Clinical therapeutics最新文献

{"title":"Comment on \"Pancreatitis and Pancreatic Cancer Risk Among Patients With Type 2 Diabetes Receiving Dipeptidyl Peptidase 4 Inhibitors: An Updated Meta-Analysis of Randomized Controlled Trials\".","authors":"Yuki Nakano, Kazuki Adachi, Kazumasa Kotake","doi":"10.1016/j.clinthera.2024.08.021","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.08.021","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343082","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":"Differences in Drug Poisonings Among Those Who Identify as Transgender Compared to Cisgender: An Analysis of the Toxicology Investigators Consortium (ToxIC) Core Registry, United States 2017-2021.","authors":"Kristine Magnusson, Emily Glidden, Desiree Mustaquim, Laura E Welder, Erin K Stokes, Gillian A Beauchamp, Marna R Greenberg, Kim Aldy, Richard J Mazzaccaro, Beth A Careyva, Judith N Sabino, Derek J Fikse, Katelyn McLain, Alexandra M Amaducci","doi":"10.1016/j.clinthera.2024.08.018","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.08.018","url":null,"abstract":"<p><strong>Purpose: </strong>In this manuscript, the abbreviation TG is defined as persons who identify as transgender, GNC is defined as persons who identify as gender nonconforming, and CG is defined as persons who identify as cisgender. TG and GNC (e.g., nonbinary), are those whose gender identity and sex assigned at birth do not align, as opposed to CG. This study describes drug poisonings among TG, GNC, and CG captured in the Toxicology Investigators Consortium (ToxIC) Core Registry during 2017-2021.</p><p><strong>Methods: </strong>Authors conducted a secondary data analysis of medical toxicology physician consultations involving intentional exposures (i.e., use with the knowledge of the exposed person) within the ToxIC Core Registry from 2017 through 2021. Demographic characteristics, exposure intent, and reported drug classes are reported by gender identity and sex assigned at birth.</p><p><strong>Findings: </strong>From a total of 15,800 medical toxicology consultations, 213 (1.3%) involved both TG (n = 187, 1.2%) and GNC (n = 26, 0.2%), and 15,587 (98.7%) involved CG. Among TG, 128 (68.8%) were transgender men, 58 (31.2%) transgender women. Sixty-two percent of TG/GNC (n = 132) and 34.8% of CG (n = 5,428) were aged ≤18 years. Reported intent for exposure (i.e., self-harm and misuse/harmful use) differed proportionally across both sexes assigned at birth and gender identity among transgender men and cisgender men.</p><p><strong>Implications: </strong>In the ToxIC Core Registry, the consultations varied proportionally by age group across TG/GNC and CG, with more than half of TG/GNC aged ≤18 years. The proportion of consultations also varied by intent across TG/GNC and CG. Further research to delineate differences between TG/GNC and CG could increase knowledge in prevention, assessment, and treatment of drug poisonings in this population.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281581","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 Predictive Potential of C-Peptide in Differentiating Type 1 Diabetes From Type 2 Diabetes in an Outpatient Population in Abu Dhabi","authors":"Sajid Iqbal MPhil, MSc ,&nbsp;Abdulrahim Abu Jayyab MSc, PhD ,&nbsp;Ayah Mohammad Alrashdi BSc ,&nbsp;Syed Shujauddin MSc, MBA ,&nbsp;Josep Lluis Clua-Espuny MD, PhD ,&nbsp;Silvia Reverté-Villarroya MSc, PhD","doi":"10.1016/j.clinthera.2024.07.002","DOIUrl":"10.1016/j.clinthera.2024.07.002","url":null,"abstract":"<div><h3>Purpose</h3><p>We aimed to investigate the predictive potential of plasma connecting peptide (C-peptide) in differentiating type 1 diabetes (T1D) from type 2 diabetes (T2D) and to inform evidence-based diabetes classification criteria.</p></div><div><h3>Methods</h3><p>A retrospective review was performed of all the patients with diabetes visiting an outpatient diabetology, endocrinology, general practice and family medicine tertiary health care center between January 2016 and December 2021.</p></div><div><h3>Findings</h3><p>Two hundred twelve individuals with diabetes were included, 85 (44.8%) with T1D and 127 (55.2%) with T2D. Mean (SD) age at diagnosis was 35.9 (15.1) years, and 112 (52.8%) men. Median (interquartile range [IQR]) duration of diabetes was 3.8 (3.0–4.5) years (T1D, 3.9 [3.5–4.6]; T2D, 3.4 [2.4–4.4]; <em>P</em> = 0.001). Body mass index was &lt;18.5 kg/m² in 5 (2.5%) individuals (T1D, 5; T2D, none), 18.5 to &lt;25 kg/m² in 57 (28.5%) (T1D, 32; T2D, 25), 25 to &lt;30 kg/m² in 58 (29%) (T1D, 28; T2D, 30), and &gt;30 kg/m² in 80 (40.0%) (T1D, 20; T2D, 60). Median (IQR) glycosylated hemoglobin was 7.4% (6.7%–8.5%) (T1D, 8.3% [7.2%–9.9%]; T2D, 7% [6.3%–7.6%]; <em>P</em> = 0.0001). Median (IQR) C-peptide concentration was 0.59 nmol/L (0.01–1.14 nmol/L) (T1D, 0.01 nmol/L [0.003–0.05 nmol/L]; T2D, 1.03 nmol/L [0.70–1.44 nmol/L]; <em>P</em> = 0.0001). C-peptide concentration of ≤0.16 nmol/L showed 92.9% sensitivity, 1-specificity of 2.4%, and AUC of 97.2% (CI, 94.7%–99.6%; <em>P</em> = 0.0001) in differentiating T1D from T2D.</p></div><div><h3>Implications</h3><p>To our knowledge, this is the first study in the Middle East and North Africa region highlighting the role of C-peptide in diabetes classification. The estimated cutoff point for C-peptide concentration (≤0.16 nmol/L) will certainly help in accurately classifying the T1D and will rule out the routine clinical judgmental approaches in the region, especially in those scenarios and periods where it is always difficult to diagnose the diabetes type. Quantifying the cutoff for C-peptide is among the vital strengths of this study that will provide a better treatment plan in diabetes care management. Also, we evaluated concomitant glucose levels to rule out the phenomenon of falsely low C-peptide values in the setting of hypoglycemia or severe glucose toxicity. Based on our findings, C-peptide testing could be included in postulating an evidence-based guideline that differentiates T1D from T2D. Despite this, our study has some limitations, including the selection bias due to the retrospective design and low C-peptide levels could be indicative of low pancreatic reserves due to other causes or long-standing T2D, and quantifying these reasons requires additional resources and time.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 9","pages":"Pages 696-701"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0149291824002030/pdfft?md5=4c7b2b00a75435f49dcf9c405758f60c&pid=1-s2.0-S0149291824002030-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Vasoactive Inotrope Score Trajectories and Their Prognostic Significance in Critically Ill Sepsis Patients: A Retrospective Cohort Analysis","authors":"Shiji Xiao ,&nbsp;Qiufeng Zhuang ,&nbsp;Yinling Li ,&nbsp;Zhibin Xue","doi":"10.1016/j.clinthera.2024.07.006","DOIUrl":"10.1016/j.clinthera.2024.07.006","url":null,"abstract":"<div><h3>Purpose</h3><p>Sepsis continues to be a critical issue in intensive care, characterized by significant morbidity and mortality. This study explores the association between Vasoactive Inotrope Score (VIS) trajectories and 28-day mortality in ICU patients with sepsis, employing VIS trajectories as a marker for assessing severity and guiding therapy.</p></div><div><h3>Methods</h3><p>We conducted a retrospective analysis of the MIMIC-IV database, which included sepsis patients admitted to the ICU between 2008 and 2019. VIS calculations were performed bi-hourly during the first 72 hours of ICU admission. Using latent growth mixture modeling, we identified distinct VIS trajectory patterns, and multivariate Cox proportional hazards models were employed to evaluate their association with 28-day mortality.</p></div><div><h3>Findings</h3><p>Among 6,802 sepsis patients who met the inclusion criteria, four distinct VIS trajectory patterns were identified: “Low-Decreasing” (52.1%), “Mild-Ascending” (13.2%), “Moderate-Decreasing” (23.0%), and “High-Stable” (11.6%). The 28-day survival analysis demonstrated that, compared to the “Low-Decreasing” group, the “Mild-Ascending” group had a hazard ratio (HR) for mortality of 2.55 (95% CI: 2.19–2.97, <em>P</em> &lt; 0.001), the “Moderate-Decreasing” group had an HR of 1.20 (95% CI: 1.03–1.41, <em>P</em> = 0.021), and the “High-Stable” group presented the highest risk with an HR of 4.19 (95% CI: 3.43–5.12, <em>P</em> &lt; 0.001).</p></div><div><h3>Implications</h3><p>This study offers significant insights into the prognostic value of VIS trajectories in sepsis patients. The identification of distinct trajectory patterns not only underscores the heterogeneity in sepsis but also emphasizes the importance of personalized management strategies. The findings underscore the potential of VIS trajectory monitoring in predicting 28-day outcomes and in guiding clinical decision-making in ICU settings.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 9","pages":"Pages 711-716"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995476","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":"One-year Efficacy and Safety of Dulaglutide in Patients with Type 2 Diabetes and Chronic Kidney Disease: A Retrospective Study of Asian Patients","authors":"Myung Jin Kim ,&nbsp;Hwi Seung Kim ,&nbsp;Yun Kyung Cho ,&nbsp;Chang Hee Jung ,&nbsp;Woo Je Lee","doi":"10.1016/j.clinthera.2024.06.024","DOIUrl":"10.1016/j.clinthera.2024.06.024","url":null,"abstract":"<div><h3>Purpose</h3><p>Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist that is not cleared by the kidneys and has proven efficacy and safety in patients with diabetic kidney disease. We aimed to evaluate the 1-year efficacy of dulaglutide in patients with diabetic kidney disease who have used the drug for more than 1 year.</p></div><div><h3>Methods</h3><p>This retrospective, observational study comprised 131 patients with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m² who had received dulaglutide for more than one year between June 2016 and May 2023. The primary outcome measures were changes in glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and body weight from baseline to the 12-month follow-up, with assessments performed at six-month intervals. Subgroup analyses were conducted based on age, sex, baseline body mass index, FPG, and HbA1c, and insulin administration at baseline and last follow-up.</p></div><div><h3>Findings</h3><p>The mean age was 60.0 ± 10.2 years, and 61.1% of the participants were males. Baseline HbA1c, FPG, and body weight were 9.1% (76.0 mmol/mol), 186.8 mg/dL, and 79.3 kg, respectively. Dulaglutide significantly reduced HbA1c, FPG, and body weight from baseline to the 12-month follow-up (mean ± standard error: –1.2 ± 0.1%, –34.8 ± 6.9 mg/dL, and –2.3 ± 0.5 kg, respectively; <em>P</em> &lt; 0.001). Subgroup analysis revealed significant differences in HbA1c reduction based on baseline HbA1c.</p></div><div><h3>Implications</h3><p>Dulaglutide exhibited sustained glucose-lowering and weight-reduction effects during the initial 1 year of treatment in patients with diabetic kidney disease. Altogether, dulaglutide could serve as a favorable long-term therapeutic option for patients with diabetic kidney disease in real-world clinical settings.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 9","pages":"Pages 683-688"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0149291824001991/pdfft?md5=1b57d901e8f076c7a69335f164773cda&pid=1-s2.0-S0149291824001991-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Propolis Consumption on Glycemic Indices and Liver Enzymes in Adults: A Grading of Recommendations Assessment, Development, and Valuation-assessed Systematic Review and Dose-Response Meta-analysis","authors":"Shaghayegh Adeli MSc ,&nbsp;Mahsa Maroofi MSc ,&nbsp;Fatemeh Pourteymour Fard Tabrizi Ph.D ,&nbsp;Beitullah Alipour Ph.D ,&nbsp;Marzieh Heidari MSc ,&nbsp;Mahdi Vajdi Ph.D ,&nbsp;Mahdieh Abbasalizad-Farhangi Ph.D","doi":"10.1016/j.clinthera.2024.06.022","DOIUrl":"10.1016/j.clinthera.2024.06.022","url":null,"abstract":"<div><h3>Purpose</h3><p>Even though various randomized controlled trials (RCTs) have assessed the effect of propolis on glycemic indices and liver enzyme concentrations in adults, results have been inconsistent, without conclusive evidence. This systematic review and meta-analysis of RCTs sought to evaluate the effects of propolis consumption on glycemic indices and liver enzymes, fasting blood glucose, insulin, homeostatic model assessment of insulin resistance, glycosylated hemoglobin, alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase in adults.</p></div><div><h3>Methods</h3><p>Two independent researchers systematically searched PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library for English-language RCTs published up to April 2024. The results were generated through a random-effects model and presented as the weighted mean difference (WMD) with a 95% CI. The Cochrane Risk of Bias Tool for RCTs and Grading of Recommendations Assessment, Development, and Evaluation assessment were used to evaluate quality assessment and certainty of evidence.</p></div><div><h3>Findings</h3><p>A total of 21 RCTs were included. A pooled analysis of 24 trials reported that propolis consumption led to a significant reduction in fasting blood glucose (WMD, −9.75 mg/dL; 95% CI, −16.14 to −3.35), insulin (WMD, −1.64 µU/mL; 95% CI, −2.61 to −0.68), glycosylated hemoglobin (WMD, −0.46%; 95% CI, −0.71 to −0.21), homeostatic model assessment of insulin resistance (WMD, −0.54; 95% CI, −0.98 to −0.09), alanine transaminase (WMD, −2.60 IU/L; 95% CI, −4.58 to −0.61), and aspartate aminotransferase (WMD, −2.07 IU/L; 95% CI, −3.05 to −1.09). However, there were no significant effects on gamma-glutamyl transferase in comparison with the control group.</p></div><div><h3>Implications</h3><p>This meta-analysis has shown that propolis supplementation may have beneficial effects on glycemic indices and liver enzymes. Future high-quality, long-term RCTs are needed to confirm our results. ClinicalTrials.gov identifiers: CRD42024524763. (<em>Clin Ther</em>. 2024;46:XXX–XXX) © 2024 Elsevier HS Journals, Inc.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 9","pages":"Pages e6-e14"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888717","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":"Efficacy and Safety of Pioglitazone Add-on in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin and Dapagliflozin: A Multicenter, Randomized, Double-blind, and Placebo-controlled Study","authors":"Yun Kyung Cho MD, PhD ,&nbsp;Kyung-Soo Kim MD, PhD ,&nbsp;Byung-Wan Lee MD, PhD ,&nbsp;Jun Hwa Hong MD, PhD ,&nbsp;Jae Myung Yu MD, PhD ,&nbsp;Soo Lim MD, PhD ,&nbsp;Ye An Kim MD, PhD ,&nbsp;Chang Beom Lee MD, PhD ,&nbsp;Sang Soo Kim MD, PhD ,&nbsp;Soo Heon Kwak MD, PhD ,&nbsp;Woo Je Lee MD, PhD","doi":"10.1016/j.clinthera.2024.06.023","DOIUrl":"10.1016/j.clinthera.2024.06.023","url":null,"abstract":"<div><h3>Purpose</h3><p>The purpose of this study was to determine the efficacy and safety profile of pioglitazone compared with placebo (PBO) in patients with type 2 diabetes (T2D) inadequately controlled with metformin and dapagliflozin.</p></div><div><h3>Methods</h3><p>In this prospective, multicenter, randomized, double-blind, PBO-controlled trial, 366 patients with T2D who did not meet glycemic targets (7.0% ≤ glycosylated hemoglobin [HbA_1c] ≤ 10.5%), despite treatment with metformin ≥1000 mg and dapagliflozin 10 mg, received either a PBO, 15 mg of pioglitazone daily (PIO15), or 30 mg of pioglitazone daily (PIO30). The primary end point was the mean change in HbA_1c from baseline at 24 weeks across the groups.</p></div><div><h3>Findings</h3><p>For the 366 participants (PBO, n = 124; PIO15, n = 118; PIO30, n = 124), the mean age was 55.6 years and mean duration of diabetes was 8.7 years, with a baseline HbA_1c of 7.9%. After 24 weeks, HbA_1c reduced significantly in the PIO15 and PIO30 groups from baseline, with intergroup differences of −0.38% and −0.83%, respectively, compared with the PBO group. The proportion of patients with HbA_1c levels &lt;7% was significantly higher in the PIO15 and PIO30 groups than in the PBO group. The adverse event rates did not significantly differ across the groups, indicating favorable safety profiles for triple combination therapy using metformin, dapagliflozin, and pioglitazone.</p></div><div><h3>Implications</h3><p>The addition of pioglitazone as a third oral antidiabetic medication is an appropriate option for patients with T2D inadequately controlled with metformin and dapagliflozin based on the resulting significant efficacy in glycemic control and favorable safety profile. ClinicalTrials.gov identifier: NCT04885712.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 9","pages":"Pages 662-669"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S014929182400198X/pdfft?md5=2c1571fd29a2772f3a3996351852b070&pid=1-s2.0-S014929182400198X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proton Pump Inhibitors Versus Histamine-2 Receptor Blockers for Stress Ulcer Prophylaxis on In-hospital Mortality Among Intensive Care Unit Patients Hospitalized for Major Adverse Cardiovascular and Cerebrovascular Events: Retrospective Cohort Study","authors":"Lanxiang Pu PhD ,&nbsp;Ting Jia MSc ,&nbsp;Shili Su MSc ,&nbsp;Liang Yang MSc ,&nbsp;Hong Yao MSc ,&nbsp;Yujie Su MSc ,&nbsp;Zhaowen Chen","doi":"10.1016/j.clinthera.2024.06.020","DOIUrl":"10.1016/j.clinthera.2024.06.020","url":null,"abstract":"<div><h3>Purpose</h3><p>Patients in the intensive care unit (ICU) commonly receive stress ulcer prophylaxis drugs, either proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs). The goal of this research was to evaluate the impact of these drugs on mortality among ICU patients hospitalized for major adverse cardiovascular and cerebrovascular events (MACCEs).</p></div><div><h3>Methods</h3><p>ICU patients hospitalized for MACCEs were sourced from the Medical Information Mart for Intensive Care-III database. We performed a propensity score matching analysis to match patients treated with PPIs to those treated with H2RBs for stress ulcer prophylaxis. The outcome was 90-day mortality. We used multivariable Cox regression analyses to compare the effect. Hazard ratio (HR), 95% CIs, and <em>P</em> values were reported from the model.</p></div><div><h3>Findings</h3><p>From 2001 to 2012, a total of 3577 patients hospitalized for MACCEs (1997 received PPIs and 1580 received H2RBs) were admitted. The 90-day mortality was 23.7% (848/3577); it was 27% (540/1997) and 19.5% (308/1580) for PPIs and H2RBs users, respectively. The PPI group exhibited a greater 90‑day mortality in comparison to the H2RBs group (relative risk = 1.17; <em>P</em> = 0.036), after conditioning on potential confounder. The results remained robust in propensity score matching, sensitivity analyses, and subgroup analyses.</p></div><div><h3>Implications</h3><p>PPIs for stress ulcer prophylaxis were linked to an increased risk of in-hospital mortality than H2RBs in patients hospitalized for MACCEs. Further investigation of this association and validation of its clinical significance is needed.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 9","pages":"Pages 677-682"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0149291824001954/pdfft?md5=372d0f6ba5c9f0036891b7b1ede02a83&pid=1-s2.0-S0149291824001954-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Landscape of Blood-based Screening Assays After the Fallacy of Theranos, Inc","authors":"Jill L. Maron MD, MPH","doi":"10.1016/j.clinthera.2024.08.005","DOIUrl":"10.1016/j.clinthera.2024.08.005","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 9","pages":"Page 661"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105141","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":"Racial Comparison of the Pharmacokinetics and Safety of Fixed-dose Combination of Dapagliflozin/Sitagliptin in Western and Korean Healthy Adults","authors":"Pradeep B. Lukka PhD ,&nbsp;Weifeng Tang PhD ,&nbsp;Ann Hammarstedt PhD ,&nbsp;Tom Conrad PhD ,&nbsp;Maria Heijer MSc ,&nbsp;Cecilia Karlsson MD, PhD ,&nbsp;David W. Boulton PhD","doi":"10.1016/j.clinthera.2024.07.007","DOIUrl":"10.1016/j.clinthera.2024.07.007","url":null,"abstract":"<div><h3>Purpose</h3><p>We evaluated the pharmacokinetics, safety, and tolerability of a fixed-dose combination (FDC) of dapagliflozin/sitagliptin versus individual component (IC) tablets in healthy Western and Korean participants. The combination of these antihyperglycemic drugs provides efficient glucose control, and the use of FDC has generally been shown to improve medication adherence in individuals with type 2 diabetes mellitus (T2DM).</p></div><div><h3>Methods</h3><p>Two randomized, open-label, two-period, two-treatment, single-dose, single-center, crossover bioequivalence studies conducted on healthy fasted German participants (aged 18–55 years; Western study) and South Korean participants (aged 19–55 years; Korean study) were included. In both studies, pharmacokinetic parameters (maximum [peak] plasma concentration [C_max], area under the plasma concentration–time curve from zero to the last quantifiable concentration [AUC_last], and area under the plasma concentration–time curve from zero to infinity [AUC_inf]) were used to assess the bioequivalence of 10 mg dapagliflozin/100 mg sitagliptin FDC (Treatment A) with their ICs (Treatment B) under fasted conditions. Safety and tolerability were assessed throughout the study.</p></div><div><h3>Findings</h3><p>Forty-six healthy participants (male, 60.9%; mean age, 39.5 years; mean body mass index [BMI], 23.9 kg/m²) were randomized in the Western study, and 51 healthy participants (male, 100.0%; mean age, 24.6 years; mean BMI, 23.9 kg/m²) were randomized in the Korean study. In both studies, the participants were randomized 1:1 into treatment sequence AB and treatment sequence BA. Dapagliflozin/sitagliptin FDC was bioequivalent to IC tablets in both Western and Korean studies, as the 90% confidence interval of the FDC to IC ratios of the geometric least-squares means of the pharmacokinetic parameters for both dapagliflozin and sitagliptin was within the 0.8000–1.2500 bioequivalence criterion limit. The observed differences in pharmacokinetic parameters, such as C_max, AUC_last, and AUC_inf, between the Western and Korean studies were not clinically meaningful. Dapagliflozin/sitagliptin FDC and their ICs were well tolerated, with no serious adverse events reported in any of the study populations.</p></div><div><h3>Implications</h3><p>The 10 mg dapagliflozin/100 mg sitagliptin FDC and IC formulations were bioequivalent in fasted healthy Western and Korean participants, with no new safety concerns identified, thus offering a useful alternative for patients currently receiving individual medications as part of their treatment regimen.</p></div><div><h3>Clinical trial registration</h3><p>Western study (clinicaltrials.gov: NCT05266404) and Korean study (clinicaltrials.gov: NCT05453786).</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 9","pages":"Pages 717-725"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046387","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}