Dataset Information

MTXPK.org: A Clinical Decision Support Tool Evaluating High-Dose Methotrexate Pharmacokinetics to Inform Post-Infusion Care and Use of Glucarpidase.

ABSTRACT: Methotrexate (MTX), an antifolate, is administered at high doses to treat malignancies in children and adults. However, there is considerable interpatient variability in clearance of high-dose (HD) MTX. Patients with delayed clearance are at an increased risk for severe nephrotoxicity and life-threatening systemic MTX exposure. Glucarpidase is a rescue agent for severe MTX toxicity that reduces plasma MTX levels via hydrolysis of MTX into inactive metabolites, but is only indicated when MTX concentrations are > 2 SDs above the mean excretion curve specific for the given dose together with a significant creatinine increase (> 50%). Appropriate administration of glucarpidase is challenging due to the ambiguity in the labeled indication. A recent consensus guideline was published with an algorithm to provide clarity in when to administer glucarpidase, yet clinical interpretation of laboratory results that do not directly correspond to the algorithm prove to be a limitation of its use. The goal of our study was to develop a clinical decision support tool to optimize the administration of glucarpidase for patients receiving HD MTX. Here, we describe the development of a novel 3-compartment MTX population pharmacokinetic (PK) model using 31,672 MTX plasma concentrations from 772 pediatric patients receiving HD MTX for the treatment of acute lymphoblastic leukemia and its integration into the online clinical decision support tool, MTXPK.org. This web-based tool has the functionality to utilize individualized demographics, serum creatinine, and real-time drug concentrations to predict the elimination profile and facilitate model-informed administration of glucarpidase.

SUBMITTER: Taylor ZL

PROVIDER: S-EPMC7484917 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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MTXPK.org: A Clinical Decision Support Tool Evaluating High-Dose Methotrexate Pharmacokinetics to Inform Post-Infusion Care and Use of Glucarpidase.

Taylor Zachary L ZL Mizuno Tomoyuki T Punt Nieko C NC Baskaran Balaji B Navarro Sainz Adriana A Shuman William W Felicelli Nicholas N Vinks Alexander A AA Heldrup Jesper J Ramsey Laura B LB

Clinical pharmacology and therapeutics 20200718 3

Methotrexate (MTX), an antifolate, is administered at high doses to treat malignancies in children and adults. However, there is considerable interpatient variability in clearance of high-dose (HD) MTX. Patients with delayed clearance are at an increased risk for severe nephrotoxicity and life-threatening systemic MTX exposure. Glucarpidase is a rescue agent for severe MTX toxicity that reduces plasma MTX levels via hydrolysis of MTX into inactive metabolites, but is only indicated when MTX conc ...[more]

PMID: 32558929

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Project description:Acute kidney injury due to high-dose methotrexate (HDMTX) is a serious, life-threatening toxicity that can occur in pediatric and adult patients. Glucarpidase is a treatment approved by the Food and Drug Administration for high methotrexate concentrations in the context of kidney dysfunction, but the guidelines for when to use it are unclear. An expert panel was convened to provide specific, expert consensus guidelines for the use of glucarpidase in patients who develop HDMTX-induced nephrotoxicity and delayed methotrexate excretion. The guideline provides recommendations to identify the population of patients who would benefit from glucarpidase rescue by more precisely defining the absolute methotrexate concentrations associated with risk for severe or life-threatening toxicity at several time points after the start of an HDMTX infusion. For an HDMTX infusion ≤24 hours, if the 36-hour concentration is above 30 µM, 42-hour concentration is above 10 µM, or 48-hour concentration is above 5 µM and the serum creatinine is significantly elevated relative to the baseline measurement (indicative of HDMTX-induced acute kidney injury), glucarpidase may be indicated. After a 36- to 42-hour HDMTX infusion, glucarpidase may be indicated when the 48-hour methotrexate concentration is above 5 µM. Administration of glucarpidase should optimally occur within 48-60 hours from the start of the HDMTX infusion, because life-threatening toxicities may not be preventable beyond this time point.Implications for practiceGlucarpidase is a rarely used medication that is less effective when given after more than 60 hours of exposure to high-dose methotrexate, so predicting early which patients will need it is imperative. There are no currently available consensus guidelines for the use of this medication. The indication on the label does not give specific methotrexate concentrations above which it should be used. An international group of experts was convened to develop a consensus guideline that was specific and evidence-based to identify the population of patients who would benefit from glucarpidase.

Project description:ImportanceHospitals ceased most elective procedures during the height of coronavirus disease 2019 (COVID-19) infections. As hospitals begin to recommence elective procedures, it is necessary to have a means to assess how resource intensive a given case may be.ObjectiveTo evaluate the development and performance of a clinical decision support tool to inform resource utilization for elective procedures.Design, setting, and participantsIn this prognostic study, predictive modeling was used on retrospective electronic health records data from a large academic health system comprising 1 tertiary care hospital and 2 community hospitals of patients undergoing scheduled elective procedures from January 1, 2017, to March 1, 2020. Electronic health records data on case type, patient demographic characteristics, service utilization history, comorbidities, and medications were and abstracted and analyzed. Data were analyzed from April to June 2020.Main outcomes and measuresPredicitons of hospital length of stay, intensive care unit length of stay, need for mechanical ventilation, and need to be discharged to a skilled nursing facility. These predictions were generated using the random forests algorithm. Predicted probabilities were turned into risk classifications designed to give assessments of resource utilization risk.ResultsData from the electronic health records of 42 199 patients from 3 hospitals were abstracted for analysis. The median length of stay was 2.3 days (range, 1.3-4.2 days), 6416 patients (15.2%) were admitted to the intensive care unit, 1624 (3.8%) received mechanical ventilation, and 2843 (6.7%) were discharged to a skilled nursing facility. Predictive performance was strong with an area under the receiver operator characteristic ranging from 0.76 to 0.93. Sensitivity of the high-risk and medium-risk groupings was set at 95%. The negative predictive value of the low-risk grouping was 99%. We integrated the models into a daily refreshing Tableau dashboard to guide decision-making.Conclusions and relevanceThe clinical decision support tool is currently being used by surgical leadership to inform case scheduling. This work shows the importance of a learning health care environment in surgical care, using quantitative modeling to guide decision-making.

Project description:BackgroundIndividualized selection of antiretroviral (ARV) therapy is complex, considering drug resistance, comorbidities, drug-drug interactions, and other factors. HIV-ASSIST (www.hivassist.com) is a free, online tool that provides ARV decision support. HIV-ASSIST synthesizes patient and virus-specific attributes to rank ARV combinations based upon a composite objective of achieving viral suppression and maximizing tolerability.ObjectiveTo evaluate concordance of HIV-ASSIST recommendations with ARV selections of experienced HIV clinicians.DesignRetrospective cohort study.PatientsNew and established patients at the Johns Hopkins Bartlett HIV Clinic and San Francisco Veterans Affairs HIV Clinic completing clinic visits were included. Chart reviews were conducted of the most recent clinic visit to generate HIV-ASSIST recommendations, which were compared to prescribed regimens.Main measuresFor each provider-prescribed regimen, we assessed its corresponding HIV-ASSIST "weighted score" (scale of 0 to 10 +, scores of < 2.0 are preferred), rank within HIV-ASSIST's ordered listing of ARV regimens, and concordance with the top five HIV-ASSIST ranked outputs.Key resultsAmong 106 patients (16% female), 23 (22%) were ARV-naïve. HIV-ASSIST outputs for ARV-naïve patients were 100% concordant with prescribed regimens (median rank 1 [IQR 1-3], median weighted score 1.1 [IQR 1-1.2]). For 18 (17%) ARV-experienced patients with ongoing viremia, HIV-ASSIST outputs were 89% concordant with prescribed regimens (median rank 2 [IQR 1-3], median weighted score 1 [IQR 1-1.2]). For 65 (61.3%) patients that were suppressed on a current ARV regimen, HIV-ASSIST recommendations were concordant 88% of the time (median rank 1 [IQR 1-1], median weighted score 1.1 [IQR 1-1.6]). In 18% of cases, HIV-ASSIST weighted score suggested that the prescribed regimen would be considered "less preferred" (score > 2.0) than other available alternatives.ConclusionHIV-ASSIST is an educational decision support tool that provides ARV recommendations concordant with experienced HIV providers from two major academic centers for a diverse set of patient scenarios.

Project description:BACKGROUND:Implementation theories, models and frameworks offer guidance when implementing and sustaining healthcare evidence-based interventions. However, selection can be challenging given the myriad of potential options. We propose to inform a decision support tool to facilitate the appropriate selection of an implementation theory, model or framework in practice. To inform tool development, this study aimed to explore barriers and facilitators to identifying and selecting implementation theories, models and frameworks in research and practice, as well as end-user preferences for features and functions of the proposed tool. METHODS:We used an interpretive descriptive approach to conduct semi-structured interviews with implementation researchers and practitioners in Canada, the United States and Australia. Audio recordings were transcribed verbatim. Data were inductively coded by a single investigator with a subset of 20% coded independently by a second investigator and analyzed using thematic analysis. RESULTS:Twenty-four individuals participated in the study. Categories of barriers/facilitators, to inform tool development, included characteristics of the individual or team conducting implementation and characteristics of the implementation theory, model or framework. Major barriers to selection included inconsistent terminology, poor fit with the implementation context and limited knowledge about and training in existing theories, models and frameworks. Major facilitators to selection included the importance of clear and concise language and evidence that the theory, model or framework was applied in a relevant health setting or context. Participants were enthusiastic about the development of a decision support tool that is user-friendly, accessible and practical. Preferences for tool features included key questions about the implementation intervention or project (e.g., purpose, stage of implementation, intended target for change) and a comprehensive list of relevant theories, models and frameworks to choose from along with a glossary of terms and the contexts in which they were applied. CONCLUSIONS:An easy to use decision support tool that addresses key barriers to selecting an implementation theory, model or framework in practice may be beneficial to individuals who facilitate implementation practice activities. Findings on end-user preferences for tool features and functions will inform tool development and design through a user-centered approach.

Project description:Appropriate thromboprophylaxis for patients with atrial fibrillation or atrial flutter (AF) remains a national challenge. The recent availability of direct oral anticoagulants (DOACs) with comparable efficacy and improved safety compared with warfarin alters the balance between risk factors for stroke and benefit of anticoagulation. Our objective was to examine the impact of DOACs as an alternative to warfarin on the net benefit of oral anticoagulant therapy (OAT) in a real-world population of AF patients.This is a retrospective cohort study of patients with paroxysmal or persistent nonvalvular AF. We updated an Atrial Fibrillation Decision Support Tool (AFDST) to include DOACs as treatment options. The tool generates patient-specific recommendations based upon individual patient risk factor profiles for stroke and major bleeding using quality-adjusted life-years (QALYs) calculated for each treatment strategy by a decision analytic model. The setting included inpatient and ambulatory sites in an academic health center in the midwestern United States. The study involved 5,121 adults with nonvalvular AF seen for any ambulatory visit or inpatient hospitalization over the 1-year period (January through December 2016). Outcome measure was net clinical benefit in QALYs.When DOACs are a therapeutic option, the AFDST recommends OAT for 4,134 (81%) patients and no antithrombotic therapy or aspirin for 489 (9%). A strong recommendation for OAT could not be made in 498 (10%) patients. When warfarin is the only option, OAT is recommended for 3,228 (63%) patients and no antithrombotic therapy or aspirin for 973 (19%). A strong recommendation for OAT could not be made in 920 (18%) patients. In total, 1,508 QALYs could be gained if treatment were changed to that recommended by the AFDST.Availability of DOACs increases the proportion of patients for whom oral anticoagulation therapy is recommended in a real-world cohort of AF patients and increased projected QALYs by more than 1,500 when all patients are receiving thromboprophylaxis as recommended by the AFDST compared with current treatment.

Dataset Information

MTXPK.org: A Clinical Decision Support Tool Evaluating High-Dose Methotrexate Pharmacokinetics to Inform Post-Infusion Care and Use of Glucarpidase.

Publications

MTXPK.org: A Clinical Decision Support Tool Evaluating High-Dose Methotrexate Pharmacokinetics to Inform Post-Infusion Care and Use of Glucarpidase.

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