Clinical therapeutics最新文献

{"title":"Socioeconomic Disparities in Intravitreal Injection Use and Anti-VEGF Agent Selection: Aflibercept/Ranibizumab Versus Bevacizumab.","authors":"Michelle Y Ko, Ramin Talebi, Fei Yu, Victoria L Tseng, Anne L Coleman, Hamid Hosseini","doi":"10.1016/j.clinthera.2025.04.010","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.04.010","url":null,"abstract":"<p><strong>Purpose: </strong>There is a paucity of research on socioeconomic factors associated with intravitreal injection use or type of anti-vascular endothelial growth factor (anti-VEGF) use. The purpose of this cross-sectional analysis is to examine the association between demographic and socioeconomic factors and intravitreal injections and type of anti-VEGF (bevacizumab, aflibercept, and ranibizumab) use for patients with diabetic macular edema, proliferative diabetic retinopathy, retinal vein occlusion, and wet age-related macular degeneration in the AllofUs Database, which is a nationwide health database initiative conducted by the National Institutes of Health in the United States to enroll participants from groups that are considered to be historically underrepresented in biomedical research.</p><p><strong>Methods: </strong>The study population included patients diagnosed with diabetic macular edema, proliferative diabetic retinopathy, retinal vein occlusion, or wet age-related macular degeneration based on the International Classification of Diseases Ninth/10th Revision, Clinical Modification diagnosis codes. Exposures included age, sex, race/ethnicity, income, and education. Outcomes included IVI use based on the Current Procedural Terminology 4 codes and anti-VEGF type based on RxNorm codes.</p><p><strong>Findings: </strong>Of 3010 participants, 25.9% ever had IVI use. In multivariate logistic regression analyses, those with older age (adjusted odds ratio [aOR] = 1.27; 95% CI, 1.18-1.37) and income >$150,000 (aOR = 1.71; CI, 1.27-2.32) were more likely to have had IVI use. Those with older age (aOR = 1.46; CI, 1.22-1.75), Asian/other race/ethnicity (aOR = 3.81; CI, 1.09-13.34), Hispanic race/ethnicity (aOR = 3.16; CI, 1.59-6.26), income >$150,000 (aOR = 3.20; CI, 1.45-7.06), and college graduate/advanced degree (aOR = 1.83; CI, 1.01-3.31) were more likely to have aflibercept/ranibizumab only versus bevacizumab use.</p><p><strong>Implications: </strong>Interventions are needed to increase health literacy and access to IVI for at-risk, low-income populations. Future research should investigate patient and provider decision-making for anti-VEGF drug choice, which may have implications for cost-saving measures and policies.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093112","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":"Analysis of the Total Immunoglobulin G (IgG) and Its Subclasses Over Time in Coronavirus Disease 2019-Recovered Patients and Its Association With Disease Severity: A Single-Center Prospective Cohort Study.","authors":"Dablu Lal Gupta, Jhasketan Meher, Fagun Sharma, Arvind K Shukla, Anjan K Giri, Eli Mohapatra, Manisha M Ruikar, Donthamsetty Nageswara Rao","doi":"10.1016/j.clinthera.2025.04.011","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.04.011","url":null,"abstract":"<p><strong>Purpose: </strong>In order to address concerns regarding the diminishing levels of antibodies over time and the variations in response between mild and severe cases, efforts are being made to determine how long immunoglobulin G (IgG) antibodies persist in patients with coronavirus disease 2019 (COVID-19).</p><p><strong>Methods: </strong>The present study was conducted in a longitudinal setting over a period of 6 months in 37 unvaccinated COVID-19-recovered patients. The spike protein and receptor-binding domain (RBD)-specific serum levels of IgG and IgG subclasses were measured at 3 time points (within ≤1 month, 1-3 months, and 3-6 months) of recovery from COVID-19.</p><p><strong>Findings: </strong>Our study found a significant (P < 0.05) reduction in the levels of antispike and anti-RBD antibodies within 3 to 6 months after recovery from COVID-19 infections. The group of patients who developed severe illness had higher levels of antispike and anti-RBD IgG compared with the group of patients who recovered from mild disease. There was a statistically significant difference in the contribution of IgG1 and IgG3 over time in COVID-19-recovered patients, indicating a potential alteration in the distribution of IgG subclasses. Serum levels of IgG1 were found to be 1.5 folds higher within 1 to 3 months of recovery from severe acute respiratory syndrome coronavirus 2 infections in severe cases than mild cases.</p><p><strong>Implications: </strong>This study found that severe COVID-19 cases in unvaccinated patients had higher antibody titers and a greater likelihood of antispike antibodies persisting after infection. The levels of IgG1 and IgG3 increased significantly with the severity of COVID-19, indicating a heightened immune response in more severe cases. The estimation of serum levels of IgG subclass may determine the vaccination strategy and the process of treatment.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093095","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":"Short-term Prognostic Value of Heart Rate Variability in Pulmonary Embolism Patients: 2-Center Cohort Study.","authors":"Junjie Mao, Chao Guan, Jun Zhang, Ayman A Mohammed, Ge Zhang, Jie Huang, Ying Huang","doi":"10.1016/j.clinthera.2025.03.012","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.03.012","url":null,"abstract":"<p><strong>Purpose: </strong>Pulmonary thromboembolism (PTE) is the third most frequent acute cardiovascular syndrome, with serious sequelae in untreated patients. Heart rate variability (HRV) has emerged as a crucial and established prognostic indicator for adverse events. Nevertheless, its correlation with PTE and its prognostic significance in anticipating adverse outcomes warrant additional investigation. This study sought to examine the 30-day prognostic utility of HRV in predicting major adverse cardiovascular events (MACEs) in individuals with PTE.</p><p><strong>Methods: </strong>This retrospective cohort study, conducted at 2 centers, enrolled 170 patients diagnosed with PTE and 174 control subjects who underwent 24-hour Holter recording, with an evaluation of time-domain HRV. PTE patients with simplified-Pulmonary-Embolism-Severity Index = 0 points are classified as a low-risk group, and ≥1 as an intermediate-risk group. The association between HRV and MACE was assessed using receiver operating characteristic curve analysis, Cox-regression, and Kaplan-Meier curve tests.</p><p><strong>Findings: </strong>Time-domain HRV was reduced in all PTE patients compared with the control group and intermediate-risk PTE than in low-risk PTE groups (P < 0.05). A total of 22 PTE patients developed MACE during follow-up. PTE patients with reduced HRV have an increased risk of MACE (log-rank P < 0.05). HRV was an independent predictor of MACE, the standard deviation of all normal-to-normal RR intervals (hazard ratio [HR], 0.968; 95% CI, 0.950-0.986, P = 0.001), and the standard deviation of 5-minute mean N-N interval (HR, 0.974; 95% CI, 0.958-0.990, P = 0.002).</p><p><strong>Implications: </strong>HRV is an independent risk factor and is associated with 30-day poor outcomes in PTE. Thus, HRV can be considered as a tool in the risk stratification of PTE patients.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093110","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":"In Law as in Science: The Importance of Process.","authors":"Paul Beninger","doi":"10.1016/j.clinthera.2025.04.012","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.04.012","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093096","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":"The FDA's Pivotal Role in Global Therapeutic Product Availability.","authors":"Lawrence Liberti, Eunjoo Pacifici","doi":"10.1016/j.clinthera.2025.04.007","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.04.007","url":null,"abstract":"<p><p>Since its inception over a century ago, the U.S. Food and Drug Administration (FDA) has been recognized as the gold standard for assessing the quality, safety, and efficacy of therapeutics. Its scientific expertise and regulatory agility have been applied to a wide range of products, including small molecules, biologics, vaccines, and medical devices. The FDA's global leadership was evident during the COVID-19 pandemic, as it expedited the development and approval of vaccines while maintaining standards for quality, safety, and effectiveness. The FDA serves both domestic and international missions. As the primary approver of most new medicines, it ensures the timely availability of innovative therapeutics for the American public. Moreover, its longstanding leadership in regulatory activities has established it as an international paragon upon which regulatory authorities serving hundreds of millions of people rely. The FDA must maintain its position as the global leader in biopharmaceutical and medical device assessments. This is essential for preserving public health in the U.S., playing a crucial role in fostering bio-innovation and the economic viability of the pharmaceutical sector, and facilitating the global availability of innovative products to benefit worldwide public health.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086004","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":"Qfitlia (fitusiran).","authors":"Paul Beninger","doi":"10.1016/j.clinthera.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.04.008","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076432","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":"Association Between Anticoagulants and Interacting Drugs and Risk of Major Bleeding in Nonvalvular Atrial Fibrillation: Case-Control Study in SIDIAP, Catalonia, Spain.","authors":"M Giner-Soriano, L A Carrasco-Ribelles, S Fernández-García, J Castel Llobet, G Cereza García, R Morros","doi":"10.1016/j.clinthera.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.04.003","url":null,"abstract":"<p><strong>Purpose: </strong>Interactions with anticoagulants causing an increase in their effect may potentially enhance the bleeding risk. We aimed to analyze the risk of major hemorrhage in anticoagulated patients simultaneously exposed to potentially interacting drugs which may enhance the bleeding risk.</p><p><strong>Methods: </strong>Case-control study nested in a cohort of anticoagulated patients in 2011-2020. Cases were all people hospitalized for a major hemorrhage (cerebral or gastrointestinal), matched to individuals without bleeding. The index date was the day of hospital admission for cases and the same date for the matched controls.</p><p><strong>Data sources: </strong>SIDIAP database, containing information from primary health care electronic records, and the database of diagnoses at hospital discharge in Catalonia, Spain. We analyzed exposure to interacting drugs during 3 months prior to the index date. The association between hemorrhage and exposure to interacting drugs was calculated through multivariate logistic regression models.</p><p><strong>Findings: </strong>We included 2,811 cases (77.9% cerebral and 22.1% gastrointestinal hemorrhages), matched to 28,054 controls. We found association between hemorrhage in patients receiving vitamin K antagonists (OR 1.30, 95% CI 1.16-1.47). All types of interactions resulted in higher bleeding risk for all anticoagulants. Proton pump inhibitors were found protective for gastrointestinal (OR 0.55, 95% CI 0.46-0.65) but not for cerebral bleeding (OR 1.18, 95% CI 1.08-1.30).</p><p><strong>Implications: </strong>We estimated the risk of major hemorrhage in anticoagulated patients simultaneously exposed to potentially interacting drugs which may enhance bleeding risk. Our study underscores the potential impact of interactions on cerebral and gastrointestinal bleeding risk in anticoagulated patients.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989273","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":"The US Supreme Court Joins the Debate Over Gender Dysphoria.","authors":"Marcia M Boumil, Paul Beninger","doi":"10.1016/j.clinthera.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.04.004","url":null,"abstract":"<p><p>US v. Skrmetti is a legal case currently pending before the US Supreme Court that addresses the constitutionality of a Tennessee statute that prohibits gender-affirming medical care for transgender individuals who have not yet reached the legal age of adulthood, and who are diagnosed with gender dysphoria. Twenty-five other states have similar bans that apply to adolescents diagnosed with gender dysphoria, who are seeking treatment recommended by a physician and who are supported by their parents. Treatment involves gonadotropin-releasing hormone agonists, such as leuprolide or histrelin, which are approved by the Food and Drug Administration for use in children with central precocious puberty and are commonly prescribed off-label for adolescents. The purpose of puberty-blocking drugs is to suppress the onset of hormonal changes of puberty to facilitate the youth's anticipated transgender transition when the youth does reach the legal age of adulthood. Certainty about the time available for a youth to consider their gender identity, with the guidance of a professional support team, minimizes the risk of disruptive anxiety that's associated with near-term onset of sexual maturation involving development of irreversible secondary sex characteristics. This Commentary presents the legal arguments in the case and discusses relevant medical literature on this important issue in anticipation of the US Supreme Court's decision on the Tennessee law.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985846","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":"Duodenal Ulcer in a Child With Cystic Fibrosis on Elexacaftor-Tezacaftor-Ivacaftor Therapy: A Casual Association or a Possible Adverse Event?","authors":"Vito Terlizzi, Martina Di Benedetto, Sara Renzo, Valeria Galici, Luca Scarallo, Jochen G Mainz, Paolo Lionetti","doi":"10.1016/j.clinthera.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.04.002","url":null,"abstract":"","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":"143983307","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":"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}