Observational studies are just as effective as randomized clinical trials.
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Humans↗
Biomedical subjects
R A Wolfe
Publications and source records attributed to R A Wolfe.
Multivariable statistical methods for clinical studies: a gentle introduction.
Multiple regression models serve the same function as careful and thoughtful evaluation of tabular data. Two examples are given that show the value of holding one factor constant while examining the effect of another factor on an outcome of interest.
Age Factors↗
Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant.
BACKGROUND AND METHODS: The extent to which renal allotransplantation - as compared with long-term dialysis - improves survival among patients with end-stage renal disease is controversial, because those selected for transplantation may have a lower base-line risk of death. In an attempt to distinguish the effects of patient selection from those of transplantation itself, we conducted a longitudinal study of mortality in 228,552 patients who were receiving long-term dialysis for end-stage renal disease. Of these patients, 46,164 were placed on a waiting list for transplantation, 23,275 of whom received a first cadaveric transplant between 1991 and 1997. The relative risk of death and survival were assessed with time-dependent nonproportional-hazards analysis, with adjustment for age, race, sex, cause of end-stage renal disease, geographic region, time from first treatment for end-stage renal disease to placement on the waiting list, and year of initial placement on the list. RESULTS: Among the various subgroups, the standardized mortality ratio for the patients on dialysis who were awaiting transplantation (annual death rate, 6.3 per 100 patient-years) was 38 to 58 percent lower than that for all patients on dialysis (annual death rate, 16.1 per 100 patient-years). The relative risk of death during the first 2 weeks after transplantation was 2.8 times as high as that for patients on dialysis who had equal lengths of follow-up since placement on the waiting list, but at 18 months the risk was much lower (relative risk, 0.32; 95 percent confidence interval, 0.30 to 0.35; P<0.001). The likelihood of survival became equal in the two groups within 5 to 673 days after transplantation in all the subgroups of patients we examined. The long-term mortality rate was 48 to 82 percent lower among transplant recipients (annual death rate, 3.8 per 100 patient-years) than patients on the waiting list, with relatively larger benefits among patients who were 20 to 39 years old, white patients, and younger patients with diabetes. CONCLUSIONS: Among patients with end-stage renal disease, healthier patients are placed on the waiting list for transplantation, and long-term survival is better among those on the waiting list who eventually undergo transplantation.
Adolescent↗
Cancer in patients on dialysis for end-stage renal disease: an international collaborative study.
BACKGROUND: Previous studies have suggested that the frequency of cancer is higher in patients with end-stage renal disease (ESRD) than in the general population, but have not established whether this increase is confined to certain cancers or to certain categories of ESRD patients. The aim of this study was to examine the risk of cancer in a large cohort of patients treated by dialysis but not transplantation. METHODS: We assembled a cohort of 831,804 patients who received dialysis during the period 1980-94 for ESRD in the USA, Europe, Australia, or New Zealand. We compared the observed frequency of cancer among these patients during 2,045,035 person-years of follow-up with the frequency of cancer in the respective background populations. FINDINGS: During average follow-up of 2.5 years, 25,044 (3%) of 831,804 patients developed cancer compared with an expected number of 21,185 (standardised incidence ratio 1.18 [95% CI 1.17-1.20]). We observed a higher risk of cancer in patients younger than 35 years (3.68 [3.39-3.99]), and the risk gradually decreased with increasing age. High risks were observed for cancer of the kidney (3.60 [3.45-3.76]), bladder (1.50 [1.42-1.57]), and thyroid and other endocrine organs (2.28 [2.03-2.54]). Excess cancers appeared in several organs for which viruses have been suspected as causative agents, whereas cancers of the lung, colorectum, prostate, breast, and stomach were not consistently increased. INTERPRETATION: The overall risk of cancer is increased in patients with ESRD, and the distribution of tumour types resembles the pattern seen after transplantation (although we have no data to make the comparison with skin cancer). The excess risk can largely be ascribed to effects of underlying renal or urinary-tract disease, or of loss of renal function, on the kidney and bladder, and to increased susceptibility to viral carcinogenesis. The relative risk, which is especially high in younger patients, gradually diminishes with age.
Adolescent↗
A practical approach to evaluate the potential donor pool and trends in cadaveric kidney donation.
BACKGROUND: The potential supply of transplantable cadaver kidneys is often expressed as donors per million population (pmp), which ignores some essential factors governing organ donation. METHODS: We performed a modeled analysis of kidney donor extraction rates by age, gender, race, cause of death, geographic region, and year in a cohort of evaluable deaths and actual cadaver donors between the ages of 1 and 65 years (1988-1993). Evaluable death was defined as an in-hospital death in patients between the ages of 1 and 65 years whose ICD-9-CM cause of death was not an obvious contraindication to kidney donation. The main outcome measures were the crude donation rate and an adjusted donor extraction rate (DER) per 1000 evaluable deaths. RESULTS: A total of 1.4x10(6) in-hospital deaths produced 300,502 evaluable deaths and 20,575 actual donors. Between 1989 and 1993, DER increased from 61.1 to 75 per 1,000 evaluable deaths. DERs were highest among the youngest age groups, declining significantly with age from 405.0 to 16.7/1,000 evaluable deaths for age groups 1-10 and 56-65 years, respectively. There was a small difference in donors pmp between blacks and whites (15 vs. 18). In contrast, DER was seven times higher in whites compared with blacks (112.5 vs. 16.5/1,000 evaluable deaths; P<0.001). The crude donation rate (per 1,000 evaluable deaths) was high for stroke (604.8) and trauma-related deaths (230.6), resulting in highly efficient donor extraction from these deaths. Region-specific DERs ranged from 49.4 to 83/1,000 evaluable deaths and differed significantly from the corresponding donors pmp. CONCLUSIONS: Estimating kidney donation relative to in-hospital evaluable deaths is a meaningful measure of organ procurement efficiency. Efforts to enhance cadaveric kidney donation should seek to understand and reduce the marked demographic and regional disparity in donor extraction rates.
Adult↗
Renal transplantation in end-stage sickle cell nephropathy.
BACKGROUND: The role of renal transplantation as treatment for end-stage sickle cell nephropathy (SCN) has not been well established. METHODS: We performed a comparative investigation of patient and allograft outcomes among age-matched African-American kidney transplant recipients with ESRD as a result of SCN (n=82) and all other causes (Other-ESRD, n=22,565). RESULTS: The incidence of delayed graft function and predischarge acute rejection in SCN group (24% and 26%) was similar to that observed in the Other-ESRD group (29% and 27%). The mean discharge serum creatinine (SCr) was 2.7 (+/-2.5) mg/dl in the SCN recipients compared to 3.0 (+/-2.5) mg/dl in the Other-ESRD recipients (P=0.42). There was no difference in the 1-year cadaveric graft survival (SCN: 78% vs. Other-ESRD: 77%), and the multivariable adjusted 1-year risk of graft loss indicated no significant effect of SCN (relative risk [RR]=1.39, P=0.149). However, the 3-year cadaveric graft survival tended to be lower in the SCN group (48% vs. 60%, P=0.055) and their adjusted 3-year risk of graft loss was significantly greater (RR= 1.60, P=0.003). There was a trend toward improved survival in the SCN transplant recipients compared to their dialysis-treated, wait-listed counterparts (RR=0.14, P=0.056). In comparison to the Other-ESRD (RR=1.00), the adjusted mortality risk in the SCN group was higher both at 1 year (RR=2.95, P=0.001) and at 3 years (RR=2.82, P=0.0001) after renal transplantation. CONCLUSIONS: The short-term renal allograft result in recipients with end-stage SCN was similar to that obtained in other causes of ESRD, but the long-term outcome was comparatively diminished. There was a trend toward better patient survival with renal transplantation relative to dialysis in end-stage SCN.
Adolescent↗
Predialysis blood pressure and mortality risk in a national sample of maintenance hemodialysis patients.
The role of predialysis blood pressure (BP) as a risk factor for the high mortality in chronic hemodialysis (HD) patients has remained controversial. The objective of the current study was to further explore in a national random sample of 4,499 US hemodialysis patients any relationship of systolic or diastolic and predialysis or postdialysis BP with mortality, while considering subgroups of patients and controlling for other patient characteristics and comorbidities. The main finding of this study is the association of a low predialysis systolic BP with an elevated adjusted mortality risk (relative mortality risk [RR] = 1.86 for systolic BP < 110, P < 0.0001). No association with an elevated mortality risk could be observed for predialysis systolic hypertension (RR = 0.98 to 0.99, not significant [NS]), except for an elevated risk of cerebrovascular deaths. Postdialysis systolic BP was associated with an elevated mortality risk both for low and high BP levels as compared with midrange BP. Further evaluation of the elevated mortality risk associated with low predialysis systolic BP indicated similar patterns for both diabetic and nondiabetic subgroups and for patients with and without congestive heart failure (CHF) or coronary artery disease, although it was more pronounced among those with CHF. The level of predialysis fluid excess did not modify these results substantially. The findings from this historical prospective national study do not argue against the treatment of hypertension and suggest greater attention to postdialysis hypertension. The strikingly elevated mortality risk with low predialysis systolic BP suggests that low predialysis BP needs to be viewed with great concern and avoided where possible.
Adult↗
Relationship of dialysis membrane and cause-specific mortality.
A number of studies have suggested that type of dialysis membrane is associated with differences in long-term outcome of patients undergoing hemodialysis, both in terms of morbidity and mortality. The purpose of this study was to determine the relationship of membrane type and specific causes of death. Data from the United States Renal Data System Case Mix Adequacy Study, a national random sample of hemodialysis patients who were alive on December 31, 1990, were used. Our study was limited to patients in this data set who were undergoing dialysis for at least 1 year (n = 4,055). For the main analytic models, membrane type was classified into two categories: unmodified cellulose or MC/SYN (which combines modified cellulose [MC] and synthetic membranes [SYN]). The relationships of membrane type and major causes of mortality were analyzed using Cox proportional hazards models, which adjusted for multiple (21) covariates, including demographics, comorbidity, Kt/V, and other parameters. Patients were censored at transplantation or 60 days after a switch to peritoneal dialysis. Compared with patients dialyzed with unmodified cellulose membranes, the adjusted relative mortality risk (RR) from infection was 31% lower (RR = 0.69; P = 0.03) and from coronary artery disease was 26% lower (RR = 0.74; P = 0.07) for patients dialyzed with MC/SYN membranes. No statistically significant difference (all P > 0.1) was found in mortality risk from cerebrovascular disease (RR = 1.08), other cardiac causes (RR = 0.86), malignancy (RR = 0.90), or other known causes (RR = 0.82) between patients dialyzed with MC/SYN compared with unmodified cellulose membranes. These results offer support to reported experimental and observational clinical studies that have found that unmodified cellulose membranes may increase the risk for both infection and atherogenesis. Further studies are necessary to evaluate the possibility of confounding factors, compare more specific membrane types, and determine the pathophysiology linking membrane type to cause-specific mortality.
Cause of Death↗
Dialysis modality and the risk of allograft thrombosis in adult renal transplant recipients.
BACKGROUND: Renal vascular thrombosis (RVT) is a rare but catastrophic complication of renal transplantation. Although a plethora of risk factors has been identified, a large proportion of cases of RVT is unexplained. Uremic coagulopathy and dialysis modality may predispose to RVT. We investigated the impact of the pretransplant dialysis modality on the risk of RVT in adult renal transplant recipients. METHODS: Renal transplant recipients (age 18 years or more) who were enrolled in the national registry between 1990 and 1996 (N = 84,513) were evaluated for RVT occurring within 30 days of transplantation. Each case was matched with two controls from the same transplant center and with the year of transplantation. The association between RVT and 18 factors was studied with multivariate conditional logistic regression. RESULTS: Forty-nine percent of all cases of RVT (365 out of 743) occurred in repeat transplant recipients with an adjusted odds ratio (OR) of 5.72 compared with first transplants (P < 0.001). There were a significantly higher odds of RVT in peritoneal dialysis (PD)-compared with hemodialysis (HD)-treated patients (OR = 1.87, P = 0.001). Change in dialysis modality was an independent predictor of RVT: switching from HD to PD (OR = 3.59, P < 0.001) and from PD to HD (OR = 1.62, P = 0.047). Compared with primary transplant recipients on HD (OR = 1.00), the highest odds of RVT were in repeat transplant recipients treated with PD (OR = 12.95, P < 0.001) and HD (OR = 4.50, P < 0.001). Other independent predictors of RVT were preemptive transplantation, relatively young and old donor age, diabetes mellitus and systemic lupus erythematosus as causes of end-stage renal disease, recipient gender, and lower panel reactive antibody levels (PRAs). CONCLUSIONS: The strongest risk factors for RVT were retransplantation and prior PD treatment. Prevention of RVT with perioperative anticoagulation should be studied in patients who have a constellation of the identified risk factors.
Adolescent↗
Survival advantage in Asian American end-stage renal disease patients.
UNLABELLED: Survival advantage in Asian American end-stage renal disease patients. BACKGROUND: An earlier study documented a lower mortality risk for end-stage renal disease (ESRD) patients in Japan compared with the United States. We compared the mortality of Caucasian (white) and Asian American dialysis patients in the United States to evaluate whether Asian ancestry was associated with lower mortality in the United States. METHODS: The study sample from the U.S. Renal Data System census of ESRD patients treated in the United States included 84,192 white or Asian patients starting dialysis during May 1995 to April 1997, of whom 18,435 died by April 30, 1997. Patient characteristics were described by race. Relative mortality risks (RRs) for Asian Americans relative to whites were analyzed by Cox proportional hazards regression models adjusting for characteristics and comorbidities. Population death rates were derived from vital statistics for the United States and Japan by age and sex. RESULTS: Adjusting for demographics, diabetes, comorbidities, and nutritional factors, the RR for Asian Americans was 0.75 (P = 0.0001). Race-specific background population death rates accounted for over half of the race-related mortality difference. For whites, mortality decreased as the body mass index (BMI) increased. For Asians, the relationship between BMI and survival was u-shaped. The ratio of Asian American/white dialysis death rates and the ratio of Asian American/white general population death rates both varied by age in a similar pattern. The population death rates of Asian American and Japanese were also similar. CONCLUSION: Among dialysis patients, Asian Americans had a markedly lower adjusted RR than whites. The effect of BMI on survival differed by race. Compared with the respective general population, dialysis patients had the same relative increase in death rates for both races. The difference in death rates between the United States and Japan does not appear to be primarily treatment related, but rather is related to background death rates.
Adult↗
Clinical and biochemical correlates of starting "daily" hemodialysis.
BACKGROUND: Daily hemodialysis has been proposed to improve outcomes for patients with end-stage renal disease. There has been increasing evidence that daily hemodialysis might have potential advantages over intermittent dialysis. However, despite these potential advantages, daily hemodialysis is infrequently used in the United States, and published accounts on the technique are few. METHODS: We describe patient outcomes after increasing their hemodialysis frequency from three to six times per week in a cohort of 72 patients treated at nine centers during 1972 to 1996. Analyses of predialysis blood pressure and laboratory parameters from 6 months before until 12 months after starting frequent hemodialysis used a repeated-measures statistical technique. RESULTS: Predialysis systolic and diastolic blood pressures fell by 7 and 4 mm Hg, respectively, after starting frequent hemodialysis (P = 0.02). Reductions were greatest among patients being treated with antihypertensive medications, despite a reduction in their dosage of medications. Postdialysis weight fell by 1.0% within one month of starting frequent hemodialysis and improved control of hypertension. After the initial drop, postdialysis weight increased at a rate of 0.85 kg per six months. Serum albumin rose by 0.29 g/dl (P < 0.001) between months 1 to 12 of treatment with daily hemodialysis. Hematocrit rose by 3.0 percentage points (P = 0.02) among patients (N = 56) not treated with erythropoietin during this period. Two years after the start of daily hemodialysis, Kaplan-Meier analyses showed a patient survival of 93%, a technique survival of 77%, and an arteriovenous fistula patency of 92%. Vascular access patency was excellent despite more frequent use of the access. CONCLUSIONS: These results suggest that in certain patients, daily hemodialysis might have advantages over three times per week hemodialysis.
Adolescent↗
Introduction to the excerpts from the United States Renal Data System 1999 Annual Data Report.
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Databases, Factual↗
Racial and gender variation in use of diagnostic colonic procedures in the Michigan Medicare population.
BACKGROUND: There is accumulating evidence that screening programs can alter the natural history of colorectal cancer, a significant cause of mortality and morbidity in the US. Understanding how the technology to diagnose colonic diseases is utilized in the population provides insight into both the access and processes of care. METHOD: Using Medicare Part B billing files from the state of Michigan from 1986 to 1989 we identified all procedures used to diagnose colorectal disease. We utilized the Medicare Beneficiary File and the Area Resource File to identify beneficiary-specific and community-sociodemographic characteristics. The beneficiary and sociodemographic characteristics were, then, used in multiple regression analyses to identify their association with procedure utilization. RESULTS: Sigmoidoscopic use declined dramatically with the increasing age cohorts of Medicare beneficiaries. Urban areas and communities with higher education levels had more sigmoidoscopic use. Among procedures used to examine the entire colon, isolated barium enema was used more frequently in African Americans, the elderly, and females. The combination of barium enema and sigmoidoscopy was used more frequently among females and the newest technology, colonoscopy, was used most frequently among White males. CONCLUSION: The existence of race, gender, and socioeconomic disparities in the use of colorectal technologies in a group of patients with near-universal insurance coverage demonstrates the necessity of understanding the reason(s) for these observed differences to improve access to appropriate technologies to all segments in our society.
Black or African American↗
Prescription of twice-weekly hemodialysis in the USA.
BACKGROUND/AIMS: The purpose of this study was to investigate the frequency and characteristics of two hemodialysis sessions/week, to identify factors which influence or predict this prescription, and to examine the outcomes of patients receiving hemodialysis two times/week as compared to the more common treatment of three times/week. METHODS: Data from a national sample of 15,067 adult hemodialysis patients were utilized to compare twice-weekly with thrice-weekly therapy by logistic regression. RESULTS: Patients treated less than one year were more likely to be treated twice-weekly (6.1%) than patients on dialysis for one year or more (2.7%) (AOR = 1.49, p = 0.002). Treatment schedules also varied significantly by geographic region. Factors predictive of twice-weekly hemodialysis (p < 0.05) were older age, Caucasian race, female gender, higher serum albumin, lower serum creatinine levels, and lower body mass index. A higher estimated renal function at the start of ESRD was also predictive of a twice-weekly schedule among incident patients (AOR = 1.05, p = 0.05). In addition, Cox-adjusted survival analysis indicated a lower mortality risk (RR = 0.76, p = 0. 02) for twice-weekly hemodialysis compared to thrice-weekly among prevalent patients. For incident patients, however, the results were not significant when adjusted for GFR at ESRD onset (RR = 0.85, p = 0.31). CONCLUSION: Geographic differences in prescribed treatment remained unexplained by measured characteristics. The survival advantage associated with twice-weekly hemodialysis is likely to be related to patient selection and greater residual renal function.
Adult↗
Prognosis after primary renal transplant failure and the beneficial effects of repeat transplantation: multivariate analyses from the United States Renal Data System.
BACKGROUND: Survival of transplant recipients after primary renal allograft failure has not been well studied. METHODS: A cohort of 19,208 renal transplant recipients with primary allograft failure between 1985 and 1995 were followed from the date of allograft loss until death, repeat transplantation, or December 31, 1996. The mortality, wait-listing, and repeat transplantation rates were assessed. The mortality risks associated with repeat transplantation were estimated with a time-dependent survival model. RESULTS: In total, 34.5% (n=6,631) of patients died during follow-up. Of these deaths, 82.9% (n=5,498) occurred in patients not wait-listed for repeat transplantation, 11.9% (n=789) occurred in wait-listed patients, and 5.2% (n=344) occurred in second transplant recipients. Before repeat transplantation, the adjusted 5-year patient survival was 36%, 49%, and 65% for type I diabetes mellitus (DM), type II DM, and nondiabetic end-stage renal disease, respectively (P<0.001; DM vs. nondiabetics). The adjusted 5-year patient survival was lower in Caucasians (57%, P<0.001) compared with African-Americans (67%) and other races (64%). The 5-yr repeat transplantation rate was 29%, 15%, and 19%, whereas the median waiting time for a second transplant was 32, 90, and 81 months for Caucasians, African-Americans, and other races, respectively (P<0.0001 each). Repeat transplantation was associated with 45% and 23% reduction in 5-year mortality for type I DM and nondiabetic end-stage renal disease, respectively, when compared with their wait-listed dialysis counterparts with prior transplant failure. CONCLUSIONS: The loss of a primary renal allograft was associated with significant mortality, especially in recipients with type I DM. Repeat transplantation was associated with a substantial improvement in 5-year patient survival. Recipients with type I DM achieved the greatest proportional benefit from repeat transplantation.
Adolescent↗
A critical examination of trends in outcomes over the last decade.
The past decade has seen substantial improvements in end-stage renal disease (ESRD) outcomes, especially mortality, in the United States. Incidence rates for treated ESRD have doubled for most age groups, probably because of improved survival among high-risk populations, such as patients with diabetes and hypertension. The ESRD patient population is becoming older and has a greater incidence of diabetes because of changes in the types of patients starting treatment. The number of patients added to the waiting list each year for transplants has increased dramatically, whereas the number of transplantations performed annually has remained relatively constant. Although transplantation is consequently less available than before, transplant survival, both of the patient and the graft, has improved dramatically. Length of stay for hospitalizations has decreased. Both dialysis mortality and all ESRD mortality have decreased. It is important to monitor such statistics to try and modify adverse trends in outcomes for patients with ESRD. The ability to monitor patient outcomes through national databases has improved greatly during the last decade. Large-scale population-based studies of practices and outcomes for patients with ESRD offer a potent addition to the previously available arsenal of research tools, which was previously dominated by studies from single or few institutions and more expensive randomized clinical trials.
Adolescent↗
Trends in treatment and survival for hemodialysis patients in the United States.
Details regarding dialysis therapy have been studied by the US Renal Data System (USRDS) in four random samples of US hemodialysis patients during the years 1986 to 1997. During this decade, the delivered dose of hemodialysis therapy has increased by at least 0.2 Kt/V. The frequency of twice weekly dialysis prescription decreased, whereas the duration of each treatment showed only minor changes. A large shift to more biocompatible membranes, particularly to synthetic membranes, was observed. The use of acetate dialysate almost disappeared. Outcomes research by the USRDS showed significantly lower mortality risk associated independently with higher delivered Kt/V, substituted cellulose or synthetic membranes, and bicarbonate dialysate. The projected reduction in mortality risk from these changes in hemodialysis therapy was of a similar magnitude to the observed 14% to 17% reduction in mortality rate during the years 1990 to 1996. National observational studies of dialysis patients may influence the practice of dialysis and lead to improved survival.
Humans↗
Reuse of dialyzers and clinical outcomes: fact or fiction.
Since its introduction in the United States more than two decades ago, the practice of dialyzer reuse has continued to grow. In recent years, it appears to have been based mainly on economic, rather than medical, considerations. However, adverse reactions, such as immune hemolytic anemia caused by anti-Nform antibody associated with dialyzer reuse, and infectious outbreaks have been reported. The validity of earlier reports suggesting improved morbidity and mortality in patients dialyzed with reprocessed dialyzers have been disputed with recent data. In the current Dialysis Morbidity and Mortality Study (DMMS), we collected demographic, comorbidity, laboratory, treatment, socioeconomic, and insurance data on a large random sample of approximately 20,000 of the US dialysis patient population over a 3-year period, using the dialysis records. Data were collected predominantly on patients receiving incenter hemodialysis as of December 31, 1993. Morbid and mortal events through 1996 were examined in relation to various patient and dialysis unit characteristics. The results show that there has been a significant increase in the practice of dialyzer reuse in the United States. Large regional differences exist, and reuse is greatest in freestanding for-profit (FSFP) units (87%) and freestanding nonprofit (FSNP) units (77%) and least in hospital units (49%). There has been a significant increase in the proportion of units using Renalin (Minntech, Minneapolis, MN) and a substantial decrease in the proportion of the units using formalin. Approximately 15% of the units each year switch the type of sterilant.
Disinfectants↗