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AbstractWith increasing opportunities for minors to undergo genomic testing, factors influencing young people's decision stability and instability regarding genomic testing are unclear. This interpretive description study examines decision stability when adolescents (13–17) and young adults (18–21) decide whether to learn genetic testing results. Adolescents and young adults enrolled in a clinical trial chose whether they wanted to learn genetic testing results and could modify their decisions during a study visit or 2 weeks later. A purposive sample of clinical trial participants was invited to participate in an interview exploring their decision preferences, confidence level, and factors impacting decision stability. Twenty‐two participants chose to learn all (n = 7), some (n = 7), or no genetic test results (n = 8). Perceptions of the impact of personal genetic information on one's quality of life and sense of reproductive goals and responsibilities were driving factors for people who chose to learn no or some genetic results, while curiosity influenced those who chose to learn all. Prior health and healthcare experiences and others' influence also factored into decision‐making about receiving results. Decision stability varied among individuals but increased over time and was positively influenced by parents, baseline decision confidence, and fear of missing out on the opportunity to learn genetic information. Participants felt favorably about the opportunity to change their decision 2 weeks after the study visit. Among study participants, decision stability was high, as was satisfaction with decisions regarding how much personal genetic information to learn. The results suggest that adolescent and young adult genetic research participants may experience high decision stability and confidence in making choices regarding personal genetic testing, especially when a window of opportunity for change is available. Researchers and clinicians should consider the benefits and challenges of offering multiple checkpoints to bolster decision stability.

Urothelial carcinoma (UC) is the most common malignancy of the urinary tract, with urothelial bladder cancer accounting for approximately 90% of cases. Metastatic UC (mUC) is a particularly aggressive subset that presents significant treatment challenges, especially in patients who are often older than 70 years and have multiple comorbidities. For several decades, cisplatin-based chemotherapy has been the standard first-line treatment for locally advanced (LA) mUC. However, its utility has been limited as many patients are ineligible owing to their health status, and overall survival rates remain suboptimal. Recent advancements, including antibody-drug conjugates and immunotherapies, have begun to reshape the treatment landscape for LA/mUC. The combination of enfortumab vedotin and pembrolizumab has shown promising clinical outcomes. The approval of multiple novel drugs and combination therapies not only provides new opportunities for patient care but also creates the need for physicians to adapt to this evolving therapeutic paradigm. This review explores the latest clinical data on the management of LA/mUC and offers insights into sequencing therapies for patients with LA/mUC.

Abstract Background Patient age can impact the safety and efficacy of ulcerative colitis (UC) treatments. Etrasimod is an oral, once daily (QD), selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active UC. Here, we evaluate the impact of age on etrasimod safety and efficacy in patients with UC in the phase 3 ELEVATE UC clinical program. Methods Data were pooled from ELEVATE UC 52 and ELEVATE UC 12 in patients receiving etrasimod 2 mg QD or placebo. Proportions and incidence rates (IRs) per 100 patient-years of treatment-emergent adverse events (AEs) were stratified by age (<40, 40-59, and ≥60 years). With the same age stratifications, efficacy was evaluated in patients with baseline Modified Mayo scores of 5-9 and 4-9 for the primary efficacy endpoint (clinical remission) and secondary efficacy endpoints. Results Overall, 787 patients were enrolled (<40 years, n = 420 [53.4%]; 40-59 years, n = 276 [35.1%]; and ≥60 years, n = 91 [11.6%]). Arthralgia, fatigue, and hypertension IRs were higher in older patients, irrespective of treatment. Serious AEs and AEs leading to treatment discontinuation were low and consistent across age groups. Significantly more patients receiving etrasimod 2 mg QD vs placebo achieved efficacy endpoints, regardless of age. Conclusions The safety profile of etrasimod 2 mg QD in the ELEVATE UC population was consistent across age groups, with no change in the incidence of AEs. Patients receiving etrasimod vs placebo showed significant clinical benefit, regardless of age. ClinicalTrials.gov NCT03945188; NCT03996369.

BACKGROUND: Childbirth can have a substantial impact on maternal health-related quality of life. Cesarean delivery is the most performed inpatient operation, yet little is known about normal postpartum recovery profiles. The primary aim of our study was to longitudinally evaluate global health visual analog scale (GHVAS; 0–100) scores up to 12 weeks after scheduled cesarean delivery and identify the time to plateau of scores. The secondary aims were to evaluate different domains of postpartum recovery using validated patient-reported outcome measures (Obstetric Quality of Recovery score [ObsQoR-10] and 5-level 5-dimensional EuroQol questionnaire [EQ-5D]). METHODS: After institutional review board approval, this single-center, prospective longitudinal study enrolled healthy women scheduled for cesarean delivery. Women were excluded for gestational age <32 weeks, neonatal demise, neonatal intensive care unit admission, inability to read or understand English, and if general anesthesia was used. Women completed baseline surveys before delivery and then at 24 and 48 hours after delivery. After hospital discharge, women completed surveys (including GHVAS, OBsQoR-10, EQ-5D, Edinburgh Postnatal Depression Scale, and activities of daily living) at 1 week, 3 weeks, 6 weeks, and 12 weeks postpartum. One-way repeated measures analysis of variance (ANOVA) was used to detect the difference in GHVAS and postpartum recovery outcomes with different follow-up time points. RESULTS: We enrolled 66 parturients and 3 were withdrawn. Response rates were 95%, 84%, 83%, and 76% at 1, 3, 6, and 12 weeks, respectively. Mean ± standard deviation [SD] GHVAS scores were 78 ± 16 at baseline, 64 ± 17 at 24 hours, 69 ± 15 at 48 hours, 75 ± 19 at 1 week, 88 ± 11 at 3 weeks, 88 ± 15 at 6 weeks, and 90 ± 12 at 12 weeks postpartum ( P < .001). The global health VAS improved up until week 3 and then plateaued close to the maximum score between 3 weeks and 12 weeks postpartum. Mean ± SD ObsQoR-10 scores were 75 ± 15 at 24 hours, 85 ± 10 at 48 hours, and 81 ± 28 at 1 week postpartum ( P = .003). The mean ± SD EQ-5D composite scores improved at 6 weeks (4.9 ± 2.9) and 3 months (4.2 ± 2.6) compared to baseline (6.5 ± 1.8) with usual activities ( P = .001) and pain/discomfort ( P < .001) showing significant improvement over time. ObsQoR-10 score at 24 hours correlated with ObsQoR-10 scores at 48 hours (r = 0.629, P < .001) and 1 week (r = 0.429, P < .001) but did not correlate with EQ-5D scores at 6 weeks and 12 weeks. CONCLUSIONS: Our study demonstrates that GHVAS after scheduled CD plateaus at week 3. This data can be used to inform patients about the anticipated trajectory of key postpartum recovery domains up to 12 weeks postpartum.

ImportanceDirect immunofluorescence (DIF) testing has been an important ancillary tool for the diagnosis of various inflammatory mucocutaneous conditions for more than 50 years. Current DIF test panels are based on historical clinical descriptions; few studies have rigorously addressed preanalytical, analytical, and/or postanalytical aspects, and even fewer have been replicated or validated. Recent unresolved key issues include whether DIF testing and test panels should be triaged or truncated based on clinical indication or histopathologic findings.ObjectiveTo assess levels of consensus regarding practical aspects of DIF testing among immunodermatology testing specialists in the US.Design, Setting, and ParticipantsUsing modified Delphi methods with a priori characterized criteria, a survey containing 54 statements pertaining to DIF testing was created and distributed to assess consensus. Statements not initially reaching consensus were discussed in 2 live virtual sessions, which were supplemented by relevant literature review and free-text survey comments. These statements were then reassessed in a second survey. Immunodermatology testing specialists in US academic institution–based and independent laboratories were invited based on serving as immunodermatology laboratory medical directors, authoring pertinent literature, or delivering relevant talks at major conferences or by referral. The first survey was conducted from January to February 2024, and the second survey was conducted from March to April 2024.Main Outcomes and MeasuresThe primary measured outcome was degree of consensus for various DIF testing practice, including DIF testing triage by histopathology/dermatopathology findings and DIF testing panel tailored truncations by clinical indication.ResultsA total of 23 respondents to the survey invitation had a mean (SD) of 18.5 (11.1) years and median (range) of 20.0 (1.5-46.0) years in immunodermatology laboratory practice. Consensus was achieved for 46 of 54 statements (85.2%) in the initial survey and for an additional 4 statements in the second survey (50 of 54 [92.6%]). Strong consensus was found against tailored truncation of DIF panel based on the clinical indication in the first survey round. The general acceptability of triaging specimens for DIF testing based on histopathology findings remained without consensus after both surveys.Conclusions and RelevanceOverall, participating US specialists in immunodermatology laboratory testing agreed on many practical aspects of DIF testing, including matters not queried previously. The findings also revealed areas of continued controversy and identified issues for prioritized future study.