Clinical therapeutics最新文献

{"title":"Sex Differences in Advanced Therapeutic Interventions for Intermediate- and High-Risk Pulmonary Embolism","authors":"Christiana K. Prucnal MD, ScM ,&nbsp;Christopher Kabrhel MD, MPH ,&nbsp;Nora K. Horick PhD ,&nbsp;Angela F Jarman MD, MPH","doi":"10.1016/j.clinthera.2024.10.018","DOIUrl":"10.1016/j.clinthera.2024.10.018","url":null,"abstract":"<div><h3>Purpose</h3><div>Advanced interventions are increasingly used to treat intermediate- and high-risk acute pulmonary embolism (PE). While sex-based differences exist in treatment of other diseases, it is unknown whether these disparities extend to PE.</div></div><div><h3>Methods</h3><div>This is a secondary analysis of a prospective cohort study of adult patients diagnosed with radiographically confirmed intermediate- and high-risk acute PE at a tertiary hospital between 1/1/2012 and 12/31/2021 for whom the PE Response Team was activated. Primary outcome was receipt of any advanced intervention. Descriptive and inferential analyses using Chi-square tests, <em>t</em> tests, and logistic regression were performed to evaluate for factors associated with the primary outcome.</div></div><div><h3>Findings</h3><div>We analyzed 902 patients, of whom 439 (49%) were female. Although women were more likely to present with right heart strain on echo (78.6% vs 71.1% <em>P</em> = 0.012) and elevated NT-proBNP (69.2% vs 55.7% <em>P</em> &lt; 0.001), there was no significant sex-based difference in clinical PE severity, defined as intermediate- versus high-risk, at presentation. Primary outcome did not differ significantly by sex (18.7% vs 23.5% <em>P</em> = 0.129). In multivariate models, high-risk PE decreased odds of receiving an advanced therapy (0.50 [0.31, 0.79] <em>P</em> = 0.003), while receiving assisted ventilation (4.70 [2.90, 7.62], <em>P</em> &lt; 0.001) and full code status (4.18 [1.60, 10.91], <em>P</em> = 0.003) increased odds.</div></div><div><h3>Implications</h3><div>This study adds to the scant literature on sex differences in interventions for acute PE. Significant baseline variation exists between female and male patients presenting with acute PE. Clinical factors were predictive of receiving advanced PE therapies, while sex was not.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 12","pages":"Pages 967-973"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779206","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":"Molecular Detection of Carbapenemases in Acinetobacter baumannii Strains of Portugal and Association With Sequence Types, Capsular Types, and Virulence","authors":"Rita Domingues ,&nbsp;Ricardo Oliveira ,&nbsp;Sónia Silva ,&nbsp;Daniela Araújo ,&nbsp;Carina Almeida ,&nbsp;Gyu-Sung Cho ,&nbsp;Charles M.A.P. Franz ,&nbsp;Maria José Saavedra ,&nbsp;Joana Azeredo ,&nbsp;Hugo Oliveira","doi":"10.1016/j.clinthera.2024.09.005","DOIUrl":"10.1016/j.clinthera.2024.09.005","url":null,"abstract":"<div><h3>Purpose</h3><div>Carbapenem-resistant <em>Acinetobacter baumannii</em> (CRAB) is an important nosocomial pathogen. The capsular type (K-type) is considered a major virulence factor, contributing to the evasion of host defenses. The global spread and dissemination dynamics between K-types, sequence types (ST), antibiotic resistance genes, and virulence factors remain largely unknown in Portugal.</div></div><div><h3>Methods</h3><div>A collection of 96 CRAB clinical samples collected between 2005 and 2019 in the northern region of Portugal were tested for antimicrobial susceptibility profile and screened by polymerase chain reaction for resistance genetic determinants. A subset of 26 representative isolates was subjected to whole-genome sequencing to assess K types, ST types, and genomic relatedness. The pathogenicity of distinct K-types was also tested using <em>Galleria mellonella</em> model.</div></div><div><h3>Findings</h3><div>For the 96 CRAB isolates analyzed, high antimicrobial resistance (&gt;90%) was observed to the carbapenems, fluoroquinolones, and miscellaneous agents. Greater antimicrobial susceptibility (∼30%–57%) was observed for aminoglycosides, particularly tobramycin, and amikacin. Genotypically, 75 strains (78.5%) carried <em>bla</em>_OXA-23-like, 18 strains (18.8%) carried <em>bla</em>_IMP-like, and 11 strains (14.9%) carried <em>bla</em>_OXA-40-like carbapenem resistance genes, respectively. Associations between OXA and ST/capsular locus (KL) types were observed over the years (eg, OXA-40-like/ST46^Past/KL120 and OXA-23-like/ST2^Past/KL2). ST2^Past of clonal complex II was present in most strains, a dominant drug-resistant lineage in the United States and Europe. KL7 was also the most prevalent KL-type (38.5%), followed by KL2 (34.6%), KL120 (23.1%), and KL9 (3.8%). Virulence assessment for different K-types in a <em>Galleria mellonella</em> model revealed a significantly increased virulence for KL120 when compared with KL7, KL9, and KL2.</div></div><div><h3>Implications</h3><div>There are specific CRAB serotypes circulating in Portugal, accounting by the low diversity of acquired carbapenemase genes (OXA-23-like and OXA-40-like), ST types (ST2 and ST46) and KL types (KL2, KL7, KL9, and KL120) identified. The high prevalent of ST2, especially when associated with KL2 and <em>bla</em>_OXA-23-like, suggest that antibiotic resistance has been driven by clonal expansion of clonal complex II. Such findings provide useful information on the diversity of multidrug-resistant bacterium that might be relevant for antibacterial interventions.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 12","pages":"Pages e9-e15"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388663","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":"Heart Breaking Differences: A Narrative Review of Sex and Gender Disparities in Sports-Related Sudden Cardiac Death","authors":"Mallory E. Shasteen MD ,&nbsp;Mary K. Wurzelmann MD ,&nbsp;Alyson J. McGregor MD ,&nbsp;Neha P. Raukar MD, MS","doi":"10.1016/j.clinthera.2024.11.002","DOIUrl":"10.1016/j.clinthera.2024.11.002","url":null,"abstract":"<div><h3>Purpose</h3><div>Sports-related sudden cardiac death (srSCD) represents a rare yet significant occurrence. This review aims to explore the epidemiology, etiology, and prevention of srSCD, with a particular focus on the influence of sex and gender. It seeks to analyze existing literature to elucidate the impact of biological variables, societal factors, and preventive measures in understanding and addressing srSCD among athletes.</div></div><div><h3>Methods</h3><div>A narrative review approach was utilized to synthesize relevant literature on srSCD, using a validated PubMed Search tool for sex and gender-related factors. The review focused on primary data investigating sex differences that may contribute to srSCD, as well as pertinent review articles.</div></div><div><h3>Findings</h3><div>The review highlights the complexity of defining and studying srSCD, with challenges stemming from varied reporting methods and lack of standardized definitions. Disparities in incidence rates between male and female athletes are evident, with males exhibiting a disproportionately higher risk. Biological factors, including cardiac adaptations to exercise and sex hormone influences, contribute to these sex-specific differences in srSCD rates. While screening programs, particularly utilizing electrocardiograms, show promise in identifying at-risk individuals, debates persist regarding their implementation and efficacy. Furthermore, legislative gaps in mandating the availability of automatic external defibrillators (AEDs) in public settings underscore the need for unified advocacy efforts to improve access to life-saving interventions.</div></div><div><h3>Implications</h3><div>Understanding the multifaceted nature of srSCD, including its biological underpinnings and societal implications, is crucial for developing effective preventive strategies. Sex-specific screening programs tailored to the unique risk profiles of male and female athletes, as well as legislative initiatives promoting AED placement and cardiopulmonary resuscitation training, are essential components of comprehensive srSCD prevention efforts. By addressing disparities and implementing evidence-based interventions, this paper advocates for a holistic approach to mitigate the risk of srSCD and enhance the safety and well-being of athletes across all levels of competition.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 12","pages":"Pages 982-987"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754837","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 Role of Sex and Gender in Precision Emergency Medicine: A Scoping Review and Proposed Hierarchy","authors":"Angela F. Jarman MD, MPH ,&nbsp;Madeleine G. Wolfe BS ,&nbsp;Bryn E. Mumma MD, MAS ,&nbsp;Tracy E. Madsen MD, PhD ,&nbsp;Basmah Safdar MD, MSc ,&nbsp;Marna R. Greenberg DO, MPH ,&nbsp;Jeannette J. Wolfe MD ,&nbsp;Bridget Gunn MSLS, MS ,&nbsp;Lauren A. Walter MD, MSPH ,&nbsp;Brandon C. Maughan MD, MHS, MSHP ,&nbsp;Alyson J. McGregor MD, MA","doi":"10.1016/j.clinthera.2024.10.007","DOIUrl":"10.1016/j.clinthera.2024.10.007","url":null,"abstract":"<div><h3>Background</h3><div>Precision medicine utilizes individual patient data to guide decision making. Sex and gender medicine is likewise focused on individual patients’ biological sex or sociocultural gender as determinants of disease. How these two fields intersect with one another and with acute care medicine is unclear.</div></div><div><h3>Methods</h3><div>We conducted a scoping literature review utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews to evaluate the primary research in three related areas: sex &amp; gender medicine, emergency medicine, and precision medicine. We searched six databases and screened eligible studies for inclusion. Included studies were reviewed in full, and study characteristics were compiled using a standardized data extraction form. Research questions were drafted by workgroup members and ranked by all participants of the consensus conference.</div></div><div><h3>Results</h3><div>A total of 401 studies were screened for inclusion. Of these, 70 met inclusion criteria and were evaluated in full text. The majority (84%, 59/70) reported evaluating sex, whereas only 16% (11/70) reported evaluating gender. The most common clinical topics were cardiovascular diseases and trauma/injury prevention, comprising 50% (35/70) of the included manuscripts. Cumulatively, 77% (54/70) of the manuscripts reviewed cited at least one funding source. The vast majority (66/70, 94%) of studies were included because their statistical analysis accounted for sex or gender, and very few studies (4/70, 6%) were included due to their use of biomarker or genomic data.</div></div><div><h3>Conclusions</h3><div>Sex- and gender-based medicine and research commonly employ precision medicine concepts to evaluate the effects of sex and gender in a variety of clinical topic areas, but much of this literature is not commonly described as precision medicine. We propose a hierarchy to categorize, label, and advance sex and gender precision medicine research. Fundamental to this advancement are implementation of guidelines regarding the correct use of sex and gender and continued research funding for sex and gender precision EM research.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 12","pages":"Pages 974-981"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616385","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":"Aqneursa (levacetylleucine)","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2024.10.011","DOIUrl":"10.1016/j.clinthera.2024.10.011","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 12","pages":"Pages 1091-1092"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681264","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 MPH ,&nbsp;Emily Glidden MPH ,&nbsp;Desiree Mustaquim PhD ,&nbsp;Laura E. Welder DrPH ,&nbsp;Erin K. Stokes MPH ,&nbsp;Gillian A. Beauchamp MD ,&nbsp;Marna R. Greenberg DO, MPH ,&nbsp;Kim Aldy DO ,&nbsp;Richard J. Mazzaccaro MD, PhD ,&nbsp;Beth A. Careyva MD ,&nbsp;Judith N. Sabino MPH, CDP ,&nbsp;Derek J. Fikse DO ,&nbsp;Katelyn McLain BS ,&nbsp;Alexandra M. Amaducci DO ,&nbsp;Toxicology Investigators Consortium (ToxIC) Study Group","doi":"10.1016/j.clinthera.2024.08.018","DOIUrl":"10.1016/j.clinthera.2024.08.018","url":null,"abstract":"<div><h3>Purpose</h3><div>In this manuscript, the abbreviation TG is defined as <em>persons who identify as transgender</em>, GNC is defined as <em>persons who identify as gender nonconforming</em>, and CG is defined as <em>persons who identify as cisgender</em>. 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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Findings</h3><div>From a total of 15,800 medical toxicology consultations, 213 (1.3%) involved both TG (<em>n</em> = 187, 1.2%) and GNC (<em>n</em> = 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 (<em>n</em> = 132) and 34.8% of CG (<em>n</em> = 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.</div></div><div><h3>Implications</h3><div>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.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 12","pages":"Pages 953-959"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","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":"Population Pharmacokinetic Model of Intravenous Immunoglobulin in Patients Treated for Various Immune System Disorders","authors":"Jian Lynn Lee PhD ,&nbsp;Noraida Mohamed Shah PhD ,&nbsp;Mohd Makmor-Bakry PhD ,&nbsp;Farida Islahudin PhD ,&nbsp;Hamidah Alias MD ,&nbsp;Shamin Mohd Saffian PhD","doi":"10.1016/j.clinthera.2024.09.018","DOIUrl":"10.1016/j.clinthera.2024.09.018","url":null,"abstract":"<div><h3>Purpose</h3><div>Intravenous immunoglobulin (IVIG) is used to treat various immune system disorders, but the factors influencing its disposition are not well understood. This study aimed to estimate the population pharmacokinetic parameters of IVIG and to investigate the effect of genetic polymorphism of the <em>FCGRT</em> gene encoding the neonatal Fc receptor (FcRn) and clinical variability on the pharmacokinetic properties of IVIG in patients with immune system disorders.</div></div><div><h3>Methods</h3><div>Patients were recruited from 4 hospitals in Malaysia. Clinical data were recorded, and blood samples were taken for pharmacokinetic and genetic studies. Population pharmacokinetic parameters were estimated by nonlinear mixed-effects modeling in Monolix. Age, weight, baseline immunoglobulin G concentration, ethnicity, sex, genotype, disease type, and comorbidity were investigated as potential covariates. Models were evaluated using the difference in objective function value, goodness-of-fit plots, visual predictive checks, and bootstrap analysis.</div></div><div><h3>Findings</h3><div>A total of 292 blood samples were analyzed from 79 patients. The IVIG concentrations were best described by a 2-compartment model with linear elimination. Weight was found to be an important covariate for volume of distribution in the central compartment (Vc), volume of distribution in the peripheral compartment (Vp), and clearance in the central compartment, whereas disease type was found to be an important covariate for Vp. Goodness-of-fit plots indicated that the model fit the data adequately. Genetic polymorphism of the <em>FCGRT</em> gene encoding the neonatal Fc receptor did not affect the pharmacokinetic properties of IVIG.</div></div><div><h3>Implications</h3><div>This study supports the use of dosage based on weight as per current practice. The study findings highlight that Vp is significantly influenced by the type of disease being treated with IVIG. This relationship suggests that different disease types, particularly inflammatory and autoimmune conditions, may alter tissue permeability and fluid distribution due to varying degrees of inflammation. Increased inflammation can lead to enhanced permeability and retention of IVIG in peripheral tissues, reflecting higher Vp values.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 12","pages":"Pages e25-e37"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375272","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":"Drug Review and Approval Policies Based on Real-world Evidence in China and the United States: A Comparative Study","authors":"Munire Mohetaer SM ,&nbsp;Adili Tuersun MA ,&nbsp;Pei Li PhD ,&nbsp;Su Wang PhD ,&nbsp;Xingyan Zhang PhD ,&nbsp;Yuwen Chen PhD","doi":"10.1016/j.clinthera.2024.09.009","DOIUrl":"10.1016/j.clinthera.2024.09.009","url":null,"abstract":"<div><h3>Purpose</h3><div>The use of real-world evidence (RWE) in regulatory reviews and approvals is currently experiencing significant changes amid increasingly active discussions, primarily reflected in relevant policies, regulations, and guidance documents. However, disparities persist between China and the United States regarding the acceptance and formulation of policies for incorporating real-world data/evidence (RWD/E) in regulatory evaluation and authorization. Furthermore, the current policies lack specific operational details necessary for effective implementation and widespread adoption.</div></div><div><h3>Methods</h3><div>After conducting a systematic literature review and comparing relevant policies, regulations, and guidelines, as well as the related information published on their official websites, we analyze key aspects of RWE-based drug review and approval policies to highlight similarities and differences in these policies between China and the United States.</div></div><div><h3>Findings</h3><div>This paper reviews the frameworks and existing guidelines in China and the U.S., discussing similarities and differences observed in key policy aspects, including relevant definitions, data sources, data standards, data quality, and connectivity, information requirements, study design, personnel training, and communication, including an example of the application of RWE in drug review and approval processes.</div></div><div><h3>Implications</h3><div>Further develop and refine RWE policies, encourage cooperation, and share best practices and successful examples to enhance the effectiveness of policy implementation and increase its social acceptance.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 12","pages":"Pages 1059-1068"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379231","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":"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}