NEJM evidence最新文献

{"title":"An Individualized Prediction Model for Early-Stage Classic Hodgkin's Lymphoma.","authors":"Angie Mae Rodday, Andrew M Evens, Matthew J Maurer, Jenica N Upshaw, Nicholas Counsell, Sara Rossetti, Cheryl Chang, Zhu Cui, Qingyan Xiang, Raphael Mwangi, Ranjana Advani, Marc Andre, Andrea Gallamini, Annette E Hay, David C Hodgson, Richard T Hoppe, Martin Hutchings, Peter Johnson, Eric Mou, Stephen Opat, John Raemaekers, Kerry J Savage, Susan K Parsons, John Radford","doi":"10.1056/EVIDoa2500115","DOIUrl":"https://doi.org/10.1056/EVIDoa2500115","url":null,"abstract":"<p><strong>Background: </strong>A predictive model for early-stage classic Hodgkin's lymphoma (cHL) does not exist. Leveraging patient-level data from large clinical trials and registries, we developed and validated a model that we term the Early-Stage cHL International Prognostication Index (E-HIPI) to predict 2-year progression-free survival (PFS).</p><p><strong>Methods: </strong>We developed the model using the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) guidelines in 3000 adults with newly diagnosed early-stage cHL from four international phase III clinical trials conducted from 1994 to 2011. External validation was performed in two cohorts, totaling 2360 treated patients from five international cHL registries (1996 to 2019). Two-year PFS was estimated using a Cox model with pretreatment variables selected using backward elimination. Internal validation corrected for overfitting. External validation assessed discrimination and calibration. The final model was also compared against European Organisation for Research and Treatment of Cancer (EORTC) favorable or unfavorable status.</p><p><strong>Results: </strong>The median age in the development cohort was 31.2 years; 77.4% had stage II disease. The estimated 2-year PFS was 93.7%. Final variables retained in the model were sex and continuous values of maximum tumor diameter (MTD), and levels of hemoglobin and albumin. The optimism-corrected C statistic in the development cohort was 0.63 (95% confidence interval, 0.60 to 0.69). Two-year PFS was lower in the validation cohorts 1 (90.3%) and 2 (91.6%). In validation cohort 1, the C statistic was 0.63 and the calibration slope was near 1, but overall calibration indicated underprediction, which improved on updating the intercept. The performance was similar in validation cohort 2. In addition, higher-risk E-HIPI scores were associated with worse outcomes in both the EORTC unfavorable and favorable subgroups. When included altogether in one Cox model, the E-HIPI was associated with PFS, whereas EORTC favorable or unfavorable status was not. Online risk calculators were developed (https://rtools.mayo.edu/holistic_ehipi/).</p><p><strong>Conclusions: </strong>Utilizing objective, continuous, and readily available variables, we developed and validated a new prediction model for early-stage cHL. Male sex, lower hemoglobin or albumin levels, and higher MTDs were associated with worse PFS. (Funded by the National Cancer Institute; grant number, NCI R01 CA 262265-04.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDoa2500115"},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Nudge toward Quality Primary Care.","authors":"William K Silverstein, Michael P Hillmer","doi":"10.1056/EVIDe2500057","DOIUrl":"https://doi.org/10.1056/EVIDe2500057","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 6","pages":"EVIDe2500057"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Intractable Cancer Pain with Resiniferatoxin - An Interim Study.","authors":"Andrew J Mannes, John D Heiss, Ann Berger, Christine C Alewine, John A Butman, Marybeth S Hughes, Nusrat Rabbee, Christina Hayes, Tracy S Williams, Matthew R Sapio, Michael J Iadarola","doi":"10.1056/EVIDoa2400423","DOIUrl":"https://doi.org/10.1056/EVIDoa2400423","url":null,"abstract":"<p><strong>Background: </strong>A substantial number of patients with advanced cancer suffer from refractory pain despite comprehensive medical management. In this article, we evaluate a nonopioid analgesic, resiniferatoxin (RTX), a potent agonist of the transient receptor potential vanilloid 1 (TRPV1) ion channel, which selectively interrupts nociceptive activity transmitted by a subpopulation of dorsal root ganglion neurons.</p><p><strong>Methods: </strong>In this interim analysis of a first-in-human, open-label, Phase 1 study, 19 patients with refractory cancer pain localized to the abdomen and/or lower extremities received one dose of intrathecal RTX. The primary outcome was safety. Secondary outcomes were efficacy assessed over the course of the study using a numerical rating scale measuring the \"worst pain\" over a 24-hour period. This is a 0 to 10 scale where 0 is \"no pain\" and 10 is the \"worst pain imaginable.\" Opioid consumption was measured as morphine equivalents used to control pain.</p><p><strong>Results: </strong>Over 188 days after RTX injection, a total of 213 treatment-emergent adverse events (AEs) were reported among 19 patients treated, including 37 serious adverse events in 14 patients. Nine deaths occurred an average of 70 days after treatment (range from 11 to 140 days). Many of these events, including death, are consistent with the course of advanced cancer. At least one AE occurred in all 19 patients. Three patients experienced loss of heat sensitivity in the dermatomes exposed to RTX (grades I and II). Seven patients experienced urinary retention lasting more than 24 hours (three were grade III). Five patients had AEs related to a transient increase in the electrocardiographic QT interval that resolved within 24 hours (grades I and II). The only grade IV AE was an unstageable decubitus ulcer. RTX was associated with decreased \"worst\" pain intensity by 38% (pretreatment 8.4±0.4 vs. posttreatment 5.2±0.6) and reduced opioid consumption by 57% measured at posttreatment day 15.</p><p><strong>Conclusions: </strong>Intrathecal RTX is a single-administration, opioid-sparing analgesic in patients with intractable cancer pain. There were expected and unexpected AEs of various grades with an encouraging initial impact on pain. (Funded by the Intramural Research Program of the National Institutes of Health Clinical Center and others; ClinicalTrials.gov number, NCT00804154).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 6","pages":"EVIDoa2400423"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computer Decision Support May Facilitate Liberation from Mechanical Ventilation.","authors":"Yu Inata, Muneyuki Takeuchi","doi":"10.1056/EVIDe2500082","DOIUrl":"https://doi.org/10.1056/EVIDe2500082","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 6","pages":"EVIDe2500082"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomized Trial of Lung and Diaphragm Protective Ventilation in Children.","authors":"Robinder G Khemani, Anoopindar Bhalla, Justin C Hotz, Margaret J Klein, Jeni Kwok, Kristen Kohler, Dinnel Bornstein, Daniel Chang, Anabel Armenta-Quiroz, Kennedy Vu, Erin Smith, Anil Suresh, David Baron, Jennifer Bonilla-Cartagena, Patrick A Ross, Timothy Deakers, Fernando Beltramo, Lara Nelson, Shilpa Shah, Marsha Elkunovich, Martha A Q Curley, Wendy Mack, Christopher J L Newth","doi":"10.1056/EVIDoa2400360","DOIUrl":"https://doi.org/10.1056/EVIDoa2400360","url":null,"abstract":"<p><strong>Background: </strong>Mechanical ventilation strategies that balance lung and diaphragm protection have not been extensively tested in clinical trials.</p><p><strong>Methods: </strong>We conducted a single-center, phase II randomized controlled trial in children with acute respiratory distress syndrome with two time points of random assignment: the acute and weaning phases of ventilation. Patients in the intervention group were managed with a computerized decision support (CDS) tool, named REDvent, and esophageal manometry to deliver lung and diaphragm protective ventilation. The control group received usual care. A daily standardized spontaneous breathing trial (SBT) was performed in both groups. The primary outcome was the length of weaning.</p><p><strong>Results: </strong>From October 2017 through March 2024, 248 children were randomly assigned to the acute phase. When participants were triggering the ventilator, the adjusted mean difference (REDvent-acute - usual care-acute) for peak inspiratory pressure was -3 cmH₂O (95% CI, -5 to -2), positive end-expiratory pressure was -2 cmH₂O (95% CI, -2 to -1), and the esophageal pressure swing was -1.8 cmH₂O (95% CI, -3.2 to -0.3). For the primary outcome, 55% of REDvent-acute patients passed their SBT or were extubated on the day of the first SBT, compared with 39% in the usual care-acute group. After adjusting for age, immunosuppression, and oxygenation index value, the REDvent-acute intervention resulted in a 1.67 (95% CI, 1.01 to 2.77; P=0.045) odds of a shorter length of weaning than usual care. The median time from intubation to SBT passage was 3.83 days in the intervention group versus 4.75 days in the usual care group. The length of ventilation among survivors was 5.0 days in the intervention group versus 5.6 days in the usual care group. When comparing weaning phase random assignment, clinical outcomes were similar between groups. There were no differences in adverse events between the groups.</p><p><strong>Conclusions: </strong>A lung and diaphragm protective ventilation strategy using a CDS tool during the acute phase of ventilation resulted in a shorter length of weaning than usual care. Phase III trials in mechanically ventilated patients are warranted. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT03266016.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 6","pages":"EVIDoa2400360"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reading and Interpreting Quality-of-Life Results in Cancer Trials.","authors":"Massimo Di Maio","doi":"10.1056/EVIDra2400340","DOIUrl":"https://doi.org/10.1056/EVIDra2400340","url":null,"abstract":"<p><p>AbstractThere is growing attention paid to patient-reported outcomes and health-related quality of life as end points in clinical trials in oncology. Such results should contribute to the definition of treatment value, inform communication with patients in clinical practice, and impact treatment choice among various options. This review seeks to help clinicians gain familiarity with the correct reading and interpretation of quality-of-life results.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 6","pages":"EVIDra2400340"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Digital Care Plan Nudge to Improve Primary Care Outcomes.","authors":"Mitesh S Patel, Thomas A Aloia, Aaron G Shoemaker, Mohamad G Fakih, Frederick A Masoudi, Luke Smith, Emily Rosenzweig, Krisda H Chaiyachati, Benjamin N Conrad, Jeevan Bandreddi, Richard I Fogel","doi":"10.1056/EVIDoa2400419","DOIUrl":"https://doi.org/10.1056/EVIDoa2400419","url":null,"abstract":"<p><strong>Background: </strong>Preventive care is underutilized in the United States. A digital care plan nudge delivered prior to primary care visits may prime patients to address these care gaps during the visit.</p><p><strong>Methods: </strong>A two-group, cluster randomized trial of 76 primary care practices in four U.S. states compared usual care with a digital care plan nudge, which sent text messages to patients before a primary care visit informing them of up to three of six possible care gaps to address at the visit. Outcomes were care gaps addressed the day of the visit (primary) and completed by 90 days after the visit (secondary). We also explored appointment engagement and patient experience.</p><p><strong>Results: </strong>The sample included 204 clinicians with 29,334 patient encounters. The mean (standard deviation) patient age was 56.9 (16.5) years, 61.0% were female, and 15.2% and 11.1% were Black and non-Hispanic or Hispanic, respectively. The primary outcome of care gaps addressed at the visit occurred in 23.5% of cases in the intervention group, compared with 20.3% of cases in the usual care group (adjusted difference 3.8 percentage points; 95% confidence interval (CI), -0.4 to 8.1; P=0.08). The intervention was associated with greater care gaps completed by 90 days (5.4 percentage points; 95% CI, 0.7 to 10.1). In post hoc analyses, the intervention was also associated with greater appointment engagement with an increase in completion (difference of 2.8 percentage points; 95% CI, 1.8 to 3.8), a decrease in no-shows (-1.2 percentage points; 95% CI, -1.7 to -0.6) and a decrease in cancellations (-1.5 percentage points; 95% CI, -2.2 to -0.8).</p><p><strong>Conclusions: </strong>This trial of a digital care plan nudge did not meet the primary outcome of addressing care gaps during the visit. Observed associations in secondary outcomes, including care gap closure within 90 days and appointment engagement, warrant further evaluation. (Funded by Ascension; ClinicalTrials.gov number, NCT05799976.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 6","pages":"EVIDoa2400419"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mepolizumab for COPD with Eosinophilic Phenotype following Hospitalization.","authors":"Cara A Flynn, Hamish J C McAuley, Omer Elneima, Hnin W W Aung, Wadah Ibrahim, Thomas J C Ward, Michelle Bourne, Tracey D Thornton, Vijay Mistry, Hannah R Gilbert, Ghazala Waheed, Adam K A Wright, Rachel A Evans, Michael C Steiner, Cassandra L Brookes, Christopher E Brightling, Neil J Greening","doi":"10.1056/EVIDoa2500012","DOIUrl":"10.1056/EVIDoa2500012","url":null,"abstract":"<p><strong>Background: </strong>Admission to hospital with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with a high risk of morbidity and mortality. Biologic treatment reduces COPD exacerbations in patients with eosinophilic inflammation. Mepolizumab, a monoclonal antibody to interleukin 5, reduces eosinophilic inflammation, but its effects on future hospitalization and mortality are uncertain.</p><p><strong>Methods: </strong>In this phase 2b, double-blind, placebo-controlled trial, we randomly assigned patients hospitalized with an AECOPD and a blood eosinophil count greater than or equal to 300 cells/μl any time in the preceding 12 months to receive either mepolizumab 100 mg or placebo every 4 weeks for 48 weeks, with treatment initiated at hospital discharge. The primary end point was the time to readmission or death from any cause. Key secondary end points included the number of hospital readmissions, exacerbations, and health-related quality of life.</p><p><strong>Results: </strong>A total of 238 patients were randomly assigned. The median time to hospitalization or death due to any cause was 25.4 weeks and 26.1 weeks in the mepolizumab and placebo groups, respectively, with Kaplan-Meier estimates of 33.9% and 31.0%, respectively (hazard ratio, 0.96; 95% confidence interval [CI], 0.70 to 1.32; P=0.811). The adjusted mean number of hospital readmissions was 1.65 (95% CI, 1.25 to 2.05) with mepolizumab and 1.85 (95% CI, 1.42 to 2.29) with placebo (risk ratio, 0.89; 95% CI, 0.64 to 1.25). The adjusted mean number of moderate or severe exacerbations was 2.80 (95% CI, 2.36 to 3.23) with mepolizumab and 3.45 (95% CI, 2.94 to 3.95) with placebo (risk ratio 0.81; 95% CI, 0.66 to 1.00). The numbers of adverse events and serious adverse events were similar between groups. No serious adverse event was attributed to the intervention.</p><p><strong>Conclusions: </strong>Patients hospitalized with an AECOPD and eosinophilic inflammation of greater than 300 cells/μl of blood within the prior 12 months, had no benefit in risk of time to readmission or death following treatment with mepolizumab for 48 weeks. The observed change in moderate or severe exacerbations, which included the null in the upper bound of the 95% confidence interval, was in the direction observed in previous trials. (Funded by GSK plc; ClinicalTrials.gov number, NCT04075331.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDoa2500012"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 47-Year-Old Woman with Left Shoulder Pain.","authors":"Justin Matthew Cheung, Daniel J Ikeda, Clement D Lee","doi":"10.1056/EVIDmr2500031","DOIUrl":"https://doi.org/10.1056/EVIDmr2500031","url":null,"abstract":"<p><p>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 47-year-old woman who presented with pain in the left shoulder, fevers, and fatigue. Through a structured clinical approach, including targeted history, physical examination, and diagnostic testing, an illness script for the presentation emerges, and the differential diagnosis is refined. As the clinical course progresses, additional investigations provide key insights, leading to the final diagnosis.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 6","pages":"EVIDmr2500031"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mepolizumab in COPD - If at First You Don't Succeed.","authors":"Mark T Dransfield, Daiana Stolz","doi":"10.1056/EVIDe2500080","DOIUrl":"10.1056/EVIDe2500080","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDe2500080"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}