搜索结果：American journal of therapeutics

The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.

Interleukin-33 and its receptor, ST2, are implicated in neutrophilic and eosinophilic inflammation during chronic obstructive pulmonary disease (COPD) exacerbations. We aimed to assess the efficacy and safety of astegolimab, an anti-ST2 human IgG2 monoclonal antibody, which were evaluated in two COPD pivotal trials. In two randomised, double-blind, placebo-controlled trials (phase 2b ALIENTO and phase 3 ARNASA), current or former smokers with COPD and a history of frequent exacerbations, irrespective of baseline blood eosinophils, were randomly assigned (1:1:1; stratification by smoking status and region) to receive subcutaneous astegolimab 476 mg every 2 weeks, every 4 weeks, or placebo, alongside optimised inhaled maintenance therapy over 52 weeks. The primary endpoint (analysed in participants receiving one or more doses) was annualised rate of moderate or severe exacerbations. Missing data were considered similar to data from other participants in the same treatment group with the same baseline characteristics. The trials were registered with ClinicalTrials.gov (NCT05037929 and NCT05595642). In ALIENTO, 1301 participants (astegolimab every 2 weeks, n=433; astegolimab every 4 weeks, n=437; and placebo, n=431) initiated treatment between Oct 5, 2021, and Feb 19, 2024. In ARNASA, 1375 participants (astegolimab every 2 weeks, n=459; astegolimab every 4 weeks, n=459; and placebo, n=457) initiated treatment between Jan 9, 2023, and June 25, 2024. Adjusted rate ratios versus placebo for the primary endpoint were 0·85 (95% CI 0·72-1·00; p=0·049) for astegolimab every 2 weeks and 0·93 (0·79-1·10; p=0·38) for astegolimab every 4 weeks in ALIENTO, and 0·85 (0·72-1·01; p=0·068) for astegolimab every 2 weeks and 0·82 (0·70-0·98; p=0·024) for astegolimab every 4 weeks in ARNASA. Adverse events were balanced between treatments, with most participants experiencing one or more adverse events (1093 [84·0%] of 1301 participants in ALIENTO and 1176 [85·5%] of 1375 in ARNASA). The most common non-COPD adverse event was nasopharyngitis in ALIENTO and upper respiratory chest infection in ARNASA. Deaths occurred in 40 (3·1%) of 1301 participants in ALIENTO and in 44 (3·2%) of 1375 participants in ARNASA, and were balanced across treatment groups. Across both trials, a total of three deaths (0·1%) were considered to be related to treatment by investigators. In ALIENTO, astegolimab every 2 weeks was associated with a lower annual rate of exacerbations versus placebo in patients with COPD and a history of frequent exacerbations. In ARNASA, these findings did not meet statistical significance. Together, these findings suggest a role for targeting the ST2/IL-33 pathway to reduce the frequency of COPD exacerbations in patients with limited treatment options. Genentech, a member of the Roche Group, and F Hoffmann-La Roche.

Propofol is widely used for deep sedation during endoscopic retrograde cholangiopancreatography (ERCP) due to its rapid onset and favorable recovery profile; however, it is associated with dose-dependent cardiopulmonary adverse effects, particularly hypoxia and hypotension. Significant heterogeneity persists in the definition, severity classification, and reporting of these adverse events, limiting comparability across studies and hindering reliable risk stratification. Therefore, the aim of this systematic review was to evaluate the incidence and clinical characteristics of propofol-associated hypoxia and hypotension in adult patients undergoing ERCP, and to assess variability in reporting practices across studies. A systematic review was conducted and reported in accordance with PRISMA guidelines. PubMed was searched for English-language studies published between 1995 and 2025 involving adult patients undergoing ERCP under propofol-based sedation. Across studies reporting extractable data, oxygen desaturation occurred in 16.9% of aggregated cases (1194/7049), whereas hypotension occurred in 13.0% (187/1440). These values represent descriptive estimates and should not be interpreted as meta-analytic pooled incidences. Both events were predominantly mild and transient, responding to standard supportive measures, whereas severe complications, including cardiopulmonary arrest, were exceptionally rare. Considerable variability in definitions, outcome reporting, and study design was observed across studies. Propofol sedation during ERCP is associated with frequent but generally manageable hypoxia and hypotension. Continuous respiratory and hemodynamic monitoring facilitates early recognition and prompt intervention. Standardization of outcome definitions and reporting, along with the development of structured risk stratification tools, may improve patient selection and enhance procedural safety.

To assess the construct validity of a modified single-item measure of bother due to side effects (the GP5 item) from the Functional Assessment of Chronic Illness Therapy (FACIT) system by comparing it to current symptomatic side effects from the Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PROCTCAE) reported by patients with rheumatoid arthritis (RA). Through a cross-sectional, web-based survey we collected information on the frequency of symptomatic side effects and bother from side effects related to RA medications. We applied multiple correspondence analysis (MCA) to reduce 80 symptomatic side effects into key dimensions (≥5% of the total variance each). We then examined associations among key dimensions, individual items, the sum of current side effects, and the single-item bother measure using Spearman rho. A total of 560 patients participated in the online survey. Our scree plot showed a clear elbow point after the first dimension, indicating that keeping just one dimension captured the most meaningful information. This overall side effect burden score appeared to reflect a broad concept influenced by a variety of symptomatic side effects, each having only a negligible to weak impact. Our results may indicate that individuals have diverse experiences of side effects, allowing the global index to capture these variations, even when they differ across patients. Thus, a single-item burden measure to side effects can potentially serve as a useful summary indicator, shedding light on the impact of symptomatic side effects experienced by RA patients.

Trigeminal neuralgia (TN) is a severe episodic facial pain that has a significant impact on mood and activities of daily living. To accurately measure pain in TN, patient diaries need to be specifically developed to capture dimensions of pain in both TN phenotypes (e.g., purely paroxysmal vs. paroxysms with concomitant continuous pain) and their impact on daily life. There is no validated pain instrument that measures specific symptoms of the pain associated with TN. Therefore, Noema Pharma decided to initiate the development and validation of such an instrument. The purpose of this study was to evaluate the content validity of the items that make up the Trigeminal Neuralgia Electronic Diary (TnED©). Participants were divided into two groups: those with purely paroxysmal pain and those with paroxysmal and concomitant continuous pain; each group was provided with a data collection instrument (diary) specific to their TN phenotype. Participants completed the instrument daily for 14 days. A qualitative, semi-structured interview was conducted to collect feedback on the instrument. A total of 30 participants were enrolled in 2 English-speaking countries (USA, UK). Nearly all participants stated that the items were clear and easy to understand, relevant, measured all symptoms of the condition, and had a suitable recall period and response options. Some participants suggested additional items to be collected. Most participants regarded pain severity as the most important concept due to its debilitating impact on their lives. Few changes to the instrument were suggested, and the study sponsor decided not to implement any of the proposed changes. Overall, the Trigeminal Neuralgia Electronic Diary was well-received and can be used to measure symptoms of TN in clinical trials or in a clinical setting. Psychometric validation of the TnED© instrument is ongoing. NCT06019338, retrospectively registered.

While the United States of America (USA) faces a substantial substance use disorder (SUD) burden on a global scale, relatively little is known about the current trends and future trajectories at both national and state levels. Using the Global Burden of Disease Study 2023, we examined estimates of prevalence and disability-adjusted life years (DALYs) for SUDs in the USA, including alcohol use disorders (AUDs) and drug use disorders (DUDs), across all 50 states and Washington, DC, from 1990 to 2023 and forecasted trends to 2050. In 2023, the USA had the highest age-standardized prevalence of SUDs across the globe. Overall, age-standardized SUD prevalence increased from 4,664.6 (95% uncertainty interval, 4,076.4-5,333.3) estimated rates per 100,000 people in 1990 to 6,430.1 (5,871.7-7,056.3) per 100,000 people in 2023, representing an increase of 37.9%. At the state level in 2023, broader geographical variations were observed in terms of estimated age-standardized DALYs for SUDs. At both the national and state levels, the age-standardized prevalence and burden of DUDs have outpaced and surpassed the increase in AUDs over time. By 2050, if existing trends continue, the age-standardized prevalence of SUDs is projected to rise to 8,956.0 (7,478.8-10,118.4) per 100,000 people, driven primarily by increasing age-standardized prevalence of DUDs, while age-standardized prevalence of AUDs is predicted to increase slightly. These findings suggest that current interventions have been insufficient to curb the SUD crisis. Without urgent, evidence-based reforms, the SUD burden will continue to increase and deepen health disparities across the USA. This work was funded by the Gates Foundation.

Motion sickness affects millions of people with common symptoms, including nausea and vomiting. Medications used for management of motion sickness since 1870 predominately have anticholinergics and antihistamines properties. For the past 40 years, there have been no advances in medication options for motion sickness until recently, a novel agent, tradipidant received the Food and Drug Administration approval for symptoms related to motion sickness. Tradipitant is a selective neurokinin-1 (NK-1) receptor antagonist, blocking the actions of substance P, a neurotransmitter from the tachykinin family. It has high affinity for NK-1 receptors that are present throughout the emetic pathway. The 4 major metabolites of this drug (ie, M2, M3, M4, and M8) have shown a similar affinity to the NK-1 receptor as the parent drug. Pharmacokinetic data have revealed that tradipitant absorption is delayed when administered with food. The volume of distribution is 1956 L and is highly plasma protein bound (∼96%). The half-life is 34 hours. Tradipitant is predominately metabolized by CYP450-mediated pathways and through glucuronidation. Approximately 80% of excretion of tradipitant occurs in the feces. Two phase 3 pivotal trials, Motion Syros (N = 365) and Motion Serifos (N = 316), randomized, double-blinded, placebo-controled, showed significant efficacy for tradipitant in preventing vomiting associated with motion sickness. In Motion Syros, tradipitant groups experienced significantly lower incidences of vomiting than placebo (170 mg tradipitant = 18.3%, 85 mg tradipitant = 19.5%, placebo = 44.3%). In Motion Serifos, 10.4% of the 170-mg tradipitant group and 18.3% of the 85-mg tradipitant group experienced vomiting, compared with 37.7% of the placebo group (P = 0.00002 and P = 0.0014, respectively). The results of the 2 trials validated tradipitant as an effective NK-1 receptor antagonist for motion sickness prevention. The drug was well tolerated with a favorable safety profile and no serious adverse events. Tradipitant works by blocking the NK-1 receptors found in the emetic pathway and it has been proven in pivotal trials effective for prevention of vomiting due to motion sickness. It reduces motion sickness symptoms in 2 phase 3 trials and offers a revolutionary new treatment option for people who experience motion sickness.

Obesity is a heterogeneous chronic disease in which excess adiposity increases the risk of morbidity and mortality. The Obesity Association, a division of the American Diabetes Association (ADA), developed comprehensive, evidence-based guidelines on screening, diagnosis, evaluation, and staging of overweight and obesity in adults. Monitoring for consistent increases in weight over time may facilitate early intervention to prevent obesity and its complications, and screening for excess adiposity should be performed at least annually using BMI. The recommended diagnostic criteria for overweight and obesity include race- and ethnicity-specific BMI thresholds supplemented with waist circumference-based measures for certain individuals to reduce the risk of underdiagnosis. healthcare professionals should perform a comprehensive clinical evaluation, including risk stratification and staging, of all adults diagnosed with overweight or obesity, which will inform the management plan and follow-up care. The ADA's Obesity Association encourages healthcare professionals to adopt these guidelines for evaluating obesity in adults.

Health disparities and inequities in the US health care system contribute to poor health outcomes. These issues affect all aspects of pharmacy practice, including medication use and adherence, and contribute to the suboptimal performance of the United States in global health care rankings compared with other industrialized nations. More robust efforts are needed to address the impact of cultural awareness/intelligence, social determinants of health (SDOH), health-related social needs (HRSN), and diversity, equity, inclusiveness, and accessibility (DEIA) within the pharmacy profession. Comprehensive knowledge, skills development, and assessment tools in these areas are lacking in pharmacy education. Research projects focused on health inequities and disparities are limited by their lack of statistical power, lack of inclusiveness of diverse populations, community partners, and researchers, and lack of rigorous study designs to conclusively document and resolve these problems. Addressing cultural intelligence, HRSN/SDOH, and DEIA barriers in health care and pharmacy practice, education, and research is therefore essential for improving patient outcomes and satisfaction. The American College of Clinical Pharmacy (ACCP) Public and Professional Relations Committee was charged to update ACCP's cultural competency white paper series. This white paper evaluates evidence and describes current challenges related to cultural intelligence, HRSN/SDOH, and DEIA in pharmacy practice, education, and research. Evidence tables are provided together with ranked recommendations for integrating these principles into doctor of pharmacy curricula, residency training, continuing education, clinical practice, and research. By implementing these changes, pharmacy professionals and organizations can help create a more equitable health care system and reduce disparities in patient care, health outcomes, and research.

AimThe phase 4 RESOLUTION trial showed that, in comparison with placebo, adding eptinezumab-an anti-calcitonin gene-related peptide monoclonal antibody-to a brief educational intervention (BEI) reduced the monthly frequency of migraine, headache, and acute medication use in participants with chronic migraine (CM) and medication-overuse headache (MOH). Herein, we report data from multiple patient-reported outcomes (PROs) evaluating treatment impact on disease burden and health-related productivity and quality of life in the RESOLUTION trial.MethodsRESOLUTION was a multi-national (conducted at 76 sites across 11 countries), double-blind, randomized, placebo-controlled trial. The trial comprised a 4-week screening period; a 12-week, double-blind, placebo-controlled period; a 12-week, open-label, extension period; and an 8-week, safety follow-up period, with results of the placebo-controlled period presented in this paper. Adults diagnosed with CM and MOH received a BEI and were randomized 1:1 to intravenous infusion with either eptinezumab 100&#x2005;mg or placebo. Several PROs were assessed at baseline, Week 4, and Week 12, including the six-item Headache Impact Test (HIT-6), modified Migraine Disability Assessment (mMIDAS), Migraine-specific Work Productivity and Activity Impairment questionnaire (WPAI:M), Patient Global Impression of Change (PGIC; assessed only at follow-up), patient-identified most bothersome symptom (PI-MBS; assessed only at follow-up), Migraine-Specific Quality-of-Life questionnaire version 2.1 (MSQ v2.1), EQ-5D-5L visual analogue scale, and nine-item Treatment Satisfaction Questionnaire for Medication (TSQM-9; assessed only at follow-up). Post hoc analyses included responder rates for HIT-6 (i.e., participants with &#x2265;5-point reduction from baseline), as well as for PGIC and PI-MBS (i.e., participants who reported "much improved" or "very much improved").ResultsOf 608 participants randomized, the full-analysis set included 302 participants in the eptinezumab arm and 300 in the placebo arm. Eptinezumab with BEI was associated with more favorable PRO scores compared to placebo with BEI, starting at Week 4 (p&#x2009;<&#x2009;0.05 for all comparisons) and up to Week 12 (p&#x2009;<&#x2009;0.01 for all comparisons except WPAI:M absenteeism). Responder rates for HIT-6, PGIC, and PI-MBS also favored eptinezumab versus placebo.ConclusionsIn participants with CM and MOH who also received patient education, eptinezumab treatment resulted in greater reductions in headache impact and migraine disability than placebo, with greater improvements in productivity, quality of life, overall disease status, and treatment satisfaction starting from Week 4 and sustained to Week 12. Eptinezumab in combination with patient education is an effective treatment for reducing disease burden and improving overall quality of life in people with CM and MOH.Trial registrationClinicalTrials.gov Identifier: NCT05452239 (https://clinicaltrials.gov/study/NCT05452239); EudraCT Number: 2021-003049-40 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=2021-003049-40).

Eating disorders (EDs) are frequently underdiagnosed in transgender and gender-diverse (TGD) adults. Many existing ED screeners were developed in cisgender, White, female samples and may miss symptom patterns relevant to TGD adults. This study evaluated internal consistency and screening accuracy of the Brief Assessment of Stress and Eating (BASE), a 10-item ED screener, in a national sample of TGD adults. Participants were 2098 TGD adults (57.5% gender diverse; 28.5% transgender men; 14.0% transgender women) enrolled in The PRIDE Study, a U.S.-based longitudinal cohort. Participants completed the BASE and SCOFF and were identified for elevated ED risk using a DSM-5-aligned Eating Disorder Diagnostic Scale algorithm. We examined internal consistency and classification accuracy using receiver operating characteristic and precision-recall curves, and compared BASE and SCOFF performance overall and by gender subgroup. The BASE showed good internal consistency (ordinal &#x3b1;&#xa0;=&#xa0;0.80). In the full sample, the BASE outperformed the SCOFF (AUC&#xa0;=&#xa0;0.803 vs. 0.764, p&#xa0;=&#xa0;.0003), with a similar pattern among transgender men (AUC&#xa0;=&#xa0;0.793 vs. 0.730). Among transgender women and gender-diverse adults, AUCs did not differ significantly between the BASE and SCOFF. Cut-scores based on Youden's J (7.5-8.5) produced balanced sensitivity (0.68-0.75) and specificity (0.70-0.77), whereas more liberal cut-scores (5-6) increased sensitivity (>0.85) with reduced specificity. The BASE is a psychometrically sound and low-burden screener for elevated ED risk in TGD adults. Its broader symptom coverage and comparable performance across TGD subgroups support use in primary care and gender-affirming services to improve identification of probable EDs.

Several studies have demonstrated that blood pressure variability (BPV) is associated with an increased risk of cardiovascular morbidity and mortality. However, the optimal BPV index in terms of prognosis and reproducibility remains unclear. In this study, we aimed to evaluate the reproducibility of ambulatory BPV indices in untreated hypertensive patients. A total of 100 never-treated hypertensive patients underwent two ambulatory BP recordings within a 4-week period. For each patient, we computed BPV indices, such as the standard deviation (SD), coefficient of variation (CV), weighted SD (wSD), average real variability (ARV), time rate (TR) of BP variation, and dipping for systolic and diastolic BP. Statistical analyses were performed using the intraclass correlation coefficient (ICC) and Cohen's kappa coefficient. Reliability analysis using ICC revealed moderate reproducibility (ICC from 0.540 to 0.715) for 24&#xa0;h systolic SD, wSD, CV, ARV, TR, dipping, diastolic SD, wSD, CV, and ARV and poor reproducibility (ICC&#xa0;< 0.5) for the 24&#xa0;h diastolic TR and dipping. The ICC values for daytime BPV revealed moderate reproducibility (ICC from 0.537 to 0.672) for daytime systolic SD, CV, diastolic SD, and CV but poor reproducibility (ICC&#xa0;< 0.5) for daytime systolic ARV, TR, diastolic ARV, and TR. All nighttime BPV indices exhibited poor reproducibility. This study demonstrated that most 24&#xa0;h and daytime BPV indices showed moderate reproducibility, whereas nighttime BPV indices and diastolic BP dipping showed poor reproducibility. Additionally, systolic BPV was more reproducible than diastolic BPV.

To characterize baseline xanthoma prevalence and severity in Alagille syndrome, assess their impact on quality of life, evaluate longitudinal changes in xanthoma burden with maralixibat therapy, and identify clinical and biochemical predictors of treatment response in children enrolled across 2 clinical trials. This integrated analysis from the ICONIC and ITCH trials assessed xanthoma severity using the Clinician Xanthoma Scale (CXS). Response was defined as a &#x2265;1-point reduction from baseline in CXS. Outcomes included changes in serum lipids, serum bile acids (sBA), pruritus, and Pediatric Quality of Life Inventory scores through week 96. Baseline characteristics were compared across xanthoma severity groups using the Jonckheere-Terpstra test for continuous variables and the Cochran-Armitage trend test for categorical variables. The changes in xanthoma severity category (3 levels) from baseline to weeks 48 and 96 were tested using Bowker's test of symmetry. Change from baseline (CFB) of continuous outcomes was tested using the Wilcoxon signed-rank test. Differences in CFB of outcomes between xanthoma responders and nonresponders were evaluated using the Wilcoxon rank-sum test for continuous variables and Fisher exact test for categorical outcomes. Among 63 children (ICONIC, n = 29; ITCH, n = 34), 43% had xanthomas at baseline. Higher CXS was associated with younger age (P = .03); elevated sBA (P < .001), bilirubin (P < .001), alanine aminotransferase (P = .008), and gamma-glutamyl transferase (P = .02); and worse lipid profiles (total cholesterol, P < .001; high-density lipoprotein, P < .001). Quality of life declined with increasing CXS. After 96 weeks of follow-up (ICONIC, n = 18; ITCH, n = 17), mean CXS decreased (P = .004), and CXS 0 prevalence increased from 60% to 86% (P = .03). There was a significant decline in cholesterol (mean CFB, -55 mg/dL, P < .001) and sBA (mean CFB, -85 &#x3bc;mol/L, P < .001). Among participants with baseline CXS &#x2265;1 (n = 14; ICONIC, n = 8; ITCH, n = 6), 71% and 64% were xanthoma responders at weeks 48 and 96. Responders had greater cholesterol reductions at week 48 (mean CFB, -189 vs -11 mg/dL, P = .005) and more frequent pruritus improvement (94% vs 68%, P = .047). Maralixibat may reduce xanthoma burden and improve metabolic parameters, supporting therapeutic potential of the drug for xanthomas in Alagille syndrome. This is not a clinical trial, but an integrated analysis of 2 trials; these trials are registered with ClinicalTrials.gov. &#x2022; ICONIC: NCT02160782, https://clinicaltrials.gov/study/NCT02160782 &#x2022; ITCH: NCT02057692, https://clinicaltrials.gov/study/NCT02057692 &#x2022; IMAGINE-II (long-term extension of ITCH): NCT02117713, https://clinicaltrials.gov/study/NCT02117713.

As cancer survivorship rises, provision of information during cancer care is increasingly important, especially regarding potential impacts on patients' health-related quality of life. We sought to understand information needs patients had before initiating anti-cancer treatment using data from a qualitative study designed to examine appropriate recall periods in patient-reported outcome measures of physical function (PF). In this secondary analysis from the Patient Reports of Physical Functioning Study (PROPS) research program, we report on: What do patients wish they had known about their PF before starting treatment? In this secondary analysis, we examined transcripts from PROPS to describe what patients wish they had known about their PF before starting treatment. We used qualitative content analysis to analyze 72 semi-structured transcripts conducted with adults with cancer who had undergone anti-cancer treatment in the previous 6 months. The purpose of this analysis was to identify categories of patient information needs. Of the 72 participants, over half indicated a desire for additional information about their PF before starting treatment, including the impact of side effects/symptoms, such as pain and fatigue, on PF, or a better understanding of expectations for PF. Most of these participants reported PF limitations during the interview. The remaining participants reported feeling fully informed, with most reporting no PF limitations. Patients are interested in learning about the impact of treatment on their PF, but the amount of detail desired varies. Providing personalized information may enhance shared decision-making, empower patients in self-management and treatment decisions, and support timely referrals to specialists. These findings highlight the need for tailored communication strategies in cancer care to better address patient concerns and improve overall treatment experiences.

Existing quality-of-life assessment tools for chemotherapy-induced alopecia may not adequately serve women of all races. Non-White patients with breast cancer receiving chemotherapy at our institution were approximately six times less likely than White patients to use scalp cooling (SC). This study examines factors contributing to this disparity through interviews with Black women undergoing chemotherapy, focusing on alopecia's impact and attitudes toward its prevention and treatment. Semi-structured, 1-hour Zoom interviews were conducted and transcribed. Content analysis using NVIVO software and a grounded theory approach identified themes. Three main domains emerged: (1) alopecia's impact, (2) barriers to SC, and (3) improving alopecia management. Key barriers included limited representation of Black women in SC advertising and concerns about SC's effectiveness on textured hair. Solutions included better counseling on SC use, camouflage options, and increased awareness of other treatment options like dermatology referrals. The study was conducted at a single institution; participation was voluntary leading to possible selection bias and the risk for recall bias in the setting of assessing patients' attitudes retrospectively. This study highlights barriers to SC use among Black women, providing insights for developing interventions to improve access to alopecia prevention and treatment.

The phase 4 RESOLUTION trial showed that the first 12&#x2009;weeks of treatment with eptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody, reduced migraine frequency, severity, and disease burden, and improved quality of life (QOL) versus placebo in participants with chronic migraine (CM) and medication-overuse headache (MOH) who also received patient education. Here, we present 24-week eptinezumab efficacy and safety in the RESOLUTION trial. RESOLUTION was a randomized, parallel-group, multinational clinical trial that included a 12-week double-blind, placebo-controlled period and a 12-week open-label extension period (OLE). Adults (18-75&#x2009;years) with CM and MOH (excluding opioid-overuse headache) received a brief educational intervention about MOH at baseline and were randomized (1:1) to IV eptinezumab 100&#x2009;mg or placebo. At Week 12, all participants received eptinezumab 100&#x2009;mg. Measures used for primary and key secondary efficacy endpoints were also captured during the OLE: mean changes from baseline in monthly migraine days (primary endpoint: Weeks 1-4), monthly headache days, monthly days with acute medication use, average daily pain, and participants no longer meeting threshold criteria for CM nor MOH. Secondary endpoints (including patient-reported-outcomes [PROs] assessing disease-related burden and health-related QOL) and treatment-emergent adverse events (TEAEs) were also captured during the OLE. Of 608 participants randomized, 593 (97.5%) were treated with eptinezumab in the OLE, and 584/608 (96.1%) completed the trial. Reductions in migraine frequency and active CM/MOH diagnosis, and improvements across multiple PROs observed in post hoc analyses during the placebo-controlled period were sustained during the OLE for participants initially treated with eptinezumab, with similar levels of improvement gained for those initially receiving placebo. The proportion of participants with TEAEs in the OLE was similar between eptinezumab-eptinezumab and placebo-eptinezumab treatment sequence groups (30% vs 34%); no new safety signals were identified. In participants with CM and MOH who received patient education, reductions in disease burden and improvements in QOL during the first 12&#x2009;weeks with eptinezumab treatment were sustained for up to 24&#x2009;weeks following a second eptinezumab infusion, with similar improvements observed in participants switched from placebo to eptinezumab. Eptinezumab was generally well tolerated, with no new safety signals. ClinicalTrials.gov Identifier: NCT05452239 (https://clinicaltrials.gov/study/NCT05452239); EudraCT Number: 2021-003049-40 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=2021-003049-40).

Skeletal muscle undergoes progressive denervation-induced muscle atrophy (DIMA) after peripheral nerve injury that severely impairs the potential for motor functional recovery with reinnervation. There are currently no therapeutic strategies to reverse the deleterious effects of chronic DIMA, leaving affected patients with lifelong disability. Herein, we used a translational rodent forelimb nerve injury model to investigate whether targeted injection of syngeneic myoblasts to chronically atrophic muscle can reverse the histologic and functional consequences of DIMA. Male Lewis rats underwent median nerve transection followed by immediate (positive control) or delayed repair. Following a plateau of motor function, myoblasts were injected into the digital flexor muscles (n&#x2009;=&#x2009;5-6 per group), delivered in either saline or a nanofiber hydrogel composite (NHC) loaded with agrin- and insulin-like growth factor 1 (IGF-1)-releasing nanoparticles (npNHC). Serial functional assessments of stimulated grip strength and terminal histological evaluation were used to measure recovery. Satellite cell-rich (Pax7 Hi ) myoblast therapy caused sustained improvement in stimulated grip strength from pretreatment baseline (p&#x2009;<&#x2009;0.05). Histological evaluation demonstrated that myoblast therapy, when delivered in npNHC, reversed whole muscle atrophy compared to positive controls [p&#x2009;=&#x2009;0.997 and 0.996] and restored mean myofiber cross-sectional area [p&#x2009;=&#x2009;0.244]. Correlation analysis demonstrated functional improvements were associated with increased myofiber cross-sectional area [r&#x2009;=&#x2009;0.900, p&#x2009;=&#x2009;3.01E-09]. This data indicates that targeted injection of syngeneic myoblasts can reverse the functional and histologic effects of DIMA in skeletal muscles and is a promising strategy for improving recovery after peripheral nerve injuries.

International Classification of Diseases, Tenth Revision (ICD-10) codes are commonly used for identifying myocardial infarction (MI) in clinical research and increasingly used to capture events in clinical trials; however, their accuracy for distinguishing MI subtypes is uncertain. In this secondary analysis of a single-center prospective cohort study, consecutive individuals who underwent highsensitivity cardiac troponin testing between October 2023 and February 2025 were adjudicated by physicians as either an MI subtype, myocardial injury, or non-elevated troponin. Clinician adjudicated diagnoses were compared to ICD-10 codes attributable to type 1 MI, type 2 MI, and type 3-5 MI. In a study of 24,524 individuals undergoing troponin testing, type 1 MI ICD-10 codes showed moderate sensitivity (53%) but high specificity (99%), whereas the ICD-10 codes for type 2 MI and types 3-5 MI demonstrated extremely low sensitivities (3% and 0%, respectively) despite high sepificitiy (99%). These data suggest the ICD-10 codes for each individual MI subtype have such low sensitivity that they may not reliably and accurately identify these MI subtypes in clinical research or in quality metrics and value-based programs.

Urinary epidermal growth factor (uEGF) and clusterin (uCLU) are emerging biomarkers in chronic kidney disease (CKD), but rigorous analytical validation is required before clinical implementation. We evaluated intra-individual variability and long-term storage stability of uEGF and uCLU in CKD. In the prospective, multicenter UVALID study, 60 adults with CKD stages 2-4 underwent urine sampling at three visits over 8 weeks. First-morning and 24-h urine samples were collected to assess intra-individual variability over 24 h, 3 days and 8 weeks. Biomarkers were measured in duplicate by ELISA and normalized to urinary creatinine (/Cr). Inter-laboratory performance was assessed using quality control samples. Stability after 12 and 15 months of storage at -20 &#xb0;C and -80 &#xb0;C and the influence of pH were evaluated. Over 24 h, 3 days, and 8 weeks, uEGF/Cr demonstrated low variability and remained stable after long-term storage at both temperatures. In contrast, uCLU/Cr showed greater variability and pronounced instability at -20 &#xb0;C, whereas stability was preserved at -80 &#xb0;C. Samples with pH > 6 partially preserved uCLU stability at -20 &#xb0;C. Inter-laboratory reproducibility was acceptable for uEGF but suboptimal for uCLU at low concentrations. Thus, uEGF showed robust analytical performance, supporting its potential clinical applicability in CKD, whereas uCLU exhibited important analytical and pre-analytical limitations, warranting further assay optimization. These findings underscore the need for rigorous validation to facilitate biomarker implementation in clinical practice.