NEJM evidence最新文献

Background: The combination of rivaroxaban plus aspirin compared with aspirin alone reduces the risk of major adverse cardiovascular and limb events for high-risk patients with peripheral artery disease. It is unknown whether rivaroxaban plus aspirin improves intermittent claudication for adults with lower-risk peripheral arterial disease.

Methods: In this randomized, open-label, multicenter, 24-week clinical trial, we randomly assigned patients with peripheral artery disease and intermittent claudication to receive either 2.5 mg of rivaroxaban twice daily plus 100 mg of aspirin once daily or 100 mg of aspirin once daily. The primary outcome was a 24-week change in total walking distance, measured by the 6-minute walking test. The primary safety outcome was the incidence of major bleeding or clinically relevant nonmajor bleeding.

Results: Eighty-eight patients were randomly assigned to either rivaroxaban plus aspirin (n=46) or aspirin alone (n=42). The mean age was 67 years, and 54% were female. The total walking distance measured by 6-minute walk test improved by 89 ± 18 m (mean±standard error) in the rivaroxaban-plus-aspirin group versus 21 ± 16 m in the aspirin-alone group. This corresponded to an absolute difference of 68 ± 24 m (95% confidence interval [CI], 19 to 116 m; P=0.007) and a relative improvement over the aspirin-alone group of 327% (95% CI, 94 to 560%). No major bleeding events were observed in either group.

Conclusions: In patients with peripheral artery disease and intermittent claudication, 2.5 mg of rivaroxaban twice daily plus 100 mg of aspirin daily improved the total walking distance by a 6-minute walking test compared with 100 mg of aspirin daily alone. (Funded by Bayer S.A.; Clinicaltrials.gov number, NCT04853719.).

AbstractMorning Report is a time-honored tradition where physicians-in-training present cases to their colleagues and clinical experts to collaboratively examine an interesting patient presentation. The Morning Report section seeks to carry on this tradition by presenting a patient's chief concern and story, inviting the reader to develop a differential diagnosis and discover the diagnosis alongside the authors of the case. This report examines the story of a 36-year-old man who sought evaluation for a persistent headache and numbness on the cheek. Using questions, physical examination, and testing, an illness script for the presentation emerges. As the clinical course progresses, the differential is refined until a diagnosis is made.

Background: Tubal sterilization is the most commonly used method of contraception in the United States. Because contraceptive effectiveness influences contraceptive selection, we examined typical use failure rates after tubal sterilization in the United States.

Methods: We estimated rates of pregnancy after tubal sterilization using data from four waves of the National Survey of Family Growth (NSFG), representative samples of U.S. women aged 15 to 44 years, collected in 2002, 2006 to 2010, 2011 to 2013, and 2013 to 2015. Survey weighting was used in survival analysis to examine time to first pregnancy after tubal sterilization. Data from these participants were censored after a tubal reversal procedure, infertility treatment, hysterectomy, or bilateral oophorectomy. Reported pregnancy rates after tubal sterilization procedures were examined by using Kaplan-Meier curves and then multivariable Cox proportional-hazards models to examine the effects of age at tubal sterilization, race/ethnicity, education, Medicaid funding, and postpartum versus interval procedures.

Results: Pregnancy after tubal sterilization was reported by 2.9 to 5.2% of participants across NSFG waves. In the most recent survey wave (2013 to 2015), the estimated percentage of participants with pregnancies within the first 12 months after a tubal sterilization procedure was 2.9%; at 120 months after tubal sterilization, the estimated percentage with a pregnancy was 8.4%. At all the time points examined, pregnancy after tubal sterilization was less common after postpartum procedures than after interval procedures; however, this difference was not evident in multivariable models. In multivariable models, chance of pregnancy decreased with age at time of tubal sterilization. Race/ethnicity, education, and Medicaid funding were not consistently associated with pregnancy after tubal sterilization.

Conclusions: These data suggest that there may be nontrivial rates of pregnancy after tubal sterilization.

Background: Tuberculosis remains a global health concern, and half of cured patients have permanent lung injury. N-acetylcysteine (NAC) has shown beneficial antimicrobial, antioxidant, and immunomodulatory effects in preclinical tuberculosis models. We examined its effects on tuberculosis treatment outcomes.

Methods: This prospective, randomized, controlled trial nested within the TB SEQUEL cohort study enrolled 140 adults with moderate or far-advanced tuberculosis. Participants were randomly assigned 1:1 to standard therapy with or without 1200 mg of oral NAC twice daily for days 1 to 112. Clinical evaluations, sputum culture, and spirometry were performed at specified intervals through day 168, after which participants returned to the TB SEQUEL cohort. The primary outcome was culture conversion. Secondary outcomes included whole-blood glutathione levels and lung function.

Results: Participants were predominantly young, male, and human immunodeficiency virus 1-negative and had heavy sputum Mycobacterium tuberculosis (MTB) infection burdens. NAC increased glutathione levels (NAC × day interaction, 8.48; 95% confidence interval [CI], 1.93 to 15.02) but did not increase stable culture conversion (hazard ratio, 0.84; 95% CI, 0.59 to 1.20; P=0.33). NAC treatment was associated with improved recovery of lung function (NAC × month, 0.49 [95% CI, 0.02 to 0.95] and 0.42 [95% CI, -0.06 to 0.91] for forced vital capacity and forced expiratory volume in the first second, respectively, as percentages of predicted values). The effects of NAC on lung function were greatest in participants with severe baseline lung impairment and appeared to persist beyond the period of NAC administration. Rates of serious or grade 3 to 4 nonserious adverse events did not differ between the groups.

Conclusions: Despite increasing whole-blood glutathione levels, NAC did not affect eradication of MTB infection in adults with pulmonary tuberculosis that was moderate to far advanced. Secondary outcomes of lung function showed changes that merit further investigation. (Funded by TB SEQUEL grant 01KA1613 of the German Ministry for Education and Research, the Health Africa Project, and the German Center for Infection Research; ClinicalTrials.gov number, NCT03702738.).

Background: Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors are an oral treatment for anemia of chronic kidney disease (CKD). In this systematic review and meta-analysis, we assessed long-term safety of HIF prolyl hydroxylase inhibitors.

Methods: We searched MEDLINE, Embase, and Cochrane databases for randomized trials comparing HIF prolyl hydroxylase inhibitors with an erythropoiesis-stimulating agent (ESA) or placebo with greater than or equal to 48 weeks of follow-up. The primary outcome was major adverse cardiovascular event (MACE), defined as a composite of all-cause death, myocardial infarction, or stroke. Treatment effects were pooled using random-effects models.

Results: Twenty-five trials involving 26,478 participants were included. Of these, 13 trials enrolled 13,230 participants with dialysis-dependent CKD, and 12 trials enrolled 13,248 participants with nondialysis-dependent CKD. There was no evidence that HIF prolyl hydroxylase inhibitors and ESA had different effects on MACE in people with dialysis-dependent CKD (risk ratio, 0.99; 95% confidence interval [CI], 0.92 to 1.08) or people with nondialysis-dependent CKD (risk ratio, 1.08; 95% CI, 0.95 to 1.22). Similarly, there was no evidence that HIF prolyl hydroxylase inhibitors and placebo had different effects on MACE (risk ratio, 1.10; 95% CI, 0.96 to 1.27) in people with nondialysis-dependent CKD. The lack of difference between HIF prolyl hydroxylase inhibitors and ESA or placebo was observed for individual components of MACE and cardiovascular death. Safety of HIF prolyl hydroxylase inhibitors for other outcomes was comparable with ESA in dialysis-dependent CKD. In nondialysis-dependent CKD, dialysis access thrombosis, venous thromboembolism, infections, and hyperkalemia occurred more frequently with HIF prolyl hydroxylase inhibitors in placebo-controlled trials but not in ESA-controlled trials.

Conclusions: There was no evidence of a difference in the long-term cardiovascular safety profile of HIF prolyl hydroxylase inhibitors and ESA in adults with dialysis-dependent CKD and adults with nondialysis-dependent CKD. (PROSPERO registration number, CRD42021278011.).