NEJM evidence最新文献

Background: Zalunfiban is a glycoprotein IIb/IIIa (integrin αIIbβ3) inhibitor designed for subcutaneous administration on first medical contact with patients with suspected ST-segment elevation myocardial infarction (STEMI).

Methods: An international, double-blind, placebo-controlled trial randomly assigned patients with STEMI in a 1:1:1 ratio to receive a single subcutaneous injection of zalunfiban (0.11 mg/kg or 0.13 mg/kg) or placebo. The primary efficacy end point was a hierarchical proportional odds model ranking seven end points from worst to best: all-cause death, stroke, recurrent myocardial infarction, acute stent thrombosis, new-onset or rehospitalization for heart failure, larger infarct size, or no end point through 30 days. The primary safety end point was the occurrence of severe or life-threatening bleeding as per the global use of strategies to open occluded coronary arteries (GUSTO) criteria.

Results: The trial randomly assigned 2467 patients (853 to zalunfiban 0.11 mg/kg, 818 to zalunfiban 0.13 mg/kg, and 796 to placebo). The primary efficacy end point was significantly improved by zalunfiban (adjusted odds ratio 0.79; 95% confidence interval, 0.65 to 0.98; P=0.028). GUSTO severe bleeding was similar between those who received zalunfiban versus placebo (1.2% vs. 0.8%; P=0.40), but GUSTO mild to moderate bleeding was increased (6.4% vs. 2.5%; P<0.001). Angiography showed faster coronary blood flow with zalunfiban versus placebo (corrected frame count of the infarct-related artery 109 [interquartile range 35 to 176] vs. 176 [interquartile range 40 to 176]; P=0.012).

Conclusions: In patients with STEMI, zalunfiban administered at first medical contact significantly improved preintervention infarct-related patency and reduced the likelihood of a worse 30-day multicomponent hierarchical clinical end point. Zalunfiban was not associated with increased severe or life-threatening bleeding but was associated with increased mild to moderate bleeding. (Funded by CeleCor Therapeutics; CELEBRATE ClinicalTrials.gov number, NCT04825743.).

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 describes the story of a 64-year-old woman with a remote history of rheumatic heart disease who presented with progressive fatigue and exertional dyspnea more than two decades after undergoing aortic- and mitral-valve replacements. Using questions, physical examination, and testing, an illness script for the presentation emerges. As the clinical course progresses, the differential is refined until a final diagnosis is made.

Background: Electronic letters have demonstrated effectiveness in improving vaccination uptake among patients with chronic diseases, but the effects of serial implementation over consecutive influenza seasons are unknown.

Methods: In a nationwide randomized implementation trial, conducted during the 2024-2025 influenza season, that included all Danish citizens 18-64 years of age who were eligible for free-of-charge influenza vaccination because of a chronic condition, we randomly assigned participants in a 2.45:1:1:1:1:1:1 ratio to usual care (no letter) or to one of six different behaviorally informed electronic letter strategies. All data were sourced from nationwide Danish health registries. The primary end point was receipt of an influenza vaccine on or before January 1, 2025, analyzed through seven coprimary comparisons (all intervention groups pooled vs. usual care, and each intervention group vs. usual care).

Results: We randomly assigned 308,978 Danish citizens 18-64 years of age; 164,100 (53.1%) were female; the median age was 52.1 years (interquartile range, 39.7-59.2). Compared with usual care, influenza vaccination rates were higher among those receiving any intervention letter (36.5% vs. 24.1%; difference, 12.4 percentage points [99.29% confidence interval [CI], 11.9-12.9]; P<0.001). Significant increases in influenza vaccination were observed with each letter type compared with usual care. Among the six different electronic letter strategies, the largest effect size was observed with a repeated cardiovascular-focused letter (39.1% vs. 24.1%; difference, 15.0 percentage points [99.29% CI, 14.2 to 15.7]; P<0.001). There was no apparent difference in the effect size of letters compared with usual care across major subgroups, including among those who had also received a similar letter during the preceding influenza season.

Conclusions: Electronically delivered, letter-based nudges significantly increased influenza vaccination among 18-to-64-year-old individuals with chronic diseases compared with usual care, when delivered during a second consecutive season. The largest effect size was with a strategy where a letter focused on the potential cardiovascular benefits of influenza vaccination was sent twice. (ClinicalTrials.gov number, NCT06600490.).

Background: Coronary artery bypass grafting using the radial artery is performed by harvesting the graft through open or endoscopic surgery. Data from randomized trials comparing harvesting techniques are limited.

Methods: We conducted a randomized controlled trial comparing endoscopic radial artery harvest with open radial artery harvest in adults scheduled for coronary artery bypass surgery. The primary outcome was patient-reported hand function at 3 months after random assignment, assessed using the Hand Function Questionnaire (scores range from 5 to 49, with lower scores indicating more favorable outcomes; a minimal clinically important difference has not been firmly established but may be approximately 3 points). Secondary outcomes included neurologic deficits.

Results: A total of 300 patients were randomly assigned to endoscopic radial artery harvest (151 patients) or open radial artery harvest (149 patients). At 3 months, the mean score on the Hand Function Questionnaire was 7.20 points in patients assigned to endoscopic radial artery harvest and 7.74 points in patients assigned to open radial artery harvest (difference, 0.52 points; 95% confidence interval [CI], 0.06 to 0.98; P=0.03). Thirty-two of 151 (21.2%) patients in the endoscopic radial artery harvest group had neurologic deficits, compared with 82 of 149 (55.0%) patients in the open radial artery harvest group (relative risk with open radial artery harvest, 2.61; 95% CI, 1.90 to 3.63). In the endoscopic radial artery harvest group, one or more serious adverse events occurred in 9 of 151 (6.0%) patients, compared with 4 of 149 (2.7%) patients in the open radial artery harvest group (relative risk with open radial artery harvest, 0.45; 95% CI, 0.13 to 1.34).

Conclusions: In patients scheduled for coronary artery bypass surgery, endoscopic radial artery harvest, compared with open radial artery harvest, led to modestly better patient-reported hand function and was associated with reduced neurologic deficits. (ClinicalTrials.gov number, NCT01848886.).

AbstractFirearm ownership in the United States is increasing, as is the belief that firearms keep households safe, even though having a firearm in the home increases household members' risk of firearm injury and death. Research shows that firearm owners and clinicians are receptive to conversations with each other about firearm injury prevention. However, these conversations rarely take place, in part because clinicians lack training on the topic. This Curbside Consult presents the Approach, Assess, Act 3As Framework, which guides clinicians through conversations with patients and clients in clinical situations where firearms pose a risk of injury.

Background: Vaso-occlusive crisis (VOC) is the most common manifestation of sickle cell disease, and acute chest syndrome (ACS) is a frequent complication with a substantial risk of death. The aim of this study was to validate the previously developed PREdictive SEVerity (PRESEV) score for the occurrence of ACS in adult patients with sickle cell disease hospitalized for VOC and to assess the safety of outpatient management of patients with a low-risk score.

Methods: To validate the PRESEV score, a prospective observational study was conducted in 13 centers across 5 countries in Africa and Europe. The score ranges from 0 to 16, with values of 5 or less considered low risk. The safety of a low-risk score (≤5) for outpatient management was then assessed in 100 patients. The primary outcome was the occurrence of ACS.

Results: A total of 393 patients were included for the validation of the score: 206 (52.4%) from Europe and 187 (47.6%) from Africa. Of these, 76 patients (19.3%) developed ACS. Of the 50 patients (12.7%) with a low-risk score, 3 (6.0%) developed ACS (negative predictive value 94.0%). Of the 76 patients who developed ACS, 73 (96.1%) did not have a low-risk score (sensitivity 96.1%). A total of five deaths (1.3%) was recorded; no individuals who died had a low-risk score. Score performance was similar across both continents. When the score was used to guide outpatient management in 100 patients with VOC, one case of ACS (1.0%) was recorded.

Conclusions: This international study validated the PRESEV predictive risk score to identify adult patients at low risk for ACS. (Funded by the Support for Actions against Red Blood Cell Diseases Association and others; trial registration number, IRB 00003835; ClinicalTrials.gov number, NCT03032055.).