Publications by authors named "Amanda Hays"

13 Publications

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Recommendations for the content and management of Certificates of Analysis for reference standards from the GCC for bioanalysis.

Bioanalysis 2021 Apr 13;13(8):609-619. Epub 2021 Apr 13.

Worldwide Clinical Trials, Austin, TX, USA.

The 13th Global CRO Council (GCC) closed forum for bioanalysis was held in New Orleans, LA, USA on 5 April 2019. This GCC meeting was organized to discuss the contents of the 2019 ICH M10 Bioanalytical Method Validation Draft Guideline published in February 2019 and consolidate the feedback of the GCC members. While ICH M10 will cover requirements for reference standards, one of the biggest challenges facing the CRO community is the lack of consistency and completeness of Certificates of Analysis for reference standards used in regulated bioanalysis. Similar challenges exist with critical reagents (e.g., capture and detection antibodies) used for assays supporting biologics. The recommendations provided in this publication are the minimum requirements for the content that GCC members believe should be included in Certificates of Analysis for reference standards obtained from commercial vendors, sponsors and compendial suppliers, for use in regulated bioanalytical studies. In addition, recommendations for internal standards, metabolites and critical reagents are discussed.
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http://dx.doi.org/10.4155/bio-2021-0046DOI Listing
April 2021

Extending flow cytometry sample stability by freezing lysed whole blood for clinical monitoring of Treg.

Bioanalysis 2020 May 3;12(10):655-663. Epub 2020 Jun 3.

PRA Health Sciences, 10836 Strang Line Road, Lenexa, KS 66215, USA.

A major challenge for flow cytometry assays supporting clinical trials is postcollection sample stability. Here we present an approach that could mitigate the stability issue while preserving sample integrity and cellular markers, especially when enumerating rare populations such as Tregs. Stability was evaluated using whole blood stored at room temperature and lysed whole blood stored at -80°C. Freezing of lysed whole blood preserved sample integrity and prolonged sample stability for Treg percentage, absolute cell count and median fluorescent intensity values to 11 versus 3 days at room temperature storage. Frozen storage of lysed whole blood can extend sample stability, improve data quality and facilitate sample batch processing during clinical study sample analysis.
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http://dx.doi.org/10.4155/bio-2020-0080DOI Listing
May 2020

Development of an antimicrobial stewardship program in an integrated healthcare system.

Am J Health Syst Pharm 2019 Jan;76(1):34-43

Washington University School of Medicine, St. Louis, MO.

Purpose: The development of an inpatient antimicrobial stewardship program (ASP) in an integrated healthcare system is described.

Summary: With increasing national focus on reducing inappropriate antimicrobial use, state and national regulatory mandates require hospitals to develop ASPs. In 2015, BJC HealthCare, a multihospital health system, developed a system-level, multidisciplinary ASP team to assist member hospitals with ASP implementation. A comprehensive gap analysis was performed to assess current stewardship resources, activities and compliance with CDC core elements at each facility. BJC system clinical leads facilitated the development of hospital-specific leadership support statements, identification of hospital pharmacy and medical leaders, and led development of staff and patient educational components. An antimicrobial-use data dashboard was created for reporting and tracking the impact of improvement activities. Hospital-level interventions were individualized based on the needs and resources at each facility. Hospital learnings were shared at bimonthly system ASP meetings to disseminate best practices. The initial gap analysis revealed that BJC hospitals were compliant in a median of 6 ASP elements (range, 4-8) required by regulatory mandates. By leveraging system resources, all hospitals were fully compliant with regulatory requirements by January 2017.

Conclusion: BJC's ASP model facilitated the development of broad-based stewardship activities, including education modules for patients and providers and clinical decision support, while allowing hospitals to implement activities based on local needs and resource availability.
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http://dx.doi.org/10.1093/ajhp/zxy002DOI Listing
January 2019

12th GCC Closed Forum: critical reagents; oligonucleotides; CoA; method transfer; HRMS; flow cytometry; regulatory findings; stability and immunogenicity.

Bioanalysis 2019 Jun 19;11(12):1129-1138. Epub 2019 Jul 19.

WuXi Apptec, Plainsboro, NJ 08536, USA.

The 12th GCC Closed Forum was held in Philadelphia, PA, USA, on 9 April 2018. Representatives from international bioanalytical Contract Research Organizations were in attendance in order to discuss scientific and regulatory issues specific to bioanalysis. The issues discussed at the meeting included: critical reagents; oligonucleotides; certificates of analysis; method transfer; high resolution mass spectrometry; flow cytometry; recent regulatory findings and case studies involving stability and nonclinical immunogenicity. Conclusions and consensus from discussions of these topics are included in this article.
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http://dx.doi.org/10.4155/bio-2019-0131DOI Listing
June 2019

Recommendations for classification of commercial LBA kits for biomarkers in drug development from the GCC for bioanalysis.

Bioanalysis 2019 Apr 17;11(7):645-653. Epub 2019 Apr 17.

WuXi Apptec, Plainsboro, NJ, USA.

Over the last decade, the use of biomarker data has become integral to drug development. Biomarkers are not only utilized for internal decision-making by sponsors; they are increasingly utilized to make critical decisions for drug safety and efficacy. As the regulatory agencies are routinely making decisions based on biomarker data, there has been significant scrutiny on the validation of biomarker methods. Contract research organizations regularly use commercially available immunoassay kits to validate biomarker methods. However, adaptation of such kits in a regulated environment presents significant challenges and was one of the key topics discussed during the 12th Global Contract Research Organization Council for Bioanalysis (GCC) meeting. This White Paper reports the GCC members' opinion on the challenges facing the industry and the GCC recommendations on the classification of commercial kits that can be a win-win for commercial kit vendors and end users.
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http://dx.doi.org/10.4155/bio-2019-0072DOI Listing
April 2019

Expediting Formulary Standardization in a Multihospital Health System Using Layered Learners.

P T 2018 Mar;43(3):163-167

Drug formularies are a necessary part of medication management in hospitals and health systems. The system-level P&T committee at BJC HealthCare, a multihospital health system in St. Louis, Missouri, developed an approach to standardization of a system-wide formulary using available layered learners to complete the work in an expedited manner before implementation of a system-wide electronic medical record. The formulary standardization work was allocated to reviewers-including pharmacy students, residents, clinical pharmacy specialists, and pharmacy leadership-according to the complexity of the drug class under review, and a pharmacist was assigned to oversee and support the learner (student or resident) as class reviews were performed. The reviewer prepared a review of the drug class, developed recommendations for formulary agents and therapeutic interchanges, and presented recommendations to key stakeholder groups in the organization before a final decision by the system P&T committee. Using this approach, 27 therapeutic class reviews were conducted in 15 months, and 153 of 346 individual agents reviewed (44%) were retained on the formulary. The alignment of formulary medications and interchanges in the 27 classes resulted in an estimated $1.185 million savings in supply costs in the 12 months after implementing the changes. Standardization of the formulary and therapeutic interchanges can be expedited by using a layered learner model, and this model can be used in other health systems to accelerate the formulary review process.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821244PMC
March 2018

Effective Antibiotic Conservation by Emergency Antimicrobial Stewardship During a Drug Shortage.

Infect Control Hosp Epidemiol 2017 03 5;38(3):356-359. Epub 2016 Dec 5.

1Division of Infectious Diseases,Washington University School of Medicine,St. Louis,Missouri.

We present the first description of an antimicrobial stewardship program (ASP) used to successfully manage a multi-antimicrobial drug shortage. Without resorting to formulary restriction, meropenem utilization decreased by 69% and piperacillin-tazobactam by 73%. During the shortage period, hospital mortality decreased (P=.03), while hospital length of stay remained unchanged. Infect Control Hosp Epidemiol 2017;38:356-359.
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http://dx.doi.org/10.1017/ice.2016.289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011860PMC
March 2017

Cysteine scanning mutagenesis of transmembrane domain 10 in organic anion transporting polypeptide 1B1.

Biochemistry 2014 Apr 4;53(14):2261-70. Epub 2014 Apr 4.

Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center , Kansas City, Kansas 66160, United States.

Organic anion transporting polypeptide (OATP) 1B1 is an important drug transporter expressed in human hepatocytes. Previous studies have indicated that transmembrane (TM) domain 2, 6, 8, 9, and in particular 10 might be part of the substrate binding site/translocation pathway. To explore which amino acids in TM10 are important for substrate transport, we mutated 34 amino acids individually to cysteines, expressed them in HEK293 cells, and determined their surface expression. Transport activity of the two model substrates estrone-3-sulfate and estradiol-17β-glucuronide as well as of the drug substrate valsartan for selected mutants was measured. Except for F534C and F537C, all mutants were expressed at the plasma membrane of HEK293 cells. Mutants Q541C and A549C did not transport estradiol-17β-glucuronide and showed negligible estrone-3-sulfate transport. However, A549C showed normal valsartan transport. Pretreatment with the anionic and cell impermeable sodium (2-sulfonatoethyl)methanethiosulfonate (MTSES) affected the transport of each substrate differently. Pretreatment of L545C abolished estrone-3-sulfate uptake almost completely, while it stimulated estradiol-17β-glucuronide uptake. Further analyses revealed that mutant L545C in the absence of MTSES showed biphasic kinetics for estrone-3-sulfate that was converted to monophasic kinetics with a decreased apparent affinity, explaining the previously seen inhibition. In contrast, the apparent affinity for estradiol-17β-glucuronide was not changed by MTSES treatment, but the Vmax value was increased about 4-fold, explaining the previously seen stimulation. Maleimide labeling of L545C was affected by preincubation with estrone-3-sulfate but not with estradiol-17β-glucuronide. These results strongly suggest that L545C is part of the estrone-3-sulfate binding site/translocation pathway but is not directly involved in binding/translocation of estradiol-17β-glucuronide.
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http://dx.doi.org/10.1021/bi500176eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004239PMC
April 2014

Transport by OATP1B1 and OATP1B3 enhances the cytotoxicity of epigallocatechin 3-O-gallate and several quercetin derivatives.

J Nat Prod 2013 Mar 17;76(3):368-73. Epub 2013 Jan 17.

Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, Kansas 66160, USA.

Organic anion transporting polypeptides (OATPs) 1B1 and 1B3 are transporters that are expressed selectively in human hepatocytes under normal conditions. OATP1B3 is also expressed in certain cancers. Flavonoids such as green tea catechins and quercetin glycosides have been shown to modulate the function of some OATPs. In the present study, the extent to which six substituted quercetin derivatives (1-6) affected the function of OATP1B1 and OATP1B3 was investigated. Uptake of the radiolabeled model substrates estradiol 17β-glucuronide, estrone 3-sulfate, and dehydroepiandrosterone sulfate (DHEAS) was determined in the absence and presence of compounds 1-6 using Chinese hamster ovary (CHO) cells stably expressing either OATP1B1 or OATP1B3. Several of compounds 1-6 inhibited OATP-mediated uptake of all three model substrates, suggesting that they could also be potential substrates. Compound 6 stimulated OATP1B3-mediated estradiol 17β-glucuronide uptake by increasing the apparent affinity of OATP1B3 for its substrate. Cytotoxicity assays demonstrated that epigallocatechin 3-O-gallate (EGCG) and most of compounds 1-6 killed preferentially OATP-expressing CHO cells. EGCG, 1, and 3 were the most potent cytotoxic compounds, with EGCG and 3 selectively killing OATP1B3-expressing cells. Given that OATP1B3 is expressed in several cancers, EGCG and some of the quercetin derivatives studied might be promising lead compounds for the development of novel anticancer drugs.
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http://dx.doi.org/10.1021/np3007292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606651PMC
March 2013

Organic anion transporting polypeptides expressed in pancreatic cancer may serve as potential diagnostic markers and therapeutic targets for early stage adenocarcinomas.

Pharm Res 2013 Sep 11;30(9):2260-9. Epub 2013 Jan 11.

Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, Kansas 66160, USA.

Purpose: Organic Anion Transporting Polypeptides (OATPs) are expressed in various epithelial tissues in the body. Because they can be expressed in cancers and because they can transport anticancer drugs, OATPs could be potential targets for cancer therapy. Therefore we examined their expression in human pancreatic ductal adenocarcinomas.

Methods: Expression of all 11 human OATPs was measured at the mRNA level and OATPs with highest expression were characterized at the protein level.

Results: Transcripts of SLCO1B3, SLCO2A1, SLCO3A1 and SLCO4A1 were detected in all the tested pancreatic tissues. OATP1B3, OATP2A1, OATP3A1 and OATP4A1 protein expression was confirmed in these tissues and expression of all four transporters increased in pancreatic adenocarcinoma compared to normal pancreas. OATP1B3 expression was highest in pancreatic hyperplasia and stage one adenocarcinomas compared to stage two and three adenocarcinomas.

Conclusion: OATP1B3, OATP2A1, OATP3A1 and OATP4A1 are up-regulated in pancreatic adenocarcinoma and could potentially be used to target anticancer drugs to pancreatic cancer. Additionally, because expression of OATP1B3 is highest in pancreatitis and stage one adenocarcinoma, which leads to pancreatic cancer, OATP1B3 is a potential marker to diagnose patients with early stage pancreatic adenocarcinomas.
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http://dx.doi.org/10.1007/s11095-012-0962-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3638072PMC
September 2013

Management of hypertensive emergencies: a drug therapy perspective for nurses.

AACN Adv Crit Care 2010 Jan-Mar;21(1):5-14; quiz 16

Alaska Native Medical Center, 4315 Diplomacy Dr, Anchorage, AK 99508, USA.

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http://dx.doi.org/10.1097/NCI.0b013e3181c69f87DOI Listing
January 2011

Pharmacotherapy for a pulseless cardiac arrest.

AACN Adv Crit Care 2007 Oct-Dec;18(4):337-43; quiz 404-5

Department of Pharmacy Services, Tampa General Hospital, PO Box 1289, Tampa, FL 33601, USA.

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http://dx.doi.org/10.1097/01.AACN.0000298623.84663.54DOI Listing
January 2008

Characterization of left ventricular diastolic function by tissue Doppler imaging and clinical status in children with hypertrophic cardiomyopathy.

Circulation 2004 Apr 15;109(14):1756-62. Epub 2004 Mar 15.

Lillie Frank Abercrombie Section of Pediatric Cardiology, Texas Children's Hospital, Houston, Tex 77030, USA.

Background: Conventional transmitral Doppler indices are unreliable in assessing clinical status in patients with hypertrophic cardiomyopathy (HCM) because they are affected by loading conditions. This study sought to determine whether tissue Doppler velocities are predictive of adverse clinical outcomes including death, cardiac arrest, ventricular tachycardia (VT), significant cardiac symptoms, and exercise capacity in children with HCM.

Methods And Results: We studied 80 consecutive children (median age 12 years, median follow-up 26 months) evaluated at 1 hospital from January 1999 to August 2003 compared with 80 age- and gender-matched controls. Patients underwent echocardiography, ambulatory Holter monitoring, and upright exercise testing. Children with HCM had significantly decreased early diastolic tissue Doppler velocities at the lateral mitral (13.2 versus 19.3 cm/s), tricuspid (13.3 versus 16.3 cm/s), and septal (9.4 versus 13.5 cm/s) annuli compared with controls (P<0.001 for each comparison). By forward stepwise regression analysis, early transmitral left ventricular filling velocity (E)/septal Ea ratio predicted death, cardiac arrest, or VT (r=0.610, R2=0.37, P<0.001). Peak oxygen consumption (VO2) was most predictive of children who developed symptoms (r=0.427, R2=0.182, P<0.001). Peak VO2 correlated inversely with E/Ea septal ratio (r=-0.740, P<0.01).

Conclusions: Transmitral E/septal Ea ratio predicts children with HCM who are at risk of adverse clinical outcomes including death, cardiac arrest, VT, and significant cardiac symptoms. Peak VO2 correlated with peak exercise capacity in HCM patients.
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http://dx.doi.org/10.1161/01.CIR.0000124723.16433.31DOI Listing
April 2004