Many randomized controlled trials (RCTs) in assisted reproductive technology (ART) face widespread misinterpretation of statistically non-significant results within the conventional frequentist framework. This study aimed to reevaluate high-quality ART RCTs using Bayesian methods to quantify the strength of the evidence for both the null and alternative hypotheses. We systematically searched ART-related RCTs published in JAMA, The Lancet, The BMJ, and NEJM between 2010 and 2025. A total of 35 trials were ultimately included for Bayesian reanalysis, which used Bayes factors (BF₁₀) to evaluate the primary outcomes. Sensitivity analyses were performed to confirm the robustness of our primary findings. The Bayesian and frequentist results were consistent in 85.7% of the studies. Among these consistent results, 62.9% supported the null hypothesis and 22.9% supported the alternative hypothesis. In 11.4% of the studies, non-significant P-values were paired with inconclusive Bayes factors, indicating data insensitivity. Another 2.9% showed significant P-values but inconclusive BF10. Overall, 71.4% of studies reported non-significant primary outcomes, with an increasing trend observed over time. Bayesian analysis offers a useful framework for interpreting "negative results" in ART RCTs. It effectively complements traditional statistics to improve the interpretation of evidence and inform future trial design in ART.
Bundibugyo virus is a relatively rare orthoebolavirus that has caused only two previously recognized disease outbreaks but remains capable of producing severe epidemic disease with substantial mortality. The 2026 outbreak of Bundibugyo virus disease in the Democratic Republic of Congo has highlighted persistent challenges in the detection of filovirus disease outbreaks, as well as in diagnosis, clinical management, and the public health response, particularly in resource-limited settings. As with other filovirus infections, effective control of the Bundibugyo virus disease outbreak depends on rapid identification of cases, laboratory confirmation of infection, isolation of cases, contact tracing, infection-prevention measures, protection of health care workers, and community engagement. Although no licensed vaccines or approved therapeutics specific to Bundibugyo virus disease are currently available, advances in supportive care have improved outcomes during recent filovirus disease outbreaks. Experimental evidence from studies involving nonhuman primates, serologic investigations with human samples, and monoclonal antibody research suggests that vaccines and therapeutics developed against Ebola virus may provide cross-protective activity against Bundibugyo virus. These observations support prototype-pathogen approaches to preparedness while underscoring the need for continued development of pathogen-specific countermeasures. The current outbreak reinforces the principle that a successful response to filovirus disease requires integration of medical countermeasures, clinical care, surveillance, diagnostics, and coordinated multinational public health operations.
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This article examines the paradox of value-based drug pricing, wherein lifesaving pharmaceuticals are increasingly priced based on perceived therapeutic value without regard to the development or production costs, with results that most observers would not recognize as offering value. Although this approach appears to promise to reward innovation and align incentives, it often results in unsustainable costs for consumers, health systems, and the government - particularly in the United States, where drug prices are dramatically higher than in other wealthy nations. This article dissects different pricing rationales and illustrates how market failures and monopolies combine with inadequate government policy to distort value-based logic into an illogical outcome. The authors propose reforms that preserve incentives for innovation while promoting affordability, including competitive market mechanisms, regulatory oversight, and international market recognition. The goal is to align value, access, innovation, and sustainability in pharmaceutical pricing.
Deep brain stimulation (DBS) is an established therapy for advanced Parkinson's disease (PD), but its long-term social and clinical impact has not been well characterized in large cohorts. We conducted a retrospective cohort study using a nationwide hospital database across the United States. Among 79,845 adults hospitalized with PD in 2018 and followed through 2023, 482 underwent DBS implantation. Overlap propensity score weighting was used to balance baseline characteristics. Weighted logistic and gamma regression models estimated adjusted odds ratios (aORs) and cost ratios at 1, 3, and 5 years after discharge. DBS was associated with significantly lower risks of institutionalization at 1, 3, and 5 years (aORs 0.25-0.27) and lower mortality at 1 and 5 years (aORs 0.09 and 0.27). Total healthcare expenditures were also lower in the DBS group (cost ratios 0.68-0.73). Readmission rates were similar between groups but tended to decline over time among DBS recipients. Sensitivity analyses excluding patients with dementia and restricting to non-emergency admissions yielded consistent results. Although DBS implantations were concentrated in large, urban teaching hospitals, outcomes were comparable between teaching and non-teaching institutions. These findings suggest sustained clinical and economic benefits of DBS and highlight the importance of improving equitable access.
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Multiple sclerosis is a chronic autoimmune disorder that affects the central nervous system, causing episodes of neurologic dysfunction and often gradual disease progression. The immune system primarily targets myelin, the protective covering of nerve fibers, leading to inflammation and damage, and secondary neurodegeneration is a major cause of long-term disability. Common symptoms include vision problems, sensory disturbances, muscle weakness, balance difficulties, and bladder dysfunction. Important advances in treatment have improved outcomes in patients with relapsing forms of multiple sclerosis, particularly through highly effective immune-modifying therapies such as CD20-targeting monoclonal antibodies. However, treatment options for progressive forms remain limited, which highlights the need for therapies that can prevent progression and promote myelin repair. Comprehensive symptom management and lifestyle support are also essential to maintaining quality of life and reducing disability.
Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a standard treatment for relapsed or refractory B-cell non-Hodgkin lymphomas. Long-term results and curative potential remain uncertain. We evaluated long-term outcomes in 38 patients with relapsed or refractory B-cell non-Hodgkin lymphomas (24 patients with large B-cell lymphoma and 14 with follicular lymphoma) who had been treated with CTL019 (now called tisagenlecleucel) - autologous T cells expressing CD19-directed, 4-1BB-costimulated chimeric receptors. Lymphoma-free survival was defined as the time from the tisagenlecleucel infusion to relapse or lymphoma-related death. The incidence of non-relapse-related death and second primary cancer was estimated with the Aalen-Johansen method. The data-cutoff date was October 1, 2025. At a median follow-up of 10.1 years (range, 7.9 to 11.5), no relapses had occurred beyond 5.4 years. The 10-year lymphoma-free survival was 32% (95% confidence interval [CI], 14 to 51) among patients with large B-cell lymphoma and 47% (95% CI, 20 to 71) among those with follicular lymphoma. In an analysis that included deaths from any cause, the 10-year progression-free survival was 17% (95% CI, 5 to 34) among patients with large B-cell lymphoma and 29% (95% CI, 9 to 52) among those with follicular lymphoma; the 10-year overall survival was 17% (95% CI, 5 to 34) and 50% (95% CI, 23 to 72), respectively. Persistent grade 2 or 3 neutropenia occurred in 2 patients (5%); no late anemia or thrombocytopenia was observed. A second primary cancer developed in 9 patients (10-year cumulative incidence, 21%). The 10-year non-relapse-related mortality was 18% (14% when deaths related to coronavirus disease 2019 were excluded). Higher CAR-transgene persistence appeared to be associated with long-term response. B-cell aplasia persisted in 44% of patients with a long-term response. Among patients with heavily pretreated B-cell non-Hodgkin lymphoma, a single infusion of tisagenlecleucel led to decade-long remissions (lymphoma-free survival) in approximately one third of the patients with large B-cell lymphomas and in nearly one half of those with follicular lymphoma. (Funded by the Richard Berman Family Innovations Center in CLL and Lymphomas and others; ClinicalTrials.gov number, NCT02030834.).
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Early introduction of peanut protein reduces allergy prevalence by approximately 80%, with efficacy diminishing as introduction is delayed. Appropriate prevention involves ingestion of approximately 2 g of peanut protein weekly for infants at low risk and 4 to 6 g weekly for infants at high risk. Population-level implementation that targets all infants achieves greater reduction in disease burden than approaches that target only high-risk groups, although disparities exist among some ethnic groups and groups with restricted access to care. Peanut immunotherapy initiated in younger children (1 to 3 years of age) shows superior efficacy and higher rates of clinical remission as compared with immunotherapy initiated in older children. The natural history of untreated peanut allergy follows a trajectory of increasing peanut-specific IgE levels and clinical reactivity over time, underscoring the importance of early intervention during this narrow developmental window.