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Impact of Renal Impairment on the Pharmacodynamic and Pharmacokinetic Profiles of Epaminurad, a Novel Uric Acid Transporter 1 Inhibitor 肾功能损害对新型尿酸转运蛋白1抑制剂依米努拉德药效学和药代动力学的影响
IF 3.1 3区 医学
Cts-Clinical and Translational Science Pub Date : 2025-06-13 DOI: 10.1111/cts.70266
Seo Yeong Park, Jun Gi Hwang, Sung Kweon Cho, Min Kyu Park
{"title":"Impact of Renal Impairment on the Pharmacodynamic and Pharmacokinetic Profiles of Epaminurad, a Novel Uric Acid Transporter 1 Inhibitor","authors":"Seo Yeong Park,&nbsp;Jun Gi Hwang,&nbsp;Sung Kweon Cho,&nbsp;Min Kyu Park","doi":"10.1111/cts.70266","DOIUrl":"https://doi.org/10.1111/cts.70266","url":null,"abstract":"<p>Epaminurad, a novel uricosuric agent, exhibits potent inhibitory activity against the human uric acid transporter. This study aimed to investigate the effects of renal function and food intake on the pharmacokinetic, pharmacodynamic, and safety characteristics of 9 mg epaminurad. This study was designed as a phase 1, partially randomized, open-label, oral administration, partial crossover trial. Participants were assigned to three groups based on renal function: normal (Group 1), moderate renal impairment classified as Stage 3a (Group 2) and Stage 3b (Group 3). Each group aimed to enroll 6–10 participants. Blood and urine samples were collected to evaluate the pharmacokinetics and pharmacodynamics of epaminurad. Safety assessments were also conducted throughout the study. A total of 27 participants completed the study, including 12 with normal renal function (Group 1) and 9 and 6 participants with moderate renal impairment (Groups 2 and 3), respectively. When a single 9 mg dose of epaminurad was administered under fasted conditions, the pharmacokinetic, pharmacodynamic, and safety profiles did not show clear differences among the renal function groups. Furthermore, no notable differences were observed in these profiles between the fasted and fed states. Patients with moderate renal impairment can receive (eGFR of 30–59 mL/min/1.73 m<sup>2</sup>) 9 mg epaminurad without dose adjustment, and the drug may be administered regardless of food intake.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity Profiles of a Single-Dose JYB1904 in Healthy Chinese Participants: A Phase Ia, Randomized, Double-Blind, Placebo-Controlled Study 单剂量JYB1904在中国健康受试者中的安全性、耐受性、药代动力学、药效学和免疫原性:一项随机、双盲、安慰剂对照的Ia期研究
IF 3.1 3区 医学
Cts-Clinical and Translational Science Pub Date : 2025-06-12 DOI: 10.1111/cts.70264
Zhen-Wei Shen, Ting-Han Jin, Kai-Qi Wu, Jie Zhao, Qi Jiang, Tong Guo, Liang Li, Xiao-Hua Feng, Pei-pei Liu, Gui-Ling Chen
{"title":"Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity Profiles of a Single-Dose JYB1904 in Healthy Chinese Participants: A Phase Ia, Randomized, Double-Blind, Placebo-Controlled Study","authors":"Zhen-Wei Shen,&nbsp;Ting-Han Jin,&nbsp;Kai-Qi Wu,&nbsp;Jie Zhao,&nbsp;Qi Jiang,&nbsp;Tong Guo,&nbsp;Liang Li,&nbsp;Xiao-Hua Feng,&nbsp;Pei-pei Liu,&nbsp;Gui-Ling Chen","doi":"10.1111/cts.70264","DOIUrl":"https://doi.org/10.1111/cts.70264","url":null,"abstract":"<p>Allergic asthma, characterized by airborne allergen sensitivity and Th2 immune responses, is a common and increasing global health concern. Omalizumab, while effective, has limitations such as weight- and IgE-dependent dosing regimens. JYB1904, a recombinant anti-IgE humanized monoclonal antibody (IgG1 subtype), showed superior preclinical properties. We performed a single-center, randomized, double-blind, placebo-controlled, single ascending-dose phase Ia trial to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of JYB1904 in healthy adult participants across five dose levels (range: 75–600 mg; subcutaneously). JYB1904 was well tolerated, with no serious adverse events or safety concerns beyond those observed with omalizumab. Immunogenicity risk was low. PK analysis revealed approximately dose-proportional parameters and an extended half-life (2.5 times that of omalizumab). PD results showed significant free IgE suppression, with JYB1904 demonstrating stronger activity than omalizumab at equivalent doses. JYB1904 offers promising clinical advantages over omalizumab, including extended dosing intervals and enhanced efficacy, warranting further investigation for allergic asthma treatment.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Risk of Thrombocytopenia by SSRIs or SNRIs in Patients With Depression Based on MID-NET: A Cohort Study in Japan 基于MID-NET的抑郁症患者服用SSRIs或SNRIs的血小板减少风险:日本的一项队列研究
IF 3.1 3区 医学
Cts-Clinical and Translational Science Pub Date : 2025-06-06 DOI: 10.1111/cts.70268
Yusuke Okada, Kazuhiro Kajiyama, Maki Komamine, Takashi Ando, Tomoaki Hasegawa, Chieko Ishiguro, Takahiro Nonaka, Mariko Tsukuda, Yukari Iwasaki, Takahiro Ueda, Naoya Horiuchi, Toyotaka Iguchi, Yoshiaki Uyama
{"title":"Risk of Thrombocytopenia by SSRIs or SNRIs in Patients With Depression Based on MID-NET: A Cohort Study in Japan","authors":"Yusuke Okada,&nbsp;Kazuhiro Kajiyama,&nbsp;Maki Komamine,&nbsp;Takashi Ando,&nbsp;Tomoaki Hasegawa,&nbsp;Chieko Ishiguro,&nbsp;Takahiro Nonaka,&nbsp;Mariko Tsukuda,&nbsp;Yukari Iwasaki,&nbsp;Takahiro Ueda,&nbsp;Naoya Horiuchi,&nbsp;Toyotaka Iguchi,&nbsp;Yoshiaki Uyama","doi":"10.1111/cts.70268","DOIUrl":"https://doi.org/10.1111/cts.70268","url":null,"abstract":"<p>Risk assessment on thrombocytopenia by selective serotonin reuptake inhibitors (SSRIs) or serotonin noradrenaline reuptake inhibitors (SNRIs) is limited. An observational study with cohort design was conducted based on the MID-NET for evaluating the risk of thrombocytopenia by SSRIs and SNRIs in patients with depression compared to paroxetine. The exposure group was categorized as each drug of SSRIs/SNRIs, SSRIs group (escitalopram, sertraline, fluvoxamine), SNRIs group (duloxetine, venlafaxine, milnacipran), or vortioxetine. We estimated the adjusted hazard ratio (aHR) of each drug compared to paroxetine for the risk of thrombocytopenia (platelet count &lt; 100,000/mm<sup>3</sup>). More severe definitions were used in sensitivity analyses. In all, 4759 patients (median age: 49 years; 31.6% male) on SSRIs, 3440 patients (62 years; 38.6% male) on SNRIs, 12 patients (42.5 years; less than 83.4% male) on vortioxetine, and 2196 patients on paroxetine (62 years; 33.2% male) were included for analysis. Compared with paroxetine, the aHRs (95% confidence interval) of SSRIs group and SNRIs group were 1.14 (0.76–1.70) and 0.77 (0.48–1.21), respectively. Among SSRIs, sertraline and fluvoxamine showed a relatively higher point estimate of aHR &gt; 1.0 (1.23 [95% confidence interval: 0.78–1.94] and 1.48 [0.87–2.51], respectively). The consistent results were also observed in the sensitivity analyses. The results suggest that the risk of thrombocytopenia by sertraline or fluvoxamine was comparable to that by paroxetine, known as having the risk of thrombocytopenia, leading to the revision of the sertraline package insert as a regulatory safety measure. Prescribers and clinicians may need to be vigilant to the possibility of sertraline-induced thrombocytopenia in clinical practice.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CD20×CD3 Bispecific Antibodies in B-NHL: A Review of Translational Science, Pharmacokinetics, Pharmacodynamics, and Dose Strategy in Clinical Research CD20×CD3 B-NHL中的双特异性抗体:临床研究中的转化科学、药代动力学、药效学和剂量策略综述
IF 3.1 3区 医学
Cts-Clinical and Translational Science Pub Date : 2025-06-05 DOI: 10.1111/cts.70250
Min Zhu, Xiaowen Guan, Samit Ganguly, Erik Welf, John D. Davis
{"title":"CD20×CD3 Bispecific Antibodies in B-NHL: A Review of Translational Science, Pharmacokinetics, Pharmacodynamics, and Dose Strategy in Clinical Research","authors":"Min Zhu,&nbsp;Xiaowen Guan,&nbsp;Samit Ganguly,&nbsp;Erik Welf,&nbsp;John D. Davis","doi":"10.1111/cts.70250","DOIUrl":"https://doi.org/10.1111/cts.70250","url":null,"abstract":"<p>Despite advancements in treatment for B-cell non-Hodgkin lymphoma (B-NHL) in recent decades, many patients still relapse or are refractory to treatment, which represents a high unmet medical need. Novel CD20 × CD3 T-cell–engaging bispecific antibodies (bsAbs) have created a new paradigm for the treatment of B-NHL. Pivotal studies of four CD20 × CD3 bsAbs, mosunetuzumab, glofitamab, epcoritamab, and odronextamab, as monotherapy, have demonstrated robust responses with generally manageable safety profiles in patients with relapsed or refractory follicular lymphoma and diffuse large B-cell lymphoma after ≥ 2 lines of systemic therapy. These agents have presented unique challenges (e.g., cytokine release syndrome [CRS]), which have required different strategies to overcome. This review provides a comprehensive overview of the clinical development of these four CD20 × CD3 bsAbs that have been investigated for the treatment of B-NHL, with a specific focus on translational assessments to select starting doses in first-in-human studies, management of CRS, application of modeling and simulation approaches to aid dose escalation and optimization/selection, and strategies used in the design of phase I–III clinical trials. By highlighting learnings and experiences from these four bsAbs assessed, which have not been summarized collectively elsewhere, we aim to promote more efficient study design for novel bsAbs in B-NHL in the future.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrating Personal Health Records to Improve Data Integrity in Trials With Decentralized Elements: A Pilot Study 整合个人健康记录以提高分散要素试验中的数据完整性:一项试点研究
IF 3.1 3区 医学
Cts-Clinical and Translational Science Pub Date : 2025-06-05 DOI: 10.1111/cts.70267
Yoonjin Kim, Ki Young Huh, Kyung-Sang Yu
{"title":"Integrating Personal Health Records to Improve Data Integrity in Trials With Decentralized Elements: A Pilot Study","authors":"Yoonjin Kim,&nbsp;Ki Young Huh,&nbsp;Kyung-Sang Yu","doi":"10.1111/cts.70267","DOIUrl":"https://doi.org/10.1111/cts.70267","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Data integrity has long been a challenge in decentralized trials compared to traditional site-based trials. One key area impacted by these challenges is eligibility assessment, which is critical in clinical trials but often limited in depth during remote screening procedures. Integrating personal health records may help address this issue. This randomized, open-label, single-center, fully remote study evaluated the feasibility of using personal health records for eligibility assessment in 20 healthy Korean adults. During initial screening interviews, most participants reported being healthy with no significant medical history or prior medication use. However, after reviewing their personal health records, including their past 2-year health check-ups and recent 3-month prescription records, medical histories were revealed for 9 participants (45.0%, 17 cases), and 10 (50.0%, 68 cases) showed prior medication use. These findings suggest that personal health record-based interviews could substantially improve data integrity in eligibility assessments. In addition, the study incorporated various decentralized elements, such as electronic consent acquisition, self-recorded diary submission, smartwatch-based AI system for drug administration monitoring, and digital reporting of adverse events and concomitant medications. While compliance was generally adequate and participants reported high satisfaction, some experienced challenges retrieving personal health records and using the smartwatch, highlighting digital accessibility as a barrier in decentralized trials. Receiving and returning research materials through the parcel and blood sampling process at local hospitals also received high ratings, but this high score reflects Korea's unique infrastructure, including extensive delivery systems and accessible local hospitals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>KCT0009827.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comprehensive Characterization of Antidepressant Pharmacogenetics: A Systematic Review of Studies in Major Depressive Disorder 抗抑郁药物遗传学的综合表征:对重度抑郁症研究的系统回顾
IF 3.1 3区 医学
Cts-Clinical and Translational Science Pub Date : 2025-06-04 DOI: 10.1111/cts.70255
Caroline W. Grant, Karina Delaney, Linsey E. Jackson, Justin Bobo, Leslie C. Hassett, Liewei Wang, Richard M. Weinshilboum, Paul E. Croarkin, Melanie T. Gentry, Ann M. Moyer, Arjun P. Athreya
{"title":"Comprehensive Characterization of Antidepressant Pharmacogenetics: A Systematic Review of Studies in Major Depressive Disorder","authors":"Caroline W. Grant,&nbsp;Karina Delaney,&nbsp;Linsey E. Jackson,&nbsp;Justin Bobo,&nbsp;Leslie C. Hassett,&nbsp;Liewei Wang,&nbsp;Richard M. Weinshilboum,&nbsp;Paul E. Croarkin,&nbsp;Melanie T. Gentry,&nbsp;Ann M. Moyer,&nbsp;Arjun P. Athreya","doi":"10.1111/cts.70255","DOIUrl":"https://doi.org/10.1111/cts.70255","url":null,"abstract":"<p>Pharmacogenetics is a promising strategy to facilitate individualized care for patients with Major Depressive Disorder (MDD). Research is ongoing to identify the optimal genetic markers for predicting outcomes to antidepressant therapies. The primary aim of this systematic review was to summarize antidepressant pharmacogenetic studies to enhance understanding of the genes, variants, datatypes/methodologies, and outcomes investigated in the context of MDD. The secondary aim was to identify clinical genetic panels indicated for antidepressant prescribing and summarize their genes and variants. Screening of <i>N</i> = 5793 articles yielded <i>N</i> = 390 for inclusion, largely comprising adult (≥ 18 years) populations. Top-studied variants identified in the search were discussed and compared with those represented on the <i>N</i> = 34 clinical genetic panels that were identified. Summarization of articles revealed sources of heterogeneity across studies and low rates of replicability of pharmacogenetic associations. Heterogeneity was present in outcome definitions, treatment regimens, and differential inclusion of mediating variables in analyses. Efficacy outcomes (i.e., response, remission) were studied at greater frequency than adverse-event outcomes. Studies that used advanced analytical approaches, such as machine learning, to integrate variants with complimentary biological datatypes were fewer in number but achieved higher rates of significant associations with treatment outcomes than candidate variant approaches. As large biological datasets become more prevalent, machine learning will be an increasingly valuable tool for parsing the complexity of antidepressant response. This review provides valuable context and considerations surrounding pharmacogenetic associations in MDD which will help inform future research and translation efforts for guiding antidepressant care.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70255","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144213918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prevalence of OATP1B-Mediated Drug–Drug Interactions in an Academic Medical Center 某学术医疗中心oatp1b介导的药物-药物相互作用的患病率
IF 3.1 3区 医学
Cts-Clinical and Translational Science Pub Date : 2025-06-04 DOI: 10.1111/cts.70260
Mathilde Bories, David Malnoë, Pascal Le Corre
{"title":"Prevalence of OATP1B-Mediated Drug–Drug Interactions in an Academic Medical Center","authors":"Mathilde Bories,&nbsp;David Malnoë,&nbsp;Pascal Le Corre","doi":"10.1111/cts.70260","DOIUrl":"https://doi.org/10.1111/cts.70260","url":null,"abstract":"<p>OATP1B is a key transporter involved in hepatic drug uptake, where its inhibition can significantly increase plasma drug levels, leading to potential adverse effects. This retrospective study aimed to determine the prevalence of potential drug–drug interactions (pDDIs) mediated by the hepatic transporter OATP1B1/3 in a cohort of 44,877 patients hospitalized at Rennes Academic Medical Center, using data from the Clinical Data Warehouse. We analyzed prescription rates of OATP1B substrates and inhibitors and estimated the prevalence of pDDIs, assessed the consistency of pDDI identification across different drug interaction databases, and performed a literature review of identified OATP1B-based pDDIs. The identification of pDDIs across different drug databases showed inconsistencies, with limited overlap and variability in reported interactions. Among hospitalized patients, 6954 (15.5%) received OATP1B substrates, while 408 (0.9%) received inhibitors, leading to 106 pDDIs observed in 99 patients (0.2%). The pDDI rate varied significantly depending on the inhibitor used, reaching up to 39.1% in patients treated with ciclosporin. Statins accounted for a large proportion of pDDIs, emphasizing the potential risks, especially in multidrug regimens. Commonly involved inhibitors included FDA drugs such as ciclosporin, clarithromycin, and rifampicin. The clinical relevance of these interactions remains uncertain due to the limited availability of supporting evidence and the restricted list of well-characterized OATP1B substrates and inhibitors. This study highlights the complexity of OATP1B-mediated pDDIs and the need for increased clinical awareness and further research to improve the detection and characterization of such pDDIs, particularly for high-risk drugs with a narrow therapeutic index.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70260","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144213919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Large-Scale Analysis of Age and Sex Effects on Corrected QT and JT Intervals: Insights From Hospital-Based Controls and Moxifloxacin-Treated Cases 年龄和性别对校正QT间期和JT间期影响的大规模分析:来自医院对照和莫西沙星治疗病例的见解
IF 3.1 3区 医学
Cts-Clinical and Translational Science Pub Date : 2025-06-01 DOI: 10.1111/cts.70263
Eunwoo Kim, Hyun Young Lee, Young-Min Ye, Anhye Kim
{"title":"Large-Scale Analysis of Age and Sex Effects on Corrected QT and JT Intervals: Insights From Hospital-Based Controls and Moxifloxacin-Treated Cases","authors":"Eunwoo Kim,&nbsp;Hyun Young Lee,&nbsp;Young-Min Ye,&nbsp;Anhye Kim","doi":"10.1111/cts.70263","DOIUrl":"https://doi.org/10.1111/cts.70263","url":null,"abstract":"<p>The corrected QT (QTc) interval is a critical marker for assessing proarrhythmic potential in drug development, while the corrected JT (JTc) interval provides specific insight into ventricular repolarization. This study quantitatively analyzed the relationships of QTc and JTc intervals with age and sex utilizing a large real-world dataset of hospital-based controls and moxifloxacin-treated patients. This retrospective study analyzed 1,039,550 electrocardiograms and associated clinical data extracted from a previously constructed electrocardiogram database, categorizing cases as hospital-based controls (<i>n</i> = 119,882) or moxifloxacin-treated (<i>n</i> = 1586) based on predefined criteria. We observed a general trend of QTc and JTc interval prolongation with age in both groups, with moxifloxacin-treated cases showing longer QTc and JTc intervals than hospital-based controls. Multiple linear regression analysis indicated that in hospital-based controls, QTc and JTc intervals increased with age, with males exhibiting shorter intervals than females. Meanwhile, in moxifloxacin-treated cases, QTc and JTc intervals showed similar age-dependent increases, although no significant sex differences were observed in the QTc interval. Therefore, this study quantified the effects of age and sex on QTc and JTc intervals in hospital-based controls and highlighted similar age-related trends in moxifloxacin-treated cases, underscoring the relevance of age and sex as key factors in interpreting QTc and JTc intervals across diverse clinical contexts.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PTPN2 and Leukopenia in Individuals With Normal TPMT and NUDT15 Metabolizer Status Taking Azathioprine 服用硫唑嘌呤后TPMT和NUDT15代谢正常个体的PTPN2和白细胞减少
IF 3.1 3区 医学
Cts-Clinical and Translational Science Pub Date : 2025-05-29 DOI: 10.1111/cts.70220
Laura L. Daniel, Puran Nepal, Jacy Zanussi, Alyson L. Dickson, Peter Straub, Tyne W. Miller-Fleming, Wei-Qi Wei, Adriana M. Hung, Nancy J. Cox, Vivian K. Kawai, Jonathan D. Mosley, Charles Michael Stein, QiPing Feng, Ge Liu, Ran Tao, Cecilia P. Chung
{"title":"PTPN2 and Leukopenia in Individuals With Normal TPMT and NUDT15 Metabolizer Status Taking Azathioprine","authors":"Laura L. Daniel,&nbsp;Puran Nepal,&nbsp;Jacy Zanussi,&nbsp;Alyson L. Dickson,&nbsp;Peter Straub,&nbsp;Tyne W. Miller-Fleming,&nbsp;Wei-Qi Wei,&nbsp;Adriana M. Hung,&nbsp;Nancy J. Cox,&nbsp;Vivian K. Kawai,&nbsp;Jonathan D. Mosley,&nbsp;Charles Michael Stein,&nbsp;QiPing Feng,&nbsp;Ge Liu,&nbsp;Ran Tao,&nbsp;Cecilia P. Chung","doi":"10.1111/cts.70220","DOIUrl":"https://doi.org/10.1111/cts.70220","url":null,"abstract":"<p>Leukopenia is a common dose-dependent side effect of azathioprine, often leading to drug discontinuation. Variants in <i>TPMT</i> and <i>NUDT15</i> are associated with azathioprine-induced leukopenia but only explain 25% of cases. Thus, we aimed to identify novel genetic risk factors among TPMT and NUDT15 normal metabolizers through a genome-wide association study (GWAS). Using BioVU, Vanderbilt's electronic health record linked to genetic data, we assembled a discovery cohort of new users of azathioprine. The analysis was conducted in 1184 new users of azathioprine who had no history of prior thiopurine use or an organ transplant. A replication cohort of 521 patients was derived from <i>All of Us</i>, an NIH-funded project that links healthcare data and genetics. The GWAS was adjusted for sex, age, indication (inflammatory bowel disease, systemic lupus erythematosus, other autoimmune condition, or unknown), concurrent use of xanthine oxidase inhibitors (allopurinol or febuxostat) or immunosuppressants, prior <i>TPMT</i> or <i>NUDT15</i> testing, and 10 principal components of ancestry. In BioVU, 65% of patients were female with a median age of 44 [IQR: 30, 57] and 125 patients developed leukopenia. In <i>All of Us,</i> 69% were female with a median age of 51 [36, 61], and 44 patients developed leukopenia. An intronic variant in <i>PTPN2</i>, rs11664064, reached genome-wide significance in BioVU (OR = 3.61; <i>p</i> = 1.96E-8) and replicated in <i>All of Us</i> (OR = 2.42, <i>p</i> = 0.039). Our finding suggests an association between rs11664064 in <i>PTPN2</i> and azathioprine-induced leukopenia. <i>PTPN2</i> plays a role in immune cell development and differentiation, providing a plausible mechanism for this association.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70220","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
GLP-1 Agonists for Pediatric Psychopharmacology: Opportunities and Cautions GLP-1激动剂用于儿童精神药理学:机会和注意事项
IF 3.1 3区 医学
Cts-Clinical and Translational Science Pub Date : 2025-05-28 DOI: 10.1111/cts.70262
Michael Bartkoski, Ethan A. Poweleit, Stephani L. Stancil
{"title":"GLP-1 Agonists for Pediatric Psychopharmacology: Opportunities and Cautions","authors":"Michael Bartkoski,&nbsp;Ethan A. Poweleit,&nbsp;Stephani L. Stancil","doi":"10.1111/cts.70262","DOIUrl":"https://doi.org/10.1111/cts.70262","url":null,"abstract":"<p>Glucagon-like peptide-1 agonists (GLP-1A) are increasingly prescribed to treat obesity and type 2 diabetes mellitus in children and adolescents. Emerging evidence suggesting neuropsychiatric effects presents an opportunity for pediatric psychopharmacology but requires careful consideration of potential adverse effects and risk of misuse. This perspective examines potential applications and cautions surrounding GLP-1As for pediatric mental health, particularly substance use, depression, and eating disorders, and advocates for research and clinical monitoring to ensure their safety and efficacy.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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