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Full-Text Articles in Pediatrics

Population Pharmacokinetics Of Olanzapine In Children, Anil R. Maharaj, Huali Wu, Kanecia O. Zimmerman, Julie Autmizguine, Rohit Kalra, Amira Al‐Uzri, Catherine M.T. Sherwin, Stuart L. Goldstein, Kevin Watt, Jinson Erinjeri, Elizabeth H. Payne, Michael Cohen‐Wolkowiez, Christoph P. Hornik Jan 2021

Population Pharmacokinetics Of Olanzapine In Children, Anil R. Maharaj, Huali Wu, Kanecia O. Zimmerman, Julie Autmizguine, Rohit Kalra, Amira Al‐Uzri, Catherine M.T. Sherwin, Stuart L. Goldstein, Kevin Watt, Jinson Erinjeri, Elizabeth H. Payne, Michael Cohen‐Wolkowiez, Christoph P. Hornik

Pediatrics Faculty Publications

Aims The aim of this study was to evaluate the population pharmacokinetics (PopPK) of olanzapine in children and devise a model-informed paediatric dosing scheme. Methods The PopPK of olanzapine was characterized using opportunistically collected plasma samples from children receiving olanzapine per standard of care for any indication. A nonlinear mixed effect modelling approach was employed for model development using the software NONMEM (v7.4). Simulations from the developed PopPK model were used to devise a paediatric dosing scheme that targeted comparable plasma exposures to adolescents and adults. Results Forty-five participants contributed 83 plasma samples towards the analysis. The median (range) postnatal …


Family Structure And Pediatric Outcomes In Ohio, Andrew J. Berman Jan 2021

Family Structure And Pediatric Outcomes In Ohio, Andrew J. Berman

Scholarship in Medicine - All Papers

Objective: The number of single-parent households has been trending upwards since the early 1900s. Studies in the past have evaluated the effects single-parent households have on pediatric outcomes nationwide. This study attempts to build upon these past studies by analyzing whether these findings remain when looked at the State level, for Ohio 2020, as well as see if the percent of children in single-parent households can predict child mortality.

Methods: Data was collected from publicly available data sets through County Health Rankings. This study utilizes SPSS for data analysis. ANOVA with post-hoc was performed to compare children in single-parent household …


Outcomes In Children And Adolescents Undergoing Cholecystectomies With A High Ejection Fraction, Salony Dighamber, Karen Herzing, Arturo Aranda, Jeffrey C. Pence, Sean Barnett Jan 2021

Outcomes In Children And Adolescents Undergoing Cholecystectomies With A High Ejection Fraction, Salony Dighamber, Karen Herzing, Arturo Aranda, Jeffrey C. Pence, Sean Barnett

Scholarship in Medicine - All Papers

Background

Cholecystectomy is commonly performed electively for symptomatic cholelithiasis and biliary hypokinesia with an ejection fraction (EF) less than 35%. Recent literature has shown that cholecystectomy in adults for biliary hyperkinesia (EF>65%) can provide resolution of symptoms (primarily pain) for the majority of patients. We seek to determine whether cholecystectomy is efficacious in the treatment of symptomatic biliary hyperkinesia in the pediatric population.

Method

The charts of over 100 patients aged 7 to 21 in the last 10 years (2008 to 2018) who had cholecystectomies were reviewed to determine ejection fraction, BMI, race, pain with CCK-HIDA, complications, and resolution …


The Safe Environment For Every Kid Model: Analyzing Demographics Related To Higher Risks Of Child Maltreatment In High-Risk Pediatric Population, Hannah Redding Jan 2021

The Safe Environment For Every Kid Model: Analyzing Demographics Related To Higher Risks Of Child Maltreatment In High-Risk Pediatric Population, Hannah Redding

Scholarship in Medicine - All Papers

Background: The Safe Environment for Every Kid (SEEK) screener was developed by Dr. Howard Dubowitz for primary care clinicians to identify and address risk factors for child maltreatment. The instrument queries parents/guardians regarding their families' needs (e.g. food insecurity) and screens for depressive symptoms in the parent/guardian.

Objective: To examine the frequency of social determinants of health (e.g., food insecurity) and its correlates using the SEEK screener during pediatric visits at a Federally Qualified Health Center in south central Ohio.

Design/Methods: The SEEK screener was distributed to parents/guardians (PG) at Rocking Horse Community Health Center, a Federally Qualified Health Center …


Spotlight Commentary: Why We Need To Pay Attention To Toxicity Associated With Herbal Medicines, Elena Y. Enioutina, Kathleen M. Job, Catherine M.T. Sherwin Aug 2020

Spotlight Commentary: Why We Need To Pay Attention To Toxicity Associated With Herbal Medicines, Elena Y. Enioutina, Kathleen M. Job, Catherine M.T. Sherwin

Pediatrics Faculty Publications

No abstract provided.


Renal Survival In Children With Glomerulonephritis With Crescents: A Pediatric Nephrology Research Consortium Cohort Study, Joseph G. Maliakkal, M. John Hicks, Mini Michael, David T. Selewski, Katherine Twombley, Michelle N. Rheault, Meredith Seamon, Jason M. Misurac, Cheryl L. Tran, Loretta Reyes, Joseph T. Flynn, Ali M. Onder, Alexandru R. Constantinescu, Vaishali Singh, Cynthia Pan, Abiodun Aderogba Omoloja, Qiang Wu, William E. Smoyer, Guillermo Hidalgo, Scott E. Wenderfer Jul 2020

Renal Survival In Children With Glomerulonephritis With Crescents: A Pediatric Nephrology Research Consortium Cohort Study, Joseph G. Maliakkal, M. John Hicks, Mini Michael, David T. Selewski, Katherine Twombley, Michelle N. Rheault, Meredith Seamon, Jason M. Misurac, Cheryl L. Tran, Loretta Reyes, Joseph T. Flynn, Ali M. Onder, Alexandru R. Constantinescu, Vaishali Singh, Cynthia Pan, Abiodun Aderogba Omoloja, Qiang Wu, William E. Smoyer, Guillermo Hidalgo, Scott E. Wenderfer

Pediatrics Faculty Publications

There is no evidence-based definition for diagnosing crescentic glomerulonephritis. The prognostic implications of crescentic lesions on kidney biopsy have not been quantified. Our objective was to determine risk factors for end-stage kidney disease (ESKD) in patients with glomerulonephritis and crescents on kidney biopsy. A query of the Pediatric Nephrology Research Consortium’s Pediatric Glomerulonephritis with Crescents registry identified 305 patients from 15 centers. A retrospective cohort study was performed with ESKD as the primary outcome. Median age at biopsy was 11 years (range 1–21). The percentage of crescents was 3–100% (median 20%). Etiologies included IgA nephropathy (23%), lupus (21%), IgA vasculitis …


Investigation Into The Reproducibility Of The Association Of Cord Blood Magnesium Concentration And Cerebral Palsy Or Death In Children, Christopher Luke Dixon, Xiaoxi Liu, Alfred Balch, Maged Costantine, Catherine M. Sherwin Mar 2020

Investigation Into The Reproducibility Of The Association Of Cord Blood Magnesium Concentration And Cerebral Palsy Or Death In Children, Christopher Luke Dixon, Xiaoxi Liu, Alfred Balch, Maged Costantine, Catherine M. Sherwin

Pediatrics Faculty Publications

Objective: To evaluate the association of cord blood magnesium concentrations at the time of birth with cerebral palsy (CP) and neonatal death. Study Design: A secondary analysis of a randomized controlled trial that randomized women at imminent risk of delivery between 24 and 31 weeks of gestation to receive magnesium sulfate or placebo. This ‘study’s primary outcome was a composite of either moderate to severe CP or death. Secondary outcomes included CP, moderate to severe CP, neonatal death, and neonatal head ultrasound findings. We used a logistic regression model to evaluate the relationship between the concentration of magnesium in cord …


The Reliability Of Histamine Pharmacodynamic Response Phenotype Classification In Children With Allergic Disease., Kumar Ss, Liu X, Sherwin Cm, Jones Bl Mar 2020

The Reliability Of Histamine Pharmacodynamic Response Phenotype Classification In Children With Allergic Disease., Kumar Ss, Liu X, Sherwin Cm, Jones Bl

Pediatrics Faculty Publications

We have identified distinct histamine pharmacodynamic response phenotypes in children with allergic disease utilizing histamine iontophoresis with laser Doppler (HILD). These response phenotypes may be relevant in guiding therapeutic decision making for agents targeting the allergic response pathways. However, the reliability of these response phenotypes has not been assessed. Therefore, we performed HILD in children with allergic rhinitis and/or asthma on two to three separate occasions. HILD response-time data were analyzed in NONMEM using a linked effect PKPD model. Examination of observed vs. classified response phenotypes predicted response plots and the sum of residuals. The intraclass correlation coefficient (ICC) was …


Therapeutic Potential Of Citrulline As An Arginine Supplement: A Clinical Pharmacology Review, Jahidur Rashid, Shaun S. Kumar, Kathleen M. Job, Xiaoxi Liu, Candice D. Fike, Catherine M. T. Sherwin Mar 2020

Therapeutic Potential Of Citrulline As An Arginine Supplement: A Clinical Pharmacology Review, Jahidur Rashid, Shaun S. Kumar, Kathleen M. Job, Xiaoxi Liu, Candice D. Fike, Catherine M. T. Sherwin

Pediatrics Faculty Publications

Supplemental arginine has shown promise as a safe therapeutic option to improve endogenous nitric oxide (NO) regulation in cardiovascular diseases associated with endothelial dysfunction. L-arginine, an endogenous amino acid, was reported in clinical studies in adults to improve cardiovascular function in hypertension, pulmonary hypertension, pre-eclampsia, angina, and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome. L-citrulline, a natural precursor of L-arginine, is more bioavailable than L-arginine because of hepatic first-pass metabolism avoidance and longer circulation time. Although not yet well studied, arginine/citrulline has immense therapeutic potential in some life-threatening diseases of children. However, optimal clinical development of arginine or …


A Phase 1 Study Of Intravenous Busulfan As A Conditioning Regimen For Multiple Myeloma, Sabarinath V. Radhakrishnan, Michael Boyer, Catherine M. Sherwin, Maurizio Zangari, Guido Tricot Dec 2019

A Phase 1 Study Of Intravenous Busulfan As A Conditioning Regimen For Multiple Myeloma, Sabarinath V. Radhakrishnan, Michael Boyer, Catherine M. Sherwin, Maurizio Zangari, Guido Tricot

Pediatrics Faculty Publications

The efficacy of melphalan (MEL) 140 mg/m 2 pre-transplant conditioning versus MEL 200 mg/m 2 for the elderly is still debated. We hypothesized that single-agent intravenous busulfan (BU) would show significant anti-myeloma efficacy and be better tolerated by elderly patients. A prospective 3+3 dose escalation study enrolled symptomatic multiple myeloma (MM) patients 65 years or older with SWOG performance 0–2 for treatment with intravenous BU pre-transplant at different administration levels. The primary objective was to determine the maximum tolerated dose (MTD) of BU that could be safely given over the least number of days. All patients, except one, received maintenance …


Statistical Multiscale Mapping Of Idh1, Mgmt, And Microvascular Proliferation Inhuman Braintumors From Multiparametric Mr And Spatially-Registered Core Biopsy, Jason G. Parker, Emily E. Diller, Sha Cao, Jeremy T. Nelson, Kristen W. Yeom, Chang Ho, Robert M. Lober Nov 2019

Statistical Multiscale Mapping Of Idh1, Mgmt, And Microvascular Proliferation Inhuman Braintumors From Multiparametric Mr And Spatially-Registered Core Biopsy, Jason G. Parker, Emily E. Diller, Sha Cao, Jeremy T. Nelson, Kristen W. Yeom, Chang Ho, Robert M. Lober

Pediatrics Faculty Publications

We propose a statistical multiscale mapping approach to identify microscopic and molecular heterogeneity across a tumor microenvironment using multiparametric MR (mp-MR). Twenty-nine patients underwent pre-surgical mp-MR followed by MR-guided stereotactic core biopsy. The locations of the biopsy cores were identified in the pre-surgical images using stereotactic bitmaps acquired during surgery. Feature matrices mapped the multiparametric voxel values in the vicinity of the biopsy cores to the pathologic outcome variables for each patient and logistic regression tested the individual and collective predictive power of the MR contrasts. A non-parametric weighted k-nearest neighbor classifier evaluated the feature matrices in a leave-one-out cross …


Myeloid-Derived Suppressor Cells And Pancreatic Cancer: Implications In Novel Therapeutic Approaches, Anita Thyagarajan, Mamdouh Salman A. Alshehri, Kelly L.R. Miller, Catherine M. Sherwin, Jeffery B. Travers, Ravi P. Sahu Oct 2019

Myeloid-Derived Suppressor Cells And Pancreatic Cancer: Implications In Novel Therapeutic Approaches, Anita Thyagarajan, Mamdouh Salman A. Alshehri, Kelly L.R. Miller, Catherine M. Sherwin, Jeffery B. Travers, Ravi P. Sahu

Pediatrics Faculty Publications

Pancreatic ductal adenocarcinoma (PDAC) remains a devastating human malignancy with poor prognosis and low survival rates. Several cellular mechanisms have been linked with pancreatic carcinogenesis and also implicated in inducing tumor resistance to known therapeutic regimens. Of various factors, immune evasion mechanisms play critical roles in tumor progression and impeding the efficacy of cancer therapies including PDAC. Among immunosuppressive cell types, myeloid-derived suppressor cells (MDSCs) have been extensively studied and demonstrated to not only support PDAC development but also hamper the anti-tumor immune responses elicited by therapeutic agents. Notably, recent efforts have been directed in devising novel approaches to target …


Antibiotic Treatment Of Suspected And Confirmed Neonatal Sepsis Within 28 Days Of Birth: A Retrospective Analysis, Jadon S. Wagstaff, Robert J. Durrant, Michael G. Newman, Rachael Eason, Robert M. Ward, Catherine M.T. Sherwin, Elena Y. Enioutina Oct 2019

Antibiotic Treatment Of Suspected And Confirmed Neonatal Sepsis Within 28 Days Of Birth: A Retrospective Analysis, Jadon S. Wagstaff, Robert J. Durrant, Michael G. Newman, Rachael Eason, Robert M. Ward, Catherine M.T. Sherwin, Elena Y. Enioutina

Pediatrics Faculty Publications

Neonatal sepsis causes significant mortality and morbidity worldwide. Diagnosis is usually confirmed via blood culture results. Blood culture sepsis confirmation can take days and suffer from contamination and false negatives. Empiric therapy with antibiotics is common. This study aims to retrospectively describe and compare treatments of blood culture-confirmed and unconfirmed, but suspected, sepsis within the University of Utah Hospital system. Electronic health records were obtained from 1,248 neonates from January 1, 2006, to December 31, 2017. Sepsis was categorized into early-onset (≤3 days of birth, EOS) and late-onset (>3 and ≤28 days of birth, LOS) and categorized as culture-confirmed …


Implementing A Novel Quality Improvement-Based Approach To Data Quality Monitoring And Enhancement In A Multipurpose Clinical Registry, Jesse Pratt, Daniel Jeffers, Eileen C. King, Michael D. Kappelman, Jennifer Collins, Peter Margolis, Howard Baron, Julie A. Bass, Mikelle D. Bassett, Genie L. Beasley, Keith J. Benkov, Jeffrey A. Bornstein, Jose M. Cabrera, Wallace Crandall, Liz D. Dancel, Monica P. Garin-Laflam, John E. Grunow, Barry Z. Hirssch, Edward Hoffenberg, Esther Israel, Traci W. Jester, Fevronia Kiparissi, Arathi Lakhole, Sameer P. Lapsia, Phillip Minar, Fernando A. Navarro, Haley Neef, Kt Park, Dinesh S. Pashankar, Ashish S. Patel, Victor M. Pineiro, Chrles M. Samson, Kelly C. Sandberg, Steven J. Steiner, Jennifer A. Strople, Boris Sudel, Jillian S. Sullivan, David L. Suskind, Vikas Uppal, Prateek D. Wali Sep 2019

Implementing A Novel Quality Improvement-Based Approach To Data Quality Monitoring And Enhancement In A Multipurpose Clinical Registry, Jesse Pratt, Daniel Jeffers, Eileen C. King, Michael D. Kappelman, Jennifer Collins, Peter Margolis, Howard Baron, Julie A. Bass, Mikelle D. Bassett, Genie L. Beasley, Keith J. Benkov, Jeffrey A. Bornstein, Jose M. Cabrera, Wallace Crandall, Liz D. Dancel, Monica P. Garin-Laflam, John E. Grunow, Barry Z. Hirssch, Edward Hoffenberg, Esther Israel, Traci W. Jester, Fevronia Kiparissi, Arathi Lakhole, Sameer P. Lapsia, Phillip Minar, Fernando A. Navarro, Haley Neef, Kt Park, Dinesh S. Pashankar, Ashish S. Patel, Victor M. Pineiro, Chrles M. Samson, Kelly C. Sandberg, Steven J. Steiner, Jennifer A. Strople, Boris Sudel, Jillian S. Sullivan, David L. Suskind, Vikas Uppal, Prateek D. Wali

Pediatrics Faculty Publications

Objective: To implement a quality improvement based system to measure and improve data quality in an observational clinical registry to support a Learning Healthcare System.

Data Source: ImproveCareNow Network registry, which as of September 2019 contained data from 314,250 visits of 43,305 pediatric Inflammatory Bowel Disease (IBD) patients at 109 participating care centers.

Study Design: The impact of data quality improvement support to care centers was evaluated using statistical process control methodology. Data quality measures were defined, performance feedback of those measures using statistical process control charts was implemented, and reports that identified data items not following data quality checks …


Learning From Experience: Avoiding Common Pitfalls In Multicenter Quality Improvement Collaboratives, Jonathan D. Thackeray, Carrie A. Baker, Rachel P. Berger Sep 2019

Learning From Experience: Avoiding Common Pitfalls In Multicenter Quality Improvement Collaboratives, Jonathan D. Thackeray, Carrie A. Baker, Rachel P. Berger

Pediatrics Faculty Publications

Clinicians and researchers often tout the newest breakthrough or latest successful intervention. Sharing wins, however, is often done at the expense of sharing obstacles, failures, and subsequent adjustments, which are the cornerstone of quality improvement (QI).1–3 Here, we share 3 key lessons from 2 hospital-based QI initiatives—the Ohio Timely Recognition of Abuse Injuries (TRAIN) Collaborative and the University of Pittsburgh Medical Center (UPMC) Child Abuse Initiative (UPMC-CAI). Both focus on early identification, proper evaluation, and accurate reporting of child maltreatment. These are important clinical issues because many children who die or nearly die from maltreatment had been …


Predicted Disease Compositions Of Human Gliomas Estimated From Multiparametric Mri Can Predict Endothelial Proliferation, Tumor Grade, And Overall Survival, Emily E. Diller, Sha Cao, Beth Ey, Robert M. Lober, Jason G. Parker Aug 2019

Predicted Disease Compositions Of Human Gliomas Estimated From Multiparametric Mri Can Predict Endothelial Proliferation, Tumor Grade, And Overall Survival, Emily E. Diller, Sha Cao, Beth Ey, Robert M. Lober, Jason G. Parker

Pediatrics Faculty Publications

Background and Purpose: Biopsy is the main determinants of glioma clinical management, but require invasive sampling that fail to detect relevant features because of tumor heterogeneity. The purpose of this study was to evaluate the accuracy of a voxel-wise, multiparametric MRI radiomic method to predict features and develop a minimally invasive method to objectively assess neoplasms. Methods: Multiparametric MRI were registered to T1-weighted gadolinium contrast-enhanced data using a 12 degree-of-freedom affine model. The retrospectively collected MRI data included T1-weighted, T1-weighted gadolinium contrast-enhanced, T2-weighted, fluid attenuated inversion recovery, and multi-b-value diffusion-weighted acquired at 1.5T or 3.0T. Clinical experts provided voxel-wise annotations …


Decreasing Door-To-Door Times For Infliximab Infusions In A Children's Hospital Observation Unit, Kelly C. Sandberg, Janet N. Lucien, Denise Stoll, Erica Yanney, Adam Mezoff Feb 2019

Decreasing Door-To-Door Times For Infliximab Infusions In A Children's Hospital Observation Unit, Kelly C. Sandberg, Janet N. Lucien, Denise Stoll, Erica Yanney, Adam Mezoff

Pediatrics Faculty Publications

Introduction:

Children with inflammatory bowel disease (IBD) often require infliximab infusions to manage their disease. Infusions administered in the hospital setting require the patient and their families to devote many hours away from home. Changing to a rapid infusion protocol has been shown in the literature to be safe and has the potential to decrease time spent in the hospital receiving infusions.

Methods:

We describe stepwise changes made over a 4-month period to improve infliximab infusion efficiency and lessen the time spent in the hospital by IBD patients and their families. These changes included the implementation of a standardized order …


Kiaa1549-Braf Expression Establishes A Permissive Tumor Microenvironment Through Nfκb-Mediated Ccl2 Production, Ran Chen, Chanel Keoni, Christopher A. Waker, Robert M. Lober, Robert M. Lober, Yihsien Chen, David H. Gutmann Jan 2019

Kiaa1549-Braf Expression Establishes A Permissive Tumor Microenvironment Through Nfκb-Mediated Ccl2 Production, Ran Chen, Chanel Keoni, Christopher A. Waker, Robert M. Lober, Robert M. Lober, Yihsien Chen, David H. Gutmann

Pediatrics Faculty Publications

KIAA1549-BRAF is the most frequently identified genetic mutation in sporadic pilocytic astrocytoma (PA), creating a fusion BRAF (f-BRAF) protein with increased BRAF activity. Fusion-BRAF-expressing neural stem cells (NSCs) exhibit increased cell growth and can generate glioma-like lesions following injection into the cerebella of naïve mice. Increased Iba1+ monocyte (microglia) infiltration is associated with murine f-BRAF-expressing NSC-induced glioma-like lesion formation, suggesting that f-BRAF-expressing NSCs attract microglia to establish a microenvironment supportive of tumorigenesis. Herein, we identify Ccl2 as the chemokine produced by f-BRAF-expressing NSCs, which is critical for creating a permissive stroma for gliomagenesis. In addition, f-BRAF regulation of Ccl2 production …


Maladjustment Of Programmable Ventricular Shunt Valves By Inadvertent Exposure To A Common Hospital Device, R. Fujimura, Robert M. Lober, K. Kamian, L. Kleiner Mar 2018

Maladjustment Of Programmable Ventricular Shunt Valves By Inadvertent Exposure To A Common Hospital Device, R. Fujimura, Robert M. Lober, K. Kamian, L. Kleiner

Pediatrics Faculty Publications

Background: Programmable ventricular shunt valves are commonly used to treat hydrocephalus. They can be adjusted to allow for varying amounts of cerebrospinal fluid (CSF) flow using an external magnetic programming device, and are susceptible to maladjustment from inadvertent exposure to magnetic fields.Case Description: We describe the case of a 3‑month‑old girl treated for hydrocephalus with a programmable StrataTM II valve found at the incorrect setting on multiple occasions during her hospitalization despite frequent reprogramming and surveillance. We found that the Vocera badge, a common hands‑free wireless communication system worn by our nursing staff, had a strong enough magnetic field to …


Preclinical Pharmacokinetic Evaluation To Facilitate Repurposing Of Tyrosine Kinase Inhibitors Nilotinib And Imatinib As Antiviral Agents, Hari Krishna Ananthula, Scott Parker, Erin Touchette, R. Mark Buller, Gopi Patel, Daniel Kalman, Johanna S. Salzer, Nadia Gallardo-Romero, Victoria Olson, Inger K. Damon, Tessa Moir-Savitz, Larry Sallans, Milton H. Werner, Catherine M.T. Sherwin, Pankaj B. Dasai Jan 2018

Preclinical Pharmacokinetic Evaluation To Facilitate Repurposing Of Tyrosine Kinase Inhibitors Nilotinib And Imatinib As Antiviral Agents, Hari Krishna Ananthula, Scott Parker, Erin Touchette, R. Mark Buller, Gopi Patel, Daniel Kalman, Johanna S. Salzer, Nadia Gallardo-Romero, Victoria Olson, Inger K. Damon, Tessa Moir-Savitz, Larry Sallans, Milton H. Werner, Catherine M.T. Sherwin, Pankaj B. Dasai

Pediatrics Faculty Publications

Background

Several tyrosine kinase inhibitors (TKIs) developed as anti-cancer drugs, also have anti-viral activity due to their ability to disrupt productive replication and dissemination in infected cells. Consequently, such drugs are attractive candidates for “repurposing” as anti-viral agents. However, clinical evaluation of therapeutics against infectious agents associated with high mortality, but low or infrequent incidence, is often unfeasible. The United States Food and Drug Administration formulated the “Animal Rule” to facilitate use of validated animal models for conducting anti-viral efficacy studies.

Methods

To enable such efficacy studies of two clinically approved TKIs, nilotinib, and imatinib, we first conducted comprehensive pharmacokinetic …


Genetic Variation In The Histamine Production, Response, And Degradation Pathway Is Associated With Histamine Pharmacodynamic Response In Children With Asthma, Bridgette L. Jones, Catherine M.T. Sherwin, Xiaoxi Liu, Hongying Dai, Carrie A. Vyhlidal Jan 2017

Genetic Variation In The Histamine Production, Response, And Degradation Pathway Is Associated With Histamine Pharmacodynamic Response In Children With Asthma, Bridgette L. Jones, Catherine M.T. Sherwin, Xiaoxi Liu, Hongying Dai, Carrie A. Vyhlidal

Pediatrics Faculty Publications

Introduction: There is growing knowledge of the wide ranging effects of histamine throughout the body therefore it is important to better understand the effects of this amine in patients with asthma. We aimed to explore the association between histamine pharmacodynamic (PD) response and genetic variation in the histamine pathway in children with asthma.

Methods: Histamine Iontophoresis with Laser Doppler Monitoring (HILD) was performed in children with asthma and estimates for area under the effect curve (AUEC), maximal response over baseline (Emax), and time of Emax (Tmax) were calculated using non-compartmental analysis and non-linear mixed-effects model with a linked effect PK/PD …


Predicting Tacrolimus Concentrations In Children Receiving A Heart Transplant Using A Population Pharmacokinetic Model, Joseph E. Rower, Chris Stockmann, Matthew W. Linakis, Shaun S. Kumar, Xiaoxi Liu, E. Kent Korgenski, Catherine M.T. Sherwin, Kimberly M. Molina Jan 2017

Predicting Tacrolimus Concentrations In Children Receiving A Heart Transplant Using A Population Pharmacokinetic Model, Joseph E. Rower, Chris Stockmann, Matthew W. Linakis, Shaun S. Kumar, Xiaoxi Liu, E. Kent Korgenski, Catherine M.T. Sherwin, Kimberly M. Molina

Pediatrics Faculty Publications

Objective Immunosuppressant therapy plays a pivotal role in transplant success and longevity. Tacrolimus, a primary immunosuppressive agent, is well known to exhibit significant pharmacological interpatient and intrapatient variability. This variability necessitates the collection of serial trough concentrations to ensure that the drug remains within therapeutic range. The objective of this study was to build a population pharmacokinetic (PK) model and use it to determine the minimum number of trough samples needed to guide the prediction of an individual’s future concentrations.

Design, setting and patients Retrospective data from 48 children who received tacrolimus as inpatients at Primary Children’s Hospital in Salt …


Calls To A Teratogen Information Service Regarding Potential Exposures In Pregnancy And Breastfeeding, Sarah C. Campbell, Tyler T. Kast, Julia Robertson, Catherine M.T. Sherwin Jul 2016

Calls To A Teratogen Information Service Regarding Potential Exposures In Pregnancy And Breastfeeding, Sarah C. Campbell, Tyler T. Kast, Julia Robertson, Catherine M.T. Sherwin

Pediatrics Faculty Publications

Background

MotherToBaby Utah is a teratogen information service that provides support for pregnant and breastfeeding women and healthcare providers regarding risks of exposures to medications, infections, herbals, homeopathic and dietary medications, chemicals and other substances. Calls are anonymous and free of charge. This study was undertaken to examine the volume and classification of calls regarding exposures during pregnancy and breastfeeding.

Methods

Data were extracted from calls requesting information about medication use and other exposures to pregnant and breastfeeding women, between January 1 2009 and December 31 2012. Descriptive statistics were calculated.

Results

A total of 27,299 calls regarding 46,031 exposures …


Incorporating Pharmacodynamic Considerations Into Caffeine Therapeutic Drug Monitoring In Preterm Neonates, Tian Yu, Alfred H. Balch, Robert Ward, E. Kent Korgenski, Catherine M.T. Sherwin Jan 2016

Incorporating Pharmacodynamic Considerations Into Caffeine Therapeutic Drug Monitoring In Preterm Neonates, Tian Yu, Alfred H. Balch, Robert Ward, E. Kent Korgenski, Catherine M.T. Sherwin

Pediatrics Faculty Publications

Background

This study sought to assess the pharmacokinetic and pharmacodynamic relationships of caffeine citrate therapy in preterm neonates who had therapeutic drug monitoring (TDM) in the post-extubation period.

Methods

A retrospective observational study was conducted in preterm neonates who received caffeine citrate therapy for apnea of prematurity and had TDM done in the post-extubation period between January 2006 and October 2011. The relationships between pharmacodynamic effects (heart rate, respiratory rate, episodes of apnea, adverse events) and caffeine serum concentrations were explored.

Results

A total of 177 blood samples were obtained from 115 preterm neonates with a median (range) gestational age …


Amikacin Pharmacokinetics In Pediatric Patients With Burn Injuries Compared To Those With Oncology Conditions, Xiaoxi Liu, Anne Smits, Tian Yu, Stephanie Wead, Alice Neely, Richard J. Kagan, Daniel P. Healy, Karel Allegaert, Catherine M.T. Sherwin Jan 2016

Amikacin Pharmacokinetics In Pediatric Patients With Burn Injuries Compared To Those With Oncology Conditions, Xiaoxi Liu, Anne Smits, Tian Yu, Stephanie Wead, Alice Neely, Richard J. Kagan, Daniel P. Healy, Karel Allegaert, Catherine M.T. Sherwin

Pediatrics Faculty Publications

Physiologic changes due to disease status can lead to highly variable pharmacokinetics (PK) of amikacin in children. Therefore, considerations should be given when determining optimal amikacin does for patients with a specific diseases. Improved understanding of factors influencing PD can allow for the optimizing of dosage regimens to reduce adverse effects.

The aim of the study was to undertake a comparative pharmacometic analysis of amikacin use in pediatric patients with burn injuries verses those with oncology conditions.


Predictors Of Increasing Injury Severity Across Suspected Recurrent Episodes Of Non-Accidental Trauma, Jonathan D. Thackeray, Peter Minneci, Jennifer N. Cooper, Jonathan I. Groner, Katherine Deans Jan 2016

Predictors Of Increasing Injury Severity Across Suspected Recurrent Episodes Of Non-Accidental Trauma, Jonathan D. Thackeray, Peter Minneci, Jennifer N. Cooper, Jonathan I. Groner, Katherine Deans

Pediatrics Faculty Publications

Background

Little is known about how the severity of injury changes with recurrent events of suspected non-accidental trauma (NAT). Our objective was to determine risk factors for escalating severity of injury in children with multiple events of suspected NAT.

Methods

This retrospective longitudinal cohort study included children from a pediatric Medicaid accountable care organization with ≥ 1 non-birth related episode containing an International Classification of Diseases, Ninth Revision, Clinical Modification or Current Procedural Terminology code for NAT or a skeletal survey between 2007 and 2011. Subsequent potential NAT events were defined as independent episodes with codes for either NAT, a …


Use Of Modeling And Simulation In The Design And Conduct Of Pediatric Clinical Trials And The Optimization Of Individualized Dosing Regimens, Chris Stockmann, J. S. Barrett, Jessica K. Roberts, Catherine M.T. Sherwin Nov 2015

Use Of Modeling And Simulation In The Design And Conduct Of Pediatric Clinical Trials And The Optimization Of Individualized Dosing Regimens, Chris Stockmann, J. S. Barrett, Jessica K. Roberts, Catherine M.T. Sherwin

Pediatrics Faculty Publications

Mathematical models of drug action and disease progression can inform pediatric pharmacotherapy. In this tutorial, we explore the key issues that differentiate pediatric from adult pharmacokinetic (PK) / pharmacodynamic (PD) studies, describe methods to calculate the number of participants to be enrolled and the optimal times at which blood samples should be collected, and therapeutic drug monitoring methods for individualizing pharmacotherapy. The development of pediatric‐specific drug dosing dashboards is also highlighted, with an emphasis on clinical‐relevance and ease of use.


Predictive Performance Of A Vancomycin Population Pharmacokinetic Model In Neonates, Chris Stockmann, Adam L. Hersh, Jessica K. Roberts, Jiraganya Bhongsatiern, E. Kent Korgenski, Michael G. Spigarelli, Catherine M.T. Sherwin, Adam Frymoyer Jun 2015

Predictive Performance Of A Vancomycin Population Pharmacokinetic Model In Neonates, Chris Stockmann, Adam L. Hersh, Jessica K. Roberts, Jiraganya Bhongsatiern, E. Kent Korgenski, Michael G. Spigarelli, Catherine M.T. Sherwin, Adam Frymoyer

Pediatrics Faculty Publications

Introduction

The pharmacokinetics of vancomycin are highly variable among neonates, which makes dosing challenging in this population. However, adequate drug exposure is critical, especially when treating methicillin-resistant Staphylococcus aureus (MRSA) infections. Utilization of population pharmacokinetic models and Bayesian methods offers the potential for developing individualized therapeutic approaches. To meet this need, a neonatal vancomycin population pharmacokinetic model was recently published. The current study sought to externally evaluate the predictive performance and generalizability of this model.

Methods

A retrospective chart review of neonates who received vancomycin and had ≥1 peak and ≥1 trough concentrations at five Intermountain Healthcare neonatal intensive care …


The Significance Of Macrocephaly Or Enlarging Head Circumference In Infants With The Triad: Further Evidence Of Mimics Of Shaken Baby Syndrome, David Miller, Patrick Barnes, Marvin E. Miller Jun 2015

The Significance Of Macrocephaly Or Enlarging Head Circumference In Infants With The Triad: Further Evidence Of Mimics Of Shaken Baby Syndrome, David Miller, Patrick Barnes, Marvin E. Miller

Pediatrics Faculty Publications

Infants with the triad (neurologic dysfunction, subdural hematoma [SDH], and retinal hemorrhage) are often diagnosed as victims of shaken baby syndrome. Medical conditions/predisposing factors to developing the triad are often dismissed: short falls, birth-related SDH that enlarges, macrocephaly, sinus/cortical vein thrombosis, and others. Six infants with the triad are described in which child abuse was diagnosed, but parents denied wrongdoing. All 6 had either macrocephaly or enlarging head circumference, which suggested medical explanations. Three infants incurred short falls, 1 had a difficult delivery in which there was likely a rebleed of a birth-related SDH, 1 had a spontaneous SDH associated …


Open Letter On Shaken Baby Syndrome And Courts: A False And Flawed Premise, Bill Bache, Patrick Barnes, Beverly Beech, Flo Bellone, Thomas L. Bohan, Harry J. Bonnell, Marta Cohen, D. L. Contostavlos, Peter Dale, Lina Davidson, Steven Gabaeff, Horace Gardner, Margaret Gardner, Jean Golding, A. N. Guthkelch, Charles M. Harvey, Helen Hayward-Brown, John Hemming, John C. Hunsaker Iii, Charles Hyman, Jan Leestma, James Lefanu, John Lloyd, Marvin E. Miller, Catherine Mills, George R. Nichols Ii, Michael Nott, John Plunkett, Charles Pragnell, Jean Robinson, Robert K. Rothfeder, Irene Scheimberg, Ron Uscinski, Michael Weinraub, Ed Willey, R. K. Wright, Lynne Wrennall Feb 2015

Open Letter On Shaken Baby Syndrome And Courts: A False And Flawed Premise, Bill Bache, Patrick Barnes, Beverly Beech, Flo Bellone, Thomas L. Bohan, Harry J. Bonnell, Marta Cohen, D. L. Contostavlos, Peter Dale, Lina Davidson, Steven Gabaeff, Horace Gardner, Margaret Gardner, Jean Golding, A. N. Guthkelch, Charles M. Harvey, Helen Hayward-Brown, John Hemming, John C. Hunsaker Iii, Charles Hyman, Jan Leestma, James Lefanu, John Lloyd, Marvin E. Miller, Catherine Mills, George R. Nichols Ii, Michael Nott, John Plunkett, Charles Pragnell, Jean Robinson, Robert K. Rothfeder, Irene Scheimberg, Ron Uscinski, Michael Weinraub, Ed Willey, R. K. Wright, Lynne Wrennall

Pediatrics Faculty Publications

The Open Letter on Shaken Baby Syndrome and Courts has been prepared under the auspices of the International Public Health Research Group [IPHRG]. It was developed from initial drafts by Bill Bache and Charles Pragnell. Final drafting and editing was by Dr Lynne Wrennall, Executive Director of the International Public Health Research Group and the Managing Editor of Argument & Critique. The process of writing the letter has relied on the published research in the field, much of it, published research by the signatories to the letter. The process has also drawn on the iterative contribution of insights by the …