Relationship between nephrologist care and progression of chronic kidney disease.

BACKGROUND: Since chronic kidney disease (CKD) affects 11% of the United States population, and its incidence is rising, experts recommend early referral to nephrologists in the hope that it may delay the onset of end-stage disease and improve survival. However, limitations in the capacity of currently practicing nephrologists may prevent widespread early referral. OBJECTIVE: To examine the relationship between disease progression and timing of nephrology referral. STUDY DESIGN AND DATA COLLECTION: We retrospectively identified 1,553 veterans at the Durham, North Carolina VA hospital between January 1998 and December 1999 who had CKD, defined as two outpatient serum creatinines > or = 1.4 mg/dL at least three months apart. Our endpoint was a composite of progression to the next CKD stage or death. We compared the time to the composite endpoint for each CKD stage and for early CKD (stages 1-3) to advanced CKD (stages 4 and 5) using a Cox proportional hazards model for two groups: those with primary care only (PCP-only) and those with primary and nephrology care (nephrology). RESULTS: Ninety-two percent had hypertension, 52% diabetes, 49% coronary artery disease, and 89% proteinuria. Angiotensin-converting enzyme inhibitors and anti-lipid medications were used by 52% and 39%, respectively. The median number of days spent in each CKD stage and the proportion of each groups reaching the composite endpoint are--stage 1: 1,149 days, 68% of the PCP-only group and 73% of the nephrology group; stage 2: 1,206 days, 60% and 65%; stage 3: 1,158 days, 69% and 63%; and stage 4: 794 days, 86% and 72%. Adjusted survival curves for the composite endpoint were similar between the two groups for CKD stages 1 (HR 1.08 for nephrology versus PCP-only) and 2 (HR 1.20); however for CKD stages 3 (HR 0.80, p < 0.05) and 4 (HR 0.75, p < 0.05), the nephrology group gained 316, 215, and 120 more days of progression-free survival, respectively. LIMITATIONS: The major limitation is difficulty accounting for unmeasured bias in specialty referrals. We were unable to analyze stage 5-to-dialysis due to the small number of individuals with the outcome. CONCLUSION: Our data suggest that an appropriate time for nephrology comanagement of patients with CKD may be stage 3; however, prospective studies are needed to clarify the role and timing of nephrology referral.

Aseptic peritonitis due to peptidoglycan contamination of pharmacopoeia standard dialysis solution.

BACKGROUND: Manufacturers of parenteral solutions adhere to European and US Pharmacopoeia standards to define safety and sterility. In response to excess cases of aseptic peritonitis in peritoneal dialysis patients using icodextrin-containing dialysate that met all pharmacopoeia standards, a global recall was issued in May, 2002. We aimed to establish the cause of aseptic peritonitis. METHODS: We analysed 186 reports of aseptic peritonitis between September, 2001, and January, 2003. Extensive physical, chemical, and microbiological investigations of recalled dialysate were done. We calculated dose-response curves for peptidoglycan-induced interleukin 6 elaboration in peripheral blood mononuclear cells (PBMCs) from healthy donors and for sterile peritonitis in rats. FINDINGS: Although its chemical constituents and concentrations of endotoxin were within pharmacopoeia specifications, the dialysis solution elicited an interlukin 6 response in vivo and in vitro. We identified peptidoglycan from thermophilic acidophilic bacteria (Alicyclobacillus acidocaldarius) as the contaminating proinflammatory substance. In the PBMC assay, strong dose-response relations were noted between peptidoglycan concentrations and interleukin 6. In rats injected with peptidoglycan, dose-dependent increases of intraperitoneal neutrophils and pyrogenic cytokines were recorded. We measured a positive relation between peptidoglycan concentrations in recalled dialysate and reports of aseptic peritonitis. After implementation of corrective actions, the rate of peritonitis returned to baseline. INTERPRETATION: Excess cases of aseptic peritonitis in peritoneal dialysis patients were due to peptidoglycan contamination of dialysate by Alicyclobacillus. This outbreak serves as an example of how contemporary parenteral products with microbial contaminants can be considered safe under current pharmacopoeia tests, but provoke adverse clinical effects.

Nephrologist care and mortality in patients with chronic renal insufficiency.

BACKGROUND: For patients with chronic renal insufficiency, rates of referral to nephrologists are highly variable, and little is known about the effect of such consultation on clinical outcomes. We sought to determine whether early or frequent access to nephrologist care prior to the initiation of dialysis was associated with a difference in mortality rates in the first year after dialysis began. METHODS: We identified all patients in the New Jersey Medicaid and Medicare programs who began maintenance dialysis during a 6-year period and who had been diagnosed with renal disease more than 12 months prior to dialysis. Use of nephrologist services was documented during this 1-year period, along with other clinical and sociodemographic variables. The outcome measure of our analysis was mortality in the first year after initiation of dialysis. RESULTS: From multivariate analyses, we found that patients who did not see a nephrologist until 90 days or less before initiation of dialysis had a 37% higher likelihood of death in the first year of dialysis compared with patients with earlier referral (95% confidence interval, 1.22-1.52; P<.001). Similarly, those who saw a nephrologist on fewer than 5 occasions in the year prior to dialysis had a 15% higher mortality rate in the first year of dialysis compared with those who had had 5 or more nephrologist visits (95% confidence interval, 1.03-1.28; P =.01). CONCLUSIONS: For patients with long-standing renal disease, earlier consultation with a nephrologist and more frequent specialist encounters is associated with lower mortality in the first year of dialysis. These findings need to be confirmed in younger and less indigent patients as well.

Potential cost savings of erythropoietin administration in end-stage renal disease.

BACKGROUND: In a Department of Veterans Affairs randomized controlled trial, a lower dose of recombinant human erythropoietin (epoetin) was shown to attain target hematocrit levels when administered subcutaneously compared with intravenously. Since epoetin is expensive, optimizing the therapeutic effect of epoetin using a strategy that includes subcutaneous administration could lead to substantial cost savings. METHODS: We used an economic cost projection model to estimate potential savings to the Medicare End-Stage Renal Disease Program that could occur during a transition from intravenous to subcutaneous administration of epoetin among hemodialysis patients. Data included clinical results from the Department of Veterans Affairs randomized controlled trial, the 1998 Centers for Medicare and Medicaid Services' End-Stage Renal Disease Core Indicators Survey, and the 1997-1998 Medicare claims files. In sensitivity analyses, we varied the expected dose reductions (10% to 50%) and the proportion of patients (25% to 100%) who switched to subcutaneous administration. RESULTS: Medicare cost savings were estimated at $47 to $142 million annually as 25% to 75% of hemodialysis patients who received epoetin intravenously switched to subcutaneous administration while reducing the dose by 32%. A minimal reduction (10%) in epoetin dose would result in Medicare cost savings of an estimated $15 to $44 million annually. CONCLUSION: Administering epoetin subcutaneously would provide substantial cost savings to Medicare. For the transition to occur, consensus among stakeholders is needed, especially among patients whose treatment satisfaction and health-related quality of life would be most affected.

Slowing the progression of diabetic nephropathy and its cardiovascular consequences.

This paper incorporates the findings from a multidisciplinary meeting on diabetic nephropathy and its renal and cardiovascular complications into a review article. The epidemic of obesity and the growing elderly population in the United States are primary drivers of a secondary epidemic of incipient type 2 diabetes mellitus and diabetic nephropathy. Current therapies aim to treat blood pressure, particularly with agents that block the renin-angiotensin system, to a target of 130/80 mm Hg. However, even lower blood pressure targets may be optimal. Control of hyperglycemia and dyslipidemia, smoking cessation, exercise, and weight loss all compliment blood pressure control and are achieved most effectively when the patient, provider, and health system are aligned with these goals. Once end-stage renal disease (ESRD) is reached, patients enter the highest cardiovascular risk-state appreciated in human medicine. Because of uniform access to care in the United States, advanced data systems, and circulatory system (intravascular) access in most patients, the ESRD population should be the future sampling frame for newer treatments tested in both prospective cohort and randomized trials. Cardiorenal risk, or the degree of excess cardiovascular risk incurred by patients with chronic kidney disease and ESRD, is a state offering considerable research opportunities for novel cardiovascular risk factors. Future studies should fully consider the possibility that improved outcomes would be achieved at a greater cost; thus, cost-effectiveness studies are essential for understanding the economic aspects of implementation. The goal of an ideal clinical trial would be ESRD prevention; however, pragmatic objectives such as a greater understanding of therapeutic toxicities should also be explored in this population.

Treatment effects of eptifibatide in planned coronary stent implantation in patients with chronic kidney disease (ESPRIT Trial).

The role of platelet glycoprotein IIb/IIIa inhibitor therapy in patients with mild renal impairment is not well characterized. Our objective was to explore the associations of creatinine clearance (CrCl) with outcomes in a trial of eptifibatide therapy in patients who underwent percutaneous coronary intervention (PCI). We analyzed 48-hour and 30-day outcomes of patients enrolled in the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial. Patients were randomly assigned to placebo or eptifibatide as an adjunct to stent implantation (1,755 with CrCl > or =60 ml/min and 289 with CrCl <60 ml/min). CrCl was calculated using the Cockcroft and Gault formula, and the associations of CrCl with outcomes were evaluated using logistic regression models. Patients with CrCl <60 ml/min were more likely to be older, women, hypertensive, and have a history of coronary artery bypass surgery, stroke, or peripheral vascular disease. The interaction of eptifibatide with CrCl had borderline significance for the 30-day outcome (p = 0.109). Treatment effect trended toward a greater magnitude in patients with lower CrCl (60 ml/min) (odds ratio 0.53, confidence interval 0.34 to 0.83) compared with those with higher CrCl (90 ml/min) (odds ratio 0.68, confidence interval 0.49 to 0.94). An accompanying increase in bleeding risk also was not apparent with lower CrCl. The treatment effect of eptifibatide is realized regardless of renal function and trends toward being greater in patients with mild renal impairment.

Developing clinical performance measures based on the Dialysis Outcomes Quality Initiative Clinical Practice Guidelines: process, outcomes, and implications.

BACKGROUND: The National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) Clinical Practice Guidelines established a widely accepted set of recommendations for high-quality dialysis care. To enhance the End-Stage Renal Disease Core Indicators Project, an ongoing effort to assess and improve dialysis care in the United States, the Centers for Medicare and Medicaid Services (CMS) commissioned a project to develop clinical performance measures (CPMs) based on the NKF-DOQI guidelines. METHODS: The CMS contracted with Qualis Health, a private nonprofit organization serving as a Medicare Quality Improvement Organization, to facilitate a 9-month project to develop dialysis CPMs with the participation of a broad range of stakeholders from the renal community. Work groups were established to develop CPMs addressing 4 areas: hemodialysis adequacy, peritoneal dialysis adequacy, vascular access management, and anemia management. The NKF-DOQI guidelines were prioritized based on the strength of the evidence supporting the guidelines, the feasibility of developing performance measures, and the significance of the areas addressed to the quality of care delivered to dialysis patients. Expert panels developed data specifications, sampling approaches, data-collection tools, and analytic strategies. RESULTS: Sixteen CPMs were developed based on 22 of 114 NKF-DOQI guidelines. After establishing reliability through field-testing of data-collection instruments, the CPMs were applied to a sample of 8,838 randomly selected hemodialysis patients and 1,650 randomly selected adult peritoneal dialysis patients in summer 1999. CONCLUSION: The development of CPMs based on the NKF-DOQI Clinical Practice Guidelines for dialysis care was accomplished in a timely and effective manner by engaging a broad range of stakeholders and technical experts. The CPMs are important tools to assess and improve the quality of dialysis care in the United States. Few comparable efforts exist in other fields of medicine.

Comparison of mortality and intermediate outcomes between medicare dialysis patients in HMO and fee for service.

End-stage renal disease (ESRD) is the only disease entitlement for Medicare; therefore, most patients with ESRD have Medicare coverage. Patients with ESRD are prohibited by law from enrolling in health maintenance organizations (HMOs), the only group prohibited within Medicare. However, they may remain in an HMO if they enrolled in such a plan before their kidneys failed. Thus, it is possible to compare patients with ESRD in HMOs with those in fee-for-service (FFS) plans. To determine whether mortality, transplantation rates, and intermediate outcomes differed between Medicare ESRD beneficiaries enrolled in HMO versus FFS providers, a retrospective cohort analysis was performed of patients with ESRD from three Health Care Financing Administration data sets containing administrative and outcome information for Medicare ESRD beneficiaries from 1990 to 1998. On December 31, 1998, a total of 278,510 prevalent patients with ESRD were in FFS plans, and 18,332 patients were in HMOs. HMO patients were older and more likely to be white and male and have diabetes mellitus and comorbid cardiovascular conditions than FFS patients. Unadjusted 2-year survival rates were 48.4% and 49.3% for FFS and HMO patients, respectively. In a multivariate model, HMO status had no significant effect on mortality, which was greater with older age, male sex, and white race. In 1998, unadjusted renal transplantation rates were 23.5% and 15.5% for FFS and HMO patients, respectively; age adjustment abrogated the apparent difference. For FFS and HMO patients, adequate hemodialysis was delivered to 72% and 82%, and 56% and 62% had hematocrits greater than the benchmark, respectively. There was no statistical difference in these outcomes in multivariate comparison. In conclusion, care by HMO for patients with an expensive chronic illness can achieve outcomes similar to those for FFS patients. Claims of poorer care and worse outcomes for patients with ESRD enrolled onto an HMO, an argument used to justify continued prohibition against widespread participation by patients with ESRD, are not supported.

Healthcare system interventions for inequality in quality: corrective action through evidence-based medicine.

Racial differences in the use of diagnostic and therapeutic services have an impact on outcomes in patients with chronic kidney disease. Important contributors to these racial disparities are inadequate insurance, poor access to health services' networks, and overt prejudice or subconscious bias. The use of an appropriate dose of hemodialysis is a fundamental health intervention for end-stage renal disease, which can act as a measure of the adequacy of healthcare provision. When the dose of hemodialysis was analyzed by race, the greatest deficiency in care was observed for African Americans, who had a 60% greater likelihood of receiving inadequate dialysis compared with whites. The Centers for Medicare and Medicaid Services (CMS) have developed and implemented evidence-based clinical practice guidelines, designed to improve the services provided by the renal community. This approach positively impacted on dialysis doses received by patients, such that between 1993 and 1997, the percentage of patients receiving a benchmark urea reduction ratio (URR) > or = 65% increased from 43% in 1993 to 72% in 1997. However, the most dramatic improvement was seen among African Americans who had a 92% increase in the proportion of patients achieving a URR > or = 65%. Rather than focusing on who is treated, processes should be adopted to focus on how patients are treated. Increasing the use of evidence-based practices offers strategies aimed at assuring equal treatment for all and encompasses physician accountability, without the need for specific race-based intervention programs.

Preparing the patient for renal replacement therapy. Teamwork optimizes outcomes.

Proper preparation of a patient with CKD for the development of ESRD and the need for RRT is essential to optimize the patient's quality and quantity of life and to help ensure positive economic and societal outcomes. A collaborative team approach involving the primary care physician team, the patient and his or her family and friends, and the nephrology team should result in improved care of the CKD patient and improved outcomes. It is not possible, feasible, or practical to attempt to provide the inclusive care necessary to attain these goals in a system that does not take advantage of the strengths of a team approach. Adopting this concept of care for patients with kidney disease results in a win-win situation for all of the participants--the patients, the physicians, and society.

Toward a continuous quality improvement paradigm for hemodialysis providers with preliminary suggestions for clinical practice monitoring and measurement.

BACKGROUND: Consensus processes using the clinical literature as the primary source for information generally drive projects to draft clinical practice guidelines (CPGs). Most such literature citations describe special projects that are not part of an organized quality management initiative, and the publication/review/consensus process tends to be long. This project describes an initiative to develop and explore a flexible and dedicated data-driven paradigm for deciding new CPGs that could be rapidly responsive to changing medical knowledge and practice. METHODS: Candidate Clinical Practice Monitoring Measures (CPMM) were selected using a large, national database according to the natures and strengths of their associations with mortality risk among patients during 1994. Thresholds above or below which risk of death increased were evaluated for each CPMM using risk profile charts and spline functions. The fractions of patients outside of those thresholds in each dialysis unit (the %Var) were determined for the years 1993, 1994, and 1995. A standardized mortality ratio (SMR) was also determined for each year for each facility. The associations between the %Var and SMR were evaluated in several single-variable and multivariable statistical models. RESULTS: Eleven CPMM were selected and evaluated based on their associations with death risk. These included the urea clearance x dialysis time product (Kt); the concentrations of albumin, potassium, phosphate, bicarbonate, hemoglobin, neutrophils, and lymphocytes in the blood; the body weight/height ratio; diastolic blood pressure; and vascular access type. Even though the CPMM were strongly associated with death risk among patients, the %Var were weakly and inconsistently associated with SMR among facilities. CONCLUSIONS: The paradigm was flexible, easy to implement, quickly executed, and potentially able to accommodate evolving medical practice assuming the availability of large database systems such as this. The primary associates of death risk were easily identified and the thresholds easily adopted. The SMR and %Var from the CPMM were only weakly associated, however, suggesting that one cannot be reliably predicted from the other. As such, quality management programs should likely monitor both the processes and outcomes of care among dialysis facilities.

Hypertension Improvement Project (HIP): study protocol and implementation challenges.

BACKGROUND: Hypertension affects 29% of the adult U.S. population and is a leading cause of heart disease, stroke, and kidney failure. Despite numerous effective treatments, only 53% of people with hypertension are at goal blood pressure. The chronic care model suggests that blood pressure control can be achieved by improving how patients and physicians address patient self-care. METHODS AND DESIGN: This paper describes the protocol of a nested 2 x 2 randomized controlled trial to test the separate and combined effects on systolic blood pressure of a behavioral intervention for patients and a quality improvement-type intervention for physicians. Primary care practices were randomly assigned to the physician intervention or to the physician control condition. Physician randomization occurred at the clinic level. The physician intervention included training and performance monitoring. The training comprised 2 internet-based modules detailing both the JNC-7 hypertension guidelines and lifestyle modifications for hypertension. Performance data were collected for 18 months, and feedback was provided to physicians every 3 months. Patient participants in both intervention and control clinics were individually randomized to the patient intervention or to usual care. The patient intervention consisted of a 6-month behavioral intervention conducted by trained interventionists in 20 group sessions, followed by 12 monthly phone contacts by community health advisors. Follow-up measurements were performed at 6 and 18 months. The primary outcome was the mean change in systolic blood pressure at 6 months. Secondary outcomes were diastolic blood pressure and the proportion of patients with adequate blood pressure control at 6 and 18 months. DISCUSSION: Overall, 8 practices (4 per treatment group), 32 physicians (4 per practice; 16 per treatment group), and 574 patients (289 control and 285 intervention) were enrolled. Baseline characteristics of patients and providers and the challenges faced during study implementation are presented. The HIP interventions may improve blood pressure control and lower cardiovascular disease risk in a primary care practice setting by addressing key components of the chronic care model. The study design allows an assessment of the effectiveness and cost of physician and patient interventions separately, so that health care organizations can make informed decisions about implementation of 1 or both interventions in the context of local resources. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00201136.

Intradialytic blood volume monitoring in ambulatory hemodialysis patients: a randomized trial.

Complications related to inadequate volume management are common during hemodialysis. This trial tested the hypothesis that availability of an intradialytic blood volume monitoring (IBVM) device improves fluid removal, reducing morbidity. A six-center, randomized trial with 6 mo of intervention comparing IBVM using Crit-Line versus conventional clinical monitoring was conducted. The average rate of non-access-related hospitalizations was compared across treatment groups using Poisson regression. Mortality analysis used the Kaplan Meier method. A total of 227 patients were randomized to Crit-Line, and 216 were randomized to conventional monitoring. Both groups had similar baseline characteristics. During the study, no differences in weight, BP, or number of dialysis-related complications were observed. There were 120 and 81 non-access-related hospitalizations in the Crit-Line and conventional monitoring groups. The adjusted risk ratio for non-access-related and access-related hospitalization was 1.61 (95% confidence interval 1.15 to 2.25; P = 0.01) and 1.52 (95% confidence interval 1.02 to 2.28; P = 0.04) for the Crit-Line monitoring group. Mortality was 8.7% in the Crit-Line monitoring group and 3.3% in the conventional group (P = 0.021). Standardized mortality ratios comparing the Crit-Line and conventional monitoring groups to the prevalent hemodialysis population were 0.77 (NS) and 0.26 (P < 0.001). Hospitalization rates were 1.51 and 1.03 events/yr in the Crit-Line and standard monitoring groups, compared with 2.01 for the prevalent hemodialysis population. IBVM was associated with higher nonvascular and vascular access-related hospitalizations and mortality compared with conventional monitoring. The atypically low hospitalization and mortality rates for the conventional monitoring group suggest that these findings should be generalized to the US hemodialysis population with caution.

Patterns of care for patients with chronic kidney disease in the United States: dying for improvement.

The burden of chronic kidney disease can be assessed by multiple criteria that underscore the need for improved detection, treatment, and outcome monitoring. Several process measures for the care of advanced CKD patients are examined herein. Twenty seven and 11% of patients with CKD in National Health and Nutrition Examination Surveys (NHANES) III had BP <140/90 and 130/85, respectively. In addition to inadequate prescription of antihypertensive drugs, another confounder is poor diagnostic recognition of CKD. Recent surveys of incident Medicare-eligible ESRD patients observed severe anemia in a preponderance of patients; mean and median hematocrit values were 27.7% +/- 5.9 and 27.8%, respectively. Only 23 to 28% of these patients were prescribed epoetin alfa. Clinical practice guidelines recommend that <10% of maintenance hemodialysis patients should be chronically dialyzed using percutaneous catheters. A recent national survey of vascular access types among incident American hemodialysis patients found that 30%, 41%, and 29% were dialyzing through a catheter, prosthetic graft, and autologous fistula, respectively. Tunneled catheters are associated with a 39% annual increased risk of death. Based on pharmacokinetic assumptions about the minimum amount of solute clearance by hemodialysis needed for patient survival in ESRD, a GFR of 10.5 ml/min per 1.73 m(2) is needed. The mean GFR of incident ESRD patients in the United States was 9.5 ml/min per 1.73 m(2) in 2000. In addition to the wide international variability in modality treatment selection, geographic variability exists within the United States; <7 to >15% of the prevalent patients are treated by peritoneal dialysis across the country. Despite survival and quality-of-life benefits with transplantation, most eligible recipients in the United States have not been placed on a transplant waiting list 6 mo after beginning dialysis. Last, <40% of incident ESRD patients in the United States have received the recommended frequency of mammography, PAP examinations, or prostate-specific antigen (PSA) or HbA1c measurements. These deficiencies in care for patients with advanced CKD likely adversely influence the survival of US ESRD patients. Contemporary outcome information supports this contention. CKD patients referred to a nephrologist for the first time within 90 d of the start of dialysis have an approximately 40% to 60% increased risk of death during their first year of renal replacement therapy (RRT). Thirty-five percent of CKD patients are seen within 90 d of receiving RRT. In addition, if fewer than five nephrology visits occur, death risks are increased by 15%. These findings confirm the urgent need for improvement in healthcare delivery for CKD patient in the United States.

Beta 2-microglobulin amyloidosis: role of monocytes/macrophages.

PURPOSE OF REVIEW: Macrophage infiltration is a distinctive histological characteristic of beta2-microglobulin amyloidosis. Studies reported during the past years have helped to clarify the role of monocytes/macrophages in the fibrillar precipitation of beta2-microglobulin and in the pathogenesis of osteoarticular pathology. RECENT FINDINGS: Contrary to the original view, macrophage infiltration is more likely a secondary phenomenon of amyloidosis rather than an initiating event. The observation that macrophages are associated with a later stage of beta2-microglobulin amyloidosis suggests a possible role of these cells in transformation of clinical silent deposits into symptomatic osteoarticular destruction. Accumulating evidence suggests that beta2-microglobulin modified with advanced glycation end products plays a key role in recruitment and activation of macrophages through an advanced glycation end products receptor-mediated pathway, and thus may contribute to the development of local cellular inflammation in beta2-microglobulin amyloidosis. SUMMARY: Beta 2-microglobulin amyloidosis arthropathies may result from progressive accumulation of advanced glycation end products in long-lived amyloid linked to a heightened cellular response. Antagonism of the interaction between advanced glycation end products and their receptor may be a relevant strategy for cellular inflammation in beta2-microglobulin amyloidosis.

Key concepts in biostatistics: using statistics to answer the question "is there a difference?".

Biostatistics seeks to answer the question "Is there a difference?" in the rate of a disease or characteristic among subgroups of patients. The goal of this article is to introduce and define measures used in epidemiology and discuss different types of analyses in clinical research with an emphasis on the concepts and implications of the analyses rather than the mathematics. The implications of the use of measures such as incidence and prevalence, as well as odds, risk, and hazards ratios may affect study conclusions. An understanding of the distinction between these summary measures is essential. The concepts of univariate and multivariate analyses, a discussion of what it means to control for potential confounders, and a description of statistical power and significance are also presented. These concepts are integral to the design and analysis of clinical studies. An understanding of their advantages and applications will enhance the reader's ability to understand and evaluate the literature.

Study designs and their potential influence on conclusions.

Epidemiology is the basic medical science that focuses on the distribution and determinants of disease frequency in human populations. An understanding of the tools of epidemiology is helpful in defining the limitations of medical research and evaluating the conclusions of studies. This is the second in a series of three articles whose objective is to present the basic concepts of epidemiology and biostatistics, highlighted by examples of these concepts applied in the medical literature studying patients receiving dialysis. This article describes the study designs of case-control, cohort, and randomized trials and issues in the conduct and analysis of each. Several studies examining the association between hematocrit and survival of dialysis patients are discussed. Their differences in design and methods are discussed in the context of their effect on study conclusions. The goal of this article is to present the reader with the issues of study design and the limitations they impose on study conclusions. Through the examination of these methods, the reader will be able to rigorously examine study methods and understand how design affects study conclusions and their application to patient care.