Clinical therapeutics最新文献

{"title":"Cost-Effectiveness of Zanubrutinib Versus Bendamustine and Rituximab in Patients With Untreated Chronic Lymphocytic Leukemia.","authors":"Jing Nie, Lihui Liu, Huina Wu, Shan Yuan, Ke Tang, Jiyong Wu","doi":"10.1016/j.clinthera.2024.08.016","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.08.016","url":null,"abstract":"<p><strong>Purpose: </strong>Zanubrutinib, a potent and specific irreversible Bruton's tyrosine kinase inhibitor, has proven to be effective in untreated chronic lymphocytic leukemia (CLL), whether used alone or in combination with other therapies. Here, we compared the cost-effectiveness of zanubrutinib with bendamustine-rituximab (R-bendamustine) to determine its effectiveness as the first-line treatment for Chinese patients with untreated CLL.</p><p><strong>Methods: </strong>The evaluation utilized a partitioned survival model, constructed using TreeAge Pro 2011 software, incorporating data from SEQUOIA trial (NCT03336333). Transition probabilities were estimated from the reported survival probabilities in trials using parametric survival modeling. In this analysis, the quality-adjusted life years (QALYs), incremental cost-effectiveness ratio, and lifetime cost were calculated from the Chinese health care system perspective. Sensitivity analyses, including 1-way analysis and probabilistic sensitivity analysis, were carried out to explore the uncertainty of the modeling results. Additionally, several scenario analyses, including different zanubrutinib price calculation and 20-year time horizon, were evaluated.</p><p><strong>Findings: </strong>The findings revealed that zanubrutinib had an incremental cost-effectiveness ratio of $58,258.18 per additional QALYs gained compared with bendamustine-rituximab, with zanubrutinib being cost-effective only if its price was reduced by more than 30%. Research indicated that zanubrutinib achieved at least a 3.70% probability of cost-effectiveness at the threshold of $38,223.34/QALY. One-way sensitivity analysis revealed that the results were sensitive to the utility of progressed disease.</p><p><strong>Implications: </strong>The study highlighted the importance of considering the cost-effectiveness of zanubrutinib at its current price point for patients with untreated CLL in China, emphasizing the need for further assessment and potential pricing adjustments to enhance its economic viability in clinical practice.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281580","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":"Clinical Update on an Anti-Alzheimer Drug Candidate CT1812: A Sigma-2 Receptor Antagonist.","authors":"Guramrit Kaur, Zahid Ahmad Dar, Ankit Bajpai, Ranjit Singh, Ranju Bansal","doi":"10.1016/j.clinthera.2024.08.013","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.08.013","url":null,"abstract":"<p><strong>Purpose: </strong>This review article summarizes the progress and latest findings related to the investigational drug candidate CT1812, which is currently in phase 2 clinical trials for Alzheimer's disease (AD). The article outlines the development of this promising molecule and provides insights into its mechanism of action as sigma-2 receptor (S2R) antagonist along with the positive outcomes of various clinical trials. Literature mentioning AD therapeutics that specifically target amyloid-beta (Aβ) oligomers is limited even though these oligomers are established as the most neurotoxic forms of the Aβ protein. This timely article highlights the potential of CT1812 as a breakthrough in AD therapeutics, providing a new avenue for addressing the neurotoxic forms of Aβ and advancing the field toward a potential cure for AD.</p><p><strong>Methods: </strong>The literature includes articles searched from PubMed and Google Scholar along with a comprehensive discussion of all the clinical research trials undertaken for CT1812. The review includes 12 clinical trials; of the total citations identified, 10 have been used to support the results of published trials.</p><p><strong>Findings: </strong>The positive outcomes in the multiple clinical trials conducted on CT1812 indicate the emergence of an effective and promising drug candidate for AD. The article mentions a gap in the literature regarding AD therapeutics specifically targeting Aβ oligomers, which reveals lack of established treatments addressing Aβ oligomers, making the novel approach of CT1812 noteworthy.</p><p><strong>Implications: </strong>Clinical treatments available today provide symptomatic relief, however, any drug providing a potential cure for AD remains an unanswered question. S2Rs mediated oligomer binding in addition to synaptic toxicity suggest the potential usefulness of CT1812 in AD treatment. Efficacy and safety of CT1812 in further clinical trials could represent a significant advancement in the field, offering a potential treatment that goes beyond the symptomatic relief and aimed at addressing the core mechanisms associated with AD.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281579","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 Prior Antiplatelet Therapy and Prognosis in Patients With Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.","authors":"Hanxu Zhang, Xiaoran Hou, Yidan Gou, Yanyan Chen, Shuo An, Yingsheng Wei, Rongcai Jiang, Ye Tian, Hengjie Yuan","doi":"10.1016/j.clinthera.2024.08.010","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.08.010","url":null,"abstract":"<p><strong>Purpose: </strong>Approximately 20% to 30% of intracerebral hemorrhage (ICH) patients were reported to be on antiplatelet therapy (APT), and association between prior APT and prognosis was unclear. We aimed to clarify the impact of APT on the prognosis of ICH through an updated systematic review and meta-analysis, and to further compare the risk of single APT (SAPT) or dual APT (DAPT) prior to ICH as well as the risk associated with various antiplatelet drugs.</p><p><strong>Methods: </strong>EMBASE, MEDLINE via Ovid SP and Web of Science were searched from inception of each database to November 4, 2023. Included studies reported prognosis in both patients with prior APT and those without.</p><p><strong>Findings: </strong>A total of 433,103 patients from 43 studies were included in the meta-analysis. Both univariate and multivariate analyses demonstrated a significant association between prior-APT and an increased mortality risk (odd ratio [OR] 1.43, 95% confidence interval [CI] 1.28-1.59; OR 1.20, 95%CI 1.10-1.30, respectively). The risk was higher in short term follow-up (Univariate OR 1.73, 95%CI 1.22-2.46; Multivariate OR 1.94, 95%CI 1.48-2.55). A notably increased risk of hematoma expansion was also observed in patients previously treated with APT (Univariate OR 1.47, 95%CI 1.12-1.94; Multivariate OR 1.88, 95%CI 1.30-2.71), which were mainly attributed to events within 24 hours. The impact of prior-APT on poor functional outcome was inconsistent between univariate and multivariate analyses. Both direct and indirect comparisons showed that SAPT significantly reduced the risk of mortality (OR 0.67, 95%CI 0.64-0.70; OR 0.84, 95%CI 0.71-0.99) and poor functional outcome (OR 0.84, 95%CI 0.72-0.98; OR 0.81, 95%CI 0.72-0.91) compared to DAPT.</p><p><strong>Implications: </strong>Prior-APT increased the risk of mortality and hematoma expansion in patients with ICH. The increased risk of mortality and hematoma expansion was more obvious in the short term follow-up and within 24 hours, respectively. The effect of APT on poor functional outcome exhibited inconsistency between univariate and multivariate analyses, suggesting that further investigation is warranted to clarify this relationship. In comparison with DAPT, SAPT could decrease the risk of mortality and poor functional outcome. Further studies focusing on antiplatelet drug response, racial differences, and specific APT regimens may help verify the influence.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281578","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":"Optimizing Acute Ischemic Stroke Outcomes: The Role of Tenecteplase Before Mechanical Thrombectomy.","authors":"Arsh Haj Mohamad Ebrahim Ketabforoush, Ali Hosseinpour, Mohamad Amin Habibi, Armin Ariaei, Maedeh Farajollahi, Rojin Chegini, Zahra Mirzaasgari","doi":"10.1016/j.clinthera.2024.08.014","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.08.014","url":null,"abstract":"<p><strong>Purpose: </strong>Acute ischemic stroke (AIS) is a life-threatening condition demanding prompt reperfusion to salvage brain tissue. Thrombolytic drugs, like tenecteplase (TNK), offer clot dissolution, but time constraints and contraindications limit their use. Mechanical thrombectomy (MT) revolutionized AIS treatment, especially for large vessel occlusions (LVO). Recent evidence suggests that administering TNK before MT improves recanalization and outcomes, challenging the dominance of alteplase.</p><p><strong>Methods: </strong>Relevant articles focusing on TNK before MT were retrieved from PubMed, Scopus, and Web of Science, looking for randomized controlled trials (RCT), clinical trials, and meta-analyses in humans until 2024.</p><p><strong>Findings: </strong>TNK, a genetically engineered thrombolytic, exhibits superior fibrin specificity and a longer half-life than alteplase. Clinical trials comparing TNK and alteplase before MT showcase enhanced recanalization, functional outcomes, and safety with TNK. Advanced neuroimaging aids patient selection, though its cost-effectiveness warrants consideration. Dosing studies favor a 0.25 mg/kg dose for efficacy and reduced complications. Clinical guidelines from various associations acknowledge TNK's potential as an alteplase alternative for AIS treatment, particularly for LVOs eligible for thrombectomy.</p><p><strong>Implications: </strong>In conclusion, TNK emerges as a promising option for bridging therapy in AIS, displaying efficacy and safety benefits, especially when administered before MT. Its fibrin specificity, longer half-life, and potential for improved outcomes position TNK as a viable alternative to alteplase, potentially transforming the landscape of AIS treatment strategies. While limitations like small sample sizes and variations in protocols exist, future research should focus on large-scale RCT, subgroup analyses, and cost-effectiveness evaluations to further elucidate TNK's role in optimizing AIS management.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281583","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":"Bariatric Surgery Underutilization in Young Postadolescent Population With Obesity","authors":"Ariana S. Ginsberg MD, Artur Chernoguz MD FACS","doi":"10.1016/j.clinthera.2024.08.012","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.08.012","url":null,"abstract":"Bariatric surgery is an established treatment option for adolescent patients struggling with obesity, yet it remains underutilized. We aimed to gain insight into patients’ views of bariatric surgery and identify the strategies for improved utilization of the procedure in early postadolescence. The electronic medical records of patients diagnosed with obesity at a tertiary medical center, ages 18–22 years old, were examined. Patients participated in a follow-up survey related to obesity treatment. While 20% of patients had BMIs ≥ 35 kg/m in adolescence, more than half (54%) of patients with obesity reached BMIs ≥ 35 kg/m after 18 y/o, thus potentially qualifying for bariatric surgery. A minority of patients (6/280, 2%) underwent bariatric surgery and experienced substantial weight loss in early postadolescence. Most remaining surgery-eligible patients (141/152, 93%) noted a BMI increase (0.05–28.6 kg/m) during the immediate young adult study period without surgical intervention. While 66.7% of patients who recall receiving surgery-specific counseling would consider surgery as a part of their treatment, only 4.6% of patients who did not recall counseling would consider undergoing bariatric surgery. In the absence of provider referral during adolescence, bariatric surgery remains underutilized in early postadolescence. Provider counseling is an essential component of patients’ willingness to consider bariatric surgery.","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250402","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":"Risk Factors for E₂SKAPE Infections and Mortality Among Liver Transplant Recipients.","authors":"Xiaoxia Wu, Chenpeng Xie, Weiting Peng, Jie Zhao, Lin Shu, Manjie Guo, Qiquan Wan","doi":"10.1016/j.clinthera.2024.08.017","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.08.017","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;Infections caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp (ESKAPE) plus Escherichia coli (E&lt;sub&gt;2&lt;/sub&gt;SKAPE), in particular multidrug-resistant (MDR) E&lt;sub&gt;2&lt;/sub&gt;SKAPE infections, occur frequently and pose a life-threatening to liver transplant (LT) recipients. To prevent E&lt;sub&gt;2&lt;/sub&gt;SKAPE infections and improve the prognosis of LT recipients, the identification of risk factors for E&lt;sub&gt;2&lt;/sub&gt;SKAPE infections and mortality is necessary.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;E&lt;sub&gt;2&lt;/sub&gt;SKAPE pathogens were isolated and identified from clinical samples following standard microbiological procedures. All episodes of E&lt;sub&gt;2&lt;/sub&gt;SKAPE infections and mortality documented among LT recipients were analyzed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;A total of 83 episodes of E&lt;sub&gt;2&lt;/sub&gt;SKAPE infections, including 75 (90.4%) episodes of MDR-E&lt;sub&gt;2&lt;/sub&gt;SKAPE infections, occurred in 23.1% (53/229) of LT recipients. E. faecium was the dominant causative bacterium (37/83; 44.6%). The most common site of infections was the urinary tract (14/53; 26.4%). Sixteen (7%) patients died within 2 months after LT, and 7 deaths were E&lt;sub&gt;2&lt;/sub&gt;SKAPE infections-related. Multivariate logistic regression analysis revealed that female sex [odds ratio (OR) = 3.665, 95% confidence interval (CI): 1.614-8.321, P = 0.002], duration of surgery ≥ 400 min [OR = 2.328, 95%CI: 1.151-4.707, P = 0.019], intraoperative red blood cell (RBC) transfusion ≥ 12U [OR = 2.542, 95%CI: 1.218-5.306, P = 0.013] and indwelling urethral catheter use ≥ 3 days [OR = 3.96, 95%CI: 1.309-11.981, P = 0.015] were independent risk factors for E&lt;sub&gt;2&lt;/sub&gt;SKAPE infections after LT, and that only exposure to more than 2 intravenous antibiotics post-LT [OR = 0.318, 95%CI: 0.15-0.674, P = 0.003] was negatively associated with acquisition of E&lt;sub&gt;2&lt;/sub&gt;SKAPE infections. The predictors of crude mortality included female sex [OR = 4.822, 95%CI: 1.299-17.904, P = 0.019], creatinine on day 3 post-LT &gt; 1.5 mg/dL [OR = 11.014, 95%CI: 2.985-40.637, P &lt; 0.001], mechanical ventilation post-LT [OR = 10.724, 95%CI: 2.695-42.676, P = 0.001] and recipients with E&lt;sub&gt;2&lt;/sub&gt;SKAPE infections [OR = 4.112, 95%CI: 1.169-14.47, P = 0.028].&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Implications: &lt;/strong&gt;A high incidence of E&lt;sub&gt;2&lt;/sub&gt;SKAPE infections was noted in the early post-LT period. The most common infection site was the urinary tract, and the dominant pathogenic bacterium was E. faecium. Female sex, prolonged surgery time, massive RBC transfusion, or delayed urethral catheter removal were associated with E&lt;sub&gt;2&lt;/sub&gt;SKAPE infections. Only exposure to more than 2 intravenous antibiotics post-LT was negatively related to the acquisition of E&lt;sub&gt;2&lt;/sub&gt;SKAPE infections. The predictors of mortality included female sex, creatinine on day 3 post-LT&gt;1.5 mg/dL, mechanical ventilation post-LT, and recipients with E&lt;sub&gt;2&lt;/sub&gt;S","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281585","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":"Budget Impact Analysis of Dapagliflozin in Treating Patients With Heart Failure With Reduced Ejection Fraction From the Perspective of Malaysian Public Healthcare System","authors":"Yi Jing Tan MPharm MSc, Joo Zheng Low MSc, Siew Chin Ong PhD","doi":"10.1016/j.clinthera.2024.08.008","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.08.008","url":null,"abstract":"This is a budget impact analysis that compared the scenario of treating heart failure with reduced ejection fraction (HFrEF) using dapagliflozin plus standard of care (SoC) versus a scenario without dapagliflozin, from the perspective of Ministry of Health (MOH) Malaysia over a 5-year time horizon. A Microsoft Excel-based cost calculator was developed for such comparison. The estimated size of eligible population, uptake rates for dapagliflozin, as well as costs related to drugs, clinical events, and adverse events were based on published data, official tariffs, and databases, and expert opinion. Clinical data from the DAPA-HF trial were used to inform efficacy and safety inputs (i.e., hospitalization for heart failure (hHF), cardiovascular death, and adverse events). Results were reported as total annual and cumulative costs (in 2023 Malaysian Ringgits [RM], United States Dollars [USD], and European Union Euros, [EUR]; with exchange rates of 1 USD = RM 4.40 and 1 EUR = RM 4.90]), as well as the number of clinical events. Sensitivity and scenario analyses were also conducted. The base-case analysis estimated that over a five-year period, the adoption of dapagliflozin for HFrEF treatment would result in a cumulative cost-saving of RM 2.6 million (USD 0.6 million/EUR 0.5 million), representing a 0.3% reduction in costs, driven primarily by reduced expenditure on hHF. Moreover, dapagliflozin treatment would lead to 731 fewer hHF and 366 fewer cardiovascular deaths. Sensitivity and scenario analyses revealed that the results were most sensitive to assumptions regarding loop diuretic requirements and the cost of dapagliflozin. Although cost savings or a net-zero balance were projected for the first four years, an anticipated 2.5% annual increase in dapagliflozin uptake in the longer term would lead to additional costs for the MOH, starting from the fifth year. Incorporating dapagliflozin into the SoC can improve health outcomes for HFrEF patients and may generate cost savings, potentially easing the economic strain of HFrEF management on Malaysia's public healthcare system in the short term. Nonetheless, a modest increase in budget should be anticipated as more patients gain access to the treatment over time.","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250403","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":"Effect of Everolimus on Prognosis of Neurofibromatosis Type 1 Lesions: A Systematic Review and Meta Analysis.","authors":"Ismail A Ibrahim, Rem Ehab Abdelkader, Ahmed Hosney Nada, Siham Younes, George Hanen, Ghena Shahwan, Mohammad Hamad, Mostafa Meshref, Abdulqadir J Nashwan","doi":"10.1016/j.clinthera.2024.08.009","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.08.009","url":null,"abstract":"<p><strong>Purpose: </strong>This study addresses the effectiveness of oral everolimus in treating various malignancies associated with Neurofibromatosis Type 1 (NF1). The purpose is to determine whether everolimus reduces lesion size in NF1 patients, considering the controversial findings from previous clinical trials. The scientific hypotheses and questions involve evaluating the impact of everolimus on NF1-associated lesions and understanding the variability in treatment outcomes.</p><p><strong>Methods: </strong>A systematic review and meta-analysis were conducted following PRISMA and Cochrane Collaboration guidelines. The study included four-phase II, single-arm, nonrandomized trials investigating the effect of oral everolimus on NF1-associated lesion size. The search covered multiple databases, and data extraction involved evaluating studies for inclusion criteria and assessing quality using the Cochrane Collaboration's Risk of Bias in Nonrandomized Studies tool. Statistical analysis utilized Open Meta(Analyst).</p><p><strong>Findings: </strong>The search yielded 388 studies, with 10 selected for full-text review and four included in the final analysis. The quality of the studies ranged from low to moderate. The meta-analysis indicated no observed heterogeneity (I^2 = 0%), and the overall estimate suggested no significant reduction in NF1-associated lesion size with everolimus (P = 0.069).</p><p><strong>Implications: </strong>The findings reveal a varied and inconsistent picture of everolimus efficacy in NF1 treatment. The study highlights the need for personalized approaches, considering individual genetic and clinical differences. The limitations, including small sample sizes and nonrandomized trials, call for larger, more standardized research efforts. The study emphasizes ongoing trials and the importance of future research in understanding predictors of everolimus response and optimizing treatment strategies for NF1 patients.</p><p><strong>Conclusion: </strong>While everolimus shows promise in reducing lesion size in a subset of NF1 patients, the study cannot draw conclusive results due to limitations in the included studies. Ongoing, adequately powered trials are crucial for advancing the evidence base and informing the potential role of everolimus in NF1 treatment.</p><p><strong>Others: </strong>There was no funding for this review and no conflicts of interest.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145350","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":null,"pages":null},"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":null,"pages":null},"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}