There lacks data clarifying the meningioma risk conferred by depot medroxyprogesterone acetate in the US. To examine the relative risk of meningioma diagnosis in women using depot medroxyprogesterone acetate and other related progestins. This retrospective population-based cohort study used data from TriNetX, a US national database of 68 health care organizations. Data were analyzed from December 2004 to December 2024. The incidence of meningioma diagnosis was compared between treatment groups through propensity-score matched analyses. Participants included a sample of females with use of only 1 of the following progestins/contraceptives: depot medroxyprogesterone acetate, oral medroxyprogesterone acetate, combined oral contraceptives, intrauterine devices, progestin only pills, or subdermal implantable contraceptive. The control group included females without use of these hormonal treatments. Of the 118 289 082 total patients in TriNetX at the time of analysis, 61 588 239 patients were female and eligible. Patients were defined using diagnostic codes from the International Classification of Diseases, Current Procedural Terminology, and RxNorm codes within TriNetX. The main outcome was meningioma diagnosis. Relative risks and number needed to harm were calculated. There were 10 425 438 patients that met inclusion criteria with a mean age of 33.4 years at inclusion. After propensity score matching, 88 667 patients with mean age of 26.2 years at inclusion were in the depot medroxyprogesterone acetate group. Use of depot medroxyprogesterone acetate had a relative risk of 2.43 (95% CI, 1.77-3.33) for meningioma diagnosis compared with controls. Notably, this risk was confined for patients with longer than 4 years of exposure or starting the prescription at ages older than 31 years. Oral medroxyprogesterone acetate had increased relative risk of 1.18 (95% CI, 1.10-1.27) compared with controls. No increased risk of meningioma diagnosis was found with any other contraceptive. The number needed to harm for the depot medroxyprogesterone acetate was 1152 patients and 3020 patients for oral medroxyprogesterone acetate. In this study, women receiving depot medroxyprogesterone acetate had a greater relative risk of subsequent meningioma diagnosis, especially with prolonged exposures and starting the medication at older ages. The high number needed to harm suggests low clinical risk overall.

Epilepsy affects approximately 65 million people worldwide, and 60% have focal seizures. Predicting seizure response and drug resistance to antiseizure medications (ASMs) in people with focal epilepsy remains difficult. To describe the expected short- and long-term response to treatment with ASMs in people with focal epilepsy using recognized definitions by the International League Against Epilepsy. The Human Epilepsy Project is an international, prospective, observational cohort study that followed up people with newly diagnosed focal epilepsy for up to 6 years between 2012 and 2020. Data were analyzed from 2023 to 2024. The Human Epilepsy Project was conducted at 34 tertiary epilepsy centers across the US, Australia, and Europe. Participants with confirmed diagnosis of focal epilepsy aged 12 to 60 years were enrolled within 4 months of treatment initiation with ASM(s). Data were analyzed from February 2024 to July 2024. ASM (variable). The primary outcome was seizure freedom, defined as a period without seizures for 12 months or 3 times the longest pretreatment seizure-free interval, whichever was longer. Treatment response was categorized as sensitive, meaning seizure free receiving 2 or fewer adequate ASM trials; resistant, meaning having 2 or more adequate ASM trials fail; or indeterminate (neither treatment sensitive nor resistant). Among 448 enrolled participants, 267 (59.6%) were female, and median (IQR) participant age was 32 (21-44) years at treatment initiation. Median (IQR) follow-up duration was 3.13 (2.33-3.55) years. Most achieved seizure freedom (267 participants of 448 [59.6%]), largely without relapse (223 [83.5%]). There were 245 treatment-sensitive participants (54.7%), 102 treatment-resistant participants (22.8%), and 101 indeterminate participants (22.5%). Among treatment-sensitive participants, most (217 [89.3%]) responded to monotherapy and half (121 [49.4%], or 27% of total cohort) became seizure free while receiving their first ASM. In the first year of treatment, 251 participants (63%) had ongoing or worsening seizures. Median time to first seizure freedom was 12.1 months (95% CI, 9.7-16.1). This occurred earlier in those who never relapsed (median, 2.2 months; 95% CI, 0.8-3.2) than those who did (median, 7.4 months; 95% CI, 4.0-10.7). Those with infrequent pretreatment seizures were 0.30-fold less likely to be treatment resistant than those with very frequent seizures (hazard ratio, 0.30; 95% CI, 0.14-0.64; P = .002; Holm-Bonferroni-corrected P = .006). Participants with self-reported comorbid psychological disorders were 1.78-fold more likely to be treatment resistant than those without (relative risk, 1.78; 95% CI, 1.26-2.52; P = .001). In the Human Epilepsy Project multicenter prospective cohort study, most people with newly diagnosed focal epilepsy took more than a year and more than 1 ASM to become seizure free. Drug resistance can be identified earlier in those with frequent pretreatment seizures, and a history of psychiatric comorbidities at epilepsy diagnosis is an important prognostic factor. ClinicalTrials.gov Identifier: NCT02126774.

This cohort study compares the risk of incident all-cause dementia among people with hearing loss who use vs do not use hearing aids.

This Viewpoint discusses how to address the inaccuracy or lack of specificity in current nomenclature, nosology, and diagnostic testing for the group of syndromes called chronic immune-mediated peripheral nerve myelinopathies.

The Original Investigation titled “Evaluation of the Revised Criteria for Biological and Clinical Staging of Alzheimer Disease,”1 published on May 19, 2025, was corrected to fix the order of the colors in the key for Figure 2B. This article was corrected online.

In women with multiple sclerosis (MS), disease-modifying therapy (DMT) management during pregnancy might impact relapse risk. To estimate the effect of DMT management during pregnancy on MS relapse rate and compare different therapeutic strategies. This was a multicenter retrospective cohort study using data from January 1990 to December 2023. Data were extracted in December 2023 from the French MS registry. Among 52 955 women in the registry, we included pregnancies identified through childbirths in patients with relapsing-onset MS who were monitored for at least 18 months before delivery and 9 months after. Pregnancies occurring less than 18 months apart or with missing month of birth were excluded. Mediation analysis was used to estimate the total, direct, and indirect (mediated by DMT management) effects of pregnancy. Different therapeutic strategies were compared: DMT interruption, switching to or maintaining interferon β or glatiramer acetate, switching to or maintaining natalizumab until the third trimester, and switching to or maintaining intravenous anti-CD20 and interrupting it 3 months before conception. The primary outcome was the annualized relapse rate (ARR) during the preconception, gestation, and postpartum periods. Within a causal inference framework, counterfactual ARRs were estimated using longitudinal g-computation, combining a random forest algorithm for predicting DMTs, and a mixed-effects Poisson model for relapses. We included 6341 pregnancies occurring in 4998 women (mean [SD] age at conception, 31.5 [4.5] years). DMT management during pregnancy significantly increased ARR during gestation (causal rate ratio [cRR], 1.13; 95% CI, 1.06-1.22) and postpartum (cRR, 1.08; 95% CI, 1.01-1.16) periods. This led to a deleterious total effect of pregnancy on ARR, particularly in women receiving natalizumab before pregnancy with prolonged interruption (ie, interruption before the second trimester or resumption more than 3 months after delivery; cRR, 2.18; 95% CI, 1.76-2.69), and in women receiving fingolimod (cRR, 2.15; 95% CI, 1.60-2.93). Compared to DMT interruption, anti-CD20 strategy was the most effective (cRR, 0.38; 95% CI, 0.25-0.52), followed by the natalizumab strategy with short interruption (cRR, 0.80; 95% CI, 0.71-0.90), whereas interferon β (cRR, 0.93; 95% CI, 0.86-0.99) and glatiramer acetate strategies (cRR, 0.91; 95% CI, 0.84-0.99) were less effective. In this study, DMT management during pregnancy significantly increased relapse risk, particularly in patients receiving natalizumab with prolonged interruption or fingolimod. The strategy based on the use of anti-CD20 before pregnancy was the most effective to mitigate this risk.

This meta-analysis of individual patient data from 6 clinical trials confirms the efficacy of existing therapies in patients with progressive multiple sclerosis showing disease activity and assesses the role of lesion reduction as a mediator of treatment effect.

This cohort study examines registry data to determine age-specific life expectancies for patients with sporadic Creutzfeldt-Jakob disease and analyze trends in median survival over the past 30 years.