2019

Podium

Chaturvedi LS and Vyas D.  Irreversible Proteasome Inhibitor Regulate CDK Inhibitor p21 & c-Jun Kinase in MDA-MB-231Cancer Cells. Presented at the Annual Academic Surgical Congress. Houston TX, February 2019.

Abstract

Introduction: It is estimated that one million cases of breast cancer are diagnosed annually worldwide. Of these, approximately 12-20% are of the triple-negative breast cancer (TNBC) that do not express receptors for estrogen (ER), progesterone (PR) or human epidermal growth factor receptor 2 (HER2). TNBC is typically treated with a combination of other therapies such as chemotherapy, radiation, and surgery. Therefore, there is urgent need of new therapy for TNBC patients. Carfilzomib (CFZ) is a selective irreversible second generation proteasome inhibitor being used for the treatment of relapsed and refractory multiple myeloma as anticancer therapy. We have previously reported antiproliferative and apoptotic effects of CFZ alone or in combination with Doxorubicin (DOX) on human TNBC-MDA-MB-231 cancer cells. Overexpression of cyclin-dependent kinase inhibitor CDKN1A/p21Waf1/Cip1 and elevated phosphorylation of stress activated c-Jun NH2-terminal kinase has been reported in TNBC with adverse pathological parameters and poor prognosis. However, the role of CFZ in the regulation of CDKN1A/p21Waf1/Cip1 protein expression and c-Jun NH2-terminal kinase activation has not been determined in human TNBC-MDA-MB-231 cancer cells. Herein, we investigated role of CFZ in the modulation of CDKN1A/p21Waf1/Cip1 and c-Jun NH2-terminal kinase activation in human TNBC-MDA-MB-231 breast cancer cells.

Methods: Human TNBC-MDA-MB-231 cell-line, a model for TNBC was treated by various concentrations of CFZ alone, in a combination with DOX or vehicle control dimethyl sulfoxide (DMSO). Cell Counting Kit-8 (CCK-8) using WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium, monosodium salt) was used to detect cell viability. Annexin V-FITC apoptosis detection kit and flow cytometry was used to analyze the cell cycle. Western blot was used to detect expression of cyclin-dependent kinase inhibitor CDKN1A/p21Waf1/Cip1 protein and phospho specific c-Jun NH2-terminal kinase antibodies


Results: We confirmed antiproliferative and apoptotic effects of CFZ alone or in combination with DOX using CCK-8 viability and Annexin V-FITC apoptosis detection Kit respectively. The immunoblot analysis revealed that CFZ alone significantly inhibited CDKN1A/p21Waf1/Cip1 in a dose dependent manner and as well as in a combination with DOX in comparison to vehicle control DMSO. Furthermore, CFZ alone and in a combination with DOX also significantly inhibited the phosphorylation of stress activated c-Jun NH2-terminal kinase in human TNBC- MDA-MB-231 cancer cells.

Conclusion: Our data suggests that irreversible proteasome inhibitor CFZ alone and in combination with DOX may induce apoptosis and inhibit proliferation by modulating CDKN1A/p21Waf1/Cip1 protein expression and phosphorylation of stress activated c-Jun NH2-terminal kinase in human MDA-MB-231 breast cancer cells. Further investigation will encourage potential use of CFZ alone and in combination of DOX against tumors harboring drug-resistant phenotypes.

 

Podium

Chaturvedi LS and Vyas D. Second Generation Irreversible Proteasome Inhibitor Carfilzomib (CFZ) Inhibits Proliferation and Induces Apoptosis by down-regulating cyclin-D1, CDKN1A/p21 and c-Jun NH2-terminal Kinase Activation in Human Triple-Negative Breast MDA-MB-231Cancer Cells. Presented at the Northern California Chapter of the American College of Surgeons (NCCACS) Russell Surgical Trainee Research Competition meeting. Berkeley CA, March 2019.

Abstract

Currently there is no targeted effective therapy available for triple-negative breast cancer (TNBC) patients. The overexpression of cyclin-dependent kinase inhibitor CDKN1A/p21Waf1/Cip1 and an elevated phosphorylation of stress-activated c-Jun NH2-terminal kinase have been reported in TNBC patients with poor prognosis. Carfilzomib (CFZ) is a selective second generation irreversible proteasome inhibitor being approved for treatment of relapsed and refractory multiple myeloma. However, the role of CFZ in the regulation of CDKN1A/p21Waf1/Cip1 and c-Jun NH2-terminal kinase activation has not been fully elucidated in human TNBC cells. Herein, we investigated the role of CFZ in the modulation of CDKN1A/p21Waf1/Cip1 and c-Jun NH2-terminal kinase activation in human TNBC-MDA-MB-231 cells. CFZ inhibited proliferation, induced cell-cycle alterations and increased apoptosis in a dose and time dependent manner in MDA-MB-231 cells. Its action was compared to Doxorubicin (DOX), a first line chemotherapeutic agent. Flow cytometry analysis revealed that a combination of both CFZ and DOX significantly enhanced early and late apoptosis in comparison to either drug alone. The immunoblot analysis revealed that CFZ enhanced the reduction of cyclin-D1 protein expression, p21, and phosphorylation of stress activated c-Jun NH2-terminal kinase and induction of DNA Double-strand breaks (DSBs) by increasing the histone phosphorylation gamma-H2AX (Ser139). Our data suggests that irreversible proteasome inhibitor CFZ induces antiproliferation and apoptosis by down-regulating cyclin-D1, p21 protein expression, c-Jun NH2-terminal kinase phosphorylation and enhancing the gamma-H2AX (Ser139) phosphorylation in MDA-MB-231 cells. These findings suggest a potential use of CFZ against tumors harboring drug-resistant phenotypes.

 

Poster

Asadirad M, Talbott G, Satow B, Sharma U, Woldemariam T, Malhotra A. Identifying Mitochondrial Targets for Pancreatic Cancer Employing Unconventional Combinations of Middle Eastern Phytoextracts with Raloxifene. Presented at the American Society of Pharmacology and Experimental Therapeutics (ASPET) Meeting. Orlando FL, April 2019.

Abstract

PCa has a high mortality, substantial chemoresistance, and a poor 5-year survival rate of 6 to 8%. It is the fourth leading cause of deaths due to cancer in the United States, killing over 53,000 Americans each year, and 250,000 people worldwide. Little is known about the regulation of mitophagy in PCa by drugs and dietary components. There is also a gap in knowledge concerning molecular interactions between drugs and food and the K-ras pathway in PCa. This is important because mutations in the human homologue of the Kirsten Rat Sarcoma (KRAS) viral oncogene occur in 90% of PCa patients and drive the early development of PCa. Our previous work showed that enhanced mitophagy, which prevents the accumulation of damaged mitochondria in PCa cells was alleviated by repurposing the FDA-approved selective estrogen receptor modulator raloxifene to treat PCa cells. Here, we used a combination of Middle Eastern dietary components (MEDC) and raloxifene to mitigate mitochondrial renewal and identify novel mitochondrial targets for PCa. We screened crude aqueous extracts from six spices and plants used in Middle Eastern and Indian cuisines, including artichoke (Cynara scolymus), curry leaf (Murraya koenigii), dill (Anethum graveolens), noni (Morinda citrifolia), olive (Olea europaea), rose (Rosa damascena), and sumac (Rhus coriaria) for cytotoxicity in the PCa cell lines, MIA PaCa-2 (similar KRAS gene mutation as majority of patients) and PANC-1 (less common KRAS gene mutation). Specifically, we treated PCa cells in vitro with exponentially increasing doses of aqueous extracts at 300 ng/mL, 3 µg/mL, 30 µg/mL, and 300 µg/mL for 48 hours followed by an MTT assays. Aqueous extracts of sumac and artichoke (AESA) induced maximum cytotoxicity, which was exacerbated by raloxifene (AESA-R). To address whether cytotoxicity was limited to PCa cells, we used NIH-3T3 cells as a non-cancer control, showing a sparing effect. We also tested 1:1 combinations of AESA and found evidence of activity. To identify specific compounds, using a fractional approach based on preparative HPLC, 100 mg of the residue was chromatographed onto a silica gel column and gradient eluted using dichloromethane/methanol (gradient, 0, 100%, v/v). Fractions and eluates were monitored by thin layer chromatography using precoated silica gel 60 F254, 0.25 mm aluminum backed plates. Cytotoxic fractions were reconstituted in deuterated solvents and analyzed by NMR spectroscopy to identify pentagalloyl glucose as the bioactive component in sumac. To elucidate the mechanism for the cytotoxicity, we showed that AESA and AESA-R activated caspase-3 and 7, induced mitochondrial ROS, and reduced mitochondrial membrane potential in PCa cells, starting within 20 minutes and sustained for 48 hours following treatment. Western blot showed changes in the expression of proapoptotic (bim) and the translocation of antiapoptotic proteins (Bcl2), sustained over 48 hours. Our data demonstrate for the first time that specific food-drug combinations alter mitochondrial biology and response including the regulation of mitophagy in PCa cells.

 

Poster

Malhotra A. Enhancing Team-based Learning of Pharmacology Using Technology-assisted Prerequisite Content Preparation. Presented at the American Society of Pharmacology and Experimental Therapeutics (ASPET) Meeting. Orlando FL, April 2019.

Abstract

Multiple modalities are encouraged for creating and enhancing active learning in pharmacology pedagogy in pharmacy and medical schools. Team-based learning engages students in a detailed pedagogy that begins with pre-class self-directed preparation, leading up to an in-class individual Readiness Assurance Test (iRAT), which can be set by the program to mandate a certain level of competency by individual students. Typically, the iRAT is subsequently administered to the entire team as a team Readiness Assurance Test (tRAT). Based on the iRAT performance, a short lecture is delivered, emphasizing possible areas of class deficiency identified by the iRAT. Finally, students are asked to work in teams on application exercises. Although TBL is very effective in encouraging active participation in and out of class, team dynamics and other factors may lead to grade inflation when team scores mask and enhance the performance of borderline students. The California Northstate University College of Pharmacy employs a hybrid-TBL approach to engage learners in an active learning environment, with multiple didactic courses in the first, second and third professional years (P1, P2, P3) of the Doctor of Pharmacy program. To enhance TBL delivery in our pharmacology courses, we prepared a series of video lectures using online technology to help students prepare for their iRATs and tRATs. These short “Info-Blast” video lectures were typically 30-40 minutes in length, posted to YouTube, and emphasized the salient learning objectives, goals, terminology, and concepts included in prerequisite content required for upcoming pharmacology course lectures. Lectures included Pharmacogenomics, Biotechnology and An Introduction to Viruses in the Cell and Molecular Biology course (P1), and the pathophysiology of arrhythmia, the pharmacology of antiarrhythmic drugs, dyslipidemia, and dyslipidemia drugs in the Pathophysiology and Pharmacology II, Cardiovascular Sciences course (P2). The YouTube videos were accompanied by documents detailing self-directed Learning Objectives and a Practice Question Workbook, all of which were posted at least two weeks ahead of the class. Students provided comments and suggestions verbally and via email which were strongly positive.  Student iRAT scores and exam performance scores were captured using TurningPoint and ExamSoft and showed a positive correlation with the number of hours spent watching the video lectures. Among the advantages mentioned by students was the ease of access, the ability to repeat the lecture and detailed clarity added to expectations regarding outcomes and performance. One disadvantage mentioned was the extra time needed to prepare using the enhanced content, which we hope to address by using online technology such as InsertLearning to incorporate textual sources with the posted video lectures.

 

Poster

Jin Z and Abdullah C. Deficiency of CD4 T cells Contributes to Cardiac Fibrosis and Myocardial Dysfunction in T cell Specific S1P Receptor 1 Knockout Mice. Presented at the Experimental Biology Conference, Orlando FL, April 2019.

Abstract

Sphingosine 1-phosphate (S1P) is a bioactive small lipid molecule involved in apoptosis, barrier formation and function, cytoskeleton rearrangement, vascular maturation, wound healing, cell trafficking, and other functions via five G protein-coupled S1P receptors or/and intracellular lipid signaling. T cell S1P receptor 1 (S1P1) is responsible for mature T cell exit from thymus to the blood and periphery. Nevertheless, effects of T lymphocyte S1P1 on cardiac function and fibrosis remains incomplete understood. To this purpose, we generated T cell S1P1 knockout

mice (TS1P1KO) by crossing S1P1loxP/loxP mice with Lck-Cre mice. Body weight (g) and glucose levels (mg/dl) in the blood were monitored. CD4 and CD8 T lymphocytes were counted by using flow cytometry. Pathological grading of heart histology was conducted in H&E stained sections. Masson Trichrome staining was utilized to evaluate cardiac fibrosis. Cardiac contractility was determined in Langendorff perfusion system. The TS1P1KO mice exhibited sustained deficiency of both CD4 and CD8 T cells in the blood compared with wild-type littermate control. The TS1P1KO mouse heart featured an altered phenotype characterized by reduced cardiac contractility and increased cardiac fibrosis as well as morphological alteration, notably, loss of interstitial space between cardiac myocytes with thickening of vascular smooth muscle cells and perivascular edema compared with littermate vehicle mice. To explore the role of CD4 T cells in altered phenotype, naïve CD4 T cells were isolated by positive selection through MS column from CD4 magnetic microbeads-labeled wild-type littermate mouse splenocytes. Isolated CD4 T cells were adoptively transferred into TS1PKO mice intravenously at a dose of one million cells. TS1P1KO mice with reconstitution of CD4 T cells showed improved heart histology and less fibrosis as well as improved cardiac function compared with TS1P1KO mice without CD4 T cell transfer. In conclusion, deficiency of CD4 T cells in T cell S1P1 knockout mice contributes to cardiac fibrosis and myocardial dysfunction.

 

Poster

Mohamed I, Thomas S, Rooney K et al. Mir-155 is a Negative Regulator of Acute Oscillatory Shear Stress-induced AT1R/ETS-1 Pathway and Downstream Vascular Inflammation and Barrier Dysfunction. Presented at the American Heart Association, Arteriosclerosis, Thrombosis & Vascular Biology (ATVB 2019) meeting, Boston MA, May 2019.

Abstract

Rationale: Atherosclerosis preferentially localizes to vascular areas exposed to low magnitude oscillatory shear stress (OSS). MicroRNA-155 (miR-155) and Angiotensin II Receptor Type 1 (AT1R) are shear stress responsive and can potentially modulate vascular inflammation through the E26 transformation-specific sequence factor-1 (ETS-1) pathway. Nevertheless, little is known about the interplay between miR-155 and AT1R/ETS-1 pathway in response to OSS in vivo and whether targeting miR-155 can prevent OSS-induced vascular inflammation.

Objective: To test the hypothesis whether acute induction of OSS in vivo increases vascular inflammation and barrier dysfunction through activation of AT1R/ETS-1 and to determine whether this pathway is modulated by shear responsive miR-155.

Methods: C57B/6J wild type (WT), miR-155 knockout mice (KO) and AT1Ra-KO were subjected to abdominal aortic coarctation (AAC), a unique model of acute induction of OSS in mouse abdominal aorta,for 3-7 days. miR-155 expression was enhanced by tail vein injections of lentivirus encoding miR-155 and Candesartan treatment was used to block AT1R in WT mice. Acute OSS segments downstream of AACwere compared to upstream unidirectional shear stress (USS) segments using RT-qPCR, western blot, TTest and two-way ANOVA.

Results: In WT mice, acute AAC resulted in differential expression of AT1Rb versus AT1Ra isoform, increased miR-155, ETS-1, vascular inflammation and permeability in OSS compared with USS aortic segments. miR-155-KO mice showed enhanced ETS-1 pathway and vascular permeability in OSS versus USS segments. Whereas, OSS-induced ETS-1 pathway was suppressed upon enhanced expression of miR-155 in WT mice. In AT1Ra-KO mice, miR-155 levels were decreased in OSS segments and vascular inflammation was enhanced. Blocking both AT1R isoforms with Candesartan treatment of WT mice partially attenuated the ETS-1 proinflammatory pathway in OSS segments.

Conclusion: These data support a negative regulatory feedback relationship between miR-155 and proinflammatory AT1R/ETS-1 pathway in response to acute OSS in vivo. Our findings suggest miR-155 as a novel potential therapeutic target for vascular inflammation.

 

Poster

Fitzpatrick LR, Moua P, Talbott G, O’Connell R, Zapf J, Cusick J. Receptor Expressed in Lymphoid Tissues (RELT) Immunostaining is enhanced in Mice with Innate Immune Colitis. Accepted for Presentation at the AACP Meeting, Chicago IL, July 2019.

Abstract

Receptor Expressed in Lymphoid Tissues (RELT) is a human Tumor Necrosis Factor (TNF) receptor that is expressed most prominently in cells and tissues of the hematopoietic system. The role of RELT in intestinal inflammation is unknown. Therefore, we evaluated immunostaining of RELT in the colonic tissue of mice with innate immune colitis.

Methods: Female CB-17 SCID mice (n =9) were injected by the intraperitoneal route with 12 mg/kg anti-CD40 monoclonal antibody to induce colitis. A control group of mice (n = 4) were not injected with this antibody. Seven days later, mice were euthanized and colonic tissue collected for histology and immunohistochemistry (IHC) evaluations. Histological pathology was evaluated using a twelve-point severity scale. Colonic IHC (n = 3 to 4 per group) was performed with a specific antibody for RELT. Using captured IHC pictures, percent areas of immunostaining were analyzed with an online grid software program.

Results: Significant evidence of histological pathology was present in the anti-CD40 injected mice (mean score = 9.0 ± 0.5), as compared to naïve mice (mean score = 2.6 ± 0.2). IHC staining was sporadic within the colons of naïve mice. The mean percent area of RELT staining was 35.1 ± 3.7. More prominent RELT immunostaining (mainly in the lamina propria) was evident in mice with innate colitis (mean percent area = 54.5 ± 3.4).

Conclusions: These results demonstrate that RELT immunostaining is enhanced within the colonic mucosa of mice with innate immune colitis. Moreover, there is an apparent association between colonic histological damage and RELT immunostaining.

 

Poster

Malhotra A, Mente W,  Kreys E, Tran H et al. Development, Implementation, and Assessment of a Comprehensive, Integrated, and Multimodal Interprofessional Education (CIM-IPE) Program. Accepted for Presentation at the AACP Meeting, Chicago IL, July 2019.

Abstract

Objective. 2016 ACPE Standard 11 mandates the inclusion of interprofessional education (IPE) in pharmacy programs. However, challenges exist in the standardized design, delivery, and assessment of an IPE curriculum. We developed and implemented a comprehensive, vertically and horizontally integrated, multimodal IPE curriculum (CIM-IPE) and assessed for student, program, and institutional outcomes. 

Methods. We established an IPE collaboration, created an institutional infrastructure, and operationalized the curriculum with pharmacy, nursing, and medical students using a five-pronged approach built around 1) a didactic component, 2) high fidelity simulation with robots with content-emphasis, 3) hospital simulation with robots with process emphasis, 4) interprofessional case conferences, and 5) a Hotspotting IPE-elective. The four 2016 Interprofessional Education Collaborative (IPEC) competencies and ACPE Standard 11 were used to assess outcomes, classifying developmental stages as initial, developing, developed, and proficient. 

Results. In seven IPE events distributed across the P1 through P3 years of the CNUCOP Pharmacy curriculum, a high total number of pharmacy, nursing and medical school participants (N=1,799) were repeatedly engaged. Overall assessment data show a high success rate of the integrated CIM-IPE program with mean performance scores of 98 (SD=13, N=117) and 95 (SD=5, N=67) for the interprofessional case conferences, 100 (SD=2, N=117), 95 (SD=4, N=67), and 95 (SD=5, N=67) for the 3 simulation based IPE events. 

Conclusion. Our curricular and assessment strategies for CIM-IPE outline a stepwise development and implementation blueprint for an inclusive and comprehensive IPE program that is readily transferable to other colleges and schools of pharmacy and other health care professional programs.

 

Poster

Malhotra A, Mente W, Phan V, Tran H. Training and engaging pharmacy residents to lead high fidelity simulation-based interprofessional education cases. Accepted for Presentation at the AACP Meeting, Chicago IL, July 2019. 

Abstract

Objective       

ACPE mandates interprofessional education (IPE) for inclusion in pharmacy programs. We created an innovative program to incentivize and engage pharmacy residents by participation in high-fidelity simulation IPE cases for P2 and P3 students.

Methods        

The Post Graduate Year 1 (PGY1) Pharmacy Residency at the California Northstate University College of Pharmacy (CNUCOP) and the Adventist Health Lodi Memorial (AHLM), and affiliated residency programs, offers a comprehensive experience in advanced clinical practice and academic teaching. The CNUCOP Residency program offered our residents opportunities to develop their teaching skills, facilitate team-based learning (TBL), and earn a Teaching and Learning Certificate. Residents interested in IPE assisted with high fidelity simulation IPE cases between the CNUCOP and the California State University Sacramento School of Nursing for P2 and N1 and P3 and N1 students. The PGY1 residents were trained to develop scripts for unfolding IPE cases, supervise student performance, assist with running the manikins, and debriefing after the case.

Results

Six pharmacy PGY1 residents contributed to IPE events (N=2) engaging large aggregate cohorts of students (N=200). The IPE cases focused on Acute Pancreatitis and Congestive Heart Failure. Residents were trained in IPE principles in a formal training by the IPE Coordinator, who also provided annotated IPE-case scripts for residents in the role of the consulting pharmacist. Residents also received training by the Residency Program Director and CNUCOP faculty.

Implications  

Our formal program for training PGY1 residents in IPE incentivized and engaged the next generation of the Pharm.D. workforce in recognizing the significance of interprofessional education and practice.

 

Podium

Malhotra A and Matthews J. Diverse Approaches to Interprofessional Education: A Two-Institution Perspective Using Simulation and Virtual Patients. Accepted for Presentation at the AACP Meeting, Chicago IL, July 2019.    

Abstract will be posted in the Near Future

 

Podium

McDowell J, Hughes J, Malhotra A, Kreys T-J, Clark S, Fuentes D. An Immersive Strategy to Enhance Recruitment and Align Program-Specific Psychological Expectations.  Accepted for Presentation at the AACP Meeting, Chicago IL, July 2019.    

Abstract will be posted in the Near Future

 

Podium (Roundtable Discussion)

Malhotra A. Developing Strategies to Overcome Social, Cultural, and Political Barriers to Care for LGBTQ Patients. Accepted for Presentation at the AACP Meeting, Chicago IL, July 2019.

Abstract will be posted in the Near Future

 

Poster

Tran T, Le U, Tran H. Machine learning based method for accurate prediction of breast cancer. Accepted for Presentation at the AACP Meeting, Chicago IL, July 2019.

Abstract

Objective.  Main objective of this study is to utilize advanced computing methods for accurate prediction of breast cancer based on preliminary clinical data.

Methods. We used a well-known dataset provided by the Wisconsin Breast Cancer Database. First, we performed data preprocessing to identify missing values, outliers and potential predictors. Next, we used the advanced machine learning method, Random Forest, for modeling. To construct our model, data is randomly divided into 70% for training and 30% testing. Performance is measured by accuracy, sensitivity (true positive) and specificity (true negative).

Results. The dataset included 698 cases with 11 attributes. We identified 16 missing values and removed these associated observations. Analysis revealed that 64.96% and 35.04% of cases were benign and malignant, respectively. In addition, correlation analysis showed that CellSize and CellShape are highly correlated with coefficient of 0.91 (p-value = 0.001). This finding helps to eliminate one of the attributes in our model to avoid multicollinearity. Our constructed model achieved very high prediction accuracy of 97.63% with 95% confident interval of (94.56% - 0.99.23%). The result is higher than our previously published accuracy of 96.63%. Additionally, the model also achieved very high sensitivity and specificity of 98.55% and 95.89%, respectively. Finally, CellShape and ClumpThickness were identified as the two most important predictors for detecting breast cancer.

Implications. The study provided an accurate and effective method for predicting breast cancer. It opened up new avenue for early breast cancer detection and treatments. Our future work will perform parameter fine-tuning to achieve higher accuracy.

 

Poster

Tran T, Le U, Titus-Lay E. Revealing trends of overdose deaths and opioid prescriptions via Google keyword search.

Abstract

Objective.  The objective of this study was to reveal trends of overdose deaths and filled opioid prescriptions in the U.S. via Google keyword search.

Methods. Data was collected from the Centers for Disease Control and Prevention (CDC), National Institute on Drug Abuse (NIDA), and Google Trends including opioid prescription rates from 2013 - 2017, number of overdose deaths per 100,000 persons in 2016 and frequencies of “opioid” keyword searches associated with geographical locations from years 2013 - 2016. Correlation analysis was used to identify trends of overdose deaths and opioid prescriptions of different states. Keyword search ranking identified the top 10 states with the most overdose deaths.

Results. Pearson correlation analysis showed strong correlation of filled prescriptions from 2013 - 2017 with coefficients greater than 0.96, p-values <= 0.001. Findings showed consistent prescription filling trends across the states over time. Analysis of Google keyword searches from 2013 - 2016 showed strong correlation with overdose deaths in 2016 with coefficients from 0.56 - 0.78, p-values <= 0.01. Additionally, high correlations of monthly keyword searches and overdose deaths in 2016 were identified, ranging from 0.61 - 0.78, p-values <= 0.01. Finally, keyword search ranking correctly identified 80% of the top 10 states having the most overdose deaths in 2016.

Implications. The study proposes a novel way for estimating trends of overdose cases and opioid prescriptions in the U.S. Policy makers can use it for public health surveillance. Our future work includes refining keyword combinations and collecting more data for predictive modeling.

California Northstate University College of Pharmacy ♦ 9700 West Taron Drive ♦ Elk Grove, CA 95757 ♦ Phone: (916) 686-7400

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