Background Women with a history of spontaneous preterm birth (SPTB) are at a significantly increased risk for recurrent preterm birth (PTB). To date, only one large U.S. clinical trial comparing 17-OHPC (17-α-hydroxyprogesterone caproate or “17P”) to placebo has been published, and this trial was stopped early due to a large treatment benefit. Objective This study aimed to assess whether 17-OHPC decreases recurrent PTB and neonatal morbidity in women with a prior SPTB in a singleton gestation. Study Design This was a double-blind, placebo-controlled international trial involving women with a previous singleton SPTB (clinicaltrials.gov: NCT 01004029). Women were enrolled at 93 clinical centers (41 in the United States and 52 outside the United States) between 160/7 to 206/7 weeks in a 2:1 ratio, to receive either weekly intramuscular (IM) injections of 250 mg of 17-OHPC or an inert oil placebo; treatment was continued until delivery or 36 weeks. Co-primary outcomes were PTB < 35 weeks and a neonatal morbidity composite index. The composite included any of the following: neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, or proven sepsis. A planned sample size of 1,707 patients was estimated to provide 98% power to detect a 30% reduction in PTB < 35 weeks (30% to 21%) and 90% power to detect a 35% reduction in neonatal composite index (17%–11%) using a two-sided type-I error of 5%. Finally, this sample size would also provide 82.8% power to rule out a doubling in the risk of fetal/early infant death assuming a 4% fetal/early infant death rate. Analysis was performed according to the intention-to-treat principle. Results Baseline characteristics between the 1,130 women who received 17-OHPC and 578 women who received placebo were similar. Overall, 87% of enrolled women were Caucasian, 12% had >1 prior SPTB, 7% smoked cigarettes, and 89% were married/lived with partner. Prior to receiving study drug, 73% women had a transvaginal cervical length measurement performed and <2% had cervical shortening <25 mm. There were no significant differences in the frequency of PTB < 35 weeks (17-OHPC 11.0% vs. placebo 11.5%; relative risk = 0.95 [95% confidence interval (CI): 0.71–1.26]) or neonatal morbidity index (17-OHPC 5.6% vs. placebo 5.0%; relative risk = 1.12 [95% CI: 0.68–1.61]). There were also no differences in frequency of fetal/early infant death (17-OHPC 1.7% vs. placebo 1.9%; relative risk = 0.87 [95% CI: 0.4–1.81]. Maternal outcomes were also similar. In the subgroup of women enrolled in the United States (n = 391; 23% of all patients), although the rate of PTB < 35 weeks was higher than the overall study population, there were no statistically significant differences between groups (15.6% vs. 17.6%; relative risk = 0.88 [95% CI: 0.55, 1.40]. Conclusion In this study population, 17-OHPC did not decrease recurrent PTB and was not associated with increased fetal/early infant death.

Conflict of interest: MW serves as a consultant to AMAG Pharmaceuticals Inc. and Luitpold Pharmaceuticals Inc. GMC serves as a consultant to AMAG Pharmaceuticals Inc. ICM received consultancy fees and honoraria from AMAG Pharmaceuticals Inc. and Vifor Pharma. At the time of the study, RK held equity in and was a full-time employee of AMAG Pharmaceuticals Inc. JK and WS hold equity in and are full-time employees of AMAG Pharmaceuticals Inc.

Few trials have examined rates of hypersensitivity reactions (HSRs) with intravenous iron formulations used to treat iron deficiency anemia (IDA). This randomized, multicenter, double‐blind clinical trial compared the safety, and efficacy of ferumoxytol versus ferric carboxymaltose (FCM), focusing on rates of HSRs and hypotension as the primary end point. Patients with IDA of any etiology in whom oral iron was unsatisfactory or intolerable received ferumoxytol (n = 997) or FCM (n = 1000) intravenously over ≥15 minutes on days 1 and 8 or 9 for total respective doses of 1.02 g and 1.50 g. Composite incidences of moderate‐to‐severe HSRs, including anaphylaxis, or moderate‐to‐severe hypotension from baseline to week 5 (primary safety end point) were 0.6% and 0.7% in the ferumoxytol and FCM groups, respectively, with ferumoxytol noninferior to FCM. No anaphylaxis was reported in either group. The secondary safety end point of incidences of moderate‐to‐severe HSRs, including anaphylaxis, serious cardiovascular events, and death from baseline to week 5 were 1.3% and 2.0% in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Least‐squares mean changes in hemoglobin at week 5 were 1.4 g/dL and 1.6 g/dL in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Incidence of hypophosphatemia was 0.4% for ferumoxytol and 38.7% for FCM.

OBJECTIVE -Although the number of elders with diabetes has increased dramatically, there are few data on rates of mortality and serious complications in older populations with diabetes. To determine such rates, we conducted a population-based, nonconcurrent cohort study using claims data from the 1994 -1996 Medicare 5% Standard Analytical File. RESEARCH DESIGN AND METHODS-Codes from the ICD-9 were used to identify diabetes and the following complications: amputation, lower extremity infection, gangrene, blindness, acute myocardial infarction, ischemic heart disease, stroke, and metabolic disorders. Using these codes, we assembled a cohort of 148,562 Medicare Part A and B beneficiaries who were Ն65 years of age, who were alive on 1 January 1995, who were not in managed care in 1994, and who had a diabetes-related claim in 1994. Age-specific rates of death and complications were then calculated.RESULTS -During 24 months of follow-up, 22,044 (14.8%) elders with diabetes died. Death rates in men and women increased significantly with age. Compared with their counterparts in the general U.S. population, elders with diabetes suffered excess mortality at every age group, corresponding to an overall standardized mortality ratio of 1.41 (95% CI 1.39,1.43). The incidence of ischemic heart disease and stroke was 181.5 and 126.2 per 1,000 person-years, respectively, which was higher than the incidence of all other diabetes-related complications.CONCLUSIONS -In every age group, elders with diabetes have significantly higher allcause mortality rates than the general population. Medicare data may be useful in monitoring trends in diabetes-related morbidity and total mortality in U.S. elders with diabetes. Diabetes Care 25:471-475, 2002D iabetes is an increasingly common disease in U.S. elders. During the 1970s and 1980s, the percentage of adults aged Ն65 years diagnosed with diabetes increased from 8 to 10% (1). The Centers for Disease Control and Prevention estimated that in 1996 there were 3.8 million elders (up from 2.3 million in 1980) with diagnosed diabetes (2), which is consistent with estimates from the 1990s that up to 13% of elders have diagnosed diabetes (3). The true prevalence of diabetes is probably higher, after accounting for those who are undiagnosed (4). Although prevalence of diabetes in the elderly is high, data on mortality and serious complication rates in older populations with diabetes are limited. Morbidity surveillance in the elderly has generally relied on death certificate data and hospital discharge surveys, but these methods are prone to undercoding of diabetes, sampling biases, and difficulties in determining the population at risk. Use of cohort studies remedies these problems, but at the expense of small numbers, particularly of ages older than 75 years (5). Several population-based studies have suggested that the excess mortality associated with diabetes in younger populations is attenuated in the elderly (6 -8).However, the precise magnitude of the excess risk in the oldest age groups with di...