NEJM evidence最新文献

AbstractGood clinical practice standards mandate that informed consent be obtained before enrollment for all trials that present more than minimal risk to participants. Deferred consent, the process of enrolling patients in a clinical trial before consent is obtained, is sometimes employed in emergency care settings when patients are unable to consent at the time of trial enrollment, are critically ill, and a delay in enrollment would preclude them from potentially benefiting from the trial treatment. This article reviews the risks and benefits associated with the use of deferred consent in randomized controlled trials and the ethical acceptability of its use within specific clinical trial contexts.

AbstractA new H3N2 variant (named subclade K) possesses several key hemagglutinin substitutions and is circulating widely during the 2025-2026 influenza season. We sought to determine whether the 2025-2026 seasonal influenza vaccine elicits antibodies in humans that recognize this variant. We found that H3N2 subclade K viruses are antigenically advanced; however, the 2025-2026 seasonal influenza vaccine elicited antibodies in many individuals that efficiently recognized these viruses. Thus, the current seasonal influenza vaccine likely will be partially effective at preventing illness associated with H3N2 subclade K virus infections.

Background: We aimed to evaluate the feasibility of conducting a multicenter, double-blind, placebo-controlled trial of prolonged (i.e., multidose) compared with single-dose amoxicillin challenge in patients with a history of delayed penicillin allergy and to assess the frequency of immune-mediated adverse events.

Methods: We conducted a parallel, double-blind, placebo-controlled multicenter randomized feasibility trial at four Australian hospitals. Adults who had a history of penicillin allergy of delayed-onset (2 or more hours after exposure) or unknown timing and had tolerated a single-dose oral challenge to amoxicillin were eligible to enroll. Participants were randomly assigned 1:1 using a permuted block design to either a 5-day amoxicillin challenge (intervention) or a placebo (control). The primary outcome measures were adherence to the intervention (N, % taking at least 80% of capsules), need for unblinding (N, %), and recruitment feasibility (N, % of eligible patients enrolled). The secondary outcome measures included positive oral challenges, defined as immune-mediated adverse events up to and including day 7.

Results: We screened 302 adults and randomly assigned 120 participants to intervention (n=60) or control (n=60). The mean (standard deviation) age was 49.4 years (17.6). Allergy histories included 42% (50/120) delayed reactions and 58% (70/120) of unknown timing. Adherence to the intervention was 83% (100/120; 95% confidence interval, 75 to 90) (88% intervention and 78% control). No patients were unblinded and recruitment feasibility was 71% (120/169). The number of positive oral challenges was 7 of 60 (12%) in the intervention group and 3 of 60 (5%) in the control group (risk difference, 6.7 percentage points; 95% confidence interval, -3.2 to 16.5). One serious adverse event (1/60, 1.7%, severe cutaneous adverse reaction) was observed in the control group.

Conclusions: Conducting a double-blind, placebo-controlled randomized trial of single-dose versus multidose oral amoxicillin challenge was feasible. A fully powered efficacy trial is needed to assess between-group differences in immune-mediated adverse events. (Funded by Austin Health and others; trial registration: ANZCTR - ACTRN12623001242617, registered on November 30, 2023.).

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: In the phase 3 SUNLIGHT trial (Study of Trifluridine/Tipiracil With and Without Bevacizumab in Refractory Metastatic Colorectal Cancer Patients), trifluridine-tipiracil+bevacizumab (FTD-TPI+bev) improved the overall survival of patients with metastatic colorectal cancer (mCRC) compared with trifluridine-tipiracil (FTD-TPI) monotherapy. We investigated the real-world outcomes of FTD-TPI+bev compared with FTD-TPI for patients with mCRC.

Methods: We analyzed U.S.-based electronic medical records and claims in the ConcertAI RWD360 dataset. Adults with mCRC were grouped by first exposure to FTD-TPI versus FTD-TPI+bev. Propensity score matching was used to balance the cohorts based on patient characteristics. Kaplan-Meier analyses were used to describe the real-world overall survival (rwOS, the primary outcome), time to treatment discontinuation (rwTTD), and time to next treatment or death (rwTTNTD).

Results: This cohort included 3151 patients treated with FTD-TPI and 529 patients treated with FTD-TPI+bev. After propensity score matching, 472 patients were included in each cohort with balanced patient characteristics. The median rwOS was 8.9 months (95% confidence interval [CI], 7.8 to 10.1) for FTD-TPI+bev and 5.8 months (95% CI, 4.9 to 6.7) for FTD-TPI (P<0.001). The median rwTTD was 3.5 months (95% CI, 3.2 to 3.8) in the FTD-TPI+bev group and 2.2 months (95% CI, 1.9 to 2.5) in the FTD-TPI group. The median rwTTNTD among the FTD-TPI+bev group was 4.9 months (95% CI, 4.5 to 5.4) and in the FTD-TPI group it was 3.5 months (95% CI, 3.1 to 3.7).

Conclusions: This U.S.-based real-world observational study found that FTD-TPI+bev was associated with longer rwOS compared with FTD-TPI in patients with mCRC. These findings align with the results of the SUNLIGHT clinical trial. (Funded by Taiho Oncology, Inc. and others.).

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.

AbstractInterventional clinical research often involves risks to participants of reproductive potential, requiring pregnancy testing, contraception, and reporting of incidental pregnancies. Since the Dobbs v. Jackson Women's Health Organization (2022) decision that eliminated the constitutional right to abortion, these routine research practices present new risks to participants, clinicians, and investigators. This review examines the emerging reproductive privacy concerns in clinical research post-Dobbs and provides practical considerations for investigators and institutional review boards navigating this evolving legal environment.