(1) Background: Cancer antigen 125 (CA-125) is a protein produced by ovarian cancer cells that is used for patients’ monitoring. However, the best ways to analyze its decline and prognostic role are poorly quantified. (2) Methods: We leveraged individual patient data from the Gynecologic Cancer Intergroup (GCIG) meta-analysis (N = 5573) to compare different approaches summarizing the early trajectory of CA-125 before the prediction time (called the landmark time) at 3 or 6 months after treatment initiation in order to predict overall survival. These summaries included observed and estimated measures obtained by a linear mixed model (LMM). Their performances were evaluated by 10-fold cross-validation with the Brier score and the area under the ROC (AUC). (3) Results: The estimated value and the last observed value at 3 months were the best measures used to predict overall survival, with an AUC of 0.75 CI 95% [0.70; 0.80] at 24 and 36 months and 0.74 [0.69; 0.80] and 0.75 [0.69; 0.80] at 48 months, respectively, considering that CA-125 over 6 months did not improve the AUC, with 0.74 [0.68; 0.78] at 24 months and 0.71 [0.65; 0.76] at 36 and 48 months. (4) Conclusions: A 3-month surveillance provided reliable individual information on overall survival until 48 months for patients receiving first-line chemotherapy.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, with its currently approved drugs, including riluzole and edaravone, showing limited therapeutic effects. Therefore, safe and effective drugs are urgently necessary. EPI-589 is an orally available, small-molecule, novel redox-active agent characterized by highly potent protective effects against oxidative stress with high blood-brain barrier permeability. Given the apparent oxidative stress and mitochondrial dysfunction involvement in the pathogenesis of ALS, EPI-589 may hold promise as a therapeutic agent. Objective: This protocol aims to describe the design and rationale for the EPI-589 Early Phase 2 Investigator-Initiated Clinical Trial for ALS (EPIC-ALS). Methods: EPIC-ALS is an explorative, open-labeled, single-arm trial that evaluates the safety and tolerability of EPI-589 in patients with ALS. This trial consists of 12-week run-in, 24-week treatment, and 4-week follow-up periods. Patients will receive 500 mg of EPI-589 3 times daily over the 24-week treatment period. Clinical assessments include the mean monthly change of Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised total score. The biomarkers are selected to analyze the effect on oxidative stress and neuronal damage. The plasma biomarkers are 8-hydroxy-2′-deoxyguanosine (8-OHdG), 3-nitrotyrosine (3-NT), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), homocysteine, and creatinine. The cerebrospinal fluid biomarkers are 8-OHdG, 3-NT, NfL, pNfH, and ornithine. The magnetic resonance biomarkers are fractional anisotropy in the corticospinal tract and N-acetylaspartate in the primary motor area. Results: This trial began data collection in September 2021 and is expected to be completed in October 2023. Conclusions: This study can provide useful data to understand the characteristics of EPI-589. Trial Registration: Japan Primary Registries Network jRCT2061210031; tinyurl.com/2p84emu6 International Registered Report Identifier (IRRID): DERR1-10.2196/42032

In this study, we investigated the sleep–wake rhythm of nursery school children with the aim of supporting their health and mental/physical development. We analyzed 4881 children from infancy to 6 years of age, using 2 week sleep tables recorded by their guardians. The tables contained night bedtimes, wake times, nighttime/daytime sleep duration, and the differences in these between weekdays and weekends. The total sleep decrement of children with increasing age is attributed to a decrease in daytime sleep, while nighttime sleep duration remains almost unchanged at about 10 h, which is, therefore, referred to as the nighttime basic sleep duration (NBSD). Although bedtime stabilizes at around 9:30 p.m. by the age of 2, wake-up times tend to be before 7 a.m., which results in sleep insufficiency during weekdays. This lack of sleep is compensated for by long naps on weekdays and by catching up on sleep on weekend mornings, which may contribute to future social jet lag. Guardians are encouraged to know their children’s exact NBSD and set an appropriate bedtime to be maintained on weekdays. This helps to prevent sleep debt and fosters a consistent daily rhythm of waking up at the same time both on weekdays and weekends. These conditions are believed to support mental/physical development and school and social adaptation.

Background: Oral anticoagulants (OACs) can help prevent stroke in patients with nonvalvular atrial fibrillation (NVAF). The aim of this study was to characterize the use of OACs other than direct thrombin inhibitors (DTIs) for NVAF.Methods: Patients with NVAF taking antithrombotics other than DTIs were enrolled in this cross‐sectional study. Patient demographics and medication history were collected, and the patients were classified as taking antiplatelet monotherapy (AP), anticoagulant monotherapy (AC), or combination therapy (AP+AC). OAC users were also stratified as naïve (N; initiated within 6 months), switcher (S; switched within 6 months), or prevalent user (P; continued for >6 months).Results: A total of 3053 patients (AP, 216; AC, 2381; AP+AC, 456) from 268 sites were enrolled from 2012 to 2013. Significant differences were observed in CHADS₂ scores (AP/AC/AP+AC: 2.0/2.1/2.7, P<0.0001), angina complications (20.1/8.6/32.1, P<0.0001), myocardial infarction (5.1/2.8/18.1, P<0.0001), prothrombin time–international normalized ratio (PT–INR) (−/2.00/1.94, P=0.0350), and others. There were 2831 OAC users (N, 328; S, 213; P, 2290). Significant differences were observed in history of bleeding (N/S/P: 2.4/9.4/4.5, P<0.001), PT–INR (1.83/2.01/2.00, P<0.0001), and others.Conclusions: Patients taking AP+AC had higher CHADS₂ scores than those taking an AP or AC alone. Additionally, the combination therapy (AP+AC) was preferred in patients with cardiovascular comorbidity. Changes in AC regimens were not influenced by CHADS₂ scores or complications but influenced by history of bleeding. These characteristics were thus identified as major factors affecting the selection of antithrombotic regimens other than DTIs in patients with NVAF.

Objective: The primary objective of the study was to evaluate the safety and effectiveness of olaparib maintenance therapy in Japanese patients with platinum-sensitive first-relapsed ovarian cancer. The secondary objective was to survey the treatment given after the olaparib maintenance therapy. Methods: The JGOG3026 study was a nationwide, multicenter historical cohort study across 43 sites. Patients receiving olaparib maintenance therapy after platinum-based chemotherapy between Jan 2018 and Jul 2020 were included as modified intention-to-treat (mITT1). Those who received any post-olaparib therapy were extracted as mITT2. The primary endpoint was adverse events; secondary endpoints included progression-free survival (PFS), the time to first subsequent therapy (TFST), progression-free survival to the second progression (PFS2), and overall survival (OS). Results: In the mITT1 (n = 413), any adverse event occurred in 41.6%; anemia was the most common (28.8%). MDS occurred in 1.0% and no AML was observed during a mean follow-up of 34.1 months. The 24-month PFS and OS rates were 31.7% and 70.1%, respectively. Median PFS and OS were 12 months (95% confidence interval [CI]: 9.9-13) and 39 months (95% CI, 33–45). The 24-month TFST and PFS2 rates were 33.3% and 34.3%. In the mITT2 (n=284), chemotherapy after olaparib therapy was used in 97.2%, with an overall response rate of 22.5%. Conclusion: Olaparib maintenance therapy showed acceptable safety and effectiveness in Japanese clinical practice. Monitoring for secondary hematologic malignancies is needed after the start of olaparib maintenance therapy. Synopsis: Our multicenter collaborative historical cohort study confirmed acceptable safety and effectiveness of olaparib maintenance therapy in Japanese patients with platinum-sensitive first-relapsed ovarian cancer; the incidence of AML/MDS was comparable to reports from Western cohorts.