Clinical therapeutics最新文献

{"title":"A Prediction Model for Postoperative Nausea and Vomiting After Laparoscopic Surgery for Gynecologic Cancers","authors":"Yabin Zhu MMed ,&nbsp;Lin Jiang MMed ,&nbsp;Canlin Sun MMed ,&nbsp;Yunxiang Li MBBS ,&nbsp;Hong Xie MD","doi":"10.1016/j.clinthera.2024.11.018","DOIUrl":"10.1016/j.clinthera.2024.11.018","url":null,"abstract":"<div><h3>Background</h3><div>Postoperative nausea and vomiting (PONV) is among the most common adverse events, accompanied with impaired prognosis. This study aimed to investigate independent predictors for PONV after laparoscopic surgery for gynecologic cancers and identify a nomogram model.</div></div><div><h3>Methods</h3><div>Elderly patients who underwent laparoscopic surgery for gynecologic cancers between 2021 and 2024 were retrospectively enrolled. The primary observational endpoint was set as the occurrence of PONV within 72 h after surgery. Independent risk factors associated with PONV were identified by binary logistic regression, and further incorporated into the nomogram prediction mode by R.</div></div><div><h3>Results</h3><div>Of 337 enrolled patients, 104 experienced PONV with an overall incidence of 30.9%. Multivariate logistic regression analysis indicated body mass index (BMI) ≥ 24.0 (OR: 2.67, 95% CI: 1.37–5.23, <em>P</em> = 0.004), Afpel score (OR: 6.54, 95% CI: 3.52–12.15, <em>P</em> &lt; 0.001), anxiety (OR: 3.14, 95% CI: 1.16–8.50, <em>P</em> = 0.025), 5-hydroxytryptamine (5-HT) (OR: 1.05, 95% CI: 1.02–1.07, <em>P</em> &lt; 0.001), prostaglandin E2 (PGE2) (OR: 1.05, 95% CI: 1.01–1.08, <em>P</em> = 0.007), and albumin/fibrinogen ratio (AFR) (OR: 0.40, 95% CI: 0.28–0.56, <em>P</em> &lt; 0.001) were six independent risk factors for PONV. The nomogram model based on these factors has good predictive value for PONV, with an AUC of 0.898.</div></div><div><h3>Conclusions</h3><div>This study identified an individual nomogram prediction model to visually represent the regression model for predicting PONV after laparoscopic surgery for gynecologic cancers.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Pages 143-147"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791226","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":"Safety and Tolerability of Home Infusions in Down Syndrome Regression Disorder","authors":"Jonathan D. Santoro MD ,&nbsp;Lina Nguyen RN ,&nbsp;Nicole A. Nishimori BS ,&nbsp;Ruby Ferris BS ,&nbsp;Benjamin N. Vogel BS ,&nbsp;Natalie K. Boyd BS ,&nbsp;Lilia Kazerooni BS ,&nbsp;Shermila Pia MD ,&nbsp;Mellad M. Khoshnood MD ,&nbsp;Saba Jafarpour MD","doi":"10.1016/j.clinthera.2024.11.023","DOIUrl":"10.1016/j.clinthera.2024.11.023","url":null,"abstract":"<div><h3>Purpose</h3><div>Down syndrome regression disorder (DSRD) is a rare neuropsychiatric condition affecting otherwise healthy individuals with Down syndrome. Multiple studies on DSRD have revealed that immunotherapy with intravenous immunoglobulin (IVIg) is both safe and effective, although site of infusion has never been studied. This study sought to evaluate the safety and tolerability of IVIg in individuals with DSRD receiving home-based infusions.</div></div><div><h3>Methods</h3><div>A single-center, retrospective chart review evaluating infusion reactions was performed for individuals meeting criteria for DSRD and having received IVIg infusions between 2019 and 2024. Adverse events (AEs) were evaluated for severity and need for alterations in infusion plan. A cohort of individuals receiving home-based infusions was compared with a cohort of individuals receiving infusions at an academic medical center.</div></div><div><h3>Findings</h3><div>A total of 315 individuals (162 institutional infusions [51%] and 153 home infusions [49%]) met the inclusion criteria. There were no statistical differences between the demographic and clinical features of the cohorts. Individuals receiving home infusions had the same rate of AE during an infusion (<em>P</em> = 0.14), although they did have a lower number of total AEs (<em>P</em> &lt; 0.001). Individuals receiving home infusions experienced a lower number of behavioral issues with infusions (<em>P</em> = 0.03) and had significantly lower discontinuations of infusions secondary to behavioral issues (<em>P</em> = 0.04).</div></div><div><h3>Implications</h3><div>Rates of AEs and serious AEs in those with DSRD were the same regardless of site of infusion. These data should be considered in policy regarding the appropriateness of home-based infusions as a safe alternative, when suitable for patients and caregivers, for individuals with DSRD.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Pages e27-e33"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845889","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 Systematic Review of Challenges and Opportunities in the Implementation of Managed Entry Agreements for Advanced Therapy Medicinal Products","authors":"Andrea Greco MSc ,&nbsp;Geert W.J. Frederix PhD ,&nbsp;Lotty Hooft PhD ,&nbsp;Renske M.T. Ten Ham PhD","doi":"10.1016/j.clinthera.2024.11.019","DOIUrl":"10.1016/j.clinthera.2024.11.019","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;Managed Entry Agreements (MEAs) are agreements between firms and competent authorities for pricing and reimbursement, designed to enable coverage of new medicines while managing uncertainties around their financial impact or performance. Although these agreements can facilitate patient access, their complexity and costs seem to dampen enthusiasm for implementation. Nevertheless, MEAs remain a potential route, particularly for high-cost drugs with uncertain value claims. Given their pivotal role in bridging Advanced Therapy Medicinal Products (ATMPs) to patients, their foreseeable future implementation calls for a specific investigation of their associated challenges and opportunities. Therefore, this work aims to identify challenges and opportunities in implementing MEAs specifically for ATMPs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A systematic literature review was conducted on PubMed, MEDLINE, Scopus, and Google Scholar, based on the updated Preferred Reporting Items for Systematic Review and Meta-Analysis. This has been supplemented by a snowball search. Through the thematic content analysis, opportunities and challenges were identified and grouped into themes and subthemes. Afterward, the subgroup analysis was performed to investigate challenges and opportunities with outcome-based agreements (OBAs) versus financial-based agreements (FBAs), jurisdiction, and ATMP type.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;Of the 787 peer-reviewed articles, 42 met the inclusion criteria. Challenges and opportunities were clustered into the mentioned themes: evidence generation and data management, financial and reimbursement, administration and resources, negotiation, and governance, law, and regulations. Of note, no specific challenges or opportunities were found to be cell- or gene-therapy-specific, but certain challenges seem amplified for ATMPs. Several differences emerged per MEA type and jurisdiction. OBAs are described to reward innovative and effective treatments and boost research and development (R&amp;D) returns. FBAs improve cost-effectiveness ratios but can negatively affect curative ATMP's revenues. Still, their versatility facilitates payer engagement in MEA combinations (eg, OBA with spread payments). The US decentralized health care system reported additional implementation challenges to OBAs. Each payer internally decides on reimbursement, and coordination among private payers is hindered by antitrust law. Yet, a new Cell and Gene Therapy Access model has been proposed. This would allow manufacturers to negotiate OBAs directly with the Centers for Medicare &amp; Medicaid Services avoiding individual negotiation with each state. In Europe, there is an evident interest in implementing spread payments, yet accounting rules currently hamper their implementation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Implications&lt;/h3&gt;&lt;div&gt;This work offers insights into challenges and opportunities in MEAs implementation for ATMPs by investigating differenc","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Pages e16-e26"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871609","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 Effects of Chia Seed (Salvia hispanica L.) Consumption on Blood Pressure and Body Composition in Adults: A Systematic Review and Meta-analysis of Randomized Controlled Trials","authors":"Mohamed J. Saadh ,&nbsp;Munthar Kadhim Abosaoda ,&nbsp;Lalji Baldaniya ,&nbsp;Rishiv Kalia ,&nbsp;Renu Arya ,&nbsp;Shivang Mishra ,&nbsp;Ashish Singh Chauhan ,&nbsp;Abhinav Kumar ,&nbsp;Mohamad Alizadeh","doi":"10.1016/j.clinthera.2024.11.012","DOIUrl":"10.1016/j.clinthera.2024.11.012","url":null,"abstract":"<div><h3>Purpose</h3><div>Growing evidence has suggested that the consumption of chia seed can decrease blood pressure and obesity in adults. However, even studies have reported uncertain findings. The current meta-analysis aimed to assess the findings of randomized controlled trials (RCTs) on the efficacy of chia seed supplementation on blood pressure (systolic blood pressure [SBP], diastolic blood pressure [DBP]) and body composition (waist circumference [WC], weight, body mass index [BMI]) in adults.</div></div><div><h3>Methods</h3><div>A systematic search of the literature was carried out in the PubMed, Web of Knowledge, Scopus, Cochrane Central Library, and EMBASE from inception up to October 2024. Data were extracted and analyzed using a random-effects model, and reported as weighted mean differences (WMD) with 95% confidence intervals (CI).</div></div><div><h3>Findings</h3><div>A total of eight RCTs involving 372 participants were included in the meta-analysis. The results showed that chia consumption significantly reduced DBP (WMD: -7.49 mmHg; 95% CI: -9.64, -5.34; <em>P</em> &lt; 0.001) and SBP (WMD: -5.61 mmHg; 95% CI: -8.77, -2.44; <em>P</em> = 0.001). Moreover, consuming chia seeds was linked to a notable decrease in WC (WMD: -1.46 cm; 95% CI: -2.68, -0.25; <em>P</em> = 0.01), but it had no significant effect on, BMI (WMD: -0.31 kg/m²; 95% CI: - 0.96, 0.34; <em>P</em> = 0.34) and weight (WMD: 0.09 kg; 95% CI: -0.76, 0.93; <em>P</em> = 0.84).</div></div><div><h3>Implications</h3><div>Chia consumption can significantly reduce SBP, DBP, and WC in adults, but no significant impact was showed on BMI and weight. To verify these results, more studies involving a greater number of participants are required.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Pages 168-175"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821900","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":"Thrombotic Microangiopathy Associated with Calcineurin Inhibitors: A Real-World Analysis of Postmarketing Surveillance Data","authors":"Xin Yu ,&nbsp;Yi Zhang ,&nbsp;Zhuoling An ,&nbsp;Xin Feng ,&nbsp;Hui Yang","doi":"10.1016/j.clinthera.2024.11.017","DOIUrl":"10.1016/j.clinthera.2024.11.017","url":null,"abstract":"<div><h3>Purpose</h3><div>Calcineurin inhibitors (CNIs) are currently the first-line drugs for preventing and treating post-transplant rejection in organ transplant recipients. However, these drugs, especially tacrolimus, have the potential to induce thrombotic microangiopathy (TMA), a rare but potentially fatal complication that can develop following transplantation. This condition has garnered considerable attention within the medical community. Consequently, the study conducted an observational retrospective pharmacovigilance study to investigate the risk signal of thrombotic microangiopathy associated with CNIs.</div></div><div><h3>Methods</h3><div>A retrospective pharmacovigilance study was conducted to investigate the relationship between CNIs and TMA using data from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. A disproportionality analysis was performed to evaluate risk signals.</div></div><div><h3>Findings</h3><div>A total of 1019 cases of CNIs-associated TMA were identified, with 785 cases attributed to tacrolimus and 234 cases to cyclosporine A. Overall, the incidence of CNIs related TMA was higher compared to the entire database (ROR = 29.76 [27.84–31.82], IC = 4.64 [4.55–4.74]). A stronger signal was observed for tacrolimus-associated TMA compared to cyclosporine A (ROR = 3.72 [3.20–4.23], IC = 0.63 [0.50–0.77]). Additionally, residing in the Americas may be a protective factor against mortality in tacrolimus-related TMA, while for cyclosporine A-related TMA, patients from Asia and female patients have a significantly higher risk of death.</div></div><div><h3>Implications</h3><div>Clinician awareness of CNIs-associated TMA needs to be heightened, particularly with tacrolimus. Special attention should be given to patients’ geographic regions and gender differences.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Pages 117-122"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845910","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":"Managed Entry Agreements: Tools of Necessity, Works in Progress","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2024.12.017","DOIUrl":"10.1016/j.clinthera.2024.12.017","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Pages 115-116"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022483","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":"Corrigendum to: “Prevalence of Potential Drug Interactions With Direct-Acting Antivirals for COVID-19 Among Hospitalized Patients” [Clin Ther 2024;46:778–784]","authors":"Essy Mozaffari PharmD, MPH, MBA ,&nbsp;Aastha Chandak PhD ,&nbsp;Andrew Ustianowski MD, PhD ,&nbsp;Christina G. Rivera PharmD, RPh ,&nbsp;Neera Ahuja MD, FACP ,&nbsp;Heng Jiang MPH ,&nbsp;Mark Berry PhD ,&nbsp;Jason F. Okulicz MD ,&nbsp;Alpesh N. Amin MD","doi":"10.1016/j.clinthera.2024.11.013","DOIUrl":"10.1016/j.clinthera.2024.11.013","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Page 178"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767045","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":"Population Pharmacokinetics of Ledipasvir/Sofosbuvir in Pediatric Patients: Impact of Acute Lymphoblastic Leukemia","authors":"Aya M. AbdelMagid PhD ,&nbsp;Maggie M. Abbassi PhD ,&nbsp;Fatma S. Ebeid MD, MRCPCH ,&nbsp;Manal H. El-Sayed MD, PhD ,&nbsp;Samar F. Farid PhD","doi":"10.1016/j.clinthera.2024.11.022","DOIUrl":"10.1016/j.clinthera.2024.11.022","url":null,"abstract":"<div><h3>Purpose</h3><div>The pharmacokinetic (PK) profile of direct-acting antivirals, namely ledipasvir/sofosbuvir (LDV/SOF), might be altered in patients with acute lymphoblastic leukemia (ALL), affecting the optimum dose needed for hepatitis C virus treatment. Limited data are available evaluating the population PK of LDV/SOF and SOF metabolite GS-331007. We aimed to study whether ALL could affect population PK parameters of LDV, SOF, and the SOF major metabolite GS-331007 in hepatitis C virus-infected children, develop and validate a predictive PK model of LDV/SOF disposition in this special population, and identify their explained and unexplained sources of variability.</div></div><div><h3>Methods</h3><div>Population PK modeling was performed using MonolixSuite software using the non-linear mixed effect modeling approach. Different compartmental models, absorption models, and lag times for absorption parameters were tested to find out the best-fitting base model. For final model development, data-driven systematic covariate analysis using conditional sampling for the stepwise approach based on the correlation tests method has been performed. The final models were then evaluated using internal validation approaches.</div></div><div><h3>Findings</h3><div>The PK results of 22 fully compliant patients were included in the population PK analysis. LDV and SOF were best described by a 1-compartment model with zero-order absorption and lag time, while the 2-compartment model with first-order absorption and lag time was the best-fitting model for the SOF metabolite. The internal validation approach confirmed the good predictive power of the selected models. The patients’ weight explained the variability in the volume of distribution of LDV and the systemic clearance of SOF and LDV. The final SOF model also included a statistically significant covariate of steatosis stage on its volume of distribution, while the final GS-331007 model included mean corpuscular volume values on GS-331007 central compartment volume, packed cell volume, and direct bilirubin values on metabolite intercompartmental clearance.</div></div><div><h3>Implications</h3><div>The presence of ALL did not explain any variability in the developed population PK models for SOF, LDV, and GS-331007. Despite weight being a significant covariate in the final models suggesting that weight-based dosing of LDV/SOF is better than fixed dosing, the fixed dosing (45/200 mg LDV/SOF) is more practical in terms of simplicity in dosing children at home besides the proved efficacy and safety through both the clinical outcomes and PK exposure results. Weight-based dosing is still hindered due to the absence of exposure-response analysis, and the unavailability of dose-flexible formulas in the market. Future studies are required to support these findings.</div></div><div><h3>ClinicalTrials.gov identifier</h3><div>NCT03903185.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Pages e5-e15"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871610","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":"Bioequivalence of Water-Soluble Progesterone Injection (GenSci070) in Healthy Chinese Postmenopausal Women Volunteers","authors":"Rong Song BS ,&nbsp;Xue Wu MS ,&nbsp;Liang Xin MS ,&nbsp;Chan Sun BS ,&nbsp;Yuzhou Gui PhD ,&nbsp;Hongjie Qian PhD ,&nbsp;Chen Yu BS ,&nbsp;Qian Chen PhD ,&nbsp;Tianhong Luo PhD ,&nbsp;Ying Ding MD ,&nbsp;Weiwei Gao PhD ,&nbsp;Xiaoyan Zhu PhD ,&nbsp;Jingying Jia MS","doi":"10.1016/j.clinthera.2024.12.015","DOIUrl":"10.1016/j.clinthera.2024.12.015","url":null,"abstract":"<div><h3>Purpose</h3><div>To study the pharmacokinetic characteristics of progesterone (GenSci070) in healthy Chinese postmenopausal women volunteers and to evaluate the bioequivalence and safety of GenSci070 and reference formulation.</div></div><div><h3>Methods</h3><div>In this randomized, open-label, single-center, single-dose, 2-period, 2-sequence, 2-way crossover study, 50 postmenopausal healthy women were recruited and received a single subcutaneous injection of test (GenSci070) or reference formulation 25 mg, respectively. Plasma progesterone concentrations were measured using liquid chromatography–tandem mass spectrometry, and pharmacokinetic parameters were calculated by noncompartmental analysis method using Phoenix WinNonlin 8.3.1 software to evaluate the bioequivalence. The safety profile was evaluated by adverse events, physical examination, vital signs, laboratory tests, 12-lead ECG, etc.</div></div><div><h3>Findings</h3><div>The geometric mean ratios (90% CIs) for C_max, AUC_0–t, and AUC_0–∞ of the test and reference formulations were 92.70% (87.29%–98.44%), 96.26% (94.02%–98.55%), and 95.46% (93.27%–97.71%), respectively. They were all within the acceptable bioequivalence range of 80% to 125%. Thirty-one treatment-emergent adverse events occurred in 22 participants (44.0%) who received test formulation and 21 treatment-emergent adverse events occurred in 16 participants (32.0%) who received reference formulation, all events were mild.</div></div><div><h3>Implications</h3><div>The water-soluble progesterone injection (GenSci070) demonstrated bioequivalence to the marketed progesterone injection (Lubion) and exhibited a good safety profile in this study.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 4","pages":"Pages 271-276"},"PeriodicalIF":3.2,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074336","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":"Potential of Albumin-Bilirubin Score for Estimating the Voriconazole-Induced Hepatotoxicity Undergoing Therapeutic Drug Monitoring: A Single-Center Retrospective Cohort Study","authors":"Yuki Asai PhD ,&nbsp;Hideo Kato PhD ,&nbsp;Isao Tawara MD, PhD ,&nbsp;Yuki Nakano PhD ,&nbsp;Takuya Iwamoto PhD","doi":"10.1016/j.clinthera.2025.01.006","DOIUrl":"10.1016/j.clinthera.2025.01.006","url":null,"abstract":"<div><h3>Purpose</h3><div>Despite implementation of therapeutic drug monitoring (TDM) for voriconazole, the incidence of hepatotoxicity remains high. The albumin-bilirubin (ALBI) score may be useful for estimating voriconazole-induced hepatotoxicity. This pilot study aimed to investigate whether the ALBI score could estimate voriconazole-induced hepatotoxicity during TDM implementation.</div></div><div><h3>Methods</h3><div>This single-center, retrospective cohort study included 134 patients. The primary outcome was voriconazole-induced hepatotoxicity. The cutoff value of the ALBI score was determined using a receiver operating characteristic curve. The cumulative risk of hepatotoxicity was evaluated using Kaplan–Meier curve analysis with a log-rank test for the cutoff value and ALBI grade. Moreover, the group of patients with the trough concentration of voriconazole 1−4 μg/mL was also investigated.</div></div><div><h3>Findings</h3><div>The incidence of hepatotoxicity was 13.4% (18/134). The cutoff value of the ALBI score was -1.91 (sensitivity, 0.611; specificity, 0.655; area under the curve, 0.615). The cumulative risk of hepatotoxicity was significantly higher in the ALBI score ≥-1.91 group than in the ALBI score &lt;-1.91 group (<em>P</em> = 0.024) and patients with higher ALBI grades tended to be at higher risk (<em>P</em> = 0.080). The cumulative risk tended to be higher with ALBI ≥-1.91 in the trough concentration 1−4 μg/mL group; however, no significant difference was found (<em>P</em> = 0.134).</div></div><div><h3>Implications</h3><div>The pilot study indicated that the ALBI score ≥-1.91 may be an indicator for voriconazole-induced hepatotoxicity even when TDM is conducted. Because this study was a single-center and small cohort design, further studies should be conducted using a large datasets and translational research.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 4","pages":"Pages 330-334"},"PeriodicalIF":3.2,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074337","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}