<div>The human ether-a-go-go-related gene (hERG, KCNH2) potassium channel has been implicated in diverse physiological and pathological processes. The KCNH2 gene encodes a rectifier voltage-gated potassium channel (Kv 11.1) that governs the chief repolarizing current, IKr, which is essential for normal electrical activity in excitable cells such as cardiomyocytes. It is also involved in cell growth and apoptosis regulation in non-excitable cells, such as tumor cells. Dysfunction of hERG is associated with potentially lethal complications, including diseases and sudden death under certain circumstances. While the mechanisms regulating KCNH2 expression remain unclear, recent data suggested that microRNAs (miRNAs) are involved, particularly in the context of several pathologic effects. </div><div>miRNA is a class of RNA defined by its conserved, short, non-coding nature. miRNAs are important regulators of gene expression at the post-transcriptional level that bind through complimentary annealing to the 3’ untranslated regions (3’ UTRs) of target mRNAs, resulting in mRNA destabilization and translational repression. The primary objectives of this research were to 1) identify miRNAs regulating KCNH2 expression in cancer, 2) investigate the potential association between miR-362-3p expression and risk of drug-induced QT interval lengthening, and 3) identify miRNAs potentially regulating KCNH2 expression and function in cardiac cells. </div><div>Through bioinformatics approaches, five miRNAs were identified to potentially regulate KCNH2 expression and function in breast cancer cells. The five identified miRNAs were validated through a Dual-Luciferase Assay using the KCNH2 3′ UTR. Only miR-362-3p was validated to bind to the KCNH2 3’ UTR, decreasing luciferase activity by 10% ± 2.3 (P < 0.001, n = 3) when compared to cells transfected with luciferase plasmid alone. miR-362-3p was also the only miRNA that its expression positively correlated with overall survival of patients with breast cancer from The Cancer Genome Atlas-Cancer Genome (TCGA) database by log-rank test (HR: 0.39, 95% CI: 0.18 to 0.82, P = 0.012). Cell proliferation was assessed by MTS assay (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) 48 hours following transfection in breast cancer cell lines, including SK-BR-3 and MCF-7. miR-362-3p significantly decreased proliferation of SK-BR-3 and MCF-7 cells by 23% ± 8.7 (P = 0.014, n = 3) and 11.7% ± 1.0 (P < 0.001, n = 3), respectively. Cell cycle phases in SK-BR-3 and MCF-7 cells were differentiated by flow cytometry 48 hours following transfection. miR-362-3p and hERG siRNA (positive control) significantly increased the accumulation of cells in G0/G1 phase in MCF-7 by 11.7% (from 51.1% ± 0.64 to 57.1 ± 0.96, P = 0.002, n = 3) and 10% (from 51.1% ± 0.64 to 56.8 ± 0.96, P < 0.001, n = 3), respectively. </div><div>The demonstrated ability of miR-362-3p to regulate hERG in breast cancer cells coupled with previously published data that indicated an alteration of miR-362-3p expression during HF and a potential association between its expression and QT interval prolongation suggesting an important role for this miRNA in regulation of hERG function during HF. Therefore, the contribution of miR-362-3p to hERG function was investigated in patients administered the QT prolonging drug ibutilide, known to inhibit hERG. A total of 22 patients completed a prospective, parallel-group comparative study during which they received subtherapeutic doses (0.003 mg/kg) of ibutilide. The study was originally designed to investigate the influence of heart failure with preserved ejection fraction (HFpEF) on response to drug-induced QT prolongation. Blood for determination of serum Ibutilide concentrations and miR-362-3p expression, along with electrocardiograms (ECGs) were serially collected over a span of 12 hours. ΔΔ-Fridericia-heart rate corrected QT (ΔΔ QTF) intervals were utilized for all analyses to account for baseline and diurnal variation. </div><div>To assess the ability of miR-362-3p to predict ibutilide QT-induced ΔΔQTF changes, nonlinear mixed effects pharmacokinetic/ pharmacodynamic (PKPD) modeling was performed to assess the contribution of miR-362-3p to drug-induced QT interval lengthening. The model that best fit serum ibutilide concentrations versus time was a 3-compartment model with first order elimination and proportional residual errors, while the model that best described the ibutilide concentration- ΔΔQTF relationship was an Emax model with an effect compartment. In addition to miR-362-3p expression, several demographic and clinical data were evaluated as potential covariates on PK and PD parameter estimates. Of tested covariates, heart failure (HF) status on Emax (ΔOFV = -4.1; P < 0.05), and miR-362-3p expression on EC50 (ΔOFV = -9.9; P < 0.05) were incorporated in the final PKPD model. The mean individual Emax was significantly higher in HF patients when compared to non-HF patients (P = 0.015), while EC50 was negatively correlated with miR-362-3p expression (P < 0.0001, R2 0.93). </div><div>Previous evidence indicates that miR-362-3p is altered in patients with HF. In addition, several miRNAs commonly regulate the same ion channel. Therefore, we have developed a large-scale high-throughput bioassay (HT-bioassay) to explore and identify other miRNAs potentially involved in KCNH2 expression and function in human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) during sustained β-adrenergic receptor (βAR) stimulation or overexpression of activated calcium/calmodulin-dependent protein kinase 2 (CaMKII), which are classical consequences of HF. </div><div>Through bioinformatic approaches, putative miRNA binding sites (n=327) were identified in the KCNH2 3′ UTR. Fragments containing these putative binding sites were synthesized, cloned into linearized plasmids, and amplified. The plasmid pool was transfected into hiPS-CM cells either treated with βAR stimulation or overexpressing CaMKII. Next-generation sequencing was performed to identify: 1) expression of putative miRNA binding sites and 2) endogenous miRNAs versus control. Eight predicted binding sites were found to be significantly downregulated in the CAMKII group (P <0.05, log fold change -0.287 to -0.59), and six significantly downregulated in the sustained βAR group (P <0.05, log fold change -0.29 to -0.72). Two binding sites were significantly reduced in both treatment groups (P < 0.05, log fold change between -0.38 and -0.61).</div><div>Thirty-one miRNAs were predicted to bind to the 16 binding sites identified from the bioassay. Of these, seven were selected for further screening using dual luciferase assays. None of the putative miRNAs reduced luciferase activity. However, hERG expression was assessed by immunoblot analysis following transfection of the seven miRNAs into HEK293 cells stably expressing hERG (HEK293-hERG). Six of the seven miRNA mimics reduced hERG protein expression. An additional validation step was performed by assessing hERG-related current density by whole cell electrophysiology, in which three of the six miRNAs inhibited hERG protein transfected into HEK293-hERG cells. Those same three miRNA mimics significantly decreased Ikr current (P <0.05). </div><div>Finally, expression of the miRNAs identified by HT-bioassay was examined in the patients enrolled in the clinical trial in which genome-wide next generation sequencing was performed on miRNAs extracted from whole blood samples. Of the 31 miRNAs identified from HT-bioassay, six were found to be expressed in patients (n = 12). A correlation analysis was performed between levels of the expressed miRNAs and corresponding QTF interval lengthening with ibutilide. Of the six miRNAs, only miR-4665-5p was significantly associated with QTF interval (P = 0.0379). </div><div>In summary, miR-362-3p was identified to regulate hERG, and reduces proliferation of breast cancer cells through a mechanism that may be partially mediated by hERG inhibition. While miR-362-3p may have modest effects in cancer, in Aim 2 we demonstrated that it along with HF status accounts for a significant amount of variability in QTF prolongation following ibutilide administration. However, it is common for several miRNAs to regulate a single ion channel. Therefore, an HT-bioassay was developed to identify all miRNAs that potentially regulate KCNH2 during HF. In addition to miR-362-3p, thirty-one miRNAs were predicted to regulate KCNH2; one miRNA (miR-4665-5p) was significantly associated with QTF prolongation. The potential for miR-362-3p and HT-bioassay-identified miRNAs to reduce hERG-related current and influence susceptibility to drug-induced QT interval prolongation warrants further investigation. </div><div><br></div>

<p>The opioid epidemic is an ongoing public health crisis in the United States (US). Although many treatment options exist for opioid use disorder (OUD), including evidence-based counseling, medications, rehabilitation programs, and support groups, access to care is a significant barrier. Pharmacists can play an important role in increasing patient access to OUD care; however, insufficient training is a well-documented barrier. Integrating comprehensive training into Doctor of Pharmacy coursework is a practical approach to preparing pharmacists to provide appropriate OUD care in a variety of practice settings. A shared OUD curriculum is one strategy to facilitate the integration of comprehensive training into Doctor of Pharmacy coursework.</p> <p><br></p> <p>My current research aimed to collect data from four key stakeholder groups – Doctor of Pharmacy program faculty, community pharmacists, multidisciplinary professionals, and patients experiencing OUD – to inform a shared OUD curriculum through a convergent, parallel, mixed methods study design. Specifically comprising this thesis are the quantitative findings from telephone surveys with Doctor of Pharmacy program faculty (“Study One”) and community pharmacists (“Study Two”); qualitative findings from multidisciplinary professional focus groups and patient interviews, as well as synthesized findings across quantitative and qualitative data sources, will be reported in future publications. Collectively, the results presented in this thesis provide a “snapshot” of the current pharmacy landscape with respect to the OUD education delivered to student pharmacists and opioid-related practices in community pharmacies.</p> <p><br></p> <p>The findings from Study One and Study Two indicate that OUD education in Doctor of Pharmacy programs and pharmacist-provided opioid interventions are inconsistent at best. The three main areas identified as needing future emphasis were: (1) the disease model of addiction and accompanying stigma of OUD; (2) harm reduction-, prescription-, screening-, and resource referral-related opioid interventions; and (3) skills-based, experiential education (vs. didactic education) for opioid intervention delivery and communication techniques. A shared OUD curriculum was of interest to faculty and is a viable solution to addressing OUD education gaps in Doctor of Pharmacy programs. Once qualitative data analyses are completed and findings from all four stakeholder groups are synthesized, development of the proposed shared OUD curriculum will commence.</p>

<div>My PhD thesis evolves around the potential protective effects of sex hormones progesterone and testosterone against drug-induced QT interval prolongation in premenopasual women and older men.<br></div>

Research indicates that tobacco cessation rates are at least doubled when smokers receive assistance from a clinician; receiving tobacco cessation advice from multiple types of clinicians increases quit rates even further.¹ To address a decades-long deficiency in the tobacco cessation training of health professionals in general, a shared curriculum, Rx for Change: Clinician-Assisted Tobacco Cessation, was developed in 1999 as a collaboration of the schools of pharmacy in California.^2,3 Between 2003 and 2005, pharmacy faculty members (n=191) participated in national train-the-trainer workshops designed to equip faculty with the necessary knowledge and skills to implement the Rx for Change curriculum at their academic institutions.⁴ <div><br></div><div> The studies that comprise this dissertation are a logical extension of this national initiative, applying a mixed-methods approach to: (a) evaluate the long-term impact of training pharmacy faculty using the Rx for Change program, (b) delineate recommendations for developing and disseminating shared curricula for health-care programs, and (c) evaluate utilization of the Rx for Change website, which hosts faculty resources and curricular files for download. In combination, these (along with a previously-conducted qualitative study) provide a comprehensive “view” of the long-term impact of this unique shared curriculum. </div><div><br></div><div>Results from the three studies provided evidence for: (1) reach to the majority of pharmacy institutions, (2) a high level of adoption of the Rx for Change in health professional schools, (3) a positive impact on faculty trainees’ careers and their level of confidence for teaching, precepting clinical students, and assisting tobacco users, (4) implementation of the Rx for Change curriculum with a variety of teaching methodologies, and (5) continuity of use within the core curriculum of pharmacy institutions. Seven key factors were found to have contributed to the success of the Rx for Change program, and thus the following are recommended for future shared curriculum developers: (1) appeal to attendees, (2) relate content to clinical practice, (3) deliver live training (in-person), (4) develop high quality materials delivered by experts, (5) meet accreditation standards, (6) provide support for teaching, and (7) demonstrate effectiveness. Data from the website analysis provided evidence for interprofessional reach of the Rx for Change website to educators, learners, and professionals.<br></div>

<p><b>Background/ Objective:</b> In our current healthcare system, information seekers have a bulk of the responsibility to initiate conversations about medications. Although older adults report the need for more information about their medications, many do not accept offers to receive more information from pharmacists during the dispensing of prescription medications. Very little previous work focuses on how older adults make decisions about seeking and avoiding information about medicines, or how these decisions impact medication outcomes. Therefore, the specific aims of this study were to: 1) describe older adults’ attitudes about medication information seeking and the relationships between those attitudes and medication information management behaviors and 2) characterize the relationship between medication information management behaviors (MIMB), medication knowledge, medication beliefs, and attitudes towards medication information seeking. </p><p><b>Methods:</b> Older adults prescribed a new, chronic medication were recruited from a specialty geriatric clinic to participate in interviews that occurred either in-person or over the phone. Participates were randomized 1:1 to usual care or to patient-prompted medication counseling (PPMC). Participants in the PPMC group agreed to ask a pharmacist questions about their new medication at their next medication refill and received a brief education. A survey instrument based on the Theory of Motivated Information Management (TMIM) was adapted from past studies to assess participants’ attitudes about information seeking. Participants were asked to report their information seeking and avoidance over the previous six-months prior to the study and at baseline and month one. Open-ended questions from a national medication safety campaign were utilized to assess medication knowledge. A rubric was developed to score participants’ answers as incorrect knowledge, no knowledge, incomplete knowledge, or complete knowledge and used by two community pharmacists to determine patient medication knowledge (PMK) scores. Structural equation modeling was utilized to identify predictors of MIMB, and hierarchical and logistic regression were used to determine the relationship between MIMB and medication outcomes. </p><p><b>Results: </b>A total of 132 participants completed baseline surveys, and 126 participants completed the month one surveys. Overall, a structural model based on the TMIM met the a priori criteria for good fit (Bollen-Stine bootstrap=0.269). Participants’ positive outcomes assessments, negative outcomes assessments were direct, positive predictors of information seeking and direct, negative predictors of information avoidance. After controlling for baseline medication knowledge, the effect of the intervention, and information seeking there were statistically significant differences in medication knowledge between those participants that sought information from a pharmacist during refill dispensing and those who did not (B=0.259, p<0.001). Of those that sought information from a pharmacist, 70% gained information from baseline to month one, while 36.9% of those that did not seek information from a pharmacist gained information baseline to month. There were no differences in medication beliefs between those that sought information from a pharmacist and those that did not.</p><p><b>Discussion/ Conclusion:</b> Patient knowledge deficits continue well beyond the initial dispensing of a medication, and older adults are also at risk for knowledge loss over the course of prescription use. Receiving additional information from a pharmacist at the time of medication refill may be protective against this information loss, and even increase the change of gaining medication knowledge over time. However, medication counseling in its current form is likely not sufficient to alter older adults’ beliefs about medications. Only one pharmacist initiated a conversation with a participant at medication refill indicating that those participants who want additional information about their medications after the initial dispensing may have to initiate the conversation with a pharmacist.</p>

<p><b>Background</b><br></p> <p>More than 90% of individuals aged 65 years or older in the United States (US) are taking at least one prescription medication, and more than 40% are taking five or more prescription medications. The potential for non-adherence and risk of medication therapy problems (MTPs) increases with the use of multiple medications. To enhance patient understanding of appropriate medication use, improve medication adherence, and reduce MTPs, the Centers for Medicare & Medicaid Services (CMS) launched Medication Therapy Management (MTM) services as part of Medicare Prescription Drug (Part D) policy; however, “best practices” for achieving positive MTM outcomes are not well understood.</p><p><br></p> <p> </p> <p><b>Objectives</b></p> <p>This study had two objectives. The first objective was to identify and explain reasons for concordance and discordance between a) consistently high, moderate, and low performing pharmacies and b) pharmacies that improve or worsen in performance overtime. The second objective was to generate hypotheses for strategies that contribute to community pharmacies’ ability to achieve high performance on widely accepted MTM quality measures. </p><p><br></p> <p> </p> <p><b>Methods</b></p> <p>This comparative mixed-methods, case study design incorporated two complementary conceptual models. First, an adaptation of the Positive Deviance (PD) model explains reasons for deviations in MTM quality measure performance among community pharmacies and informs study design. Second, the Chronic Care Model (CCM) guided data collection and analysis. Data consisted of pharmacy/staff demographics and staff interviews. When appropriate, quantitative and qualitative data were analyzed within and across pharmacy MTM performance (i.e., high, moderate, low) or change-in-performance (i.e., consistent, improved, worsened) categories using descriptive statistics and cross-tabulation respectively. MTM performance component measures used to evaluate and rank pharmacy MTM performance mirrored measures under Domain 4 (Drug Safety and Accuracy of Drug Pricing) of the 2017 CMS Medicare Part D Plan’ Star Rating measures. This study was approved by the Institutional Review Board for the Purdue University Human Research Protection Program. </p><p><br></p> <p> </p> <p><b>Results </b></p> <p>Across the sample of eligible pharmacies (N = 56), MTM performance composite scores varied by 21.3%. Of the five component scores, the <i>Comprehensive Medication Review (CMR)</i> component score had the highest percent variation (88.3%). Pharmacy staff at 13 pharmacies of the 18 pharmacies selected as case study sites participated in interviews, yielding a 72.2% case pharmacy participation rate. Of the 13 pharmacies, five were categorized as high performers, four were moderate performers, and four were low performers. Of the 39 pharmacy staff approached across all pharmacies, 25 participated in interviews, yielding a 64.1% participation rate. Interviewees included 11 pharmacists, 11 technicians and three student interns. Eight strategies were hypothesized as positively (7) or negatively (1) contributing to pharmacies’ MTM performance. Hypotheses generated were organized by CCM elements and included: <i>Delivery System Design (DSD)</i> – Having a high degree of technician involvement with MTM activities; Inability to meet cultural, linguistic, and socioeconomic needs of patients (negative); Having sufficient capacity to provide CMRs to patients in person compared to telephone alone; Pharmacy staff placing high priority on addressing MTM activities<i>; Clinical Information Systems (CIS) </i>– Faxing adherence-related MTP recommendations and calling providers on indication-related MTP recommendations; Technicians’ use of CISs to collect/document information for pharmacists; Using maximum number of available CISs to identify eligible MTM patients; <i>Health System Organizations (HSO) </i>– Strong pharmacist-provider relationships and trust. No hypotheses were generated for the remaining three CCM elements.</p><p><br></p> <p> </p> <p><b>Conclusions </b></p> <p></p>A total of eight strategies were hypothesized as contributing to community pharmacies’ ability to achieve high performance on MTM quality measures. Notable strategies were related to three of the six chronic care model elements. Future research should engage stakeholders to assist with prioritizing hypotheses to be statistically tested in a larger representative sample of pharmacies.

Background: The sensitivity to drug-induced QT prolongation is highly variable in heart failure (HF) patients. QT interval prolongation can lead to a life-threatening ventricular arrhythmia known as torsade de Pointes (TdP), which can result in sudden cardiac death. Although QT prolongation is a surrogate marker for sudden cardiac death, the extent of drug-induced QT prolongation, and thus TdP, is largely unpredictable. Therefore, developing a biomarker to predict patients’ sensitivity to drug-induced QTc prolongation could have a profound clinical impact. MicroRNA (miR) are recognized as important regulators of cardiovascular function as they shape the transcriptome by targeting mRNAs for repression of translation. Our multidisciplinary research group has demonstrated that miR-362-3p regulates a potassium channel (i.e., hERG) that is the most widely implicated in drug-induced QTc prolongation. The primary objects of this analysis focus on characterizing serum miR-362-3p expression in the circulation as a potential biomarker to predict subject’s susceptibility to ibutilide exposure induced QT-interval prolongation.<div><br></div><div>Methods: The dataset utilized to develop the PK-PD models were collected from a previous clinical study carried out by Tisdale et al. (Tisdale,et al. 2020).A total of 22 adult subjects who met the inclusion and exclusion criteria were enrolled and divided into three groups: a group of patients with heart failure with preserved ejection fraction (HFpEF, n=10), a group of patients with heart failure with reduced ejection fraction (HFrEF, n=2), and ten healthy subjects in the control group who were matched to subjects in the HFpEF group for age and sex. Following a baseline day of triplicate 12-lead ECGs, all subjects received ibutilide 0.003mg/kg intravenously infused over 10 minutes. Serial collection of blood samples to determine serum Ibutilide concentrations (HPLC/MS), serum miR-362-3 expression (qPCR), with triplicate ECG readings were obtained pre-and-post ibutilide administration. To describe ibutilide serum concentration exposure and the9relationship with Fridericia-corrected QT (QTF) intervals, a non-linear mixed effect modeling approach was used along with clinical and demographic data, and serum miR-362-3p expression was evaluated as potential covariates on the PK/PD model.<div><br></div><div>Results: A three-compartment model best described the time course of ibutilide concentrations profile with a proportional residual error. The individual ibutilide concentrations time profile was then used in an indirect response model where ibutilide concentrations are indirectly driving the QT interval prolongation through inhibition of the output (Kout) parameters linked to an indirect response model with zero‐order input parameter best described the ibutilide concentrations QT interval lengthening relationship. The Individual PK/PD parameters using the base model for the Imax and IC50 were 11.4% (9.9%RES) and 0.36(8.4% RES)ng/mL, respectively. Following stepwise forwarding inclusion steps, the final covariate analyses identified circulating miR-362-3p expression associated with a history of myocardial infarction covariate influencing both the Imax and IC50( p<0.05). <div><br></div><div>Conclusions: An indirect response model has been developed to describe the effects of ibutilide concentrations on QT-intervals. Although the semi-mechanistic model could not be developed; serummiR-362-3p expression was identified as a significant predictor for ibutilide-induced QT-interval prolongation. Moreover, the upregulation of serum miR-362-3p expression enhanced IC50 seen after ibutilide administration. The potential use of miR-362-3p as a biomarker warrants further investigation to identify patients at the greatest risk of TdP </div></div></div>

<p>  </p> <p><strong>OBJECTIVES:</strong> Medication synchronization (med-sync) aligns patients’ chronic medications to a predetermined routine pickup date at a community pharmacy. An appointment-based model (ABM) med-sync service includes a comprehensive medication review at the pharmacy. We had the following objectives: (1) To systematically characterize literature describing healthcare utilization, cost clinical, and humanistic outcomes for patients enrolled in medication synchronization, (2) to determine the characteristics of Medicare Part D beneficiaries’ receipt of medication synchronization program and (3) to compare healthcare utilization outcomes of Medicare beneficiaries enrolled in an ABM med-sync program to beneficiaries not enrolled in such a program.</p> <p><br></p> <p><strong>METHODS:</strong> A systematic literature review was conducted using electronic databases from January 2008 to October 2022. The retrospective cohort study analyzed Medicare claims data from 2014-16 for a sample of 1 million beneficiaries utilizing community pharmacies identified as offering a med-sync program. Medicare inpatient, outpatient, emergency, and pharmacy claims data were used to create med-sync and non-med-sync cohorts. We applied Andersen’s Health Services Utilization model to determine factors associated with med-sync enrollment. We constructed logistic regression models with med-sync enrollment as the dependent variable adding predisposing, enabling, and need variables. Descriptive statistics and bi-variate analysis were performed on the cohorts. All patients were followed longitudinally for 12 months before and after a 2015 index/enrollment month to calculate healthcare utilization. Difference-in-differences (DID) was used to compare mean changes in utilization outcomes between cohorts before and after enrollment.</p> <p><br></p> <p><strong>RESULTS:</strong> Through systematic review, we found limited studies related to costs and healthcare utilization. Med-sync programs have shown to increase drug adherence to medications and improve patient satisfaction. For our study with Medicare beneficiaries, we identified 13,193 beneficiaries in the med-sync cohort and 156,987 beneficiaries in non-med sync (control) cohort. As age of beneficiaries increased, likelihood of med-sync enrollment increased (AOR=1.003, 95% CI:1.001-1.005). There were ​higher odds of enrollment for beneficiaries residing in Northeast (AOR=1.094, 95% CI:1.018-1.175), South (AOR=1.109, 95% CI:1.035-1.188), and West (AOR=1.113, 95% CI:1.020-1.215) than the Midwest. Beneficiaries residing in non-metro areas had lower odds of enrollment​ (AOR: 0.914, 95% CI: 0.863-0.969) than metro areas. Beneficiaries with less previous inpatient hospitalizations (AOR=0.945, 95% CI:0.914-0.977) were less likely to be enrolled whereas those with higher outpatient visits (AOR=1.003, 95% CI:1.001-1.004) were more likely to be enrolled. Beneficiaries taking a higher number of oral chronic medications (AOR=1.005, 95% CI:1.002-1.008) had greater odds of enrollment in med-sync. After propensity matching, 13,193 beneficiaries in each cohort were used for analysis. Mean pharmacy utilizations increased before and after enrollment for both cohorts while mean outpatient utilization decreased before and after enrollment for med-sync cohort only. Healthcare utilization mean DID were significantly less in the med-sync cohort compared to the non-med-sync cohort for outpatient visits (DID: 0.01, p=0.0073) and pharmacy fills (DID: 0.01, p<0.0001). There was no significant DID for inpatient and emergency visits between cohorts.</p> <p><br></p> <p><strong>CONCLUSION:</strong> Disparities in age, geographic region, type of residence and prior health utilization for med-sync enrollment were identified. Outpatient and pharmacy utilization changes were significantly lower in med-sync cohort compared to the non-med-sync cohort in the 12-months after enrollment. Lower pharmacy utilization could be due to optimization of therapy during medication reviews of ABM med-sync. As Medicare is approaching to a value-based system, there needs to be a greater focus on systems such as med-sync that has shown to improve a patient’s adherence. </p>

<p dir="ltr">Over 50% of ambulatory older adults administer at least one anticholinergic medication. Older adults may be more susceptible to the adverse effects of anticholinergic medications, and there is evidence showing an association between anticholinergic exposure and increased risk of dementia. The primary objective of this research is to assess the impact of one-year of prescriptions for strong anticholinergics, with a score of 2 or 3 on the Anticholinergic Cognitive Burden (ACB) Scale, on cognitive measures indicative of dementia, followed by a comparative assessment of the relative impact of medication classes with anticholinergic activity.</p><p dir="ltr">The study utilizes a retrospective observational design to evaluate the relationship between anticholinergic medication prescriptions and cognitive measures. We used one-year EMR prescription data gleaned from R2D2 and BrainSafe clinical trials’ participants prior to baseline for the exposure variable along with the cognitive measures captured at the baseline visit. Total Standardized Daily Dose (TSDD) was computed from prescription records to quantify exposure to strong anticholinergics. Generalized Linear Models and Least Square means with Tukey’s adjustment were computed to detect the relationship between anticholinergic TSDD and anticholinergic medication classes and cognitive measures in multiple models.</p>

<p>  </p> <p>Polypharmacy in older adults presents several challenges, such as suboptimal therapeutic outcomes and increased adverse effects. Deprescribing, a clinically supervised process of decreasing dosage or stopping the medication when risks outweigh benefits, has emerged as one possible solution to these problems. However, the literature describing deprescribing intervention frameworks is heterogenous regarding targeted medications to deprescribe, population characteristics, clinical settings, and measured outcomes. This dissertation utilizes Linsky et al.'s deprescribing conceptual model, which details factors influencing decisions regarding initiating deprescribing interventions and their direct impact on the process. </p> <p>This dissertation utilizes a multimethod approach to investigate factors that facilitate and improve the deprescribing of anticholinergic medications for older adults, addressing gaps in this population's anticholinergic medication use. The three studies included in this dissertation provide a comprehensive understanding of deprescribing anticholinergic medications for this population, each contributing unique insights and results. </p> <p>The first study explores the feasibility of in-person and remote Home Medication Inventory Method (HMIM) approaches to evaluate over-the-counter (OTC) and prescription medication possession and use, including anticholinergics. Results demonstrate that both methods can accurately assess anticholinergic medication usage patterns, providing healthcare providers with reproducible methods and detailed medication profiles to make informed deprescribing decisions based on complete medication lists.</p> <p>The second study examined the intertwined roles of social determinants of health and health beliefs in predicting older adults' self-reported deprescribing behaviors, proposing the Deprescribing Health Belief Model (DeRx-HBM) framework that can be utilized for these efforts. These results emphasize the importance of considering these elements when creating a patient-centric and culturally sensitive intervention since they significantly shape deprescribing behaviors.</p> <p>In the third study, we explored the use of a symptom-specific scale for measuring the symptom burden in older adults during the deprescribing of anticholinergic medications prescribed for urinary incontinence, depression, and pain management. This research introduces a validated scale for assessing anticholinergic symptom burden prior to, throughout, and following the deprescribing attempt. The implementation of this scale has the potential to enhance the reproducibility and standardization of deprescribing decisions. Furthermore, it can improve communication between healthcare professionals and patients, as well as monitor the effectiveness of interventions during and after the deprescribing process.</p> <p>Collectively, these studies provide invaluable insights into factors influencing deprescribing decisions, obstacles to implementing deprescribing practices, and potential strategies to optimize medication management in older adults. The major takeaway from these studies is that addressing these factors leads to more informed decisions among healthcare professionals and patients - potentially leading to improved patient outcomes, ensure the ongoing effectiveness of deprescribing initiatives among older adults, and the promotion of health equity throughout the deprescribing process.</p>