A5076482060- Hematopoietic Stem Cell Transplantation
- Sexual Differentiation and Disorders
- Adrenal Hormones and Disorders
- Hormonal and reproductive studies
- Statistical Methods in Clinical Trials
- Acute Lymphoblastic Leukemia research
- Analytical Methods in Pharmaceuticals
- Antibiotics Pharmacokinetics and Efficacy
- Computational Drug Discovery Methods
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Antifungal resistance and susceptibility
- Childhood Cancer Survivors' Quality of Life
- Statistical Methods and Bayesian Inference
- Growth Hormone and Insulin-like Growth Factors
- HIV, Drug Use, Sexual Risk
- Drug-Induced Ocular Toxicity
- Neutropenia and Cancer Infections
- Metabolism and Genetic Disorders
- Fungal Infections and Studies
- LGBTQ Health, Identity, and Policy
- Antibiotic Use and Resistance
- Ocular Infections and Treatments
- Influenza Virus Research Studies
- Bacterial Identification and Susceptibility Testing
Dana-Farber Cancer Institute
2024
Boston Children's Hospital
2024
University of Minnesota
2020-2023
Jordan University of Science and Technology
2020
Hydroxychloroquine is an antimalarial drug being tested as a potential treatment for the novel coronavirus disease 2019 (COVID‐19) pandemic caused by severe acute respiratory syndrome 2. Although efficacy of hydroxychloroquine COVID‐19 remains uncertain, it may serve prophylactic agent especially in those at high risk, such healthcare workers, household contacts infected patients, and immunocompromised. Our aim was to identify possible dosing regimens through simulation risk infections...
Objectives: It is a common yet optimistic assumption that pharmacokinetic (PK) and pharmacodynamic (PD) studies are error-free when employing nonlinear mixed-effect approach. However, errors can arise at any phase of clinical drug development studies, potentially influencing the residual unexplained variability (RUV). Previous research highlighted neglecting these could lead to biased PK estimates [1]. We aim 1) assess impact manufacturing(ME), dosing time(DE), sampling time(SE),...
Abstract Hematopoietic cell transplantation (HCT) for hematologic malignancies with non‐remission disease and/or prior post‐transplant relapse have poor relapse‐free survival. We previously demonstrated the efficacy of haploidentical reduced‐intensity HCT regimen glucocorticoid‐based graft‐versus‐host (GVHD) prophylaxis. recently showed a possible association between rabbit antithymocyte globulin (rATG) exposure and acute GVHD (aGVHD) risk, leading to hypothesize that optimization rATG may...
The aim of this study was to characterize the pharmacokinetic/pharmacodynamic relationships cortisol and adrenal biomarkers 17-hydroxyprogesterone androstenedione in children with congenital hyperplasia (CAH).A nonlinear mixed-effect modelling approach used analyse cortisol, concentrations obtained over 6 hours from CAH (n = 50). A circadian rhythm evident model leveraged literature information on untreated CAH. Indirect response models were applied which inhibited production rate all three...
Prophylactic voriconazole use is recommended for children undergoing hematopoietic cell transplantation (HCT). Dosing considerations are essential, due to the narrow therapeutic window of voriconazole. Known covariates do not sufficiently explain large interindividual pharmacokinetic (PK) variability Moreover, knowledge PK age <2 years limited. We investigated genetic and clinical covariate associations with subsequently simulated dosing regimens in children. This study was conducted as part...
Objectives: The current study aimed to evaluate the prevalence, level of knowledge and attitudes seasonal influenza vaccination among older adults in Jordan.Methods: This was a cross-sectional which close-ended questionnaire administered (65 years or older) two major cities Jordan between May 2018 July 2018. A p-value less than 0.05 considered cutoff for statistical significance.Results: Among 500 participants, only 1.2% (n = 6) received vaccine during previous year. In assessing disease...
Abstract Currently there are no commercially available hydrocortisone formulations for the treatment of children with congenital adrenal hyperplasia (CAH) that allow smaller doses (0.1-1.25 mg) and incremental adjustments needed to control excess androgen production avoid negative effects overtreatment. This lack availability has led physicians recommend dividing 5-mg tablets into 4 6 pieces, compounding capsules or suspension, crushing 5- 10-mg in 5 10 mL water. We report a case iatrogenic...
Most children with non-classic congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency are asymptomatic and do not require cortisol replacement therapy unless they develop symptoms of hyperandrogenemia. The current practice is treat symptomatic hydrocortisone aimed at suppressing excess androgen production irrespective the child's level endogenous production. Once on therapy, even normal stress dosing. Some NC-CAH may present premature adrenarche, growth acceleration,...
To quantify antimicrobial use in inpatients setting as part of stewardship program surveillance.Antimicrobial was obtained using a pre-designed data collection form this point prevalence study. Setting: The study conducted tertiary academic hospital the North Jordan on 13 August 2018. Main outcome measures: determined two methods: defined daily (DDD) and days therapy (DOT).This identified 144 patients. Carbapenems, glycopeptides, piperacillin-tazobactam were most utilized antimicrobials...
Voriconazole is a widely used antifungal agent in immunocompromised patients, but its utility limited by variable exposure and narrow therapeutic index. Population pharmacokinetic (PK) models have been to characterize voriconazole PK derive individualized dosing regimens. However, determinants of temporal within-patient variability were not well established. We aimed within individuals identify predictive clinical factors. This study was conducted as part single-institution, phase I...
Absorption processes are complex but rarely have sufficient data to capture parameters of a mechanistic model. Typically, single absorption model (e.g., first-order, mixed-order, lag, or distributive delay model), is assumed apply all individuals with the expectation that random effects will accommodate individual differences. However, distinct profiles may coexist in given dataset. We propose individualized models should be considered when multiple evident population analysis....
Introduction The Centers for Disease Control and Prevention (CDC) World Health Organization (WHO) created separate growth charts girls boys because patterns rates differ between sexes. However, scenarios exist in which this dichotomizing “girls versus boys” approach may not be ideal, including the care of non-binary youth or transgender undergoing transitions consistent with their gender identity. There is therefore a need that age smooth differences pubertal timing sexes to determine how...
Concentration data below the limit of quantification (BLQ) are common in population pharmacokinetic (PK) analyses, and one method used to accommodate these during nonlinear mixed effects modeling is M3 method. A recent community discussion questioned potential bias weighted residual plots when applied, a simulation study was conducted evaluate this bias. Weighted-residual subjects with BLQ found be small probably ignorable both intense sparse sampling designs. Weighted residuals, traditional...
Abstract Background Young children with congenital adrenal hyperplasia (CAH) require small doses (0.1-1.25 mg) of hydrocortisone (HC) to control excess androgen production and avoid the negative effects overtreatment. The smallest commercially available HC formulation, before recent US Food Drug Administration approval granules, was a scored 5-mg tablet. options achieve were limited using pharmacy-compounded suspension, which CAH Clinical Practice Guidelines recommended against, or splitting...
Phosphoramide mustard (PM) is the final cytotoxic metabolite formed from parent compound cyclophosphamide through a complex metabolic pathway, primarily hepatic metabolism. Little known about effect of renal elimination on disposition PM. We evaluated function PM exposure after single doses in 85 patients undergoing allogeneic hematopoietic cell transplantation using nonlinear mixed-effects modeling. Mixed linear and pathways were required to adequately describe Creatinine clearance (CrCL)...
Cyclophosphamide (CY) is an alkylating agent widely used in the field of oncology and hematopoietic cell transplantation (HCT). It recommended to use adjusted body weight with adjustment factor 0.25 (ABW25) for dosing CY obese patients undergoing HCT. However, evidence based on pharmacokinetics (PK) support this recommendation lacking. We aimed identify a strategy that achieves equivalent exposures among nonobese patients. The present study secondary analysis previously conducted...
A specific model for drug absorption is necessarily assumed in pharmacokinetic (PK) analyses following extravascular dosing. Unfortunately, an inappropriate may force other parameters to be poorly estimated. An added complexity arises population PK when different individuals appear have patterns. The aim of this study demonstrate that a deep neural network (DNN) can used prescreen data and assign individualized consistent with either first-order, Erlang, or split-peak process. Ten thousand...
Abstract Young children with CAH require small doses (0.1–1.25mg) and incremental adjustments of hydrocortisone (HC) to control excess androgen production avoid the negative effects overtreatment. A recent 6 hour pharmacokinetic/pharmacodynamic study reported that alcohol-free HC suspension provides similar cortisol exposure tablets (1), but more data is needed assess its clinical efficacy. We performed a chart review determine effect compared on height, weight, BMI, bone age z-scores...