Pharmacotherapy最新文献

筛选
英文 中文
Cross-titration from risperidone to clozapine utilizing clozapine serum concentrations: A case report. 利用氯氮平血清浓度交叉滴定从利培酮到氯氮平:1例报告。
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-03-01 Epub Date: 2025-01-21 DOI: 10.1002/phar.4649
Nicolette Centanni, Kayla Garvey, Elizabeth Mullany, Stephanie Nichols
{"title":"Cross-titration from risperidone to clozapine utilizing clozapine serum concentrations: A case report.","authors":"Nicolette Centanni, Kayla Garvey, Elizabeth Mullany, Stephanie Nichols","doi":"10.1002/phar.4649","DOIUrl":"10.1002/phar.4649","url":null,"abstract":"<p><strong>Introduction: </strong>Clozapine and risperidone are second-generation antipsychotics used in the treatment of schizophrenia. There are no guidelines on cross-titration of antipsychotics and, additionally, there is a paucity of published data to support the potential utility of using serum drug levels to guide dosing in these situations.</p><p><strong>Case report: </strong>A 68-year-old female patient with a history of schizophrenia, taking risperidone and fluoxetine, and a recent diagnosis of Parkinson's disease was admitted to the hospital after a fall at home. During the patient's hospital stay, utilizing serum clozapine levels as guidance, the patient was cross-titrated from risperidone 12 mg daily to a final dose of clozapine 75 mg daily over the span of 17 days, in the setting of multiple possible drug-drug interactions.</p><p><strong>Discussion: </strong>There is no evidence-based guidance on transitioning patients from one antipsychotic to another especially in the setting of drug-drug interactions. In this case, the patient was successfully transitioned from risperidone to clozapine using serum clozapine levels and clinical status to guide decision-making.</p><p><strong>Conclusions: </strong>Utilizing serum clozapine levels may be helpful in guiding dose changes during antipsychotic cross-titration, especially when multiple drug interactions are involved.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"187-190"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comment on "Intravenous ketamine successfully treats treatment-resistant catatonia in schizophrenia: A case report". 点评“静脉注射氯胺酮成功治疗精神分裂症难治性紧张症1例”。
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-02-01 DOI: 10.1002/phar.4647
João Gama Marques, Josef Finsterer
{"title":"Comment on \"Intravenous ketamine successfully treats treatment-resistant catatonia in schizophrenia: A case report\".","authors":"João Gama Marques, Josef Finsterer","doi":"10.1002/phar.4647","DOIUrl":"https://doi.org/10.1002/phar.4647","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"45 2","pages":"145-146"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Response to comment on "Intravenous ketamine successfully treats treatment-resistant catatonia in schizophrenia: A case report". 对“静脉注射氯胺酮成功治疗精神分裂症难治性紧张症1例报告”评论的回应。
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-02-01 DOI: 10.1002/phar.4645
Atif Siddiqui
{"title":"Response to comment on \"Intravenous ketamine successfully treats treatment-resistant catatonia in schizophrenia: A case report\".","authors":"Atif Siddiqui","doi":"10.1002/phar.4645","DOIUrl":"https://doi.org/10.1002/phar.4645","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"45 2","pages":"147-148"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Associating regulatory actions on diclofenac use with Danish trends in utilization by route of administration 1999-2023. 将双氯芬酸使用监管行动与1999-2023年丹麦按给药途径使用趋势联系起来。
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-02-01 Epub Date: 2025-01-02 DOI: 10.1002/phar.4643
Anna Emilie Møller, Anne Bech-Drewes, Lotte Rasmussen, Søren Friis, Morten Schmidt
{"title":"Associating regulatory actions on diclofenac use with Danish trends in utilization by route of administration 1999-2023.","authors":"Anna Emilie Møller, Anne Bech-Drewes, Lotte Rasmussen, Søren Friis, Morten Schmidt","doi":"10.1002/phar.4643","DOIUrl":"10.1002/phar.4643","url":null,"abstract":"<p><strong>Aims: </strong>With the growing evidence of cardiovascular risks associated with diclofenac use, regulatory measures governing its application and sales have intensified since 2008. We evaluated the association between central regulatory actions and trends in diclofenac use in Denmark from 1999 to 2023, according to different dosage forms and routes of administration.</p><p><strong>Methods and results: </strong>Data on diclofenac sales in Denmark from 1999 to 2023 were retrieved from the publicly available web database MEDSTAT, based on the Danish Register of Medicinal Products Statistics. The annual sales of various diclofenac dosage forms, including systemic (tablets, modified-release dosage forms, and suppositories) and topical (nonspecific and ophthalmic) dosage forms, were calculated and displayed by sales unit. From 1999 to 2008, sales of all systemically administered diclofenac forms increased: tablets by 51% (2000-2008), modified-release dosage forms by 40% (2003-2007), and suppositories by 44% (1999-2008). Thereafter, sales of tablets declined by 86% and modified-release dosage forms by 90% through 2023. The sales of suppositories declined somewhat lesser, by 34%, during 2008 to 2018 and then increased by 67% through 2023. Sales of nonspecific topical diclofenac increased by several thousandfold from 2005, although with brief periods of decline.</p><p><strong>Conclusion: </strong>Sales of systemically administered diclofenac dosage forms, particularly tablets and modified-release drugs, declined by approximately 90% from about 2008 to 2023, indicating compliance with Danish and international regulatory actions. Conversely, sales of topically administered diclofenac increased heavily from 2005 to 2023, denoting a policy-driven shift toward these lower risk dosage forms.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"104-110"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Disease-modifying therapies for amyloid transthyretin cardiomyopathy: Current and emerging medications. 淀粉样蛋白转甲状腺素心肌病的疾病改善疗法:当前和新兴药物。
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-02-01 Epub Date: 2024-12-23 DOI: 10.1002/phar.4639
Erika L Hellenbart, Heather J Ipema, Mary C Rodriguez-Ziccardi, Hema Krishna, Robert J DiDomenico
{"title":"Disease-modifying therapies for amyloid transthyretin cardiomyopathy: Current and emerging medications.","authors":"Erika L Hellenbart, Heather J Ipema, Mary C Rodriguez-Ziccardi, Hema Krishna, Robert J DiDomenico","doi":"10.1002/phar.4639","DOIUrl":"10.1002/phar.4639","url":null,"abstract":"<p><p>Transthyretin amyloidosis (ATTR) is a rare disease that results in amyloid fibril misfolding and deposition in multiple organs, including the heart, leading to the development of ATTR cardiomyopathy (ATTR-CM), which is associated with poor outcomes. In the last decade, several disease-modifying medications are in advanced stages of clinical development or have been approved to treat ATTR-CM. The purpose of this review is to critically evaluate clinical trial data investigating the use of approved and investigational medications for the treatment of ATTR-CM. We performed a comprehensive literature search via PubMed and EMBASE to identify randomized controlled trials evaluating medications for the treatment of ATTR-CM published through August 2024. This narrative review describes the pathophysiology of ATTR-CM, highlights important screening and diagnostic work-up, and summarizes the existing clinical evidence resulting from our literature search. Several classes of disease-modifying medications are in development for ATTR-CM. The tetramer stabilizers and transthyretin silencers have proven to be the most effective therapies to date. Tafamidis and acoramidis are currently approved for ATTR-CM while vutrisiran approval for ATTR-CM may be forthcoming. Other disease-modifying medication classes in development include antisense oligonucleotides, gene editing therapies, and monoclonal antibodies. However, several unmet needs exist including the lack of cost-effectiveness due to the extremely high acquisition costs of these medications. Disease-modifying medications approved and in development to treat ATTR-CM offer hope for patients with this disease, but their lack of affordability is the biggest barrier to their use.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"124-144"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Creation and validation of an extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) clinical risk scoring tool for select Enterobacterales in non-urinary isolates. 非尿路分离肠杆菌中产生β -内酰胺酶的广谱肠杆菌(ESBL-E)临床风险评分工具的创建和验证
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-02-01 Epub Date: 2025-01-10 DOI: 10.1002/phar.4646
Jordan Jones, Taylor Morrisette, Aaron Hamby, Krutika Mediwala Hornback, Rachel Burgoon
{"title":"Creation and validation of an extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) clinical risk scoring tool for select Enterobacterales in non-urinary isolates.","authors":"Jordan Jones, Taylor Morrisette, Aaron Hamby, Krutika Mediwala Hornback, Rachel Burgoon","doi":"10.1002/phar.4646","DOIUrl":"10.1002/phar.4646","url":null,"abstract":"<p><strong>Background: </strong>Infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) are increasing in the United States. Although many risk factor scoring tools exist, many are specific to bloodstream isolates and may not represent all patient populations. The purpose of this study was to create and validate an institution-specific scoring tool for select ESBL-E of non-urinary origin based on previously identified risk factors.</p><p><strong>Methods: </strong>This retrospective, case-control analysis included inpatient adults at an academic medical center from July 2021 through August 2023 with a documented ESBL-E or non-ESBL-E infection of non-urinary origin. Patients with ESBL-E isolates were matched in a 1:1 ratio to non-ESBL-E isolates by organism and specimen type. Points for each risk factor were assigned by dividing their respective regression coefficient by half of the smallest regression coefficient and rounding to the nearest integer (prior ESBL-E within the past 12 months: 6 points, urinary catheter: 3 points, central venous catheter: 2 points, cirrhosis: 2 points). Sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) were calculated for each score, and discriminatory power was assessed via the receiver operating characteristic (ROC)-area under the curve (AUC).</p><p><strong>Results: </strong>Of the 1139 identified cultures, 140 patients met the criteria for inclusion into the ESBL-E case arm, thus 140 patients with non-ESBL-E cultures were matched as controls. Baseline characteristics were relatively similar between the groups. A score of 0 was associated with low risk of ESBL-E (PPV 0.31, NPV 0.36), whereas scores between 2 and 5 were considered moderate risk (PPV 0.56, NPV 0.55), and scores ≥6 were associated with high risk (PPV 0.91, NPV 0.56). The ROC curve AUC was 0.705.</p><p><strong>Conclusions: </strong>The majority of ESBL-E risk factor scoring tools are specific to isolates causing bloodstream infections. This institution-specific scoring tool may be used to tailor empiric antimicrobial regimens and decrease unnecessary exposure to carbapenems in non-ESBL-E infections of non-urinary origin.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"87-93"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The effect of carbamazepine, a strong CYP3A inducer, on the pharmacokinetics of zongertinib in healthy male volunteers. 强CYP3A诱导剂卡马西平对宗尼替尼在健康男性志愿者体内药代动力学的影响
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-02-01 Epub Date: 2024-12-27 DOI: 10.1002/phar.4641
Xiaofan Tian, Habib Esmaeili, David Minich, Friedeborg Seitz, Philipp M Roessner, Sven Wind, Rolf Grempler, Guanfa Gan, Tom S Chan, Mazyar Mahmoudi, Behbood Sadrolhefazi, Fabian Müller
{"title":"The effect of carbamazepine, a strong CYP3A inducer, on the pharmacokinetics of zongertinib in healthy male volunteers.","authors":"Xiaofan Tian, Habib Esmaeili, David Minich, Friedeborg Seitz, Philipp M Roessner, Sven Wind, Rolf Grempler, Guanfa Gan, Tom S Chan, Mazyar Mahmoudi, Behbood Sadrolhefazi, Fabian Müller","doi":"10.1002/phar.4641","DOIUrl":"10.1002/phar.4641","url":null,"abstract":"<p><strong>Introduction: </strong>Zongertinib (BI 1810631) is a potent, selective, and epidermal growth factor receptor (EGFR) wild-type sparing human epidermal growth factor receptor 2 (HER2) inhibitor. Based on in vitro data, the oxidative hepatic metabolism of zongertinib is principally driven by cytochrome P450 (CYP) 3A4/5. Therefore, zongertinib may be affected by strong CYP3A inducers, like carbamazepine.</p><p><strong>Objective: </strong>This study aimed to investigate the effect of multiple oral doses of carbamazepine on the pharmacokinetics of a single oral dose of zongertinib in healthy male subjects.</p><p><strong>Methods: </strong>This open-label, two-period, fixed-sequence clinical drug-drug interaction study examined the pharmacokinetics of a single 60-mg oral dose of zongertinib in the absence or presence of multiple oral doses of carbamazepine. The extent of drug-drug interaction was estimated using the adjusted geometric mean ratios (and 90% confidence intervals [CIs]) for the test treatment (zongertinib in the presence of carbamazepine) versus the reference treatment (zongertinib alone) for areas under the plasma concentration-time curve from time 0 to infinity and to the last quantifiable time point (AUC<sub>0-∞</sub>, AUC<sub>0-tz</sub>) and maximum measured plasma concentration (C<sub>max</sub>).</p><p><strong>Results: </strong>Sixteen subjects (all Caucasian males) received zongertinib alone in Study Period 1, and 15 of them received both zongertinib and carbamazepine in Study Period 2. Upon co-administration with carbamazepine in Study Period 2, AUC<sub>0-∞</sub> and AUC<sub>0-tz</sub> of zongertinib were both reduced to 36.5% (90% CI: 32.0%-41.6% for AUC<sub>0-∞</sub> and 31.9%-41.7% for AUC<sub>0-tz</sub>). The C<sub>max</sub> of zongertinib was reduced to 56.4% (90% CI: 45.1%-70.6%).</p><p><strong>Conclusion: </strong>Zongertinib exposure was reduced by 63.5% when coadministered with the strong CYP3A inducer, carbamazepine.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"94-103"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unsupervised machine learning analysis to identify patterns of ICU medication use for fluid overload prediction. 无监督机器学习分析,以确定ICU药物使用模式,用于流体过载预测。
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-02-01 Epub Date: 2025-01-03 DOI: 10.1002/phar.4642
Kelli Henry, Shiyuan Deng, Xianyan Chen, Tianyi Zhang, John W Devlin, David J Murphy, Susan E Smith, Brian Murray, Rishikesan Kamaleswaran, Amoreena Most, Andrea Sikora
{"title":"Unsupervised machine learning analysis to identify patterns of ICU medication use for fluid overload prediction.","authors":"Kelli Henry, Shiyuan Deng, Xianyan Chen, Tianyi Zhang, John W Devlin, David J Murphy, Susan E Smith, Brian Murray, Rishikesan Kamaleswaran, Amoreena Most, Andrea Sikora","doi":"10.1002/phar.4642","DOIUrl":"10.1002/phar.4642","url":null,"abstract":"<p><strong>Background: </strong>Fluid overload (FO) in the intensive care unit (ICU) is common, serious, and may be preventable. Intravenous medications (including administered volume) are a primary cause for FO but are challenging to evaluate as a FO predictor given the high frequency and time-dependency of their use and other factors affecting FO. We sought to employ unsupervised machine learning methods to uncover medication administration patterns correlating with FO.</p><p><strong>Methods: </strong>This retrospective cohort study included 927 adults admitted to an ICU for ≥72 h. FO was defined as a positive fluid balance ≥7% of admission body weight. After reviewing medication administration record data in 3-h periods, medication exposure was categorized into clusters using principal component analysis (PCA) and Restricted Boltzmann Machine (RBM). Medication regimens of patients with and without FO were compared within clusters to assess their temporal association with FO.</p><p><strong>Results: </strong>FO occurred in 127 (13.7%) of 927 included patients. Patients received a median (interquartile range) of 31(13-65) discrete intravenous medication administrations over the 72-h period. Across all 47,803 intravenous medication administrations, 10 unique medication clusters, containing 121 to 130 medications per cluster, were identified. The mean number of Cluster 7 medications administered was significantly greater in the FO cohort compared with patients without FO (25.6 vs.10.9, p < 0.0001). A total of 51 (40.2%) of 127 unique Cluster 7 medications were administered in more than five different 3-h periods during the 72-h study window. The most common Cluster 7 medications included continuous infusions, antibiotics, and sedatives/analgesics. Addition of Cluster 7 medications to an FO prediction model including the Acute Physiologic and Chronic Health Evaluation (APACHE) II score and receipt of diuretics improved model predictiveness from an Area Under the Receiver Operation Characteristic (AUROC) curve of 0.719 to 0.741 (p = 0.027).</p><p><strong>Conclusions: </strong>Using machine learning approaches, a unique medication cluster was strongly associated with FO. Incorporation of this cluster improved the ability to predict FO compared to traditional prediction models. Integration of this approach into real-time clinical applications may improve early detection of FO to facilitate timely intervention.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"76-86"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intravenous thrombolysis for patients with acute ischemic stroke while receiving a direct oral anticoagulant: A systematic review and meta-analysis. 静脉溶栓治疗急性缺血性卒中患者同时接受直接口服抗凝剂:一项系统回顾和荟萃分析。
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-02-01 Epub Date: 2025-01-20 DOI: 10.1002/phar.4644
Megan Z Roberts, Spencer H Durham, Nathan A Pinner, Jessica A Starr
{"title":"Intravenous thrombolysis for patients with acute ischemic stroke while receiving a direct oral anticoagulant: A systematic review and meta-analysis.","authors":"Megan Z Roberts, Spencer H Durham, Nathan A Pinner, Jessica A Starr","doi":"10.1002/phar.4644","DOIUrl":"10.1002/phar.4644","url":null,"abstract":"<p><p>Recent guidelines for acute ischemic stroke (AIS) indicate administration of intravenous thrombolysis (IVT) in patients receiving direct oral anticoagulants (DOAC) is not firmly established and may be harmful unless certain potential parameters are met. This systematic review and meta-analysis explores safety outcomes and other clinical parameters from the growing number of publications describing patients taking a DOAC who experience an AIS that is treated acutely with IVT alone. Embase, International Pharmaceutical Abstracts, and PubMed were searched up to January 9, 2024 for studies including adult patients taking a DOAC who experienced an AIS treated with IVT and did not undergo endovascular therapy (EVT), regardless of the use of an anticoagulation reversal agent. Primary safety outcomes evaluated included symptomatic intracranial hemorrhage (sICH), any intracranial hemorrhage, and in-hospital mortality. A total of 873 patients from 78 studies, primarily case reports or case series of patients receiving dabigatran with or without idarucizumab reversal (n = 340), were included in the review. The rate of sICH during the index hospitalization was 3.3%. Seven high-quality studies with low risk of bias included outcomes for patients on DOAC and comparator groups of either patients not taking an oral anticoagulant (no OAC) or patients taking a vitamin K antagonist (VKA) with INR primarily <1.7 at the time of AIS. No significant difference was observed in the incidence of sICH among patients receiving DOAC vs. no OAC (odds ratio [OR] 0.8, 95% confidence interval [CI]: 0.48-1.33) or among patients receiving DOAC vs. VKA (OR 1.02, 95% CI 0.59-1.75). Similar findings of no difference were observed for other safety outcomes. Findings from this study suggest that utilization of IVT as sole recanalization therapy for AIS may be safe in patients taking a DOAC; however, further studies are needed to elucidate specific parameters that differentiate timepoints and variables to ensure safe, optimal treatment.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"111-123"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluation of methotrexate Pharmacogenomic variation to predict acute neurotoxicity in children with acute lymphoblastic leukemia. 甲氨蝶呤药物基因组变异预测急性淋巴细胞白血病儿童急性神经毒性的评估。
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-01-01 Epub Date: 2024-12-29 DOI: 10.1002/phar.4638
Rachel D Harris, Olga A Taylor, M Monica Gramatges, Amy E Hughes, Mark Zobeck, Sandi Pruitt, M Brooke Bernhardt, Ashley Chavana, Van Huynh, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Ashley Choi, Yuu Ohno, Melissa A Richard, Alanna C Morrison, Han Chen, Bing Yu, Philip J Lupo, Karen Rabin, Michael E Scheurer, Austin L Brown
{"title":"Evaluation of methotrexate Pharmacogenomic variation to predict acute neurotoxicity in children with acute lymphoblastic leukemia.","authors":"Rachel D Harris, Olga A Taylor, M Monica Gramatges, Amy E Hughes, Mark Zobeck, Sandi Pruitt, M Brooke Bernhardt, Ashley Chavana, Van Huynh, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Ashley Choi, Yuu Ohno, Melissa A Richard, Alanna C Morrison, Han Chen, Bing Yu, Philip J Lupo, Karen Rabin, Michael E Scheurer, Austin L Brown","doi":"10.1002/phar.4638","DOIUrl":"10.1002/phar.4638","url":null,"abstract":"<p><strong>Background: </strong>Methotrexate is an important component of curative therapy in childhood acute lymphoblastic leukemia (ALL), but the role of genetic variation influencing methotrexate clearance and transport in toxicity susceptibility in children with ALL is not well established. Therefore, we evaluated the association between suspected methotrexate pharmacogenomic variants and methotrexate-related neurotoxicity.</p><p><strong>Methods: </strong>This study included children (aged 2-20 years) diagnosed with ALL (2005-2019) at six treatment centers in the southwest United States. Clinical information was abstracted from medical records. Suspected neurotoxic events occurring within 21 days of intravenous and/or intrathecal methotrexate delivered between the end of induction and start of maintenance therapy were independently reviewed by at least two pediatric oncologists. Germline DNA was genotyped and 97 methotrexate pharmacogenomic variants of interest with at least grade 3 evidence were identified using the Pharmacogenomics Knowledge Base. Associations between variants and neurotoxicity were assessed by logistic regression. Data were randomly split (80/20) and random forest was constructed to estimate the ability of the variants to correctly classify neurotoxicity.</p><p><strong>Results: </strong>Of the 763 patients included in the study, 8.2% (n = 63) developed methotrexate-associated neurotoxicity. In logistic models, none of the 97 available pharmacogenomic variants reached adjusted statistical significance. However, two variants, rs17222723 (odds ratio [OR] = 2.83 [ref. = T allele], 95% confidence interval [CI]: 1.20-6.15) in ABCC2 and rs1045642 (OR = 0.66 [ref. = minor A allele], 95% CI: 0.44-0.98) in ABCB1, were nominally associated (p-value < 0.05) with neurotoxicity susceptibility. The addition of pharmacogenomic variants did not improve the predictive performance of random forest model (AUC = 0.73) compared to clinical information alone (AUC = 0.74).</p><p><strong>Conclusion: </strong>Overall, our results suggest that associations between neurotoxicity susceptibility and methotrexate pharmacogenomic variants are generally modest and these variants do not significantly improve neurotoxicity risk stratification among children with ALL.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"4-11"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信