Clinical therapeutics最新文献

{"title":"Evaluation of Dexmedetomidine Withdrawal and Management After Prolonged Infusion","authors":"Christine S. Kim PharmD, BCCCP ,&nbsp;Kevin C. McLaughlin PharmD, BCCCP, BCPS ,&nbsp;Natasha Romero PharmD, BCCCP, BCPS ,&nbsp;Kaitlin E. Crowley PharmD, BCCCP, BCPS","doi":"10.1016/j.clinthera.2024.09.006","DOIUrl":"10.1016/j.clinthera.2024.09.006","url":null,"abstract":"<div><h3>Purpose</h3><div>Dexmedetomidine is often used for longer than its labeled indication of 24 hours, raising concerns for potential withdrawal. Data are limited regarding this syndrome in adult patients. This study aimed to further characterize dexmedetomidine withdrawal in critically ill adult patients after prolonged use.</div></div><div><h3>Methods</h3><div>This was an institutional review board–exempt, single-center, retrospective chart review conducted at a tertiary academic medical center. Adult intensive care unit (ICU) patients on dexmedetomidine for ≥72 hours in 2019 were screened for inclusion. Exclusion criteria were interruption of dexmedetomidine for &gt;6 hours, indications for dexmedetomidine other than sedation, or patients with neurological or burn injury. The major end point was the incidence of dexmedetomidine withdrawal, defined as meeting ≥2 of the following criteria within 24 hours of discontinuation: newly positive Confusion Assessment Method for ICU, Richmond Agitation Sedation Scale score of ≥+2, hypertension, and tachycardia. Minor end points were incidence of individual withdrawal signs as previously described, additional sedatives or antipsychotics required, dose and duration of dexmedetomidine infusion, length of ventilation, ICU and hospital length of stay, and new onset of the following: fever, vomiting, loose stools/diarrhea, diaphoresis, or seizure.</div></div><div><h3>Findings</h3><div>Of the 152 patients included, dexmedetomidine withdrawal occurred in 54 patients (35.5%). Rebound hypertension was the most common withdrawal sign (47 patients [87.0%]). In the withdrawal group, significantly more patients required additional β-blockers (29 [53.7%] vs 10 [10.2%]; <em>P</em> &lt; 0.01), were reinitiated on dexmedetomidine (16 [29.6%] vs 10 [10.2%]; <em>P</em> &lt; 0.01), and required a start or increased dose of clonidine (6 [11.1%] vs 3 [3.1%]; <em>P</em> = 0.04). There was no significant difference in the cumulative dose or duration of dexmedetomidine between the groups. Length of ventilation was longer in the withdrawal group (171 hours [83.7–280.8 hours] vs 159 hours [149.0–335.7 hours]; <em>P</em> &lt; 0.01), but there was no difference in ICU or hospital length of stay.</div></div><div><h3>Implications</h3><div>Prolonged use of dexmedetomidine was associated with withdrawal syndrome in 35.5% of patients in our study. Larger trials are needed to confirm the risk factors for dexmedetomidine withdrawal and identify measures to prevent withdrawal.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 12","pages":"Pages 1034-1040"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388662","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":"Cost-effectiveness Analysis of Prophylaxis Versus On-demand Treatment for Children With Moderate or Severe Hemophilia A in China","authors":"Yaohan Zhou ,&nbsp;Zhengping Li ,&nbsp;Guoqing Liu ,&nbsp;Zhenping Chen ,&nbsp;Wanru Yao ,&nbsp;Gang Li ,&nbsp;Yingzi Zhen ,&nbsp;Xiaoling Cheng ,&nbsp;Di Ai ,&nbsp;Kun Huang ,&nbsp;Wang Cao ,&nbsp;Runhui Wu MD, PhD","doi":"10.1016/j.clinthera.2024.09.003","DOIUrl":"10.1016/j.clinthera.2024.09.003","url":null,"abstract":"<div><h3>Background</h3><div>It is still being determined if prophylaxis (PR) has superior cost effectiveness compared with on-demand (OD) treatment for moderate or severe hemophilia A (HA) children in China.</div></div><div><h3>Objective/Purpose</h3><div>To evaluate the cost-effectiveness of PR and OD treatment for children with moderate or severe HA without inhibitors in China.</div></div><div><h3>Methods</h3><div>A retrospective cost-effectiveness study was conducted on 640 HA children (373 and 267 children were on the PR and OD treatment, respectively) from January 2021 to November 2022. The Markov model was used to estimate the economic and clinical outcomes and would run for 17 yearly cycles with the initial age at 2 years. The transfer probabilities were extracted from the data of “Hemophilia Home Care Center” and the literature published. All patients’ drug costs were collected from the data of “Hemophilia Home Care Center”. One-way and probabilistic sensitivity analyses were conducted on the data to evaluate the robustness of the results.</div></div><div><h3>Results/Findings</h3><div>PR was consistently associated with higher overall quality-adjusted life years (QALYs) compared with OD treatment (9.59 QALYs vs. 6.85 QALYs). The incremental cost-effectiveness ratio (ICER) of PR compared with the OD treatment was calculated to be approximately US$12,151.35 (RMB¥81,778.55) per QALY gained. This amount was lower than the willingness-to-pay (WTP) threshold of US$38,212.74 (RMB¥257,171.71). One-way sensitivity analysis found that the results were sensitive to the cost of OD and PR treatments.</div></div><div><h3>Conclusions/Implications</h3><div>This study indicated that PR is cost-effective compared with OD treatment for children with moderate or severe HA without inhibitors in China.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 12","pages":"Pages 1010-1015"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459922","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":"Machine Learning for Prediction of Postoperative Delirium in Adult Patients: A Systematic Review and Meta-analysis","authors":"Hao Chen MSc ,&nbsp;Dongdong Yu MSc ,&nbsp;Jing Zhang MSc ,&nbsp;Jianli Li PhD","doi":"10.1016/j.clinthera.2024.09.013","DOIUrl":"10.1016/j.clinthera.2024.09.013","url":null,"abstract":"<div><h3>Purpose</h3><div>This meta-analysis aimed to evaluate the performance of machine learning (ML) models in predicting postoperative delirium (POD) and to provide guidance for clinical application.</div></div><div><h3>Methods</h3><div>PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to April 29, 2024. Studies reported ML models for predicting POD in adult patients were included. Data extraction and risk of bias assessment were performed using the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis - AI (TRIPOD-AI) and Prediction model Risk Of Bias ASsessment Tool (PROBAST) tools. Meta-analysis with the area under the curve (AUC) was performed using MedCalc software.</div></div><div><h3>Findings</h3><div>A total of 23 studies were included after screening. Age (n = 20, 86.95%) and Random Forest (RF) (n = 24, 17.27%) were the most frequently used feature and ML algorithm, respectively. The meta-analysis showed an overall AUC of 0.792. The ensemble models (AUC = 0.805) showed better predictive performance than single models (AUC = 0.782). Additionally, considerable variations in AUC were found among different ML algorithms, with AdaBoost (AB) demonstrating good performance with AUC of 0.870. Notably, the generalizability of these models was uncertain due to limitations in external validation and bias assessment.</div></div><div><h3>Implications</h3><div>The performance of ensemble models were higher than single models, and the AB algorithms demonstrated better performance, compared with other algorithms. However, further research was needed to enhance the generalizability and transparency of ML models.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 12","pages":"Pages 1069-1081"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459923","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":"Systematic Review of Sex-specific High Sensitivity Cardiac Troponin I and T Thresholds","authors":"Mengchen Cao MD,&nbsp;Ava E. Pierce MD,&nbsp;Marquita S. Norman MD, MBA,&nbsp;Bhaskar Thakur PhD,&nbsp;Kiersten Diercks BA,&nbsp;Cooper Hale MD,&nbsp;Yacine Issioui MD,&nbsp;Deborah B. Diercks MD, MSc, MBA","doi":"10.1016/j.clinthera.2024.09.025","DOIUrl":"10.1016/j.clinthera.2024.09.025","url":null,"abstract":"<div><h3>Purpose</h3><div>High-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) have been demonstrated to have lower sex-specific 99th percentiles in healthy females. However, these sex-specific thresholds are not widely adopted in clinical practice which could lead to underdiagnosis of acute myocardial infarction in females. We conducted a systematic review to explore sex-specific 99th percentiles for hs-cTnI and hs-cTnT from healthy reference populations.</div></div><div><h3>Methods</h3><div>The principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to complete this systematic review. We used PubMed and OVID EMBASE to search for original studies published between November 2017 and November 2021 that included reference populations used to establish the 99th percentiles of hs-cTnI and hs-cTnT with the following inclusion criteria: adults; English language; samples taken as part of a healthy, reference population; studies using high-sensitivity troponin assay; and sample size &gt; 300. Studies were excluded if the reference population sample size was &lt; 300, if a conventional troponin assay was used, or if they did not include independently derived, sex-specific 99th percentiles. Data was extracted from the studies through Covidence to perform a qualitative data synthesis. Female-specific, male-specific, and overall 99th percentiles for hs-cTn were compared.</div></div><div><h3>Findings</h3><div>We reviewed 131 articles of which 19 met inclusion criteria. These 19 studies derived sex-specific 99th percentiles for 11 different hs-cTnI assays and 9 different hs-cTnT assays. More than 90% (13 of 14 studies) of hs-cTnI assays found lower female 99th percentiles compared to male and to overall 99th percentiles. One study included nine different hs-cTnI assays, of which only one assay resulted in a higher female 99th percentile compared to male and to overall 99th percentiles. Eight of nine hs-cTnT studies (88.9%) found lower female 99th percentiles compared to male and to overall 99th percentiles.</div></div><div><h3>Implications</h3><div>The data shows significantly lower 99th percentiles in females compared to 99th percentiles in males and overall. Incorporating these sex-specific 99th percentile cut-offs into clinical practice could lead to increased diagnosis and potentially better outcomes for females presenting with acute myocardial infarction.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 12","pages":"Pages 988-994"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590359","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":"Chest Pain in the Setting of Acute Stress: A Tale of Two Women","authors":"Bryn E. Mumma MD, MAS ,&nbsp;Joseph M. Kim MD ,&nbsp;Jason H. Rogers MD","doi":"10.1016/j.clinthera.2024.10.012","DOIUrl":"10.1016/j.clinthera.2024.10.012","url":null,"abstract":"<div><div>Chest pain is one of the most common reasons for emergency department visits in the United States. Common etiologies of chest pain include both anxiety and myocardial infarction (MI); furthermore, anxiety and stress may contribute to the development of MI, particularly MI with non-obstructed coronary arteries (MINOCA). We present the cases of two women with acute chest pain in the setting of acute life stressors who were found to have MINOCA. We discuss the relationship between acute stress, chest pain, and MINOCA, as well as the importance of considering a broad differential diagnosis in women with acute chest pain.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 12","pages":"Pages 1005-1009"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Letter Regarding Article, “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":"Adili Tuersun ,&nbsp;Munire Mohetaer ,&nbsp;Munire Tuerhong ,&nbsp;Guanxin Hou ,&nbsp;Gang Cheng","doi":"10.1016/j.clinthera.2024.09.002","DOIUrl":"10.1016/j.clinthera.2024.09.002","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 12","pages":"Pages 1087-1088"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343083","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":"Unraveling the Spectrum of Ocular Toxicity with Oxaliplatin: Clinical Feature Analysis of Cases and Pharmacovigilance Assessment of the US Food and Drug Administration Adverse Event Reporting System Database","authors":"Wensheng Liu ,&nbsp;Xuan Ye ,&nbsp;Han Shan ,&nbsp;Mengmeng Wang ,&nbsp;Yingbin Wang ,&nbsp;Zihan Guo ,&nbsp;Jiyong Liu ,&nbsp;Qiong Du","doi":"10.1016/j.clinthera.2024.09.019","DOIUrl":"10.1016/j.clinthera.2024.09.019","url":null,"abstract":"<div><h3>Purpose</h3><div>Ocular adverse events (oAEs) are a class of adverse events associated with oxaliplatin that are realistically observed in real-world settings. Herein, we aim to describe the clinical characteristics of oAEs associated with oxaliplatin through a systematic review of case reports and to assess a potential safety signal.</div></div><div><h3>Methods</h3><div>PubMed, Embase, and Cochrane Library databases were used to retrieve case reports. The global disproportionality study was performed leveraging the US Food and Drug Administration Adverse Event Reporting System database from January 2004 to September 2023. Bayesian information component (IC) and reporting odds ratio (ROR) were applied to identify and evaluate potential oAEs associated oxaliplatin.</div></div><div><h3>Findings</h3><div>A total of 20 cases from the systematic case review (of 13 screened articles) were reported on oAEs associated with oxaliplatin, with ages between 26 and 76 years. Therein, 16 (84.2%) cases described loss of vision, and the remaining cases presented with bilateral blepharoptosis, papilledema, and optic disc swelling. Insights from the US Food and Drug Administration Adverse Event Reporting System database showed that oAEs accounted for 4.28% (n = 1194) of the overall oxaliplatin-related adverse event reports, of which 1140 (95.48%) had a serious outcome. The median (interquartile range) onset time of oAEs with oxaliplatin was day 1 (0–25; n = 649). Disproportionality analysis revealed that ocular injuries NEC (n = 28, ROR, 22.72; lower limit of the 95% 2-sided CI for IC, 3.12) was the most significant signals detected. Additionally, unexpected significant oAEs, including eyelid ptosis, eyelid edema, eye movement disorder, blepharospasm, periorbital edema, swelling of eyelid, ophthalmoplegia, retinal vein thrombosis, cataract nuclear, blindness cortical, cataract subcapsular, and lacrimation disorder, were also reported disproportionality.</div></div><div><h3>Implications</h3><div>Our study systematically described the characteristics and outcomes of oxaliplatin-related ocular toxicity and also uncovered potential oAEs that were not disclosed in the package insert. Further prospective epidemiologic studies to validate these findings are warranted.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 12","pages":"Pages 1049-1058"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459925","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":"Correlation of Triethylamine N-oxide (TMAO), LPS, and TNF-Alpha Levels With Clinical Features of the Disease in Patients With and Without Septic Shock Infected With COVID-19 Virus","authors":"Kübra Polat ,&nbsp;Mehtap Gömleksiz ,&nbsp;Kübra Oral ,&nbsp;Nevzat Gözel ,&nbsp;Gaweł Sołowski ,&nbsp;Tugҫe Kaymaz ,&nbsp;Mehmet Ferit Gürsu","doi":"10.1016/j.clinthera.2024.09.021","DOIUrl":"10.1016/j.clinthera.2024.09.021","url":null,"abstract":"<div><h3>Background</h3><div>Inflammation is a response of the immune system to protect the body against various diseases or injuries. Serum trimethylamine N-oxide (TMAO) levels may vary depending on age, gender, habits, comorbidities, and microbiota.</div></div><div><h3>Aims</h3><div>In this study, we investigated whether TMAO levels have diagnostic significance and their potential as a marker in the early diagnosis of the disease. Another aim of the research was to identify changes in TMAO levels as a reflection of the deterioration in the microflora, and IL-6, IL-10, IL-1β, TNF-alpha, and LPS levels in patient groups. Then, we recognized relationships between these parameters in patients infected with COVID-19 without septic shock and with COVID-19 who were without transmission of COVID-19 in septic shock.</div></div><div><h3>Study Design</h3><div>A total of 160 patients were investigated, including 40 patients infected with COVID-19 without septic contact, 40 patients with COVID-19 positive septic shock, 40 patients with COVID-19 negative septic shock, and 40 healthy individuals as the control group.</div></div><div><h3>Results</h3><div>TNF-α and IL-1β levels were significantly lower (<em>P</em> &lt; 0.001) and IL-6 and IL-10 levels were significantly higher (<em>P</em> &lt; 0.001) in patient groups than in control groups. IL-1β showed a significant decrease, especially in the groups infected with COVID-19. Although IL-6, increased even more in the groups infected with COVID-19.</div></div><div><h3>Conclusions</h3><div>LPS level was remarkably high in the sepsis group infected with COVID-19 compared to the other groups. TMAO level was significantly higher (<em>P</em> &lt; 0.001) in the sepsis group. Therefore, TMAO is a potential biomarker in sepsis and septic shock.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 12","pages":"Pages e1-e8"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496506","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":"Advances in Enrolling Pregnant Persons Into Acute Care Clinical Trials, A Discussion With the Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (ICECAP) Trial Principal Investigators","authors":"Sarah M. Perman MD, MSCE,&nbsp;William Meurer MD, MS,&nbsp;Robert Silbergleit MD,&nbsp;Angela F. Jarman MD, MPH","doi":"10.1016/j.clinthera.2024.11.006","DOIUrl":"10.1016/j.clinthera.2024.11.006","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 12","pages":"Pages 945-948"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754835","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":"Letter to the Editor, Regarding \"Optimizing Acute Ischemic Stroke Outcomes: The Role of Tenecteplase Before Mechanical Thrombectomy\" Recently Published by Ketabforoush and Colleagues.","authors":"Senta Frol, René Chapot","doi":"10.1016/j.clinthera.2024.11.008","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.11.008","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767052","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}