Clinical therapeutics最新文献

英文中文

Experimental Evidence of Dexamethasone in Reversing Endothelial Dysfunction in COVID-19: Therapeutic Insights from Intranasal Administration 地塞米松逆转COVID-19内皮功能障碍的实验证据：鼻内给药的治疗见解

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2026-01-01 DOI: 10.1016/j.clinthera.2025.11.005

Celeste Trejo-Moreno DSc , Marisol Méndez-Martínez DSc , Zimri A. Alvarado-Ojeda MSc , Sergio Sifontes-Rodríguez PhD , Jaquelynne Cervantes-Torres DSc , Raul J. Bobes DSc , Juan P. Laclette PhD , Edda Sciutto DSc , Gladis Fragoso DSc , Gabriela Rosas-Salgado DSc

Purpose

Vascular endothelial dysfunction (ED) plays a critical role in the pathogenesis of severe COVID-19. Intranasal dexamethasone (IN-DXM) has been reported to improve clinical outcomes more efficiently than intravenous (IV-DXM) administration in hospitalized patients. This study compared the efficacy of both regimens in improving ED.

Methods

Hospitalized COVID-19 patients from the REVIVAL trial received either intranasal dexamethasone (IN-DXM) via a MAD-Nasal device (0.12 mg/kg for 3 days followed by 0.06 mg/kg for 7 days; n = 10) or intravenous dexamethasone (IV-DXM; 6 mg/day for 10 days; n = 7). Respiratory and inflammatory parameters were analyzed before and 10 days after treatment. Serum levels of IL-6, malondialdehyde (MDA), and nitric oxide (NO) metabolites (nitrites) were quantified, along with their effects on human microvascular endothelial cells (HMEC-1) incubated with patient or control sera.

Findings

COVID-19 infection significantly increased IL-6 and MDA and reduced NO levels. Only IN-DXM significantly improved respiratory parameters (FiO₂, SatO₂, pO₂) and reduced serum IL-6. Both regimens decreased peripheral inflammatory markers (C-reactive protein, neutrophil-to-lymphocyte ratio and fibrinogen) and increased NO approaching control levels, improving the vascular function. Notably, only sera from IN-DXM–treated patients normalized IL-6 levels in HMEC-1 supernatants to those of controls. Regardless of the administration route, supernatants from HMEC-1 cells incubated with sera from treated patients showed decreased MDA and increased NO compared with those obtained before treatment.

Implications

The IN-DXM regimen produced greater improvement in respiratory and inflammatory parameters than IV-DXM, supporting its potential as a practical and effective alternative for managing severe COVID-19–associated endothelial dysfunction.

目的：血管内皮功能障碍（ED）在重症COVID-19的发病机制中起关键作用。据报道，在住院患者中，鼻内地塞米松（in - dxm）比静脉注射（IV-DXM）更有效地改善临床结果。方法：来自REVIVAL试验的住院COVID-19患者通过madd - nasal装置接受鼻内地塞米松（in - dxm）治疗（0.12 mg/kg，连续3天，随后0.06 mg/kg，连续7天，n = 10）或静脉内地塞米松（IV-DXM， 6 mg/天，连续10天，n = 7）。分析治疗前和治疗后10天的呼吸和炎症参数。定量血清中IL-6、丙二醛（MDA）和一氧化氮（NO）代谢物（亚硝酸盐）的水平，以及它们对患者或对照血清培养的人微血管内皮细胞（HMEC-1）的影响。结果：COVID-19感染显著升高IL-6和MDA水平，降低NO水平。只有IN-DXM能显著改善呼吸参数（FiO₂、SatO₂、pO₂）和降低血清IL-6。两种方案都降低了外周炎症标志物（c反应蛋白、中性粒细胞与淋巴细胞的比率和纤维蛋白原），并使NO升高至接近控制水平，从而改善了血管功能。值得注意的是，只有接受in - ddxm治疗的患者血清中HMEC-1上清液中的IL-6水平高于对照组。无论给药途径如何，与治疗前相比，HMEC-1细胞与治疗患者血清孵育的上清液显示MDA降低，NO升高。意义：in - dxm方案比IV-DXM方案在呼吸和炎症参数方面产生了更大的改善，支持其作为治疗严重covid -19相关内皮功能障碍的实用有效替代方案的潜力。

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引用次数: 0

What is a “Cannabis User”? 什么是“大麻使用者”？

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2026-01-01 DOI: 10.1016/j.clinthera.2025.11.003

Ruth Fisher PhD

Purpose

The increasing legalization and use of cannabis necessitate robust, standardized methods for identifying and characterizing cannabis users in research and clinical settings. Variability in user demographics, consumption patterns, and product types complicates comparisons across studies, hindering the development of evidence-based policies and interventions. This commentary aims to highlight the need for urgent development and adoption of uniform methodologies to enhance the reliability and generalizability of cannabis-related research.

Methods

A review was conducted of correlational studies on outcomes associated with cannabis use to assess methods for identifying and characterizing cannabis users in study populations. Gaps in standardization were identified through comparisons of survey tools, self-report measures, health records, and biochemical assays. A review of existing frameworks for characterizing cannabis use was conducted.

Findings

Current methods lack consistency in defining key variables such as “occasional use” or “heavy use” (ranging from monthly to weekly to daily); they fail to capture sufficient nuance in cannabis use patterns, such as lifetime patterns of use, form (eg, flower, concentrate, edibles), dose, and content (eg, THC, CBD) of use; and they fail to identify cannabis users, due to self-report biases, lack of health codes for general cannabis use, and inaccuracies in biological tests. A standardized framework, including the development of validated, easy-to-administer surveys, together with the assurance that study participants are safe from repercussions associated with honestly reporting cannabis use, could address these issues.

Implications

Standardized methods would improve the comparability of cannabis research, enabling meta-analyses and longitudinal studies to inform public health strategies. Consistent user characterization could guide clinical practices, such as tailored interventions for dependence or therapeutic use. Policymakers would benefit from reliable data to shape regulations. There is an urgency for collaborative efforts to develop and adopt global standards for identifying and characterizing cannabis users.

目的：大麻的日益合法化和使用需要强有力的、标准化的方法，以便在研究和临床环境中识别和确定大麻使用者的特征。用户人口统计、消费模式和产品类型的差异使研究间的比较复杂化，阻碍了基于证据的政策和干预措施的制定。本评论旨在强调迫切需要发展和采用统一的方法，以提高大麻相关研究的可靠性和普遍性。方法：对大麻使用相关结果的相关研究进行了回顾，以评估在研究人群中识别和描述大麻使用者的方法。通过比较调查工具、自我报告措施、健康记录和生化分析，确定了标准化方面的差距。对大麻使用特征的现有框架进行了审查。发现：目前的方法在定义关键变量(如“偶尔使用”或“大量使用”（从每月到每周到每天）方面缺乏一致性；未能充分把握大麻使用模式的细微差别，例如终身使用模式、使用形式（如花、浓缩物、可食用）、剂量和含量（如四氢大麻酚、CBD）；由于自我报告的偏见、缺乏一般大麻使用的健康代码以及生物测试的不准确性，它们无法识别大麻使用者。一个标准化的框架，包括制定有效的、易于管理的调查，以及确保研究参与者不会因诚实报告大麻使用而受到影响，可以解决这些问题。影响：标准化方法将提高大麻研究的可比性，使荟萃分析和纵向研究能够为公共卫生战略提供信息。一致的用户特征可以指导临床实践，例如针对依赖或治疗使用量身定制的干预措施。决策者将受益于可靠的数据来制定法规。迫切需要开展合作，制定和采用全球标准，以确定大麻使用者的身份和特征。

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引用次数: 0

Recognizing Arthralgia as a Potential Adverse Effect of CFTR Modulators: A Case Report 认识到关节痛是CFTR调节剂的潜在不良影响：一个病例报告。

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2026-01-01 DOI: 10.1016/j.clinthera.2025.11.007

Flora Charbonneau Pharm , Magali Dupuy-Grasset MD , Jeanne Languepin MD , Marie-Laure Laroche MD, PhD

引用次数: 0

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2026-01-01

引用次数: 0

Medical Cannabis Formulations, Administration Routes, and Dosing: Perspectives of Patients With Cancer Who Consume 医用大麻制剂，管理路线和剂量：癌症患者消费的观点。

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2026-01-01 DOI: 10.1016/j.clinthera.2025.11.004

Manan M. Nayak PhD, MA , Peter R. Chai MD, MS , Stephanie Tung MD , Anna Revette PhD , Ilana M. Braun MD

Purpose

Medical cannabis (MC) is used by 1 in 3 patients with cancer. Scientific work suggests a disconnect between patients’ cannabis therapeutics practices and oncologists’ clinical preferences. This qualitative study explores the preferences of patients with cancer as they relate to MC formulations, administration routes, and dosing.

Methods

Semistructured interviews were conducted with patients with cancer consuming MC in 8 states and examined using thematic analysis.

Findings

Among study participants (N = 24), the mean age was 54 years, 67% were female, and 51% had metastatic disease. A powerful theme identified across interviews was of myriad MC dispensary product formulations, triggering astonishment and burden. Common strategies among participants included purchasing and sampling multiple store-bought formulations, modifying dispensary products, and altering intended routes of administration. Preferred dispensary products were not consistently available. Top-cited modes of administration included oral, followed by topical, sublingual, vaporization, combustion, and rectal suppository. Three-quarters of participants alternated between modes. Medical cannabis dosing imprecision represented another powerful theme due to the lack of dispensary quality assurance and accuracy in home measurements.

Implications

This investigation suggests that MC preparations, dosing, and administration routes vary among patients with cancer, and that common consumption patterns (for instance, reliance on multiple routes of cannabis administration) are not rooted in science. Although these findings should be further interrogated, they suggest a need for lay-facing cannabis therapeutics education and standardization of dispensary products to strengthen cannabis-related care.

目的：三分之一的癌症患者使用医用大麻。科学研究表明，患者的大麻治疗实践与肿瘤学家的临床偏好之间存在脱节。本定性研究探讨了癌症患者对MC配方、给药途径和剂量的偏好。方法：对8个州的癌症患者进行半结构化访谈，并采用主题分析进行检验。结果：在研究参与者（N = 24）中，平均年龄为54岁，67%为女性，51%患有转移性疾病。采访中发现的一个强有力的主题是无数MC药房产品配方，引发惊讶和负担。参与者的共同策略包括购买和抽样多种商店购买的配方，修改药房产品，以及改变预期的管理途径。首选的药房产品并不总是可用的。引用最多的给药方式包括口服，其次是局部、舌下、汽化、燃烧和直肠栓剂。四分之三的参与者在两种模式之间交替。由于药房缺乏质量保证和家庭测量的准确性，医用大麻剂量不精确是另一个强有力的主题。含义：这项调查表明，MC制剂、剂量和给药途径因癌症患者而异，常见的消费模式（例如，依赖多种大麻给药途径）没有科学依据。尽管这些发现还有待进一步研究，但它们表明，有必要开展面向普通人群的大麻治疗学教育和药房产品的标准化，以加强大麻相关护理。

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引用次数: 0

Exposure to Budesonide, Glycopyrronium, and Formoterol With a Next-Generation Propellant Does Not Exceed Exposure With Hydrofluoroalkane-134a Propellant When Administered Via Pressurized Metered-Dose Inhaler With a Spacer 通过带间隔剂的加压计量吸入器给药时，布地奈德、甘溴铵和福莫特罗与下一代推进剂的暴露不超过与氢氟烷烃-134a推进剂的暴露。

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2026-01-01 DOI: 10.1016/j.clinthera.2025.10.011

Hitesh Pandya MBChB, MD , Mehul Patel MBBS, PhD, FRCP , Michael Gillen BS, PhD , Jitendar Reddy MPharm , Artur Bednarczyk MD , Marek Kokot MD, MBA , Yubo Tan MSc , Maria Heijer MSc , Magdalena Andersson MSc, MSBA , David Petullo MSc , Mandeep Jassal MD

Purpose

Hydrofluoroalkane-134a (HFA-134a), the propellant in the marketed budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) formulation, has a global warming potential (GWP) that falls above environmental regulation thresholds and therefore will be phased out. With global efforts to minimize carbon emissions, the hydrofluoroolefin-1234ze (HFO-1234ze) propellant, with a >99% lower GWP than HFA-134a, is in development for pressurized metered-dose inhalers (pMDIs). Spacers support drug delivery in patients with poor pMDI inhalation technique, but it is unknown if BGF exposure with HFO-1234ze exceeds that observed with HFA-134a when using a spacer.

Methods

This Phase I study assessed systemic BGF component exposure with HFO-1234ze versus HFA-134a when using a spacer, and for HFO-1234ze with and without a spacer. Participants (N = 42) were randomized to BGF with HFA-134a with a spacer (reference), HFO-1234ze with a spacer (test), and HFO-1234ze without a spacer (descriptive treatment) over 3 treatment periods in 1 of 6 sequences. As spacer devices help to increase exposure, the upper limit of the 90% confidence interval (CI) of geometric mean ratios (GMRs) was of interest, and bioequivalence was not included as a study objective.

Findings

Analyses demonstrated the upper 90% CI of the GMRs for maximum observed plasma concentration (Cmax) and area under the plasma concentration curve from time zero to the time of the last quantifiable concentration (AUClast) were <125% for all BGF components for HFO-1234ze versus HFA-134a when using a spacer, indicating exposure with HFO-1234ze did not exceed exposure with HFA-134a. Additionally, Cmax was increased for all BGF components with HFO-1234ze when using versus not using a spacer, with the largest increases observed among participants with the lowest exposure when not using a spacer, likely due to poor inhalation technique. No new safety findings, and no deaths or serious adverse events, occurred during the study.

Implications

These findings provide evidence that may help to support the future use of HFO-1234ze propellant in BGF pMDIs.

目的：已上市布地奈德/甘溴铵/富马酸福莫特罗二水合物（BGF）制剂中的推进剂氢氟烷烃-134a （HFA-134a）具有高于环境法规阈值的全球变暖潜能值（GWP），因此将被逐步淘汰。随着全球努力减少碳排放，正在开发用于加压计量吸入器（pmdi）的氢氟烯烃-1234ze （HFO-1234ze）推进剂，其全球升温潜能值比HFA-134a低约99%。在pMDI吸入技术不佳的患者中，隔离剂支持给药，但尚不清楚使用隔离剂时，HFO-1234ze是否会超过HFA-134a所观察到的BGF暴露量。方法：本I期研究评估了使用间隔剂时HFO-1234ze与HFA-134a的全身BGF成分暴露，以及使用和不使用间隔剂的HFO-1234ze。参与者（N = 42）被随机分为含有HFA-134a和间隔物的BGF组（参考组）、含有间隔物的HFO-1234ze组（测试组）和不含间隔物的HFO-1234ze组（描述性组），在6个序列中的1个治疗期间进行3次治疗。由于间隔装置有助于增加暴露，几何平均比率（GMRs）的90%置信区间（CI）的上限值得关注，生物等效性未被纳入研究目标。研究结果：分析表明，最大观察到的血浆浓度（Cmax）的gmr的上90% CI和从时间0到最后可量化浓度（AUClast）的血浆浓度曲线下面积是有意义的：这些发现提供了证据，可能有助于支持HFO-1234ze推进剂在BGF pmdi中的未来使用。

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IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2026-01-01

引用次数: 0

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2026-01-01

引用次数: 0

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2026-01-01

引用次数: 0

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics

Pub Date : 2026-01-01

引用次数: 0

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