Controlling confounding of treatment effects in administrative data in the presence of time-varying baseline confounders.

PURPOSE: Confounding, a concern in nonexperimental research using administrative claims, is nearly ubiquitous in claims-based pharmacoepidemiology studies. A fixed-length look-back window for assessing comorbidity from claims is common, but it may be advantageous to use all historical claims. We assessed how the strength of association between a baseline-identified condition and subsequent mortality varied by when the condition was measured and investigated methods to control for confounding. METHODS: For Medicare beneficiaries undergoing maintenance hemodialysis on 1 January 2008 (n = 222 343), we searched all Medicare claims, 1 January 2001 to 31 December 2007, for four conditions representing chronic and acute diseases, and classified claims by number of months preceding the index date. We used proportional hazard models to estimate the association between time of condition and subsequent mortality. We simulated a confounded comorbidity-exposure relationship and investigated an alternative method of adjustment when the association between the condition and mortality varied by proximity to follow-up start. RESULTS: The magnitude of the mortality hazard ratio estimates for each condition investigated decreased toward unity as time increased between index date and most recent manifestation of the condition. Simulation showed more biased estimates of exposure-outcome associations if proximity to follow-up start was not considered. CONCLUSIONS: Using all-available claims information during a baseline period, we found that for all conditions investigated, the association between a comorbid condition and subsequent mortality varied considerably depending on when the condition was measured. Improved confounding control may be achieved by considering the timing of claims relative to follow-up start.

Diabetic Cardiovascular Disease Predicts Chronic Kidney Disease Awareness in the Kidney Early Evaluation Program.

AIMS: Lack of chronic kidney disease (CKD) awareness is common. Recent data suggest that the presence of concurrent diabetes may heighten CKD awareness, but current data have not supported the hypothesis that healthcare delivery or insurance status improves awareness in the diabetic population. Diabetes is associated with high cardiovascular disease (CVD) morbidity, especially in patients with CKD. We hypothesized that a highly prevalent co-morbid condition such as CVD in patients with diabetes would predict CKD awareness. METHODS: We utilized data from theNational Kidney Foundation-Kidney Early Evaluation Program (KEEPTM), a large screening program designed to identify high-risk individuals for CKD and promote awareness. RESULTS: Among 77,077 participants, CKD was identified in 20,200 and diabetes in 23,082. Prevalence of CVD was higher in participants with than without diabetes (39.5 vs. 22.0%) and in stage 3-5 compared to stage 1-2 CKD (43.3 vs. 34.4%). Patients with diabetes and CVD had a higher level of awareness than those without diabetes (8.2 vs. 2.2%). Among patients with diabetes and CVD, the presence of congestive heart failure was a better predictor of awareness [odds ratio (OR) 1.84; 95% confidence interval (CI) 1.40-2.43] than endpoints such as myocardial infarction or stroke [OR 1.35 (95% CI 1.04-1.73) and OR 1.34 (95% CI 1.04-1.72), respectively]. CONCLUSIONS: While prevalence of CKD awareness remained low, our data suggest that in patients with diabetes the presence of CVD was associated with increased awareness in a targeted screening program for CKD awareness.

Mortality from cancer among US hemodialysis patients, 1995-2005.

BACKGROUND/AIMS: Concern has emerged that erythropoiesis-stimulating agents (ESAs) may decrease survival for cancer patients; many patients beginning dialysis have previous cancer diagnoses. As ESA doses have more than tripled in the USA since ESAs were introduced, we aimed to compare annual trends in cancer-specific mortality rates among incident maintenance hemodialysis patients. METHODS: This national, retrospective, incident cohort study included 873,493 patients aged > or =20 years who initiated hemodialysis between 1995 and 2005. Cancer-specific mortality rates were adjusted for baseline characteristics, determined from the Centers for Medicare & Medicaid Services (CMS) Medical Evidence Report (form CMS-2728). Follow-up extended to December 31, 2006. Cause of death was ascertained from the Death Notification (form CMS-2746). RESULTS: Crude first-year cancer-specific mortality rates, per 1,000 patient-years, 1995-2005, were as follows: 13.8, 13.7, 14.2, 14.9, 13.8, 15.4, 15.4, 16.5, 16.4, 15.8, 15.2. Mortality rates remained stable year to year within subsequent follow-up intervals; for the first and last annual cohorts, mortality rates by follow-up interval were: year 2, 9.1 and 8.7; year 3, 8.6 and 8.3; years 4-5, 7.9 and 6.8. Annual comparisons were similar after adjustment for patient characteristics at dialysis initiation. CONCLUSION: Cancer-specific mortality rates remained stable among US hemodialysis patients between 1995 and 2005.

Diabetes mellitus and CKD awareness: the Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: Diabetes contributes to increased morbidity and mortality in patients with chronic kidney disease (CKD). We sought to describe CKD awareness and identify factors associated with optimal glycemic control in diabetic and nondiabetic individuals both aware and unaware of CKD. METHODS: This cross-sectional analysis compared Kidney Early Evaluation Program (KEEP) and National Health and Nutrition and Examination Survey (NHANES) 1999 to 2006 participants with diabetes and CKD. CKD was defined and staged using glomerular filtration rate (estimated by using the 4-variable Modification of Diet in Renal Disease Study equation) and urine albumin-creatinine ratio. NHANES defined diabetes as self-reported diabetes or fasting plasma blood glucose level of 126 mg/dL or greater, and KEEP as self-reported diabetes or diabetic retinopathy, use of diabetes medications, fasting blood glucose level of 126 mg/dL or greater, or nonfasting glucose level of 200 mg/dL or greater. RESULTS: Of 77,077 KEEP participants, 20,200 (26.2%) were identified with CKD and 23,082 (29.9%) were identified with diabetes. Of 9,536 NHANES participants, 1,743 (18.3%) were identified with CKD and 1,127 (11.8%) were identified with diabetes. Of KEEP participants with diabetes and CKD (n = 7,853), 736 (9.4%) were aware of CKD. Trends in lack of CKD awareness were similar for KEEP participants with and without diabetes. Unaware participants with and without diabetes identified with stages 1 and 2 CKD were less likely to reach target glucose levels, defined as fasting glucose level less than 126 mg/dL or nonfasting glucose level less than 140 mg/dL, than those with stages 3 to 5 (odds ratio, 0.69; 95% confidence interval, 0.62 to 0.78; odds ratio, 0.69; 95% confidence interval, 0.58 to 0.81; P < 0.001, respectively). CONCLUSION: Our data support that KEEP, as a targeted screening program, is a more enriched population with CKD and comorbid diabetes than NHANES. In addition, our findings highlight the relationship between dysglycemia and early stages of unidentified CKD.

Anaemia and mortality in haemodialysis patients: interaction of propensity score for predicted anaemia and actual haemoglobin levels.

BACKGROUND: Haemoglobin levels in haemodialysis patients could represent unknown comorbidities, more severe levels of known comorbidities, as well as therapeutic choice. Thus, integrating factors predictive of anaemia with actual haemoglobin levels might improve prognostic discrimination. METHODS: We retrospectively studied 93,087 patients who started haemodialysis between 1998 and 2000. Clinical and treatment factors from months 4 through 9, derived from Medicare claims, were used to develop propensity scores for anaemia (mean haemoglobin <11 g/dl). Tertiles of propensity scores were interacted with five levels of actual mean haemoglobin to form 15 groups, ranging from low (anaemia) probability with (mean) haemoglobin <10 g/dl to high probability with haemoglobin >or=13 g/dl. Cox proportional hazards regression evaluated mortality and first hospitalization among these groups. RESULTS: The anaemia propensity score improved overall prognostic discrimination. Propensity score adjustment significantly improved prediction of mortality (P<0.0001) after covariate adjustments including haemoglobin. For mortality, the highest and lowest adjusted hazard ratios (AHR) appeared in these groups, respectively: high probability with haemoglobin <10 g/dl (AHR 1.64 [1.54, 1.75], P<0.0001), and low probability with haemoglobin 12 to <13 g/dl (AHR 0.79 [0.74, 0.85], P<0.0001). Higher haemoglobin levels were associated with lower mortality even after propensity score adjustment. Similar patterns resulted for first hospitalization; however, the interaction was significant only for hospitalization (P = 0. 0212). CONCLUSIONS: Integrating factors predictive of anaemia improves overall prognostic discrimination. Propensity score adjustment refines the prognostic association of haemoglobin levels in haemodialysis patients.

Trends in intravenous iron use among dialysis patients in the United States (1994-2002).

BACKGROUND: Two new intravenous (IV) iron products, ferric gluconate and iron sucrose, recently were approved for use in the United States. We report trends in IV iron use in both incident (1994 to 2001) and prevalent (1994 to 2002) Medicare US dialysis patients. METHODS: Included patients had Medicare as a primary payer. Recombinant human erythropoietin doses, IV iron use, and hemoglobin data were obtained from Medicare outpatient files. The most recent cohorts included 241,770 prevalent hemodialysis (HD) patients in 2002 and 11,744 incident HD patients in 2001. RESULTS: For incident HD patients in the first 9 months of dialysis therapy, the percentage of patients administered IV iron increased sharply between 1994 and 1997 and then increased gradually between 1997 and 2001. In 2002, a total of 84.4% of HD and 19.3% of peritoneal dialysis (PD) patients were administered IV iron. Ferric gluconate use increased slowly in 2000, increased from 5.7% to 18.6% from December 2000 to January 2001, increased to 29.8% in April 2002, and was 23.3% in December 2002. Iron sucrose use increased to 26% by December 2002. The absolute monthly percentage of HD patients administered IV iron dextran decreased from 49.6% in January 2000 to 3.6% in December 2002. CONCLUSION: In US patients with end-stage renal disease, IV iron use has increased, although slowly, from 1997 to 2002. Ferric gluconate and iron sucrose have become the predominant form of therapy. IV iron therapy was used in a much smaller percentage of PD compared with HD patients, and racial and geographic variability was observed.

A comparison of peritonitis rates from the United States Renal Data System database: CAPD versus continuous cycling peritoneal dialysis patients.

BACKGROUND: Previous comparisons of peritonitis rates between continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis (CCPD) have produced varying results. METHODS: Using United States Renal Data System data, the authors evaluated peritonitis rates in 1994 through 1997 incident CAPD (n = 9,190) and CCPD (n = 2,785) Medicare patients. Patients were characterized during a 6-month entry period (months 4 through 9) and followed for a maximum of 2 years (months 10 through 33). Medicare claims data provided the date of the first peritonitis episode during the follow-up period. The time to first peritonitis after 9 months of PD was compared by the log-rank test, and then by Cox regression with adjustment for peritoneal dialysis modality, age, sex, race, primary end-stage renal disease (ESRD) diagnosis, number of entry-period hospital days, peritonitis during the entry period, hematocrit value, and congestive heart failure. RESULTS: For CAPD and CCPD, the adjusted average months to first peritonitis after 9 months of PD were 17.1 and 16.1, respectively. The probabilities of remaining without a peritonitis episode after 1 year of follow-up were 0.53 and 0.50, respectively ( P = 0.008). The risk of peritonitis was lower for CAPD than for CCPD (relative risk, 0.939; 95% confidence interval, 0.883 to 0.998). Other significant risk factors included age or=36% had lower risk of peritonitis. CONCLUSION: Compared with CCPD, CAPD is associated with a slightly but significantly lower risk for development of a first peritonitis episode after 9 months of peritoneal dialysis therapy.

Relationship among catheter insertions, vascular access infections, and anemia management in hemodialysis patients.

BACKGROUND: Arteriovenous fistulas are the recommended permanent vascular access (VA) for chronic hemodialysis. However, in the United States most patients begin chronic hemodialysis with a catheter. Recent data suggest that VA type contributes to recombinant human erythropoietin (rHuEPO) resistance. We examined catheter insertions, VA infections, and anemia management in Medicare, rHuEPO-treated, chronic hemodialysis patients. METHODS: We compared hemoglobin values and rHuEPO and intravenous iron dosing with concurrent catheter insertions and VA infections in 186,348 period-prevalent patients in 2000. We studied anemia management after catheter insertions and VA infections in 67,410 incident patients from 1997 to 1999. Multiple linear regression models examined follow-up hemoglobin and rHuEPO dose per week (rHuEPO/wk) by numbers of catheter insertions and hospitalizations for VA infection. RESULTS: In the prevalent cohort, increasing temporary and permanent catheter insertions and VA infections were associated with slightly lower hemoglobin, higher rHuEPO doses, and higher intravenous iron doses. In the incident cohort, compared to patients with no VA infections or no catheter insertions (temporary or permanent), respectively, patients with 2+ VA infections or 2+ catheter insertions had 0.12 g/dL and 0.06 g/dL lower mean hemoglobin (P = 0.0028 and P < 0.0001), and 25.7% and 12.2% higher mean rHuEPO/wk (P < 0.0001). CONCLUSION: Higher rHuEPO doses may be required to maintain similar or slightly lower mean hemoglobin values among chronic hemodialysis patients with higher numbers of catheter insertions and VA infections, compared to patients without any.

Prevalence of anemia in erythropoietin-treated pediatric as compared to adult chronic dialysis patients.

BACKGROUND: Recent guidelines recommend a target hemoglobin range of 11 to 12 g/dL in pediatric and adult dialysis patients. We compared anemia prevalence in United States Medicare pediatric and adult dialysis patients. METHODS: Prevalent hemodialysis patients (0 to 19 years, pediatric: N= 1692; adult: N= 352,291) and peritoneal dialysis patients (pediatric: N= 597; adult: N= 39,136) treated with recombinant human erythropoietin (rHuEPO) from 1996 to 2000 were selected. Mean annual hemoglobin values were calculated by modality, age, sex, and race. RESULTS: Among hemodialysis patients, mean annual hemoglobin values less than 11 g/dL were present in pediatric and adult patients during 54.1% versus 39.8% patient years, respectively (P < 0.0001); for peritoneal dialysis patients, 69.5% versus 55.1% (P < 0.0001). Mean hemoglobin values increased over time and were 11.2, 11.5, 10.8, and 11.2 g/dL for pediatric and adult hemodialysis and peritoneal dialysis patients, respectively, in 2000. Pediatric hemodialysis patients received intravenous iron less frequently than adults (66.3% vs. 82.5% patient years; P < 0.0001). CONCLUSION: Hemoglobin values in rHuEPO-treated pediatric dialysis patients lagged behind those of adult patients, with pediatric patients achieving target hemoglobin values only a minority of the time (45.9% and 30.5% patient years, respectively, for hemodialysis and peritoneal dialysis). Trends show recent improvement in anemia treatment of children on dialysis. Still, further attention to and analysis of rHuEPO and iron therapy in pediatric dialysis patients is warranted.

United States Renal Data System assessment of the impact of the National Kidney Foundation-Dialysis Outcomes Quality Initiative guidelines.

Since 1989, significant efforts have focused on improving the care of dialysis patients in the United States. Numerous organizations have developed clinical practice guidelines; however, few guidelines have received the broad support given to the National Kidney Foundation-Dialysis Outcomes Quality Initiative (DOQI). These guidelines, independently developed from an extensive review of the literature, include sections on dialysis adequacy, anemia treatment, and vascular access. To assess the impact of these guidelines on clinical practice, we evaluated data on hematocrits, recombinant human erythropoietin dosing, hemodialysis adequacy, and simple fistula and dialysis catheter utilization using Medicare dialysis provider claims and Medicare Part B physician services. Hematocrits have increased steadily, with the exception of the period when the Hematocrit Measurement Audit was in effect. After cancellation of the policy, hematocrits increased to the midpoint of the DOQI target range (34.4%). Although the level of dialysis therapy has stabilized, with the average urea reduction rate of 68% to 69.9% in 1997 to 1999 being slightly greater than the DOQI target of 65% or greater, geographic variability is apparent. Simple fistula placement rates increased by 45% during the pre-DOQI and post-DOQI period from 1994 to 1999. The use of temporary catheters decreased, whereas placement of permanent catheters has increased, which may reflect recommended practice guidelines. Although it appears that clinical practice guidelines have improved the clinical care of dialysis patients, considerable regional variations in care across the country should be given significant attention.