NEJM evidence最新文献

Background: Antibiotic use during the coronavirus disease 2019 (Covid-19) pandemic was common in the outpatient setting, but was not supported by guidelines. We sought to evaluate the role of this antibiotic use on downstream antibiotic resistance.

Methods: We performed a population-wide cohort study of all nonhospitalized adults 66 years of age or older in Ontario, Canada, from January 1, 2020, to June 30, 2021, with a first identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the relationship between outpatient peri-Covid-19 antibiotic exposure (within a period of 7 days before or after index SARS-CoV-2 reporting) and downstream isolation of an antibiotic-resistant organism from clinical culture within 6 months. We calculated adjusted odds ratios of the association between peri-Covid-19 prescribing and antibiotic-resistant organism detection, as well as the adjusted attributable fractions of downstream antibiotic-resistant organisms.

Results: Of the 53,533 eligible individuals included, 8228 (15%) were prescribed a peri-Covid-19 antibiotic, and 1477 (3%) had a downstream antibiotic-resistant organism identified. The adjusted odds ratio for the presence of any antibiotic-resistant organism with peri-Covid-19 antibiotic use was 1.24 (95% confidence interval [CI], 1.09 to 1.41), while the adjusted odds ratio for the presence of gram-negative antibiotic-resistant organisms was 1.27 (95% CI, 1.11 to 1.46) and for gram-positive antibiotic-resistant organisms it was 1.02 (95% CI, 0.70 to 1.48). Among all individuals who received an antibiotic within 7 days of SARS-CoV-2 diagnosis, the attributable fraction of downstream antimicrobial resistance related to peri-Covid-19 antibiotic use was 17% (95% CI, 7 to 26%). Among all individuals with a SARS-CoV-2 diagnosis, the population-attributable fraction of downstream antimicrobial resistance related to peri-Covid-19 antibiotic use was 4% (95% CI, 2 to 7%).

Conclusions: Peri-Covid-19 antibiotic use was associated with downstream antimicrobial resistance, and particularly the presence of gram-negative antibiotic-resistant organisms. (Funded by the Canadian Institutes of Health Research Operating Grant [grant number 179461] and others).

Background: Eosinophilic esophagitis (EoE) is a chronic type 2 inflammatory esophageal disease driven by interleukin 13 (IL-13). Cendakimab, a high-affinity monoclonal antibody, binds IL-13, blocking interaction with receptors IL-13 receptor alpha 1 and IL-13 receptor alpha 2.

Methods: In this phase 3 trial, we randomly assigned patients with EoE 12 to 75 years of age to cendakimab 360 mg once weekly for 48 weeks (QW/QW), cendakimab 360 mg once weekly (QW) for 24 weeks, then 360 mg every other week for weeks 24 to 48 (QW/Q2W), or placebo for 48 weeks. Coprimary end points at week 24 were change from baseline in dysphagia days, measured by a validated patient-reported modified Daily Symptom Diary, and histologic response (peak esophageal eosinophil count ≤6 per high-power field). Secondary end points included endoscopic features and safety. Cendakimab QW/QW and QW/Q2W regimens were assessed as a single treatment group in the analyses from week 0 to week 24 (cendakimab QW) and as separate treatment groups versus placebo in the analyses from weeks 24 to 48.

Results: Among 430 patients randomly assigned to cendakimab (QW/QW, n=143; QW/Q2W, n=143) or placebo (n=144), reduction from baseline in dysphagia days at week 24 was significantly greater with cendakimab QW versus placebo (least-squares mean change [standard error], -6.1 [0.3] vs. -4.2 [0.4] days; P<0.001). Histologic response at week 24 was achieved in 28.6% of patients with cendakimab QW versus 2.2% with placebo (P<0.001). Cendakimab improved endoscopic severity from baseline to week 24, compared with placebo (least-squares mean change [standard error] -5.2 [0.24] points vs. -1.2 [0.34] points). Efficacy was maintained at week 48. Adverse events occurred in 83.8%, QW/QW, and 84.6%, QW/Q2W, of patients with cendakimab and 73.4% with placebo through week 48.

Conclusions: Cendakimab demonstrated statistically significant improvements in symptoms, histologic response, and endoscopic features of EoE versus placebo; the adverse-event and side-effect profile was not dose limiting. (Funded by Bristol Myers Squibb; ClinicalTrials.gov number, NCT04753697.).

Background: RSV/ΔNS2/Δ1313/I1314L (RSVt) (Sanofi) is a candidate live-attenuated intranasal respiratory syncytial virus (RSV) vaccine for infants and toddlers.

Methods: This phase I/II randomized clinical trial, conducted at sites in the United States (N=22), Chile (N=2), and Honduras (N=2), enrolled participants 6-18 months of age in four cohorts. In cohort 4, the primary cohort reported in this article, participants were randomly assigned to receive vaccinations on days 0 and 56 of either low-dose (LD) RSVt, high-dose (HD) RSVt, or placebo. Primary safety end points included: unsolicited systemic adverse events 30 minutes post vaccination, and solicited site and systemic reactions 28 days post vaccination. The primary immunogenicity end points were the geometric mean titers of RSV A serum neutralizing antibody after vaccinations 1 (day 56) and 2 (day 84) among RSV-naive participants at baseline.

Results: Among 180 participants (LD, N=61; HD, N=58; placebo, N=61), 115 were RSV-naive at baseline (LD, N=45; HD, N=32; placebo, N=38). No unsolicited systemic adverse events occurred within 30 minutes post vaccination in the LD or HD groups. Solicited site reactions were reported by 83.1%, 74.5%, and 68.9% of participants post vaccination 1, and 75.6%, 77.8%, and 55.6% post vaccination 2, in the LD, HD, and placebo groups, respectively. Solicited systemic reactions were reported by 79.7%, 73.2%, and 77.0% of participants post vaccination 1, and 66.7%, 66.7%, and 48.1% post vaccination 2, in the LD, HD, and placebo groups, respectively. Neutralizing antibody titers among RSV-naive participants were 83.7 (95% confidence interval (CI), 49.5 to 142.0), 79.4 (95% CI, 47.2 to 134.0), and 20.6 (95% CI, 16.4 to 25.9) post vaccination 1, and 142.0 (95% CI, 86.4 to 232.2), 107.0 (95% CI, 70.0 to 163.0), and 26.3 (95% CI, 18.8 to 37.0) post vaccination 2, in the LD, HD, and placebo groups, respectively.

Conclusions: The RSVt vaccine demonstrated promising immunogenicity profiles at both LD and HD strengths among infants and toddlers, without identified safety concerns. (Funded by Sanofi; ClinicalTrials.gov number, NCT04491877).

Background: Advances in acute ST-elevation myocardial infarction (STEMI) care have substantially decreased in-hospital mortality; however, in absolute terms, in-hospital mortality still remains high. Reperfusion injury, particularly intramyocardial hemorrhage following primary percutaneous coronary intervention (PCI), is a major predictor of adverse cardiovascular outcomes in the long term, but whether it contributes to in-hospital mortality is not known.

Methods: We performed a multicenter study to investigate the use of post-PCI high-sensitivity cardiac troponin I (hs-cTn-I) as a diagnostic tool to identify hemorrhagic myocardial infarction (MI) by determining hourly hs-cTn-I thresholds (every hour up to 12 hours, and at 16, 20, 24, and 48 hours post-PCI). We then investigated the relationship between patients classified as having hemorrhagic MI based on post-PCI hs-cTn-I cutoff values and in-hospital mortality using STEMI registries containing information about 6180 patients across seven hospitals in a single large health system in the United States.

Results: We enrolled 154 patients in a discovery cohort and 53 patients in a validation cohort. Hemorrhagic MI was diagnosed by cardiac magnetic resonance imaging. Post-PCI hs-cTn-I cutoff values for the determination of hemorrhagic MI were time dependent, with a sensitivity greater than 0.91, a specificity greater than 0.86, and an area under the curve (AUC) greater than 0.92 over the first 10 hours post-PCI, decreasing to a sensitivity greater than>0.84, a specificity greater than 0.80, and an AUC greater than 0.84 thereafter. The STEMI registry analysis demonstrated that patients classified as having hemorrhagic MI based on hs-cTn-I cutoff values had a 2.81-fold greater risk for in-hospital mortality than those classified as having had nonhemorrhagic MI (adjusted odds ratio, 2.81; 95% confidence interval, 2.17 to 3.64).

Conclusions: Post-PCI troponin kinetics may have the potential to diagnose hemorrhagic MI, which was associated with in-hospital mortality. (Funded by the National Institutes of Health National Heart, Lung, and Blood Institute (grant numbers HL133407, HL136578, and HL147133) and others; ClinicalTrials.gov ID, NCT05872308).

AbstractPatients who have previously undergone coronary artery bypass grafting (CABG) may present with non-ST-elevation acute coronary syndromes (NSTE-ACSs). In this setting, guidelines recommend routine invasive angiography. However, patients with CABG were often excluded from key trials that informed contemporary guidelines and invasive angiography is known to be of higher risk in these patients. In this article, the authors review the evidence and propose a trial to address the question, "Should patients with prior CABG who present with NSTE-ACSs routinely undergo invasive angiography?"

AbstractType 2 diabetes (T2D) is a complex chronic disorder with an increasing prevalence. Treatment of T2D involves both lifestyle and pharmacologic interventions aimed at lowering blood glucose levels to help counteract the negative effects of long-term hyperglycemia. The range of pharmacologic treatments for T2D has grown substantially, with newer agents demonstrating not only glucose-lowering efficacy, but also reductions in long-term cardiometabolic complications. This review discusses the newest pharmacologic agents for the treatment of T2D and the evidence regarding their cardiometabolic benefits. We highlight key considerations for their use based on patient characteristics and clinical context. In addition, we discuss emerging pharmacologic therapies that target the underlying pathogenesis of T2D, underscoring ongoing advances in diabetes care.

AbstractDecentralized clinical trials (DCTs), meaning those trials in which activities are conducted outside of hospital or clinic settings, offer many advantages over traditional clinical trials and, when properly operationalized, provide unique benefits to researchers, participants, and society. The ability of individuals to participate remotely from their homes adds convenience, but, more importantly, democratizes access to trials that would otherwise be limited by geographic constraints. As personal interactions with participants are diminished in DCTs, trialists must be intentional when strategizing recruitment, retention, and return of value for participants. Engaging clinical trial participants as partners in DCTs requires researchers to consider participant priorities at each stage of the trial. This article highlights technical and procedural considerations needed to support DCTs and identifies areas for trial innovation. By making DCTs and technology platforms participant centric and continuing to advance opportunities for innovation, researchers may accelerate scientific discovery, help participants feel their contributions are meaningful, and foster long-term trust in the biomedical research process.See also in NEJM: As-Needed Albuterol-Budesonide in Mild Asthma See also in NEJM: Your Combination Asthma Inhaler - Don't Leave Home without It!