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.

Mitral valve-tricuspid valve distance as a sonographic marker of trisomy 21.

OBJECTIVE: Pathologic studies suggest that a decreased mitral valve-tricuspid valve distance (MTD) is found in trisomy 21 fetuses without cardiac defects. We assessed the feasibility of using the MTD as a second-trimester sonographic marker for trisomy 21. METHODS: We performed a retrospective case-control study of all cases of trisomy 21 at our institution from 1998 to 2008. Cases without a prenatally identified cardiac defect and with adequate images from 15 to 26 weeks' gestation were assessed. The distance between the medial insertions of the mitral and tricuspid valves (i.e. the MTD) onto the ventricular septum was obtained. We also obtained the MTD from normal controls during the study period. Multiple linear regression analysis was used to assess the effects of gestational age and trisomy 21 on MTD. Gestational age-specific percentiles and multiples of the median were calculated, and curves were fitted using linear regression analysis. RESULTS: We identified 57 trisomy 21 fetuses with a measurable MTD and compared these with 634 control fetuses. Multiple linear regression analysis revealed a positive correlation between MTD and gestational age and a negative correlation between trisomy 21 and MTD. Using a cut-off of the 5(th) percentile, the MTD detected 70% of trisomy 21 cases with a 3.8% false-positive rate in the controls. CONCLUSIONS: The MTD increases with gestational age and is lower in fetuses with trisomy 21. Twenty (35%) of the 57 cases had no sonographic marker of trisomy 21 except an MTD below the 5(th) percentile for gestational age. The MTD was a useful independent marker for trisomy 21 in the second trimester.

Frequent Hemodialysis Network (FHN) randomized trials: study design.

Observational studies suggest improvements with frequent hemodialysis (HD), but its true efficacy and safety remain uncertain. The Frequent Hemodialysis Network Trials Group is conducting two multicenter randomized trials of 250 subjects each, comparing conventional three times weekly HD with (1) in-center daily HD and (2) home nocturnal HD. Daily HD will be delivered for 1.5-2.75 h, 6 days/week, with target eK(t)/V(n) > or = 0.9/session, whereas nocturnal HD will be delivered for > or = 6 h, 6 nights/week, with target stdK(t)/V of > or = 4.0/week. Subjects will be followed for 1 year. The composite of mortality with the 12-month change in (i) left ventricular mass index (LVMI) by magnetic resonance imaging, and (ii) SF-36 RAND Physical Health Composite (PHC) are specified as co-primary outcomes. The seven main secondary outcomes are between group comparisons of: change in LVMI, change in PHC, change in Beck Depression Inventory score, change in Trail Making Test B score, change in pre-HD serum albumin, change in pre-HD serum phosphorus, and rates of non-access hospitalization or death. Changes in blood pressure and erythropoiesis will also be assessed. Safety outcomes will focus on vascular access complications and burden of treatment. Data will be obtained on the cost of delivering frequent HD compared to conventional HD. Efforts will be made to reduce bias, including blinding assessment of subjective outcomes. Because no large-scale randomized trials of frequent HD have been previously conducted, the first year has been designated a Vanguard Phase, during which feasibility of randomization, ability to deliver the interventions, and adherence will be evaluated.

End-stage renal disease in diabetic persons: is the pandemic subsiding?

Analysis of data compiled by the United States Renal Data System and the National Health Interview Survey as reported in the Centers for Disease Control and Prevention's Weekly Morbidity and Mortality Report indicates that between 1990 and 2002, there has been a sharp decline in incidence rate of the number of persons with diabetes who develop end-stage renal disease. Although it is comforting to practitioners to attribute this improvement to a widely advocated regimen of renoprotection, consisting of careful regulation of hypertensive blood pressure, improved glycemic control, and lifestyle modification, evidence for this causal relationship is appearing only now. There is need to clarify the source of this epidemiologic change that will lessen the projected burden on medical and socioeconomic resources in the immediate future.

Improved survival in HIV-infected African-Americans with ESRD.

AIMS: To determine if there has been improvement in survival of HIV-infected patients with end-stage renal failure subsequent to widespread use of highly active antiretroviral therapy. METHODS: The United States Renal Data System is a national data system funded by the National Institute of Diabetes and Digestive and Kidney Disease with the Centers for Medicare and Medicaid. Using the United States Renal Data System Standard Analysis Files, we analyzed all African-American end-stage renal failure patients in the United States from 1990-2001. We compared survival rates for patients with HIV disease, sickle cell anemia, diabetes, and all other diagnoses for the time periods 1990-1994 and 1995-2001. The main outcome measure was one- and five-year survival in each cohort. RESULTS: One-year survival of African-American patients with end-stage renal disease and HIV increased from 46.6% during 1990-1994 to 65.1% during 1995-2001 (odds ratio 2.139). One-year survival decreased in the sickle cell group (odds ratio 0.595) and decreased slightly in the diabetic group (odds ratio 0.927) and all others (odds ratio 0.941). Five-year survival in the HIV group increased from 13.3% in 1990-1995 to 30.4% in 1995-2001 (odds ratio 2.847). There was no corresponding increase in survival for the sickle cell group (odds ratio 0.987), the diabetic group (odds ratio 1.06), or all others (odds ratio 1.137). CONCLUSIONS: We conclude that survival in African-American end-stage renal disease patients and HIV infection has substantially improved subsequent to introduction of highly active antiretroviral therapy. Our data support aggressive multi-drug treatment of end-stage renal failure patients with HIV infection.

Ion channels from linear and branched bola-amphiphiles.

The synthesis and characterization of the ion channel activity of three new bola-amphiphiles is described. These compounds are conceptually derived from a previously reported bis-cyclophane bola-amphiphile through opening of the cyclophanes to acyclic structures and were found to readily form ion channels in planar bilayer membranes as assessed by bilayer clamp single-channel analysis. All three compounds behaved very similarly: the dominant channels formed by all three are Ohmic with specific conductance of 10 +/- 1 pS (NaCl electrolyte) and 39 +/- 1 pS (CsCl electrolyte). Single-ion permeability ratios, determined from dissymmetric electrolyte experiments, showed the selectivity P(Cs(+)) > P(Na(+)) > P(Cl(-)). Less frequently, lower conductance channels were also observed to act independently of the dominant channels. The lifetimes of the dominant channels range from 70 to 280 ms for the three compounds with some very long-lived openings (20-40 s) observed for two of the three. The lower conductance states have shorter lifetimes. This study demonstrates that bis-macrocyclic compounds are not essential for channel formation by bola-amphiphiles, and opens a new class of channel-forming compounds for structure-activity optimization.

A quarter century of medicare expenditures for ESRD.

Medicare's end-stage renal disease (ESRD) program is unique in that it is the only example of an entitlement program based solely on the basis of a clinical condition. Medicare payments on behalf of ESRD beneficiaries is a combination of ESRD-specific payment policies such as those for dialysis, physician oversight, erythropoeitin, and immunosuppression and general Medicare payment policies such as hospital payments, nondialysis physician services, home health, and skilled nursing care. Over the 25-year history of the program, much of the ESRD-related care has been subject to cost controls more stringent than elsewhere in Medicare. Total payments for ESRD beneficiaries continue to consume an ever-increasing percentage of Medicare expenditures, largely because of ever-expanding patient treatment criteria. However, increases in per capita expenditures for ESRD beneficiaries have been far below that of Medicare in general.

Racial and ethnic differences in hospitalization rates among aged Medicare beneficiaries, 1998.

Efforts to study racial variations in access to health care for minorities other than black persons have been hampered by a paucity of data. The Health Care Financing Administration (HCFA) has made efforts in the past few years to enhance the racial codes on the Medicare enrollment files to include Hispanic, Asian American, and Native American designations. This study examines hospitalization rates by these more detailed racial/ethnic groupings. The results show black, Hispanic, and Native American aged beneficiaries compared with white beneficiaries have higher hospitalization rates. Asian American beneficiaries have lower hospitalization rates. Rates of revascularization--coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty (PTCA)--are lower for black, Hispanic, and Native American beneficiaries compared with white beneficiaries, while rates for Asian Americans are similar to rates for white beneficiaries.

Trends in use, cost, and outcomes of human recombinant erythropoietin, 1989-98.

In this article the authors present descriptive data showing trends in human recombinant erythropoietin (EPO) doses, charges, and patient hematocrits from the fourth quarter of calendar year 1989 to the first quarter of 1998 for all recipients and recent data for patients treated by in-center hemodialysis. In 1997 nearly all in-center hemodialysis patients received EPO regularly at an average cost per recipient of $6,245 per year for total allowed charges of $842.2 million per year. The study shows that policy changes may have both anticipated and unanticipated effects on medical practice.

Nontraumatic lower extremity amputations in the Medicare end-stage renal disease population.

BACKGROUND: Nontraumatic lower limb amputation is a serious complication of both diabetic neuropathy and peripheral vascular disease. Many people with end-stage renal disease (ESRD) suffer from advanced progression of these diseases. This study presents descriptive information on the rate of lower limb amputation among people with ESRD who are covered by the Medicare program. METHODS: Using hospital bill data for the years 1991 through 1994 from the Health Care Financing Administration's ESRD program management and medical information system (PMMIS), amputations were based on ICD9 coding. These hospitalizations were then linked back to the PMMIS enrollment database for calculation of rates. RESULTS: The rate of lower limb amputation increased during the four-year period from 4.8 per 100 person years in 1991 to 6.2 in 1994. Among persons whose renal failure was attributed to diabetic nephropathy, the rates in 1991 and 1994 were 11.8 and 13.8, respectively. The rate among diabetic persons with ESRD was 10 times as great as among the diabetic population at large. Two thirds died within two years following the first amputation. CONCLUSIONS: The ESRD population is at an extremely high risk of lower limb amputation. Coordinated programs to screen for high-risk feet and to provide regular foot care for those at high risk combined with guidelines for treatment and referral of ulceration are needed.

Development of an end-stage renal disease managed care demonstration.

At present, end-stage renal disease (ESRD) beneficiaries cannot enroll in health maintenance organizations (HMOs) or social health maintenance organizations (SHMOs), but HMO members who develop ESRD may remain enrolled, and the Health Care Financing Administration (HCFA) pays the HMO a state-specific, but otherwise unadjusted, capitation rate that is 95% of fee-for-service (FFS) costs. Thus, more than 6,000 ESRD beneficiaries were enrolled in HMOs in 1993, when Congress mandated an ESRD SHMO demonstration in which not only Medicare-covered services, but extra benefits were to be provided to Medicare beneficiaries, with the SHMO receiving a capitation rate based on 100% of FFS costs. The demonstration will test (1) the feasibility of year-round open enrollment of ESRD beneficiaries in HMOs; (2) a capitation system based on treatment status--dialysis, transplant, or functioning graft--and adjusted for age and whether diabetes was the cause of renal failure; (3) the effect of the additional benefits; and (4) whether managed care can improve ESRD quality outcomes. HCFA made demonstration awards in September 1996 to Kaiser-Permanente in Southern California; Health Options in Southern Florida; and Phoenix Healthcare in Central Tennessee. The sites are expected to have 1 year of planning and development before beginning the congressionally mandated 3 years of service delivery. There will be an independent evaluation.

Magnitude of end-stage renal disease in IDDM: a 35 year follow-up study.

Significant improvements were made during the last two decades in the treatment of IDDM patients. To assess the risk of ESRD in a population that was exposed to these improvements, we determined the cumulative incidence of ESRD in a cohort of 142 white patients who were aged less than 21 years when they came to the Joslin Diabetes Center in 1959 with recently diagnosed IDDM. The first case of ESRD occurred after 13 years of IDDM, and a total of 25 cases have developed by 35 years' duration (cumulative incidence 21.3%). Median survival after the diagnosis of ESRD for the 16 patients who began dialysis was only 3.5 years. A strong predictor of the development of ESRD was the level of glycemic control during the first two decades of IDDM. ESRD developed in 36.3% of patients in the worst tertile for glycemic control but only in 14.4% and 9.2% of those in the middle and best tertiles. In comparison with two population based studies, the onset of ESRD in the Joslin Cohort was postponed by about five years. This advantage is more plausibly attributable to differences arising after the diagnosis of diabetes than to referral of less severe cases of IDDM to the Joslin Diabetes Center. What differences in diabetes care accounted for the postponement of ESRD cannot be discerned from comparisons among published studies, but likely candidates include Joslin's long-term advocacy of good glycemic control and the prompt implementation of new clinical interventions, such as antihypertensive treatment.

Effects of race and income on mortality and use of services among Medicare beneficiaries.

BACKGROUND: There are wide disparities between blacks and whites in the use of many Medicare services. We studied the effects of race and income on mortality and use of services. METHODS: We linked 1990 census data on median income according to ZIP Code with 1993 Medicare administrative data for 26.3 million beneficiaries 65 years of age or older (24.2 million whites and 2.1 million blacks). We calculated age-adjusted mortality rates and age- and sex-adjusted rates of various diagnoses and procedures according to race and income and computed black:white ratios. The 1993 Medicare Current Beneficiary Survey was used to validate the results and determine rates of immunization against influenza. RESULTS: For mortality, the black:white ratios were 1.19 for men and 1.16 for women (P<0.001 for both). For hospital discharges, the ratio was 1.14 (P<0.001), and for visits to physicians for ambulatory care it was 0.89 (P<0.001). For every 100 women, there were 26.0 mammograms among whites and 17.1 mammograms among blacks. As compared with mammography rates in the respective most affluent group, rates in the least affluent group were 33 percent lower among whites and 22 percent lower among blacks. The black:white rate ratio was 2.45 for bilateral orchiectomy and 3.64 for amputations of all or part of the lower limb (P<0.001 for both). For every 1000 beneficiaries, there were 515 influenza immunizations among whites and 313 among blacks. As compared with immunization rates in the respective most affluent group, rates in the least affluent group were 26 percent lower among whites and 39 percent lower among blacks. Adjusting the mortality and utilization rates for differences in income generally reduced the racial differences, but the effect was relatively small. CONCLUSIONS: Race and income have substantial effects on mortality and use of services among Medicare beneficiaries. Providing health insurance is not enough to ensure that the program is used effectively and equitably by all beneficiaries.

Racial differences in access to kidney transplantation.

Previous work has documented large differences between black and white populations in overall kidney transplantation rates and in transplantation waiting times. This article examines access to transplantation using three measures: time from renal failure to transplant; time from renal failure to wait listing; and time from wait listing to transplantation. This study concludes the following First, no matter what measure of transplant access is used, black end stage renal disease (ESRD) beneficiaries fare worse than white, Asian-American, or Native American ESRD beneficiaries. Second, because the rate of renal failure exceeds the number of cadaver organs, access to kidney transplantation will deteriorate in future years for all races.

Renal replacement therapy in the United States: data from the United States Renal Data System.

This report is a summary of the discussion on the United States Renal Data System and its data contents, as presented at the Symposium on World Renal Registries on December 10, 1993. The United States Rental Data System is a national database that collects and analyzes information on the incidence, prevalence, morbidity, and mortality, as well as the modalities of therapy of patients with end-stage renal disease (ESRD) in the United States. The database is funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. Data on the patients are provided by the Health Care Financing Administration Medicare Program. The coordinating center for the database, operated through a contract mechanism, was formerly at the Urban Institute in Washington, DC, but is currently located at the University of Michigan, Ann Arbor, MI. The data system contains information on over 462,000 patients with more than 4 million dialysis records, 2.3 million inpatient records, 94,000 transplant reports, and more than 290,000 follow-up reports. The incidence rate of ESRD is approximately 180 per million population. However, the rate is higher in African-Americans (430) and Native Americans (281) than in whites (153) and Asian/Pacific Islanders (133). The gross mortality rate of the entire ESRD population is approximately 168 deaths per 1,000 patient-years at risk. The death rate is higher in diabetic than in nondiabetic ESRD patients. It is also higher in ESRD patients older than 65 years (357) than in patients in the 45- to 64-year-old age group (158) or those in the 20- to 44-year-old age group (62).

Cost issues in transplantation.

Major clinical progress has been made in recent years in solid organ transplantation. With the exception of kidney transplantation, very little reliable information is available concerning the costs of organ transplantation. This article addresses problems in assessing organ transplantation costs and makes recommendations about research approaches. It is suggested that the United Network for Organ Sharing waiting lists are good sources for developing transplant cost studies.

The use of Health Care Financing Administration data for the development of a quality improvement project on the treatment of anemia.

The Health Care Financing Administration maintains a wide array of data systems that are essential to the functioning of the Medicare program. These data, collected and maintained for the purposes of ensuring entitlements and payment for services, also can be used to monitor programmatic changes and to define potential problem areas. The end-stage renal disease (ESRD) Program Management and Medical Information System (PMMIS) is a subset of the larger Medicare statistical system. It is a historic record of all Medicare ESRD beneficiaries dating back to 1978. Basic Medicare enrollment information on ESRD beneficiaries is enhanced with the addition of information on the cause of renal failure, type of dialysis therapy, transplantation history, and cause of death. The ESRD PMMIS has been put to a number of uses in the past decade or so, ranging from basic descriptive epidemiology to analyses of mortality rates to assessments of programmatic issues such as the composite rate and dialyzer reuse. Because of the limited clinical detail in the PMMIS, there are many specific questions that cannot be adequately addressed. With approval of the Food and Drug Administration and Medicare coverage of erythropoietin, a erythropoietin monitoring system was developed to assess utilization trends of this anemia control drug. Within a few months it became evident that dosing levels for erythropoietin were much lower than expected from the clinical trials. Following a change in the payment method from a fixed amount to one based on dose level, dosing has increased markedly. However, hematocrit levels still remain below optimal levels. This lack of hematocrit response has led the Health Care Financing Administration, in concert with the renal community, to target anemia control as a potential health care quality improvement project. This paper presents an example of the type of data presentation that can be derived from the current PMMIS. The Health Standards and Quality Bureau has made a commitment to a program of continuous quality improvement. Part of this process is the provision of descriptive data that can be the starting point for an iterative approach to quality improvement.