Clinical therapeutics最新文献_第6页

High Adherence to Repeat Multitarget Stool DNA Testing and Follow-Up Colonoscopy in Average-Risk United States Adults: Results from a Nationally Insured Cohort. 在平均风险的美国成年人中，高依从性重复多靶点粪便DNA检测和随访结肠镜检查：来自全国保险队列的结果。

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2025-11-28 DOI: 10.1016/j.clinthera.2025.10.015

Mallik Greene, Shrey Gohil, Juliana Vanessa Rincón López, Jerry Lovelace, A Mark Fendrick, Martha Duarte, Michael Dore, Joseph C Anderson, Jordan K Karlitz, Quang A Le

Purpose: Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the United States, despite available screening programs, making regular screening essential for early detection and prevention. This study evaluated adherence to repeat multitarget stool DNA (mt-sDNA) testing and follow-up colonoscopy rates among average-risk individuals in the United States METHODS: This retrospective study used mt-sDNA lab data linked to a national multipayer claims database from 2017 to 2023. Adults aged 45 to 75 years at average risk for CRC who underwent repeat mt-sDNA screening after one or more prior negative results were included. The primary outcome was adherence to repeat mt-sDNA testing, defined as the return of a successfully completed test with valid results within 365 days of shipment. The secondary outcome was the rate of follow-up colonoscopy after a positive mt-sDNA result. Baseline characteristics, adherence rates, and follow-up colonoscopy rates were summarized descriptively. Logistic regression was used to identify factors independently associated with adherence.

Findings: The study included 326,329 individuals, predominantly female (62.0%) and White (62.5%). Adherence to repeat mt-sDNA screening was high across all racial and ethnic subgroups, exceeding 80% in every group analyzed. White individuals had the highest adherence at 86.6%, followed by Asian individuals at 85.7%, Black individuals at 83.1%, and Hispanic or Latino individuals at 82.7% (P < 0.001).Among those with two prior mt-sDNA tests, adherence increased to 90.6%. The rate of follow-up colonoscopy among those with a positive mt-sDNA result was 76.0%. Logistic regression analysis showed higher odds of mt-sDNA adherence among individuals aged 65-75 years (OR: 1.27; 95% CI: 1.25-1.30; P < 0.001), those residing in rural (OR: 1.21; 95% CI: 1.13-1.28; P < 0.001), patients whose tests were ordered by OB/GYNs (OR: 1.19; 95% CI: 1.13-1.28; P < 0.001), individuals receiving digital outreach (OR: 1.34; 95% CI: 1.30-1.37; P < 0.001), and individuals with two or more prior mt-sDNA tests (OR: 1.44; 95% CI: 1.31-1.58; P < 0.001).

Implications: The mt-sDNA test was associated with high repeat screening adherence (86.1%) and a follow-up colonoscopy rate of 76.0%, with mt-sDNA adherence exceeding 80% in most subgroups. These findings support its utility as a reliable, home-based CRC screening option.

目的：结直肠癌（CRC）是美国癌症相关死亡的主要原因，尽管有筛查项目，但定期筛查对于早期发现和预防至关重要。本研究评估了美国平均风险个体对重复多靶点粪便DNA （mt-sDNA）检测的依从性和随访结肠镜检查率。方法：本回顾性研究使用了2017年至2023年与国家多付款人索赔数据库相关的mt-sDNA实验室数据。年龄在45 - 75岁之间，有CRC平均风险的成年人，在一次或多次既往阴性结果后接受重复mt-sDNA筛查。主要结果是坚持重复mt-sDNA检测，定义为在发货后365天内成功完成检测并获得有效结果。次要结果是mt-sDNA阳性后随访结肠镜检查的比率。对基线特征、依从率和随访结肠镜检查率进行描述性总结。使用逻辑回归来确定与依从性独立相关的因素。研究结果：该研究包括326,329人，主要是女性（62.0%）和白人（62.5%）。重复mt-sDNA筛查的依从性在所有种族和民族亚组中都很高，在每个分析组中都超过80%。白人的依从性最高，为86.6%，其次是亚洲人，为85.7%，黑人为83.1%，西班牙裔或拉丁裔为82.7% （P < 0.001）。在先前进行过两次mt-sDNA检测的患者中，依从性增加到90.6%。mt-sDNA阳性的结肠镜随访率为76.0%。Logistic回归分析显示，年龄65-75岁的患者（OR: 1.27; 95% CI: 1.25-1.30; P < 0.001）、居住在农村的患者（OR: 1.21; 95% CI: 1.13-1.28; P < 0.001）、由妇产科医生开具检查单的患者（OR: 1.19; 95% CI: 1.13-1.28; P < 0.001）、接受数字化外联的患者（OR: 1.34; 95% CI: 1.30-1.37; P < 0.001）以及之前进行过两次或两次以上mt-sDNA检查的患者（OR: 1.44; 95% CI: 1.31-1.58; P < 0.001）坚持mt-sDNA检查的几率较高。意义：mt-sDNA检测与高重复筛查依从性（86.1%）和随访结肠镜检查率76.0%相关，在大多数亚组中，mt-sDNA依从性超过80%。这些发现支持它作为一种可靠的、基于家庭的CRC筛查选择的效用。

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引用次数: 0

Increased Bone Mineral Content in Response to Electrical Stimulation. 增加骨矿物质含量对电刺激的反应。

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2025-11-23 DOI: 10.1016/j.clinthera.2025.10.009

Alain S Comtois, James A Hodgdon, Jean P Boucher

Background: Osteoporosis is widespread, underdiagnosed, and disproportionately affects women and marginalized populations. With limitations in pharmacologic treatments, particularly in underserved populations, accessible, non-invasive interventions like electrical stimulation (ES) that promote osteogenesis are needed. We evaluated the effects of a portable low-frequency ES device on bone health in premenopausal women.

Methods: In a 10-week, double-blind, randomized pilot study, 48 healthy premenopausal women aged 18 - 45 were assigned to either a stimulation (STIM) or placebo (NSTIM) group. Participants completed 30 supervised interval training exercise sessions with or without ES targeting the greater trochanter of the femur. Bone mineral content, area, and mineral density (BMC, BA, BMD) were assessed via DXA scans at baseline, mid-point, and post-intervention. Data were analyzed using mixed-design ANOVA and ANCOVA.

Results: Significant Group × Time interactions were observed for leg BMC (P = 0.013) and leg BA (P = 0.015), with the STIM group showing increases in both outcomes. The NSTIM group showed declines or incomplete recovery. No significant changes were observed in whole-body BMC or BMD. Follow-up ANCOVA confirmed significant adjusted final differences in leg BMC and BA favoring the STIM group. BMD remained stable across both groups.

Conclusion: Targeted low-frequency ES with exercise may produce localized skeletal benefits in premenopausal women. Although a third of participants identified as Black, high attrition and randomization limited subgroup analysis. Future studies should enhance inclusion strategies and explore other anatomical sites to evaluate differential responses better. This intervention shows promise as a scalable, non-pharmacologic option for improving bone health.

背景：骨质疏松症广泛存在，但未得到充分诊断，并且不成比例地影响妇女和边缘人群。由于药物治疗的局限性，特别是在服务不足的人群中，需要电刺激（ES）等可获得的非侵入性干预措施来促进成骨。我们评估了便携式低频ES装置对绝经前妇女骨骼健康的影响。方法：在一项为期10周的双盲随机先导研究中，48名年龄在18 - 45岁的健康绝经前妇女被分配到刺激组（STIM）或安慰剂组（NSTIM）。参与者完成了30次有或无ES的间歇训练，目标是股骨大转子。在基线、中点和干预后通过DXA扫描评估骨矿物质含量、面积和矿物质密度（BMC、BA、BMD）。数据分析采用混合设计方差分析和方差分析。结果：腿部BMC （P = 0.013）和腿部BA （P = 0.015）存在显著的组与时间交互作用，STIM组两项结果均升高。NSTIM组表现出下降或不完全恢复。未观察到全身BMC或BMD的显著变化。随访ANCOVA证实了有利于STIM组的腿部BMC和BA的显著调整后最终差异。两组的骨密度都保持稳定。结论：有针对性的低频ES与运动可能对绝经前妇女产生局部骨骼益处。虽然三分之一的参与者被确定为黑人，但高流失率和随机化限制了亚组分析。未来的研究应加强纳入策略和探索其他解剖部位，以更好地评估差异反应。这种干预作为一种可扩展的、非药物的改善骨骼健康的选择显示出了希望。

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引用次数: 0

Increasing the Time Interval Suppresses Adverse Effects After Concomitant Use of Nafamostat Mesylate and Levocarnitine in Dialysis Patients: Case Series 增加透析患者同时使用甲磺酸纳莫他和左卡尼汀后的时间间隔抑制不良反应：病例系列。

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2025-11-01 DOI: 10.1016/j.clinthera.2025.08.014

Lili Jiang , Jiaoyan Chen , Jurong Yang, Yan Sun, Mingyue Hou, Yunyan Wang

Purpose

This is a series of reports describing how increasing the time interval between the administration of nafamostat mesylate (NM) and levocarnitine can suppress adverse reactions in maintenance hemodialysis patients after medication.

Methods

Clinical assessments and medical record collection were conducted by nephrologists and nurses, while laboratory tests were performed by specialist doctors.

Findings

Increasing the time interval between NM and levocarnitine administration (15–25 minutes) reduced adverse drug reactions, including nausea and vomiting, in 4 patients.

Implications

This may provide clinical doctors with new insights and research directions when using levocarnitine and NM for dialysis treatment.

目的：这是一系列报道，描述了增加甲磺酸那莫他酯（NM）和左卡尼汀给药之间的时间间隔如何抑制维持性血液透析患者用药后的不良反应。方法：临床评估和病历收集由肾内科医生和护士进行，实验室检查由专科医生进行。结果：增加NM与左卡尼汀给药的时间间隔（15-25分钟）减少了4例患者的药物不良反应，包括恶心和呕吐。意义：这可能为临床医生使用左卡尼汀和NM进行透析治疗提供新的见解和研究方向。

引用次数: 0

Real-world Hepatobiliary Toxicity After Bispecific T-Cell Engager Therapy: A 10-Year Disproportionality Analysis of the Food and Drug Administration Adverse Event Reporting System and the World Health Organization's Global Individual Case Safety Report Database 双特异性t细胞介入治疗后的实际肝胆毒性：美国食品和药物管理局不良事件报告系统和世界卫生组织全球个案安全报告数据库的10年歧化分析。

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2025-11-01 DOI: 10.1016/j.clinthera.2025.09.001

Rong Hu PhD , Junyi Shen MD , Peng Luo MD , Hui Zhang MD, PhD , Yingyi He MD, PhD

Purpose

Relapsed/refractory hematological malignancies increasingly utilize bispecific T-cell engagers (BiTEs), yet their postmarketing hepatobiliary toxicity profiles remain inadequately characterized. This study aimed to bridge this knowledge gap by conducting the first comprehensive pharmacovigilance analysis of BiTE-associated hepatobiliary toxicity using real-world data from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and the World Health Organization's global Individual Case Safety Report database (VigiBase).

Methods

Hepatobiliary reports were extracted from patients with hematological malignancy deposited in FAERS and VigiBase (2015–2024). Disproportionality analyses, multivariate logistic regression analyses, and time-to-onset analyses were employed to identify safety signals across CD19, non-CD19-targeting BiTE, and non-BiTE receivers, characterize hepatobiliary toxicity, and assess their impact on patients’ survival.

Findings

Sixteen safety signals emerged, including four previously under-reported adverse events beyond package insert documentation: ascites, hepatobiliary disease, graft-versus-host disease in liver, and veno-occlusive liver disease. This analysis revealed that non-CD19 BiTEs were relatively safe in terms of hepatobiliary toxicities, whereas CD19 BiTE receivers had significantly earlier hepatobiliary toxicity onset (median: 6 vs 14 days; P = 0.002) and higher mortality rate compared with non-BiTE users (OR_FAERS = 3.28 [2.8–3.82]; P_FAERS = 2.05E–16; OR_VigiBase = 3.13 [2.60–3.76]; P_VigiBase = 2.0E–16).

Implications

These real-world insights complement clinical trial data; however, the disproportionality analyses employed are susceptible to reporting and utilization biases due to the lack of denominator data. The reported odds ratios and significance should be interpreted as measures of reporting association rather than true risk.

目的：复发/难治性血液恶性肿瘤越来越多地使用双特异性t细胞结合物（BiTEs），但其上市后肝胆毒性谱仍未充分表征。本研究旨在通过使用来自美国食品和药物管理局（FDA）不良事件报告系统（FAERS）和世界卫生组织全球个案安全报告数据库（VigiBase）的真实数据，对咬伤相关的肝胆毒性进行首次全面的药物警戒分析，从而弥合这一知识差距。方法：从FAERS和VigiBase（2015-2024）存储的血液学恶性肿瘤患者中提取肝胆报告。采用歧化分析、多变量logistic回归分析和发病时间分析来确定CD19、非CD19靶向BiTE和非BiTE受体的安全信号，表征肝胆毒性，并评估其对患者生存的影响。结果：出现了16个安全信号，包括4个先前未被报道的不良事件：腹水、肝胆疾病、肝脏移植物抗宿主病和静脉闭塞性肝病。该分析显示，非CD19 BiTE在肝胆毒性方面相对安全，而CD19 BiTE受体与非BiTE使用者相比，其肝胆毒性发作明显更早（中位数：6 vs 14天；P = 0.002），死亡率更高（ORFAERS = 3.28 [2.8-3.82]; PFAERS = 2.05E-16; ORVigiBase = 3.13 [2.60-3.76]; PVigiBase = 2.0E-16）。启示：这些现实世界的见解补充了临床试验数据；然而，由于缺乏分母数据，所采用的歧化分析容易受到报告和利用偏差的影响。报告的优势比和显著性应被解释为报告相关性的措施，而不是真正的风险。

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引用次数: 0

When Does a Team Start the Discussion on Inclusion and Diversity in Early-phase Clinical Trials? 团队何时开始讨论早期临床试验的包容性和多样性？

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2025-11-01 DOI: 10.1016/j.clinthera.2025.09.013

Sheila Mathias MBA, PhD , Matthew Barnes BS

Purpose

The purpose of a clinical trial is to determine whether a new drug is safe, efficacious, and has fewer side effects than products that may already be on the market. They are essential for ensuring that new potential therapies will advance patient outcomes in some way. This may represent a therapy for a previously untreatable condition, or it may represent an improvement in the efficacy or safety compared with an existing treatment. A new therapy should improve patients’ quality of life in a meaningful way, and it should do so for as many potential patients as possible.

Methods

To meet this goal, companies should consider the lived experiences and exposures of different populations that are included in the target population for therapies in development. This is why it is generally beneficial to advocate diversity in trials as early as possible in the drug development (Phase I and II trials), as doing so expands the number of trials having inclusivity of racial and ethnic minority groups and are inclusive of more women. Although some improvements in diversity in early-phase trials have been observed in recent years, the overall participation of minority populations in these types of trials continues to be disproportionately lower than their representation in the overall population. In 2023, the minority makeup of the US population was 18.7% Latino and 12.1% Black. In comparison, data reported by the National Cancer Institute in 2023 found the racial makeup in early-phase trials to be 6.9% Latino and 7.1% Black, well below their representation in the larger population.

Findings

The authors, who have been involved in numerous clinical trial study design discussions, understand that people from different backgrounds can experience the same disease differently, and thus, it is important to explore these differences in all communities. These differences represent an important consideration in addition to the acknowledged benefit diversity plays to ensure therapies are appropriately tested in the target patient population.

Implications

This article explores the need for earlier collaboration/discussion on including diversity in the earlier clinical studies. Our commentary calls for key opinion leaders, study Investigators, study leads, study site recruiters, and coordinators to be open to going beyond the current paradigm of diversity only in pivotal trials, generally Phase III, and explore remedies for inclusion of diversity in early trials.

目的：临床试验的目的是确定一种新药是否安全、有效，并且与市场上已经上市的产品相比，其副作用是否更小。它们对于确保新的潜在疗法以某种方式改善患者的预后至关重要。这可能代表了一种治疗以前无法治疗的疾病的方法，或者它可能代表了与现有治疗相比在疗效或安全性方面的改进。一种新的治疗方法应该以一种有意义的方式改善患者的生活质量，并且应该为尽可能多的潜在患者做到这一点。方法：为了实现这一目标，公司应该考虑不同人群的生活经历和暴露，这些人群包括在开发治疗的目标人群中。这就是为什么在药物开发（I期和II期试验）中尽早提倡试验的多样性通常是有益的，因为这样做可以扩大具有种族和少数民族群体包容性的试验数量，并包括更多的妇女。尽管近年来观察到早期试验的多样性有所改善，但这些类型的试验中少数民族人口的总体参与度仍然不成比例地低于他们在总体人口中的代表性。2023年，美国人口的少数族裔构成是18.7%的拉丁裔和12.1%的黑人。相比之下，美国国家癌症研究所（National Cancer Institute）在2023年报告的数据显示，早期试验中的种族构成为6.9%的拉丁裔和7.1%的黑人，远低于他们在更大人群中的代表性。研究结果：参与了大量临床试验研究设计讨论的作者了解，来自不同背景的人可能会以不同的方式经历相同的疾病，因此，探索所有社区的这些差异是很重要的。这些差异代表了一个重要的考虑，除了公认的利益多样性发挥作用，以确保治疗在目标患者群体中得到适当的测试。含义：本文探讨了在早期临床研究中包括多样性的早期合作/讨论的必要性。我们的评论呼吁关键意见领袖、研究研究者、研究负责人、研究地点招聘人员和协调员对目前仅在关键试验（通常是III期试验）中的多样性范式持开放态度，并探索在早期试验中纳入多样性的补救措施。

{"title":"When Does a Team Start the Discussion on Inclusion and Diversity in Early-phase Clinical Trials?","authors":"Sheila Mathias MBA, PhD , Matthew Barnes BS","doi":"10.1016/j.clinthera.2025.09.013","DOIUrl":"10.1016/j.clinthera.2025.09.013","url":null,"abstract":"<div><h3>Purpose</h3><div>The purpose of a clinical trial is to determine whether a new drug is safe, efficacious, and has fewer side effects than products that may already be on the market. They are essential for ensuring that new potential therapies will advance patient outcomes in some way. This may represent a therapy for a previously untreatable condition, or it may represent an improvement in the efficacy or safety compared with an existing treatment. A new therapy should improve patients’ quality of life in a meaningful way, and it should do so for as many potential patients as possible.</div></div><div><h3>Methods</h3><div>To meet this goal, companies should consider the lived experiences and exposures of different populations that are included in the target population for therapies in development. This is why it is generally beneficial to advocate diversity in trials as early as possible in the drug development (Phase I and II trials), as doing so expands the number of trials having inclusivity of racial and ethnic minority groups and are inclusive of more women. Although some improvements in diversity in early-phase trials have been observed in recent years, the overall participation of minority populations in these types of trials continues to be disproportionately lower than their representation in the overall population. In 2023, the minority makeup of the US population was 18.7% Latino and 12.1% Black. In comparison, data reported by the National Cancer Institute in 2023 found the racial makeup in early-phase trials to be 6.9% Latino and 7.1% Black, well below their representation in the larger population.</div></div><div><h3>Findings</h3><div>The authors, who have been involved in numerous clinical trial study design discussions, understand that people from different backgrounds can experience the same disease differently, and thus, it is important to explore these differences in all communities. These differences represent an important consideration in addition to the acknowledged benefit diversity plays to ensure therapies are appropriately tested in the target patient population.</div></div><div><h3>Implications</h3><div>This article explores the need for earlier collaboration/discussion on including diversity in the earlier clinical studies. Our commentary calls for key opinion leaders, study Investigators, study leads, study site recruiters, and coordinators to be open to going beyond the current paradigm of diversity only in pivotal trials, generally Phase III, and explore remedies for inclusion of diversity in early trials.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 11","pages":"Pages 960-965"},"PeriodicalIF":3.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dissolution of Once-Nightly Sodium Oxybate in Soft Foods and Alternative Liquid Reconstitution Vehicles 每晚一次的氧化钠在软性食品中的溶解和替代性液体重构载体。

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2025-11-01 DOI: 10.1016/j.clinthera.2025.08.004

Maggie Lavender MSN, RN, FNP-C , Anne Marie Morse DO , Bahador Mark Tafazoli MD , Feri Ascencion MBA , Ellen Wermter FNP, DBSM , Laura B. Herpel MD , Jennifer Gudeman PharmD , William John Schaefer BS , Jason Vaughn PhD

Purpose

Narcolepsy is a chronic neurologic disorder characterized by excessive daytime sleepiness (EDS) and can occur with or without cataplexy. Once-nightly sodium oxybate (ON-SXB) is approved for the treatment of cataplexy or EDS in patients 7 years of age or older with narcolepsy. ON-SXB contains both immediate-release and pH-dependent, controlled-release granules designed to be reconstituted in water and administered orally once at bedtime. This study evaluated the dissolution profile of ON-SXB after reconstitution with soft foods and alternative liquid vehicles compared to water.

Methods

ON-SXB 4.5 g and 9 g were reconstituted in soft foods (lemon pudding, low-fat vanilla yogurt, and applesauce) or liquid vehicles (raspberry lemonade solution, fruit punch solution, and alkaline water). Milli-Q water served as the control. Acceptance criteria for product specifications required 40% to 60%, 42% to 62%, and ≥80% dissolution at 15 minutes, 2 hours, and 4 hours, respectively.

Findings

For ON-SXB 4.5 g and 9 g, respectively, mean dissolution at 15 minutes was 48% and 45% for lemon pudding, 50% and 50% for low-fat vanilla yogurt, 49% and 48% for applesauce, 51% and 50% for raspberry lemonade solution, 51% and 51% for fruit punch solution, and 49% and 51% alkaline water; at 2 hours, 50% and 51% for lemon pudding, 51% and 50% for low-fat vanilla yogurt, 50% and 49% for applesauce, 51% and 51% for raspberry lemonade solution, 50% and 51% fruit punch solution, and 50% and 51% alkaline water; and at 4 hours, 96% and 94% for lemon pudding, 91% and 88% for low-fat vanilla yogurt, 95% and 87% for applesauce, 97% and 88% for raspberry lemonade solution, 96% and 89% for fruit punch solution, and 92% and 87% for alkaline water. All tested vehicles met acceptance criteria with ON-SXB 4.5 g and 9 g.

Implications

Lemon pudding, low-fat vanilla yogurt, applesauce, raspberry lemonade solution, fruit punch solution, and alkaline water are viable reconstitution alternatives and maintain the drug dissolution characteristics of ON-SXB when compared to water. Flexibility in the administration of ON-SXB may improve narcolepsy management, enhance medication adherence, and support medication persistency.

目的：发作性睡病是一种以白天过度嗜睡（EDS）为特征的慢性神经系统疾病，可伴发或不伴发猝厥。每晚一次的氧酸钠（ON-SXB）被批准用于治疗7岁或以上发作性睡病患者的猝厥或EDS。ON-SXB含有立即释放和ph依赖性控释颗粒，可在水中重组，并在睡前口服一次。本研究评估了ON-SXB在软性食物和替代液体载体中与水相比较后的溶解情况。方法：将ON-SXB 4.5 g和9 g分别溶于软性食品（柠檬布丁、低脂香草酸奶和苹果酱）或液体载体（覆盆子柠檬水溶液、果汁饮料溶液和碱性水）中。密立q水作为对照。产品规格的验收标准分别要求在15分钟、2小时和4小时溶出度为40% ~ 60%、42% ~ 62%和≥80%。结果：ON-SXB分别为4.5 g和9 g， 15分钟的平均溶出度在柠檬布丁中分别为48%和45%，在低脂香草酸奶中分别为50%和50%，在苹果酱中分别为49%和48%，在覆盆子柠檬水溶液中分别为51%和50%，在果汁饮料溶液中分别为51%和51%，在碱性水中分别为49%和51%；2小时后，50%和51%的柠檬布丁，51%和50%的低脂香草酸奶，50%和49%的苹果酱，51%和51%的覆盆子柠檬水溶液，50%和51%的水果潘酒溶液，50%和51%的碱性水；4小时时，柠檬布丁96%和94%，低脂香草酸奶91%和88%，苹果酱95%和87%，覆盆子柠檬水97%和88%，果汁潘酒96%和89%，碱性水92%和87%。所有测试车辆均符合ON-SXB 4.5 g和9 g的验收标准。结论：与水相比，柠檬布丁、低脂香草酸奶、苹果酱、覆盆子柠檬水溶液、水果潘趣酒溶液和碱性水是可行的重构替代品，并保持ON-SXB的药物溶出特性。ON-SXB给药的灵活性可以改善发作性睡病的治疗，增强药物依从性，并支持药物的持久性。

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引用次数: 0

Efficacy and Safety of Direct Oral Anticoagulants in Patients After Heart Valve Replacement or Repair: A Systematic Review and Network Meta-Analysis 心脏瓣膜置换术或修复后直接口服抗凝剂的疗效和安全性：一项系统综述和网络meta分析。

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2025-11-01 DOI: 10.1016/j.clinthera.2025.08.017

Weiqi Gao , Zhijiao Zhang , Pengyan Jia , Lingjun Dong , Ruijuan Li , Juan Xu , Jingmin Zhang , Weihong Chen

Purpose

The optimal anticoagulation strategy following bioprosthetic heart valve replacement or valve repair remains controversial. Therefore, we conducted a meta-analysis to compare the efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with heart valve disease.

Methods

We searched PubMed, Cochrane Library, Embase, Web of Science, CNKI, and Wanfang for clinical studies comparing DOACs and VKAs in patients following bioprosthetic heart valve replacement or repair, up to November 1, 2023. The meta-analysis was conducted using RevMan 5.3 and Stata 17.0.

Findings

Thirty-three studies involving 59,660 individuals were included in the meta-analysis. Compared with VKAs, DOACs may reduce the risk of stroke or systemic embolism (risk ratios [RR] = 0.83, 95% confidence interval [CI] 0.75-0.93, P = 0.0007) and major bleeding (RR = 0.76, 95% CI 0.62-0.94, P = 0.009), while the risks of all-cause death and intracranial bleeding were similar. DOACs may increase the risk of gastrointestinal bleeding (RR = 1.42, 95% CI 1.04-1.95, P = 0.03). Twelve studies (4,789 patients) were included in a network meta-analysis. Indirect comparisons suggested rivaroxaban appears most favorable in reducing stroke or systemic embolism and major bleeding, though based on indirect evidence.

Implications

In patients following bioprosthetic heart valve replacement or repair, DOACs may reduce the risk of stroke or systemic embolism and major bleeding, but may increase gastrointestinal bleeding compared with VKAs. Among DOACs, rivaroxaban appears to be the optimal choice. These findings should be interpreted cautiously due to limited RCT evidence and incomplete drug-specific reporting.

目的：生物人工心脏瓣膜置换术或瓣膜修复后的最佳抗凝策略仍然存在争议。因此，我们进行了一项荟萃分析，比较直接口服抗凝剂（DOACs）和维生素K拮抗剂（VKAs）在心脏瓣膜疾病患者中的疗效和安全性。方法：我们检索PubMed、Cochrane Library、Embase、Web of Science、CNKI和万方，检索截至2023年11月1日比较生物人工心脏瓣膜置换术或修复后患者DOACs和vka的临床研究。meta分析采用RevMan 5.3和Stata 17.0进行。研究结果：meta分析包括33项研究，涉及59,660人。与vka相比，DOACs可降低卒中或全身性栓塞的风险（风险比[RR] = 0.83, 95%可信区间[CI] 0.75 ~ 0.93, P = 0.0007）和大出血的风险（RR = 0.76, 95% CI 0.62 ~ 0.94, P = 0.009），而全因死亡和颅内出血的风险相似。DOACs可能增加胃肠道出血的风险（RR = 1.42, 95% CI 1.04-1.95, P = 0.03）。12项研究（4789例患者）纳入网络荟萃分析。间接比较表明，利伐沙班在减少中风或全身栓塞和大出血方面最有利，尽管这是基于间接证据。意义：在生物人工心脏瓣膜置换术或修复后的患者中，doac可能降低中风或全身性栓塞和大出血的风险，但与vka相比，doac可能增加胃肠道出血。在doac中，利伐沙班似乎是最佳选择。由于有限的随机对照试验证据和不完整的药物特异性报告，这些发现应谨慎解释。

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引用次数: 0

Building Equitable Partnerships Between Industry Sponsors and Indigenous Communities to Enhance Engagement in Clinical Trials 在工业赞助商和土著社区之间建立公平的伙伴关系，以加强临床试验的参与。

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2025-11-01 DOI: 10.1016/j.clinthera.2025.08.013

Lancer Stephens , Nicole Redvers , Maile Taualii , Angela Cimino , Kasey Boynton , Allison Kelliher MD , Heather Angel Mars-Martins , Dean S. Seneca , Natalia Burgess , Jenny Garcia , Monique Adams

Introduction

American Indians, Alaska Natives, and Native Hawaiians (AI/AN/NH) have among the lowest representation in clinical trial participation in the United States (US) compared with other racial/ethnic groups and experience many barriers to health care access. To promote equitable and justice-centered inclusion of Indigenous Peoples in clinical trials and improve health equity, industry sponsors need to be better attuned to community-based priorities. This article summarizes perspectives including strategies to build more effective and equitable partnerships with Indigenous communities in the US and to advance access to medical care.

Methods

A panel of advisors on AI/AN/NH health care assembled for a virtual roundtable discussion in March 2024. A narrative review, supported by key publications, was conducted to summarize and contextualize the discussions.

Results

AI/AN/NH face various health inequities and challenges in clinical trial enrollment, including justified distrust of medical research environments, inaccessible and unaffordable health care, and limited community engagement by the research community. Proposed methods for engagement based on advisor insights were developed to guide industry sponsors in building more effective partnerships with Indigenous communities. Engagement methods consist of several strategies such as investing in community priorities, building a long-term commitment, identifying trusted messengers, and codeveloping engagement initiatives.

Conclusions

Current challenges regarding clinical trial diversity are impacting health outcomes among Indigenous Peoples, furthering disparities. Based on advisor engagement, establishing effective, equitable, and justice-centered partnerships between industry sponsors and Indigenous Peoples has the potential to result in community-driven priorities being recognized in clinical trials, and thus expanding benefit of medical innovation.

与其他种族/族裔群体相比，美洲印第安人、阿拉斯加原住民和夏威夷原住民（AI/AN/NH）在美国临床试验参与中的代表性最低，并且在获得医疗保健方面遇到许多障碍。为了促进以公平和正义为中心将土著人民纳入临床试验并改善卫生公平，行业发起人需要更好地适应以社区为基础的优先事项。本文总结了一些观点，包括与美国土著社区建立更有效和公平的伙伴关系以及促进获得医疗保健的战略。方法：AI/AN/NH卫生保健顾问小组于2024年3月召开虚拟圆桌会议讨论。在主要出版物的支持下，进行了一项叙述性审查，以总结和说明讨论的背景。结果：AI/AN/NH在临床试验招募方面面临各种卫生不公平和挑战，包括对医学研究环境的合理不信任，难以获得和负担不起的卫生保健，以及研究界的社区参与有限。提出了基于顾问见解的参与方法，以指导产业赞助者与土著社区建立更有效的伙伴关系。参与方法包括多种策略，如投资于社区优先事项、建立长期承诺、确定可信赖的信使以及共同制定参与计划。结论：目前关于临床试验多样性的挑战正在影响土著人民的健康结果，进一步扩大了差异。在顾问参与的基础上，在行业赞助商和土著人民之间建立有效、公平和以正义为中心的伙伴关系，有可能导致在临床试验中认识到社区驱动的优先事项，从而扩大医疗创新的效益。

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引用次数: 0

Advancing Decentralized and Pragmatic Clinical Trials as a Path Toward Improved Representativeness and Greater Generalizability of Clinical Trial Evidence 推进分散和实用的临床试验，以提高临床试验证据的代表性和更大的普遍性。

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2025-11-01 DOI: 10.1016/j.clinthera.2025.07.010

Caroline Marra PhD, MEM , Krisda H. Chaiyachati MPH, MSHP, MD , Vindell Washington MD , Amy P. Abernethy MD, PhD

Despite efforts to improve research equity in clinical trials, a lack of representativeness continues to threaten the generalizability of clinical trial evidence and leads to several ethical and economic consequences. Decentralized clinical trials (DCTs) and pragmatic clinical trials (PCTs), novel clinical trial models that use technology to enable alternative data collection methods and integrate studies into clinical care, hold great promise for addressing representativeness challenges but also face several limitations. Leveraging technology and clinical care settings to conduct trial visits and collect trial data inherently limits participation from people without reliable access to technology and consistent medical care. Further, representativeness needs to be improved across the full spectrum of clinical trials, from trials conducted in early product development phases to trials conducted after a product is approved, but the DCT and PCT elements that can improve representativeness are more likely to be deployed after seminal evidence for a new medical product’s regulatory approval has already been generated. We propose three solutions to help ensure the defining aspects of DCTs and PCTs increase representativeness and the generalizability of evidence generated in clinical trials conducted at all phases in the product lifecycle. We suggest that efforts should be centered around collaborative work with regulators to define data standards and validate outcomes when alternative data sources and collection methods are used, the creation of technical support resources and transparent processes for the conduct of trials facilitated by technology, and the incorporation of health equity principles into the design and deployment of technology-based tools used to facilitate DCTs and PCTs.

尽管努力提高临床试验的研究公平性，但缺乏代表性继续威胁着临床试验证据的普遍性，并导致一些伦理和经济后果。分散临床试验（dct）和实用临床试验（pct）是一种新型临床试验模式，利用技术实现替代数据收集方法并将研究整合到临床护理中，它们在解决代表性挑战方面前景广阔，但也面临一些局限性。利用技术和临床护理环境进行试验访问和收集试验数据，从本质上限制了无法获得可靠技术和一致医疗服务的人的参与。此外，从早期产品开发阶段进行的试验到产品获得批准后进行的试验，需要在整个临床试验范围内提高代表性，但可以提高代表性的DCT和PCT要素更有可能在新医疗产品获得监管部门批准的重要证据已经产生之后才被部署。我们提出了三种解决方案，以帮助确保dct和pct的定义方面增加代表性和在产品生命周期的所有阶段进行的临床试验中产生的证据的普遍性。我们建议，应集中努力与监管机构开展协作，以确定数据标准，并在使用替代数据源和收集方法时验证结果，为开展技术促进的试验创建技术支持资源和透明流程，并将卫生公平原则纳入用于促进dct和pct的基于技术的工具的设计和部署。

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引用次数: 0

Addressing Barriers to Inclusive Enrollment in Clinical Trials: Let’s Talk About It 解决临床试验中包容性招募的障碍：让我们谈谈。

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2025-11-01 DOI: 10.1016/j.clinthera.2025.09.016

Jill L. Maron MD, MPH

引用次数: 0