Citations

Background: Chordoma is a rare bone cancer with limited treatment options. Clinical trials are crucial for developing effective therapies, but their success depends on including diverse patient populations. The objective of this study was to systematically evaluate the reporting of racial, ethnic, and socioeconomic diversity in United States clinical trials exploring treatment for chordoma. Methods: A literature search was conducted through PubMed/Medline, Cochrane, Epistemonikos, and ClinicalTrials.gov databases for published US chordoma trials up until 19 August 2024. The data collected included trial characteristics and racial and ethnic data, as well as socioeconomic indicators when available. Methodological Index for Non-Randomized Studies (MINORS) and Revised Cochrane Risk-of-Bias Tool for Randomized Trials (RoB2) analyses were adopted to assess the methodological quality. The N-1 Chi-squared (χ2) test was implemented to compare the reported racial and ethnic data with the most recent US Census Bureau data. Results: Five trials involving 111 patients (median age: 63 years; 34% female) were included. Four studies (80%) were single-arm non-randomized studies with one study (25%) having a high methodological quality and three (75%) having a moderate quality based on the MINORS analysis. Most patients (91%, n = 82) were White/Caucasian, representing a proportion which was significantly higher than the reported 75% in the US population (p = 0.0005). Black/African American patients (2%, n = 2) were significantly underrepresented compared to the 14% in the US population (p = 0.0015). Regarding ethnicity, Hispanic/Latino patients (7%, n = 6) were significantly underrepresented compared to the 20% in the US population (p = 0.0021). No measures of socioeconomic status were reported. Conclusions: This systematic review highlighted the need for improved racial and ethnic diversity in chordoma trials and the better reporting of socioeconomic data. The underrepresentation of minority groups may obscure potential disparities in disease incidence, treatment access, and clinical outcomes.

Importance Office-based phototherapy is cost-effective for psoriasis but difficult to access. Home-based phototherapy is patient preferred but has limited clinical data, particularly in patients with darker skin. Objective To compare the effectiveness of home- vs office-based narrowband UV-B phototherapy for psoriasis. Design, Setting, and Participants The Light Treatment Effectiveness study was an investigator-initiated, pragmatic, open-label, parallel-group, multicenter, noninferiority randomized clinical trial embedded in routine care at 42 academic and private clinical dermatology practices in the US. Enrollment occurred from March 1, 2019, to December 4, 2023, with follow-up through June 2024. Participants were 12 years and older with plaque or guttate psoriasis who were candidates for home- and office-based phototherapy. Interventions Participants were randomized to receive a home narrowband UV-B machine with guided mode dosimetry or routine care with office-based narrowband UV-B for 12 weeks, followed by an additional 12-week observation period. Main Outcomes and Measures The coprimary effectiveness outcomes were Physician Global Assessment (PGA) dichotomized as clear/almost clear skin (score of ≤1) at the end of the intervention period and Dermatology Life Quality Index (DLQI) score of 5 or lower (no to small effect on quality of life) at week 12. Results Of 783 patients enrolled (mean [SD] age, 48.0 [15.5] years; 376 [48.0%] male), 393 received home-based phototherapy and 390 received office-based phototherapy, with 350 (44.7%) having skin phototype (SPT) I/II, 350 (44.7%) having SPT III/IV, and 83 (10.6%) having SPT V/VI. A total of 93 patients (11.9%) were receiving systemic treatment. At baseline, mean (SD) PGA was 2.7 (0.8) and DLQI was 12.2 (7.2). At week 12, 129 patients (32.8%) receiving home-based phototherapy and 100 patients (25.6%) receiving office-based phototherapy achieved clear/almost clear skin, and 206 (52.4%) and 131 (33.6%) achieved DLQI of 5 or lower, respectively. Home-based phototherapy was noninferior to office-based phototherapy for PGA and DLQI in the overall population and across all SPTs. Home-based phototherapy, compared to office-based phototherapy, was associated with better treatment adherence (202 patients [51.4%] vs 62 patients [15.9%]; P < .001), lower burden of indirect costs to patients, and more episodes of persistent erythema (466 of 7957 treatments [5.9%] vs 46 of 3934 treatments [1.2%]; P < .001). Both treatments were well tolerated with no discontinuations due to adverse events. Conclusions and Relevance In this randomized clinical trial, home-based phototherapy was as effective as office-based phototherapy for plaque or guttate psoriasis in everyday clinical practice and had less burden to patients. Trial Registration ClinicalTrials.gov Identifier: NCT03726489

Abstract Objective To identify and disseminate research priorities for the headache field that should be areas of research focus during the next 10 years. Background Establishing research priorities helps focus and synergize the work of headache investigators, allowing them to reach the most important research goals more efficiently and completely. Methods The Headache Research Priorities organizing and executive committees and working group chairs led a multistakeholder and international group of experts to develop headache research priorities. The research priorities were developed and reviewed by clinicians, scientists, people with headache, representatives from headache organizations, health‐care industry representatives, and the public. Priorities were revised and finalized after receiving feedback from members of the research priorities working groups and after a public comment period. Results Twenty‐five research priorities across eight categories were identified: human models, animal models, pathophysiology, diagnosis and management, treatment, inequities and disparities, research workforce development, and quality of life. The priorities address research models and methods, development and optimization of outcome measures and endpoints, pain and non‐pain symptoms of primary and secondary headaches, investigations into mechanisms underlying headache attacks and chronification of headache disorders, treatment optimization, research workforce recruitment, development, expansion, and support, and inequities and disparities in the headache field. The priorities are focused enough that they help to guide headache research and broad enough that they are widely applicable to multiple headache types and various research methods. Conclusions These research priorities serve as guidance for headache investigators when planning their research studies and as benchmarks by which the headache field can measure its progress over time. These priorities will need updating as research goals are met and new priorities arise.

Vitamin B12 is critical for hematopoiesis and myelination. Deficiency can cause neurologic deficits including loss of coordination and cognitive decline. However, diagnosis relies on measurement of vitamin B12 in the blood, which may not accurately reflect the concentration in the brain. Using programmable phage display, we identified an autoantibody targeting the transcobalamin receptor (CD320) in a patient with progressive tremor, ataxia, and scanning speech. Anti-CD320 impaired cellular uptake of cobalamin (B12) in vitro by depleting its target from the cell surface. Despite a normal serum concentration, B12 was nearly undetectable in her cerebrospinal fluid (CSF). Immunosuppressive treatment and high-dose systemic B12 supplementation were associated with increased B12 in the CSF and clinical improvement. Optofluidic screening enabled isolation of a patient-derived monoclonal antibody that impaired B12 transport across an in vitro model of the blood-brain barrier (BBB). Autoantibodies targeting the same epitope of CD320 were identified in seven other patients with neurologic deficits of unknown etiology, 6% of healthy controls, and 21.4% of a cohort of patients with neuropsychiatric lupus. In 132 paired serum and CSF samples, detection of anti-CD320 in the blood predicted B12 deficiency in the brain. However, these individuals did not display any hematologic signs of B12 deficiency despite systemic CD320 impairment. Using a genome-wide CRISPR screen, we found that the low-density lipoprotein receptor serves as an alternative B12 uptake pathway in hematopoietic cells. These findings dissect the tissue specificity of B12 transport and elucidate an autoimmune neurologic condition that may be amenable to immunomodulatory treatment and nutritional supplementation.