NEJM evidence最新文献

AbstractInvasive infections due to Paenibacillus species pose a serious risk to young infants and have a high risk of neurologic sequelae. This report describes two infants with severe neurologic manifestations secondary to Paenibacillus dendritiformis infection who were recently identified in the United States. Clinicians who care for young infants should be aware of this emerging infection.

Background: Mobile stroke units (MSUs) accelerate prehospital acute stroke care and improve outcomes. Both onboard and telemedicine neurologist models of care are used but have not been directly compared.

Methods: MSU-TELEMED was a randomized, open-label, blinded-endpoint trial comparing onboard neurologist care to a telemedicine care model for people presenting to an MSU with suspected stroke. MSU care was prospectively randomized by day to onboard versus telemedicine care. The primary outcome was a hierarchical composite outcome using a win-odds approach that prioritized: (1) safety, (2) scene-to-treatment-decision time, and (3) percentage of the total case time the neurologist spent in direct care (higher values denote better resource use). Every participant in each group was compared to those in the other, resulting in a "win/tie/loss" distribution for telemedicine compared to onboard.

Results: A total of 275 participants were assigned to telemedicine (n=135) or onboard (n=140) neurologist care groups. The primary outcome of win/tie/loss distribution favored the telemedicine model (76%/4%/20%) with an adjusted win odds of 3.5 (95% confidence interval [CI], 2.4-5.1). Safety events were similar (13% telemedicine vs. 12% onboard, risk ratio 0.9; 95% CI, 0.5-1.8). Median scene-to-treatment-decision time was 19 minutes in the telemedicine group and 13 minutes in the onboard group (adjusted difference in median time 4 minutes; 95% CI, 1.9-5.9). The median percentage of the neurologist's time directly involved in patient care was 100% in the telemedicine group and 33% in the onboard group (adjusted difference in median percentage 63 percentage points; 95% CI, 53-74).

Conclusions: Compared to an onboard model, an MSU telemedicine model of care was superior based on a composite hierarchical outcome of safety, scene-to-treatment-decision time, and percentage of the neurologist's time spent in direct care. (Funded by the Sylvia and Charles Viertel Charitable Foundation and the Medical Research Future Fund "Golden Hour"; ClinicalTrials.gov number, NCT05991310.).

AbstractThe influenza virus constantly evolves through antigenic shift and drift, requiring annual review to inform the development of seasonal influenza vaccines. The Department of Defense Global Respiratory Pathogen Surveillance Program and Global Emerging Infections Surveillance program-funded partner laboratories perform routine respiratory pathogen surveillance across a wide-reaching global network of service members and their beneficiaries, U.S. civilians, and some foreign national populations. This report describes the influenza viruses circulating during the 2024-2025 influenza season.

AbstractPopulation screening is a long-established tool for effectively identifying disease risk when existing approaches are inadequate for optimizing care. DNA-based population screening (DNAPS) in adult populations has the power to identify individuals at an increased genetic risk of cancer, heart disease, and other health conditions, thus allowing for evidence-based interventions to reduce associated morbidity and mortality. One example of the type of risk identified in such screening is BRCA1- and BRCA2-associated cancer risk, where current risk-identification strategies have been shown to miss greater than 70% of at-risk individuals. Since the first DNA-based screening pilot in adults was initiated in 2008, a growing number of other large-scale projects carrying out DNAPS in adults have followed, and, in aggregate, these projects are engaging millions of people around the world. There are features of DNAPS that make this population screening approach distinct from other population health screens, such as the scale of the datasets that will be created and stored for each participant. This review focuses on an examination of DNAPS in the context of other population health screens, the state of the evidence for this screening approach, and gaps to be addressed to optimize implementation of this population screening approach.

Background: More individuals work early-morning shifts than night shifts, yet investigations into the treatment of shift work disorder (SWD) in this population are lacking.

Methods: This randomized, double-blind, placebo-controlled trial evaluated the efficacy of solriamfetol, a selective dopamine and norepinephrine reuptake inhibitor, for treating excessive sleepiness in 78 early-morning shift workers (shift starting between 3 and 7 a.m.) with excessive sleepiness associated with SWD. The primary outcome was change in objective sleepiness, as measured by sleep latency on the Maintenance of Wakefulness Test (longer latency reflects less sleepiness). Secondary outcomes included subjective sleepiness measured by the Karolinska Sleepiness Scale (range 1-9, with higher values indicating greater sleepiness) as well as clinician- and patient-assessed change in clinical condition, using the Clinical Global Impression of Change and Patient Global Impression of Change questionnaires (scores range from 1-7 for both scales, but higher scores indicate worse condition for the clinical scale and improved condition for the patient scale).

Results: After 4 weeks, patients treated with solriamfetol were significantly less sleepy than those treated with placebo (9.4-minute longer sleep latency; 95% confidence interval [CI], 5.7 to 13.0; P<0.001). Solriamfetol treatment was associated with changed subjective sleepiness (Karolinska Sleepiness Scale difference, -1.2; 95% CI, -1.7 to -0.7), and changed clinician (odds ratio 3.7; 95% CI, 1.3 to 10.4) and patient (odds ratio, 4.2; 95% CI, 1.5 to 11.6) ratings. Overall, 55% of patients who received any treatment with solriamfetol and 63% of patients receiving placebo reported any adverse event; the most common adverse events were headache and nausea.

Conclusions: In this randomized trial of a treatment for excessive sleepiness in early-morning shift workers with SWD, solriamfetol significantly improved sleepiness compared with placebo. (Funded by Axsome Therapeutics and others; ClinicalTrials.gov number, NCT04788953.).

Background: Antenatal treatment with nipocalimab, a neonatal Fc receptor (FcRn) blocker, delayed or prevented fetal anemia, as compared with a historical benchmark, in a phase 2 study of early-onset severe hemolytic disease of the fetus and newborn (HDFN). We report on the fetal and neonatal pharmacokinetics of nipocalimab and infant immunity through 96 weeks after birth.

Methods: The UNITY study was a single-group, open-label study assessing pregnant individuals at high risk of early-onset severe HDFN treated with weekly intravenous nipocalimab (30 or 45 mg/kg) from 14 to 35 weeks' gestation, unless discontinued for safety-related stopping criteria or intrauterine transfusion initiation. Pharmacokinetics were assessed in maternal, fetal, and infant blood and colostrum or breast milk; FcRn receptor occupancy and immunoglobulin G (IgG) were measured in neonatal and maternal blood; and infant IgG and safety were monitored through 96 weeks after birth.

Results: Safety analysis included 12 live-born infants from 13 pregnancies (one fetal loss occurred following intrauterine transfusion complications). Nipocalimab concentrations were maintained in maternal participants at pharmacologically active concentrations (greater than 10 μg/ml) during the weekly dosing intervals, but were observed at low concentrations (10 μg/ml or less) in one of four fetal cordocenteses (0.04 μg/ml), one of 11 cord blood samples (0.7 μg/ml), three of seven colostrum samples (less than 4 μg/ml), and two of nine breast milk samples (less than 2 μg/ml). Low infant IgG at birth (cord blood median, 175 mg/dl; range, 92-941) reached levels consistent with a physiologic nadir by 24 weeks after birth (median, 273 mg/dl; range, 153-429) and recovered to normal range (with one exception) between 16 and 96 weeks (median, 762 mg/dl; range, 407-925). Infectious adverse events were primarily mild to moderate and typical for early childhood. Protective titers to age-appropriate vaccinations (diphtheria and tetanus) were observed in six of seven infants at or before 96 weeks.

Conclusions: In this cohort of 12 live-born infants, antenatal treatment with nipocalimab resulted in low levels of detectable drug in fetal, neonatal, and infant samples. Treatment was associated with low IgG levels at birth; however, unusual or unexpected childhood illnesses or impaired vaccine responses were not observed. (Funded by Johnson & Johnson; ClinicalTrials.gov number, NCT03842189.).