The University of Maryland School of Pharmacy, founded in 1841, is a thriving center for life sciences research and community service. Through its education, research, and service programs, the School of Pharmacy strives to improve the health and well-being of society by aiding in the discovery, development, and use of medicines.

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  • Atrial Fibrillation Risk-Stratification Schemes: Improving Patient-Centeredness and Precision

    Oehrlein, Elisabeth Maria; Perfetto, Eleanor M. (2018)
    Background: Despite treatment-guideline recommendations and availability medications to reduce stroke risk, widespread underutilization of oral anticoagulants (OACs) has been previously documented among individuals with atrial fibrillation (AF). Younger age and female gender are important in light of evidence that these groups, in particular, may not receive optimal AF care. The objective of this dissertation was to identify: 1) What are the barriers to patients initiating OACs? 2) Are providers aware of and using the RSSs and do disparities exist by age and gender? 3) Are RSSs predictive of stroke and OAC initiation among subpopulations (women and <65 years of age)? Methods: In Aim 1, we invited patients and health care providers (HCPs) to participate in in-depth interviews. In aims 2 and 3, we conducted retrospective cohort studies using Optum’s Clinformatic Data Mart (2008-2016). We used logistic regression to calculate odds ratios and 95% confidence intervals to identify whether RSSs were associated with OAC initiation and whether disparities exist by age or gender in aim 2. For Aim 3, we used a discrete time approach to estimate the risk of ischemic stroke associated with RSSs. Separately, we tested whether incorporating risk factors identified in the literature as predictive of ischemic stroke improved prediction among women and patients ≤65 years. Results: Themes from qualitative interviews include: specialists heightened perception of stroke risk compared to generalists and comorbidities/characteristics absent from RSSs also factor into risk consideration. The proportion of patients initiating OACs was only approximately 30%. CHADS2, but not CHA2DS2-VASc, scores corresponded with higher odds of OAC initiation. We found no statistically significant differences between odds of initiating OACs among OAC-recommended males/females or age categories. Among women and those ≤65 years, all CHA2DS2-VASc scores >1 and CHADS2 scores >0 were significant predictors of stroke. Prognostic models developed within subpopulations were no better at predicting stroke than existing RSSs. Conclusions: RSSs are associated with ischemic stroke among newly diagnosed females and <65 years of age patients. Initiation of OAC treatment was consistently low. More research is needed to more clearly understand why RSSs might not be followed and why OACs are not initiated.
  • Innovation of Vancomycin Treatment in Neonates Via A Bayesian Dose Optimization Toolkit For Adaptive Individualized Therapeutic Management

    Pastoor, Devin DeForest; Gobburu, Jogarao (2018)
    Personalized medicine continues to gain momentum as a topic for discussion, yet directly linking patient-level decision support to more advanced analytical techniques, such as nonlinear mixed effects modeling, is not being practiced in most hospitals. Current practice for Vancomycin therapy uses dosing nomograms to determine the dosing regimen for patients. For simplicity, these nomograms stratify patients into bins based on some combination of weight, serum creatinine, and/or age to adjust starting regimens. Yet, studies across the US and Europe have shown as few as 37% of neonates achieve recommended target concentrations using such nomograms. The purpose of this research was to develop a bayesian decision support toolkit to provide adaptive, individualized dose recommendations for neonates. First, a bayesian nonlinear mixed effect model was developed and qualified for predictive forecasting in individual patients. Second, this model was used to develop a novel algorithm for dose individualization. Finally, a web application was developed to allow clinicians to provide decision support for clinicians involved in vancomycin dosing decisions. The proposed strategy can decrease the number of patients improperly dosed up to 90%, drastically reducing the chance for treatment failure, toxicity-related adverse events, and resistance development.
  • University of Maryland School of Pharmacy. Annual Report 2015-2016

    Unknown author (University of Maryland, Baltimore. School of Pharmacy, 2016)
  • Data Snapshot 2018

    Unknown author (University of Maryland, Baltimore. School of Pharmacy. Maryland Poison Center, 2018)
  • Maryland Mentor : 2019

    Unknown author (University of Maryland, Baltimore. School of Pharmacy. Experiential Learning Program, 2019)
  • Poison Prevention Press 2019

    Unknown author (University of Maryland, Baltimore. School of Pharmacy. Maryland Poison Center, 2019)
  • The possible harms of statins: What do product labels, patient package inserts, and pharmacy leaflets tell us?

    Doshi, Peter; Sieluk, Jan; Hung, Anna (American Pharmacists Association, 2019)
    Objectives: To evaluate the degree to which health care professionals and patients receive consistent messages regarding the possible harms of statins. Design: Cross-sectional study of prescribing information (PI), patient package inserts (PPIs), and pharmacy leaflets for 8 statins approved by the U.S. Food and Drug Adminstration. Setting: Not applicable. Participants: Not applicable. Main Outcome Measures: All passages describing 7 adverse events (diarrhea, arthralgia, dyspepsia, confusion, memory loss, rhabdomyolysis, and kidney failure) were extracted from PIs, PPIs, and pharmacy leaflets. For each type of information source and adverse event (drug-harm pair), 2 reviewers independently judged passages as indicating either a confirmed, unconfirmed, or mixed causal relationship between statin and adverse event (drug-harm pair). Disagreements were resolved through consensus, and the consistency between information sources was calculated. Results: PI and PPI consistently conveyed the relationship between a given statin and given adverse event (either both “confirmed” or both “unconfirmed”) in 12 of 17 evaluable drug-harm pairs. PPIs and pharmacy leaflets were consistent in 10 of 10 evaluable drug-harm pairs. PIs indicated a confirmed, causal relationship in 15 drug-harm pairs that were not mentioned in pharmacy leaflets. Likewise, PPIs indicated a confirmed, causal relationship in 7 drug-harm pairs that were not listed in pharmacy leaflets. Conclusion: Despite the widespread use of statins, we discovered considerable ambiguity in language used to describe the evidence concerning their possible harms and variable consistency between PIs, PPIs, and pharmacy leaflets. Further study is needed to understand the reason why pharmacy leaflets did not list, in 15 cases, adverse events that PIs indicated were causally related to the statin.
  • ToxTidbits 2019

    Unknown author (University of Maryland, Baltimore. School of Pharmacy. Maryland Poison Center, 2019)
  • A Method to Streamline Management of Excused Absences

    Klimas, Christopher; Tucker, Shannon R.; Coop, Andrew; Layson-Wolf, Cherokee (2018-07)
  • When to include clinical study reports and regulatory documents in systematic reviews

    Doshi, Peter (BMJ Publishing Group, 2018-10-11)
    Reporting bias is a major threat to the validity and credibility of systematic reviews. This article outlines the rationale for accessing clinical study reports and other regulatory documents (regulatory data) as a means of addressing reporting bias and identifies factors that may help decide whether (or not) to include regulatory data in systematic reviews. The article also describes the origins and current state of regulatory data access and summarises a survey of current systematic reviewers' practices in considering regulatory data for inclusion in systematic reviews. How to access and extract regulatory data is not addressed. Organisations and other stakeholders such as Cochrane should encourage the use of data from clinical study reports as an important source of data in reviews of pharmaceutical interventions particularly when the intervention in question is of high importance and the risk of reporting bias is great.
  • Maryland Poison Center Annual Report 2017

    Unknown author (University of Maryland, Baltimore. School of Pharmacy. Maryland Poison Center, 2017)
  • Pandemrix vaccine: why was the public not told of early warning signs?

    Doshi, Peter (BMJ Publishing Group, 2018-09-20)
    Eight years after the pandemic influenza outbreak, a lawsuit alleging that GlaxoSmithKline’s Pandemrix vaccine caused narcolepsy has unearthed internal reports suggesting problems with the vaccine’s safety. Peter Doshi asks what this means for the future of transparency during public health emergencies.
  • Impact of Prescription Verification Activities in a Skills-Based Laboratory Course

    Sera, Leah; Mattingly, T. Joseph, II; Tran, Deanna (2018)
  • Maryland Poison Center Statistical Report 2017

    Unknown author (University of Maryland, Baltimore. School of Pharmacy. Maryland Poison Center, 2017)
  • Novel WNT/beta-catenin Signaling Pathway Inhibitors for the Treatment of Metabolic Disorders

    Obianom, Obinna N.; Shu, Yan, Ph.D. (2018)
    The WNT/β-catenin signaling (β-cat) pathway is critical for embryonic development and tissue homeostasis. For this reason, alterations in the β-cat pathway are associated with many ailments including metabolic disorders, which may result from defects in the energy metabolism. The contribution of β-cat pathway to energy metabolism has become a subject of many investigations following the identification of polymorphisms in β-cat pathway components that predispose individuals to type-2-diabetes. Current evidence suggests that downregulation of the β-cat pathway activity may help treat metabolic disorders. Given these findings, the overarching goal of this thesis was to discover and develop novel β-cat pathway inhibitors and to examine their efficacy on glucose and lipid metabolism. We started with an FDA approved anthelmintic, pyrvinium, which is a potent inhibitor of the β-cat pathway. Our results showed that pyrvinium improved glucose tolerance by inhibiting glucose output, hepatic lipid accumulation and activating the AMPK pathway. Despite these beneficial effects, pyrvinium is unsuitable for repurposing to use orally in the treatment of metabolic disorders due to its almost zero bioavailability and other unspecific toxic effects in mice at higher doses. Based on the structure of pyrvinium, we decided to discover new potent β-cat pathway inhibitors with lower toxicity and improved bioavailability. Our screening of more than 150 newly synthesized pyrvinium derivatives led to the discovery of YW1128 as such a candidate having the aforementioned properties. Administration of YW1128 led to decreased lipid accumulation and improved glucose tolerance in the mice fed with high fat diet. Previous studies had suggested a critical role of hepatic β-cat pathway in determining the whole body metabolic homeostasis. So we next sought to achieve a selective delivery of the new derivatives to the liver without having significant disposition in other tissues. We performed a proof-of-concept study where we took advantage of high expression of organic cation transporter 1 (OCT1) in the liver to modify the compounds that were not specifically permeable to OCT1 expressing cells. We inserted a biguanide, which is a major backbone of several OCT1 substrates, into these compounds and showed that they became highly permeable to cells overexpressing OCT1. This suggests that insertion of the biguanide moiety into YW1128 may be an approach to improve its selective liver targeting. In conclusion, this thesis uncovered the efficacy by small molecule inhibition of β-cat pathway in the treatment of metabolic disorders and established that incorporating a biguanide moiety to the compounds may serve as a strategy to achieve selective liver targeting.

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