Clinical therapeutics最新文献

{"title":"Words Matter: An Attack on Evidence-Based, Peer-Reviewed Science.","authors":"Jill L Maron","doi":"10.1016/j.clinthera.2025.02.010","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.02.010","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718183","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}

{"title":"Ethambutol Optic Neuropathy Surveillance: Variations in Real-World Screening Practices and Associated Factors in a Nationwide Cohort Study.","authors":"Jiyeong Kim, Seong Joon Ahn","doi":"10.1016/j.clinthera.2025.03.002","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.03.002","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate real-world screening practices for ethambutol optic neuropathy (EON) and how these practices vary across demographic and clinical factors in a nationwide cohort in South Korea.</p><p><strong>Methods: </strong>We analyzed data from a cohort of 119,636 individuals in South Korea who initiated ethambutol therapy between January 1, 2015, and December 31, 2021, sourced from the National Health Insurance Review and Assessment (HIRA) database. We compared the screening practices of ethambutol users, focusing on demographic and clinical characteristics between those who underwent baseline examinations (the first ophthalmic examination after starting ethambutol) and those who did not, as well as between individuals who received subsequent monitoring and those who did not.</p><p><strong>Findings: </strong>We found significant variations in baseline and subsequent monitoring examinations influenced by factors such as age, sex, geographic location, hospital type, and medical specialty prescribing ethambutol. The results indicated disparities in screening uptake, with younger patients, those in metropolitan areas, and those treated by infectious disease specialists being more likely to undergo baseline examinations. Subsequent monitoring was more common in older patients and those with longer treatment durations. Multivariate analysis revealed that females, individuals receiving ethambutol for non-pulmonary tuberculosis indications or from referral centers, and those residing in metropolitan areas or large cities were less likely to undergo baseline and monitoring examinations.</p><p><strong>Implications: </strong>These findings emphasize the need for standardized screening guidelines across different specialties and clinical settings, along with targeted interventions to improve screening, particularly for individuals with lower screening rates, to prevent vision loss in patients undergoing ethambutol therapy.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718180","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}

{"title":"A Phase III Randomized, Double-Blind, Active-Controlled, Multicenter Study on the Efficacy and Safety of Ezetimibe/Atorvastatin/Amlodipine Combination in Patients With Comorbid Primary Hypercholesterolemia and Essential Hypertension.","authors":"Chan Joo Lee, Ji Yong Choi, Seung Hwan Han, Jinho Shin, Jung Hyun Choi, Eung Ju Kim, Jin-Oh Choi, Jung-Hoon Sung, Kye Hun Kim, Pil Hyung Lee, Byung-Hee Hwang, Young Won Yoon, Seok-Min Kang","doi":"10.1016/j.clinthera.2025.03.001","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.03.001","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to evaluate the efficacy and safety of triple combination of ezetimibe (Eze)/atorvastatin (Ato) 10/40 mg + amlodipine (Aml) 10 mg therapy for lowering the low-density lipoprotein cholesterol (LDL-C) and blood pressure compared with either Eze/Ato 10/40 mg or Aml 10 mg therapies in patients with comorbid primary hypercholesterolemia and essential hypertension.</p><p><strong>Methods: </strong>This was a randomized, multicenter, double-blind, active-controlled, Phase III clinical trial. Participants underwent a wash-out period (2 weeks for nonfibrate medications, 6 weeks for fibrates) followed by 4 weeks of therapeutic lifestyle changes. Subsequently, 109 participants were randomly assigned to 3 groups: (1) Eze/Ato 10/40 mg + Aml 10 mg, (2) Eze/Ato 10/40 mg, and (3) Aml 10 mg. The coprimary end points were percentage change in LDL-C and change in mean sitting systolic blood pressure (SBP) compared with baseline at week 8.</p><p><strong>Findings: </strong>A total of 109 participants were enrolled in the study, and there were no statistically significant differences in the baseline characteristics of participants across the 3 groups. After 8 weeks of treatment, the least-square (LS) mean (SE) of percent change from baseline in LDL-C was -57.95% (3.52%) for the Eze/Ato 10/40 mg + Aml 10 mg group and 8.93% (3.54%) for the Aml 10 mg group. The LS mean difference (SE) between these 2 groups was statistically significant at -66.88 (4.95) (95% CI, -76.77% to -56.99%) (P < 0.0001). Furthermore, at week 8, the LS mean (SE) change in mean sitting SBP between the Eze/Ato 10/40 mg + Aml 10 mg group and the Eze/Ato 10/40 mg group was -19.24 (2.42) mm Hg and -4.43 (2.56) mm Hg, respectively. The LS mean difference (SE) between the 2 groups was statistically significant -14.81 (3.53) (95% CI, -21.87 to -7.74) mm Hg (P < 0.0001). No serious adverse drug reactions occurred in any of the study groups.</p><p><strong>Implications: </strong>Triple combination therapy with Eze/Ato + Aml has effectively reduced the LDL-C and SBP independently, compared with either Eze/Ato or Aml therapies over 8 weeks of treatment period. In terms of safety, there were no significant differences among the 3 treatment groups. This research lays the groundwork for the development of a triple fixed-dose combination in the future, which could improve patient convenience and adherence by reducing pill burden. Clinical Research Information Service (CRIS), Republic of Korea: KCT0006283.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691397","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}

{"title":"Serum Golgi Protein 73 as a Predictor of Virologic Response to Entecavir Antiviral Therapy in Patients with Chronic Hepatitis B and Liver Fibrosis: A Retrospective Study.","authors":"Yangqing Ma, Zhimin Zhao, Kai Huang, Yingzi Tan, Wei Zhou, Xin Sun, Feng Xing, Haina Fan, Chenghai Liu","doi":"10.1016/j.clinthera.2025.02.009","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.02.009","url":null,"abstract":"<p><strong>Purpose: </strong>Golgi protein 73 (GP73) facilitates hepatitis B virus (HBV) replication, and it is associated with persistent infection in patients with chronic hepatitis B (CHB). However, the predictive value of serum GP73 (sGP73) for virologic response (VR) remains unexplored. This study evaluated the value of sGP73 in predicting VR in patients with CHB and liver fibrosis during initial antiviral therapy with entecavir (ETV).</p><p><strong>Methods: </strong>In total, 235 patients with CHB and liver fibrosis were included in this retrospective cohort study. The patients received antiviral therapy with ETV for 48 weeks, and sGP73 levels and virologic markers were examined every 12 weeks for 48 weeks. The performance of sGP73 for VR was evaluated using the receiver operating characteristic (ROC) curve method.</p><p><strong>Findings: </strong>Patients who achieved VR at 48 weeks exhibited significantly lower baseline sGP73. Correlation analysis revealed significant positive associations of baseline sGP73 with HBV DNA and alanine aminotransferase (ALT). Using a cutoff of 105.9 ng/mL, patients with baseline sGP73 ≤ 105.9 ng/mL had a significantly higher cumulative VR rate. In the performance evaluation of sGP73 in predicting VR at 48 weeks, the area under the ROC curve (AUC) was 0.770 [95% confidence interval (CI) = 0.711-0.822), which was higher than that for ALT (AUC = 0.624; 95% CI = 0.558-0.687) and HBV DNA (AUC = 0.626; 95% CI = 0.559-0.688).</p><p><strong>Implications: </strong>This study demonstrated the predictive value of sGP73 for VR, suggesting its potential as a novel biomarker for predicting VR in patients with CHB. The correlation between changes in GP73 and HBV DNA levels may be related to inflammation.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691400","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}

{"title":"Carboplatin Therapeutic Drug Monitoring in Intermittent Hemodialysis-A Case Report and Review of the Literature.","authors":"Martin Christian Bucher, Daniel Andreas Bossard, Marco Bonani, Michael Paul, Christopher Geinitz, Jérôme Bonzon","doi":"10.1016/j.clinthera.2025.02.007","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.02.007","url":null,"abstract":"<p><strong>Purpose: </strong>We present the case of a 45-year-old female patient with hemodialysis-dependent renal failure due to FSGS who was diagnosed with FIGO IIIc ovarian cancer and treated with carboplatin/gemcitabine under hemodialysis.</p><p><strong>Methods: </strong>A carboplatin dose of 200 mg/m² was administered (target AUC 4.0 min*mg/mL). Hemodialysis was started 2 hours after carboplatin administration and continued over 4 hours, with an additional dialysis session the day after.</p><p><strong>Findings: </strong>The measured AUC was 5.8 min*mg/mL.</p><p><strong>Implications: </strong>A dose reduction to 250 mg resulted in an AUC of 2.3 min*mg/mL. This is the first case of an ovarian cancer treated with a high-dose scheme of carboplatin under hemodialysis.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673553","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}

{"title":"Journavx (suzetrigine).","authors":"Paul Beninger","doi":"10.1016/j.clinthera.2025.02.008","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.02.008","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639445","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}

{"title":"Antidiabetic Drugs Consumption in France Over a Decade: An Observational Study.","authors":"De Bandt David, Johanna Mezence, Claire Rives Lange, Dominik Menges, Claire Carette","doi":"10.1016/j.clinthera.2025.02.005","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.02.005","url":null,"abstract":"<p><strong>Aims: </strong>The prevalence of type 2 diabetes has increased in France over the past decade, with changes in available pharmacologic treatments. This study aimed to assess trends in the sales of antidiabetic drugs in France over the last decade.</p><p><strong>Methods: </strong>This retrospective cohort study used data from French national health insurance databases. Defined daily doses per 1000 inhabitants per day (DDD/TID), expenditures associated, and the proportion of the population receiving treatment were analyzed from January 2013 to December 2022.</p><p><strong>Results: </strong>Between 2013 and 2022, the proportion of patients purchasing at least one antidiabetic drug per month increased from 3.07% to 4.12%, with average monthly consumption rising from 82.62 to 101.68 DDD/TID. Biguanides were the most sold antidiabetic drug, followed by sulfonylureas and insulin. The greatest increases in consumption and expenditures were observed for GLP-1 analogs and SGLT2 inhibitors.</p><p><strong>Conclusion: </strong>The consumption and cost of antidiabetic drugs increased with the diabetes prevalence. GLP-1 analogs and SGLT2 inhibitors accounted for the main growth, reflecting their growing clinical adoption and evidence of efficacy, while sales of sulfonylureas and DPP4 inhibitors remained substantial despite concerns regarding their benefit-risk profiles. In 2022, expenditures for GLP-1 analogs surpassed insulin. These findings have implications for healthcare policy and resource allocation planning.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630052","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}

{"title":"PHEMI-Phenylbutyrate in Patients With Lactic Acidosis: A Pilot, Single Arm, Phase I/II, Open-Label Trial.","authors":"Silvia Marchet, Alessia Catania, Anna Ardissone, Vincenzo Montano, Krisztina Einvag, Maria Pia Iermito, Daniele Sala, Manuela Spagnolo, Elena Mauro, Eleonora Lamantea, Giulia Cecchi, Piervito Lopriore, Michelangelo Mancuso, Costanza Lamperti","doi":"10.1016/j.clinthera.2025.02.004","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.02.004","url":null,"abstract":"<p><strong>Purpose: </strong>The 6 months pilot, single arm, phase I/II, open-label clinical trial PHEMI investigated the safety and efficacy of daily administration of phenylbutyrate in reducing lactic acidosis by at least 20% in 3 children (ages 7-10 yrs) with pyruvate dehydrogenase deficiency and 6 adults with mitochondrial myopathy encephalopathy lactic acidosis and stroke-like episodes. As a side study, we investigated the response to phenylbutyrate treatment in skin fibroblasts and cybrids derived from PHEMI patients with the aim of unraveling a possible in vivo-in vitro correlation.</p><p><strong>Methods: </strong>Safety was assessed through the collection of vital signs, clinical evaluations, blood samples, and reported adverse events. Efficacy was evaluated on biochemical and clinical endpoints. In vitro analysis explored the effects of phenylbutyrate in patients' fibroblasts and cybrids.</p><p><strong>Findings: </strong>At the starting dosage regimen of 10 g/m²/day, phenylbutyrate was effective in reducing lactic acidosis (by a mean of 13%), but lead to the development of adverse events in all adults. The reduced dose of 5 g/m²/day was well tolerated but did not meet the study's primary outcome. In parallel, the in vitro analyses confirmed that phenylbutyrate led to a reduction in lactate measured in culture medium, an increase in cellular respiration, and a slight increase in the activity of the Respiratory Chain Complexes.</p><p><strong>Implications: </strong>Our study fosters further research on phenylbutyrate in individuals with primary mitochondrial disease suffering from lactic acidosis. Future investigation should focus on a highly bioavailable, easier-to-administer drug formulation that allows the administration of a lower dosage regimen.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630060","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}

{"title":"Therapeutic Inertia Quantification in Diabetes Care: A Narrative Review and Synthesis.","authors":"Ikram Zoukh, Zeinab Dabbous, Yaw Owusu, Ahmed Awaisu","doi":"10.1016/j.clinthera.2025.02.003","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.02.003","url":null,"abstract":"<p><strong>Purpose: </strong>Therapeutic inertia, which refers to the failure to adjust therapy despite suboptimal glycemic control, is a growing concern. This phenomenon is associated with significant adverse health consequences and reflects the gap between population health goals and patient outcomes. Current research lacks harmonized and effective ways to measure therapeutic inertia, posing significant challenges to addressing this issue in diabetes care. This review aimed to summarize the approaches used to quantify therapeutic inertia in diabetes care, with the goal of improving clinical management and patient outcomes.</p><p><strong>Methods: </strong>A narrative review was conducted to identify relevant articles through a search of MEDLINE (PubMed), Embase, and Web of Science databases from their inception until August 2024, employing search terms related to therapeutic inertia, quantification, and diabetes care. We included all articles that focused on quantifying therapeutic inertia in diabetes care. Quantification methods were summarized with respect to key aspects of formula, scoring, validation, advantages, and limitations.</p><p><strong>Findings: </strong>Four approaches for quantifying therapeutic inertia were identified from the retrieved articles. However, these methods have several limitations that have led to the development of a therapeutic inertia index. The primary goal of the index as a quality measure is to describe healthcare providers' practices and establish a connection between the implemented process measures and key glycemic outcomes. Three commonly used therapeutic inertia indices have been reported in the literature: the norm-based method, standard-based method (SBM), and American Diabetes Association method.</p><p><strong>Implications: </strong>There is a need to standardize therapeutic inertia measurement approaches and develop comprehensive interventions to enhance the management of diabetes.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623968","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}

{"title":"Letter to the Editor Regarding \"Analgesic Effects and Pharmacokinetics of Ropivacaine at Different Concentrations in Serratus Anterior Plane Block in Patients Undergoing Video-Assisted Thoracoscopic Surgery: A Prospective Randomized Trial\" Recently Published by Tang and Colleagues.","authors":"Xiao-Ying Chen, Dan-Feng Wang, Fu-Shan Xue","doi":"10.1016/j.clinthera.2025.02.006","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.02.006","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596564","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}