A Report of the Event-Free Survival (EFS) and Neurotoxicity for Children with Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia (ALL) on Pediatric Oncology Group (POG) Protocol 9405.
Stephen RodesBeverly BellSharon AbishJeanette PullenAllen R. ChauvenetJoanne KurtzbergMeenakshi DevidasJonathan J. ShusterBruce M. Camitta
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Long term daily dosing for patients and families may be challenging due to food aversions, dosing protocols, and age of the patient. The few long term studies suggest that low quantity daily dosing is associated with passing higher dose challenges over the long term, whereas high dose maintenance may protect for longer avoidance intervals. We review the data for peanut and suggest several strategies for your patients.
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This chapter explains the rational behind the concept of pharmacokinetics-guided dosing and dashboards, and the expected benefit of dashboards in improving therapy with monoclonal antibodies in inflammatory disease. It outlines a brief description of the various dosing strategies (both the induction and maintenance phases). In four dosing strategies, induction phase doses were administered as a two-hour intravenous infusion fixed at 5 mg kg-1 at Weeks 0, 2, and 6 as per label recommendations. Maintenance phase doses varied depending on the strategy: label dosing, stepwise adaptive dosing, proportional adaptive dosing, and Bayesian adaptive dosing. The goal of adaptive dosing strategies using Bayesian systems is to identify a dose/dosing frequency that maximizes the likelihood of an individual patient achieving a target exposure associated with an improved clinical outcome. The development of Bayes dosing systems in inflammatory bowel diseases currently presents challenges in defining how the development and implementation of such devices are funded, reimbursed, and implemented clinically.
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Sensitivity and specificity of dosing alerts for dosing errors among hospitalized pediatric patients
To determine the sensitivity and specificity of a dosing alert system for dosing errors and to compare the sensitivity of a proprietary system with and without institutional customization at a pediatric hospital.A retrospective analysis of medication orders, orders causing dosing alerts, reported adverse drug events, and dosing errors during July, 2011 was conducted. Dosing errors with and without alerts were identified and the sensitivity of the system with and without customization was compared.There were 47,181 inpatient pediatric orders during the studied period; 257 dosing errors were identified (0.54%). The sensitivity of the system for identifying dosing errors was 54.1% (95% CI 47.8% to 60.3%) if customization had not occurred and increased to 60.3% (CI 54.0% to 66.3%) with customization (p=0.02). The sensitivity of the system for underdoses was 49.6% without customization and 60.3% with customization (p=0.01). Specificity of the customized system for dosing errors was 96.2% (CI 96.0% to 96.3%) with a positive predictive value of 8.0% (CI 6.8% to 9.3). All dosing errors had an alert over-ridden by the prescriber and 40.6% of dosing errors with alerts were administered to the patient. The lack of indication-specific dose ranges was the most common reason why an alert did not occur for a dosing error.Advances in dosing alert systems should aim to improve the sensitivity and positive predictive value of the system for dosing errors.The dosing alert system had a low sensitivity and positive predictive value for dosing errors, but might have prevented dosing errors from reaching patients. Customization increased the sensitivity of the system for dosing errors.
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Studies have reported high prevalence of inappropriate dosing in patients with renal impairment, which was significantly reduced with pharmacists' interventions. The objective of this study was to assess the proportions of renal drug dosing errors following the implementation of pharmacists-led renal drug dosing adjustment program. This was a quasi-experimental study conducted at the King Abdul Aziz Medical City, a tertiary teaching hospital, Jeddah, Saudi Arabia. The study comprised of 3 phases. The pre-phase and post-phase evaluated drug orders for dosing appropriateness. During the intervention phase, a renal drug dosing adjustment program was implemented, which included educational sessions on dosing in renal insufficiency and a renal drug dosing guidance. The primary outcome was to assess the change in the proportions of dosing errors following the intervention. In the pre-phase, inappropriate dosing was noted in 20.1% (70/348) of orders that required dosing adjustment. Among the total dosing errors, 44.2% (31/70) were further corrected, and pharmacists have documented intervention in 48.3% (15/31) of the corrected orders. In the post-phase, inappropriate dosing was noted in 21.9% (76/346) of orders that required dosing adjustment. Among the total dosing errors, 39.4% (30/76) were further corrected, and pharmacists have documented intervention in 66.6% (20/30) of the corrected orders. There was no statistically significant difference in inappropriate drug dosing between pre-phase and post-phase with a P = 0.56. The intervention was not associated with significant reduction in renal dosing errors, although pharmacist involvement in the corrected orders orders increased after the implementation of the intervention. This may indicate the need to integrate renal dosing guidance into the hospital prescribing system to optimize drug dosing in renal patients.
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Phosphate binders (PBs) account for a large proportion of the daily pill burden in hemodialysis patients. However, patients do not take them all at once but at several dosing timings.We analyzed the dosing timings of all 322 types of oral drugs prescribed to 533 hemodialysis patients.The median daily dosing frequency for all drugs was 6 (4-7) times/day/patient. Patients prescribed PBs had a markedly higher daily dosing frequency than those not taking PBs (7 [5-8] times/day/patient vs. 4 [3-5] times/day/patient, respectively [p < 0.001]). In addition, the ratio of the number of PB pills to other drugs varied greatly at each dosing timing. Furthermore, it was simulated that the daily dosing frequency could be reduced by approximately two times/day/patient by combining the dosing timings of PBs.Changing PB dosing timings can reduce the daily dosing frequency, which may lead to improved medication adherence.
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Nivolumab has received regulatory approval to be given by weight-based or flat dosing every two weeks or by flat dosing every four weeks. However, flat dosing would lead to unnecessarily high doses for patients with lower body weight, increasing the drug usage and probability of toxicity. We review the rationale of using a four-weekly hybrid dosing strategy using weight-based and flat-dosing regimens adopted by some jurisdictions.
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Six-mercaptopurine in the free form and complexed with Pt, Pd, or Bi metals was used at various dosage levels to treat L1210 leukemia in mice. Anticarcinogenic activity was shown by six-mercaptopurine and the Pd and Bi complexes, inactivity by the Pt complex, and toxicity by the highest dosage level of six-mercaptopurine.
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