BACKGROUND At the beginning of the 2018-2020 outbreak of Ebola virus disease (EVD) in eastern Democratic Republic of Congo (DRC), no vaccine had been licensed. However, cluster-randomized evidence from Guinea in 2015 had indicated that ring vaccination around new cases (targeting contacts and contacts-of-contacts) with the use of single-dose live-replicating rVSV-ZEBOV-GP vaccine reduced EVD rates

BACKGROUND Worldwide, approximately 2 million children younger than 15 years of age are infected with multidrug-resistant (MDR) Mycobacterium tuberculosis, with MDR tuberculosis developing in approximately 30,000 annually. Evidence from randomized, controlled trials on tuberculosis preventive treatment in persons exposed to MDR tuberculosis is lacking. METHODS In this community-based, multisite, double-blind

BACKGROUND Prevention of drug-resistant tuberculosis is a global health priority. However, trials evaluating the effectiveness of treating Mycobacterium tuberculosis infection among contacts of persons with drug-resistant tuberculosis are lacking. METHODS We conducted a double-blind, randomized, controlled trial comparing 6 months of daily levofloxacin (weight-based doses) with placebo to treat M.

BACKGROUND Whether surgical axillary staging as part of breast-conserving therapy can be omitted without compromising survival has remained unclear. METHODS In this prospective, randomized, noninferiority trial, we investigated the omission of axillary surgery as compared with sentinel-lymph-node biopsy in patients with clinically node-negative invasive breast cancer staged as T1 or T2 (tumor size

BACKGROUND Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations in the gene encoding ERα (ESR1). METHODS In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed

BACKGROUND Severe hemophilia A is managed with factor VIII replacement or hemostatic products that stop or prevent bleeding. Data on gene therapy with hematopoietic stem-cell (HSC)-based expression of factor VIII for the treatment of severe hemophilia A are lacking. METHODS We conducted a single-center study involving five participants 22 to 41 years of age with severe hemophilia A without factor VIII

BACKGROUND The effect of a liberal red-cell transfusion strategy as compared with a restrictive strategy in patients during the critical care period after an aneurysmal subarachnoid hemorrhage is unclear. METHODS We randomly assigned critically ill adults with acute aneurysmal subarachnoid hemorrhage and anemia to a liberal strategy (mandatory transfusion at a hemoglobin level of ≤10 g per deciliter)

BACKGROUND Daratumumab, an anti-CD38 monoclonal antibody, has been approved for the treatment of multiple myeloma. Data are needed regarding the use of daratumumab for high-risk smoldering multiple myeloma, a precursor disease of active multiple myeloma for which no treatments have been approved. METHODS In this phase 3 trial, we randomly assigned patients with high-risk smoldering multiple myeloma

BACKGROUND B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common childhood cancer. Despite a high overall cure rate, relapsed B-cell ALL remains a leading cause of cancer-related death among children. The addition of the bispecific T-cell engager molecule blinatumomab (an anti-CD19 and anti-CD3 single-chain molecule) to therapy for newly diagnosed standard-risk (as defined by the National

BACKGROUND Patients with microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) metastatic colorectal cancer have poor outcomes with standard chemotherapy with or without targeted therapies. Nivolumab plus ipilimumab has shown clinical benefit in nonrandomized studies of MSI-H or dMMR metastatic colorectal cancer. METHODS In this phase 3 open-label trial, we randomly assigned patients

BACKGROUND After pneumococcal disease and colonization have been controlled through vaccination campaigns, a reduced pneumococcal conjugate vaccine (PCV) schedule may be sufficient to sustain that control at reduced costs. METHODS We investigated whether a single primary dose and booster dose (1p+1) of the 10-valent PCV (PCV10) would be noninferior to alternative dose schedules in sustaining control

BACKGROUND Obecabtagene autoleucel (obe-cel) is an autologous 41BB-ζ anti-CD19 chimeric antigen receptor (CAR) T-cell therapy which uses an intermediate-affinity CAR to reduce toxic effects and improve persistence. METHODS We conducted a phase 1b-2 multicenter study of obe-cel in adults (≥18 years of age) with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). The main cohort, cohort

BACKGROUND Twice-yearly subcutaneous lenacapavir has been shown to be efficacious for prevention of HIV infection in cisgender women. The efficacy of lenacapavir for preexposure prophylaxis (PrEP) in cisgender men, transgender women, transgender men, and gender-nonbinary persons is unclear. METHODS In this phase 3, double-blind, randomized, active-controlled trial, we randomly assigned participants

BACKGROUND The effect of embolization of the middle meningeal artery in patients with subacute or chronic subdural hematoma is uncertain. METHODS We performed a multicenter, open-label, randomized trial in China, involving patients with symptomatic nonacute subdural hematoma with mass effect. Patients were assigned to undergo burr-hole drainage or receive nonsurgical treatment at the surgeon's discretion

BACKGROUND Subacute and chronic subdural hematomas are common and frequently recur after surgical evacuation. The effect of adjunctive middle meningeal artery embolization on the risk of reoperation remains unclear. METHODS In a prospective, multicenter, interventional, adaptive-design trial, we randomly assigned patients with symptomatic subacute or chronic subdural hematoma with an indication for

BACKGROUND Currently licensed and approved malaria subunit vaccines provide modest, short-lived protection against malaria. Immunization with live-attenuated Plasmodium falciparum malaria parasites is an alternative vaccination strategy that has potential to improve protection. METHODS We conducted a double-blind, controlled clinical trial to evaluate the safety, side-effect profile, and efficacy of