PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-5 (5)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
Document Types
1.  Retrospective analysis of the diagnostic yield of newborn drug testing 
Background
The objective of this study was to identify high-yield screening risk factors for detecting maternal non-medical drug use during pregnancy.
Methods
A four year retrospective analysis was conducted at an academic medical center. Detailed chart review of both the newborn and mother’s medical record was performed on all cases for which one or more drug(s) or metabolite(s) were identified and confirmed in meconium or urine.
Results
229 (9.2%) of 2,497 meconium samples out of 7,749 live births confirmed positive for one or more non-medical drugs. History of maternal non-medical drug and/or tobacco use in pregnancy was present in 90.8% of non-medical drug use cases. Addition of social risk factors and inadequate prenatal care increased the yield to 96.9%.
Conclusions
Use of focused screening criteria based on specific maternal and social risk factors may detect many prenatal non-medical drug exposures.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2393-14-250) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2393-14-250
PMCID: PMC4124162  PMID: 25073780
Meconium drug abuse detection/testing; Urine drug abuse detection/testing; Non-medical drug use; Fetal drug exposure; Prenatal drug abuse; Substance abuse testing
2.  Genetics InFormatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis (DVT): Rationale and Study Design 
The pharmacogenomics journal  2011;12(5):417-424.
The risk of venous thromboembolism (VTE) is higher after total hip or knee replacement surgery than after almost any other surgical procedure; warfarin sodium is commonly prescribed to reduce this peri-operative risk. Warfarin has a narrow therapeutic window with high inter-individual dose variability and can cause hemorrhage. The Genetics-InFormatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis (DVT) is a 2×2 factorial-design, randomized controlled trial designed to compare the safety and effectiveness of warfarin-dosing strategies. GIFT will answer two questions: (1) Does pharmacogenetic (PGx) dosing reduce the rate of adverse events in orthopedic patients; and (2) Is a lower target International Normalized Ratio (INR) non-inferior to a higher target INR in orthopedic participants? The composite primary endpoint of the trial is symptomatic and asymptomatic VTE (identified on screening ultrasonography), major hemorrhage, INR ≥ 4, and death.
doi:10.1038/tpj.2011.18
PMCID: PMC3175019  PMID: 21606949
pharmacogenetics; warfarin; randomized controlled trial; dosing algorithm
3.  Prospective Pilot Trial of PerMIT Versus Standard Anticoagulation Service Management of Patients Initiating Oral Anticoagulation 
Thrombosis and haemostasis  2012;108(3):561-569.
Summary
We performed a randomized pilot trial of PerMIT, a novel decision support tool for genotype-based warfarin initiation and maintenance dosing, to assess its efficacy for improving warfarin management. We prospectively studied 26 subjects to compare PerMIT-guided management with routine anticoagulation service management. CYP2C9 and VKORC1 genotype results for 13 subjects randomly assigned to the PerMIT arm were recorded within 24 h of enrollment. To aid in INR interpretation, PerMIT calculates estimated loading and maintenance doses based on a patient’s genetic and clinical characteristics and displays calculated S-warfarin plasma concentrations based on planned or administered dosages. In comparison to control subjects, patients in the PerMIT study arm demonstrated a 3.6-day decrease in the time to reach a stabilized INR within the target therapeutic range (4.7 vs. 8.3 days, p = 0.015); a 12.8% increase in time spent within the therapeutic interval over the first 25 days of therapy (64.3% vs. 55.3%, p = 0.180); and a 32.9% decrease in the frequency of warfarin dose adjustments per INR measurement (38.3% vs. 57.1%, p = 0.007). Serial measurements of plasma S-warfarin concentrations were also obtained to prospectively evaluate the accuracy of the pharmacokinetic model during induction therapy. The PerMIT S-warfarin plasma concentration model estimated 62.8% of concentrations within 0.15 mg/L. These pilot data suggest that the PerMIT method and its incorporation of genotype/phenotype information may help practitioners increase the safety, efficacy, and efficiency of warfarin therapeutic management.
Clinical Trials Registration
http://www.clinicaltrials.gov. Unique identifier: NCT00993200
doi:10.1160/TH12-03-0159
PMCID: PMC3434319  PMID: 22836303
anticoagulation; warfarin; pharmacogenetics; algorithm; clinical trial
4.  Pharmacogenetic Warfarin Dose Refinements Remain Significantly Influenced by Genetic Factors after One Week of Therapy 
Thrombosis and Haemostasis  2011;107(2):232-240.
Summary
Introduction
By guiding initial warfarin dose, pharmacogenetic (PGx) algorithms may improve the safety of warfarin initiation. However, once INR response is known, the contribution of PGx to dose refinements is uncertain. This study sought to develop and validate clinical and PGx dosing algorithms for warfarin dose refinement on days 6–11 after therapy initiation.
Materials and Methods
An international sample of 2,022 patients at 13 medical centers on 3 continents provided clinical, INR, and genetic data at treatment days 6–11 to predict therapeutic warfarin dose. Independent derivation and retrospective validation samples were composed by randomly dividing the population (80%/20%). Prior warfarin doses were weighted by their expected effect on S-warfarin concentrations using an exponential-decay pharmacokinetic model. The INR divided by that “effective” dose constituted a treatment response index.
Results
Treatment response index, age, amiodarone, body surface area, warfarin indication, and target INR were associated with dose in the derivation sample. A clinical algorithm based on these factors was remarkably accurate: in the retrospective validation cohort its R2 was 61.2% and median absolute error (MAE) was 5.0 mg/week. Accuracy and safety was confirmed in a prospective cohort (N=43). CYP2C9 variants and VKORC1-1639 G→A were significant dose predictors in both the derivation and validation samples. In the retrospective validation cohort, the PGx algorithm had: R2= 69.1% (P<0.05 vs. clinical algorithm), MAE= 4.7 mg/week.
Conclusions
A pharmacogenetic warfarin dose-refinement algorithm based on clinical, INR, and genetic factors can explain at least 69.1% of therapeutic warfarin dose variability after about one week of therapy.
doi:10.1160/TH11-06-0388
PMCID: PMC3292349  PMID: 22186998
warfarin; VKORC1; CYP2C9; pharmacogenetic
5.  An ImmunoChip prototype for simultaneous detection of antiepileptic drugs using an enhanced one-step homogeneous immunoassay1 2 3 4 
Analytical biochemistry  2007;365(2):222-229.
The development and characterization of a one-step homogeneous immunoassay-based multi-well ImmunoChip is reported for the simultaneous detection and quantitation of antiepileptic drugs (AEDs). The assay platform utilizes a Cloned Enzyme Donor Immunoassay (CEDIA), and a Beta-Glo assay system for generation of bioluminescent signal. Results of the one-step CEDIA for three AEDs (CBZ, carbamazepine; PHT, phenytoin; VPA, valproic acid), in the presence of serum, correlate well with the values determined by Fluorescence Polarization Immunoassay. CEDIA intra-assay and inter-assay coefficients of variation are lower than 10%. A microfabrication process, xurography, was utilized to produce the multi-well ImmunoChip. Assay reagents were dispensed, and lyophilized, in a three-layer pattern. The multi-well ImmunoChip prototype was used to detect and quantify AEDs in serum samples containing all three drugs. Luminescent signals generated from each well were recorded with a Charged Coupled Device (CCD) camera. The assays performed on an ImmunoChip were fast (5 min), requiring only small volumes of both the reagents (< 1 μl per well) and the serum sample. The ImmunoChip assay platform described herein may be well suited for therapeutic monitoring of drugs and metabolites at the point-of-care.
doi:10.1016/j.ab.2007.03.019
PMCID: PMC2043085  PMID: 17448436
Homogeneous Immunoassay; CEDIA; Bioluminescence; ImmunoChip; Therapeutic Drug Monitoring; Antiepileptic Drugs

Results 1-5 (5)