Pushkal P. Garg

Racial Differences in Access to the Kidney Transplant Waiting List for Children and Adolescents With End-Stage Renal Disease

Context. Renal transplantation is the treatment of choice for pediatric patients with end-stage renal disease (ESRD). Black patients wait longer for kidney transplants than do white patients. Objective. To determine whether the increased time to transplantation for black pediatric patients is attributable not only to a shortage of suitable donor organs, but also to racial differences in the time from a childs first treatment for ESRD until activation on the cadaveric kidney transplant waitlist. Design. National longitudinal cohort study. Setting. US Medicare-eligible, pediatric ESRD population. Patients. Children and adolescents ≤19 years old at the time of their first dialysis for ESRD between 1988 and 1993, followed through 1996. Patients who received living donor renal transplants were excluded from study. Main Outcome Measures. Time from first dialysis for ESRD until activation on the kidney transplant waiting list, relative hazard of activation on the waiting list for black compared with white pediatric patients. Results. Comparisons of the time from first dialysis for ESRD to waitlisting among the 2162 white (60.7%) and 1122 black (31.5%) patients studied using survival analysis revealed that blacks were less likely to be waitlisted at any given time in follow-up. In multivariate analysis, even after controlling for patient age, gender, socioeconomic status, geographic region, incident year of renal failure, and cause of ESRD, blacks were 12% less likely to be waitlisted than were whites at any point in time (relative hazard: .88: 95% confidence interval: .79–.97). Conclusions. Racial disparities in access to the renal transplant waiting list exist in pediatrics. Whether these disparities are attributable to differences in time of presentation to a nephrologist, physician bias in identification of transplant candidates, or patient preferences warrants further study.

Impact of Underuse, Overuse, and Discretionary Use on Geographic Variation in the Use of Coronary Angiography After Acute Myocardial Infarction

Background.Geographic variation in the use of medical procedures has been well documented. However, it is not known whether this variation is due to differences in use when procedures are indicated, discretionary, or contraindicated. Objectives.To examine whether use of coronary angiography after acute myocardial infarction (AMI) according to appropriateness criteria varied across geographic regions and whether underuse, overuse, or discretionary use accounted for variation in overall use. Design.Retrospective cohort study using data from the Cooperative Cardiovascular Project. Setting.Ninety-five hospital referral regions. Patients.There were 44,294 Medicare patients hospitalized with AMI during 1994 or 1995, classified according to appropriateness for angiography. MainOutcomeMeasure.Variation in use of angiography, as measured by the difference between high and low rates of use across regions. Results.Across regions, variation in the use of angiography was similar for indications judged necessary; appropriate, but not necessary; or uncertain. Variation was lowest for indications judged unsuitable (difference between high rate and low rate across regions = 16.3%; 95% CI = 12.6%; 20.6%). The primary cause of variation in the overall rate of angiography was due to use for indications judged appropriate, but not necessary or uncertain. When variation associated with these indications was accounted for, the difference between the resulting high and low overall rates was 10.8% (9.4%, 12.4%). In contrast, variation in the overall rate remained high when underuse in necessary situations or overuse in unsuitable situations was accounted for. Conclusions.Across regions, practice was more similar for patients categorized unsuitable for angiography than for patients with other indications. Variation in overall use of angiography appeared to be driven by utilization for discretionary indications rather than by underuse or overuse. If equivalent rates across geographic areas are judged desirable, then greater effort must be directed toward defining care for patients with discretionary indications.

Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy

Background Current hemophilia treatment involves frequent intravenous infusions of clotting factors, which is associated with variable hemostatic protection, a high treatment burden, and a risk of the development of inhibitory alloantibodies. Fitusiran, an investigational RNA interference (RNAi) therapy that targets antithrombin (encoded by SERPINC1), is in development to address these and other limitations. Methods In this phase 1 dose‐escalation study, we enrolled 4 healthy volunteers and 25 participants with moderate or severe hemophilia A or B who did not have inhibitory alloantibodies. Healthy volunteers received a single subcutaneous injection of fitusiran (at a dose of 0.03 mg per kilogram of body weight) or placebo. The participants with hemophilia received three injections of fitusiran administered either once weekly (at a dose of 0.015, 0.045, or 0.075 mg per kilogram) or once monthly (at a dose of 0.225, 0.45, 0.9, or 1.8 mg per kilogram or a fixed dose of 80 mg). The study objectives were to assess the pharmacokinetic and pharmacodynamic characteristics and safety of fitusiran. Results No thromboembolic events were observed during the study. The most common adverse events were mild injection‐site reactions. Plasma levels of fitusiran increased in a dose‐dependent manner and showed no accumulation with repeated administration. The monthly regimen induced a dose‐dependent mean maximum antithrombin reduction of 70 to 89% from baseline. A reduction in the antithrombin level of more than 75% from baseline resulted in median peak thrombin values at the lower end of the range observed in healthy participants. Conclusions Once‐monthly subcutaneous administration of fitusiran resulted in dose‐dependent lowering of the antithrombin level and increased thrombin generation in participants with hemophilia A or B who did not have inhibitory alloantibodies. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov number, NCT02035605.)

Understanding individual and small area variation in the underuse of coronary angiography following acute myocardial infarction.

Background. Underuse of coronary angiography is common among patients with acute myocardial infarction (AMI) and the magnitude of underuse varies across geographic areas. Objectives. To examine the influence of patient demographic, clinical and hospital characteristics on underuse of coronary angiography, and the contribution of these factors to variation in underuse across geographic regions. Research Design. Cohort study using data from the Cooperative Cardiovascular Project. Subjects. Nine thousand four hundred fifty-eight patients in 95 hospital referral regions (HRRs) hospitalized for AMI in 1994 to 1995 and for whom angiography was rated necessary. Measures. Odds ratios (95% confidence intervals) associated with underuse of angiography according to patient and hospital characteristics. The difference between low and high rates of underuse of angiography across regions after controlling for regional differences in patient and hospital characteristics. Results. Of those for whom angiography was rated necessary, 42% did not undergo the procedure. Underuse of angiography was associated with several patient demographic and hospital attributes (eg, female gender, black race, treatment in a hospital without angiography, treatment by a general practitioner) as well as with prevalent clinical characteristics, such as renal insufficiency, congestive heart failure, prior coronary artery bypass surgery, and chronic obstructive pulmonary disease. Across HRRs, variation in underuse ranged from 24.0% to 58.3%. The difference between low and high rates did not decline significantly after controlling for regional differences in patient or hospital characteristics. Conclusions. At the patient-level, rates of necessary angiography may be improved if we address disparities in care related to sociodemographic characteristics and to the technological capabilities of hospitals. In addition, practice guidelines should be updated to reflect clinical concerns about the risks and benefits of angiography and subsequent revascularization in certain patient sub-groups, both to provide appropriate guidance to physicians and to facilitate better estimates of underuse. The causes of regional variation in underuse do not appear to be related to regional differences in patient or hospital characteristics, and therefore, require further study.

Reducing racial disparities in transplant activation:Whom should we target?

Several studies have documented that blacks with end-stage renal disease (ESRD) are less likely than whites to be placed on the waiting list for a renal transplant. We examined trends in access over time to determine whether publication of these reports resulted in a reduction in disparity and identified those blacks who were most affected to focus future interventions. Three nationally representative groups of adult patients with ESRD (first dialysis in 1986 to 1987, 1990, or 1993) were followed up longitudinally to ascertain the date of first placement on the renal transplant waiting list. Cox proportional hazards models were used to characterize the magnitude of racial disparities in access to the waiting list with adjustment for clinical and sociodemographic factors. Lower rates of placement on the waiting list for blacks than whites persisted after adjustment for differences in both sociodemographic characteristics and health status (relative hazard [RH], 0.68; 95% confidence interval [CI], 0.59 to 0.79). The gap between blacks and whites did not narrow over time (blacks versus whites: 1986 to 1987 group, RH, 0.71; 95% CI, 0.59 to 0.86; 1990 group, RH, 0.69; 95% CI, 0.54 to 0.91; 1993 group, RH, 0.57; 0.43 to 0.77) and was greatest for the youngest and healthiest black patients, who were 50% and 40% less likely to be listed than corresponding whites, respectively. Interventions targeted toward young and healthy blacks, who are most likely to benefit from transplantation, are urgently needed to narrow black-white differences in transplant activation.

Are critical pathways effective for reducing postoperative length of stay

Background. Many hospitals use critical pathways to attempt to reduce postoperative length of stay (PLOS) for diverse conditions and procedures. Objective. To evaluate whether critical pathways were associated with reductions in postoperative PLOS after accounting for prepathway trends in PLOS. Research Design. Retrospective cohort study, from 1988 to 1998. Setting. Academic medical center department of surgery. Subjects. A total of 10,960 admissions eligible for 1 of 26 critical pathways implemented from 1990 to 1996, from 2 years before to 2 years after each pathway implementation date. Coding definitions were developed and validated to identify admissions eligible for each pathway, and data were abstracted from the hospital’s discharge database. Measure. A pathway was considered effective if, after its implementation, there was a statistically significant decrease in the prepathway trend for PLOS. Results. Median number of annual eligible admissions per pathway was 59 (range, 18–706). Median PLOS for the prepathway periods was 8 days (interquartile range, 5–10 days). For 16 (62%) pathways, PLOS was already declining in the prepathway period. After adjusting for demographics, comorbidity, admission characteristics, and prepathway time trends in PLOS, 7 (27%) pathways were associated with a significant postimplementation decrease in the rate of change in PLOS (range among the 7 pathways, 5–45% decrease) and none with a significant increase from the prepathway trend for PLOS. Conclusion. Critical pathways may decrease postoperative stay for some, but not all, surgeries. Trends toward decreasing length of stay over time may reduce the impact of critical pathways on this outcome.