Life Sciences Commons^™

A Genomics Driven Induced Pluripotent Stem Cell Model Of Infant Acute Lymphoblastic Leukemia - Early Results, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Bradley Thornton, Molly Leyda, Priyanka Prem Kumar, Midhat Farooqi, Jay L. Vivian, Erin M. Guest, John M. Perry

Research Days

While the cure rates for pediatric ALL have improved over the decades, infants with ALL (iALL) have not benefitted from these advances and continue to have a devastating prognosis. Unfortunately progress in treatment has also been slowed by inadequate research models. With this project, we address this unmet need by investigating a novel model to understand the cellular and molecular changes that occur during iALL onset and progression.

Identification Of Genetic Disorders Based On Phenotype And Subsequent Medical Management, Sara J. Strandlund, Jotishna Sharma, Bonnie R. Sullivan, Ashley K. Sherman, Laura A. Cross

Research Days

Many genetic disorders in the neonatal period contribute to significant morbidity and mortality. This study evaluates the indications for genetic testing based on phenotype and compares these with the diagnostic yield of symptom driven exome sequencing and chromosome microarray in the NICU. Overall, this study highlights that while there are diagnostic limitations to exome sequencing, genetic testing remains an important adjunct to clinical care.

Improving Nutritional Delivery To Pediatric Patients While Using Continuous Renal Replacement Therapy, Jennifer Ruiz-Boada, Sarah Brunner, Tara Benton, Vimal Chadha

Research Days

This quality improvement guide aims to enhance early nutritional delivery to pediatric patients with renal failure who require renal replacement therapy.ng renal replacement therapy.

Pediatric Beta Blocker Therapy: A Comprehensive Review Of Development And Genetic Variation To Guide Precision-Based Therapy In Children, Adolescents, And Young Adults., Mollie Walton, Jonathan B. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

Beta adrenergic receptor antagonists, known as beta blockers, are one of the most prescribed medications in both pediatric and adult cardiology. Unfortunately, most of these agents utilized in the pediatric clinical setting are prescribed off-label. Despite regulatory efforts aimed at increasing pediatric drug labeling, a majority of pediatric cardiovascular drug agents continue to lack pediatric-specific data to inform precision dosing for children, adolescents, and young adults. Adding to this complexity is the contribution of development (ontogeny) and genetic variation towards the variability in drug disposition and response. In the absence of current prospective trials, the purpose of this comprehensive review …

Developing A National-Scale Exposure Index For Combined Environmental Hazards And Social Stressors And Applications To The Environmental Influences On Child Health Outcomes (Echo) Cohort., Sheena E. Martenies, Mingyu Zhang, Anne E. Corrigan, Anton Kvit, Timothy Shields, William Wheaton, Deana Around Him, Judy Aschner, Maria M. Talavera-Barber, Emily S. Barrett, Theresa M. Bastain, Casper Bendixsen, Carrie V. Breton, Nicole R. Bush, Ferdinand Cacho, Carlos A. Camargo, Kecia N. Carroll, Brian S. Carter, Andrea E. Cassidy-Bushrow, Whitney Cowell, Lisa A. Croen, Dana Dabelea, Cristiane S. Duarte, Anne L. Dunlop, Todd M. Everson, Rima Habre, Tina V. Hartert, Jennifer B. Helderman, Alison E. Hipwell, Margaret R. Karagas, Barry M. Lester, Kaja Z. Lewinn, Sheryl Magzamen, Rachel Morello-Frosch, Thomas G. O'Connor, Amy M. Padula, Michael Petriello, Sheela Sathyanarayana, Joseph B. Stanford, Tracey J. Woodruff, Rosalind J. Wright, Amii M. Kress, Program Collaborators For Environmental Influences On Child Health Outcomes

Manuscripts, Articles, Book Chapters and Other Papers

Tools for assessing multiple exposures across several domains (e.g., physical, chemical, and social) are of growing importance in social and environmental epidemiology because of their value in uncovering disparities and their impact on health outcomes. Here we describe work done within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort Study to build a combined exposure index. Our index considered both environmental hazards and social stressors simultaneously with national coverage for a 10-year period. Our goal was to build this index and demonstrate its utility for assessing differences in exposure for pregnancies enrolled in the ECHO-wide Cohort Study. Our unitless …

Pharmacogenetic Testing For The Pediatric Gastroenterologist: Actionable Drug-Gene Pairs To Know., Tracy L. Sandritter, Rachel Chevalier, Rebecca Abt, Valentina Shakhnovich

Manuscripts, Articles, Book Chapters and Other Papers

Gastroenterologists represent some of the earlier adopters of precision medicine through pharmacogenetic testing by embracing upfront genotyping for thiopurine S-methyltransferase nucleotide diphosphatase (TPMT) before prescribing 6-mercaptopurine or azathioprine for the treatment of inflammatory bowel disease. Over the last two decades, pharmacogenetic testing has become more readily available for other genes relevant to drug dose individualization. Common medications prescribed by gastroenterologists for conditions other than inflammatory bowel disease now have actionable guidelines, which can improve medication efficacy and safety; however, a clear understanding of how to interpret the results remains a challenge for many clinicians, precluding wide implementation of …

Climate Change Imperils Pediatric Health: Child Advocacy Through Fossil Fuel Divestment., Sandra H. Jee, Elizabeth Friedman, Ruth A. Etzel, Vi T. Nguyen, Todd L. Sack, Kathi J. Kemper

Manuscripts, Articles, Book Chapters and Other Papers

Climate change poses an existential threat to children's health. Divestment of ownership stakes in fossil fuel companies is one tool available to pediatricians to address climate change. Pediatricians are trusted messengers regarding children's health and therefore bear a unique responsibility to advocate for climate and health policies that affect children. Among the impacts of climate change on pediatric patients are allergic rhinitis and asthma; heat-related illnesses; premature birth; injuries from severe storms and fires; vector-borne diseases; and mental illnesses. Children are disproportionately affected as well by climate-related displacement of populations, drought, water shortages, and famine. The human-generated burning of fossil …

Developmental Pharmacokinetics Of Indomethacin In Preterm Neonates: Severely Decreased Drug Clearance In The First Week Of Life., Wojciech Krzyzanski, Bradley Stockard, Andrea Gaedigk, Allison Scott, Whitney M. Nolte, Kim T. Gibson, J Steven Leeder, Tamorah Lewis

Manuscripts, Articles, Book Chapters and Other Papers

Indomethacin is used commonly in preterm neonates for the prevention of intracranial hemorrhage and closure of an abnormally open cardiac vessel. Due to biomedical advances, the infants who receive this drug in the neonatal intensive care unit setting have become younger, smaller, and less mature (more preterm) at the time of treatment. To develop a pharmacokinetics (PK) model to aid future dosing, we designed a prospective cohort study to characterize indomethacin PK in a dynamically changing patient population. A population PK base model was created using NONMEM, and a covariate model was developed in a primary development cohort and subsequently …

Pharmacometabolomics Profiling Of Preterm Infants Validates Patterns Of Metabolism Associated With Response To Dexamethasone Treatment For Bronchopulmonary Dysplasia., Bradley Stockard, Cheri Gauldin, William E. Truog, Tamorah Lewis

Manuscripts, Articles, Book Chapters and Other Papers

Bronchopulmonary dysplasia (BPD) is one of the most common health complications of premature birth. Corticosteroids are commonly used for treatment of BPD, but their use is challenging due to variability in treatment response. Previous pharmacometabolomics study has established patterns of metabolite levels with response to dexamethasone. We obtained additional patient samples for metabolomics analysis to find associations between the metabolome and dexamethasone response in a validation cohort. A total of 14 infants provided 15 plasma and 12 urine samples. The measure of treatment response was the calculated change in respiratory severity score (deltaRSS) from pre-to-post treatment. Each metabolite was assessed …

Pharmacometabolomics Profiling Of Preterm Infants Validates Patterns Of Metabolism Associated With Response To Dexamethasone Treatment For Bronchopulmonary Dysplasia, Bradley C. Stockard

Research Days

Background: Bronchopulmonary dysplasia (BPD) is one of the most common health complications of premature birth. Corticosteroids are commonly used for treatment of BPD, but their use is challenging due to variability in treatment response.

Objectives/Goal: Previous pharmacometabolomics study has established patterns of metabolite levels with response to dexamethasone. We obtained additional patient samples for metabolomics analysis to find associations between the metabolome and dexamethasone response in a validation cohort.

Methods/Design: 14 infants provided 15 plasma and 12 urine samples. The measure of treatment response was the calculated change in respiratory severity score (deltaRSS) from pre-to-post treatment. Each metabolite was assessed …

Case Report: Pharmacogenetics Applied To Precision Psychiatry Could Explain The Outcome Of A Patient With A New Cyp2d6 Genotype, Elena Marcos-Vadillo, Lorena Carrascal-Laso, Ignacio Ramos-Gallego, Andrea Gaedigk, Belén García-Berrocal, Eduardo Mayor-Toranzo, Alfonso Sevillano-Jiménez, Almudena Sánchez, María Isidoro-García, Manuel Franco-Martín

Manuscripts, Articles, Book Chapters and Other Papers

Precision medicine applied to psychiatry provides new insight into the promising field of precision psychiatry. Psychotic disorders are heterogeneous, complex, chronic, and severe mental disorders. Not only does the prognosis and the course of the disease vary among patients suffering from psychotic disorders, but the treatment response varies as well. Although antipsychotic drugs are the cornerstone of the treatment of schizophrenia, many patients only partially respond to these drugs. Furthermore, patients often experience adverse events which can lead to poor treatment adherence. Interindividual variability in drug response could be related to age, gender, ethnicity, lifestyle factors, pharmacological interactions, obesity, and …

Ten Years Of Experience Support Pharmacogenetic Testing To Guide Individualized Drug Therapy., María Celsa Peña-Martín, Belén García-Berrocal, Almudena Sánchez-Martín, Elena Marcos-Vadillo, María Jesús García-Salgado, Santiago Sánchez, Carolina Lorenzo, David González-Parra, Francisco Sans, Manuel Franco, Andrea Gaedigk, María José Mateos-Sexmero, Catalina Sanz, María Isidoro-García

Manuscripts, Articles, Book Chapters and Other Papers

Precision medicine utilizing the genetic information of genes involved in the metabolism and disposition of drugs can not only improve drug efficacy but also prevent or minimize adverse events. Polypharmacy is common among multimorbid patients and is associated with increased adverse events. One of the main objectives in health care is safe and efficacious drug therapy, which is directly correlated to the individual response to treatment. Precision medicine can increase drug safety in many scenarios, including polypharmacy. In this report, we share our experience utilizing precision medicine over the past ten years. Based on our experience using pharmacogenetic (PGx)-informed prescribing, …

Evaluation Of Placentation And The Role Of The Aryl Hydrocarbon Receptor Pathway In A Rat Model Of Dioxin Exposure., Khursheed Iqbal, Stephen H. Pierce, Keisuke Kozai, Pramod Dhakal, Regan L. Scott, Katherine F Roby, Carrie A. Vyhlidal, Michael J. Soares

Manuscripts, Articles, Book Chapters and Other Papers

Background: Our environment is replete with chemicals that can affect embryonic and extraembryonic development. Dioxins, such as 2,3,7,8-tetrachlorodibenzo-p" role="presentation" style="box-sizing: inherit; display: inline-block; line-height: 0; font-size: 18.08px; overflow-wrap: normal; word-spacing: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; margin: 0px; padding: 1px 0px; position: relative;">pp-dioxin (TCDD), are compounds affecting development through the aryl hydrocarbon receptor (AHR).

Objectives: The purpose of this investigation was to examine the effects of TCDD exposure on pregnancy and placentation and to evaluate roles for AHR and cytochrome P450 1A1 (CYP1A1) in TCDD action.

Methods: Actions …

Profiling Pretomanid As A Therapeutic Option For Tb Infection: Evidence To Date., Stephani L. Stancil, Fuad Mirzayev, Susan M. Abdel-Rahman

Manuscripts, Articles, Book Chapters and Other Papers

Tuberculosis (TB) is the most deadly infectious disease globally. Although most individuals achieve a cure, a substantial portion develop multi-drug resistant TB which is exceedingly difficult to treat, and the number of effective agents is dwindling. Development of new anti-tubercular medications is imperative to combat existing drug resistance and accelerate global eradication of TB. Pretomanid (PA-824) represents one of the newest drug classes (ie, nitroimidazooxazines) approved in 2019 by the United States Food and Drug Administration as part of a multi-drug regimen (with bedaquiline and linezolid, BPaL) and recommended by the World Health Organization (WHO) to treat extensively-resistant (XR-TB) and …

Germline Variants Associated With Cancer Predisposition And Bone Marrow Failure Are Common In Kmt2a-R Infant Acute Lymphoblastic Leukemia Patients, Sarah E. Mc Dermott

Research Days

Background: Infant acute lymphoblastic leukemia (ALL), is a particularly aggressive subtype of leukemia with an early onset and unfavorable clinical outcome. Most (~70%) cases of infant ALL involve chromosomal rearrangement of KMT2A (KMT2A- r) on chromosome 11q23, the strongest independent predictor of a poor prognosis. To date, genomics studies have consistently demonstrated KMT2A-r infant ALL to have a strikingly silent landscape of DNA mutations. Germline mutations in cancer predisposition genes are found in 8.6% of pediatric malignancies and 4.4% of pediatric leukemias, compared to 1.1% in persons in the 1000 Genomes Project.

Objectives/Goal: We hypothesized that germline variants may contribute …

Many Clinical Laboratories Performing Next-Generation Sequencing Have No Future Plans To Migrate To The Most Recent Human Reference Genome Build (Grch38), Lisa A. Lansdon

Research Days

Background: Analysis of clinical next-generation sequencing (NGS) data requires the Human Reference Genome (HRG) for alignment. Build GRCh38 was released in December 2013 and resolved ~1,000 issues from GRCh37, including erroneous calls within clinically-relevant genes.

Objectives/Goal: Despite this new release becoming available over seven years ago, most clinical laboratories continue to use build GRCh37. We were interested to learn other clinical laboratory’s plans for migration to GRCh38, including their proposed timelines and related concerns; therefore, we conducted a survey to define the current landscape of genome alignment in clinical NGS.

Methods/Design: Seventy-one clinical laboratories performing constitutional NGS testing were invited …

Activation Of Aryl Hydrocarbon Receptor Signaling In Human Trophoblasts Alters Markers Of Growth And Differentiation, Asmaa Alsousi

Research Days

Background: It is estimated that 1.7% of pregnant women smoke during their pregnancy globally, with the highest levels observed in Europe at 8.1%, and lowest in Africa at 0.8. The association of maternal cigarette smoking with increased risk of poor birth outcomes such as preterm birth, congenital anomalies, and neonatal mortality is well-established. In addition, evidence suggests that intrauterine exposure to maternal smoking impacts the risk of developing diseases later in life; however, we still do not understand the exact mechanism(s) leading to these outcomes. Once components of cigarette smoke (CS) cross the placenta and enter the fetal compartment, several …

Novel Hsp40/J-Domain Protein Inhibitors To Deplete Misfolded Mutant P53, Shigeto Nishikawa

Research Days

Background: Accumulation of oncogenic mutant p53 (mutp53) greatly contributes to cancer progression. Heat shock protein 40 (HSP40), also known as J-domain proteins (JDPs), has been implicated in stabilization of misfolded forms of mutp53. Specifically, we demonstrate that DNAJA1, a member of HSP40/JDPs, binds to and stabilizes misfolded mutp53, while knockdown of DNAJA1 results in CHIP ubiquitin ligase-mediated degradation of misfolded mutp53 and inhibition of tumor growth. Since no HSP40/JDPs inhibitors are currently available in clinics, these findings prompted us to identify inhibitors for DNAJA1 or HSP40/JDPs.

Objectives/Goal: The goal of this study is to identify and characterize potential anti-cancer compounds …

Cyp2d6 Genetic Variation And Its Implication For Vivax Malaria Treatment In Madagascar, Rajeev K. Mehlotra, Andrea Gaedigk, Rosalind E. Howes, Tovonahary A. Rakotomanga, Arsene C. Ratsimbasoa, Peter A. Zimmerman

Manuscripts, Articles, Book Chapters and Other Papers

Plasmodium vivax is one of the five human malaria parasite species, which has a wide geographical distribution and can cause severe disease and fatal outcomes. It has the ability to relapse from dormant liver stages (hypnozoites), weeks to months after clearance of the acute blood-stage infection. An 8-aminoquinoline drug primaquine (PQ) can clear the hypnozoites, and thus can be used as an anti-relapse therapeutic agent. Recently, a number of studies have found that its efficacy is compromised by polymorphisms in the cytochrome P450 2D6 (CYP2D6) gene; decreased or absence of CYP2D6 activity contributes to PQ therapeutic failure. The …

Efficacy Of Weight Reduction On Pediatric Nonalcoholic Fatty Liver Disease: Opportunities To Improve Treatment Outcomes Through Pharmacotherapy., Chance S. Friesen, Chelsea Hosey-Cojocari, Sherwin S. Chan, Iván L. Csanaky, Jonathan B. Wagner, Brooke Sweeney, Alec Friesen, Jason D. Fraser, Valentina Shakhnovich

Manuscripts, Articles, Book Chapters and Other Papers

Obesity is the single greatest risk factor for nonalcoholic fatty liver disease (NAFLD). Without intervention, most pediatric patients with NAFLD continue to gain excessive weight, making early, effective weight loss intervention key for disease treatment and prevention of NAFLD progression. Unfortunately, outside of a closely monitored research setting, which is not representative of the real world, lifestyle modification success for weight loss in children is low. Bariatric surgery, though effective, is invasive and can worsen NAFLD postoperatively. Thus, there is an evolving and underutilized role for pharmacotherapy in children, both for weight reduction and NAFLD management. In this perspective article, …

Effect Of Crohn's Disease On Villous Length And Cyp3a4 Expression In The Pediatric Small Intestine., Carrie A. Vyhlidal, Brian D. Chapron, Atif Ahmed, Vivekanand Singh, Rebecca Casini, Valentina Shakhnovich

Manuscripts, Articles, Book Chapters and Other Papers

Changes in absorptive capacity and first-pass metabolism in the small intestine affect oral drug bioavailability. Characterization of such changes as a consequence of inflammation is important for developing physiologically-based pharmacokinetic (PBPK) models for inflammatory bowel disease. We sought to elucidate the impact of small intestinal Crohn's disease (CD) on villous length and CYP3A4 expression in children. Freshly frozen duodenal and terminal ileum (TI) biopsies from 107 children (1-19 years) with and without CD were evaluated for active inflammation. Villous length and CYP3A4 mRNA/protein expression were compared among regions of active and inactive inflammation in CD and controls. A twofold reduction …

Utilization Of The Naranjo Scale To Evaluate Adverse Drug Reactions At A Free-Standing Children's Hospital., Madhavi Murali, Sarah Suppes, Keith Feldman, Jennifer Goldman

Manuscripts, Articles, Book Chapters and Other Papers

The relationship between the Naranjo scaling system and pediatric adverse drug reactions (ADR) is poorly understood. We performed a retrospective review of 1,676 pediatric ADRs documented at our hospital from 2014-2018. We evaluated patient demographics, implicated medication, ADR severity, calculated Naranjo score, associated symptoms, and location within the hospital in which the ADR was documented. ADR severity was poorly correlated with Naranjo interpretation. Out of the 10 Naranjo scale questions, 4 had a response of "unknown" greater than 85% of the time. Cardiovascular and oncological/immunologic agents were more likely to have a probable or definite Naranjo interpretation compared to antimicrobials. …

Retrospective Review Of Pharmacogenetic Testing At An Academic Children's Hospital., Timothy A. Roberts, Jennifer A. Wagner, Tracy L. Sandritter, Benjamin T. Black, Andrea Gaedigk, Stephani L. Stancil

Manuscripts, Articles, Book Chapters and Other Papers

There is limited evidence to support pharmacogenetic (PGx) testing in children. We conducted a retrospective review of PGx testing among 452 patients at an academic children's hospital to determine the potential utility of PGx in diseases of childhood and to identify targets for future pediatric pharmacogenetic research. An actionable gene-drug pair associated with the 28 genes tested (Clinical Pharmacogenetics Implementation Consortium (CPIC) level A or B, Pharmacogenomics Knowledge Base (PharmGKB) level 1A or B, or US Food and Drug Administration (FDA) recommendation and a PharmGKB level) was present in 98.7% of patients. We identified 203 actionable gene-drug-diagnosis groups based on …

Effect Of Intrauterine Smoke Exposure On Microrna-15a Expression In Human Lung Development And Subsequent Asthma Risk., Sunita Sharma, Alvin T. Kho, Divya Chhabra, Kathleen Haley, Carrie A. Vyhlidal, R Gaedigk, J Steven Leeder, Kelan G. Tantisira, Benjamin Raby, Scott T. Weiss

Manuscripts, Articles, Book Chapters and Other Papers

Background: In utero smoke (IUS) exposure is associated with asthma susceptibility.

Objective: We sought to test the hypothesis that changes in miRNA expression by IUS exposure during human lung development is associated with asthma susceptibility.

Methods: Gene expression was profiled from 53 IUS unexposed and 51 IUS exposed human fetal lung tissues. We tested for the differential expression of miRNAs across post-conception age and by IUS using linear models with covariate adjustment. We tested the IUS-associated miRNAs for association with their gene expression targets using pair-wise inverse correlation. Using our mouse model, we investigated the persistence of the IUS-associated miRNA …

Transfer Learning Enables Prediction Of Cyp2d6 Haplotype Function., Gregory Mcinnes, Rachel Dalton, Katrin Sangkuhl, Michelle Whirl-Carrillo, Seung-Been Lee, Philip S. Tsao, Andrea Gaedigk, Russ B. Altman, Erica L. Woodahl

Manuscripts, Articles, Book Chapters and Other Papers

Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic gene whose protein product metabolizes more than 20% of clinically used drugs. Genetic variations in CYP2D6 are responsible for interindividual heterogeneity in drug response that can lead to drug toxicity and ineffective treatment, making CYP2D6 one of the most important pharmacogenes. Prediction of CYP2D6 phenotype relies on curation of literature-derived functional studies to assign a functional status to CYP2D6 haplotypes. As the number of large-scale sequencing efforts grows, new haplotypes continue to be discovered, and assignment of function is challenging to maintain. To address this challenge, we have trained a convolutional neural …

Cyp2d6 Predicts Plasma Donepezil Concentrations In A Cohort Of Thai Patients With Mild To Moderate Dementia., Monpat Chamnanphon, Sorawit Wainipitapong, Teeravut Wiwattarangkul, Phenphichcha Chuchuen, Kunathip Nissaipan, Weeraya Phaisal, Sookjaroen Tangwongchai, Chonlaphat Sukasem, Supeecha Wittayalertpanya, Andrea Gaedigk, Daruj Aniwattanapong, Pajaree Chariyavilaskul

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Donepezil, a drug frequently used to treat dementia, is mainly metabolized by cytochrome P450 2D6 (CYP2D6). This study investigated the relationships between CYP2D6 genotype and activity scores as well as predicted phenotype of plasma donepezil concentrations in 86 Thai dementia participants.

Materials and methods: CYP2D6 was genotyped using bead-chip technology (Luminex xTAG® v.3). Steady-state trough plasma donepezil concentrations were measured using high-performance liquid chromatography.

Results: Sixteen genotypes were found but the most frequent genotypes detected among our participants were CYP2D6*10/*10 (27.9%) and *1/*10 (26.7%). One-third of the participants had an activity score of 1.25 which predicted that they were …

Ontogeny Related Changes In The Pediatric Liver Metabolome., Christopher M. Wilson, Qian Li, R Gaedigk, Chengpeng Bi, Saskia N. De Wildt, J Steven Leeder, Brooke L. Fridley

Manuscripts, Articles, Book Chapters and Other Papers

Background: A major challenge in implementing personalized medicine in pediatrics is identifying appropriate drug dosages for children. The majority of drug dosing studies have been based on adult populations, often with modification of the dosing for children based on size and weight. However, the growth and development experienced by children between birth and adulthood represents a dynamically changing biological system, with implications for effective drug dosing, efficacy as well as potential drug toxicity. The purpose of this study was to apply a metabolomics approach to gain preliminary insights into the ontogeny of liver function from newborn to adolescent.

Methods: Metabolites …

Medicine And Media: The Ranitidine Debate., Jennifer A. Wagner, Jennifer Colombo

Manuscripts, Articles, Book Chapters and Other Papers

Ranitidine has been the topic of recent media reports. Current findings, confirmed by the US Food and Drug Administration, indicate that some ranitidine products contain a substance that may be carcinogenic. Providers and patients require additional information on the risks of continuing therapy vs. the benefits of the medication. This article comments on what is currently known about the evolving situation of elevated N-nitrosodimethylamine levels in ranitidine and the limits of the existing information to assess best practices.

Indomethacin Exposure Is Associated With Birthweight In Extremely Preterm Infants: Non-Standard Exposure With Standard Weight-Based Dosing, Bradley C. Stockard

Research Days

No abstract provided.

Performance Analysis Of Three Bioinformatic Variant Callers Using A Somatic Reference Standard, Binu Porath, Binu Porath

Research Days

No abstract provided.