The health-related quality of life was not improved by targeting higher hemoglobin in the Normal Hematocrit Trial

The Normal Hematocrit Trial (NHT) was the largest trial of epoetin randomizing 1265 hemodialysis patients with cardiac disease to lower (9–11 g/dl) or higher (13–15 g/dl) hemoglobin (Hgb), hypothesizing that higher Hgb would reduce mortality, and improve survival and quality of life. The trial was terminated early, and a 1998 publication reported that targeting higher hematocrit levels led to an insignificant increase in the primary end points (death or myocardial infarct), or risk ratio 1.3, 95% confidence interval (CI), 0.9–1.90, but the P-value was not given, and all-cause death risk was not reported. A higher target reportedly did not increase hospitalization rates, but did significantly improve the ‘physical function' domain of quality of life. Comparing the 1996 Food and Drug Administration (FDA)-filed clinical trial report to the 1998 publication, however, found several discrepancies. Among these, the 1998 article reported interim trial results with only the adjusted CI but did not state that the unadjusted CIs were 99.912th percentile, and despite being a secondary end point, reported only the association of achieved Hgb with higher quality of life score. Randomization to the higher target had actually increased the risk for the primary end point (risk ratio 1.28, 95% CI=1.06–1.56; P=0.0112; 99.92% CI=0.92–1.78), the risk of death (risk ratio 1.27, 95% CI=1.04–1.54), non-access thrombotic events (P=0.041), and hospitalization rate (P=0.04), while ‘physical function' did not improve (P=0.88). Hence, disclosure of these results in the 1998 publication or access to the FDA-filed report on the NHT in the late 1990s would likely have led to earlier concerns about epoetin safety and greater doubts about its benefits

Hospital Liability: Implications of Recent Physician\u27s Assistant Statutes

New methods must be devised to increase the efficient use of the available supply of physicians. Among the innovations being tried with physicians is the development of new disciplines involving assistants to physicians. Increasing utilization of returning medics from the armed forces is being undertaken to help relieve the civilian manpower shortage. The legal implications of these developments range from problems of licensure to considerations of vicarious liability for an assistant\u27s negligence (malpractice) or for the negligence of the assistant\u27s supervising physician. It is with a species of this latter problem that this paper will be concerned. But one ought to take at least a passing glance at the professional medical development of this latest member of the health care team

Hospital Liability: Implications of Recent Physician\u27s Assistant Statutes

New methods must be devised to increase the efficient use of the available supply of physicians. Among the innovations being tried with physicians is the development of new disciplines involving assistants to physicians. Increasing utilization of returning medics from the armed forces is being undertaken to help relieve the civilian manpower shortage. The legal implications of these developments range from problems of licensure to considerations of vicarious liability for an assistant\u27s negligence (malpractice) or for the negligence of the assistant\u27s supervising physician. It is with a species of this latter problem that this paper will be concerned. But one ought to take at least a passing glance at the professional medical development of this latest member of the health care team

Roxadustat for CKD-related anemia in non-dialysis patients

INTRODUCTION: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and improves iron metabolism. We assessed the efficacy and tolerability of roxadustat in patients with chronic kidney disease (CKD)-related anemia not on dialysis. METHODS: ANDES was a global Phase 3 randomized study in which adults with stage 3-5 CKD not on dialysis received roxadustat or placebo. Patients were initially dosed thrice weekly; dose was titrated to achieve a hemoglobin level ≥11.0 g/dl, followed by titration for maintenance. The primary endpoints were change in hemoglobin (weeks 28-52) and proportion of patients achieving a hemoglobin response (hemoglobin ≥11.0 g/dl and increase ≥1.0 g/dl [baseline \u3e8.0 g/dl], or increase ≥2.0 g/dl [baseline ≤8.0 g/dl]) (week 24). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were recorded. RESULTS: In roxadustat (n = 616) and placebo (n = 306) groups, hemoglobin mean (SD) change from baseline over weeks 28-52 was significantly larger for roxadustat (2.00 [0.95]) versus placebo (0.16 [0.90]), corresponding to least-squares mean difference of 1.85 g/dl (95% confidence interval [CI] 1.74-1.97; CONCLUSION: This study showed that roxadustat corrected and maintained hemoglobin and was well tolerated in patients with CKD-related anemia not on dialysis (ClinicalTrials.gov NCT01750190)