NEJM evidence最新文献

Background: We previously demonstrated that sputum total mucin concentration is an objective marker for chronic bronchitis (CB). This current study introduces a novel Mucin Quantitative Score (MUCQ) that combines total mucin concentration and mucin composition to improve the assessment of risk, onset of clinically diagnosed disease, and progression of muco-obstructive lung diseases.

Methods: Patients from the SPIROMICS (SubPopulations and InteRmediate Outcome Measures in COPD Study) cohort were classified as having CB, or not, based on clinical questionnaires. Using the measured total mucin, MUC5AC, and MUC5B concentrations in sputum samples, we calculated MUCQ as [Total mucin]×([MUC5AC]÷[MUC5B])÷100 μg/ml, which is a unitless, weighted concentration score. Our primary outcome was the net reclassification of patients with a diagnosis of CB, or not, based on total mucin concentrations in their sputum compared with using the MUCQ score. Participants were first classified as CB- positive or -negative using a total mucin concentration threshold of 2306 μg/ml, then reclassified using the MUCQ threshold of 4.30. Associated z statistics and a P value for the primary outcome are reported.

Results: Among 164 patients in the SPIROMICS cohort with clinically defined CB, using the MUCQ score up-classified 18 patients who were currently smoking to a diagnosis of CB and down-classified 5 patients who were currently smoking and 3 control participants who had never smoked, compared with the classification of CB was based on total mucin concentrations alone (P=0.001). In addition, MUCQ correlated with other clinical and pathological indices of chronic airway disease and airway obstruction.

Conclusions: The MUCQ metric was superior in distinguishing patients with CB compared to a total mucin concentration. Trials are needed to ascertain the prospective use of MUCQ metrics in research and clinical settings for assessment, management, and tracking therapeutic responses in CB and potentially other muco-obstructive conditions. (Funded by the National Institutes of Health and others.).

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 discusses the story of a 44-year-old man who sought evaluation for back pain and weakness. 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.

AbstractAlthough evidence-based therapies for patients with heart failure (HF) have decreased all-cause mortality, the residual risk of other clinically relevant outcomes - such as worsening HF - remains high. In this context, contemporary HF trials have increasingly employed composite primary outcomes that include worsening HF, commonly defined as episodes resulting in hospitalization for HF or urgent ambulatory visits with use of intravenous HF pharmacotherapies. In this Clinical Trials Workshop, we propose that the definition of worsening HF in clinical trials be expanded to include HF episodes treated with ambulatory oral diuretic intensification (ODI). Using previously reported post hoc analyses of pharmacotherapy trials in chronic HF, we highlight the prognostic significance of ODI and examine the implications of including ODI on anticipated event rates and estimated treatment effect. We propose a standardized definition of ODI and discuss challenges and regulatory considerations of incorporating ODI into HF trial end points.

AbstractA clade Ib mpox virus (MPXV) outbreak in Central and Eastern Africa has led to multiple travel-associated infections. In October 2025, clade Ib MPXV infection was confirmed in three unvaccinated, hospitalized men in California reporting no international travel. Phylogenetic analysis revealed clustering of these three MPXV infections with one recent travel-associated MPXV infection. This report provides evidence for local transmission of clade Ib MPXV in the Americas, occurring among gay, bisexual, and other men who have sex with men and their social networks.

AbstractTo inform public health actions during the current influenza season, the authors describe activity, vaccination, and pediatric mortality during the 2024-2025 influenza season in Massachusetts using public health surveillance data. Influenza activity was elevated, as measured by influenza-like illness, emergency department visits, and hospitalizations. Vaccination coverage was low in pediatric patients but remained high in people 65 years of age and older. There were 10 reported pediatric deaths; 7 of those occurred among children with preexisting conditions; 8 of 10 had not received that year's influenza vaccination.

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.).