosis of obstructive sleep apnea and narcolepsy was made for 1.3% of patients. The narcolepsy component of this diagnosis was typically made only after the obstructive sleep apnea had been resolved (eg, nasal CPAP, tracheostomy).(ABSTRACT TRUNCATED AT 250 WORDS)