Additional Steps for Maintaining Public Trust in the FDA.

This letter responds to the essay "Securing the Trustworthiness of the FDA to Build Public Trust in Vaccines," by Leah Z. Rand, Daniel P. Carpenter, Aaron S. Kesselheim, Anushka Bhaskar, Jonathan J. Darrow, and William B. Feldman, in the special report "Time to Rebuild: Essays on Trust in Health Care and Science," in the September-October 2023 issue of the Hastings Center Report.

Analysis of Learning Agendas Highlights Need for More Specific Discussions of Collaboration in Federal Agency Behavioral Health Plans.

In his analysis of federal agency learning agendas, Tsai notes that these plans may address some key issues such as trauma and Veteran needs but place limited emphasis on other key emerging topics. Some topics may be covered in other agency documents such as strategic plans. However, his analysis highlights the need for further collaboration in developing learning agendas and strategic plans and other planning documents. As well, it is important to obtain stakeholder and public input in developing these plans and to identify with specificity implementation details and roles and responsibilities of key federal and other partners.

Isocitrate dehydrogenase (IDH) mutant gliomas: A Society for Neuro-Oncology (SNO) consensus review on diagnosis, management, and future directions.

Isocitrate dehydrogenase (IDH) mutant gliomas are the most common adult, malignant primary brain tumors diagnosed in patients younger than 50, constituting an important cause of morbidity and mortality. In recent years, there has been significant progress in understanding the molecular pathogenesis and biology of these tumors, sparking multiple efforts to improve their diagnosis and treatment. In this consensus review from the Society for Neuro-Oncology (SNO), the current diagnosis and management of IDH-mutant gliomas will be discussed. In addition, novel therapies, such as targeted molecular therapies and immunotherapies, will be reviewed. Current challenges and future directions for research will be discussed.

Phase I Study of High-Dose L-methylfolate in Combination with Temozolomide and Bevacizumab in Recurrent IDH wild-type High-Grade Glioma.

Purpose: IDH mutations in low-grade gliomas (LGGs) results in improved survival and DNA hypermethylation compared to IDH wild-type LGGs. IDH-mutant LGGs become hypomethylated during progression. It's uncertain if methylation changes occur during IDH wild-type GBM progression and if the methylome can be reprogrammed. This phase I study evaluated the safety, tolerability, efficacy and methylome changes after L-methylfolate (LMF) treatment, in combination with temozolomide and bevacizumab in patients with recurrent high-grade glioma. Patients and Methods: Fourteen patients total, 13 with GBM, one with anaplastic astrocytoma, all IDH wild-type were enrolled in the study. All patients received LMF at either 15, 30, 60, or 90 mg daily plus temozolomide (75mg/m2 5 days per month) and bevacizumab (10mg/kg every two weeks). Results: No MTD was identified. LMF treated had mOS of 9.5 months (95% CI, 9.1-35.4) comparable to bevacizumab historical control 8.6 months (95% CI, 6.8-10.8). Six patients treated with LMF survived more than 650 days. Across all treatment doses the most adverse events were diarrhea (7%, 1 patient, grade 2), reflux (7%, 1 patient, grade 2), and dysgeusia (7%, 1 patient, grade 2). In the six brains donated at death, there was a 25% increase in DNA methylated CpGs compared to the paired initial tumor. Conclusions: LMF in combination with temozolomide and bevacizumab was well tolerated in patients with recurrent IDH wild-type high-grade glioma. This small study did not establish a superior efficacy with addition of LMF compared to standard bevacizumab therapy, however, this study did show methylome reprogramming in high-grade glioma.

Stigma Associated With Pelvic Floor Disorders.

OBJECTIVES: Although the impact of stigma is known for women with urinary incontinence, it has not been well studied among the full spectrum of pelvic floor disorders. This study quantifies the level of stigma among women presenting for urogynecologic care and tests the hypothesis that stigma related to pelvic floor disorders results in a delay in care seeking for these problems. METHODS: Women presenting for new patient visits (N = 523) in university medical center-based urogynecology clinics completed 2 anonymous questionnaires (Stigma Scale for Chronic Illnesses 8-item version and Pelvic Floor Bother Questionnaire) before their visit. The Kruskal-Wallis test was used to compare the distributions of stigma scores. Logistic regression was used to model factors associated with a delay in seeking care. Spearman correlation was used to determine whether there was an association between stigma and bother scores. RESULTS: Median stigma score was significantly higher for those presenting with complaints of urine leakage (P = 0.015), accidental bowel leakage (P < 0.001), and constipation (P < 0.001) compared with women without these symptoms. Women presenting with accidental bowel leakage had the highest median stigma score, and those presenting with pelvic organ prolapse had the lowest. Total stigma score had a moderately positive correlation (r = 0.5, P < 0.001) with bother score. In a logistic regression model, higher stigma score was associated with a decreased likelihood of waiting 1 year or more to seek care (odds ratio = 0.92, 95% confidence interval = 0.86-0.98). CONCLUSIONS: Pelvic floor disorders carry varying levels of stigma. Women who feel more stigmatized by pelvic floor disorders seem to seek care earlier.