Advances in Therapy最新文献

Introduction: Type 2 diabetes mellitus (T2DM) presents a major challenge in low- and middle-income countries (LMICs) due to workforce shortages, limited primary-care capacity, and fragmented chronic-care delivery. Community-based diabetes care models have emerged as scalable approaches to strengthen self-management and extend service reach. With this background, we aimed to synthesize global evidence on community-based diabetes care models, classify major intervention typologies, examine their alignment with the diabetes care continuum, and assess their effectiveness and implementation characteristics.

Methods: A narrative review was conducted using a structured search of PubMed, Scopus, Web of Science, and Embase for studies published between January 2010 and March 2025. Eligible studies focused on community-based T2DM interventions delivered by community health workers (CHWs), peer educators, or digital-community hybrids. Interventions were categorized and mapped across the diabetes care continuum, and evaluated using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework, as well as complementary integration models.

Results: Eleven studies were included, in which peer-led models were common in high-income countries, while CHW-led and hybrid models were predominant in LMICs. Interventions demonstrated clinically significant improvements in glycated hemoglobin (HbA1c), BMI, and self-efficacy. Successful models embedded within existing public health systems or culturally rooted community platforms showed higher adoption and long-term maintenance. Digital interventions enhanced reach, but faced challenges with sustained engagement and infrastructure support. The RE-AIM analysis revealed strong effectiveness and reach; however, long-term maintenance and adoption varied based on the level of contextual integration and supervision structures.

Conclusion: Community-based T2DM care models offer scalable, sustainable strategies to improve disease control. Integration into national health platforms, supportive supervision, and digital augmentation enhance implementation success. Challenges persist in follow-up, cost-effectiveness, and equity design; scale-up should prioritize integration, financing, and CHW capacity.

Introduction: Efsubaglutide alfa is a novel, long-acting GLP-1RA, which imparts human homology, molecular flexibility and enhanced GLP-1 receptor-specific binding. This drug-free, observational follow-up evaluated remission and durability of glycemic control in drug-naïve T2D participants who had completed 52 weeks of once-weekly efsubaglutide alfa in the SUPER-1 randomized trial.

Methods: Adults who completed SUPER-1 with HbA1c ≤ 7.0% discontinued all glucose-lowering therapy and entered a 52-week, medication-free observation. The primary endpoint was diabetes remission, defined as HbA1c < 6.5% (American Diabetes Association criteria, ADA 2021) measured ≥ 3 months after the last efsubaglutide dose. Kaplan-Meier (KM) analysis was employed to estimate the probability of maintaining HbA1c < 7% over 12 months post-treatment. Continuous glucose monitoring (CGM) assessed changes in time in range (TIR). Factors contributing to diabetes remission were analyzed using logistic regression and subgroup KM analyses.

Results: Twenty-nine participants were enrolled; at 3 months post-discontinuation, the diabetes remission rate was 60% (12/20). The probabilities of maintaining HbA1c < 7% at 6- and 12-month post-treatment were 58.1% (17/29; 95% CI 39.0-73.1%) and 41.4% (12/29; 95% CI 24.0-58.0%), respectively. Efsubaglutide alfa treatment during the 52-week period significantly improved TIR (baseline: 46.4%; 52 week: 89.1%, p < 0.001). TIR levels off therapy were 70.1% at 3 months, 68.1% at 6 months and 64.1% at 12 months. Patients who achieved remission had relatively lower baseline HbA1c and higher body mass index (BMI) values before treatment, demonstrating significantly greater reductions in waist circumference (- 3.3 cm) and postprandial glucose (PPG) levels compared to those who did not remit. Post-treatment HbA1c levels and improvements in homeostasis model assessment of β-cell (HOMA-β) scores were strongly associated with a higher probability of remission (p = 0.03 and 0.05, respectively). Body weight remained stable throughout the 12-month drug-free observation without rebound.

Conclusions: Efsubaglutide alfa demonstrated efficacy in achieving stable glycemic control and drug-free diabetes remission. Enhanced β-cell function emerged as a key factor contributing to long-term remission.

Trial registration: ClinicalTrials.gov identifier, NCT06605287.

While immunotherapy has been widely adopted for the treatment of melanoma, its application in patients with complex comorbidities remains challenging. This review explores evidence on the efficacy, safety, and special considerations for the use of immunotherapy in patients with altered immune systems, including patients with human immunodeficiency virus (HIV), tuberculosis, solid organ or hematopoietic cell transplantation, autoimmune diseases, and pregnant women. Despite data emphasizing the feasibility of immunotherapy treatment in these populations, standardized management algorithms are lacking. Future research should consider either including these patients in prospective trials or attempting to collect data via registries to provide more clarity on the management of immunologically vulnerable patients with melanoma.

Introduction: Individuals with Duchenne muscular dystrophy (DMD) require increasing care as they age, and caregiver impact can be considerable. The objectives were to investigate the amount of time spent caregiving and working, the extent of adjustments to paid work, and impact on productivity among DMD caregivers in the USA.

Methods: Caregivers of individuals with DMD were recruited through a US-based DMD advocacy group. Measures of impact included time spent on caregiving activities, an overall caregiver impact rating scale ranging from 0 to 10, frequency of work adjustments, and the Work Productivity and Activity Impairment Questionnaire for DMD (WPAI:DMD-CG, v2.0). Survey responses were stratified by care recipient ambulatory status and caregiver employment status.

Results: Of 106 caregivers, 82% were mothers; mean (standard deviation) caregiver age was 46 (8.0) years. Eighty-nine percent of respondents reported caring for one individual with DMD and 11% for two individuals with DMD. Sixty-eight percent of respondents were employed. WPAI scores indicated an overall activity impairment of 41%; work time missed was 8%; impairment at work was 31%; work productivity loss was 35%. Across all caregivers, 77% experienced at least one job-related change due to caregiving: 26% took a job with less income potential, 25% quit, 34% changed their role/responsibilities, 29% reduced their hours, and 34% took leave from work to care for their child(ren) with DMD.

Conclusions: This survey extends prior work by providing contemporary, US-specific estimates of work adjustments necessary among caregivers of individuals with DMD. The results demonstrate the considerable impact caregiving has on paid work and productivity.

Introduction: Depemokimab, the first ultra-long-acting respiratory biologic, is under investigation for diseases with underlying type 2 (T2) inflammation. Subcutaneous depemokimab 100 mg was efficacious in patients with T2 asthma characterized by blood eosinophil count and in chronic rhinosinusitis with nasal polyps (CRSwNP) when administered twice-yearly in four Phase III randomized, double-blind, placebo-controlled studies (SWIFT-1/-2 and ANCHOR-1/-2, respectively). This pooled analysis examined the safety and tolerability of subcutaneous depemokimab 100 mg versus placebo in patients with T2 asthma and in CRSwNP.

Methods: Adverse event (AE) frequency, severity, time-to-onset, duration, and relative risk (RR) were evaluated for depemokimab 100 mg and placebo administered subcutaneously every 26 weeks for 52 weeks using pooled SWIFT-1/-2 and ANCHOR-1/-2 data. The impact of immunogenicity on safety was also evaluated.

Results: Overall, 1290 patients from the four studies were included in the safety analysis population (773 [60%] received depemokimab; 517 [40%] received placebo). On-treatment AEs were reported by 73% and 78% of patients in the depemokimab and placebo groups, respectively; the majority were mild or moderate in intensity and transient, with similar durations between treatment groups. Serious AEs (SAEs; 5% and 10%, with depemokimab and placebo, respectively), and discontinuations due to AEs (< 1% and 1%, respectively) were infrequent. No fatal AEs or treatment-related SAEs (per investigator assessment) were reported. RRs (vs. placebo) were similar for all common on-treatment AEs except asthma and back pain, which occurred less frequently in the depemokimab group compared with the placebo group. Antidrug antibodies and neutralizing antibodies occurred infrequently, and no association between antidrug antibody status and depemokimab efficacy was identified.

Conclusions: In these studies, twice-yearly depemokimab 100 mg was generally well tolerated by patients with T2 asthma or CRSwNP over the 52-week treatment period, supporting the safety of the first ultra-long-acting biologic for these diseases.

Clinical trial identifier(s): NCT04719832/NCT04718103/NCT05274750/NCT05281523.

Introduction: Spinal muscular atrophy (SMA) is a central nerve system disease characterized by a broad spectrum of clinical presentations, mainly manifested as muscle atrophy and weakness. The effectiveness and safety of nusinersen in Chinese adults with SMA have not been well reported. This analysis aimed to describe the effectiveness and safety of nusinersen among Chinese adults with 5q-SMA.

Methods: This analysis leveraged a longitudinal, multicenter disease registry including both prospective and retrospective data from adults with 5q-SMA in China. Nusinersen's effectiveness was assessed by the changes in the Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), and 6-Minute Walk Test (6-MWT) from baseline and at 6, 10, and 14 months among participants receiving nusinersen as their first disease-modifying therapy (DMT). Nusinersen's safety was evaluated among prospective participants who used nusinersen as their first DMT and initiated nusinersen on or after the enrollment date.

Results: A total of 171 and 19 participants were included in the effectiveness and safety analysis, respectively. For HFMSE, the mean [standard deviation (SD)] change from baseline at 14 months after treatment initiation was 3.4 (5.34) among 17 sitters and 3.4 (4.03) among 25 walkers. For RULM, the mean (SD) change from baseline at 14 months after treatment initiation was 2.6 (3.07) among 11 non-sitters, 1.6 (4.06) among 20 sitters, and 1.3 (1.84) among 13 walkers. For 6-MWT, the mean (SD) change from baseline at 14 months after treatment initiation was 15.0 (35.80) m among 13 walkers. No death was reported in the registry. Three participants reported five mild adverse events, none of which were considered related to nusinersen by the investigators.

Conclusion: Despite the limited sample size, the analysis appears to show the benefit of nusinersen among Chinese adults of a wide range of ages and disease severity with 5q-SMA. The registry was registered on Clinicaltrials.gov (NCT05618379).

Introduction: Detecting paroxysmal atrial fibrillation (pAF) from sinus rhythm could enable earlier intervention and stroke prevention. We developed a deep-learning Holter electrocardiograph (ECG) algorithm and prospectively evaluated its patient-level performance against 7-day AF outcomes.

Methods: We curated 20,000 30-s sinus rhythm blocks (125 Hz) from Holter ECG data of patients with and without pAF, trained convolutional models with tenfold cross-validation, and assessed a separate validation set (n = 54; 27 pAF, 27 controls) to select the operating threshold. A multicenter prospective study then evaluated the algorithm using ten consecutive 30-s sinus rhythm blocks per patient with a 4/10 positive rule; patients with pAF underwent concurrent 7-day patch monitoring to anchor outcomes.

Results: Cross-validation during development yielded mean sensitivity 84.2% and specificity 66.2%; the best tuned model achieved 84.9% sensitivity and 69.9% specificity on the separate set. In the clinical trial, among 24 patients with AF documented within 7 days and 20 controls, the device showed sensitivity 91.7% (95% confidence interval (CI) 73.0-99.0) and specificity 65.0% (40.8-84.6). No device-related adverse events occurred.

Conclusion: An artificial intelligence (AI) analyzing short sinus rhythm Holter segments can identify patients who develop pAF within 7 days, supporting use as a triage tool for intensified rhythm monitoring.

Trial registration: UMIN-CTR UMIN000047182.

Introduction: Chronic kidney disease (CKD) symptom burden and associated treatments can impact patients' ability to work and financial well-being. Informal caregivers provide support and may also be affected. This multinational study aimed to characterise the impact of CKD on work productivity and the financial health of patients and caregivers.

Methods: National cohorts of patients with CKD, caregivers and matched general populations were recruited for Australia, Germany, Egypt, UK, Italy, Taiwan, and the US and surveyed via the Work Productivity and Activity Impairment (WPAI) questionnaire and the Consumer Financial Protection Bureau (CFPB) Financial Well-Being Scale. Financial toxicity was assessed using the COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (FACIT-COST).

Results: A total of 1303 patients and 674 caregivers were recruited. Compared with matched general populations, patients showed marked impairment in work and daily activities, particularly in presenteeism (difference: min, 7.4%; max, 43.6%) and activity impairment (difference: min, 25.9%; max, 46.4%). Work productivity and activity impairment were greatest among dialysis patients, a trend also observed among caregivers for patients on dialysis. CFPB Financial Well-Being scores indicated poorer financial health in patients versus general populations; variable outcomes were reported by caregivers. Financial toxicity, assessed by FACIT-COST, showed inter-country variation, and was most pronounced in younger, working-age patients.

Conclusion: The indirect burden of CKD extends beyond clinical costs to include significant financial and work productivity impacts on patients and caregivers, with greater challenges for patients on dialysis. Strategies to prevent CKD progression appear warranted to alleviate burden on financial health and work productivity for patients and caregivers.

Introduction: Obesity management medications influence eating behavior and promote substantial weight reduction in individuals with obesity or overweight. Existing patient-reported outcome measures do not adequately measure appetite and eating behavior concepts relevant to individuals with these conditions. This study presents psychometric properties of the Eating Behavior and Appetite Questionnaire (EBAQ), a new patient-reported outcome measure to assess appetite and eating behaviors in adults with obesity or overweight.

Methods: Participants (n = 120) completed two web-based surveys (baseline, week 2). Survey 1 included the 21-item EBAQ, Control of Eating Questionnaire, Food Cravings Questionnaire-Trait-reduced, Impact of Weight on Quality of Life-Lite Clinical Trials Version, and Patient Global Impression of Severity (PGIS) items for appetite, eating control, cravings, and overall eating behavior. Survey 2 included the EBAQ and PGIS items. Factor structure, reliability, and validity of the EBAQ were assessed.

Results: Exploratory factor analysis of the EBAQ supported a 2-factor structure. Items loaded moderately to strongly (≥ 0.48) on factors corresponding to appetite control or eating behavior (inter-factor correlation 0.57). Four items with factor loadings ≤ 0.43 were dropped. Internal consistency for the 17-item EBAQ was good/excellent for the domain scores (0.84-0.91) and excellent for the total score (0.92). Test-retest reliability was good (intraclass correlation coefficients ≥ 0.84). Convergent validity was demonstrated via large correlations with the Control of Eating Questionnaire craving subscales, Food Cravings Questionnaire-Trait-reduced total score, and PGIS items, and smaller correlations with less similar PRO measures. EBAQ domain and total scores demonstrated known-groups validity, with higher EBAQ scores in participants who reported a well-controlled appetite, feeling in control of their eating, fewer food cravings, and better eating habits (i.e., higher PGIS scores).

Conclusion: Results support the 2-factor structure, reliability, and validity of the final 17-item EBAQ. The EBAQ can be used in observational studies, clinical trials, and clinical practice to comprehensively assess appetite and eating behaviors in individuals with obesity or overweight.