Retrospective Review of Maternal and Fetal Outcomes for Indigent Gestational Diabetes Clinic

This poster presentation will detail the history of indigent gestational diabetes clinic as well as describe methods, results and conclusions for 2 year retrospective chart review for 157 pregestational and gestational Latino diabetes patients. The objective of this review was to determine if there were statistically significant differences in maternal and fetal outcomes between diet only and diet + insulin groups

Cost-Effectiveness Model Shows Superiority of Wireless Spinal Cord Stimulation Implantation Without a Separate Trial.

OBJECTIVE: We evaluated the cost-effectiveness of wireless spinal cord stimulation (Wireless SCS) with single stage direct to permanent implantation vs. screening with temporary electrodes and an external pulse generator followed by implantation of a system for long-term use (IPG SCS). MATERIALS AND METHODS: We created a cost model that takes a 2019 United States (U.S.) payer perspective and is based on IPG SCS cost models for subjects with chronic back and/or leg pain. Our six-month decision tree includes the screening trial period (success ≥50% relief) and leads to various levels of pain relief with or without complications for IPG SCS and Wireless SCS and without complications for conventional medical management (CMM). Every three months in the follow-on 15-year Markov model (with costs and quality-adjusted life years discounted 3.5% annually), subjects remain stable or transition to deteriorated health or death. Subjects who fail SCS receive CMM. After 60 Markov cycles, a 100,000-sample simulation reveals the impact of maximum willingness-to-pay (WTP) from $10,000 to$100,000 per quality-adjusted life year on net monetary benefit (NMB). Sensitivity analyses considered the impact of the Wireless SCS screening success rate, Wireless SCS device cost, and IPG SCS device longevity. RESULTS: Compared with IPG SCS, Wireless SCS offers higher clinical effectiveness at a lower cost and a higher NMB for our WTP thresholds and is, thus, dominant. Wireless SCS is also cost-effective compared with CMM. Results remain robust with 1) Wireless SCS screening success rates as low as 85% (dominant), 2) the cost of the Wireless SCS devices as high as $55,000 (cost-effective), and 3) IPG SCS devices lasting 12 years (dominant). CONCLUSIONS: In this model, compared with IPG SCS or with CMM, Wireless SCS is a superior strategy

Trends in Hospital Admissions Due to Antidepressant-Related Adverse Drug Events from 2001 to 2011 in the U.S.

BACKGROUND: Depression is a prevalent mental health disorder and the fourth leading cause of disability in the world as per the World Health Organization. Use of antidepressants can lead to adverse drug events (ADEs), defined as any injury resulting from medication use. This study aimed to examine changes in hospital admissions due to antidepressant-related ADEs (ArADEs) among different socio-demographic groups and changes in lengths of stay (LOS) and hospital charges in ArADE admissions from 2001 to 2011. METHODS: The Healthcare Cost and Utilization Project database was used. ArADE admissions in different socio-demographic groups were examined including characteristics such as age, gender, rural/urban, and income. LOS and hospital charges for ArADE cases were compared between 2001 and 2011. Chi-square test and t test were used for statistical analyses. RESULTS: There were 17,375 and 20,588 ArADE related admissions in 2001 and 2011, respectively. There was a 17.6% increase among the group of 18 to 64 years old and a 64.8% increase among the group of 65 years or older while the other age groups experienced decreased admission rates. Males and females had similar increases. Patients from the lower income areas experienced a two-fold increase while those from the higher income areas experienced a decrease. The mean LOS for all ArADE related admissions increased from 2.18 to 2.81 days and mean hospital charges increased from $8,456.2 to$21,572.5. CONCLUSIONS: There was an increase in ArADE hospital admissions. The greater increase in ArADE admissions among elderly, urban or low-income patients should be noted and addressed by practitioners and policy makers. The large increase in hospital charges needs further research

Immune Complex-Induced, Nitric Oxide-Mediated Vascular Endothelial Cell Death by Phagocytes Is Prevented with Decoy FcyReceptors

Autoimmune vasculitis is an endothelial inflammatory disease that results from the deposition of immune-complexes (ICs) in blood vessels. The interaction between Fcgamma receptors (FcyRs) expressed on inflammatory cells with ICs is known to cause blood vessel damage. Hence, blocking the interaction of ICs and inflammatory cells is essential to prevent the IC-mediated blood vessel damage. Thus we tested if uncoupling the interaction of FcyRs and ICs prevents endothelium damage. Herein, we demonstrate that dimeric FcyR-Igs prevented nitric oxide (NO) mediated apoptosis of human umbilical vein endothelial cells (HUVECs) in an in vitro vasculitis model. Dimeric FcyR-Igs significantly inhibited the IC-induced upregulation of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) release by murine monocytic cell line. However, FcyR-Igs did not affect the exogenously added NO-induced upregulation of pro-apoptotic genes such as Bax (15 fold), Bak (35 fold), cytochrome-C (11 fold) and caspase-3 (30 fold) in HUVECs. In conclusion, these data suggest that IC-induced NO could be one of the major inflammatory mediator promoting blood vessel inflammation and endothelial cell death during IC-mediated vasculitis which can be effectively blocked by dimeric decoy FcyRs

Functional group interactions of a 5-HT3R antagonist

Background: Lerisetron, a competitive serotonin type 3 receptor (5-HT 3R) antagonist, contains five functional groups capable of interacting with amino acids in the 5-HT3R binding site. Site directed mutagenesis studies of the 5-HT3AR have revealed several amino acids that are thought to form part of the binding domain of this receptor. The specific functional groups on the ligand that interact with these amino acids are, however, unknown. Using synthetic analogs of lerisetron as molecular probes in combination with site directed mutagenesis, we have identified some of these interactions and have proposed a model of the lerisetron binding site. Results: Two analogs of lerisetron were synthesized to probe 5-HT3R functional group interactions with this compound. Analog 1 lacks the N1 benzyl group of lerisetron and analog 2 contains oxygen in place of the distal piperazine nitrogen. Both analogs show significantly decreased binding affinity to wildtype 5-HT3ASRs. Mutations at W89, R91, Y142 and Y152 produced significant decreases in binding compared to wildtype receptors. Binding affinities of analogs 1 and 2 were altered only by mutations at W89, and Y152. Conclusions: Based on the data obtained for lerisetron and analogs 1 and 2, we have proposed a tentative model of the lerisetron binding pocket of the 5-HT3ASR. According to this model, The N-benzyl group interacts in a weak interaction with R91 while the benzimidazole group interacts with W89. Our data support an interaction of the distal amino nitrogen with Y142 and Y152

Functional group interactions of a 5-HT(3)R antagonist

BACKGROUND: Lerisetron, a competitive serotonin type 3 receptor (5-HT(3)R) antagonist, contains five functional groups capable of interacting with amino acids in the 5-HT(3)R binding site. Site directed mutagenesis studies of the 5-HT(3A)R have revealed several amino acids that are thought to form part of the binding domain of this receptor. The specific functional groups on the ligand that interact with these amino acids are, however, unknown. Using synthetic analogs of lerisetron as molecular probes in combination with site directed mutagenesis, we have identified some of these interactions and have proposed a model of the lerisetron binding site. RESULTS: Two analogs of lerisetron were synthesized to probe 5-HT(3)R functional group interactions with this compound. Analog 1 lacks the N1 benzyl group of lerisetron and analog 2 contains oxygen in place of the distal piperazine nitrogen. Both analogs show significantly decreased binding affinity to wildtype 5-HT(3AS)Rs. Mutations at W89, R91, Y142 and Y152 produced significant decreases in binding compared to wildtype receptors. Binding affinities of analogs 1 and 2 were altered only by mutations at W89, and Y152. CONCLUSIONS: Based on the data obtained for lerisetron and analogs 1 and 2, we have proposed a tentative model of the lerisetron binding pocket of the 5-HT(3AS)R. According to this model, The N-benzyl group interacts in a weak interaction with R91 while the benzimidazole group interacts with W89. Our data support an interaction of the distal amino nitrogen with Y142 and Y152

Oct4 Is Crucial for Transdifferentiation of Hepatocytes to Biliary Epithelial Cells in an in Vitro Organoid Culture Model

BACKGROUND: Hepatocyte to biliary transdifferentiation has been documented in various models of bile duct injury. In this process, mature hepatocytes transform into mature biliary epithelial cells by acquiring biliary phenotypic markers. Several signaling pathways including PI3 kinase, Notch, Hes1, Sox9, and Hippo are shown to be involved in the process. However, if Oct4 is involved in hepatocyte to biliary transdifferentiation is unknown. METHODS: We investigated the role of Oct4 in hepatocyte to biliary transdifferentiation utilizing an in vitro organoid culture system as a model of transdifferentiation. Oct4 was inhibited using adenovirus containing Oct4 shRNA. Hepatocyte specific HNF-4α and biliary specific HNF-1β & CK19 expression were assessed to gauge the extent of transdifferentiation. RESULTS: Oct4 was induced during hepatocyte to biliary transdifferentiation. Oct4 inhibition significantly downregulated the appearance of biliary cells from hepatocytes. This was accompanied by a significant downregulation of signaling pathways including Notch, Sox9, and Hippo. CONCLUSION: Our findings suggest that Oct4 is crucial for hepatocyte to biliary transdifferentiation and maturation and that it acts upstream of Notch, Sox9, and Hippo signaling in this model. This finding identifies new signaling through Oct4 in plasticity between hepatocytes and biliary epithelial cells, which can be potentially utilized to identify new strategies in chronic biliary diseases

Retrospective Analysis of T2DM Prescribing Trends in the US from 1996 to 2012

Background: Prevalence of diabetes has more than doubled between 1990 and 2012 in adults age 20 to 79 in the United States, 3.5 to 8.3%. This growing concern of diabetes over the last two decades in both youth and adults has brought about a variety of novel treatment options. Objective: The primary objective of this study was to determine if prescribing patterns reflected guideline recommendations with regards to pharmacologic and non-pharmacologic treatment of diabetes. In addition to a comparison of guidelines, a secondary objective was to determine any other factors that have influenced prescribing trends over the last two decades. Methods: Ambulatory care visit data from 1996 to 2012 was extracted from the NAMCS and NHAMCS using T2DM diagnosis codes. Medication was sorted into categories including oral, insulin and insulin analogs, non-pharmacological treatment (diet, exercise). Trends were identified for different age groups (10-17, 18-39, 39+) from 1996-2012. Results: Among 10-17 year-olds, insulin use increased (8221 to 144809) and use of medication with non-pharmacologic therapy decreased (239606 to 109572). Among 18-39 year-olds, increase in oral medication use (558871 to 1410509) and an increase in multiple medication use (5580 to 264246). Among those 39 and older, there was an increase in insulin use, oral medication use, non-pharmacologic therapy, and multiple medication use. Discussion: Prescribing of non-pharmacologic therapy remained steady among 10 - 39 year-olds while increasing among those above age 39. Prescribing of insulin saw an increase in those 10-17 and above 39. Oral agent use remained steady among youth while increasing for those over 18. Use of diet and exercise is a mainstay of treatment and with the increase in prevalence, use should have increased among all age groups. Providers should aim to involve patients in their treatment through diet, exercise, and education before use of pharmacologic therapy

A capstone course with a comprehensive and integrated review of the pharmacy curriculum and student assessment as a preparation for advanced pharmacy practice experiences

Objective. To create a capstone course that provides a comprehensive and integrated review of the pharmacy curriculum with a broad range of assessment tools to evaluate student knowledge and skills as a final preparation prior to beginning fourth-year advanced pharmacy practice experiences (APPEs). Design. The capstone course was a 4 credit-hour, case-based course. Eight comprehensive cases were assigned to students over the course of the term. The cases were designed to mimic complex clinical scenarios that students were likely to encounter during an APPE. Students were required to prepare a written and oral presentation for each case and were assessed on material covered during the cases. Faculty members presented weekly reviews on selected topics such as calculations, pharmacokinetics, and pharmaceutical compounding. At the end of the course, students took an observed structured clinical examination (OSCE), which simulated the Georgia Board of Pharmacy Practical Examination, and a comprehensive examination designed to mimic the NAPLEX (North American Pharmacy Licensure Examination). Assessment. Evaluation of student outcomes was based on written and verbal presentations of the cases, multiple-choice examinations, a short-answer calculations examination, an Errors and Omissions examination, a standardized patient encounter, and pharmaceutical compounding examinations. Ninety-five percent of students successfully passed the course on their first attempt. Student feedback indicated satisfaction with the depth, breadth, and organization of material covered and felt that the course helped prepare them for APPEs. Conclusion. The culminating experience of the capstone course gave students a thorough review of practical, clinical, and communication skills and provided faculty members with feedback regarding the curriculum through robust assessment