BACKGROUND:Although continuous glucose monitoring (CGM)-derived summary metrics are widely used, they may obscure the intraday temporal organization and potentially overlook clinically relevant differences in daily glucose patterning across time. We aimed to identify distinct daily glycemic phenotypes using time-resolved clustering and to examine whether the diversity of these patterns is independently associated with glycated hemoglobin (HbA1c). METHODS:We analyzed 5902 days of CGM data from 103 participants with type 1 (n = 19) and type 2 (n = 84) diabetes. Daily waveforms were clustered using k-means with dynamic time warping (DTW) to capture temporal features independent of phase shifts. A "Phenotype Diversity Score" (Shannon entropy of each individual's cluster-label distribution) quantified the variety of phenotypes expressed per participant. Multivariable regression assessed its association with HbA1c, adjusting for established variability metrics, insulin use, and estimated glomerular filtration rate (eGFR). RESULTS:Eight distinct daily glycemic phenotypes were identified. The Phenotype Diversity Score strongly correlated with HbA1c (r = 0.600, P < .0001). In a fully adjusted model, including mean of daily differences, coefficient of variation, insulin use, and eGFR, the Phenotype Diversity Score remained independently associated with HbA1c (β = 0.322, P = .004). CONCLUSIONS:Time-resolved CGM clustering reveals clinically meaningful daily glycemic phenotypes and demonstrates that phenotype diversity is independently associated with HbA1c. This pattern-based perspective complements conventional summary metrics and may help explain glycemic heterogeneity among individuals with similar average glucose levels.
AIM:Ring pessary therapy is a widely used conservative treatment for pelvic organ prolapse (POP). In Japan, pessary self-management (SM) is recognized as a management option that may reduce adverse events; however, its adoption in routine clinical practice remains limited, and clinical data are scarce. This study aimed to identify factors associated with successful fitting and continuation of ring pessary therapy, focusing on the role of SM. METHODS:We retrospectively reviewed the medical records of 90 patients with POP who initiated ring pessary therapy at our institution between 2010 and 2020. Patient characteristics, anatomical parameters, pessary management methods (SM or clinic management [CM]), and reasons for discontinuation were analyzed. Kaplan-Meier analysis, multivariate logistic regression, and Cox proportional hazards models were used to evaluate factors associated with fitting success and continuation. RESULTS:Among the 90 patients, 66 (73.3%) selected SM and 24 (26.7%) CM. Successful fitting was achieved in 62 patients (93.9%) in the SM group and in 8 patients (33.3%) in the CM group. SM was independently associated with successful fitting and longer continuation. Among patients with successful fitting, continuation rates were significantly higher in the SM group than in the CM group (p < 0.0001). The median pessary size among successfully fitted patients was 62 mm. In exploratory analyses, patients who discontinued therapy due to pain or discomfort tended to have shorter total vaginal length (TVL) and lower TVL/height ratios. CONCLUSIONS:Ring pessary therapy is a useful conservative treatment option for Japanese women with POP. SM may facilitate successful fitting and prolonged continuation when appropriate patient instruction and follow-up are provided.
BACKGROUND:Narcolepsy type 1 is characterized by excessive daytime sleepiness, cataplexy, disrupted sleep, sleep paralysis, and hypnagogic or hypnopompic hallucinations. Oveporexton (TAK-861), an oral orexin receptor 2-selective agonist, reduced symptoms of narcolepsy type 1 in a previous phase 2 trial. METHODS:We conducted two phase 3, randomized, placebo-controlled trials evaluating the efficacy and safety of oveporexton over a period of 12 weeks. Participants 16 to 70 years of age with narcolepsy type 1 were randomly assigned in a 3:3:2 ratio to receive twice-daily oveporexton (1 mg or 2 mg) or placebo in the First Light trial and in a 2:1 ratio to receive twice-daily oveporexton (2 mg) or placebo in the Radiant Light trial. The primary end point was the change from baseline to week 12 in mean sleep latency (the ability to stay awake under soporific conditions) on the Maintenance of Wakefulness Test (MWT; range, 0 to 40 minutes; normal, ≥20). Key secondary end points included the change from baseline to week 12 in the Epworth Sleepiness Scale (ESS) total score (range, 0 to 24; normal, <10) and the weekly cataplexy rate at week 12. RESULTS:A total of 168 participants were enrolled in the First Light trial and 105 in the Radiant Light trial. Mean changes from baseline to week 12 in mean sleep latency on the MWT ranged from 14.3 to 19.8 minutes with oveporexton, as compared with -0.4 to -0.8 minutes with placebo (adjusted P<0.001 for all comparisons vs. placebo). Mean changes in the ESS total score ranged from -9.7 to -11.8 with oveporexton, as compared with -1.5 to -1.7 with placebo (adjusted P<0.001 for all comparisons vs. placebo). Median percent reductions in the weekly cataplexy rate ranged from 79.0 to 88.8% with oveporexton, as compared with 27.7 to 39.1% with placebo (adjusted P<0.001 for all comparisons vs. placebo). Adverse events occurred in 86 to 89% of the participants with oveporexton, as compared with 43 to 54% with placebo; the most common adverse events were increased urinary frequency and transient insomnia, which occurred in a majority of participants receiving oveporexton. CONCLUSIONS:Over a period of 12 weeks, oveporexton significantly improved measures of wakefulness, sleepiness, and cataplexy in participants with narcolepsy type 1. Increased urinary frequency and transient insomnia were common side effects. (Funded by Takeda Development Center Americas; the First Light and Radiant Light ClinicalTrials.gov numbers, NCT06470828 and NCT06505031.).
