Clinical therapeutics最新文献

{"title":"Prescription of Pharmacologic Venous Thromboembolism Prophylaxis Upon Hospital Discharge After Surgery for Lower Limb Fracture-A 3-Center Study in the North-West of England.","authors":"Fatima Kayali, Hritik Nautiyal, Jonathan Topping, Chea Tze Ong, Emadeldin M Ahmed, Martin Sharrock, Jenny Oakley, Makaram Srinivasan, Kuntal Patel, Amit Shah, Paul M Sutton, Charalambos P Charalambous","doi":"10.1016/j.clinthera.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.04.001","url":null,"abstract":"<p><strong>Purpose: </strong>The risk of venous thromboembolism (VTE) after surgery for lower limb trauma may be reduced with pharmacologic prophylaxis upon hospital admission and hospital discharge. To determine the rate and duration of prescription of VTE pharmacologic prophylaxis upon hospital discharge in patients who have surgery for a lower limb fracture.</p><p><strong>Methods: </strong>Retrospective analysis of patients who had surgery for a lower limb fracture at 3 National Health Trust hospitals in the North-West of England.</p><p><strong>Findings: </strong>Data from 127 patients were collected. All patients were prescribed pharmacologic VTE prophylaxis upon hospital admission, and 125 (98%) upon discharge, with 91.3% of patients discharged with low-molecular weight heparin. There was substantial variation in the duration of pharmacologic VTE prescription upon hospital discharge, with a median duration of 42 days (interquartile range, 28-42 days; range, 1-84 days). In our cohort, 7 (5.5%) of patients were prescribed VTE prophylaxis for less than 14 days, and 30(23.6%) prescribed for less than 35 days.</p><p><strong>Implications: </strong>This study reported that pharmacologic prophylaxis for VTE was prescribed for almost all patients upon hospital discharge. However, there was substantial variation in the duration of the prescribed prophylaxis upon hospital discharge, with almost a quarter of patients prescribed less than 35 days. National level prescription guidance for VTE prophylaxis upon hospital discharge may improve consistency within and between centers.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971672","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":"Improved Liver Fibrosis Regression After Direct-Acting Antiviral Therapy in Hepatitis C Patients: A Comparison of Patients With and Without MASLD.","authors":"Alexis McCary, Yi-Shin Sheu, Karen Chesbrough, M Cabell Jonas","doi":"10.1016/j.clinthera.2025.03.011","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.03.011","url":null,"abstract":"<p><strong>Purpose: </strong>Chronic Hepatitis C (CHC) often results in liver fibrosis. Therefore, an important benefit of CHC treatment with direct-acting antiviral (DAA) medication is liver fibrosis regression. However, it is unclear how concurrent liver steatosis affects fibrosis regression following DAA therapy. Recent guidelines have defined liver steatosis associated with metabolic syndrome as metabolic dysfunction-associated steatotic liver disease (MASLD). We sought to examine the association of MASLD with the fibrosis regression benefits of DAA treatment for CHC.</p><p><strong>Methods: </strong>We conducted an observational retrospective analysis using electronic health records of patients aged 18-65 who completed DAA therapy for CHC from 2016 through 2022. FIB-4 scores were calculated during three time periods: just prior to DAA initiation, within 6 months post-DAA completion, and within 6-12 months post-DAA completion. These scores categorized liver fibrosis as high risk (>3.25), intermediate risk (1.45-3.25), or low risk (<1.45). An ordinal logistic regression model assessed the degree of fibrosis regression across these periods in CHC patients with and without MASLD.</p><p><strong>Findings: </strong>We identified 845 patients with CHC who received DAA therapy, of whom 225 met MASLD criteria. Both CHC patients with and without MASLD exhibited a decrease in FIB-4 category (coefficient = -0.361, P < 0.001) within the year following DAA therapy. The reduction in FIB-4 category post-treatment was more pronounced in the MASLD group compared to the non-MASLD group, as evidenced by a significant interaction between group and time period (coefficient = -0.439, P = 0.004).</p><p><strong>Implications: </strong>In our cohort, MASLD was associated with greater liver fibrosis regression in the year following DAA therapy for CHC. This suggests that the concurrent presence of MASLD is not associated with diminished fibrosis regression from DAA therapy. Additional research is needed to determine the exact mechanism responsible for DAA-associated fibrosis regression in patients with MASLD.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971642","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":"Mycobacterium tuberculosis: A Resurgent Scourge Writing Another Chapter in Its History","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2025.03.013","DOIUrl":"10.1016/j.clinthera.2025.03.013","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 6","pages":"Pages 403-404"},"PeriodicalIF":3.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903958","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":"Pharmacokinetic/Pharmacodynamic Analysis of Extended/Two-Step Infusion Ceftazidime/Avibactam in Children With Gram-Negative Bacterial Infections","authors":"Ruiying Han MPharm,&nbsp;Ying Zhang BPharm,&nbsp;Baosen Yue MPharm,&nbsp;Yuan Zhi BPharm,&nbsp;Weihua Zhang MPharm,&nbsp;Dan Sun MPharm","doi":"10.1016/j.clinthera.2025.03.008","DOIUrl":"10.1016/j.clinthera.2025.03.008","url":null,"abstract":"<div><h3>Purpose</h3><div>To simulate the pharmacokinetic/pharmacodynamic (PK/PD) exposure of ceftazidime/avibactam (CZA) in children with gram-negative bacterial infections, and explore the appropriateness of the CZA standard dosing regimen (STD), further optimize the dosing regimen by extended/two-step infusion.</div></div><div><h3>Methods</h3><div>Monte Carlo simulations were performed to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR) of CZA with varying weight in two age groups (≥6–12 and ≥12–18 years old, respectively), utilizing PK parameters and PD data (from the EUCAST as well as the published data on US children). The simulated dosing regimens included STD and extended/two-step infusion.</div></div><div><h3>Findings</h3><div>When the PK/PD target for ceftazidime was set at 50% of time that free drug concentrations remain above the minimum inhibitory concentration of the pathogen during the dosing interval (50% <em>f</em>T &gt; MIC), the CZA STD achieved PTAs of ≥90% at susceptibility breakpoint (MIC = 8 mg/L) for children in weighed 15–30 kg (≥6–12years old) and 35–45 kg (≥12–18 years old). However, when the PK/PD target for ceftazidime was set at 100% <em>f</em>T &gt; MIC, none could achieve PTAs of ≥90%. The CFR results showed that the STD couldn't provide CFRs ≥90% in all children, but extended infusion or two-step infusion could achieve the target CFRs in all children based on the MIC distribution of US children, and improve the CFRs based on EUCAST's MIC distribution. Compared with extended infusion, two-step infusion could reduce total infusion time in partial patients.</div></div><div><h3>Implications</h3><div>The current STD of CZA may not adequately meet the therapeutic requirements in children, thus it is recommended to optimize the dosing regimen by extended/two-step infusion or increasing the daily dose, guided by therapeutic drug monitoring.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 6","pages":"Pages 412-419"},"PeriodicalIF":3.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903959","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 Canadian Real-World Study of Fixed-DOSE combination of Halobetasol Propionate 0.01%/Tazarotene 0.045% Lotion for the Treatment of Moderate-to-Severe Plaque Psoriasis","authors":"R Vender MD ,&nbsp;C Lynde MD ,&nbsp;V Prajapati MD ,&nbsp;R Zeinab PhD ,&nbsp;M Legault PhD ,&nbsp;HC-H Hong MD ,&nbsp;M Barakat MD PhD","doi":"10.1016/j.clinthera.2025.03.005","DOIUrl":"10.1016/j.clinthera.2025.03.005","url":null,"abstract":"<div><h3>Background</h3><div>A fixed-dose combination of HP/TAZ has demonstrated efficacy with a favorable safety profile for treating moderate-to-severe plaque psoriasis.</div></div><div><h3>Objective</h3><div>The present single-arm, open-label study evaluated the use of HP/TAZ in real-world practice.</div></div><div><h3>Methods</h3><div>Adults with moderate-to-severe psoriasis were enrolled and treated with HP/TAZ according to the Canadian label. The primary endpoint was the percentage of patients with treatment success at week 8, defined as an Investigator's Global Assessment score of clear or almost clear with a minimum 2-grade improvement.</div></div><div><h3>Results</h3><div>202 patients received at least one dose of HP/TAZ, 138 patients had efficacy assessments at baseline and week 8. Treatment success was achieved by 26.1% and 43.5% of patients (week 4 and 8 respectively) . Patient-rated average and worst itch were 4.5 and 5.3 points at baseline, with a subsequent reduction to 1.7 and 2.1 points, respectively, at week 8. Patients were satisfied-very satisfied with the HP/TAZ. Application site reactions (13.4%) and dermatitis/eczema (3.5%) were the most frequently reported adverse events (mild-moderate in severity) .</div></div><div><h3>Limitations</h3><div>The study design may limit generalizability of the results as an open label real world evidence study lacking a placebo or comparator arm.</div></div><div><h3>Conclusion</h3><div>Results confirm that HP/TAZ can be beneficial moderate-to-severe psoriasis patients.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 6","pages":"Pages 445-449"},"PeriodicalIF":3.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903279","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":"Long-term Antithrombotic Therapy in Patients With Chronic Coronary Syndrome: An Updated Review of Current Evidence.","authors":"Mario Enrico Canonico, Marisa Avvedimento, Raffaele Piccolo, Connie N Hess, Luca Bardi, Federica Ilardi, Giuseppe Giugliano, Anna Franzone, Giuseppe Gargiulo, Scott D Berkowitz, Christopher P Cannon, Giovanni Esposito, Marc P Bonaca","doi":"10.1016/j.clinthera.2025.03.010","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.03.010","url":null,"abstract":"<p><strong>Purpose: </strong>Despite improvements in the secondary prevention of atherothrombosis in patients with coronary artery disease during the past decade, it is estimated that approximately 19 million people annually die from cardiovascular diseases worldwide. Atherothrombosis remains the core pathobiology of acute complications including myocardial infarction (MI), and therefore, antithrombotic therapy plays a pivotal role in the strategies for major adverse cardiovascular event (MACE) prevention. Unlike early antithrombotic management after acute coronary syndrome, less evidence is available on long-term antithrombotic therapy in patients with chronic coronary syndrome (CCS). In addition, greater recognition of the impact of bleeding complications of such therapies has led to a more complex and personalized approach to their application. The purpose of this article is to review the available evidence on long-term antithrombotic therapy in patients with CCS including those with high-risk characteristics such as prior MI or polyvascular disease.</p><p><strong>Methods: </strong>A comprehensive literature review was performed in major databases including PubMed, Embase, and the Cochrane Library. The main focus of this narrative review was on available data from guidelines, meta-analysis, randomized controlled trials, and observational studies that assessed the efficacy and safety profile of long-term antithrombotic therapy in patients with CCS.</p><p><strong>Findings: </strong>Several studies suggest that long-term antithrombotic therapy is effective in reducing the risk of recurrent MACEs in patients with CCS. Current clinical guidelines recommend single antiplatelet therapy with aspirin as a first-line long-term strategy for patients without indication for oral anticoagulation. However, novel approaches focused on P2Y₁₂ inhibitor monotherapy are emerging. More intensive antithrombotic strategies including long-term dual antiplatelet therapy and dual pathway inhibition further reduce ischemic risk but at the cost of increased bleeding.</p><p><strong>Implications: </strong>This review highlights the importance of close monitoring and regular reassessment of the risk-benefit balance of antithrombotic therapy in patients with CCS. Overall, long-term antithrombotic therapy with either single antiplatelet therapy or dual antiplatelet therapy/dual pathway inhibition is effective in reducing the risk of MACEs in patients with CCS. The choice of antithrombotic therapy should be individualized based on the patient's clinical profile, particularly for thrombohemorrhagic risk. Future research should focus on identifying the optimal antithrombotic regimen for specific subgroups of patients with prior MI particularly for those with high bleeding risk.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989547","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":"Drug-Related Gastric Perforation Secondary to Prolonged Febuxostat Administration: A Case Report.","authors":"Xiaoxu Fan, Ran Wang","doi":"10.1016/j.clinthera.2025.03.009","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.03.009","url":null,"abstract":"<p><p>Febuxostat, a selective xanthine oxidase inhibitor, is regarded as the first-line therapeutic option for gout and hyperuricemia. With its extensive application, there has been a growing number of reports regarding associated adverse reactions. In this case, a 71-year-old male patient, who had been under long-term febuxostat treatment for gout, was admitted to the hospital approximately one year later due to persistent upper abdominal pain. Abdominal CT imaging revealed thickening of the gastric antrum wall, accompanied by peripheral exudation and the presence of free gas in the abdominal cavity, which was diagnosed as gastric perforation. After excluding other potential causative factors of gastric perforation, the serious adverse reaction potentially induced by febuxostat was taken into consideration.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983706","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":"Epidemiology and Economic Burden of Diagnosed Congenital Cytomegalovirus Infection in the First 2 Years of Life among Commercially Insured and Medicaid-Insured Individuals in the United States","authors":"John Diaz-Decaro MS, PhD ,&nbsp;Gail J. Demmler-Harrison MD ,&nbsp;Jessica R. Marden ScD ,&nbsp;Annika Anderson MPH ,&nbsp;Sandeep Basnet MD ,&nbsp;Katherine Gaburo BA ,&nbsp;Noam Kirson PhD ,&nbsp;Urvi Desai PhD ,&nbsp;Philip O. Buck MPH, PhD","doi":"10.1016/j.clinthera.2025.03.006","DOIUrl":"10.1016/j.clinthera.2025.03.006","url":null,"abstract":"<div><h3>Purpose</h3><div>Congenital cytomegalovirus (cCMV) is the leading infectious cause of congenital birth defects. Although approximately 20% to 25% of infants born with cCMV develop long-term health complications such as sensorineural hearing loss, developmental issues, and microcephaly, studies on the disease burden of cCMV are limited. In this study, we assessed the epidemiology, economic burden, and disease burden of clinically diagnosed cCMV in the United States using insurance claims data.</div></div><div><h3>Methods</h3><div>This retrospective study utilized Merative MarketScan Commercial Claims and Encounters and Multi-State Medicaid data from 2010 to 2019. Annual prevalence of clinically diagnosed cCMV at birth was estimated separately for each payer population. To assess economic burden, infants whose first cCMV diagnosis (index date) was within 1 month of birth were included in the cCMV cohort and matched to infants without cCMV infection for whom an index date was selected at random from all medical claims within 1 month of birth. Cohorts were matched 1:1 on demographics, insurance type, birth, and index years. All infants were required to have ≥2 years of continuous enrollment with prescription drug coverage after the index date (study period). Health care resource use and costs in 2021 USD ($) were summarized separately for the first and second years of the study period. Costs for birth admissions were also described.</div></div><div><h3>Findings</h3><div>The prevalence of clinically diagnosed cCMV at birth peaked in 2018 at 18.43 and 34.37 per 100,000 in the commercial and Medicaid populations, respectively. One hundred eighteen commercially insured (mean age at index date, 0.3 months; 46.6% female) and 351 Medicaid-insured matched pairs (mean age at index date, 0.2 months; 43.6% female) were included in the economic burden analyses. Mean (median) birth admission costs for commercially and Medicaid-insured infants with clinically diagnosed cCMV were $195,630 ($22,896; vs $24,195 [$3105]) and $57,182 ($9807; vs $5732 [$1566]), respectively. Additionally, excess costs due to cCMV in years 1 and 2 were $9427 ($5089) and $15,901 ($1573) for commercially insured, and $11,104 ($1446) and $12,205 ($721) for Medicaid-insured, respectively. Among potential cCMV sequelae, infants in the cCMV cohort experienced higher rates of hearing loss and developmental/motor delays during the first 2 years.</div></div><div><h3>Implications</h3><div>Diagnosed prevalence of cCMV at birth increased over time from 2010 to 2018. Infants with clinically diagnosed cCMV have costlier birth admissions and substantial disease burden in the first 2 years of life. These results emphasize the need for primary prevention methods, such as vaccination, to decrease the burden of cCMV.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 6","pages":"Pages 426-435"},"PeriodicalIF":3.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904033","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":"Response to Letter Regarding Article, “Optimizing Acute Ischemic Stroke Outcomes: The Role of Tenecteplase Before Mechanical Thrombectomy”","authors":"Arsh Haj Mohamad Ebrahim Ketabforoush MD ,&nbsp;Ali Hosseinpour MD ,&nbsp;Zahra Mirzaasgari MD","doi":"10.1016/j.clinthera.2025.03.004","DOIUrl":"10.1016/j.clinthera.2025.03.004","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 6","pages":"Pages 458-459"},"PeriodicalIF":3.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794978","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":"CTEXLI (chenodiol)","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2025.03.007","DOIUrl":"10.1016/j.clinthera.2025.03.007","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 6","pages":"Pages 460-461"},"PeriodicalIF":3.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787715","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}