NEJM evidence最新文献

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 66-year-old woman with a history of remote renal transplantation and residual chronic kidney disease who was found unresponsive and presented with coma, respiratory distress, and abnormal limb movements. Using questions, physical examination, and testing, an illness script for the presentation emerges. As the clinical course progresses, the differential is refined until a diagnosis is made.

Background: There is concern about the increased risk of neurodevelopmental disorders (NDDs) among offspring of fathers taking valproate within 90 days before conception.

Methods: Using nationwide databases from Norway and Taiwan, this cohort study examined associations between exposure to paternal valproate monotherapy during the 90 days preceding conception and incidence of NDDs among offspring after at least 6 years of follow-up. Pooled logistic regression analyses compared risks of NDDs among offspring whose fathers were treated versus not treated with valproate in the overall cohort (population control); treated versus not treated with valproate among fathers with an indication for antiseizure medication (indication-restricted); and treated with valproate versus lamotrigine or levetiracetam (active-comparator). Adjusted hazard ratios and 95% confidence intervals (CIs) were generated with adjustment for confounding variables using propensity score fine stratification weighting (PS-FSW) in the indication-restricted and active-comparator analyses.

Results: Paternal valproate exposure in the 90 days before conception occurred in 319 of 339,500 (0.09%) offspring in Norway and 564 of 1,051,488 (0.05%) in Taiwan. In the population control analyses, the crude hazard ratios of NDDs among offspring exposed versus unexposed to valproate were 1.67 (95% CI, 1.10 to 2.54) in Norway and 1.35 (95% CI, 1.13 to 1.63) in Taiwan. In the indication-restricted PS-FSW analyses, the adjusted hazard ratios of NDDs among offspring exposed versus unexposed to valproate among fathers with an antiseizure medication indication were 1.20 (95% CI, 0.75 to 1.94) in Norway and 1.12 (95% CI, 0.92 to 1.35) in Taiwan. In the active-comparator PS-FSW analyses, the adjusted hazard ratios of NDDs in offspring with exposure to valproate versus lamotrigine or levetiracetam were 1.02 (95% CI, 0.57 to 1.82) in Norway and 1.22 (95% CI, 0.64 to 2.33) in Taiwan.

Conclusions: Paternal use of valproate within the 90 days before conception was not associated with an increased risk of NDDs in offspring after adjustment for confounding in Norwegian and Taiwanese cohorts. (Funded by the Research Council of Norway and the National Science and Technology Council of Taiwan.).

AbstractThe win ratio is a method for analyzing a clinical hierarchy of outcomes. It is most commonly applied to randomized clinical trials to evaluate the superiority of an intervention versus the standard of care. Once an intervention is approved, a noninferiority trial may be used to assess whether or not an alternative intervention is as effective. The authors explain how to select an appropriate noninferiority margin in terms of the win ratio, while emphasizing the importance of translating it into familiar metrics (e.g., rate ratios, differences in means) for easier interpretation. This framework is illustrated with a worked example of a hypothetical trial. The authors provide practical guidance on how the win ratio could be effectively used in future noninferiority trials.

Background: Chronic hyponatremia is associated with adverse outcomes, including falls, neurocognitive disorders, and mortality, but whether hyponatremia itself increases morbidity and mortality, or is simply an indicator of underlying disease severity, remains unclear. We aimed to evaluate the effects of targeted hyponatremia correction versus routine care on mortality and rehospitalization rates.

Methods: We conducted a randomized, controlled, parallel-group, multicenter trial across nine European centers. Hospitalized participants with plasma sodium lower than 130 mmol/l were assigned to undergo either a multifaceted targeted correction of hyponatremia (intervention) or routine care for hyponatremia (control). The primary outcome was the combined risk of death or rehospitalization within 30 days of trial inclusion.

Results: A total of 2173 patients were randomly assigned to intervention (n=1079) or control (n=1094). The median age was 73 years (interquartile range, 63 to 81) and 48% were male. The median baseline sodium levels were 127 mmol/l (interquartile range, 124 to 128) in both groups. The mean (± standard deviation) maximum absolute change in sodium levels during the treatment period was 10.0 mmol/l (±5.6) in the intervention group, compared with 8.7 mmol/l (±5.6) in the control group, resulting in normal sodium levels (defined as 135-145 mmol/l) in 641 (60.4%) and 492 (46.2%) patients in the intervention and control groups, respectively. Within 30 days after inclusion, the primary outcome occurred in 20.5% (218 of 1065 patients) in the intervention group and 21.8% (234 of 1073 patients) in the control group (estimated absolute difference, -1.3 percentage points; 95% confidence interval, -4.9 to 2.2; P=0.45). Death occurred in 86 (8.0%) patients and rehospitalization in 141 (13.2%) patients in the intervention group compared with 88 (8.0%) patients and 151 (14.1%) patients in the control group. Overcorrection occurred in 25 (2.3%) patients in the intervention group and 16 (1.4%) patients in the control group; no cases of osmotic demyelination syndrome were observed.

Conclusions: In hospitalized patients with chronic hyponatremia, a targeted correction intervention resulted in higher normonatremia rates but did not reduce a composite outcome of 30-day mortality and rehospitalization. (Funded by the Swiss National Science Foundation [grant number, 33 IC30_192979]; ClinicalTrials.gov number, NCT03557957.).

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.).

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.

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.